“Data from animal studies in one country are usually comparable with that of another, provided the animal species and strain are the same. This provides a consistent picture of the basic pharmacological and toxicological actions of a candidate drug in a living organism […] it has been obvious since animal testing began that there would be large differences in the way a drug might perform in man compared with animal species […]. Unfortunately, there is no experimental model yet designed that can not only consider human biochemistry and physiology, but also the effects of age, smoking, legal and illegal drug usage, gender, diet, environment, disease and finally genetic variation. Indeed, many clinical studies have revealed enormous differences in drug clearance and pharmacological effect even in age, sex and ethnically matched individuals. In effect, this means that the first year or so of a drug’s clinical life is a vast, but monitored experiment, involving hundreds of thousands of patients and there is no guarantee of success.”
“Most biotransformational polymorphisms that might potentially cause a problem clinically are due to an inability of those with defective enzymes to remove the drug from the system. Drug failure can occur if the agent is administered as a pro-drug and requires some metabolic conversion to an active metabolite. Drug accumulation can lead to unpleasant side effects and loss of patient tolerance for the agent. […] Overall, there are a large number of factors that can influence drug metabolism, either by increasing clearance to cause drug failure, or by preventing clearance to lead to toxicity. In the real world, it is often impossible to delineate the different conflicting factors which result in net changes in drug clearance which cause a drug to fall out of, or climb above, the therapeutic window. It may only be possible clinically in many cases to try to change what appears to be the major cause to bring about a resolution of the situation to restore curative and non-toxic drug levels.”
“Most population studies of human polymorphisms list the allelic frequency, that is, how many of an ethnic group contain the alleles in question. […] The actual haplotypes in the population, that is, which individuals express which combinations of alleles, are not the same as the population allelic frequency. […] If an SNP or a combination of SNPs is a fairly mild defect in the enzyme when it is homozygously expressed, then the heterozygotes will show little impairment and the polymorphism may be clinically irrelevant. With other SNPs, the enzyme produced may be completely non-functional. Homozygotes will be virtually unable to clear the drug and heterozygotes will show impairment also. There are also smaller populations of UMs, or ultra rapid metabolizers which may have a feature of their enzyme which either makes it super efficient or expressed in abnormally high amounts. […] Phenotyping will group patients in very broad EMs [extensive metabolizers], IMs [intermediate metabolizers] or PM [poor metabolizers] categories, but will be unable to distinguish between heterozygous and homozygous EMs. Although genotyping may be very helpful in dosage estimation in the initiation of therapy, there is no substitute for the normal process of therapeutic monitoring, which is effectively phenotyping the individual in the real world in terms of maximizing response and minimizing toxicity.”
“it is clear that there is a vast amount of genetic variation across humanity in terms of biotransformational capability and so the idea that in therapeutics, ‘one size fits all’ is not only outdated, but fabulously naïve. […] Unfortunately, detecting and responding successfully to human biotransformational polymorphisms has proved to be extremely problematic. In terms of polymorphism detection, this area is a classic illustration of how the exploration of the human genome with powerful molecular biological tools may unearth many apparently marked polymorphic defects that may not necessarily translate into a measurable clinical impact in terms of efficacy and toxicity. In reality, many more scientists have the opportunity to discover and publish such polymorphisms in vitro, than there are clinical scientists, resources and indeed cooperative volunteers or patients in sufficient quantity to determine practical clinical relevance.”
“the CYP3A group (chromosome 7) metabolize around half of all drugs […] variation in the metabolism of CYP3A substrates […] can be up to ten-fold in terms of drug clearances and up to 90-fold in liver protein expression. […] It is likely that the full extent of the variation in CYP3A4 is still to be discovered […] While it is thought that CYP3A4 is not subject to an obvious major polymorphism, CYP3A5 definitely is. […] *3/*3 individuals form no serviceable CYP3A5. Functional CYP3A5 is found in around 20 per cent of Caucasians, half of Chinese/Japanese, 70 per cent of Hispanics and more than 80 per cent of African Americans.”
“A particularly dangerous polymorphism clinically was identified in the 1980s for one of the methyltransferases. The endogenous role of S-methylating thiopurine S-methyltransferase (TPMT) is not that clear, but […] [t]hese drugs are […] effective in some childhood leukaemias […] TPMT highlights the genotyping/phenotyping issue mentioned earlier in the management of patients with polymorphisms. Genotyping will reveal the level of TPMT expression that should be expected in the otherwise healthy patient. However, there are many factors which impact day-to-day TPMT expression during thiopurine therapy. […] Hence, what might be predicted from a genotype test may bear little resemblance to how the enzyme is performing on a particular day in a treatment cycle. So clinically, it is preferred to test actual TPMT activity.”
“Understanding of sulphonation and its roles in endogenous as well as xenobiotic metabolism is not as advanced compared with that of CYPs; however, the role of SULTs in the activation of carcinogens is becoming more apparent. One of the major influences on SULT activity is their polymorphic nature; in the case of one of the most important toxicologically relevant SULTs, SULT1A1, this isoform exists as three variants, SULT1A1*1 (wild-type), SULT1A1*2 and SULT1A1*3. The *1 variant allele is found in the majority of Caucasians (around 65 per cent), whilst the *2 variant differs only in the exchange of one amino acid for another. This single amino acid change has profound effects on the stability and catalytic activity of the isoform. The *2 variant is found in approximately 32 per cent of Caucasians and catalytically faulty […] About 9 in 10 Chinese people have the *1 allele and about 8 per cent have allele *2. About half of African-Americans have *1 and a third have *2. Interestingly, there is a *3 which is rare in most races but accounts for more than 22 per cent of African Americans. There is also considerable variation in SULT2A1 and SULT2B1, which are the major hydroxysteroid sulphators in the body, which may have implications for sex steroid and cholesterol handling. […] from the cancer-risk viewpoint, a highly active SULT1A1 *1 is usually an advantage in that it usually removes reactive species rapidly as stable sulphates. With some agents it is problematic as certain carcinogens such as acetylfluorene are indirectly activated to reactive species by SULTs. In addition, protective dietary flavonoids […] are also rapidly cleared by SULT1A1 *1, so there is a combination of production of toxins and loss of protective dietary agents. In terms of carcinogenesis risk, SULT1A1*2 could be a liability as potentially damaging substrates such as electrophilic toxins cannot be cleared rapidly. However, in some circumstances the *2 allele can be rather protective as […] it also allows protective agents [to] remain in tissues for longer periods. The combinations are endless and so it is often extremely difficult to predict risks of carcinogenicity for individuals and toxin exposures.”
“GSTs are polymorphic and much research has been directed at linking increased predisposition to cytotoxicity and carcinogenicity with defective GST phenotypes. Active wild-type GSTMu-1 is found in around 60 per cent of Caucasians, but a non-functional version of the isoform is found in the remainder. […] GST-M1 null (non-functional alleles) can predispose to risks of prostate abnormalities and GST Pi is subject to several SNPs and many attempts have been made to link these SNPs with the consequences of failure to detoxify reactive species, such as the risk of lung cancer. […] Carcinogenesis may be due to a complex mix of factors, where different enzyme expression and activities may combine with particular reactive species from specific parent xenobiotics that lead to DNA damage only in certain individuals. Resolving specific risk factors may be extremely difficult in such circumstances. […] in cancer chemotherapy, there is evidence that the presence of GST-M1 and GST-T1 null (non-functional) alleles predisposes children to a six-fold higher level of adverse events usually seen with antineoplastic drugs, such as bone marrow damage, nephrotoxicity and neurotoxicity.”
“The effects of age on drug clearance and metabolism have been known since the 1950s, but they have been extensively investigated in the last 20 or so years. It is now generally accepted that at the extremes of life, neonatal and geriatric, drug clearance can be significantly different from the rest of humanity. In general, neonates, i.e. those less than four weeks old, cannot clear certain agents due to immaturity of drug metabolizing systems. Those over retirement age cannot clear the drugs due to loss of efficiency in their metabolizing systems. Either way, the net result can be toxicity due to drug accumulation. […] It seems that the inability of older people to clear drugs is not necessarily related to the efficacy of their CYP-mediated oxidations, which are often not much different from that of younger individuals. Studies with the major CYPs in vitro have revealed that CYP2D6 is unaffected by age, as are most other CYPs, with the exception of CYP1A2, which does decline in activity in the elderly. […] In general, there is little significant change in the inducibility in most CYPs, or in the capability of conjugation systems in vitro. […] there are significant changes in the liver itself, as it decreases in mass and its blood flow is reduced as we age. This occurs at the rate of around 0.5–1.5 per cent per year, so by the time we hit 60–70, we may have up to a 40 per cent decline in liver blood flow compared with a 30-year-old. Other factors include gradual decline in renal function, increased fat deposits and reduction in gut blood flow, which affects absorption. […] The problem arises that the drug’s bioavailability increases due to lack of first-pass clearance; this means that from a standard dose, blood levels can be considerably higher than would be expected in a 40-year-old. This can be a serious problem in drugs with a narrow TI, such as antiarrhythmics. In addition, average doses of warfarin required to provide therapeutic anticoagulation in the elderly are less than half those required for younger people. The person’s lifelong smoking and drinking habits, as well as older individuals ’ sometimes erratic diet also complicate this situation. Among the drugs cleared more slowly in older people are antipsychotics, paracetamol, antidepressants, benzodiazepines, warfarin, beta-blockers and indomethicin.”
“Thousands of polyphenols are found in plants, vegetables, fruit, as well as tea, coffee, wine and fruit juices. […] Flavonoids such as quercetin and fisetin are excellent substrates for COMT, so competitively inhibiting the metabolism of endogenous catecholamine and catechol oestrogens. Quercetin and other polyphenols are found in various foods such as soy (genestein) and they are potent inhibitors of SULT1A1 which sulphate endogenous oestrogens, so potentiating the effects of oestrogens in the body. Many of these flavonoids and isoflavonoids are manufactured and sold as cancer preventative agents; however, it is more likely that their elevation of oestrogen levels may have the opposite effect in the long term. It is also likely that various polyphenols influence other endogenous substrates of sulphotransferases, such as thyroid hormones and various catecholamines. It is gradually becoming apparent that polyphenols can induce UGTs, indeed; it would be surprising if they did not. […] Overall, it is likely that there are a large number of polyphenols that are potent modulators of CYPs and conjugative enzymes. […] It is clear that diet can substantially modulate biotransformation […] As to the effects on prescription drugs, […] abrupt changes in a person’s diet may significantly alter the clearance of drugs and lead to loss of efficacy or toxicity.”
“In general, experimental or ‘probe’ drugs […] which are used to study the activities of a number of CYPs, are metabolized more quickly by women than men. This is allowing for differences in weight, fat distribution (body mass index) and volume of distribution […] It appears that CYP expression is linked to growth hormone (GH) and about the same amount is secreted over 24 hours in both sexes. In animals the pattern of release of the hormone is crucial to the effects on the CYPs; in females, GH is secreted in small but more or less continuous pulses, while males secrete large pulses, then periods of no secretion. The system is thought to be similar in humans. […] Little is known of the effects of the menopause and hormone replacement, where steroid metabolism changes dramatically. It is highly likely that these events could have profound effects on female drug clearance. […] females in general are more susceptible to drug adverse reactions than males, especially hepatotoxic effects.”
“For those chronically dependent on ethanol their CYP2E1 levels can be ten-fold higher than non-drinkers and they would clear CYP2E1 substrates extremely quickly if they chose to be sober for a period of time. This may lead to the accumulation of metabolites of the substrates. It is apparent that alcoholics who are sober can suffer paracetamol (acetaminophen)-induced liver toxicity at overdoses of around half that of non-drinkers, which is due to CYP2E1 induction. […] the vast variation in ADH [alcohol dehydrogenase] catalytic activity across the human race is mainly due to just a few SNPs that profoundly change the efficiency of the isoforms. ADH1B/*1 is the most effective variant and is the ADH wild-type […] Part of a ‘successful’ career as an alcoholic depends possessing the ADH1B/*1 isoform. The other defective isoforms are found in low frequencies in alcoholics and cirrhotics. […] in the vast majority of individuals, whatever their variant of ADH, they are able to process acetaldehyde to acetate and water, as the consequences of failing to do this are severe. With ALDH, the wild-type and gold standard is ALDH2*1/*1, which has the highest activity of all these isoforms and is the second essential component for an alcoholic career. […] the variant ALDH2*1/*2 has less than a quarter of the wild-type’s capacity and is found predominantly in Eastern races. The variant ALDH2*2/*2 is completely useless and renders the individuals very sensitive to acetaldehyde poisoning, although the toxin is removed eventually by ALDH1A1 which does not seem to be affected by polymorphisms. In a survey of 1300 Japanese alcoholics, there was nobody at all with the ALDH2*2/*2 variant. […] Women are much more vulnerable to ethanol damage and on average die in half the time it generally takes for a male alcoholic to drink himself to death. Women drink much less than men also – one study indicated that a group of women consumed about 14,000 drinks to induce cirrhosis, whilst men required more than 44,000 to achieve the same effect. Ethanol distributes in total body water only, so in women their greater fat content means that blood ethanol levels are higher than men of similar weight and age.“
I have had a look at two sources, the Office of Refugee Resettlement’s annual reports to Congress for the financial years 2013 and 2014. I have posted some data from the reports below. In the cases where the page numbers are not included directly in the screen-caps, all page numbers given below are the page numbers of the pdf version of the documents.
I had some trouble with how to deal with the images included in the post; I hope it looks okay now, at least it does on my laptop – but if it doesn’t, I’m not sure I care enough to try to figure out how to resolve the problem. Anyway, to the data!
The one above is the only figure/chart from the 2014 report, but I figured it was worth including here. It’s from page 98 of the report. It’s of some note that, despite the recent drop, 42.8% of the 2014 US arrivals worked/had worked during the year they arrived; in comparison, only 494 of Sweden’s roughly 163.000 asylum seekers who arrived during the year 2015 landed a job that year (link).
All further images/charts below are from the 2013 report.
It’s noteworthy here how different the US employment gap is to e.g. the employment gap in Denmark. In Denmark the employment rate of refugees with fugitive status who have stayed in the country for 5 years is 34%, and the employment rate of refugees with fugitive status who have stayed in the country for 15 years is 37%, compared to a native employment rate of ~74% (link). But just like in Denmark, in the US it matters a great deal where the refugees are coming from:
“Since their arrival in the U.S., 59 percent of refugees in the five-year population worked at one point. This rate was highest for refugees from Latin America (85 percent) and lowest for refugees from the Middle East (48 percent), while refugees from South/Southeast Asia (61 percent) and Africa (59 percent) were positioned in between. […] The highest disparity between male and female labor force participation rates was found for respondents from the Middle East (64.1 percent for males vs. 34.5 percent for females, a gap of 30 points). A sizeable gender gap was also found among refugees from South/Southeast Asia (24 percentage points) and Africa (18 percentage points), but there was hardly any gap among Latin American refugees (3 percentage points). Among all refugee groups, 71 percent of males were working or looking for work at the time of the 2013 survey, compared with 49 percent of females.” (p.94)
Two tables (both are from page 103 of the 2013 report):
When judged by variables such as home ownership and the proportion of people who survive on public assistance, people who have stayed longer do better (Table II-16). But if you consider table II-17, a much larger proportion of the refugees surveyed in 2013 than in 2008 are partially dependent on public assistance, and it seems that a substantially smaller proportion of the refugees living in the US in the year 2013 was totally self-reliant than was the case 5 years earlier. Fortunately the 2013 report has a bit more data on this stuff (p. 107):
The table has more information on page 108, with more details about specific public assistance programs.Table II-22 includes data on how public assistance utilization has developed over time (it’s clear that utilization rates increased substantially during the half-decade observed):
Some related comments from the report:
“Use of non-cash assistance was generally higher than cash assistance. This is probably because Medicaid, the Supplemental Nutrition Assistance Program (SNAP), and housing assistance programs, though available to cash assistance households, also are available more broadly to households without children. SNAP utilization was lowest among Latin Americans (37 percent) but much higher for the other groups, reaching 89 to 91 percent among the refugees from Africa and the Middle East. […] Housing assistance varied by refugee group — as low as 4 percent for Latin American refugees and as high as 32 percent for refugees from South/Southeast Asia in the 2013 survey. In the same period, other refugee groups averaged use of housing assistance between 19 and 31 percent.” (pp. 107-108)
The report includes some specific data on Iraqi refugees – here’s one table from that section:
The employment rate of the Iraqis increased from 29.8% in the 2009 survey to 41.3% in 2013. However the US female employment rate is still actually not much different from the female employment rates you observe when you look at European data on these topics – just 29%, up from 18.8% in 2009. As a comparison, in the year 2010 the employment rate of Iraqi females living in Denmark was 28% (n=10163) (data from p.55 of the Statistics Denmark publication Indvandrere i Danmark 2011), almost exactly the same as the employment rate of female Iraqis in the US.
Of note in the context of the US data is perhaps also the fact that despite the employment rate going up for females in the time period observed, the labour market participation rate of this group actually decreased between 2009 and 2013, as it went from 42.2% to 38.1%. So more than 3 out of 5 Iraqi female refugees living in the US are outside the labour market, and almost one in four of those that are not are unemployed. A few observations from the report:
“The survey found that the overall EPR [employment rate, US] for the 2007 to 2009 Iraqi refugee group in the 2013 survey9 was 41 percent (55 percent for males and 29 percent for females), a steady increase in the overall rate from 39 percent in the 2012 survey, 36 percent in the 2011 survey, 31 percent in the 2010 survey, and 30 percent in the 2009 survey. As a point of further reference, the EPR for the general U.S. population was 58.5 percent in 2013, about 17 percentage points higher than that of the 2007 to 2009 Iraqi refugee group (41.3 percent). The U.S. male population EPR was nine percentage points higher than the rate for Iraqi males who arrived in the U.S. in 2007 to 2009 (64 percent versus 55 percent), while the rate for the Iraqi females who arrived in the U.S. in 2007 to 2009 was 24 points higher for all U.S. women (53 percent versus 29 percent). The difference between the male and female EPRs among the same group of Iraqi refugees (26 percentage points) also was much larger than the gap between male and female EPRs in the general U.S. population (11 points) […] The overall unemployment rate for the 2007 to 2009 Iraqi refugee group was 22.9 percent in the 2013 survey, about four times higher than that of the general U.S. population (6.5 percent) in 2013” (pp. 114-115).
“To date, no prospective study has directly compared the efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs), serotonin/ norepinephrine reuptake inhibitors (SNRIs), or other second-generation antidepressants in patients with diabetes versus patients without diabetes.”
“Weight is a common and well-known adverse effect of short-term and long-term treatment with TCAs, primarily as a result of excessive appetite. […] weight gain is the most common cause for premature discontinuation of all TCAs. […] TCAs are […] likely to impair diabetes control, because they increase serum glucose levels by up to 150%, increase appetite (particularly carbohydrate craving), and reduce the metabolic rate. […] SSRIs have been associated with both weight gain and weight loss. […] Weight gain is less likely with SSRIs when they are used short term — for 6 months or less. Contradictory evidence exists about whether an increase in body weight occurs in patients using SSRIs for 1 year or longer. […] The mean incidence of weight gain across comparative randomized controlled trials ranges from 4.1% for fluoxetine, 7.6% for sertraline, and 9.6% for paroxetine. […] SSRIs may reduce serum glucose by up to 30% and cause appetite suppression, resulting in weight loss. Fluoxetine should be used cautiously in patients with diabetes, because of its increased potential for hypoglycemia […]. Its side effects of tremor, nausea, sweating, and anxiety may also be misinterpreted as due to hypoglycemia.”
