Econstudentlog

Utilitarianism (and some comments about ethics)

“The system of normative ethics which I am here concerned to defend is [...] act-utilitarianism. [...] Roughly speaking, act-utilitarianism is the view that the rightness or wrongness of an action depends only on the total goodness or badness of its consequences, i.e. on the effect of the action on the welfare of all human beings (or perhaps all sentient beings).”

The book is simple: The first half tells you why (act-)utilitarianism is great, and the second half tells you why utilitarianism sucks.

I’ve been unsure how to blog this book, and as I’m writing this I have still yet to decide what’s the best approach. It probably makes sense to start out with some general remarks. The first general remark is that I liked Smart’s half (the first half) better than Bernard Williams’ half, and I did that to a significant degree because it is in my opinion much easier to read and understand than especially the first half of the second half of the book – regardless of the merits of the arguments, I simply think J.C.C. Smart is a much better writer than is Bernard Williams. There are some important points hidden away in Williams’ account, but in my opinion he waffles so much you sometimes don’t really care one way or the other. Trained philosophers may disagree, but I’m not used to read philosophical texts and stuff like that is part of the reason.

The second general remark is that this book reminded me why I don’t really care about moral philosophy in the first place. Moral judgments don’t really interest me very much. Coming up with elaborate systems (or, in some cases, not-so-elaborate systems) of thought which allows some action patterns and disallows others, evaluated by considering how these systems perform in hypothetical scenarios which may or may not ever happen to anyone you know (“the common methodology of testing general ethical principles by seeing how they square with our felings in particular instances”, as Smart puts it in the book..), or perhaps evaluated by figuring out if the systems are self-consistent or not, simply seems to me a strange approach to how to identify good decision(/justification) rules.

I have come to realize that my opinion of the coverage – but perhaps especially Smart’s account – is influenced by some thoughts I had a while back and discussed with a friend last week. I was at the time considering blogging some of those thoughts, but I decided against it. Anyway these thoughts relate to how knowledge may shape how you think about stuff; this specific topic is actually covered in the book, though from a very different angle. I hold to the view that thinking which is more or less unconstrained by knowledge will most often be a very inferior type of thinking to the kind of (‘directed…’ was the word my friend used, a good word in this context I think) thinking which is constrained by data. What I came to realize along the way was that what I was really missing in this book was some actual knowledge about how humans behave, some understanding of why people behave the way they do, and how such aspects intersect both with which types of behaviours may in theory be ‘permissible’ or not, and why people think the way they do about the thoughts they have and the actions they engage in. We know some stuff about those kinds of things, books have been written about such things – for a neat little book on related topics, see Tavris & Aronson’s account. Smart mentions in his part of the book that: “If [...] act-utilitarianism were put forward as a descriptive systematization of how ordinary men, or even we ourselves in our unreflective and uncritical moments, actually think about ethics, then it is of course easy to refute [...] [But] it is precisely because a doctrine is false as description and as explanation that it becomes important as a possible recommendation.”

‘People don’t seem to make moral judgments the way I’d like them to, but if they did the world would be a better place’ may be true or it may not be true, but when your argument is founded on logic and you don’t really have good data to suggest that this approach to making moral judgments actually leads to better ‘moral outcomes’ (whatever that may mean – but then again the proponent of such a view is free to define his terms and then argue why his system is better, as that is how people do in other areas, so this caveat may not be important) then I don’t really think you have a very strong case. People (well, some people – it’s probably mostly other economists…) occasionally criticize economists harshly when they fail to take general equilibrium effects into account when making policy recommendations based on partial-equilibrium analyses (‘the employment effects of a job programme involving 500 people may be very different from the employment effects of the same type of job programme scaled up so that it involves 50.000 people’); what these guys are doing is in some sense even worse, as they’re really arguing without any data at all – “I think this”, “I think that”.

I’m sure this kind of stuff related to things like how you approach the topic of meta-ethics and where people stand on things like the non-cognitivist approach Smart talks about in his introduction, but I’m not well-versed in such matters. What I will say is that given what I know about many other topics (primatology, (/behavioural) economics, medicine, psychology, evolutionary biology, anthropology, …), I think the sort of approach these guys have to all of this stuff is not very ‘useful’; in my opinion you need to know and understand a lot of stuff about why people behave the way they do in order to even be in a position where you are justified in having any sort of opinion about how to evaluate the things people do or think in the first place. And these guys have not convinced me they know a lot about things aside from the sort of things philosophers know about this sort of stuff. I’ll go into more detail about these aspects below, but before doing that I would point out that another way to approach moral questions from the one they apply would be to identify/define specific outcomes, behaviours or motivations of interest, analyze variation in data on these variables, and figure out if there are some useful patterns to be found. Perhaps people who commit murder have things in common, and perhaps some of the variables they have in common can be addressed/modified by policies and/or behavioural change at the individual level. I’m not a philosopher, this is more along the lines of ‘where I’m coming from’.

In terms of ‘the stuff I know’ I alluded to above, a few examples are probably in order to get at some of the issues:

i. “Research on parent-child conflict during the first decade of life most often has focused on emotional outbursts, such as temper tantrums [...] and coercive behavior of children toward other family members as evidence of conflict. The frequency of such behavior begins to decline during early childhood and continues to do so during middle childhood [...] The frequency of episodes during which parents discipline their children also decreases between the ages of three and nine [...] research on conflict management in this period has focused on the relative effectiveness of various parental strategies for gaining compliance and managing negative behaviors.” (link)

ii. “The result of an interview is usually a decision. Ideally this process involves collecting, evaluating and integrating specific salient information into a logical algorithm that has shown to be predictive. However, there is an academic literature on impression formation that has examined experimentally how precisely people select particular pieces of information. Studies looking at the process in selection interviews have shown all too often how interviewers may make their minds up before the interview even occurs (based on the application form or CV of the candidate), or that they make up their minds too quickly based on first impression (superficial data) or their own personal implicit theories of personality. Equally, they overweigh or overemphasise negative information or bias information not in line with the algorithm they use.” (link)

iii. “many doors in life are opened or closed to you as a function of how your personality is perceived. Someone who thinks you are cold will not date you, someone who thinks you are uncooperative will not hire you, and someone who thinks you are dishonest will not lend you money. This will be the case regardless of how warm, cooperative, or honest you might really be. [...] a long tradition of research on expectancy effects shows that to a small but important degree, people have a way of living up, or down, to the impressions others have of them. [...] judges use stereotypes as an important basis for their judgment only when they have little information about the target. [...] When you know someone well you can base your judgments on what you have seen. When you have little information, you fall back on stereotypes and self-knowledge.” (link)

iv. “The need for closure (NFC) has been defined as a desire for a definite answer to a question, as opposed to uncertainty, confusion, or ambiguity [...] People exhibit stable personal differences in the degree to which they value closure. Some people may form definitive, and perhaps extreme, opinions regardless of the situation, whereas others may resist making decisions even in the safest environments. [...] Taken together, the research on intrapersonal processes demonstrates that people who are high in NFC seek less information, generate fewer hypotheses, and rely on early, initial information when making judgments.  [...] The manner in which people interpret their own and other people’s behaviors and outcomes is linked predictably with their self-esteem and self-concepts. [...] a large body of research on attribution processes shows that people high in self-esteem take credit for their successes and blame their failures on external factors [...] In contrast, people low in self-esteem are less inclined to take credit for their successes and more inclined to assume responsibility for their failures” (link)

v. “All addictive drugs are subjectively rewarding, reinforcing and pleasurable [1]. Laboratory animals volitionally self- administer them [2], just as humans do. Furthermore, the rank order of appetitiveness in animals parallels the rank order of appetitiveness in humans [...] it is relatively easy to selectively breed laboratory animals for the behavioral phenotype of drug-seeking behavior (the behavioral phenotype breeds true after about 15 generations in laboratory rodents)” (link)

vi. “Psychological autopsy studies in the West have consistently demonstrated strong associations between suicide and mental disorder, reporting that 90% of people who die by suicide have one or more diagnosable mental illness” (link)

vii. “Evolutionary explanations are recursive. Individual behavior results from an interaction of inherited attributes and environmental contingencies. In most species, genes are the main inherited attributes, but inherited cultural information is also important for humans. Individuals with different inherited attributes may develop different behaviors in the same environment. Every generation, evolutionary processes — natural selection is the prototype — impose environmental effects on individuals as they live their lives. Cumulated over the whole population, these effects change the pool of inherited information, so that the inherited attributes of individuals in the next generation differ, usually subtly, from the attributes in the previous generation. [...] Culture is a system of inheritance. We acquire behavior by imitating other individuals much as we get our genes from our parents. A fancy capacity for high-fidelity imitation is one of the most important derived characters distinguishing us from our primate relatives [...] We are also an unusually docile animal (Simon 1990) and unusually sensitive to expressions of approval and disapproval by parents and others (Baum 1994). Thus parents, teachers, and peers can rapidly, easily, and accurately shape our behavior compared to training other animals using more expensive material rewards and punishments.” (link)

viii. “When two people produce entirely different memories of the same event, observers usually assume that one of them is lying. [...] But most of us, most of the time, are neither telling the whole truth nor intentionally deceiving. We aren’t lying; we are self-justifying. All of us, as we tell our stories, add details and omit inconvenient facts [...] History is written by the victors, and when we write our own histories, we do so just as the conquerors of nations do: to justify our actions and make us look and feel good about ourselves and what we did or what we failed to do. If mistakes were made, memory helps us remember that they were made by someone else. If we were there, we were just innocent bystanders. [...] We remember the central events of our life stories. But when we do misremember, our mistakes aren’t random. The everyday, dissonance-reducing distortions of memory help us make sense of the world and our place in it, protecting our decisions and beliefs. The distortion is even more powerful when it is motivated by the need to keep our self-concept consistent; by the wish to be right; by the need to preserve self-esteem; by the need to excuse failures or bad decisions; or by the need to find an explanation, preferably one safely in the past” (link)

ix. “The basic idea behind self-signaling is that despite what we tend to think, we don’t have a very clear notion of who we are. We generally believe that we have a privileged view of our own preferences and character, but in reality we don’t know ourselves that well (and definitely not as well as we think we do). Instead, we observe ourselves in the same way we observe and judge the actions of other people—inferring who we are and what we like from our actions. [...] We may not always know exactly why we do what we do, choose what we choose, or feel what we feel. But the obscurity of our real motivations doesn’t stop us from creating perfectly logical-sounding reasons for our actions, decisions, and feelings.” (link)

One key point is that people are different, in all sorts of ways. They’re systematically different in terms of behavioural dispositions, and some behaviours may to a great extent be simply the result of biological factors (drug abuse is certainly relevant here, and suicide probably is as well. These are relevant to the discussion not just because there are relevant differences in behavioural dispositions, but also because people tend to think they ought to have views about the ethics of these behaviours). If individuals are different and such differences are important in terms of which actions the individuals are likely to engage in, it might be natural to suggest that taking such differences into account may be an important component in the evaluation of the ethical properties of a given behaviour. That was actually not the point I was going for, as I’m not sure I really care a great deal about how moral systems should look like. However it does seem to me that people are taking many individual-level differences into account, to varying degrees, when making moral jugments, whether or not they ‘should’.

The basic point is that people are different, and so they have different moral systems. This is not a new idea of mine, and I’ve previously touched upon factors of relevance in this analysis; see for example this post (key point: “If you’re better able to handle complexity you’re able to make use of more complex moral algorithms.”). Another way to think about it, which also relates to the quotes above, would be to say that as people use their moral systems repeatedly to justify their own behaviours and as people behave in different ways, it’s really beyond doubt that people have different moral systems which incorporate different stuff. When looked at from that point of view, utilitarianism is really just one system (or family of systems), which appeal to some specific people due to specific reasons related to why those people are the way they are and behave the way they do. This is my observation, not an observation made in the book, but Williams does touch very briefly upon related aspects, in the sense that he talks about “the spirit of utilitarianism, and [...] its demand for a rational, decideable, empirically based, and unmysterious set of values”, and at the end of his contribution charges the system with “simplemindedness”.

The social dimension alluded to in the quotes above seems relevant as well. Individuals are different from each other, but so are different groups of individuals (see e.g. vii). Groups are particularly important because stuff like social feedback systems are really important determinants of individual behaviours, and important determinants in terms of how individuals approach various questions and actions. For example people may act differently when they’re in a group than they do when they’re on their own – ethicists may or may not agree that such differences are relevant to the ethical judgment of behaviour, but there’s a potential variable lurking here which some people may consider to be important. Another related example might be that some people may search out social environments that contain people who are likely to approve of their behaviours and avoid social environments including people who do not – they may, in short, behave in a manner which may make enforcement of ethical systems more difficult. Some people may also respond differently to social feedback than do other people. If some people do consider such variables to be important when making moral judgments, and you’re planning to discuss ethics with such people, then you probably need to have some knowledge about how groups of people work, and how social aspects impact behaviour (i.e. you need to know some stuff about social psychology, sociology and related fields).

One argument here which is implicit is that if you have a moral system which makes judgments without regards to the knowledge we actually have of how people behave and why they behave the way they do, you’re likely to end up ‘left behind’ in the long run. You end up with something like religious rules, where you have a system of behavioural rules which perhaps sort of made sense, kind of, during a period where people didn’t really know anything about anything, but which makes a lot less sense now because we know better. It’s not hard to argue, though I’m sure some moral philosophers might disagree with me, that it is better to medicate the schizophrenic than to deem him mad and incarcerate him. I make this point explicit because at least judging from this book, I got the impression that the philosophical approach to how to handle ethical systems and evaluate their attributes seems to me to have many things in common with the religious approach, and much less in common with a behavioural sciences approach. Thought-experiments asking questions like how you would/should behave if you happened to find yourself in front of a guy who’s threatening to shoot 20 other people unless you shoot one of them yourself may be useful in terms of illustrating key aspects of an ethical system, but is this kind of analysis really likely to lead you very far? Some of this stuff seems to me not that different from theology. ‘People who act friendly and non-threatening in social situations are more likely to find friends and keeping them’ (or whatever) seems to me to be much more useful information, in terms of how to answer questions such as ‘what is a good (‘ethical’) way to live your life’, than are thought experiments like these and discussions about key assumptions related to those thought experiments. It seems to me that a lot of what these people are doing is adding new floors to the ivory tower and not much else.

In terms of the risk of being left behind comment above, I should note that I’m aware this is perhaps a problematic way to think about things. Some people (especially religious people, presumably) would certainly argue that it makes a lot of sense to adopt sort of a Darwinian approach to meta-ethics and consider the moral systems likely to persist and ‘survive’ to be ‘better’ than the alternatives; in which case religious systems have a lot of things going for them, in part because they’re very good at constraining thinking and suppressing certain lines of thought likely to weaken the systems (like the thought that all this stuff is just made up). Williams talks about related stuff in his coverage – his view is incidentally that such implicit constraints on moral thinking is a good thing, and he considers the absence of such constraints to be a problem with utilitarianism – I decided to include a few relevant quotes on that matter below:

“It could be a feature of a man’s moral outlook that he regarded certain courses of action [...or thought, US] as unthinkable, in the sense that he would not entertain the idea of doing them [...] Entertaining certain alternatives, regarding them indeed as alternatives, is itself something which he regards as dishonourable or morally absurd. But, further, he might equally find it unacceptable to consider what to do in certain conceivable situations. [...] Consequentialist rationality, however, and in particular utilitarian rationality, has no such limitations: making the best of a bad job is one of its maxims”

Something I found interesting in that part is that Williams does not make clear that constraints on moral thinking have the potential to lead to both good and bad ‘outcomes’ (‘lead to ‘better’ or ‘worse’ performing moral systems’ would be a statement inclusive enough to also incorporate non-consequentialist ethical systems, it seems to me, but then a different problem related to what we mean by ‘better’ or ‘worse’ of course pops up. Anyway if you have difficulty conceptualizing this idea it probably makes sense to just model it this way: Constraints on moral thinking may stop you from thinking that it might be a good idea to kill all the jews (the argument being that where people are free to think this thought, the associated outcome becomes more likely), but such constraints may also stop you from thinking that killing jews is wrong, if you happen to live in a society where killing jews is the morally enforced norm), even though a related symmetry argument seems to be used by both proponents and opponents of utilitarianism in the context of events taking place in the far future. Note incidentally on a related, if different, note that when people make moral judgments about a given action, in terms of how long time has passed since the event in question, may have a significant influence on the judgment in question (see viii).

I do not think people use utilitarian systems of thought to decide upon which actions to engage in, and as mentioned previously neither does Smart; he’s careful to point out in his coverage that what he’s defending is a normative system, not a descriptive system. In my view people often don’t know why they do the things they do, and even when they think they do, they probably don’t, really, because there are an incredible number of aspects which are relevant, and people probably often don’t know about half of them. “But the obscurity of our real motivations doesn’t stop us from creating perfectly logical-sounding reasons for our actions, decisions, and feelings”, as pointed out in ix. We’re not rational creatures, but we are rationalizing creatures. People may use a utilitarian framework to present the decision context and the decision process, but it’s just a model. I probably differ from Smart also in the sense that Smart may be a lot more optimistic about the feasibility of even applying such a scheme than I am. Smart would probably think about a hypothetical situation in this way: ‘I have thought about this potential action X, and it seems to me that the consequences of this action X would be that one person is made much better off and another person is made slightly worse off. If I do nothing instead, no-one is made either better off or worse off. I wish to maximize average happiness, and so this action seems justified. Thus I shall now proceed to do X.’ I would be more likely to think along these lines: ‘Smart’s primate brain had decided after 2/10ths of a second that Smart wanted to do X. Smart’s primate brain is good at making Smart think he’s in charge, so now Smart’s brain will engage in a bit of work which will yield him the answer ‘he’ already decided upon.’

The utilitarian model is just a model, and/but it’s the type of model which appeal to some types of people more than others. When you look at it like this, it sort of changes how you view the question of whether the question of whether ‘people should use utilitarian systems of thought more’ even makes sense. A book like this will probably in some ways tell you more about the personalities of the authors than it will tell you about the desirability of the more widespread ‘implementation’ (whatever that may mean) of a specific ethical system of thought. There’s no data here, just arguments, so neither of the authors really have a clue, would be my contention, and they probably would not be able to agree about how to even evaluate competing systems if they did. It is not perfectly true that they ‘have no clue’, as e.g. the information problems pointed out in Williams’ account towards the end, where he talks a bit about collective decision making rather than individual-level decision making in a utilitarian framework (the point being that you need a lot of data, which is not available, in order to engage in utilitarian analyses and semi-sensible utilitarian-inspired decision making at e.g. the population level), certainly do have at least some real-world relevance, but I think it’s close enough. One aspect that really irritated me about this coverage is that although there are some potentially valuable distinctions made along the way (people may employ the correct decision rule yet end up with a bad outcome anyway, and such things may be important when making moral judgments (…or judgments about how to best set up compensation schemes in organizations, I’ll add…); when deciding whether or not to praise an action a potentially relevant distinction is to be made between the desirability of the action and the desirability of praising the action), they don’t really get very far. If I ever find myself facing a Mexican who’s about to kill 20 people, I’ll know what to do, but…

Some people might have read some of the stuff above and thought to him/herself that if you’re a hardcore consequentialist/utilitarian who does not care about anything but the consequences of actions and the utility derived from them, then you probably don’t care about whether or not the individual made the decision because he was sleep-deprived or had high levels of testosterone in his blood due to an untreated medical condition. That’s the whole point, that you disregard irrelevant factors like intentions and similar stuff, right? I have sort of assumed this would not be the utilitarian’s reply because in that case the system seems to me to devolve into a caricature very fast (on account of the ‘and similar stuff’ part, not the intentions part), where you lock away the schizophrenic. I think there’s a big difference between including in the analysis people’s explicit justifications for their actions (leading to a ‘you meant well’ judgment) and other, implicit, factors which might also have influenced behaviour (‘the cancer patient was tired and in pain, and that was why she yelled at her neighbour when his dog ran into her garden’). There’s a difference between explaining and explaining away, but they sort of go hand in hand. In case you were not aware of this, this objection does not only relate to individual-level decision-making, as objections with a similar structure can be made in the contexts of population-level decision making, where the behaviours of groups of people may also have explanations/reasons which are relevant to the ethical judgment yet unrelated to the explicit justifications people forward for behaving the way they do. I’m not sure how I feel about the validity of some of the specific arguments to be made in the latter case and how relevant they are/ought to be to the moral judgments to be made, but I did want to mention this aspect to preclude people from perhaps assuming erroneously that even if there are problems at the level of the individual, such problems go away when you start looking at groups of people instead. I don’t think this is true at all, though of course details are different in different social contexts.

I know that I have not really talked a great deal about the actual contents of the book in this post, and if you’re really curious to learn more about what’s in there you’re welcome to ask and maybe I can be persuaded to provide some more details. I was planning to perhaps include a few quotes from the book in a future quotes post, but aside from that I’m not really considering spending any more time on the book here on the blog.

Feedback to the thoughts and ideas presented here are very welcome.

July 23, 2014 Posted by | books, ethics, philosophy | 5 Comments

Sexually Transmitted Viral Pathogens

The stuff below covers material from the last half of part V in Holmes et al. This previous post also dealt with this topic (the title of this post is the title of part 5 of the book, which if not hidden away in a 2000+ page textbook might well have been a book of its own; I’m quite sure you can find entire books on these topics which go into much less detail than does part 5 of this book). Some of the stuff was really hard to read; I’ve tried to include in this post mainly stuff people who have not read the rest of the coverage might be expected to understand without too much difficulty.

“Antibody to EBV [Epstein-Barr Virus] can be detected in 90-95% of the population by adulthood.10 Primary exposure often occurs in the first years of life, with seroconversion evident before the age of 5 years in 50% of children studied in the United States and Great Britain.22,23 In economically advantaged communities, primary infection may be delayed until adolescence or early adulthood,24 at which time acquisition of virus produces the clinical syndrome acute infectious mononucleosis. [...] Primary EBV infection in infancy or early childhood is usually subclinical, but when delayed until the second decade of life, it manifests as infectious mononucleosis in up to 50% of patients. A self-limiting lymphoproliferative disease, the syndrome consists of fever, headache, pharyngitis, lymphadenopathy, and general malaise. Resolution of symptoms may take weeks to months, but primary infection is always followed by the establishment of a permanent viral carrier state.”

“a highly significant correlation between seropositivity for EBV, sexual intercourse, and an increasing number of sexual partners was found in a cross-sectional analysis of 1006 new University students.50 In this study, two-thirds of infectious mononucleosis cases were statistically attributable to sexual intercourse, whereas only a tenth of asymptomatic primary infections were linked to sexual activity.” [This is of course just a cross-sectional analysis, but even so - 'kissing disease' may perhaps be a slightly inaccurate term...]

“The overall size of the EBV-infected B cell reservoir is largely controlled by CD8+, HLA class I-restricted, EBV-specific cytotoxic T lymphocytes (CTLs). Up to 5% of the total circulating CD8+ T cell pool may be committed to this single virus in the EBV-carrier state,110 indicating the critical role for T-cell surveillance in maintaining the host: virus balance. Impaired CTL responses in immunosuppressed patients such as transplant recipients or HIV-1-infected individuals32,111 leads to an expansion of the infected B cell population and potentially fatal lymphoproliferative disease. The contribution of virus-specific CTLs in immune regulation of EBV-induced lymphoproliferation has been made clear by recent therapeutic interventions involving adoptive transfer of virus-specific T lymphocytes to restore immunity against EBV infection in bone marrow transplant recipients.112, 113, 114

Non-Hodgkin’s lymphoma, an AIDS-defining cancer some 60 times more common in AIDS patients than in the general population,122 can be divided morphologically into Burkitt-like and immunoblastic lymphomas [...]. Both have a higher association with EBV (30-40% and 75-80%, respectively) in AIDS than in non-AIDS groups.123,124 [...] Burkitt’s lymphomas appear early in the course of AIDS, prior to profound immunosuppression, whereas immunoblastic lymphomas typically occur in late-stage AIDS when cellular immunity is compromised. [...] Hodgkin’s lymphomas in the setting of AIDS contain EBV in 75-90% of the cases,140,141 reflecting the unusually high frequency in the HIV-infected population of mixed-cellularity and lymphocyte-depletion subtypes142 known to be most closely associated with EBV in the general population.15,16 Although not considered an AIDS-defining illness, Hodgkin’s lymphoma occurs with increased frequency in the setting of HIV infection. [...] Our understanding of the precise role of EBV in the biology of each malignancy remains rudimentary.”

“Papillomaviruses are a group of small DNA viruses that primarily induce epithelial cell proliferation, or papillomas, in higher vertebrates. Infections are strictly genus or species specific and there is considerable tropism among the viruses for particular anatomic sites. [...] The genomes of over 100 human papillomavirus (HPV) types have been molecularly cloned and completely sequenced and partial sequences for potentially up to another hundred types have been detected by PCR-based assays.9,10

[You can skip this part without missing out on anything important:] “A basal level of transcription from the p97/p105 promoter is regulated by the keratinocyte-dependent enhancer in the NCR and can be repressed by binding of E2 to its cognate recognition sequences located adjacent to the p97/p105 TATA boxes.82,87 E2 has a role in repressing transcription from the viral promoter and its loss on viral DNA integration allows increased expression of the oncogenic proteins E6 and E7. E2 also activates transcription under some circumstances.88 Variations in binding to four different E2 binding sites may contribute to transcriptional regulation.89 Interestingly, the E8E2C protein of HPV-31 had an ability to repress transcription from a single promoter-distal E2 binding site. This activity was lacking in the full-length E2, suggesting that E8E2C has a role in regulating transcription.90 E2 binds the general transcription factor TFIIB91 and is thought to directly inhibit HPV transcription at a step subsequent to binding of TBP or TFIID to the TATA box.92 It interacts with numerous other transcription factors and chromatin modification factors including CBP,93 p/CAF,94 C/EBP,95 nucleosome assembly protein 1,96 and Top BP1.97 An interaction between bromodomain protein 4 and E2 is required for transcriptional activation by E2.98 Two crystal structure studies of the amino terminal transcription activation domain of E2 suggested that dimerization of E2 helps recruit distal transcription factors to the viral transcription complex99 …” [I decided to include a quote like this as well to indicate what kind of stuff the book is also full of, and illustrate why it was hard to read. There's a lot of stuff in some of these chapters which I had a really hard time following.]

