Econstudentlog

National EM Board Review Course: Environmental Emergencies

Some links to resources on stuff covered in the lecture:

Drowning.
Diving disorders.
Henry’s law/Boyle’s law/Dalton’s law.
Nitrogen narcosis.
Decompression Sickness.
Hyperbaric Oxygen Therapy.
Blast Injuries.
Altitude sickness.
High Altitude Flatus Expulsion (HAFE).
High-Altitude Pulmonary Edema.
Hypothermia.
Cold-induced vasodilation.
Osborn Waves.
Frostbite (‘think of this as a thermal burn equivalent caused by cold’).
Trench foot.
Heat stroke.
Heat cramps.
Thermal Burns.
Parkland formula.
Escharotomy and Burns.
Electrical Injuries in Emergency Medicine.
Lightning Injuries.
Radiation exposure.
Inhalation Anthrax.
Botulism As a Bioterrorism Agent.
Chemical weapon/vessicants/nerve agent.
Bite injuries.
Cat scratch disease.
Rabies.
Rattlesnake Bite.
Snakebites: First aid.
Snake bite: coral snakes.
Black widow spider bite.
Brown recluse spider bite.
Marine envenomation.

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September 22, 2017 Posted by | Lectures, Medicine | Leave a comment

The Biology of Moral Systems (III)

This will be my last post about the book. It’s an important work which deserves to be read by far more people than have already read it. I have added some quotes and observations from the last chapters of the book below.

“If egoism, as self-interest in the biologists’ sense, is the reason for the promotion of ethical behavior, then, paradoxically, it is expected that everyone will constantly promote the notion that egoism is not a suitable theory of action, and, a fortiori, that he himself is not an egoist. Most of all he must present this appearance to his closest associates because it is in his best interests to do so – except, perhaps, to his closest relatives, to whom his egoism may often be displayed in cooperative ventures from which some distant- or non-relative suffers. Indeed, it may be arguable that it will be in the egoist’s best interest not to know (consciously) or to admit to himself that he is an egoist because of the value to himself of being able to convince others he is not.”

“The function of [societal] punishments and rewards, I have suggested, is to manipulate the behavior of participating individuals, restricting individual efforts to serve their own interests at others’ expense so as to promote harmony and unity within the group. The function of harmony and unity […] is to allow the group to compete against hostile forces, especially other human groups. It is apparent that success of the group may serve the interests of all individuals in the group; but it is also apparent that group success can be achieved with different patterns of individual success differentials within the group. So […] it is in the interests of those who are differentially successful to promote both unity and the rules so that group success will occur without necessitating changes deleterious to them. Similarly, it may be in the interests of those individuals who are relatively unsuccessful to promote dissatisfaction with existing rules and the notion that group success would be more likely if the rules were altered to favor them. […] the rules of morality and law alike seem not to be designed explicitly to allow people to live in harmony within societies but to enable societies to be sufficiently united to deter their enemies. Within-society harmony is the means not the end. […] extreme within-group altruism seems to correlate with and be historically related to between-group strife.”

“There are often few or no legitimate or rational expectations of reciprocity or “fairness” between social groups (especially warring or competing groups such as tribes or nations). Perhaps partly as a consequence, lying, deceit, or otherwise nasty or even heinous acts committed against enemies may sometimes not be regarded as immoral by others withing the group of those who commit them. They may even be regarded as highly moral if they seem dramatically to serve the interests of the group whose members commit them.”

“Two major assumptions, made universally or most of the time by philosophers, […] are responsible for the confusion that prevents philosophers from making sense out of morality […]. These assumptions are the following: 1. That proximate and ultimate mechanisms or causes have the same kind of significance and can be considered together as if they were members of the same class of causes; this is a failure to understand that proximate causes are evolved because of ultimate causes, and therefore may be expected to serve them, while the reverse is not true. Thus, pleasure is a proximate mechanism that in the usual environments of history is expected to impel us toward behavior that will contribute to our reproductive success. Contrarily, acts leading to reproductive success are not proximate mechanisms that evolved because they served the ultimate function of bringing us pleasure. 2. That morality inevitably involves some self-sacrifice. This assumption involves at least three elements: a. Failure to consider altruism as benefits to the actor. […] b. Failure to comprehend all avenues of indirect reciprocity within groups. c. Failure to take into account both within-group and between-group benefits.”

“If morality means true sacrifice of one’s own interests, and those of his family, then it seems to me that we could not have evolved to be moral. If morality requires ethical consistency, whereby one does not do socially what he would not advocate and assist all others also to do, then, again, it seems to me that we could not have evolved to be moral. […] humans are not really moral at all, in the sense of “true sacrifice” given above, but […] the concept of morality is useful to them. […] If it is so, then we might imagine that, in the sense and to the extent that they are anthropomorphized, the concepts of saints and angels, as well as that of God, were also created because of their usefulness to us. […] I think there have been far fewer […] truly self-sacrificing individuals than might be supposed, and most cases that might be brought forward are likely instead to be illustrations of the complexity and indirectness of reciprocity, especially the social value of appearing more altruistic than one is. […] I think that […] the concept of God must be viewed as originally generated and maintained for the purpose – now seen by many as immoral – of furthering the interests of one group of humans at the expense of one or more other groups. […] Gods are inventions originally developed to extend the notion that some have greater rights than others to design and enforce rules, and that some are more destined to be leaders, others to be followers. This notion, in turn, arose out of prior asymmetries in both power and judgment […] It works when (because) leaders are (have been) valuable, especially in the context of intergroup competition.”

“We try to move moral issues in the direction of involving no conflict of interest, always, I suggest, by seeking universal agreement with our own point of view.”

“Moral and legal systems are commonly distinguished by those, like moral philosophers, who study them formally. I believe, however, that the distinction between them is usually poorly drawn, and based on a failure to realize that moral as well as legal behavior occurs as a result of probably and possible punishments and reward. […] we often internalize the rules of law as well as the rules of morality – and perhaps by the same process […] It would seem that the rules of law are simply a specialized, derived aspect of what in earlier societies would have been a part of moral rules. On the other hand, law covers only a fraction of the situations in which morality is involved […] Law […] seems to be little more than ethics written down.”

“Anyone who reads the literature on dispute settlement within different societies […] will quickly understand that genetic relatedness counts: it allows for one-way flows of benefits and alliances. Long-term association also counts; it allows for reliability and also correlates with genetic relatedness. […] The larger the social group, the more fluid its membership; and the more attenuated the social interactions of its membership, the more they are forced to rely on formal law”.

“[I]ndividuals have separate interests. They join forces (live in groups; become social) when they share certain interests that can be better realized for all by close proximity or some forms of cooperation. Typically, however, the overlaps of interests rarely are completely congruent with those of either other individuals or the rest of the group. This means that, even during those times when individual interests within a group are most broadly overlapping, we may expect individuals to temper their cooperation with efforts to realize their own interests, and we may also expect them to have evolved to be adept at using others, or at thwarting the interests of others, to serve themselves (and their relatives). […] When the interests of all are most nearly congruent, it is essentially always due to a threat shared equally. Such threats almost always have to be external (or else they are less likely to affect everyone equally […] External threats to societies are typically other societies. Maintenance of such threats can yield situations in which everyone benefits from rigid, hierarchical, quasi-military, despotic government. Liberties afforded leaders – even elaborate perquisites of dictators – may be tolerated because such threats are ever-present […] Extrinsic threats, and the governments they produce, can yield inflexibilities of political structures that can persist across even lengthy intervals during which the threats are absent. Some societies have been able to structure their defenses against external threats as separate units (armies) within society, and to keep them separate. These rigidly hierarchical, totalitarian, and dictatorial subunits rise and fall in size and influence according to the importance of the external threat. […] Discussion of liberty and equality in democracies closely parallels discussions of morality and moral systems. In either case, adding a perspective from evolutionary biology seems to me to have potential for clarification.”

“It is indeed common, if not universal, to regard moral behavior as a kind of altruism that necessarily yields the altruist less than he gives, and to see egoism as either the opposite of morality or the source of immorality; but […] this view is usually based on an incomplete understanding of nepotism, reciprocity, and the significance of within-group unity for between-group competition. […] My view of moral systems in the real world, however, is that they are systems in which costs and benefits of specific actions are manipulated so as to produce reasonably harmonious associations in which everyone nevertheless pursues his own (in evolutionary terms) self-interest. I do not expect that moral and ethical arguments can ever be finally resolved. Compromises and contracts, then, are (at least currently) the only real solutions to actual conflicts of interest. This is why moral and ethical decisions must arise out of decisions of the collective of affected individuals; there is no single source of right and wrong.

I would also argue against the notion that rationality can be easily employed to produce a world of humans that self-sacrifice in favor of other humans, not to say nonhuman animals, plants, and inanimate objects. Declarations of such intentions may themselves often be the acts of self-interested persons developing, consciously or not, a socially self-benefiting view of themselves as extreme altruists. In this connection it is not irrelevant that the more dissimilar a species or object is to one’s self the less likely it is to provide a competitive threat by seeking the same resources. Accordingly, we should not be surprised to find humans who are highly benevolent toward other species or inanimate objects (some of which may serve them uncomplainingly), yet relatively hostile and noncooperative with fellow humans. As Darwin (1871) noted with respect to dogs, we have selected our domestic animals to return our altruism with interest.”

“It is not easy to discover precisely what historical differences have shaped current male-female differences. If, however, humans are in a general way similar to other highly parental organisms that live in social groups […] then we can hypothesize as follows: for men much of sexual activity has had as a main (ultimate) significance the initiating of pregnancies. It would follow that when a man avoids copulation it is likely to be because (1) there is no likelihood of pregnancy or (2) the costs entailed (venereal disease, danger from competition with other males, lowered status if the event becomes public, or an undesirable commitment) are too great in comparison with the probability that pregnancy will be induced. The man himself may be judging costs against the benefits of immediate sensory pleasures, such as orgasms (i.e., rather than thinking about pregnancy he may say that he was simply uninterested), but I am assuming that selection has tuned such expectations in terms of their probability of leading to actual reproduction […]. For women, I hypothesize, sexual activity per se has been more concerned with the securing of resources (again, I am speaking of ultimate and not necessarily conscious concerns) […]. Ordinarily, when women avoid or resist copulation, I speculate further, the disinterest, aversion, or inhibition may be traceable eventually to one (or more) of three causes: (1) there is no promise of commitment (of resources), (2) there is a likelihood of undesirable commitment (e.g., to a man with inadequate resources), or (3) there is a risk of loss of interest by a man with greater resources, than the one involved […] A man behaving so as to avoid pregnancies, and who derives from an evolutionary background of avoiding pregnancies, should be expected to favor copulation with women who are for age or other reasons incapable of pregnancy. A man derived from an evolutionary process in which securing of pregnancies typically was favored, may be expected to be most interested sexually in women most likely to become pregnant and near the height of the reproductive probability curve […] This means that men should usually be expected to anticipate the greatest sexual pleasure with young, healthy, intelligent women who show promise of providing superior parental care. […] In sexual competition, the alternatives of a man without resources are to present himself as a resource (i.e., as a mimic of one with resources or as one able and likely to secure resources because of his personal attributes […]), to obtain sex by force (rape), or to secure resources through a woman (e.g., allow himself to be kept by a relatively undesired woman, perhaps as a vehicle to secure liaisons with other women). […] in nonhuman species of higher animals, control of the essential resources of parenthood by females correlates with lack of parental behavior by males, promiscuous polygyny, and absence of long-term pair bonds. There is some evidence of parallel trends within human societies (cf. Flinn, 1981).” [It’s of some note that quite a few good books have been written on these topics since Alexander first published his book, so there are many places to look for detailed coverage of topics like these if you’re curious to know more – I can recommend both Kappeler & van Schaik (a must-read book on sexual selection, in my opinion) & Bobby Low. I didn’t think too highly of Miller or Meston & Buss, but those are a few other books on these topics which I’ve read – US].

“The reason that evolutionary knowledge has no moral content is [that] morality is a matter of whose interests one should, by conscious and willful behavior, serve, and how much; evolutionary knowledge contains no messages on this issue. The most it can do is provide information about the reasons for current conditions and predict some consequences of alternative courses of action. […] If some biologists and nonbiologists make unfounded assertions into conclusions, or develop pernicious and fallible arguments, then those assertions and arguments should be exposed for what they are. The reason for doing this, however, is not […should not be..? – US] to prevent or discourage any and all analyses of human activities, but to enable us to get on with a proper sort of analysis. Those who malign without being specific; who attack people rather than ideas; who gratuitously translate hypotheses into conclusions and then refer to them as “explanations,” “stories,” or “just-so-stories”; who parade the worst examples of argument and investigation with the apparent purpose of making all efforts at human self-analysis seem silly and trivial, I see as dangerously close to being ideologues at least as worrisome as those they malign. I cannot avoid the impression that their purpose is not to enlighten, but to play upon the uneasiness of those for whom the approach of evolutionary biology is alien and disquieting, perhaps for political rather than scientific purposes. It is more than a little ironic that the argument of politics rather than science is their own chief accusation with respect to scientists seeking to analyze human behavior in evolutionary terms (e.g. Gould and Levontin, 1979 […]).”

“[C]urrent selective theory indicates that natural selection has never operated to prevent species extinction. Instead it operates by saving the genetic materials of those individuals or families that outreproduce others. Whether species become extinct or not (and most have) is an incidental or accidental effect of natural selection. An inference from this is that the members of no species are equipped, as a direct result of their evolutionary history, with traits designed explicitly to prevent extinction when that possibility looms. […] Humans are no exception: unless their comprehension of the likelihood of extinction is so clear and real that they perceive the threat to themselves as individuals, and to their loved ones, they cannot be expected to take the collective action that will be necessary to reduce the risk of extinction.”

“In examining ourselves […] we are forced to use the attributes we wish to analyze to carry out the analysis, while resisting certain aspects of the analysis. At the very same time, we pretend that we are not resisting at all but are instead giving perfectly legitimate objections; and we use our realization that others will resist the analysis, for reasons as arcane as our own, to enlist their support in our resistance. And they very likely will give it. […] If arguments such as those made here have any validity it follows that a problem faced by everyone, in respect to morality, is that of discovering how to subvert or reduce some aspects of individual selfishness that evidently derive from our history of genetic individuality.”

“Essentially everyone thinks of himself as well-meaning, but from my viewpoint a society of well-meaning people who understand themselves and their history very well is a better milieu than a society of well-meaning people who do not.”

September 22, 2017 Posted by | Anthropology, Biology, Books, Evolutionary biology, Genetics, Philosophy, Psychology, Religion | Leave a comment

The fall of Rome

“According to the conventional view of things, the military and political disintegration of Roman power in the West precipitated the end of a civilization. Ancient sophistication died, leaving the western world in the grip of a ‘Dark Age’ of material and intellectual poverty, out of which it was only slowly to emerge. […] a much more comfortable vision of the end of empire [has been] spreading in recent years through the English-speaking world. […] There has been a sea change in the language used to describe post-Roman times. Words like ‘decline’ and ‘crisis’ […] have largely disappeared from historians’ vocabularies, to be replaced by neutral terms, like ‘transition’, ‘change’, and ‘transformation’. […] some historians in recent decades have also questioned the entire premiss that the dissolution of the Roman empire in the West was caused by hostile and violent invasion. […] some recent works […] present the theory of peaceful accommodation as a universally applicable model to explain the end of the Roman empire.”

Ward Perkins’ book is a work which sets out to show why he thinks those people are wrong, presenting along the way much evidence for widespread violence and disruption throughout the Western Empire towards the end. Despite the depressing topics covered therein I really enjoyed the book; Perkins spends a lot of time on material culture aspects and archaeological remains – it’s perhaps a telling fact that the book’s appendix deals with the properties of pottery and potsherds, and how important these kinds of material remains might be in terms of helping to make sense of things which happened in the far past. A general problem in a collapse setting is that when conditions deteriorate a lot, the sort of high-quality evidence that historians and archaeologists love to look at tend to disappear; censuses stop being taken (so you have to guess at how many people were around, instead of knowing it reasonably well – which can be particularly annoying if the disrupting factor was also killing people), innumeracy and illiteracy increase (translating to fewer written sources available), and so on. I should perhaps interpose that these sorts of issues do not just pertain to historical sources from the past; similar problems also arise in various analytical contexts today. Countries in a state of crisis (war, epidemics) tend to produce poor and questionable data, if any data can be gathered at all, a point I recall being covered in Newman & DeRouen’s book; related topics were also discussed in M’ikanatha & Iskander’s book as people working in public health sometimes face these problems as well (that work was of course focused on disease surveillance aspects, and in that context I might mention that the authors mentioned that poor data availability does not really necessarily mean that no data is ‘available’; for example in such settings (cheap) proxy data of various kinds may sometimes be usefully employed to inform resource allocation decisions, even if the use of such data would not be cost-effective or meaningful in a different setting). Another point of relevance is of course that some types of evidence survive the passage of time much better than others; pottery is much harder to destroy than low-quality parchment.

The point of looking at things like pottery and coins (a related topic I recall Webster covering in some detail in his book about The Roman Invasion of Britain) is not mainly that it’s super interesting to look at different types of pottery or coins – the point is that these types of material remains tend to be extremely informative about many things besides the artifacts themselves. Pottery was used for storing goods, and those goods aren’t around any longer but the pottery still is. And ‘pottery’ is not just ‘pottery’; different types of pottery required different levels of skill, and an important variable here is the level of standardization – Roman pottery was in general of high quality and was highly standardized; by examining e.g. clay content you can actually often tell where the pottery was made; specific producers produced pottery that was easily date-able. Coins were used for purchasing things and widespread use of them implies the existence of trading networks not relying on barter trade. Different coins had different values and there are important insights to be gathered from the properties of these artifacts; Joseph Tainter e.g. talks in his book about how the silver content of Roman coins gradually decreased over time, indicating at some periods that the empire was apparently undergoing quite severe inflation (the Roman military was compensated in coin, not goods, so by tweaking the amount of copper or silver in those coins the emperors could save a bit of money – which many of them did). If the amount of low-denomination coins drops a lot this might be an indication that people were reverting to barter trade. And so on. If you find some Roman coins in a field in Britain, it might mean that there used to be a Roman garrison there. If people used to use roof tiles and build buildings out of stone, rather than wood, and you observe that they stopped doing that, that’s also a clue that something changed.

A lot of the kind of evidence Perkins looks at in his book is to some extent indirect evidence, but the point is that there’s a lot of it, and if different sources tell roughly similar stories it sort of starts getting hard to argue against. To give a sense of the scale of the material remains available, one single source in Rome, Monte Testaccio, is made up entirely of broken oil amphorae imported to Rome from south-western Spain during the 2nd and 3rd century and is estimated to contain the remains of 53 million amphorae. An image of how the remains of one particular pottery manufacturer operating in Oxford in the 3rd and 4th century are distributed throughout Britain yield something like 100 different English sites where that pottery has been found. Again, the interesting thing here is not only the pottery itself, but also all the things people transported using those vessels, and all those other things (lost from the archaeological record) that might have been transported from A to B if they were willing to transport brittle pottery vessels that far around. And it’s very interesting to see distributions like that and then start comparing them with the sort of distributions you’ll get if you look for stuff produced, say, 200 years later. Coins, pottery, roof tiles, amphorae, animal bones (there’s evidence that Roman cows were larger than their Early Medieval counterparts), new construction (e.g. temples) – look at what people left behind, compare the evidence you get from the time of the Empire with what came after; this is a very big part of what Perkins does in his book.

While looking at the evidence it becomes obvious that some regions were more severely affected than others, and Perkins goes into those details as well. In general it seems that Britain was the most severely affected region, with other regions doing somewhat better; the timing also varied greatly. Greece (and much of the Eastern Empire) actually experienced a period of expansion (increased density of settlements, new churches and monasteries, stone rural houses) during the fifth century but around 600 AD the Aegean was severely hit and experienced severe disruption where former great cities became little but abandoned ghost towns. Perkins also takes care to deal with the ‘barbarians’ in at least some detail (Peter Heather covers that stuff in a lot more detail in his book Empires and Barbarians, if people are curious to know more about these topics), not lumping them all together into One Great Alliance to Take Down the Empire (quite often these guys were at war with each other). The evidence is presented in some detail, which also means that if you walk away from the book still thinking Perkins hasn’t made a good case for his beliefs, well, you’ll at least know where the author is coming from and why he holds the views he does.

I’ve added some more quotes from the book below. If you’re interested in these topics this book is a must read.

“The Germanic invaders of the western empire seized or extorted through the threat of force the vast majority of the territories in which they settled, without any formal agreement on how to share resources with their new Roman subjects. The impression given by some recent historians that most Roman territory was formally ceded to them as part of a treaty is quite simply wrong. Whenever the evidence is moderately full, as it is from the Mediterranean provinces, conquest or surrender to the threat of force was definitely the norm, not peaceful settlement. […] The experience of conquest was, of course, very varied across the empire. Some regions were overrun brutally but swiftly. […] Other regions, particularly those near the frontiers of the empire, suffered much more prolonged violence. […] Even those few regions that eventually passed relatively peacefully into Germanic control had all previously experienced invasion and devastation.”

“Throughout the time that the Roman empire existed, the soldiery of many towns were maintained at public expense for the defence of the frontier. When this practice fell into abeyance, both these troops and the frontier disappeared. […] It has rightly been observed that the deposition in 476 of the last emperor resident in Italy, Romulus Augustulus, caused remarkably little stir: the great historian of Antiquity, Momigliano, called it the ‘noiseless fall of an empire’.39 But the principal reason why this event passed almost unnoticed was because contemporaries knew that the western empire, and with it autonomous Roman power, had already disappeared in all but name. […] The story of the loss of the West is not a story of great set-piece battles, like Hadrianopolis, heroically lost by the Romans in the field. […] The West was lost mainly through failure to engage the invading forces successfully and to drive them back. This caution in the face of the enemy, and the ultimate failure to drive him out, are best explained by the severe problems that there were in putting together armies large enough to feel confident of victory. Avoiding battle led to a slow attrition of the Roman position, but engaging the enemy on a large scale would have risked immediate disaster […] Roman military dominance over the Germanic peoples was considerable, but never absolute and unshakable. […] even at the best of times, the edge that the Romans enjoyed over their enemies, through their superior equipment and organization, was never remotely comparable, say, to that of Europeans in the nineteenth century […] although normally the Romans defeated barbarians when they met them in battle, they could and did occasionally suffer disasters.”

“Italy suffered from the presence of large hostile armies in 401-2 (Alaric and the Goths), in 405-6 (Radagaisus), and again from 408 to 412 (Alaric, for the second time); Gaul was devastated in the years 407-9 by the Vandals, Alans, and Sueves; and the Iberian peninsula by the same peoples, from 409. The only regions of the western empire that had not been profoundly affected by violence by 410 were Africa and the islands of the Mediterranean […] Radagaisus’ incursion was successfully crushed, but it was immediately followed by a disastrous sequence of events: the crossing of the Rhine by Vandals, Sueves, and Alans at the very end of 406; the usurpation of Constantine III in 407, taking with him the resources of Britain and much of Gaul; and the Goths’ return to Italy in 408. […] Some of the lost territories were temporarily recovered in the second decade of the century; but much (the whole of Britain and a large part of Gaul and Spain) was never regained, and even reconquered provinces took many years to get back to full health […] the imperial recovery was only short-lived; in 429 it was brought definitely to an end by the successful crossing of the Vandals into Africa, and the devastation of the western empire’s last remaining secure tax base. […] There was, of course, a close connection between failure ‘abroad’ and the usurpations and rebellions ‘at home’. […] As in other periods of history, failure against foreign enemies and civil war were very closely linked, indeed feeding off each other.”

