Perception (I)

Here’s my short goodreads review of the book. In this post I’ll include some observations and links related to the first half of the book’s coverage.

“Since the 1960s, there have been many attempts to model the perceptual processes using computer algorithms, and the most influential figure of the last forty years has been David Marr, working at MIT. […] Marr and his colleagues were responsible for developing detailed algorithms for extracting (i) low-level information about the location of contours in the visual image, (ii) the motion of those contours, and (iii) the 3-D structure of objects in the world from binocular disparities and optic flow. In addition, one of his lasting achievements was to encourage researchers to be more rigorous in the way that perceptual tasks are described, analysed, and formulated and to use computer models to test the predictions of those models against human performance. […] Over the past fifteen years, many researchers in the field of perception have characterized perception as a Bayesian process […] According to Bayesian theory, what we perceive is a consequence of probabilistic processes that depend on the likelihood of certain events occurring in the particular world we live in. Moreover, most Bayesian models of perceptual processes assume that there is noise in the sensory signals and the amount of noise affects the reliability of those signals – the more noise, the less reliable the signal. Over the past fifteen years, Bayes theory has been used extensively to model the interaction between different discrepant cues, such as binocular disparity and texture gradients to specify the slant of an inclined surface.”

“All surfaces have the property of reflectance — that is, the extent to which they reflect (rather than absorb) the incident illumination — and those reflectances can vary between 0 per cent and 100 per cent. Surfaces can also be selective in the particular wavelengths they reflect or absorb. Our colour vision depends on these selective reflectance properties […]. Reflectance characteristics describe the physical properties of surfaces. The lightness of a surface refers to a perceptual judgement of a surface’s reflectance characteristic — whether it appears as black or white or some grey level in between. Note that we are talking about the perception of lightness — rather than brightness — which refers to our estimate of how much light is coming from a particular surface or is emitted by a source of illumination. The perception of surface lightness is one of the most fundamental perceptual abilities because it allows us not only to differentiate one surface from another but also to identify the real-world properties of a particular surface. Many textbooks start with the observation that lightness perception is a difficult task because the amount of light reflected from a particular surface depends on both the reflectance characteristic of the surface and the intensity of the incident illumination. For example, a piece of black paper under high illumination will reflect back more light to the eye than a piece of white paper under dim illumination. As a consequence, lightness constancy — the ability to correctly judge the lightness of a surface under different illumination conditions — is often considered to be an ‘achievement’ of the perceptual system. […] The alternative starting point for understanding lightness perception is to ask whether there is something that remains constant or invariant in the patterns of light reaching the eye with changes of illumination. In this case, it is the relative amount of light reflected off different surfaces. Consider two surfaces that have different reflectances—two shades of grey. The actual amount of light reflected off each of the surfaces will vary with changes in the illumination but the relative amount of light reflected off the two surfaces remains the same. This shows that lightness perception is necessarily a spatial task and hence a task that cannot be solved by considering one particular surface alone. Note that the relative amount of light reflected off different surfaces does not tell us about the absolute lightnesses of different surfaces—only their relative lightnesses […] Can our perception of lightness be fooled? Yes, of course it can and the ways in which we make mistakes in our perception of the lightnesses of surfaces can tell us much about the characteristics of the underlying processes.”

“From a survival point of view, the ability to differentiate objects and surfaces in the world by their ‘colours’ (spectral reflectance characteristics) can be extremely useful […] Most species of mammals, birds, fish, and insects possess several different types of receptor, each of which has a a different spectral sensitivity function […] having two types of receptor with different spectral sensitivities is the minimum necessary for colour vision. This is referred to as dicromacy and the majority of mammals are dichromats with the exception of the old world monkeys and humans. […] The only difference between lightness and colour perception is that in the latter case we have to consider the way a surface selectively reflects (and absorbs) different wavelengths, rather than just a surface’s average reflectance over all wavelengths. […] The similarities between the tasks of extracting lightness and colour information mean that we can ask a similar question about colour perception [as we did about lightness perception] – what is the invariant information that could specify the reflectance characteristic of a surface? […] The information that is invariant under changes of spectral illumination is the relative amounts of long, medium, and short wavelength light reaching our eyes from different surfaces in the scene. […] the successful identification and discrimination of coloured surfaces is dependent on making spatial comparisons between the amounts of short, medium, and long wavelength light reaching our eyes from different surfaces. As with lightness perception, colour perception is necessarily a spatial task. It follows that if a scene is illuminated by the light of just a single wavelength, the appropriate spatial comparisons cannot be made. This can be demonstrated by illuminating a real-world scene containing many different coloured objects with yellow, sodium light that contains only a single wavelength. All objects, whatever their ‘colours’, will only reflect back to the eye different intensities of that sodium light and hence there will only be absolute but no relative differences between the short, medium, and long wavelength lightness records. There is a similar, but less dramatic, effect on our perception of colour when the spectral characteristics of the illumination are restricted to just a few wavelengths, as is the case with fluorescent lighting.”

“Consider a single receptor mechanism, such as a rod receptor in the human visual system, that responds to a limited range of wavelengths—referred to as the receptor’s spectral sensitivity function […]. This hypothetical receptor is more sensitive to some wavelengths (around 550 nm) than others and we might be tempted to think that a single type of receptor could provide information about the wavelength of the light reaching the receptor. This is not the case, however, because an increase or decrease in the response of that receptor could be due to either a change in the wavelength or an increase or decrease in the amount of light reaching the receptor. In other words, the output of a given receptor or receptor type perfectly confounds changes in wavelength with changes in intensity because it has only one way of responding — that is, more or less. This is Rushton’s Principle of Univariance — there is only one way of varying or one degree of freedom. […] On the other hand, if we consider a visual system with two different receptor types, one more sensitive to longer wavelengths (L) and the other more sensitive to shorter wavelengths (S), there are two degrees of freedom in the system and thus the possibility of signalling our two independent variables — wavelength and intensity […] it is quite possible to have a colour visual system that is based on just two receptor types. Such a colour visual system is referred to as dichromatic.”

“So why is the human visual system trichromatic? The answer can be found in a phenomenon known as metamerism. So far, we have restricted our discussion to the effect of a single wavelength on our dichromatic visual system: for example, a single wavelength of around 550 nm that stimulated both the long and short receptor types about equally […]. But what would happen if we stimulated our dichromatic system with light of two different wavelengths at the same time — one long wavelength and one short wavelength? With a suitable choice of wavelengths, this combination of wavelengths would also have the effect of stimulating the two receptor types about equally […] As a consequence, the output of the system […] with this particular mixture of wavelengths would be indistinguishable from that created by the single wavelength of 550 nm. These two indistinguishable stimulus situations are referred to as metamers and a little thought shows that there would be many thousands of combinations of wavelength that produce the same activity […] in a dichromatic visual system. As a consequence, all these different combinations of wavelengths would be indistinguishable to a dichromatic observer, even though they were produced by very different combinations of wavelengths. […] Is there any way of avoiding the problem of metamerism? The answer is no but we can make things better. If a visual system had three receptor types rather than two, then many of the combinations of wavelengths that produce an identical pattern of activity in two of the mechanisms (L and S) would create a different amount of activity in our third receptor type (M) that is maximally sensitive to medium wavelengths. Hence the number of indistinguishable metameric matches would be significantly reduced but they would never be eliminated. Using the same logic, it follows that a further increase in the number of receptor types (beyond three) would reduce the problem of metamerism even more […]. There would, however, also be a cost. Having more distinct receptor types in a finite-sized retina would increase the average spacing between the receptors of the same type and thus make our acuity for fine detail significantly poorer. There are many species, such as dragonflies, with more than three receptor types in their eyes but the larger number of receptor types typically serves to increase the range of wavelengths to which the animal is sensitive into the infra-red or ultra-violet parts of the spectrum, rather than to reduce the number of metamers. […] the sensitivity of the short wavelength receptors in the human eye only extends to ~540 nm — the S receptors are insensitive to longer wavelengths. This means that human colour vision is effectively dichromatic for combinations of wavelengths above 540 nm. In addition, there are no short wavelength cones in the central fovea of the human retina, which means that we are also dichromatic in the central part of our visual field. The fact that we are unaware of this lack of colour vision is probably due to the fact that our eyes are constantly moving. […] It is […] important to appreciate that the description of the human colour visual system as trichromatic is not a description of the number of different receptor types in the retina – it is a property of the whole visual system.”

“Recent research has shown that although the majority of humans are trichromatic there can be significant differences in the precise matches that individuals make when matching colour patches […] the absence of one receptor type will result in a greater number of colour confusions than normal and this does have a significant effect on an observer’s colour vision. Protanopia is the absence of long wavelength receptors, deuteranopia the absence of medium wavelength receptors, and tritanopia the absence of short wavelength receptors. These three conditions are often described as ‘colour blindness’ but this is a misnomer. We are all colour blind to some extent because we all suffer from colour metamerism and fail to make discriminations that would be very apparent to any biological or machine vision system with a greater number of receptor types. For example, most stomatopod crustaceans (mantis shrimps) have twelve different visual pigments and they also have the ability to detect both linear and circularly polarized light. What I find interesting is that we believe, as trichromats, that we have the ability to discriminate all the possible shades of colour (reflectance characteristics) that exist in our world. […] we are typically unaware of the limitations of our visual systems because we have no way of comparing what we see normally with what would be seen by a ‘better’ visual system.”

“We take it for granted that we are able to segregate the visual input into separate objects and distinguish objects from their backgrounds and we rarely make mistakes except under impoverished conditions. How is this possible? In many cases, the boundaries of objects are defined by changes of luminance and colour and these changes allow us to separate or segregate an object from its background. But luminance and colour changes are also present in the textured surfaces of many objects and therefore we need to ask how it is that our visual system does not mistake these luminance and colour changes for the boundaries of objects. One answer is that object boundaries have special characteristics. In our world, most objects and surfaces are opaque and hence they occlude (cover) the surface of the background. As a consequence, the contours of the background surface typically end—they are ‘terminated’—at the boundary of the occluding object or surface. Quite often, the occluded contours of the background are also revealed at the opposite side of the occluding surface because they are physically continuous. […] The impression of occlusion is enhanced if the occluded contours contain a range of different lengths, widths, and orientations. In the natural world, many animals use colour and texture to camouflage their boundaries as well as to fool potential predators about their identity. […] There is an additional source of information — relative motion — that can be used to segregate a visual scene into objects and their backgrounds and to break any camouflage that might exist in a static view. A moving, opaque object will progressively occlude and dis-occlude (reveal) the background surface so that even a well-camouflaged, moving animal will give away its location. Hence it is not surprising that a very common and successful strategy of many animals is to freeze in order not to be seen. Unless the predator has a sophisticated visual system to break the pattern or colour camouflage, the prey will remain invisible.”

Some links:

Ames room. Inverse problem in optics.
Hermann von Helmholtz. Richard Gregory. Irvin Rock. James Gibson. David Marr. Ewald Hering.
Optical flow.
La dioptrique.
Necker cube. Rubin’s vase.
Perceptual constancy. Texture gradient.
Ambient optic array.
Checker shadow illusion.
Shape from shading/Photometric stereo.
Colour vision. Colour constancy. Retinex model.
Cognitive neuroscience of visual object recognition.
Motion perception.
Horace Barlow. Bernhard Hassenstein. Werner E. Reichardt. Sigmund Exner. Jan Evangelista Purkyně.
Phi phenomenon.
Motion aftereffect.
Induced motion.


October 14, 2018 Posted by | Biology, Books, Ophthalmology, Physics, Psychology | Leave a comment

Oncology (I)

I really disliked the ‘Pocket…’ part of this book, so I’ll sort of pretend to overlook this aspect also in my coverage of the book here. This’ll be a hard thing to do, given the way the book is written – I refer to my goodreads review for details, I’ll include only one illustrative quote from that review here:

“In terms of content, the book probably compares favourably with many significantly longer oncology texts (mainly, but certainly not only, because of the publication date). In terms of readability it compares unfavourably to an Egyptian translation of Alan Sokal’s 1996 article in Social Text, if it were translated by a 12-year old dyslexic girl.”

I don’t yet know in how much detail I’ll blog the book; this may end up being the only post about the book, or I may decide to post a longer sequence of posts. The book is hard to blog, which is an argument against covering it in detail – and also the reason why I haven’t already blogged it – but some of the content included in the book is really, really nice stuff to know, which is a strong argument in favour of covering at least some of the material here. The book has a lot of stuff, so regardless of the level of detail of my future coverage a lot of interesting stuff will of necessity have been left out.

My coverage below includes some observations and links related to the first 100 pages of the book.

“Understanding Radiation Response: The 4 Rs of Radiobiology
Repair of sublethal damage
Reassortment of cells w/in the cell cycle
Repopulation of cells during the course of radiotherapy
Reoxygenation of hypoxic cells […]

*Oxygen enhances DNA damage induced by free radicals, thereby facilitating the indirect action of IR [ionizing radiation, US] *Biologically equivalent dose can vary by a factor of 2–3 depending upon the presence or absence of oxygen (referred to as the oxygen enhancement ratio) *Poorly oxygenated postoperative beds frequently require higher doses of RT than preoperative RT [radiation therapy] […] Chemotherapy is frequently used sequentially or concurrently w/radiotherapy to maximize therapeutic benefit. This has improved pt outcomes although also a/w ↑ overall tox. […] [Many chemotherapeutic agents] show significant synergy with RT […] Mechanisms for synergy vary widely: Include cell cycle effects, hypoxic cell sensitization, & modulation of the DNA damage response”.

“Specific dose–volume relationships have been linked to the risk of late organ tox. […] *Dose, volume, underlying genetics, and age of the pt at the time of RT are critical determinants of the risk for 2° malignancy *The likelihood of 2° CA is correlated w/dose, but there is no threshold dose below which there is no additional risk of 2° malignancy *Latent period for radiation-induced solid tumors is generally between 10 and 60 y […]. Latent period for leukemias […] is shorter — peak between 5 & 7 y.”

“The immune system plays an important role in CA surveillance; Rx’s that modulate & amplify the immune system are referred to as immunotherapies […] tumors escape the immune system via loss of molecules on tumor cells important for immune activation […]; tumors can secrete immunosuppressing cytokines (IL-10 & TGF-β) & downregulate IFN-γ; in addition, tumors often express nonmutated self-Ag, w/c the immune system will, by definition, not react against; tumors can express molecules that inhibit T-cell function […] Ubiquitous CD47 (Don’t eat me signal) with ↑ expression on tumor cells mediates escape from phagocytosis. *Tumor microenvironment — immune cells are found in tumors, the exact composition of these cells has been a/w [associated with, US] pt outcomes; eg, high concentration of tumor-infiltrating lymphocytes (CD8+ cells) are a/w better outcomes & ↑ response to chemotherapy, Tregs & myeloid-derived suppressor cells are a/w worse outcomes, the exact role of Th17 in tumors is still being elucidated; the milieu of cytokines & chemokines also plays a role in outcome; some cytokines (VEGF, IL-1, IL-8) lead to endothelial cell proliferation, migration, & activation […] Expression of PD-L1 in tumor microenvironment can be indicator of improved likelihood of response to immune checkpoint blockade. […] Tumor mutational load correlates w/increased response to immunotherapy (NEJM; 2014;371:2189.).”

“Over 200 hereditary CA susceptibility syndromes, most are rare […]. Inherited CAs arise from highly penetrant germline mts [mutations, US]; “familial” CAss may be caused by interaction of low-penetrance genes, gene–environment interactions, or both. […] Genetic testing should be done based on individual’s probability of being a mt carrier & after careful discussion & informed consent”.

Pharmacogenetics: Effect of heritable genes on response to drugs. Study of single genes & interindividual differences in drug metabolizing enzymes. Pharmacogenomics: Effect of inherited & acquired genetic variation on drug response. Study of the functions & interactions of all genes in the genome & how the overall variability of drug response may be used to predict the right tx in individual pts & to design new drugs. Polymorphisms: Common variations in a DNA sequence that may lead to ↓ or ↑ activity of the encoded gene (SNP, micro- & minisatellites). SNPs: Single nucleotide polymorphisms that may cause an amino acid exchange in the encoded protein, account for >90% of genetic variation in the human genome.”

Tumor lysis syndrome [TLS] is an oncologic emergency caused by electrolyte abnormalities a/w spontaneous and/or tx-induced cell death that can be potentially fatal. […] 4 key electrolyte abnormalities 2° to excessive tumor/cell lysis: *Hyperkalemia *Hyperphosphatemia *Hypocalcemia *Hyperuricemia (2° to catabolism of nucleic acids) […] Common Malignancies Associated with a High Risk of Developing TLS in Adult Patients [include] *Acute leukemias [and] *High-grade lymphomas such as Burkitt lymphoma & DLBCL […] [Disease] characteristics a/w TLS risk: Rapidly progressive, chemosensitive, myelo- or lymphoproliferative [disease] […] [Patient] characteristics a/w TLS risk: *Baseline impaired renal function, oliguria, exposure to nephrotoxins, hyperuricemia *Volume depletion/inadequate hydration, acidic urine”.

Hypercalcemia [affects] ~10–30% of all pts w/malignancy […] Symptoms: Polyuria/polydipsia, intravascular volume depletion, AKI, lethargy, AMS [Altered Mental Status, US], rarely coma/seizures; N/V [nausea/vomiting, US] […] Osteolytic Bone Lesions [are seen in] ~20% of all hyperCa of malignancy […] [Treat] underlying malignancy, only way to effectively treat, all other tx are temporizing”.

“National Consensus Project definition: Palliative care means patient and family-centered care that optimizes quality of life by anticipating, preventing, and treating suffering. Palliative care throughout the continuum of illness involves addressing physical, intellectual, emotional, social, and spiritual needs to facilitate patient autonomy, access to information, and choice.” […] *Several RCTs have supported the integration of palliative care w/oncologic care, but specific interventions & models of care have varied. Expert panels at NCCN & ASCO recently reviewed the data to release evidence-based guidelines. *NCCN guidelines (2016): “Palliative care should be initiated by the primary oncology team and then augmented by collaboration with an interdisciplinary team of palliative care experts… All cancer patients should be screened for palliative care needs at their initial visit, at appropriate intervals, and as clinically indicated.” *ASCO guideline update (2016): “Inpatients and outpatients with advanced cancer should receive dedicated palliative care services, early in the disease course, concurrent with active tx. Referral of patients to interdisciplinary palliative care teams is optimal […] Essential Components of Palliative Care (ASCO) *Rapport & relationship building w/pts & family caregivers *Symptom, distress, & functional status mgmt (eg, pain, dyspnea, fatigue, sleep disturbance, mood, nausea, or constipation) *Exploration of understanding & education about illness & prognosis *Clarification of tx goals *Assessment & support of coping needs (eg, provision of dignity therapy) *Assistance w/medical decision making *Coordination w/other care providers *Provision of referrals to other care providers as indicated […] Useful Communication Tips *Use open-ended questions to elicit pt concerns *Clarify how much information the pt would like to know […] Focus on what can be done (not just what can’t be done) […] Remove the phrase “do everything” from your medical vocabulary […] Redefine hope by supporting realistic & achievable goals […] make empathy explicit”.

Some links:

Radiation therapy.
External beam radiotherapy.
Image-guided radiation therapy.
Stereotactic Radiosurgery.
Total body irradiation.
Cancer stem cell.
Cell cycle.
Carcinogenesis. Oncogene. Tumor suppressor gene. Principles of Cancer Therapy: Oncogene and Non-oncogene Addiction.
Cowden syndrome. Peutz–Jeghers syndrome. Familial Atypical Multiple Mole Melanoma Syndrome. Li–Fraumeni syndrome. Lynch syndrome. Turcot syndrome. Muir–Torre syndrome. Von Hippel–Lindau disease. Gorlin syndrome. Werner syndrome. Birt–Hogg–Dubé syndrome. Neurofibromatosis type I. -ll- type 2.
Knudson hypothesis.
DNA sequencing.
Fluorescence in situ hybridization.
CAR T Cell therapy.
Antimetabolite. Alkylating antineoplastic agentAntimicrotubule agents/mitotic inhibitors. Chemotherapeutic agentsTopoisomerase inhibitorMonoclonal antibodiesBisphosphonatesProteasome inhibitors. [The book covers all of these agents, and others I for one reason or another decided not to include, in great detail, listing many different types of agents and including notes on dosing, pharmacokinetics & pharmacodynamics, associated adverse events and drug interactions etc. These parts of the book were very interesting, but they are impossible to blog – US).
Syndrome of inappropriate antidiuretic hormone secretion.
Acute lactic acidosis (“Often seen w/liver mets or rapidly dividing heme malignancies […] High mortality despite aggressive tx [treatment]”).
Superior vena cava syndrome.