“Predictions about the role of HPV in neoplasia obtained from experimental studies are consistent with the natural history of cervical cancer. Among women who develop squamous intraepithelial lesions, the time from first detection of viral DNA to lesions is short, ~2 years, though factors like number of partners and infection with other STDs may influence the interval [...]. Even mildly dysplastic lesions show an increase in proliferation and polyploidization. These changes result as a direct consequence of expression of E6/E7. The median age of carcinoma in situ (CIS) in the United States is 29,223,224 indicating that approximately a decade has elapsed between the initial infection and severe dysplasia. CIS lesions are characterized by their aneuploid DNA content and thus reflect the genetic instability that accompanies prolonged expression of E6/E7. The preneoplastic lesions can regress spontaneously. One principle explanation for their regression is likely to be an effective immune response, and generalized T-cell deficiency has been associated with increased dysplasia [...]. Other explanations may include the fact that some, perhaps most, alterations will be deleterious, resulting in cell death. The median age of invasive cervical cancer in the United States is 49, indicating that additional changes required for invasion and metastasis are acquired slowly over time.”

“All HPV types are linked to the development of low-grade cervical SILs [squamous intraepithelial lesions],16 whereas high-grade cervical SILs are usually positive for oncogenic HPV types.272 In a cohort of young women in the United States, Moscicki et al.155 reported that 15% developed LSIL within 3 years after initial HPV infection, and in the UK, Woodman et al.70 reported that the 3-year cumulative incidence of any cytologic abnormality after initial infection was 33%. In another cohort of young women in the United States, Winer et al.132 reported that approximately 50% developed a low-grade lesion within 3 years after initial HPV infection [...]. The latter study also reported that rates of lesion detection tend to increase with increased screening frequency, due to spontaneous regression of most low-grade lesions. Therefore, the shorter interval between follow-up visits (4 vs. 6 months) may explain why that study detected LSIL in a higher proportion of women. Half of newly detected low-grade lesions appear to regress within 6-9 months.70,132,273 It also appears that vaginal SIL is not uncommon among women with incident HPV infections. While less commonly detected than cervical SIL, one study reported that almost 30% of women with incident HPV infections developed vaginal SIL within 3 years (Fig. 28-3B), and the median duration of these lesions was less than 5 months.132

Results from natural history studies suggest that LSILs are transient manifestations of productive HPV infections, whereas HSILs are cervical cancer precursor lesions. This is in contrast to the previously held theory that cervical carcinogenesis always follows a progression from persistent HPV infection to development of low- and then high-grade lesions. Several recent studies have shown that cervical highgrade lesions are a relatively early manifestation of HPV infections in young women. Woodman et al.70 reported that the risk of high-grade lesions was highest in the first 6 months after initial HPV infection. It has also been shown that histologically confirmed high-grade lesions are common after infection with HPV 16 and 18 infections,132,274 with one study reporting that 27% of women with incident HPV 16 or 18 infections developed histologically confirmed CIN grade 2 or 3 within 3 years [...] and that the median time to development was 14 months.132

“Although viral hepatitis is unquestionably an ancient disease, it is only in the past 40 years that an appreciation has emerged of the diversity of infectious agents capable of causing the clinical syndrome of acute hepatitis. [...] at least five distinctly different human viruses (classified as hepatitis A through E) are now generally recognized to be causative agents of acute and/or chronic viral hepatitis [...].

Hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus (HDV), and hepatitis E virus (HEV) all share a remarkable tropism for the liver despite profound differences in their physical structure, pathobiology, and epidemiology. Each of these viruses is a cause of clinically overt acute hepatitis associated with frank jaundice. The severity of the liver disease, which frequently accompanies acute infection with these viruses, generally distinguishes them from cytomegalovirus and Epstein-Barr virus, which typically cause much milder liver dysfunction during primary infections. Within the United States, almost all cases of acute hepatitis are caused by infection with HAV (51%), HBV (40%), or HCV (9%).3 These acute hepatitis virus infections cannot be distinguished from each other without serologic testing. Acute hepatitis represents a considerable disease burden within the United States, with an estimated 40,000-60,000 clinical cases occurring annually during the past 5 years. Only a fraction of these cases are reported to public health authorities, and a substantial number of additional infections do not come to medical attention because they are asymptomatic. Fulminant hepatic failure and death occur in a very small proportion of patients with acute hepatitis A or B, but these clinical endpoints are rarely associated with acute HCV infection in the United States.4,5

“The major burden of disease due to hepatitis virus infections stems from the chronic liver damage that occurs in individuals who develop persistent infections. The proportion of persons who become persistently infected is highly dependent on the infecting virus. Persistent infections with HAV are not well documented and may never occur. On the other hand, more than 50% of persons infected with HCV fail to clear the virus and most eventually develop biochemical and histologic evidence of chronic liver disease.6 HBV has an intermediate tendency to establish persistence, with the risk of persistent infection being highly dependent on the age at the time of infection and immunologic competence of the individual.

It is appropriate to focus attention on the hepatitis viruses in a textbook concerned with sexually transmitted diseases (STDs). Although these are systemic infections that are also commonly transmitted by other means, HBV is a sexually transmitted infection, and sexual activity may profoundly influence the risks for acquisition of HAV. To a lesser extent, sexual behavior may also influence the risk of infection with HCV and HDV.”

“Several factors account for the high risk of HBV infection among MSM [Males who have Sex with Males], which was noted in [...] early studies. One of the most important factors was the number of sexual partners. The typical homosexually active male frequenting Denver’s steam baths in the late 1970s had eight different male sexual contacts per month.206 These contacts were largely anonymous and could total as many as 1000 over the lifetime of a gay man.”

“The endemicity of HBV infection varies greatly worldwide and is influenced primarily by the predominant age at which infection occurs.121,190 Endemicity of infection is considered high in those parts of the world where at least 8% of the population is HBsAg positive, and 70-90% of the population has serological evidence of previous HBV infection. Almost all infections occur during either the perinatal period or early in childhood, which accounts for the high rates of chronic HBV infection in these populations. Risk of HBV infection continues after the first 5 years of life, but its eventual contribution to the high rate of chronic infection is less significant. Chronic infection with HBV is strongly associated with HCC [liver cancer], and areas with a high endemicity of chronic HBV infection have the highest death rates from this neoplasm. [...]

In most developed parts of the world, including the United States and Western Europe, the prevalence of chronic HBV infection is <1%, and the overall infection rate is 5-7%. The highest incidence of acute hepatitis B is among young adults, and high-risk sexual activity and injectable drug use account for most cases of newly acquired hepatitis B.191, 192, 193, 194 In the United States, heterosexual activity accounts for 40% of new hepatitis B cases, while MSM represent 15% of new cases.”

“HCV infection accounts for 15% of acute viral hepatitis cases within the United States. However, it is by far the leading cause of chronic viral hepatitis and is present in over 40% of persons with chronic liver disease. The morbidity and mortality associated with HCV infection are due to its unique propensity to cause persistent infection in most persons, a feature that distinguishes this virus from other hepatitis viruses. The specific mechanisms underlying viral persistence are not known.

Although it has been controversial, the balance of evidence now favors the occasional sexual transmission of HCV. The risk of infection with HCV, like HBV, has been independently related to numbers of sexual partners in some STD clinic studies.226,285 Although the risk of HCV infection has been shown to correlate with numbers of partners and/or specific sexual practices in some studies of homosexual men,286,287 the risk of infection is overwhelmingly more closely tied to injection drug use. [...] About 60-85% of all infections lead to virus persistence, and this is often associated with evidence of chronic liver disease [...]. After many years, this process may culminate in cirrhosis and liver failure, or the development of hepatocellular carcinoma. These end-stage events in chronic hepatitis C may claim as many as 10,000 lives annually in the United States.326 [...] As many as a third of patients found to have chronic hepatitis C will ultimately develop cirrhosis6,284,333,334; although it is not well defined, the fraction of all patients who are infected with the virus and progress to cirrhosis is undoubtedly far lower. Cirrhosis may be present within as little as 60 months of the initial infection but is identified typically in persons who have been infected for decades. Factors associated with disease progression include age at infection, regular alcohol consumption, coinfection with HIV or HBV, and more recently obesity and insulin resistance.335, 336 Some patients, usually with well-established cirrhosis, develop primary hepatocellular carcinoma.283 Chronic HCV infection is the most important etiology of hepatocellular carcinoma in western countries.

The major challenge to clinical investigators has been the discovery of specific markers that are predictive of progression of chronic hepatitis C to a clinically significant disease state. This remains an exceptionally difficult problem. There is no good correlation between biochemical markers and the extent of fibrosis or the presence or absence of cirrhosis. Indeed, many patients with cirrhosis have no obvious laboratory abnormalities.333 In addition, quantitative measurements of the viremia (“virus load”) are not useful in determining the extent of disease resistance.335, 336

 

July 20, 2014 Posted by | books, cancer, medicine | Leave a comment

One of Our Thursdays Is Missing

(Sorry for the long wait for another update; in general I’d say I try quite hard not to let more than three days pass between updates, but due to personal stuff I wasn’t really able to find the time to blog anything over the last few days.)

The book mentioned in the post title is the sixth novel in the Thursday Next series by Jasper Fforde. I liked it better than the fifth book in the series, and this one is probably in my top three of the books in this series. In general I really like the books in this series; Fforde is playing around with a lot of ‘meta’ stuff other books are not playing around with, and the best way to illustrate this stuff is probably through quotes (so I’ve added some of those below). Part of why I liked this book better than the previous one is also that it further develops the universe in which the action takes place; in a way the previous book did not really do this, at least not in my opinion to nearly the same extent.

If you plan on reading this series, you should start from the beginning; you’ll get a lot less out of this book than you otherwise would if you are not familiar with the context.

I’ve added a little stuff from the book below – I have tried hard to not include any spoilers. The book is full of completely absurd stuff, and it has so much quote-worthy stuff that it would be easy for me to write at least another post or two like this one.

“‘I’m Alyona Ivanovna,’ said the third Russian with a trace of annoyance, ‘the rapacious old pawnbroker whose apparent greed and wealth lead you to murder.’
‘Are you sure you’re Ivanovna?’ asked Raskolnikov in a worried tone.
‘Absolutely.’
‘And you’re still alive?’
‘So it seems.’
He stared at the bloody axe.
‘Then who did I just kill?’
And they all looked at each other in confusion.”

“To a text-based life-form, unpredictable syntax and poor grammar are sources of huge discomfort. Ill-fitting grammar are like ill-fitting shoes. You can get used to it for a bit, but then one day your toes fall off and you can’t walk to the bathroom. Poor syntax is even worse. Change word order and sentence useless that for anyone Yoda except you have.”

“My book was first-person narrative, and if I wanted to have any sort of life outside my occasional readings – such as a date with Whitby or a secondary career – I needed someone to stand in for me.”

“reality was a pit of vipers for the unwary. Forget to breathe, miscalculate gravity or support the wrong god or football team and they’d be sending you home in a zinc coffin.”

“We fell silent for a moment as the tram rumbled on. I didn’t tell him that I yearned for the most under-appreciated luxury of the human race – free will. My life was by definition preordained. I had to do what I was written to do, say what I was written to say, without variance all day every day, whenever someone read me. Despite conversations like this where I could think philosophically rather than narratively, I could never shrug off the peculiar feeling that someone was controlling my movements, and eavesdropping on my every thought.”

“The queue to get out of Poetry was long, as always. The smuggling of Metaphor out of the genre was a serious problem [...] The increased scarcity of raw Metaphor in Fiction had driven prices sky high, and people would take unbelievably foolish risks to smuggle it across. I’d heard stories of Metaphor being hidden in baggage, swallowed, even dressed up to look like ordinary objects whose meanings were then disguised to cloak the Metaphor. The problem then was trying to explain why you had a ‘Brooding Thunderstorm’ or ‘Broad sunlit uplands’ in your luggage. [...] Distilling Metaphor out of raw euphemism was wasteful and expensive”

“‘The less people that know the better.’
‘Fewer. The fewer people that know the better.’
‘That’s what I meant.’
‘That’s what who meant?’
‘Wait – who’s speaking now?’
‘I don’t know.’
‘You must know.’
‘Damn. It must be me – you wouldn’t say “Damn”, would you?’
‘I might.’
We both sat there for an empty moment, waiting for either a speech marker or a descriptive line. It was one of those things that happened every now and then in the Bookworld – akin to an empty, pregnant silence in the middle of an Outland dinner party. [...] The taxi slowed down and stopped as the traffic ground to a halt. The cabby made some enquiries and found that a truckload of their had collided with a trailer containing there going in the opposite direction, and had spread the contents across the road.
‘Their will be a few hiccups after that,’ said the cabby, and I agreed. Homophone mishaps often seeped out into the RealWorld and infected the Outlanders, causing theire to be all manner of confusions.”

“Comedy was never straightforward. When all the good jokes had left, only the dubiously amusing stuff remained. Was the mimefield funny or not? To us, I think not. But it might have been funny to someone.” (well, this reader laughed…)

“I’m on leave and certainly not stealing military equipment, no ma’am.’ [...] The clown sighed resignedly and opened his kitbag to reveal boxes of Military Grade Custard Pies. He wasn’t a very good smuggler. Few were.”

“‘[The Realworld is] highly disorderly,’ he explained, ‘not like here. There is no easily definable plot and you can run yourself ragged wondering what the significance of a chance encounter can be. You’ll also find that for the most part there is no shorthand to the narrative, so everything happens in a long and painfully drawn-out sequence. Apparently, the talk can be confusing – in general, most people just say the first thing that comes into their head.’
‘Is it as bad as they say?’
‘I’ve heard it’s worse. Here in the Bookworld we say what needs to be said for the story to proceed. Out there? Well, you can discount at least eighty per cent of chat as just meaningless drivel. [...] The people to listen to are the ones who don’t say very much. [...] above all, don’t be annoyed or distracted when random things happen to absolutely no purpose.’
‘There’s always a purpose,’ I said, amused by the notion of utter pointlessness, ‘even if you don’t understand what it is until much later.’
‘That’s a big difference between here and there,’ said Plum. ‘When things happen after a randomly pointless event, all that follows is simply unintended consequences, and not a coherent narrative thrust that propels the story forward.’
I rolled the idea of ‘unintended consequences’ around in my head.
‘Nope,’ I said finally, ‘you’ve got me on that one.’
‘It confuses me too,’ admitted Plum, ‘but that’s the RealWorld for you.’”

“It felt like covering for a character in a book without being told what the book was about, who was in it, or even what your character had been doing up until then. I’d done it twice in the BookWorld, so had some experience in these matters.”

“‘What about Red Herring, ma’am?’
‘I’m not sure. Is Red Herring a red herring? Or is it the fact that we’re meant to think Red Herring is a red herring that is actually the red herring?’
‘Or perhaps the fact that you’re meant to think Red Herring isn’t a red herring makes Red Herring a red herring after all.’
‘We’re talking serious meta-herrings here. Oh, craps, I’m lost again. Who’s talking now?’”

“‘Who is that?’ I asked as a man with his face obscured by a large pair of dark glasses hurried past and went below decks, followed by a porter carrying his suitcases.
‘He’s the mandatory MP-MC12: Mysterious Passenger in Cabin Twelve. All sweaty journeys upriver have to carry the full complement of odd characters. It’s a union thing.’”

 

 

 

July 19, 2014 Posted by | books | Leave a comment

Ayer

The stuff below is excerpts and quotes from Pojman‘s reprint of Ayer’s Language, Truth and Logic. I wasn’t quite sure how to blog this, and in particular I was not sure if I should wait with covering Ayer to I’d also finished reading Russell (I’m currently reading Russell’s The Problems of Philosophy from the same book. I may decide to read William James later on as well), covering both in one post. I somewhat dislike writing long posts based on paper-books, so in the end I decided to just post what I’d got. I haven’t really commented much on the stuff below and given my own views, partly because I’m lazy, but I guess I don’t mind going on the record here as someone who’s probably not exactly a big fan of metaphysics (…to the extent that I even know what it is; it’s not like I’ve wasted a lot of time on this kind of stuff.).

“Like Hume, I divide all genuine propositions into two classes: those which, in his terminology, concern “relations of ideas,” and those which concern “matters of fact.” The former class comprises the a priori propositions of logic and pure mathematics, and these I allow to be necessary and certain only because they are analytic. That is, I maintain that the reason why these propositions cannot be confuted in eperience is that they do not make any assertion about the empirical world, but simply record our determination to use symbols in a certain fashion. Propositions concerning empirical matters of fact, on the other hand, I hold to be hypotheses, which can be probable but never certain. [...] no proposition, other than a tautology, can possibly be more than a probable hypothesis. [...] A hypothesis cannot be conclusively confuted any more than it can be conclusively verified.”

“I adopt what may be called a modified verification principle. For I require of an empirical hypothesis, not indeed that it should be conclusively verifiable, bu that some possible sense-experience should be relevant to the determination of its truth or falsehood. If a putative proposition fails to satisfy this principle, and is not a tautology, then I hold that it is metaphysical, and that, being metaphysical, it is neither true nor false but literally senseless. [...] much of what ordinarily passes for philosophy is metaphysical according to this criterion [...] The traditional disputes of philosophers are, for the most part, as unwarranted as they are unfruitful. [I included this quote in the recent quotes post as well] [...] philosophy, as a genuine branch of knowledge, must be distinguished from metaphysics.”

“the fact that a conclusion does not follow from its putative premise is not sufficient to show that it is false.”

“We say that the question that must be asked about any putative statement of fact is not, Would any observations make its truth or falsehood logically certain? but simply, Would any observations be relevant to the determination of its truth or falsehood? And it is only if a negative answer is given to this second question that we conclude that the statement under consideration is nonsensical.”

“It must, of course, be admitted that our senses do sometimes deceive us. We may, as the result of having certain sensations, expect certain other sensations to be obtainable which are, in fact, not obtainable. But, in all such cases, it is further sense-experience that informs us of the mistakes that arise out of sense-experience. We say that the senses sometimes deceive us, just because the expectations to which our sense-experiences give rise do not always accord with what we subsequently experience. That is, we rely on our senses to substantiate or confute the judgments which are based on our sensations. [...] Consequently, anyone who comdemns the sensible world as a world of mere appearance, as opposed to reality, is saying something which, according to our criterion of significance, is literally nonsensical.” [On a related note I have always found it hard to figure out what's the point of discussions about 'whether we really live in a simulation or not', and I'm slightly mystified by how many presumably very smart and in other respects seemingly sensible people consider exploring such questions in depth to be a good use of their limited time here on Earth.]

“existence is not an attribute. For, when we ascribe an attribute to a thing, we covertly assert that it exists: so that if existence were itself an attribute, it would follow that all positive existential propositions were tautologies, and all negative existential propositions self-contradictory; and this is not the case. [...] In general, the postulation of real non-existent entities results from the superstition [...] that, to every word or phrase that can be the grammatical subject of a sentence, there must somewhere be a real entity corresponding. For as there is no place in the empirical world for many of these “entities”, a special non-empirical world is invoked to house them. To this error must be attributed, not only the utterances of a Heidegger, who bases his metaphysics on the assumption that “Nothing” is a name which is used to denote something peculiarly mysterious, but also the prevalence of such problems as those concerning the reality of propositions and universals whose senselessness, though less obvious, is no less complete. [...] The metaphysician [...] does not intend to write nonsense. He lapses into it through being deceived by grammar, or through committing errors of reasoning”

 

July 14, 2014 Posted by | books, philosophy | Leave a comment

Quotes

i. “A part of kindness consists in loving people more than they deserve.” (Joseph Joubert)

ii. “There is only one thing about which I am certain, and this is that there is very little about which one can be certain.” (W. Somerset Maugham)

iii. “Sometimes people carry to such perfection the mask they have assumed that in due course they actually become the person they seem.” (-ll-)

iv. “… habits in writing as in life are only useful if they are broken as soon as they cease to be advantageous.” (-ll-)

v. “We are not the same persons this year as last; nor are those we love. It is a happy chance if we, changing, continue to love a changed person.” (-ll-)

vi. “It was not till quite late in life that I discovered how easy it is to say: “I don’t know.”” (-ll-)

vii. “Nothing in the world is permanent, and we’re foolish when we ask anything to last, but surely we’re still more foolish not to take delight in it while we have it.” (-ll-)

viii. “The traditional disputes of philosophers are, for the most part, as unwarranted as they are unfruitful.” (Alfred Ayer)

ix. “The less justified a man is in claiming excellence for his own self, the more ready he is to claim all excellence for his nation, his religion, his race or his holy cause.” (Eric Hoffer)

x. “Passionate hatred can give meaning and purpose to an empty life. Thus people haunted by the purposelessness of their lives try to find a new content not only by dedicating themselves to a holy cause but also by nursing a fanatical grievance. A mass movement offers them unlimited opportunities for both.” (-ll-)

xi. “The uncompromising attitude is more indicative of an inner uncertainty than of deep conviction. The implacable stand is directed more against the doubt within than the assailant without.” (-ll-)

xii. “When people are free to do as we please, they usually imitate each other.” (-ll-)

xiii. “To most of us nothing is so invisible as an unpleasant truth. Though it is held before our eyes, pushed under our noses, rammed down our throats — we know it not.” (-ll-)

xiv. “We lie loudest when we lie to ourselves.” (-ll-)

xv. “Kindness can become its own motive. We are made kind by being kind.” (-ll-)

xvi. “Wisdom never comes to those who believe they have nothing left to learn.” (Charles de Lint)

xvii. “Any impatient student of mathematics or science or engineering who is irked by having algebraic symbolism thrust on him should try to get on without it for a week.” (Eric Temple Bell)

xviii. “There are many things that seem impossible only so long as one does not attempt them.” (André Gide)

xix. “The most decisive actions of our life — I mean those that are most likely to decide the whole course of our future — are, more often than not, unconsidered.” (-ll-)

xx. “Experience is what you get when you didn’t get what you wanted.” (Randy Pausch)

 

July 14, 2014 Posted by | quotes | Leave a comment

Infectious Agents and Cancer

“[H]uman papilloma virus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, human herpes virus 8, human T-cell lymphotropic virus 1, human immunodeficiency virus, Merkel cell polyomavirus, Helicobacter pylori, Opisthorchis viverrini, Clonorchis sinensis, Schistosoma haematobium [...] are recognized as carcinogens and probable carcinogens by [the] International Agency for Research on Cancer (IARC). They are not considered in this book [...] The aim of this monograph is to analyze associations of other infectious agents with cancer risk [...] virology is not considered in our monograph: although there are some viruses that can be connected with cancer but are not included into the IARC list (John Cunningham virus, herpes simplex virus-1 and -2, human cytomegalovirus, simian virus 40, xenotropic murine leukemia virus-related virus), we decided to leave them for the virologists and to concentrate our efforts on other infectious agents (bacteria, protozoa, helminths and fungi) [...] To the best of our knowledge, this is the first book devoted to this problem”

Here’s what I wrote on goodreads:

“This book is written by three Russian researchers, and you can tell; the language is occasionally hilariously bad, but it’s not too difficult to figure out what they’re trying to say. The content partially made up for the poor language, as the book covers quite a bit of ground considering the low page count.”

I gave the book two stars. I’m glad they wrote the book, because it covered some stuff I didn’t know much about. I think I’m closer to one star than three, but it’s mostly because it’s terribly written, not because I have major objections to the coverage as such. What I mean by this is that they talk about a lot of studies and they include a lot of data – they’re scientists who write about scientific research, they just happen to be Russian scientists who are not very good at English. It’s terribly written, but the stuff is interesting.

As mentioned above there are quite a few viruses which we know may lead to cancer in humans. I’ve recently read a lot of stuff about this topic as it was covered in both Boffetta at el. and also rather extensively in part 5 of the Sexually Transmitted Diseases text, which covered sexually transmitted viral pathogens (that section of the book was with its 230 pages actually a ‘book-length section’; it was significantly longer than this book is..). I’ve even covered some of that stuff here on the blog, e.g. here. I may incidentally write more about these things and related stuff later, as I’m quite far behind in terms of my intended coverage of the STD book at the moment.

Anyway, viruses aren’t the only bad guys around. So these guys decided to write a book about some other infectious diseases affecting humans, and how these infectious diseases may relate to cancer risk. As they point out in the book, “there is only one bacterium, Helicobacter pylori, which is recognized by IARC as an established human carcinogen.” After reading this book you’ll realize that there are some others which perhaps look a bit suspicious as well. In some cases a lot of studies have been done and you have both animal-models, lab-analyses, case-control studies, cohort studies, … In other cases you have just a few small studies to judge from. As is always the case when people have a close look at epidemiological research, this stuff is messy. Sometimes studies that looked really convincing turn out to not replicate in larger samples, sometimes dramatically different effect sizes are found in different areas of the world (which may of course both be interpreted as an indicator that the ‘true’ effect sizes are different in the different subpopulations, or it may be interpreted as a result e.g. of faulty study design which makes those Swedish data look really fishy..), sometimes different results can be explained by differences in data quality/type of data applied/etc. (classic cases are different effects based on whether you rely on self reports or biological disease markers, and different results from analyses of bacterial cultures vs PCR analyses), and so on and so forth. There are a lot of details, and they cover them in the book. I occasionally see people criticize epidemiological research online on the grounds that many (‘all?’) results published in this area are just random correlations without any deeper meaning. Sometimes this criticism may well be warranted, and the authors of this book certainly in some cases seem to go quite a bit further than I would do based on the same data. But there’s another part of the story here. When you start out with a couple of case-control studies indicating that guys with cancer type X are more likely to have positive lab cultures for this specific micro-organism, that may not be a big deal. But perhaps then a few microbiologists show up and tell you that it would actually make a lot of sense if there was a connection here (and they might start talking about fancy stuff like various ‘modulations of host immune responses’, ‘inflammatory markers’, ‘the role of nitric oxides’, …). They conduct some studies as well and perhaps one of the things they find is that the observed cancer grades in the patients seem to depend quite a lot upon which of the pathogen subtypes the individual happen to be infected with (perhaps suddenly also providing an explanation for some previously surprising negative results in specific cases). And then perhaps you get a couple of animal studies that show that these animals get cancer when you infect them with these bugs and don’t treat the infection. Perhaps you have a few more studies as well in different populations, because Chinese people get cancer too, and you start seeing that people around the world who happen to be infected with these bugs are all more likely to get cancer, compared to the locals who are not infected (…or perhaps not, and then it just gets more fun…). This process goes on for a while, until at some point it starts getting really hard to think these positive correlations are all just the result of random p-value hunting done by bored researchers who don’t know what else to do with their time, and you start asking yourself if perhaps this idea is not as stupid as it was when you first encountered it. Most of the time the process stops before then because the proposed link isn’t there, but modern epidemiology is not just random collections of correlations.

In the context of the specific infectious diseases covered in the book the people who have in some sense the final say in these things (the IARC) think we’re not quite there yet, but you have some cases where some different lines of evidence all seem to indicate that a link may be present and relevant. It would be highly surprising to me if in 20 years time we’d have realized that none of the infectious diseases they talk about in this book are at all involved in cancer pathogenesis. A related point is that most likely we’ve missed some ‘true connections’ along the way, and will continue to do so in the future, because even if a link is there, it’s sometimes really hard to find it and easy to overlook it, for many different reasons.