“Some accounts of the invasions [and maps of them] […] seem to be describing successive campaigns in a single war, with the systematic and progressive seizure of territory by the various armies of a united German coalition. If this had really been the case, the West would almost certainly have fallen definitely in the very early fifth century, and far less of the structures of imperial times would have survived into the post-Roman period. The reality was very much more messy and confused […] The different groups of incomers were never united, and fought each other, sometimes bitterly, as often as they fought the ‘Romans’ – just as the Roman side often gave civil strife priority over warfare against the invaders.35 When looked at in detail, the ‘Germanic invasions’ of the fifth century break down into a complex mosaic of different groups, some imperial, some local, and some Germanic, each jockeying for position against or in alliance with the others, with the Germanic groups eventually coming out on top. [As already mentioned, Heather is the book to read if you’re interested in these topics – US] […] Because the military position of the imperial government in the fifth century was weak, and because the Germanic invaders could be appeased, the Romans on occasion made treaties with particular groups, formally granting them territory on which to settle in return for their alliance. […] The interests of the centre when settling Germanic peoples, and those of the locals who had to live with the arrangements, certainly did not always coincide. […] The imperial government was entirely capable of selling its provincial subjects downriver, in the interests of short-term political and military gain. […] Sidonius Apollinaris, bishop of Clermont and a leader of the resistance to the Visigoths, recorded his bitterness: ‘We have been enslaved, as the price of other people’s security.41‘”

“[A]rchaeological evidence now available […] shows a startling decline in western standards of living during the fifth to seventh centuries.1 […] Ceramic vessels, of different shapes and sizes, play an essential part in the storage, preparation, cooking, and consumption of foodstuffs. They certainly did so in Roman times […] amphorae, not barrels, were the normal containers for transport and domestic storage of liquids. […] Pots are low-value, high-bulk items, with the additional disadvantage of being brittle […] and they are difficult and expensive to pack and transport, being heavy, bulky, and easy to break. If, despite these disadvantages, vessels (both fine tableware and more functional items) were being made to a high standard and in large quantities, and if they were travelling widely and percolating through even the lower levels of society – as they were in the Roman period – then it is much more likely than not that other goods, whose distribution we cannot document with the same confidence, were doing the same. […] There is, for instance, no reason to suppose that the huge markets in clothing, footware, and tools were less sophisticated than that in pottery. […] In the post-Roman West, almost all this material sophistication disappeared. Specialized production and all of the most local distribution became rare, unless for luxury goods; and the impressive range and quantity of high-quality functional goods, which had characterized the Roman period, vanished, or, at the very least, were drastically reduced. The middle and lower markets, which under the Romans had absorbed huge quantities of basic, but good-quality, items, seem to have almost entirely disappeared. […] There is no area of the post-Roman West that I know of where the range of pottery available in the sixth and seventh centuries matches that of the Roman period, and in most areas the decline in quality is startling. Furthermore, it was not only quality and diversity that declined; the overall quantities of pottery in circulation also fell dramatically. […] what had once been widely diffused products had become luxury items.”

“What we observe at the end of the Roman world is not a ‘recession’ […] with an essentially similar economy continuing to work at a reduced pace. Instead, what we see is a remarkable qualitative change, with the disappearance of entire industries and commercial networks. The economy of the post-Roman West is not that of the fourth century reduced in scale, but a very different and far less sophisticated entity.43 This is at its starkest and most obvious in Britain. A number of basic skills disappeared entirely during the fifth century, to be reintroduced only centuries later. […] All over Britain the art of making pottery on a wheel disappeared in the early fifth century, and was not reintroduced for almost 300 years. The potter’s wheel is not an instrument of cultural identity. Rather, it is a functional innovation that facilitates the rapid production of thin-walled ceramics; and yet it disappeared from Britain. […] post-Roman Britain in fact sank to a level of economic complexity well below that of the pre-Roman Iron Age. Southern Britain, in the years before the Roman conquest of AD 43, was importing quantities of Gaulish wine and Gaulish pottery; it had its own native pottery industries with regional distribution of their wares; it even had native silver coinages […] The settlement pattern of later iron-age Britain also reflects emerging economic complexity, with substantial coastal settlements […] which were at least partly dependent on trade. None of these features can be found reliably in fifth- and sixth-century post-Roman Britain. It is really only in about AD 700, three centuries after the disintegration of the Romano-British economy, that southern Britain crawled back to the level of economic complexity foudn in the pre-Roman Iron Age, with evidence of pots imported from the Continents, the first substantial and wheel-turned Anglo-Saxon pottery industry […], the striking of silver coins, and the emergence of coastal trading towns […] In the western Mediterranean, the economic regression was by no means as total as it was in Britain. […] But it must be remembered that in the Mediterranean world the level of economic complexity and sophistication reached in the Roman period was very considerably higher than anything ever attained in Britain. The fall in economic complexity may in fact have been as remarkable as that in Britain; but, since in the Mediterranean it started from a much higher point, it also bottomed out at a higher level. […] in some areas at least a very similar picture can be found to that sketched out above – of a regression, taking the economy way below levels of complexity reached in the pre-Roman period.”

“The enormity of the economic disintegration that occurred at the end of the empire was almost certainly a direct result of […] specialization. The post-Roman world reverted to levels of economic simplicity […] with little movement of goods, poor housing, and only the most basic manufactured items. The sophistication of the Roman period, by spreading high-quality goods widely in society, had destroyed the local skills and local networks that, in pre-Roman times, had provided lower-level economic complexity. It took centuries for people in the former empire to reacquire the skills and the regional networks that would take them back to these pre-Roman levels of sophistication. […] The Roman period is sometimes seen as enriching only the elite, rather than enhancing the standard of living of the population at large. […] I think this, and similar views, are mistaken. For, me, what is most striking about the Roman economy is precisely the fact that it was not solely an elite phenomenon, but one that made basic good-quality items available right down the social scale. […] good-quality pottery was widely available, and in regions like Italy even the comfort of tiled roofs. I would also seriously question the romantic assumption that economic simplicity meant a freer or more equal society.”

“There was no single moment, nor even a single century of collapse. The ancient economy disappeared at different times and at varying speeds across the empire. […] It was […] the fifth-century invasions that […] brought down the ancient economy in the West. However, this does not mean that the death of the sophisticated ancient world was intended by the Germanic peoples. The invaders entered the empire with a wish to share in its high standard of living, not to destroy it […] But, although the Germanic peoples did not intend it, their invasions, the disruptions these caused, and the consequent dismembering of the Roman state were undoubtedly the principal cause of death of the Roman economy.”

“Reading and writing (and a grounding in classical literature) were in Roman times an essential mark of status. […] illiterates amongst the Roman upper classes were very rare indeed. […] In a much simpler world, the urgent need to read and write declined, and with it went the social pressure on the secular elite to be literate. Widespread literacy in the post-Roman West definitely became confined to the clergy. […] It is a striking fact, and a major contrast with Roman times, that even great rulers could be illiterate in the early Middle Ages.”

“The changing perspectives of scholarship are always shaped in part by wider developments in modern society. There is inevitably a close connection between the way we view our own world and the way we interpret the past. […] [T]here is a real danger for the present day in a vision of the past that explicitly sets out to eliminate all crisis and all decline. The end of the Roman West […] destroyed a complex civilization, throwing the inhabitants of the West back to a standard of living typical of prehistoric times. Romans before the fall were as certain as we are today that their world would continue for ever substantially unchanged. They were wrong.”

 

September 18, 2017 Posted by | Archaeology, Books, History | Leave a comment

A few diabetes papers of interest

i. Glycated Hemoglobin and All-Cause and Cause-Specific Mortality in Singaporean Chinese Without Diagnosed Diabetes: The Singapore Chinese Health Study.

“Previous studies have reported that elevated levels of HbA1c below the diabetes threshold (<6.5%) are associated with an increased risk for cardiovascular morbidity and mortality (312). Yet, this research base is not comprehensive, and data from Chinese populations are scant, especially in those without diabetes. This gap in the literature is important since Southeast Asian populations are experiencing epidemic rates of type 2 diabetes and related comorbidities with a substantial global health impact (1316).

Overall, there are few cohort studies that have examined the etiologic association between HbA1c levels and all-cause and cause-specific mortality. There is even lesser insight on the nature of the relationship between HbA1c and significant clinical outcomes in Southeast Asian populations. Therefore, we examined the association between HbA1c and all-cause and cause-specific mortality in the Singapore Chinese Health Study (SCHS).”

“The design of the SCHS has been previously summarized (17). Briefly, the cohort was drawn from men and women, aged 45–74 years, who belonged to one of the major dialect groups (Hokkien or Cantonese) of Chinese in Singapore. […] Between April 1993 and December 1998, 63,257 individuals completed an in-person interview that included questions on usual diet, demographics, height and weight, use of tobacco, usual physical activity, menstrual and reproductive history (women only), medical history including history of diabetes diagnosis by a physician, and family history of cancer. […] At the follow-up interview (F1), which occurred in 1999–2004, subjects were asked to update their baseline interview information. […] The study population derived from 28,346 participants of the total 54,243 who were alive and participated at F1, who provided consent at F1 to collect subsequent blood samples (a consent rate of ∼65%). The participants for this study were a random selection of individuals from the full study population who did not report a history of diabetes or CVD at the baseline or follow-up interview and reported no history of cancer.”

“During 74,890 person-years of follow-up, there were 888 total deaths, of which 249 were due to CVD, 388 were due to cancer, and 169 were recorded as respiratory mortality. […] There was a positive association between HbA1c and age, BMI, and prevalence of self-reported hypertension, while an inverse association was observed between educational attainment and HbA1c. […] The crude mortality rate was 1,186 deaths per 100,000 person-years. The age- and sex-standardized mortality rates for all-cause, CVD, and cerebrovascular each showed a J-shaped pattern according to HbA1c level. The CHD and cancer mortality rates were higher for HbA1c ≥6.5% (≥48 mmol/mol) and otherwise displayed no apparent pattern. […] There was no association between any level of HbA1c and respiratory causes of death.”

“Chinese men and women with no history of cancer, reported diabetes, or CVD with an HbA1c level ≥6.5% (≥48 mmol/mol) were at a significant increased risk of mortality during follow-up relative to their peers with an HbA1c of 5.4–5.6% (36–38 mmol/mol). No other range of HbA1c was significantly associated with risk of mortality during follow-up, and in secondary analyses, when the HbA1c level ≥6.5% (≥48 mmol/mol) was divided into four categories, this increased risk was observed in all four categories; thus, these data represent a clear threshold association between HbA1c and mortality in this population. These results are consistent with previous prospective cohort studies identifying chronically high HbA1c, outside of diabetes, to be associated with increased risk for all-cause and CVD-related mortality (312,22).”

“Hyperglycemia is a known risk factor for CVD, not limited to individuals with diabetes. This may be in part due to the vascular damage caused by oxidative stress in periods of hypo- and hyperglycemia (23,24). For individuals with impaired fasting glucose and impaired glucose tolerance, increased oxidative stress and endothelial dysfunction are present before the onset of diabetes (25). The association between chronically high levels of HbA1c and development of and death from cancer is not as well defined (9,2630). Abnormal metabolism may play a role in cancer development and death. This is important, considering cancer is the leading cause of death in Singapore for adults 15–59 years of age (31). Increased risk for cancer mortality was found in individuals with impaired glucose tolerance (30). […] Hyperinsulinemia and IGF-I are associated with increased cancer risk, possibly through mitogenic effects and tumor formation (27,28,37). This is the basis for the insulin-cancer hypothesis. Simply put, chronic levels of hyperinsulinemia reduce the production of IGF binding proteins 1 and 2. The absence of these proteins results in excess bioactive IGF-I, supporting tumor development (38). Chronic hyperglycemia, indicating high levels of insulin and IGF-I, may explain inhibition of cell apoptosis, increased cell proliferation, and increased cancer risk (39).”

ii. The Cross-sectional and Longitudinal Associations of Diabetic Retinopathy With Cognitive Function and Brain MRI Findings: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial.

“Brain imaging studies suggest that type 2 diabetes–related microvascular disease may affect the central nervous system in addition to its effects on other organs, such as the eye and kidney. Histopathological evidence indicates that microvascular disease in the brain can lead to white matter lesions (WMLs) visible with MRI of the brain (1), and risk for them is often increased by type 2 diabetes (26). Type 2 diabetes also has recently been associated with lower brain volume, particularly gray matter volume (79).

The association between diabetic retinopathy and changes in brain tissue is of particular interest because retinal and cerebral small vessels have similar anatomy, physiology, and embryology (10). […] the preponderance of evidence suggests diabetic retinopathy is associated with increased WML burden (3,1214), although variation exists. While cross-sectional studies support a correlation between diabetic retinopathy and WMLs (2,3,6,15), diabetic retinopathy and brain atrophy (16), diabetic retinopathy and psychomotor speed (17,18), and psychomotor speed and WMLs (5,19,20), longitudinal evidence demonstrating the assumed sequence of disease development, for example, vascular damage of eye and brain followed by cognitive decline, is lacking.

Using Action to Control Cardiovascular Risk in Diabetes (ACCORD) data, in which a subset of participants received longitudinal measurements of diabetic retinopathy, cognition, and MRI variables, we analyzed the 1) cross-sectional associations between diabetic retinopathy and evidence of brain microvascular disease and 2) determined whether baseline presence or severity of diabetic retinopathy predicts 20- or 40-month changes in cognitive performance or brain microvascular disease.”

“The ACCORD trial (21) was a multicenter randomized trial examining the effects of intensive glycemic control, blood pressure, and lipids on cardiovascular disease events. The 10,251 ACCORD participants were aged 40–79 years, had poorly controlled type 2 diabetes (HbA1c > 7.5% [58.5 mmol/mol]), and had or were at high risk for cardiovascular disease. […] The ACCORD-Eye sample comprised 3,472 participants who did not report previous vitrectomy or photocoagulation surgery for proliferative diabetic retinopathy at baseline […] ACCORD-MIND included a subset of 2,977 ACCORD participants who completed a 30-min cognitive testing battery, 614 of whom also had useable scans from the MRI substudy (23,24). […] ACCORD-MIND had visits at three time points: baseline, 20 months, and 40 months. MRI of the brain was completed at baseline and the 40-month time point.”

“Baseline diabetic retinopathy was associated with more rapid 40-month declines in DSST and MMSE [Mini-Mental State Examination] when adjusting for demographics and lifestyle factors in model 1 […]. Moreover, increasing severity of diabetic retinopathy was associated with increased amounts of decline in DSST [Digit Symbol Substitution Test] performance (−1.30, −1.76, and −2.81 for no, mild, and moderate/severe NPDR, respectively; P = 0.003) […Be careful about how to interpret that p-value – see below, US] . The associations remained virtually unchanged after further adjusting for vascular and diabetes risk factors, depression, and visual acuity using model 2.”

“This longitudinal study provides new evidence that diabetic retinopathy is associated with future cognitive decline in persons with type 2 diabetes and confirms the finding from the Edinburgh Type 2 Diabetes Study derived from cross-sectional data that lifetime cognitive decline is associated with diabetic retinopathy (32). We found that the presence of diabetic retinopathy, independent of visual acuity, predicts greater declines in global cognitive function measured with the MMSE and that the magnitude of decline in processing speed measured with the DSST increased with increasing severity of baseline diabetic retinopathy. The association with psychomotor speed is consistent with prior cross-sectional findings in community-based samples of middle-aged (18) and older adults (17), as well as prospective studies of a community-based sample of middle-aged adults (33) and patients with type 1 diabetes (34) showing that retinopathy with different etiologies predicted a subsequent decline in psychomotor speed. This study extends these findings to patients with type 2 diabetes.”

“we tested a number of different associations but did not correct P values for multiple testing” [Aargh!, US.]

iii. Incidence of Remission in Adults With Type 2 Diabetes: The Diabetes & Aging Study.

(Note to self before moving on to the paper: these people identified type 1 diabetes by self-report or diabetes onset at <30 years of age, treated with insulin only and never treated with oral agents).

“It is widely believed that type 2 diabetes is a chronic progressive condition, which at best can be controlled, but never cured (1), and that once treatment with glucose-lowering medication is initiated, it is required indefinitely and is intensified over time (2,3). However, a growing body of evidence from clinical trials and case-control studies (46) has reported the remission of type 2 diabetes in certain populations, most notably individuals who received bariatric surgery. […] Despite the clinical relevance and importance of remission, little is known about the incidence of remission in community settings (11,12). Studies to date have focused largely on remission after gastric bypass or relied on data from clinical trials, which have limited generalizability. Therefore, we conducted a retrospective cohort study to describe the incidence rates and variables associated with remission among adults with type 2 diabetes who received usual care, excluding bariatric surgery, in a large, ethnically diverse population. […] 122,781 individuals met our study criteria, yielding 709,005 person-years of total follow-up time.”

“Our definitions of remission were based on the 2009 ADA consensus statement (10). “Partial remission” of diabetes was defined as having two or more consecutive subdiabetic HbA1c measurements, all of which were in the range of 5.7–6.4% [39–46 mmol/mol] over a period of at least 12 months. “Complete remission” was defined as having two or more consecutive normoglycemic HbA1c measurements, all of which were <5.7% [<39 mmol/mol] over a period of at least 12 months. “Prolonged remission” was defined as having two or more consecutive normoglycemic HbA1c measurements, all of which were <5.7% [<39 mmol/mol] over a period of at least 60 months. Each definition of remission requires the absence of pharmacologic treatment during the defined observation period.”

“The average age of participants was 62 years, 47.1% were female, and 51.6% were nonwhite […]. The mean (SD) interval between HbA1c tests in the remission group was 256 days (139 days). The mean interval (SD) between HbA1c tests among patients not in the remission group was 212 days (118 days). The median time since the diagnosis of diabetes in our cohort was 5.9 years, and the average baseline HbA1c level was 7.4% [57 mmol/mol]. The 18,684 individuals (15.2%) in the subset with new-onset diabetes, defined as ≤2 years since diagnosis, were younger, were more likely to have their diabetes controlled by diet, and had fewer comorbidities […] The incidence densities of partial, complete, and prolonged remission in the full cohort were 2.8 (95% CI 2.6–2.9), 0.24 (95% CI 0.20–0.28), and 0.04 (95% CI 0.01–0.06) cases per 1,000 person-years, respectively […] The 7-year cumulative incidences of partial, complete, and prolonged remission were 1.5% (95% CI 1.4–1.5%), 0.14% (95% CI 0.12–0.16%), and 0.01% (95% CI 0.003–0.02%), respectively. The 7-year cumulative incidence of any remission decreased with longer time since diagnosis from a high of 4.6% (95% CI 4.3–4.9%) for individuals diagnosed with diabetes in the past 2 years to a low of 0.4% (95% CI 0.3–0.5%) in those diagnosed >10 years ago. The 7-year cumulative incidence of any remission was much lower for individuals using insulin (0.05%; 95% CI 0.03–0.1%) or oral agents (0.3%; 95% CI 0.2–0.3%) at baseline compared with diabetes patients not using medication at baseline (12%; 95% CI 12–13%).”

“In this large cohort of insured adults with type 2 diabetes not treated with bariatric surgery, we found that 1.5% of individuals with recent evidence of clinical diabetes achieved at least partial remission over a 7-year period. If these results were generalized to the 25.6 million U.S. adults living with type 2 diabetes in 2010 (25), they would suggest that 384,000 adults could experience remission over the next 7 years. However, the rate of prolonged remission was extremely rare (0.007%), translating into only 1,800 adults in the U.S. experiencing remission lasting at least 5 years. To provide context, 1.7% of the cohort died, while only 0.8% experienced any level of remission, during the calendar year 2006. Thus, the chances of dying were higher than the chances of any remission. […] Although remission of type 2 diabetes is uncommon, it does occur in patients who have not undergone surgical interventions. […] Our analysis shows that remission is rare and variable. The likelihood of remission is more common among individuals with early-onset diabetes and those not treated with glucose-lowering medications at the point of diabetes diagnosis. Although rare, remission can also occur in individuals with more severe diabetes and those previously treated with insulin.”

iv. Blood pressure control for diabetic retinopathy (Cochrane review).

“Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Simultaneous blood pressure control has been advocated for the same purpose, but findings reported from individual studies have supported varying conclusions regarding the ocular benefit of interventions on blood pressure. […] The primary aim of this review was to summarize the existing evidence regarding the effect of interventions to control or reduce blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs. A secondary aim was to compare classes of anti-hypertensive medications with respect to the same outcomes.”

“We included 15 RCTs, conducted primarily in North America and Europe, that had enrolled 4157 type 1 and 9512 type 2 diabetic participants, ranging from 16 to 2130 participants in individual trials. […] Study designs, populations, interventions, and lengths of follow-up (range one to nine years) varied among the included trials. Overall, the quality of the evidence for individual outcomes was low to moderate.”

“The evidence from these trials supported a benefit of more intensive blood pressure control intervention with respect to 4- to 5-year incidence of diabetic retinopathy (estimated risk ratio (RR) 0.80; 95% confidence interval (CI) 0.71 to 0.92) and the combined outcome of incidence and progression (estimated RR 0.78; 95% CI 0.63 to 0.97). The available evidence provided less support for a benefit with respect to 4- to 5-year progression of diabetic retinopathy (point estimate was closer to 1 than point estimates for incidence and combined incidence and progression, and the CI overlapped 1; estimated RR 0.88; 95% CI 0.73 to 1.05). The available evidence regarding progression to proliferative diabetic retinopathy or clinically significant macular edema or moderate to severe loss of best-corrected visual acuity did not support a benefit of intervention on blood pressure: estimated RRs and 95% CIs 0.95 (0.83 to 1.09) and 1.06 (0.85 to 1.33), respectively, after 4 to 5 years of follow-up. Findings within subgroups of trial participants (type 1 and type 2 diabetics; participants with normal blood pressure levels at baseline and those with elevated levels) were similar to overall findings.”

“The available evidence supports a beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to 4 to 5 years. However, the lack of evidence to support such intervention to slow progression of diabetic retinopathy or to prevent other outcomes considered in this review, along with the relatively modest support for the beneficial effect on incidence, weakens the conclusion regarding an overall benefit of intervening on blood pressure solely to prevent diabetic retinopathy.”

v. Early Atherosclerosis Relates to Urinary Albumin Excretion and Cardiovascular Risk Factors in Adolescents With Type 1 Diabetes: Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT).

“Children with type 1 diabetes are at greatly increased risk for the development of both renal and cardiovascular disease in later life (1,2). Evidence is accumulating that these two complications may have a common pathophysiology, with endothelial dysfunction a key early event.

Microalbuminuria is a recognized marker of endothelial damage (3) and predicts progression to proteinuria and diabetic nephropathy, as well as to atherosclerosis (4) and increased cardiovascular risk (5). It is, however, rare in adolescents with type 1 diabetes who more often have higher urinary albumin excretion rates within the normal range, which are associated with later progression to microalbuminuria and proteinuria (6).”

“The Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT) (10) is designed to examine the impact of minor differences in albumin excretion in adolescents on the initiation and progression of cardiovascular and renal disease. The primary cardiovascular end point in AdDIT is carotid intima-media thickness (cIMT). Subclinical atherosclerosis can be detected noninvasively using high-resolution ultrasound to measure the intima-media thickness (IMT) of the carotid arteries, which predicts cardiovascular morbidity and mortality (11,12). […] The primary aim of this study was to examine the relationship of increased urinary albumin excretion and cardiovascular risk factors in adolescents with type 1 diabetes with structural arterial wall changes. We hypothesized that even minor increases in albumin excretion would be associated with early atherosclerosis but that this would be detectable only in the abdominal aorta. […] A total of 406 adolescents, aged 10–16 years, with type 1 diabetes for more than 1 year, recruited in five centers across Australia, were enrolled in this cross-sectional study”.

“Structural changes in the aorta and carotid arteries could be detected in >50% of adolescents with type 1 diabetes […] The difference in aIMT [aortic intima-media thickness] between type 1 diabetic patients and age- and sex-matched control subjects was equivalent to that seen with a 5- to 6-year age increase in the type 1 diabetic patients. […] Aortic IMT was […] able to better differentiate adolescents with type 1 diabetes from control subjects than was carotid wall changes. Aortic IMT enabled detection of the very early wall changes that are present with even small differences in urinary albumin excretion. This not only supports the concept of early intervention but provides a link between renal and cardiovascular disease.

The independent relationship between aIMT and urinary albumin excretion extends our knowledge of the pathogenesis of cardiovascular and renal disease in type 1 diabetes by showing that the first signs of the development of cardiovascular disease and diabetic nephropathy are related. The concept that microalbuminuria is a marker of a generalized endothelial damage, as well as a marker of renal disease, has been recognized for >20 years (3,20,21). Endothelial dysfunction is the first critical step in the development of atherosclerosis (22). Early rises in urinary albumin excretion precede the development of microalbuminuria and proteinuria (23). It follows that the first structural changes of atherosclerosis could relate to the first biochemical changes of diabetic nephropathy. To our knowledge, this is the first study to provide evidence of this.”