“Prior to the development of the second-generation antipsychotics (SGAs), or atypical antipsychotics, phenothiazines were the dominant therapy for schizophrenia. Numerous studies at this time began documenting that the use of phenothiazines led to aggravation of preexisting diabetes and the development of new-onset type 2 diabetes. […] high-potency neuroleptics […] appeared to be less implicated in the development of diabetes. These drugs eventually became the predominant form of therapy for schizophrenia […] Unfortunately, the high-potency neuroleptics are also associated with a high rate of occurrence of extrapyramidal symptoms, tardive dyskinesia, and subsequent noncompliance […] In the late 1980s, a new class of antipsychotics, the thiobenzodiazepines or “atypical antipsychotics,” was introduced. […] One major advantage of these agents was a marked reduction in the occurrence of extrapyramidal symptoms. […] However, the atypical antipsychotics have also proven to carry their own unique side-effect profile. Side effects include substantial weight gain […] lipid abnormalities […] Hyperglycemia and diabetes are strongly associated with some of the newer atypical antipsychotics […] Thus, many psychiatrists are finding themselves in the difficult position of trading efficacy in the treatment of schizophrenia for an array of adverse metabolic side effects.”
“Weight gain is one of the more noticeable effects of all of the psychotropics. Although the SGAs appear to be a major culprit, TCAs, lithium, and mood stabilizers such as valproic acid or divalproex sodium and carbamazepine are also associated with weight gain. […] A range of evidence suggests that treatment with certain antipsychotic medications is associated with an increased risk of insulin resistance, hyperglycemia, and type 2 diabetes, compared with no treatment or treatment with alternative antipsychotics. […] A growing body of evidence supports the key observation that treatments producing the greatest increases in body weight and adiposity are also associated with a consistent pattern of clinically significant adverse effects on insulin resistance and changes in blood glucose and lipid levels. However, there are a growing number of cases of antipsychotic-associated hyperglycemia that involve patients without substantial weight gain, and reports that involve patients who improve when the offending agent is discontinued or who experience deterioration of glycemic control when re-challenged with the drug. […] Antipsychotics may lead to diabetes in susceptible individuals by causing decreased insulin secretion, increased insulin resistance, or a combination of both. Data suggest, however, that insulin resistance is primarily the responsible mechanism. […] The mechanism through which antipsychotics lead to insulin resistance is not clear.”
“Many drugs may influence glucose insulin homeostasis. Commonly prescribed drugs that may have adverse effects on carbohydrate metabolism, especially in patients with diabetes mellitus or those at risk of developing glucose intolerance, include diuretics, beta-blockers, sympathomimetics, corticosteroids, and sex hormones”.
The book’s Table 4.11 include a really nice list of drugs, or drug classes, that can increase blood glucose levels, which includes quite a few commonly used drugs. A couple of to me surprising culprits on that list were marijuana and oral contraceptives; the oral contraceptives one certainly makes a lot of sense in retrospect (I don’t really know much about the metabolism of marijuana/cannabis, all I’ve ever learned about that stuff includes what was covered in the appendix of Coleman’s excellent textbook – and I have no personal experience…), I just hadn’t thought about the fact that very commonly used drugs like these may also have side effects of this nature).
“Patients with depression or bipolar depression may lack interest in their well-being and suffer from difficulty maintaining focus. Furthermore, many depressed patients suffer from decreased energy, psychomotor retardation, and changes in appetite, which may further promote weight gain. All of these make it very challenging to successfully implement a weight loss program in depressed patients. […] In addition, many patients with mental illnesses such as depression […] often state that eating is one of the few highlights of their day.” (So it’s probably a good idea to avoid giving these people drugs which will cause them to gain a substantial amount of weight/increase appetite/increase carbohydrate cravings, to the extent that this is possible…)
“Diabetes is considered a coronary artery disease equivalent by the National Cholesterol Education Panel (NCEP) […] Aspirin therapy is considered a routine part of secondary prevention in people with diabetes and a history of cardiovascular disease, and it is also recommended as part of primary prevention for cardiovascular disease in all patients with diabetes older than 40 years of age; additionally treatment with 75 to 325 mg/day of aspirin should be considered in patients 30 to 40 years of age with one additional cardiovascular risk factor.1,13 […] for all people older than 40 years of age with diabetes, statin therapy is recommended to lower the LDL by 30% to 40%, regardless of baseline levels.14 […] Lowering triglycerides to levels less than 150 mg/dL also confers cardiovascular benefit.1,14 However, hyperglycemia and hypertriglyceridemia are intricately linked, likely through elevations of free fatty acids. Free fatty acids are potent inhibitors of insulin action and transport, and act to disrupt glucose transport into skeletal muscle. Thus, triglyceride goals are often difficult to attain in uncontrolled diabetes.”
In some weird way some aspects of the last part of the book’s coverage was quite funny. So you have a diabetic whose disease has caused extensive damage to the nervous system leading to painful neuropathy. How do you treat the (in general difficult to treat) symptoms of neuropathy? Why, you give him tricyclic antidepressants (which will of course make his diabetes harder to treat, and cause him to gain weight). No, I’m not making this up:
“The most widely used medical treatments for symptoms of diabetic neuropathy include gabapentin and tricyclic antidepressants.”
Or how about this one – you have a type 2 diabetic who’s most likely overweight and who could probably benefit quite a bit from losing weight; why, let’s treat his diabetes with a drug that causes him to gain weight! People actually do this: “Thiazolidinediones (rosiglitazone, pioglitazone) act as agonists of the peroxisome proliferator-activator receptor gamma and improve insulin sensitivity at the tissue level. These agents are contraindicated in patients with heart failure and can worsen peripheral edema. Unfortunately, a common side effect of the glitazone class of agents is weight gain.” They’re not first-line agents, but they are used in diabetics. Just to make things even better, these drugs also seem to increase the risk of osteoporosis, a risk which is already somewhat elevated in type 2 diabetics: “Additionally, these drugs [thiazolidinediones] appear to decrease appendicular bone mass with associated increased risk of fractures.34“
…or perhaps now some people might start thinking here: ‘Is stuff like this actually part of the explanation for Vestergaard’s findings described in the link above?’ I should add to these people that this is unlikely to be the case, especially considering the big difference between the (really quite substantial) type 1- and (significantly lower) type 2 fracture risk elevation; thiazolidinediones are not used in the treatment of type 1, and it’s not even a first-line treatment of type 2 – other explanations, such as those covered in Czernik & Fowlkes’s text, seem much more likely to matter (though in the context of a few individuals these drugs may still be of relevance).
“In addition to glycemic goals, nonglycemic treatment goals of blood pressure control, lipid management, and initiation of aspirin therapy are often necessary. For many patients, the diagnosis of diabetes results in multidrug therapy. For patients with mental illness who are likely to already be on multiple medications, the addition of several new agents can be difficult. Several studies have suggested that medication adherence in patients with psychiatric illness is poor at baseline,38 and may worsen when an increasing number of medications are prescribed.”
It’s also worth remembering here that “asymptomatic and chronic diseases needing long-term treatment […] result in poorer compliance”, although on the other hand “patient-controlled non-compliance [is] lower in treatment for diseases in which the relationship between non-compliance and recurrence is very clear, such as diabetes, compared to treatment for diseases in which this relationship is less clear” (Kermani and Davies). Combine psychiatric disease with chronic illnesses of a different kind and potential polypharmacy and non-compliance certainly becomes an issue worth taking into account when considering what might be the optimal treatment regime. It’s also worth keeping in mind that even in people without psychiatric problems adherence tends to be low in the case of antihypertensives and lipid-lowering drugs – again I refer to Kermani and Davies’ text:
“Chapman et al. (2005) recently examined compliance with concomitant antihypertensive and lipid-lowering drug therapy in 8406 enrollees in a US-managed care plan […] Less than half of patients (44.7 per cent) were adherent with both therapies three months after medication initiation, a figure that decreased to 35.8 per cent at 12 months.”
No other interpretation of this piece even comes close to Zimerman’s, in my opinion. This is as good as it gets.
A few days ago I decided to have a closer look at goodreads’ quotes and how that part of the site worked. I have now added a little more than 1000 quotes to my personal quote collection on the site, many (literally hundreds) of which are quotes I have added myself to the goodreads quote library. Most of them are naturally quotes taken from the blog – the quote collection I have here is still far larger than is my goodreads collection, but at least in terms of the ‘better than average quotes’ posted here on the blog I do believe I’ve transferred/duplicated a rather substantial proportion of those quotes to goodreads by now.
Although some aspects of the site’s functionality is nice, I thoroughly dislike other aspects of the way the goodreads site works and handles specific problems. Wikiquote has for a long time been my go-to place for quotes, and it’ll remain so for the foreseeable future, barring any sudden unexpected changes of a profoundly negative nature. A really huge problem I have with the way goodreads handles these things is that if a specific quote contains an error, e.g. is missing a comma or is attributed to the wrong person, you cannot correct the error yourself, even if you know it’s an error and you literally sit there with the book in front of you, and to make matters (much) worse you often cannot even add a new quote with correct attribution; if a new quote you add is ‘sufficiently similar’ to an erroneous/misattributed quote already added to the site, you trying to add a correct quote will only lead to you automatically ‘liking’ the original flawed quote you were annoyed about and the corrected quote you tried to add will not be added. I’m still quite annoyed that one of Marie von Ebner-Eschenbach‘s really nice maxims on goodreads have been attributed by some ignorant £$@! to Jane Austen, but that’s just one of several examples I’ve encountered. There are multiple cases where I have decided not to add a specific quote because I refuse on principle to ‘like’ a quote containing an error, and/but there are also a few cases where I have bit the metaphorical bullet, after some thought, and liked a quote despite it not matching perfectly the version of the quote with which I was myself familiar (this has mostly been in the case of quotes by non-English speaking individuals, where at least some leeway can be argued to exist on account of issues pertaining to translation). I found it somewhat irritating that some really quite notable people seem to not be considered notable on goodreads (notability is a requirement for quotation, and goodreads does not allow anonymous quotes/proverbs etc. in the quotes section); for example I found myself trying in vain to add a quote by a Nobel Prize winner in Physics at some point, but the guy hadn’t written any books added to the site and so when trying to add the name after having written out the quote I realized I couldn’t do that; at least it was not immediately obvious to me how to handle this problem, and so I let it go on account of it being just one quote. Books with multiple authors also cause some problems (one specific one of which I’ve now at least partially figured out how to handle, fortunately), and books with many contributors still pose questions to which I do not know the answer; it doesn’t seem to me like the goodreads site in its current format even enables you theoretically in any way to attribute quotes taken from such books correctly – at least I haven’t found out how to do it.
So all in all I’m not particularly impressed with the site in terms of how it handles quotes, but on the other hand if you’re less interested in adding obscure quotes by people almost nobody alive today have ever heard about than I am, and would rather just like an easy way to collect/manage/remember quotes you happen to like, the site’s probably not really bad at all; it’s very easy to add new quotes to your collection if the quote is already in the goodreads library (it takes a little bit of work if it’s not). You can let my collection be a starting point if you like the sort of quotes I do; I know a few people in the past have said that they liked the quotes I’ve posted on the blog and now you have a quite easy way to just ‘grab’ those of ‘my’ quotes (quotes are posted anonymously on goodreads, so the quotes I have added are no more my quotes than they are yours) you like, and leave the rest.
Below I’ve added the 20 new quotes I usually post in my regular quotes posts, all of which (as far as I have been able to ascertain) have not been posted here before.
i. “Though what we accept be true, it is a prejudice unless we ourselves have considered and understood why and how it is true.” (John Lancaster Spalding)
ii. “However firmly thou holdest to thy opinions, if truth appears on the opposite side, throw down thy arms at once.” (-ll-)
iii. “The ultimate result of shielding men from the effects of folly, is to fill the world with fools.” (Herbert Spencer)
iv. “We often do not see what we do not expect to see.” (Alan Lightman)
v. “The past and future are veiled; but the past wears the widow’s veil; the future, the virgin’s.” (Jean Paul Richter)
vi. “There is no duty we so much underrate as the duty of being happy.” (Robert Louis Stevenson)
vii. “Science may be described as the art of systematic over-simplification — the art of discerning what we may with advantage omit.” (Karl Popper)
viii. “I hold that he who teaches that not reason but love should rule opens up the way for those who rule by hate.” (-ll-)
ix. “You cannot have a rational discussion with a man who prefers shooting you to being convinced by you.” (-ll-)
x. “There is an almost universal tendency, perhaps an inborn tendency, to suspect the good faith of a man who holds opinions that differ from our own opinions.” (-ll-)
xi. “Always remember that it is impossible to speak in such a way that you cannot be misunderstood: there will always be some who misunderstand you.” (-ll-)
xii. “The more we learn about the world, and the deeper our learning, the more conscious, specific, and articulate will be our knowledge of what we do not know, our knowledge of our ignorance.” (-ll-)
xiii. “Methodological rules are for science what rules of law and custom are for conduct.” (Émile Durkheim)
xiv. “Men apt to promise, are apt to forget.” (Thomas Fuller)
xv. “Since people of necessity see things from their own perspective, much of what they say adds up to comforting ideas or outright propaganda for themselves and the groups to which they belong.” (Patricia Crone, Pre-Industrial Societies: Anatomy of the Pre-Modern World)
xvi. “… humans are animals. It would not occur to an ethologist studying ants, lions, wolves or giraffes to argue that ‘ultimately’ it is the animal’s need for food which determines the type of society in which it lives, or its need to reproduce, or its mechanisms of defence against predators, or whatever. On the contrary, he will see the society in question as the outcome of a compromise between a variety of fundamental needs and the environment in which it is set. Precisely the same is true of human societies. […] all attempts to explain human history in terms of a single factor are misguided.” (-ll-)
xvii. “Science doesn’t purvey absolute truth. Science is a mechanism. It’s a way of trying to improve your knowledge of nature. It’s a system for testing your thoughts against the universe and seeing whether they match.” (Isaac Asimov)
xviii. “Where any answer is possible, all answers are meaningless.” (-ll-)
xix. “There are no happy endings in history, only crisis points that pass.” (-ll-)
xx. “To write is to read one’s own self” (Max Frisch)
I recently read Nick Middleton’s short publication on this topic and decided it was worth blogging it here. I gave the publication 3 stars on goodreads; you can read my goodreads review of the book here.
In this post I’ll quote a bit from the book and add some details I thought were interesting.
“None of [the] approaches to desert definition is foolproof. All have their advantages and drawbacks. However, each approach delivers […] global map[s] of deserts and semi-deserts that [are] broadly similar […] Roughly, deserts cover about one-quarter of our planet’s land area, and semi-deserts another quarter.”
“High temperatures and a paucity of rainfall are two aspects of climate that many people routinely associate with deserts […] However, desert climates also embrace other extremes. Many arid zones experience freezing temperatures and snowfall is commonplace, particularly in those situated outside the tropics. […] For much of the time, desert skies are cloud-free, meaning deserts receive larger amounts of sunshine than any other natural environment. […] Most of the water vapour in the world’s atmosphere is supplied by evaporation from the oceans, so the more remote a location is from this source the more likely it is that any moisture in the air will have been lost by precipitation before it reaches continental interiors. The deserts of Central Asia illustrate this principle well: most of the moisture in the air is lost before it reaches the heart of the continent […] A clear distinction can be made between deserts in continental interiors and those on their coastal margins when it comes to the range of temperatures experienced. Oceans tend to exert a moderating influence on temperature, reducing extremes, so the greatest ranges of temperature are found far from the sea while coastal deserts experience a much more limited range. […] Freezing temperatures occur particularly in the mid-latitude deserts, but by no means exclusively so. […] snowfall occurs at the Algerian oasis towns of Ouagla and Ghardaia, in the northern Sahara, as often as once every 10 years on average.”
“[One] characteristic of rainfall in deserts is its variability from year to year which in many respects makes annual average statistics seem like nonsense. A very arid desert area may go for several years with no rain at all […]. It may then receive a whole ‘average’ year’s rainfall in just one storm […] Rainfall in deserts is also typically very variable in space as well as time. Hence, desert rainfall is frequently described as being ‘spotty’. This spottiness occurs because desert storms are often convective, raining in a relatively small area, perhaps just a few kilometres across. […] Climates can vary over a wide range of spatial scales […] Changes in temperature, wind, relative humidity, and other elements of climate can be detected over short distances, and this variability on a small scale creates distinctive climates in small areas. These are microclimates, different in some way from the conditions prevailing over the surrounding area as a whole. At the smallest scale, the shade given by an individual plant can be described as a microclimate. Over larger distances, the surface temperature of the sand in a dune will frequently be significantly different from a nearby dry salt lake because of the different properties of the two types of surface. […] Microclimates are important because they exert a critical control over all sorts of phenomena. These include areas suitable for plant and animal communities to develop, the ways in which rocks are broken down, and the speed at which these processes occur.”
“The level of temperature prevailing when precipitation occurs is important for an area’s water balance and its degree of aridity. A rainy season that occurs during the warm summer months, when evaporation is greatest, makes for a climate that is more arid than if precipitation is distributed more evenly throughout the year.”
“The extremely arid conditions of today[‘s Sahara Desert] have prevailed for only a few thousand years. There is lots of evidence to suggest that the Sahara was lush, nearly completely covered with grasses and shrubs, with many lakes that supported antelope, giraffe, elephant, hippopotamus, crocodile, and human populations in regions that today have almost no measurable precipitation. This ‘African Humid Period’ began around 15,000 years ago and came to an end around 10,000 years later. […] Globally, at the height of the most recent glacial period some 18,000 years ago, almost 50% of the land area between 30°N and 30°S was covered by two vast belts of sand, often called ‘sand seas’. Today, about 10% of this area is covered by sand seas. […] Around one-third of the Arabian subcontinent is covered by sandy deserts”.
“Much of the drainage in deserts is internal, as in Central Asia. Their rivers never reach the sea, but take water to interior basins. […] Salt is a common constituent of desert soils. The generally low levels of rainfall means that salts are seldom washed away through soils and therefore tend to accumulate in certain parts of the landscape. Large amounts of common salt (sodium chloride, or halite), which is very soluble in water, are found in some hyper-arid deserts.”
“Many deserts are very rich in rare and unique species thanks to their evolution in relative geographical isolation. Many of these plants and animals have adapted in remarkable ways to deal with the aridity and extremes of temperature. Indeed, some of these adaptations contribute to the apparent lifelessness of deserts simply because a good way to avoid some of the harsh conditions is to hide. Some small creatures spend hot days burrowed beneath the soil surface. In a similar way, certain desert plants spend most of the year and much of their lives dormant, as seeds waiting for the right conditions, brought on by a burst of rainfall. Given that desert rainstorms can be very variable in time and in space, many activities in the desert ecosystem occur only sporadically, as pulses of activity driven by the occasional cloudburst. […] The general scarcity of water is the most important, though by no means the only, environmental challenge faced by desert organisms. Limited supplies of food and nutrients, friable soils, high levels of solar radiation, high daytime temperatures, and the large diurnal temperature range are other challenges posed by desert conditions. These conditions are not always distributed evenly across a desert landscape, and the existence of more benign microenvironments is particularly important for desert plants and animals. Patches of terrain that are more biologically productive than their surroundings occur in even the most arid desert, geographical patterns caused by many factors, not only the simple availability of water.”