I have quoted a bit from the book below and added some comments here and there. I have corrected some of the spelling/language errors the authors made to ease reading; if a word is placed in brackets, it’s an indicator that I’ve replaced a misspelled word by the correct one (‘they meant to use’). The authors do not even have any clue how and when to use the word ‘the’, often using it when it’s not needed and forgetting to use it in cases where it is needed, which made quoting from the book painful. Read it for the content.

“Chronic inflammation substantially increases the probability of neoplastic transformation of the surrounding cells, inducing mutations and epigenetic alterations by the activity of inflammatory molecules [...] through the formation of free radicals and DNA damage [...] Since infectious agents persisting in the organism may cause chronic inflammation, they can also promote local carcinogenesis. [...] Chronic inflammation can also specifically affect the functioning of [an] organ, for instance, promoting cholelithiasis and urolithiasis that increase the time of exposure of the gallbladder, bile ducts, urinary bladder and ureters to chemical carcinogens and carcinogenic bacteria. [...] In addition to [...] metabolic and immune mechanisms, a number of bacteria [...] and protozoa [...] [produce] or [contain] in their cell wall their own toxins [...] possessing [carcinogenic] activity, affecting cell-cell interactions, intracellular signal transduction or induction of mutations and epigenetic alterations that can influence vital cell processes (apoptosis, proliferation, survival, growth, differentiation, invasion). Intracellular protozoan (Toxoplasma gondii) may induce resistance to multiple mechanisms of apoptosis [...]. So, bacterial and [protozoan toxins] may function like initiating or like promoting agents.”

“Typhoid fever, which is a systemic infection caused by Salmonella enterica serovar Typhi (S. typhi), is a major health problem in developing countries. There are approximately 21.6 million cases of typhoid fever worldwide and an estimated 200,000 deaths every year. It is known that S. typhi may colonize the gallbladder, causing [...] chronic inflammation. Welton et al. (1979) were the very first to [establish] an association between the typhoid-carrier state and death due to malignancies of the hepatobiliary tract. They recruited 471 U.S. carriers of [S. typhi] , matched them with 942 controls and demonstrated that chronic typhoid carriers died of hepatobiliary cancer six times more often than the controls. [...] The absence of basic research analyzing the carcinogenic properties of S. typhi does not allow placing it in the short list of the infectious agents that may be a cause of cancer development but are not included in the IARC roster, but this bacterium undoubtedly should be [on] the extended list. If [basic] studies on cell lines and animal models [support] the results of [the] epidemiological investigations, S. typhi can be placed [on] the short list.” [I included this in part because it is one of several examples in the book of how even strong correlations and high relative risks are not considered sufficient on their own by epidemiologists to settle matters. Some relative risks in other studies have been even higher - a study on gall-bladder cancer found an RR of 12.7].

“Tuberculosis (TB), a destructive disease [affecting] the lungs [...] is a major global health burden, with about nine million of new cases and 1.1 million deaths annually. When the host protective immunity fails to control M. tuberculosis growth, progression to active disease occurs. [...] According to the data of the last comprehensive systematic review and [meta-analysis] published by Brenner et al. (2011), there were 30 studies [...] conducted in North America, Europe and Asia, which investigated the association of tuberculosis on lung cancer risk with adjustment for smoking. The relative risk (RR) of lung cancer development among patients with TB history was 1.76 (95% CI = 1.49–2.08).”

“22 studies from North America, Europe and East Asia [have] investigated the association between pneumonia and lung cancer risk while adjusting for smoking [...] A significant increase in lung cancer risk was observed among all studies (RR = 1.43, 95% CI = 1.22–1.68). [...] To sum up, there are basic as well as extensive epidemiological evidence that С. pneumoniae may cause lung cancer” [However effect sizes seem to be different in different countries. I was skeptical about this one in part because a non-smoker's absolute risk of getting lung cancer is very low, meaning that relative risks in the neighbourhood reported above although statistically significant probably are clinically insignificant. How pneumonia and smoking interact seems to me a much more important question. Then again we haven't got an explanation for all of the non-smoking-related lung cancers yet, and they are caused by something, so it's also not like researching this is a complete waste of time.]

“Primary infection with C. trachomatis [Chlamydia], the most prevalent sexually transmitted bacterium worldwide with an estimated 90 million new cases occurring each year, is often asymptomatic and may persist for several months or years. The first study analyzing possible association of C. trachomatis with cervical cancer was carried out by Schachter et al. (1975) who assessed the prevalence of antibodies to TRIC (trachoma-inclusion conjunctivitis) agents in women with cervical dysplasia and in women attending selected clinics [...]. According to this investigation, antibodies to chlamydiae were identified in 77.6% of the women with dysplasia or cervical cancer whereas antichlamydial antibodies were less prevalent in the other clinic populations. Four years later, Paavonen et al. (1979) obtained [similar] results in 93 of patients with cervical dysplasia comparing them to the controls. [...] Smith et al. (2001, 2002) examined 499 women with incident invasive cervical cancer cases and 539 control patients from Brazil and the Philippines, detecting that C. trachomatis increased risk of squamous cervical cancer among HPV-positive women (OR=2.1; 95% CI=1.1–4.0). The results were similar in both countries.” [As I recently pointed out elsewhere, "Chronic infection with HPV is a necessary cause of cervical cancer. Using sensitive molecular techniques, virtually all tumours are positive for the virus." But as this finding (and other related findings) indicate, other infectious processes may play a role as well in HPV-related cancers. Synergistic effects are common in this area (recall for example also the herpes simplex virus-HIV link).]

Trichomonas vaginalis (T. vaginalis), a protozoan parasite, is the causative agent of trichomoniasis, the most common nonviral sexually transmitted disease in humans. This parasite has a worldwide distribution and it infects 250–350 million people worldwide. [wiki says ~150 mil, but these guesstimates should always be taken with a grain of salt. Either way it affects a lot of people] [...] Zhang et al. (1995) observed a relationship between T. vaginalis infection and cervical cancer in [their] prospective study in a cohort of 16,797 Chinese women. T. vaginalis-infection correlated with higher cervical cancer risk (RR=3.3, 95% CI=1.5–7.4). In a large cohort study conducted in Finland by Viikki et al. (2000) T. vaginalis was associated with a high RR of cervical cancer, 6.4 (95% CI = 3.7–10) and SIR [standardized incidence ratio]=5.5 (95% CI=4.2–7.2s), respectively. [...] Mekki and Ivić (1979), detected that T. vaginalis were of a significantly smaller diameter in invasive carcinoma and carcinoma in situ in comparison with dysplasia. In the control group with trichomoniasis alone, the diameter of T. vaginalis was twice as large as that in carcinoma and larger compared to dysplasia, indicating that small forms of T. vaginalis are more carcinogenic than large ones. [...] To sum up, there are basic as well as epidemiological evidence that T. vaginalis may be a cause of cervical and prostate cancer [...] For cervical cancer it is evident, for prostate cancer it is arguable. According to our criteria, it is possible to include it in the short list of the infectious agents that may be a cause of cancer development but are not placed in the IARC roster.”

“At the moment of publication, IARC [recognizes] Schistosoma haematobium [and] [S. mansoni], Opisthorchis viverrini, and Clonorchis sinensis as causative agents of cancer, leaving a possibility to enlarge this list by [Schistosoma japonicum] [and] Opisthorchis felineus.” [The authors think the list should be enlarged even more, but I did not find their helmith data/coverage very convincing (not much research has been done in this area), so I decided not to cover these things here].

 

July 12, 2014 Posted by | books, cancer, medicine | Leave a comment

Wikipedia articles of interest

i. Albert Stevens.

Albert Stevens (1887–1966), also known as patient CAL-1, was the subject of a human radiation experiment, and survived the highest known accumulated radiation dose in any human.[1] On May 14, 1945, he was injected with 131 kBq (3.55 µCi) of plutonium without his knowledge or informed consent.[2]

Plutonium remained present in his body for the remainder of his life, the amount decaying slowly through radioactive decay and biological elimination. Stevens died of heart disease some 20 years later, having accumulated an effective radiation dose of 64 Sv (6400 rem) over that period. The current annual permitted dose for a radiation worker in the United States is 5 rem. [...] Steven’s annual dose was approximately 60 times this amount.”

“Plutonium was handled extensively by chemists, technicians, and physicists taking part in the Manhattan Project, but the effects of plutonium exposure on the human body were largely unknown.[2] A few mishaps in 1944 had caused certain alarm amongst project leaders, and contamination was becoming a major problem in and outside the laboratories.[2] [...] As the Manhattan Project continued to use plutonium, airborne contamination began to be a major concern.[2] Nose swipes were taken frequently of the workers, with numerous cases of moderate and high readings.[2][5] [...] Tracer experiments were begun in 1944 with rats and other animals with the knowledge of all of the Manhattan project managers and health directors of the various sites. In 1945, human tracer experiments began with the intent to determine how to properly analyze excretion samples to estimate body burden. Numerous analytic methods were devised by the lead doctors at the Met Lab (Chicago), Los Alamos, Rochester, Oak Ridge, and Berkeley.[2] The first human plutonium injection experiments were approved in April 1945 for three tests: April 10 at the Manhattan Project Army Hospital in Oak Ridge, April 26 at Billings Hospital in Chicago, and May 14 at the University of California Hospital in San Francisco. Albert Stevens was the person selected in the California test and designated CAL-1 in official documents.[2] [...] The plutonium experiments were not isolated events.[2] During this time, cancer researchers were attempting to discover whether certain radioactive elements might be useful to treat cancer.[2] Recent studies on radium, polonium, and uranium proved foundational to the study of Pu toxicity. [...] The mastermind behind this human experiment with plutonium was Dr. Joseph Gilbert Hamilton, a Manhattan Project doctor in charge of the human experiments in California.[6] Hamilton had been experimenting on people (including himself) since the 1930s at Berkeley. [...] Hamilton eventually succumbed to the radiation that he explored for most of his adult life: he died of leukemia at the age of 49.”

“Although Stevens was the person who received the highest dose of radiation during the plutonium experiments, he was neither the first nor the last subject to be studied. Eighteen people aged 4 to 69 were injected with plutonium. Subjects who were chosen for the experiment had been diagnosed with a terminal disease. They lived from 6 days up to 44 years past the time of their injection.[2] Eight of the 18 died within 2 years of the injection.[2] All died from their preexisting terminal illness, or cardiac illnesses. [...] As with all radiological testing during World War II, it would have been difficult to receive informed consent for Pu injection studies on civilians. Within the Manhattan Project, plutonium was referred to often by its code “49″ or simply the “product.” Few outside of the Manhattan Project would have known of plutonium, much less of the dangers of radioactive isotopes inside the body. There is no evidence that Stevens had any idea that he was the subject of a secret government experiment in which he would be subjected to a substance that would have no benefit to his health.[2][6]

The best part is perhaps this: Stevens was not terminal: “He had checked into the University of California Hospital in San Francisco with a gastric ulcer that was misdiagnosed as terminal cancer.” It seems pretty obvious from the fact that one of the people involved in these experiments survived for 44 years and the fact that four other experimentees were still alive by the time Stevens died that he was not the only one who was misdiagnosed, and one interpretation of the fact that more than half survived beyond two years might be that the definition of ‘terminal’ applied in this context may have been, well, slightly flexible (especially considering how large injections of radioactive poisons in these people may not exactly have increased their life expectancies). Today people usually use this term for conditions which people can expect to die from within 6 months – 2 years is a long time in this context. It may however also to some extent just have reflected the state of medical science at the time – also illustrative in that respect is how the surgeons screwed him over during his illness: “Half of the left lobe of the liver, the entire spleen, most of the ninth rib, lymph nodes, part of the pancreas, and a portion of the omentum… were taken out”[1] to help prevent the spread of the cancer that Stevens did not have.” In case you were wondering, not only did they not tell him he was part of an experiment; they also did not ever tell him he had been misdiagnosed with cancer.

ii. Aberration of light.

“The aberration of light (also referred to as astronomical aberration or stellar aberration) is an astronomical phenomenon which produces an apparent motion of celestial objects about their locations dependent on the velocity of the observer. Aberration causes objects to appear to be angled or tilted towards the direction of motion of the observer compared to when the observer is stationary. The change in angle is typically very small, on the order of v/c where c is the speed of light and v the velocity of the observer. In the case of “stellar” or “annual” aberration, the apparent position of a star to an observer on Earth varies periodically over the course of a year as the Earth’s velocity changes as it revolves around the Sun [...] Aberration is historically significant because of its role in the development of the theories of light, electromagnetism and, ultimately, the theory of Special Relativity. [...] In 1729, James Bradley provided a classical explanation for it in terms of the finite speed of light relative to the motion of the Earth in its orbit around the Sun,[1][2] which he used to make one of the earliest measurements of the speed of light. However, Bradley’s theory was incompatible with 19th century theories of light, and aberration became a major motivation for the aether drag theories of Augustin Fresnel (in 1818) and G. G. Stokes (in 1845), and for Hendrick Lorentzaether theory of electromagnetism in 1892. The aberration of light, together with Lorentz’ elaboration of Maxwell’s electrodynamics, the moving magnet and conductor problem, the negative aether drift experiments, as well as the Fizeau experiment, led Albert Einstein to develop the theory of Special Relativity in 1905, which provided a conclusive explanation for the aberration phenomenon.[3] [...]

Aberration may be explained as the difference in angle of a beam of light in different inertial frames of reference. A common analogy is to the apparent direction of falling rain: If rain is falling vertically in the frame of reference of a person standing still, then to a person moving forwards the rain will appear to arrive at an angle, requiring the moving observer to tilt their umbrella forwards. The faster the observer moves, the more tilt is needed.

The net effect is that light rays striking the moving observer from the sides in a stationary frame will come angled from ahead in the moving observer’s frame. This effect is sometimes called the “searchlight” or “headlight” effect.

In the case of annual aberration of starlight, the direction of incoming starlight as seen in the Earth’s moving frame is tilted relative to the angle observed in the Sun’s frame. Since the direction of motion of the Earth changes during its orbit, the direction of this tilting changes during the course of the year, and causes the apparent position of the star to differ from its true position as measured in the inertial frame of the Sun.

While classical reasoning gives intuition for aberration, it leads to a number of physical paradoxes [...] The theory of Special Relativity is required to correctly account for aberration.”

The article has much more, in particular it has a lot of stuff about historical aspects pertaining to this topic.

iii. Spanish Armada.

“The Spanish Armada (Spanish: Grande y Felicísima Armada or Armada Invencible, literally “Great and Most Fortunate Navy” or “Invincible Fleet”) was a Spanish fleet of 130 ships that sailed from A Coruña in August 1588 under the command of the Duke of Medina Sidonia with the purpose of escorting an army from Flanders to invade England. The strategic aim was to overthrow Queen Elizabeth I of England and the Tudor establishment of Protestantism in England, with the expectation that this would put a stop to English interference in the Spanish Netherlands and to the harm caused to Spanish interests by English and Dutch privateering.

The Armada chose not to attack the English fleet at Plymouth, then failed to establish a temporary anchorage in the Solent, after one Spanish ship had been captured by Francis Drake in the English Channel, and finally dropped anchor off Calais.[10] While awaiting communications from the Duke of Parma‘s army the Armada was scattered by an English fireship attack. In the ensuing Battle of Gravelines the Spanish fleet was damaged and forced to abandon its rendezvous with Parma’s army, who were blockaded in harbour by Dutch flyboats. The Armada managed to regroup and, driven by southwest winds, withdrew north, with the English fleet harrying it up the east coast of England. The commander ordered a return to Spain, but the Armada was disrupted during severe storms in the North Atlantic and a large portion of the vessels were wrecked on the coasts of Scotland and Ireland. Of the initial 130 ships over a third failed to return.[11] [...] The expedition was the largest engagement of the undeclared Anglo-Spanish War (1585–1604). The following year England organised a similar large-scale campaign against Spain, the Drake-Norris Expedition, also known as the Counter-Armada of 1589, which was also unsuccessful. [...]

The fleet was composed of 130 ships, 8,000 sailors and 18,000 soldiers, and bore 1,500 brass guns and 1,000 iron guns. [...] In the Spanish Netherlands 30,000 soldiers[17] awaited the arrival of the armada, the plan being to use the cover of the warships to convey the army on barges to a place near London. All told, 55,000 men were to have been mustered, a huge army for that time. [...] The English fleet outnumbered the Spanish, with 200 ships to 130,[18] while the Spanish fleet outgunned the English—its available firepower was 50% more than that of the English.[19] The English fleet consisted of the 34 ships of the royal fleet (21 of which were galleons of 200 to 400 tons), and 163 other ships, 30 of which were of 200 to 400 tons and carried up to 42 guns each; 12 of these were privateers owned by Lord Howard of Effingham, Sir John Hawkins and Sir Francis Drake.[1] [...] The Armada was delayed by bad weather [...], and was not sighted in England until 19 July, when it appeared off The Lizard in Cornwall. The news was conveyed to London by a system of beacons that had been constructed all the way along the south coast.”

“During all the engagements, the Spanish heavy guns could not easily be run in for reloading because of their close spacing and the quantities of supplies stowed between decks [...] Instead the gunners fired once and then jumped to the rigging to attend to their main task as marines ready to board enemy ships, as had been the practice in naval warfare at the time. In fact, evidence from Armada wrecks in Ireland shows that much of the fleet’s ammunition was never spent.[26] Their determination to fight by boarding, rather than cannon fire at a distance, proved a weakness for the Spanish; it had been effective on occasions such as the battles of Lepanto and Ponta Delgada (1582), but the English were aware of this strength and sought to avoid it by keeping their distance. With its superior manoeuvrability, the English fleet provoked Spanish fire while staying out of range. The English then closed, firing repeated and damaging broadsides into the enemy ships. This also enabled them to maintain a position to windward so that the heeling Armada hulls were exposed to damage below the water line. Many of the gunners were killed or wounded, and the task of manning the cannon often fell to the regular foot soldiers on board, who did not know how to operate the guns. The ships were close enough for sailors on the upper decks of the English and Spanish ships to exchange musket fire. [...] The outcome seemed to vindicate the English strategy and resulted in a revolution in naval battle tactics with the promotion of gunnery, which until then had played a supporting role to the tasks of ramming and boarding.”

“In September 1588 the Armada sailed around Scotland and Ireland into the North Atlantic. The ships were beginning to show wear from the long voyage, and some were kept together by having their hulls bundled up with cables. Supplies of food and water ran short. The intention would have been to keep well to the west of the coast of Scotland and Ireland, in the relative safety of the open sea. However, there being at that time no way of accurately measuring longitude, the Spanish were not aware that the Gulf Stream was carrying them north and east as they tried to move west, and they eventually turned south much further to the east than planned, a devastating navigational error. Off the coasts of Scotland and Ireland the fleet ran into a series of powerful westerly winds [...] Because so many anchors had been abandoned during the escape from the English fireships off Calais, many of the ships were incapable of securing shelter as they reached the coast of Ireland and were driven onto the rocks. Local men looted the ships. [...] more ships and sailors were lost to cold and stormy weather than in direct combat. [...] Following the gales it is reckoned that 5,000 men died, by drowning, starvation and slaughter at the hands of English forces after they were driven ashore in Ireland; only half of the Spanish Armada fleet returned home to Spain.[30] Reports of the passage around Ireland abound with strange accounts of hardship and survival.[31]

In the end, 67 ships and fewer than 10,000 men survived.[32] Many of the men were near death from disease, as the conditions were very cramped and most of the ships ran out of food and water. Many more died in Spain, or on hospital ships in Spanish harbours, from diseases contracted during the voyage.”

iv. Viral hemorrhagic septicemia.

Viral hemorrhagic septicemia (VHS) is a deadly infectious fish disease caused by the Viral hemorrhagic septicemia virus (VHSV, or VHSv). It afflicts over 50 species of freshwater and marine fish in several parts of the northern hemisphere.[1] VHS is caused by the viral hemorrhagic septicemia virus (VHSV), different strains of which occur in different regions, and affect different species. There are no signs that the disease affects human health. VHS is also known as “Egtved disease,” and VHSV as “Egtved virus.”[2]

Historically, VHS was associated mostly with freshwater salmonids in western Europe, documented as a pathogenic disease among cultured salmonids since the 1950s.[3] Today it is still a major concern for many fish farms in Europe and is therefore being watched closely by the European Community Reference Laboratory for Fish Diseases. It was first discovered in the US in 1988 among salmon returning from the Pacific in Washington State.[4] This North American genotype was identified as a distinct, more marine-stable strain than the European genotype. VHS has since been found afflicting marine fish in the northeastern Pacific Ocean, the North Sea, and the Baltic Sea.[3] Since 2005, massive die-offs have occurred among a wide variety of freshwater species in the Great Lakes region of North America.”

The article isn’t that great but I figured I should include it anyway because I find it sort of fascinating how almost all humans alive can and do live their entire lives without necessarily ever knowing anything about stuff like this. Humans have some really obvious blind spots when it comes to knowledge about some of the stuff we put into our mouths on a regular basis.

v. Bird migration.

Bird migration is the regular seasonal movement, often north and south along a flyway between breeding and wintering grounds, undertaken by many species of birds. Migration, which carries high costs in predation and mortality, including from hunting by humans, is driven primarily by availability of food. Migration occurs mainly in the Northern Hemisphere where birds are funnelled on to specific routes by natural barriers such as the Mediterranean Sea or the Caribbean Sea.”

Migrationroutes.svg

“Historically, migration has been recorded as much as 3,000 years ago by Ancient Greek authors including Homer and Aristotle [...] Aristotle noted that cranes traveled from the steppes of Scythia to marshes at the headwaters of the Nile. [...] Aristotle however suggested that swallows and other birds hibernated. [...] It was not until the end of the eighteenth century that migration as an explanation for the winter disappearance of birds from northern climes was accepted [...] [and Aristotle's hibernation] belief persisted as late as 1878, when Elliott Coues listed the titles of no less than 182 papers dealing with the hibernation of swallows.”

“Approximately 1800 of the world’s 10,000 bird species are long-distance migrants.[9][10] [...] Within a species not all populations may be migratory; this is known as “partial migration”. Partial migration is very common in the southern continents; in Australia, 44% of non-passerine birds and 32% of passerine species are partially migratory.[17] In some species, the population at higher latitudes tends to be migratory and will often winter at lower latitude. The migrating birds bypass the latitudes where other populations may be sedentary, where suitable wintering habitats may already be occupied. This is an example of leap-frog migration.[18] Many fully migratory species show leap-frog migration (birds that nest at higher latitudes spend the winter at lower latitudes), and many show the alternative, chain migration, where populations ‘slide’ more evenly North and South without reversing order.[19]

Within a population, it is common for different ages and/or sexes to have different patterns of timing and distance. [...] Many, if not most, birds migrate in flocks. For larger birds, flying in flocks reduces the energy cost. Geese in a V-formation may conserve 12–20% of the energy they would need to fly alone.[21][22] [...] Seabirds fly low over water but gain altitude when crossing land, and the reverse pattern is seen in landbirds.[25][26] However most bird migration is in the range of 150 m (500 ft) to 600 m (2000 ft). Bird strike aviation records from the United States show most collisions occur below 600 m (2000 ft) and almost none above 1800 m (6000 ft).[27] Bird migration is not limited to birds that can fly. Most species of penguin migrate by swimming.”

“Some Bar-tailed Godwits have the longest known non-stop flight of any migrant, flying 11,000 km from Alaska to their New Zealand non-breeding areas.[36] Prior to migration, 55 percent of their bodyweight is stored fat to fuel this uninterrupted journey. [...] The Arctic Tern has the longest-distance migration of any bird, and sees more daylight than any other, moving from its Arctic breeding grounds to the Antarctic non-breeding areas.[37] One Arctic Tern, ringed (banded) as a chick on the Farne Islands off the British east coast, reached Melbourne, Australia in just three months from fledging, a sea journey of over 22,000 km (14,000 mi). [...] The most pelagic species, mainly in the ‘tubenose’ order Procellariiformes, are great wanderers, and the albatrosses of the southern oceans may circle the globe as they ride the “roaring forties” outside the breeding season. The tubenoses spread widely over large areas of open ocean, but congregate when food becomes available. Many are also among the longest-distance migrants; Sooty Shearwaters nesting on the Falkland Islands migrate 14,000 km (8,700 mi) between the breeding colony and the North Atlantic Ocean off Norway. Some Manx Shearwaters do this same journey in reverse. As they are long-lived birds, they may cover enormous distances during their lives; one record-breaking Manx Shearwater is calculated to have flown 8 million km (5 million miles) during its over-50 year lifespan.[39]

“Bird migration is primarily, but not entirely, a Northern Hemisphere phenomenon.[50] This is because land birds in high northern latitudes, where food becomes scarce in winter, leave for areas further south (including the Southern Hemisphere) to overwinter, and because the continental landmass is much larger in the Northern Hemisphere [see also this post]. In contrast, among (pelagic) seabirds, species of the Southern Hemisphere are more likely to migrate. This is because there is a large area of ocean in the Southern Hemisphere, and more islands suitable for seabirds to nest.[51]

 

July 10, 2014 Posted by | biology, history, medicine, Physics, wikipedia, Zoology | Leave a comment

Sexually Transmitted Diseases (4th edition) (IV)

Here’s a link to a previous post about the book, which includes links to the first two posts I wrote about it.

I was not super impressed with the coverage in part 3, although there was a lot of interesting stuff as well. However the level of coverage and amount of detail included is high in part four and five. There were a lot of details which evaded me in some of the recent chapters, but I also learned a great deal. There’s quite a lot of coverage of various ‘related topics’ (microbiology, biochemistry, immunology, oncology) in the parts of the book I’ve read recently, and like many other medical texts this book will help you realize that many things you in your mind had thought of as unrelated actually are connected in various interesting ways. It’s worth noting that given how many aspects of these things the book covers (again, 2000+ pages…) you actually get to know a lot of stuff about a lot of other things besides just ‘classic STDs’. It turns out that in Jamaica and Trinidad, over 70% of all lymphoid malignancies are attributable to exposure to a specific herpes virus most people probably haven’t heard about, HTLV-1 (prevalence is also high in other parts of the world, e.g. southern Japan). I didn’t expect to learn this from a book about sexually transmitted diseases, but there we are.

I hope that I’ve picked out stuff from this part of the coverage which is also intelligible to people who didn’t read the 95+% of those chapters I didn’t quote (I always like feedback on such aspects).

