Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

Initial responses to questionnaires used to assess participants' understanding of informed consent for malaria vaccine trials conducted in the United States and Mali were tallied. Total scores were analyzed by age, sex, literacy (if known), and location. Ninety-two percent (92%) of answers by United States participants and 85% of answers by Malian participants were correct. Questions more likely to be answered incorrectly in Mali related to risk, and to the type of vaccine. For adult participants, independent predictors of higher scores (...) were younger age and female sex in the United States, and male sex in Mali. Scores in the United States were higher than in Mali (P = 0.005). Despite this difference participants at both sites were well informed overall. Although interpretation must be qualified because questionnaires were not intended as research tools and were not standardized among sites, these results do not support concerns about systematic low understanding among research participants in developing versus developed countries. (shrink)

Placebo-controlled trials are controversial when individuals might be denied existing beneficial medical interventions. In the case of malaria, most patients die in rural villages without healthcare facilities. An artesunate suppository that can be given by minimally skilled persons might be of value when patients suddenly become too ill for oral treatment but are several hours from a facility that can give injectable treatment for severe disease. In such situations, by default, no treatment is (or can be) given until the patient (...) reaches a facility, making the placebo control design clinically relevant; alternative bioequivalence designs at the facility would misrepresent reality and risk incorrect conclusions. We describe the ethical issues underpinning a placebo-controlled trial in severe malaria. To protect patients and minimise risk, all patients were referred immediately to hospital so that each had a higher chance of prompt treatment through participation. There was no difference between artesunate and placebo in patients who reached clinic rapidly; among those who could not, a single artesunate suppository significantly reduced death or permanent disability, a finding of direct and indirect benefit to patients in participating villages and elsewhere. (shrink)

A cross-cultural survey experiment revealed a dominant tendency to rely on a rule’s letter over its spirit when deciding which behaviors violate the rule. This tendency varied markedly across (k = 15) countries, owing to variation in the impact of moral appraisals on judgments of rule violation. Compared with laypeople, legal experts were more inclined to disregard their moral evaluations of the acts altogether and consequently exhibited stronger textualist tendencies. Finally, we evaluated a plausible mechanism for the emergence of textualism: (...) in a two-player coordination game, incentives to coordinate in the absence of communication reinforced participants’ adherence to rules’ literal meaning. Together, these studies (total n = 5,794) help clarify the origins and allure of textualism, especially in the law. Within heterogeneous communities in which members diverge in their moral appraisals involving a rule’s purpose, the rule’s literal meaning provides a clear focal point—an identifiable point of agreement enabling coordinated interpretation among citizens, lawmakers, and judges. (shrink)

Iranian research on anomie; enjoining good and forbidding evil.

Planned home birth has been considered by some to be consistent with professional responsibility in patient care. This article critically assesses the ethical and scientific justification for this view and shows it to be unjustified. We critically assess recent statements by professional associations of obstetricians, one that sanctions and one that endorses planned home birth. We base our critical appraisal on the professional responsibility model of obstetric ethics, which is based on the ethical concept of medicine from the Scottish and (...) English Enlightenments of the 18th century. Our critical assessment supports the following conclusions. Because of its significantly increased, preventable perinatal risks, planned home birth in the United States is not clinically or ethically benign. Attending planned home birth, no matter one’s training or experience, is not acting in a professional capacity, because this role preventably results in clinically unnecessary and therefore clinically unacceptable perinatal risk. It is therefore not consistent with the ethical concept of medicine as a profession for any attendant to planned home birth to represent himself or herself as a “professional.” Obstetric healthcare associations should neither sanction nor endorse planned home birth. Instead, these associations should recommend against planned home birth. Obstetric healthcare professionals should respond to expressions of interest in planned home birth by pregnant women by informing them that it incurs significantly increased, preventable perinatal risks, by recommending strongly against planned home birth, and by recommending strongly for planned hospital birth. Obstetric healthcare professionals should routinely provide excellent obstetric care to all women transferred to the hospital from a planned home birth. The professional responsibility model of obstetric ethics requires obstetricians to address and remedy legitimate dissatisfaction with some hospital settings and address patients’ concerns about excessive interventions. Creating a sustained culture of comprehensive safety, which cannot be achieved in planned home birth, informed by compassionate and respectful treatment of pregnant women, should be a primary focus of professional obstetric responsibility. (shrink)

Summary A study of the metallurgy and manufacturing techniques of a group of eight astrolabes (seven from Lahore, one attributed to India) using non-destructive methods has produced the earliest evidence for systematic use of high-zinc (α?+??) brass. To produce this alloy, the brass industry supplying the Lahore instrument makers must have co-melted metallic copper and zinc. This brass-making technology was previously believed to have been developed on an industrial scale in the nineteenth century in Europe. This work hypothesizes that this (...) technology was used in Lahore on an industrial scale as early as ad 1601. In addition, this work hypothesizes that the α?+?? brass alloy was used specifically for its ease in manufacturing the thin sheet brass required for astrolabe-component manufacture. (shrink)

