Econstudentlog

The Second World War (II)

Here’s my first post about Churchill’s book(s). In this post I’ll add some further observations and data; I’m roughly two-thirds through the book(s) at this point.

“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 [1941] 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 [1942] proved the toughest [year] of the whole war. […] By the end of January [1942] 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.”

April 19, 2016 Posted by | books, history | Leave a comment

Einstein quotes

“Einstein emerges from this collection of quotes, drawn from many different sources, as a complete and fully rounded human being […] Knowledge of the darker side of Einstein’s life makes his achievement in science and in public affairs even more miraculous. This book shows him as he was – not a superhuman genius but a human genius, and all the greater for being human.”

I’ve recently read The Ultimate Quotable Einstein, from the foreword of which the above quote is taken, which contains roughly 1600 quotes by or about Albert Einstein; most of the quotes are by Einstein himself, but the book also includes more than 50 pages towards the end of the book containing quotes by others about him. I was probably not in the main target group, but I do like good quote collections and I figured there might be enough good quotes in the book for it to make sense for me to give it a try. On the other hand after having read the foreword by Freeman Dyson I knew there would probably be a lot of quotes in the book which I probably wouldn’t find too interesting; I’m not really sure why I should give a crap if/why a guy who died more than 60 years ago and whom I have never met and never will was having an affair during the early 1920s, or why I should care what Einstein thought about his mother or his ex-wife, but if that kind of stuff interests you the book has stuff about those kinds of things as well. My own interest in Einstein, such as it is, is mainly in ‘Einstein the scientist’ (and perhaps also in this particular context ‘Einstein the aphorist’), not ‘Einstein the father’ or ‘Einstein the husband’. I also don’t find the political views which he held to be very interesting, but again if you want to know what Einstein thought about things like Zionism, pacifism, and world government the book includes quotes about such topics as well.

Overall I should say that I was a little underwhelmed by the book and the quotes it includes, but I would also note that people who are interested in knowing more about Einstein will likely find a lot of valuable source material here, and that I did give the book 3 stars on goodreads. I did learn a lot of new things about Einstein by reading the book, but this is not surprising given how little I knew about him before I started reading the book; for example I had no idea that he was offered the presidency of Israel a few years before his death. I noticed only two quotes which were included more than once (a quote on pages 187-188 was repeated on page 453, and a quote on page 295 was repeated on page 455), and although I cannot guarantee that there aren’t any other repeats almost all quotes included in the book are unique, in the sense that they’re only included once in the coverage. However it should also be mentioned in this context that there are a few quotes on specific themes which are very similar to other quotes included elsewhere in the coverage. I do consider this unavoidable considering the number of quotes included, though.

I have included some sample quotes from the book below – I have tried to include quotes on a wide variety of topics. All quotes without a source below are sourced quotes by Einstein (the book also contains a small collection of quotes ‘attributed to Einstein’, many of which are either not sourced or sourced in such a manner that Calaprice did not feel convinced that the quote was actually by Einstein – none of the quotes from that part of the book’s coverage are included below).

“When a blind beetle crawls over the surface of a curved branch, it doesn’t notice that the track it has covered is indeed curved. I was lucky enough to notice what the beetle didn’t notice.” (“in answer to his son Eduard’s question about why he is so famous, 1922.”)

“The most valuable thing a teacher can impart to children is not knowledge and understanding per se but a longing for knowledge and understanding” (see on a related note also Susan Engel’s book – US)

“Teaching should be such that what is offered is perceived as a valuable gift and not as a hard duty.”

“I am not prepared to accept all his conclusions, but I consider his work an immensely valuable contribution to the science of human behavior.” (Einstein said this about Sigmund Freud during an interview. Yeah…)

“I consider him the best of the living writers.” (on Bertrand Russell. Russell incidentally also admired Einstein immensely – the last part of the book, including quotes by others about Einstein, includes this one by him: “Of all the public figures that I have known, Einstein was the one who commanded my most wholehearted admiration.”)

“I cannot understand the passive response of the whole civilized world to this modern barbarism. Doesn’t the world see that Hitler is aiming for war?” (1933. Related link.)

“Children don’t heed the life experience of their parents, and nations ignore history. Bad lessons always have to be learned anew.”

“Few people are capable of expressing with equanimity opinions that differ from the prejudices of their social environment. Most people are even incapable of forming such opinions.”

“Sometimes one pays most for things one gets for nothing.”

“Thanks to my fortunate idea of introducing the relativity principle into physics, you (and others) now enormously overrate my scientific abilities, to the point where this makes me quite uncomfortable.” (To Arnold Sommerfeld, 1908)

“No fairer destiny could be allotted to any physical theory than that it should of itself point out the way to the introduction of a more comprehensive theory, in which it lives on as a limiting case.”

“Mother nature, or more precisely an experiment, is a resolute and seldom friendly referee […]. She never says “yes” to a theory; but only “maybe” under the best of circumstances, and in most cases simply “no”.”

“The aim of science is, on the one hand, a comprehension, as complete as possible, of the connection between the sense experiences in their totality, and, on the other hand, the accomplishment of this aim by the use of a minimum of primary concepts and relations.” A related quote from the book: “Although it is true that it is the goal of science to discover rules which permit the association and foretelling of facts, this is not its only aim. It also seeks to reduce the connections discovered to the smallest possible number of mutually independent conceptual elements. It is in this striving after the rational unification of the manifold that it encounters its greatest successes.”

“According to general relativity, the concept of space detached from any physical content does not exist. The physical reality of space is represented by a field whose components are continuous functions of four independent variables – the coordinates of space and time.”

“One thing I have learned in a long life: that all our science, measured against reality, is primitive and childlike – and yet it is the most precious thing we have.”

“”Why should I? Everybody knows me there” (upon being told by his wife to dress properly when going to the office). “Why should I? No one knows me there” (upon being told to dress properly for his first big conference).”

“Marriage is but slavery made to appear civilized.”

“Nothing is more destructive of respect for the government and the law of the land than passing laws that cannot be enforced.”

“Einstein would be one of the greatest theoretical physicists of all time even if he had not written a single line on relativity.” (Max Born)

“Einstein’s [violin] playing is excellent, but he does not deserve his world fame; there are many others just as good.” (“A music critic on an early 1920s performance, unaware that Einstein’s fame derived from physics, not music. Quoted in Reiser, Albert Einstein, 202-203″)

April 12, 2016 Posted by | books, history, Physics, quotes, science | Leave a comment

Quotes

i. “Only half of writing is saying what you mean. The other half is preventing people from reading what they expected you to mean.” (James Richardson)

ii. “How often feelings are circular. How embarrassing to be embarrassed. How annoying to be annoyed.” (-ll-)

iii. “I worked so hard to understand it that it must be true.” (-ll-)

iv. “Always tell the Truth: where it is not loved, it is respected and feared.” (Thomas Fuller)

v. “the wise Man that holds his Tongue, says more than the Fool who speaks.” (-ll-)

vi. “‘Tis better for thee to be wise and not seem so, than to seem wise and not be so: Yet Men, for the most Part, desire and endeavor the contrary.” (-ll-)

vii. “If any one giveth thee excessive Praises more than can handsomely belong to thee, thou art to think of him, that he taketh thee for vain and credulous, and easy to be deceived, and effectually a Fool.” (-ll-)

viii. “When thou shewest Respect to any one, see that thy Submissions be proportionable to the Homage thou owest him. There is Stupidity and Pride in doing too little; but in over acting of it, there is Abjection and Hypocrisy.” (-ll-)

ix. “The Way to think we have enough, is not to desire to have too much.” (-ll-)

x. “A Friend to all, is a Friend to none.” (-ll-)

xi. “One needs time to free oneself of wrong convictions. If it happens too suddenly, they go on festering.” (Elias Canetti)

xii. “Duty largely consists of pretending that the trivial is critical.” (John Fowles)

xiii. “You have not converted a man, because you have silenced him.” (John Morley)

xiv. “It is a test of true theories not only to account for but to predict phenomena.” (William Whewell)

xv. “Personally, I find the concept of a “final theory,” or a “theory of everything,” rather limiting. The fun of discovery will most likely last as long as the human race continues.” (F. J. Duarte)

xvi. “There is no meaning to space that is independent of the relationships among real things of the world. …Space is nothing apart from the things that exist. …If we take out all the words we are not left with an empty sentence, we are left with nothing.” (Lee Smolin)

xvii. “One should never forget, that society would rather be amused than instructed.” (Adolph Freiherr Knigge)

xviii. “Clearly, a civilization that feels guilty for everything it is and does will lack the energy and conviction to defend itself.” (Jean-François Revel; quoted by Jeane Kirkpatrick during a speech she gave in 1984).

xix. “Democratic civilization is the first in history to blame itself because another power is working to destroy it.” (Jean-François Revel, 1983)

xx. “The only excuse for God is that He does not exist.” (Stendhal)

 

 

April 9, 2016 Posted by | quotes | Leave a comment

Human Drug Metabolism (I)

“It has been said that if a drug has no side effects, then it is unlikely to work. Drug therapy labours under the fundamental problem that usually every single cell in the body has to be treated just to exert a beneficial effect on a small group of cells, perhaps in one tissue. Although drug-targeting technology is improving rapidly, most of us who take an oral dose are still faced with the problem that the vast majority of our cells are being unnecessarily exposed to an agent that at best will have no effect, but at worst will exert many unwanted effects. Essentially, all drug treatment is really a compromise between positive and negative effects in the patient. […] This book is intended to provide a basic grounding in human drug metabolism, although it is useful if the reader has some knowledge of biochemistry, physiology and pharmacology from other sources. In addition, a qualitative understanding of chemistry can illuminate many facets of drug metabolism and toxicity. Although chemistry can be intimidating, I have tried to make the chemical aspects of drug metabolism as user-friendly as possible.”

I’m currently reading this book. To say that it is ‘useful if the reader has some knowledge’ of the topics mentioned is putting it mildly; I’d say it’s mandatory – my advice would be to stay far away from this book if you know nothing of pharmacology, biochem, and physiology. I know enough to follow most of the coverage, at least in terms of the big picture stuff, but some of the biochemistry details I frankly have been unable to follow; I think I could probably understand all of it if I were willing to look up all the words and concepts with which I’m unfamiliar, but I’m not willing to spend the time to do that. In this context it should also be mentioned that the book is very well written, in the sense that it is perfectly possible to read the book and follow the basic outline of what’s going on without necessarily understanding all details, so I don’t feel that the coverage in any way discourages me from reading the book the way I am – the significance of that hydrogen bond in the diagram will probably become apparent to you later, and even if it doesn’t you’ll probably manage.

In terms of general remarks about the book, a key point to be mentioned early on is also that the book is very dense and has a lot of interesting stuff. I find it hard at the moment to justify devoting time to blogging, but if that were not the case I’d probably feel tempted to cover this book in a lot of detail, with multiple posts delving into specific fascinating aspects of the coverage. Despite this being a book where I don’t really understand everything that’s going on all the time, I’m definitely at a five star rating at the moment, and I’ve read close to two-thirds of it at this point.

A few quotes:

“The process of drug development weeds out agents [or at least tries to weed out agents… – US] that have seriously negative actions and usually releases onto the market drugs that may have a profile of side effects, but these are relatively minor within a set concentration range where the drug’s pharmacological action is most effective. This range, or ‘therapeutic window’ is rather variable, but it will give some indication of the most ‘efficient’ drug concentration. This effectively means the most beneficial pharmacodynamic effects for the minimum side effects.”

If the dose is too low, you have a case of drug failure, where the drug doesn’t work. If the dose is too high, you experience toxicity. Both outcomes are problematic, but they manifest in different ways. Drug failure is usually a gradual process (days – “Therapeutic drug failure is usually a gradual process, where the time frame may be days before the problem is detected”), whereas toxicity may be of very rapid onset (hours).

“To some extent, every patient has a unique therapeutic window for each drug they take, as there is such huge variation in our pharmacodynamic drug sensitivities. This book is concerned with what systems influence how long a drug stays in our bodies. […] [The therapeutic index] has been defined as the ratio between the lethal or toxic dose and the effective dose that shows the normal range of pharmacological effect. In practice, a drug […] is listed as having a narrow TI if there is less than a twofold difference between the lethal and effective doses, or a twofold difference in the minimum toxic and minimum effective concentrations. Back in the 1960s, many drugs in common use had narrow TIs […] that could be toxic at relatively low levels. Over the last 30 years, the drug industry has aimed to replace this type of drug with agents with much higher TIs. […] However, there are many drugs […] which remain in use that have narrow or relatively narrow TIs”.

“metabolites are usually removed from the cell faster than the parent drug”

“The kidneys are mostly responsible for […] removal, known as elimination. The kidneys cannot filter large chemical entities like proteins, but they can remove the majority of smaller chemicals, depending on size, charge and water solubility. […] the kidney is a lipophilic (oil-loving) organ […] So the kidney is not efficient at eliminating lipophilic chemicals. One of the major roles of the liver is to use biotransforming enzymes to ensure that lipophilic agents are made water soluble enough to be cleared by the kidney. So the liver has an essential but indirect role in clearance, in that it must extract the drug from the circulation, biotransform (metabolize) it, then return the water-soluble product to the blood for the kidney to remove. The liver can also actively clear or physically remove its metabolic products from the circulation by excreting them in bile, where they travel through the gut to be eliminated in faeces.”

“Cell structures eventually settled around the format we see now, a largely aqueous cytoplasm bounded by a predominantly lipophilic protective membrane. Although the membrane does prevent entry and exit of many potential toxins, it is no barrier to other lipophilic molecules. If these molecules are highly lipophilic, they will passively diffuse into and become trapped in the membrane. If they are slightly less lipophilic, they will pass through it into the organism. So aside from ‘ housekeeping ’ enzyme systems, some enzymatic protection would have been needed against invading molecules from the immediate environment. […] the majority of living organisms including ourselves now possess some form of effective biotransformational enzyme capability which can detoxify and eliminate most hydrocarbons and related molecules. This capability has been effectively ‘stolen’ from bacteria over millions of years. The main biotransformational protection against aromatic hydrocarbons is a series of enzymes so named as they absorb UV light at 450 nm when reduced and bound to carbon monoxide. These specialized enzymes were termed cytochrome P450 monooxygenases or sometimes oxido-reductases. They are often referred to as ‘CYPs’ or ‘P450s’. […] All the CYPs accomplish their functions using the same basic mechanism, but each enzyme is adapted to dismantle particular groups of chemical structures. It is a testament to millions of years of ‘ research and development ’ in the evolution of CYPs, that perhaps 50,000 or more man-made chemical entities enter the environment for the first time every year and the vast majority can be oxidized by at least one form of CYP. […] To date, nearly 60 human CYPs have been identified […] It is likely that hundreds more CYP-mediated endogenous functions remain to be discovered. […] CYPs belong to a group of enzymes which all have similar core structures and modes of operation. […] Their importance to us is underlined by their key role in more than 75 per cent of all drug biotransformations.”