“At the simplest level, infection of a cell by a virus or bacterium may lead to cell death. In the case of viruses, specific disease syndromes may be caused by destruction of certain subsets of cells that express essential differentiated functions. A classic example of this is the development of the AIDS following HIV-1 mediated depletion of the CD4 lymphocyte population. Virus-induced cell death may result from one or more specific mechanisms. Many viruses express specific proteins that have as their major function the induction of a blockade in normal host cell metabolism (cellular translation and transcription) such that the metabolic machinery of the cell is subverted preferentially to viral replication. For obvious reasons, the expression of such proteins is usually highly toxic to the cell. Cellular destruction or “direct cytopathic effect” is considered responsible for the disease manifestations of many lytic viruses, including, for example, HSV and poliovirus. On the other hand, many cells may respond to the presence of an invading virus by the induction of apoptosis and the initiation of programmed cell death. Some viruses appear to have evolved mechanisms to prevent or delay apoptosis, thus potentially prolonging productive infection and maximizing replication. For example, HSV-1 infection induces apoptosis at multiple metabolic checkpoints but has also evolved mechanisms to block apoptosis at each point.28 Importantly, the inhibition of apoptosis by HSV-1 also prevents apoptosis induced by virus-specific cytotoxic T lymphocytes, thereby conferring on the infected cell a certain measure of resistance to the host’s cell-mediated immune responses.29

However, many viruses are not intrinsically cytopathic. HBV is a prime example, as many infected HBsAg carriers are asymptomatic and without overt evidence of active liver disease. Despite this, such carriers may be very infectious [...] The presence or absence of liver disease is largely determined by the T-cell response to the virus.30 Thus, chronic hepatitis B results from a relatively vigorous but unsuccessful attempt on the part of the host to eliminate the infection. [...] chronic liver inflammation and the occurrence of hepatocellular carcinoma reflect the immune response to the virus, rather than specific virus effects. Similar indirect mechanisms may contribute to the progressive immune destruction of infected CD4-positive lymphocytes in patients with HIV-1 infection.

Some bacterial disease processes may also be caused largely to immunopathologic responses. For instance, there is substantial evidence that complications of genital chlamydia infections (salpingitis, Reiter’s syndrome) are correlated with and may be owing to stimulation of antibodies against a heatshock protein (hsp60).33,34 [...] In contrast, gonococcal tissue damage appears to be caused by the direct toxic effects of lipid A and peptidoglycan fragments”

“Some viruses are capable of altering differentiated cellular functions, resulting in the production of disease by mechanisms that do not exist among bacteria. A prime example is the altered cellular growth that follows infections by molluscum contagiosum virus (MCV) [...]. A more extreme example is the proliferation of epithelial cells that is induced by infection with HPVs. HPV-related epithelial malignancies and cellular transformation are related to the expression of two specific HPV proteins, the E6 and E7 oncoproteins, by high-risk HPV subtypes.22 These proteins interact with p53 and pRb, both promoting cellular proliferation and cell survival. Oncogenic transformation is usually associated with high-level expression of E7 from integrated HPV DNA. The Kaposi’s sarcoma-associated herpes virus (KSHV) also expresses a number of proteins that mimic important host regulators of cellular proliferation and survival [...] Expression of these proteins may result in deregulation of cell growth, with changes in the cellular morphology and/or acquisition of the ability of the cells to form colonies in soft agar, changes that are indicative of transformation.

On the other hand, hepatocellular cancers occurring in the context of chronic viral hepatitis are likely to have an alternative explanation. Although it is possible that integration of HBV DNA may be responsible for altered cellular growth control in some hepatitis B-associated cases, liver cancer in this setting may be primarily immunopathogenic.30,32 Chronic inflammation accompanied by oxidative stress and cellular DNA damage are likely to pla[y] important roles.”

“The human immunodeficiency viruses (HIV-1 and HIV-2) and the simian immunodeficiency viruses (SIV) (with a subscript indicating the species of origin) are members of the lentivirus genus of the Retroviridae family, commonly called retroviruses. [...] Retroviruses are divided into two subfamilies: Orthoretrovirinae and Spumaretrovirinae [...] The spumaretroviruses have distinctive features of their replication cycle that require this more distant classification. They have been isolated from primates, but not humans, and are not associated with any known disease. The orthoretroviruses are divided into six genera and represent viruses that infect snakes, fish, birds, and mammals. [...] Human infections occur with viruses from two of these genera. The Deltaretrovirus genus includes human T-cell leukemia virus type I (HTLV-I), the causative agent of adult T-cell leukemia,5, 6, 7 and human T-cell leukemia virus type II (HTLV-II), which is not known to be associated with any disease syndrome. HTLV-I is also associated with another syndrome called HTLV-associated myelopathy (HAM). HTLV-I and HTLV-II are related to viruses found in primates and more distantly related to bovine leukemia virus. The lentivirus genus includes HIV-18 and HIV-29 as well as viruses found in a variety of mammals ranging from primates to sheep. Viruses within these different genera vary widely in the diseases they cause and the mechanisms of disease induction, in contrast to the many common features of their replication cycle. [...] In its DNA form the viral genome is inserted into the host genome [...]. This step in the virus life cycle has important implications for several features of virus-host interactions. For example, viral DNA that integrates into the genome of a cell but is not expressed becomes silently carried in the descendents of that cell. When this happens in a germline cell, or in the cell of an early embryo that becomes a germline cell, this copy of viral DNA becomes a linked physical part of the host genome, is present in every cell in the body, and is passed on to subsequent generations. Such a genetic element is called an endogenous retrovirus. Most of the elements that become fixed are defective, as there is probably a strong selective pressure against elements that can activate to produce infectious virus. Thus, they represent an archive within the host genome of previous waves of retroviral infections. In fact, the human genome carries a record of retroviral infections over the last 40 million years of primate evolution. These are viruses that we do not recognize as active in the human population at present but are represented by 110,000 genomic inserts of gammaretroviruses, 10,000 inserts of betaretroviruses, and 80,000 inserts of a genus that may be distantly related to spumaretroviruses or may represent an uncharacterized lineage.10 Most of these elements contain large deletions; however, if these deletions had been retained, our genomes would be 40% endogenous retroviruses by mass and outnumber our normal genes 7 to 1.”

“Most histories of retroviruses start with the dramatic discovery by Peyton Rous in 1911 that a virus, Rous sarcoma virus (RSV), could cause cancer. [...] The isolation of other tumor-causing retroviruses followed and in time it became apparent that there were two broad classes of agents: one class of viruses caused cancer after a long latency period [...], while the other class caused tumors that appeared rapidly [...]. We now know that the acutely transforming retroviruses carry a cell-derived oncogene that is responsible for the transforming activity,14 while the slowly transforming retroviruses act by the chance integration of viral DNA near these cellular oncogenes in the host genome to induce their expression and promote tumor formation.15,16 Importantly, many of these same genes can be mutated or overexpressed in human cancers, and the proteins they encode are now the targets of new generations of specific antitumor therapies [...] One can confidently surmise that the remnants of the beta- and gammaretroviruses littered in our genomes had such oncogenic effects when they were active. Ironically, for the active human retroviruses, HTLV-I causes tumors by a different but still poorly understood mechanism, and HIV is involved in tumor formation only indirectly through immune suppression. [...] There are two fundamental differences between lentiviruses and most other retroviruses: Lentiviruses do not cause cancer [directly...] and they establish chronic infections that result in a long incubation period followed by a chronic symptomatic disease. The “slow” (lenti is Latin for slow), chronic nature of these viral infections was first appreciated for a disease of sheep called maedi-visna (maedi = labored breathing, visna = paralysis and wasting).”

“Using the current sequence diversity in the HIV-1 population, the 1959 sequence, and estimates of the rate of sequence change per year, it has been possible to suggest that the cross-species transmission event that gave rise to the M group of HIV-1 occurred early in the twentieth century.38 If we accept that SIVcpz [HIV in chimps...] has entered the human population three times in the last century (the three groups N,O, and M), then it follows that this virus likely has been transmitted to humans any number of times over the last 10,000 years. Only in the last century the human institutions of large cities and efficient transportation corridors have given these transmission events access to a human environment that could support an epidemic.”

“Over 100 herpesviruses have been identified, with at least eight infecting humans [I had no idea there were that many of them, and I had no clue some of the ones mentioned were actually herpes viruses...]. All human herpesviruses are well adapted to their natural host, being endemic in all human populations studied and carried by a significant fraction of persons in each population. The human herpesviruses include herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7), and human herpesvirus 8 (HHV-8) or Kaposi’s sarcoma (KS)-associated herpesvirus. Disease caused by human herpesviruses tends to be relatively mild and self-limited in immunocompetent persons, although severe and quite unusual disease can be seen with immunosuppression. [...] all herpesviruses share biologic traits. These include expression of a large number of viral enzymes, assembly of the nucleocapsid in the cell nucleus, cytopathic effects on the cell during productive infection, and ability to establish latent infections in an infected host.”

“Vaccine development poses great challenges in the case of herpesviruses because recovery from natural disease is not associated with elimination of virus and does not always protect against another episode of disease.
Live-attenuated, killed, and recombinant subunit herpesvirus vaccines have all been studied. Whole-virus vaccines have the advantage of exposing the immune system to all viral antigens. Live-attenuated vaccines have tended to produce longer-lasting immunity than killed preparations. However, live-attenuated herpesvirus vaccines may be capable of establishing latent infections. The risks are not clear and there is concern that vaccine recipients who subsequently become immunosuppressed may develop disease caused by reactivated virus. Two avirulent HSV strains have been shown to generate lethal recombinants in mice.127 Thus, recombination between an attenuated vaccine strain and a superinfecting wild-type strain could occur. Because several herpesviruses have been associated with malignancies in humans, the long-term safety of any live-attenuated vaccine needs careful study.”

“In the most recent data from NHANES, the prevalence of HSV-1 appears to have fallen slightly from 62% in the years 1988-1994 to 57.7% in the years 1999-2004 in the general population.30 In Western Europe, the prevalence of HSV-1 infection in young adults remains 10-20% higher than that in the United States.31 In STD clinics in the United States, about 60% of attendees have HSV-1 antibodies. In Asia and Africa, HSV-1 infection remains almost universal [...] The cumulative lifetime incidence of HSV-2 reaches 25% in white women, 20% in white men, 80% in African American women and 60% in African American men [...] Transmission of HSV between sexual partners has been addressed most often in prospective studies of serologically discordant couples, i.e., in couples in whom one partner has and the other does not have HSV-2. Longitudinal studies of such couples have shown that the transmission rate varies from 3% to 12% per year. [...] Unlike other STDs, persons usually acquire genital HSV-1 and genital HSV-2 in the context of a steady rather than casual relationship.91 Women have higher rates of acquisition than men; in one study the attack rate among seronegative women approached 30% per year.88 [...] Subclinical or asymptomatic viral shedding is an important aspect of the clinical and epidemiologic understanding of genital herpes, as most episodes of sexual and vertical transmission appear to occur during such shedding. [...] the risk of HSV transmission is likely similar regardless of the presence of lesions, supporting the epidemiologic observation that most HSV is acquired from asymptomatic partners. [...] Subclinical HSV reactivation is highest in the first year after acquisition of infection. During this time period, HSV can be detected from genital sites by PCR on a mean of 25-30% of days [...]. This is about 1.5 times higher than patients sampled later in their disease course.”

“The major morbidity of recurrent genital herpes is its frequent reactivation rate. Most likely, all HSV-2 seropositive persons reactivate HSV-2 in the genital region. Moreover, because of the extensive area enervated by the sacral nerve root ganglia, reactivation of HSV-2 is widespread over a large anatomic area.

A prospective study of 457 patients with documented first-episode genital herpes infection has shown that 90% of patients with genital HSV-2 developed recurrences in the first 12 months of infection.93 The median recurrence rate was 0.33 recurrences/month. Most patients experienced multiple clinical reactivations. After primary HSV-2 infection, 38% of patients had at least 6 recurrences and 20% had more than 10 recurrences in the first year of infection. Men had slightly more frequent recurrences than women, median 5 per year compared with 4 recurrences per year [it's important to note that the recurrence rate is substantial even in patients on suppressive therapy: "About 25% of persons on suppressive therapy will develop a breakthrough recurrence each 3-month period"] [...] Recently, long-term cohort studies indicate that the frequency of symptomatic recurrences gradually decreases over time. In the initial years of infection, reported recurrence rate decreases by a median of 1 recurrence per year. [...] subclinical shedding episodes account for one-third to one-half of the total episodes of HSV reactivation as measured by viral isolation and for 50-75% of reactivations as measured by PCR. [...] Rather than regarding HSV-2 as a predominantly silent infection with occasional clinical outbreaks with marked viral shedding, HSV is a dynamic infection, with very frequent reactivation, mostly subclinical, and active effort on the part of the immune system of the host is required to control mucosal viral replication. [...] Immunocompromised patients have frequent and prolonged mucocutaneous HSV infections.226, 227, 228 Over 70% of renal and bone marrow transplant recipients who have serologic evidence of HSV infection reactivate HSV infection clinically within the first month after transplantation [...] Recurrent genital herpes in immunosuppressed patients often results in the development of large numbers of vesicles which coalesce into extensive deep, often necrotic, ulcerative lesions.228 [...] about 70% of HIV-infected persons in the developed world and 95% in the developing world have HSV-2 antibody. [...] The epidemiologic interactions between HIV and HSV-2 have led to calculation of potential population-level impact of these intersecting epidemics. [...] The population attributable risk will depend on the prevalence of HSV-2 in the population at risk; at 50% HSV-2 prevalence, common among MSM [Males who have Sex with Males, US], or African Americans in the United States, or general population in sub-Saharan Africa, 35% of HIV infections will be attributable to HSV-2. [...] the risk of transmitting HSV [from the mother] to the neonate is 30-50% in women with newly acquired HSV [during the last part of the pregnancy] versus <1% in women with established infection.” [This is relevant not only because herpes sucks, but also because it sucks even more when a newborn child gets it].

“More than 50% of individuals in most populations throughout the world demonstrate serological evidence of prior CMV infection.6 The coevolution with and adaptation to its human host over millions of years may account for the observation that in most cases, CMV infection causes few if any symptoms.5 However, in immunocompromised individuals, primary infection or reactivation of latent virus can be life-threatening. As well, congenital infections are common and can result in serious lifelong sequelae. [...] Although CMV does not typically come to medical attention as a result of genital tract lesions or disease, it can be transmitted sexually and has important consequences for the sexually active, child-bearing population. [...] As with many viruses that cause chronic infection, CMV seems to have coevolved with humans to a balanced state in which the virus persists but generally causes little clinical illness. The host’s innate and adaptive immune responses are usually successful at limiting CMV infection as is evident by the clear association of immune system dysfunction with CMV disease. In the absence of prophylactic antiviral treatment, CMV often reactivates in seropositive individuals who undergo hematopoietic stem cell transplantation (HSCT).41 Immunosuppression resulting from drugs used to treat cancer and autoimmune disorders, and from impaired T-cell function that occurs with advanced AIDS, is also associated with reactivation of CMV. [...] The development of primary CMV infection has been noted in up to 79% of liver transplants and 58% of kidney or heart transplants in which the donor is seropositive and the recipient is seronegative.134,135 In the setting of HSCT, several studies have documented that CMV seropositivity of the recipient results in significantly increased overall posttransplant mortality compared to CMV seronegative recipients with a seronegative donor.136 When the recipient is CMV seronegative, overall mortality is increased when the donor is seropositive compared to the situation where the donor is seronegative.137 [...] the transplant recipient is at particularly high risk of CMV reactivation during periods of potent immunosuppression that accompany graft rejection or graft-versus-host disease.”

 

July 7, 2014 Posted by | books, evolution, genetics, medicine | Leave a comment

Sexually Transmitted Diseases (4th edition) (III)

I read the first nine chapters of this very long book a while back, and I decided to have another go at it. I have now read chapters 10-18, the first seven of which deal with ‘Profiles of Vulnerable Populations’ (including chapters about: Gender and Sexually Transmitted Diseases (10), Adolescents and STDs Including HIV Infection (11), Female Sex Workers and Their Clients in the Epidemiology and Control of Sexually Transmitted Diseases (12), Homosexual and Bisexual Behavior in Men in Relation to STDs and HIV Infection (13), Lesbian Sexual Behavior in Relation to STDs and HIV Infection (14) (some surprising stuff in that chapter, but I won’t cover that here), HIV and Other Sexually Transmitted Infections in Injection Drug Users and Crack Cocaine Smokers (15), and STDs, HIV/AIDS, and Migrant Populations (16)), and the last two of which deal with ‘Host Immunity and Molecular Pathogenesis and STD’ (Chapters about: ‘Genitourinary Immune Defense’ (17) and ‘Normal Genital Flora’ (19 as well as ‘Pathogenesis of Sexually Transmitted Viral and Bacterial Infections’ (19) – I have only read the first two chapters in that section so far, and so I won’t cover the last chapter here. I also won’t cover the content of the first of these chapters, but for different reasons). The book has 108 chapters and more than 2000 pages, so although I’ve started reading the book again I’m sure I won’t finish the book this time either. My interest in the things covered in this book is purely academical in the first place.

You can read my first two posts about the book here and here.

Some observations and comments below…

“A major problem when assessing the risk of men and women of contracting an STI [sexually transmitted infection], is the differential reporting of sexual behavior between men and women. It is believed that women tend to underreport sexual activity, whereas men tend to over-report. This has been highlighted by studies assessing changes in reported age at first sexual intercourse between successive birth cohorts15 and by studies that compared the numbers of sex partners reported by men and by women.10,13,16, 17, 18 [...] There is widespread agreement that women are more frequently and severely affected by STIs than men. [...] In the studies in the general population that have assessed the prevalence of gonorrhea, chlamydial infection, and active syphilis, the prevalence was generally higher in women than in men [...], with differences in prevalence being more marked in the younger age groups. [...] HIV infection is also strikingly more prevalent in women than in men in most populations where the predominant mode of transmission is heterosexual intercourse and where the HIV epidemic is mature [...] It is generally accepted that the male-to-female transmission of STI pathogens is more efficient than female-to-male transmission. [...] The high vulnerability to STIs of young women compared to young men is [however] the result of an interplay between psychological, sociocultural, and biological factors.33

“Complications of curable STIs, i.e., STIs caused by bacteria or protozoa, can be avoided if infected persons promptly seek care and are managed appropriately. However, a prerequisite to seeking care is that infected persons are aware that they are infected and that they seek treatment. A high proportion of men and of women infected with N. gonorrhoeae, C. trachomatis, or T. vaginalis, however, never experience symptoms. Women are asymptomatic more often than men. It has been estimated that 55% of episodes of gonorrhea in men and 86% of episodes in women remain asymptomatic; 89% of men with chlamydial infection remain asymptomatic and 94% of women.66 For chlamydial infection, it has been well documented that serious complications, including infertility due to tubal occlusion, can occur in the absence of a history of symptoms of pelvic inflammatory disease.65

“Most population-based STD rates underestimate risk for sexually active adolescents because the rate is inappropriately expressed as cases of disease divided by the number of individuals in this age group. Yet only those who have had intercourse are truly at risk for STDs. For rates to reflect risk among those who are sexually experienced, appropriate denominators should include only the number of individuals in the demographic group who have had sexual intercourse. [...] In general, when rates are corrected for those who are sexually active, the youngest adolescents have the highest STD rates of any age group.5

“Although risk of HPV acquisition increases with number of partners,67,74,75 prevalence of infection is substantial even with limited sexual exposure. Numerous clinic-based studies,76,77 supported by population-based data, indicate that HPV prevalence typically exceeds 10% among young women with only one or two partners.71

“while 100 years ago young men in the United States spent approximately 7 years between [sexual] maturation and marriage, more recently the interval was 13 years, and increasing; for young women, the interval between menarche and marriage has increased from 8 years to 14. [...] In 1970, only 5% of women in United States had had premarital intercourse by age 15, whereas in 1988, 26% had engaged in intercourse by this age. However, in 1988, 37% of never married 15-17-year-olds had engaged in intercourse but in 2002, only 30% had. Comparable data from males demonstrated even greater declines — 50% of never married 15-17-year-olds reported having had intercourse in 1988, compared with only 31% in 200299

“Infection with herpes simplex type 2 (HSV-2) is extremely common among FSWs [female sex workers], and because HSV-2 infection increases the likelihood of both HIV acquisition in HIV-uninfected individuals, and HIV transmission in HIV-infected individuals, HSV-2 infection plays a key role in HIV transmission dynamics.100 Studies of FSWs in Kenya,67 South Africa,101 Tanzania,36 and Mexico72 have found HSV-2 prevalences ranging from 70% to over 80%. In a prospective study of HIV seronegative FSWs in Nairobi, Kenya, 72.7% were HSV-2 seropositive at baseline.67 Over the course of over two years of observation [...] HSV-2 seropositive FSWs were over six times more likely to acquire HIV infection than women who were HSV-2 seronegative.”

“Surveys in the UK133 and New Zealand134 found that approximately 7% of men reported ever paying for sex. A more recent telephone survey in Australia found that almost 16% of men reported having ever paid for sex, with 1.9% reporting that they had paid for sex in the past 12 months.135 Two national surveys in Britain found that the proportion of men who reported paying women for sex in the previous 5 years increased from 2.0% in 1990 to 4.2% in 2000.14 A recent review article summarizing the findings of various surveys in different global regions found that the median proportion of men who reported “exchanging gifts or money for sex” in the past 12 months was approximately 9-10%, whereas the proportion of men reporting who engaged in “paid sex” or sex with a sex worker was 2-3%.136

“There are currently around 175-200 million people documented as living outside their countries of birth.3 This number includes both voluntary migrants, people who have chosen to leave their country of origin, and forced migrants, including refugees, trafficked people, and internally displaced people.4 [...] Each year about 700 million people travel internationally with an estimated 50 million originating in developed countries traveling to developing ones.98 [...] Throughout history, infectious diseases of humans have followed population movements. The great drivers of population mobility including migration, economic changes, social change, war, and travel have been associated with disease acquisition and spread at individual and population levels. There have been particularly strong associations of these key modes of population mobility and mixing for sexually transmitted diseases (STDs), including HIV/AIDS. [...] Epidemiologists elucidated early in the HIV/AIDS epidemic that there was substantial geographic variability in incidence, as well as different risk factors for disease spread. As researchers better understood the characteristics of HIV transmission, its long incubation time, relatively low infectivity, and chronic disease course, it became clear that mobility of infected persons was a key determinant for further spread to new populations.6 [...] mobile populations are more likely to exhibit high-risk behaviors”

“Studies conducted over the past decade have relied on molecular techniques to identify previously noncultivable organisms in the vagina of women with “normal” and “abnormal” flora. [...] These studies have confirmed that the microflora of some women is predominated by species belonging to the genus Lactobacillus, while women having BV [bacterial vaginosis] have a broad range of aerobic and anaerobic microorganisms. It has become increasingly clear that even with these more advanced tools to characterize the microbial ecology of the vagina the full range of microorganisms present has yet to be fully described. [...] the frequency and concentration of many facultative organisms depends upon whether the woman has BV or Lactobacillus-predominant microflora.36 However, even if “normal” vaginal microflora is restricted to those women having a Lactobacillus-dominant flora as defined by Gram stain, 46% of women are colonized by G. vaginalis, 78% are colonized by Ureaplasma urealyticum, and 31% are colonized by Candida albicans.36 [...] Nearly all women are vaginally colonized by obligately anaerobic gram-negative rods and cocci,36 and several species of anaerobic bacteria, which are not yet named, are also present. While some species of anaerobes are present at higher frequencies or concentrations among women with BV, it is clear that the microbial flora is complex and cannot be defined simply by the presence or absence of lactobacilli, Gardnerella, mycoplasmas, and anaerobes. This observation has been confirmed with molecular characterization of the microflora.26, 27, 28, 29, 30, 31, 32, 33, 34, 35

Vaginal pH, which is in some sense an indicator of vaginal health, varies over the lifespan (I did not know this..): In premenarchal girls vaginal pH is around 7, whereas it drops to 4.0-4.5 in healthy women of reproductive age. It increases again in post-menopausal women, but postmenopausal women receiving hormone replacement therapy have lower average vaginal pH and higher numbers of lactobacilli in their vaginal floras than do postmenopausal women not receiving hormone replacement therapy, one of several findings indicating that vaginal pH is under hormonal control (estrogen is important). Lactobacilli play an important role because those things produce lactic acid which lowers pH, and women with a reduced number of lactobacilli in their vaginal floras have higher vaginal pH. Stuff like sexual intercourse, menses, and breastfeeding all affect vaginal pH and -microflora, as does antibiotic usage, and such things may play a role in disease susceptibility. Aside from lowering pH some species of Lactobacilli also play other helpful roles which are likely to be important in terms of disease susceptibility, such as producing hydrogen peroxide in their microenvironments, which is the kind of stuff a lot of (other) bacteria really don’t like to be around: “Several clinical studies conducted in populations of pregnant and nonpregnant women in the United States and Japan have shown that the prevalence of BV is low (4%) among women colonized with H2O2-producing strains of lactobacilli. By comparison, approximately one third of women who are vaginally colonized by Lactobacillus that do not produce H2O2 have BV.45, 46, 47“.

My interest in the things covered in this book is as mentioned purely academical, but I’m well aware that some of the stuff may not be as ‘irrelevant’ to other people reading along here as it is to me. One particularly relevant observation I came across which I thought I should include here is this:

“The lack of reliable plenotypic methods for identification of lactobacilli have led to a broad misunderstanding of the species of lactobacilli present in the vagina, and the common misperception that dairy and food derived lactobacilli are similar to those found in the vagina. [...] Acidophilus in various forms have been used to treat yeast vaginitis.144 Some investigators have gone so far as to suggest that ingestion of yogurt containing acidophilus prevents recurrent Candida vaginitis.145 Nevertheless, clinical studies of women with acute recurrent vulvovaginitis have demonstrated that women who have recurrent yeast vaginitis have the same frequency and concentration of Lactobacillus as women without recurrent infections.146 [...] many women who seek medical care for chronic vaginal symptoms report using Lactobacillus-containing products orally or vaginally to restore the vaginal microflora in the mistaken belief that this will prevent recurrent vaginitis.147 Well-controlled trials have failed to document any decrease in vaginal candidiasis whether orally or vaginally applied preparations of lactobacilli are used by women.148 Microbial interactions in the vagina probably are much more complex than have been appreciated in the past.”