Patient safety has only recently been subjected to wide-spread systematic study. Healthcare differs from other high risk industries in being more diverse and multi-contextual, and less certain and regulated. Also many patient safety problems are low-frequency events associated with many, varied contributing factors. The subject of this paper is the epistemology of patient safety (the science of the method of finding out about patient safety). Patient safety research is considered here on the background of a risk management framework which requires (...) researchers to: • Understand the context - as a subset of healthcare quality, services and systems research, with technical and human behavioural (cultural) components and a range of external and internal organisational influences, a wide range of research disciplines is necessary • Identify the risks - identify the things that go wrong and the frequency and nature of different types of incidents from sources such as medical record review, observational studies, audit, incident and medico-legal reports • Analyse the risks - deconstruct the things that go wrong, identifying contributing factors and trying to detect trends and patterns in contributing factors, detection, mitigation factors, ameliorating factors and actions taken to reduce risk • Evaluate the risks - decide on priorities, identifying preventive and corrective strategies and judging the risk- and cost-benefit of potential corrective strategies such as standardisation or simplification of a process or device • Manage the risk - evaluate and scope preventive and/or corrective strategies and then implement these, or place the problem on a risk register pending solution, or accept that what is needed is unaffordable • Communicate and consult - use interactive sessions, audit, on-going feedback, reminders and patient mediated prompts • Monitor and review the state of the problem - get baseline trends and patterns so that changes can be tracked and properly attributed to an intervention A hierarchy of levels of evidence has been proposed for clinical research and we argue that insufficient weighting has been given to lower ranked levels of research and to qualitative research, although critical interpretive synthesis is now gaining acceptance in mainstream thinking (e.g. by the Cochrane Collaboration). Fundamental challenges remain including how to grasp the elusive concept of patient safety, how to quantify, characterise and cost the problems, how to judge the extent to which harm can be attributed to errors, violations or system failures, how to identify contributing factors and the extent to which they can be implicated, how to judge whether incidents or their precursors are preventable, how to generate strong evidence to make healthcare safer and how to translate research into practice. Future directions include addressing the mundane as well as rare, dramatic events, and developing further research in non-hospital settings and in developing countries. In summary, a mixture of qualitative and quantitative methods, using information from all available data sources and combining retrospective, real time and prospective study designs, is necessary to address some of the more difficult patient safety problems. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

The main objective of this essay is to validate some of the principal, currently competing, mammalian consciousness-brain theories by comparing these theories with data on both cognitive abilities and brain organization in birds. Our argument is that, given that multiple complex cognitive functions are correlated with presumed consciousness in mammals, this correlation holds for birds as well. Thus, the neuroanatomical features of the forebrain common to both birds and mammals may be those that are crucial to the generation of both (...) complex cognition and consciousness. The general conclusion is that most of the consciousness-brain theories appear to be valid for the avian brain. Even though some specific homologies are unresolved, most of the critical structures presumed necessary for consciousness in mammalian brains have clear homologues in avian brains. Furthermore, considering the fact that the reptile-bird brain transition shows more structural continuity than the stem amniote-mammalian transition, the line drawn at the origin of mammals for consciousness by several of the theorists seems questionable. An equally important point is that consciousness cannot be ruled out in the absence of complex cognition; it may in fact be the case that consciousness is a necessary prerequisite for complex cognition. (shrink)

In this paper Popper formulates and discusses a new aspect of the theory of mind. This theory is partly based on his earlier developed interactionistic theory. It takes as its point of departure the observation that mind and physical forces have several properties in common, at least the following six: both are located, unextended, incorporeal, capable of acting on bodies, dependent upon body, capable of being influenced by bodies. Other properties such as intensity and extension in time may be added. (...) It is argued that a fuller understanding of the nature of forces is essential for the analysis of the mind-brain problem. The relative autonomy and indeterministic nature of mind is stressed. Indeterminism is treated in relation to a theorem of Hadamard. The computer theory of mind and the Turing test are criticized. Finally the evolution of mind is discussed. (shrink)

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

© 2016 Regents of the University of California.The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous (...) tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 117 reviews are many that are new or heavily revised, including those on Pentaquarks and Inflation. The complete Review is published online in a journal and on the website of the Particle Data Group. The printed PDG Book contains the Summary Tables and all review articles but no longer includes the detailed tables from the Particle Listings. A Booklet with the Summary Tables and abbreviated versions of some of the review articles is also available. (shrink)