I would add a note here that a very large proportion of this book is, perhaps unsurprisingly in view of the above, about those CYPs; how they work, what exactly it is that they do, which different kinds there are and what roles they play in the metabolism of specific drugs and chemical compounds, variation in gene expression across individuals and across populations in the context of specific CYPs and how such variation may relate to differences in drug metabolism, etc.

“Drugs often parallel endogenous molecules in their oil solubility, although many are considerably more lipophilic than these molecules. Generally, drugs, and xenobiotic compounds, have to be fairly oil soluble or they would not be absorbed from the GI tract. Once absorbed these molecules could change both the structure and function of living systems and their oil solubility makes these molecules rather ‘elusive’, in the sense that they can enter and leave cells according to their concentration and are temporarily beyond the control of the living system. This problem is compounded by the difficulty encountered by living systems in the removal of lipophilic molecules. […] even after the kidney removes them from blood by filtering them, the lipophilicity of drugs, toxins and endogenous steroids means that as soon as they enter the collecting tubules, they can immediately return to the tissue of the tubules, as this is more oil-rich than the aqueous urine. So the majority of lipophilic molecules can be filtered dozens of times and only low levels are actually excreted. In addition, very high lipophilicity molecules like some insecticides and fire retardants might never leave adipose tissue at all […] This means that for lipophilic agents:
*the more lipophilic they are, the more these agents are trapped in membranes, affecting fluidity and causing disruption at high levels;
* if they are hormones, they can exert an irreversible effect on tissues that is outside normal physiological control;
*if they are toxic, they can potentially damage endogenous structures;
* if they are drugs, they are also free to cause any pharmacological effect for a considerable period of time.”

“A sculptor was once asked how he would go about sculpting an elephant from a block of stone. His response was ‘knock off all the bits that did not look like an elephant’. Similarly, drug-metabolizing CYPs have one main imperative, to make molecules more water-soluble. Every aspect of their structure and function, their position in the liver, their initial selection of substrate, binding, substrate orientation and catalytic cycling, is intended to accomplish this deceptively simple aim.”

“The use of therapeutic drugs is a constant battle to pharmacologically influence a system that is actively undermining the drugs’ effects by removing them as fast as possible. The processes of oxidative and conjugative metabolism, in concert with efflux pump systems, act to clear a variety of chemicals from the body into the urine or faeces, in the most rapid and efficient manner. The systems that manage these processes also sense and detect increases in certain lipophilic substances and this boosts the metabolic capability to respond to the increased load.”

“The aim of drug therapy is to provide a stable, predictable pharmacological effect that can be adjusted to the needs of the individual patient for as long is deemed clinically necessary. The physician may start drug therapy at a dosage that is decided on the basis of previous clinical experience and standard recommendations. At some point, the dosage might be increased if the desired effects were not forthcoming, or reduced if side effects are intolerable to the patient. This adjustment of dosage can be much easier in drugs that have a directly measurable response, such as a change in clotting time. However, in some drugs, this adjustment process can take longer to achieve than others, as the pharmacological effect, once attained, is gradually lost over a period of days. The dosage must be escalated to regain the original effect, sometimes several times, until the patient is stable on the dosage. In some cases, after some weeks of taking the drug, the initial pharmacological effect seen in the first few days now requires up to eight times the initial dosage to reproduce. It thus takes a significant period of time to create a stable pharmacological effect on a constant dose. In the same patients, if another drug is added to the regimen, it may not have any effect at all. In other patients, sudden withdrawal of perhaps only one drug in a regimen might lead to a gradual but serious intensification of the other drug’s side effects.”

“acceleration of drug metabolism as a response to the presence of certain drugs is known as ‘enzyme induction’ and drugs which cause it are often referred to as ‘inducers’ of drug metabolism. The process can be defined as: ‘An adaptive increase in the metabolizing capacity of a tissue’; this means that a drug or chemical is capable of inducing an increase in the transcription and translation of specific CYP isoforms, which are often (although not always) the most efficient metabolizers of that chemical. […] A new drug is generally regarded as an inducer if it produces a change in drug clearance which is equal to or greater than 40 per cent of an established potent inducer, usually taken as rifampicin. […] inducers are usually (but not always) lipophilic, contain aromatic groups and consequently, if they were not oxidized, they would be very persistent in living systems. CYP enzymes have evolved to oxidize this very type of agent; indeed, an elaborate and very effective system has also evolved to modulate the degree of CYP oxidation of these agents, so it is clear that living systems regard inducers as a particular threat among lipophilic agents in general. The process of induction is dynamic and closely controlled. The adaptive increase is constantly matched to the level of exposure to the drug, from very minor almost undetectable increases in CYP protein synthesis, all the way to a maximum enzyme synthesis that leads to the clearance of grammes of a chemical per day. Once exposure to the drug or toxin ceases, the adaptive increase in metabolizing capacity will subside gradually to the previous low level, usually within a time period of a few days. This varies according to the individual and the drug. […] it is clear there is almost limitless capacity for variation in terms of the basic pre-set responsiveness of the system as well as its susceptibility to different inducers and groups of inducers. Indeed, induction in different patients has been observed to differ by more than 20-fold.”

This one I added mostly because I didn’t know this and I thought it was worth including it here because it would make it easier for me to remember later (i.e., not because I figured other people might find this interesting):

CYP2E1 is very sensitive to diet, even becoming induced by high fat/low carbohydrate intakes. Surprisingly, starvation and diabetes also promote CYP2E1 functionality. Insulin levels fall during diet restriction, starvation and in diabetes and the formation of functional 2E1 is suppressed by insulin, so these conditions promote the increase of 2E1 metabolic capability. One of the consequences of diabetes and starvation is the major shift from glucose to fatty acid/tryglyceride oxidation, of which some of the by-products are small, hydrophilic and potentially toxic ‘ketone bodies’. These agents can cause a CNS intoxicating effect which is seen in diabetics who are very hypoglycaemic, they may appear ‘drunk’ and their breath will smell as if they had been drinking.”

A more general related point which may be of more interest to other people reading along here is that this is far from the only CYP which is sensitive to diet, and that diet-mediated effects may be very significant. I may go into this in more detail in a later post. Note that grapefruit is a major potentially problematic dietary component in many drug contexts:

“Although patients have been heroically consuming grapefruit juice for their health for decades, it took until the late 1980s before its effects on drug clearance were noted and several more years before it was realized that there could be a major problem with drug interactions […] The most noteworthy feature of the effect of grapefruit juice is its potency from a single ‘dose’ which coincides with a typical single breakfast intake of the juice, say around 200–300 ml. Studies with CYP3A substrates such as midazolam have shown that it can take up to three days before the effects wear off, which is consistent with the synthesis of new enzyme. […] there are a number of drugs that are subject to a very high gut wall component to their ‘first-pass’ metabolism […]; these include midazolam, terfenadine, lovastatin, simvastatin and astemizole. Their gut CYP clearance is so high that if the juice inhibits it, the concentration reaching the liver can increase six- or sevenfold. If the liver normally only extracts a relatively minor proportion of the parent agent, then plasma levels of such drugs increase dramatically towards toxicity […] the inhibitor effects of grapefruit juice in high first – pass drugs is particularly clinically relevant as it can occur after one exposure of the juice.”

It may sound funny, but there are two pages in this book about the effects of grapefruit juice, including a list of ‘Drugs that should not be taken with grapefruit juice’. Grapefruit is a well-known so-called mechanism-based inhibitor, and it may impact the metabolism of a lot of different drugs. It is far from the only known dietary component which may cause problems in a drug metabolism context – for example “cranberry juice has been known for some time as an inhibitor of warfarin metabolism”. On a general note the author remarks that: “There are hundreds of fruit preparations available that have been specifically marketed for their […] antioxidant capacities, such as purple grape, pomegranate, blueberry and acai juices. […] As they all contain large numbers of diverse phenolics and are pharmacologically active, they should be consumed with some caution during drug therapy.”

April 7, 2016 Posted by | biology, books, medicine, Pharmacology | Leave a comment

The Second World War (I?)

“I am perhaps the only man who has passed through both the two supreme cataclysms of recorded history in high executive office. Whereas […] in the First World War I filled responsible but subordinate posts, I was in this second struggle with Germany for more than five years the head of His Majesty’s Government. I write therefore from a different standpoint and with more authority than was possible in my earlier books. I do not describe it as history, for that belongs to another generation. But I claim with confidence that it is a contribution to history which will be of service to the future.”

“Let no one look down on those honourable, well-meaning men whose actions are chronicled in these pages without searching his own heart, reviewing his own discharge of public duty, and applying the lessons of the past to his future conduct.”

I am currently reading this book, which is really an abridgement of 6 different volumes written by Churchill. All of the stuff included is Churchill’s own stuff; the only thing that has been done is that some stuff has been left out, and some of the remaining stuff has been rearranged. Which means that you in this book get four books/subsections, rather than six. The titles of these are: Milestones to disaster (1919-May 10, 1940), Alone (May 10, 1940-June 22, 1941), The Grand Alliance (Sunday, December 7, 1941 and onwards), and Triumph and Tragedy (1943-1945). I have by now finished Book 1 (the Milestones to Disaster part), and I’ve read close to 100 pages of Book 2. It’s great stuff, and very detailed. In this post I have included quotes from roughly the first 150 pages of the book’s coverage, all of which belong to the ‘Milestones to disaster’ part.

“When Marshall Foch heard of the signing of the Peace Treaty of Versailles he observed with singular accuracy: “This is not peace. It is an Armistice for twenty years.””

[In the context of the reparations:] “whereas about £1,000 millions of German assets were appropriated by the victorious Powers, more than £1,500 millions were lent a few years later to Germany, principally by the United States and Great Britain […] until 1931 the victors, and particularly the United States, concentrated their efforts upon extorting by vexatious foreign controls their annual reparations from Germany. The fact that these payments were made only from far larger American loans reduced the whole process to the absurd. Nothing was reaped except ill-will. […] History will characterize all these transactions as insane. […] All this is a sad story of complicated idiocy”

“Deliberate extermination of whole populations was contemplated and pursued by both Germany and Russia in the Eastern war.”

“”We are apparently finished and done with economic cycles as we have known them,” said the President of the New York Stock Exchange in September.” [That would be September, 1929. Talk about bad timing… – US]

“The opinions of the Press and public were in no way founded upon reality […] delight in smooth-sounding platitudes, refusal to face unpleasant facts, desire for popularity and electoral success irrespective of the vital interests of the State, genuine love of peace and pathetic belief that love can be its sole foundation, obvious lack of intellectual vigour […] marked ignorance […] the utter devotion […] to sentiment apart from reality […]: all these constituted a picture of British fatuity and fecklessness which, though devoid of guile, was not devoid of guilt, and, though free from wickedness or evil design, played a definite part in the unleashing upon the world of horrors and miseries which, even so far as they have unfolded, are already beyond comparison in human experience. […] It is difficult to find a parallel to the unwisdom of the British and weakness of the French Governments, who none the less reflected the opinion of their Parliaments in this disastrous period” [the period in question being the early thirties – US].

“Several visitors of consequence came to me from Germany and poured their hearts out in their bitter distress. Most of these were executed by Hitler during the war.”

“It would be wrong in judging the policy of the British Government not to remember the passionate desire for peace which animated the uninformed, misinformed majority of the British people, and seemed to threaten with political extinction any party or politician who dared to take any other line. This, of course, is no excuse for political leaders who fall short of their duty. It is much better for parties or politicians to be turned out of office than to imperil the life of the nation. […] To be so entirely convinced and vindicated in a matter of life and death to one’s country, and not to be able to make Parliament and the nation heed the warning, or bow to the proof by taking action, was an experience most painful.”

“the number of Germans under regular military training in 1936 was 1,511,000 men. The effective strength of the French Army, apart from reserves, in the same year was 623,000 men, of whom only 407,000 were in France.”

Abyssinia [see also this] was a member of the League of Nations. By a curious inversion it was Italy who had in 1923 pressed for her inclusion, and Britain who had opposed it. The British view was that the character of the Ethiopian Government and the conditions prevailing in that wild land of tyranny, slavery, and tribal war were not consonant with membership of the League. But the Italians had had their way” [incidentally if you want an update on how things are going in that part of the world, apropos all those migrants coming to Europe from that region these days, here’s some updated information: “Eritrea is a one-party state in which national legislative elections have been repeatedly postponed.[111] According to Human Rights Watch, the government’s human rights record is considered among the worst in the world. […] In June 2015, a 500-page United Nations Human Rights Council report accused Eritrea’s government of extrajudicial executions, torture, indefinitely prolonged national service and forced labour, and indicated that sexual harassment, rape and sexual servitude by state officials are also widespread.” (wikipedia)]

“One day in 1937 I had a meeting with Herr von Ribbentrop, German ambassador to Britain. […] he had asked Hitler to let him come over to London in order to make the full case for an Anglo-German entente or even alliance. […] What was required was that Britain should give Germany a free hand in the East of Europe. She must have her Lebensraum […] All that was asked of the British Commonwealth and Empire was not to interfere. There was a large map on the wall, and the Ambassador several times led me to it to illustrate his projects. After hearing all this I said at once that I was sure the British Government would not agree to give Germany a free hand in Eastern Europe. […] Ribbentrop turned abruptly away. He then said, “In that case, war is inevitable. There is no way out. The Fuehrer is resolved. Nothing will stop him and nothing will stop us.” We then returned to our chairs.” [At this time Churchill was just an MP, so Ribbentrop was not asking Churchill himself to consent to the proposed scheme and ‘make a deal’; he was trying to figure out if there was any deal to be made. The year after, on July 26, 1938, Lord Halifax, the British Foreign Minister, incidentally stated in Parliament that: “I do not believe that those responsible for the Government of any country in Europe to-day want war.” – US]

“On the day of the march of the German armies into Austria we heard that Goering had given a solemn assurance to the Czech Minister in Berlin that Germany had “no evil intentions towards Czechoslovakia” […] On the evening of the 26th [of September, 1938 – US] Hitler spoke in Berlin. […] He said categorically that the Czechs must clear out of the Sudetenland, but once this was settled he had no more interest in what happened to Czechoslovakia. “This is the last territorial claim I have to make in Europe.” […] Chamberlain returned to England [after signing the agreement – US]. […] from the windows of Downing Street he waved his piece of paper again and used these words, “This is the second time in our history that there has come back from Germany to Downing Street peace with honour. I believe it is peace for our time.”