October 12, 2018 Posted by | Biology, Books, Cancer/oncology, Genetics, Immunology, Medicine, Pharmacology | Leave a comment

Principles of memory (II)

I have added a few more quotes from the book below:

Watkins and Watkins (1975, p. 443) noted that cue overload is “emerging as a general principle of memory” and defined it as follows: “The efficiency of a functional retrieval cue in effecting recall of an item declines as the number of items it subsumes increases.” As an analogy, think of a person’s name as a cue. If you know only one person named Katherine, the name by itself is an excellent cue when asked how Katherine is doing. However, if you also know Cathryn, Catherine, and Kathryn, then it is less useful in specifying which person is the focus of the question. More formally, a number of studies have shown experimentally that memory performance systematically decreases as the number of items associated with a particular retrieval cue increases […] In many situations, a decrease in memory performance can be attributed to cue overload. This may not be the ultimate explanation, as cue overload itself needs an explanation, but it does serve to link a variety of otherwise disparate findings together.”

Memory, like all other cognitive processes, is inherently constructive. Information from encoding and cues from retrieval, as well as generic information, are all exploited to construct a response to a cue. Work in several areas has long established that people will use whatever information is available to help reconstruct or build up a coherent memory of a story or an event […]. However, although these strategies can lead to successful and accurate remembering in some circumstances, the same processes can lead to distortion or even confabulation in others […]. There are a great many studies demonstrating the constructive and reconstructive nature of memory, and the literature is quite well known. […] it is clear that recall of events is deeply influenced by a tendency to reconstruct them using whatever information is relevant and to repair holes or fill in the gaps that are present in memory with likely substitutes. […] Given that memory is a reconstructive process, it should not be surprising to find that there is a large literature showing that people have difficulty distinguishing between memories of events that happened and memories of events that did not happen […]. In a typical reality monitoring experiment […], subjects are shown pictures of common objects. Every so often, instead of a picture, the subjects are shown the name of an object and are asked to create a mental image of the object. The test involves presenting a list of object names, and the subject is asked to judge whether they saw the item (i.e., judge the memory as “real”) or whether they saw the name of the object and only imagined seeing it (i.e., judge the memory as “imagined”). People are more likely to judge imagined events as real than real events as imagined. The likelihood that a memory will be judged as real rather than imagined depends upon the vividness of the memory in terms of its sensory quality, detail, plausibility, and coherence […]. What this means is that there is not a firm line between memories for real and imagined events: if an imagined event has enough qualitative features of a real event it is likely to be judged as real.”

“One hallmark of reconstructive processes is that in many circumstances they aid in memory retrieval because they rely on regularities in the world. If we know what usually happens in a given circumstance, we can use that information to fill in gaps that may be present in our memory for that episode. This will lead to a facilitation effect in some cases but will lead to errors in cases in which the most probable response is not the correct one. However, if we take this standpoint, we must predict that the errors that are made when using reconstructive processes will not be random; in fact, they will display a bias toward the most likely event. This sort of mechanism has been demonstrated many times in studies of schema-based representations […], and language production errors […] but less so in immediate recall. […] Each time an event is recalled, the memory is slightly different. Because of the interaction between encoding and retrieval, and because of the variations that occur between two different retrieval attempts, the resulting memories will always differ, even if only slightly.”

In this chapter we discuss the idea that a task or a process can be a “pure” measure of memory, without contamination from other hypothetical memory stores or structures, and without contributions from other processes. Our impurity principle states that tasks and processes are not pure, and therefore one cannot separate out the contributions of different memory stores by using tasks thought to tap only one system; one cannot count on subjects using only one process for a particular task […]. Our principle follows from previous arguments articulated by Kolers and Roediger (1984) and Crowder (1993), among others, that because every event recruits slightly different encoding and retrieval processes, there is no such thing as “pure” memory. […] The fundamental issue is the extent to which one can determine the contribution of a particular memory system or structure or process to performance on a particular memory task. There are numerous ways of assessing memory, and many different ways of classifying tasks. […] For example, if you are given a word fragment and asked to complete it with the first word that pops in your head, you are free to try a variety of strategies. […] Very different types of processing can be used by subjects even when given the same type of test or cue. People will use any and all processes to help them answer a question.”

“A free recall test typically provides little environmental support. A list of items is presented, and the subject is asked to recall which items were on the list. […] The experimenter simply says, “Recall the words that were on the list,” […] A typical recognition test provides more environmental support. Although a comparable list of items might have been presented, and although the subject is asked again about memory for an item in context, the subject is provided with a more specific cue, and knows exactly how many items to respond to. Some tests, such as word fragment completion and general knowledge questions, offer more environmental support. These tests provide more targeted cues, and often the cues are unique […] One common processing distinction involves the aspects of the stimulus that are focused on or are salient at encoding and retrieval: Subjects can focus more on an item’s physical appearance (data driven processing) or on an item’s meaning (conceptually driven processing […]). In general, performance on tasks such as free recall that offer little environmental support is better if the rememberer uses conceptual rather than perceptual processing at encoding. Although there is perceptual information available at encoding, there is no perceptual information provided at test so data-driven processes tend not to be appropriate. Typical recognition and cued-recall tests provide more specific cues, and as such, data-driven processing becomes more appropriate, but these tasks still require the subject to discriminate which items were presented in a particular specific context; this is often better accomplished using conceptually driven processing. […] In addition to distinctions between data driven and conceptually driven processing, another common distinction is between an automatic retrieval process, which is usually referred to as familiarity, and a nonautomatic process, usually called recollection […]. Additional distinctions abound. Our point is that very different types of processing can be used by subjects on a particular task, and that tasks can differ from one another on a variety of different dimensions. In short, people can potentially use almost any combination of processes on any particular task.”

Immediate serial recall is basically synonymous with memory span. In one the first reviews of this topic, Blankenship (1938, p. 2) noted that “memory span refers to the ability of an individual to reproduce immediately, after one presentation, a series of discrete stimuli in their original order.”3 The primary use of memory span was not so much to measure the capacity of a short-term memory system, but rather as a measure of intellectual abilities […]. Early on, however, it was recognized that memory span, whatever it was, varied as function of a large number of variables […], and could even be increased substantially by practice […]. Nonetheless, memory span became increasingly seen as a measure of the capacity of a short-term memory system that was distinct from long-term memory. Generally, most individuals can recall about 7 ± 2 items (Miller, 1956) or the number of items that can be pronounced in about 2 s (Baddeley, 1986) without making any mistakes. Does immediate serial recall (or memory span) measure the capacity of short-term (or working) memory? The currently available evidence suggests that it does not. […] The main difficulty in attempting to construct a “pure” measure of immediate memory capacity is that […] the influence of previously acquired knowledge is impossible to avoid. There are numerous contributions of long-term knowledge not only to memory span and immediate serial recall […] but to other short-term tasks as well […] Our impurity principle predicts that when distinctions are made between types of processing (e.g., conceptually driven versus data driven; familiarity versus recollection; automatic versus conceptual; item specific versus relational), each of those individual processes will not be pure measures of memory.”

“Over the past 20 years great strides have been made in noninvasive techniques for measuring brain activity. In particular, PET and fMRI studies have allowed us to obtain an on-line glimpse into the hemodynamic changes that occur in the brain as stimuli are being processed, memorized, manipulated, and recalled. However, many of these studies rely on subtractive logic that explicitly assumes that (a) there are different brain areas (structures) subserving different cognitive processes and (b) we can subtract out background or baseline activity and determine which areas are responsible for performing a particular task (or process) by itself. There have been some serious challenges to these underlying assumptions […]. A basic assumption is that there is some baseline activation that is present all of the time and that the baseline is built upon by adding more activation. Thus, when the baseline is subtracted out, what is left is a relatively pure measure of the brain areas that are active in completing the higher-level task. One assumption of this method is that adding a second component to the task does not affect the simple task. However, this assumption does not always hold true. […] Even if the additive factors logic were correct, these studies often assume that a task is a pure measure of one process or another. […] Again, the point is that humans will utilize whatever resources they can recruit in order to perform a task. Individuals using different retrieval strategies (e.g., visualization, verbalization, lax or strict decision criteria, etc.) show very different patterns of brain activation even when performing the same memory task (Miller & Van Horn, 2007). This makes it extremely dangerous to assume that any task is made up of purely one process. Even though many researchers involved in neuroimaging do not make task purity assumptions, these examples “illustrate the widespread practice in functional neuroimaging of interpreting activations only in terms of the particular cognitive function being investigated (Cabeza et al., 2003, p. 390).” […] We do not mean to suggest that these studies have no value — they clearly do add to our knowledge of how cognitive functioning works — but, instead, would like to urge more caution in the interpretation of localization studies, which are sometimes taken as showing that an activated area is where some unique process takes place.”

October 6, 2018 Posted by | Biology, Books, Psychology | Leave a comment

Circadian Rhythms (II)

Below I have added some more observations from the book, as well as some links of interest.

“Most circadian clocks make use of a sun-based mechanism as the primary synchronizing (entraining) signal to lock the internal day to the astronomical day. For the better part of four billion years, dawn and dusk has been the main zeitgeber that allows entrainment. Circadian clocks are not exactly 24 hours. So to prevent daily patterns of activity and rest from drifting (freerunning) over time, light acts rather like the winder on a mechanical watch. If the clock is a few minutes fast or slow, turning the winder sets the clock back to the correct time. Although light is the critical zeitgeber for much behaviour, and provides the overarching time signal for the circadian system of most organisms, it is important to stress that many, if not all cells within an organism possess the capacity to generate a circadian rhythm, and that these independent oscillators are regulated by a variety of different signals which, in turn, drive countless outputs […]. Colin Pittendrigh was one of the first to study entrainment, and what he found in Drosophila has been shown to be true across all organisms, including us. For example, if you keep Drosophila, or a mouse or bird, in constant darkness it will freerun. If you then expose the animal to a short pulse of light at different times the shifting (phase shifting) effects on the freerunning rhythm vary. Light pulses given when the clock ‘thinks’ it is daytime (subjective day) will have little effect on the clock. However, light falling during the first half of the subjective night causes the animal to delay the start of its activity the following day, while light exposure during the second half of the subjective night advances activity onset. Pittendrigh called this the ‘phase response curve’ […] Remarkably, the PRC of all organisms looks very similar, with light exposure around dusk and during the first half of the night causing a delay in activity the next day, while light during the second half of the night and around dawn generates an advance. The precise shape of the PRC varies between species. Some have large delays and small advances (typical of nocturnal species) while others have small delays and big advances (typical of diurnal species). Light at dawn and dusk pushes and pulls the freerunning rhythm towards an exactly 24-hour cycle. […] Light can act directly to modify behaviour. In nocturnal rodents such as mice, light encourages these animals to seek shelter, reduce activity, and even sleep, while in diurnal species light promotes alertness and vigilance. So circadian patterns of activity are not only entrained by dawn and dusk but also driven directly by light itself. This direct effect of light on activity has been called ‘masking’, and combines with the predictive action of the circadian system to restrict activity to that period of the light/dark cycle to which the organism has evolved and is optimally adapted.”

“[B]irds, reptiles, amphibians, and fish (but not mammals) have ‘extra-ocular’ photoreceptors located within the pineal complex, hypothalamus, and other areas of the brain, and like the invertebrates, eye loss in many cases has little impact upon the ability of these animals to entrain. […] Mammals are strikingly different from all other vertebrates as they possess photoreceptor cells only within their eyes. Eye loss in all groups of mammals […] abolishes the capacity of these animals to entrain their circadian rhytms to the light/dark cycle. But astonishingly, the visual cells of the retina – the rods and cones – are not required for the detection of the dawn/dusk signal. There exists a third class of photoreceptors within the eye […] Studies in the late 1990s by Russell Foster and his colleagues showed that mice lacking all their rod and cone photoreceptors could still regulate their circadian rhythms to light perfectly normally. But when their eyes were covered the ability to entrain was lost […] work on the rodless/coneless mouse, along with [other] studies […], clearly demonstrated that the mammalian retina contains a small population of photosensitive retinal ganglion cells or pRGCs, which comprise approximately 1-2 per cent of all retinal ganglion cells […] Ophthalmologists now appreciate that eye loss deprives us of both vision and a proper sense of time. Furthermore, genetic diseases that result in the loss of the rods and cones and cause visual blindness, often spare the pRGCs. Under these circumstances, individuals who have their eyes but are visually blind, yet possess functional pRGCs, need to be advised to seek out sufficient light to entrain their circadian system. The realization that the eye provides us with both our sense of space and our sense of time has redefined the diagnosis, treatment, and appreciation of human blindness.”

“But where is ‘the’ circadian clock of mammals? […] [Robert] Moore and [Irving] Zucker’s work pinpointed the SCN as the likely neural locus of the light-entrainable circadian pacemaker in mammals […] and a decade later this was confirmed by definitive experiments from Michael Menaker’s laboratory undertaken at the University of Virginia. […] These experiments established the SCN as the ‘master circadian pacemaker’ of mammals. […] There are around 20,000 or so neurons in the mouse SCN, but they are not identical. Some receive light information from the pRGCs and pass this information on to other SCN neurons, while others project to the thalamus and other regions of the brain, and collectively these neurons secrete more than one hundred different neurotransmitters, neuropeptides, cytokines, and growth factors. The SCN itself is composed of several regions or clusters of neurons, which have different jobs. Furthermore, there is considerable variability in the oscillations of the individual cells, ranging from 21.25 to 26.25 hours. Although the individual cells in the SCN have their own clockwork mechanisms with varying periods, the cell autonomous oscillations in neural activity are synchronized at the system level within the SCN, providing a coherent near 24-hour signal to the rest of the mammal. […] SCN neurons exhibit a circadian rhythm of spontaneous action potentials (SAPs), with higher frequency during the daytime than the night which in turn drives many rhythmic changes by alternating stimulatory and inhibitory inputs to the appropriate target neurons in the brain and neuroendocrine systems. […] The SCN projects directly to thirty-five brain regions, mostly located in the hypothalamus, and particularly those regions of the hypothalamus that regulate hormone release. Indeed, many pituitary hormones, such as cortisol, are under tight circadian control. Furthermore, the SCN regulates the activity of the autonomous nervous system, which in turn places multiple aspects of physiology, including the sensitivity of target tissues to hormonal signals, under circadian control. In addition to these direct neuronal connections, the SCN communicates to the rest of the body using diffusible chemical signals.”

“The SCN is the master clock in mammals but it is not the only clock. There are liver clocks, muscle clocks, pancreas clocks, adipose tissue clocks, and clocks of some sort in every organ and tissue examined to date. While lesioning of the SCN disrupts global behavioural rhythms such as locomotor activity, the disruption of clock function within just the liver or lung leads to circadian disorder that is confined to the target organ. In tissue culture, liver, heart, lung, skeletal muscle, and other organ tissues such as mammary glands express circadian rhythms, but these rhythms dampen and disappear after only a few cycles. This occurs because some individual clock cells lose rhythmicity, but more commonly because the individual cellular clocks become uncoupled from each other. The cells continue to tick, but all at different phases so that an overall 24-hour rhythm within the tissue or organ is lost. The discovery that virtually all cells of the body have clocks was one of the big surprises in circadian rhythms research. […] the SCN, entrained by pRGCs, acts as a pacemaker to coordinate, but not drive, the circadian activity of billions of individual peripheral circadian oscillators throughout the tissues and organs of the body. The signalling pathways used by the SCN to phase-entrain peripheral clocks are still uncertain, but we know that the SCN does not send out trillions of separate signals around the body that target specific cellular clocks. Rather there seems to be a limited number of neuronal and humoral signals which entrain peripheral clocks that in turn time their local physiology and gene expression.”

“As in Drosophilia […], the mouse clockwork also comprises three transcriptional-translational feedback loops with multiple interacting components. […] [T]he generation of a robust circadian rhythm that can be entrained by the environment is achieved via multiple elements, including the rate of transcription, translation, protein complex assembly, phosphorylation, other post-translation modification events, movement into the nucleus, transcriptional inhibition, and protein degradation. […] [A] complex arrangement is needed because from the moment a gene is switched on, transcription and translation usually takes two hours at most. As a result, substantial delays must be imposed at different stages to produce a near 24-hour oscillation. […] Although the molecular players may differ from Drosophilia and mice, and indeed even between different insects, the underlying principles apply across the spectrum of animal life. […] In fungi, plants, and cyanobacteria the clock genes are all different from each other and different again from the animal clock genes, suggesting that clocks evolved independently in the great evolutionary lineages of life on earth. Despite these differences, all these clocks are based upon a fundamental TTFL.”

“Circadian entrainment is surprisingly slow, taking several days to adjust to an advanced or delayed light/dark cycle. In most mammals, including jet-lagged humans, behavioural shifts are limited to approximately one hour (one time zone) per day. […] Changed levels of PER1 and PER2 act to shift the molecular clockwork, advancing the clock at dawn and delaying the clock at dusk. However, per mRNA and PER protein levels fall rapidly even if the animal remains exposed to light. As a result, the effects of light on the molecular clock are limited and entrainment is a gradual process requiring repeated shifting stimuli over multiple days. This phenomenon explains why we get jet lag: the clock cannot move immediately to a new dawn/dusk cycle because there is a ‘brake’ on the effects of light on the clock. […] The mechanism that provides this molecular brake is the production of SLK1 protein. […] Experiments on mice in which SLK1 has been suppressed show very rapid entrainment to simulated jet-lag.”

“We spend approximately 36 per cent of our entire lives asleep, and while asleep we do not eat, drink, or knowingly pass on our genes. This suggests that this aspect of our 24-hour behaviour provides us with something of huge value. If we are deprived of sleep, the sleep drive becomes so powerful that it can only be satisfied by sleep. […] Almost all life shows a 24-hour pattern of activity and rest, as we live on a planet that revolves once every 24 hours causing profound changes in light, temperature, and food availability. […] Life seems to have made an evolutionary ‘decision’ to be active at a specific part of the day/night cycle, and a species specialized to be active during the day will be far less effective at night. Conversely, nocturnal animals that are beautifully adapted to move around and hunt under dim or no light fail miserably during the day. […] no species can operate with the same effectiveness across the 24-hour light/dark environment. Species are adapted to a particular temporal niche just as they are to a physical niche. Activity at the wrong time often means death. […] Sleep may be the suspension of most physical activity, but a huge amount of essential physiology occurs during this time. Many diverse processes associated with the restoration and rebuilding of metabolic pathways are known to be up-regulated during sleep […] During sleep the body performs a broad range of essential ‘housekeeping’ functions without which performance and health during the active phase deteriorates rapidly. But these housekeeping functions would not be why sleep evolved in the first place. […] Evolution has allocated these key activities to the most appropriate time of day. […] In short, sleep has probably evolved as a species-specific response to a 24-hour world in which light, temperature, and food availability change dramatically. Sleep is a period of physical inactivity when individuals avoid movement within an environment to which they are poorly adapted, while using this time to undertake essential housekeeping functions demanded by their biology.”

