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)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (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. Africa has seen an increase in the number of health research projects being conducted on the continent, particularly clinical trials. Ideally, this should be accompanied by a commensurate improvement in research ethics review capacity to competently provide the much-required research ethics oversight. Unfortunately, this is not the case in many African countries, which are still grappling with weak research ethics oversight capacity, not only at national level but also at institutional level. Objectives. To describe the proposal by Kenya’s national (...) research ethics regulatory authority, the National Commission for Science Technology and Innovation (NACOSTI), to build the capacity of its National Scientific and Ethics Committee (NSEC), tasked with providing the required research ethics oversight in the country. Methods. This is the proposal submitted by NACOSTI to the European and Developing Countries Clinical Trials Partnership for funding of a project entitled ‘Strengthening Research Ethics and Oversight in Kenya’ (STReK). It describes the activities involved to strengthen the NSEC to provide the required research ethics in the country, and to build the research ethics capacity of research ethics committees (RECs) it has accredited, through training and mentorship programmes, to enable them to efficiently review research proposals. Results. Proposed activities of the project are presented. Implementation of the activities described is ongoing. Conclusion. Lessons learnt in this regard may be of benefit to other research ethics regulatory authorities in resource-constrained countries aiming to strengthen their research ethics oversight capacity. (shrink)

In the conclusion to this multi-part article I first review the discussions carried out around the six essential questions in psychiatric diagnosis – the position taken by Allen Frances on each question, the commentaries on the respective question along with Frances’ responses to the commentaries, and my own view of the multiple discussions. In this review I emphasize that the core question is the first – what is the nature of psychiatric illness – and that in some manner all further (...) questions follow from the first. Following this review I attempt to move the discussion forward, addressing the first question from the perspectives of natural kind analysis and complexity analysis. This reflection leads toward a view of psychiatric disorders – and future nosologies – as far more complex and uncertain than we have imagined. (shrink)

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role (...) of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM - whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article will take up the first two questions. With the first question, invited commentators express a range of opinion regarding the nature of psychiatric disorders, loosely divided into a realist position that the diagnostic categories represent real diseases that we can accurately name and know with our perceptual abilities, a middle, nominalist position that psychiatric disorders do exist in the real world but that our diagnostic categories are constructs that may or may not accurately represent the disorders out there, and finally a purely constructivist position that the diagnostic categories are simply constructs with no evidence of psychiatric disorders in the real world. The second question again offers a range of opinion as to how we should define a mental or psychiatric disorder, including the possibility that we should not try to formulate a definition. The general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances. (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)

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role (...) of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM - whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article took up the first two questions. Part II will take up the second two questions. Question 3 deals with the question as to whether DSM-V should assume a conservative or assertive posture in making changes from DSM-IV. That question in turn breaks down into discussion of diagnoses that depend on, and aim toward, empirical, scientific validation, and diagnoses that are more value-laden and less amenable to scientific validation. Question 4 takes up the role of pragmatic consideration in a psychiatric nosology, whether the purely empirical considerations need to be tempered by considerations of practical consequence. As in Part 1 of this article, the general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances. (shrink)

Traction forces developed by most cell types play a significant role in the spatial organisation of biological tissues. However, due to the complexity of cell-extracellular matrix interactions, these forces are quantitatively difficult to estimate without explicitly considering cell properties and extracellular mechanical matrix responses. Recent experimental devices elaborated for measuring cell traction on extracellular matrix use cell deposits on a piece of gel placed between one fixed and one moving holder. We formulate here a mathematical model describing the dynamic behaviour (...) of the cell-gel medium in such devices. This model is based on a mechanical force balance quantification of the gel visco-elastic response to the traction forces exerted by the diffusing cells. Thus, we theoretically analyzed and simulated the displacement of the free moving boundary of the system under various conditions for cells and gel concentrations. This modelis then used as the theoretical basis of an experimental device where endothelial cells are seeded on a rectangular biogel of fibrin cast between two floating holders, one fixed and the other linked to a force sensor. From a comparison of displacement of the gel moving boundary simulated by the model and the experimental data recorded from the moving holder displacement, the magnitude of the traction forces exerted by the endothelial cell on the fibrin gel was estimated for different experimental situations. Different analytical expressions for the cell traction term are proposed and the corresponding force quantifications are compared to the traction force measurements reported for various kind of cells with the use of similar or different experimental devices. (shrink)

Although written consent forms are standard in clinical research, there is little regulatory or empirical guidance regarding how to most effectively review consent forms with potential participants. We developed an algorithm for embedding five questions with corrective feedback while reading consent forms with potential participants, and then applied it in the context of seven clinical research studies. A substantial proportion of participants within each protocol displayed initially inadequate responses to at least one question, but after the protocol elements were explained (...) again, most people demonstrated adequate understanding of them. These data illustrate the need for more attention not just to the content of consent forms, but also to the manner in which the forms are incorporated into the consent process. Embedding explicit inquiries about key protocol elements during consent form review and giving corrective feedback appears to be a simple yet effective way to foster better understanding of disclosed information. (shrink)