“In 1938-39 British military expenditure of all kinds reached £304 millions,* and German was at least £1,500 millions. It is probable that in the last year before the outbreak Germany manufactured at least double, and possibly treble, the munitions of Britain and France put together […] in the single year 1938 Hitler had annexed to the Reich and brought under his absolute rule […] a total of over ten millions of subjects, toilers, and soldiers. […] The German armies were not capable of defeating the French in 1938 or 1939. The vast tank production with which they broke the French front did not come into existence till 1940”

“if you will not fight for the right when you can easily win without bloodshed, if you will not fight when your victory will be sure and not too costly, you may come to the moment when you will have to fight with all the odds against you and only a precarious chance of survival. There may even be a worse case. You may have to fight when there is no hope of victory, because it is better to perish than live as slaves.”

“At the Kremlin in August 1942 Stalin, in the early hours of the morning, gave me one aspect of the Soviet position. “We formed the impression,” said Stalin, “that the British and French governments were not resolved to go to war if Poland were attacked, but that they hoped the diplomatic line-up of Britain, France, and Russia would deter Hitler. We were sure it would not.””

“There were known to be twenty thousand organised German Nazis in England at this time [at the end of August, 1939US], and it would only have been in accord with their procedure in other friendly countries that the outbreak of war should be preceded by a sharp prelude of sabotage and murder. I had at that time no official protection, and I did not wish to ask for any; but I thought myself sufficiently prominent to take precautions. I had enough information to convince me that Hitler recognised me as a foe. My former Scotland Yard detective, Inspector Thompson, was in retirement. I told him to come along and bring his pistol with him. I got out my own weapons, which were good. While one slept the other watched.”

 

April 6, 2016 Posted by | books, history | Leave a comment

Quotes

i. “I prefer to be true to myself, even at the hazard of incurring the ridicule of others, rather than to be false, and incur my own abhorrence.” (Frederick Douglass)

ii. “To make a contented slave it is necessary to make a thoughtless one. It is necessary to darken the moral and mental vision and, as far as possible, to annihilate the power of reason.” (-ll-)

iii. “The part of life we really live is small. For all the rest of existence is not life, but merely time. […] In guarding their fortune men are often closefisted, yet, when it comes to the matter of wasting time, in the case of the one thing in which it is right to be miserly, they show themselves most prodigal.” (Seneca the Younger, On the shortness of life)

iv. “It takes the whole of life to learn how to live, and — what will perhaps make you wonder more — it takes the whole of life to learn how to die.” (-ll-)

v. “those who forget the past, neglect the present, and fear for the future have a life that is very brief and troubled […] They lose the day in expectation of the night, and the night in fear of the dawn.” (-ll-)

vi. “The best way to know your faults is to notice which ones you accuse others of.” (James Richardson)

vii. “To condemn your sin in another is hypocrisy. Not to condemn is to reserve your right to sin.” (-ll-)

viii. “Let me have my dreams but not what I dream of.” (-ll-)

ix. “The man who sticks to his plan will become what he used to want to be.” (-ll-)

x. “The new gets old much faster than the old gets older.” (-ll-)

xi. “Embarrassment is the greatest teacher, but since its lessons are exactly those we have tried hardest to conceal from ourselves, it may teach us, also, to perfect our self-deception.” (-ll-)

xii. “Bitterness is a greater failure than failure.” (-ll-)

xiii. “The surest sign that a man has a genuine taste of his own is that he is uncertain of it.” (W. H. Auden)

xiv. “All the things that happen and seem so important at the time, and yet you forget them, one after another.” (Thomas M. Disch)

xv. “Inspiration usually comes during work, rather than before it.” (Madeleine L’Engle)

xvi. “A man who knows how little he knows is well, a man who knows how much he knows is sick.” (Witter Bynner)

xvii. “What is well done is done soon enough.” (Guillaume de Salluste Du Bartas)

xviii. “Be advised that all flatterers live at the expense of those who listen to them.” (John de La Fontaine)

xix. “We are what we think. To change how people act, we must change what they believe.” (Mark Riebling)

xx. “Sometimes, only one person is missing, and the whole world seems depopulated.” (Alphonse de Lamartine)

March 23, 2016 Posted by | quotes | Leave a comment

Quotes

i. When you counsel someone, you should appear to be reminding him of something he had forgotten, not of the light he was unable to see. (Baltasar Gracián)

ii. “If you cannot make knowledge your servant, make it your friend.” (-ll-)

iii. “Knowing how to keep a friend is more important than gaining a new one.” (-ll-)

iv. “There are persons who, when they cease to shock us, cease to interest us.” (F. H. Bradley)

v. “Never curse an illness; better ask for health.” (Andrzej Majewski)

vi. “He who makes a paradise of his bread makes a hell of his hunger.” (Antonio Porchia)

vii. “The less you think you are, the more you bear. And if you think you are nothing, you bear everything.” (-ll-)

viii. “In its last moment, the whole of my life will last only a moment.” (-ll-)

ix. “I know what I have given you, I do not know what you have received.” (-ll-)

x. “The condemnation of an error is another error.” (-ll-)

xi. “If you are good to this one and that one, this one and that one will say you are good. If you are good to everyone, no one will say that you are good.” (-ll-)

xii. “All that can’t be is almost always a reproach against what can be.” (-ll-)

xiii. “Value yourself according to the burdens you carry, and you will find everything a burden.” (James Richardson)

xiv. “The single sin is less of a problem than the good reasons for it.” (-ll-)

xv. “The first abuse of power is not realizing that you have it.” (-ll-)

xvi. “Only the dead have discovered what they cannot live without.” (-ll-)

xvii. “Success is whatever humiliation everyone has agreed to compete for.” (-ll-)

xviii. “What did you do today? Nothing say our little children, and so do I. What we most are is what we keep mistaking for nothing.” (-ll-)

xix. “A day is only a day. But a life is only a life.” (-ll-)

xx. “Beware of knowing your virtues; you may lose them. Beware of knowing your vices; you may forgive them.” (-ll-)

March 12, 2016 Posted by | quotes | Leave a comment

Books 2016

I have been reading way too much fiction this year and not enough non-fiction and I have been feeling guilty about that, but I hope that I can make up for the shortfall of non-fiction (‘serious’) reading later in the year. We’ll see how it goes.

Regarding the ‘technical aspects’ of the list below, as usual the letters ‘f’ and ‘nf.’ in the parentheses correspond to ‘fiction’ and ‘non-fiction’, respectively. The numbers in the parentheses correspond to the goodreads ratings I thought the books deserved.

This post is ‘a work in progress’ and it’ll remain so for the rest of the year – I’ll update the post regularly throughout the year, so that new books, blogposts and reviews will be continuously added to the list/post as time goes by.

1. 4.50 from Paddington (4, f). Agatha Christie.

2. Explaining Behavior: Reasons in a World of Causes (1, nf. Bradford Book). Goodreads review here.

3. Hickory Dickory Dock (3, f). Agatha Christie.

4. Death Comes As the End (3, f). Agatha Christie. Short goodreads review here.

5. At Bertram’s Hotel (3, f). Agatha Christie. Very short goodreads review here.

6. A Caribbean Mystery (3, f). Agatha Christie.

7. A Rulebook for Arguments (Hackett Student Handbooks) (1, nf. Hackett Publishing). Very short goodreads review here.

8. The Clocks (2, f). Agatha Christie.

9. Third Girl (2, f). Agatha Christie. Very short goodreads review here.

10. The Misanthrope (2, f). Molière. Very short goodreads review here.

11. The Secret Adversary (2, f). Agatha Christie. Short goodreads review here.

12. The Social Psychology of Nonverbal Communication (2, nf. Palgrave Macmillan). Goodreads review here. Blog coverage here.

13. N or M? (2, f). Agatha Christie. Goodreads review – with spoilers – here.

14. The Emergence of Norms (4, nf. Oxford University Press). Goodreads review here. Blog coverage here.

15. By the Pricking of My Thumbs (2, f). Agatha Christie.

16. The Godfather (4, f). Mario Puzo.

17. Partners in Crime (1, f). Agatha Christie. Short goodreads review here.

18. Elephants can Remember (1, f). Agatha Christie. Short goodreads review here.

19. Hallowe’en Party (1, f). Agatha Christie. Short goodreads review here.

20. French Leave (4, f). P. G. Wodehouse. Short goodreads review here.

21. A Few Quick Ones (3, f). P. G. Wodehouse.

22. Ice in the Bedroom (4, f). P. G. Wodehouse.

23. Over Seventy (4, f). P. G. Wodehouse. Short goodreads review here.

24. The Secret of Chimneys (2, f). Agatha Christie.

25. World Regions in Global Context (1, nf. Prentice Hall). Very long (600+ pages of content). Goodreads review here.

26. Something Fishy (3, f). P. G. Wodehouse.

27. Do Butlers Burgle Banks? (3,f). P.G. Wodehouse.

28. The Mirror Crack’d from Side to Side (1, f). Agatha Christie. Boring story, almost didn’t finish it.

29. Frozen Assets (4, f). P. G. Wodehouse.

30. A Cooperative Species: Human Reciprocity and Its Evolution (5, nf. Princeton University Press). Goodreads review here.

31. If I Were You (4, f). P. G. Wodehouse.

32. On the Shortness of Life (nf.). Seneca the Younger.

33. Barmy in Wonderland (3, f). P. G. Wodehouse.

34. A Gentleman of Leisure (3, f). P. G. Wodehouse. Very short goodreads review here.

35. Pearls, Girls and Monty Bodkin (5, f). P. G. Wodehouse. Short goodreads review here.

36. The Ultimate Quotable Einstein (3, nf. Princeton University Press). Blog coverage here.

37. The Luck Stone (2, f). P. G. Wodehouse. Goodreads review here.

38. Company for Henry (4, f). P. G. Wodehouse.

39. Bachelors Anonymous (5, f). P. G. Wodehouse. A short book, but very funny.

40. The Second World War (5, nf.) Winston Churchill. Very long, the book is a thousand pages long abridgement of 6 different volumes written by Churchill. Blog coverage here and here.

 

March 10, 2016 Posted by | books | Leave a comment

Random Stuff

i. Some new words I’ve encountered (not all of them are from vocabulary.com, but many of them are):

Uxoricide, persnickety, logy, philoprogenitive, impassive, hagiography, gunwale, flounce, vivify, pelage, irredentism, pertinacity,callipygous, valetudinarian, recrudesce, adjuration, epistolary, dandle, picaresque, humdinger, newel, lightsome, lunette, inflect, misoneism, cormorant, immanence, parvenu, sconce, acquisitiveness, lingual, Macaronic, divot, mettlesome, logomachy, raffish, marginalia, omnifarious, tatter, licit.

ii. A lecture:

I got annoyed a few times by the fact that you can’t tell where he’s pointing when he’s talking about the slides, which makes the lecture harder to follow than it ought to be, but it’s still an interesting lecture.

iii. Facts about Dihydrogen Monoxide. Includes coverage of important neglected topics such as ‘What is the link between Dihydrogen Monoxide and school violence?’ After reading the article, I am frankly outraged that this stuff’s still legal!

iv. Some wikipedia links of interest:

Steganography.

Steganography […] is the practice of concealing a file, message, image, or video within another file, message, image, or video. The word steganography combines the Greek words steganos (στεγανός), meaning “covered, concealed, or protected”, and graphein (γράφειν) meaning “writing”. […] Generally, the hidden messages appear to be (or be part of) something else: images, articles, shopping lists, or some other cover text. For example, the hidden message may be in invisible ink between the visible lines of a private letter. Some implementations of steganography that lack a shared secret are forms of security through obscurity, whereas key-dependent steganographic schemes adhere to Kerckhoffs’s principle.[1]

The advantage of steganography over cryptography alone is that the intended secret message does not attract attention to itself as an object of scrutiny. Plainly visible encrypted messages—no matter how unbreakable—arouse interest, and may in themselves be incriminating in countries where encryption is illegal.[2] Thus, whereas cryptography is the practice of protecting the contents of a message alone, steganography is concerned with concealing the fact that a secret message is being sent, as well as concealing the contents of the message.”

H. H. Holmes. A really nice guy.

Herman Webster Mudgett (May 16, 1861 – May 7, 1896), better known under the name of Dr. Henry Howard Holmes or more commonly just H. H. Holmes, was one of the first documented serial killers in the modern sense of the term.[1][2] In Chicago, at the time of the 1893 World’s Columbian Exposition, Holmes opened a hotel which he had designed and built for himself specifically with murder in mind, and which was the location of many of his murders. While he confessed to 27 murders, of which nine were confirmed, his actual body count could be up to 200.[3] He brought an unknown number of his victims to his World’s Fair Hotel, located about 3 miles (4.8 km) west of the fair, which was held in Jackson Park. Besides being a serial killer, H. H. Holmes was also a successful con artist and a bigamist. […]

Holmes purchased an empty lot across from the drugstore where he built his three-story, block-long hotel building. Because of its enormous structure, local people dubbed it “The Castle”. The building was 162 feet long and 50 feet wide. […] The ground floor of the Castle contained Holmes’ own relocated drugstore and various shops, while the upper two floors contained his personal office and a labyrinth of rooms with doorways opening to brick walls, oddly-angled hallways, stairways leading to nowhere, doors that could only be opened from the outside and a host of other strange and deceptive constructions. Holmes was constantly firing and hiring different workers during the construction of the Castle, claiming that “they were doing incompetent work.” His actual reason was to ensure that he was the only one who fully understood the design of the building.[3]

Minnesota Starvation Experiment.

“The Minnesota Starvation Experiment […] was a clinical study performed at the University of Minnesota between November 19, 1944 and December 20, 1945. The investigation was designed to determine the physiological and psychological effects of severe and prolonged dietary restriction and the effectiveness of dietary rehabilitation strategies.