“In conclusion, atherosclerosis is detectable from early adolescence in type 1 diabetes. Its early independent associations are male sex, age, systolic blood pressure, LDL cholesterol, and, importantly, urinary albumin excretion. […] Early rises in urinary albumin excretion during adolescence not only are important for determining risk of progression to microalbuminuria and diabetic nephropathy but also may alert the clinician to increased risk of cardiovascular disease.”

vi. Impact of Islet Autoimmunity on the Progressive β-Cell Functional Decline in Type 2 Diabetes.

“Historically, type 2 diabetes (T2D) has not been considered to be immune mediated. However, many notable discoveries in recent years have provided evidence to support the concept of immune system involvement in T2D pathophysiology (15). Immune cells have been identified in the pancreases of phenotypic T2D patients (35). Moreover, treatment with interleukin-1 receptor agonist improves β-cell function in T2D patients (68). These studies suggest that β-cell damage/destruction mediated by the immune system may be a component of T2D pathophysiology.

Although the β-cell damage and destruction in autoimmune diabetes is most likely T-cell mediated (T), immune markers of autoimmune diabetes have primarily centered on the presence of circulating autoantibodies (Abs) to various islet antigens (915). Abs commonly positive in type 1 diabetes (T1D), especially GAD antibody (GADA) and islet cell Abs (ICA), have been shown to be more common in patients with T2D than in nondiabetic control populations, and the presence of multiple islet Abs, such as GADA, ICA, and tyrosine phosphatase-2 (insulinoma-associated protein 2 [IA-2]), have been demonstrated to be associated with an earlier need for insulin treatment in adult T2D patients (14,1620).”

“In this study, we observed development of islet autoimmunity, measured by islet Abs and islet-specific T-cell responses, in 61% of the phenotypic T2D patients. We also observed a significant association between positive islet-reactive T-cell responses and a more rapid decline in β-cell function as assessed by FCP and glucagon-SCP responses. […] The results of this pilot study led us to hypothesize that islet autoimmunity is present or will develop in a large portion of phenotypic T2D patients and that the development of islet autoimmunity is associated with a more rapid decline in β-cell function. Moreover, the prevalence of islet autoimmunity in most previous studies is grossly underestimated because these studies have not tested for islet-reactive T cells in T2D patients but have based the presence of autoimmunity on antibody testing alone […] The results of this pilot study suggest important changes to our understanding of T2D pathogenesis by demonstrating that the prevalence of islet autoimmune development is not only more prevalent in T2D patients than previously estimated but may also play an important role in β-cell dysfunction in the T2D disease process.”

September 18, 2017 Posted by | Cancer/oncology, Cardiology, Diabetes, Epidemiology, Immunology, Medicine, Nephrology, Neurology, Ophthalmology, Studies | Leave a comment

Ophthalmology – National EM Board Review Course

The lecture covers a lot of different stuff. Some links:

Blepharitis.
Dacryocystitis.
Dacryoadenitis.
Chalazion.
Orbital Cellulitis.
Cranial Nerves III, IV, and VI: The Oculomotor System.
Argyll Robertson pupil.
Marcus Gunn pupil.
Horner syndrome.
Third nerve palsy.
Homonymous hemianopsia.
Central Retinal Artery Occlusion.
Central Retinal Vein Occlusion.
Optic Neuritis.
Retinal detachment.
Temporal Arteritis.
Conjunctivitis.
Epidemic Keratoconjunctivitis (EKC).
Uveitis.
Hypopyon.
Keratitis.
Herpes Zoster Ophthalmicus.
Subconjunctival Hemorrhage.
Corneal Abrasion.
Corneal Laceration.
Globe Rupture.
Acute Angle-Closure Glaucoma.
Hyphema.
Endophthalmitis.
Retrobulbar hemorrhage.

September 15, 2017 Posted by | Lectures, Medicine, Ophthalmology, Pharmacology | Leave a comment

Quotes

i. “I’m opposed to any sport that reduces the coefficient of friction between me and the ground.” (Alan Kotok)

ii. “If God wanted us to believe in him, he’d exist.” (Linda Smith)

iii. “[A] man who contradicts himself may have succeeded in exercising his vocal chords. But from the point of view of imparting information, of communicating facts (or falsehoods) it is as if he had never opened his mouth. He utters words, but does not say anything.” (P. F. Strawson)

iv. “What is very important to me is two points: A theory should be internally consistent and it should have some contact with observation. Well, I’m told by all the experts that this theory [String theory] is internally consistent, although they think up new interpretations every time I turn my back. But contact with reality? Nobody’s given me anything. I just watch. I’m somewhat unhappy that so many people are working on it. To me, as a physicist, it’s sort of sad that so many people at the same time work at something that doesn’t seem to have any contact with experiment.” (Valentine Telegdi)

v. “By definition, the conventional wisdom of the day is widely accepted, continually reiterated and regarded not as ideology but as reality itself. Rebelling against “reality,” even when its limitations are clearly perceived, is always difficult. It means deciding things can be different and ought to be different; that your own perceptions are right and the experts and authorities wrong; that your discontent is legitimate and not merely evidence of selfishness, failure or refusal to grow up. […] rebels risk losing their jobs, failing in school, incurring the wrath of parents and spouses, suffering social ostracism. Often vociferous conservatism is sheer defensiveness: People are afraid to be suckers, […] to be branded bad or crazy.” (Ellen Willis)

vi. “If you want truth, you should begin by giving it.” (Lloyd Alexander)

vii. “All the greatest blessings are a source of anxiety, and at no time is fortune less wisely trusted than when it is best” (Seneca the Younger, On the shortness of life)

viii. “Killing oneself is, anyway, a misnomer. We don’t kill ourselves. We are simply defeated by the long, hard struggle to stay alive. When somebody dies after a long illness, people are apt to say, with a note of approval, “He fought so hard.” And they are inclined to think, about a suicide, that no fight was involved, that somebody simply gave up. This is quite wrong.” (Sally Brampton)

ix. “…to make the mistakes of youth is no crime, but not to learn from them is.” (Jim Butcher, Summer Knight)

x. “…a guest is a jewel on the cushion of hospitality” (Rex Stout, A right to die)

xi. ““Mr. Wolfe is in the middle of a fit. It’s complicated. There’s a fireplace in the front room, but it’s never lit because he hates open fires. He says they stultify mental processes. But it’s lit now because he’s using it. He’s seated in front of it, on a chair too small for him, tearing sheets out of a book and burning them. The book is the new edition, the third edition, of Webster’s New International Dictionary, Unabridged, published by the G. & C. Merriam Company of Springfield, Massachusetts. He considers it subversive because it threatens the integrity of the English language. In the past week he has given me a thousand examples of its crimes. He says it is a deliberate attempt to murder the— I beg your pardon. I describe the situation at length because he told me to bring you in there, and it will be bad. Even if he hears what you say, his mental processes are stultified. Could you come back later? After lunch he may be human.”
She was staring up at me. “He’s burning up a dictionary?”
“Right. That’s nothing. Once he burned up a cookbook because it said to remove the hide from a ham end before putting it in the pot with lima beans.” (Rex Stout, Gambit)

xii. “A friend in need is a friend to be avoided.” (David Gemmell)

xiii. “Virtually all ideologues, of any variety, are fearful and insecure, which is why they are drawn to ideologies that promise prefabricated answers for all circumstances.” (Jane Jacobs)

xiv. “To science, not even the bark of a tree or a drop of pond water is dull or a handful of dirt banal. They all arouse awe and wonder.” (-ll-)

xv. “Hydrogen is a light, odorless gas, which, given enough time, turns into people.” (Edward Robert Harrison)

xvi. “There is an obesity epidemic. One out of every three Americans… weighs as much as the other two.” (Richard Jeni)

xvii. “We learn, when we learn, only from experience, and then we only learn from our mistakes. Our successes only serve to reinforce our superstitions.” (Arthur Jones)

xviii. “How old am I? Old enough to know it’s impossible to change the thinking of fools, but young and foolish enough to keep on trying.” (-ll-)

xix. “There is no greater impotence in all the world like knowing you are right and that the wave of the world is wrong, yet the wave crashes upon you.” (Norman Mailer)

xx. “We never have any understanding of any subject matter except in terms of our own mental constructs of “things” and “happenings” of that subject matter.” (Douglas T. Ross)

September 14, 2017 Posted by | Books, Quotes/aphorisms | Leave a comment

Sound

I gave the book two stars. As I was writing this post I was actually reconsidering, thinking about whether that was too harsh, whether the book deserved a third star. When I started out reading it I was assuming it would be a ‘physics book’ (I found it via browsing a list of physics books, so…), but that quickly turned out to be a mistaken assumption. There’s stuff about wave mechanics in there, sure, but this book also includes stuff about anatomy (a semi-detailed coverage of how the ear works), how musical instruments work, how bats use echolocation to find insects, and how animals who live underwater hear differently from the way we hear things. This book is really ‘all over the place’, which was probably part of why I didn’t like it as much as I might otherwise have. Lots of interesting stuff included, though – I learned quite a bit from this book.

I’ve added some quotes from the book below, and below the quotes I’ve added some links to stuff/concepts/etc. covered in the book.

“Decibels aren’t units — they are ratios […] To describe the sound of a device in decibels, it is vital to know what you are comparing it with. For airborne sound, the comparison is with a sound that is just hearable (corresponding to a pressure of twenty micropascals). […] Ultrasound engineers don’t care how much ‘louder than you can just about hear’ their ultrasound is, because no one can hear it in the first place. It’s power they like, and it’s watts they measure it in. […] Few of us care how much sound an object produces — what we want to know is how loud it will sound. And that depends on how far away the thing is. This may seem obvious, but it means that we can’t ever say that the SPL [sound pressure level] of a car horn is 90 dB, only that it has that value at some stated distance.”

“For an echo to be an echo, it must be heard more than about 1/ 20 of a second after the sound itself. If heard before that, the ear responds as if to a single, louder, sound. Thus 1/ 20 second is the auditory equivalent to the 1/ 5 of a second that our eyes need to see a changing thing as two separate images. […] Since airborne sounds travel about 10 metres in 1/ 20 second, rooms larger than this (in any dimension) are echo chambers waiting to happen.”

“Being able to hear is unremarkable: powerful sounds shake the body and can be detected even by single-celled organisms. But being able to hear as well as we do is little short of miraculous: we can quite easily detect a sound which delivers a power of 10−15 watts to the eardrums, despite the fact that it moves them only a fraction of the width of a hydrogen atom. Almost as impressive is the range of sound powers we can hear. The gap between the quietest audible sound level (the threshold of hearing, 0 dB) to the threshold of pain (around 130 dB) is huge: 130 dB is 1013 […] We can also hear a fairly wide range of frequencies; about ten octaves, a couple more than a piano keyboard. […] Our judgement of directionality, by contrast, is mediocre; even in favourable conditions we can only determine the direction of a sound’s source within about 10° horizontally or 20° vertically; many other animals can do very much better. […] Perhaps the most impressive of all our hearing abilities is that we can understand words whose levels are less than 10 per cent of that of background noise level (if that background is a broad spread of frequencies): this far surpasses any machine.”

“The nerve signals that emerge from the basilar membrane are not mimics of sound waves, but coded messages which contain three pieces of information: (a) how many nerve fibres are signalling at once, (b) how far along the basilar membrane those fibres are, and (c) how long the interval is between bursts of fibre signals. The brain extracts loudness information from a combination of (a) and (c), and pitch information from (b) and (c). […] The hearing system is a delicate one, and severe damage to the eardrums or ossicles is not uncommon. […] This condition is called conductive hearing loss. If damage to the inner ear or auditory nerve occurs, the result is sensorineural or ‘nerve’ hearing loss. It mostly affects higher frequencies and quieter sounds; in mild forms, it gives rise to a condition called recruitment, in which there is a sudden jump in the ‘hearability’ of sounds. A person suffering from recruitment and exposed to a sound of gradually increasing level can at first detect nothing and then suddenly hears the sound, which seems particularly loud. Hence the ‘there’s no need to shout’ protest in response to those who raise their voices just a little to make themselves heard on a second attempt. Sensorineural hearing loss is the commonest type, and its commonest cause is physical damage inflicted on the hair cells. […] About 360 million people worldwide (over 5 per cent of the global population) have ‘disabling’ hearing loss — that is, hearing loss greater than 40 dB in the better-hearing ear in adults and a hearing loss greater than 30 dB in the better-hearing ear in children […]. About one in three people over the age of sixty-five suffer from such hearing loss. […] [E]veryone’s ability to hear high-frequency sounds declines with age: newborn, we can hear up to 20 kHz, by the age of about forty this has fallen to around 16 kHz, and to 10 kHz by age sixty. Aged eighty, most of us are deaf to sounds above 8 kHz. The effect is called presbyacusis”.

“The acoustic reflex is one cause of temporary threshold shift (TTS), in which sounds which are usually quiet become inaudible. Unfortunately, the time the reflex takes to work […] is usually around 45 milliseconds, which is far longer than it takes an impulse sound, like a gunshot or explosion, to do considerable damage. […] Where the overburdened ear differs from other abused measuring instruments (biological and technological) is that it is not only the SPL of noise that matters: energy counts too. A noise at a level which would cause no more than irritation if listened to for a second can lead to significant hearing loss if it continues for an hour. The amount of TTS is proportional to the logarithm of the time for which the noise has been present — that is, doubling the exposure time more than doubles the amount. […] The amount of TTS reduces considerably if there is a pause in the noise, so if exposure to noise for long periods is unavoidable […], there is very significant benefit in removing oneself from the noisy area, if only for fifteen minutes.”

“Many highly effective technological solutions to noise have been developed. […] The first principle of noise control is to identify the source and remove it. […] Having dealt as far as possible with the noise source, the next step is to contain it. […] When noise can be neither avoided not contained, the next step is to keep its sources well separated from potential sufferers. One approach, used for thousands of years, is zoning: legislating for the restriction of noisy activities to particular areas, such as industrial zones, which are distant from residential districts. […] Where zone separation by distance is impracticable […], sound barriers are the main solution: a barrier that just cuts off the sight of a noise source will reduce the noise level by about 5 dB, and each additional metre will provide about an extra 1.5 dB reduction. […] Since barriers largely reflect rather than absorb, reflected sounds need consideration, but otherwise design and construction are simple, results are predictable, and costs are relatively low.”

“[T]he basic approaches to home sound reduction are simple: stop noise entering, destroy what does get in, and don’t add more to it yourself. There are three ways for sound to enter: via openings; by structure-borne vibration; and through walls, windows, doors, ceilings, and floors acting as diaphragms. In all three cases, the main point to bear in mind is that an acoustic shell is only as good as its weakest part: just as even a small hole in an otherwise watertight ship’s hull renders the rest useless, so does a single open window in a double-glazed house. In fact, the situation with noise is much worse than with water due to the logarithmic response of our ears: if we seal one of two identical holes in a boat we will halve the inflow. If we close one of two identical windows into a house, […] that 50 per cent reduction in acoustic intensity is only about a 2 per cent reduction in loudness. The second way to keep noise out is double glazing, since single-glazed windows make excellent diaphragms. Structure-borne sound is a much greater challenge […] One inexpensive, adaptable, and effective solution […] is the hanging of heavy velour drapes, with as many folds as possible. If something more drastic is required, it is vital to involve an expert: while an obvious solution is to thicken walls, it’s important to bear in mind that doubling thickness reduces transmission loss by only 6 dB (a sound power reduction of about three-quarters, but a loudness reduction of only about 40 per cent). This means that solid walls need to be very thick to work well. A far better approach is the use of porous absorbers and of multi-layer constructions. In a porous absorber like glass fibre, higher-frequency sound waves are lost through multiple reflections from the many internal surfaces. […] A well-fitted acoustically insulated door is also vital. The floor should not be neglected: even if there are no rooms beneath, hard floors are excellent both at generating noise when walked on and in transmitting that noise throughout the building. Carpet and underlay are highly effective at high frequencies but are almost useless at lower ones […] again there is no real alternative to bringing in an expert.”

“There are two reasons for the apparent silence of the sea: one physical, the other biological. The physical one is the impedance mismatch between air and water, in consequence of which the surface acts as an acoustic mirror, reflecting back almost all sound from below, so that land-dwellers hear no more than the breaking of the waves. […] underwater, the eardrum has water on one side and air on the other, and so impedance mismatching once more prevents most sound from entering. If we had no eardrums (nor air-filled middle ears) we would probably hear very well underwater. Underwater animals don’t need such complicated ears as ours: since the water around them is a similar density to their flesh, sound enters and passes through their whole bodies easily […] because the velocity of sound is about five times greater in water than in air, the wavelength corresponding to a particular frequency is also about five times greater than its airborne equivalent, so directionality is harder to come by.”

“Although there is little that electromagnetic radiation does above water that sound cannot do below it, sound has one unavoidable disadvantage: its velocity in water is much lower than that of electromagnetic radiation in air […]. Also, when waves are used to send data, the rate of that data transmission is directly proportional to the wave frequency — and audio sound waves are around 1,000 times lower in frequency than radio waves. For this reason ultrasound is used instead, since its frequencies can match those of radio waves. Another advantage is that it is easier to produce directional beams at ultrasonic frequencies to send the signal in only the direction you want. […] The distances over which sound can travel underwater are amazing. […] sound waves are absorbed far less in water than in air. At 1 kHz, absorption is about 5 dB/ km in air (at 30 per cent humidity) but only 0.06 dB/ km in seawater. Also, underwater sound waves are much more confined; a noise made in mid-air spreads in all directions, but in the sea the bed and the surface limit vertical spreading. […] The range of sound velocities underwater is [also] far larger than in air, because of the enormous variations in density, which is affected by temperature, pressure, and salinity […] somewhere under all oceans there is a layer at which sound velocity is low, sandwiched between regions in which it is higher. By refraction, sound waves from both above and below are diverted towards the region of minimum sound velocity, and are trapped there. This is the deep sound channel, a thin spherical shell extending through the world’s oceans. Since sound waves in the deep sound channel can move only horizontally, their intensity falls in proportion only to the distance they travel, rather than to the square of the distance, as they would in air or in water at a single temperature (in other words, they spread out in circles, not spheres). Sound absorption in the deep sound channel is very low […] and sound waves in the deep channel can readily circumnavigate the Earth.”

Links:

Sound.
Neuromast.
Monochord.
Echo.
Pierre-Simon Laplace.
Sonar.
Foley.
Long Range Acoustic Device.
Physics of sound.
Speed of sound.
Shock wave.
Doppler effect.
Acoustic mirror.
Acoustic impedance.
Snell’s law.
Diffraction grating.
Interference (wave propagation).
Acousto-optic effect.
Sound pressure.
Sound intensity.
Square-cube law.
Decibel.
Ultrasound.
Sound level meter.
Phon.
Standing wave.
Harmonic.
Resonance.
Helmholtz resonance.
Phonautograph.
Spectrogram.
Fourier series/Fourier transform/Fast Fourier transform.
Equalization (audio).
Absolute pitch.
Consonance and dissonance.
Pentatonic scale.
Major and minor.
Polyphony.
Rhytm.
Pitched percussion instrument/Unpitched percussion instrument.
Hearing.
Ear/pinna/tympanic membrane/Eustachian tube/Middle ear/Inner ear/Cochlea/Organ of Corti.
Otoacoustic emission.
Broca’s area/primary auditory cortex/Wernicke’s area/Haas effect.
Conductive hearing loss/Sensorineural hearing loss.
Microphone/Carbon microphone/Electret microphone/Ribbon microphone.
Piezoelectric effect.
Loudspeaker.
Missing fundamental.
Huffman coding.
Animal echolocation.
Phonon.
Infrasound.
Hydrophone.
Deep sound channel.
Tonpilz.
Stokes’ law of sound attenuation.
Noise.
Acoustic reflex.
Temporary threshold shift.
Active noise cancellation.
Sabine equation.

September 14, 2017 Posted by | Books, Physics | Leave a comment

Words

Most of the words below are words which I encountered while reading the Rex Stout books: Too Many Clients, The Final Deduction, Homicide Trinity, Gambit, The Mother Hunt, Trio for Blunt Instruments, A Right to Die, The Doorbell Rang, Death of a Doxy, The Father Hunt, Death of a Dude, Please Pass the Guilt, A Family Affair, Death Times Three, and Red Threads.

Commissure. Nonfeasance. Bodice. Binnacle. Episiotomy. Amplexus. Bayou. Jetty. Crisper. Conurbation. Splotch. Tarradiddle. Lamia. Prink/primp. Thaumaturgy/thaumaturge. Allspice. Panjandrum. Subdulous. Overweening. Perspicacity.

Jejune. Hamper. Cloche. Ulster. Bevel. Auto-da-fé. Buckram. Peccant. Fatuity. Dissension. Chipper. Analeptic. Cluck. Moll. Posy. Peeve. Wrangle. Chervil. Wile. Vim.

Huffy. Callow. Crabby. Locution. Scrapple. Jamb. Cockatrice. Wink. Spatter. Sororicide. Discomfiture. Diphthong. Twaddle. Rassle. Headcheese. Flimflam. Brioche. Doxy. Mooch. Incumbency.

Cogitable. Punctilio. Mantic. Frowzy. Burgoo. Boodle. Toplofty. Ell. Slue. Fulcrum. Piffle. Amphigoric. Subreption. Cynosure. ConcupiscenceCarceral. Descant. Pretermit. Hickory. Ingénue.

September 13, 2017 Posted by | Books, Language | Leave a comment

A few diabetes papers of interest

i. Impact of Parental Socioeconomic Status on Excess Mortality in a Population-Based Cohort of Subjects With Childhood-Onset Type 1 Diabetes.

“Numerous reports have shown that individuals with lower SES during childhood have increased morbidity and all-cause mortality at all ages (10–14). Although recent epidemiological studies have shown that all-cause mortality in patients with T1D increases with lower SES in the individuals themselves (15,16), the association between parental SES and mortality among patients with childhood-onset T1D has not been reported to the best of our knowledge. Our hypothesis was that low parental SES additionally increases mortality in subjects with childhood-onset T1D. In this study, we used large population-based Swedish databases to 1) explore in a population-based study how parental SES affects mortality in a patient with childhood-onset T1D, 2) describe and compare how the effect differs among various age-at-death strata, and 3) assess whether the adult patient’s own SES affects mortality independently of parental SES.”

“The Swedish Childhood Diabetes Registry (SCDR) is a dynamic population-based cohort reporting incident cases of T1D since 1 July 1977, which to date has collected >16,000 prospective cases. […] All patients recorded in the SCDR from 1 January 1978 to 31 December 2008 were followed until death or 31 December 2010. The cohort was subjected to crude analyses and stratified analyses by age-at-death groups (0–17, 18–24, and ≥25 years). Time at risk was calculated from date of birth until death or 31 December 2010. Kaplan-Meier analyses and log-rank tests were performed to compare the effect of low maternal educational level, low paternal educational level, and family income support (any/none). Cox regression analyses were performed to estimate and compare the hazard ratios (HRs) for the socioeconomic variables and to adjust for the potential confounding variables age at onset and sex.”

“The study included 14,647 patients with childhood-onset T1D. A total of 238 deaths (male 154, female 84) occurred in 349,762 person-years at risk. The majority of mortalities occurred among the oldest age-group (≥25 years of age), and most of the deceased subjects had onset of T1D at the ages of 10–14.99 years […]. Mean follow-up was 23.9 years and maximum 46.5 years. The overall standardized mortality ratio up to the age of 47 years was 2.3 (95% CI 1.35–3.63); for females, it was 2.6 (1.28–4.66) and for males, 2.1 (1.27–3.49). […] Analyses on the effect of low maternal educational level showed an increased mortality for male patients (HR 1.43 [95% CI 1.01–2.04], P = 0.048) and a nonsignificant increased mortality for female patients (1.21 [0.722–2.018], P = 0.472). Paternal educational level had no significant effect on mortality […] Having parents who ever received income support was associated with an increased risk of death in both males (HR 1.89 [95% CI 1.36–2.64], P < 0.001) and females (2.30 [1.43–3.67], P = 0.001) […] Excluding the 10% of patients with the highest accumulated income support to parents during follow-up showed that having parents who ever received income support still was a risk factor for mortality.”