“Sleep propensity in humans is closely correlated with the melatonin profile but this may be correlation and not causation. Indeed, individuals who do not produce melatonin (e.g. tetraplegic individuals, people on beta-blockers, or pinealectomized patients) still exhibit circadian sleep/wake rhythms with only very minor detectable changes. Another correlation between melatonin and sleep relates to levels of alertness. When melatonin is suppressed by light at night alertness levels increase, suggesting that melatonin and sleep propensity are directly connected. However, increases in alertness occur before a significant drop in blood melatonin. Furthermore, increased light during the day will also improve alertness when melatonin levels are already low. These findings suggest that melatonin is not a direct mediator of alertness and hence sleepiness. Taking synthetic melatonin or synthetic analogues of melatonin produces a mild sleepiness in about 70 per cent of people, especially when no natural melatonin is being released. The mechanism whereby melatonin produces mild sedation remains unclear.”


Teleost multiple tissue (tmt) opsin.
Suprachiasmatic nucleus.
Neuromedin S.
Food-entrainable circadian oscillators in the brain.
John Harrison. Seymour Benzer. Ronald Konopka. Jeffrey C. Hall. Michael Rosbash. Michael W. Young.
Circadian Oscillators: Around the Transcription-Translation Feedback Loop and on to Output.
Period (gene). Timeless (gene). CLOCK. Cycle (gene). Doubletime (gene). Cryptochrome. Vrille Gene.
Basic helix-loop-helix.
The clockwork orange Drosophila protein functions as both an activator and a repressor of clock gene expression.
RAR-related orphan receptor. RAR-related orphan receptor alpha.
The two-process model of sleep regulation: a reappraisal.

September 30, 2018 Posted by | Books, Genetics, Medicine, Molecular biology, Neurology, Ophthalmology | Leave a comment


The words included in the post below were mostly words which I encountered while reading the books Personal Relationships, Circadian Rhythms, Quick Service, Principles of memory, Feet of Clay, The Reverse of the Medal, and The Letter of Marque.

Camouflet. Dissimulation. Nomological. Circumlocutory. EclosionPuissant. Esurient. Hisperic. Ambigram. Scotophilic. Millenarianism. Sonder. Pomology. Oogonium. Vole. Tippler. Autonoetic. Engraphy/engram. Armigerous. Gazunder/guzunder.

Frizzle. Matorral. SclerophyllXerophyte. Teratoma. Shallop. Quartan. Ablative. Prolative. Dispart. Ptarmigan. Starbolins. Idolatrous. Spoom. Cablet. Hostler. Chelonian. Omnium. Toper. Rectitude.

Marthambles. Combe. Holt. Stile. Plover. Andiron. Delf. Boreen. Thief-taker. Patten. Subvention. Hummum. Bustard. Lugger. Vainglory. Penetralia. Limicoline. Astragal. Fillebeg/filibeg. Voluptuous.

Civet. Moil. Impostume. Frowsty. Bob. Snuggery. Legation. Brindle. Epergne. Chough. Shoneen. Pilaff. Phaeton. Gentian. Poldavy. Grebe. Orotund. Panoply. Chiliad. Quiddity.

September 27, 2018 Posted by | Books, Language | Leave a comment

Principles of memory (I)

This book was interesting, but it was more interesting to me on account of the fact that it’s telling you a lot about what sort of memory research has taken place over the years, than it was interesting on account of the authors having presented a good model of how this stuff works. It’s the sort of book that makes you think.

I found the book challenging to blog, for a variety of reasons, but I’ve tried adding some observations of interest from the first four chapters of the coverage below.

“[I]n over 100 years of scientific research on memory, and nearly 50 years after the so-called cognitive revolution, we have nothing that really constitutes a widely accepted and frequently cited law of memory, and perhaps only one generally accepted principle.5 However, there are a plethora of effects, many of which have extensive literatures and hundreds of published empirical demonstrations. One reason for the lack of general laws and principles of memory might be that none exists. Tulving (1985a, p. 385), for example, has argued that “no profound generalizations can be made about memory as a whole,”because memory comprises many different systems and each system operates according to different principles. One can make “general statements about particular kinds of memory,” but one cannot make statements that would apply to all types of memory. […] Roediger (2008) also argues that no general principles of memory exist, but his reasoning and arguments are quite different. He reintroduces Jenkins’ (1979) tetrahedral model of memory, which views all memory experiments as comprising four factors: encoding conditions, retrieval conditions, subject variables, and events (materials and tasks). Using the tetrahedral model as a starting point, Roediger convincingly demonstrates that all of these variables can affect memory performance in different ways and that such complexity does not easily lend itself to a description using general principles. Because of the complexity of the interactions among these variables, Roediger suggests that “the most fundamental principle of learning and memory, perhaps its only sort of general law, is that in making any generalization about memory one must add that ‘it depends'” (p. 247). […]  Where we differ is that we think it possible to produce general principles of memory that take into account these factors. […] The purpose of this monograph is to propose seven principles of human memory that apply to all memory regardless of the type of information, type of processing, hypothetical system supporting memory, or time scale. Although these principles focus on the invariants and empirical regularities of memory, the reader should be forewarned that they are qualitative rather than quantitative, more like regularities in biology than principles of geometry. […] Few, if any, of our principles are novel, and the list is by no means complete. We certainly do not think that there are only seven principles of memory nor, when more principles are proposed, do we think that all seven of our principles will be among the most important.7″

“[T]he two most popular contemporary ways of looking at memory are the multiple systems view and the process (or proceduralist) view.1 Although these views are not always necessarily diametrically opposed […], their respective research programs are focused on different questions and search for different answers. The fundamental difference between structural and processing accounts of memory is whether different rules apply as a function of the way information is acquired, the type of material learned, and the time scale, or whether these can be explained using a single set of principles. […] Proponents of the systems view of memory suggest that memory is divided into multiple systems. Thus, their endeavor is focused on discovering and defining different systems and describing how they work. A “system” within this sort of framework is a structure that is anatomically and evolutionarily distinct from other memory systems and differs in its “methods of acquisition, representation and expression of knowledge” […] Using a variety of techniques, including neuropsychological and statistical methods, advocates of the multiple systems approach […] have identified five major memory systems: procedural memory, the perceptual representation system (PRS), semantic memory, primary or working memory, and episodic memory. […] In general, three criticisms are raised most often: The systems approach (a) has no criteria that produce exactly five different memory systems, (b) relies to a large extent on dissociations, and (c) has great difficulty accounting for the pattern of results observed at both ends of the life span. […] The multiple systems view […] lacks a principled and consistent set of criteria for delineating memory systems. Given the current state of affairs, it is not unthinkable to postulate 5 or 10 or 20 or even more different memory systems […]. Moreover, the specific memory systems that have been identified can be fractionated further, resulting in a situation in which the system is distributed in multiple brain locations, depending on the demands of the task at hand. […] The major strength of the systems view is usually taken to be its ability to account for data from amnesic patients […]. Those individuals seem to have specific deficits in episodic memory (recall and recognition) with very few, if any, deficits in semantic memory, procedural memory, or the PRS. […] [But on the other hand] age-related differences in memory do not follow the pattern predicted by the systems view.”

“From our point of view, asking where memory is “located” in the brain is like asking where running is located in the body. There are certainly parts of the body that are more important (the legs) or less important (the little fingers) in performing the task of running but, in the end, it is an activity that requires complex coordination among a great many body parts and muscle groups. To extend the analogy, looking for differences between memory systems is like looking for differences between running and walking. There certainly are many differences, but the main difference is that running requires more coordination among the different body parts and can be disrupted by small things (such as a corn on the toe) that may not interfere with walking at all. Are we to conclude, then, that running is located in the corn on your toe? […] although there is little doubt that more primitive functions such as low-level sensations can be organized in localized brain regions, it is likely that more complex cognitive functions, such as memory, are more accurately described by a dynamic coordination of distributed interconnected areas […]. This sort of approach implies that memory, per se, does not exist but, instead, “information … resides at the level of the large-scale network” (Bressler & Kelso, 2001, p. 33).”

“The processing view […] emphasizes encoding and retrieval processes instead of the system or location in which the memory might be stored. […] Processes, not structures, are what is fundamental. […] The major criticisms of the processing approaches parallel those that have been leveled at the systems view: (a) number of processes or components (instead of number of systems), (b) testability […], and (c) issues with a special population (amnesia rather than life span development). […] The major weakness of the processing view is the major strength of the systems view: patients diagnosed with amnesic syndrome. […] it is difficult to account for data showing a complete abolishment of episodic memory with no apparent effect on semantic memory, procedural memory, or the PRS without appealing to a separate memory store. […] We suggest that in the absence of a compelling reason to prefer the systems view over the processing view (or vice versa), it would be fruitful to consider memory from a functional perspective. We do not know how many memory systems there are or how to define what a memory system is. We do not know how many processes (or components of processing) there are or how to distinguish them. We do acknowledge that short-term memory and long-term memory seem to differ in some ways, as do episodic memory and semantic memory, but are they really fundamentally different? Both the systems approach and, to a lesser extent, the proceduralist approach emphasize differences. Our approach emphasizes similarities. We suggest that a search for general principles of memory, based on fundamental empirical regularities, can act as a spur to theory development and a reexamination of systems versus process theories of memory.”

Our first principle states that all memory is cue driven; without a cue, there can be no memory […]. By cue we mean a specific prompt or query, such as “Did you see this word on the previous list?” […] cues can also be nonverbal, such as odors […], emotions […], nonverbal sounds […], and images […], to name only a few. Although in many situations the person is fully aware that the cue is part of a memory test, this need not be the case. […] Computer simulation models of memory acknowledge the importance of cues by building them into the system; indeed, computer simulation models will not work unless there is a cue. In general, some input is provided to these models, and then a response is provided. The so-called global models of memory, SAM, TODAM, and MINERVA2, are all cue driven. […] it is hard to conceive of a computer model of memory that is not cue dependent, simply because the computer requires something to start the retrieval process. […] There is near unanimity in the view that memory is cue driven. The one area in which this view is contested concerns a particular form of memory that is characterized by highly restrictive capacity limitations.”

The most commonly cited principle of memory, according to [our] literature search […], is the encoding specificity principle […] Our version of this is called the encoding-retrieval principle [and] states that memory depends on the relation between the conditions at encoding and the conditions at retrieval. […] An appreciation for the importance of the encoding-retrieval interaction came about as the result of studies that examined the potency of various cues to elicit items from memory. A strong cue is a word that elicits a particular target word most of the time. For example, when most people hear the word bloom, the first word that pops into their head is often flower. A weak cue is a word that only rarely elicits a particular target. […] A reasonable prediction seems to be that strong cues should be better than weak cues for eliciting the correct item. However, this inference is not entirely correct because it fails to take into account the relationship between the encoding and retrieval conditions. […] the effectiveness of even a long-standing strong cue depends crucially on the processes that occurred at study and the cues available at test. This basic idea became the foundation of the transfer-appropriate processing framework. […] Taken literally, all that transfer-appropriate processing requires is that the processing done at encoding be appropriate given the processing that will be required at test; it permits processing that is identical and permits processing that is similar. It also, however, permits processing that is completely different as long as it is appropriate. […] many proponents of this view act as if the name were “transfer similar processing” and express the idea as requiring a “match” or “overlap” between study and test. […] However, just because increasing the match sometimes leads to enhanced retention does not mean that it is the match that is the critical variable. […] one can easily set up situations in which the degree of match is improved and memory retention is worse, or the degree of match is decreased and memory is better, or the degree of match is changed (either increased or decreased) and it has no effect on retention. Match, then, is simply not the critical variable in determining memory performance. […] The retrieval conditions include other possible responses, and these other items can affect performance. The most accurate description, then, is that it is the relation between encoding and retrieval that matters, not the degree of match or similarity. […] As Tulving (1983, p. 239) noted, the dynamic relation between encoding and retrieval conditions prohibits any statements that take the following forms:
1. “Items (events) of class X are easier to remember than items (events) of class Y.”
2. “Encoding operations of class X are more effective than encoding operations of class Y.”
3. “Retrieval cues of class X are more effective than retrieval cues of class Y.”
Absolute statements that do not specify both the encoding and the retrieval conditions are meaningless because an experimenter can easily
change some aspect of the encoding or retrieval conditions and greatly change the memory performance.”

In most areas of memory research, forgetting is seen as due to retrieval failure, often ascribed to some form of interference. There are, however, two areas of memory research that propose that forgetting is due to an intrinsic property of the memory trace, namely, decay. […] The two most common accounts view decay as either a mathematical convenience in a model, in which a parameter t is associated with time and leads to worse performance, or as some loss of information, in which it is unclear exactly what aspect of memory is decaying and what parts remain. In principle, a decay theory of memory could be proposed that is specific and testable, such as a process analogous to radioactive decay, in which it is understood precisely what is lost and what remains. Thus far, no such decay theory exists. Decay is posited as the forgetting mechanism in only two areas of memory research, sensory memory and short-term/working memory. […] One reason that time-based forgetting, such as decay, is often invoked is the common belief that short-term/working memory is immune to interference, especially proactive interference […]. This is simply not so. […] interference effects are readily observed in the short term. […] Decay predicts the same decrease for the same duration of distractor activity. Interference predicts differential effects depending on the presence or absence of interfering items. Numerous studies support the interference predictions and disconfirm predictions made on the basis of a decay view […] You might be tempted to say, yes, well, there are occasions in which the passage of time is either uncorrelated with or even negatively correlated with memory performance, but on average, you do worse with longer retention intervals. However, this confirms that the putative principle — the memorability of an event declines as the length of the storage interval increases — is not correct. […] One can make statements about the effects of absolute time, but only to the extent that one specifies both the conditions at encoding and those at retrieval. […] It is trivially easy to construct an experiment in which memory for an item does not change or even gets better the longer the retention interval. Here, we provide only eight examples, although there are numerous other examples; a more complete review and discussion are offered by Capaldi and Neath (1995) and Bjork (2001).”

September 22, 2018 Posted by | Books, Psychology | Leave a comment

Supermassive BHs Mergers

This is the first post I’ve posted in a while; as mentioned earlier the blogging hiatus was due to internet connectivity issues secondary to me moving. Those issues should now have been solved and I hope to soon get back to blogging regularly.

Some links related to the lecture’s coverage:

Supermassive black hole.
Binary black hole. Final parsec problem.
LIGO (Laser Interferometer Gravitational-Wave Observatory). Laser Interferometer Space Antenna (LISA).
Dynamical friction.
Science with the space-based interferometer eLISA: Supermassive black hole binaries (Klein et al., 2016).
Off the Beaten Path: A New Approach to Realistically Model The Orbital Decay of Supermassive Black Holes in Galaxy Formation Simulations (Tremmel et al., 2015).
Dancing to ChaNGa: A Self-Consistent Prediction For Close SMBH Pair Formation Timescales Following Galaxy Mergers (Tremmel et al., 2017).
Growth and activity of black holes in galaxy mergers with varying mass ratios (Capelo et al., 2015).
Tidal heating. Tidal stripping.
Nuclear coups: dynamics of black holes in galaxy mergers (Wassenhove et al., 2013).
The birth of a supermassive black hole binary (Pfister et al., 2017).
Massive black holes and gravitational waves (I assume this is the lecturer’s own notes for a similar talk held at another point in time – there’s a lot of overlap between these notes and stuff covered in the lecture, so if you’re curious you could go have a look. As far as I could see all figures in the second half of the link, as well as a few of the earlier ones, are figures which were also included in this lecture).

September 18, 2018 Posted by | Astronomy, Lectures, Physics, Studies | Leave a comment

Brief update

I recently moved, and it’s taking a lot longer than I’d have liked to get a new internet connection set up. I probably won’t blog much, if at all, in the next couple of weeks.

September 5, 2018 Posted by | Personal | Leave a comment

A few diabetes papers of interest

i. Islet Long Noncoding RNAs: A Playbook for Discovery and Characterization.

“This review will 1) highlight what is known about lncRNAs in the context of diabetes, 2) summarize the strategies used in lncRNA discovery pipelines, and 3) discuss future directions and the potential impact of studying the role of lncRNAs in diabetes.”

“Decades of mouse research and advances in genome-wide association studies have identified several genetic drivers of monogenic syndromes of β-cell dysfunction, as well as 113 distinct type 2 diabetes (T2D) susceptibility loci (1) and ∼60 loci associated with an increased risk of developing type 1 diabetes (T1D) (2). Interestingly, these studies discovered that most T1D and T2D susceptibility loci fall outside of coding regions, which suggests a role for noncoding elements in the development of disease (3,4). Several studies have demonstrated that many causal variants of diabetes are significantly enriched in regions containing islet enhancers, promoters, and transcription factor binding sites (5,6); however, not all diabetes susceptibility loci can be explained by associations with these regulatory regions. […] Advances in RNA sequencing (RNA-seq) technologies have revealed that mammalian genomes encode tens of thousands of RNA transcripts that have similar features to mRNAs, yet are not translated into proteins (7). […] detailed characterization of many of these transcripts has challenged the idea that the central role for RNA in a cell is to give rise to proteins. Instead, these RNA transcripts make up a class of molecules called noncoding RNAs (ncRNAs) that function either as “housekeeping” ncRNAs, such as transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), that are expressed ubiquitously and are required for protein synthesis or as “regulatory” ncRNAs that control gene expression. While the functional mechanisms of short regulatory ncRNAs, such as microRNAs (miRNAs), small interfering RNAs (siRNAs), and Piwi-interacting RNAs (piRNAs), have been described in detail (810), the most abundant and functionally enigmatic regulatory ncRNAs are called long noncoding RNAs (lncRNAs) that are loosely defined as RNAs larger than 200 nucleotides (nt) that do not encode for protein (1113). Although using a definition based strictly on size is somewhat arbitrary, this definition is useful both bioinformatically […] and technically […]. While the 200-nt size cutoff has simplified identification of lncRNAs, this rather broad classification means several features of lncRNAs, including abundance, cellular localization, stability, conservation, and function, are inherently heterogeneous (1517). Although this represents one of the major challenges of lncRNA biology, it also highlights the untapped potential of lncRNAs to provide a novel layer of gene regulation that influences islet physiology and pathophysiology.”

“Although the role of miRNAs in diabetes has been well established (9), analyses of lncRNAs in islets have lagged behind their short ncRNA counterparts. However, several recent studies provide evidence that lncRNAs are crucial components of the islet regulome and may have a role in diabetes (27). […] misexpression of several lncRNAs has been correlated with diabetes complications, such as diabetic nephropathy and retinopathy (2931). There are also preliminary studies suggesting that circulating lncRNAs, such as Gas5, MIAT1, and SENCR, may represent effective molecular biomarkers of diabetes and diabetes-related complications (32,33). Finally, several recent studies have explored the role of lncRNAs in the peripheral metabolic tissues that contribute to energy homeostasis […]. In addition to their potential as genetic drivers and/or biomarkers of diabetes and diabetes complications, lncRNAs can be exploited for the treatment of diabetes. For example, although tremendous efforts have been dedicated to generating replacement β-cells for individuals with diabetes (35,36), human pluripotent stem cell–based β-cell differentiation protocols remain inefficient, and the end product is still functionally and transcriptionally immature compared with primary human β-cells […]. This is largely due to our incomplete knowledge of in vivo differentiation regulatory pathways, which likely include a role for lncRNAs. […] Inherent characteristics of lncRNAs have also made them attractive candidates for drug targeting, which could be exploited for developing new diabetes therapies.”

“With the advancement of high-throughput sequencing techniques, the list of islet-specific lncRNAs is growing exponentially; however, functional characterization is missing for the majority of these lncRNAs. […] Tens of thousands of lncRNAs have been identified in different cell types and model organisms; however, their functions largely remain unknown. Although the tools for determining lncRNA function are technically restrictive, uncovering novel regulatory mechanisms will have the greatest impact on understanding islet function and identifying novel therapeutics for diabetes. To date, no biochemical assay has been used to directly determine the molecular mechanisms by which islet lncRNAs function, which highlights both the infancy of the field and the difficulty in implementing these techniques. […] Due to the infancy of the lncRNA field, most of the biochemical and genetic tools used to interrogate lncRNA function have only recently been developed or are adapted from techniques used to study protein-coding genes and we are only beginning to appreciate the limits and challenges of borrowing strategies from the protein-coding world.”