As illustrated above, there seems to be some things ‘we’ know which ‘people’ (including some doctors..) don’t know. But there are also some really quite relevant things ‘we’ don’t know a lot about yet. One example would be whether/how hygiene products mediate the impact of menses on vaginal flora: “It is unknown whether the use of tampons, which might absorb red blood cells during menses, may minimize the impact of menses on colonization by lactobacilli. However, some observational data suggests that women who routinely use tampons for catamenial protection are more likely to maintain colonization by lactobacilli compared to women who use pads for catamenial protection”. Just to remind you, colonization by lactobacilli is desirable. On a related and more general note: “Many young women use vaginal products including lubricants, contraceptives, antifungals, and douches. Each of these products can alter the vaginal ecosystem by changing vaginal pH, altering the vaginal fluid by direct dilution, or by altering the capacity of organisms to bind to the vaginal epithelium.” There are a lot of variables at play here and my reading of the results indicate that it’s not always obvious what is actually the best advice. For example an in this context large (n=235) prospective study about the effect of N-9, a compound widely used in contraceptives, on vaginal flora “demonstrated that N-9 did have a dose-dependent impact on the prevalence of anaerobic gram-negative rods, and was associated with a twofold increase in BV (OR 2.3, 95% CI 1.1-4.7).” Using spermicides like those may on the one hand perhaps decrease the likelihood of getting pregnant and perhaps lower the risk of contracting a sexually transmitted disease during intercourse, but on the other hand usage of such preparations may also affect the vaginal flora in a way which may make users more vulnerable to sexually transmitted diseases by promoting E. coli colonization of the vaginal flora. On a more general note, “The impact of contraceptives on the vaginal ecosystem, including their impact on susceptibility to infection, has not been adequately investigated to date.” The book does cover various studies on different types of contraceptives, but most of the studies are small and probably underpowered, so I decided not to go into this stuff in more detail. An important point to take away here is however that there’s no doubt that the vaginal flora is important for disease susceptibility: “longitudinal studies [have] showed a consistent link between increased incidence of HIV, HSV-2 and HPV and altered vaginal microflora [...] there is a strong interaction between the health of the vaginal ecosystem and susceptibility to viral STIs.” Unfortunately, “use of probiotic products for treatment of BV has met with limited success.”

I should note that although multiple variables and interactions are involved in ‘this part of the equation’, it is of course only part of the bigger picture. One way in which it’s only part of the bigger picture is that the vaginal flora plays other roles besides the one which relates to susceptibility to sexually transmitted disease – one example: “Studies have established that some organisms considered to be part of the normal vaginal microflora are associated with an increased risk of preterm and/or low birth weight delivery when they are present at high-density concentrations in the vaginal fluid”. (And once again the lactobacilli in particular may play a role: “high-density vaginal colonization by Lactobacillus species has been linked with a decreased risk of most adverse outcomes of pregnancy”). Another major way in which this stuff is only part of the equation is that human females have a lot of other ways to defend themselves as well besides relying on bacterial colonists. If you don’t like immunology there are some chapters in here which you’d be well-advised to skip.

 

July 5, 2014 Posted by | books, data, demographics, health, medicine | Leave a comment

Discrete Time Stochastic Control and Dynamic Potential Games: The Euler Equation Approach

I was very conflicted about blogging this book at all, but I figured that given I have blogged all other non-fiction books this year so far I probably ought to at least talk a little bit about this one as well. I wrote this on goodreads:

The book contained a brief review of some mathematics used in a couple of previous courses I’ve taken, with some new details added to the mix. Having worked with this stuff before is probably a requirement to get anything much out of it, as it is highly technical.

Here are some observations/comments from the conclusion, providing a brief outline:

“In this book we have studied discrete-time stochastic optimal control problems (OCPs) and dynamic games by means of the Euler equation (EE) approach. [...] In Chap. 2 we studied the EE approach to nonstationary OCPs in discrete-time. OCPs are usually solved by dynamic programming and the Lagrange method. The latter techniques for solving OCPs are based on iteration methods or rely on guessing the form of the value or the policy functions [...] In contrast, the EE approach does not require an iteration method nor knowledge about the form of the value function; on the contrary, the value function can be computed after the OCP is solved. Following the EE approach, we have to solve a second-order difference equation (possibly nonlinear and/or nonhomogeneous); there are, however, many standard methods to do this. Both the EE [...] and the transversality condition (TC) [...] are known in the literature. The EE [...] is typically deduced from the Bellman equation whereas the necessity of the TC [...] is obtained by using approximation or perturbation results. Our main results in Chap. 2 require milder assumptions [...] In Theorem 2.1 we obtain the EE (2.14) and the TC (2.15), as necessary conditions for optimality, using Gâteaux differentials. [...] Chapter 3 was devoted to an inverse optimal problem in stochastic control. [...] Finally, in Chap. 4, some results from Chaps. 2 and 3 were applied to dynamic games. Sufficient conditions to identify MNE [Markov–Nash equilibria] and OLNE [Open-loop Nash equilibria], by following the EE approach, were given [...] one of our main objectives was to identify DPGs [Dynamic potential games] by generalizing the procedure of Dechert and O’Donnell for the SLG

Some advantages and shortcomings of the EE approach. A first advantage of using the EE to solve discrete-time OCPs is that it is very natural and straightforward, because it is an obvious extension of results on the properties of maxima (or minima) of differentiable functions. Indeed, as shown in Sect. 2.2, using Gâteaux differentials, the EE and some transversality condition are straightforward consequences of the elementary calculus approach. From our present point of view, the main advantage of the EE approach is that it allows us to analyze certain inverse OCPs required to characterize the dynamic potential games we are interested in. It is not clear to us that these inverse OCPs can be analyzed by other methods (e.g.,, dynamic programming or the maximum principle). On the other hand, a possible disadvantage is that the Euler equation might require some “guessing” to obtain a sequence that solves it. This feature, however, is common to other solution techniques such as dynamic programming.”

If none of the above makes much sense to you, I wouldn’t worry too much about it. Stuff like this, this, and this was covered in previous coursework of mine so I was familiar with some of the stuff covered in this book; stuff like this is part of what many economists learn during their education. I figured it’d be interesting to see a more ‘pure-math’ coverage of these things. It turned out, however, that many of the applications in the book are economics-related, so in a way the coverage was ‘less pure’ than I’d thought before I started out.

A couple of links I looked up along the way are these: Gâteaux derivative, Riccati equation, Borel set. I haven’t read this, but a brief google for some of the relevant terms above made that one pop up; it looks as if it may be a good resource if you’re curious to learn more about what this kind of stuff is about.

 

July 3, 2014 Posted by | books, economics, mathematics | 2 Comments

Books 2014 (January-June)

The first six months of 2014 are at an end, and I thought it made sense to make a post providing an overview of the books I’ve read during the first half of this year. I decided to be a bit more thorough in this post than I was when I wrote the 2013 book overview post; for example in this post I’ve at least tried to include in the links below all relevant posts I’ve written about the books on the blog, rather than just a subset of them. The corresponding goodreads list is here. Aside from links to relevant posts I’ve also added a bit of information about the books – the numbers in the parentheses are the goodreads ratings I have given the books (for information about how to interpret those ratings, see incidentally the comments here and here), whereas the various letters following those numbers indicate which ‘type’ of book it is – ‘f’ = fiction, ‘nf’ = non-fiction.

I was seriously considering adding other dimensions/categories to the categorization scheme as well, but in the end I decided against doing much of that because such things tend to get messy and I didn’t want to bother with figuring out which other categories might be interesting to include and which books fit into which categories. The only additional variables I added were the names of the publishers of the non-fiction books (it didn’t take any mental effort to add this variable and it seemed to me like it might be relevant information), as well as the names of the authors of the fiction books (-ll-). As people reading along here can’t be expected to necessarily know all the publishers included, I decided to also add a link to some information about each of the publishers featured on the list – the link is added the first place where they are mentioned – in order to make it easier to assess relatively fast which type of book it might be. Aside from these things I’ve written very little about each book; I have added a few other remarks here and there where they seemed relevant, but I’ve tried to keep such comments brief and to the point. If you don’t do this a post like this can get very long very fast.

I have not rated all the books on the list, but I have added the goodreads ratings in the great majority of cases where I have – usually the posts about the book will in the cases where no ratings are provided give you both some idea why I did not rate them and some idea as to what I think about those books. In general it’s safe to say that books I have not rated have some (to me) problematic features which I’ve felt somewhat ambivalent about. On a related note it should be clear from the list that I have not blogged all the books I’ve read this year; this is because I decided a while back to limit fiction blogging a bit – I have however covered all non-fiction books I’ve read this year so far, and many of them I have written more than one post about. Roughly two-thirds of the books I read were non-fiction; of the 53 books on the list there are 18 fiction books and 35 non-fiction books. There are 70 links to book-related posts below, and the great majority (64) deal with the non-fiction books, meaning that I’ve written slightly less than two blog posts about each non-fiction book on average.

On the list below I have only included books which I have read in full and have actually finished, meaning that as usual some books are left out – this is incidentally the reason, in case you were wondering, why the list below looks slightly different from the list on goodreads. The list may also look slightly different because although when writing an early draft of the post I organized the books according to how they were listed on goodreads – i.e. the books are not necessarily listed in the order they were read, or in the order they were covered here on the blog – I did not really care about this stuff when updating the draft later on to include new books I’d read (I should note that given the number of links you need to add and posts that you need to track down, a post like this actually takes a while to write). The category of books I’ve read significant chunks of this year but have not finished include books such as Microeconomic Theory, Ecological Dynamics, and Introduction to Quantum Mechanics, so ’20 pages of light reading’ is not in all cases an accurate characterization of the type of books excluded from the list.

I hope you’ll find the list helpful in terms of navigating the site and that it’ll make it easier for you to find stuff I’ve written here about things you consider interesting. I should note that I occasionally have a bit of trouble keeping track of the stuff I read myself, so this post was not only written for you guys..

Okay, here we go:

1. Pathophysiology of disease (5, nf. Lange medical text. Long, takes a lot of work compared to most of the other books on this list). I took a few quite long breaks from the book along the way, which is why the posts are somewhat spread out over time. I decided in the end to add all relevant posts about the book here, even the ones which were not written this year. Relevant links: 1, 2, 3, 4, 5, 6.

2. The Complete Maus (4, f). Art Spiegelman. I was seriously considering not including this one on the list at all (is this even a book?), but on the other hand it took me longer to read this than it took me to read Calvino so I figured I might as well add it to the list.

3. Why Women Have Sex (2, nf. Times Books. There are two non-fiction books on this list which are not either academic publications (the great majority) or technical publications (#40, 42 and 45) – this book is one of those two books. Don’t be fooled by the fact that the book is written by two university professors; the level of coverage here is much lower than that of pretty much every other non-fiction book on this list). Blog links: 1, 2.

4. The Fifth Elephant (5, f). Pratchett. Blog coverage here.

5. Chronic Pain and Addiction (3, nf. Karger medical text). Blog coverage here.

6. Handbook of Individual Differences in Social Behavior (4, nf. Guilford Press psychology text. Long). Blog coverage here, here, and here. Note that I changed my mind about the goodreads rating after I’d written the last of my posts about the book.

7. Evolution of Island Mammals: Adaptation and Extinction of Placental Mammals on Islands (4, nf. Wiley-Blackwell biology text). Blog coverage here.

8. Invisible cities (4, f). Calvino. Blog coverage here.

9. Intelligence: A Very Short Introduction (2, nf. Oxford University Press. Short and very easy to read). Blog coverage here.

10. The Oxford Handbook of Health Economics (5, nf. Oxford University Press economics textbook. Long). Blog coverage here, here and here.

11. Death in the clouds (4, f). Agatha Christie.

12. Geomorphological Landscapes of the World (3, nf. Springer. Not easy to read.). Blog coverage here and here.

13. Metabolic Risk for Cardiovascular Disease (3, nf. Wiley-Blackwell medical text). Blog coverage here.

14. Screening for Depression and Other Psychological Problems in Diabetes: A Practical Guide (2, nf. Springer). Blog coverage here.

15. Psycho-Oncology (3, nf. Springer medical text). Blog coverage here and here.

16. The Daughter Of Time (4, f). Josephine Tey.

17. Cards on the Table (5, f). Agatha Christie.

18. A Practical Manual of Diabetic Retinopathy Management (2, nf. Wiley-Blackwell medical text). Blog coverage here.

19. The Cambridge Economic History of Modern Europe: Volume 1, 1700-1870 (3, nf. Cambridge University Press economics text). Blog coverage here and here.

20. Handbook of Cognitive-Behavioral Therapies (2, nf. Guilford Press psychology text). Blog coverage here and here.

21. Personality Judgment: A Realistic Approach to Person Perception (3, nf. An Academic Press psychology publication). Blog coverage here and here.

22. The Remains of the Day (5, f). Kazuo Ishiguro.

23. The Origin and Evolution of Cultures (5, nf. Oxford University Press. Takes a lot of work, but it’s an awesome book – “Highly recommended. Probably the best book I’ve read this year”). Blog coverage here, here, here, here and here.

24. What Did the Romans Know?: An Inquiry into Science and Worldmaking (2, nf. University of Chicago Press). Blog coverage here and here.

25. Bioterrorism and Infectious Agents: A New Dilemma for the 21st Century (3, nf. Springer medical text). Blog coverage here.

26. The Waste Books (2, f(?) – a collection of aphorims). Lichtenberg. Blog coverage here.

27. The Eyre Affair (5, f). Jasper Fforde. Blog coverage here.

28. The Biology of Happiness (nf. Springer (SpringerBriefs)). Easy to read, and also quite short. Blog coverage here.

29. Lost in a Good Book (5, f). Jasper Fforde.

30. The Well of Lost Plots (5, f). Jasper Fforde. Blog coverage here.

31. Body language (nf. Pocket. This is the other book to which I alluded in my comments about book #3. This book is most decidedly not an academic publication, and you can tell). Blog coverage here.

32. Do Androids Dream of Electric Sheep? (3, f). Philip K. Dick.

33. Acute Muscle Injuries (3, nf. Springer medical text). Blog coverage here.

34. Military Geography: For Professionals and the Public (3, nf. Potomac Books/University of Nebraska Press). Blog coverage here, here and here.

35. The Psychology of Personnel Selection (3, nf. Cambridge University Press). Blog coverage here and here.

36. To Kill a Mockingbird (2, f). Harper Lee. Overrated.

37. Impact of Sleep and Sleep Disturbances on Obesity and Cancer (5, nf. Springer medical text). Blog coverage here and here.

38. Lupus: The Essential Clinician’s Guide (4, nf. Oxford University Press). Blog coverage here.

39. Something Rotten (5, f). Jasper Fforde.

40. 100 Cases in Acute Medicine (3, nf. Published by CRC Press – review book for medical students/junior doctors). Blog coverage here.

41. Plant Animal Interactions: An Evolutionary Approach (5, nf. Blackwell Publishing biology text). A really great book, high average goodreads rating. Blog coverage here, here, and here.

42. 100 Cases in Clinical Medicine (3, nf. Published by CRC Press – see #40). Blog coverage here.

43. Peril at End House (4, f). Agatha Christie.

44. The Structure of Scientific Revolutions (nf. University of Chicago Press). Blog coverage here.

45. 100 Cases in General Practise (2, nf. Published by CRC Press – see again #40). Blog coverage here.

46. The TET Offensive: A Concise History (3, nf. Columbia University Press military history book). Blog coverage here.

47. Nutrition at a Glance (nf. John Wiley & Sons). Blog coverage here.

48. Poirot Investigates (3, f). Agatha Christie. Unlike the other books by her on the list, this book is a collection of short stories, rather than a novel.

49. Natural Conflict Resolution (4, nf. University of California Press). Blog coverage here, here, and here.

50. First Among Sequels (5, f). Jasper Fforde. Goodreads review: “(Maybe I shouldn’t give all these [Jasper Fforde] books five stars, but as long as they keep being awesome I’ll keep giving them five stars.)“. Blog coverage here.

51. Managing Cardiovascular Complications in Diabetes (3, nf. Wiley-Blackwell medical text). Blog coverage here and here.

52. A Quick Guide to Cancer Epidemiology (nf. Springer – Springer Briefs in Cancer research). Blog coverage here.

53. Murder in Mesopotamia (4, f). Agatha Christie.

June 30, 2014 Posted by | books, personal | Leave a comment

Managing Cardiovascular Complications in Diabetes (2)

My first post about the book, which includes a few general remarks and observations, can be read here. In this post I’ll cover some stuff from the last 150 pages. I’ve bolded relevant key points here the same way I did in the first post about the book.

“Atherosclerosis-related disease, coronary heart disease (CHD), peripheral vascular disease (PVD), and thrombotic stroke are major complications in people with type 2 diabetes mellitus [1]. A recent meta-analysis of 102 prospective studies demonstrated a hazard ratio of 2 for coronary death and non-fatal myocardial infarction (MI) and 2.5 for ischemic stroke [2]. In the United Kingdom Prospective Diabetes Study (UKPDS), for each 1% increase in HbA1c there was a 28% increase in PVD [3]. [...] In the National Health and Nutrition Examination (NHANES III) performed in the USA, the prevalence of metabolic syndrome in diabetes was 86%. The prevalence of CHD in this group was 19.2%. In those with diabetes and no evidence of metabolic syndrome, CHD prevalence was 7.5%, which is comparable to those without diabetes or metabolic syndrome [10]. Many studies in different populations have confirmed that dyslipidemia is a common finding in type 2 diabetes. [...] A basic abnormality is the overproduction of large VLDL from the liver [...] LDL-cholesterol concentrations are generally similar to those of the background population. However, LDL-cholesterol remains a major risk factor [...] Qualitative changes in LDL particles increase their atherogenicity. The particles are smaller and denser with less lipid core. [...] Statins are first-line pharmacotherapy for diabetic dyslipidemia. Their use is based on a wealth of data from robust, randomized trials for both primary and secondary prevention of CVD events. [...] A large number of diabetic patients (n=2,912) was included in HPS. Simvastatin, which reduced LDL-cholesterol by 0.9 mmol/l, was associated with a 33% relative risk reduction in major CVD events (p = 0.0003). This benefit was independent of baseline lipids, diabetes duration, glycemic control, and age. The authors [of the HPS] calculated that simvastatin therapy over five years should prevent a first major cardiovascular event in about 45 people per 1,000 treated [...] It is clear that patients with diabetes and CHD respond in a similar way to the nondiabetic population. However, a substantial residual vascular risk persists [...] A contributory factor to the failure to achieve therapeutic goals is statin intolerance [...] in practice there is a significant minority of patients who cannot tolerate statins at all, or can only tolerate a small dose, insufficient to achieve the LDL goal.”

Subjects with both type 1 and type 2 diabetes are at increased risk of developing cardiovascular disease, with approximately three-quarters of patients with diabetes ultimately dying from vascular causes.” [In the first post I included this quote from a previous chapter: "Mortality from CVD accounts for more than 60% of deaths in patients with type 2 diabetes mellitus". I took notice of the 'more than', also because previous estimates I'd seen had been higher than that. Anyway estimates vary, and for many reasons there's likely to be substantial variation from country to country; but regardless of the differences, this is 'the big one'.]

“Overall, the available data indicate that diabetes is associated with a range of metabolic abnormalities that adversely influence platelet function [I should note that they go into a lot of detail about these 'metabolic abnormalities', and this is stuff I deliberately excluded from the coverage because it's very technical stuff]. Management of the platelet aspect of this prothrombotic state should involve normalization of the metabolic changes seen in diabetes and the appropriate use of antiplatelet therapy [...] aspirin is used for secondary cardiovascular protection in diabetes [38, 39], a practice supported by two large meta-analyses [40, 41]. [...] data indicate that aspirin may be less effective in secondary cardiovascular protection in diabetes [...] there is no convincing evidence for the use of aspirin monotherapy for primary cardiovascular protection in diabetes, although some guidelines recommend its use in high-risk subjects. [...] There is evidence to suggest that the type of hypoglycemic agent used may modulate predisposition to future ischemic events. Metformin is normally used as first-line therapy in subjects with type 2 diabetes. The UK Prospective Diabetes Study (UKPDS) has demonstrated reduced ischemic heart disease (IHD) risk in overweight patients using metformin compared with subjects not on this therapy [...] Insulin is mainly used in type 2 diabetes after the failure of other hypoglycemic agents. Insulin-treated type 2 diabetes subjects are at a greater risk of cardiovascular events compared with noninsulin-treated subjects, which may simply be a reflection of longer disease duration, with a consequent increase in the risk of complications [91]. In healthy individuals, insulin has antithrombotic effects, but it has the opposite effects in the presence of insulin resistance [...] There are no clear guidelines for the treatment of diabetes with ACS and there is a great variability between countries and even centers in the same country, which is largely dependent on local resources and data interpretation of different trials. [...] Antithrombotic therapy following ACS has been through major changes over the past decade. [...] Despite major advances in therapy, atherothrombotic complications remain the main cause of morbidity and mortality in individuals with diabetes. [...] Considered together, current evidence indicates that diabetes subjects have a differential response to antiplatelet and anticoagulant drug therapy compared to subjects with normal glucose metabolism. Further studies are still needed to clarify the optimal antithrombotic strategy in this high-risk population.”

“It is difficult, if not impossible, to assess directly the efficacy of individual dietary components on CVD risk because of the challenges, both practical and financial, in modifying the diets of a large group of people for long periods of time, as well as the difficulty that arises in studying individual dietary components within the context of habitual dietary patterns. Therefore, most dietary factors with the intent of reducing CVD risk are evaluated on the basis of short-term interventions (weeks or months) using biomarkers [...] rather than hard endpoints. By combining data from different types of studies, dietary patterns have emerged that are associated with a lower risk of CVD [...] Moderate fat intake (25% to 35% of energy) is associated with lower triglyceride concentrations than a low-fat diet. [...] Current recommendations are to consume a diet containing 25%E [read: 25 percent of daily energy intake] to 35%E as total fat [3, 4]. For individuals with diabetes, the recommendation is to consume diets toward the higher end of this range [5, 6]. [...] Low-fat diets are associated with elevated triglyceride concentrations and depressed high-density lipoprotein (HDL)-cholesterol concentrations resulting from what is commonly referred to as carbohydrate-induced hypertriglyceridemia [...] Carbohydrate-induced hypertriglyceridemia, resulting in elevated triglyceride concentrations, is caused by an enhanced rate of hepatic fatty acid synthesis and is precipitated by an excess flow of glucose from the gut to the liver [14, 15] and subsequent production of hepatic triglyceride-rich particles, termed very low-density lipoprotein (VLDL) [...]. In some cases delayed triglyceride clearance associated with low-fat diets has also been observed, contributing to the elevated triglyceride concentrations [...] Within the context of a stable body weight, replacement of dietary fat with carbohydrate results in higher triglyceride and VLDL-cholesterol concentrations, lower HDL-cholesterol concentrations, and a higher (less favorable) total cholesterol to HDL-cholesterol ratio [20, 21, 22, 23, 24, 25].” [Eckel et al. pointed this out as well and I included coverage of this in my post about that book as well; but this is an important piece of information that I do not mind repeating here. Note that not all carbohydrates are the same, and that dietary fiber seems to have a protective effect. The chapter from which the above quote, and the paragraph below, was taken covered many of the same things covered in Barasi].

“a series of randomized controlled intervention trials [...] have failed to demonstrate a benefit of supplemental vitamin E, beta-carotene, vitamin C, or folate on CVD risk reduction [156, 157]. Recently, interest has been focused on the potential effect of supplemental vitamin D in CVD risk reduction. In contrast to the prior vitamins, the relationship between vitamin D and CVD risk is focused on nutrient insufficiency rather than supplemental amounts [156, 158]. Until the results of randomized controlled trials with vitamin D become available, it is premature to make any recommendations.”

“Diabetics are more likely than nondiabetics to experience ACS, and diabetes is an independent predictor for mortality in ACS. Diabetics are also more likely to develop complications of ACS and its management such as heart failure and bleeding. With a few exceptions, the management of ACS is similar in patients with and without diabetes. In patients with diabetes, management does not differ between patients who are insulin dependent and patients who do not require insulin. [...] The management of ACS begins with determining the appropriate timing for coronary artery reperfusion. Patients with STEMI [ST-elevation myocardial infarction - see this] or an equivalent should receive emergent reperfusion, preferably with PCI. Patients with UA/NSTEMI [see the link in the brackets above] can be risk stratified to determine the appropriate timing for coronary angiography. In these patients angiography is used to decide if medical therapy, PCI, or CABG [Coronary Artery Bypass Grafting] is the preferred treatment strategy. All patients with ACS should be treated with antiplatelet and antithrombin therapy, as well as adjuvant therapy with a statin, ACEI, and beta-blocker.” [there's an entire chapter about these things where they go into quite a bit of detail, but I decided against covering this stuff here as most of it is once again highly technical stuff which is not easy to blog].

Amputation of the lower limb is one of the most feared adverse health outcomes among patients with diabetes. [...] PAD [Peripheral Artery Disease], referring to atherosclerotic occlusive disease of the lower limb arteries is a common, debilitating complication that correlates with cardiovascular disease mortality [2]. Diabetes is a significant independent risk factor for PAD (odds ratio of 2–3) [3], together with hypertension, cardiovascular disease, hyperlipidemia, smoking, and obesity [3, 4]. The prevalence of PAD in patients with type 2 diabetes has been estimated at 23.5% in a UK population [5], and is strongly dependent on the duration of diabetes [6, 7]. Compared with men without diabetes, the adjusted relative risk of PAD among men with diabetes increased from 1.39 with diabetes duration of 1–5 years’ to 4.53 for diabetes of >25 years’ duration [7]. [...] a very high prevalence (71%) of PAD was recently reported in 1,462 elderly patients with diabetes (>70 years) in Spain as evaluated by a pathological ABI (ankle-brachial index) [8]. [...] A recent meta-analysis [7] including 94,640 participants and 1,227 LEA [Lower-Extremity Amputation] cases reported in 14 studies demonstrated a substantial increase in the risk of LEA associated with glycemia in individuals with diabetes. The overall risk reduction (RR) for LEA was 1.26 (95% CI 1.16–1.36) for each percentage point increase in HbA1c.”

“A Scottish study showed that after LEA diabetic subjects had a 55% greater risk of death than those without diabetes [10]. [...] Median time to death [...] was 27.2 months with diabetes versus 46.7 months without diabetes (p<0.01) and survival rate 10 years after amputation was 22.9% in nondiabetic patients but only 8.4% in diabetic patients (p=0.0007). [I've read about these things before, and I should note that I do not believe these estimates are unique or aberrant. It's not just that losing a leg sucks - when you're so far along in the disease process that they have to start cutting off parts of you to keep you alive, you're really quite likely not to live for a very long time. The prognosis of a diabetic who just had a LEA is much worse than that of the average breast cancer patient.] [...] The clinical stage of symptomatic PAD can be classified using the Fontaine staging system [21]. Fontaine stage I represents those who have PAD but are asymptomatic; stages IIa and IIb include patients with mild and moderate-to-severe intermittent claudication, respectively; those with ischemic rest pain are classified in Fontaine stage III; and patients with distal ulceration and gangrene represent Fontaine stage IV. Diagnosing PAD in patients with diabetes is of clinical importance for two reasons. The first is to identify a patient who has a high risk of subsequent MI or stroke regardless of whether symptoms of PAD are present. Indeed, patients with diabetes and PAD have a fivefold increased risk [of MI/stroke] compared to the presence of either disease alone [22, 23, 24, 25]. An observational study less then ten years ago demonstrated that patients with diabetes and PAD stage IV (=ulcer) have a 100% mortality within six years [26]. The second reason is to elicit and treat symptoms of PAD, which may be associated with functional disability and limb loss.”