A small side note here: The book includes brief coverage of things like crassulacean acid metabolism and related topics covered in much more detail in Beer et al. I’m not going to go into that stuff here as this stuff was in my opinion much better covered in the latter book (some people might disagree, but people who would do that would at least have to admit that the coverage in Beer et al. is/was much more comprehensive than is Middleton’s coverage in this book). There are quite a few other topics included in the book which I did not include coverage of here in the post but I mention this topic in particular in part because I thought it was actually a good example underscoring how this book is very much just a very brief introduction; you can write book chapters, if not books, about some of the topics Middleton devotes a couple of paragraphs to in his coverage, which is but to be expected given the nature and range of coverage of the publication.
Plants aren’t ‘smart’ given any conventional definition of the word, but as I’ve talked about before here on the blog (e.g. here) when you look closer at the way they grow and ‘behave’ over the very long term, some of the things they do are actually at the very least ‘not really all that stupid’:
“The seeds of annuals germinate only when enough water is available to support the entire life cycle. Germinating after just a brief shower could be fatal, so mechanisms have developed for seeds to respond solely when sufficient water is available. Seeds germinate only when their protective seed coats have been broken down, allowing water to enter the seed and growth to begin. The seed coats of many desert species contain chemicals that repel water. These compounds are washed away by large amounts of water, but a short shower will not generate enough to remove all the water-repelling chemicals. Other species have very thick seed coats that are gradually worn away physically by abrasion as moving water knocks the seeds against stones and pebbles.”
What about animals? One thing I learned from this publication is that it turns out that being a mammal will, all else equal, definitely not give you a competitive edge in a hot desert environment:
“The need to conserve water is important to all creatures that live in hot deserts, but for mammals it is particularly crucial. In all environments mammals typically maintain a core body temperature of around 37–38°C, and those inhabiting most non-desert regions face the challenge of keeping their body temperature above the temperature of their environmental surrounds. In hot deserts, where environmental temperatures substantially exceed the body temperature on a regular basis, mammals face the reverse challenge. The only mechanism that will move heat out of an animal’s body against a temperature gradient is the evaporation of water, so maintenance of the core body temperature requires use of the resource that is by definition scarce in drylands.”
Humans? What about them?
“Certain aspects of a traditional mobile lifestyle have changed significantly for some groups of nomadic peoples. Herders in the Gobi desert in Mongolia pursue a way of life that in many ways has changed little since the times of the greatest of all nomadic leaders, Chinggis Khan, 750 years ago. They herd the same animals, eat the same foods, wear the same clothes, and still live in round felt-covered tents, traditional dwellings known in Mongolian as gers. Yet many gers now have a set of solar panels on the roof that powers a car battery, allowing an electric light to extend the day inside the tent. Some also have a television set.” (these remarks incidentally somehow reminded me of this brilliant Gary Larson cartoon)
“People have constructed dams to manage water resources in arid regions for thousands of years. One of the oldest was the Marib dam in Yemen, built about 3,000 years ago. Although this structure was designed to control water from flash floods, rather than for storage, the diverted flow was used to irrigate cropland. […] Although groundwater has been exploited for desert farmland using hand-dug underground channels for a very long time, the discovery of reserves of groundwater much deeper below some deserts has led to agricultural use on much larger scales in recent times. These deep groundwater reserves tend to be non-renewable, having built up during previous climatic periods of greater rainfall. Use of this fossil water has in many areas resulted in its rapid depletion.”
“Significant human impacts are thought to have a very long history in some deserts. One possible explanation for the paucity of rainfall in the interior of Australia is that early humans severely modified the landscape through their use of fire. Aboriginal people have used fire extensively in Central Australia for more than 20,000 years, particularly as an aid to hunting, but also for many other purposes, from clearing passages to producing smoke signals and promoting the growth of preferred plants. The theory suggests that regular burning converted the semi-arid zone’s mosaic of trees, shrubs, and grassland into the desert scrub seen today. This gradual change in the vegetation could have resulted in less moisture from plants reaching the atmosphere and hence the long-term desertification of the continent.” (I had never heard about this theory before, and so I of course have no idea if it’s correct or not – but it’s an interesting idea).
i. “The more I write, the more I am convinced that the only way to write a popular story is to split it up into scenes, and have as little stuff between the scenes as possible.” (P. G. Wodehouse, Performing Flea. A long time ago I was working on a blog post covering this book, but I realized I’m probably not going to finish that one so I decided to include some of the quotes from the post here instead. He emphasizes the point made in this quote more than once in his letters, for example he writes in another letter that: “The longer I write, the more I realize the necessity for telling a story as far as possible in scenes, especially at the start.”)
ii. “The principle I always go on in writing a long story is to think of the characters in terms of actors in a play. I say to myself, when I invent a good character for an early scene: ‘If this were a musical comedy we should have to get somebody like Leslie Henson to play this part, and if he found that all he had was a short scene in act one, he would walk out. How, therefore, can I twist the story so as to give him more to do and keep him alive till the fall of the curtain?’ This generally works well and improves the story.” (P. G. Wodehouse, Performing Flea)
iii. “The absolute cast-iron good rule, I’m sure, in writing a story, is to introduce all your characters as early as possible – especially if they are going to play important parts later.” (-ll-)
iv. “I think the success of every novel depends largely on one or two high spots. The thing to do is to say to yourself ‘Which are my big scenes?’ and then get every drop of juice out of them.” (-ll-)
v. “I sometimes wonder if I really am a writer. When I look at the sixty-odd books in the shelf with my name on them, and reflect that ten million of them have been sold, it amazes me that I can have done it. I don’t know anything, and I seem incapable of learning … I feel like I’ve been fooling the public for fifty years.” (-ll-)
vi. “I don’t suppose that anything you say or anything I say will make the slightest damn bit of difference. You need dynamite to dislodge an idea that has got itself firmly rooted in the public mind.” (-ll-)
vii. “The day after graduating from college, I found fifty dollars in the foyer of my Chicago apartment building. The single bill had been folded into eighths and was packed with cocaine. It occurred to me then that if I played my cards right, I might never have to find a job. People lost things all the time. They left class rings on the sinks of public bathrooms and dropped gem-studded earrings at the doors of the opera house. My job was to keep my eyes open and find these things. I didn’t want to become one of those coots who combed the beaches of Lake Michigan with a metal detector, but if I paid attention and used my head, I might never have to work again.
The following afternoon, hung over from cocaine, I found twelve cents and an unopened tin of breath mints. Figuring in my previous fifty dollars, that amounted to an average of twenty-five dollars and six cents per day, which was still a decent wage. The next morning I discovered two pennies and a comb matted with short curly hairs. The day after that I found a peanut. It was then that I started to worry.” (David Sedaris, Naked)
viii. “If she’d had it her way, we would never have known about the cancer. It was our father’s idea to tell us, and she had fought it, agreeing only when he threatened to tell us himself. Our mother worried that once we found out, we would treat her differently, delicately. We might feel obliged to compliment her cooking and laugh at all her jokes, thinking always of the tumor she was trying so hard to forget. And that is exactly what we did. […] We were no longer calling our mother. Now we were picking up the telephone to call our mother with cancer.” (-ll-)
ix. “It was rather annoying to hear how kind she’d been; it entailed putting tiresome qualifications on his dislike for her.” (Kingsley Amis, Lucky Jim)
x. “the most noticeable characteristic of the past, as seen by him, at least, was that there was so much more of it now than formerly, with bits that were longer ago than had once seemed possible.” (Kingsley Amis, The Old Devils)
xi. “Why, you might wonder, should prisoners wear themselves out, working hard, ten years on end, in the camps? You’d think they’d say: No thank you, and that’s that. […] But that didn’t work. To outsmart you they thought up work-teams – but not teams like the ones in freedom, where every man is paid his separate wage. Everything was so arranged in the camp that the prisoners egged one another on. It was like this: either you got a bit extra or you all croaked.” (Aleksandr Solzhenitsyn, One Day in the Life of Ivan Denisovich)
xii. “‘Well, brothers, good-bye,’ said the captain with an embarrassed nod to his team-mates, and followed the guard out.
A few voices shouted: ‘Keep your pecker up.’ But what could you really say to him? They knew the cells, the 104th did, they’d built them. Brick walls, cement floor, no windows, a stove they lit only to melt the ice on the walls and make pools on the floor. You slept on bare boards, and if you’d any teeth left to eat with after all the chattering they’d be doing, they gave you three hundred grammes of bread day after day and hot skilly only on the third, sixth, and ninth.
Ten days. Ten days ‘hard’ in the cells – if you sat them out to the end your health would be ruined for the rest of your life. […] As for those who got fifteen ‘hard’ and sat them out – they went straight into a hole in the cold earth.” (-ll-)
xiii. “Shukhov gazed at the ceiling in silence. Now he didn’t know either whether he wanted freedom or not. At first he’d longed for it. Every night he’d counted the days of his stretch – how many had passed, how many were coming. And then he’d grown bored with counting. And then it became clear that men of his like wouldn’t ever be allowed to return home, that they’d be exiled. And whether his life would be any better there than here – who could tell?
Freedom meant one thing to him – home.
But they wouldn’t let him go home.” (-ll-)
xiv. “You want to know what I do? All right. Some guy comes in with a bandage around his head. We don’t mess about. We’ll soon have that off. He’s got a hole in his head. So what do we do. We stick a nail in it. Get the nail – a good rusty one – from the trash or wherever. And lead him out to the Waiting Room where he’s allowed to linger and holler for a while before we ferry him back to the night. […] Because I am a healer, everything I do heals, somehow. The thing called society is, I believe, insane. In the locker room the steel grilles are pasted with letters that say, Thanks for your kindness for making a tough time much easier to bear, and, If it wasn’t for all of you there at the hospital I don’t know how we would have survived. The doctors read these thankyou notes with tears in their eyes, especially when gratitude is expressed in a childish hand. Not Johnny Young, though. Perhaps he knows, as I do, that the letters are propitiatory. The children (‘7 yrs’) haven’t been here yet. They won’t be so grateful when we’re through.” (Martin Amis, Time’s Arrow.)
xv. “Like all of my friends, she’s a lousy judge of character.” (David Sedaris, Me Talk Pretty One Day)
xvi. “Nobody dreams of the things he already has.” (-ll-)
xvii. “The word phobic has its place when properly used, but lately it’s been declawed by the pompous insistence that most animosity is based upon fear rather than loathing. No credit is given for distinguishing between these two very different emotions. I fear snakes. I hate computers. My hatred is entrenched, and I nourish it daily. I’m comfortable with it, and no community outreach program will change my mind.” (-ll-)
xviii. “Of all the stumbling blocks inherent in learning this language [French], the greatest for me is the principle that each noun has a corresponding sex that affects both its articles and its adjectives. Because it is a female and lays eggs, a chicken is masculine. Vagina is masculine as well, while the word masculinity is feminine. Forced by the grammar to take a stand one way or the other, hermaphrodite is male and indecisiveness female. I spent months searching for some secret code before I realized that common sense has nothing to do with it. Hysteria, psychosis, torture, depression: I was told that if something is unpleasant, it’s probably feminine. This encouraged me, but the theory was blown by such masculine nouns as murder, toothache, and Rollerblade.” (-ll-)
xix. “By the time I reached my thirties, my brain had been strip-mined by a combination of drugs, alcohol, and the chemical solvents used at the refinishing company where I worked. Still, there were moments when, against all reason, I thought I might be a genius. These moments were provoked not by any particular accomplishment but by cocaine and crystal methamphetamine — drugs that allow you to lean over a mirror with a straw up your nose, suck up an entire week’s paycheck, and think, “God, I’m smart.”” (-ll-)
xx. “As youngsters, we participated in all the usual seaside activities — which were fun, until my father got involved and systematically chipped away at our pleasure. Miniature golf was ruined with a lengthy dissertation on impact, trajectory, and wind velocity, and our sand castles were critiqued with stifling lectures on the dynamics of the vaulted ceiling. We enjoyed swimming, until the mystery of tides was explained in such a way that the ocean seemed nothing more than an enormous saltwater toilet, flushing itself on a sad and predictable basis. […] [“]The goal is to better yourself. Meet some intellectuals. Read a book!” After all these years our father has never understood that we, his children, tend to gravitate toward the very people he’s spent his life warning us about.” (-ll-. There were several reasons why I really enjoyed Sedaris’ book, but the fact that here in this book was actually a character who in some respects seemed to find it natural to behave in a manner similar to the way I could see myself behave – in a setting where the behaviour in question might by some people be considered unusual, that is – was definitely one of them. (Though I’m also slightly conflicted here; I don’t like children very much, and there’s no conceivable universe in which I’d ever have six of them; in such a universe ‘I’ would not be ‘me‘. I’d also on a related note be much more inclined to warn children to stay away from ‘intellectuals’, rather than the opposite…)).
I was debating whether to blog this book at all, as it’s neither very long nor very good, but I decided it was worth adding a few observations from the book here. You can read my goodreads review of the publication here. Whenever quotes look a bit funny in the coverage below (i.e. when you see things like words in brackets or strangely located ‘[…]’, assume that the reason for this is that I tried to improve upon the occasionally frankly horrible language of some of the contributors to the publication. If you want to know exactly what they wrote, rather than what they presumably meant to write (basic grammar errors due to the authors having trouble with the English language are everywhere in this publication, and although I did choose to do so here I do feel a bit uncomfortable quoting a publication like this one verbatim on my blog), read the book.
I went off on a tangent towards the end of the post and I ended up adding some general remarks about medical cost, insurance and various other topics. So the post may have something of interest even to people who may not be highly interested in any of the stuff covered in the book itself.
“Despite intensive recommendations, [the] influenza vaccination rate in medical staff in Poland ranges from about 20 % in physicians to 10 % in nurses. […] It has been demonstrated that vaccination of health care workers against influenza significantly decreases mortality of elderly people remaining under [long-term care]. […] Vaccinating health care workers also substantially reduces sickness absenteeism, especially in emergency units […] Concerning physicians, vaccination avoidance stemmed from the lack of knowledge of protective value of vaccine (33 %), lack of time to get vaccinated (29 %), and Laziness (24 %). In nurses, these figures amounted to 55 %, 12 %, and 5 %, respectively (Zielonka et al. 2009).”
I just loved the fact that ‘laziness’ was included here as an explanatory variable, but on the other hand the fact that one-third of doctors cited lack of knowledge about the protective value of vaccination as a reason for not getting vaccinated is … well, let’s use the word ‘interesting’. But it gets even better:
“The questions asked and opinions expressed by physicians or nurses on vaccinations showed that their knowledge in this area was far from the current evidence-based medicine recommendations. Nurses, in particular, commonly presented opinions similar to those which can be found in anti-vaccination movements and forums […] The attitude of physicians toward influenza vaccination vary greatly. In many a ward, a majority of physicians were vaccinated (70–80 %). However, in the neurology and intensive care units the proportion of vaccinated physicians amounted only to 20 %. The reason for such a small yield […] was a critical opinion about the effectiveness and safety of vaccination. Similar differences, depending on medical specialty, were observed in Germany (4–71% of vaccines) (Roggendorf et al. 2011) […] It is difficult to explain the fear of influenza vaccination among the staff of intensive care units, since these are exactly the units where many patients with most severe cases of influenza are admitted and often die (Ayscue et al. 2014). In this group of health care workers, high efficiency of influenza vaccination has been clearly demonstrated […] In the present study a strong difference between the proportion of vaccinated physicians (55 %) and nurses (21 %) was demonstrated, which is in line with some data coming from other countries. In the US, 69 % of physicians and 46 % of nurses get a vaccine shot […] and in Germany the respective percentages are 39 % and 17 % […] In China, 21 % of nurses and only 13 % of physicians are vaccinated against influenza (Seale et al. 2010a), and in [South] Korea, 91 % and 68 % respectively (Lee et al. 2008).”
“[A] survey was conducted among Polish (243) and foreign (80) medical students at the Pomeranian Medical University in Szczecin, Poland. […] The survey results reveal that about 40 % of students were regular or occasional smoker[s]. […] 60 % of students declared themselves to be non-smokers, 20 % were occasional smokers, and 20 % were regular smokers”
40 % of medical students in a rather large sample turned out to be smokers. Wow. Yeah, I hadn’t seen that one coming. I’d probably expect a few alcoholics and I would probably not have been surprised about a hypothetical higher-than-average alcohol consumption in a sample like that (they don’t talk about alcohol so I don’t have data on this, I’m just saying I wouldn’t be surprised – after all I do know that doctors are high-risk for suicide), but such a large proportion smoking? That’s unexpected. It probably shouldn’t have been, considering that this is very much in line with the coverage included in Thirlaway & Upton’s book. I include some remarks about their coverage about smoking in my third post about the book here. The important observation of note from that part of the book’s coverage is probably that most smokers want to quit and yet very few manage to actually do it. “Although the majority of smokers want to stop smoking and predict that they will have stopped in twelve months, only 2–3 per cent actually stops permanently a year (Taylor et al. 2006).” If those future Polish doctors know that smoking is bad for them, but they assume that they can just ‘stop in time’ when ‘the time’ comes – well, some of those people are probably in for a nasty surprise (and they should have studied some more, so that they’d known this?).
“A prospective study of middle-aged British men […] revealed that the self-assessment of health status was strongly associated with mortality. Men who reported poor health had an eight-fold increase in total mortality compared with those reporting excellent health. Those who assessed their health as poor were manual workers, cigarette smokers, and often heavy drinkers. Half of those with poor health suffered from chest pain on exertion and other chronic diseases. Thus, self-assessment of health status appears to be a good measure of current physical health and risk of death“.
“It is estimated that globally 3.1 million people die each year due to chronic obstructive pulmonary disease (COPD). According to the World Health Organization (WHO 2014), the disease was the third leading cause of death worldwide in 2012. [In the next chapter of the book they state that: “COPD is currently the fourth leading cause of death among adult patients globally, and it is projected that it will be the third most common cause of death by 2020.” Whether it’s the third or fourth most common cause of death, it definitely kills a lot of people…] […] Approximately 40–50 % of lifelong smokers will go on to develop COPD […] the number of patients with a primary diagnosis of COPD […] constitutes […] 1.33 % of the total population of Poland. This result is consistent with that obtained during the Polish Spirometry Day in 2011 (Dabrowiecki et al. 2013) when 1.1 % of respondents declared having had a diagnosed COPD, while pulmonary function tests showed objectively the presence of obstruction in 12.3 % of patients.”
Based on numbers like these I feel tempted to conclude that the lungs may be yet another organ in which a substantial proportion of people of advanced age experience low-level organ dysfunction arguably not severe enough to lead to medical intervention. The kidneys are similar, as I also noted when I covered Longmore et al.‘s text.
“Generally, the costs of treatment of patients with COPD are highly variable […] estimates suggest […] that the costs of treatment of moderate stages of COPD may be 3–4-fold higher in comparison with the mild form of the disease, and in the severe form they reach up to 6–10 times the basic cost […] every second person with COPD is of working age […] Admission rates for COPD patients differ as much as 10-fold between European countries (European Lung White Book 2013).”