“The discovery of lncRNAs as a novel class of tissue-specific regulatory molecules has spawned an exciting new field of biology that will significantly impact our understanding of pancreas physiology and pathophysiology. As the field continues to grow, there is growing appreciation that lncRNAs will provide many of the missing components to existing molecular pathways that regulate islet biology and contribute to diabetes when they become dysfunctional. However, to date, most of the experimental emphasis on lncRNAs has focused on large-scale discovery using genome-wide approaches, and there remains a paucity of functional analysis.”

ii. Diabetes and Trajectories of Estimated Glomerular Filtration Rate: A Prospective Cohort Analysis of the Atherosclerosis Risk in Communities Study.

“Diabetes is among the strongest common risk factors for end-stage renal disease, and in industrialized countries, diabetes contributes to ∼50% of cases (3). Less is known about the pattern of kidney function decline associated with diabetes that precedes end-stage renal disease. Identifying patterns of estimated glomerular filtration rate (eGFR) decline could inform monitoring practices for people at high risk of chronic kidney disease (CKD) progression. A better understanding of when and in whom eGFR decline occurs would be useful for the design of clinical trials because eGFR decline >30% is now often used as a surrogate end point for CKD progression (4). Trajectories among persons with diabetes are of particular interest because of the possibility for early intervention and the prevention of CKD development. However, eGFR trajectories among persons with new diabetes may be complex due to the hypothesized period of hyperfiltration by which GFR increases, followed by progressive, rapid decline (5). Using data from the Atherosclerosis Risk in Communities (ARIC) study, an ongoing prospective community-based cohort of >15,000 participants initiated in 1987 with serial measurements of creatinine over 26 years, our aim was to characterize patterns of eGFR decline associated with diabetes, identify demographic, genetic, and modifiable risk factors within the population with diabetes that were associated with steeper eGFR decline, and assess for evidence of early hyperfiltration.”

“We categorized people into groups of no diabetes, undiagnosed diabetes, and diagnosed diabetes at baseline (visit 1) and compared baseline clinical characteristics using ANOVA for continuous variables and Pearson χ2 tests for categorical variables. […] To estimate individual eGFR slopes over time, we used linear mixed-effects models with random intercepts and random slopes. These models were fit on diabetes status at baseline as a nominal variable to adjust the baseline level of eGFR and included an interaction term between diabetes status at baseline and time to estimate annual decline in eGFR by diabetes categories. Linear mixed models were run unadjusted and adjusted, with the latter model including the following diabetes and kidney disease–related risk factors: age, sex, race–center, BMI, systolic blood pressure, hypertension medication use, HDL, prevalent coronary heart disease, annual family income, education status, and smoking status, as well as each variable interacted with time. Continuous covariates were centered at the analytic population mean. We tested model assumptions and considered different covariance structures, comparing nested models using Akaike information criteria. We identified the unstructured covariance model as the most optimal and conservative approach. From the mixed models, we described the overall mean annual decline by diabetes status at baseline and used the random effects to estimate best linear unbiased predictions to describe the distributions of yearly slopes in eGFR by diabetes status at baseline and displayed them using kernel density plots.”

“Because of substantial variation in annual eGFR slope among people with diagnosed diabetes, we sought to identify risk factors that were associated with faster decline. Among those with diagnosed diabetes, we compared unadjusted and adjusted mean annual decline in eGFR by race–APOL1 risk status (white, black– APOL1 low risk, and black–APOL1 high risk) [here’s a relevant link, US], systolic blood pressure […], smoking status […], prevalent coronary heart disease […], diabetes medication use […], HbA1c […], and 1,5-anhydroglucitol (≥10 and <10 μg/mL) [relevant link, US]. Because some of these variables were only available at visit 2, we required that participants included in this subgroup analysis attend both visits 1 and 2 and not be missing information on APOL1 or the variables assessed at visit 2 to ensure a consistent sample size. In addition to diabetes and kidney disease–related risk factors in the adjusted model, we also included diabetes medication use and HbA1c to account for diabetes severity in these analyses. […] to explore potential hyperfiltration, we used a linear spline model to allow the slope to change for each diabetes category between the first 3 years of follow-up (visit 1 to visit 2) and the subsequent time period (visit 2 to visit 5).”

“There were 15,517 participants included in the analysis: 13,698 (88%) without diabetes, 634 (4%) with undiagnosed diabetes, and 1,185 (8%) with diagnosed diabetes at baseline. […] At baseline, participants with undiagnosed and diagnosed diabetes were older, more likely to be black or have hypertension and coronary heart disease, and had higher mean BMI and lower mean HDL compared with those without diabetes […]. Income and education levels were also lower among those with undiagnosed and diagnosed diabetes compared with those without diabetes. […] Overall, there was a nearly linear association between eGFR and age over time, regardless of diabetes status […]. The crude mean annual decline in eGFR was slowest among those without diabetes at baseline (decline of −1.6 mL/min/1.73 m2/year [95% CI −1.6 to −1.5]), faster among those with undiagnosed diabetes compared with those without diabetes (decline of −2.1 mL/min/1.73 m2/year [95% CI −2.2 to −2.0][…]), and nearly twice as rapid among those with diagnosed diabetes compared with those without diabetes (decline of −2.9 mL/min/1.73 m2/year [95% CI −3.0 to −2.8][…]). Adjustment for diabetes and kidney disease–related risk factors attenuated the results slightly, but those with undiagnosed and diagnosed diabetes still had statistically significantly steeper declines than those without diabetes (decline among no diabetes −1.4 mL/min/1.73 m2/year [95% CI −1.5 to −1.4] and decline among undiagnosed diabetes −1.8 mL/min/1.73 m2/year [95% CI −2.0 to −1.7], difference vs. no diabetes of −0.4 mL/min/1.73 m2/year [95% CI −0.5 to −0.3; P < 0.001]; decline among diagnosed diabetes −2.5 mL/min/1.73 m2/year [95% CI −2.6 to −2.4], difference vs. no diabetes of −1.1 mL/min/1.73 m2/ year [95% CI −1.2 to −1.0; P < 0.001]). […] The decline in eGFR per year varied greatly across individuals, particularly among those with diabetes at baseline […] Among participants with diagnosed diabetes at baseline, those who were black, had systolic blood pressure ≥140 mmHg, used diabetes medications, had an HbA1c ≥7% [≥53 mmol/mol], or had 1,5-anhydroglucitol <10 μg/mL were at risk for steeper annual declines than their counterparts […]. Smoking status and prevalent coronary heart disease were not associated with significantly steeper eGFR decline in unadjusted analyses. Adjustment for risk factors, diabetes medication use, and HbA1c attenuated the differences in decline for all subgroups with the exception of smoking status, leaving black race along with APOL1-susceptible genotype, systolic blood pressure ≥140 mmHg, current smoking, insulin use, and HbA1c ≥9% [≥75 mmol/mol] as the risk factors indicative of steeper decline.”

CONCLUSIONS Diabetes is an important risk factor for kidney function decline. Those with diagnosed diabetes declined almost twice as rapidly as those without diabetes. Among people with diagnosed diabetes, steeper declines were seen in those with modifiable risk factors, including hypertension and glycemic control, suggesting areas for continued targeting in kidney disease prevention. […] Few other community-based studies have evaluated differences in kidney function decline by diabetes status over a long period through mid- and late life. One study of 10,184 Canadians aged ≥66 years with creatinine measured during outpatient visits showed results largely consistent with our findings but with much shorter follow-up (median of 2 years) (19). Other studies of eGFR change in a general population have found smaller declines than our results (20,21). A study conducted in Japanese participants aged 40–79 years found a decline of only −0.4 mL/min/1.73 m2/year over the course of two assessments 10 years apart (compared with our estimate among those without diabetes: −1.6 mL/min/1.73 m2/year). This is particularly interesting, as Japan is known to have a higher prevalence of CKD and end-stage renal disease than the U.S. (20). However, this study evaluated participants over a shorter time frame and required attendance at both assessments, which may have decreased the likelihood of capturing severe cases and resulted in underestimation of decline.”

“The Baltimore Longitudinal Study of Aging also assessed kidney function over time in a general population of 446 men, ranging in age from 22 to 97 years at baseline, each with up to 14 measurements of creatinine clearance assessed between 1958 and 1981 (21). They also found a smaller decline than we did (−0.8 mL/min/year), although this study also had notable differences. Their main analysis excluded participants with hypertension and history of renal disease or urinary tract infection and those treated with diuretics and/or antihypertensive medications. Without those exclusions, their overall estimate was −1.1 mL/min/year, which better reflects a community-based population and our results. […] In our evaluation of risk factors that might explain the variation in decline seen among those with diagnosed diabetes, we observed that black race, systolic blood pressure ≥140 mmHg, insulin use, and HbA1c ≥9% (≥75 mmol/mol) were particularly important. Although the APOL1 high-risk genotype is a known risk factor for eGFR decline, African Americans with low-risk APOL1 status continued to be at higher risk than whites even after adjustment for traditional risk factors, diabetes medication use, and HbA1c.”

“Our results are relevant to the design and conduct of clinical trials. Hard clinical outcomes like end-stage renal disease are relatively rare, and a 30–40% decline in eGFR is now accepted as a surrogate end point for CKD progression (4). We provide data on patient subgroups that may experience accelerated trajectories of kidney function decline, which has implications for estimating sample size and ensuring adequate power in future clinical trials. Our results also suggest that end points of eGFR decline might not be appropriate for patients with new-onset diabetes, in whom declines may actually be slower than among persons without diabetes. Slower eGFR decline among those with undiagnosed diabetes, who are likely early in the course of diabetes, is consistent with the hypothesis of hyperfiltration. Similar to other studies, we found that persons with undiagnosed diabetes had higher GFR at the outset, but this was a transient phenomenon, as they ultimately experienced larger declines in kidney function than those without diabetes over the course of follow-up (2325). Whether hyperfiltration is a universal aspect of early disease and, if not, whether it portends worse long-term outcomes is uncertain. Existing studies investigating hyperfiltration as a precursor to adverse kidney outcomes are inconsistent (24,26,27) and often confounded by diabetes severity factors like duration (27). We extended this literature by separating undiagnosed and diagnosed diabetes to help address that confounding.”

iii. Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars.

OBJECTIVE Nonalcoholic fatty liver disease (i.e., increased intrahepatic triglyceride [IHTG] content), predisposes to type 2 diabetes and cardiovascular disease. Adipose tissue lipolysis and hepatic de novo lipogenesis (DNL) are the main pathways contributing to IHTG. We hypothesized that dietary macronutrient composition influences the pathways, mediators, and magnitude of weight gain-induced changes in IHTG.

RESEARCH DESIGN AND METHODS We overfed 38 overweight subjects (age 48 ± 2 years, BMI 31 ± 1 kg/m2, liver fat 4.7 ± 0.9%) 1,000 extra kcal/day of saturated (SAT) or unsaturated (UNSAT) fat or simple sugars (CARB) for 3 weeks. We measured IHTG (1H-MRS), pathways contributing to IHTG (lipolysis ([2H5]glycerol) and DNL (2H2O) basally and during euglycemic hyperinsulinemia), insulin resistance, endotoxemia, plasma ceramides, and adipose tissue gene expression at 0 and 3 weeks.

RESULTS Overfeeding SAT increased IHTG more (+55%) than UNSAT (+15%, P < 0.05). CARB increased IHTG (+33%) by stimulating DNL (+98%). SAT significantly increased while UNSAT decreased lipolysis. SAT induced insulin resistance and endotoxemia and significantly increased multiple plasma ceramides. The diets had distinct effects on adipose tissue gene expression.”

CONCLUSIONS NAFLD has been shown to predict type 2 diabetes and cardiovascular disease in multiple studies, even independent of obesity (1), and also to increase the risk of progressive liver disease (17). It is therefore interesting to compare effects of different diets on liver fat content and understand the underlying mechanisms. We examined whether provision of excess calories as saturated (SAT) or unsaturated (UNSAT) fats or simple sugars (CARB) influences the metabolic response to overfeeding in overweight subjects. All overfeeding diets increased IHTGs. The SAT diet induced a greater increase in IHTGs than the UNSAT diet. The composition of the diet altered sources of excess IHTGs. The SAT diet increased lipolysis, whereas the CARB diet stimulated DNL. The SAT but not the other diets increased multiple plasma ceramides, which increase the risk of cardiovascular disease independent of LDL cholesterol (18). […] Consistent with current dietary recommendations (3638), the current study shows that saturated fat is the most harmful dietary constituent regarding IHTG accumulation.”

iv. Primum Non Nocere: Refocusing Our Attention on Severe Hypoglycemia Prevention.

“Severe hypoglycemia, defined as low blood glucose requiring assistance for recovery, is arguably the most dangerous complication of type 1 diabetes as it can result in permanent cognitive impairment, seizure, coma, accidents, and death (1,2). Since the Diabetes Control and Complications Trial (DCCT) demonstrated that intensive intervention to normalize glucose prevents long-term complications but at the price of a threefold increase in the rate of severe hypoglycemia (3), hypoglycemia has been recognized as the major limitation to achieving tight glycemic control. Severe hypoglycemia remains prevalent among adults with type 1 diabetes, ranging from ∼1.4% per year in the DCCT/EDIC (Epidemiology of Diabetes Interventions and Complications) follow-up cohort (4) to ∼8% in the T1D Exchange clinic registry (5).

One the greatest risk factors for severe hypoglycemia is impaired awareness of hypoglycemia (6), which increases risk up to sixfold (7,8). Hypoglycemia unawareness results from deficient counterregulation (9), where falling glucose fails to activate the autonomic nervous system to produce neuroglycopenic symptoms that normally help patients identify and respond to episodes (i.e., sweating, palpitations, hunger) (2). An estimated 20–25% of adults with type 1 diabetes have impaired hypoglycemia awareness (8), which increases to more than 50% after 25 years of disease duration (10).

Screening for hypoglycemia unawareness to identify patients at increased risk of severe hypoglycemic events should be part of routine diabetes care. Self-identified impairment in awareness tends to agree with clinical evaluation (11). Therefore, hypoglycemia unawareness can be easily and effectively screened […] Interventions for hypoglycemia unawareness include a range of behavioral and medical options. Avoiding hypoglycemia for at least several weeks may partially reverse hypoglycemia unawareness and reduce risk of future episodes (1). Therefore, patients with hypoglycemia and unawareness may be advised to raise their glycemic and HbA1c targets (1,2). Diabetes technology can play a role, including continuous subcutaneous insulin infusion (CSII) to optimize insulin delivery, continuous glucose monitoring (CGM) to give technological awareness in the absence of symptoms (14), or the combination of the two […] Aside from medical management, structured or hypoglycemia-specific education programs that aim to prevent hypoglycemia are recommended for all patients with severe hypoglycemia or hypoglycemia unawareness (14). In randomized trials, psychoeducational programs that incorporate increased education, identification of personal risk factors, and behavior change support have improved hypoglycemia unawareness and reduced the incidence of both nonsevere and severe hypoglycemia over short periods of follow-up (17,18) and extending up to 1 year (19).”

“Given that the presence of hypoglycemia unawareness increases the risk of severe hypoglycemia, which is the strongest predictor of a future episode (2,4), the implication that intervention can break the life-threatening and traumatizing cycle of hypoglycemia unawareness and severe hypoglycemia cannot be overstated. […] new evidence of durability of effect across treatment regimen without increasing the risk for long-term complications creates an imperative for action. In combination with existing screening tools and a body of literature investigating novel interventions for hypoglycemia unawareness, these results make the approach of screening, recognition, and intervention very compelling as not only a best practice but something that should be incorporated in universal guidelines on diabetes care, particularly for individuals with type 1 diabetes […] Hyperglycemia is […] only part of the puzzle in diabetes management. Long-term complications are decreasing across the population with improved interventions and their implementation (24). […] it is essential to shift our historical obsession with hyperglycemia and its long-term complications to equally emphasize the disabling, distressing, and potentially fatal near-term complication of our treatments, namely severe hypoglycemia. […] The health care providers’ first dictum is primum non nocere — above all, do no harm. ADA must refocus our attention on severe hypoglycemia as an iatrogenic and preventable complication of our interventions.”

v. Anti‐vascular endothelial growth factor combined with intravitreal steroids for diabetic macular oedema.


The combination of steroid and anti‐vascular endothelial growth factor (VEGF) intravitreal therapeutic agents could potentially have synergistic effects for treating diabetic macular oedema (DMO). On the one hand, if combined treatment is more effective than monotherapy, there would be significant implications for improving patient outcomes. Conversely, if there is no added benefit of combination therapy, then people could be potentially exposed to unnecessary local or systemic side effects.


To assess the effects of intravitreal agents that block vascular endothelial growth factor activity (anti‐VEGF agents) plus intravitreal steroids versus monotherapy with macular laser, intravitreal steroids or intravitreal anti‐VEGF agents for managing DMO.”

“There were eight RCTs (703 participants, 817 eyes) that met our inclusion criteria with only three studies reporting outcomes at one year. The studies took place in Iran (3), USA (2), Brazil (1), Czech Republic (1) and South Korea (1). […] When comparing anti‐VEGF/steroid with anti‐VEGF monotherapy as primary therapy for DMO, we found no meaningful clinical difference in change in BCVA [best corrected visual acuity] […] or change in CMT [central macular thickness] […] at one year. […] There was very low‐certainty evidence on intraocular inflammation from 8 studies, with one event in the anti‐VEGF/steroid group (313 eyes) and two events in the anti‐VEGF group (322 eyes). There was a greater risk of raised IOP (Peto odds ratio (OR) 8.13, 95% CI 4.67 to 14.16; 635 eyes; 8 RCTs; moderate‐certainty evidence) and development of cataract (Peto OR 7.49, 95% CI 2.87 to 19.60; 635 eyes; 8 RCTs; moderate‐certainty evidence) in eyes receiving anti‐VEGF/steroid compared with anti‐VEGF monotherapy. There was low‐certainty evidence from one study of an increased risk of systemic adverse events in the anti‐VEGF/steroid group compared with the anti‐VEGF alone group (Peto OR 1.32, 95% CI 0.61 to 2.86; 103 eyes).”

“One study compared anti‐VEGF/steroid versus macular laser therapy. At one year investigators did not report a meaningful difference between the groups in change in BCVA […] or change in CMT […]. There was very low‐certainty evidence suggesting an increased risk of cataract in the anti‐VEGF/steroid group compared with the macular laser group (Peto OR 4.58, 95% 0.99 to 21.10, 100 eyes) and an increased risk of elevated IOP in the anti‐VEGF/steroid group compared with the macular laser group (Peto OR 9.49, 95% CI 2.86 to 31.51; 100 eyes).”

“Authors’ conclusions

Combination of intravitreal anti‐VEGF plus intravitreal steroids does not appear to offer additional visual benefit compared with monotherapy for DMO; at present the evidence for this is of low‐certainty. There was an increased rate of cataract development and raised intraocular pressure in eyes treated with anti‐VEGF plus steroid versus anti‐VEGF alone. Patients were exposed to potential side effects of both these agents without reported additional benefit.”

vi. Association between diabetic foot ulcer and diabetic retinopathy.

“More than 25 million people in the United States are estimated to have diabetes mellitus (DM), and 15–25% will develop a diabetic foot ulcer (DFU) during their lifetime [1]. DFU is one of the most serious and disabling complications of DM, resulting in significantly elevated morbidity and mortality. Vascular insufficiency and associated neuropathy are important predisposing factors for DFU, and DFU is the most common cause of non-traumatic foot amputation worldwide. Up to 70% of all lower leg amputations are performed on patients with DM, and up to 85% of all amputations are preceded by a DFU [2, 3]. Every year, approximately 2–3% of all diabetic patients develop a foot ulcer, and many require prolonged hospitalization for the treatment of ensuing complications such as infection and gangrene [4, 5].

Meanwhile, a number of studies have noted that diabetic retinopathy (DR) is associated with diabetic neuropathy and microvascular complications [610]. Despite the magnitude of the impact of DFUs and their consequences, little research has been performed to investigate the characteristics of patients with a DFU and DR. […] the aim of this study was to investigate the prevalence of DR in patients with a DFU and to elucidate the potential association between DR and DFUs.”