“A Cox model including maternal educational level together with parental income support, adjusting for age at onset and sex, showed that having parents who received income support was associated with a doubled mortality risk (HR 1.96 [95% CI 1.49–2.58], P < 0.001) […] In a Cox model including the adult patient’s own SES, having parents who received income support was still an independent risk factor in the younger age-at-death group (18–24 years). Among those who died at age ≥25 years of age, the patient’s own SES was a stronger predictor for mortality (HR 2.46 [95% CI 1.54–3.93], P < 0.001)”

“Despite a well-developed health-care system in Sweden, overall mortality up to the age of 47 years is doubled in both males and females with childhood-onset T1D. These results are in accordance with previous Swedish studies and reports from other comparable countries […] Previous studies indicated that low SES during childhood is associated with low glycemic control and diabetes-related morbidity in patients with T1D (8,9), and the current study implies that mortality in adulthood is also affected by parental SES. […] The findings, when stratified by age-at-death group, show that adult patients’ own need of income support independently predicted mortality in those who died at ≥25 years of age, whereas among those who died in the younger age-group (18–24 years), parental requirement of income support was still a strong independent risk factor. None of the present SES measures seem to predict mortality in the ages 0–17 years perhaps due to low numbers and, thus, power.”

ii. Exercise Training Improves but Does Not Normalize Left Ventricular Systolic and Diastolic Function in Adolescents With Type 1 Diabetes.

“Adults and adolescents with type 1 diabetes have reduced exercise capacity (810), which increases their risk for cardiovascular morbidity and mortality (11). The causes for this reduced exercise capacity are unclear. However, recent studies have shown that adolescents with type 1 diabetes have lower stroke volume during exercise, which has been attributed to alterations in left ventricular function (9,10). Reduced left ventricular compliance resulting in an inability to fill the left ventricle appropriately during exercise has been shown to contribute to the lower stroke volume during exercise in both adults and adolescents with type 1 diabetes (12).

Exercise training is recommended as part of the management of type 1 diabetes. However, the effects of exercise training on left ventricular function at rest and during exercise in adolescents with type 1 diabetes have not been investigated. In particular, it is unclear whether exercise training improves cardiac hemodynamics during exercise in adolescents with diabetes. Therefore, we aimed to assess left ventricular volumes at rest and during exercise in a group of adolescents with type 1 diabetes compared with adolescents without diabetes before and after a 20-week exercise-training program. We hypothesized that exercise training would improve exercise capacity and exercise stroke volume in adolescents with diabetes.”

RESEARCH DESIGN AND METHODS Fifty-three adolescents with type 1 diabetes (aged 15.6 years) were divided into two groups: exercise training (n = 38) and nontraining (n = 15). Twenty-two healthy adolescents without diabetes (aged 16.7 years) were included and, with the 38 participants with type 1 diabetes, participated in a 20-week exercise-training intervention. Assessments included VO2max and body composition. Left ventricular parameters were obtained at rest and during acute exercise using MRI.

RESULTS Exercise training improved aerobic capacity (10%) and stroke volume (6%) in both trained groups, but the increase in the group with type 1 diabetes remained lower than trained control subjects. […]

CONCLUSIONS These data demonstrate that in adolescents, the impairment in left ventricular function seen with type 1 diabetes can be improved, although not normalized, with regular intense physical activity. Importantly, diastolic dysfunction, a common mechanism causing heart failure in older subjects with diabetes, appears to be partially reversible in this age group.”

“This study confirms that aerobic capacity is reduced in [diabetic] adolescents and that this, at least in part, can be attributed to impaired left ventricular function and a blunted cardiac response to exercise (9). Importantly, although an aerobic exercise-training program improved the aerobic capacity and cardiac function in adolescents with type 1 diabetes, it did not normalize them to the levels seen in the training group without diabetes. Both left ventricular filling and contractility improved after exercise training in adolescents with diabetes, suggesting that aerobic fitness may prevent or delay the well-described impairment in left ventricular function in diabetes (9,10).

The increase in peak aerobic capacity (∼12%) seen in this study was consistent with previous exercise interventions in adults and adolescents with diabetes (14). However, the baseline peak aerobic capacity was lower in the participants with diabetes and improved with training to a level similar to the baseline observed in the participants without diabetes; therefore, trained adolescents with diabetes remained less fit than equally trained adolescents without diabetes. This suggests there are persistent differences in the cardiovascular function in adolescents with diabetes that are not overcome by exercise training.”

“Although regular exercise potentially could improve HbA1c, the majority of studies have failed to show this (3134). Exercise training improved aerobic capacity in this study without affecting glucose control in the participants with diabetes, suggesting that the effects of glycemic status and exercise training may work independently to improve aerobic capacity.”

….

iii. Change in Medical Spending Attributable to Diabetes: National Data From 1987 to 2011.

“Diabetes care has changed substantially in the past 2 decades. We examined the change in medical spending and use related to diabetes between 1987 and 2011. […] Using the 1987 National Medical Expenditure Survey and the Medical Expenditure Panel Surveys in 2000–2001 and 2010–2011, we compared per person medical expenditures and uses among adults ≥18 years of age with or without diabetes at the three time points. Types of medical services included inpatient care, emergency room (ER) visits, outpatient visits, prescription drugs, and others. We also examined the changes in unit cost, defined by the expenditure per encounter for medical services.”

RESULTS The excess medical spending attributed to diabetes was $2,588 (95% CI, $2,265 to $3,104), $4,205 ($3,746 to $4,920), and $5,378 ($5,129 to $5,688) per person, respectively, in 1987, 2000–2001, and 2010–2011. Of the $2,790 increase, prescription medication accounted for 55%; inpatient visits accounted for 24%; outpatient visits accounted for 15%; and ER visits and other medical spending accounted for 6%. The growth in prescription medication spending was due to the increase in both the volume of use and unit cost, whereas the increase in outpatient expenditure was almost entirely driven by more visits. In contrast, the increase in inpatient and ER expenditures was caused by the rise of unit costs. […] The increase was observed across all components of medical spending, with the greatest absolute increase in the spending on prescription medications ($1,528 increase), followed by inpatient visits ($680 increase) and outpatient visits ($430 increase). The absolute change in the spending on ER and other medical services use was relatively small. In relative terms, the spending on ER visits grew more than five times, faster than that of prescription medication and other medical components. […] Among the total annual diabetes-attributable medical spending, the spending on inpatient and outpatient visits dropped from 40% and 23% to 31% and 19%, respectively, between 1987 and 2011, whereas spending on prescription medication increased from 27% to 41%.”

“The unit costs rose universally in all five measures of medical care in adults with and without diabetes. For each hospital admission, diabetes patients spent significantly more than persons without diabetes. The gap increased from $1,028 to $1,605 per hospital admission between 1987 and 2001, and dropped slightly to $1,360 per hospital admission in 2011. Diabetes patients also had higher spending per ER visit and per purchase of prescription medications.”

“From 1999 to 2011, national data suggest that growth in the use and price of prescription medications in the general population is 2.6% and 3.6% per year, respectively; and the growth has decelerated in recent years (22). Our analysis suggests that the growth rates in the use and prices of prescription medications for diabetes patients are considerably higher. The higher rate of growth is likely, in part, due to the growing emphasis on achieving glycemic targets, the use of newer medications, and the use of multidrug treatment strategies in modern diabetes care practice (23,24). In addition, the growth of medication spending is fueled by the rising prices per drug, particularly the drugs that are newly introduced in the market. For example, the prices for newer drug classes such as glitazones, dipeptidyl peptidase-4 inhibitors, and incretins have been 8 to 10 times those of sulfonylureas and 5 to 7 times those of metformin (9).”

“Between 1987 and 2011, medical spending increased both in persons with and in persons without diabetes; and the increase was substantially greater among persons with diabetes. As a result, the medical spending associated with diabetes nearly doubled. The growth was primarily driven by the spending in prescription medications. Further studies are needed to assess the cost-effectiveness of increased spending on drugs.”

iv. Determinants of Adherence to Diabetes Medications: Findings From a Large Pharmacy Claims Database.

“Adults with type 2 diabetes are often prescribed multiple medications to treat hyperglycemia, diabetes-associated conditions such as hypertension and dyslipidemia, and other comorbidities. Medication adherence is an important determinant of outcomes in patients with chronic diseases. For those with diabetes, adherence to medications is associated with better control of intermediate risk factors (14), lower odds of hospitalization (3,57), lower health care costs (5,79), and lower mortality (3,7). Estimates of rates of adherence to diabetes medications vary widely depending on the population studied and how adherence is defined. One review found that adherence to oral antidiabetic agents ranged from 36 to 93% across studies and that adherence to insulin was ∼63% (10).”

“Using a large pharmacy claims database, we assessed determinants of adherence to oral antidiabetic medications in >200,000 U.S. adults with type 2 diabetes. […] We selected a cohort of members treated for diabetes with noninsulin medications (oral agents or GLP-1 agonists) in the second half of 2010 who had continuous prescription benefits eligibility through 2011. Each patient was followed for 12 months from their index diabetes claim date identified during the 6-month targeting period. From each patient’s prescription history, we collected the date the prescription was filled, how many days the supply would last, the National Drug Code number, and the drug name. […] Given the difficulty in assessing insulin adherence with measures such as medication possession ratio (MPR), we excluded patients using insulin when defining the cohort.”

“We looked at a wide range of variables […] Predictor variables were defined a priori and grouped into three categories: 1) patient factors including age, sex, education, income, region, past exposure to therapy (new to diabetes therapy vs. continuing therapy), and concurrent chronic conditions; 2) prescription factors including refill channel (retail vs. mail order), total pill burden per day, and out of pocket costs; and 3) prescriber factors including age, sex, and specialty. […] Our primary outcome of interest was adherence to noninsulin antidiabetic medications. To assess adherence, we calculated an MPR for each patient. The ratio captures how often patients refill their medications and is a standard metric that is consistent with the National Quality Forum’s measure of adherence to medications for chronic conditions. MPR was defined as the proportion of days a patient had a supply of medication during a calendar year or equivalent period. We considered patients to be adherent if their MPR was 0.8 or higher, implying that they had their medication supplies for at least 80% of the days. An MPR of 0.8 or above is a well-recognized index of adherence (11,12). Studies have suggested that patients with chronic diseases need to achieve at least 80% adherence to derive the full benefits of their medications (13). […] [W]e [also] determined whether a patient was persistent, that is whether they had not discontinued or had at least a 45-day gap in their targeted therapy.”

“Previous exposure to diabetes therapy had a significant impact on adherence. Patients new to therapy were 61% less likely to be adherent to their diabetes medication. There was also a clear age effect. Patients 25–44 years of age were 49% less likely to be adherent when compared with patients 45–64 years of age. Patients aged 65–74 years were 27% more likely to be adherent, and those aged 75 years and above were 41% more likely to be adherent when compared with the 45–64 year age-group. Men were significantly more likely to be adherent than women […I dislike the use of the word ‘significant’ in such contexts; there is a difference in the level of adherence, but it is not large in absolute terms; the male vs female OR is 1.14 (CI 1.12-1.16) – US]. Education level and household income were both associated with adherence. The higher the estimated academic achievement, the more likely the patient was to be adherent. Patients completing graduate school were 41% more likely to be adherent when compared with patients with a high school equivalent education. Patients with an annual income >$60,000 were also more likely to be adherent when compared with patients with a household income <$30,000.”

“The largest effect size was observed for patients obtaining their prescription antidiabetic medications by mail. Patients using the mail channel were more than twice as likely to be adherent to their antidiabetic medications when compared with patients filling their prescriptions at retail pharmacies. Total daily pill burden was positively associated with antidiabetic medication adherence. For each additional pill a patient took per day, adherence to antidiabetic medications increased by 22%. Patient out-of-pocket costs were negatively associated with adherence. For each additional $15 in out-of-pocket costs per month, diabetes medication adherence decreased by 11%. […] We found few meaningful differences in patient adherence according to prescriber factors.”

“In our study, characteristics that suggest a “healthier” patient (being younger, new to diabetes therapy, and taking few other medications) were all associated with lower odds of adherence to antidiabetic medications. This suggests that acceptance of a chronic illness diagnosis and the potential consequences may be an important, but perhaps overlooked, determinant of medication-taking behavior. […] Our findings regarding income and costs are important reminders that prescribers should consider the impact of medication costs on patients with diabetes. Out-of-pocket costs are an important determinant of adherence to statins (26) and a self-reported cause of underuse of medications in one in seven insured patients with diabetes (27). Lower income has previously been shown to be associated with poor adherence to diabetes medications (15) and a self-reported cause of cost-related medication underuse (27).”

v. The Effect of Alcohol Consumption on Insulin Sensitivity and Glycemic Status: A Systematic Review and Meta-analysis of Intervention Studies.

“Moderate alcohol consumption, compared with abstaining and heavy drinking, is related to a reduced risk of type 2 diabetes (1,2). Although the risk is reduced with moderate alcohol consumption in both men and women, the association may differ for men and women. In a meta-analysis, consumption of 24 g alcohol/day reduced the risk of type 2 diabetes by 40% among women, whereas consumption of 22 g alcohol/day reduced the risk by 13% among men (1).

The association of alcohol consumption with type 2 diabetes may be explained by increased insulin sensitivity, anti-inflammatory effects, or effects of adiponectin (3). Several intervention studies have examined the effect of moderate alcohol consumption on these potential underlying pathways. A meta-analysis of intervention studies by Brien et al. (4) showed that alcohol consumption significantly increased adiponectin levels but did not affect inflammatory factors. Unfortunately, the effect of alcohol consumption on insulin sensitivity has not been summarized quantitatively. A review of cross-sectional studies by Hulthe and Fagerberg (5) suggested a positive association between moderate alcohol consumption and insulin sensitivity, although the three intervention studies included in their review did not show an effect (68). Several other intervention studies also reported inconsistent results (9,10). Consequently, consensus is lacking about the effect of moderate alcohol consumption on insulin sensitivity. Therefore, we aimed to conduct a systematic review and meta-analysis of intervention studies investigating the effect of alcohol consumption on insulin sensitivity and other relevant glycemic measures.”

“22 articles met criteria for inclusion in the qualitative synthesis. […] Of the 22 studies, 15 used a crossover design and 7 a parallel design. The intervention duration of the studies ranged from 2 to 12 weeks […] Of the 22 studies, 2 were excluded from the meta-analysis because they did not include an alcohol-free control group (14,19), and 4 were excluded because they did not have a randomized design […] Overall, 14 studies were included in the meta-analysis”

“A random-effects model was used because heterogeneity was present (P < 0.01, I2 = 91%). […] For HbA1c, a random-effects model was used because the I2 statistic indicated evidence for some heterogeneity (I2 = 30%).” [Cough, you’re not supposed to make these decisions that way, coughUS. This is not the first time I’ve seen this approach applied, and I don’t like it; it’s bad practice to allow the results of (frequently under-powered) heterogeneity tests to influence model selection decisions. As Bohrenstein and Hedges point out in their book, “A report should state the computational model used in the analysis and explain why this model was selected. A common mistake is to use the fixed-effect model on the basis that there is no evidence of heterogeneity. As [already] explained […], the decision to use one model or the other should depend on the nature of the studies, and not on the significance of this test”]

“This meta-analysis shows that moderate alcohol consumption did not affect estimates of insulin sensitivity or fasting glucose levels, but it decreased fasting insulin concentrations and HbA1c. Sex-stratified analysis suggested that moderate alcohol consumption may improve insulin sensitivity and decrease fasting insulin concentrations in women but not in men. The meta-regression suggested no influence of dosage and duration on the results. However, the number of studies may have been too low to detect influences by dosage and duration. […] The primary finding that alcohol consumption does not influence insulin sensitivity concords with the intervention studies included in the review of Hulthe and Fagerberg (5). This is in contrast with observational studies suggesting a significant association between moderate alcohol consumption and improved insulin sensitivity (34,35). […] We observed lower levels of HbA1c in subjects consuming moderate amounts of alcohol compared with abstainers. This has also been shown in several observational studies (39,43,44). Alcohol may decrease HbA1c by suppressing the acute rise in blood glucose after a meal and increasing the early insulin response (45). This would result in lower glucose concentrations over time and, thus, lower HbA1c concentrations. Unfortunately, the underlying mechanism of glycemic control by alcohol is not clearly understood.”

vi. Predictors of Lower-Extremity Amputation in Patients With an Infected Diabetic Foot Ulcer.

“Infection is a frequent complication of diabetic foot ulcers, with up to 58% of ulcers being infected at initial presentation at a diabetic foot clinic, increasing to 82% in patients hospitalized for a diabetic foot ulcer (1). These diabetic foot infections (DFIs) are associated with poor clinical outcomes for the patient and high costs for both the patient and the health care system (2). Patients with a DFI have a 50-fold increased risk of hospitalization and 150-fold increased risk of lower-extremity amputation compared with patients with diabetes and no foot infection (3). Among patients with a DFI, ∼5% will undergo a major amputation and 20–30% a minor amputation, with the presence of peripheral arterial disease (PAD) greatly increasing amputation risk (46).”

“As infection of a diabetic foot wound heralds a poor outcome, early diagnosis and treatment are important. Unfortunately, systemic signs of inflammation such as fever and leukocytosis are often absent even with a serious foot infection (10,11). As local signs and symptoms of infection are also often diminished, because of concomitant peripheral neuropathy and ischemia (12), diagnosing and defining resolution of infection can be difficult.”

“The system developed by the International Working Group on the Diabetic Foot (IWGDF) and the Infectious Diseases Society of America (IDSA) provides criteria for the diagnosis of infection of ulcers and classifies it into three categories: mild, moderate, or severe. The system was validated in three relatively small cohorts of patients […] The European Study Group on Diabetes and the Lower Extremity (Eurodiale) prospectively studied a large cohort of patients with a diabetic foot ulcer (17), enabling us to determine the prognostic value of the IWGDF system for clinically relevant lower-extremity amputations. […] We prospectively studied 575 patients with an infected diabetic foot ulcer presenting to 1 of 14 diabetic foot clinics in 10 European countries. […] Among these patients, 159 (28%) underwent an amputation. […] Patients were followed monthly until healing of the foot ulcer(s), major amputation, or death — up to a maximum of 1 year.”

“One hundred and ninety-nine patients had a grade 2 (mild) infection, 338 a grade 3 (moderate), and 38 a grade 4 (severe). Amputations were performed on 159 (28%) patients (126 minor and 33 major) within the year of follow-up; 103 patients (18%) underwent amputations proximal to and including the hallux. […] The independent predictors of any amputation were as follows: periwound edema, HR 2.01 (95% CI 1.33–3.03); foul smell, HR 1.74 (1.17–2.57); purulent and nonpurulent exudate, HR 1.67 (1.17–2.37) and 1.49 (1.02–2.18), respectively; deep ulcer, HR 3.49 (1.84–6.60); positive probe-to-bone test, HR 6.78 (3.79–12.15); pretibial edema, HR 1.53 (1.02–2.31); fever, HR 2.00 (1.15–3.48); elevated CRP levels but less than three times the upper limit of normal, HR 2.74 (1.40–5.34); and elevated CRP levels more than three times the upper limit, HR 3.84 (2.07–7.12). […] In comparison with mild infection, the presence of a moderate infection increased the hazard for any amputation by a factor of 2.15 (95% CI 1.25–3.71) and 3.01 (1.51–6.01) for amputations excluding the lesser toes. For severe infection, the hazard for any amputation increased by a factor of 4.12 (1.99–8.51) and for amputations excluding the lesser toes by a factor of 5.40 (2.20–13.26). Larger ulcer size and presence of PAD were also independent predictors of both any amputation and amputations excluding the lesser toes, with HRs between 1.81 and 3 (and 95% CIs between 1.05 and 6.6).”

“Previously published studies that have aimed to identify independent risk factors for lower-extremity amputation in patients with a DFI have noted an association with older age (5,22), the presence of fever (5), elevated acute-phase reactants (5,22,23), higher HbA1c levels (24), and renal insufficiency (5,22).”

“The new risk scores we developed for any amputation, and amputations excluding the lesser toes had higher prognostic capability, based on the area under the ROC curve (0.80 and 0.78, respectively), than the IWGDF system (0.67) […] which is currently the only one in use for infected diabetic foot ulcers. […] these Eurodiale scores were developed based on the available data of our cohort, and they will need to be validated in other populations before any firm conclusions can be drawn. The advantage of these newly developed scores is that they are easier for clinicians to perform […] These newly developed risk scores can be readily used in daily clinical practice without the necessity of obtaining additional laboratory testing.”

September 12, 2017 Posted by | Cardiology, Diabetes, Economics, Epidemiology, Health Economics, Infectious disease, Medicine, Microbiology, Statistics | Leave a comment

Gastroenterology – Amal Mattu

If I hadn’t just read Horowitz & Samsom’s book I’m fairly sure this lecture would have been difficult to follow, but a lot of the stuff covered here is (naturally) closely related to the stuff covered in that book; this is mostly a revision lecture aimed at reminding you of stuff you already (supposedly?) know and/or dealing with topics closely related to stuff you already know, I don’t think it’s the right lecture for someone who knows very little about gastroenterology. I like Mattu’s approach to lecturing; this lecture was both fun and enjoyable to watch, despite (?) including a lot of information.

A few links to stuff covered/mentioned in the lecture:

Mediastinitis.
Boerhaave syndrome.
Does This Patient Have a Severe Upper Gastrointestinal Bleed? (JAMA).
Acute Liver Failure (NEJM review article).
Charcot’s cholangitis triad.
Ranson criteria.
Volvulus.
Crohn’s disease.
Ulcerative colitis.
Abdominal aortic aneurysm.
Mesenteric ischemia.
Shigella infection.
Amebiasis.
Clostridium perfringens.
Pseudomembranous colitis.

September 11, 2017 Posted by | Gastroenterology, Lectures, Medicine, Microbiology | Leave a comment

Gastrointestinal Function in Diabetes Mellitus (III)

Below some observations from chapters 5 and 6.

“The major functions of the small intestine are to digest and absorb nutrients, while those of the large bowel are to extract water and process faeces before expulsion. Diabetes mellitus may be associated with both small intestinal and colonic dysfunction, potentially resulting in a wide range of clinical manifestations, including gastrointestinal symptoms, poor nutritional status and impaired glycaemic control. […] The prevalence of small intestinal and colonic dysfunction in diabetes has not been formally evaluated and remains uncertain. However, small intestinal motor abnormalities are evident in about 80% of patients with diabetic gastroparesis, suggesting that the prevalence of intestinal dysmotility is likely to be comparable to the prevalence of gastroparesis in diabetic patients, i.e. 30–50% of unselected patients [1–6]. […] symptoms resulting from intestinal dysfunction are not cause-specific and are heterogeneous, potentially giving rise to diverse complaints, including anorexia, nausea, vomiting, constipation, diarrhoea and abdominal pain or discomfort. […] Transport of chyme through the small intestine is closely linked to intraluminal digestion and absorption of nutrients. The efficacy of absorption of nutrients is, therefore, potentially affected by dysmotility of the small intestine observed in diabetes, and by alterations in the transport mechanisms facilitating nutrient uptake across the intestinal membrane.”

“After meal ingestion, food is initially stored in the proximal stomach, then triturated in the distal stomach, and finally transported to the small intestine […]. The major functions of the small intestine are to mix and propel food particles in order to optimise intraluminal digestion and absorption. Those food particles that escape absorption, as well as indigestible solids, are transported to the colon, where water is extracted and faeces processed before expulsion. The motility patterns of the small intestine and colon are designed to efficiently serve these functions of controlled mixing and transport. When the small intestine is not exposed to nutrients, it exhibits a cyclic pattern of motility […] termed the migrating motor complex (MMC). […] The major function of the colon is to absorb water and electrolytes in order to concentrate and solidify the intraluminal content. Colonic motility plays an important role in these processes. In contrast to small intestinal motility, colonic motility follows a diurnal rhythm, with relative motor quiescence during sleep [55,56]. […] Transit and absorption of intestinal contents are regulated by the autonomic and enteric nervous systems. […] Numerous neuropeptides have been shown to play an important role in controlling the smooth muscle function of the small intestine and colon […] studies using experimental animal models of diabetes have shown altered activity of many neurotransmitters known to be of importance in preserving the integrity of intestinal motility […] Recently, the so-called interstitial cells of Cajal have been identified in the gastrointestinal tract [64–66] and appear to be responsible for the generation of the slow wave activity present in the entire gastrointestinal tract. […] The interplay between the enteric nervous system and the interstitial cells of Cajal is essential for normal gut motility.”