“PAD is often more subtle in its presentation in patients with diabetes than in those without diabetes [...] Importantly, PAD in individuals with diabetes is usually accompanied by peripheral neuropathy with impaired sensory feedback [...] The majority of patients with early PAD are either asymptomatic or have atypical leg symptoms, with “classical” claudication in only 10–35%, therefore detection is elusive unless actively sought. Given shared risk factors, it is axiomatic that there exists a high coprevalence of atherosclerosis in other vascular beds, including the coronary arteries in PAD patients [74]. [...] patients with PAD are at a high risk of cardiovascular events and therefore benefit from aggressive secondary prevention [...] Many studies have documented that secondary prevention is underused in patients with PAD [...] Antiplatelet drugs that have been shown to reduce the incidence of vascular death, nonfatal myocardial infarction, and nonfatal stroke in patients with PAD are aspirin, ticlopidine, and clopidogrel [101]. Aspirin plus dipyridamole has not been proven to be more efficacious than aspirin alone in the treatment of patients with PAD [101].”

“Compared to patients with intermittent claudication (IC; stage II of PAD), patients with critical limb ischemia (CLI; stages III and IV after Fontaine) are in a more difficult situation: while amputation is rather infrequently necessary in patients with IC [108], amputation rates of 23% at 12 months were reported in patients with CLI [109]. In patients with CLI, the incidence of diabetes mellitus and chronic renal insufficiency is 70.4% and 27.8%, respectively [109]. Thus, patients with CLI are in the majority among patients with diabetes [...] The prevalence of gangrene is about 20 to 30 times higher in patients with diabetes mellitus [110].” [In terms of the treatment options, they put it frankly in their recommendations in that chapter: "Primary amputations only in a leg-for-life situation"].

June 30, 2014 Posted by | books, diabetes, medicine | Leave a comment

A Quick Guide to Cancer Epidemiology

“Neoplasms include several hundreds of diseases, which can be distinguished by localization, morphology, clinical behaviour and response to therapy. [...] Malignant neoplasms are characterized by progressive growth of tissue with structural and functional alterations with respect to the normal tissue. In some cases, the alterations can be so important that it becomes difficult to identify the tissue of origin. A peculiarity of most malignant tumours is the ability to migrate and colonize other organs (metastatization) via blood and lymph vessel penetration. The presence and extension of metastases are often the critical factors to determine the success of therapy and the survival of cancer patients. The pace of growth of malignant neoplasms varies widely, and asymptomatic neoplasms are often found at autopsy of individuals deceased from other causes. [...] Most malignant neoplasms (about 90 %) in adults arise from epithelial tissues and are defined as carcinomas. [...] Knowledge about the causes and the possible preventive strategies for malignant neoplasms has greatly advanced during the last decades. This has been largely based on the development of cancer epidemiology.”

I finished this book yesterday. I complained in my coverage of Managing Cardiovascular Complications in Diabetes that that book was full of formatting errors and that it seemed that nobody had proofread the book before publication, and I said in that post that ‘It’s much rarer, I think, to see stuff like that in Springer publications.’ I might be wrong about this, or at least I’ve updated my priors on that one; this specific book was even worse than the Managing Cardiovascular complications book in that respect – errors are all over the place. It’s odd and also slightly annoying, because if not for that problem I would consider this book to be a really nice little resource.

The book deals mainly with the data, and it is not a methodology text. Occasionally how we know what we know is important and the limits of our knowledge is important, so methodological questions are addressed here and there; but you certainly don’t need to have read a book like this to understand it, and although many specific details in the book presumably would not be understood by a random guy who’d just finished high school, most of the book is relatively easy to follow. This disease is this common in this area and that common in that area and the difference between these two areas may be due to these things; it kills this many people; these are some of the risk factors we know about, and the role they play is this – most of the book deals with questions such as these, and there are only so many ways you can make stuff like that impossible to understand by using a lot of fancy medical terms.

The book provides an excellent overview and the data and the level of coverage is actually quite excellent considering the length of the book – if not for the many errors and general sloppiness I’d feel tempted to give it a high rating. We know more than I thought we knew about these things, which is nice, and a few of the observations included were surprising to me. Of course a lot of details are missing but this is to be expected – people have written books about topics covered in a few pages here (e.g. this). If you read Mukherjee and this book, I think you’ll be off to a great start in terms of understanding cancer better; the obvious next step would be a book like this, but most people are probably not going to read stuff like that.

I should point out that perhaps I was a bit too hard on the lecture about the UK million women study in the recent Open Thread – I find it important to note in particular that specific topics also covered in this book, such as the role of birth control and hormone replacement therapy in cancer development, are covered in more detail in that lecture than they are in this book; so I refer you to that lecture, rather than covering that stuff below. Some of this stuff is the sort of stuff I’d probably want to know about if I were of the opposite gender. I should point out as well here that one of the reasons I did not think too highly of her lecture relates to her comments about cancer screening during the lecture (I think it’s around the 35 minute mark or so). Those comments annoyed me because I think she’s being intellectually dishonest during her lecture by not addressing the main problems with the pro-screening position, but only presents a weaker argument (to an audience unlikely to know any better) which is much easier to knock down – in the context of breast cancer screening the main argument against them, from what I’ve gathered, is not that these things do not save any lives (though there’s also a lively debate about how many lives are actually saved and how you should go about estimating this number), but rather that the costs – both monetary and non-monetary (the latter e.g. relating to the mental anguish experienced by the many, many women who get a false positive test result) – are not justified; there’s much more about these and related things in this book. In general it’s safe to say that it’s quite a bit harder to ‘properly justify’ screening programmes than many doctors often seem to think it is. Anyway the book doesn’t go into much detail about these things, and you’ll have to look elsewhere (e.g. Juth and Munthe) for detailed coverage of stuff like that.

I have added some observations from the book below and a few comments.

“Analytical studies (case–control and cohort) have shown the causal role of specific exposures in the aetiology of several malignant neoplasms. One limitation of the epidemiological approach, which may prove of critical importance in trying to detect comparatively small increases in risk, as in the case of environmental pollutants, is that even in the best conditions it is impossible to confidently identify by epidemiological means an increase in risk smaller than say 10–20 % (and serious problems arise in the interpretation of increases below 50 %), as the biases inherent in any observational study are of at least this order of magnitude (Adami et al. 2008).”

“In addition to lead-time bias, three types of bias are peculiar to the assessment of screening programmes. Because of self-selection, persons who elect to receive early detection may be different from those who do not: for instance, they may belong to better educated classes, be generally healthier and health conscious, and this could produce a longer survival independent of any effect of early detection. In addition, cancers with longer pre-clinical phases, which may mean less biological aggressiveness and better prognosis, are, in any case, more likely to be intercepted by a programme of periodical screening than cancers with a short pre-clinical phase, and a rapid, aggressive clinical course (length bias). Finally, because of criteria of positivity adopted to maximize yield of early cases, a number of lesions which in fact would never become malignant growths are included as ‘cases’, thus falsely improve the survival statistics (over-diagnosis bias).”

“The number of new cases of cancer which occurred worldwide in 2008 has been estimated at about 12,700,000 [...]. Of these, 6,600,000 occurred in men and 6,000,000 in women. About 5,600,000 cases occurred in high-resource countries (North America, Japan, Europe including Russia, Australia and New Zealand) and 7,100,000 in low- and medium-resource countries. Among men, lung, stomach, colorectal, prostate and liver cancers are the most common malignant neoplasms [...], while breast, colorectal, cervical, lung and stomach are the most common neoplasms among women [...] The number of deaths from cancer was estimated at about 7,600,000 in 2008 [...] No global estimates of survival from cancer are available: data from selected cancer registries suggest wide disparities between high- and low-resource countries for neoplasms with effective but expensive treatment, such as leukaemia, while the gap is narrow for neoplasms without an effective therapy, such as lung cancer [...] The overall 5-year survival of cases diagnosed during 1995–1999 in 23 European countries was 49.6 % (Sant et al. 2009).”

“Survival from breast cancer has slowly increased in high-resource countries, where it now achieves 85 %, following improvements in screening practices and treatments. Survival in low-resource countries remains poor, in the order of 50–60 %. Breast cancer is the most common cancer among women worldwide: the estimated number of new cases in 2012 was 1,680,000″ [I had no idea survival rates were that high in 'high-resource countries', though it's a bit problematic that it is not spelled out what is actually meant by 'survival'; I gather from this link that it's the 5-year survival rate.]

“Tobacco smoking is the main single cause of human cancer worldwide (IARC 2004) and the largest cause of death and disease. It is the key cause of lung cancer, and a major cause of cancers of the oral cavity, pharynx, nasal cavity, larynx, oesophagus, stomach, pancreas, uterine cervix, kidney and bladder, as well as of myeloid leukemia. In high-resource countries, tobacco smoking causes approximately 30 % of all human cancers (Doll and Peto 2005). [...] A benefit of quitting tobacco smoking in adulthood has been shown for all major cancers causally associated with the habit. Smokers who stop around age 50 avoid over 50 % of overall excess mortality from all causes (Doll et al. 2004; Jha et al. 2013; Pirie et al. 2013), from lung cancers (Peto et al. 2000) and well as from other tobacco-related cancers (Bosetti et al. 2008a), and those who stop around age 40 or earlier avoid most of their tobacco-related cancer risk. [...] “The risk of lung cancer among smokers relative to the risk among never-smokers is in the order of over 20-fold [...] In the UK million women study, the RRs [relative risks] of lung cancer were 10.5 for current smokers of 10 cigarettes per day, 22.0 for 15, and 36.0 for ≥20 cigarettes per day. [...] An association has been shown in many studies between exposure to involuntary smoking and lung cancer risk in non-smokers. The magnitude of the excess risk among non-smokers exposed to involuntary smoking is in the order 20 % (IARC 2004).” [You have a 20% risk increase from passive smoking and a twenty-fold increase from smoking. My conclusion from these observations would be that in terms of cancer risk passive smoking doesn't really matter in the big picture, and that it is overhyped as a disease risk factor - the excess cancer risk attributable to smoking probably causes more than 100 cancers in smokers for each cancer case in a non-smoker, and most of the non-smokers who develop cancerous lesions will have been exposing themselves for years - questioning the assumption that they did not willingly take on this risk]. Lung cancer is “the most important cause of cancer death worldwide. It accounts for an estimated 1,250,000 new cases and 1,100,000 deaths each year among men and 580,000 cases and 500,000 deaths among women [...]. Survival from lung cancer is poor (around 10 % at 5 years).”

“The role of dietary factors in causing human cancer remains largely obscure. For no dietary factor other than alcohol [...] and aflatoxin (a carcinogen produced by some fungi in certain tropical areas) there is sufficient evidence of an increased or decreased risk of cancer. [...] Alcohol drinking increases the risk of cancers of the oral cavity, pharynx, larynx, oesophagus and liver, colorectum and female breast (Baan et al. 2007). For all cancer sites, risk is a function of the amount of alcohol consumed [...] The global burden of cancer attributable to alcohol drinking has been estimated at 3.6 and 3.5 % of cancer deaths (Boffetta 2006), although this figure is higher in high-resource countries (e.g., the figure of 6 % has been proposed for United Kingdom (Doll and Peto 2005) , and 9 % in Central and Eastern Europe). These included over 5 % of cancers and cancer deaths in men and about 1.5 % of cancers and cancer deaths in women. [...] Systematic reviews have concluded that nutritional factors may be responsible for about one-fourth of human cancers in high-resource countries, although, because of the limitations of the current understanding of the precise role of diet in human cancer, the proportion of cancers known to be avoidable in practicable ways is much smaller (Doll and Peto 2005). The only justified dietary recommendation for cancer prevention is to reduce total caloric intake, which would contribute to a decrease in obesity, an established risk factor for human cancer [...] There is sufficient evidence for a cancer preventive effect of avoidance of weight gain, based on a decreased risk of cancers of the colon, gallbladder, post- menopausal breast, endometrium, kidney and esophagus (adenocarcinoma) [...] Estimates of the proportion of cancers attributable to overweight and obesity in Europe range from 2 % (Doll and Peto 2005) to 5 % (Bergstrom et al. 2001).”

“There is growing evidence that chronic infection with some viruses, bacteria and parasites represents a major risk factor for human cancer, in particular in low-income countries [...] The population attributable fraction for infectious agents was 16.1 % in 2008, meaning that around two million new cancer cases were attributable to infections. HBV and HCV-related liver cancer, HPV-related cervical cancer and Helicobacter pylori-related stomach cancer overall are responsible for 95 % of the total number of infection-related cancers. The estimate of the attributable fraction is higher in less developed countries than in high-resource countries (22.9 % of total cancer versus 7.4 %). [...] Cervical cancer is a major public health problem in many low and middle income countries. Incidence rates are high (20–40/100,000) in sub-Saharan Africa and Latin America countries, as well as in India and southern Asia. [...] Chronic infection with HPV is a necessary cause of cervical cancer. Using sensitive molecular techniques, virtually all tumours are positive for the virus [...]. Different types of HPV exist, and those associated with cervical cancer are mainly types 16, 18, 31, 45 and 58. In particular, HPV 16 is the main cervical carcinogen in most populations”.

“Approximately 40 occupational agents, groups of agents and mixtures have been classified as carcinogenic by IARC [...] Estimates of the global burden of cancer attributable to occupation in high-income countries result in figures in the order of 1–5 % (Doll and Peto 2005 ; Schottenfeld et al. 2013). In the past, almost 50 % of these were due to asbestos alone, while in recent years the impact of asbestos on lung cancer [...] is levelling off [...] However, these cancers concentrate in some sectors of the population (mainly male blue-collar workers), among whom they may represent a sizable proportion of total cancers [...] The available evidence suggests, in most populations, a small role of air, water, and soil pollutants. Global estimates are in the order of 1 % or less of total cancers (Doll and Peto 2005; Schottenfeld et al. 2013). This is in striking contrast with public perception, which often identifies pollution as a major cause of human cancer. However, in selected areas (e.g., residence near asbestos processing plants or in areas with drinking water contaminated by arsenic), environmental exposure to carcinogens may represent an important cancer hazard.”

“No precise estimates are available for the global contribution of drug use to human cancer. It is unlikely, however, that they represent more than 1 % in high-resource countries (Doll and Peto 2005). Furthermore, the benefits of therapies are usually much greater than the potential cancer risk.”

“A number of inherited mutations of a high-penetrance cancer gene increase dramatically the risk of some neoplasms. However, these are rare conditions in most populations and the number of cases attributable to them is rather small.” [An example: "breast cancer risk is greatly increased in carriers of mutations of several high-penetrance genes, in particular BRCA1, BRCA2, ATM, CHECK2 and p53. Although the cumulative lifetime risk in carriers of these genes is over 50 %, they are rare in most populations and explain only a small fraction (2–5 %) of total cases."]

 

June 29, 2014 Posted by | books, cancer, medicine | Leave a comment

Open Thread

It’s been a while since I’ve posted one of these. This is where you share interesting stuff you’ve come across since the last time I posted one of these things (or perhaps it is where you don’t share interesting stuff; the latter is by far the most common decision, after all). I don’t really have anything interesting to share here myself, but I figured I should post something anyway, so… :

I was considering adding this lecture as well, but it’s not a particularly good lecture so that seemed like a bad idea.

A friend of mine recently made me aware of the existence of this resource, which one of two of you may consider to be worth checking out.

June 28, 2014 Posted by | Lectures, medicine, music, Open Thread, philosophy | 7 Comments

Natural Conflict Resolution (3)

This will be my last post about the book, which I gave four stars on goodreads. You can read my previous posts about the book here and here.

The last part had some interesting stuff, but I think I liked some of the chapters in the middle best. There are obvious parallels to be drawn between the coverage in a few of the last chapters and some of the work of Boyd and Richerson, though these guys’ approach and methodology is quite different.

I’ve included some stuff from the last part of the book below. Although I haven’t exactly read the works of a lot of moral philosophers (except perhaps random quotes of theirs – I’ve probably read quite a few of those over the years), I do think that some of the ideas and observations included in this part of the book are ideas and observations which many of them might benefit (/have benefited) from knowing (/more) about.

“The social interactions between two animals depend not only on their individual characteristics (e.g., age, sex, dominance rank, temperament) but also on the history of interactions between them, provided that they possess the capacity for individual recognition, have sufficient memory to remember the outcome of social interactions, and repeatedly meet each other. The two animals can thus be said to have developed a social relationship. This relationship is not directly visible. Observers decide it exists because the history of previous interactions allows them to predict the outcome of subsequent interactions between the same animals [...]. Of course, it also allows the animals to predict the actions and responses of the partner with reasonable accuracy. This makes social intercourse much more efficient, obviating the need for thorough reassessment of the partner’s strength and possible other qualities every time they come close, which is why the establishment of relationships is adaptive for the participants. [...] Social behavior is about conflict and cooperation, and relationships characterized by only one of these two probably do not exist. Even the most collaborative relationships tend to contain an element of competition — for instance, because collaborators need to decide on how to divide the benefits of their cooperative effort [...] social relationships always contain elements of both cooperation and competition.”

“The partners in an established relationship need to communicate about their relative balance of power (i.e., physical strength and social influence) and about the exchange rate of services. The need for some form of communication is clear in even the simplest relationship. For example, individuals can alternate grooming each other and thus provide benefits in terms of hygiene [...], tension reduction [...], and endorphin release [...] By varying the duration and frequency of their own grooming bouts, the partners can express their perceived relative power in the relationship and, through refusals of grooming invitations or variations in length, negotiate the actual power balance. Communication about the relationship is all the more important because the partners’ values change all the time. Individual qualities, such as strength or experience, change over time, as do their needs for services. External factors—for instance, group composition—may change the value of a partner because they affect the number of other group members who can offer the same service [these effects are termed 'market effects' in the literature] [...] Changing assessments can be communicated by ceasing to support or share, by taking larger shares than before, or even by punishing partners after they failed to reciprocate [...] Communication before engaging in the interaction [...] is critical when interactions involve high risks, especially when the partners do not have reliable relationships. Agonistic support between males is a prime example because it involves high risks and because male alliances are fickle.”

“Given the dynamic nature of relationships, it is critical for one or both partners to establish whether the conflict signifies a growing mismatch in the assessments of each other’s value or whether it is a mere hiccup in an otherwise unchanged relationship. We believe this is why reconciliation evolved [...] Reconciliation can be viewed as communication about the value of the relationship: it shows how much each partner is interested in the relationship and thereby is willing to repair it after the disturbance due to the conflict. According to this view, reconciliation is not only an effective way to end the conflict but is also a primary tool for relationship management [...] The most important generalization to emerge from two decades of work on reconciliation (i.e., post-conflict friendly reunion between opponents) in primates is that individuals that reconcile are likely to have a strong social bond (de Waal, Chapter 2; Cords & Aureli, Chapter 9).”

“In primates, the benefits [of relationships] include selective tolerance around resources [...], cooperative hunting [...], food sharing [...], services for mating privileges [...], agonistic support, and protection against harassment. The last two are probably the most widespread and critical benefits related to relationship-dependent cooperation in primates. [...] A coalition takes place when individuals support one another in an agonistic conflict [...] An alliance is a type of relationship in which the two partners repeatedly form coalitions. Thus, coalitions are interactions that can be formed on a case-by-case basis, whereas alliances are enduring cooperative relationships [...] The basic rule for coalitions and alliances is simple: they should be formed when they improve access to limiting resources for both partners [...] The limiting resources are usually different for the two sexes because the fitness of males and females is limited by very different factors [...] Male mammals [...] usually contribute little to the development of the young. [...] females usually compete for food or shelter, whereas males compete for mating opportunities (Emlen & Oring 1977).”

“Some of the most significant threats faced by female primates are social ones, in particular, sexual harassment and infanticide by males. Protective bonds between females, and especially those between males and females, may serve to reduce these social threats [...] Species with lactational amenorrhea are vulnerable to infanticide by males unlikely to have fathered the infant, because this will speed up the female’s next conception. Many primates have lactational amenorrhea; male infanticide is reported for a remarkably high proportion of primate species [...]. Yet male infanticide is rare in most of the species in which it occurs. Perhaps this is because of effective social counterstrategies [...] Associations and social relationships can often be seen as strategies to reduce the negative impact of some challenge. Paradoxically, the selective forces that produced particular social behavior are often hard to discern because the behavior it has produced is effective in eliminating the fitness impact of these ultimate causes. Hence, their action is rarely apparent.”

“Among primate males, strong bonds to maintain alliances are expected to serve to improve mating access to females, and indeed they do. However, they are less common and shorter-lived than those among females [...]. In various primate species, only a single male stays in a group of females, preventing the establishment of male bonds. But even in the all-male bands commonly found in these species [...] or in many species with multimale groups, male bonds are not pervasive. The reasons for this are largely speculative at this stage. [...] Most examples of male-female alliances are from species with limited sexual dimorphism, in which males and females can potentially provide mutual agonistic support.”

“When a group is faced with external threats, relationships within the group and with allies increase in importance. Group pressure is exerted on disputants to reconcile conflicts that threaten valued defensive alliances or solidarity. [...] in-group/out-group distinctions are also a very salient dimension of nonhuman primate interactions.”

“we make two fundamental assertions regarding the evolution of morality: (1) there are specific types of behavior demonstrated by both human and nonhuman primates that hint at a shared evolutionary background to morality; and (2) there are theoretical and actual connections between morality and conflict resolution in both nonhuman primates and human development. [...] the transition from nonmoral or premoral to moral is more gradual than commonly assumed. No magic point appears in either evolutionary history or human development at which morality suddenly comes into existence. In both early childhood and in animals closely related to us, we can recognize behaviors (and, in the case of children, judgments) that are essential building blocks of the morality of the human adult. [...] The obvious common ground between current evolutionary and developmental approaches is that, instead of looking at human morality as coming from the outside — imposed by adults on the passive child, or imposed by culture on a fundamentally nasty human nature — it is generated from the inside. What we mean by “inside” is not that things happen in isolation from outside influences: evolution operates on the basis of ecological pressures, which come from the outside, and development takes place in constant interplay with the outside world. What we mean instead is that the decision making and emotions underlying moral judgments are generated within the individual rather than being simply imposed by society. They are a product of evolution, an integrated part of the human genetic makeup, that makes the child construct a moral perspective through interactions with other members of its species. [...] Much research has shown that children acquire morality through a social-cognitive process; children make connections between acts and consequences. Through a gradual process, children develop concepts of justice, fairness, and equality, and they apply these concepts to concrete everyday situations (Killen & Hart 1995).”

“From our perspective, we assert that emotions such as empathy and sympathy provide an experiential basis by which children construct moral judgments. Emotional reactions from others, such as distress or crying, provide experiential information that children use to judge whether an act is right or wrong [...] when a child hits another child, a crying response provides emotional information about the nature of the act, and this information enables the child, in part, to determine whether and why the transgression is wrong. Therefore, recognizing signs of distress in another person may be a basic requirement of the moral judgment process. The fact that responses to distress in another have been documented both in infancy and in the nonhuman primate literature provides initial support for the idea that these types of moral-like experiences are common to children and nonhuman primates. As an illustration, de Waal (1996) documents reactions to distressed individuals and the tendency to share food with others. Generally, it seems that our closest relatives, the great apes, go further in this regard than more distantly related primates, such as the monkeys. For example, “consolation” has thus far been demonstrated only in chimpanzees despite systematic attempts to find it in monkeys. Consolation is defined as friendly or reassuring contact provided by a bystander to a recipient of aggression [...]. In the chimpanzee, this kind of interaction typically consists of putting an arm around the victim or patting him or her gently on the back or shoulder. Because of the contrast between monkeys and apes in this regard, de Waal & Aureli (1996) have recently speculated that consolation may require empathy. Since higher forms of empathy and sympathy require the ability to take someone else’s perspective, the difference may result from Hominoids (i.e., humans and apes) possessing this ability but not monkeys.”

“No biologist and few social scientists would deny that our species has natural aggressive potentials, but we possess many other natural tendencies as well, some of which serve to keep aggression in check. Thus, to call us naturally peaceful (which is, after all, a state observed far more often than war and strife) would be at least as justified as calling us naturally aggressive.”

“the “ought” question, which has occupied moral philosophers over the ages, may reach all the way back to rather mundane mechanisms of how to get along and when to repair relationships.”

June 27, 2014 Posted by | anthropology, biology, books, ethics, evolution, Zoology | Leave a comment

Managing Cardiovascular Complications in Diabetes (1)

I finished the book today. I wrote a brief review of the book on goodreads and gave it three stars. Many things covered in this book I’ve read about in detail elsewhere, e.g. in Sperling et al., Edwards et al., or, say, Eckel et al, but there was some new stuff in here as well. I really liked the first chapter, about ‘The Vascular Endothelium in Diabetes’; it covered some stuff which I’d never really gotten to the bottom of before (but due to the technical nature of that chapter I decided against covering it here). There are still a lot of details which I will not claim to fully understand, but I understand some of the main principles/mechanisms much better than I did. The book was occasionally difficult for me to read because it required knowledge about areas about which I didn’t know a great deal (e.g. haematology), and you should certainly not read this book if you don’t read more or less fluent medical textbook (“The focus of this book is to assist the physician or surgeon in preventing and managing CVD and CVD risk in diabetic patients”). As I pointed out in my goodreads review, the book was difficult for me to read for another reason as well. Authors of academic books should not use acronyms which they do not explain to the reader. Authors of such books should not explain unexplained acronyms five pages after they have used them for the first time. If they do, people might get angry at them.

I’m sure some people don’t care about such things, but this is the sort of stuff that can really piss me off, and it’s part of the reason why this book got three stars. Combining behaviour like that with some formatting errors and a few sentences which don’t make any sense because nobody seems to have proofread the damn thing, and you can end up with an academic publication which looks amateurish, even if it’s most certainly nothing of the sort. In terms of the formatting errors I will note that this is not the first Wiley-Blackwell publication like this I’ve seen – as I point out in my review of that book, the Edwards et al publication to which I link above had similar problems. It’s much rarer, I think, to see stuff like that in Springer publications.

I have added some observations from the book below. I plan to write another post about the book later on as I don’t think it’s fair to only give this book one post, considering how much stuff is in there. When I started out writing this post I was thinking that I’d make the quotes easier to read by adding relevant links where they might help. I realized quite fast that adding enough links to actually make a huge difference would most certainly not be worth it, though I have added a link here and there anyway in order to make the post more readable. I have also added a few bold sections below – I don’t like writing long posts and then have people not reading them because they’re long, so if you don’t particularly care about the topic covered below you might want to read the bolded parts in order to at least learn something from the post. There’s a lot more stuff about type 2 diabetes than about type 1 in this book, so when reading ‘diabetes’ below you should probably just think ‘type 2′.