“A retrospective review was conducted on DFU patients who underwent ophthalmic and vascular examinations within 6 months; 100 type 2 diabetic patients with DFU were included. The medical records of 2496 type 2 diabetic patients without DFU served as control data. DR prevalence and severity were assessed in DFU patients. DFU patients were compared with the control group regarding each clinical variable. Additionally, DFU patients were divided into two groups according to DR severity and compared. […] Out of 100 DFU patients, 90 patients (90%) had DR and 55 (55%) had proliferative DR (PDR). There was no significant association between DR and DFU severities (R = 0.034, p = 0.734). A multivariable analysis comparing type 2 diabetic patients with and without DFUs showed that the presence of DR [OR, 226.12; 95% confidence interval (CI), 58.07–880.49; p < 0.001] and proliferative DR [OR, 306.27; 95% CI, 64.35–1457.80; p < 0.001), higher HbA1c (%, OR, 1.97, 95% CI, 1.46–2.67; p < 0.001), higher serum creatinine (mg/dL, OR, 1.62, 95% CI, 1.06–2.50; p = 0.027), older age (years, OR, 1.12; 95% CI, 1.06–1.17; p < 0.001), higher pulse pressure (mmHg, OR, 1.03; 95% CI, 1.00–1.06; p = 0.025), lower cholesterol (mg/dL, OR, 0.94; 95% CI, 0.92–0.97; p < 0.001), lower BMI (kg/m2, OR, 0.87, 95% CI, 0.75–1.00; p = 0.044) and lower hematocrit (%, OR, 0.80, 95% CI, 0.74–0.87; p < 0.001) were associated with DFUs. In a subgroup analysis of DFU patients, the PDR group had a longer duration of diabetes mellitus, higher serum BUN, and higher serum creatinine than the non-PDR group. In the multivariable analysis, only higher serum creatinine was associated with PDR in DFU patients (OR, 1.37; 95% CI, 1.05–1.78; p = 0.021).


Diabetic retinopathy is prevalent in patients with DFU and about half of DFU patients had PDR. No significant association was found in terms of the severity of these two diabetic complications. To prevent blindness, patients with DFU, and especially those with high serum creatinine, should undergo retinal examinations for timely PDR diagnosis and management.”

August 29, 2018 Posted by | Diabetes, Epidemiology, Genetics, Medicine, Molecular biology, Nephrology, Ophthalmology, Statistics, Studies | Leave a comment

Nephrology Board Review

Some links related to the lecture’s coverage:

Diabetic nephropathy.
Henoch–Schönlein purpura.
Leukocytoclastic Vasculitis.
Glomerulonephritis. Rapidly progressive glomerulonephritis.
Analgesic nephropathy.
Allergic Interstitial Nephritis: Clinical Features and Pathogenesis.
Nonsteroidal anti-inflammatory drugs: effects on kidney function (Whelton & Hamilton, J Clin Pharmacol. 1991 Jul;31(7):588-98).
Goodpasture syndrome.
Creatinine. Limitations of serum creatinine as a marker of renal function.
U wave.
Nephrolithiasis. Calcium oxalate.
Calcium gluconate.
Effect of various therapeutic approaches on plasma potassium and major regulating factors in terminal renal failure (Blumberg et al., 1988).
Effect of prolonged bicarbonate administration on plasma potassium in terminal renal failure (Blumberg et al., 1992).
Renal tubular acidosis.
Urine anion gap.
Metabolic acidosis.
Contrast-induced nephropathy.
Lipiduria. Urinary cast.
Membranous glomerulonephritis.
Postinfectious glomerulonephritis.

August 28, 2018 Posted by | Cardiology, Chemistry, Diabetes, Lectures, Medicine, Nephrology, Pharmacology, Studies | Leave a comment

Circadian Rhythms (I)

“Circadian rhythms are found in nearly every living thing on earth. They help organisms time their daily and seasonal activities so that they are synchronized to the external world and the predictable changes in the environment. These biological clocks provide a cross-cutting theme in biology and they are incredibly important. They influence everything, from the way growing sunflowers track the sun from east to west, to the migration timing of monarch butterflies, to the morning peaks in cardiac arrest in humans. […] Years of work underlie most scientific discoveries. Explaining these discoveries in a way that can be understood is not always easy. We have tried to keep the general reader in mind but in places perseverance on the part of the reader may be required. In the end we were guided by one of our reviewers, who said: ‘If you want to understand calculus you have to show the equations.’”

The above quote is from the book‘s foreword. I really liked this book and I was close to giving it five stars on goodreads. Below I have added some observations and links related to the first few chapters of the book’s coverage (as noted in my review on goodreads the second half of the book is somewhat technical, and I’ve not yet decided if I’ll be blogging that part of the book in much detail, if at all).

“There have been over a trillion dawns and dusks since life began some 3.8 billion years ago. […] This predictable daily solar cycle results in regular and profound changes in environmental light, temperature, and food availability as day follows night. Almost all life on earth, including humans, employs an internal biological timer to anticipate these daily changes. The possession of some form of clock permits organisms to optimize physiology and behaviour in advance of the varied demands of the day/night cycle. Organisms effectively ‘know’ the time of day. Such internally generated daily rhythms are called ‘circadian rhythms’ […] Circadian rhythms are embedded within the genomes of just about every plant, animal, fungus, algae, and even cyanobacteria […] Organisms that use circadian rhythms to anticipate the rotation of the earth are thought to have a major advantage over both their competitors and predators. For example, it takes about 20–30 minutes for the eyes of fish living among coral reefs to switch vision from the night to daytime state. A fish whose eyes are prepared in advance for the coming dawn can exploit the new environment immediately. The alternative would be to wait for the visual system to adapt and miss out on valuable activity time, or emerge into a world where it would be more difficult to avoid predators or catch prey until the eyes have adapted. Efficient use of time to maximize survival almost certainly provides a large selective advantage, and consequently all organisms seem to be led by such anticipation. A circadian clock also stops everything happening within an organism at the same time, ensuring that biological processes occur in the appropriate sequence or ‘temporal framework’. For cells to function properly they need the right materials in the right place at the right time. Thousands of genes have to be switched on and off in order and in harmony. […] All of these processes, and many others, take energy and all have to be timed to best effect by the millisecond, second, minute, day, and time of year. Without this internal temporal compartmentalization and its synchronization to the external environment our biology would be in chaos. […] However, to be biologically useful, these rhythms must be synchronized or entrained to the external environment, predominantly by the patterns of light produced by the earth’s rotation, but also by other rhythmic changes within the environment such as temperature, food availability, rainfall, and even predation. These entraining signals, or time-givers, are known as zeitgebers. The key point is that circadian rhythms are not driven by an external cycle but are generated internally, and then entrained so that they are synchronized to the external cycle.”

“It is worth emphasizing that the concept of an internal clock, as developed by Richter and Bünning, has been enormously powerful in furthering our understanding of biological processes in general, providing a link between our physiological understanding of homeostatic mechanisms, which try to maintain a constant internal environment despite unpredictable fluctuations in the external environment […], versus the circadian system which enables organisms to anticipate periodic changes in the external environment. The circadian system provides a predictive 24-hour baseline in physiological parameters, which is then either defended or temporarily overridden by homeostatic mechanisms that accommodate an acute environmental challenge. […] Zeitgebers and the entrainment pathway synchronize the internal day to the astronomical day, usually via the light/dark cycle, and multiple output rhythms in physiology and behaviour allow appropriately timed activity. The multitude of clocks within a multicellular organism can all potentially tick with a different phase angle […], but usually they are synchronized to each other and by a central pacemaker which is in turn entrained to the external world via appropriate zeitgebers. […] Most biological reactions vary greatly with temperature and show a Q10 temperature coefficient of about 2 […]. This means that the biological process or reaction rate doubles as a consequence of increasing the temperature by 10°C up to a maximum temperature at which the biological reaction stops. […] a 10°C temperature increase doubles muscle performance. By contrast, circadian rhythms exhibit a Q10 close to 1 […] Clocks without temperature compensation are useless. […] Although we know that circadian clocks show temperature compensation, and that this phenomenon is a conserved feature across all circadian rhythms, we have little idea how this is achieved.”

“The systematic study of circadian rhythms only really started in the 1950s, and the pioneering studies of Colin Pittendrigh brought coherence to this emerging new discipline. […] From [a] mass of emerging data, Pittendrigh had key insights and defined the essential properties of circadian rhythms across all life. Namely that: all circadian rhythms are endogenous and show near 24-hour rhythms in a biological process (biochemistry, physiology, or behaviour); they persist under constant conditions for several cycles; they are entrained to the astronomical day via synchronizing zeitgebers; and they show temperature compensation such that the period of the oscillation does not alter appreciably with changes in environmental temperature. Much of the research since the 1950s has been the translation of these formalisms into biological structures and processes, addressing such questions as: What is the clock and where is it located within the intracellular processes of the cell? How can a set of biochemical reactions produce a regular self-sustaining rhythm that persists under constant conditions and has a period of about 24 hours? How is this internal oscillation synchronized by zeitgebers such as light to the astronomical day? Why is the clock not altered by temperature, speeding up when the environment gets hotter and slowing down in the cold? How is the information of the near 24-hour rhythm communicated to the rest of the organism?”

“There have been hundreds of studies showing that a broad range of activities, both physical and cognitive, vary across the 24-hour day: tooth pain is lowest in the morning; proofreading is best performed in the evening; labour pains usually begin at night and most natural births occur in the early morning hours. The accuracy of short and long badminton serves is higher in the afternoon than in the morning and evening. Accuracy of first serves in tennis is better in the morning and afternoon than in the evening, although speed is higher in the evening than in the morning. Swimming velocity over 50 metres is higher in the evening than in the morning and afternoon. […] The majority of studies report that performance increases from morning to afternoon or evening. […] Typical ‘optimal’ times of day for physical or cognitive activity are gathered routinely from population studies […]. However, there is considerable individual variation. Peak performance will depend upon age, chronotype, time zone, and for behavioural tasks how many hours the participant has been awake when conducting the task, and even the nature of the task itself. As a general rule, the circadian modulation of cognitive functioning results in an improved performance over the day for younger adults, while in older subjects it deteriorates. […] On average the circadian rhythms of an individual in their late teens will be delayed by around two hours compared with an individual in their fifties. As a result the average teenager experiences considerable social jet lag, and asking a teenager to get up at 07.00 in the morning is the equivalent of asking a 50-year-old to get up at 05.00 in the morning.”

“Day versus night variations in blood pressure and heart rate are among the best-known circadian rhythms of physiology. In humans, there is a 24-hour variation in blood pressure with a sharp rise before awakening […]. Many cardiovascular events, such as sudden cardiac death, myocardial infarction, and stroke, display diurnal variations with an increased incidence between 06.00 and 12.00 in the morning. Both atrial and ventricular arrhythmias appear to exhibit circadian patterning as well, with a higher frequency during the day than at night. […] Myocardial infarction (MI) is two to three times more frequent in the morning than at night. In the early morning, the increased systolic blood pressure and heart rate results in an increased energy and oxygen demand by the heart, while the vascular tone of the coronary artery rises in the morning, resulting in a decreased coronary blood flow and oxygen supply. This mismatch between supply and demand underpins the high frequency of onset of MI. Plaque blockages are more likely to occur in the morning as platelet surface activation markers have a circadian pattern producing a peak of thrombus formation and platelet aggregation. The resulting hypercoagulability partially underlies the morning onset of MI.”

“A critical area where time of day matters to the individual is the optimum time to take medication, a branch of medicine that has been termed ‘chronotherapy’. Statins are a family of cholesterol-lowering drugs which inhibit HMGCR-reductase […] HMGCR is under circadian control and is highest at night. Hence those statins with a short half-life, such as simvastatin and lovastatin, are most effective when taken before bedtime. In another clinical domain entirely, recent studies have shown that anti-flu vaccinations given in the morning provoke a stronger immune response than those given in the afternoon. The idea of using chronotherapy to improve the efficacy of anti-cancer drugs has been around for the best part of 30 years. […] In experimental models more than thirty anti-cancer drugs have been found to vary in toxicity and efficacy by as much as 50 per cent as a function of time of administration. Although Lévi and others have shown the advantages to treating individual patients by different timing regimes, few hospitals have taken it up. One reason is that the best time to apply many of these treatments is late in the day or during the night, precisely when most hospitals lack the infrastructure and personnel to deliver such treatments.”

“Flying across multiple time zones and shift work has significant economic benefits, but the costs in terms of ill health are only now becoming clear. Sleep and circadian rhythm disruption (SCRD) is almost always associated with poor health. […] The impact of jet lag has long been known by elite athletes […] even when superbly fit individuals fly across time zones there is a very prolonged disturbance of circadian-driven rhythmic physiology. […] Horses also suffer from jet lag. […] Even bees can get jet lag. […] The misalignments that occur as a result of the occasional transmeridian flight are transient. Shift working represents a chronic misalignment. […] Nurses are one of the best-studied groups of night shift workers. Years of shift work in these individuals has been associated with a broad range of health problems including type II diabetes, gastrointestinal disorders, and even breast and colorectal cancers. Cancer risk increases with the number of years of shift work, the frequency of rotating work schedules, and the number of hours per week working at night [For people who are interested to know more about this, I previously covered a text devoted exclusively to these topics here and here.]. The correlations are so strong that shift work is now officially classified as ‘probably carcinogenic [Group 2A]’ by the World Health Organization. […] the partners and families of night shift workers need to be aware that mood swings, loss of empathy, and irritability are common features of working at night.”

“There are some seventy sleep disorders recognized by the medical community, of which four have been labelled as ‘circadian rhythm sleep disorders’ […] (1) Advanced sleep phase disorder (ASPD) […] is characterized by difficulty staying awake in the evening and difficulty staying asleep in the morning. Typically individuals go to bed and rise about three or more hours earlier than the societal norm. […] (2) Delayed sleep phase disorder (DSPD) is a far more frequent condition and is characterized by a 3-hour delay or more in sleep onset and offset and is a sleep pattern often found in some adolescents and young adults. […] ASPD and DSPD can be considered as pathological extremes of morning or evening preferences […] (3) Freerunning or non-24-hour sleep/wake rhythms occur in blind individuals who have either had their eyes completely removed or who have no neural connection from the retina to the brain. These people are not only visually blind but are also circadian blind. Because they have no means of detecting the synchronizing light signals they cannot reset their circadian rhythms, which freerun with a period of about 24 hours and 10 minutes. So, after six days, internal time is on average 1 hour behind environmental time. (4) Irregular sleep timing has been observed in individuals who lack a circadian clock as a result of a tumour in their anterior hypothalamus […]. Irregular sleep timing is [also] commonly found in older people suffering from dementia. It is an extremely important condition because one of the major factors in caring for those with dementia is the exhaustion of the carers which is often a consequence of the poor sleep patterns of those for whom they are caring. Various protocols have been attempted in nursing homes using increased light in the day areas and darkness in the bedrooms to try and consolidate sleep. Such approaches have been very successful in some individuals […] Although insomnia is the commonly used term to describe sleep disruption, technically insomnia is not a ‘circadian rhythm sleep disorder’ but rather a general term used to describe irregular or disrupted sleep. […] Insomnia is described as a ‘psychophysiological’ condition, in which mental and behavioural factors play predisposing, precipitating, and perpetuating roles. The factors include anxiety about sleep, maladaptive sleep habits, and the possibility of an underlying vulnerability in the sleep-regulating mechanism. […] Even normal ‘healthy ageing’ is associated with both circadian rhythm sleep disorders and insomnia. Both the generation and regulation of circadian rhythms have been shown to become less robust with age, with blunted amplitudes and abnormal phasing of key physiological processes such as core body temperature, metabolic processes, and hormone release. Part of the explanation may relate to a reduced light signal to the clock […]. In the elderly, the photoreceptors of the eye are often exposed to less light because of the development of cataracts and other age-related eye disease. Both these factors have been correlated with increased SCRD.”

“Circadian rhythm research has mushroomed in the past twenty years, and has provided a much greater understanding of the impact of both imposed and illness-related SCRD. We now appreciate that our increasingly 24/7 society and social disregard for biological time is having a major impact upon our health. Understanding has also been gained about the relationship between SCRD and a spectrum of different illnesses. SCRD in illness is not simply the inconvenience of being unable to sleep at an appropriate time but is an agent that exacerbates or causes serious health problems.”


Circadian rhythm.
Phase (waves). Phase angle.
Jean-Jacques d’Ortous de Mairan.
John Harrison.
Munich Chronotype Questionnaire.
Seasonal affective disorder. Light therapy.
Parkinson’s disease. Multiple sclerosis.

August 25, 2018 Posted by | Biology, Books, Cancer/oncology, Cardiology, Medicine | Leave a comment

Combinatorics (II)

I really liked this book. Below I have added some links and quotes related to the second half of the book’s coverage.

“An n × n magic square, or a magic square of order n, is a square array of numbers — usually (but not necessarily) the numbers from 1 to n2 — arranged in such a way that the sum of the numbers in each of the n rows, each of the n columns, or each of the two main diagonals is the same. A semi-magic square is a square array in which the sum of the numbers in each row or column, but not necessarily the diagonals, is the same. We note that if the entries are 1 to n2, then the sum of the numbers in the whole array is
1 + 2 + 3 + … + n2n2 (n2 + 1) / 2
on summing the arithmetic progression. Because the n rows and columns have the same ‘magic sum’, the numbers in each single row or column add up to (1/n)th of this, which is n (n2+1) / 2 […] An nn latin squareor a latin square of order n, is a square array with n symbols arranged so that each symbol appears just once in each row and column. […] Given a latin square, we can obtain others by rearranging the rows or the columns, or by permuting the symbols. For an n × n latin square with symbols 1, 2, … , n, we can thereby arrange that the numbers in the first row and the first column appear in order as 1, 2, … , n. Such a latin square is called normalized […] A familiar form of latin square is the sudoku puzzle […] How many n x n latin squares are there for a given order of n? The answer is known only for n ≤ 11. […] The number of normalized latin squares of order 11 has an impressive forty-eight digits.”

“A particular type of latin square is the cyclic square, where the symbols appear in the same cyclic order, moving one place to the left in each successive row, so that the entry at the beginning of each line appears at the end of the next one […] An extension of this idea is where the symbols move more places to the left in each successive row […] We can construct a latin square row by row from its first row, always taking care that no symbol appears twice in any column. […] An important concept […] is that of a set of orthogonal latin squares […] two n × n latin squares are orthogonal if, when superimposed, each of the n2 possible pairings of a symbol from each square appears exactly once. […] pairs of orthogonal latin squares are […] used in agricultural experiments. […] We can extend the idea of orthogonality beyond pairs […] A set of mutually orthogonal latin squares (sometimes abbreviated to MOLS) is a set of latin squares, any two of which are orthogonal […] Note that there can be at most n-1 MOLS of order n. […] A full set of MOLS is called a complete set […] We can ask the following question: For which values of n does there exist a complete set of n × n mutually orthogonal latin squares? As several authors have shown, a complete set exists whenever n is a prime number (other than 2) or a power of a prime […] In 1922, H. L. MacNeish generalized this result by observing that if n has prime factorization p, then the number of MOLS is at least min (p1a x p2b, … , pkz) – 1″.

“Consider the following [problem] involving comparisons between a number of varieties of a commodity: A consumer organization wishes to compare seven brands of detergent and arranges a number of tests. But since it may be uneconomic or inconvenient for each tester to compare all seven brands it is decided that each tester should compare just three brands. How should the trials be organized if each brand is to be tested the same number of times and each pair of brands is to be compared directly? […] A block design consists of a set of v varieties arranged into b blocks. […] [if we] further assume that each block contains the same number k of varieties, and each variety appears in the same number r of blocks […] [the design is] called [an] equireplicate design […] for every block design we have v x r = b x k. […] It would clearly be preferable if all pairs of varieties in a design were compared the same number of times […]. Such a design is called balanced, or a balanced incomplete-block design (often abbreviated to BIBD). The number of times that any two varieties are compared is usually denoted by λ […] In a balanced block design the parameters v, b, k, r, and λ are not independent […] [Rather it is the case that:] r x (k -1) = λ x (v – 1). […] The conditions v x r = b x k and r x (k -1) = λ x (v – 1) are both necessary for a design to be balanced, but they’re not sufficient since there are designs satisfying both conditions which are not balanced. Another necessary condition for a design to be balanced is v ≤ b, a result known as Fisher’s inequality […] A balanced design for which v = b, and therefore k = r, is called a symmetric design“.