“[N]europathy of the autonomic (vagal and sympathetic) and enteric nerves may result in intestinal dysmotility. Autonomic neuropathy at the level of the gut can be assessed using cardiac autonomic nerve (CAN) function tests as a surrogate marker […] at present CAN function tests are the best tests available in the clinical situation. Studies using CAN function tests to assess involvement of the autonomic nerve system indicate that in patients with CAN the prevalence and severity of dysmotility of the small intestine and colon is substantially greater when compared to patients with normal CAN function. […] there is evidence that intestinal secretion may be abnormal in diabetes, due to increased secretion of fluids in response to a meal, rather than an increased basal secretory state [176]. […] These observations suggest that progressive neuropathy of the enteric and autonomic nervous system is likely to be responsible for the impaired intestinal secretion, rather than hyperglycaemia.”

“Studies that have investigated small intestinal motility in diabetes mellitus have revealed a wide spectrum of motor patterns, ranging from normal to grossly abnormal motility […] Postprandial small intestinal motor abnormalities include early recurrence of phase III and burst activity […] Both […] are thought to indicate neuropathic changes in either the intrinsic or extrinsic innervation of the gut. […] The data relating to colonic function in patients with diabetes mellitus are even more limited than those that exist for the small intestine […] [Some results suggest that] symptoms may not be a good indicator of the presence or absence of delayed colonic transit in diabetic patients.”

“There is little or no evidence that diabetes per se affects protein absorption to a clinically relevant extent. However, when diabetes mellitus is associated with severe pancreatic insufficiency […], coeliac disease […] or bacterial overgrowth, malabsorption of protein may occur. […] Since lipid absorption is dependent on the interplay of several organs (small intestine, pancreas, liver, gall bladder), diabetes mellitus has the potential to be associated with fat malabsorption […] Although it is not known whether small intestinal dysmotility per se can lead to fat malabsorption, it certainly can when the dysmotility is associated with bacterial overgrowth [160,161]. […] Recently, drug-induced malabsorption of fat has become a treatment option in diabetes mellitus. The inhibition of pancreatic lipase activity by orlistat prevents the hydrolysis of triglycerides, resulting in fat malabsorption. This approach has been reported to improve glycaemic control in type 2 diabetes”.

“The superior and inferior mesenteric arteries supply blood to the small and large intestine, while the superior, middle and inferior rectal arteries provide the arterial blood supply of the rectum. About 25% of the cardiac output in the fasting state circulates through the splanchnic arteries […] Animal models of diabetes are associated with abnormalities of neurotransmitters in the mesenteric veins and arteries […] Human diabetes may be associated with abnormalities in mesenteric blood flow. In diabetic patients with autonomic neuropathy, preprandial superior mesenteric arterial blood flow is greater than that in both control subjects and patients without autonomic neuropathy […] patients with autonomic dysfunction […] are at particular risk of postprandial hypotension and often exhibit a marked fall in systemic blood pressure after a meal […] the magnitude of the postprandial fall in blood pressure is dependent on meal composition (glucose has the greatest effect) and the rate of nutrient entry into the small intestine [196]. […] Patients with diabetes mellitus also frequently report symptoms attributable to orthostatic hypotension. A large survey of type 1 diabetes mellitus reported that the frequency of feeling faint on standing was 18% [200]. Symptomatic orthostatic hypotension in diabetic patients has been shown to be related to cardiovascular autonomic neuropathy”.

“Disordered defaecation, characterised by incontinence, constipation and diarrhoea, occurs frequently in patients with diabetes mellitus [1–3] but is often overlooked as a cause of morbidity. For example, in a study of 136 unselected diabetic outpatients referred to a tertiary centre, Feldman and Schiller found that constipation occurred in 60%, diarrhoea in 22% and faecal incontinence in 20% of their patients [1]. […] Disordered defaecation appears to be less common among patients with diabetes attending secondary referral centres [4,5], where constipation has been reported in about 20% and faecal incontinence in about 9% [5].”

“[D]efaecation and the preservation of continence are both complex territorial behaviours in humans. They are generated in the cerebral cortex and are […] markedly influenced by psychosocial factors. The multiple physiological functions required to control the passage of faeces are under the influence of a control centre in the pontine brain stem and orchestrated by the neuronal activity in the terminal expansion of the spinal cord. The instructions are conveyed via pelvic parasympathetic nerves, lumbar sympathetic nerves and sacral somatic nerves, influencing the function of the enteric nervous system and visceral smooth muscle and also the muscles of the pelvic floor. […] the muscles of the colon, abdominal wall and pelvic floor must be able to contract with sufficient power to propel faeces or resist that propulsion. But more important, the arrival of faeces in the rectum or even quite small increases in intra-abdominal pressure need to be detected immediately, so that appropriate responses can be rapidly triggered through spinal and enteric reflexes. These actions can be influenced at many levels by the diabetic process. […] Impairment of neural function caused by diabetic microangiopathy can affect to a lesser or greater extent all the mechanisms involved in the maintenance of faecal continence. So whether a person develops faecal incontinence or not depends on the interplay between all of these. Physiological studies have demonstrated that cohorts of patients with long-standing diabetes have an abnormally low anal tone, weak squeeze pressures and impaired rectal sensation [58–60]. […] Patients with long-standing diabetes mellitus are more likely to be afflicted by the shame of nocturnal incontinence of faeces than non-diabetics with faecal incontinence. […] Faecal incontinence in diabetic patients is also often associated with urinary incontinence [63]. […] Patients with faecal incontinence may only rarely be ‘cured’ — the major aim of treatment is to improve symptoms to a level where there is minimal impact on lifestyle.”

“It is important to recognise that the most common factor responsible for pudendal neuropathy in women is […] damage to the pelvic floor sustained during childbirth. […] Endo-anal ultrasonography has shown that 35% of primiparous women tested after delivery had sustained sphincter damage that persisted for at least 6 months [66]. The percentages are higher in those who had undergone forceps delivery and for multiparous women […] Diabetic women, especially those with less than optimal diabetic control, are more liable to suffer from obstetric complications, such as traumatic disruption of the anal sphincter or weakness of the pelvic floor, leading to chronic stretching of the pudendal nerve. This is because diabetics tend to give birth to large babies when glycaemic control is poor, and are more likely to experience long and difficult labours and require assisted delivery with forceps or ventouse [67].”

September 10, 2017 Posted by | Books, Diabetes, Gastroenterology, Neurology | Leave a comment

First Farmers (I?)

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(link)

This year I have so far read 113 books and I have added 5 of those books to my list of favourite books on goodreads. I have mentioned Herriot here on the blog despite the fact that this type of book is not really the type of book I usually blog, and I blogged Yashin et al.‘s biodemography text in a decent amount of detail. I have posted a couple of posts about Horowitz and Samsom’s book and I intend to blog that book in more detail later this week. However there are a few great non-fiction books which I’ve read this year which I have not yet blogged at all, including Boyd and Richerson and the excellent book by Bellwood to which the title of this post refers. These books have one thing in common: They are ‘paper books’, not books stored in an electronic format, which means that blogging them take more time than is ideal. The extra amount of time it takes to blog paper books makes it hard for me to justify blogging such books in general, even books I think are great.

Aside from the time expenditure there are at least two other major problems I have with justifying blogging such books. One problem is that this blog is not really the proper place for me to recommend books to others, a state of affairs of which I am well aware. I sometimes do it anyway, but I know perfectly well that very few people will ever know or care that I liked a particular book if I write about that book here. If I actually wanted others to know about books like these there would be lots of other channels of communication much better suited for such purposes; such as e.g. the comment sections of large blogs/reddit threads/etc. To a first approximation nobody reads this blog, which is the way I like it. The other major problem – in the context of me justifying to myself blogging such books – is that I actually usually spend quite a bit of effort while reading such (paper) books, e.g. in the form of note taking and highlighting. A major reason I have for blogging non-fiction books is that blogging books means that the content therein gets processed a few extra times, which helps aid recall and understanding. This incidentally goes both for the stuff that eventually finds its way into these posts, and to some extent also for the content that does not. When I’m reading paper books I tend to do a lot of this work while actively reading the books. Part of the reason why is actually precisely due to the fact that I know from experience that these kinds of books are bothersome to blog; if I know beforehand that I’m not particularly likely to blog a book I’ll usually spend a bit more time and effort while reading it. That extra amount of work of course makes me even less likely to end up blogging the book eventually; at some point diminishing marginal returns really kick in.

One take-away from all of the above is, I guess, that if you’re one of those three-four(?) people who semi-regularly read my blog and you also happen to actually care about which books I like and recommend, you should keep in mind that some of the really great books I read may end up not being covered here in ‘classical book posts’, simply because blogging great books may sometimes simply be too much work to justify the effort; and those books you may spot quite easily by having an occasional look at my book collection posts (see the sidebar) or my goodreads favourites.

What made me decide to finally write this post was that I had been considering whether or not to write a post about Tainter’s The Collapse of Complex Societies, which I didn’t really like all that much. While thinking about this stuff I realized that it would frankly be madness for me to cover that book (also a paper book) here before I’d at least talked a bit about Boyd and Richerson and Bellwood’s books, as those books are just much better and more interesting. And then I concluded that I really ought to cover Bellwood …and here we are.

I’ve read about some of the topics Bellwood covers elsewhere, e.g. here, here, and here, but the other works I’ve read on these topics have not covered the topics Bellwood covers in the amount of detail he does (if at all); one of the reasons why I really enjoyed Bellwood’s book was that it covers in a great amount of detail precisely some of the questions I’ve been asking myself while reading other works on related topics. The book covers things I had been looking for elsewhere, but hadn’t been able to find. This admittedly mainly relates to the agriculture and archaeology parts, rather than the linguistics part, but the linguistics is interesting as well.

If you’re interested in the origins of agriculture, this book is a must-read.

Below I’ve added some quotes from the book, as well as a few comments.

“This book suggests that major episodes of human movement occurred from time to time, in various parts of the world, as different populations developed or adopted agriculture and then spread farming, languages, and genes, in some cases across vast distances. […] In order to approach what often appears to be a debate in which specialists all talk past each other, concerned only with data from their own discipline, this book is framed around a fairly simple multidisciplinary hypothesis. The early farming dispersal hypothesis postulates that the spreads of early farming lifestyles were often correlated with prehistoric episodes of human population and language dispersal from agricultural homelands. The present-day distribution of language families and racially varied populations across the globe, allowing for the known reassortments that have ensued in historical times, still reflect to a high degree those early dispersals. […] [However] the early farming dispersal hypothesis is not claiming that only farmers ever dispersed into new lands or established language families in prehistory. Hunter-gatherers feature widely in this book since their lifestyle, in terms of long-term stability and reliability, has been the most successful in human history. It fueled the initial human colonization of the whole world, apart from a number of oceanic islands.”

“We have clear signs of relatively independent agricultural origins in western Asia, central China, the New Guinea highlands, Mesoamerica, the central Andes, the Mississippi basin, and possibly western Africa and southern India. These developments occurred at many different times between about 12,000 and 4,000 years ago. The agricultural systems concerned spread at remarkably different rates – some quickly, some slowly, some hardly at all.”

“This book owes its origin to a consideration of two primary observations: 1. Prior to the era of European colonization there existed (and still exist) a number of very widespread families of languages, the term “family” in this sense meaning that the languages concerned share common ancestry, having diverged from a common forebear […]. These language families exist because they have spread in some way from homeland regions, not because they have converged in place out of hundreds of formerly unrelated languages. 2. Within the early agricultural past of mankind there have existed many widespread archaeological complexes of closely linked artifactual style, shared economic basis, and relatively short-lived temporal placement. […] Again, these spreads have occurred from homeland regions, and most such complexes tend to become younger as one moves away from regions of agricultural origin […]. Most importantly, many agricultural homelands overlap geographically with major language family homelands, in highly significant ways.”

“The expansions of early farming populations that form the subject matter of this book reflect two consecutive processes: 1. the periodic genesis of new cultural (archaeological) or linguistic configurations in homeland circumstances; 2. the dispersal of such configurations into surrounding regions […] The transformations within such configurations, both during and after dispersal, can occur via adaptive or chance modifications to the inherited pattern (thus giving relationships of descent, or phylogeny), or via interactions with other contemporary human populations, including culturally and linguistically related as well as unrelated groups (thus giving rise to a process termed reticulation). […] One of the suggestions that will dominate the chapters in this book is that short bursts, or “punctuations,” of dispersal by closely related populations over very large areas have occurred from time to time in human prehistory, especially following the regional beginnings of agriculture or the acquisitions of some other material, demographic, or ideological advantages. Punctuations also occurred when humans first entered regions previously uninhabited, such as Australia, the Americas, and the Pacific Islands. These bursts have actually occupied very little of the total time span of human history. Often their effects are confusingly hidden beneath the reticulate interactive networks that have linked varied populations through the long millenia of subsequent history. But their underlying impact on the course of human history and on the generation of subsequent patterns of human diversity have been immense.”

“Many hunters and gatherers of the etnographic record have resource management skills that can mimic agriculture, and some have even adopted minor forms of casual cultivation. […] Resource management […] can be defined as any technique that propagates, tends, or protects a species, reduces competition, prolongs or increases the harvest, insures the appearance of a species at a particular time in a particular place, extends the range of or otherwise modifies the nature, distribution, and density of a species […]. Resource management is not synonymous with agriculture or cultivation and it has obviously been practiced to some degree by all plant and animal exploiters since long before agriculture began. Cultivation, an essential component of any agricultural system, defines a sequence of human activity whereby crops are planted […], protected, harvested, then deliberately sown again […] Domesticated plants […] are those that show recognizable indications of morphological change away from the wild phenotype, attributable to human interference in the genotype through cultivation […] For animals, the concept of domestication is invoked when there are relatively undisputed signs of human control and breeding of a species. Such signs can normally be claimed in situations where animals were transported out of their homeland regions […] In putative homeland areas for such animals, especially where there was exploitation of wild ancestral species in pre-agricultural times, it can often be difficult to distinguish animal husbandry from hunting in early agricultural contexts. […] the term agriculture will be used to apply in a general sense to all activities involving cultivation and domestication of plants.”

“In general, whereas a family of hunters and gatherers might need several square kilometers of territory for subsistence, an average family of shifting cultivators will be able to get by with a few hectares of crop-producing land. A family of irrigation agriculturalists will normally be able to manage with less than one hectare. Thus, along the scale of increasing intensification of production, less land is needed to feed a standard unit such as a family or individual. […] The reason why agriculturalists can live at much higher densities than hunters and collectors is because food is produced, on average, more intensively per unit of exploited area. Food-collecting mothers also tend to space births more widely than sedentary cultivators for reasons believed to relate in part to factors of mobility and diet2, leading in combination to biologically reduced frequencies of conception. This form of birth control maximizes the number of hunter-gatherer children able to survive to adulthood, but keeps the overall populations small.”

“With the Holocene amelioration of climate to conditions like those of the present, a rapid change that occurred about 11,500 years ago, the world’s climates became warmer, wetter, and a good deal more reliable on a short term basis […] It was this reliability that gave the early edge to farming […] Holocene climate was clearly the ultimate enabler of early farming, but it was not the proximate cause behind individual transitions. [The importance of climate was also emphasized in Boyd and RichersonUS.] […] A combined explanation of affluence alternating with mild environmental stress, especially in “risky” but highly productive early Holocene environments with periodic fluctuations in food supplies, is becoming widely favored by many archaeologists today as one explanation for the shift to early agriculture. […] It is necessary […] to emphasize that the regional beginnings of agriculture must have involved such a complex range of variables that we would be blind to ignore any of the above factors – prior sedentism, affluence and choice, human-plant co-evolution, environmental change and periodic stress, population pressure, and certainly the availability of suitable candidates for domestication. […] most suggested “causes” overlap so greatly that it is often hard to separate them. […] there can be no one-line explanation for the origins of agriculture.”

“[M]any recent hunter-gatherers have been observed to modify their environments to some degree to encourage food yields, whether by burning, replanting, water diversion, or keeping of decoy animals or domesticated dogs […] Most agriculturalists also hunt if the opportunity is presented and always have done so throughout the archaeological record. […] there is good evidence in recent societies for some degree of overlap between food collection and food production. But the whole issue here revolves around just what level of “food production” is implied. […] any idea that mobile hunters and gatherers can just shift in and out of agricultural (or pastoral) dependent lifestyle at will seems unrealistic in terms of the major scheduling shifts required by the annual calendars of resource availability, movement, and activity associated with the two basic modes of production. There are very few hints of such circumstances ever occurring in the ethnographic record […] Mobile foragers must give an increasing commitment to sedentism if agriculture is to become a successful mainstay of their economy […] In general for the Old World, we see that hunters and gatherers may practice a small amount of agriculture, and agriculturalists may practice a small amount of hunting and gathering, but the two modes of production most decisively do not merge or reveal a gentle cline. […] both Old and New World populations evidently found it problematic to shift in and out of agricultural dependence on a regular basis.”

“In order to approach the ethnographic record systematically and to extract useful comparative information, it is essential not to treat all recorded ethnographic hunter-gatherer societies as being one simple category, or as having had the same basic historical trajectories stretching back far into the Pleistocene past […] Hunter-gatherers have had histories just as tumultuous in many cases as have agriculturalists”.

Bellwood favours in his coverage of this topic a model with three different groups of hunter-gatherers. I’m not sure ‘favours’ is the right word; perhaps it’d be more accurate to state that he uses such a model to illustrate one of the ways in which different groups of hunters and gatherers are dissimilar, and why overlooking such dissimilarities may be problematic. In the model he presents in the book one group of hunter-gatherers consists of hunter-gatherers who live/d in close proximity to agricultural societies. These people tend to live in marginal areas where it’s hard to make agriculture work and they tend to be surrounded by agriculturalists (‘encapsulation’). Many places where you’d encounter such people, what you’d see/saw is/would be some sort of established exchange system, where farmers trade/d e.g. cereals in exchange for e.g. meat procured by the hunter-gatherers. One thing to always keep in mind here is that although long-term the hunter-gatherers were displaced and circumscribed by agricultural societies far from all interactions between these groups were hostile; mutually beneficial arrangements could be arrived at, even if they might not have been stable long-term. A related point is that hunter-gathering was probably a much more attractive option in the past than it is today, as the encapsulation process was not nearly so far advanced as it is today; they had better land, and despite not being farmers they might still benefit from the activities of some of those farmers who lived nearby. Bellwood is of course very interested in why agriculture spread originally, and he mentions in this context that although some such circumscribed hunter-gatherer societies may adopt agriculture eventually, such hunter-gatherer societies are not the place to look if you’re interested in the question of how agriculture originally spread throughout the world – which seems very reasonable to me. As he puts it in the notes, “while low-level food production can exist in theory, my feeling is that it has always been a child of marginal environments, where farmers necessarily retracted into food collection or where foragers were able to invest in minor cultivation without too much competition from other farmers. Such societies represent the ends, rather than the sources, of historical trajectories of agricultural expansion.”

The second group in Bellwood’s hunter-gatherer ‘model’ are ‘unenclosed’ hunter-gatherers. A few quotes:

“This group comprises those hunter-gatherers who inhabited agricultural latitudes in Australia, the Andaman Islands, and many regions of North America, especially in West Coast and Florida, but who (unlike the members of group 1) lived lives generally apart from farmers prior to European colonization. Many of these societies in North America lived in coastal regions with prolific maritime resources […] Some were also in periodic but non-threatening contact with farmers in adjacent regions in prehistory and thus had opportunities, never taken, to adopt agriculture […] Socially, […] such groups overlapped greatly with agriculturalists, indicating that social complexity of the chiefdom type can relate in terms of origin more to the intensity and reliability of resources and population density than to any simple presence of food production as opposed to hunting and gathering. […] The ranked and populous hunter-gatherer societies of norther California were no more interested in adopting agriculture than were Cape York Aborigines or the Semang, and perhaps even the majority of hunter-gatherers in prehistory. It does not follow that hunter-gatherers who have “complex” social institutions will necessarily become farmers whenever they are introduced to the farming concept.”

The third group in Bellwood’s model was really interesting to me, as it’s a group I’d previously wanted to read about and find quite fascinating. This is hunter-gatherers who used to be agriculturalists, i.e. former agriculturalists who later ‘reverted’ to hunter-gathering for one reason or another. A few quotes:

“Some hunter-gatherers appear to have descended from original farming or pastoralist societies, via specializations into environments where agriculture was not possible or decidedly marginal. Some also exist in direct contact with agriculturalist groups closely related in terms of cultural and biological ancestry. […] Some of the rain-forest hunters and gatherers of Island Southeast Asia […] descend from original agricultural populations, if the linguistic and biological data are any guide.16 In this view, the ancestral Punan and Kubu became hunter-gatherers, especially wild sago collectors in the case of the Punan, via conscious decisions to move into interfluvial rain-forest hunting and gathering in regions that riverine agriculturalists found hard to penetrate. Other hunter-gatherers descended from cultivators include some Bantu speakers in southern Africa, possibly the honey-collecting Dorobo or Okiek of the Kenyan Highlands of East Africa, probably [as he notes elsewhere, “this is a difficult group to deal with in terms of authentication”] some marginal sago-collecting groups […] in the Sepik basin of New Guinea, and some Indian groups such as the Chenchu and Birhor. […] the Numic-speaking Uto-Aztecan peoples of the Great Basin and adjacent areas […] appear to have abandoned a former agricultural lifestyle around 1,000 years ago. These people, linguistic descendants of original maize-cultivators in Mexico and the Southwest, eventually found themselves in a dry region where maize agriculture had become marginal or no longer possible [Joseph Tainter covers the collapse of the ‘Chacoans’ in some detail in his book – US] […] Group 3 hunter-gatherer societies are of especial interest because it is far easier for a relatively marginal food-producing community to turn to hunting and gathering than it is for hunters and gatherers to move in the opposite direction. Thus, it is a fair expectation that members of this third group of hunter-gatherers will always have been quite numerous, particularly around the ecological margins of expanding agricultural societies. […] the group 3 societies offer one trajectory of cultural evolution that can terminate for ever the idea that evolution from foraging to farming is a one-way street.”

“[I]t is certainly not being suggested here that ancient hunter-gatherers could never have adopted agriculture from outside sources. But they would only have been likely to do so in situations where they had some demographic or environmental advantage over any farmers in the vicinity, and where there would have been significant reasons why the normal hunter-gatherer disinterest in agricultural adoptions should be overturned. We cannot assume that hunter-gatherers would automatically adopt agriculture just because it was sitting under their noses. We also need to remember that many populations of hunters and gatherers survived alongside agriculturalists in many parts of the world for millenia, without adopting agriculture […] The following chapters will demonstrate that the spread of agriculture in the past could not simply have occurred only because hunter-gatherers everywhere adopted it. Agriculture spread in Neolithic/Formative circumstances mainly because the cultural and linguistic descendants of the early cultivators increased their demographic profiles and pushed their cultural and linguistic boundaries outwards.”

September 7, 2017 Posted by | Anthropology, Archaeology, Books, Language, Personal | Leave a comment

Interactive Coding with “Optimal” Round and Communication Blowup

The youtube description of this one was rather longer than usual, and I decided to quote it in full below:

“The problem of constructing error-resilient interactive protocols was introduced in the seminal works of Schulman (FOCS 1992, STOC 1993). These works show how to convert any two-party interactive protocol into one that is resilient to constant-fraction of error, while blowing up the communication by only a constant factor. Since these seminal works, there have been many follow-up works which improve the error rate, the communication rate, and the computational efficiency. All these works assume that in the underlying protocol, in each round, each party sends a *single* bit. This assumption is without loss of generality, since one can efficiently convert any protocol into one which sends one bit per round. However, this conversion may cause a substantial increase in *round* complexity, which is what we wish to minimize in this work. Moreover, all previous works assume that the communication complexity of the underlying protocol is *fixed* and a priori known, an assumption that we wish to remove. In this work, we consider protocols whose messages may be of *arbitrary* lengths, and where the length of each message and the length of the protocol may be *adaptive*, and may depend on the private inputs of the parties and on previous communication. We show how to efficiently convert any such protocol into another protocol with comparable efficiency guarantees, that is resilient to constant fraction of adversarial error, while blowing up both the *communication* complexity and the *round* complexity by at most a constant factor. Moreover, as opposed to most previous work, our error model not only allows the adversary to toggle with the corrupted bits, but also allows the adversary to *insert* and *delete* bits. In addition, our transformation preserves the computational efficiency of the protocol. Finally, we try to minimize the blowup parameters, and give evidence that our parameters are nearly optimal. This is joint work with Klim Efremenko and Elad Haramaty.”