The motivation of the study was twofold: First, to produce a definitive treatise on the subject of human starvation based on a laboratory simulation of severe famine and, second, to use the scientific results produced to guide the Allied relief assistance to famine victims in Europe and Asia at the end of World War II. It was recognized early in 1944 that millions of people were in grave danger of mass famine as a result of the conflict, and information was needed regarding the effects of semi-starvation—and the impact of various rehabilitation strategies—if postwar relief efforts were to be effective.”

“most of the subjects experienced periods of severe emotional distress and depression.[1]:161 There were extreme reactions to the psychological effects during the experiment including self-mutilation (one subject amputated three fingers of his hand with an axe, though the subject was unsure if he had done so intentionally or accidentally).[5] Participants exhibited a preoccupation with food, both during the starvation period and the rehabilitation phase. Sexual interest was drastically reduced, and the volunteers showed signs of social withdrawal and isolation.[1]:123–124 […] One of the crucial observations of the Minnesota Starvation Experiment […] is that the physical effects of the induced semi-starvation during the study closely approximate the conditions experienced by people with a range of eating disorders such as anorexia nervosa and bulimia nervosa.”

Post-vasectomy pain syndrome. Vasectomy reversal is a risk people probably know about, but this one seems to also be worth being aware of if one is considering having a vasectomy.

Transport in the Soviet Union (‘good article’). A few observations from the article:

“By the mid-1970s, only eight percent of the Soviet population owned a car. […]  From 1924 to 1971 the USSR produced 1 million vehicles […] By 1975 only 8 percent of rural households owned a car. […] Growth of motor vehicles had increased by 224 percent in the 1980s, while hardcore surfaced roads only increased by 64 percent. […] By the 1980s Soviet railways had become the most intensively used in the world. Most Soviet citizens did not own private transport, and if they did, it was difficult to drive long distances due to the poor conditions of many roads. […] Road transport played a minor role in the Soviet economy, compared to domestic rail transport or First World road transport. According to historian Martin Crouch, road traffic of goods and passengers combined was only 14 percent of the volume of rail transport. It was only late in its existence that the Soviet authorities put emphasis on road construction and maintenance […] Road transport as a whole lagged far behind that of rail transport; the average distance moved by motor transport in 1982 was 16.4 kilometres (10.2 mi), while the average for railway transport was 930 km per ton and 435 km per ton for water freight. In 1982 there was a threefold increase in investment since 1960 in motor freight transport, and more than a thirtyfold increase since 1940.”

March 3, 2016 Posted by | biology, history, language, Lectures, random stuff, wikipedia, Zoology | Leave a comment

Quotes

i. “Almost every wise saying has an opposite one, no less wise, to balance it.” (George Santayana)

ii. “The truth is cruel, but it can be loved, and it makes free those who have loved it.” (-ll-)

iii. “[I]t is a great advantage to be intelligent and not to look it.” (Agatha Christie, Partners in Crime)

iv. “He claimed that there was no greater natural advantage in life than having an enemy overestimating your faults, unless it was to have a friend underestimate your virtues.” (Mario Puzo, The Godfather)

v. “That is the saving grace of humor, if you fail no one is laughing at you.” (A. Whitney Brown)

vi. “We may forgive those who bore us, we cannot forgive those whom we bore.” (Rochefoucauld)

vii. “A wise man changes his mind sometimes, but a fool never. To change your mind is the best evidence you have one.” (Desmond Ford)

viii. “No man was ever wise by chance.” (Nulli sapere casu obtigit. Seneca the Younger)

ix. “National unity is the basis of national security.” (Felix Frankfurter)

x. “Wisdom too often never comes, and so one ought not to reject it merely because it comes late.” (-ll-)

xi. “The most constructive way of resolving conflicts is to avoid them.” (-ll-)

xii. “Some men never spake a wise word, yet doe wisely; some on the other side doe never a wise deed, and yet speake wisely.” (Sir Thomas Overbury)

xiii. “One of the most interesting features of the open borders project is that it makes war obsolete by virtue of automatic surrender. Who needs tanks and rifles when your people can just walk across the border unarmed?” (‘Outis‘)

xiv. “War most often promotes the internal unity of each state involved. The state plagued by internal strife may then, instead of waiting for the accidental attack, seek the war that will bring internal peace.” (Kenneth Waltz)

xv. “War may achieve a redistribution of resources, but labor, not war, creates wealth.” (-ll-)

xvi. “Nerds do not think they are better than you. Nerds are better than you, in their particular fields, unless you happen to be an even more devoted nerd.” (Laura Penny)

xvii. “Posthumous fame, book fame, nerd fame is not like the good kind of fame. It might last for centuries and let antique egg heads torture the young from the grave, but it just doesn’t pay the bills.” (-ll-)

xviii. “Pedantry and mastery are opposite attitudes toward rules. To apply a rule to the letter, rigidly, unquestioningly, in cases where it fits and in cases where it does not fit, is pedantry. … To apply a rule with natural ease, with judgment, noticing the cases where it fits, and without ever letting the words of the rule obscure the purpose of the action or the opportunities of the situation, is mastery.” (George Pólya)

xix. “If you cannot solve the proposed problem, try to solve first a simpler related problem.” (-ll-)

xx. “Simplicity is worth buying if we do not have to pay too great a loss of precision for it.” (-ll-)

 

February 22, 2016 Posted by | books, quotes | Leave a comment

Nonverbal Communication

“The purpose of the book is to bring together a number of nonverbal behavior researchers to discuss current themes and research. The book is meant for senior undergraduates, graduates, academics and nonverbal communication researchers, as well as for everyone else who wants to interpret and understand better nonverbal behavior and the states of their interlocutors. The texts in this book show the results of contemporary research and theorization of the nature, functions, and modalities of nonverbal behavior in different areas of life.”

From the introduction of the book. The book has two parts; a theoretical part and an applied part. The first half of the book covers theoretical research and as I also noted in my goodreads review I found this part of the book quite weak, but a few of the chapters in the second half of the book, dealing with applied research into these topics, had some interesting stuff (‘If you decide to have a go at this book I’d probably be tempted to recommend only reading the first four chapters of part 2’ – from my goodreads review). My coverage of the book in this post will skip a lot of chapters; I’ll focus on the stuff I found interesting and just ignore the rest. The four chapters mentioned above cover ‘Nonverbal Firsts: When Nonverbal Cues Are the Impetus of Relational and Personal Change in Romantic Relationships’ (chapter 7), ‘Beyond Facial Expression: Spatial Distance as a Factor in the Communication of Discrete Emotions’ (chapter 8), Theoretical Foundation for Emotion-Based Strategies in Political Campaigns (chapter 9), and ‘The Impact of Nonverbal Behavior in the Job Interview’ (chapter 10).

I would note that I actually emailed a few quotes from the last of these chapters to a good friend of mine who recently had a job interview coming up, which is perhaps a good illustration of how potentially useful I consider some of the content covered here to be – this is worth keeping in mind when interpreting the two star (and ‘much closer to one star than three’) goodreads rating. It should however also be recalled that the authors of chapter 8, which is incidentally far from the worst chapter in the book, claim/think the so-called McClintock effect is real, based on outdated research. They write in the chapter that: “Martha McClintock and colleagues reported evidence that the menstrual cycles of co-habiting women can become synchronized, a phenomenon termed the McClintock effect (McClintock, 1971; Hummer & McClintock, 2009). Although controversial, the reality of the phenomenon is now generally accepted (Wysocki & Preti, 2004).” Compare with wikipedia: “A 2013 review of menstrual synchrony concluded that menstrual synchrony is an erroneous theory. […] Harris and Vitzthum concluded, “In light of the lack of empirical evidence for MS [menstrual synchrony] sensu stricto, it seems there should be more widespread doubt than acceptance of this hypothesis””.

Below I have added some quotes from the book, as well as a few observations of my own. I would note that I have read and written about stuff related to the content covered in this post before here on the blog, so if you’re curious to learn more after having read this post, you might consider following some of those links.

“[N]onverbal behaviors have the potential to be transformative. That is, they may act as triggers for a change in a relationship, perception, behavior, or affect. In particular, […] when a nonverbal behavior occurs or is noticed for the first time, these behavioral “firsts” can have big implications, positive or negative, for people in relationships. […] the authors find that touch, eye behavior, and personal space are the cues reported most commonly as triggers for change and which help bring about the start of a romantic relationship, perception of how much or little another cares, relational problems, instant break-ups, and indicators of another’s untrustworthiness.”

“Baxter and Bullis (1986) found that the first time their participants kissed or had sex with a partner altered the degree of commitment that they had to the relationship. In this way, the first appearance of certain nonverbal cues or acts may be important triggers of change within a relationship. […] In our respondents’ reports, we read many accounts of how a single behavior, used for what the respondent recalled was the first time, instantly changed the relationship or the perception of the relationship between the two individuals. There was some variety in the behaviors, but most typically they were handholding, prolonged gaze, kisses, closer proximity, and “changes” in touch behavior. In most of the situations described by our participants, the behavior was received positively and started a romantic relationship. In a few instances, however, it indicated to the respondent that they or another person had romantic feelings that were unreciprocated. These latter situations reportedly resulted in either the termination of the existing relationship or awkwardness in the relationship. […] the same actions – kisses, close personal distance – may have very different outcomes, depending on the reciprocity of the behaviors and feelings. […] a rather common claim about touch is that it “is a signal in the communication process that, above all other communication channels, most directly and immediately escalates the balance of intimacy” […]. Perhaps above all other nonverbal cues, touch has been shown to facilitate dramatic “surge[s] in affective involvement” […] nonverbal cues, although sometimes subtle and easy to miss, may actually be “big” actions in relational change.”

“[P]articipants often commented on the lack of a behavior (e.g., no eye contact, ignoring behavior [which presumably was determined by lack of gaze, not responding, and the like], and not talking [silence]). The themes were consistent whether they were discussing their own or their partner’s behaviors. […] Avoidance of eye contact, silence, and “ignoring,” rather than immediate, engaged, intimate, behavior was common in this group of entries and marked the beginning (or the first signal) of the relationship’s decline.”

The research they presented in the chapter was disappointing to me in a way, due to the methodology applied. Basically they asked people (…well, psychology undergrads…) which non-verbal behaviours ‘stood out’ to them, and then they interpreted the behaviours based on these accounts. Recall biases are a potentially serious problem, and if you ask people to explain relationship changes as a function of nonverbal behaviours then you’ll probably get answers indicating that nonverbal behaviours are important, regardless of whether they really are or not. But on a related note it seems hard to do ‘naturalistic/observational’ research into these topics (‘follow people around with video cameras and try to spot which nonverbal behaviours on display might be associated with relationship formation?’), and even if the self-reports are not wholly reliable they may provide some information. A big problem in the context of research into these things is of course that you can’t really directly observe relationships and relationship formation; these things are to a very large extent nothing but mental constructs in the minds of the people involved, meaning that you probably to some extent sort of have to rely on things like self-report variables. This makes everything quite a bit more ‘fuzzy’ than it otherwise would be. Note that the fact that ‘relationships are mental constructs existing only in the minds of the people involved’ does not to me seem to necessarily indicate that asking people what they think caused a relationship to change will yield reliable answers; people may not know why they feel the way they do about a given individual or why their feelings changed at some point, and/but if you give them a specific reason/variable to consider they’ll be likely to overestimate the importance of said variable. If they’d asked the same people if specific verbal exchanges (‘first time he said ‘I love you’?’) had changed how they felt about that individual, they might have got different answers.

When you consider how ‘squishy’ this stuff is, I think other approaches besides the ones considered by the authors might also be useful to consider if you want to get at the extent to which nonverbal behaviour is important; for example I feel tempted to conclude that the poor relationship outcomes of autistics (“In terms of outcome studies to date, very few adults with ASD have been reported to have successful, long-term romantic relationships […] Between 10 and 30 % of adults in recent studies […] had experience in a romantic relationship.” – link), a population including people who often have great difficulties interpreting nonverbal behaviours and cues, might provide stronger evidence in favour of the importance of nonverbal behaviours in relationship contexts than the study in question provides. Although I’d certainly agree that important confounders are present in this context (…as well), making it very difficult to take the poor relationship outcomes of this group as solely a consequence of nonverbal behavioural aspects.

“[In political contexts,] candidates and issues that emphasize freedom (e.g., fewer restrictions and external constraints on behavior and opportunities, less limitation on social and economic mobility) are more likely to appeal to men than to women. […] political messages or tactics that repeatedly produce anxious feelings (e.g., bewilderment, distress, pain, insecurity, fear) in voters are likely to magnify the influence of voter emotions on voter political judgments. Additional related effects are expected to include greater polarization of competing groups and simplification of decision rules and belief systems (e.g., increased single-issue voting, greater reliance on candidates’ physical features and communication styles than on candidates’ ideological positions).”

“Research shows that there is a positive relation between [job] applicant positive nonverbal behavior and recruiter evaluation. Positive nonverbal behavior can be defined as immediacy behavior which elicits proximity and liking in the interaction partner as for example a high level of eye contact, smiling, confirmative nodding, hand gestures, and variation in pitch and speaking rate […]. Applicants who used more immediacy behavior (i.e., eye contact, smiling, body orientation toward interviewer, less personal distance) were perceived as being more suitable for the job, more competent, more motivated, and more successful than applicants using less immediacy behavior […] Forbes and Jackson (1980) showed that selected applicants maintained more direct eye contact, smiled more, and nodded more during the job interview than applicants who were not selected for the job. Moreover, applicants who maintained a high amount of eye contact with the recruiter, who showed a high energy level, were affective, modulated their voice, and spoke fluently during the job interview were more likely to be invited for a second job interview than applicants revealing less of those nonverbal behaviors”.

“In terms of applicant characteristics, applicants high in communication apprehension who used more nonverbal avoidance behavior (i.e., less talking, less eye contact, less fluent talking) were less effective in mock job interviews and were perceived as less suitable for the job than applicants with low levels of communication apprehension […] Overall, there are only few studies that did not show an effect between applicant nonverbal immediacy behavior and a favorable hiring decision […] and meta-analyses reveal a clear net effect showing that the more the applicant uses nonverbal immediacy behavior, the better the interview outcome for the applicant (i.e., better chances of getting hired or of being evaluated positively) […] Applicant nonverbal behavior seems to have a remarkable impact on the job interview outcome. The more immediacy (or positive) nonverbal behavior the applicant shows during the job interview, the more positive recruiter evaluations of the applicant are.”