I remember recently reading an article somewhere stating that there are many errors in medicine-related wikipedia articles and how that’s a problem, and I actually encountered an example of this while reading the book, though I can’t now remember which article it was. You should take it for granted that wiki articles to which I link in posts like these may have errors and inaccuracies (they may actually contain statements which are contradicted by the material covered in the book…), and I usually only link to them in posts like these to ‘translate’ the terms used without having to add a lot of additional text to the post in question. I’ll often not have read the articles to which I link when I link to as many as I do in this post, and a link to an article does not mean that I think all the stuff included in the article is correct. Okay, on to the book coverage:

“There is no doubt that diabetes is a significant contributor to the global burden of chronic non-communicable disease which accounts for over 36 million (63%) of deaths worldwide. Importantly, 80% of these deaths occur in low and middle income countries. [here's a link to the source, the data above is from page 16. Note that "17.3 million (30%) [of all 57 million deaths worldwide] were due to CVDs.”] [...] In an important contribution from the Global Burden of Metabolic Risk Factor of Chronic Disease Collaborating Group [4] national, regional and global trends in fasting plasma glucose and diabetes prevalence since 1980 were studied in a systematic analysis of health examination surveys involving over two and a half million participants and 370 country-years observations. They estimated that the number of people with diabetes increased from 153 (95% uncertainty interval 127–182) million in 1980 to 347 (314382) million in 2008 [4]. [I included the quote partly because those numbers are interesting, partly because this quote from the introduction contains a good example of the kind of sloppiness I mention in the goodreads review; that last parenthesis was surely meant to say 314-382. But it doesn't. And those kinds of small errors are all over the place.] [...] In addition to increased risk of CVD patients with diabetes and established vascular disease have a poorer outcome than those without diabetes [7, 8]. Peripheral arterial disease is increased 2-4 fold in the diabetic population and lower limb amputations are at least 10 fold more common such that half of non-traumatic amputations are performed in diabetic patients [3, 7, 8].”

a mean duration of diabetes of about a decade appears to confer an equivalent risk of CVD to a prior history of MI. In addition, recent work has shown that a history of DM results in six years of life years lost, mostly from CVD [3]. [...] 20% of all vascular events occur in patients without any traditional risk factors, necessitating the need for more precise clinical tools that aid clinicians in identifying those at highest risk [4]. To help achieve this goal, there is growing interest in the development and exploitation of new biomarkers. [...] A biomarker was defined by a National Institutes of Health (NIH) working group as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention” [5]. [...] A biomarker should meet several criteria to be deemed clinically useful. This is structured around three fundamental questions [6]: 1 Is the biomarker measurable? 2 Does the biomarker add new information? 3 Will the biomarker help the clinician to manage patients? Additional criteria include cost-effectiveness, safety, and replication of the biomarker in clinical scenarios. [...] [Reclassification] is a relatively new concept, but potentially the most clinically relevant [of four criteria covered] as it assesses the ability of a test to reclassify individuals correctly into a different risk category; for example, an intermediate-risk subject into a high-risk subject, or a low-risk subject into an intermediate-risk subject [...] The ability of the new test to achieve reclassification can be statistically examined by net reclassification improvement (NRI) or integrated discrimination improvement (IDI). The NRI method, which is determined by the proportion of individuals whose risk is correctly escalated or de-escalated, is more useful in primary prevention, where well-accepted categories of risk exist. The IDI estimates the change in predicted probability of an outcome between those with and without the outcome after the biomarker is added to the prediction model. The larger the value of the NRI or the IDI, the better the biomarker.”

Quite a few biomarkers are covered in the chapter, but I’d rather not talk too much about that stuff. There are various types of circulating biomarkers, imaging biomarkers and genetic biomarkers. A few have been included in national guidelines and the only class which does not seem to be useful in this context is the genetic one ["The AHA has given genomic testing in risk assessment in asymptomatic adults a Class III recommendation (no benefit)"]. Naturally reasons besides those related to assessing cardiovascular risk exist for doing genetic testing on diabetics, but if such tests are not useful in that respect then of course that limits their potential somewhat. Incidentally many biomarkers they talk about seem to measure similar things, meaning that adding them together don’t add a lot of information:

“It is logical to assume that if one biomarker measure gives a small incremental gain in risk prediction, multiple biomarkers would result in a larger one. However, trials of multiple biomarkers have disappointingly only shown at best a moderate improvement in usefulness when compared to standard risk factors [72].”

The biomarkers are assumed to hold most promise in the context of primary prevention, but “there is scant data on cost-effectiveness or differential benefit from specific treatments”. Okay, on to other stuff:

“Diabetic kidney disease [...] is a clinical diagnosis and is defined by the presence of albuminuria, often with associated abnormal kidney function (an increase in creatinine or a decrease in creatinine clearance or estimated glomerular filtration rate [eGFR]) [...] Diabetic nephropathy is a histological diagnosis, characterized by typical histopathological features including mesangial expansion, glomerular basement membrane thickening, and glomerulosclerosis with Kimmelstiel–Wilson lesions. Diabetic kidney disease is most commonly caused by diabetic nephropathy, but other kidney pathologies may be present [...] Diabetic kidney disease is a chronic complication of diabetes and affects approximately one third of all diabetic patients [1, 2]. It is the most common cause of kidney failure requiring renal replacement therapy in Western countries [3] and can occur in both type 1 and type 2 diabetes with equivalent risks [4]. The natural history and prognosis of diabetic kidney disease differ somewhat based on the type of diabetes and whether microalbuminuria is present [...] In people with type 1 diabetes who have microalbuminuria, if left untreated, approximately 80% will develop macroalbuminuria (also called overt nephropathy) within 6–14 years [6, 7]. Subsequently, half of these will develop end-stage kidney disease (ESKD) over 10 years if there is still a lack of specific intervention. In contrast, approximately 20–40% of people with type 2 diabetes and microalbuminuria develop macroalbuminuria without intervention, and ESKD has been reported to develop in 20% of patients with overt nephropathy within 20 years [8]. Some of these differences may relate to the older age and greater burden of comorbidity experienced by people with type 2 diabetes for a given duration of diabetes, meaning that more of them will die of cardiovascular and other complications before developing kidney disease.”

“Diabetic kidney disease has a heterogeneous presentation. Early stages are often asymptomatic and only detected by abnormal laboratory tests (albuminuria and changes in GFR). Albuminuria is one of the earliest detectable features of diabetic kidney disease [...] As diabetes manifests as a systemic disease, patients with type 1 DM almost always have other signs of diabetic microvascular complications, such as retinopathy and neuropathy. Diabetic retinopathy usually precedes the onset of overt nephropathy, while the relationship between diabetic kidney disease and retinopathy is less predictable in type 2 diabetes. [...] For people with type 1 diabetes, approximately 20–30% will have microalbuminuria after a mean duration of diabetes of 15 years [37, 38]. Similarly, 25% of individuals with type 2 diabetes have microalbuminuria after 10 years [...] Proteinuria and abnormal kidney function are independent risk factors for renal outcomes in diabetes [28]. [...] As with treatment strategies for end-stage kidney disease secondary to other causes, dialysis and renal transplantation are both options for treatment for ESKD caused by diabetes. Lower survival rates have been observed for people with ESKD caused by diabetic kidney disease, with five years’ survival of 30%, according to USRDS data.”

Cardiovascular disease (CVD) including coronary heart disease (CHD) is the major cause of mortality in patients with diabetes [...] no more than 25% of the excess CHD risk in diabetes can be accounted for by established risk factors [...] Hyperglycemia as a risk factor for CVD has been established for many years. Mortality from CVD accounts for more than 60% of deaths in patients with type 2 diabetes mellitus and clearly accounts for this ultimate complication of diabetes [3, 8]. The association between differing degrees of hyperglycemia and CVD risk has been an area of debate. The United Kingdom Prospective Diabetes Study (UKPDS) demonstrated that the incidence of myocardial infarction rose by 14% per 1% rise in HBA1c [9]. This is in line with other studies showing that glucose is a continuous risk factor in people with both type 1 and type 2 diabetes. [...] There is also evidence that glucose fluctuations (the highs and lows) are associated with increased oxidative stress [...] Increased oxidative stress results from an imbalance between oxidant production and antioxidant defenses [...] Diabetes mellitus, obesity, micro- and macrovascular complications have been consistently associated with increased oxidative stress [37, 38, 39] and several studies have demonstrated that hyperglycemia per se is associated with increased oxidative stress [39, 40]. [...] Hypoglycemia is also associated with increased cardiovascular mortality [58, 59], although the mechanisms behind this remain unclear. [...] As well as being associated with increased oxidative stress [62], hypoglycemia also has pro-inflammatory effects on the vasculature. [...] These changes contribute to a hypercoagulable state associated with increased platelet aggregation and plasma concentrations of coagulation factors [...] Acute hypoglycemia has also been associated with long QT syndrome, which is associated with an increased risk of sudden cardiac death [65].”

“The majority of people with type 2 DM [diabetes mellitus] are hypertensives [...] There is no question about the need to treat hypertension in either the primary prevention or secondary prevention settings for cerebrovascular disease, irrespective of the presence of diabetes. A systematic review of the effects of different BP-lowering drug regimens in people with hypertension, diabetes, or vascular disease found that the relative risks of stroke and other major vascular outcomes were proportional to the BP reduction achieved [62]. [...] there is a general consensus that ACE inhibitors or ARB are the first-line drugs of choice in both diabetes and metabolic syndrome. In primary prevention, the only question is the level of BP above which treatment is indicated. [...] The recommended threshold for treatment in primary prevention is currently under discussion in both diabetics and nondiabetics. [...] there is increasing uncertainty about the use of absolute thresholds of BP to determine the need for treatment [...] Although “lower should be better,” the results of recent clinical trials examining the benefits of normalizing risk-factor levels have been counter-intuitive and, sometimes, disconcerting, and have called into question this belief [...] Many hypertensive patients in clinical practice receive more than one antihypertensive drug, and the use of combination therapy is widely recommended in hypertension guidelines. Combinations may be especially important for patients with diabetes, for whom recommended BP targets are challenging.”

June 26, 2014 Posted by | books, diabetes, medicine | Leave a comment

Plant-Animal Interactions: An Evolutionary Approach (3)

This will be my last post about the book. You can read my previous posts about the book here and here.

As I have already mentioned, I really liked this book. Below I have covered some of the parts of the book which I have not yet talked about here on the blog, and in particular I’ve included stuff about how plants and animals cooperate with each other. I have of course had to leave a lot of stuff out.

“The lack of mobility in plants creates a physical obstacle in the dispersal of their genes. In a majority of all plants, this obstacle has been alleviated through the formation of mutualisms with animals that transport pollen grains between stigmas and also disperse seeds. In the case of pollination, the goal for the plant is to receive pollen on its stigma and to have pollen picked up and deposited on conspecific stigmas of other plants. The animal most commonly seeks a food reward. It is important to appreciate that mutualisms such as these represent reciprocal exploitation with an underlying evolutionary conflict. Selection in mutualisms favours selfish behaviour [...] One manifestation of such selection [...] is the widespread phenomenon of plant species that no longer reward pollinators but instead attract visitors by deception. [...] Non-rewarding plants species constitute a substantial portion of all angiosperms, especially among orchids, but they are mostly minor components of the plant community in which they grow. [...] Likewise, many flower-visitors (if not most) do not contribute to pollination but do remove floral resources such as nectar and pollen. [...] A fair number of plants mimic not flowers but rather pollinator mates or oviposition sites. Flowers of the well-studied European fly orchids (Ophrys) and caladeniine Australian hammer orchids provide visual, olfactory and tactile cues mistaken by naïve wasp males for conspecific females (Stowe 1988), and pollination happens as males attempt copulation with the flowers.” [This sentence made me laugh!]

“pollination mutualisms evolve amid simultaneous antagonistic interactions; the plant is under selection to maximize the net fitness of attracting potentil mutualists at the lowest net cost while minimizing the detrimental effects of non-mutualists or low-quality mutualists. This tradeoff does not exist in antagonistic interactions [...] Floral traits are likely to be as much the result of selection for avoidance of some animals as for attraction of others. [...] The vast majority of all extant pollination mutualisms [...] involve flowering plants, which dominate most biota on earth today.”

“Given that the benefit to plants of animals as pollen vectors is transport across longer distances, it is not surprising that the three extant groups of animals that have evolved flight – insects, birds and bats – contain a very large proportion of all pollinators. Among the insects, flower-visiting species are particularly frequent within the large orders Hymenoptera (bees and wasps), Lepidoptera (moths and butterflies), Diptera (flies) and Coleoptera (bettles). [...] The Lepidoptera alone, whose coiling tongues make them flower specialists and effective consumers of nectar, constitute 11% of all described species on Earth [...] Among birds, six phylogenetically independent groups have diversified as flower-visitors and often as pollinators [...] Together these groups constitute over 10% of all recognized bird species. [...] Flowers offer an extraordinary range of shapes, colours and scents, reflecting high rates of evolutionary change in these traits. [...] Almost any flower part or even adjacent leaves are modified for the purpose of attracting pollinators. There is arguably more plasticity in these secondary reproductive traits in plants than in any other organismal groups, with the possible exception of birds.”

“Specificity among visitors is a necessity for effective pollination; if animals visit flowers of different species indiscriminately, heterospecific pollen transfer will result, which reduces the probability of pollen reaching a conspecific stigma [...] The number of plant species visited varies greatly among flower-visiting species. [...] Individual visitors often tend to specialize on a subset of potential flowers during any one foraging bout; in bees perhaps 90% of all visits may be made to a given species, with occasional visits to other species. This short-term specialization is referred to as floral constancy. The dominant flower may vary among simultaneously foraging conspecifics, and within individual visitors on successive foraging bouts. Reasons for such short-term selectivity have been explored in insects, and focus on the effects of foraging rate as a result of memory constraints. Insects must learn by trial and error how to effectively access a reward such as nectar in more complex flowers, as the rewards are concealed and most quickly accessed using a particular approach. Minimum handling time may be approached only after as many as 100 visits to a given zygomorphic flower [...] visitors may be unable to keep more than one sensorimotor protocol in active memory, thus making it a superior strategy to focus on one food source at a time [...] Specialization is often not in the evolutionary interest of a flower-visiting animal, as its ultimate interest is to optimize the reward harvesting rate over time. A foraging pattern that maximizes the harvesting rate of commodities such as nectar and pollen can include two or more coexisting plant species, especially if their floral structure is fairly similar so that the visitor can use a single visit behaviour protocol. [...] The vast majority of all plants are pollinated by two or more species”

“With the [...] exception of ants [...], invertebrates play only an anecdotal role as seed-dispersers [...] All major lineages of vertebrates take part in fruit consumption and seed dispersal, but their importance as dispersal agents is very unequal. Birds and mammals are the only or main dispersers of the vast majority of vertebrate-dispersed plants [...] About 36% of 135 extant families of terrestrial birds, and 20% of 107 families of non-marine mammals, are partly or predominately frugivorous [...] Fruit consumption by vertebrate dispersers [...] has selected for fruit traits that enhance detectability by frugivores [...] Although exceptions abound, fruits that are green or otherwise dull-coloured when ripe tends to be associated with seed dispersal by mammals, whereas fruits dispersed by birds tend to be brightly pigmented. The partial dichotomy between ‘bright’ and ‘dull’ ripe fruits has probably been selected for by the contrasting sensory capacities of birds and mammals [...] Size is an important attribute of fruits, because it sets limits to ingestion by relatively small-sized dispersers that swallow them whole, like birds. [...] Fruits eaten by mammals tend to be larger than those eaten by birds [...] Fruit pulp is the reward offered by plants to dispersers, and its nutritional value is a critical element in the plant-disperser interaction. Compared to other biological materials, fruit pulp is characterized, on average, by high water and carbohydrate content, and low protein and lipid content. [...] the occurence of secondary metabolites within ripe pulp presumably represents a tradeoff with respect to defence from damaging agents and palatability for dispersers [...] A number of studies provide unequivocal support for the ‘palatability-defence tradeoff hypothesis’. [...] increased frugivory is quite often associated with increased intestinal length, as an adaptive response for increasing intestinal absorption of the water-diluted nutrients in fruit juice. [...] Most fruits are very deficient in nitrogen, which perhaps represents the most important nutritional constraint that frugivorous animals must cope with. Regular ingestion of small amounts of animal food seems to be the commonest way of complementing the poor protein intake associated with frugivory.”

“Abundance of fruit varies markedly among years and seasons, and within as well as between habitats, which generally leads to patchy and unpredictable distributions in time and space [...] A distinct suite of behavioural and physiological traits allow frugivores to withstand or escape from temporary situations of fruit scarcity and efficiently locate unpredictable fruit sources. Seasonal migration and habitat shifts are the two most common generalized responses of frugivores to fluctuations in fruit availability. [...] Plant-vertebrate dispersal systems are characterized not only by the absence of obligate partnershipts, but also by weak mutual dependence between species of plants and animals, and by the prevalence of unspecific relationships. [...] the general picture is one of loose interdependence between species of plants and species of dispersers. [...] pollen and seed dispersal by animals are fundamentally dissimilar [...], and their differences have manifold evolutionary implications. The two most important distinctions are (i) that a definite target exists for dispersing pollen grains (the conspecific stigma) but not for dispersing seeds; and (ii) that the plant can control pollinators movements by providing incentives at the target site (nectar, pollen), but there are no similar incentives for seed dispersers to drop seeds in appropriate places. These differences are best framed in terms of the departure-related versus arrival-related advantages of dispersal [You can say that seed-dispersal systems work on the basis of 'advance payment' alone, whereas pollen dispersal mechanisms also include 'payment upon delivery' aspects].”

Finally, ants! Ants are awesome…

“Ants are one of the most abundant, diverse and ecologically dominant animal groups in the world. They make up from 10 to 15% of the entire animal biomass in many habitats, and in the Amazonian rainforest, for example, one hectare of soil may contain 8 million individuals. The impact of ants on the terrestrial environment is correspondingly great. In most habitats they are among the leading predators of other insects and small invertebrates, and in some environments they are the principal herbivores and seed predators. Ants can alter their physical environment profoundly, moving more soil than earthworms, and being major channellers of energy and cyclers of nutrients. [...] It is probably fair to say that no other animal group interacts with plants in such diverse ways. Indeed, the fact that ants are the only specific taxa mentioned in the chapter headings of this book reflects their ecological importance in the lives of most plant species. Ants can protect plants directly from herbivores or from competition with other plants. They can also affect plant-community composition and dynamics by selective weeding or ‘gardening’, altering nutrient availability, pollinating flowers, or dispersing and harvesting seeds. Plants provide ants with food and shelter [...]. Some relationships between ants and plants appear to be highly coevolved mutualisms and it is these interactions that have received the most study. But the majority of ant and plant species interact in more generalized ways, often through the influence of ants on the chemical and physical properties of soil. [...] The oldest ant species, Sphecomyrma freyi, has been dated from amber to be about 80 million years old. [....] there is evidence that ants have been both remarkably diverse and ecologically successful for at least 50 million years”

“Cultivation of fungus by attine ants originated about 50 million years ago. The relationship between the higher attine ants and the symbiotic fungus they cultivate is obligate. Foundress queens propagate the fungus clonally by carrying a pellet of fungus in their mouths during their nuptial flight to establish new colonies. [...] The relationship between the attines and their fungus has been termed an ‘unholy alliance’ because it combines the ants’ ability to circumvent plants’ anti-fungal defences with the ability of the fungus to subvert plants’ anti-insect defences. The ants benefit because the fungus breaks down plant tissue such as cellulose, starch and xylan, and possibly detoxifies insecticidal plant compounds. The fungus thus enable them to make use of plant material that would otherwise be unavailable and allows the ants to be truly polyphagous in the midst of diverse flora. [...] the relationship between the ants and the fungus has recently been found to be a triumvirate, with evidence that an antibiotic-producing bacterium is an important component of the symbiosis. [...] fungus gardens are particularly prone to infection by a group of closely related, highly specialized parasites in the fungal genus Escovopsis. [...] Escovopsis is found in gardens of virtually all species of fungus-growing ants, but not elsewhere. The parasite is usually found at low levels, but if the health of the garden is compromised it can quickly take over and destroy the fungal crop. In healthy gardens, Currie et al. (1999) have shown that the fungus is kept in check by specific antibiotics produced by Streptomyces bacteria living on the bodies of the ants [...] The bacterium can also promote the growth of the cultivated fungi. The position of the bacterium on the ant integument is genus-specific, indicating that the association with the ants is both highly evolved and of ancient origin [...] Attine symbiosis appears to be a coevolutionary arms race between the garden parasite Escovopsis on the one hand, and the tripartite association of the actinomycete, the ant hosts and the fungus on the other. The relationship raises the interesting question of how the attine antibiotics have remained effective against the fungus-garden pathogens for such a long time, given that resistance to antibiotics is a well known problem in human and other populations.”

“The coevolution of ants and plants involving systems of rewards and services has resulted in a variety of elaborate and complex mutualistic interactions collectively known as ant-guard systems. Here the rewards are extra-floral nectar, specialized food bodies and nest sites, while the service is the protection of the plants from herbivory. [...] Plant structures known as domatia are developmentally determined and appear to be specific adaptions for ant occupation. They are often formed by the hypertrophy of internal tissue at particular locations in the plant, creating internal cavities attractive to ants [...] the plant species that bear them are known as myrmecophytes. [...] Some myrmecophytes are actually ‘fed’ by the ants they house. Experiments have shown that two genera in the family Rubiaceae [...] absorb nutrients from the wastes of the Iridomyrmex colonies they house in tunnels inside large tubers [...] A variety of field studies have shown there is strong competition among ants for dormatia [...] Ant-guard systems involving extra-floral nectaries are often complicated by the presence of Homoptera or lepidopteran larvae that secrete nectar-like fluids collectively known as honeydew. In such situations, the ants have a choice of food and the outcome of these three-way interactions between plants, ants and herbivores appears to be extremely variable. The Homoptera include herbivores such as aphids, leafhoppers, scale insects and coccids. Each animal is armed with a proboscis that penetrates plant vascular tissue, tapping into the nutrient supply. With little apparent effort, the sap enters the front end of the homopteran gut, later appearing at the back end as droplets, somewhat depleted in quality but still containing many nutrients, where it is ejected as honeydew. Many ant species harvest the honeydew and, in return, protect the homopterans from predators and parasites [...] As a result, ant activity can increase levels of herbivory as well as other forms of damage [...] Ant interactions with plant species that produce extra-floral nectaries, food bodies and domatia have evolved both in the presence of homopterans and lepidopteran larvae and the ant behaviour that protects them. For example, homopterans of various kinds are routinely maintained within domatia and they frequently feed on plants that bear extra-floral nectaries. This leads to the situation where plants are providing rewards for ant-guards that attack some of the plant’s enemies but protect others. A solution to this apparent conflict of interest was first proposed by Janzen (1979) who suggested that the presence of homopterans was part of the cost of the ant-guard system [...] The evoluation of extra-floral nectaries has itself been viewed as a defence against homopteran attack, weaning ants away from the herbivores [...] Homopterans are common herbivores and have been around for a very long time; thus, given their ubiquity, selection for extra-floral nectaries may have resulted in the plants exerting greater control over the ant-guards, provided ants preferred nectar to honeydew.”

June 24, 2014 Posted by | biology, books, Botany, evolution, Zoology | Leave a comment

First among Sequels

When it’s easy for me to blog a novel and it makes sense to do it because it has a lot of quoteworthy stuff, I can justify doing it here. This blog is perhaps a little dry at times.

I’ve given Fforde’s book five stars on goodreads, just like the four previous books I’ve read by him. I pointed out in a brief review on goodreads that perhaps I should stop giving all of his books five stars, but as long as they keep being awesome I’ll keep giving them that rating. And this stuff is awesome. It’s also a bit silly, but that’s the price you pay. I saw many of the major plot-developments coming, but even so it was a very entertaining read.

I have added some quotes from the book below – I don’t think there are any spoilers in the stuff I have included:

….

“I opened a small parcel that contained a copy of the third book in my series: The Well of Lost Plots. I showed it to Landen, who pulled a face. ‘Are they still selling?’ ‘Unfortunately.’”

“Since I’d made it into print I’d been naturally curious about meeting the fictional me”

“‘I’m barely eighty-two,’ she said indignantly, ‘I’m not on the scrapheap yet. [...] I’ve got a few friends coming around, and after we’ve discussed who is the most unwell, we’ll agree voluably with one another about the sorry state of the nation and then put it all to rights with poorly thought-out and totally impractical ideas.” [that passage reminded me of this]

“we are finding that more and more minor classics and a lot of general fiction are going for long periods of time without even being opened. Because of this, Text Grand Central are worried that bored characters in lesser books might try and move to more popular novels for work, which will doubtless cause friction.’
We were all silent. The inference was not lost on any of us – the fictional characters in the BookWorld could be a jittery bunch and it didn’t take much to set off a riot. [...] The last thing we need right now is a band of disgruntled bookpeople besieging the Council of Genres, demanding the right to be read.”

“the Health and Safety Inspectorate are coming in to make sure we’re up to speed.’
‘On safety procedures?’
‘Good Lord, no! On how to fill the forms in properly.’”

“A chunk of burning Camembert on your doorstep meant only one thing – a warning from the Swindon Old Town Cheese Mafia”

“‘You’ll forgive me for saying this,’ said Webastow, looking over his spectacles, ‘but this is the most hare-brained piece of unadulterated stupidity that any government has ever undertaken anywhere.’
‘Thank you very much, replied Ms Yogert courteously. ‘I’ll make sure your compliments are forwarded to Mr Van de Poste.’”

“The young girl came and sat down next to me. She patted my hand reassuringly.
‘I didn’t want to be rescued anyway,’ she announced. ‘If I survive, the whole point of the poem is lost – Henry will be furious.’
‘Don’t worry,’ I said, ‘it’ll all be repaired.’
‘And everyone keeps on giving me their jackets,’ she continued in a huffy tone. ‘Honestly, it gets harder and harder to freeze to death these days.’”

“We were standing in the opening chapter of The Eyre Affair, or at least, the refurbished first chapter.”

“there was room on the hangar floor for not only Darcy’s country home of Pemberley, but also Rosings, Netherfield and Longbourn as well. They had all been hoisted from the book by a massive overhead crane so the empty husk of the novel could be checked for fatigue cracks before being fumigated for nesting grammasites and repainted. At the same time an army of technicians, plasterers, painters, chippies and so forth were crawling over the houses, locations, props, furnishings and costumes, all of which had to be removed for checking and maintenance.”