A few links to stuff covered/mentioned in the lecture:

Coding for interactive communication correcting insertions and deletions.
Efficiently decodable insertion/deletion codes for high-noise and high-rate regimes.
Common reference string model.
Small-bias probability spaces: Efficient constructions and applications.
Interactive Channel Capacity Revisited.
Collision (computer science).
Chernoff bound.

September 6, 2017 Posted by | Computer science, Cryptography, Lectures, Mathematics | Leave a comment

Gastrointestinal Function in Diabetes (II)

Some more observations from the book below.

“In comparison with other parts of the gastrointestinal tract, the human oesophagus is a relatively simple organ with relatively simple functions. Despite this simplicity, disordered oesophageal function is not uncommon. […] The human oesophagus is a muscular tube that connects the pharyngeal cavity to the stomach. […] The most important functions of the human oesophagus and its sphincters are to propel swallowed food boluses to the stomach and to prevent gastro-oesophageal and oesophagopharyngeal reflux. […] Whereas the passage of liquid and solid food boluses through the oesophagus, and even acid gastrooesophageal reflux, are usually not perceived, the likelihood of perception is greater under pathological circumstances […] However, the relationship between oesophageal perception and stimulation is highly variable, e.g. patients with severe oesophagitis may deny any oesophageal symptom, while others with an endoscopically normal oesophagus may suffer from severe reflux symptoms.”

“While it is clear that oesophageal dysfunction occurs frequently in diabetes mellitus, there is considerable variation in the reported prevalence between different studies. […] Numerous studies have shown that oesophageal transit, as measured with radionuclide techniques, is slower in patients with diabetes than in age- and sex-matched healthy controls […] oesophageal transit appears to be delayed in 40–60% of patients with long-standing diabetes […] Although information relating to the prevalence of manometric abnormalities of the oesophagus [relevant link] is limited, the available data indicate that these are evident in approximately 50% of patients with diabetes […] A variety of oesophageal motor abnormalities has been demonstrated in patients with diabetes mellitus […]. These include a decreased amplitude […] and number […] of peristaltic contractions […], and an increased incidence of simultaneous […] and nonpropagated [10] contractions, as well as abnormal wave forms [17,30,32]. […] there is unequivocal evidence of damage to the extrinsic nerve supply to the oesophagus in diabetes mellitus. The results of examination of the oesophagus in 20 patients who died from diabetes disclosed histologic abnormalities in 18 of them […] The available information indicates that the prevalence of gastro-oesophageal reflux disease is higher in diabetes. Murray and co-workers studied 20 diabetic patients (14 type 1, six type 2), of whom nine (45%) were found to have excessive gastro-oesophageal acid reflux […] In a larger study of 50 type 1 diabetic patients without symptoms or history of gastro-oesophageal disease, abnormal gastro-oesophageal reflux, defined as a percentage of time with esophageal pH < 4 exceeding 3.5%, was detected in 14 patients (28%) [37].”

“Several studies have shown that the gastrointestinal motor responses to various stimuli are impaired during acute hyperglycaemia in both healthy subjects and diabetic patients […] acute hyperglycaemia reduces LOS [lower oesophageal sphincter, US] pressure and impairs oesophageal motility […] Several studies have shown that abnormal oesophageal motility is more frequent in diabetic patients who have evidence of peripheral or autonomic neuropathy than in those without […] In one of the largest studies that focused on the relationship between neuropathy and disordered oesophageal function, 50 […] insulin-requiring diabetics were stratified into three groups: (a) patients without peripheral neuropathy (n = 18); (b) patients with peripheral neuropathy but no autonomic neuropathy (n = 20); and (c) patients with both peripheral and autonomic neuropathy (n = 12). Radionuclide oesophageal emptying was found to be abnormal in 55%, 70% and 83% of patients in groups A, B and C, respectively [17]. […] It must be emphasised, however, that although several studies have provided evidence for the existence of a relationship between disordered oesophageal function and diabetic autonomic neuropathy, this relationship is relatively weak [13,14,17,27,37,49].”

“There is considerable disagreement in the literature as to the prevalence of symptoms of oesophageal dysfunction in diabetes mellitus. Some publications indicate that patients with diabetes mellitus usually do not complain about oesophageal symptoms, even when severe oesophageal dysfunction is present. […] However, in other studies a high prevalence of oesophageal symptoms in diabetics has been documented. For example, 27% of 137 unselected diabetics attending an outpatient clinic admitted to having dysphagia when specifically asked […] The poor association between oesophageal dysfunction and symptoms in patients with diabetes may reflect impaired perception of oesophageal stimuli caused by neuropathic abnormalities in afferent pathways. The development of symptoms and signs of gastro-oesophageal reflux disease in diabetics may in part be counteracted by a decrease in gastric acid secretion [59]. […] [However] oesophageal acid exposure is increased in about 40% of diabetics and it is known that the absence of reflux symptoms does not exclude the presence of severe oesophagitis and/or Barrett’s metaplasia. Due to impaired oesophageal perception, the proportion of asymptomatic patients with reflux disease may be higher in the presence of diabetes than when diabetes is absent. It might, therefore, be argued that a screening upper gastrointestinal endoscopy should be performed in diabetic patients, even when no oesophageal or gastric symptoms are reported. However, [a] more cost-effective
and realistic approach may be to perform endoscopy in diabetics with other risk factors for reflux disease, in particular severe obesity.
[…] Since upper gastrointestinal symptoms correlate poorly with objective abnormalities of gastrointestinal motor function in diabetes, the symptomatic benefit that could be expected from correction of these motor abnormalities is questionable. […] Little or nothing is known about the prognosis of disordered oesophageal function in diabetes. Long-term follow-up studies are lacking.

“Abnormally delayed gastric emptying, or gastroparesis, was once considered to be a rare sequela of diabetes mellitus, occurring occasionally in patients who had long-standing diabetes complicated by symptomatic autonomic neuropathy, and inevitably associated with both intractable upper gastrointestinal symptoms and a poor prognosis [1]. Consequent upon the development of a number of techniques to quantify gastric motility […] and the rapid expansion of knowledge relating to both normal and disordered gastric motor function in humans over the last ∼ 20 years, it is now recognised that these concepts are incorrect. […] Delayed gastric emptying represents a frequent, and clinically important, complication of diabetes mellitus. […] Cross-sectional studies […] have established that gastric emptying of solid, or nutrient liquid, meals is abnormally slow in some 30–50% of outpatients with longstanding type 1 [7–20] or type 2 [20–26] diabetes […]. Early studies, using insensitive barium contrast techniques to quantify gastric emptying, clearly underestimated the prevalence substantially [1,27]. The reported prevalence of delayed gastric emptying is highest when gastric emptying of both solid and nutrient-containing liquids (or semi-solids) are measured, either simultaneously or on separate occasions [17,28,29], as there is a relatively poor correlation between gastric emptying of solids and liquids in diabetes [28–30]. […] It is now recognised that delayed gastric emptying also occurs frequently (perhaps about 30%) in children and adolescents with type 1 diabetes [37–39]. […] intragastric meal distribution is also frequently abnormal in outpatients with diabetes, with increased retention of food in both the proximal and distal stomach [31,33]. The former may potentially be important in the aetiology of gastro-oesophageal reflux [34], which appears to occur more frequently in patients with diabetes […] Diabetic gastroparesis is often associated with motor dysfunction in other areas of the gut, e.g. oesophageal transit is delayed in some 50% of patients with long-standing diabetes [8].”

“Overall patterns of gastric emptying are critically dependent on the physical and chemical composition of a meal, so that there are substantial differences between solids, semi-solids, nutrient liquids and non-nutrient liquids [70]. […] The major factor regulating gastric emptying of nutrients (liquids and ‘liquefied’ solids) is feedback inhibition, triggered by receptors that are distributed throughout the small intestine [72]; as a result of this inhibition, nutrient-containing liquids usually empty from the stomach at an overall rate of about 2 kcal/min, after an initial emptying phase that may be somewhat faster [73]. These small intestinal receptors also respond to pH, osmolality and distension, as well as nutrient content. […] While the differential emptying rates of solids, nutrient and non-nutrient liquids when ingested alone is well established, there is much less information about the interaction between different meal components. When liquids and solids are consumed together, liquids empty preferentially (∼ 80% before the solid starts to empty) […] and the presence of a solid meal results in an overall slowing of a simultaneously ingested liquid [71,75,76]. Therefore, while it is clear that the stomach can, to some extent, regulate the emptying of liquids and solids separately, the mechanisms by which this is accomplished remain poorly defined. Extracellular fat has a much lower density than water and is liquid at body temperature. The pattern of gastric emptying of fat, and its effects on emptying of other meal components are, therefore, dependent on posture — in the left lateral posture oil accumulates in the stomach and empties early, which markedly delays emptying of a nutrient liquid [77]. Gastric emptying is also influenced by patterns of previous nutrient intake. In healthy young and older subjects, supplementation of the diet with glucose is associated with acceleration of gastric emptying of glucose [78,79], while short-term starvation slows gastric emptying”.

“[I]n animal models of diabetes a number of morphological changes are evident in the autonomic nerves supplying the gut and the myenteric plexus, including a reduction in the number of myelinated axons in the vagosympathetic trunk and neurons in the dorsal root ganglia, abnormalities in neurotransmitters […] as well as a reduced number of interstitial cells of Cajal in the fundus and antrum [89–92]. In contrast, there is hitherto little evidence of a fixed pathological process in the neural tissue of humans with diabetes […] While a clear-cut association between disordered gastrointestinal function in diabetes mellitus and the presence of autonomic neuropathy remains to be established, it is now recognised that acute changes in the blood glucose concentration have a substantial, and reversible, effect on gastric (as well as oesophageal, intestinal, gallbladder and anorectal) motility, in both healthy subjects and patients with diabetes […] Marked hyperglycaemia (blood glucose concentration ∼ 15 mmol/l) affects motility in every region of the gastrointestinal tract [103]. […] In healthy subjects [114] and patients with uncomplicated type 1 diabetes […] gastric emptying is accelerated markedly during hypoglycaemia […] this response is likely to be important in the counterregulation of hypoglycaemia. It is not known whether the magnitude of the effect of hypoglycaemia on gastric emptying is influenced by gastroparesis and/or autonomic neuropathy. Recent studies have established that changes in the blood glucose concentration within the normal postprandial range also influence gastric emptying and motility [104–106]; emptying of solids and nutrient-containing liquids is slower at a blood glucose of 8 mmol/l than at 4 mmol/l in both healthy subjects and patients with type 1 diabetes […] Recent studies suggest that the rate of gastric emptying is a significant factor in postprandial hypotension. The latter, which may lead to syncope and falls, is an important clinical problem, particularly in the elderly and patients with autonomic dysfunction (usually diabetes mellitus), occurring more frequently than orthostatic hypotension [154].”

“Gastric emptying is potentially an important determinant of oral drug absorption; most orally administered drugs (including alcohol) are absorbed more slowly from the stomach than from the small intestine because the latter has a much greater surface area [179,180]. Thus, delayed gastric emptying (particularly that of tablets or capsules, which are not degraded easily in the stomach) and a reduction in antral phase 3 activity, may potentially lead to fluctuations in the serum concentrations of orally administered drugs. This may be particularly important when a rapid onset of drug effect is desirable, as with some oral hypoglycaemic drugs […]. There is relatively little information about drug absorption in patients with diabetic gastroparesis [179] and additional studies are required.”

“Glycated haemoglobin is influenced by both fasting and postprandial glucose levels; while their relative contributions have not been defined precisely [181], it is clear that improved overall glycaemic control, as assessed by glycated haemoglobin, can be achieved by lowering postprandial blood glucose concentrations, even at the expense of higher fasting glucose levels [182]. Accordingly, the control of postprandial blood glucose levels, as opposed to glycated haemoglobin, now represents a specific target for treatment […] It remains to be established whether postprandial glycaemia per se, including the magnitude of postprandial hyperglycaemic spikes, has a distinct role in the pathogenesis of diabetic complications, but there is increasing data to support this concept [181,183,184]. It is also possible that the extent of blood glucose fluctuations is an independent determinant of the risk for long-term diabetic complications [184]. […] postprandial blood glucose levels are potentially determined by a number of factors, including preprandial glucose concentrations, the glucose content of a meal, small intestinal delivery and absorption of nutrients, insulin secretion, hepatic glucose metabolism and peripheral insulin sensitivity. Although the relative contribution of these factors remains controversial, and is likely to vary with time after a meal, it is now recognised that gastric emptying accounts for at least 35% of the variance in peak glucose levels after oral glucose (75 g) in both healthy individuals and patients with type 2 diabetes […] It is also clear that even modest perturbations in gastric emptying of carbohydrate have a major effect on postprandial glycaemia [76,79]. […] it appears that much of the observed variation in the glycaemic response to different food types (‘glycaemic indices’) in both normal subjects and patients with diabetes is attributable to differences in rates of gastric emptying [103]. […] In type 1 patients with gastroparesis […] less insulin is initially required to maintain euglycaemia after a meal when compared to those with normal gastric emptying [187]. […] There are numerous uncontrolled reports supporting the concept […] that in type 1 patients gastroparesis is a risk factor for poor glycaemic control.”

“The potential for the modulation of gastric emptying, by dietary or pharmacological means, to minimise postprandial glucose excursions and optimise glycaemic control, represents a novel approach to the optimisation of glycaemic control in diabetes, which is now being explored actively. It is important to appreciate that the underlying strategies are likely to differ fundamentally between type 1 and type 2 diabetes. In type 1 diabetes, interventions that improve the coordination between nutrient absorption and the action of exogenous insulin are likely to be beneficial, even in those patients who have delayed gastric emptying, i.e. by accelerating or even slowing gastric emptying, so that the rate of nutrient delivery (and hence absorption) is more predictable. In contrast, in type 2 diabetes, it may be anticipated that slowing of the absorption of nutrients would be desirable […] In the treatment of type 2 diabetes mellitus, dietary modifications potentially represent a more attractive and cost-effective approach than drugs […] A number of dietary strategies may slow carbohydrate absorption […] an increase in dietary fibre […] Fat is a potent inhibitor of gastric emptying and […] these effects may be dependent on posture [77]; there is the potential for relatively small quantities of fat given immediately before consumption of, or with, a meal to slow gastric emptying of other meal components, so that the postprandial rise in blood glucose is minimised [210] (this is analogous to the slowing of alcohol absorption and liquid gastric emptying when alcohol is ingested after a solid meal, rather than in the fasted state [75]). […] there is evidence that the suppression of subsequent food intake by the addition of fat to a meal may exceed the caloric value of the fat load [212]. In the broadest sense, the glycaemic response to a meal is also likely to be critically dependent on whether food from the previous meal is still present in the stomach and/or small intestine at the time of its ingestion, so that glucose tolerance may be expected to be worse in the fasted state […] than after a meal.”

“At present it is not known whether normalisation of gastric emptying in either type 1 or type 2 patients with gastroparesis improves glycaemic control. […] prokinetic drugs would not be expected to have a beneficial effect on glycaemic control in type 2 patients who are not using insulin. Erythromycin may, however, as a result of its interaction with motilin receptors, also stimulate insulin secretion (and potentially improve glycaemic control by this mechanism) in type 2 diabetes [220] […] It should […] be recognised that any drug that slows gastric emptying has the potential to induce or exacerbate upper gastrointestinal symptoms, delay oral drug absorbtion and impair the counter-regulation of glycaemia. […] At present, the use of prokinetic drugs (mainly cisapride, domperidone, metoclopramide and erythromycin) forms the mainstay of therapy [167,244–259], and most patients will require drug treatment. In general, these drugs all result in dose-related improvements in gastric emptying after acute administration […] The response to prokinetic therapy (magnitude of acceleration in gastric emptying) tends to be greater when gastric emptying is more delayed. It should be recognised that relatively few controlled studies have evaluated the effects of ‘prolonged’ (> 8 weeks) prokinetic therapy, that in many studies the sample sizes have been small, and that the assessments of gastrointestinal symptoms have, not infrequently, been suboptimal; furthermore, the results of some of these studies have been negative [32]. There have hitherto been relatively few randomised controlled trials of high quality, and those that are available differ substantially in design. […] In general, there is a poor correlation between effects on symptoms and gastric emptying — prokinetic drugs may improve symptoms by effects unrelated to acceleration of gastric emptying or central anti-emetic properties [254].”

“Autoimmune factors are well recognised to play a role in the aetiology of type 1 diabetes [316,317]. In such patients there is an increased prevalence of autoimmune aggression against non-endocrine tissues, including the gastric mucosa. The reported prevalence of parietal cell antibodies in patients with type 1 diabetes is in the range 5–28%, compared to 1.4–12% in non-diabetic controls […] The autoimmune response to parietal cell antibodies may lead to atrophic gastritis, pernicious anaemia and iron deficiency anaemia […] Parietal cell antibodies can inhibit the secretion of intrinsic factor, which is necessary for the absorption of vitamin B12, potentially resulting in pernicious anaemia. The prevalence of latent and overt pernicious anaemia in type 1 diabetes has been reported to be 1.6–4% and 0.4%, respectively […] screening for parietal cell antibodies in patients with type 1 diabetes currently appears inappropriate. However, there should be a low threshold for further investigation in those patients presenting with anaemia”.

September 1, 2017 Posted by | Books, Diabetes, Gastroenterology, Immunology, Medicine, Neurology | Leave a comment

Quotes

i. “A theorist can explain any correlation, and its inverse.” (Thomas Gold)

ii. “The utility of a language as a tool of thought increases with the range of topics it can treat, but decreases with the amount of vocabulary and the complexity of grammatical rules which the user must keep in mind. Economy of notation is therefore important.” (Kenneth Iverson)

iii. “Paradoxically, it has turned out that game theory is more readily applied to biology than to the field of economic behavior for which it was originally designed” (John Maynard Smith)

iv. “It is an occupational risk of biologists to claim, towards the end of their careers, that the problems which they have not solved are insoluble.” (-ll-)

v. “Curiosity is the beginning of all wisdom.” (Françoise Sagan)

vi. ” To be gentle, tolerant, wise and reasonable requires a goodly portion of toughness.” (Peter Ustinov)

vii. “Once we are destined to live out our lives in the prison of our mind, our one duty is to furnish it well.” (-ll-)

viii. “Her virtue was that she said what she thought, her vice that what she thought didn’t amount to much.” (-ll-)

ix. “Politicians only get to the top because they have no qualifications to detain them at the bottom.” (-ll-)

x. “A great deal of intelligence can be invested in ignorance when the need for illusion is deep.” (Saul Bellow)

xi. “All science is full of statements where you put the best face on your ignorance, where you say: true enough, we know awfully little about this, but more or less irrespective of the stuff we don’t know about, we can make certain useful deductions.” (Hermann Bondi)

xii. “…the final test of a theory is its capacity to solve the problems which originated it.” (George Dantzig)

xiii. “A success that has outlived its usefulness may, in the end, be more damaging than failure.” (Peter Drucker)

xiv. “Unperformed experiments have no results.” (Asher Peres)

xv. “Ideas appropriate to a past social order have a strange power of influencing thought and action within a later institutional frame work.” (Eric Roll)

xvi. “…the ‘size’ of science has doubled steadily every 15 years. In a century this means a factor of 100. For every single scientific paper or for every single scientist in 1670, there were 100 in 1770, 10,000 in 1870 and 1,000,000 in 1970.” (John Ziman)

xvii. “One of the big secrets of finding time is not to watch television.” (Robert Keeshan)

xviii. “Dying is something we human beings do continuously, not just at the end of our physical lives on this earth.” (Elisabeth Kübler-Ross)

xix. “I told my psychiatrist that everyone hates me. He said I was being ridiculous, everyone hasn’t met me yet.” (Rodney Dangerfield)

xx. “In the country of the blind, who are not as unobservant as they look, the one-eyed is not king, he is spectator.” (Clifford Geertz)

August 31, 2017 Posted by | Quotes/aphorisms | Leave a comment

Light

I gave the book two stars. Some quotes and links below.

“Lenses are ubiquitous in image-forming devices […] Imaging instruments have two components: the lens itself, and a light detector, which converts the light into, typically, an electrical signal. […] In every case the location of the lens with respect to the detector is a key design parameter, as is the focal length of the lens which quantifies its ‘ray-bending’ power. The focal length is set by the curvature of the surfaces of the lens and its thickness. More strongly curved surfaces and thicker materials are used to make lenses with short focal lengths, and these are used usually in instruments where a high magnification is needed, such as a microscope. Because the refractive index of the lens material usually depends on the colour of light, rays of different colours are bent by different amounts at the surface, leading to a focus for each colour occurring in a different position. […] lenses with a big diameter and a short focal length will produce the tiniest images of point-like objects. […] about the best you can do in any lens system you could actually make is an image size of approximately one wavelength. This is the fundamental limit to the pixel size for lenses used in most optical instruments, such as cameras and binoculars. […] Much more sophisticated methods are required to see even smaller things. The reason is that the wave nature of light puts a lower limit on the size of a spot of light. […] At the other extreme, both ground- and space-based telescopes for astronomy are very large instruments with relatively simple optical imaging components […]. The distinctive feature of these imaging systems is their size. The most distant stars are very, very faint. Hardly any of their light makes it to the Earth. It is therefore very important to collect as much of it as possible. This requires a very big lens or mirror”.

“[W]hat sort of wave is light? This was […] answered in the 19th century by James Clerk Maxwell, who showed that it is an oscillation of a new kind of entity: the electromagnetic field. This field is effectively a force that acts on electric charges and magnetic materials. […] In the early 19th century, Michael Faraday had shown the close connections between electric and magnetic fields. Maxwell brought them together, as the electromagnetic force field. […] in the wave model, light can be considered as very high frequency oscillations of the electromagnetic field. One consequence of this idea is that moving electric charges can generate light waves. […] When […] charges accelerate — that is, when they change their speed or their direction of motion — then a simple law of physics is that they emit light. Understanding this was one of the great achievements of the theory of electromagnetism.”

“It was the observation of interference effects in a famous experiment by Thomas Young in 1803 that really put the wave picture of light as the leading candidate as an explanation of the nature of light. […] It is interference of light waves that causes the colours in a thin film of oil floating on water. Interference transforms very small distances, on the order of the wavelength of light, into very big changes in light intensity — from no light to four times as bright as the individual constituent waves. Such changes in intensity are easy to detect or see, and thus interference is a very good way to measure small changes in displacement on the scale of the wavelength of light. Many optical sensors are based on interference effects.”

“[L]ight beams […] gradually diverge as they propagate. This is because a beam of light, which by definition has a limited spatial extent, must be made up of waves that propagate in more than one direction. […] This phenomenon is called diffraction. […] if you want to transmit light over long distances, then diffraction could be a problem. It will cause the energy in the light beam to spread out, so that you would need a bigger and bigger optical system and detector to capture all of it. This is important for telecommunications, since nearly all of the information transmitted over long-distance communications links is encoded on to light beams. […] The means to manage diffraction so that long-distance communication is possible is to use wave guides, such as optical fibres.”