“A block design with v varieties is resolvable if its blocks can be rearranged into subdesigns, called replicates, each of which contains every variety just once. [….] we define a finite projective plane to be an arrangement of a finite number of points and a finite number of lines with the properties that: [i] Any two points lie on exactly one line. [ii] Any two lines pass through exactly one point.
Note that this differs from our usual Euclidean geometry, where any two lines pass through exactly one point unless they’re parallel. Omitting these italicized words produces a completely different type of geometry from the one we’re used to, since there’s now a ‘duality’ or symmetry between points and lines, according to which any statement about points lying on lines gives rise to a statement about lines passing through points, and vice versa. […] We say that the finite projective plane has order n if each line contains n + 1 points. […] removing a single line from a projective plane of order n, and the n + 1 points on this line, gives a square pattern with n2 points and n2 + n lines where each line contains n points and each point lies on n + 1 lines. Such a diagram is called an affine plane of order n. […] This process is reversible. If we start with an affine plane of order n and add another line joined up appropriately, we get a projective plane of order n. […] Every finite projective plane gives rise to a symmetric balanced design. […] In general, a finite projective plane of order n, with n2 + n + 1 points and lines and with n + 1 points on each line and n + 1 lines through each point, gives rise to a balanced symmetric design with parameters v = b = n2 + n + 1, k = r = n + 1, and λ = 1. […] Every finite affine plane gives rise to a resolvable design. […] In general, an affine plane of order n, obtained by removing a line and n + 1 points from a projective plane of order n, gives rise to a resolvable design with parameters v = n2 , b = n2 + n , k = n , and r = n + 1. […] Every finite affine plane corresponds to a complete set of orthogonal latin squares.”


Regular polygon.
Internal and external angles.
Triangular tiling. Square tiling. Hexagonal tiling.
Semiregular tessellations.
Penrose tiling.
Platonic solid.
Euler’s polyhedron formula.
Prism (geometry). Antiprism.
Geodesic dome.
Graph theory.
Complete graph. Complete bipartite graph. Cycle graph.
Degree (graph theory).
Handshaking lemma.
Ramsey theory.
Tree (graph theory).
Eulerian and Hamiltonian Graphs. Hamiltonian path.
Icosian game.
Knight’s tour problem.
Planar graph. Euler’s formula for plane graphs.
Kuratowski’s theorem.
Dual graph.
Lo Shu Square.
Melencolia I.
Euler’s Thirty-six officers problem.
Steiner triple system.
Partition (number theory).
Pentagonal number. Pentagonal number theorem.
Ramanujan’s congruences.

August 23, 2018 Posted by | Books, Mathematics, Statistics | Leave a comment

Personal Relationships… (III)

Some more observations from the book below:

Early research on team processes […] noted that for teams to be effective members must minimize “process losses” and maximize “process gains” — that is, identify ways the team can collectively perform at a level that exceeds the average potential of individual members. To do so, teams need to minimize interpersonal disruptions and maximize interpersonal facilitation among its members […] the prevailing view — backed by empirical findings […] — is that positive social exchanges lead to positive outcomes in teams, whereas negative social exchanges lead to negative outcomes in teams. However, this view may be challenged, in that positive exchanges can sometime lead to negative outcomes, whereas negative exchanges may sometime lead to positive outcomes. For example, research on groupthink (Janis, 1972) suggests that highly cohesive groups can make suboptimal decisions. That is, cohesion […] can lead to suboptimal group performance. As another example, under certain circumstances, negative behavior (e.g., verbal attacks or sabotage directed at another member) by one person in the team could lead to a series of positive exchanges in the team. Such subsequent positive exchanges may involve stronger bonding among other members in support of the targeted member, enforcement of more positive and cordial behavioral norms among members, or resolution of possible conflict between members that might have led to this particular negative exchange.”

“[T]here is […] clear merit in considering social exchanges in teams from a social network perspective. Doing so requires the integration of dyadic-level processes with team-level processes. Specifically, to capture the extent to which certain forms of social exchange networks in teams are formed (e.g., friendship, instrumental, or rather adversary ties), researchers must first consider the dyadic exchanges or ties between all members in the team. Doing so can help researchers identify the extent to which certain forms of ties or other social exchanges are dense in the team […] An important question […] is whether the level of social exchange density in the team might moderate the effects of social exchanges, much like social exchanges strength might strengthen the effects of social exchanges […]. For example, might teams with denser social support networks be able to better handle negative social exchanges in the team when such exchanges emerge? […] the effects of differences in centrality and subgroupings or fault lines may vary, depending on certain factors. Specifically, being more central within the team’s network of social exchange may mean that the more central member receives more support from more members, or, rather, that the more central member is engaged in more negative social exchanges with more members. Likewise, subgroupings or fault lines in the team may lead to negative consequences when they are associated with lack of critical communication among members but not when they reflect the correct form of communication network […] social exchange constructs are likely to exert stronger influences on individual team members when exchanges are more highly shared (and reflected in more dense networks). By the same token, individuals are more likely to react to social exchanges in their team when exchanges are directed at them from more team members”.

“[C]ustomer relationship management (CRM) has garnered growing interest from both research and practice communities in marketing. The purpose of CRM is “to efficiently and effectively increase the acquisition and retention of profitable customers by selectively initiating, building and maintaining appropriate relationships with them” […] Research has shown that successfully implemented CRM programs result in positive outcomes. In a recent meta-analysis, Palmatier, Dant, Grewal, and Evans (2006) found that investments in relationship marketing have a large, direct effect on seller objective performance. In addition, there has been ample research demonstrating that the effects of relationship marketing on outcomes are mediated by relational constructs that include trust […] and commitment […]. Combining these individual predictors by examining the effects of the global construct of relationship quality is also predictive of positive firm performance […] Meta-analytic findings suggest that CRM is more effective when relationships are built with an individual person rather than a selling firm […] Gutek (1995) proposed a typology of service delivery relationships with customers: encounters, pseudo-relationships, and relationships. […] service encounters usually consist of a solitary interaction between a customer and a service employee, with the expectation that they will not interact in the future. […] in a service encounter, customers do not identify with either the individual service employee with whom they interact or with the service organization. […] An alternate to the service encounter relationship is the pseudorelationship, which arises when a customer interacts with different individual service employees but usually (if not always) from the same service organization […] in pseudo-relationships, the customer identifies with the service of a particular service organization, not with an individual service employee. Finally, personal service relationships emerge when customers have repeated interactions with the same individual service provider […] We argue that the nature of these different types of service relationships […] will influence the types and levels of resources exchanged between the customer and the employee during the service interaction, which may further affect customer and employee outcomes from the service interaction.”

“According to social exchange theory, individuals form relationships and engage in social interactions as a means of obtaining needed resources […]. Within a social exchange relationship, individuals may exchange a variety of resources, both tangible and intangible. In the study of exchange relationships, the content of the exchange, or what resources are being exchanged, is often used as an indicator of the quality of the relationship. On the one hand, the greater the quality of resources exchanged, the better the quality of the relationship; on the other hand, the better the relationship, the more likely these resources are exchanged. Therefore, it is important to understand the specific resources exchanged between the service provider and the customer […] Ferris and colleagues (2009) proposed that several elements of a relationship develop because of social exchange: trust, respect, affect, and support. In an interaction between a service provider and a customer, most of the resources that are exchanged are non-economic in nature […]. Examples include smiling, making eye contact, and speaking in a rhythmic (non-monotone) vocal tone […]. Through these gestures, the service provider and the customer may demonstrate a positive affect toward each other. In addition, greeting courteously, listening attentively to customers, and providing assistance to address customer needs may show the service provider’s respect and support to the customer; likewise, providing necessary information, clarifying their needs and expectations, cooperating with the service provider by following proper instructions, and showing gratitude to the service provider may indicate customers’ respect and support to the service provider. Further, through placing confidence in the fairness and honesty of the customer and accuracy of the information the customer provides, the service provider offers the customer his or her trust; similarly, through placing confidence in the expertise and good intentions of the service provider, the customer offers his or her trust in the service provider’s competence and integrity. Some of the resources exchanged, particularly special treatment, between a service provider and a customer are of both economic and social value. For example, the customer may receive special discounts or priority service, which not only offers the customer economic benefits but also shows how much the service provider values and supports the customer. Similarly, a service provider who receives an extra big tip from a customer is not only better off economically but also gains a sense of recognition and esteem. The more these social resources of trust, respect, affect, and support, as well as special treatment, are mutually exchanged in the provider–customer interactions, the higher the quality of the service interaction for both parties involved. […] we argue that the potential for the exchange of resources […] depends on the nature of the service relationship. In other words, the quantity and quality of resources exchanged in discrete service encounters, pseudo-relationships, and personal service relationships are distinct.”

Though customer–employee exchanges can be highly rewarding for both parties, they can also “turn ugly,” […]. In fact, though negative interactions such as rudeness, verbal abuse, or harassment are rare, employees are more likely to report them from customers than from coworkers or supervisors […] customer–employee exchanges are more likely to involve negative treatment than exchanges with organizational insiders. […] Such negative exchanges result in emotional labor and employee burnout […], covert sabotage of services or goods, or, in atypical cases […] direct retaliation and withdrawal […] Employee–customer exchanges are characterized by a strong power differential […] customers can influence the employees’ desired resources, have more choice over whether to continue the relationship, and can act in negative ways with few consequences (Yagil, 2008) […] One common way to conceptualize the impact of negative customer–employee interactions is Hirschman’s (1970) Exit-Voice-loyalty model. Management can learn of customers’ dissatisfaction by their reduced loyalty, voice, or exit. […] Customers rarely, if ever, see themselves as the source of the problem; in contrast, employees are highly likely to see customers as the reason for a negative exchange […] when employees feel customers’ allocation of resources (e.g., tips, purchases) are not commensurate with the time or energy expended (i.e., distributive injustice) or interpersonal treatment of employees is unjustified or violates norms (i.e., interactional injustice), they feel anger and anxiety […] Given these strong emotional responses, emotional deviance is a possible outcome in the service exchange. Emotional deviance is when employees violate display rules by expressing their negative feelings […] To avoid emotional deviance, service providers engage in emotion regulation […]. In lab and field settings, perceived customer mistreatment is linked to “emotional labor,” specifically regulating emotions by faking or suppressing emotions […] Customer mistreatment — incivility as well as verbal abuse — is well linked to employee burnout, and this effect exists beyond other job stressors (e.g., time pressure, constraints) and beyond mistreatment from supervisors and coworkers”.

Though a customer may complain or yell at an employee in hopes of improving service, most evidence suggests the opposite occurs. First, service providers tend to withdraw from negative or deviant customers (e.g., avoiding eye contact or going to the back room[)] […] Engaging in withdrawal or other counterproductive work behaviors (CWBs) in response to mistreatment can actually reduce burnout […], but the behavior is likely to create another dissatisfied customer or two in the meantime. Second, mistreatment can also result in the employees reduced task performance in the service exchange. Stressful work events redirect attention toward sense making, even when mistreatment is fairly ambiguous or mild […] and thus reduce cognitive performance […]. Regulating those negative emotions also requires attentional resources, and both surface and deep acting reduce memory recall compared with expressing felt emotions […] Moreover, the more that service providers feel exhausted and burned out, the less positive their interpersonal performance […] Finally, perceived incivility or aggressive treatment from customers, and the resulting job dissatisfaction, is a key predictor of intentional customer-directed deviant behavior or service sabotage […] Dissatisfied employees engage in less extra-effort behavior than satisfied employees […]. More insidious, they may engage in intentionally deviant performance that is likely to be covert […] and thus difficult to detect and manage […] Examples of service sabotage include intentionally giving the customer faulty or damaged goods, slowing down service pace, or making “mistakes” in the service transaction, all of which are then linked to lower service performance from the customers’ perspective […]. This creates a feedback loop from employee behaviors to customer perceptions […] Typical human resource practices can help service management […], and practices such as good selection and providing training should reduce the likelihood of service failures and the resulting negative reactions from customers […]. Support from colleagues can help buffer the reactions to customer-instigated mistreatment. Individual perceptions of social support moderate the strain from emotional labor […], and formal interventions increasing individual or unit-level social support reduce strain from emotionally demanding interactions with the public (Le Blanc, Hox, Schaufeli, & Taris, 2007).”

August 19, 2018 Posted by | Books, Psychology | Leave a comment

Some observations on a cryptographic problem

It’s been a long time since I last posted one of these sort of ‘rootless’ posts which are not based on a specific book or a specific lecture or something along those lines, but a question on r/science made me think about these topics and start writing a bit about it, and I decided I might as well add my thoughts and ideas here.

The reddit question which motivated me to write this post was this one: “Is it difficult to determine the password for an encryption if you are given both the encrypted and unencrypted message?

By “difficult” I mean requiring an inordinate amount of computation. If given both an encrypted and unencrypted file/message, is it reasonable to be able to recover the password that was used to encrypt the file/message?”

Judging from the way the question is worded, the inquirer obviously knows very little about these topics, but that was part of what motivated me when I started out writing; s/he quite obviously has a faulty model of how this kind of stuff actually works, and just by virtue of the way he or she asks his/her question s/he illustrates some ways in which s/he gets things wrong.

When I decided to transfer my efforts towards discussing these topics to the blog I also implicitly decided against using language that would be expected to be easily comprehensible for the original inquirer, as s/he was no longer in the target group and there’s a cost to using that kind of language when discussing technical matters. I’ve sort of tried to make this post both useful and readable to people not all that familiar with the related fields, but I tend to find it difficult to evaluate the extent to which I’ve succeeded when I try to do things like that.

I decided against adding stuff already commented on when I started out writing this, so I’ll not e.g. repeat noiwontfixyourpc’s reply below. However I have added some other observations that seem to me to be relevant and worth mentioning to people who might consider asking a similar question to the one the original inquirer asked in that thread:

i. Finding a way to make plaintext turn into cipher text (…or cipher text into plaintext; and no, these two things are not actually always equivalent, see below…) is a very different (and in many contexts a much easier problem) than finding out the actual encryption scheme that is at work producing the text strings you observe. There can be many, many different ways to go from a specific sample of plaintext to a specific sample of ciphertext, and most of the solutions won’t work if you’re faced with a new piece of ciphertext; especially not if the original samples are small, so only a small amount of (potential) information would be expected to be included in the text strings.

If you only get a small amount of plaintext and corresponding cipher text you may decide that algorithm A is the one that was applied to the message, even if the algorithm actually applied was a more complex algorithm, B. To illustrate in a very simple way how this might happen, A might be a particular case of B, because B is a superset of A and a large number of other potential encryption algorithms applied in the encryption scheme B (…or the encryption scheme C, because B also happens to be a subset of C, or… etc.). In such a context A might be an encryption scheme/approach that perhaps only applies in very specific contexts; for example (part of) the coding algorithm might have been to decide that ‘on next Tuesday, we’ll use this specific algorithm to translate plaintext into cipher text, and we’ll never use that specific translation-/mapping algorithm (which may be but one component of the encryption algorithm) again’. If such a situation applies then you’re faced with the problem that even if your rule ‘worked’ in that particular instance, in terms of translating your plaintext into cipher text and vice versa, it only ‘worked’ because you blindly fitted the two data-sets in a way that looked right, even if you actually had no idea how the coding scheme really worked (you only guessed A, not B, and in this particular instance A’s never actually going to happen again).

On a more general level some of the above comments incidentally in my view quite obviously links to results from classical statistics; there are many ways to link random variables through data fitting methods, but reliably identifying proper causal linkages through the application of such approaches is, well, difficult (and, according to some, often ill-advised)…

ii. In my view, it does not seem possible in general to prove that any specific proposed encryption/decryption algorithm is ‘the correct one’. This is because the proposed algorithm will never be a unique solution to the problem you’re evaluating. How are you going to convince me that The True Algorithm is not a more general/complex one (or perhaps a completely different one – see iii. below) than the one you propose, and that your solution is not missing relevant variables? The only way to truly test if the proposed algorithm is a valid algorithm is to test it on new data and compare its performance on this new data set with the performances of competing variables/solution proposals which also managed to correctly link cipher text and plaintext. If the algorithm doesn’t work on the new data, you got it wrong. If it does work on new data, well, you might still just have been lucky. You might get more confident with more correctly-assessed (…guessed?) data, but you never get certain. In other similar contexts a not uncommon approach for trying to get around these sorts of problems is to limit the analysis to a subset of the data available in order to obtain the algorithm, and then using the rest of the data for validation purposes (here’s a relevant link), but here even with highly efficient estimation approaches you almost certainly will run out of information (/degrees of freedom) long before you get anywhere if the encryption algorithm is at all non-trivial. In these settings information is likely to be a limiting resource.

iii. There are many different types of encryption schemes, and people who ask questions like the one above tend, I believe, to have a quite limited view of which methods and approaches are truly available to one who desires secrecy when exchanging information with others. Imagine a situation where the plaintext is ‘See you next Wednesday’ and the encrypted text is an English translation of Tolstoy’s book War and Peace (or, to make it even more fun, all pages published on the English version of Wikipedia, say on November the 5th, 2017 at midnight GMT). That’s an available encryption approach that might be applied. It might be a part (‘A’) of a more general (‘B’) encryption approach of linking specific messages from a preconceived list of messages, which had been considered worth sending in the future when the algorithm was chosen, to specific book titles decided on in advance. So if you want to say ‘good Sunday!’, Eve gets to read the Bible and see where that gets her. You could also decide that in half of all cases the book cipher text links to specific messages from a list but in the other half of the cases what you actually mean to communicate is on page 21 of the book; this might throw a hacker who saw a combined cipher text and plaintext combination resulting from that part of the algorithm off in terms of the other half, and vice versa – and it illustrates well one of the key problems you’re faced with as an attacker when working on cryptographic schemes about which you have limited knowledge; the opponent can always add new layers on top of the ones that already exist/apply to make the problem harder to solve. And so you could also link the specific list message with some really complicated cipher-encrypted version of the Bible. There’s a lot more to encryption schemes than just exchanging a few letters here and there. On related topics, see this link. On a different if related topic, people who desire secrecy when exchanging information may also attempt to try to hide the fact that any secrets are exchanged in the first place. See also this.

iv. The specific usage of the word ‘password’ in the original query calls for comment for multiple reasons, some of which have been touched upon above, perhaps mainly because it implicitly betrays a lack of knowledge about how modern cryptographic systems actually work. The thing is, even if you might consider an encryption scheme to just be an advanced sort of ‘password’, finding the password (singular) is not always the task you’re faced with today. In symmetric-key algorithm settings you might sort-of-kind-of argue that it sort-of is – in such settings you might say that you have one single (collection of) key(s) which you use to encrypt messages and also use to decrypt the messages. So you can both encrypt and decrypt the message using the same key(s), and so you only have one ‘password’. That’s however not how asymmetric-key encryption works. As wiki puts it: “In an asymmetric key encryption scheme, anyone can encrypt messages using the public key, but only the holder of the paired private key can decrypt.”

This of course relates to what you actually want to do/achieve when you get your samples of cipher text and plaintext. In some cryptographic contexts by design the route you need to to go to get from cipher text to plaintext is conceptually different from the route you need to go to get from plaintext to cipher text. And some of the ‘passwords’ that relate to how the schemes work are public knowledge by design.

v. I have already touched a bit upon the problem of the existence of an information constraint, but I realized I probably need to spell this out in a bit more detail. The original inquirer to me seems implicitly to be under the misapprehension that computational complexity is the only limiting constraint here (“By “difficult” I mean requiring an inordinate amount of computation.”). Given the setting he or she proposes, I don’t think that’s true, and why that is is sort of interesting.