BACKGROUND: Serotonin transporter promoter genotype appears to increase risk for depression in the context of stressful life events. However, the effects of this genotype on measures of stress sensitivity are poorly understood. Therefore, this study examined whether 5-HTTLPR genotype was associated with negative information processing biases in early childhood. METHOD: Thirty-nine unselected seven-year-old children completed a negative mood induction procedure and a Self-Referent Encoding Task designed to measure positive and negative schematic processing. Children were also genotyped for the 5-HTTLPR gene. (...) RESULTS: Children who were homozygous for the short allele of the 5-HTTLPR gene showed greater negative schematic processing following a negative mood prime than those with other genotypes. 5-HTTLPR genotype was not significantly associated with positive schematic processing. LIMITATIONS: The sample size for this study was small. We did not analyze more recently reported variants of the 5-HTTLPR long alleles. CONCLUSIONS: 5-HTTLPR genotype is associated with negative information processing styles following a negative mood prime in a non-clinical sample of young children. Such cognitive styles are thought to be activated in response to stressful life events, leading to depressive symptoms; thus, cognitive styles may index the "stress-sensitivity" conferred by this genotype. (shrink)

Everywhere the 1990s have been characterized by an odd mixture of ideological triumphalism-Fukuyama's "end of history" being only the crassest example-and of ideological uncertainty-can there be, should there be, a "third way"? For all its pretensions to universality, the "New World Order" has never lost a fragility in appearance. Students of historiography can scarcely be surprised to learn that an uneasiness over the present and future has in turn frequently entailed uncertainty about the past and particularly about those parts of (...) the past which had seemed most able to give clear and significant "lessons."One evident example is the history of what in my Explaining Auschwitz and Hiroshima I called the "long" Second World War, that is, that crisis in confidence in the relationship between political and economic liberalism and the nation-state which, by the end of 1938, had left only Britain, France, the Low Countries, and Scandinavia as in any sense preserving those "liberal" freedoms which had spread across Europe since 1789. In this article, I briefly review the most recent difficulties World War II combatant societies have had in locating a usable past in the history of those times. However, my major focus is on the specific case of Italy, very much a border state in the Cold War system, and today the political home of an "Olive Tree" and a "Liberty Pole" whose historical antecedents and whose philosophical base for the future are less than limpid. 1990s Italian historians thus give very mixed messages about the Fascist past; these are the messages I describe and decode. (shrink)

OBJECTIVES: Early-emerging, temperamental differences in fear-related traits may be a heritable vulnerability factor for anxiety disorders. Previous research indicates that the serotonin transporter promoter region polymorphism is a candidate gene for such traits. METHODS: Associations between 5-HTTLPR genotype and indices of fearful child temperament, derived from maternal report and standardized laboratory observations, were examined in a community sample of 95 preschool-aged children. RESULTS: Children with one or more long alleles of the 5-HTTLPR gene were rated as significantly more nervous during (...) standardized laboratory tasks than children who were homozygous for the short alleles. Children homozygous for the short alleles were also rated as significantly shyer, by maternal report, than those with at least one copy of the long allele of the 5-HTTLPR gene. CONCLUSIONS: This study extends the literature linking the short alleles of the serotonin transporter promoter region polymorphism to fear and anxiety-related traits in early childhood and adulthood, and is one of very few studies to examine the molecular genetics of preschoolers' temperament using multiple measures of traits in a normative sample. (shrink)

How do people understand questions about cause and prevent? Some theories propose that people affirm that A causes B if A's occurrence makes a difference to B's occurrence in one way or another. Other theories propose that A causes B if some quantity or symbol gets passed in some way from A to B. The aim of our studies is to compare these theories' ability to explain judgements of causation and prevention. We describe six experiments that compare judgements for causal (...) paths that involve a mechanism, i.e. a continuous process of transmission or exchange from cause to effect, against paths that involve no mechanism yet a change in the cause nevertheless brings about a change in the effect. Our results show that people prefer to attribute cause when a mechanism links cause to effect. In contrast, prevention is sensitive both to the presence of an interruption to a causal mechanism and to a change in the outcome in the absence of a mechanism. In this sense, ‘prevent’ means something different than ‘cause not'. We discuss the implications of our results for existing theories of causation. (shrink)

Quite rightly, philosophers of physics examine the theories of physics, theories like Quantum Mechanics, Quantum Field Theory, the Special and General Theories of Relativity, and Statistical Mechanics. Far fewer, however, examine how these theories are put to use; that is to say, little attention is paid to the practices of theoretical physicists. In the early 1950s David Bohm and David Pines published a sequence of four papers, collectively entitled, ‘A Collective Description of Electron Interaction.’ This essay uses that quartet as (...) a case study in theoretical practice. In Part One of the essay, each of the Bohm-Pines papers is summarized, and within each summary an overview is given, framing a more detailed account. In Part Two theoretical practice is broken into six elements: (a) the use of models, (b) the use of theory, (c) modes of description and narrative, (d) the use of approximations, (e) experiment and theory, (f) the varied steps employed in a deduction. The last element is the largest, drawing as it does from the earlier ones. Part Three enlarges on the concept of ‘theoretical practice,’ and briefly outlines the subsequent theoretical advances which rendered the practices of Bohm and Pines obsolete, if still respected. (shrink)