“[O]ptical waves […] guided along a fibre or in a glass ‘chip’ […] underpins the long-distance telecommunications infrastructure that connects people across different continents and powers the Internet. The reason it is so effective is that light-based communications have much more capacity for carrying information than do electrical wires, or even microwave cellular networks. […] In optical communications, […] bits are represented by the intensity of the light beam — typically low intensity is a 0 and higher intensity a 1. The more of these that arrive per second, the faster the communication rate. […] Why is optics so good for communications? There are two reasons. First, light beams don’t easily influence each other, so that a single fibre can support many light pulses (usually of different colours) simultaneously without the messages getting scrambled up. The reason for this is that the glass of which the fibre is made does not absorb light (or only absorbs it in tiny amounts), and so does not heat up and disrupt other pulse trains. […] the ‘crosstalk’ between light beams is very weak in most materials, so that many beams can be present at once without causing a degradation of the signal. This is very different from electrons moving down a copper wire, which is the usual way in which local ‘wired’ communications links function. Electrons tend to heat up the wire, dissipating their energy. This makes the signals harder to receive, and thus the number of different signal channels has to be kept small enough to avoid this problem. Second, light waves oscillate at very high frequencies, and this allows very short pulses to be generated This means that the pulses can be spaced very close together in time, making the transmission of more bits of information per second possible. […] Fibre-based optical networks can also support a very wide range of colours of light.”

“Waves can be defined by their wavelength, amplitude, and phase […]. Particles are defined by their position and direction of travel […], and a collection of particles by their density […] and range of directions. The media in which the light moves are characterized by their refractive indices. This can vary across space. […] Hamilton showed that what was important was how rapidly the refractive index changed in space compared with the length of an optical wave. That is, if the changes in index took place on a scale of close to a wavelength, then the wave character of light was evident. If it varied more smoothly and very slowly in space then the particle picture provided an adequate description. He showed how the simpler ray picture emerges from the more complex wave picture in certain commonly encountered situations. The appearance of wave-like phenomena, such as diffraction and interference, occurs when the size scales of the wavelength of light and the structures in which it propagates are similar. […] Particle-like behaviour — motion along a well-defined trajectory — is sufficient to describe the situation when all objects are much bigger than the wavelength of light, and have no sharp edges.”

“When things are heated up, they change colour. Take a lump of metal. As it gets hotter and hotter it first glows red, then orange, and then white. Why does this happen? This question stumped many of the great scientists [in the 19th century], including Maxwell himself. The problem was that Maxwell’s theory of light, when applied to this problem, indicated that the colour should get bluer and bluer as the temperature increased, without a limit, eventually moving out of the range of human vision into the ultraviolet—beyond blue—region of the spectrum. But this does not happen in practice. […] Max Planck […] came up with an idea to explain the spectrum emitted by hot objects — so-called ‘black bodies’. He conjectured that when light and matter interact, they do so only by exchanging discrete ‘packets’, or quanta, or energy. […] this conjecture was set to radically change physics.”

“What Dirac did was to develop a quantum mechanical version of Maxwell’s theory of electromagnetic fields. […] It set the quantum field up as the fundamental entity on which the universe is built — neither particle nor wave, but both at once; complete wave–particle duality. It is a beautiful reconciliation of all the phenomena that light exhibits, and provides a framework in which to understand all optical effects, both those from the classical world of Newton, Maxwell, and Hamilton and those of the quantum world of Planck, Einstein, and Bohr. […] Light acts as a particle of more or less well-defined energy when it interacts with matter. Yet it retains its ability to exhibit wave-like phenomena at the same time. The resolution [was] a new concept: the quantum field. Light particles — photons — are excitations of this field, which propagates according to quantum versions of Maxwell’s equations for light waves. Quantum fields, of which light is perhaps the simplest example, are now regarded as being the fundamental entities of the universe, underpinning all types of material and non-material things. The only explanation is that the stuff of the world is neither particle nor wave but both. This is the nature of reality.”

Some links:

Light.
Optics.
Watt.
Irradiance.
Coherence (physics).
Electromagnetic spectrum.
Joseph von Fraunhofer.
Spectroscopy.
Wave.
Transverse wave.
Wavelength.
Spatial frequency.
Polarization (waves).
Specular reflection.
Negative-index metamaterial.
Birefringence.
Interference (wave propagation).
Diffraction.
Young’s interference experiment.
Holography.
Photoactivated localization microscopy.
Stimulated emission depletion (STED) microscopy.
Fourier’s theorem (I found it hard to find a good source on this one. According to the book, “Fourier’s theorem says in simple terms that the smaller you focus light, the broader the range of wave directions you need to achieve this spot”)
X-ray diffraction.
Brewster’s angle.
Liquid crystal.
Liquid crystal display.
Wave–particle duality.
Fermat’s principle.
Wavefront.
Maupertuis’ principle.
Johann Jakob Balmer.
Max Planck.
Photoelectric effect.
Niels Bohr.
Matter wave.
Quantum vacuum.
Lamb shift.
Light-emitting diode.
Fluorescent tube.
Synchrotron radiation.
Quantum state.
Quantum fluctuation.
Spontaneous emission/stimulated emission.
Photodetector.
Laser.
Optical cavity.
X-ray absorption spectroscopy.
Diamond Light Source.
Mode-locking.
Stroboscope.
Femtochemistry.
Spacetime.
Atomic clock.
Time dilation.
High harmonic generation.
Frequency comb.
Optical tweezers.
Bose–Einstein condensate.
Pump probe spectroscopy.
Vulcan laser.
Plasma (physics).
Nonclassical light.
Photon polarization.
Quantum entanglement.
Bell test experiments.
Quantum key distribution/Quantum cryptography/Quantum computing.

August 31, 2017 Posted by | Books, Chemistry, Computer science, Physics | Leave a comment

Gastrointestinal Function in Diabetes (I)

“During the last 15–20 years, primarily as a result of the application of novel investigative techniques, there has been a rapid expansion of knowledge relating to the function of the gastrointestinal tract in diabetes mellitus. These insights have been substantial and have led to the recognition that gastrointestinal function represents a hitherto inappropriately neglected, as well as important, aspect of diabetes management. In particular, disordered gastrointestinal motor and sensory function occur frequently in both type 1 and type 2 diabetes and may be associated with significant clinical sequelae. Recent epidemiological studies have established that there is a high prevalence of gastrointestinal symptoms in the diabetic population and that these are associated with impaired quality of life. Furthermore, upper gastrointestinal motility, even when normal, is central to the regulation of postprandial blood glucose concentrations. Hence, diabetes and the gastrointestinal tract are inextricably linked. […] This book, which to our knowledge represents the first of its kind, was stimulated by the need to consolidate these advances, to illuminate an area that is perceived as increasingly important, but somewhat difficult to understand. […] The book aims to be comprehensive and to present the relevant information in context for both the clinician and clinical researcher. There are nine chapters: five are organ-specific, relating to oesophageal, gastric, intestinal, anorectal and hepatobiliary function; the four other chapters address epidemiological aspects of gastrointestinal function in diabetes, the effects of diabetes mellitus on gastrointestinal function in animal models, the impact of gastrointestinal function on glycaemic control, and the evaluation of gastrointestinal autonomic function. All of the authors are recognised internationally for their expertise in the field”.

I added this book to my list of favourite books on goodreads – it’s a great book, from which I learned a lot.

I have added some more quotes and observations from the book below, as well as a few comments.

“Population-based studies of gastrointestinal symptoms in diabetic patients have been relatively few and the results conflicting […] To date, a total of nine population-based studies have been undertaken evaluating gastrointestinal symptoms in subjects with diabetes mellitus […] Depending on the population studied, the prevalence of symptoms has varied considerably in patients with both type 1 and type 2 diabetes mellitus. […] there is evidence that gastrointestinal symptoms are linked with diabetes mellitus, but the prevalence over and above the general population is at most only modestly increased. Some studies have failed to detect an association between diabetes and gastrointestinal symptoms, but several confounders may have obscured the findings. For example, it is well documented that chronic gastrointestinal symptoms are common in non-diabetics in the community, presumably due to functional gastrointestinal disorders such as the irritable bowel syndrome [33,34]. Moreover, the presence of diabetic complications and possibly long-term glycaemic control appear to be important factors in symptom onset [31,32]. This may explain the difficulty in establishing a firm link between diabetes and chronic gastrointestinal complaints in population-based studies.”

It is perhaps important to interpose already at this early stage of the coverage that diabetes seems to be related to many changes in gastrointestinal function that do not necessarily cause symptoms which lead to patient complaints, but which even so may still affect individuals with the disease in a variety of ways. For example drug metabolism may be altered in diabetics secondary to hyperglycemia-induced delayed gastric emptying, which can naturally be very important in some situations (drugs don’t work, or don’t work when they’re supposed to). Symptomatic disease is important to observe and address, but there are many other aspects that may be relevant as well. The symptomatology of diabetes-related gastrointestinal changes is of course complicated by the fact that nervous system involvement is an important player, and a player we know from other contexts may both generate symptoms (in this setting you’d e.g. think of altered peristalsis in severe neuropathy, causing constipation) and may also lead to an absence of symptoms in settings where symptoms would otherwise have been present (‘silent ischemia‘ is common in diabetics). I may or may not go much more into these topics, there’s a lot of interesting stuff in this book.

“In patients with long-standing type 1 and type 2 diabetes, the prevalence of delayed gastric emptying of a nutrient meal is reported to range from 27% to 40% [40–42] and the prevalence is similar in insulin-dependent and non-insulindependent diabetes mellitus […]. In a minority of patients (less than 10%) with long-standing diabetes, gastric emptying is accelerated [42–44]. […] A number of studies have shown that acute changes in blood glucose concentrations can have a profound effect on motor function throughout the gastrointestinal tract in both normal subjects and patients with diabetes mellitus [54]. Recent studies have demonstrated that the blood glucose concentration may also modulate the perception of sensations arising from the gastrointestinal tract [56–58]. However, there is relatively little information about the mechanisms mediating the effects of the blood glucose concentration on gastrointestinal motility. While some studies have implicated impaired glycaemic control in the genesis of chronic gastrointestinal symptoms [24,31], this remains controversial.”

“As part of the Medical Outcomes Study, that determined the impact of nine different chronic illnesses upon HRQL [Health-Related Quality of Life, US], Stewart et al. [90] used the Short Form (SF-20) of the General Health Survey to evaluate HRQL ratings in 9385 patients, 844 of whom had diabetes […] gastrointestinal disorders had a more negative impact on HRQL than all other conditions with the exception of heart disease [90]. Others have reported similar findings [120,121]. […] A study of diabetic patients undergoing transplantation [122] indicated that, of all the factors likely to compromise HRQL, the single most important one was gastrointestinal dysfunction.”

“In animal studies of gastrointestinal function in diabetes mellitus, most information has been generated using insulinopenic rats with severe hyperglycaemia; around one-third of the literature has been generated using BB rats (autoimmune spontaneous diabetic) and two-thirds using streptozotocin (STZ; chemically-induced) diabetic models. In the choice of these animal models, an assumption appears to have been often made that hyperglycaemia per se, or at least some aspect of the metabolic disturbance secondary to insulin lack, is the aetiopathologic insult. A common hypothesis is that neurotoxicity of the autonomic nervous system, secondary to this metabolic insult, is responsible for the gastrointestinal effects of diabetes. This hypothesis is described here as the ‘autonomic neuropathic’ hypothesis.”

“Central nervous structures, especially those in the brain stem […] are implicated in the normal autonomic control of gastrointestinal function […] over two-thirds of the literature regarding gastrointestinal dysfunction in diabetes is derived from chemically-induced models in which, alarmingly, much of the reported gut dysfunction could be an artifact of selective damage to central structures. It is now recognised that there are major differences in gastrointestinal function between animals in which β-cell damage was caused by chemical means and those in which damage was a result of an autoimmune process. These differences prompt an examination of the extent to which gastrointestinal dysfunction in some models is a consequence of diabetes per se, perhaps applicable to human disease, as opposed to being a consequence of damage to specific central structures.”

“The […] most accepted hypothesis in the past to explain gastrointestinal dysfunction in diabetes has been the proposal that autonomic neuropathy has disturbed the normal regulation of gut function. But there are recently identified disturbances in several of the neurohormones found in gut in different diabetic states. Several of these, including amylin, GLP-1 and PYY have effects on gut function, and should now be considered in explanations of diabetes-associated changes in gut function. […] A ‘neurocrine’ alternative to the neuropathic hypothesis focuses on the possibility that absolute or relative deficiency of the pancreatic β-cell hormone, amylin, may be of importance in the aetiology of disordered gastrointestinal function in diabetes. […] STZ diabetic rats most often show increased gastric acid secretion [63,64] and increased rates of ulceration [65–71]. This effect is exacerbated by fasting [67] and is reversed by hyperglycaemia [72] but not by insulin replacement [73]. It thus appears that insulin lack is not the ulcerogenic stimulus, and raises the possibility that absence of gastric-inhibitory factors (e.g. amylin, PYY, GLP-1), which may be absent or reduced in diabetes, could be implicated. […] autoimmune type 1 diabetic BB rats [76] and autoimmune non-obese diabetic (NOD) mice [77] in which the gastric mucosa is not an immune target, also show a marked increase in gastric erosions. The constancy of findings of acid hypersecretion and ulceration in insulinopenic diabetes invoked by diverse insults (chemical and autoimmune) indicates that this gastrointestinal disturbance is a direct consequence of the diabetes, and perhaps of β-cell deficiency. […] Amylin […] is a potent inhibitor of gastric acid secretion [88], independent of changes in plasma glucose [89] and prevents gastric erosion in response to a number of irritants [90–92]. These effects appear to be specific to amylin […] It is possible that amylin deficiency could be implicated in a propensity to ulceration in some forms of diabetes. It is unclear whether such a propensity exists in type 1 diabetic adults. However, type 1 diabetic children are reported to have a three- to four-fold elevation in rate of peptic disease [93].”

“Changes in intestinal mucosal function are observed in diabetic rodents, but it is unclear whether these are intrinsic and contributory to the disease process, or are secondary to the disease. […] It […] appears likely […] that diabetes-associated changes in gut enzyme expression represent a response to some aspect of the diabetic state, since they occur in both chemically-induced and genetic models, and are reversible with vigorous treatment of the diabetes. […] While there appear to be no reports that quantify the relationship between acid secretion and rates of nutrient assimilation, there is evidence that type 1 diabetes, in animal models at least, is characterised by disturbed acid regulation.”

“[D]isordered gastrointestinal motility has long been recognised as a frequent feature in diabetic patients who also exhibit neuropathy [125]. Disturbances in gastrointestinal function have been estimated by some to have a prevalence of ∼ 30% (range 5–60% [126–128]). Both peripheral and autonomic [126–128] neuropathy are frequent complications of diabetes mellitus. Since the autonomic nervous system (ANS) plays a prominent role in the regulation of gut motility, a prevailing hypothesis has been that autonomic neuropathic dysfunction could account for much of this disturbance. […] Motor disturbances associated with autonomic neuropathy include dilation of the oesophagus, gastrointestinal stasis, accumulation of digesta and constipation, mainly signs associated with vagal (parasympathetic) dysfunction. There are also reports of faecal incontinence, related to decreased sphincter pressure, and diarrhoea.”

“The best-characterised signs of damage to the autonomic nervous system during diabetes are morphological […] For example, the number of myelinated axons in the vagosympathetic trunk is decreased in diabetic rats [131], as is the number of neurones in dorsal root ganglia and peripheral postganglionic sympathetic nerves. […] In addition to alterations in numbers and morphology of axons, the tissue around the axons is also often disturbed. […] It is of interest that autonomic neuropathy can be prevented or partially reversed by rigorous glycaemic control [137], suggesting that hyperglycaemia per se is of major aetiological importance in autonomic neuropathy. […] Morphological evidence of neuropathy in BB rats includes axonal degeneration, irregularity of myelin sheaths and Mullerian degeneration […] It has been proposed that periodic hypoglycaemia in BB rats may induce Wallerian degeneration and reduced conduction velocity […] while abnormalities associated with chronic hyperglycaemia include sensory (afferent) axonopathy […] The secretion of a number of neuroendocrine substances may be decreased in diabetes. Glucagon, pancreatic polypeptide, gastrin, somatostatin and gastric inhibitory peptide levels are reportedly reduced in the gastrointestinal tract of diabetic patients […] In addition to peripheral autonomic neuropathy, neurons within the central nervous system are also reported to be damaged in animal models of diabetes, including areas […] which are important in controlling those parts of the autonomic nervous system that innervate the gut.”

“Despite ample evidence of morphologic and functional changes in nerves of rodent models of type 1 diabetes mellitus, it is not clear to what extent these changes underly the gastrointestinal dysfunction evident in these animals. Coincidence of neuropathic and gastrointestinal changes does not necessarily prove a causal association between autonomic neuropathy and gastrointestinal dysfunction in diabetes. […] recently recognised neuroendocrine disturbances in diabetes, especially of the β-cell hormone amylin, provide an alternative to the neuropathic hypothesis […] In considering primary endocrine changes associated with type 1 diabetes mellitus, it should be recognised that the central pathogenic event is a selective and near-absolute autoimmune destruction of pancreatic β-cells. Other cell types in the islets, and other tissues, are preserved. The only confirmed hormones currently known to be specific to pancreatic β-cells are insulin and amylin [251]. Recent evidence also suggests that C-peptide, cleaved from proinsulin during intracellular processing and co-secreted with insulin, may also be biologically active [252] […] It is therefore only insulin, C-peptide and amylin that disappear following the selective destruction of β-cells. The implications of this statement are profound; all diabetes-associated sequelae are somehow related to the absence of these (and/or other possibly undiscovered) hormones, whether directly or indirectly […]. Since insulin has minimal direct effect on gut function, until recently the most plausible explanation linking β-cell destruction to changes in gastrointestinal functions was a neuropathic effect secondary to hyperglycaemia. With the recent discovery of multiple physiological gastrointestinal effects of the second β-cell hormone, amylin [255], a plausible alternate explanation of gut dysfunction following β-cell loss has emerged. That is, instead of being due to insulin lack, some gut dysfunction in insulinopenic diabetes may instead be due to the loss of its co-secreted partner, amylin. […] While insulin and amylin are essentially absent in type 1 diabetes, in states of impaired glucose tolerance and early type 2 diabetes, each of these hormones may in fact be hypersecreted […] The ZDF rat is a model of insulin resistance, with some strains developing type 2 diabetes. These animals, which hypersecrete from pancreatic β-cells, exhibit both hyperinsulinaemia and hyperamylinaemia.”

If amylin is hypersecreted in type 2 diabetics and the hormone is absent in type 1 and you do population studies on mixed populations of type 1 and type 2 patients and try to figure out what is going on, you’re going to have some potential issues. The picture seems not too dissimilar to what you see when you look at bone disease in diabetes; type 1s have a high fracture risk, type 2s also have a higher than normal fracture risk, but ‘the effect of diabetes’ is in fact very different in the two groups (in part – but certainly not only – because most type 2s are overweight or obese, and overweight decreases the fracture risk). Some of the relevant pathways of pathophysiological interest are identical in the two patient populations (this is also the case here; acute hyperglycemia is known to cause delayed gastric emptying even in non-diabetics), some are completely different – it’s a mess. This is one reason why I don’t think the confusing results of some of the population studies included early in the book’s coverage – which I decided not to cover in detail here – are necessarily all that surprising.

“Many gastrointestinal reflexes are glucose-sensitive, reflecting their often unrecognised glucoregulatory (restricting elevations of glucose during hyperglycaemia) and counter-regulatory functions (promoting elevation of glucose during hypoglycaemia). Glucose-sensitive effects include inhibition of food intake, control of gastric emptying rate, and regulation of gastric acid secretion and pancreatic enzyme secretion […] Some gastrointestinal manifestations of diabetes may therefore be secondary, and compensatory, to markedly disturbed plasma glucose concentrations. […] It has emerged in recent years that several of the most potent of nearly 60 reported biological actions of amylin [286] are gastrointestinal effects that appear to collectively restrict nutrient influx and promote glucose tolerance. These include inhibition of gastric emptying, inhibition of food intake, inhibition of digestive functions (pancreatic enzyme secretion, gastric acid secretion and bile ejection), and inhibition of nutrient-stimulated glucagon secretion. […] In rats, amylin is the most potent of any known mammalian peptide in slowing gastric emptying […] An amylin agonist (pramlintide), several GLP-1 agonists and exendin-4 are being explored as potential therapies for the treatment of diabetes, with inhibition of gastric emptying being recognised as a mode of therapeutic action. […] The concept of the gut as an organ of metabolic control is yet to be widely accepted, and antidiabetic drugs that moderate nutrient uptake as a mode of therapy have only begun to emerge. A potential advantage such therapies hold over those that enhance insulin action, is their general glucose dependence and low propensity to (per se) induce hypoglycaemia.”

August 29, 2017 Posted by | Books, Diabetes, Gastroenterology, Medicine, Neurology | Leave a comment

Magnetism

This book was ‘okay…ish’, but I must admit I was a bit disappointed; the coverage was much too superficial, and I’m reasonably sure the lack of formalism made the coverage harder for me to follow than it could have been. I gave the book two stars on goodreads.

Some quotes and links below.

Quotes:

“In the 19th century, the principles were established on which the modern electromagnetic world could be built. The electrical turbine is the industrialized embodiment of Faraday’s idea of producing electricity by rotating magnets. The turbine can be driven by the wind or by falling water in hydroelectric power stations; it can be powered by steam which is itself produced by boiling water using the heat produced from nuclear fission or burning coal or gas. Whatever the method, rotating magnets inducing currents feed the appetite of the world’s cities for electricity, lighting our streets, powering our televisions and computers, and providing us with an abundant source of energy. […] rotating magnets are the engine of the modern world. […] Modern society is built on the widespread availability of cheap electrical power, and almost all of it comes from magnets whirling around in turbines, producing electric current by the laws discovered by Oersted, Ampère, and Faraday.”

“Maxwell was the first person to really understand that a beam of light consists of electric and magnetic oscillations propagating together. The electric oscillation is in one plane, at right angles to the magnetic oscillation. Both of them are in directions at right angles to the direction of propagation. […] The oscillations of electricity and magnetism in a beam of light are governed by Maxwell’s four beautiful equations […] Above all, Einstein’s work on relativity was motivated by a desire to preserve the integrity of Maxwell’s equations at all costs. The problem was this: Maxwell had derived a beautiful expression for the speed of light, but the speed of light with respect to whom? […] Einstein deduced that the way to fix this would be to say that all observers will measure the speed of any beam of light to be the same. […] Einstein showed that magnetism is a purely relativistic effect, something that wouldn’t even be there without relativity. Magnetism is an example of relativity in everyday life. […] Magnetic fields are what electric fields look like when you are moving with respect to the charges that ‘cause’ them. […] every time a magnetic field appears in nature, it is because a charge is moving with respect to the observer. Charge flows down a wire to make an electric current and this produces magnetic field. Electrons orbit an atom and this ‘orbital’ motion produces a magnetic field. […] the magnetism of the Earth is due to electrical currents deep inside the planet. Motion is the key in each and every case, and magnetic fields are the evidence that charge is on the move. […] Einstein’s theory of relativity casts magnetism in a new light. Magnetic fields are a relativistic correction which you observe when charges move relative to you.”

“[T]he Bohr–van Leeuwen theorem […] states that if you assume nothing more than classical physics, and then go on to model a material as a system of electrical charges, then you can show that the system can have no net magnetization; in other words, it will not be magnetic. Simply put, there are no lodestones in a purely classical Universe. This should have been a revolutionary and astonishing result, but it wasn’t, principally because it came about 20 years too late to knock everyone’s socks off. By 1921, the initial premise of the Bohr–van Leeuwen theorem, the correctness of classical physics, was known to be wrong […] But when you think about it now, the Bohr–van Leeuwen theorem gives an extraordinary demonstration of the failure of classical physics. Just by sticking a magnet to the door of your refrigerator, you have demonstrated that the Universe is not governed by classical physics.”

“[M]ost real substances are weakly diamagnetic, meaning that when placed in a magnetic field they become weakly magnetic in the opposite direction to the field. Water does this, and since animals are mostly water, it applies to them. This is the basis of Andre Geim’s levitating frog experiment: a live frog is placed in a strong magnetic field and because of its diamagnetism it becomes weakly magnetic. In the experiment, a non-uniformity of the magnetic field induces a force on the frog’s induced magnetism and, hey presto, the frog levitates in mid-air.”