If you think about what kind of problem you’re facing, what you have here in this setting is really a very limited amount of data which relates in an unknown manner to an unknown data-generating process (‘algorithm’). There are, as has been touched upon, in general many ways to obtain linkage between two data sets (the cipher text and the plaintext) using an algorithm – too many ways for comfort, actually. The search space is large, there are too many algorithms to consider; or equivalently, the amount of information supplied by the data will often be too small for us to properly evaluate the algorithms under consideration. An important observation is that more complex algorithms will both take longer to calculate (‘identify’ …at least as candidates) and be expected to require more data to evaluate, at least to the extent that algorithmic complexity constrains the data (/relates to changes in data structure/composition that needs to be modeled in order to evaluate/identify the goal algorithm). If the algorithm says a different encryption rule is at work on Wednesdays, you’re going to have trouble figuring that out if you only got hold of a cipher text/plaintext combination derived from an exchange which took place on a Saturday. There are methods from statistics that might conceivably help you deal with problems like these, but they have their own issues and trade-offs. You might limit yourself to considering only settings where you have access to all known plaintext and cipher text combinations, so you got both Wednesday and Saturday, but even here you can’t be safe – next (metaphorical, I probably at this point need to add) Friday might be different from last (metaphorical) Friday, and this could even be baked into the algorithm in very non-obvious ways.

The above remarks might give you the idea that I’m just coming up with these kinds of suggestions to try to foil your approaches to figuring out the algorithm ‘by cheating’ (…it shouldn’t matter whether or not it was ‘sent on a Saturday’), but the main point is that a complex encryption algorithm is complex, and even if you see it applied multiple times you might not get enough information about how it works from the data suggested to be able to evaluate if you guessed right. In fact, given a combination of a sparse data set (one message, or just a few messages, in plaintext and cipher text) and a complex algorithm involving a very non-obvious mapping function, the odds are strongly against you.

vi. I had the thought that one reason why the inquirer might be confused about some of these things is that s/he might well be aware of the existence of modern cryptographic techniques which do rely to a significant extent on computational complexity aspects. I.e., here you do have settings where you’re asked to provide ‘the right answer’ (‘the password’), but it’s hard to calculate the right answer in a reasonable amount of time unless you have the relevant (private) information at hand – see e.g. these links for more. One way to think about how such a problem relates to the other problem at hand (you have been presented with samples of cipher text and plaintext and you want to guess all the details about how the encryption and decryption schemes which were applied work) is that this kind of algorithm/approach may be applied in combination with other algorithmic approaches to encrypt/decrypt the text you’re analyzing. A really tough prime factorization problem might for all we know be an embedded component of the cryptographic process that is applied to our text. We could call it A.

In such a situation we would definitely be in trouble because stuff like prime factorization is really hard and computationally complex, and to make matters worse just looking at the plaintext and the cipher text would not make it obvious to us that a prime factorization scheme had even been applied to the data. But a really important point is that even if such a tough problem was not present and even if only relatively less computationally demanding problems were involved, we almost certainly still just wouldn’t have enough information to break any semi-decent encryption algorithm based on a small sample of plaintext and cipher text. It might help a little bit, but in the setting contemplated by the inquirer a ‘faster computer’ (/…’more efficient decision algorithm’, etc.) can only help so much.

vii. Shannon and Kerckhoffs may have a point in a general setting, but in specific settings like this particular one I think it is well worth taking into account the implications of not having a (publicly) known algorithm to attack. As wiki notes (see the previous link), ‘Many ciphers are actually based on publicly known algorithms or are open source and so it is only the difficulty of obtaining the key that determines security of the system’. The above remarks were of course all based on an assumption that Eve does not here have the sort of knowledge about the encryption scheme applied that she in many cases today actually might have. There are obvious and well-known weaknesses associated with having security-associated components of a specific cryptographic scheme be independent of the key, but I do not see how it does not in this particular setting cause search space blow-up making the decision problem (did we actually guess right?) intractable in many cases. A key feature of the problem considered by the inquirer is that you here – unlike in many ‘guess the password-settings’ where for example a correct password will allow you access to an application or a document or whatever – do not get any feedback neither in the case where you guess right nor in the case where you guess wrong; it’s a decision problem, not a calculation problem. (However it is perhaps worth noting on the other hand that in a ‘standard guess-the-password-problem’ you may also sometimes implicitly face a similar decision problem due to e.g. the potential for a combination of cryptographic security and steganographic complementary strategies like e.g. these having been applied).

August 14, 2018 Posted by | Computer science, Cryptography, Data, rambling nonsense, Statistics | Leave a comment

Personal Relationships… (II)

Some more observations from the book below:

Coworker support, or the processes by which coworkers provide assistance with tasks, information, or empathy, has long been considered an important construct in the stress and strain literature […] Social support fits the conservation of resources theory definition of a resource, and it is commonly viewed in that light […]. Support from coworkers helps employees meet the demands of their job, thus making strain less likely […]. In a sense, social support is the currency upon which social exchanges are based. […] The personality of coworkers can play an important role in the development of positive coworker relationships. For example, there is ample evidence that suggests that those higher in conscientiousness and agreeableness are more likely to help coworkers […] Further, similarity in personality between coworkers (e.g., coworkers who are similar in their conscientiousness) draws coworkers together into closer relationships […] cross-sex relationships appear to be managed in a different manner than same-sex relationships. […] members of cross-sex friendships fear the misinterpretation of their relationship by those outside the relationship as a sexual relationship rather than platonic […] a key goal of partners in a cross-sex workplace friendship becomes convincing “third parties that the friendship is authentic.” As a result, cross-sex workplace friends will intentionally limit the intimacy of their communication or limit their non-work-related communication to situations perceived to demonstrate a nonsexual relationship, such as socializing with a cross-sex friend only in the presence of his or her spouse […] demographic dissimilarity in age and race can reduce the likelihood of positive coworker relationships. Chattopadhyay (1999) found that greater dissimilarity among group members on age and race were associated with less collegial relationships among coworkers, which was subsequently associated with less altruistic behavior […] Sias and Cahill (1998) found that a variety of situational characteristics, both inside and outside the workplace setting, helps to predict the development of workplace friendship. For example, they found that factors outside the workplace, such as shared outside interests (e.g., similar hobbies), life events (e.g., having a child), and the simple passing of time can lead to a greater likelihood of a friendship developing. Moreover, internal workplace characteristics, including working together on tasks, physical proximity within the office, a common problem or enemy, and significant amounts of “downtime” that allow for greater socialization, also support friendship development in the workplace (see also Fine, 1986).”

“To build knowledge, employees need to be willing to learn and try new things. Positive relationships are associated with a higher willingness to engage in learning and experimentation […] and, importantly, sharing of that new knowledge to benefit others […] Knowledge sharing is dependent on high-quality communication between relational partners […] Positive relationships are characterized by less defensive communication when relational partners provide feedback (e.g., a suggestion for a better way to accomplish a task; Roberts, 2007). In a coworker context, this would involve accepting help from coworkers without putting up barriers to that help (e.g., nonverbal cues that the help is not appreciated or welcome). […] A recent meta-analysis by Chiaburu and Harrison (2008) found that coworker support was associated with higher performance and higher organizational citizenship behavior (both directed at individuals and directed at the organization broadly). These relationships held whether performance was self- or supervisor related […] Chiaburu and Harrison (2008) also found that coworker support was associated with higher satisfaction and organizational commitment […] Positive coworker exchanges are also associated with lower levels of employee withdrawal, including absenteeism, intention to turnover, and actual turnover […]. To some extent, these relationships may result from norms within the workplace, as coworkers help to set standards for behavior and not “being there” for other coworkers, particularly in situations where the work is highly interdependent, may be considered a significant violation of social norms within a positive working environment […] Perhaps not surprisingly, given the proximity and the amount of time spent with coworkers, workplace friendships will occasionally develop into romances and, potentially, marriages. While still small, the literature on married coworkers suggests that they experience a number of benefits, including lower emotional exhaustion […] and more effective coping strategies […] Married coworkers are an interesting population to examine, largely because their work and family roles are so highly integrated […]. As a result, both resources and demands are more likely to spill over between the work and family role for married coworkers […] Janning and Neely (2006) found that married coworkers were more likely to talk about work-related issues while at home than married couples that had no work-related link.”

Negative exchanges [between coworkers] are characterized by behaviors that are generally undesirable, disrespectful, and harmful to the focal employee or employees. Scholars have found that these negative exchanges influence the same outcomes as positive, supporting exchanges, but in opposite directions. For instance, in their recent meta-analysis of 161 independent studies, Chiaburu and Harrison (2008) found that antagonistic coworker exchanges are negatively related to job satisfaction, organizational commitment, and task performance and positively related to absenteeism, intent to quit, turnover, and counterproductive work behaviors. Unfortunately, despite the recent popularity of the negative exchange research, this literature still lacks construct clarity and definitional precision. […] Because these behaviors have generally referred to acts that impact both coworkers and the organization as a whole, much of this work fails to distinguish social interactions targeting specific individuals within the organization from the nonsocial behaviors explicitly targeting the overall organization. This is unfortunate given that coworker-focused actions and organization-focused actions represent unique dimensions of organizational behavior […] negative exchanges are likely to be preceded by certain antecedents. […] Antecedents may stem from characteristics of the enactor, of the target, or of the context in which the behaviors occur. For example, to the extent that enactors are low on socially relevant personality traits such as agreeableness, emotional stability, or extraversion […], they may be more prone to initiate a negative exchange. Likewise, an enactor who is a high Machiavellian may initiate a negative exchange with the goal of gaining power or establishing control over the target. Antagonistic behaviors may also occur as reciprocation for a previous attack (real or imagined) or as a proactive deterrent against a potential future negative behavior from the target. Similarly, enactors may initiate antagonism based on their perceptions of a coworker’s behavioral characteristics such as suboptimal productivity or weak work ethic. […] The reward system can also play a role as an antecedent condition for antagonism. When coworkers are highly interdependent and receive rewards based on the performance of the group as opposed to each individual, the incidence of antagonism may increase when there is substantial variance in performance among coworkers.”

“[E]mpirical evidence suggests that some people have certain traits that make them more vulnerable to coworker attacks. For example, employees with low self-esteem, low emotional stability, high introversion, or high submissiveness are more inclined to be the recipients of negative coworker behaviors […]. Furthermore, research also shows that people who engage in negative behaviors are likely to also become the targets of these behaviors […] Two of the most commonly studied workplace attitudes are employee job satisfaction […] and affective organizational commitment […] Chiaburu and Harrison (2008) linked general coworker antagonism with both attitudes. Further, the specific behaviors of bullying and incivility have also been found to adversely affect both job satisfaction and organizational commitment […]. A variety of behavioral outcomes have also been identified as outcomes of coworker antagonism. Withdrawal behaviors such as absenteeism, intention to quit, turnover, effort reduction […] are typical responses […] those who have been targeted by aggression are more likely to engage in aggression. […] Feelings of anger, fear, and negative mood have also been shown to mediate the effects of interpersonal mistreatment on behaviors such as withdrawal and turnover […] [T]he combination of enactor and target characteristics is likely to play an antecedent role to these exchanges. For instance, research in the diversity area suggests that people tend to be more comfortable around those with whom they are similar and less comfortable around people with whom they are dissimilar […] there may be a greater incidence of coworker antagonism in more highly diverse settings than in settings characterized by less diversity. […] research has suggested that antagonistic behaviors, while harmful to the target or focal employee, may actually be beneficial to the enactor of the exchange. […] Krischer, Penney, and Hunter (2010) recently found that certain types of counterproductive work behaviors targeting the organization may actually provide employees with a coping mechanism that ultimately reduces their level of emotional exhaustion.”

CWB [counterproductive work behaviors] toward others is composed of volitional acts that harm people at work; in our discussion this would refer to coworkers. […] person-oriented organizational citizenship behaviors (OCB; Organ, 1988) consist of behaviors that help others in the workplace. This might include sharing job knowledge with a coworker or helping a coworker who had too much to do […] Social support is often divided into the two forms of emotional support that helps people deal with negative feelings in response to demanding situations versus instrumental support that provides tangible aid in directly dealing with work demands […] one might expect that instrumental social support would be more strongly related to positive exchanges and positive relationships. […] coworker social support […] has [however] been shown to relate to strains (burnout) in a meta-analysis (Halbesleben, 2006). […] Griffin et al. suggested that low levels of the Five Factor Model […] dimensions of agreeableness, emotional stability, and extraversion might all contribute to negative behaviors. Support can be found for the connection between two of these personality characteristics and CWB. […] Berry, Ones, and Sackett (2007) showed in their meta-analysis that person-focused CWB (they used the term deviance) had significant mean correlations of –.20 with emotional stability and –.36 with agreeableness […] there was a significant relationship with conscientiousness (r = –.19). Thus, agreeable, conscientious, and emotionally stable individuals are less likely to engage in CWB directed toward people and would be expected to have fewer negative exchanges and better relationships with coworkers. […] Halbesleben […] suggests that individuals high on the Five Factor Model […] dimensions of agreeableness and conscientiousness would have more positive exchanges because they are more likely to engage in helping behavior. […] a meta-analysis has shown that both of these personality variables relate to the altruism factor of OCB in the direction expected […]. Specifically, the mean correlations of OCB were .13 for agreeableness and .22 for conscientiousness. Thus, individuals high on these two personality dimensions should have more positive coworker exchanges.”

There is a long history of research in social psychology supporting the idea that people tend to be attracted to, bond, and form friendships with others they believe to be similar […], and this is true whether the similarity is rooted in demographics that are fairly easy to observe […] or in attitudes, beliefs, and values that are more difficult to observe […] Social network scholars refer to this phenomenon as homophily, or the notion that “similarity breeds connection” […] although evidence of homophily has been found to exist in many different types of relationships, including marriage, frequency of communication, and career support, it is perhaps most evident in the formation of friendships […] We extend this line of research and propose that, in a team context that provides opportunities for tie formation, greater levels of perceived similarity among team members will be positively associated with the number of friendship ties among team members. […] A chief function of friendship ties is to provide an outlet for individuals to disclose and manage emotions. […] friendship is understood as a form of support that is not related to work tasks directly; rather, it is a “backstage resource” that allows employees to cope with demands by creating distance between them and their work roles […]. Thus, we propose that friendship network ties will be especially important in providing the type of coping resources that should foster team member well-being. Unfortunately, however, friendship network ties negatively impact team members’ ability to focus on their work tasks, and, in turn, this detracts from taskwork. […] When friends discuss nonwork topics, these individuals will be distracted from work tasks and will be exposed to off-task information exchanged in informal relationships that is irrelevant for performing one’s job. Additionally, distractions can hinder individuals’ ability to become completely engaged in their work (Jett & George).”

Although teams are designed to meet important goals for both companies and their employees, not all team members work together well.
Teams are frequently “cruel to their members” […] through a variety of negative team member exchanges (NTMEs) including mobbing, bullying, incivility, social undermining, and sexual harassment. […] Team membership offers identity […], stability, and security — positive feelings that often elevate work teams to powerful positions in employees’ lives […], so that members are acutely aware of how their teammates treat them. […] NTMEs may evoke stronger emotional, attitudinal, and behavioral consequences than negative encounters with nonteam members. In brief, team members who are targeted for NTMEs are likely to experience profound threats to personal identity, security, and stability […] when a team member targets another for negative interpersonal treatment, the target is likely to perceive that the entire group is behind the attack rather than the specific instigator alone […] Studies have found that NTMEs […] are associated with poor psychological outcomes such as depression; undesirable work attitudes such as low affective commitment, job dissatisfaction, and low organization-based self-esteem; and counterproductive behaviors such as deviance, job withdrawal, and unethical behavior […] Some initial evidence has also indicated that perceptions of rejection mediate the effects of NTMEs on target outcomes […] Perceptions of the comparative treatment of other team members are an important factor in reactions to NTMEs […]. When targets perceive they are “singled out,” NTMEs will cause more pronounced effects […] A significant body of literature has suggested that individuals guide their own behaviors through environmental social cues that they glean from observing the norms and values of others. Thus, the negative effects of NTMEs may extend beyond the specific targets; NTMEs can spread contagiously to other team members […]. The more interdependent the social actors in the team setting, the stronger and more salient will be the social cues […] [There] is evidence that as team members see others enacting NTMEs, their inhibitions against such behaviors are lowered.”

August 13, 2018 Posted by | Books, Psychology | Leave a comment

Promoting the unknown…






August 10, 2018 Posted by | Music | Leave a comment

Personal Relationships… (I)

“Across subdisciplines of psychology, research finds that positive, fulfilling, and satisfying relationships contribute to life satisfaction, psychological health, and physical well-being whereas negative, destructive, and unsatisfying relationships have a whole host of detrimental psychological and physical effects. This is because humans possess a fundamental “need to belong” […], characterized by the motivation to form and maintain lasting, positive, and significant relationships with others. The need to belong is fueled by frequent and pleasant relational exchanges with others and thwarted when one feels excluded, rejected, and hurt by others. […] This book uses research and theory on the need to belong as a foundation to explore how five different types of relationships influence employee attitudes, behaviors, and well-being. They include relationships with supervisors, coworkers, team members, customers, and individuals in one’s nonwork life. […] This book is written for a scientist–practitioner audience and targeted to both researchers and human resource management professionals. The contributors highlight both theoretical and practical implications in their respective chapters, with a common emphasis on how to create and sustain an organizational climate that values positive relationships and deters negative interpersonal experiences. Due to the breadth of topics covered in this edited volume, the book is also appropriate for advanced specialty undergraduate or graduate courses on I/O psychology, human resource management, and organizational behavior.”

The kind of stuff covered in books like this one relates closely to social stuff I lack knowledge about and/or is just not very good at handling. I don’t think too highly of this book’s coverage so far, but that’s at least partly due to the kinds of topics covered – it is what it is.

Below I have added some quotes from the first few chapters of the book.

“Work relationships are important to study in that they can exert a strong influence on employees’ attitudes and behaviors […].The research evidence is robust and consistent; positive relational interactions at work are associated with more favorable work attitudes, less work-related strain, and greater well-being (for reviews see Dutton & Ragins, 2007; Grant & Parker, 2009). On the other side of the social ledger, negative relational interactions at work induce greater strain reactions, create negative affective reactions, and reduce well-being […]. The relationship science literature is clear, social connection has a causal effect on individual health and well-being”.

“[One] way to view relationships is to consider the different dimensions by which relationships vary. An array of dimensions that underlie relationships has been proposed […] Affective tone reflects the degree of positive and negative feelings and emotions within the relationship […] Relationships and groups marked by greater positive affective tone convey more enthusiasm, excitement, and elation for each other, while relationships consisting of more negative affective tone express more fear, distress, and scorn. […] Emotional carrying capacity refers to the extent that the relationship can handle the expression of a full range of negative and position emotions as well as the quantity of emotion expressed […]. High-quality relationships have the ability to withstand the expression of more emotion and a greater variety of emotion […] Interdependence involves ongoing chains of mutual influence between two people […]. Degree of relationship interdependency is reflected through frequency, strength, and span of influence. […] A high degree of interdependence is commonly thought to be one of the hallmarks of a close relationship […] Intimacy is composed of two fundamental components: self-disclosure and partner responsiveness […]. Responsiveness involves the extent that relationship partners understand, validate, and care for one another. Disclosure refers to verbal communications of personally relevant information, thoughts, and feelings. Divulging more emotionally charged information of a highly personal nature is associated with greater intimacy […]. Disclosure tends to proceed from the superficial to the more intimate and expands in breadth over time […] Power refers to the degree that dominance shapes the relationship […] relationships marked by a power differential are more likely to involve unidirectional interactions. Equivalent power tends to facilitate bidirectional exchanges […] Tensility is the extent that the relationship can bend and endure strain in the face of challenges and setbacks […]. Relationship tensility contributes to psychological safety within the relationship. […] Trust is the belief that relationship partners can be depended upon and care about their partner’s needs and interests […] Relationships that include a great deal of trust are stronger and more resilient. A breach of trust can be one of the most difficult relationships challenges to overcome (Pratt & dirks, 2007).”