“In the EU, the costs of respiratory diseases are estimated at 6 % of the budget allocated to health care. Of this amount, 56 % is allocated for the treatment of COPD patients. […] Studies show that one per ten Poles over 30 year of age have COPD symptoms. Each year, around 4 % of all hospitalizations are due to COPD. […] One of the most important parameters regarding pharmacoeconomics is the hospitalization rate […] a high number of hospitalizations due to COPD exacerbations in Poland dramatically increase direct medical costs.”
I bolded the quote above because I knew this but had never seen it stated quite as clearly as it’s stated here, and I may be tempted to quote that one later on. Hospitalizations are often really expensive compared to drugs people who are not hospitalized take for their various health conditions, for example you can probably buy a year’s worth of anti-diabetic drugs, or more, for the costs of just one hospital admission due to drug mis-dosing. Before you get the idea that this might have ‘obvious implications’ for how ‘one’ should structure medical insurance arrangements in terms of copay structures etc., do however keep in mind that the picture here is really confusing:
Here’s the link, with more details – the key observation is that: “There is no consistency […] in the direction of change in costs resulting from changes in compliance”. That’s not diabetes, that’s ‘stuff in general’.
It would be neat if you could e.g. tell a story about how high costs of a drug always lead to non-compliance, which lead to increased hospitalization rates, which lead to higher costs than if the drugs had been subsidized. That would be a very strong case for subsidization. Or it would be neat if you could say that it doesn’t matter whether you subsidize a drug or not, because the costs of drugs are irrelevant in terms of usage patterns – people are told to take one pill every day by their doctor, and by golly that’s what they’re doing, regardless of what those pills cost. I know someone personally who wrote a PhD thesis about a drug where that clearly wasn’t the case, and the price elasticity was supposed to be ‘theoretically low’ in that case, so that one’s obviously out ‘in general’, but the point is that people have looked at this stuff, a lot. I’m assuming you might be able to spot a dynamic like this in some situations, and different dynamics in the case of other drugs. It gets even better when you include complicating phenomena like cost-switching; perhaps the guy/organization responsible for potentially subsidizing the drug is not the same guy(/-…) as the guy who’s supposed to pay for the medical admissions (this depends on the insurance structure/setup). But that’s not always the case, and the decision as to who pays for what is not necessarily a given; it may depend e.g. on health care provider preferences, and those preferences may themselves depend upon a lot of things unrelated to patient preferences or -incentives. A big question even in the relatively simple situation where the financial structure is – for these purposes at least – simple, is also the extent to which relevant costs are even measured, and/or how they’re measured (if a guy dies due to a binding budget constraint resulting in no treatment for a health condition that would have been treatable with a drug, is that outcome supposed to be ‘very cheap’ (he didn’t pay anything for drugs, so there were no medical outlays) or very expensive (he could have worked for another two decades if he’d been treated, and those productivity losses need to be included in the calculation somehow; to focus solely on medical outlays is thus to miss the point)? An important analytical point here is that if you don’t explicitly make those deaths/productivity losses expensive, they are going to look very cheap, because the default option will always be to have them go unrecorded and untallied.
A problem not discussed in the coverage was incidentally the extent to which survey results pertaining to the cost of vaccination are worth much. You ask doctors why they didn’t get vaccinated, and they tell you it’s because it’s too expensive. Well, how many of them would you have expected to tell you they did not get vaccinated because the vaccines were too cheap? This is more about providing people with a perceived socially acceptable out than it is about finding stuff out about their actual reasons for behaving the way they do. If the price of vaccination does not vary across communities it’s difficult to estimate the price elasticity, true (if it does, you probably got an elasticity estimate right there), but using survey information to implicitly assess the extent to which the price is too high? Allow the vaccination price to vary next year/change it/etc. (or even simpler/cheaper, if those data exist; look at price variation which happened in the past and observe how the demand varied), and see if/how the doctors and nurses respond. That’s how you do this, you don’t ask people. Asking people is also actually sort of risky; I’m pretty sure a smart doctor could make an argument that if you want doctors to get vaccinated you should pay them for getting the shot – after all, getting vaccinated is unpleasant, and as mentioned there are positive externalities here in terms of improved patient outcomes, which might translate into specific patients not dying, which is probably a big deal, for those patients at least. The smart doctor wouldn’t necessarily be wrong; if the price of vaccination was ‘sufficiently low’, i.e. a ‘large’ negative number (‘if you get vaccinated, we give you $10.000’), I’m pretty sure coverage rates would go up a lot. That doesn’t make it a good idea. (Or a bad idea per se, for that matter – it depends upon the shape of the implicit social welfare function we’re playing around with. Though I must add – so that any smart doctors potentially reading along here don’t get any ideas – that a ‘large’ negative price of vaccination for health care workers is a bad idea if a cheaper option which achieves the same outcome is potentially available to the decision makers in question, which seems highly likely to me. For example vaccination rates of medical staff would also go up a lot if regular vaccinations were made an explicit condition of their employment, the refusal of which would lead to termination of their employment… There would be implicit costs of such a scheme, in terms of staff selection effects, but if you’re comparing solely those options and you’re the guy who makes the financial decisions..?)
i. On the youtube channel of the Institute for Advanced Studies there has been a lot of activity over the last week or two (far more than 100 new lectures have been uploaded, and it seems new uploads are still being added at this point), and I’ve been watching a few of the recently uploaded astrophysics lectures. They’re quite technical, but you can watch them and follow enough of the content to have an enjoyable time despite not understanding everything:
This is a good lecture, very interesting. One major point made early on: “the take-away message is that the most common planet in the galaxy, at least at shorter periods, are planets for which there is no analogue in the solar system. The most common kind of planet in the galaxy is a planet with a radius of two Earth radii.” Another big take-away message is that small planets seem to be quite common (as noted in the conclusions, “16% of Sun-like stars have an Earth-sized planet”).
Of the lectures included in this post this was the one I liked the least; there are too many (‘obstructive’) questions/interactions between lecturer and attendants along the way, and the interactions/questions are difficult to hear/understand. If you consider watching both this lecture and the lecture below, I would say that it would probably be wise to watch the lecture below this one before you watch this one; I concluded that in retrospect some of the observations made early on in the lecture below would have been useful to know about before watching this lecture. (The first half of the lecture below was incidentally to me somewhat easier to follow than was the second half, but especially the first half hour of it is really quite good, despite the bad start (which one can always blame on Microsoft…)).
ii. Words I’ve encountered recently (…or ‘recently’ – it’s been a while since I last posted one of these lists): Divagations, periphrasis, reedy, architrave, sett, pedipalp, tout, togs, edentulous, moue, tatty, tearaway, prorogue, piscine, fillip, sop, panniers, auxology, roister, prepossessing, cantle, catamite, couth, ordure, biddy, recrudescence, parvenu, scupper, husting, hackle, expatiate, affray, tatterdemalion, eructation, coppice, dekko, scull, fulmination, pollarding, grotty, secateurs, bumf (I must admit that I like this word – it seems fitting, somehow, to use that word for this concept…), durophagy, randy, (brief note to self: Advise people having children who ask me about suggestions for how to name them against using this name (or variants such as Randi), it does not seem like a great idea), effete, apricity, sororal, bint, coition, abaft, eaves, gadabout, lugubriously, retroussé, landlubber, deliquescence, antimacassar, inanition.
iii. “The point of rigour is not to destroy all intuition; instead, it should be used to destroy bad intuition while clarifying and elevating good intuition. It is only with a combination of both rigorous formalism and good intuition that one can tackle complex mathematical problems; one needs the former to correctly deal with the fine details, and the latter to correctly deal with the big picture. Without one or the other, you will spend a lot of time blundering around in the dark (which can be instructive, but is highly inefficient). So once you are fully comfortable with rigorous mathematical thinking, you should revisit your intuitions on the subject and use your new thinking skills to test and refine these intuitions rather than discard them. One way to do this is to ask yourself dumb questions; another is to relearn your field.” (Terry Tao, There’s more to mathematics than rigour and proofs)
iv. A century of trends in adult human height. A figure from the paper (Figure 3 – Change in adult height between the 1896 and 1996 birth cohorts):
(Click to view full size. WordPress seems to have changed the way you add images to a blog post – if this one is even so annoyingly large, I apologize, I have tried to minimize it while still retaining detail, but the original file is huge). An observation from the paper:
“Men were taller than women in every country, on average by ~11 cm in the 1896 birth cohort and ~12 cm in the 1996 birth cohort […]. In the 1896 birth cohort, the male-female height gap in countries where average height was low was slightly larger than in taller nations. In other words, at the turn of the 20th century, men seem to have had a relative advantage over women in undernourished compared to better-nourished populations.”
v. I found this paper, on Exercise and Glucose Metabolism in Persons with Diabetes Mellitus, interesting in part because I’ve been very surprised a few times by offhand online statements made by diabetic athletes, who had observed that their blood glucose really didn’t drop all that fast during exercise. Rapid and annoyingly large drops in blood glucose during exercise have been a really consistent feature of my own life with diabetes during adulthood. It seems that there may be big inter-individual differences in terms of the effects of exercise on glucose in diabetics. From the paper:
“Typically, prolonged moderate-intensity aerobic exercise (i.e., 30–70% of one’s VO2max) causes a reduction in glucose concentrations because of a failure in circulating insulin levels to decrease at the onset of exercise.12 During this type of physical activity, glucose utilization may be as high as 1.5 g/min in adolescents with type 1 diabetes13 and exceed 2.0 g/min in adults with type 1 diabetes,14 an amount that quickly lowers circulating glucose levels. Persons with type 1 diabetes have large interindividual differences in blood glucose responses to exercise, although some intraindividual reproducibility exists.15 The wide ranging glycemic responses among individuals appears to be related to differences in pre-exercise blood glucose concentrations, the level of circulating counterregulatory hormones and the type/duration of the activity.2“
As I stated in my goodreads review, ‘If you’re a schizophrenic and/or you have a strong interest in e.g. the metabolic effects of various anti-psychotics, the book is a must-read’. If that’s not true, it’s a different matter. One reason why I didn’t give the book a higher rating is that many of the numbers in there are quite dated, which is a bit annoying because it means you might feel somewhat uncertain about how valid the estimates included still are at this point.
As pointed out in my coverage of the human drug metabolism text there are a lot of things that can influence the way that drugs are metabolized, and this text includes some details about a specific topic which may help to illustrate what I meant by stating in that post that people ‘self-experimenting’ may be taking on risks they may not be aware of. Now, diabetics who need insulin injections are taking a drug with a narrow therapeutic index, meaning that even small deviations from the optimal dose may have serious repercussions. A lot of things influence what is actually the optimal dose in a specific setting; food (“food is like a drug to a person with diabetes”, as pointed out in Matthew Neal’s endocrinology text, which is yet another text I, alas, have yet to cover here), sleep patterns, exercise (sometimes there may be an impact even days after you’ve exercised), stress, etc. all play a role, and even well-educated diabetics may not know all the details.
A lot of drugs also affect glucose metabolism and insulin sensitivity, one of the best known drug types of this nature probably being the corticosteroids because of their widespread use in a variety of disorders, including autoimmune disorders which tend to be more common in autoimmune forms of diabetes (mainly type 1). However many other types of drugs can also influence blood glucose, and on the topic of antidepressants and antipsychotics we actually know some stuff about these things and about how various medications influence glucose levels; it’s not a big coincidence that people have looked at this, they’ve done that because it has become clear that “[m]any medications, in particular psychotropics, including antidepressants, antipsychotics, and mood stabilizers, are associated with elevations in blood pressure, weight gain, dyslipidemias, and/or impaired glucose homeostasis.” (p. 49). Which may translate into an increased risk of type 2 diabetes, and impaired glucose control in diabetics. Incidentally the authors of this text observes in the text that: “Our research group was among the first in the field to identify a possible link between the development of obesity, diabetes, and other metabolic derangements (e.g., lipid abnormalities) and the use of newer, second-generation antipsychotic medications.” Did the people who took these drugs before this research was done/completed know that their medications might increase their risk of developing diabetes? No, because the people prescribing it didn’t know, nor did the people who developed the drugs. Some probably still don’t know, including some of the medical people prescribing these medications. But the knowledge is out there now, and the effect size is in the case of some drugs argued to be large enough to be clinically relevant. In the context of a ‘self-experimentation’-angle the example is also interesting because the negative effect in question here is significantly delayed; type 2 diabetes takes time to develop, and this is an undesirable outcome which you’re not going to spot the way you might link a headache the next day to a specific drug you just started out with (another example of a delayed adverse event is incidentally cancer). You’re not going to spot dyslipidemia unless you keep track of your lipid levels on your own or e.g. develop xanthomas as a consequence of it, leading you to consult a physician. It helps a lot if you have proper research protocols and large n studies with sufficient power when you want to discover things like this, and when you want to determine whether an association like this is ‘just an association’ or if the link is actually causal (and then clarifying what we actually mean by that, and whether the causal link is also clinically relevant and/or for whom it might be clinically relevant). Presumably many people taking all kinds of medical drugs these days are taking on risks which might in a similar manner be ‘hidden from view’ as was the risk of diabetes in people taking second-generation antipsychotics in the near-past; over time epidemiological studies may pick up on some of these risks, but many will probably remain hidden from view on account of the amount of complexity involved. Even if a drug ‘works’ as intended in the context of the target variable in question, you can get into a lot of trouble if you only focus on the target variable (“if a drug has no side effects, then it is unlikely to work“). People working in drug development know this.
The book has a lot of blog-worthy stuff so I decided to include some quotes in the coverage below. The quotes are from the first half of the book, and this part of the coverage actually doesn’t talk much about the effects of drugs; it mainly deals with epidemiology and cost estimates. I thus decided to save the ‘drug coverage’ to a later post. It should perhaps be noted that some of the things I’d hoped to learn from Ru-Band Lu et al.’s book (blog coverage here) was actually included in this one, which was nice.
“Those with mental illness are at higher risk and are more likely to suffer the severe consequences of comorbid medical illness. Adherence to treatment is often more difficult, and other factors such as psychoneuroendocrine interactions may complicate already problematic treatments. Additionally, psychiatric medications themselves often have severe side effects and can interact with other medications, rendering treatment of the mental illness more complicated. Diabetes is one example of a comorbid medical illness that is seen at a higher rate in people with mental illness.”
“Depression rates have been studied and are increased in type 1 and type 2 diabetes. In a meta-analysis, Barnard et al. reviewed 14 trials in which patients with type 1 diabetes were surveyed for rates of depression.16 […] subjects with type 1 diabetes had a 12.0% rate of depression compared with a rate of 3.4% in those without diabetes. In noncontrolled trials, they found an even higher rate of depression in patients with type 1 diabetes (13.4%). However, despite these overall findings, in trials that were considered of an adequate design, and with a substantially rigorous depression screening method (i.e., use of structured clinical interview rather than patient reported surveys), the rates were not statistically significantly increased (odds ratio [OR] 2.36, 95% confidence interval [CI] 0.69–5.4) but had such substantial variation that it was not sufficient to draw a conclusion regarding type 1 diabetes. […] When it comes to rates of depression, type 2 diabetes has been studied more extensively than type 1 diabetes. Anderson et al. compiled a large metaanalysis, looking at 42 studies involving more than 21,000 subjects to assess rates of depression among patients with type 1 versus type 2 diabetes mellitus.18 Regardless of how depression was measured, type 1 diabetes was associated with lower rates of depression than type 2 diabetes. […] Depression was significantly increased in both type 1 and type 2 diabetes, with increased ORs for subjects with type 1 (OR = 2.9, 95% CI 1.6 –5.5, […] p=0.0003) and type 2 disease (OR = 2.9, 95% CI 2.3–3.7, […] p = 0.0001) compared with controls. Overall, with multiple factors controlled for, the risk of depression in people with diabetes was approximately twofold. In another large meta-analysis, Ali et al. looked at more than 51,000 subjects in ten different studies to assess rates of depression in type 2 diabetes mellitus. […] the OR for comorbid depression among the diabetic patients studied was higher for men than for women, indicating that although women with diabetes have an overall increased prevalence of depression (23.8 vs. 12.8%, p = 0.0001), men with diabetes have an increased risk of developing depression (men: OR = 1.9, 95% CI = 1.7–2.1 vs. women: OR = 1.3, 95% CI = 1.2–1.4). […] Research has shown that youths 12–17 years of age with type 1 diabetes had double the risk of depression compared with a teenage population without diabetes.21 This amounted to nearly 15% of children meeting the criteria for depression.”
“As many as two-thirds of patients with diabetes and major depression have been ill with depression for more than 2 years.44 […] Depression has been linked to decreased adherence to self-care regimens (exercise, diet, and cessation of smoking) in patients with diabetes, as well as to the use of diabetes control medications […] Patients with diabetes and depression are twice as likely to have three or more cardiac risk factors such as smoking, obesity, sedentary lifestyle, or A1c > 8.0% compared with patients with diabetes alone.47 […] The costs for individuals with both major depression and diabetes are 4.5 times greater than for those with diabetes alone.53”
“A 2004 cross-sectional and longitudinal study of data from the Health and Retirement Study demonstrated that the cumulative risk of incident disability over an 8-year period was 21.3% for individuals with diabetes versus 9.3% for those without diabetes. This study examined a cohort of adults ranging in age from 51 to 61 years from 1992 through 2000.”
“Although people with diabetes comprise just slightly more than 4% of the U.S. population,3 19% of every dollar spent on health care (including hospitalizations, outpatient and physician visits, ambulance services, nursing home care, home health care, hospice, and medication/glucose control agents) is incurred by individuals with diabetes” (As I noted in the margin, these are old numbers, and prevalence in particular is definitely higher today than it was when that chapter was written, so diabetics’ proportion of the total cost is likely even higher today than it was when that chapter was written. As observed multiple times previously on this blog, most of these costs are unrelated to the costs of insulin treatment and oral anti-diabetics like metformin, and indirect costs make out a quite substantial proportion of the total costs).