“the question can be asked how accurate recruiters are when inferring applicant characteristics. For many personality characteristics, they seem to use the “wrong,” meaning non-diagnostic, cues. […] many more nonverbal cues are used to infer applicant’s personality traits than are cues actually revealing these traits. […] recruiters seem to use the nonverbal cues that are not diagnostic to assess applicants – in a sense they use the wrong cues – and [yet] are still accurate in assessing applicants’ personality. It remains therefore largely unknown how the recruiters make those correct inferences.”

How accurate the inferences are is to some extent an open question (though it’s probably safe to say that interviews provide less relevant information than many people think – including the authors of that chapter: “[interviews] provide very little unique information about a candidate and show little incremental validity over established psychometric tests (of ability and personality) in the prediction of future job performance […] All sorts of extraneous factors like the perfume a person wears at interview have been shown to influence ratings.” – link). A related observation is that assessment accuracy definitely depends upon the dimension of the variable of interest; some personality characteristics are much easier to observe/deduce than are others, as noted e.g. in Funder’s (‘some behaviors are more dependent on the situation than are others’) book (‘traits like extraversion and agreeableness are the ones most likely to become visible in overt social behavior’).

February 17, 2016 Posted by | books, Psychology | Leave a comment

The Emergence of Norms

“Put very crudely, the main thesis of this book is that certain types of norms are possible solutions to problems posed by certain types of social interaction situations. […] Three types of paradigmatic situations are dealt with. They are referred to as (1) Prisoner’s Dilemma-type situations; (2) Co-ordination situations; (3) Inequality (or Partiality) situations. Each of them, it is claimed, poses a basic difficulty, to some or all of the individuals involved in them. Three types of norms, respectively, are offered as solutions to these situational problems. It is shown how, and in what sense, the adoption of these norms of social behaviour can indeed resolve the specified problem.”

I should probably before moving on apologize for the infrequent updates – you should expect blogging to be light also in the months to come. With that out of the way, the book to which the title of this post refers and from which the above quote is taken is this Oxford University Press publication. Here’s what I wrote about the book on goodreads:

“The last chapter wasn’t in my opinion nearly as good as the others, presumably in part because I was unfamiliar with a lot of the literature to which she referred, but also because I could not really agree with all the distinctions and arguments made, and I was close to giving the book 3 stars as a result of this [I gave the book 4 stars on goodreads]. I think she overplays the ‘impersonal’ nature of norms in that chapter; if a norm based on sanctions is not enforced then it is irrelevant, and to the extent that it is enforced *someone* needs to impose the sanction on the transgressor. The fact that it’s actually in some contexts considered ‘a problem that needs explaining’ to figure out exactly how to support a model with sanctioning in a context where enforcement is costly to the individual (it’s a problem because of the free-riding issue – it’s always easier to let someone else do the sanctioning…) seems to have eluded Margalit (for details on this topic, see e.g. Boyd and Richerson).

It’s probably helpful to be familiar with basic game theoretic concepts if you’re planning on reading this book (it has a lot of game theory, though most of it is quite simple stuff), as well as perhaps having some familiarity with basic economics (rationality assumptions, utility functions, etc.) but I’m not sure it’s strictly necessary – I think the author does cover most of the basic things you need to know to be able to follow the arguments. The first three chapters are quite good.”

I should point out here that when I was writing the review above I had been completely unaware of how long ago the book was written; the book is pretty self-contained and I hadn’t really noticed when I picked up the book that it’s actually a rather old book. If I had been aware of this I would not have been nearly as vocal in my criticism of the content of the last chapter in my review as was the case, given that some of the insights I blame the author for being unaware of were only discussed in the literature after the publication of this book; the unaddressed problems do remain unaddressed and they are problematic, but it’s probably unfair to blame the author for not thinking about stuff which probably nobody really had given any thought at the time of publication.

In the post below I’ll talk a little bit about the book and add some more quotes. It probably makes sense to start out by giving a brief outline of the problems encountered in the three settings mentioned above. The basic problem encountered in prisoner’s dilemma-type situations is that unilateral defection is an attractive proposition, but if everybody yields to this temptation and defect then that will lead to a bad outcome. The problem faced is thus to figure out some way to make sure that defection is not an attractive option. In the co-ordination setting, there are several mutually beneficial states, none of which are strictly preferred to the others; that is, there is a coincidence of interests among the parties involved. The problem is that it’s difficult to come to an an explicit agreement as to which of the states to aim for. An example could be whether to drive in the right side of the road or the left side of the road. It probably doesn’t really matter much which side of the road you’re driving on, as long as you’re driving in the same side of the road as the other drivers do. The coincidence of interests here need not be perfect; one person might slightly prefer to drive in the right side of the road, all else equal, but even so it’ll be in his or her interest to drive in the same side of the road as do the other drivers; there’s no incentive for unilateral defection, and the main problem is figuring out how to achieve the outcome where behaviour is coordinated so that one of the available equilibria is reached. In the third setting, there’s some inequality present and one party is at an advantage; the problem here is how to maintain this advantageous position and how to fortify it so that it’s stable.

Some quotes and a few more comments:

“[One] angle from which it may be illuminating to view the account of norms offered here is that of evolutionary explanations. […] I propose to regard the argument underlying this book as, in a borrowed and somewhat metaphorical sense, a natural selection theory of the development of norms.”

“Norms do not as a rule come into existence at a definite point in time, nor are they the result of a manageable number of identifiable acts. The are, rather, the resultant of complex patterns of behaviour of a large number of people over a protracted period of time.”

“it is proposed that the main elements in the characterization of norms of obligation be: a significant social pressure for conformity to them and against deviation – actual or potential – from them; the belief by the people concerned in their indispensability for the proper functioning of society; and the expected clashes between their dictates on the one hand and personal interests and desires on the other.”

It should be noted here that far from all norms qualify as norms of obligation; this is but one norm subgroup, though it’s an important one. The author notes explicitly that norms encountered in the context of coordination problems are not norms of obligation.

“A situation of the generalized PD variety poses a problem to the participants involved. The problem is that of protecting an unstable yet jointly beneficial state of affairs from deteriorating, so to speak, into a stable yet jointly destructive one. My contention concerning such a situation is that a norm, backed by appropriate sanctions, could solve this problem. In this sense it can be said that such situations ‘call for’ norms. It can further be said that a norm solving the problem inherent in a situation of this type is generated by it. Such norms I shall call PD norms. […] the smaller and the more determinate the class of participants in a generalized PD-structured situation, and the more isolated the occurrence of the dilemma among them, the more likely it is that there might be solutions other than (PD) norms to the pertinent problem […] And conversely, the larger and the more indeterminate the class of participants, and the more frequent the occurrence of the dilemma among them, the more likely it is that a solution, if any, would be in the form of a PD norm. […] the more difficult (or costly) it is to ensure […] personal contact, […] the more acute the need for some impersonal device, such as social norms, which would induce the desired co-operation.”

You can easily add more details to the conceptual framework underlying the analysis in order to refine it in various ways, and the author does talk a little bit about how you might go about doing that; for example it might not be realistic that nobody ever deviates, and so you might decide to replace an unrealistic stability condition that nobody deviates with another one which might be that at most some percentage, say X, of the population deviates. Such refined theoretical models can incidentally yield very interesting and non-trivial theoretical results – Boyd and Richerson cover such models in The Origin and Evolution of Cultures. It should perhaps be noted that even relatively simple models dealing with these sorts of topics may easily end up nevertheless being sufficiently complicated for analytical solutions to not be forthcoming.

“there are norms whose function is to maintain social control on certain groups of people through preventing them from solving the problem inherent in the PD-structured situation in which they are placed. That is, these norms are designed to help keep these people in a state of affairs which, while disadvantageous to them […] is considered beneficial to society as a whole. A conspicuous example of norms of this type are anti-trust laws.”

In the context of coordination problems, the author distinguishes between two solution mechanisms/norms; conventions and decrees. Broadly speaking conventions can be thought of as established solutions to coordination problems encountered in the past, whereas decrees are solutions to novel problems where no equilibrium has yet been established – see also the more detailed quotes below. In the context of sanctions an important difference between coordination norms and PD norms is that sanctions can be said to play a primary role in the context of PD norms but only a secondary role in the context of coordination norms; nobody has a unilateral incentive to deviate in the context of coordination-type situations/problems and so defection so to speak carries its own punishment independent of the potential level of an associated sanction. If everybody else drive in the right side of the road, you don’t gain anything from driving in the left side of the road – and it’s unlikely to be the size of the fine which is the primary reason why you don’t drive in the left side of the road in such a context.

“It is worth noting that within the large class of problems of strategy (i.e. problems of interdependent decision), the problems of co-ordination stand in opposition to problems of conflict, the contrast being particularly acute between the extreme cases of pure co-ordination on the one hand and of pure conflict (the so-called zero-sum problems) on the other. Whereas in the pure co-ordination case the parties’ interests converge completely, and the agents win or lose together, in the pure conflict case the parties’ interests diverge completely, and one person’s gain is the other’s loss. […] [Shelling argues] that games of strategy range over a continuum with games of pure conflict […] and games of pure co-ordination as opposite limits. All other games […] involve mixtures in varying proportions of conflict and co-ordination, of competition and partnership, and are referred to as mixed-motive games.”

One thing to add here, which is of course not mentioned in the book, is that whereas the situation does play a sometimes major role in terms of which setting you find yourself in, there’s also a relevant mental/psychological aspect to consider here; in the context of bargaining, it’s a very well-established result that bargainers who conceive of the bargaining situation as a zero-sum (‘conflict’) game do worse than bargainers who do not.

“Very generally, where communities which have their own ways of going about things – their own arrangements, regularities, conventions – come into contact, and where the situation demands that barriers between them be dropped, or that one – any one – of them absorb the other, various co-ordination problems are likely to crop up and to call for […] decree-type co-ordination norms to solve them.”

“Conventions are, typically:

(1) Non-statutory norms, which need not be enacted, formulated, or promulgated.
(2) They are neither issued nor promulgated by any identifiable authority, and are hence what is usually called impersonal, or anonymous norms.
(3) They involve in the main non-institutionalized, non-organized, and informal sanctions (i.e. punishments or rewards).

Decrees, in contrast, are, typically:
(1) Statutory;
(2) Issued and promulgated by some appropriately endowed authority (not necessarily at the level of the state);
(3) The sanctions they involve might be organized, institutionalized, and formal, even physical.”

Conventions and decrees are quite different, but in terms of what they do they solve similar problems:

“Since a co-ordination problem is a situation such that any of its co-ordination equilibria is preferred, by all involved, to any combination of actions which is not a co-ordination equlibrium, each of those involved is interested in there being something which will point – in a way conspicuous to all and perceived to be conspicuous to all – to one particular co-ordination equilibrum as the solution. This precisely is what our co-ordination norms, whether conventions or decrees, do.”

“Thibaut and Kelley note that norms ‘will develop more rapidly and more surely in highly cohesive groups than in less cohesive groups’ – assuming that the majority of the members have about the same degree of dependence on the group […] To the extent that norms reduce interference, cut communication costs, heighten value similarity and insure the interaction sequence necessary for task performance, norms improve the reward-cost positions attained by the members of a dyad and thus increase the cohesiveness of the dyad”

“[I]n so far as conformity to a co-ordination norm ensures the achievement of some co-ordination equilibrium, which for everyone involved in the corresponding co-ordination problem belongs of necessity to the group of preferred outcomes, it is rational for everyone to conform to it. Are we to conclude from this, however, that the social choice to which the co-ordination norm is instrumental is itself rational? My answer to this question is that although it is rational to conform to a prevailing co-ordination norm, the social choice resulting from it is not necessarily rational. […] it may not be optimal, for some or for all involved. It can in principle be changed into a better one, only this involves an explicit process which is not always feasible. […] The changing of an existing convention in favour of a ‘better’, more rational one, has to be explicit. It can be achieved through an explicit agreement of all concerned, or through a regulation (decree) issued and properly promulgated by some appropriately endowed authority. Where communication, or promulgation, is impossible, it is difficult to see how an existing convention (which is a co-ordination norm) might be changed. It is of some interest to note that whereas an ‘act of convening’ is not necessary for a convention to form, it might be necessary for an existing convention to be exchanged for an alternative one.”

“The difference in the role played by the two types of norms might now be formulated thus: a co-ordination norm helps those involved ‘meet’ each other; a PD norm helps those involved protect themselves from damaging, even ruining, each other.”

“[T]here are states of inequality which appear on the surface to be stable but which are, in a somewhat subtle and complicated way, strategically unstable. They may be in equilibrium, but it is a rather flimsy one; far from being self-perpetuating, they are susceptible to threats. Now the assumption that the party discriminated in favour of is interested in the preservation of such a status quo leads reasonably to the assumption that he will seek to fortify it against its potential undermining. […] it is the central thesis of this chapter that [a] significant device to render the status quo stable [is] to fortify it by norms. The idea is that once it is in some sense normatively required that the status quo endure, the nature of the possible calculations and considerations of deviance fundamentally changes: it is no longer evaluated only in terms of being ‘costly’ or ‘risky’, but as being ‘wrong‘ or ‘subversive‘. […] the methods of norms and force as possible fortifiers of the status quo in question are functionally equivalent […] provided the norms are effective, they both amount to making deviance from the status quo more costly through the impositions of sanctions.”

“Once norms are internalized, one abides by them not out of fear of the pending sanctions associated with them, but out of some inner conviction. And when this is so, one is likely to conform to the norms even in one’s thoughts, intentions, and in what one does in private.”

“The function of norms, generally speaking, is to put restraints on possible courses of conduct, to restrict the number of alternatives open for action. When a certain course of conduct is normatively denounced (is considered ‘wrong’), it becomes a less eligible course of conduct than it might otherwise have been: although through lying, for example, one might quite conveniently get away with some misdeed, its being recognized and acknowledged as normatively (morally) prohibited normally makes it a less attractive way out, or even precludes its having been considered an alternative in the first place. In this sense, then, norms might be said to be coercive, to the extent that they function as constraints on actions; that is, to the extent that they prevent one for doing an ation one might have done had there been no norm denouncing it, or at least to the extent that they render a certain course of action less eligible than it might otherwise have been.”

“[N]orms are rather easily accepted as part of the ‘natural order of things’. To be sure, one might be quite resentful of this natural order, or of one’s lot therein, and regard it as discriminating against one. But usually there is very little one is going to do about it unless – and until – the object of one’s resentment is personified: only few will start a revolution against an elusive oppressive ‘system’; many more might revolt against an identifiable oppressive ruler. […] These norms have to apply to the privileged as well as to the deprived, or else they lose much of their effectiveness as a disguise for the real exercise of power underlying them. […] The absence of any precedents in which someone privileged was spared the sanction, the absence of any loopholes which might facilitate a discriminatory application of the norms, contribute to their deterrence value”.