 

June 24, 2014 Posted by | books | Leave a comment

Natural Conflict Resolution (2)

I took a short break from this book, but now I’ve started reading it again and I’ll probably finish it later today. Here’s the first post I wrote about the book. This is not going to be the last post about the book and I still have some chapters to go, so I’ll refrain from passing judgment on it just yet; but I must say that I find the book very interesting, and based on the coverage so far I’d probably give it four stars. It’s a bit too speculative at times, but aside from that it’s really good. People with a ‘science approach’ to life and other stuff may say that ‘we’re just apes’ (or ‘monkeys’, if they’re confused about the terminology), but precisely what this actually implies may even so still not be completely clear to them, because most people probably don’t know a great deal about how, say, chimpanzees behave and live their lives. This book will enlighten you about some of the ways in which common human behavioural patterns have close analogues in other species, and some of the patterns will probably surprise you (…and fascinate you, if you’re like me). We really are quite a bit like those other guys, in ways many of us probably have never even thought about. The book has certainly tempted me to explore the field of ethology in more detail later on.

Before moving on to the main coverage I feel the need to once again (I did this in my first post about the book as well) point out that this book is not in any way a book about strategies for how to make your aggressive colleague back off, or something like that. Quite a few of the chapters of this book are about conflict resolution/conflict management behaviours and strategies seen applied by primates in nature, and none of them are about behavioural strategies applied in the office. You’ll probably gain some valuable insights as to how humans may behave in a conflict setting as well from the book, but how many such insights you’ll take away from the book will surely depend on how confident you feel about extrapolating and drawing inferences from studies conducted on members of species related to us. There’s stuff on humans as well – there was indeed enough of that kind of stuff in the first part of the book for me to have no problem limiting my coverage in the first post about the book to the results of studies on humans alone – but the focus is decidedly different from the focus I imagine people are forced to apply when participating e.g. in anger management classes; this book is a different kettle of fish, this is mainly about understanding why animals behave the way they do, and specifically it is about understanding how they deal with conflict.

I have added some stuff from the book below. There’s a lot of good stuff in this book.

“Displacement activities are behavior patterns (often body care activities) exhibited by an animal that are “apparently irrelevant” to its ongoing activity [...] and are thought to occur in situations of motivational conflict. [...] displacement activities may be used as a behavioral measure of anxiety [...] [Reviewing our results] [t]wo patterns emerge [...] First, all group-living species show increased post-conflict affiliation between former opponents; second, all species for which information is available show increased post-conflict displacement activities. Out of four non-primate species studied thus far—the bottlenose dolphin, spotted hyena, domestic goat, and domestic cat—only the last did not show any evidence of post-conflict affiliation between former opponents. Dolphins, hyenas, and goats are all group-living animals that form stable social groups or fission/fusion societies [...]. The domestic cat, on the contrary, is an opportunistic species that may aggregate at rich food sources (as seems to be the case for urban stray cats) but probably cannot be considered as a truly social species [...]. Accordingly, cats lack the mechanisms of conflict regulation typical of social species [...]. The observation of post-conflict affiliation in species as phylogenetically distant as primates, dolphins, hyenas, and goats implies that conflict-regulation mechanisms must have evolved independently several times in association with the rise of social life. Whether group life and the consequent inevitable frictions are invariably linked to the evolution of conflict-regulation mechanisms or whether only a fraction of group-living species have evolved post-conflict conciliatory behaviors is a question that awaits further theoretical [...] and empirical studies. [...] The observation of conciliatory behaviors in species that differ widely in their cognitive capacities suggests that reconciliation does not require special abilities such as introspection and self-awareness but that good memory and individual recognition probably suffice (see de Waal & Yoshihara 1983). Obviously, stating that high cognitive abilities are not necessary does not imply that they cannot actually be involved in the process of reconciliation, at least in a few species. In other words, it is unlikely that the cognitive mechanisms underlying reconciliation are entirely the same in goats and chimpanzees (Pan troglodytes). Similar functions do not imply similar mechanisms. [...] All species for which information is available (several primates, goats, and cats) show an increase in the frequency of displacement activities after a conflict. Furthermore, in both goats and primates reconciliation caused a faster return of displacement activities to their baseline frequency. These results suggest that the post-conflict increase in displacement activities may be a general phenomenon and that one of the functions of post-conflict friendly reunions may be a reduction in the anxiety and arousal experienced by the recipient of aggression (see Aureli & Smucny, Chapter 10). [...] cognitive or ecological constraints may [...] limit the complexities of the social life of non-primates, but we are certainly very far from having identified such limits.”

“Across the five cultures girls and boys did not differ significantly in their peacemaking tendency [...]. However, girls and boys sometimes differed in the acts and gestures they used to make peace. [...] Acting silly to make others laugh may be a male strategy [...] girls may be especially responsive to clowning by boys. Research in adults has shown that women laugh and smile more often when they are observers rather than actors, especially when the speaker is male (Provine 1993). [...] Children classified as acquaintances interact differently than those classified as friends. [...] acquaintances engaged in more intense conflicts and were less likely to use conciliatory resolution strategies than friends. The distinction between friends and acquaintances is thus an important one. [...] Perhaps the simplest way of explaining [the] results is to suggest that both interactions and relationships matter to young children and that young children’s peacemaking reflects children’s motivation to repair damage to both. Friends may be motivated to protect their existing relationship from damage caused by conflict, whereas nonfriends may be motivated to restore peaceful interaction simply because playing together is more fun than playing alone. [...] Our studies [on children] showed that reunions between former opponents generally occurred within the first two minutes after the end of the conflict. This timing is remarkably similar to the timing of post-conflict peacemaking in most nonhuman primate species”

“Tantrums are a common, if not ubiquitous, phenomenon of early childhood. Tantrums also occur in infant and juvenile nonhuman primates [...]. Trivers (1985) proposes that tantrums may be a solution to a basic intergenerational conflict: the young benefit by maintaining parental nurturance as long as possible while parents’ inclusive fitness is eventually better served in other ways. When a juvenile primate has a tantrum following maternal rejection (e.g., while being weaned), its mother usually accepts it [...]. Historically, the “terrible twos” are the age of weaning in Western culture, as it remains in other cultures to this day. A disposition to have tantrums that develop at an age when weaning occurred over most of human history might well reflect an evolutionary strategy to retain parental attention. [...] the majority of post-tantrum reconciliations are initiated by the child. [...] The great similarity between children’s temper tantrums and those of young primates, and the similarity in response by the caregiver (initial distancing but eventual affiliation), suggest a shared developmental underpinning of reconciliation.”

“if a conflict-provoking situation arises between two animals and one grooms the other, then aggression may be less likely than when no affiliative behavior is exchanged. One method for evaluating such conflict management is to observe primate groups in contexts known to increase social tension and the potential for aggression. If submission, tension-regulating behavior, and friendly responses increase in such competitive situations, then animals may be attempting to reduce escalation of conflict. Two such contexts have been investigated in primate groups: scheduled feeding and crowding. Scheduled feeding of provisioned groups produces a tense situation in anticipation of competition for food and does elicit attempts to reduce conflict beforehand [...]. Crowding produces another situation in which increased competition for space produces a context in which aggression may be reduced through behavioral mechanisms. With respect to crowding, two main questions arise: Does crowding increase aggression, and do animals modify behavior under crowded conditions to reduce the potential for conflict? The answer to both questions is a qualified yes”

“In addition to post-conflict reconciliation (the focus of many chapters in this volume), nonhuman primates also use other, more powerful pre-conflict methods to maintain peace and harmony within their group. They adopt specific strategies to dissipate tension and reduce conflict before it erupts, suggesting that they possess the ability to anticipate these events and plan their behavior accordingly [...] it may be naive to expect a simple relationship between density and aggression in primates because primates have complex and flexible social behavior and advanced cognitive abilities. They do not react passively to changing situations, such as increases in density, but may actively change their behavior to cope with adverse situations. [...] Results indicate that different species may have unique reactions to short-term crowding and that more than one strategy may be used in response to increased density [...] there is evidence that primates adopt different strategies (e.g., inhibition, conflict avoidance, or tension reduction) depending on the duration of crowding, the species studied, and the individual characteristics of the interacting partners (i.e., the age, sex, and kinship of particular dyads). [...] Mongoose responses to crowding indicate that species other than primates modify behavior under high density and that the behavioral changes may be adaptive strategies to manage conflict. [...] The behavioral reactions of humans to crowding are variable [...], but the most common result is an increase in aggression [...] and a decrease in affiliative interactions under higher density [...] The decrease in social interaction has generally been interpreted as a withdrawal strategy to cope with the increased social stimulation at higher density [...]. Remarkably, the pattern of response is quite similar to the conflict-avoidance strategy observed in macaques under short-term crowding [...] individuals differ in their responses to crowding. Increased aggression during crowding appears to be more likely in males than in females [...] Individual personality traits may also influence reactions to crowding. [...] Such differential effects preclude describing a singular human pattern of response to crowding. [...] [the results] appear to show some behavioral similarities between humans and other animals. Freedman (1979) argues that we should not assume that the reactions of human and non-human primates to crowding differ until data indicate otherwise.”

“young animals especially are highly motivated to form attachments for their own safety, and when they perceive themselves to be at risk, they react strongly when separated from attachment figures. Although a dramatic protest-despair reaction may be less marked in older individuals whose attachments are less strong [...], we think that even among adults there are likely to be detectable signs of distress upon separation, and relief from distress upon reunion, when an individual values its relationship with a particular partner. Indeed, Cubicciotti & Mason (1975) showed such effects in adult titi and squirrel monkey (Saimiri sciureus) pair mates that were separated from each other for only 90 minutes and then reunited. Similarly, adult humans with close relationships often report emotional reactions (such as loneliness, anxiety, or even despair) to physical separation (Feeny 1998). [...] Studies of attachment in humans have used mother-infant separations and reunions as a way of assessing the security of the attachment bond. The separation is itself a stressful experience for the infant, and the infant’s response to separation, and especially reunion with the mother, is characteristically different for infants with secure versus ambivalent attachments [...]. Analogous results have been reported for nonhuman primates (e.g., Dettling et al. 1998).”

“[We embrace] MacLean’s (1952) view of emotions as brain functions involved in maintaining individual survival. His evolutionary approach to brain anatomy led him to point out that emotions are not uniquely human traits because most of the brain structures involved in emotions are essentially the same in all mammals and perhaps in all vertebrates. Escaping from danger, for example, is a basic survival response for all animals. [...] MacLean’s conceptual framework is still at the basis of the current evolutionary view of emotion (LeDoux 1996), and significant advances in neurophysiology have supported this view [...] [An] important class of indicators of emotion is self-directed behavior, such as self-touch, self-scratching, and self-grooming. Apart from the hygienic function of self-directed behaviors, recent ethological studies on nonhuman primates have documented their occurrence in situations of uncertainty, social tension, or impending danger [...]. Similarly, high levels of self-directed behavior are characteristic of humans experiencing anxiety [...] Measures of variation in hormones and neurotransmitters associated with the stress response (e.g., cortisol, norepinephrine) have provided biological support for individual differences in emotional profiles of children, baboons, and macaques [...] Behavioral indicators of anxiety [...] increase in frequency under [...] conditions that are associated with high risk of aggressive conflict. In captive group-living chimpanzees (Pan troglodytes) vocalizations of neighboring groups increase the likelihood of intragroup aggression and, as a consequence, are followed by higher rates of self-scratching”

“Testosterone may influence aggressive tendencies, and serotonin may regulate the threshold and intensity of the behavioral expression of aggression. Individuals with low serotonin levels exhibit impaired impulse control and a low threshold to escalate when facing potential conflict [...] Territorial disputes occur naturally in the wild in many species, and when staged in laboratories, they result in marked physiological differences between winners and losers. For example, the levels of hormones associated with the stress response, such as glucocorticoids, are higher in losers than in winners after dyadic confrontations in a variety of species (e.g., swordtail fish, [...] guinea pigs [...], tree shrews [...] In rats (Rattus norvegicus) differences between winners and losers may persist for several hours, even when the two opponents are separated from each other after the encounter [...] Interestingly, hostile behavior during marital conflict in otherwise happy human couples produces changes in blood pressure, immunological function, and hormonal concentration typical of the stress response [...] Even if overt aggression is reduced by establishing dominance relationships, conflicts of interest are usually not resolved in favor of subordinate individuals. In addition, subordinates have less control over the social environment and are strongly constrained in their actions. Accordingly, dominant and subordinate individuals differ in their physiological states [...] evidence from different sources supports the view that reconciliation has an emotional impact by reducing post-conflict anxiety. [...] there is now evidence from a number of different species that many of the most common vocalizations given by nonhuman primates function to initiate and facilitate social interactions. Playback experiments with adult female baboons have demonstrated that vocalizations also serve to diminish the strength of recipients’ responses to former aggressors’ potentially threatening behavior. Most important, apparently reconciliatory vocalizations influence recipients’ willingness to approach and be approached by former aggressors.”

“The tendency of human beings to respond with distress to the end of a close relationship is a consistent phenomenon across different cultures and across the age span [...]. Recent social psychology studies have concluded that threats to social bonds are a primary source of anxiety [...] and that social exclusion is probably the most common cause of anxiety [...]. Behavioral and physiological responses to the disturbance and restoration of social relationships emerge early in life. These responses have been extensively studied in nonhuman primates through experimental manipulations of the mother-infant relationship [...] disturbance through experimental separation provokes strong responses, such as increased plasma cortisol and heart rate, in the infant and the mother; reunions of mothers with their infants restore their physiological responses to baseline [in both nonhuman primates and rodents] [...]. Similar physiological changes also are found when adults of established pairs of the monogamous titi monkeys (Callicebus moloch) are separated from each other [...], suggesting that the disruption of strong bonds has similar effects throughout the life span. [...] The marked stress response normally evoked by stimuli, such as exposure to novel environments or objects, exposure to naturally occurring predators (e.g., snakes), or separation of infants from their mothers, is buffered by the presence of familiar conspecifics”

“The mediation of reunions and other forms of conflict resolution does not need to involve only “negative” emotions, such as anxiety, fear, or distress. Conflict resolution often occurs through affiliative contacts that are likely to be associated with positive sensations. Gentle touching causes relaxation and a reduction in heart rate in humans, rhesus monkeys, and horses [...] Allogrooming in monkeys decreases heart rate [...] Although the actions of endogenous brain opioids affect and are affected by several hormones and neurotransmitters, their involvement in mother-infant attachment and separation distress is certain [...]. The experience of separation distress likely provides the basic motivation for social reunion, and the subsequent opioid release alleviates separation distress, replacing it with positive sensations. This is probably also true for relationships between adults. For example, adult talapoin monkeys (Miopithecus talapoin) that have been socially isolated show a significant increase in brain opioids following affiliative behavior with their peers upon reunion [...] The perspective of emotional mediation of social processes, including conflict resolution, does not require the identification of specific humanlike emotions, especially when the conscious feeling is not considered. It is only necessary to characterize the conditions (e.g., post-escalation relationship disturbance), the various changes (e.g., increased self-scratching), and the factors affecting them (e.g., relationship quality). [...] this perspective can explain the effects of relationship quality on reconciliation without necessarily implying conscious knowledge of relationship value.”

June 22, 2014 Posted by | anthropology, biology, books, Psychology, Zoology | Leave a comment

Nutrition at a Glance

This is a Wiley-Blackwell publication about human nutrition. It is also perhaps the strangest W-B publication I’ve ever read, because of the combination of the following two facts: i. Each chapter is two pages long (the book has 62 chapters). ii. This is an academic text without a single source or reference. The latter of those two points is the main reason why I have not rated the book.

The chapters are denser than you’d think (they have a lot of information considering what you’d expect from two-page chapters), and many chapters ‘come in pairs’ or deal with related stuff; for example there are three main chapters dealing exclusively with proteins – one about the ‘chemistry and digestion’ of proteins, another one about the ‘functions of proteins in the body’, and a third one about the ‘needs and sources’ of proteins. Carbohydrates and fats also get multiple chapters each, and micronutrients get 7 chapters of ‘exclusive coverage’ dealing only with those things. The level of detail is reasonably high (again considering what you’d expect), but of course there’s only so much stuff you can cram into a chapter two pages long. I think in many ways it is a really neat book to have for looking up stuff in this area that you’re wondering about and/or can’t quite remember (‘what was the role of butyric acid in the colon again?’ ‘Which factors affect calcium absorption?’ ‘What are the roles of the various B-vitamins in metabolism? How might I get into trouble if I don’t get enough riboflavin, and what can I do to avoid that situation?’). Quite a few of the things she talks about I don’t really consider it too problematic that she does not source; she knows a lot more about which role folate plays in the regulation of homocysteine levels than I do, and I don’t think there’s a big risk involved in just taking her word for it that those things work the way she says they do. Much of the book covers stuff on a level where I could justify thinking along such lines; many of the chapters are a bit like book versions of short Khan Academy nutrition lectures (perhaps a bit like lectures like this and this, I guess without having watched those lectures), and I figure if I’m okay with watching lectures like those I should be okay with reading a book like this as well, which is a big part of the reason why I didn’t just throw it away the moment I realized that there was actually not a single page of references to be found anywhere.

As I didn’t rate the book because of it, the lack of sourcing of course bothered me. One thing which puzzled me is why she decided to write the book this way – I simply do not understand that decision at all. Given the current state of affairs of nutritional science (and the current state at the time the book was written in 2007), I will say that I think the way she has chosen to write this book is simply flabbergasting to me. Nothing tempts people to disregard your information like not telling them where it comes from. There is not a single sentence in this book with the words ‘[X & Y] found that…’ – she only ever writes ‘a study found that…’, and this is just infuriating. There are various recommendations of daily intake of various substances in the book, but you have no idea who came up with those recommendations or which evidence base they are based on – there’s not even a source indicated in the headings in those cases. I simply don’t understand why she’d write the book that way – the lack of sources makes much of the stuff look deeply suspect, regardless of whether or not it’s actually all of it based on ‘the best available evidence’, and occasionally it seems as if she’s gone out of her way to avoid adding a source even in situations where it would make a lot more sense to add it than to not do that. To add insult to injury, a couple of the reported estimates in the last half of the book were so out of line with other estimates I could find elsewhere that I seriously considered throwing the book away. So, yeah.

But the book has a lot of good stuff as well which presumably a lot of people would benefit from knowing about, so it’s really hard for me to know what to think about it. To take an example of what I’m talking about here, Rees et al. observed in their book – as I have pointed out – that: “Vegans who omit all animal products from their diet often have subclinical vitamin B12 deficiency.” They probably wouldn’t have if they’d read this book. Anemia is a very common condition worldwide, and iron deficiency is estimated to be the most common cause. An estimated 250 million preschool children are vitamin A deficient. We humans need a lot of different stuff to keep going, and the food we eat plays many roles most of us probably haven’t given any thought. Everybody needs to eat, so there aren’t many people who would not benefit from knowing more about how these things work; even people following ‘an ideal balanced diet’ can be at risk of developing deficiency states due to malabsorption syndromes or various disease states which may change nutritional requirements.

I’ve added some ‘sample observations’ from the book, as well as a few comments, below:

“There is a continuous turnover of protein in the body, which in healthy adults exhibits a balance between synthesis and breakdown, and amounts to 3–6 g/kg body weight per day. During growth there is an excess of synthesis over breakdown, and in wasting conditions (e.g. starvation, cancer and after surgery or trauma), breakdown exceeds synthesis. Protein synthesis is regulated principally by insulin, and catabolism by glucocorticoids. [...] The body is unable to make nine of the amino acids used in protein synthesis [...] Lack of any one of these will limit the synthesis of protein, even if all the other required amino acids are present in adequate amounts. [...] In addition, there are a number of other amino acids that can be synthesised in the body under normal conditions, given the necessary supply of precursor molecules. In the absence of these precursors, the amino acids become ‘conditionally indispensable [...] Protein synthesis is an energy-demanding process; it has been calculated that the energy requirement is 4.2 kJ (1 kcal)/g of protein synthesised. Protein synthesis occurs more rapidly after a meal than in the fasting state, due to the greater supply of amino acids. On average the energy used in protein synthesis accounts for 12% of the basal metabolic rate. [...] The digestibility of proteins from animal sources is much greater than that from plant sources. Digestibility for egg is given as 97%. [...] Poor digestibility, of between 60 and 80%, is found in legumes and cereals with tough cell walls, particularly when uncooked, and is a factor in diets that are low in protein. [...] Worldwide, the availability of plant proteins is relatively consistent, at about 50 g/person/day. However, the availability of animal protein sources varies widely, from <5 to 50 g/head/day, highest in most Western countries. [...] Inadequate protein intakes rarely occur alone, and are generally found within a wider picture of undernutrition. Insufficient intakes of energy cause protein to be used for energy, and make it unavailable for tissue maintenance or growth.”

“The most rapid period of brain growth occurs from mid-gestation to 18 months after birth. At birth the brain accounts for 10% of the body weight; an adult brain weighs about 1.4 kg, and comprises 2% of body weight. Different components of the brain grow at different rates and have ‘critical periods’ when growth is most rapid and vulnerable to adverse influence.”

‘Alcohol and folic acid’ would probably be two factors most people would know about in this context. But there’s of course a lot more to developing a human brain than these variables. Generalized undernutrition can lead to smaller brain and less extensive neural networks, long-chain polyunsaturated fatty acids are quite important for brain development, you need copper for myelin synthesis but too much of it may be toxic, iodine deficiency leads to cretinism, severe iron deficiency may lead to long-term reductions in cognitive performance whereas too much of it again may lead to toxicity, excess vitamin A intake may be teratogenic, pyridoxine deficiency may lead to seizures/neurologic symptoms, … Incidentally the arrow doesn’t just go from food intake to brain performance; the brain is also helping you figure out what to eat: “neurotransmitters acting within the brain are thought to regulate preferences for particular macronutrients. Serotonin may influence the balance between carbohydrate and protein intakes. Noradrenaline and opiates are also believed to have a role. [...] Disturbances of neurotransmitter release, whether of endogenous (e.g. in disorders of brain function) or exogenous origin (e.g. by drugs), are likely therefore to affect food intake.”

Some more stuff about childhood growth from a few chapters on related matters:

“The fastest rate of growth is in the first 6 months of life, with a doubling of birth weight, and slows towards 12 months, to achieve about three times birth weight. Body weight only doubles between the ages of 1 and 5 years. Standard growth charts are useful to check that growth is progressing appropriately [...] During the years of [school-age] childhood, mean growth is relatively constant, and averages 2.5 kg and 6 cm per year. During puberty, on average: • girls increase by 20 cm (height) and 20 kg (weight); • boys increase by 30 cm (height) and 30 kg (weight). These increases represent 40% of eventual adult weight. Growth is vulnerable to faltering if nutritional intakes do not keep pace with the demands. [...] Body fat percentage levels increase rapidly in the first months of life, but start to fall after the first year. [...] There is a further increase from about the age of 5 years (adiposity rebound), which may start earlier in larger, fatter children [...] In boys, the fat content starts to fall during the pubertal growth spurt, but in girls it continues to increase, resulting in the average 10% fat content differential between the sexes seen in adults. [...] Growth in infants and young children, usually recorded as weight, should progress along a centile line on standard growth charts. Reasons for centile crossing (moving from one centile line to another) need to be established. [...] Infants of diabetic mothers, who are often born very large (>4.5 kg), may exhibit ‘catch-down’ growth during the first year of life. Once removed from the oversupply of nutrients in the womb, their growth rate slows. [...] An infant undernourished in the womb may show ‘catch-up’ growth. This should be an increase in lean body mass, rather than fat; the latter is linked to risk of later disease.”

“It is now recognised that vitamin D is synthesised in the skin by the action of ultraviolet light on a precursor, and could strictly be termed a hormone rather than a vitamin. Further, niacin [vitamin B3] can be made in the body from the amino acid tryptophan, so a separate supply may not be needed if protein intakes are adequate. However, in both of these cases, there are situations where synthesis is insufficient, and so a dietary need remains.”

“Inadequate intakes of macronutrients will most obviously be reflected in disturbed growth in children and body weight changes in adults. [...] Undernutrition in the elderly is poorly reported, but is believed to be widespread [...] The consequences of undernutrition can manifest both in the short and long term, and may have intergenerational effects, through poor pregnancy outcome and low birth weight. [...] Worldwide, deficiencies of iron, vitamin A and iodine affect the greatest numbers of people. [...] Several other micronutrients may become deficient when diets lack specific food groups. These include: • vitamin B12, when vegan diets are consumed; • calcium, when dairy products are excluded from the diet; • riboflavin, when diets are low in green vegetables and dairy products.”

“The typical increase in weight (in the UK) during pregnancy is 11–16 kg but varies widely. Gains in the second and third trimesters should average 0.4 kg/week for normal weight women, less (0.3 kg/ week) for overweight women and more (0.5 kg/week) for women who are underweight. [...] The extra energy costs of pregnancy are estimated at 310 MJ (77 000 kcal) [...] The mother’s nutritional status is unlikely to affect the volume or the macronutrient content of her milk for the first few weeks of lactation. However, poorly nourished women will not be able to sustain the same level of nutrients for prolonged periods. The fat content of the milk correlates with the mother’s levels of body fat, and the pattern of fatty acids secreted in the milk partly reflects those in the mother’s dietary intake. Neither the fat-soluble vitamin content nor the mineral content of the milk fluctuates with maternal dietary intake.”

ATP is the fundamental molecule that on breakdown to ADP provides energy for contracting muscle. ATP stores are very limited and require continual replenishment; the amount stored would fuel only about two seconds of exercise. [...] CHO [Carbohydrate] stores in muscle (300–800 g) and liver (80 g) are limited; fats stored mainly in subcutaneous tissue are found in very much greater amounts (minimum 5 kg in males, more in females). • Lipids are considerably more energy dense than CHOs. Metabolism of one gram of fat will deliver considerably more ATP molecules than one gram of CHO; however, more oxygen is required to metabolise fats, and fats cannot be metabolised anaerobically [...] An important principle is that carbohydrates are the preferred energy source particularly for more intense and prolonged exercise [...] Most athletes already consume sufficient protein in a mixed diet [...] With the exception of energy intake the evidence that normal dietary supplements enhance sporting performance is poor.”

I found the two chapters about nutrition and sport interesting in a way, but mostly because they helped me figure out what happens in normal people – a book like this (which I have considered reading in the past, but has never gotten around to actually reading) is probably better at elucidating relevant mechanisms in my case.

“Consumers generally believe that foods produced organically, often by more traditional agricultural methods, have superior nutritional quality. This is not currently supported by the scientific literature, in which studies find no difference in nutrient content between organic and non-organic produce; there is also no information about impact on human health.”

June 21, 2014 Posted by | books, health, medicine | Leave a comment

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