“In 1997, only 8% of the population with a medical claim of diabetes was treated for diabetes alone. Other conditions influenced health care spending, with 13.8% of the population with one other condition, 11.2% with two comorbidities, and 67% with three or more related conditions.6 Patients with diabetes who suffer from comorbid conditions related to diabetes have a greater impact on health services compared with those patients who do not have comorbid conditions. […] Overall, comorbid conditions and complications are responsible for 75% of total medical expenditures for diabetes.” (Again, these are old numbers)
“Heart disease and stroke are the largest contributors to mortality for individuals with diabetes; these two conditions are responsible for 65% of deaths. Death rates from heart disease in adults with diabetes are two to four times higher than in adults without diabetes. […] Adults with diabetes are more than twice as likely to have multiple diagnoses related to macrovascular disease compared to patients without diabetes […] Although the prevalence of cardiovascular disease increases with age for both diabetics and nondiabetics, adults with diabetes have a significantly higher rate of disease. […] The management of macrovascular disease, such as heart attacks and strokes, represents the largest factor driving medical service use and related costs, accounting for 52% of costs to treat diabetes over a lifetime. The average costs of treating macrovascular disease are $24,330 of a total of $47,240 per person (in year 2000 dollars) over the course of a lifetime.17 Moreover, macrovascular disease is an important determinant of cost at an earlier time than other complications, accounting for 85% of the cumulative costs during the first 5 years following diagnosis and 77% over the initial decade. [Be careful here: This is completely driven by type 2 diabetics; a 10-year old newly diagnosed type 1 diabetic does not develop heart disease in the first decade of disease – type 1s are also at high risk of cardiovascular disease, but the time profile here is completely different] […] Cardiovascular disease in the presence of diabetes affects not only cost but also the allocation of health care resources. Average annual individual costs attributed to the treatment of diabetes with cardiovascular disease were $10,172. Almost 51% of costs were for inpatient hospitalizations, 28% were for outpatient care, and 21% were for pharmaceuticals and related supplies. In comparison, the average annual costs for adults with diabetes and without cardiovascular disease were $4,402 for management and treatment of diabetes. Only 31.2% of costs were for inpatient hospitalizations, 40.3% were for outpatient care, and 28.6% were for pharmaceuticals.16“
“Of individuals with diabetes, 2% to 3% develop a foot ulcer during any given year. The lifetime incidence rate of lower extremity ulcers is 15% in the diabetic population.20 […] The rate of amputation in individuals with diabetes is ten times higher than in those without diabetes.5 Diabetic lower-extremity ulcers are responsible for 92,000 amputations each year,21 accounting for more than 60% of all nontraumatic amputations.5 The 10-year cumulative incidence of lower-extremity amputation is 7% in adults older than 30 years of age who are diagnosed with diabetes.22 […] Following amputation, the 5-year survival rate is 27%.23 […] The majority of annual costs associated with treating diabetic peripheral neuropathy are associated with treatment of ulcers […] Overall, inpatient hospitalization is a major driver of cost, accounting for 77% of expenditures associated with individual episodes of lower-extremity ulcers.24“
“By 2003, diabetes accounted for 37% of individuals being treated for renal disease in the United States. […] Diabetes is the leading cause of kidney failure, accounting for 44% of all newly diagnosed cases. […] The amount of direct medical costs for ESRD attributed to diabetes is substantial. The total adjusted costs in a 24-month period were 76% higher among ESRD patients with diabetes compared with those without diabetes. […] Nearly one half of the costs of ESRD are due to diabetes.27” [How much did these numbers change since the book was written? I’m not sure, but these estimates do provide some sort of a starting point, which is why I decided to include the numbers even though I assume some of them may have changed since the publication of the book]
“Every percentage point decrease in A1c levels reduces the risk of microvascular complications such as retinopathy, neuropathy, and nephropathy by 40%.5 However, the trend is for A1c to drift upward at an average of 0.15% per year, increasing the risk of complications and costs.17 […] A1c levels also affect the cost of specific complications associated with diabetes. Increasing levels affect overall cost and escalate more dramatically when comorbidities are present. A1c along with cardiovascular disease, hypertension, and depression are significant independent predictors of health care
costs in adults with diabetes.”
My first post covering Coleman’s excellent book can be found here, and here you can read my goodreads review of the book; I think it makes sense to read those things before reading this post, if you have not already done that. As I believe I’ve previously mentioned (?) most non-fiction books I read, including those I do not blog, usually get a goodreads review, and actually I’m much more active on goodreads these days than I am on this blog. I have considered cross-posting goodreads reviews here on the blog, but I decided it might be best to just keep these things separate for the time being. I might change my mind about this, though; I don’t like how inactive the blog has become during the last few months, and goodreads reviews I’ve already written take almost no work to cross-post, so this would be an easy way to at least get some ‘activity’ here.
The book includes a lot of information that really pretty much everybody would be likely to benefit from knowing (how many people for example live their entire lives without consuming any alcohol, tobacco, or medical drugs? If you’ve ever consumed any of these things, the book has material of relevance included in the coverage…). I repeat myself here, but some of the general observations included in the following seem to me to be important takeaways from the book: Drugs work (sometimes very) differently in different people, they interact with different things, including innocuous things like what you eat and drink and whether you exercise or not; drugs may interact with each other, in a very confusing variety of ways; some drugs are metabolized differently in people who have taken the drug for a while (‘induction’), compared to how the drug might be metabolized in someone who’s not taken the drug before (drug-naïve), and sometimes the ability to metabolize the drug faster/more efficiently may be lost (inhibition) because of a third factor, such as e.g. another drug or a dietary factor, which can be very dangerous (an improved ability to metabolize the drug because of habituation may also be lost due to non-consumption of the drug for some time, leading to a ‘reset’ of the metabolic pathway of relevance, an important factor in an abuse context where this can lead to overdose); there are huge racial and genetic differences in terms of how specific drugs are metabolized; the consequences of getting too much of a specific drug (toxicity) tend to be foreseeably different from the consequences of getting not enough of a drug (drug failure); efficient metabolism of a drug may depend upon the body’s ability not just to transform the xenobiotic compound into something useful, but also the ability to get rid of sometimes really quite toxic metabolites which might be created along the way as the body tries to get rid of that thing you just injected/ingested/etc. Many people don’t consider herbal remedies to be ‘real drugs’ and so neglect to tell their medical practitioner that they’re taking them/have recently stopped taking them, despite some of these having the potential to cause quite serious drug interactions (even if nothing is taken but herbal remedies; St. John’s Wort + kava kava = acute hepatitis? As noted in the book, “One point important to emphasize, is that assuming various herbal remedies do contain active and potent substituents, there is virtually nothing known clinically about what effects mixing herbal remedies might have, in terms of pharmacology and toxicity. This area is unfortunately left for patients to discover for themselves”).
This book is not ‘the whole story’ about drug metabolism and related stuff, it just scratches the surface, but the coverage serves to make it clear to you just how much stuff is to be found ‘below the surface’, and this is something I really like about the book. It makes you appreciate how little you know and how complex this stuff is. People write 500+ page textbooks like this one simply about CYP subtypes (I came across a different 1000+ page textbook also about a CYP subtype while reading the book so I know this one is hardly unique, but unfortunately I did not bookmark the book and I didn’t find the book after a brief search for it – but take my word for it, those books are out there…) and alcohol metabolism, they write 700 page textbooks about the side effects of psychiatric drugs (not the intended effects, that is – the side effects!) they write 800 page textbooks about aspirin and related drugs and about how drugs affect the liver… I know that in some circles it’s somewhat common for people to ‘experiment’ with various drugs and substances, illicit or otherwise; I also assume that most people who do this sort of thing have little idea what they’re actually doing and are likely taking a lot of risks the very existence of which they’re likely not aware of. Simply because there’s just so much stuff you need to know to even have a proper concept of what you’re doing when you’re dealing with how the human body works and how it responds to foreign substances we might choose to introduce into it. It might be that they wouldn’t care even if they knew because you’re probably rather low in risk aversion if you engage in that sort of experimentation in the first place (I incidentally am highly risk averse), but I do find it curious.
I have added some observations from the middle of the book below.
“Although there is growing awareness of the clinical problems posed by P-gp [P-glycoprotein] inhibition on drug bioavailability and toxicity, until recently it was very difficult to generalize and predict which classes of drug might be inhibitors of P-gp. […] There are dozens of drugs which are known inhibitors of P-gp […] it is often difficult to establish what contribution cellular transport systems make to bioavailability. Indeed, it is emerging that one of the reasons for the very wide variety of drug bioavailability in modern medicine could be the sheer number of possible inhibitors and substrates that exist for P-gp in the diet, such as a number of natural products like the flavonols, which can be as potent as cyclosporine or verapamil as P-gp inhibitors. Natural dietary inhibitors have advantages in their general lack of toxicity, but the basic problem of a lack of predictability in their effects on P-gp substrates remains. Since no two people’s diets are identical, the impact of P-gp modulation on drug absorption could be simply too complex to unravel.”
“the objectives of metabolizing systems could be summed up thus:
• To terminate the pharmacological effect of the molecule.
• Make the molecule so water-soluble that it cannot escape clearance, preferably by more than one route to absolutely guarantee its removal.
These objectives could be accomplished by:
• Changing the molecular shape so it no longer binds to its receptors.
• Changing the molecular lipophilicity to hydrophilicity to ensure high water solubility.
• Making the molecule larger and heavier, so it can be eliminated in bile as well as urine.
• Efflux pump systems, which ensure that a highly water-soluble metabolite actually leaves the cell to enter the bloodstream, before it is excreted in bile and urine. […]
CYP-mediated metabolism can increase hydrophilicity, but it does not always increase it enough and it certainly does not make the molecule any bigger and heavier, indeed, sometimes the molecule becomes lighter […] CYP-mediated metabolism does not always alter the pharmacological effects of the drug either […] However, CYPs do perform two essential tasks: the initial destabilization of the molecule, creating a ‘handle’ on it. […] CYPs also ‘unmask’ groups that could be more reactive for further metabolism. […] CYP-mediated preparation can make the molecule vulnerable to the attachment of a very water-soluble and plentiful agent to the drug or steroid, which accomplishes the objectives of metabolism. This is achieved through the attachment of a modified glucose molecule (glucuronidation), or a soluble salt such as a sulphate (sulphation) [see also this] to the prepared site. Both adducts usually make the drug into a stable, heavier and water-soluble ex-drug. […] with many drugs, their stability and lipophilicity mean that their clearance must take more than one metabolic operation to make them water-soluble.”
“PXR [Pregnane X receptor], CAR [constitutive androstane receptor] and FXR [Farnesoid X receptor] are […] part of the process whereby the liver can sense whether its own metabolic capacity and physical size is sufficient to respond to homeostatic demands. Hence, alongside various growth factors, the NRs [nuclear receptors] facilitate the amazing process whereby the liver regenerates itself after areas of the organ are removed or damaged. […] As CYPs, UGTs [Glucuronosyltransferases], other biotransforming systems and efflux transporters are meeting the same xenobiotic or endobiotic stimuli in different tissues and degrees of exposure, it is logical that the […] receptor systems integrate and coordinate their responses. […] These multi-receptor mechanisms enable levels of induction to be customized for individual tissues to deal with different chemical threats. Essentially, according to diet, chemical and drug exposure, each individual will possess a unique expression array of UGTs and CYPs which will be constantly fine-tuned throughout life.”
“Sulphonation is accomplished by a set of enzyme systems known as sulphotransferases (SULTs) and they are found in most tissues to varying degrees of activity. […] The general aim of sulphonation is to make the substrate more water-soluble and usually less active pharmacologically. Sulphonated molecules are more readily eliminated in bile and urine. […] All SULTs are subject to genetic polymorphisms, with a high degree of individual variation in their expression and catalytic activities […] Regarding classification of the superfamily of SULTs, it is assumed that 47 per cent amino acid sequence homology is indicative of same family members and 60 per cent homology for subfamily members. To date, there are 47 mammalian SULT isoforms so far discovered, which are derived from ten human sulphotransferase gene families […] knowledge of the role of NRs and AhR [Aryl hydrocarbon receptor] in human SULT expression has progressed in animals but not really in humans. This is partly due to the fact that rodent SULT profiles are quite different to ours […] Many studies have been carried out in rodents, which have produced rather contradictory results […] It seems that whilst SULTs in general are not as responsive to inducers as CYPs and UGTs, their basal expression is much higher, although interindividual expression does vary considerably and this may have severe toxicological consequences, in terms of xenobiotic toxicity and carcinogenicity. There is also some evidence that diet is a strong influence on individual SULT profiles.”
“One of the main problems with the oxidation of various molecules by CYP enzymes is that they are often destabilized and sometimes form highly reactive products. […] CYPs occasionally form metabolites so reactive that they immediately destroy the enzyme by reacting with it, changing its structure and, therefore, its function. […] The most dangerous forms of reactive species are those that evade UGTs and SULT enzymes, or are inadvertently created by conjugation processes. These species escape into the cytosol and even into the nucleus, where potentially carcinogenic events may result. […] CYPs are not the only source of reactive species generated within cells. Around 75 per cent of our food intake is directed at maintaining our body temperature and a great deal of energy must be liberated from the food to accomplish this. Cells derive the vast majority of their energy through oxidative phosphorylation and this takes place in […] the mitochondria. […] In cells almost all the oxygen we breathe is consumed in oxidative phosphorylation, forming ATP, heat and reactive oxidant species in the mitochondria that could cause severe damage to the structure and function of the cell if they were allowed to escape. So all cells, particularly hepatocytes, have evolved a separate system to accommodate such reactive toxic products and this is based on a three amino acid (cysteine, glycine and glutamate) thiol known as glutathione, or GSH. Thiols in general are extremely effective at reducing and thus ‘quenching’ highly reactive, electrophilic species. […] if cells are depleted of GSH by blocking its synthesis (by using buthionine sulphoxime), cell death follows and the organism itself will die in a few days, due to uncontrolled activity of endogenous radicals. […] If GSH levels are not maintained in the cell over a long period of time, the cell wears out more quickly; for example, diabetic complications and HIV infection are linked with poor GSH maintenance.” [I did not know this…]
“There are several enzymes that promote and catalyze the reaction of GSH with potential toxins to ensure that reactive species are actively dealt with, rather than just passive GSH-mediated reduction. Probably the most important from the standpoint of drug metabolism are the GSH-S-transferases [‘GSTs’, which] are the key cellular defence against electrophilic agents formed from endogenous or xenobiotic oxidative metabolism. […] The GSTs are found in humans in several major classes. […] The classes contain several subfamilies […] These enzymes are polymorphic […] and their individual expression ranges from complete absence in some isoforms to overabundance as a response to anticancer therapy. […] The upregulation of GST is a serious problem within cancer therapeutics and resistance to a range of drugs including melphalan and doxorubicin is linked with GST detoxification. Much research has been directed at inhibitors of GST isoforms to reverse or even prevent the development of resistance to anti-neoplastic agents. Unfortunately this strategy has not been successful”
“once xenobiotics have been converted into low-toxicity, higher-molecular-weight and high-water-solubility metabolites by the combination of CYPs, UGTs, SULTs and GSTs, this appears at first sight to be ‘mission accomplished’. However, these conjugates must be transported against a concentration gradient out of the cell into the interstitial space between cells. Then they will enter the capillary system and thence to the main bloodstream and filtration by the kidneys. The biggest hurdle is the transport out of the cell, which is a tall order, as once a highly water-soluble entity has been created, it will effectively be ‘ion-trapped’ in the cell, as the cell membrane is highly lipophilic and is an effective barrier to the exit as well as entry of most hydrophilic molecules. […] failure to remove the hydrophilic products of conjugation reactions [from the cells] can lead to:
• toxicity of conjugates to various cell components;
• hydrolysis of conjugates back to the original reactive species;
• inhibition of conjugating enzymes.
If the cell can manage to transport them out, then they should be excreted in urine or bile and detoxification can proceed at a maximal rate. […] Consequently, an impressive array of multi-purpose membrane bound transport carrier systems has evolved which can actively remove hydrophilic metabolites and many other low molecular weight drugs and toxins from cells. The relatively recent […] term of Phase III metabolism has been applied to the study of this essential arm of the detoxification process. […] The main thrust of research into efflux transporters has been directed at the ABC-type transporters [this link actually has quite a bit of content, unlike some of the other wiki articles on these topics], of which there are 48 genes that code of a variety of ATP-powered pumps.”
“it is clear that the whole process of detection, metabolism and elimination of endobiotic and xenobiotic agents is minutely coordinated and is responsive to changes in load in individual tissues. The CYPs, UGTs, MRPs [Multidrug Resistance Proteins] and P-gp are all tightly regulated through the NR system of PXR, CAR, FXE, PPAR α, LXR etc, as well as the AhR receptor system [does it even make sense to keep adding links here? I’m not sure it does…]. Some enzyme/pump processes are closely linked, such as CYP3A4 and P-gp, as inducers powerfully increase both systems capacity. The reactive species protection ‘arm’ of biotransformation is also controlled through a separate but almost certainly ‘cross-talking’ Nrf2/Keap1 system which coordinates not only the interception of reactive species by GSTs, but also the supply of their GSH substrate, UGTs and the MRPs. This latter coordination is particularly relevant in resistance to cancer chemotherapy and happens because overexpression of any one entity alone cannot rid the cell of the toxin. […] The MRPs, GSH production and GST/UGT activity must be induced in concert. […] much of the integration and coordination of detoxification processes remains to be uncovered”.
Chapter 7, about ‘factors affecting drug metabolism’, has some very interesting stuff, but I think this post is quite long enough as it is. I might talk about that stuff in detail later on, but I make no promises.
i. “It wasn’t what was done to you. Life was what you did with what was done to you.” (Kameron Hurley)
ii. “Stepan Arkadyevitch was a truthful man in his relationship with himself. He was incapable of deceiving himself and persuading himself that he repented of his conduct. He could not at this date repent of the fact that he, a handsome, susceptible man of thirty-four, was not in love with his wife, the mother of five living and two dead children, and only a year younger than himself. All he repented of was that he had not succeeded better in hiding it from his wife.” (Tolstoy, Anna Karenina)
iii “”And is it true the younger Vlassieva girl’s to marry Topov?”
“Yes, they say it’s quite a settled thing.”
“I wonder at the parents! They say it’s a marriage for love.”
“For love? What antediluvian notions you have! Can one talk of love in these days?” said the ambassador’s wife.
“What’s to be done? It’s a foolish old fashion that’s kept up still,” said Vronsky.
“So much the worse for those who keep up the fashion. The only happy marriages I know are marriages of prudence.” (-ll-)
iv. “To be treated with mercy, some must reveal their handicaps, while others must conceal them.” (Yahia Lababidi)
v. “It is only in appearance that time is a river. It is rather a vast landscape and it is the eye of the beholder that moves.” (Thornton Wilder)
vi. “The instinct for self-deception in human beings makes them try to banish from their minds dangers of which at bottom they are perfectly aware by declaring them non-existent.” (Stefan Zweig)
vii. “When one does another person an injustice, in some mysterious way it does one good to discover (or to persuade oneself) that the injured party has also behaved badly or unfairly in some little matter or other; it is always a relief to the conscience if one can apportion some measure of guilt to the person one has betrayed.” (-ll-)
viii. “One can run away from anything but oneself.” (-ll-)
ix. “Nothing is harder than to accept oneself.” (Max Frisch)
x. “To a certain degree we are really the person others have seen in us” (-ll-)
xi. “Time does not change us[,] it just unfolds us” (-ll-)
xii. “I feel fairly certain that my hatred harms me more than the people whom I hate.” (-ll-)
xiii. “A society needs famous people; the question is whom it chooses for that role. Any criticism of its choice is by implication a criticism of that society.” (-ll-)
xiv. “‘You know what most of the milit’ry training is, Perks?’ he went on. […] It’s to turn you into a man who will, on the word of command, stick his blade into some poor sod just like him who happens to be wearing the wrong uniform. He’s like you, you’re like him. He doesn’t really want to kill you, you don’t really want to kill him. But if you don’t kill him first, he’ll kill you. That’s the start and finish of it. It don’t come easy without trainin’.” (Terry Pratchett, Monstrous Regiment)
xv. “Polly felt questing eyes boring into her. She was embarrassed, of course. But not for the obvious reason. It was for the other one, the little lesson that life sometimes rams home with a stick: you are not the only one watching the world. Other people are people; while you watch them they watch you, and they think about you while you think about them. The world isn’t just about you.” (-ll-)
xiv. “Fifty miles away, Lord Lynchknowle’s dinner had been interrupted by the arrival of a police car and the news of his daughter’s death. The fact that it had come between the mackerel pâté and the game pie, and on the wine side, an excellent Montrachet and a Château Lafite 1962, several bottles of which he’d opened to impress the Home Secretary and two old friends from the Foreign Office, particularly annoyed him. Not that he intended to let the news spoil his meal by announcing it before he’d finished, but he could foresee an ugly episode with his wife afterwards for no better reason than that he had come back to the table with the rather unfortunate remark that it was nothing important. Of course, he could always excuse himself on the grounds that hospitality came first, and old Freddie was the Home Secretary after all, and he wasn’t going to let that Lafite ’62 go to waste, but somehow he knew Hilary was going to kick up the devil of a fuss about it afterwards.” (Tom Sharpe, Wilt on High. As I also noted on goodreads I really liked Sharpe’s Wilt series; these books are very funny.)
xvii. “‘England’s ruin, damned Socialists,’ growled Sir Cathcart. ‘Turned the country into a benevolent society. Seem to think you can rule a nation with good intentions. Damned nonsense. Discipline. That’s what the country needs. A good dose of unemployment to bring the working classes to their senses.’ […] ‘It’s the dole. Man can earn more not working than he can at his job. All wrong. A bit of genuine starvation would soon put that right.’