“In a conventional hard disk technology, the disk needs to be spun very fast, around 7,000 revolutions per minute. […] The read head floats on a cushion of air about 15 nanometres […] above the surface of the rotating disk, reading bits off the disk at tens of megabytes per second. This is an extraordinary engineering achievement when you think about it. If you were to scale up a hard disk so that the disk is a few kilometres in diameter rather a few centimetres, then the read head would be around the size of the White House and would be floating over the surface of the disk on a cushion of air one millimetre thick (the diameter of the head of a pin) while the disk rotated below it at a speed of several million miles per hour (fast enough to go round the equator a couple of dozen times in a second). On this scale, the bits would be spaced a few centimetres apart around each track. Hard disk drives are remarkable. […] Although hard disks store an astonishing amount of information and are cheap to manufacture, they are not fast information retrieval systems. To access a particular piece of information involves moving the head and rotating the disk to a particular spot, taking perhaps a few milliseconds. This sounds quite rapid, but with processors buzzing away and performing operations every nanosecond or so, a few milliseconds is glacial in comparison. For this reason, modern computers often use solid state memory to store temporary information, reserving the hard disk for longer-term bulk storage. However, there is a trade-off between cost and performance.”

“In general, there is a strong economic drive to store more and more information in a smaller and smaller space, and hence a need to find a way to make smaller and smaller bits. […] [However] greater miniturization comes at a price. The point is the following: when you try to store a bit of information in a magnetic medium, an important constraint on the usefulness of the technology is how long the information will last for. Almost always the information is being stored at room temperature and so needs to be robust to the ever present random jiggling effects produced by temperature […] It turns out that the crucial parameter controlling this robustness is the ratio of the energy needed to reverse the bit of information (in other words, the energy required to change the magnetization from one direction to the reverse direction) to a characteristic energy associated with room temperature (an energy which is, expressed in electrical units, approximately one-fortieth of a Volt). So if the energy to flip a magnetic bit is very large, the information can persist for thousands of years […] while if it is very small, the information might only last for a small fraction of a second […] This energy is proportional to the volume of the magnetic bit, and so one immediately sees a problem with making bits smaller and smaller: though you can store bits of information at higher density, there is a very real possibility that the information might be very rapidly scrambled by thermal fluctuations. This motivates the search for materials in which it is very hard to flip the magnetization from one state to the other.”

“The change in the Earth’s magnetic field over time is a fairly noticeable phenomenon. Every decade or so, compass needles in Africa are shifting by a degree, and the magnetic field overall on planet Earth is about 10% weaker than it was in the 19th century.”

Below I have added some links to topics and people covered/mentioned in the book. Many of the links below have likely also been included in some of the other posts about books from the A Brief Introduction OUP physics series which I’ve posted this year – the main point of adding these links is to give some idea what kind of stuff’s covered in the book:

Magnetism.
Magnetite.
Lodestone.
William Gilbert/De Magnete.
Alessandro Volta.
Ampère’s circuital law.
Charles-Augustin de Coulomb.
Hans Christian Ørsted.
Leyden jar
/voltaic cell/battery (electricity).
Solenoid.
Electromagnet.
Homopolar motor.
Michael Faraday.
Electromagnetic induction.
Dynamo.
Zeeman effect.
Alternating current/Direct current.
Nikola Tesla.
Thomas Edison.
Force field (physics).
Ole Rømer.
Centimetre–gram–second system of units.
James Clerk Maxwell.
Maxwell’s equations.
Permittivity.
Permeability (electromagnetism).
Gauss’ law.
Michelson–Morley experiment
.
Special relativity.
Drift velocity.
Curie’s law.
Curie temperature.
Andre Geim.
Diamagnetism.
Paramagnetism.
Exchange interaction.
Magnetic domain.
Domain wall (magnetism).
Stern–Gerlach experiment.
Dirac equation.
Giant magnetoresistance.
Spin valve.
Racetrack memory.
Perpendicular recording.
Bubble memory (“an example of a brilliant idea which never quite made it”, as the author puts it).
Single-molecule magnet.
Spintronics.
Earth’s magnetic field.
Aurora.
Van Allen radiation belt.
South Atlantic Anomaly.
Geomagnetic storm.
Geomagnetic reversal.
Magnetar.
ITER (‘International Thermonuclear Experimental Reactor’).
Antiferromagnetism.
Spin glass.
Quantum spin liquid.
Multiferroics.
Spin ice.
Magnetic monopole.
Ice rules.

August 28, 2017 Posted by | Books, Computer science, Geology, Physics | Leave a comment

Quotes

i. “If you don’t understand something, break it apart; reduce it to its components. Since they are simpler than the whole, you have a much better chance of understanding them; and when you have succeeded in doing that, put the whole thing back together again.” (Hans Christian Von Baeyer)

ii. “It is the great glory of the quest for human knowledge that, while making some small contribution to that quest, we can also continue to learn and to take pleasure in learning.” (William A. Fowler)

iii. “The younger we are, the more each individual object represents for us the whole class to which it belongs.” (Arthur Schopenhauer)

iv. “You never know what is enough unless you know what is more than enough.” (William Blake)

v. “The least offensive way of refusing a request is not to let it be made.” (Rex Stout)

vi. “Memory is the medium of the must-have-been.” (Julian Jaynes)

vii. “Words do not change their meanings so drastically in the course of centuries as, in our minds, names do in the course of a year or two.” (Marcel Proust)

viii. “In all pointed sentences, some degree of accuracy must be sacrificed to conciseness.” (Samuel Johnson)

ix. “An infant of two or three months will smile at even half a painted dummy face, if that half of the face is fully represented and has at least two clearly defined points or circles for eyes; more the infant does not need, but he will not smile for less. The infant’s instinctive smile seems to have exactly that purpose which is its crowning effect, namely, that the adult feels recognized, and in return expresses recognition in the form of loving and providing.” (Erik Homburger Erikson)

x. “It is death, and not what comes after death, that men are generally afraid of.” (Samuel Butler)

xi. “All I desire for my own burial is not to be buried alive.” (Philip Dormer Stanhope, 4th Earl of Chesterfield)

xii. “Every man who deserves to be famous knows it is not worth the trouble.” (Fernando Pessoa)

xiii. “We cannot tear out a single page of our life, but we can throw the whole book in the fire.” (George Sand)

xiv. “People pontificate, “Suicide is selfishness.” Career churchmen like Pater go a step further and call it a cowardly assault on the living. Oafs argue this specious line for varying reasons: to evade fingers of blame, to impress one’s audience with one’s mental fiber, to vent anger, or just because one lacks the necessary suffering to sympathize. Cowardice is nothing to do with it – suicide takes considerable courage. Japanese have the right idea. No, what’s selfish is to demand another to endure an intolerable existence, just to spare families, friends, and enemies a bit of soul-searching” (David Mitchell)

xv. “Those who do not feel pain seldom think that it is felt.” (Samuel Johnson)

xvi. “In quarreling, the truth is always lost.” (Publilius Syrus)

xvii. “La recherche de la vérité est la plus noble des occupations, et sa publication un devoir.” (Anne Louise Germaine De Staël)

xviii. “The present enables us to understand the past, not the other way round.” (Alan John Percivale Taylor)

xix. “The long habit of living indisposeth us for dying.” (Thomas Browne)

xx. “People who think they’re generous to a fault usually think that’s their only fault.” (Sydney J. Harris)

August 26, 2017 Posted by | Quotes/aphorisms | Leave a comment

A few diabetes papers of interest

i. Eating Disorders in Girls and Women With Type 1 Diabetes: A Longitudinal Study of Prevalence, Onset, Remission, and Recurrence.

If these results can be trusted, then the prevalence of eating disorders in young female diabetics is disturbingly high. Some quotes:

“The prevalence, clinical characteristics, and medical consequences of disturbed eating behavior (DEB) and eating disorders (EDs) in individuals with type 1 diabetes has received increasing attention since case reports of this dangerous combination were first published in the 1980s (1,2). Although the specificity of this association was initially unclear, systematic research has demonstrated that teenage girls and women with type 1 diabetes are at significantly increased risk of DEB compared with their nondiabetic peers (3). Such DEB includes dieting, fasting, binge-eating, and a range of compensatory and purging behaviors that can directly interfere with optimal diabetes management. […] Deliberately underdosing or omitting insulin to induce hyperglycemia and loss of glucose in the urine, and thereby control weight, is a unique purging behavior to control weight that is available to individuals with type 1 diabetes (4). This is an important mediator of the association of DEB and EDs with poorer metabolic control (5,6) and contributes to an increased risk of a range of short-term and long-term diabetes-related medical complications. These include abnormal lipid profiles (7), diabetic ketoacidosis (6), retinopathy (8), neuropathy (9), and nephropathy (10), as well as higher than expected mortality (11).”

“Bryden et al. (13) assessed a group of individuals with type 1 diabetes in adolescence and then again in early adulthood. […] They found EDs or other significant eating problems in 26% of participants, as well as significant associations between eating problems, insulin misuse, and microvascular complications (14). Goebel-Fabbri et al. (15) assessed 234 adult women with type 1 diabetes twice over an 11-year period. They found insulin omission for weight control to be very common (reported by 30% at baseline). Insulin omission frequently persisted over the lengthy follow-up period and was associated with higher rates of diabetes-related medical complications and tripled risk of mortality.”

“This study describes the longitudinal course of disturbed eating behavior (DEB) and EDs in a cohort with type 1 diabetes. […] A total of 126 girls with type 1 diabetes receiving care for diabetes at The Hospital for Sick Children in Toronto participated in a series of seven interview-based assessments of ED behavior and psychopathology over a 14-year period, beginning in late childhood. […] Mean age was 11.8 ± 1.5 years at time 1 and 23.7 ± 2.1 years at time 7. At time 7, 32.4% (23/71) met the criteria for a current ED, and an additional 8.5% (6/71) had a subthreshold ED. Mean age at ED onset (full syndrome or below the threshold) was 22.6 years (95% CI 21.6–23.5), and the cumulative probability of onset was 60% by age 25 years. […] The average time between remission of ED and subsequent recurrence was 6.5 years (95% CI 4.4–8.6), and the cumulative probability of recurrence was 53% by 6 years after remission.”

“In this longitudinal study, EDs were common and persistent, and new onset of ED was documented well into adulthood. […] [The] rates provide evidence that disordered eating is a common and serious concern among girls and young women with type 1 diabetes. Although adolescent and adult women in the general population also frequently report dieting, rates of more extreme weight loss behaviors and clinical eating disorders tend to be lower than those that occurred in this study (22,2830). […] The point prevalence for DEB and ED continued to increase across the study, largely because of marked increases in reported insulin omission for weight loss. Of particular concern, insulin omission as a weight control method was reported by 27% of participants at time 7. This dangerous method of purging directly compromises metabolic control and confers both short-term and long-term medical risk. Other researchers found it to be highly persistent among adult women with type 1 diabetes and associated with increased morbidity and mortality (10,15). […] In this study, both DEB and EDs tended to be persistent, with a mean time from observed onset to detected remission of 6.0 and 4.3 years, respectively, and significant estimated risk of recurrence among those whose eating disturbances initially remitted. […] The high prevalence of DEB and EDs among women with type 1 diabetes, in addition to high incidence of new ED cases continuing into the young adult years, suggests that sustained efforts at prevention, detection, and treatment of eating disturbances are needed across the adolescent and young adult years among women with type 1 diabetes.”

ii. Excess Risk of Dying From Infectious Causes in Those With Type 1 and Type 2 Diabetes.

“Individuals with type 1 and type 2 diabetes are widely considered to be more prone to infections than those without diabetes (1). […] The underlying pathology for an increased risk of infections among people with diabetes is not fully elucidated and is probably multifactorial. However, there are some data to suggest that it could, in part, relate to a compromised immune system. Short- and long-term hyperglycemia may disturb immune functions such as neutrophil bactericidal function (13), cellular immunity (14), and complement activation (15). These defects in the immune system, along with vascular insufficiency, render patients with diabetes at higher risk for a variety of severe or invasive infections compared with those without diabetes (16).”

“While there is a reasonably good understanding of the biological link between diabetes and infection, there are few data quantifying the excess risk of acquiring an infection or dying from infections associated with diabetes. […] the objective of this study was to examine the excess risk of death from several infectious causes in those with type 1 and type 2 diabetes compared with the general population and to see if this excess risk differs by age and over time. […] A total of 1,108,982 individuals with diabetes who were registered with the Australian Diabetes register between 2000 and 2010 were linked to the National Death Index. Mortality outcomes were defined as infection-relatedA-B death (ICD codes A99–B99), pneumonia (J12–J189), septicemia (A40 and A41), and osteomyelitis (M86). […] During a median follow-up of 6.7 years, there were 2,891, 2,158, 1,248, and 147 deaths from infection-relatedA-B causes, pneumonia, septicemia, or osteomyelitis, respectively. Crude mortality rates from infectionsA-B were 0.147 and 0.431 per 1,000 person-years in type 1 and type 2 diabetes, respectively. Standardized mortality ratios (SMRs) were higher in type 1 and type 2 diabetes for all outcomes after adjustment for age and sex. For infection-relatedA-B mortality, SMRs were 4.42 (95% CI 3.68–5.34) and 1.47 (1.42–1.53) for type 1 and type 2 diabetes (P < 0.001), respectively. For pneumonia in type 1 diabetes, SMRs were approximately 5 and 6 in males and females, respectively, while the excess risk was ∼20% for type 2 (both sexes). For septicemia, SMRs were approximately 10 and 2 for type 1 and type 2 diabetes, respectively, and similar by sex. For osteomyelitis in type 1 diabetes, SMRs were 16 and 58 in males and females, respectively, and ∼3 for type 2 diabetes (both sexes).”

“This prospective study of more than one million people with diabetes provides evidence that individuals with type 1 and type 2 diabetes are more likely to die of infection-related death, in particular death due to pneumonia, septicemia, and osteomyelitis, compared with the general population. These data show that infection in those with diabetes is an important cause of mortality. […] the increased risk appears to be greater for type 1 than type 2 diabetes. […] Patients with diabetes have a higher case fatality from infections than those without diabetes (17,30), which is both due to altered host immunity and due to having a higher prevalence of comorbidities, which places them at increased risk of death.”

iii. Effects of Acute Hypoglycemia on Working Memory and Language Processing in Adults With and Without Type 1 Diabetes.

“Cognitive function is impaired during acute hypoglycemia and frequently affects people with type 1 diabetes (1,2); elucidation of which cognitive domains are affected and by how much is of practical importance. Although cognitive domains do not function independently of each other, it is pertinent to design studies that investigate how everyday activities are affected by hypoglycemia as this has direct relevance to people with diabetes. Previous studies have demonstrated the effects of hypoglycemia on specific cognitive domains, including memory, attention, nonverbal intelligence, visual and auditory information processing, psychomotor function, spatial awareness, and executive functioning (314). However, the effects of hypoglycemia on language processing have seldom been explored.”

“Slurred speech and language difficulties are recognized features of hypoglycemia, but to our knowledge, the effects of hypoglycemia on linguistic processing have not been studied systematically. The current study used transient insulin-induced hypoglycemia in adults with and without type 1 diabetes to examine its effects on three aspects of language: the relationship between working memory and language (reading span), grammatical decoding (self-paced reading), and grammatical encoding (producing subject-verb agreement). Tests of these issues have been used extensively to understand the nature of language processing and its relationship to other cognitive abilities, specifically working memory (17).”

“Forty adults were studied (20 with type 1 diabetes and 20 healthy volunteers) using a hyperinsulinemic glucose clamp to lower blood glucose to 2.5 mmol/L (45 mg/dL) (hypoglycemia) for 60 min, or to maintain blood glucose at 4.5 mmol/L (81 mg/dL) (euglycemia), on separate occasions. Language tests were applied to assess the effects of hypoglycemia on the relationship between working memory and language (reading span), grammatical decoding (self-paced reading), and grammatical encoding (subject-verb agreement). […] Hypoglycemia caused a significant deterioration in reading span (P < 0.001; η2 = 0.37; Cohen d = 0.65) and a fall in correct responses (P = 0.005; η2 = 0.19; Cohen d = 0.41). On the self-paced reading test, the reading time for the first sentence fragment increased during hypoglycemia (P = 0.039; η2 = 0.11; Cohen d = 0.25). […] Hypoglycemia caused a deterioration of subject-verb agreement (correct responses: P = 0.011; η2 = 0.159; Cohen d = 0.31).”

“[We] demonstrated a significant deterioration in the accuracy of subject-verb agreement and also in reading span, a measure of working memory. This latter finding is compatible with the results of a previous study by our group (14) that used a different cognitive test battery but had an identical study design. In the current study, performance in the TMB and DST was significantly impaired during hypoglycemia, consistent with previous observations (57,1012,24) and confirming that adequate hypoglycemia had been achieved to impair cognitive function. […] Different mental functions have been shown to vary in their sensitivity to neuroglycopenia. […] higher-level skills are more vulnerable to hypoglycemia than simple cognitive tasks (1). In addition, during hypoglycemia, speed is usually killed in order to preserve accuracy (1). […] results strongly suggest that hypoglycemia induces difficulties in seemingly easy linguistic tasks such as correctly reading aloud a simple sentence fragment and its completion. Compared with other clamp studies exploring the effects of hypoglycemia on cognitive function, this was a large study that recruited both participants with and participants without diabetes. The fact that similar results were obtained in both groups suggests that these effects on language relate to acute hypoglycemia rather than to a chronic alternation of glycemic status in diabetes.” [My bold – US. These observations seem to corroborate observations I’ve made myself in the past.]

iv. Current State of Type 1 Diabetes Treatment in the U.S.: Updated Data From the T1D Exchange Clinic Registry.

Figure 1 from this paper is the sort of image which is worth a 1000 words.

Some observations from the paper:

“Data from 16,061 participants updated between 1 September 2013 and 1 December 2014 were compared with registry enrollment data collected from 1 September 2010 to 1 August 2012. […] The overall average HbA1c was 8.2% (66 mmol/mol) at enrollment and 8.4% (68 mmol/mol) at the most recent update. During childhood, mean HbA1c decreased from 8.3% (67 mmol/mol) in 2–4-year-olds to 8.1% (65 mmol/mol) at 7 years of age, followed by an increase to 9.2% (77 mmol/mol) in 19-year-olds. Subsequently, mean HbA1c values decline gradually until ∼30 years of age, plateauing at 7.5–7.8% (58–62 mmol/mol) beyond age 30 until a modest drop in HbA1c below 7.5% (58 mmol/mol) in those 65 years of age. Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) remain all too common complications of treatment, especially in older (SH) and younger patients (DKA). […] Although the T1D Exchange registry findings are not population based and could be biased, it is clear that there remains considerable room for improving outcomes of treatment of type 1 diabetes across all age-groups.”

“[M]ean HbA1c values showed a gradual decline until ∼30 years of age, plateauing at a level of 7.5–7.8% (58–62 mmol/mol) beyond age 30 until a modest drop in HbA1c below 7.5% (58 mmol/mol) after 65 years of age. The ADA HbA1c goal of <7.5% (58 mmol/mol) was achieved by only a small percentage of children and adolescents <18 years of age (17–23%), and even fewer 18–25-year-olds (14%) met the ADA goal for adults of <7.0% (53 mmol/mol); this percentage increased to ∼30% in older adults […] across all age-groups, HbA1c was highest among non-Hispanic black participants, participants with lower annual household income, and those who performed SMBG less than four times per day […] On average, participants using an insulin pump or continuous glucose monitor tended to have lower HbA1c values [….] Among the subset of 2,561 participants who completed the participant questionnaire, 6% reported having had a seizure or loss of consciousness due to hypoglycemia in the prior 3 months, with the highest occurrence being among those who were 50 years old or older.”

“The most troubling aspect of the data is that the mean HbA1c level of 9.0% (75 mmol/mol) in 13–17-year-olds in the registry is only slightly lower than the 9.5% (80 mmol/mol) seen in 13–17-year-olds at the start of the DCCT in the 1980s (15). Clearly, advances in diabetes management over the past two decades have been less successful in overcoming the special challenges in managing teenagers than adults with type 1 diabetes. Our data also indicate that the majority of “emerging adults” in their 20s do not fully emerge with regard to glycemic control until they reach 30 years of age. […] In a cross-sectional comparison, the average HbA1c at the most recent update was higher than at enrollment (8.4 vs. 8.2% [68 vs. 66 mmol/mol]), suggesting a worsening in glycemic control over time. The greatest increase in HbA1c was observed in the 13–17 (9.0 vs. 8.7% [75 vs. 72 mmol/mol]) and 18–26-year-old (8.7 vs. 8.3% [72 vs. 67 mmol/mol]) groups. Although this could reflect differences in age and type 1 diabetes duration, the results nevertheless indicate that there certainly is no indication of improving glycemic control in these age-groups.”

v. Prevention and Reversal of Type 1 Diabetes — Past Challenges and Future Opportunities.

“Over the past three decades there have been a number of clinical trials directed at interdicting the type 1 diabetes (T1D) disease process in an attempt to prevent the development of the disease in those at increased risk or to stabilize — potentially even reverse — the disease in people with T1D, usually of recent onset. Unfortunately, to date there has been no prevention trial that has resulted in delay or prevention of T1D. […] Since the completion of the early trials, particularly during the past decade, a number of additional randomized, double-masked, adequately powered, controlled clinical trials have been conducted using many different immunological strategies. For the most part, these have been disappointing, with none showing unambiguous benefit in preserving β-cell function. […] [M]ost immune intervention trials in T1D have either failed to achieve success in preserving β-cell function or have met that hurdle but have nonetheless shown only a transient effect.”

vi. Diabetic Peripheral Neuropathy Compromises Balance During Daily Activities.

“Patients with diabetic peripheral neuropathy (DPN) have an altered gait strategy (13) and a fivefold increased risk of falling (46). Falling is a major health risk in many developed countries; for example, in the general U.K. population, over a quarter of accidents that required hospital treatment were the result of a fall (7). A fall is preceded by loss of balance, which may be recoverable in some individuals, but requires rapid responses and a high level of strength from the lower-limb muscles (8,9). Nevertheless, the more likely an individual is to lose balance, the more likely they will at some point experience a fall. Therefore, quantifying balance control during every day gait activities may be considered one of the closest proxies for the risk of falling.”

“During walking activities, when an individual transfers their weight from one limb to another there are brief periods of large separation between the center of mass and the center of pressure. High levels of muscular strength are required to maintain balance during these periods. These large separations between the center of mass and center of pressure experienced during the single stance periods of dynamic gait activities may be a contributing factor toward understanding why the risk of falling during gait activities is much greater than during quiet standing. Few studies, however, have attempted to address the issue of balance during walking in patients with diabetes, and none have addressed the much more physically challenging activities of stair ascent and descent, during which the risk of falling is known to be very high (7). We therefore investigated a more “dynamic” measure of balance during stair ascent, stair descent, and level walking — three activities with the highest risk of fall-related injury (7) — with the hypothesis that individuals with peripheral neuropathy would display greater separations between their center of mass and center of pressure (i.e., poorer balance), thereby contributing to explaining why they are at high risk of falls.”

“Gait analysis during level walking and stair negotiation was performed in 22 patients with diabetic neuropathy (DPN), 39 patients with diabetes without neuropathy (D), and 28 nondiabetic control subjects (C) using a motion analysis system and embedded force plates in a staircase and level walkway. Balance was assessed by measuring the separation between the body center of mass and center of pressure during level walking, stair ascent, and stair descent. […] DPN patients demonstrated greater (P < 0.05) maximum and range of separations of their center of mass from their center of pressure in the medial-lateral plane during stair descent, stair ascent, and level walking compared with the C group, as well as increased (P < 0.05) mean separation during level walking and stair ascent. The same group also demonstrated greater (P < 0.05) maximum anterior separations (toward the staircase) during stair ascent. […] Greater separations of the center of mass from the center of pressure present a greater challenge to balance. Therefore, the higher medial-lateral separations found in patients with DPN will require greater muscular demands to control upright posture. This may contribute to explaining why patients with DPN are more likely to fall, with the higher separations placing them at a higher risk of experiencing a sideways fall than nondiabetic control subjects. […] balance is markedly impaired in patients with DPN during the gait activities of level ground walking, stair ascent, and stair descent. […] During the gait tasks, we found no significant balance impairments in patients with diabetes without DPN, clearly emphasizing that the link between diabetes and instability is a symptom of peripheral neuropathy.”

August 26, 2017 Posted by | Diabetes, Infectious disease, Language, Neurology, Studies | Leave a comment