February 13, 2016 Posted by | anthropology, books, Game theory, philosophy | Leave a comment

A few lectures

The sound quality of this lecture is not completely optimal – there’s a recurring echo popping up now and then which I found slightly annoying – but this should not keep you from watching the lecture. It’s a quite good lecture, and very accessible – I don’t really think you even need to know anything about genetics to follow most of what he’s talking about here; as far as I can tell it’s a lecture intended for people who don’t really know much about population genetics. He introduces key concepts as they are needed and he does not go much into the technical details which might cause people trouble (this of course also makes the lecture somewhat superficial, but you can’t get everything). If you’re the sort of person who wants details not included in the lecture you’re probably already reading e.g. Razib Khan (who incidentally recently blogged/criticized a not too dissimilar paper from the one discussed in the lecture, dealing with South Asia)…

I must admit that I actually didn’t like this lecture very much, but I figured I might as well include it in this post anyway.

I found some questions included and some aspects of the coverage a bit ‘too basic’ for my taste, but other people interested in chess reading along here may like Anna’s approach better; like Krause’s lecture I think it’s an accessible lecture, despite the fact that it actually covers many lines in quite a bit of detail. It’s a long lecture but I don’t think you necessarily need to watch all of it in one go (…or at all?) – the analysis of the second game, the Kortschnoj-Gheorghiu game, starts around 45 minutes in so that might for example be a good place to include a break, if a break is required.

February 1, 2016 Posted by | anthropology, archaeology, Chess, Computer science, genetics, history, Lectures | Leave a comment

Quotes

i. “to esteem every one is to esteem no one. […] the friend of all mankind is no friend of mine.” (Alceste, The Misanthrope, by Molière)

ii. “The art of not reading is a very important one. It consists in not taking an interest in whatever may be engaging the attention of the general public at any particular time. When some political or ecclesiastical pamphlet, or novel, or poem is making a great commotion, you should remember that he who writes for fools always finds a large public. A precondition for reading good books is not reading bad ones: for life is short.” (Schopenhauer)

iii. “people are never like what you remember them. You make them, as the years go by, more and more the way you wish them to be, and as you think you remember them. If you want to remember them as agreeable and gay and handsome, you make them far more so than they actually were.” (Poirot, in Agatha Christie’s Third Girl)

iv. “Youth is a failing only too easily outgrown.” (Agatha Christie, The Secret Adversary)

v. “There are faults which show heart and win hearts, while the virtue in which there is no love, repels.” (John Lancaster Spalding)

vi. “Solitude is unbearable for those who can not bear themselves.” (-ll-)

vii. “If we learn from those only, of whose lives and opinions we altogether approve, we shall have to turn from many of the highest and profoundest minds.” (-ll-)

viii. “The lover of education labors first of all to educate himself.” (-ll-)

ix. “The smaller the company, the larger the conversation.” (-ll-)

x. “What we acquire with joy, we possess with indifference.” (-ll-)

xi. “The innocence which is simply ignorance is not virtue.” (-ll-)

xii. “If our opinions rest upon solid ground, those who attack them do not make us angry, but themselves ridiculous.” (-ll-)

xiii. “(Respect)/(Required math) determines what academic field you should go into. Thus, economics is always a bad choice.” (Zach Weinersmith)

xiv. “there are important information effects of emotion. Emotions provide information about a situation that might be used in reasoning; it alters the way information provided in the reasoning statements is processed; and it influences what additional information may be activated during reasoning. […] emotional states are used strategically to orient reasoning strategies. For instance, sadness might indicate that there is a problem to be solved, and thus that a more careful, analytical mode of reasoning may be indicated. By contrast, positive moods signal that the individual is progressing towards their goals and that there is no urgent problem to solve; habitual, stereotypical ways of reasoning can thus be relied upon. […] anger seems to lead to more heuristic, less systematic processing […]. Similar effects have been observed for positive mood […] inducing positive or negative moods can be effective argumentative strategies to cover up weak arguments.” (Emotion and Reasoning, by Blanchette et al.).

xv. “People vary not only in the emotions they experience, but also in the degree to which they are aware of their own emotions, and emotional awareness influences the impact of emotions on beliefs. […] High emotional awareness has positive consequences when beliefs are adaptive. When the beliefs are maladaptive or destructive (the government is spying on me; I am worthless), high emotional awareness is linked to adverse consequences.” (-ll-)

xvi. “everyone knows they’re going to die, but no one really believes it.” (Spalding Gray)

xvii. “I guess this is why most maps of the solar system aren’t drawn to scale. It’s not hard to draw the planets. It’s the empty space that’s a problem. […] Most space charts leave out the most significant part – all the space.” (If the Moon Were Only 1 Pixel – A tediously accurate map of the solar system)

xviii. “There is no dress which embellishes the body more than science does the mind.” (Laurent Clerc)

xix. “It’s easier to hold to your principles 100% of the time than it is to hold to them 98% of the time.” (Clayton M. Christensen)

xx. “It would be a terrible mistake to go through life thinking that people are the sum total of what you see.” (Jonathan Tropper)

February 1, 2016 Posted by | books, quotes | Leave a comment

Eating disorders (II)

You can read my first post about the book, which lead to a brief comment exchange which may be of interest to people curious about diagnostics aspects, here. The book has a lot of stuff; in this post I’ll discuss the immune system, covered in chapter 5 of the book, as well as some ways that eating disorders may affect the skin (many of the remaining chapters of the book cover this topic). This will be my last post about the book.

In chapter 5 the authors start out by noting that adequate nutrition is an important factor in terms of maintaining immunocompetence and that malnutrition increases the risk of infection. Quite a few details are known about how specific aspects of nutritional deficiencies affect specific parts of the immune system. When both energy- and protein intake is insufficient (protein-energy malnutrition, PEM) this state of affairs is associated with atrophy of immune organs such as the thymus and spleen, as well as impairments in T cell populations (likely a natural consequence of thymus atrophy – the ‘T’ in ‘T cell’ stands for thymus…). Cytokine prodution (e.g. IL-1, IL-2, interferon-γ) is down-regulated in PEM, and the ability of T cells to respond appropriately to those cytokines is decreased. Impairments in macrophage phagocytotic function and neutrophils have been observed in malnourished individuals.

The authors note in the coverage that there now “seems to be consensus accepting that, overall, the manifestations of the immunocompromised status of ED patients are less frequent and severe than in PEM [3]. In general, the immune function seems to be better preserved than would be expected, considering the highly defective nutritional status of the patients. […] [some of] the most frequent findings described are leukopenia [white blood cell deficiency] with relative lymphocytosis [increased proportion of lymphocytes in the blood], [and] thrombocytopenia [platelet deficiency] […] immunocompetence and particularly T cell subsets are useful tools to follow-up the nutritional status in patients with ED. This asseveration applies also to BN patients, since T cell subsets seem to reflect their subclinical malnutrition, which is not evident from their weight status. […] Vomiting as a purging strategy is associated with a more deleterious effect on T cells […] Complement-system proteins […] have been found decreased in AN [anorexia nervosa] and BN [bulimia nervosa] [6,79] [and] seem to depend also on white adipose tissue mass. […] These proteins might be useful in the follow-up of AN patients, since C3 and C4 falls seem to occur when treated patients resume their restricting habits increasing their risk of relapse [81].”

Despite eating disorders having significant effects on the immune system, infection risk in people with eating disorders seems surprisingly to not be elevated, at least not until an advanced stage of the disease has been reached. There are multiple explanations offered for this observation, but the answer as to why this is is not completely clear. One reason might be that people with eating disorders tend to maintain relatively high protein and vitamin intake in a manner dissimilar from the intake patterns associated with classic starvation, mediating the effects of energy deficiency. Two other reasons offered both relate to the fact that the immune system does not respond normally to pathogens, and so to the extent that symptoms relate to immune responses to infection people with eating disorders have fewer symptoms; this relates to both down-regulation of memory T-cells and suppressed capacity to mount the classic acute-phase response to infection; a reduced febrile response to bacterial infection has been observed in anorexics. In the context of muted responses to infection, the hormone leptin (‘the satiety hormone’) may also be implicated; “there is a function for leptin as an up-regulator factor of inflammatory immune responses. Moreover, leptin production is acutely increased during infection and inflammation […] an impairment in this acute increase in leptin production in AN patients might be related to the lack of infection symptoms in these patients [26].” Interestingly leptin also seems to be downregulated in BN.

Okay, let’s move on and talk a little bit about how eating disorders may affect the skin. The book has a lot of stuff about this so this will not be an exhaustive review of the material covered in the book – but I did think I ought to talk a little bit about this stuff. Skin signs are important in a diagnostic context: “As most patients with eating disorders tend to minimize or even deny their disorder, the skin changes are sometimes the only indication that the patient has an eating disorder.” Some of the skin signs described in the book relate quite directly to specific behaviours (e.g. vomiting in purging subtypes), whereas others are of a more generalized nature and are rather due to the fact that the body does not get enough energy/micronutrients/etc. to handle all the tasks it’s supposed to handle. Some skin signs are considered ‘guiding signs’ of eating disorders, in the sense that they’re signs often found in an eating disorder context but are not usually found in the differential diagnoses natural to consider in the given clinical context, so they can be used as guiding tools in a diagnostic context. Examples of guiding signs include “lanugo-like body hair [very fine, soft, and usually unpigmented, downy hair] due to starvation, Russell’s sign [calluses on the knuckles or back of the hand] and [tooth] enamel erosions due to self-induced vomiting, and self-induced dermatoses due to psychiatric comorbidity.”

Frequent skin signs in eating disorders include dry, scaly skin; orange discolouration of the skin due to excessive consumption of beta carotene (carrots); the aforementioned lanugo-like body hair; coldness of the extremities (feet, toes) and bluish/purplish colouring of the hands and feet, caused by slow circulation (acrocyanosis); hair loss; inflammation of the lips and nail changes. “With a BMI between 17.5 and 16, the skin is usually pale or yellowish and cold, but no specific signs are found.” They note in the book that “Russell sign, dental enamel erosion, and salivary gland enlargement [elsewhere in the coverage they also dub this phenomenon ‘“chipmunk” cheeks of the bulimic’] are pathognomonic of purging behavior”. Dry skin is reported in 70% of people with anorexia nervosa (-AN), and acne is reported in 47–59% of patients – these are very common symptoms/consequences of AN. The same is the case for lanugo; in one study of AN patients (n=62), 77% had lanugo. In one study, alopecia was present in 67% of bulimics (n=122) and 61% of anorexics (n=62).

Observing the hands may be important: “Strumia [1], observing the hand of the patients with anorexia nervosa (AN), noticed that many peculiar skin signs, such as xerosis, acrocyanosis, carotenoderma, evident blood vessels due to decreased subcutaneous tissue, cold hand, nail dystrophy [“Brittle nails affect approximately 30% of patients with anorexia nervosa and bulimia nervosa”], Russell’s sign and artefacta, were located on the hands. Strumia used the term “anorectic’s hand” and suggested that, by examining the hand of a young patient, one can reasonably suspect an eating disorder. Only Russell’s sign is pathognomonic of eating disorders, but at least three signs, excluding Russell’s sign, are required for the diagnosis of “anorectic’s hand”, for example, xerosis, carotenoderma and cold hand. A perspicacious dermatologist should pay attention to this important sign when it appears in young females that show signs of reduced self-esteem and distorted perception of body weight.”

It is noted in the book that classical deficiency syndromes such as scurvy are very rare in AN because “AN is not commonly associated with vitamin deficiencies” – rather it’s the case that many anorectics over-supplement on vitamin supplements, which can paradoxically induce or worsen some skin complaints, such as e.g. xerosis (dry skin).

“the progression of anorexic pathology is accompanied by changing patterns in dietary habits [5]. These patterns include periods of low or no carbohydrate intake and an avoidance of dietary fats. They can also include patterns in which the primary foods consumed are fruits and vegetables. During this period, meat is often avoided. Changes in relative amounts of heavy to light isotopes [of nitrogen] in the hair indicate changes in the body’s metabolic state and dietary intake. […] By definition, individuals with anorexia or anorexia and bulimia are losing weight and do not get adequate nutrition. These individuals get their nitrogen largely from plants, and/or do not get sufficient nitrogen in their diet and are in nitrogen imbalance. By contrast, individuals diagnosed with only bulimia are maintaining their weight, and therefore get adequate nutrition and are likely not to be in nitrogen imbalance. […] Hatch et al. […] suggest that a distinction may be possible between anorexia and bulimia nervosa using 15N/14N and 13C/12C ratios in hair.”

“A reduced pain sensitivity has been found in eating disorder (ED) patients, but it is unclear what physiological and psychological factors are associated with this abnormality.”

January 26, 2016 Posted by | books, medicine | Leave a comment

Prioritization in medicine

This book is not exactly the first book I’ve read on these kinds of topics (see for example my previous coverage of related topics here, here, here, here, here, and here), but the book did have some new stuff and I decided in the end that it was worth blogging, despite the fact that I did not think the book was particularly great. The book is slightly different from previous books I’ve read on related topics because normative aspects are covered in much greater detail – as they put it in the preface:

“This volume addresses normative dimensions of methodological and theoretical approaches, international experiences concerning the normative framework and the process of priority setting as well as the legal basis behind priorities. It also examines specific criteria for prioritization and discusses economic evaluation. […] Prioritization is necessary and inevitable – not only for reasons of resource scarcity, which might become worse in the next few years. But especially in view of an optimization of the supply structures, prioritization is an essential issue that will contribute to the capability and stability of healthcare systems. Therefore, our volume may give useful impulses to face challenges of appropriate prioritization.”

I’m generally not particularly interested in normative questions, preferring instead to focus on the empirical side of things, but the book did have some data as well. In the post I’ll focus on topics I found interesting, and I have made no attempt here to make the coverage representative of the sort of topics actually covered in the book; this is (as usual) a somewhat biased account of the material covered.