‘I suppose the argument is that the wives and children suffer,’ said the Dean.
‘Can’t see much harm in that,’ the General continued. ‘Nothing like a hungry woman to put some pep into a man.” (Tom Sharpe, Porterhouse Blue. The Cathcart character is funny. He also has in his ’employment’ “A Japanese gardener, a prisoner of war, whom Sir Cathcart kept carefully ignorant of world news and who was, thanks to the language barrier, incapable of learning it for himself…” The book was published in 1974..)
xviii. “I believe that something crucial has been missing from all of the great debates of history, among philosophers, politicians, theologians, and thinkers from other and diverse backgrounds, on the issues of morality, ethics, justice, right and wrong. […] those who have tried to analyze morality have failed to treat the human traits that underlie moral behavior as outcomes of evolution […] for many conflicts of interest, compromises and enforceable contracts represent the only real solutions. Appeals to morality, I will argue, are simply the invoking of such compromises and contracts in particular ways. […] the process of natural selection that has given rise to all forms of life, including humans, operates such that success has always been relative. One consequence is that organisms resulting from the long-term cumulative effects of selection are expected to resist efforts to reveal their interests fully to others, and also efforts to place limits on their striving or to decide for them when their interests are being “fully” satisfied. These are all reasons why we should expect no “terminus” – ever – to debates on moral and ethical issues.” (Richard D. Alexander, The Biology of Moral Systems)
xix. “Should a traveller give an account of men who were entirely divested of avarice, ambition, or revenge; who knew no pleasure but friendship, generosity, and public spirit, we should immediately detect the falsehood and prove him a liar with the same certitude as if he had stuffed his narration with centaurs and dragons.” (David Hume, Essays and Treatises, 1772)
xx. “In plucking the fruit of memory one runs the risk of spoiling its bloom.” (Joseph Conrad)
This will be my last post about the book(s). You can read my previous posts about it(/them) here, here, and here. In this post I’ve included some quotes and observations from the last few hundred pages.
“In wartime […] truth is so precious that she should always be attended by a bodyguard of lies.”
“On June 10  General Montgomery reported that he was sufficiently established ashore to receive a visit. […] Montgomery, smiling and confident, met me at the beach as we scrambled out of our landing craft. His army had already penetrated seven or eight miles inland. There was very little firing or activity. […] The General was in the highest spirits. I asked him how far away was the actual front. He said about three miles. I asked him if he had a continuous line. He said, “No.” “What is there then to prevent an incursion of German armour breaking up our luncheon?” He said he did not think they would come. […] In the first six days 326,000 men, 54,000 vehicles, and 104,000 tons of stores were landed. […] [German] divisions arrived piecemeal, short of equipment, and fatigued by long night marches, and were thrown into the line as they came. […] On June 17, at Margival, near Soissons, Hitler held a conference with Rundstedt and Rommel. His two generals pressed on him strongly the folly of bleeding the German Army to death in Normandy. They urged that before it was destroyed the Seventh Army should make an orderly withdrawal towards the Seine […] Hitler would not agree. Here, as in Russia and Italy, he demanded that no ground should be given up and all should fight where they stood. The generals were of course right. […] by the middle of July thirty Allied divisions were ashore. Half were American and half British and Canadian. Against these the Germans had gathered twenty-seven divisions. But they had already suffered 160,000 casualties, and General Eisenhower estimated their fighting value as no higher than sixteen divisions. […] By August 30 our troops were crossing the Seine at many points. Enemy losses had been tremendous: 400,000 men, half of them prisoners, 1,300 tanks, 20,000 vehicles, 1,500 field guns. […] the Seine was reached six days ahead of the planned time.”
[During a visit to the Italian front:] [General] Alexander had planned an early start and a long day on the front. He had also promised to take me wherever I wanted to go. […] We first climbed by motor up a high outstanding rock pinnacle, upon the top of which a church and village were perched. The inhabitants, men and women, came out to greet us from the cellars in which they had been sheltering. It was at once plain that the place had just been bombarded. Masonry and wreckage littered the single street. “When did this stop?” Alexander asked the small crowd who gathered round us, grinning rather wryly. “About a quarter of an hour ago,” they said. […] Presently Alexander said that we had better not stay any longer, as the enemy would naturally be firing at observation posts like this and might begin again. […] We got into our cars accordingly, and in half an hour were across the river, where the road ran into undulating groves of olives, brightly patched with sunshine. Having got an officer guide from one of the battalions engaged, we pushed on through these glades till the sounds of rifle and machine-gun fire showed we were getting near to the front line. Presently warning hands brought us to a standstill. It appeared there was a minefield, and it was only safe to go where other vehicles had already gone without mishap. […] [We] found a very good place in the stone building, which was in fact an old château overlooking a rather sharp declivity. Here one certainly could see all that was possible. The Germans were firing with rifles and machine-guns from thick scrub on the farther side of the valley, about five hundred yards away. Our front line was beneath us. The firing was desultory and intermittent. But this was the nearest I got to the enemy and the time I heard the most bullets in the Second World War. After about half an hour we went back to our motor-cars and made our way to the river”.
The book has some interesting coverage of the Warsaw Uprising. The short story to people who don’t know it is that the Polish resistance movement started a major uprising in the city of Warsaw when the Soviet forces were very close to the city, a move encouraged by the Soviets [“Soviet broadcasting stations had for a considerable time been urging the Polish population to drop all caution and start a general revolt against the Germans”]. What the Soviets did as a response to the uprising was then to halt their advance rather than keep it going, in order to let the German army help Stalin get rid of the non-communist Polish resistance. Stalin also explicitly refused to allow British and American aircraft providing supplies to the Poles to land on Soviet […Polish…] territory. The tactics changed slightly over time: “On September 10, after six weeks of Polish torment, the Kremlin appeared to change their tactics. […] They wished to have the non-Communist Poles destroyed to the full, but also to keep alive the idea that they were going to their rescue.” So they pretended to try to help, but really did very little. “The struggle in Warsaw had lasted more than sixty days. Of the 40,000 men and women of the Polish Underground Army about 15,000 fell. Out of a population of a million nearly 200,000 had been stricken. […] When the Russians entered the city three months later [they were at points less than 10 miles away from the city when the uprising began] they found little but shattered streets and the unburied dead. Such was their liberation of Poland, where they now rule.” It should perhaps be obvious, but of course Stalin’s deceit did not stop there – this later sequence of events is also illustrative:
“At the beginning of March 1945 the Polish Underground were invited by the Russian Political Police to send a delegation to Moscow to discuss the formation of a united Polish Government along the lines of the Yalta agreement. This was followed by a written guarantee of personal safety and it was understood that the party would later be allowed if the negotiations were successful to travel to London for talks with the Polish Government in exile. On March 27 General Leopold Okulicki, the successor of General Bor-Komorowski in command of the Underground Army, two other leaders, and an interpreter had a meeting in the suburbs of Warsaw with a Soviet representative. They were joined the following day by eleven leaders representing the major political parties in Poland. One other Polish leader was already in Russian hands. No one returned from the rendezvous. On April 6 the Polish Government in exile issued a statement in London giving the outline of this sinister episode. The most valuable representatives of the Polish Underground had disappeared without a trace in spite of the formal Russian offer of safe-conduct. Questions were asked in Parliament and stories have since spread of the shooting of local Polish leaders in the areas at this time occupied by the Soviet armies […] On May 18 Stalin publicly denied that the arrested Polish leaders had ever been invited to Moscow […] The prisoners were accused of subversion, terrorism, and espionage, and all except one admitted wholly or in part the charges against them. […] This was in fact the judicial liquidation of the leadership of the Polish Underground which had fought so heroically against Hitler. The rank and file had already died in the ruins of Warsaw.”
“In the autumn of 1942 only three American aircraft-carriers were afloat; a year later there were fifty; by the end of the war there were more than a hundred. This achievement had been matched by an increase in aircraft production which was no less remarkable.”
“The number of divisions that could be sustained [in Europe, 1944], and the speed and range of their advance, depended […] entirely on harbours, transport, and supplies. Relatively little ammunition was being used, but food, and above all petrol, governed every movement.”
“You are responsible for maintaining order in Athens and for neutralising or destroying all E.A.M–E.L.A.S. bands approaching the city. […] Naturally E.L.A.S will try to put women and children in the van where shooting may occur. You must be clever about this and avoid mistakes. But do not hesitate to fire at any armed male in Athens who assails the British authority or Greek authority with which we are working. Do not […] hesitate to act as if you were in a conquered city where a local rebellion is in progress.” (Telegram to General Scobie. Here’s a related wiki link. Churchill observes in the book that: “I felt grave concern about the whole business, but I was sure that there should be no room for doubts or hedging. I had in my mind Arthur Balfour’s celebrated telegram in the eighties to the British authorities in Ireland: “Don’t hesitate to shoot.” […] There was a furious storm about it in the House of Commons of those days, but it certainly prevented loss of life.”)
“I saw quite plainly that Communism would be the peril civilization would have to face after the defeat of Nazism and Fascism. It did not fall to us to end the task in Greece. […] I told the President [Roosevelt] that we ought to occupy as much of Austria as possible, as it was “undesirable that more of Western Europe than necessary should be occupied by the Russians.”” [Churchill’s subsequent italics] […] “I deem it highly important that we should shake hands with the Russians as far to the east as possible.” [telegram from Churchill to Eisenhower sent in the late stage of the war.]
“Poland was discussed at no fewer than seven out of the eight plenary meetings of the Yalta Conference, and the British record contains an interchange on this topic of nearly eighteen thousand words between Stalin, Roosevelt, and myself. […] A large body of opinion in Great Britain was shocked at the idea of moving millions of people by force. Great success had been achieved in disentangling the Greek and Turkish populations after the last war […] but in that case under a couple of millions of people had been moved. […] I was not afraid of the problem of transferring populations, so long as it was proportionate to what the Poles could manage and to what could be put into Germany. But it was a matter which required study, not as a question of principle, but of the numbers which would have to be handled.”
“As war waged by a coalition draws to its end political aspects have a mounting importance. […] At this time the points at issue did not seem to the United States Chiefs of Staff to be of capital importance. They were of course unnoticed by and unknown to the public, and were all soon swamped, and for the time being effaced, by the flowing tide of victory. Nevertheless, as will not now be disputed, they played a dominating part in the destiny of Europe […] The indispensable political direction was lacking [due to Roosevelt’s illness and death] at the moment when it was most needed. The United States stood on the scene of victory, master of world fortunes, but without a true and coherent design. Britain, though still very powerful, could not act decisively alone. I could at this stage only warn and plead. Thus the climax of apparently measureless success was to me a most unhappy time. I moved amid cheering crowds, or sat at a table adorned with congratulations and blessings from every part of the Grand Alliance, with an aching heart and a mind oppressed by forebodings.
The destruction of German military power had brought with it a fundamental change in the relations between Communist Russia and the Western democracies. They had lost their common enemy, which was almost their sole bond of union. […] Apprehension for the future and many perplexities filled my mind as I moved among the cheering crowds of Londoners in their hour of well-won rejoicing after all they had gone through. […] Japan was still unconquered. The atomic bomb was still unborn. The world was in confusion. […] The Soviet menace, to my eyes, had already replaced the Nazi foe. But no comradeship against it existed. […] I had seen it all before. I remembered that other joy-day nearly thirty years before, when I had driven with my wife from the Ministry of Munitions through similar multitudes convulsed with enthusiasm to Downing Street to congratulate the Prime Minister. Then, as at this time, I understood the world situation as a whole. But then at least there was no mighty army that we need fear […] How stands the scene after eight years have passed? The Russian occupation line in Europe runs from Lübeck to Linz. Czechoslovakia has been engulfed. The Baltic states, Poland, Roumania, and Bulgaria have been reduced to satellite States under totalitarian Communist rule. Yugoslavia has broken loose. Greece alone is saved. Our armies are gone, and it will be a long time before even sixty divisions can be again assembled opposite Russian forces, which in armour and manpower are in overwhelming strength. This also takes no account of all that has happened in the Far East. The danger of a third World War, under conditions at the outset of grave disadvantage, casts its lurid shadow over the free nations of the world.” [The last quote in the above paragraph was written in 1953.]
“Over a million prisoners were taken in the first three weeks of April”.
“there never was a moment’s discussion as to whether the atomic bomb should be used or not. […] the decision whether or not to use the atomic bomb to compel the surrender of Japan was never even an issue. There was unanimous, automatic, unquestioned agreement around our table; nor did I ever hear the slightest suggestion that we should do otherwise.”
“In sixty-eight months of fighting 781 German U-boats were lost. For more than half this time the enemy held the initiative. […] In the final count British and British-controlled forced destroyed 500 out of the 632 submarines known to have been sunk at sea by the Allies. In the First World War eleven million tons of shipping were sunk, and in the second fourteen and a half million tons, by U-boats alone. If we add the loss from other causes the totals become twelve and three-quarter million and twenty-one and a half million. Of this the British bore over 60 per cent. in the first war and over half in the second. […] It would be a mistake to suppose that the fate of Japan was settled by the atomic bomb. Her defeat was certain before the first bomb fell, and was brought about by overwhelming maritime power. […] Her shipping had been destroyed. She had entered the war with over five and a half million tons, later much augmented by captures and new construction, but her convoy system and escorts were inadequate and ill-organised. Over eight and a half million tons of Japanese shipping were sunk, of which five million fell to submarines. We, an island power, equally dependent on the sea, can read the lesson and understand our own fate had we failed to master the U-boats.”
i. “Disgrace does not consist in the punishment, but in the crime.” (Vittorio Alfieri)
ii. “In countries and epochs in which communication is impeded, soon all other liberties wither; discussion dies by inanition, ignorance of the opinion of others becomes rampant, imposed opinions triumph. […] Intolerance is inclined to censor, and censorship promotes ignorance of the arguments of others and thus intolerance itself: a rigid, vicious circle that is hard to break.” (Primo Levi)
iii. “A good listener is not only popular everywhere, but after a while he gets to know something.” (Wilson Mizner)
iv. “Any author who uses mathematics should always express in ordinary language the meaning of the assumptions he admits, as well as the significance of the results obtained. The more abstract his theory, the more imperative this obligation.” (Maurice Allais)
v. “There are no small number of people in this world who, solitary by nature, always try to go back into their shell like a hermit crab or a snail.” (Anton Chekhov)
vi. “Love, friendship, respect, do not unite people as much as a common hatred for something.” (-ll-)
vii. “Although you may tell lies, people will believe you, if only you speak with authority.” (-ll-)
viii. “What seems to us serious, significant and important will, in future times, be forgotten or won’t seem important at all.” (-ll-)
ix. “Future me is a great guy. He deals with all my problems which allows me to just relax and not worry about anything. Sometimes I worry I’m giving him too much work, but he needs the motivation.” (‘Batmaners’, here)
x. “You’re not raising a child, you’re raising an adult.” (u/DankJemo, reddit, unknown original source)
xi. “She was a good woman, a good mother, a woman of quality and character. The fact that she had left him after twenty years to marry her lover did not, could not, change those facts. For at this moment, now that the months had passed, Jordan saw clearly the justice of her decision. She had a right to be happy. […] Not that he had been a bad husband. Just an inadequate one. He had been a good father. He had done his duty in every way. His only fault was that after twenty years he no longer made his wife happy.” (Fools Die, Mario Puzo)
xii. “There warn’t nothing to do now but to look out sharp for the town, and not pass it without seeing it. He said he’d be mighty sure to see it, because he’d be a free man the minute he seen it, but if he missed it he’d be in a slave country again and no more show for freedom. […] I begun to get it through my head that he WAS most free — and who was to blame for it? Why, ME. I couldn’t get that out of my conscience, no how nor no way. It got to troubling me so I couldn’t rest; I couldn’t stay still in one place. It hadn’t ever come home to me before, what this thing was that I was doing. But now it did; and it stayed with me, and scorched me more and more. I tried to make out to myself that I warn’t to blame, because I didn’t run Jim off from his rightful owner; but it warn’t no use, conscience up and says, every time, “But you knowed he was running for his freedom, and you could a paddled ashore and told somebody.” That was so — I couldn’t get around that noway. That was where it pinched. Conscience says to me, “What had poor Miss Watson done to you that you could see her nigger go off right under your eyes and never say one single word? What did that poor old woman do to you that you could treat her so mean?” (Mark Twain, The Adventures of Huckleberry Finn)
xiii. “In Detroit, Mrs Dorothy Van Dorn, suing for divorce, complained that her husband 1) put all their food in a freezer, 2) kept the freezer locked, 3) made her pay for any food she ate, and 4) charged her the 3% Michigan sales tax.” (Time magazine, 10 December 1951. I came across the quote while reading The Life and Times of the Thunderbolt Kid, by Bill Bryson).
xiv. “The trouble with the rat race is that even if you win, you’re still a rat.” (Jane Wagner)
xv. “Don’t be afraid of missing opportunities. Behind every failure is an opportunity somebody wishes they had missed.” (-ll-)
xvi. “A man has only one escape from his old self: to see a different self — in the mirror of some woman’s eyes.” (Clare Luce)
xvii. “What is success? It is a toy balloon among children armed with pins.” (Gene Fowler)
xviii. “Writing is easy. All you do is stare at a blank sheet of paper until drops of blood form on your forehead.” (-ll-)
xix. “The best way to become a successful writer is to read good writing, remember it, and then forget where you remember it from.” (-ll-)
xx. “Just because you’re living in blissful oblivion doesn’t mean you’re not responsible.” (Arthur M. Jolly)
i. A very long but entertaining chess stream by Peter Svidler was recently uploaded on the Chess24 youtube account – go watch it here, if you like that kind of stuff. The fact that it’s five hours long is a reason to rejoice, not a reason to think that it’s ‘too long to be watchable’ – watch it in segments…
People interested in chess might also be interested to know that Magnus Carlsen has made an account on the ICC on which he has played, which was a result of his recent participation in the ICC Open 2016 (link). A requirement for participation in the tournament was that people had to know whom they were playing against (so there would be no ultra-strong GMs playing using anonymous accounts in the finals – they could use accounts with strange names, but people had to know whom they were playing), so now we know that Magnus Carlsen has played under the nick ‘stoptryharding’ on the ICC. Carlsen did not win the tournament as he lost to Grischuk in the semi-finals. Some very strong players were incidentally kicked out in the qualifiers, including Nepomniachtchi, the current #5 in the world on the FIDE live blitz ratings.
ii. A lecture:
iii. Below I have added some new words I’ve encountered, most of them in books I’ve read (I have not spent much time on vocabulary.com recently). I’m sure if I were to look all of them up on vocabulary.com some (many?) of them would not be ‘new’ to me, but that’s not going to stop me from including them here (I included the word ‘inculcate’ below for a reason…). Do take note of the spelling of some of these words – some of them are tricky ones included in Bryson’s Dictionary of Troublesome Words: A Writer’s Guide to Getting It Right, which people often get wrong for one reason or another:
Conurbation, epizootic, equable, circumvallation, contravallation, exiguous, forbear, louche, vituperative, thitherto, congeries, inculcate, obtrude, palter, idiolect, hortatory, enthalpy (see also wiki, or Khan Academy), trove, composograph, indite, mugginess, apodosis, protasis, invidious, inveigle, inflorescence, kith, anatopism, laudation, luxuriant, maleficence, misogamy (I did not know this was a word, and I’ll definitely try to remember it/that it is…), obsolescent, delible, overweening, parlay (this word probably does not mean what you think it means…), perspicacity, perspicuity, temblor, precipitous, quinquennial, razzmatazz, turpitude, vicissitude, vitriform.
iv. Some quotes from this excellent book review, by Razib Khan:
“relatively old-fashioned anti-religious sentiments […] are socially acceptable among American Left-liberals so long as their targets are white Christians (“punching up”) but more “problematic” and perhaps even “Islamophobic” when the invective is hurled at Muslim “people of color” (all Muslims here being tacitly racialized as nonwhite). […] Muslims, as marginalized people, are now considered part of a broader coalition on the progressive Left. […] most Left-liberals who might fall back on the term Islamophobia, don’t actually take Islam, or religion generally, seriously. This explains the rapid and strident recourse toward a racial analogy for Islamic identity, as that is a framework that modern Left-liberals and progressives have internalized and mastered. The problem with this is that Islam is not a racial or ethnic identity, it is a set of beliefs and practices. Being a Muslim is not about being who you are in a passive sense, but it is a proactive expression of a set of ideas about the world and your behavior within the world. This category error renders much of Left-liberal and progressive analysis of Islam superficial, and likely wrong.”