“Relationships are separate entities from the individuals involved in the relationships. The relationship unit (typically a dyad) operates at a different level of analysis from the individual unit. […] For those who conduct research on groups or organizations, it is clear that operations at a group level […] operate at a different level than individual psychology, and it is not merely the aggregate of the individuals involved in the relationship. […] operations at one level (e.g., relationships) can influence behavior at the other level (e.g., individual). […] relationships are best thought of as existing at their own level of analysis, but one that interacts with other levels of analysis, such as individual and group or cultural levels. Relationships cannot be reduced to the actions of the individuals in them or the social structures where they reside but instead interact with the individual and group processes in interesting ways to produce behaviors. […] it is challenging to assess causality via experimental procedures when studying relationships. […] Experimental procedures are crucial for making inferences of causation but are particularly difficult in the case of relationships because it is tough to manipulate many important relationships (e.g., love, marriage, sibling relationships). […] relationships are difficult to observe at the very beginning and at the end, so methods have been developed to facilitate this.”

“[T]he organizational research could […] benefit from the use of theoretical models from the broader relationships literature. […] Interdependence theory is hardly ever seen in organizations. There was some fascinating work in this area a few decades ago, especially in interdependence theory with the investment model […]. This work focused on the precursors of commitment in the workplace and found that, like romantic relationships, the variables of satisfaction, investments, and alternatives played key roles in this process. The result is that when satisfaction and investments are high and alternative opportunities are low, commitment is high. However, it also means that if investments are sufficiently high and alternatives are sufficiently low, then satisfaction can by lowered and commitment will remain high — hence, the investment model is useful for understanding exploitation (Rusbult, Campbell, & Price, 1990).”

“Because they cross formal levels in the organizational hierarchy, supervisory relationships necessarily involve an imbalance in formal power. […] A review by Keltner, Gruenfeld, and Anderson (2003) suggests that power affects how people experience emotions, whether they attend more to rewards or threats, how they process information, and the extent to which they inhibit their behavior around others. The literature clearly suggests that power influences affect, cognition, and behavior in ways that might tend to constrain the formation of positive relationships between individuals with varying degrees of power. […] The power literature is clear in showing that more powerful individuals attend less to their social context, including the people in it, than do less powerful individuals, and the literature suggests that supervisors (compared with subordinates) might tend to place less value on the relationship and be less attuned to their partner’s needs. Yet the formal power accorded to supervisors by the organization — via the supervisory role — is accompanied by the role prescribed responsibility for the performance, motivation, and well-being of subordinates. Thus, the accountability for the formation of a positive supervisory relationship lies more heavily with the supervisor. […] As we examine the qualities of positive supervisory relationships, we make a clear distinction between effective supervisory behaviors and positive supervisory relationships. This is an important distinction […] a large body of leadership research has focused on traits or behaviors of supervisors […] and the affective, motivational, and behavioral responses of employees to those behaviors, with little attention paid to the interactions between the two. There are two practical implications of moving the focus from individuals to relationships: (1) supervisors who use “effective” leadership behaviors may or may not have positive relationships with employees; and (2) supervisors who have a positive relationship with one employee may not have equally positive relationships with other employees, even if they use the same “effective” behaviors.”

There is a large and well-developed stream of research that focuses explicitly on exchanges between supervisors and the employees who report directly to them. Leader–member exchange theory addresses the various types of functional relationships that can be formed between supervisors and subordinates. A core assumption of LMX theory is that supervisors do not have the time or resources to develop equally positive relationships with all subordinates. Thus, to minimize their investment and yield the greatest results for the organization, supervisors would develop close relationships with only a few subordinates […] These few high-quality relationships are marked by high levels of trust, loyalty, and support, whereas the balance of supervisory relationships are contractual in nature and depends on timely rewards allotted by supervisors in direct exchange for desirable behaviors […] There has been considerable confusion and debate in the literature about LMX theory and the construct validity of LMX measures […] Despite shortcomings in LMX research, it is [however] clear that supervisors form relationships of varying quality with subordinates […] Among factors associated with high LMX are the supervisor’s level of agreeableness […] and the employee’s level of extraversion […], feedback seeking […], and (negatively) negative affectivity […]. Those who perceived similarity in terms of family, money, career strategies, goals in life, education […], and gender […] also reported high LMX. […] Employee LMX is strongly related to attitudes, such as job satisfaction […] Supporting the notion that a positive supervisory relationship is good for employees, the LMX literature is replete with studies linking high LMX with thriving and autonomous motivation. […] The premise of the LMX research is that supervisory resources are limited and high-quality relationships are demanding. Thus, supervisor will be most effective when they allocate their resources efficiently and effectively, forming some high-quality and some instrumental relationships. But the empirical research from the lMX literature provides little (if any) evidence that supervisors who differentiate are more effective”.

The norm of negative reciprocity obligates targets of harm to reciprocate with actions that produce roughly equivalent levels of harm — if someone is unkind to me, I should be approximately as unkind to him or her. […] But the trajectory of negative reciprocity differs in important ways when there are power asymmetries between the parties involved in a negative exchange relationship. The workplace revenge literature suggests that low-power targets of hostility generally withhold retaliatory acts. […] In exchange relationships where one actor is more dependent on the other for valued resources, the dependent/less powerful actor’s ability to satisfy his or her self-interests will be constrained […]. Subordinate targets of supervisor hostility should therefore be less able (than supervisor targets of subordinate hostility) to return the injuries they sustain […] To the extent subordinate contributions to negative exchanges are likely to trigger disciplinary responses by the supervisor target (e.g., reprimands, demotion, transfer, or termination), we can expect that subordinates will withhold negative reciprocity.”

“In the last dozen years, much has been learned about the contributions that supervisors make to negative exchanges with subordinates. […] Several dozen studies have examined the consequences of supervisor contributions to negative exchanges. This work suggests that exposure to supervisor hostility is negatively related to subordinates’ satisfaction with the job […], affective commitment to the organization […], and both in-role and extra-role performance contributions […] and is positively related to subordinates’ psychological distress […], problem drinking […], and unit-level counterproductive work behavior […]. Exposure to supervisor hostility has also been linked with family undermining behavior — employees who are the targets of abusive supervision are more likely to be hostile toward their own family members […] Most studies of supervisor hostility have accounted for moderating factors — individual and situational factors that buffer or exacerbate the effects of exposure. For example, Tepper (2000) found that the injurious effects of supervisor hostility on employees’ attitudes and strain reactions were stronger when subordinates have less job mobility and therefore feel trapped in jobs that deplete their coping resources. […] Duffy, Ganster, Shaw, Johnson, and Pagon (2006) found that the effects of supervisor hostility are more pronounced when subordinates are singled out rather than targeted along with multiple coworkers. […] work suggests that the effects of abusive supervision on subordinates’ strain reactions are weaker when subordinates employ impression management strategies […] and more confrontational (as opposed to avoidant) communication tactics […]. It is clear that not all subordinates react the same way to supervisor hostility and characteristics of subordinates and the context influence the trajectory of subordinates’ responses. […] In a meta-analytic examination of studies of the correlates of supervisor-directed hostility, Herschovis et al. (2007) found support for the idea that subordinates who believe that they have been the target of mistreatment are more likely to lash out at their supervisors. […] perhaps just as interesting as the associations that have been uncovered are several hypothesized associations that have not emerged. Greenberg and Barling (1999) found that supervisor-directed aggression was unrelated to subordinates’ alcohol consumption, history of aggression, and job security. Other work has revealed mixed results for the prediction that subordinate self-esteem will negatively predict supervisor-directed hostility (Inness, Barling, & Turner, 2005). […] Negative exchanges between supervisors and subordinates do not play out in isolation — others observe them and are affected by them. Yet little is known about the affective, cognitive, and behavioral responses of third parties to negative exchanges with supervisors.”

August 8, 2018 Posted by | Books, Psychology | Leave a comment

Combinatorics (I)

This book is not a particularly easy read, compared to what is the general format of the series in which it is published, but this is a good thing in my view as it also means the author managed to go into enough details in specific contexts to touch upon at least some properties/topics of interest. You don’t need any specific background knowledge to read and understand the book – at least not any sort of background knowledge one would not expect someone who might decide to read a book like this one to already have – but you do need when reading it to have the sort of mental surplus that enables you to think carefully about what’s going on and devote a few mental resources to understanding the details.

Some quotes and links from the first half of the book below.

“The subject of combinatorial analysis or combinatorics […] [w]e may loosely describe [as] the branch of mathematics concerned with selecting, arranging, constructing, classifying, and counting or listing things. […] the subject involves finite sets or discrete elements that proceed in separate steps […] rather than continuous systems […] Mathematicians sometimes use the term ‘combinatorics’ to refer to a larger subset of discrete mathematics that includes graph theory. In that case, what is commonly called combinatorics is then referred to as ‘enumeration’. […] Combinatorics now includes a wide range of topics, some of which we cover in this book, such as the geometry of tilings and polyhedra […], the theory of graphs […], magic squares and latin squares […], block designs and finite projective planes […], and partitions of numbers […]. [The] chapters [of the book] are largely independent of each other and can be read in any order. Much of combinatorics originated in recreational pastimes […] in recent years the subject has developed in depth and variety and has increasingly become a part of mainstream mathematics. […] Undoubtedly part of the reason for the subject’s recent importance has arisen from the growth of computer science and the increasing use of algorithmic methods for solving real-world practical problems. These have led to combinatorial applications in a wide range of subject areas, both within and outside mathematics, including network analysis, coding theory, probability, virology, experimental design, scheduling, and operations research.”

“[C]ombinatorics is primarily concerned with four types of problem:
Existence problem: Does □□□ exist?
Construction problem: If □□□ exists, how can we construct it?
Enumeration problem: How many □□□ are there?
Optimization problem: Which □□□ is best? […]
[T]hese types of problems are not unrelated; for example, the easiest way to prove that something exists may be to construct it explicitly.”

“In this book we consider two types of enumeration problem – counting problems in which we simply wish to know the number of objects involved, and listing problems in which we want to list them all explicitly. […] It’s useful to have some basic counting rules […] In what follows, all the sets are finite. […] In general we have the following rule; here, subsets are disjoint if they have no objects in common: Addition rule: To find the number of objects in a set, split the set into disjoint subsets, count the objects in each subset, and add the results. […] Subtraction rule: If a set of objects can be split into two subsets A and B, then the number of objects in B is obtained by subtracting the number of objects in A from the number in the whole set. […] The subtraction rule extends easily to sets that are split into more than two subsets with no elements in common. […] the inclusion-exclusion principle […] extends this simple idea to the situation where the subsets may have objects in common. […] In general we have the following result: Multiplication rule: If a counting problem can be split into stages with several options at each stage, then the total number of possibilities is the product of options at each stage. […] Another useful principle in combinatorics is the following: Correspondence rule: We can solve a counting problem if we can put the objects to be counted in one-to-one correspondence with the objects of a set that we have already counted. […] We conclude this section with one more rule: Division rule: If a set of n elements can be split into m disjoint subsets, each of size k, then m = n / k.”

“Every algorithm has a running time […] this may be the time that a computer needs to carry out all the necessary calculations, or the actual number of such calculations. Each problem [also] has an input size […] the running time T usually depends on the input size n. Particularly important, because they’re the most efficient, are the polynomial-time algorithms, where the maximum running time is proportional to a power of the input size […] The collection of all polynomial-time algorithms is called P. […] In contrast, there are inefficient algorithms that don’t take polynomial time, such as the exponential-time algorithms […] At this point we introduce NP, the set of ‘non-deterministic polynomial-time problems’. These are algorithms for which a solution, when given, can be checked in polynomial time. Clearly P is contained in NP, since if a problem can be solved in polynomial time then a solution can certainly be checked in polynomial time – checking solutions is far easier than finding them in the first place. But are they the same? […] Few people people believe that the answer is ‘yes’, but no one has been able to prove that P ≠ NP. […] a problem is NP-complete if its solution in polynomial time means that every NP problem can be solved in polynomial time. […] If there were a polynomial algorithm for just one of them, then polynomial algorithms would exist for the whole lot and P would equal NP. On the other hand, if just one of them has no polynomial algorithm, then none of the others could have a polynomial algorithm either, and P would be different from NP.”

“In how many different ways can n objects be arranged? […] generally, we have the following result: Arrangements: The number of arrangements of n objects is n x (n -1) x (n – 2) x … x 3 x 2 x 1. This number is called n factorial and is denoted by n!. […] The word permutation is used in different ways. We’ll use it to mean an ordered selection without repetition, while others may use it to mean an arrangement […] generally, we have the following rule: Ordered selections without repetition (permutations): If we select k items from a set of n objects, and if the selections are ordered and repetition is not allowed, then the number of possible selections is n x (n – 1) x (n – 2) x … x (n – k +1). We denote this expression by P(n,k). […] Since P(n, n) = n x (n -1) x (n – 2) x … x 3 x 2 x 1 = n!, an arrangement is a permutation for which k = n. […] generally, we have the following result: P(n,k) = n! /(n-k)!. […] unordered selections without repetition are called combinations, giving rise to the words combinatorial and combinatorics. […] generally, we have the following result: Unordered selections without repetition (combinations): If we select k items from a set of n objects, and if the selections are unordered and repetition is not allowed, then the number of possible selections is P(n,k)/k! = n x (n-1) x (n-2) x … x (n – k + 1)/k!. We denote this expression by C(n,k) […] Unordered selections with repetition: If we select k items from a set of n objects, and if the selections are unordered and repetition is allowed, then the number of possible selections is C(n + k – 1, k). […] Combination rule 1: For any numbers k and n with n, C(n,k) = C(n,n-k) […] Combination rule 2: For any numbers n and k with n, C(n, n-k) = n!/(n-k)!(n-(n-k))! = n!/(n-k)!k! = C(n,k). […] Combination rule 3: For any number n, C(n,0) + C(n,1) + C(n,2) + … + C(n,n-1) + C(n,n) = 2n


Knight’s tour.
Seven Bridges of Königsberg problem.
Three utilities problem.
Four color theorem.
Tarry’s algorithm (p.7) (formulated slightly differently in the book, but it’s the same algorithm).
Arthur Cayley.
Combinatorial principles.
Minimum connector problem.
Travelling salesman problem.
Algorithmic efficiency. Running time/time complexity.
Boolean satisfiability problem. Cook–Levin theorem.
Mersenne primes.
Permutation. Factorial. Stirling’s formula.
Birthday problem.
Manhattan distance.
Fibonacci number.
Pascal’s triangle. Binomial coefficient. Binomial theorem.
Pigeonhole principle.
Venn diagram.
Derangement (combinatorial mathematics).
Tower of Hanoi.
Stable marriage problem. Transversal (combinatorics). Hall’s marriage theorem.
Generating function (the topic covered in the book more specifically is related to a symbolic generator of the subsets of a set, but a brief search yielded no good links to this particular topic – US).
Group theory.
Ferdinand Frobenius. Burnside’s lemma.

August 4, 2018 Posted by | Books, Computer science, Mathematics | 1 Comment


The words below are mostly words which I encountered while reading the books Pocket oncology, Djinn Rummy, Open Sesame, and The Far Side of the World.

Hematochezia. Neuromyotonia. Anoproctitis. Travelator. Brassica. Physiatry. Clivus. Curettage. Colposcopy. Trachelectomy. Photopheresis. Myelophthisis. Apheresis. Vexilloid. Gonfalon. Eutectic. Clerisy. Frippery. Scrip. Bludge.

Illude. Empyrean. Bonzer. Vol-au-vent. Curule. Entrechat. Winceyette. Attar. Woodbine. Corolla. Rennet. Gusset. Jacquard. Antipodean. Chaplet. Thrush. Coloratura. Biryani. Caff. Scrummy.

Beatific. Forecourt. Hurtle. Freemartin. Coleoptera. Hemipode. Bespeak. Dickey. Bilbo. Hale. Grampus. Calenture. Reeve. Cribbing. Fleam. Totipalmate. Bonito. Blackstrake/Black strake. Shank. Caiman.

Chancery. Acullico. Thole. Aorist. Westing. Scorbutic. Voyol. Fribble. Terraqueous. Oviparous. Specktioneer. Aprication. Phalarope. Lough. Hoy. Reel. Trachyte. Woulding. Anthropophagy. Risorgimento.


August 2, 2018 Posted by | Books, Language | Leave a comment


i. “Progress in science is often built on wrong theories that are later corrected. It is better to be wrong than to be vague.” (Freeman Dyson)

ii. “The teacher’s equipment gives him an everlasting job. His work is never done. His getting ready for this work is never quite complete.” (George Trumbull Ladd)

iii. “The crust of our earth is a great cemetery, where the rocks are tombstones on which the buried dead have written their own epitaphs.” (Louis Agassiz)

iv. “Fortunately science, like that nature to which it belongs, is neither limited by time nor by space. It belongs to the world, and is of no country and of no age. The more we know, the more we feel our ignorance […] there are always new worlds to conquer.” (Humphrey Davy)

v. “Nothing is so fatal to the progress of the human mind as to suppose that our views of science are ultimate; that there are no mysteries in nature; that our triumphs are complete, and that there are no new worlds to conquer.” (-ll-)

vi. “The best way to learn Japanese is to be born as a Japanese baby, in Japan, raised by a Japanese family.” (Dave Barry)

vii. “What makes a date so dreadful is the weight of expectation attached to it. There is every chance that you may meet your soulmate, get married, have children and be buried side by side. There is an equal chance that the person you meet will look as if they’ve already been buried for some time.” (Guy Browning)

viii. “Always judge your fellow passengers to be the opposite of what they strive to appear to be. […] men never affect to be what they are, but what they are not.” (Thomas Chandler Haliburton)

ix. “Some folks can look so busy doin’ nothin’ that they seem indispensable.” (Kin Hubbard)

x. “Men are not punished for their sins, but by them.” (-ll-)

xi. “Do what we will, we always, more or less, construct our own universe. The history of science may be described as the history of the attempts, and the failures, of men “to see things as they are.”” (Matthew Moncrieff Pattison Muir)

xii. “You simply cannot invent any conspiracy theory so ridiculous and obviously satirical that some people somewhere don’t already believe it.” (Robert Anton Wilson)

xiii. “You know you are getting old when work is a lot less fun and fun is a lot more work.” (Joan Rivers)

xiv. “When I was a little boy, I used to pray every night for a new bicycle. Then I realised, the Lord, in his wisdom, doesn’t work that way. So I just stole one and asked Him to forgive me.” (Emo Philips)

xv. “I was walking down Fifth Avenue today and I found a wallet, and I was gonna keep it, rather than return it, but I thought: “Well, if I lost a hundred and fifty dollars, how would I feel?” And I realized I would want to be taught a lesson.” (-ll-)

xvi. “When I said I was going to become a comedian, they all laughed. Well, they’re not laughing now, are they?” (Robert Monkhouse)

xvii. “Things said in embarrassment and anger are seldom the truth, but are said to hurt and wound the other person. Once said, they can never be taken back.” (Lucille Ball)

xviii. “The beginning of wisdom for a programmer is to recognize the difference between getting his program to work and getting it right. A program which does not work is undoubtedly wrong; but a program which does work is not necessarily right. It may still be wrong because it is hard to understand; or because it is hard to maintain as the problem requirements change; or because its structure is different from the structure of the problem; or because we cannot be sure that it does indeed work.” (Michael Anthony Jackson)

xix. “One of the difficulties in thinking about software is its huge variety. A function definition in a spreadsheet cell is software. A smartphone app is software. The flight management system for an Airbus A380 is software. A word processor is software. We shouldn’t expect a single discipline of software engineering to cover all of these, any more than we expect a single discipline of manufacturing to cover everything from the Airbus A380 to the production of chocolate bars, or a single discipline of social organization to cover everything from the United Nations to a kindergarten. Improvement in software engineering must come bottom-up, from intense specialized attention to particular products.” (-ll-)

xx. “Let the world know you as you are, not as you think you should be, because sooner or later, if you are posing, you will forget the pose, and then where are you?” (Fanny Brice)

July 30, 2018 Posted by | Quotes/aphorisms | Leave a comment