The book observes early and often that there’s no way around prioritization in medicine; you can’t not prioritize, because “By giving priority to one group, you ration care to the second group.” Every time you spend a dollar on cancer treatment, well, that’s a dollar you can’t spend on heart disease. So the key question in this context is how best to prioritize, rather than whether you should do it. It is noted in the text that there is a wide consensus that approaching and handling health care allocation rules explicitly is preferable to implicit rationing, a point I believe was also made in Glied and Smith. A strong argument can be made that clear and well-defined decision-rules will lead to better outcomes than implicit allocation decisions made by doctors during their day-to-day workload. The risks of leaving allocation decisions to physicians involve overtaxing medical practitioners (they are implicitly required to repeatedly take decisions which may be emotionally very taxing), problematic and unfair distribution patters of care, and there’s also a risk that such practices may erode trust between patients and physicians.

A point related to the fact that any prioritization decision made within the medical sector, regardless of whether the decision is made implicitly or explicitly, will necessarily affect all patient populations by virtue of the fact that resources used for one purpose cannot be used for another purpose, is that the health care sector is not the only sector in the economy; when you spend money on medicine that’s also money you can’t be spending on housing or education: “The competition between health-related resources and other goods is generally left to a political process. The fact that a societal budget for meeting health needs is the result of such a political process means that in all societies, some method of resolving disagreements about priorities is needed.” Different countries have different approaches to how to resolve these disagreements (and in large countries in particular, lower-level regional differences may also be important in terms of realized care provision allocation decisions), and the book covers systems applied in multiple different countries, including England, Germany, Norway, Sweden, and the US state of Oregon.

Some observations and comments:

“A well-known unfairness objection against conventional cost-effectiveness analysis is the severity of diseases objection – the objection that the approach is blind as to whether the QALYs go to severely or to slightly ill patients. Another is the objection of disability discrimination – the objection that the approach is not blind between treating a life-threatening disease when it befalls a disabled patient and treating the same disease when it befalls a non-disabled patient. An ad hoc amendment for fairness problems like these is equity weighting. Equity weights are multiplication factors that are introduced in order to make some patient group’s QALYs count more than others.”

“There were an estimated 3 million people with diabetes in England in 2009; estimates suggest that the number of people with diabetes could rise to 4.6 million by 2030. There has also been a rapid rise in gastrointestinal diseases, particularly chronic liver disease where the under-65 mortality rate has increased 5-fold since 1970. Liver disease is strongly linked to the harmful use of alcohol and rising levels of obesity. […] the poorest members of the community are at most risk of neglecting their health. This group is more likely to eat, drink and smoke to excess and fail to take sufficient exercise.22 Accordingly, life expectancy in this community is shorter and the years spent of suffering from disability are much longer. […] Generic policies are effective in the sense that aggregate levels of health status improve and overall levels of morbidity and mortality fall. However, they are ineffective in reducing health inequalities; indeed, they may make them worse. The reason is that better-off groups respond more readily to public health campaigns. […] If policy-makers [on the other hand] disinvest from the majority to narrow the inequality gap with a minority resistant to change, this could reduce aggregate levels of health status in the community as a whole. [Health behaviours also incidentally tend to be quite resistant to change in general, and we really don’t know all that much about which sort of interventions work and/or how well they work – see also Thirlaway & Upton’s coverage] […] two out of three adults [in the UK] are overweight or obese; and inequalities in health remain widespread, with people in the poorest areas living on average 7 years fewer than those in the richest areas, and spending up to 17 more years living with poor health. […] the proportion of the total health budget invested in preventive medicine and health promotion […] is small. The UK spends about 3.6 % of its entire healthcare budget on public health projects of this nature (which is more than many other EU member states).”

Let’s talk a little bit about rationing. Rationing by delay (waiting lists) is a well-known method of limiting care, but it’s far from the only way to implicitly ration care in a manner which may be hidden from view; another way to limit care provision is to ration by dilution. This may happen when patients are seen on time (do recall that waiting lists are very common in the medical sector, for very natural reasons which I’ve discussed here on the blog before), but the quality of care that is provided to patients receiving care goes down. Rationing by dilution may sometimes be a result of attempts to limit rationing by delay; if you measure hospitals on whether or not they treat people within a given amount of time, the time dimension becomes very important in the treatment context and it may thus end up dominating other decision variables which should ideally take precedence over this variable in the specific clinical context. The book mentions as an example the Bristol Eye Hospital, where it is thought that 25 patients may have lost their sights because even though they were urgent cases which should have been high priority, they were not treated in time because there was a great institutional focus on not allowing waiting times of any patients on the waiting lists to cross the allowed maximum waiting time, meaning that much less urgent cases were treated instead of the urgent cases in order to make the numbers look good. A(n excessive?) focus on waiting lists may thus limit focus on patient needs, and similar problems pop up when other goals aside from patient needs are emphasized in an institutional context; hospital reorganisations undertaken in order to improve financial efficiency may also result in lower standards of care, and in the book multiple examples of this having happened in a British context are discussed. The chapter in question does not discuss this aspect, but it seems to me likely that rationing by dilution, or at least something quite similar to this, may also happen in the context of a rapid increase in capacity as a result of an attempt to address long waiting lists; if you for example decide to temporarily take on a lot of new and inexperienced nurses to lower the waiting list, these new nurses may not provide the same level of care as do the experienced nurses already present. A similar dynamic may probably be observed in a setting where the number of nurses does not change, but each patient is allocated less time with any given nurse than was previously the case.

“Public preferences have been shown not to align with QALY maximization (or health benefit maximization) across a variety of contexts […] and considerations affecting these preferences often extend well beyond strict utilitarian concerns […] age has been shown to be among the most frequently cited variables affecting the public’s prioritization decisions […] Most people are willing to use age as a criterion at least in some circumstances and at least in some ways. This is shown by empirical studies of public views on priority setting […] most studies suggest that a majority accepts that age can have some role in priority setting. […] Oliver [(2009)] found […] a wide range of context-dependent ‘decision rules’ emerged across the decision tasks that appeared to be dependent on the scenario presented. Respondents referenced reasons including maximizing QALYs,11 maximizing life-years or post-treatment quality of life,12 providing equal access to health care, maximizing health based on perceptions of adaptation, maximizing societal productivity (including familial roles, i.e. ‘productivity ageism’), minimizing suffering, minimizing costs, and distributing available resources equitably. As an illustration of its variability, he noted that 46 of the 50 respondents were inconsistent in their reasoning across the questions. Oliver commented that underlying values influence the respondents’ decisions, but if these values are context dependent, it becomes a challenge – if not impossible – to identify a preferred, overarching rule by which to distribute resources. […] Given the empirical observations that respondents do not seem to rely upon a consistent decision rule that is independent of the prioritization context, some have suggested that deliberative judgments be used to incorporate equity considerations […]. This means that decision makers may call upon a host of different ‘rules’ to set priorities depending on the context. When the patients are of similar ages, prioritization by severity may offer a morally justifiable solution, for example. In contrast, as the age discrepancy becomes greater between the two patients, there may be a point at which ‘the priority view’ (i.e. those who in the most dire conditions take precedence) no longer holds […] There is some evidence that indicates that public preferences do not support giving priority in instances where the intervention has a poor prognosis […] If older patients have poorer health outcomes as a result of certain interventions, [this] finding might imply that in these instances, they should receive lower priority or not be eligible for certain care. […] A substantial body of evidence indicates that the utilitarian approach of QALY maximization fails to adequately capture public preferences for a greater degree of equity into health-care distribution; however, how to go about incorporating these concerns remains unresolved.”

“roughly 35 % of the […] [UK] health expenditures were spent on the 13 % of our population over the age of 65. A similar statistic holds true for the European Union as well […] the elderly, on average, have many more health needs than the non-elderly. In the United States, 23 % of the elderly have five or more chronic health problems, some life-threatening, some quality-of-life diminishing (Thorpe et al. 2010). Despite this statistic, the majority of the elderly in any given year is quite healthy and makes minimal use of the health care system. Health needs tend to be concentrated. The sickest 5 % of the Medicare population consume 39 % of total Medicare expenditures, and the sickest 10 % consume 58 % of Medicare expenditures (Schoenman 2012). […] we are […] faced with the problem of where to draw the line with regard to a very large range of health deficiencies associated with advanced age. It used to be the case in the 1970s that neither dialysis nor kidney transplantation were offered as an option to patients in end-stage kidney failure who were beyond age 65 because it was believed they were not medically suitable. That is, both procedures were judged to be too burdensome for individuals who already had diminished health status. But some centers started dialyzing older patients with good results, and consequently, the fastest growing segment of the dialysis population today (2015) is over age 75. This phenomenon has now been generalized across many areas of surgery and medicine. […] What [many new] procedures have in common is that they are very expensive: $70,000 for coronary bypass surgery (though usually much more costly due to complication rates among the hyper-elderly); $200,000 for the LVAD [Left Ventricular Assist Device]; $100,000+ per month for prolonged mechanical ventilation. […] The average older recipient of an LVAD will gain one to two extra years of life […] there are now (2015) about 5.5 million Americans in various stages of heart failure and 550,000 new cases annually. Versions of the LVAD are still being improved, but the potential is that 200,000 of these devices could be implanted annually in the United States. That would add at least $40 billion per year to the cost of the Medicare program.”

“In the USA, around 40 % of premature mortality is attributed to behavioral patterns,2 and it is estimate[d] that around $1.3 trillion annually — around a third of the total health budget — is spent on preventable diseases.3 […] among the ten leading risk factors contributing to the burden of disease in high-income countries, seven can be directly attributed to unhealthy lifestyles. […] Private health insurance takes such factors into account when calculating premiums for health insurances (Olsen 2009). In contrast, publicly funded health-care systems are mainly based on the so-called solidarity principle, which generally excludes risk-based premiums. However, in some countries, several incentive schemes such as “fat taxes” […], bonuses, or reductions of premiums […] have recently been implemented in order to incorporate aspects of personal responsibility in public health-care systems. […] [An important point in this context is that] there are fundamental questions about whether […] better health leads to lower cost. Among other things, cost reductions are highly dependent on the period of time that one considers. What services are covered by a health system, and how its financing is managed, also matters. Regarding the relative lifetime cost of smokers, obese, and healthy people (never smokers, normal body mass index [BMI]) in the Netherlands, it has been suggested that the latter, and not the former two groups, are most costly — chiefly due to longer life and higher cost of care at the end of life.44 Other research suggests that incentivizing disease management programs rather than broader prevention programs is far more effective.45 Cost savings can therefore not be taken for granted but require consideration of the condition being incentivized, the organizational specifics of the health system, and, in particular, the time horizon over which possible savings are assessed. […] Policies seeking to promote personal responsibility for health can be structured in a very wide variety of ways, with a range of different consequences. In the best case, the stars are aligned and programs empower people’s health literacy and agency, reduce overall healthcare spending, alleviate resource allocation dilemmas, and lead to healthier and more productive workforces. But the devil is often in the detail: A focus on controlling or reducing cost can also lead to an inequitable distribution of benefits from incentive programs and penalize people for health risk factors that are beyond their control.”

January 21, 2016 Posted by | books, economics, medicine | Leave a comment

Oxford Handbook of Clinical Medicine (IV)

Here you can read my first three posts about the book. In this post I’ll talk a little bit about the book’s coverage of surgery; this is a major chapter with a lot of content.

In a surgical context prophylactic antibiotics are very often given to counter the risk of wound infection, especially in the gastrointestinal surgical context. The authors of the chapter don’t discuss the demerits of this approach at all, but I’ve read other people before who are critical of this way of doing things and before moving on to what the book has to say about related matters I thought I should remind you of some of the problems associated with the widespread prophylactic use of antibiotics in the surgical context – here’s part of what Gould and van der Meer had to say about this topic:

“Surgical prophylaxis is a common area of overuse [of antibiotics] as shown in many publications. Measured by total DDDs [defined daily doses], it can amount to around one third of a hospital’s total antibiotic use. This illustrates the potential for ecological damage although surgeons often ask whether 24 h or even single dose prophylaxis can really select for resistance. The simple answer is yes, but of course much of the problem is extension of prophylaxis beyond the perioperative period, often for several days in critical patients, perhaps until all lines and drains are removed. There is no evidence base in favour of such practices.” (link to further blog coverage of related topics here)

Omissions like these is incidentally one of several reasons why I did not give the Oxford handbook a higher rating than I did. With that out of the way let’s get back to the Oxford handbook coverage. They note in the surgery chapter that wound infection occurs in roughly one in five cases of elective GI surgery, and in up to 60 per cent of emergency surgery settings. Infections in surgical patients are not trivial events; they can lead to bleeding, wounds that reopen, and they can ultimately kill the patient. Another major risk associated with surgery in many different surgical contexts is the risk of deep vein thrombosis (-DVT). According to the book DVTs occur in 25-50% of surgical patients. That said, almost two-thirds of below-knee DVTs are asymptomatic and these rarely embolize to the lungs. Aside from surgery some other DVT risk factors worth knowing about include age (older patients are at higher risk), pregnancy, trauma, synthetic oestrogen (i.e., oral contraceptives), past DVT, cancer, obesity, and immobility.

As for DVTs in non-surgical contexts, I found it interesting that the book observes that “the evidence linking air travel to an increased risk of DVT is still largely circumstantial” – it also adds some additional data to contextualize the risk. For someone in the general population, the risk of DVT from a long-distance flight is estimated to be somewhere between one in 10.000 to one in 40.000, however for people in high-risk subgroups the incidence of DVT from flights lasting longer than 10 hours has been estimated at 4-6%. They argue in the book that travelers with multiple risk factors should consider compression stockings and/or a single prophylactic dose of low molecular-weight heparin for flights lasting longer than 6 hours; other ways to minimize risk include leg exercises, increased water intake and refraining from alcohol or caffeine during the flight. “There is no evidence to support the use of prophylactic aspirin.”

Even though I think a common impression is that surgeons always want to cut people open whereas internal medicine people will often think this is not necessary, ‘even surgeons’ are sometimes hesitant to cut you open. There are many reasons for this – the book covers a lot of surgical complications, but a perhaps particularly important long-term problem is this:
“Any surgical procedure that breaches the abdominal or pelvic cavities can predispose to the formation of adhesions [‘Adhesions are fibrous bands[1] that form between tissues and organs, often as a result of injury during surgery. They may be thought of as internal scar tissue that connects tissues not normally connected’], which are found in up to 90% of those with previous abdominal surgery; this is why we do not rush to operate on small bowel obstruction: the operation predisposes to yet more adhesions. Handling of the serosal surface of the bowel causes inflammation, which over weeks to years can lead to the formation of fibrous bands that tether the bowel to itself or adjacent structures […] Their main sequelae are intestinal obstruction (the cause in ~60% of cases […]) and chronic abdominal or pelvic pain.”