“To get a genuine understanding of a topic as broad and boundless as Islam one needs to both set aside emotional considerations, as Ben Affleck can not, and dig deeply into the richer and more complex empirical texture, which Sam Harris has not.”
“One of the most obnoxious memes in my opinion during the Obama era has been the popularization of the maxim that “The arc of the moral universe is long, but it bends towards justice.” It is smug and self-assured in its presentation. […] too often it becomes an excuse for lazy thinking and shallow prognostication. […] Modern Western liberals have a particular idea of what a religion is, and so naturally know that Islam is in many ways just like United Methodism, except with a hijab and iconoclasm. But a Western liberalism that does not take cultural and religious difference seriously is not serious, and yet all too often it is what we have on offer. […] On both the American Left and Right there is a tendency to not even attempt to understand Islam. Rather, stylized models are preferred which lead to conclusions which are already arrived at.”
“It’s fine to be embarrassed by reality. But you still need to face up to reality. Where Hamid, Harris, and I all start is the fact that the vast majority of the world’s Muslims do not hold views on social issues that are aligned with the Muslim friends of Hollywood actors. […] Before the Green Revolution I told people to expect there to be a Islamic revival, as 86 percent of Egyptians polled agree with the killing of apostates. This is not a comfortable fact for me, as I am technically an apostate.* But it is a fact. Progressives who exhibit a hopefulness about human nature, and confuse majoritarian democracy with liberalism and individual rights, often don’t want to confront these facts. […] Their polar opposites are convinced anti-Muslims who don’t need any survey data, because they know that Muslims have particular views a priori by virtue of them being Muslims. […] There is a glass half-full/half-empty aspect to the Turkish data. 95 percent of Turks do not believe apostates should be killed. This is not surprising, I know many Turkish atheists personally. But, 5 percent is not a reassuring fraction as someone who is personally an apostate. The ideal, and frankly only acceptable, proportion is basically 0 percent.”
“Harris would give a simple explanation for why Islam sanctions the death penalty for apostates. To be reductive and hyperbolic, his perspective seems to be that Islam is a totalitarian cult, and its views are quite explicit in the Quran and the Hadith. Harris is correct here, and the views of the majority of Muslims in Egypt (and many other Muslim nations) has support in Islamic law. The consensus historical tradition is that apostates are subject to the death penalty. […] the very idea of accepting atheists is taboo in most Arab countries”.
“Christianity which Christians hold to be fundamental and constitutive of their religion would have seemed exotic and alien even to St. Paul. Similarly, there is a much smaller body of work which makes the same case for Islam.
A précis of this line of thinking is that non-Muslim sources do not make it clear that there was in fact a coherent new religion which burst forth out of south-central Arabia in the 7th century. Rather, many aspects of Islam’s 7th century were myths which developed over time, initially during the Umayyad period, but which eventually crystallized and matured into orthodoxy under the Abbasids, over a century after the death of Muhammad. This model holds that the Arab conquests were actually Arab conquests, not Muslim ones, and that a predominantly nominally Syrian Christian group of Arab tribes eventually developed a new religion to justify their status within the empire which they built, and to maintain their roles within it. The mawali (convert) revolution under the Abbasids in the latter half of the 8th century transformed a fundamentally Arab ethnic sect, into a universal religion. […] The debate about the historical Jesus only emerged when the public space was secularized enough so that such discussions would not elicit violent hostility from the populace or sanction form the authorities. [T]he fact is that the debate about the historical Muhammad is positively dangerous and thankless. That is not necessarily because there is that much more known about Muhammad than Jesus, it is because post-Christian society allows for an interrogation of Christian beliefs which Islamic society does not allow for in relation to Islam’s founding narratives.”
“When it comes to understanding religion you need to start with psychology. In particular, cognitive psychology. This feeds into the field of evolutionary anthropology in relation to the study of religion. Probably the best introduction to this field is Scott Atran’s dense In Gods We Trust: The Evolutionary Landscape of Religion. Another representative work is Theological Incorrectness: Why Religious People Believe What They Shouldn’t. This area of scholarship purports to explain why religion is ubiquitous, and, why as a phenomenon it tends to exhibit a particular distribution of characteristics.
What cognitive psychology suggests is that there is a strong disjunction between the verbal scripts that people give in terms of what they say they believe, and the internal Gestalt mental models which seem to actually be operative in terms of informing how they truly conceptualize the world. […] Muslims may aver that their god is omniscient and omnipresent, but their narrative stories in response to life circumstances seem to imply that their believe god may not see or know all things at all moments.
The deep problem here is understood [by] religious professionals: they’ve made their religion too complex for common people to understand without their intermediation. In fact, I would argue that theologians themselves don’t really understand what they’re talking about. To some extent this is a feature, not a bug. If the God of Abraham is transformed into an almost incomprehensible being, then religious professionals will have perpetual work as interpreters. […] even today most Muslims can not read the Quran. Most Muslims do not speak Arabic. […] The point isn’t to understand, the point is that they are the Word of God, in the abstract. […] The power of the Quran is that the Word of God is presumably potent. Comprehension is secondary to the command.”
“the majority of the book […] is focused on political and social facts in the Islamic world today. […] That is the best thing about Islamic Exceptionalism, it will put more facts in front of people who are fact-starved, and theory rich. That’s good.”
“the term ‘fundamentalist’ in the context of islam isn’t very informative.” (from the comments).
Below I have added some (very) superficially related links of my own, most of them ‘data-related’ (in general I’d say that I usually find ‘raw data’ more interesting than ‘big ideas’):
*My short review of Theological Correctness, one of the books Razib mentions.
*An analysis of Danish data conducted by the Rockwool Foundation found that for family-reunificated spouses/relatives etc. to fugitives, 22 % were employed after having lived in Denmark for five years (the family-reunificated individuals, that is, not the fugitives themselves). Only one in three of the family-reunificated individuals had managed to find a job after having stayed here for fifteen years. The employment rate of family-reunificated to immigrants is 49 % for people who have been in the country for 5 years, and the number is below 60 % after 15 years. In Denmark, the employment rate of immigrants from non-Western countries was 47,7 % in November 2013, compared to 73,8 % for people of (…’supposedly’, see also my comments and observations here) Danish origin, according to numbers from Statistics Denmark (link). When you look at the economic performance of the people with fugitive status themselves, 34 % are employed after 5 years, but that number is almost unchanged a decade later – only 37 % are employed after they’ve stayed in Denmark for 15 years.
Things of course sometimes look even worse at the local level than these numbers reflect, because those averages are, well, averages; for example of the 244 fugitives and family-reunificated who had arrived in the Danish Elsinore Municipality within the last three years, exactly 5 of them were in full-time employment.
*Rotherham child sexual exploitation scandal (“The report estimated that 1,400 children had been sexually abused in the town between 1997 and 2013, predominantly by gangs of British-Pakistani Muslim men […] Because most of the perpetrators were of Pakistani heritage, several council staff described themselves as being nervous about identifying the ethnic origins of perpetrators for fear of being thought racist […] It was reported in June 2015 that about 300 suspects had been identified.”)
*A memorial service for the terrorist and murderer Omar El-Hussein who went on a shooting rampage in Copenhagen last year (link) gathered 1500 people, and 600-700 people also participated at the funeral (Danish link).
*Pew asked muslims in various large countries whether they thought ‘Suicide Bombing of Civilian Targets to Defend Islam [can] be Justified?’ More than a third of French muslims think that it can, either ‘often/sometimes’ (16 %) or ‘rarely’ (19 %). Roughly a fourth of British muslims think so as well (15 % often/sometimes, 9 % rarely). Of course in countries like Jordan, Nigeria, and Egypt the proportion of people who do not reply ‘never’ is above 50 %. In such contexts people often like to focus on what the majorities think, but I found it interesting to note that in only 2 of 11 countries (Germany – 7 %, & the US – 8 %) queried was it less than 10 % of muslims who thought suicide bombings were not either ‘often’ or ‘sometimes’ justified. Those numbers are some years old. Newer numbers (from non-Western countries only, unfortunately) tell us that e.g. fewer than two out of five Egyptians (38%) and fewer than three out of five (58%) Turks would answer ‘never’ when asked this question just a couple of years ago, in 2014.
*A few non-data related observations here towards the end. I do think Razib is right that cognitive psychology is a good starting point if you want to ‘understand religion’, but a more general point I would make is that there are many different analytical approaches to these sorts of topics which one might employ, and I think it’s important that one does not privilege any single analytical framework over the others (just to be clear, I’m not saying that Razib’s doing this); different approaches may yield different insights, perhaps at different analytical levels, and combining different approaches is likely to be very useful in order to get ‘the bigger picture’, or at least to not overlook important details. ‘History’, broadly defined, may provide one part of the explanatory model, cognitive psychology another part, mathematical anthropology (e.g. stuff like this) probably also has a role to play, etc., etc.. Survey data, economic figures, scientific literatures on a wide variety of topics like trust, norms, migration analysis, and conflict studies, e.g. those dealing with civil wars, may all help elucidate important questions of interest, if not by adding relevant data then by providing additional methodological approaches/scaffoldings which might be fruitfully employed to make sense of the data that is available.
vi. The Level and Nature of Autistic Intelligence. Autistics may be smarter than people have been led to believe:
“Autistics are presumed to be characterized by cognitive impairment, and their cognitive strengths (e.g., in Block Design performance) are frequently interpreted as low-level by-products of high-level deficits, not as direct manifestations of intelligence. Recent attempts to identify the neuroanatomical and neurofunctional signature of autism have been positioned on this universal, but untested, assumption. We therefore assessed a broad sample of 38 autistic children on the preeminent test of fluid intelligence, Raven’s Progressive Matrices. Their scores were, on average, 30 percentile points, and in some cases more than 70 percentile points, higher than their scores on the Wechsler scales of intelligence. Typically developing control children showed no such discrepancy, and a similar contrast was observed when a sample of autistic adults was compared with a sample of nonautistic adults. We conclude that intelligence has been underestimated in autistics.”
I recall that back when I was diagnosed I was subjected to a battery of different cognitive tests of various kinds, and a few of those tests I recall thinking were very difficult, compared to how difficult they somehow ‘ought to be’ – it was like ‘this should be an easy task for someone who has the mental hardware to solve this type of problem, but I don’t seem to have that piece of hardware; I have no idea how to manipulate these objects in my head so that I might answer that question’. This was an at least somewhat unfamiliar feeling to me in a testing context, and I definitely did not have this experience when doing the Mensa admissions test later on, which was based on Raven’s matrices. Despite the fact that all IQ tests are supposed to measure pretty much the same thing I do not find it hard to believe that there are some details here which may complicate matters a bit in specific contexts, e.g. for people whose brains may not be structured quite the same way ‘ordinary brains’ are (to put it very bluntly). But of course this is just one study and a few personal impressions – more research is needed, etc. (Even though the effect size is huge.)
Slightly related to the above is also this link – I must admit that I find the title question quite interesting. I find it very difficult to picture characters featuring in books I’m reading in my mind, and so usually when I read books I don’t form any sort of coherent mental image of what the character looks like. It doesn’t matter to me, I don’t care. I have no idea if this is how other people read (fiction) books, or if they actually imagine what the characters look like more or less continuously while those characters are described doing the things they might be doing; to me it would be just incredibly taxing to keep even a simplified mental model of the physical attributes of a character in my mind for even a minute. I can recall specific traits like left-handedness and similar without much difficulty if I think the trait might have relevance to the plot, which has helped me while reading e.g. Agatha Christie novels before, but actively imagining what people look like in my mind I just find very difficult. I find it weird to think that some people might do something like that almost automatically, without thinking about it.
vii. Computer Science Resources. I recently shared the link with a friend, but of course she was already aware of the existence of this resource. Some people reading along here may not be, so I’ll include the link here. It has a lot of stuff.
i. “The lucky man is he who knows how much to leave to chance.” (C. S. Forester)
ii. “even the meanest person has still at his disposition high-sounding words wherewith to mask his real character.” (Henryk Sienkiewicz)
iii. “Fine, large, meaningless, general terms like romance and business can always be related. They take the place of thinking, and are highly useful to optimists and lecturers.” (Sinclair Lewis)
iv. “Indians, of course, have no ‘theology,’ and indeed no word for the system of credulity in which the white priests arrange for God, who must be entirely bewildered by it, a series of excuses for his failures.” (-ll-)
v. “Believe those who seek the truth, doubt those who find it” (André Gide)
vi. “The surest defense against Evil is extreme individualism, originality of thinking, whimsicality, even — if you will — eccentricity. That is, something that can’t be feigned, faked, imitated; something even a seasoned imposter couldn’t be happy with. […] Evil is a sucker for solidity. It always goes for big numbers, for confident granite, for ideological purity, for drilled armies and balanced sheets. Its proclivity for such things has to do with its innate insecurity, but this realization, again, is of small comfort when Evil triumphs.” (Joseph Brodsky)
vii. “None of us can help the things life has done to us. They’re done before you realize it, and once they’re done they make you do other things until at last everything comes between you and what you’d like to be, and you’ve lost your true self forever.” (Eugene O’Neill)
viii. “Intelligence is almost useless to the person whose only quality it is.” (Alexis Carrel)
ix. “The value of a sentiment is the amount of sacrifice you are prepared to make for it.” (John Galsworthy)
x. “Vulgarized knowledge characteristically gives birth to a feeling that everything is understandable and explained. It is like a system of bridges built over chasms. One can travel boldly ahead over these bridges, ignoring the chasms. It is forbidden to look down into them; but that, alas, does not alter the fact that they exist.” (Czesław Miłosz)
xi. “The more the universe seems comprehensible, the more it also seems pointless.” (Steven Weinberg)
xii. “Most men resemble great deserted palaces: the owner occupies only a few rooms and has closed off wings where he never ventures.” (François Mauriac)
xiii. “You may turn a bad idea into a good idea — don’t kill the bad idea prematurely. A bad idea can evolve into a good idea.” (Martin Lewis Perl)
xiv. “When, as we must often do, we fear science, we really fear ourselves. Human dignity is better served by embracing knowledge.” (John Polanyi)
xv. “Authority in science exists to be questioned, since heresy is the spring from which new ideas flow.” (-ll-)
xvi. “no one of mature age cares to make a complete confession of his past life.” (W. B. Maxwell, The Devil’s Garden)
xvii. “Whenever a government feels the need of promising peace and prosperity to its citizens by means of a proclamation, it is time to be on guard and expect the opposite.” (Ivo Andrić)
xviii. “When we lose one we love, our bitterest tears are called forth by the memory of hours when we loved not enough.” (Maurice Maeterlinck)
xix. “War is the outcome, not mainly of evil intentions, but on the whole, of good intentions which miscarry or are frustrated. It is made, not usually by evil men knowing themselves to be wrong, but is the outcome of policies pursued by good men usually passionately convinced that they are right.” (Norman Angell)
xx. “The real point of honor [for a scientist] is not to be always right. It is to dare to propose new ideas, and then to check them.” (Pierre-Gilles de Gennes)
You can read my previous posts about the book here and here. I gave the book 5 stars on goodreads. Below I have added some more quotes from the stuff in the middle, on various topics. I expect to post at least one more post about the book later on; there’s a lot of interesting stuff in here, and in order for me to have at least some chance of remembering some of that stuff later on I think I need to blog it.
“The battle [of Crete] began on the morning of May 20  […] It was the first large-scale airborne attack in the annals of war. […] When the battle joined we did not know what were the total resources of Germany in parachute troops. The 11th Air Corps might have been only one of half a dozen such units. It was not till many months afterwards that we were sure it was the only one.” (This quote highlights, I think, one aspect of the war which is easy to miss for people who ‘wasn’t there’; how much uncertainty there was, about a lot of things that the enemy might be doing, or might not be doing, or might be planning to do. Espionage will get you only so far).
“Prime Minister to Stafford Cripps 3 Apr 41
Following from me to M. Stalin, provided it can be personally delivered by you:
I have sure information from a trusted agent that when the Germans thought they had got Yugoslavia in the net – that is to say, after March 20 – they began to move three out of the five Panzer divisions from Roumania to Southern Poland. The moment they heard of the Serbian revolution this movement was countermanded. Your Excellency will readily appreciate the significance of these facts.”
(If the significance of these facts is not clear to people unfamiliar with the scene at the time, here’s what Churchill thought: “This shuffling and reversal of about sixty trains could not be concealed from our agents on the spot. To me it illuminated the whole Eastern scene like a lightning-flash. The sudden movement to Cracow of so much armour needed in the Balkan sphere could only mean Hitler’s intention to invade Russia in May. […] The fact that the Belgrade revolution had required their return to Roumania involved perhaps a delay from May to June. I cast about for some means of warning Stalin […] I made the message short and cryptic, hoping that this very fact, and that it was the first message I had sent him since my formal telegram of June 25, 1940, commending Sir Stafford Cripps as Ambassador, would arrest his attention and make him ponder. […] This was the only message before the attack that I sent Stalin direct.” When Churchill and Stalin later briefly discussed the warning during their 1942 Moscow conference, Stalin remarked that he remembered the warning, and added: “I did not need any warnings. I knew war would come, but I thought I might gain another six months or so.”)
“Almost all responsible military opinion held that the Russian armies would soon be defeated and largely destroyed. […] President Roosevelt was considered very bold when he proclaimed in September that the Russian front would hold and that Moscow could not be taken. […] Even in August 1942, after my visit to Moscow and the conferences there, General Brooke, who had accompanied me, adhered to the opinion that the Caucasus Mountains would be traversed and the basin of the Caspian dominated by German forces, and we prepared accordingly on the largest possible scale for a defensive campaign in Syria and Persia.”