Appendicitis is a lot more common than I’d thought; lifetime incidence is 6%, with risk peaking during the second decade of life; according to the book it is the most common surgical emergency. A diagnosis of appendicitis is often wrong; in up to one in five patients a healthy appendix is removed. Another very common surgical procedure is surgical repair of an inguinal hernia; more than 100.000 of these surgeries are performed in the UK each year.

Though the book has a separate chapter specifically dealing with the topic of oncology (and palliative care), the surgical chapter of course also covers various cancers and their treatments. You’ll encounter the usual encouraging remarks about diseases with a ‘gloomy prognosis and non-specific presentation’, ‘[m]ost patients […] present with locally advanced (inoperable) or metastatic disease’ (both quotes are on the topic of carcinoma of the stomach); ‘[s]urvival rates are poor with or without treatment’ (carcinoma of the oesophagus); ‘rare, have an overall poor prognosis and are difficult to diagnose’ (bile duct and gallbladder cancers), ‘~80% present with inoperable disease’ (bile duct cancer). It’s sort of hard to find it encouraging that colorectal carcinoma, another cancer covered in that chapter, in general tend to have lower mortality than these others (“Overall 5yr survival is ~50%”) when you also keep in mind that it’s one of the most common cancers (it is the second most common cause of cancer deaths in the United Kingdom, and the third most common cancer), and so kill a lot more people overall (16.000 deaths/year). Another thing to note is that the survival rate of patients with metastatic disease in this context is still really terrible; the treated 5-year survival rate for patients with distant metastases is reported to be 6.6%, compared to e.g. a 48% survival rate in treated cases with ‘only’ regional lymph node involvement. They observe in their coverage that “[l]aparoscopic surgery has revolutionized surgery for colon cancer. It is as safe as open surgery and there is no difference in overall survival or disease recurrence.”

There are many bodily changes which take place in people as they age, and some of the potentially problematic changes only occasionally cause symptoms despite their presence in a large number of people. One example is gastrointestinal diverticula. These are outpouchings of the gut wall which are present in many people but do not always cause problems. According to the authors, diverticulosis is a term used to indicate that diverticula are present, whereas diverticular disease implies they the diverticula are symptomatic; the term diverticulitis is used when there’s inflammation of the diverticula. 30 % of people at the age of 60 living in the West are estimated to have diverticulosis, but the majority are asymptomatic – they are a common incidental finding when people have colonoscopies. Although they often do not cause problems they can cause perforation and hemorrhage (e.g. large rectal bleeds); the former complication has a high mortality, ~40%. Lack of dietary fiber is thought to be implicated in the pathophysiological processes leading to diverticulosis. Gallstones is another example of a common condition many people have without knowing it; gallstone prevalence is estimated at 8% at the age of 40. Risk is increasing in age and is higher in obese people. 90% remain asymptomatic. Smoking is known to increase the risk that gallstones become symptomatic. Renal stones are also common, with lifetime incidence estimated to be ‘up to’ (?) 15%. However males are three times as likely to get renal stones as are females, so in males in particular these things are very common. In the case of small stones (<5mm in lower ureter) ~90-95 % pass spontaneously on their own. The simplest and easiest way to lower risk of kidney stones is to drink plenty of fluids (but keep in mind that tea increases oxalate levels and thus may contribute to stone formation…). They note that calculi may be asymptomatic but do not provide estimates of how often this is the case; I assume one reason is that it’s really very difficult to get a good estimate of how often people pass stones they did not know they had – you mostly learn about these things when they cause trouble. Making a brief jump back to the topic of cancers it should perhaps be noted that although cancer is not usually thought of as a really not very worrisome asymptomatic condition, some forms of cancer actually sometimes may be just that; autopsy studies have indicated that 80% of men above the age of 80 have some form of prostate cancer.

Stress incontinence is leakage from an incompetent sphincter for example when intra-abdominal pressure rises, which it may do when people laugh or cough. It is very common in pregnancy and following birth, and it “occurs to some degree in ~50% of post-menopausal women”.

Although I didn’t think much of the epidemiology chapter, I did want to include a few observations from the chapter in this post:

“In one study looking at recommendations of meta-analyses where there was a later ‘definitive’ big trial, it turned out that meta-analyses got it wrong 30% of the time”.

“During the time it takes you to read this page, your better-connected patients may have checked out the latest recommendations of Guatemalan Guidelines on Gynaecomastia, or the NICE’S Treatise on Toxoplasmosis. Patients have time and motivation, whereas we have little time and our motivation may be flickering. This can seem threatening to the doctor who sees himself as a dispenser of wisdom and precious remedies. It is less threatening if we consider ourselves to be in partnership with our patients. The evidence is that those who use the internet to question their therapy receive a better service.” (A lot of related topics were incidentally covered in the Cochrane handbook The Knowledgeable Patient: Communication and Participation in Health – see this post for data on and discussion of these things).

 

January 18, 2016 Posted by | books, medicine | Leave a comment

Quotes

i. “The combination of some data and an aching desire for an answer does not ensure that a reasonable answer can be extracted from a given body of data.” (John Tukey)

ii. “Far better an approximate answer to the right question, which is often vague, than an exact answer to the wrong question, which can always be made precise.” (-ll-)

iii. “They who can no longer unlearn have lost the power to learn.” (John Lancaster Spalding)

iv. “If there are but few who interest thee, why shouldst thou be disappointed if but few find thee interesting?” (-ll-)

v. “Since the mass of mankind are too ignorant or too indolent to think seriously, if majorities are right it is by accident.” (-ll-)

vi. “As they are the bravest who require no witnesses to their deeds of daring, so they are the best who do right without thinking whether or not it shall be known.” (-ll-)

vii. “Perfection is beyond our reach, but they who earnestly strive to become perfect, acquire excellences and virtues of which the multitude have no conception.” (-ll-)

viii. “We are made ridiculous less by our defects than by the affectation of qualities which are not ours.” (-ll-)

ix. “If thy words are wise, they will not seem so to the foolish: if they are deep the shallow will not appreciate them. Think not highly of thyself, then, when thou art praised by many.” (-ll-)

x. “Since all models are wrong the scientist cannot obtain a “correct” one by excessive elaboration. On the contrary following William of Occam he should seek an economical description of natural phenomena. Just as the ability to devise simple but evocative models is the signature of the great scientist so overelaboration and overparameterization is often the mark of mediocrity. ” (George E. P. Box)

xi. “Intense ultraviolet (UV) radiation from the young Sun acted on the atmosphere to form small amounts of very many gases. Most of these dissolved easily in water, and fell out in rain, making Earth’s surface water rich in carbon compounds. […] the most important chemical of all may have been cyanide (HCN). It would have formed easily in the upper atmosphere from solar radiation and meteorite impact, then dissolved in raindrops. Today it is broken down almost at once by oxygen, but early in Earth’s history it built up at low concentrations in lakes and oceans. Cyanide is a basic building block for more complex organic molecules such as amino acids and nucleic acid bases. Life probably evolved in chemical conditions that would kill us instantly!” (Richard Cowen, History of Life, p.8)

xii. “Dinosaurs dominated land communities for 100 million years, and it was only after dinosaurs disappeared that mammals became dominant. It’s difficult to avoid the suspicion that dinosaurs were in some way competitively superior to mammals and confined them to small body size and ecological insignificance. […] Dinosaurs dominated many guilds in the Cretaceous, including that of large browsers. […] in terms of their reconstructed behavior […] dinosaurs should be compared not with living reptiles, but with living mammals and birds. […] By the end of the Cretaceous there were mammals with varied sets of genes but muted variation in morphology. […] All Mesozoic mammals were small. Mammals with small bodies can play only a limited number of ecological roles, mainly insectivores and omnivores. But when dinosaurs disappeared at the end of the Cretaceous, some of the Paleocene mammals quickly evolved to take over many of their ecological roles” (ibid., pp. 145, 154, 222, 227-228)

xiii. “To consult the statistician after an experiment is finished is often merely to ask him to conduct a post mortem examination. He can perhaps say what the experiment died of.” (Ronald Fisher)

xiv. “Ideas are incestuous.” (Howard Raiffa)

xv. “Game theory […] deals only with the way in which ultrasmart, all knowing people should behave in competitive situations, and has little to say to Mr. X as he confronts the morass of his problem. ” (-ll-)

xvi. “One of the principal objects of theoretical research is to find the point of view from which the subject appears in the greatest simplicity.” (Josiah Williard Gibbs)

xvii. “Nothing is as dangerous as an ignorant friend; a wise enemy is to be preferred.” (Jean de La Fontaine)

xviii. “Humility is a virtue all preach, none practice; and yet everybody is content to hear.” (John Selden)

xix. “Few men make themselves masters of the things they write or speak.” (-ll-)

xx. “Wise men say nothing in dangerous times.” (-ll-)

 

 

January 15, 2016 Posted by | biology, books, Paleontology, quotes, statistics | Leave a comment

A few lectures

Below are three new lectures from the Institute of Advanced Study. As far as I’ve gathered they’re all from an IAS symposium called ‘Lens of Computation on the Sciences’ – all three lecturers are computer scientists, but you don’t have to be a computer scientist to watch these lectures.

Should computer scientists and economists band together more and try to use the insights from one field to help solve problems in the other field? Roughgarden thinks so, and provides examples of how this might be done/has been done. Applications discussed in the lecture include traffic management and auction design. I’m not sure how much of this lecture is easy to follow for people who don’t know anything about either topic (i.e., computer science and economics), but I found it not too difficult to follow – it probably helped that I’ve actually done work on a few of the things he touches upon in the lecture, such as basic auction theory, the fixed point theorems and related proofs, basic queueing theory and basic discrete maths/graph theory. Either way there are certainly much more technical lectures than this one available at the IAS channel.

I don’t have Facebook and I’m not planning on ever getting a FB account, so I’m not really sure I care about the things this guy is trying to do, but the lecturer does touch upon some interesting topics in network theory. Not a great lecture in my opinion and occasionally I think the lecturer ‘drifts’ a bit, talking without saying very much, but it’s also not a terrible lecture. A few times I was really annoyed that you can’t see where he’s pointing that damn laser pointer, but this issue should not stop you from watching the video, especially not if you have an interest in analytical aspects of how to approach and make sense of ‘Big Data’.

I’ve noticed that Scott Alexander has said some nice things about Scott Aaronson a few times, but until now I’ve never actually read any of the latter guy’s stuff or watched any lectures by him. I agree with Scott (Alexander) that Scott (Aaronson) is definitely a smart guy. This is an interesting lecture; I won’t pretend I understood all of it, but it has some thought-provoking ideas and important points in the context of quantum computing and it’s actually a quite entertaining lecture; I was close to laughing a couple of times.

January 8, 2016 Posted by | Computer science, economics, Game theory, Lectures, mathematics, Physics | Leave a comment

Quotes

i. “The educated don’t get that way by memorizing facts; they get that way by respecting them.” (Tom Heehler)

ii. “The things you think about determine the quality of your mind. Your soul takes on the color of your thoughts.” (Marcus Aurelius)

iii. “There is no man so fortunate that there shall not be by him when he is dying some who are pleased with what is going to happen.” (-ll-)

iv. “Most of what we say and do is not necessary, and its omission would save both time and trouble. At every step, therefore, a man should ask himself, ‘Is this one of the things that are superfluous?’.” (Marcus Aurelius, as quoted in Bill Gillham’s book Case Study Research Methods, page 97)).

v. “statistics only lie to those who don’t understand them.” (Bill Gillham, Case Study Research Methods, page 80).

vi. “Few know the joys that spring from a disinterested curiosity. It is like a cheerful spirit that leads us through worlds filled with what is true and fair, which we admire and love because it is true and fair.” (John Lancaster Spalding)

vii. “The teacher does best, not when he explains, but when he impels his pupils to seek themselves the explanation.” (-ll-)

viii. “As our power over others increases, we become less free; for to retain it, we must make ourselves its servants.” (-ll-)

ix. “They who truly know have had to unlearn hardly less than they have had to learn.” (-ll-)

x. “They who no longer believe in principles still proclaim them, to conceal, both from themselves and others, the selfishness of the motives by which they are dominated.” (-ll-)

xi. “When we have not the strength or the courage to grasp a new truth, we persuade ourselves that it is not a truth at all.” (-ll-)

xii. “We neglect the opportunities which are always present, and imagine that if those that are rare were offered, we should put them to good use. Thus we waste life waiting for what if it came we should be unprepared for.” (-ll-)

xiii. “The inclination to seek the truth is safer than the presumption which regards unknown things as known.” (Augustine of Hippo)

xiv. “It is no advantage to be near the light if the eyes are closed.” (-ll-)

xv. “The true test of intelligence is not how much we know how to do, but how we behave when we don’t know what to do.” (John Holt)

xvi. “The most important thing any teacher has to learn […] can be expressed in seven words: Learning is not the product of teaching. Learning is the product of the activity of learners.” (-ll-)

xvii. “It is not just power, but impotence, that corrupts people. It gives them the mind and soul of slaves. It makes them indifferent, lazy, cynical, irresponsible, and, above all, stupid.” (-ll-)

xviii. “No man ever became extremely wicked all at once.” (Juvenal)

xix. “those who live in the West or in middle-class urban enclaves in the Non-west […] have to make a determined effort to grasp the grimness of past reality for most of humankind. In non-privileged, non-modern societies, most people in times past were malnourished, inadequately clothed against the elements, unwashed and filthy, living with insect parasites in overcrowded hovels. […] In these circumstances, “ill-health” […] very often simply meant that one was too incapacitated to carry on working in the fields or in the shop. It did not mean that one woke up feeling slightly off-color […] in the world we have lost, feeling somewhat off-color (or worse) was the standard condition.” (Disease and Medicine in World History, by Sheldon Watts, pp. 9-10).

xx. “In pre-modern China […] the task of establishing standard medical-related interpretations and texts was undertaken largely by philosophers and other scholars intent on building up grand systems which explained everything in the universe. Given that purpose, they did not attempt to build systems based on knowledge of the organs in an actual human body. […] At least until the mid-eighteenth century CE, well-known medico-philosophers [in China] wove the concept of “demon” as disease-cause-to-be-cleansed-away-by-exorcism into textual interpretations of what actually caused disease and what should be done about it.” (ibid., pp. 70, 72).

January 7, 2016 Posted by | quotes | Leave a comment

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