“In the whole of the war ninety-one merchant ships were lost on the Arctic route, amounting to 7.8 per cent. of the loaded vessels outward bound and 3.8 per cent. of those returning. Only fifty-five of these were in escorted convoys. Of about four million tons of cargo dispatched from America and the United Kingdom, an eighth was lost. In this arduous work the Merchant Navy lost 829 lives, while the Royal Navy paid a still heavier price. Two cruisers and seventeen other war-ships were sunk and 1,840 officers and men died. The forty convoys to Russia carried the huge total of £428,000,000 worth of material, including 5,000 tanks and over 7,000 aircraft from Britain alone. […] The […] extreme difficulties of the Arctic route, together with future strategic possibilities, made [the] creation of a major supply route to Russia through the Persian gulf [a] prime objective. […] Starting in September 1941, this enterprise, begun and developed by the British Army, and presently to be adopted and expanded by the United States, enabled us to send to Russia, over a period of four and a half years, five million tons of supplies.”
“As we had flown [back to Britain, after the Arcadia Conference] for more than ten hours through mist and had had only one sight of a star in that time, we might well be slightly off our course. Wireless communication was of course limited by the normal war-time rules. It was evident from the discussions which were going on that we did not know where we were. Presently Portal, who had been studying the position, had a word with the captain, and then said to me, “We are going to turn north at once.” […] As I left the aircraft [after the landing] the [air] captain remarked, “I never felt so much relieved in my life as when I landed you safely in the harbour.” I did not appreciate the significance of his remark at the moment. Later on I learnt that if we had held on our course for another five or six minutes before turning northwards we should have been over the German batteries in Brest. We had slanted too much to the southward during the night. Moveover, the decisive correction which had been made brought us in, not from the south-west, but from just east of south – that is to say, from the enemy’s direction rather than from that from which we were expected. This had the result, as I was told some weeks later, that we were reported as a hostile bomber coming in from Brest, and six Hurricanes from Fighter Command were ordered out to shoot us down. However, they failed in their mission.”
“By the end of March  the first phase of the Japanese war plan had achieved a success so complete that it surprised even its authors. Japan was master of Hong Kong, Siam, Malaya, and nearly the whole of the immense island region forming the Dutch East Indies. Japanese troops were plunging deeply into Burma. In the Philippines the Americans still fought on at the Corregidor, but without hope of relief. […] Whether it was wiser to organize their new perimeter thoroughly or by surging forward to gain greater depth for its defence seemed for [the Japanese leaders] a balanced strategic problem. After deliberations in Tokyo the more ambitious course was adopted. […] The Japanese High Command had shown the utmost skill and daring in making and executing their plans. They started however upon a foundation which did not measure world forces in true proportion. They never comprehended the latent might of the United States. […] they were drawn into a gamble, which even if it had won would only have lengthened their predominance by perhaps a year, and, as they lost, cut it down by an equal period. In the actual result they exchanged a fairly strong and gripped advantage for a wide and loose domain, which it was beyond their power to hold; and, being beaten in this outer area, they found themselves without the forces to make a coherent defence of their inner and vital zone. Nevertheless at this moment in the world struggle no one could be sure that Germany would not break Russia, or drive her beyond the Urals, and then be able to come back and invade Britain; or as an alternative spread through the Caucasus and Persia to join hands with the Japanese vanguards in India.”
Churchill included these interesting thoughts on the status of affairs roughly in the middle of the war: “I had now been twenty-eight months at the head of affairs, during which we had sustained an almost unbroken series of military defeats. […] The fact that we were no longer alone, but instead had the two most mighty nations in the world in alliance fighting desperately at our side, gave indeed assurances of ultimate victory. But this, by removing the sense of mortal peril, only made criticism more free. Was it strange that the whole character and system of the war direction, for which I was responsible, should have been brought into question and challenge? It is indeed remarkable that I was not […] dismissed from power, or confronted with demands for changes in my methods, which it was known I should never accept. I should then have vanished from the scene with a load of calamity on my shoulders, and the harvest, at last to be reaped, would have been ascribed to my belated disappearance.”
“In September  30 per cent. of Axis shipping supplying North Africa was sunk, largely by air action. In October the figure rose to 40 per cent. The loss of petrol was 66 per cent. […] There had been serious derangements in the enemy’s command. Rommel had gone to hospital in Germany at the end of September and his place was taken by General Stumme. Within twenty-four hours of the start of the battle [of El Alamein] Stumme died of a heart attack. [Talk about bad timing…] […] The Battle of El Alamein differed from all previous fighting in the Desert. The front was limited, heavily fortified, and held in strength. There was no flank to turn. A break-through must be made by whoever was the stronger and wished to take the offensive. In this way we are led back to the battles of the First World War on the Western Front. […] It may almost be said, “Before Alamein we never had a victory. After Alamein we never had a defeat.”
An important thing I learned from the book was the answer to the question why the (Western) Allied forces were mainly fighting in Africa during the first part of the war, but didn’t seemingly really do much else aside from trying to keep the Germans from bombing their cities and sinking their ships. A very important point is that landing craft was the binding constraint, and these were in desperately short supply, and it took a lot of time to build up the supply. It would have made no sense for the Allied to have tried to unload substantial numbers of soldiers in Europe during the first years; they would have been slaughtered, and valuable landing crafts would have been lost. What might have happened, had such a strategy been pursued, might have been repeated experiences like those of the Dieppe raid, where almost 60 % of the soldiers who made it ashore were killed, wounded or captured, and the rest had to be evacuated within hours. So instead the Allied leaders tried to seek out the enemy where they were actually capable of taking him on, and that way bind resources of his which could not be used on the Eastern front – which ended up meaning mainly military engagements in Africa and the Mediterranean. Operation Torch could be initiated successfully significantly sooner than any sort of successful cross-Channel operation could.
“[In May 1943] there were 185 German divisions on the Russian front. […] Brooke [during a strategy meeting at that time] set out our whole Mediterranean strength [available for operations in the near future]. Deducting seven divisions to be sent home for the cross-Channel operation and two to cover British commitments to Turkey, there would be twenty-seven Allied divisions available in the Mediterranean area. […] In the initial assault [of the invasion of Sicily] nearly 3,000 ships and landing-craft took part, carrying between them 160,000 men, 14,000 vehicles, 600 tanks, and 1,800 guns.” And still this was small potatoes compared to the forces engaged in conflict on the Eastern front – which makes you think…
“In 1940 and 1941 we lost four million tons of merchant shipping a year. In 1942, after the United States was our Ally, this figure nearly doubled, and the U-boats sank ships faster than the Allies could build them. During 1943, thanks to the immense shipbuilding programme of the United States, the new tonnage at last surpassed losses at sea from all causes, and the second quarter saw, for the first time, U-boat losses exceed their rate of replacement. […] In May alone forty U-boats perished in the ocean. […] The convoys came through intact, the supply line was safe, the decisive battle had been fought and won. […] The extirpation of Axis power in North Africa opened to our convoys the direct route to Egypt, India, and Australia […] The long haul round the Cape, which had cost us so dear in time, effort, and tonnage, would soon be ended. The saving of an average of forty-five days for each convoy to the Middle East increased magnificently at one stroke the fertility of our shipping.”
i. “It is both more difficult and more complicated to die than people think.” (Halldór Laxness)
ii. “There’s a cruel lot of sorrow in most people’s lives.” (W. B. Maxwell, The Devil’s Garden)
iii. “the best causes sometimes need the best advocates.” (-ll-)
iv. “Mavis, taking a present of tea and sugar to one of the Cross Roads cottages, had found her digging in the garden, and, struck by her pitiful aspect, had questioned her and elicited her history. It was a common enough one in those parts. Not being wanted at home, she had been “lent” to Mrs. Neath, the cottage woman, in exchange for her keep, and was mercilessly used by the borrower. She rose at dawn, worked as the regular household drudge till within an hour of school-time, then walked into Rodchurch for the day’s schooling with a piece of dry bread in her pocket as dinner; and on her return from school worked again till late at night. She admitted that she felt always hungry, always tired, always miserable; that she suffered from cold at night in her wretched little bed; and that Mrs. Neath often beat her.” (-ll-)
v. “Despair itself if it goes on long enough, can become a kind of sanctuary in which one settles down and feels at ease.” (Charles Augustin Sainte-Beuve) (Le désespoir lui-même, pour peu qu’il se prolonge, devient une sorte d’asile dans lequel on peut s’asseoir et reposer)
vi. “Most often we are judging not others, but rather our own faculties in others.” (-ll-) (Le plus souvent nous ne jugeons pas les autres, mais nous jugeons nos propres facultés dans les autres)
vii. “It is comfortable to live in the belief that you are great, though your greatness is latent.” (Italo Svevo) (È un modo comodo di vivere quello di credersi grande di una grandezza latente.)
viii. “There are some people who can receive a truth by no other way than to have their understanding shocked and insulted.” (Carl Sandburg)
ix. “More people are flattered into virtue than bullied out of vice.” (Robert Smith Surtees)
x. “Among other things Jonestown was an example of a definition well known to sociologists of religion: a cult is a religion with no political power.” (Tom Wolfe)
xi. “Life resembles a novel more often than novels resemble life.” (George Sand) (La vie ressemble plus souvent à un roman qu’un roman ne ressemble à la vie)
xii. “Life is a long ache which rarely sleeps and can never be cured.” (George Sand)
xiii. “What egotism, what stupid vanity, to suppose that a thing could not happen because you could not conceive it!” (Philip Wylie)
xiv. “All creeds and opinions are nothing but the mere result of chance and temperament.” (Joseph Henry Shorthouse)
xv. “I have no particular political views but I was and am struck by the idea that the left and the right are always entirely similar when they become extreme – they click together like two edges of a magnet.” (Alan Williams)
xvi. “We see things not as they are, but as we are ourselves.” (H. M. Tomlinson)
xvii. “Strange as it may seem, no amount of learning can cure stupidity, and formal education positively fortifies it.” (Stephen Vizinczey)
xviii. “A life postponed too long might never be lived.” (Joan Slonczewski)
xix. “Hell is being alive, and being alive is all there is.” (Michael Marshall Smith)
xx. “It is fortunate that each generation does not comprehend its own ignorance. We are thus enabled to call our ancestors barbarous.” (Charles Dudley Warner)
I find it difficult to find the motivation to finish the half-finished drafts I have lying around, so this will have to do. Some random stuff below.
(15.000 views… In some sense that seems really ‘unfair’ to me, but on the other hand I doubt neither Beethoven nor Gilels care; they’re both long dead, after all…)
ii. New/newish words I’ve encountered in books, on vocabulary.com or elsewhere:
Agley, peripeteia, dissever, halidom, replevin, socage, organdie, pouffe, dyarchy, tauricide, temerarious, acharnement, cadger, gravamen, aspersion, marronage, adumbrate, succotash, deuteragonist, declivity, marquetry, machicolation, recusal.
iii. A lecture:
It’s been a long time since I watched it so I don’t have anything intelligent to say about it now, but I figured it might be of interest to one or two of the people who still subscribe to the blog despite the infrequent updates.
iv. A few wikipedia articles (I won’t comment much on the contents or quote extensively from the articles the way I’ve done in previous wikipedia posts – the links shall have to suffice for now):
Russian political jokes. Some of those made me laugh (e.g. this one: “A judge walks out of his chambers laughing his head off. A colleague approaches him and asks why he is laughing. “I just heard the funniest joke in the world!” “Well, go ahead, tell me!” says the other judge. “I can’t – I just gave someone ten years for it!”).
v. World War 2, if you think of it as a movie, has a highly unrealistic and implausible plot, according to this amusing post by Scott Alexander. Having recently read a rather long book about these topics, one aspect I’d have added had I written the piece myself would be that an additional factor making the setting seem even more implausible is how so many presumably quite smart people were so – what at least in retrospect seems – unbelievably stupid when it came to Hitler’s ideas and intentions before the war. Going back to Churchill’s own life I’d also add that if you were to make a movie about Churchill’s life during the war, which you could probably relatively easily do if you were to just base it upon his own copious and widely shared notes, then it could probably be made into a quite decent movie. His own comments, remarks, and observations certainly made for a great book.
“a significant proportion of our whole war effort had to be devoted to combating the mine. A vast output of material and money was diverted from other tasks, and many thousands of men risked their lives night and day in the minesweepers alone. The peak figure was reached in June 1944, when nearly sixty thousand were thus employed.”
“On January 10, 1940, anxieties about the Western Front received confirmation. A German staff major of the 7th Air Division had been ordered to take some documents to headquarters in Cologne. He missed his train and decided to fly. His machine overshot the mark and made a forced landing in Belgium, where Belgian troops arrested him and impounded his papers, which he tried desperately to destroy. These contained the entire and actual scheme for the invasion of Belgium, Holland, and France on which Hitler had resolved. […] I was told about all this at the time […] It was argued in all three countries concerned that probably it was a plant. But this could not be true. There could be no sense in the Germans trying to make the Belgians believe that they were going to attack them in the near future. This might make them do the very last thing the Germans wanted, namely, make a plan with the French and British Armies […] I therefore believed in the impending attack. We appealed to Belgium, but the Belgian King and his Army staff merely waited, hoping that all would turn out well. […] no further action of any kind was taken by the Allies or the threatened States. […] Hitler, […] ordered, after venting his anger, new variants [of the invasion plans] to be prepared.”
“until July 1944 Britain and her Empire had a substantially larger number of divisions in contact with the enemy than the United States. This general figure includes not only the European and African spheres but also all the war in Asia against Japan. […] Out of 781 German and 85 Italian U-boats destroyed in the European theatre, the Atlantic and Indian Oceans, 594 were accounted for by British sea and air forces […] of shipping losses by enemy action suffered by all nations throughout the war […] 80 per cent. were suffered in the Atlantic Ocean, including British coastal waters and the North Sea. Only 5 per cent. were lost in the Pacific. […] Up till the end of 1943 the British discharge of bombs upon Germany had in the aggregate exceeded by eight tons to one those cast from American machines”
“My relations with the President [Roosevelt – US] gradually became so close that the chief business between our two countries was virtually conducted by […] personal interchanges between him and me. […] In all I sent him nine hundred and fifty messages, and received about eight hundred in reply.”
“Altogether there came to the rescue of the Army under the ceaseless air bombardment of the enemy about eight hundred and sixty vessels […] at 2.23 p.m. on June 4 the Admiralty, in agreement with the French, announced that Operation “Dynamo” was now completed. More than 338,000 British and Allied troops had been landed in England. […] On June 17 it was announced that the Pétain Government had asked for an armistice, ordering all French forces to cease fighting, without even communicating this information to our troops. General Brooke was consequently told to come away with all men he could embark and any equipment he could save. We repeated now on a considerable scale, though with larger vessels, the Dunkirk evacuation. Over twenty thousand Polish troops who refused to capitulate cut their way to the sea and were carried by our ships to Britain. […] In all there were evacuated from all French harbours 136,000 British troops and 310 guns; a total, with the Poles, of 156,000 men.”
“Hitler and Stalin had much in common as totalitarians, and their systems of government were akin. […] On June 14, the day Paris fell, Moscow sent an ultimatum to Lithuania accusing her and the other Baltic States of military conspiracy against the U.S.S.R. and demanding radical changes of government and military concessions. On June 15 Red Army troops invaded the country. Latvia and Estonia were exposed to the same treatment. […] A Russian ultimatum to Roumania was delivered to the Roumanian Minister in Moscow at 10 p.m. on June 26. The cession of Bessarabia and the norther part of the province of Bukovina was demanded […] On June 27 Roumanian troops were withdrawn from the two provinces concerned, and the territories passed into Russian hands. […] On August 3-6 the pretence of pro-Soviet friendly and democratic Governments [in the Baltic] was swept away, and the Kremlin annexed the Baltic States to the Soviet Union.”
“From September 7 to November 3 an average of two hundred German bombers attacked London every night. […] The night raids were accompanied by more or less continuous daylight attacks by small groups or even single enemy planes, and the sirens often sounded at brief intervals throughout the whole twenty-four hours. To this curious existence the seven million inhabitants of London accustomed themselves. […] We did not know how long it would last. We had no reason to suppose that it would not go on getting worse. […] In the twelve months from June 1940 to June 1941 our civilian casualties were 43,381 killed and 40,856 seriously injured, a total of 94,237.”
“The only thing that ever really frightened me during the war was the U-boat peril. […] we poised and pondered together on this problem. It did not take the form of flaring battles and glittering achievements. It manifested itself through statistics, diagrams, and curves unknown to the nation, incomprehensible to the public. […] At the outset the Admiralty naturally thought first of bringing the ships safely to port, and judged their success by a minimum of sinkings. But now this was no longer the test. We all realised that the life and war effort of the country depended equally upon the weight of imports safely landed. In the week ending June 8, during the height of the battle in France, we had brought into the country about a million and a quarter tons of cargo, exclusive of oil. From this peak figure imports had declined at the end of July to less than 750,000 tons a week. […] I became increasingly concerned about this ominous fall in imports. “I see,” I minuted to the First Lord in the middle of February, 1941, “that entrances of ships with cargo in January were less than half of what they were last January.” The very magnitude and refinement of our protective measures – convoy, diversion, degaussing [a method employed to counteract magnetic mines – US], mine-clearance, the avoidance of the Mediterranean – the lengthening of most voyages in time and distance and the delays at the ports through bombing and the black-out, all reduced the operative fertility of our shipping to an extent even more serious than the actual losses. […] To the U-boat scourge was soon added air attack far out on the ocean by long-range aircraft. […] Powerful German cruisers were active. […] formidable vessels compelled the employment on convoy duty of nearly every available British capital ship. At one period the Commander-in-Chief of the Home Fleet had only one battleship in hand.”
“In the three months ending with May  U-boats alone sank 142 ships, of 818,000 tons, of which 99 were British. […] in the same three months of March, April, and May 179 ships, of 545,000 tons, were sunk by air attack, mainly in the coastal regions. […] In the Atlantic  proved the toughest [year] of the whole war. […] By the end of January  thirty-one ships, of nearly 200,000 tons, had been sunk off the coast off the United States and Canadian coast. […] In February they destroyed seventy-one ships, of 384,000 tons, in the Atlantic, of which all but two were sunk in the American zone. […] The American Army Air Force, which controlled almost all military shore-based aircraft, had no training in anti-submarine warfare, whereas the Navy, equipped with float-planes and amphibians, had no means to carry it out, and in these crucial months an effective American defence system was only achieved with painful, halting steps. […] It was not until the end of the year that a complete interlocking convoy system covering all [the] immense areas [involved] became fully effective. […] In seven months the Allied losses in the Atlantic from U-boats alone amounted to over three million tons, which included 181 British ships of 1,130,000 tons. Less than one-tenth occurred in convoys. All this cost the enemy up to July no more than fourteen U-boats sunk throughout the Atlantic and Arctic Oceans, and of these kills only six were in North American waters. […] during [August] U-boats sank 108 vessels […] Between January and October 1942 the number of U-boats had more than doubled. 196 were operational […] All our escorts had to be cut to the bone for the sake of our main operations in Africa, and in November our losses at sea were the heaviest of the whole war, including 117 ships, of over 700,000 tons, by U-boats alone, another 100,000 from other causes.”