European animal disease policy seems to find its justification in a “harm to other” principle. Limiting the freedom of animal keepers—e.g., by culling their animals—is justified by the aim to prevent harm, i.e., the spreading of the disease. The picture, however, is more complicated. Both during the control of outbreaks and in the prevention of notifiable, animal diseases the government is confronted with conflicting claims of stakeholders who anticipate running a risk to be harmed by each other, and who ask (...) for government intervention. In this paper, we first argue that in a policy that aims to prevent animal diseases, the focus shifts from limiting “harm” to weighing conflicting claims with respect to “risks of harm.” Therefore, we claim that the harm principle is no longer a sufficient justification for governmental intervention in animal disease prevention. A policy that has to deal with and distribute conflicting risks of harm needs additional value assumptions that guide this process of assessment and distribution. We show that currently, policies are based on assumptions that are mainly economic considerations. In order to show the limitations of these considerations, we use the interests and position of keepers of backyard animals as an example. Based on the problems they faced during and after the recent outbreaks, we defend the thesis that in order to develop a sustainable animal disease policy other than economic assumptions need to be taken into account. (shrink)

We report specific heat and μSR measurements on Th and/or B substituted UBe13. The specific heat data show that either Th or B substitution reduces the Kondo temperature TK and increases the entropy at the superconducting transition by almost 20%, indicating an enhanced density of states. However, whereas μSR shows clear evidence for magnetic correlations for Th substitutions, no magnetism is observed for B substitutions. The enhanced specific heat jump in the B-substituted material is associated with a change in the (...) superconducting properties as TK is reduced. (shrink)

1 Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2 During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for (...) generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3 The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4 The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5 Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible. (shrink)

© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate (...) assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)

Structured interviews were held with 149 registered nurses in seven countries in America, Asia, Australia and Europe concerning the feeding of severely demented patients who do not accept food. The most common reasons for nurses being willing to change their decision to feed or not to feed were an order from the medical head, a request from the patient's husband and/or the staff meeting. There was a connection between the willingness to feed and the ranking of ethical principles. Nurses who (...) were most prone to feed the patient most often gave a high rank to the ethical principle of sanctity of life, while those who primarily chose not to feed the patient gave a high rank to the ethical principle of autonomy. All nurses stressed the ethical principle of beneficence. Des interviews structurés ont eu lieu avec 149 infirmiers/ères dans sept pays en Amérique, Asie, Australie et Europe concernant l'alimentation des malades gravement dément qui refusent de manger. La raison la plus générale pour des infirmiers/ères d'être prêt à changer leures décisions de donner à manger ou non sont: un ordre du médecin, la demande du mari de la malade ou de la réunion du personnel. Il y avait un lien entre la volonté de nourir et le rang des principes éthiques. Les infirmiers/ères les plus enclins de nourir la malade le plus souvent donnaient un rang supérieur au principe éthique de la sainteté de vie, pendant que ceux et celles qui choisissaient de ne pas nourrir la malade donnaient un rang supérieur au principe éthique de l'autonomie. Tous insistaient sur l'importance du principe éthique de la bienfaisance. Konstruktive Interviews wurden mit 149 ausgebildeten Krankenschwestern und Pfleger in sieben Ländern in Amerika, Asien, Australien und Europa gehalten über die Ernährung von schwer von Dementia praecox leidenden Patienten, die das Essen verweigern. Die gewöhnlichsten Gründe des Pflegepersonals für die Bereitwilligkeit, ihre Entscheidung, zu ernähren oder nicht, zu ändern, waren Anordnungen vom medizinischen Chef, Anfragen vom Ehemann der Patientin und/oder einer Personalsitzung. Es bestand ein Zusammenhang zwischen der Bereitwilligkeit zur Ernährung und dem Rang der ethischen Prinzipien. Die Pflegenden, die sich am meisten neigten, die Patientin zu ernähren, gaben dem ethischen Prinzip der Heiligkeit des Lebens einen hohen Rang, während die, die meistens vorzogen, die Patientin nicht zu ernähren, gaben dem ethischen Prinzip der Autonomie einen hohen Rang. Alle Pflegenden legten grossen Wert auf das ethische Prinzip der Wohltätigkeit. (shrink)

The aim of the study was to determine the acceptance and perception of Nigerian patients to medical photography. A self-administered questionnaire was distributed among Nigerian patients attending oral and maxillofacial surgery and plastic surgery clinics of 3 tertiary health institutions. Information requested included patients' opinion about consent process, capturing equipment, distribution and accessibility of medical photographs. The use of non-identifiable medical photographs was more acceptable than identifiable to respondents for all purposes (P = 0.003). Most respondents were favourably disposed to (...) photographs being taken for inclusion in the case note, but opposed to identifiable photographs being used for other purposes most especially in medical websites and medical journals. Female respondents preferred non-identifiable medical photographs to identifiable ones (P = 0.001). Most respondents (78%) indicated that their consent be sought for each of the outline needs for medical photography. Half of the respondents indicated that identifiable photographs may have a negative effect on their persons; and the most commonly mentioned effects were social stigmatization, bad publicity and emotional/psychological effects. Most of the respondents preferred the use of hospital-owned camera to personal camera/personal camera-phone for their medical photographs. Most respondents (67.8%) indicated that they would like to be informed about the use of their photographs on every occasion, and 74% indicated that they would like to be informed of the specific journal in which their medical photographs are to be published. In conclusion, non-identifiable rather than identifiable medical photography is acceptable to most patients in the studied Nigerian environment. The use of personal camera/personal camera-phone should be discouraged as its acceptance by respondents is very low. Judicious use of medical photography is therefore advocated to avoid breach of principle of privacy and confidentiality in medical practice. (shrink)

The many well-publicized food scandals in recent years have resulted in a general state of vulnerable trust. As a result, building consumer trust has become an important goal in agri-food policy. In their efforts to protect trust in the agricultural and food sector, governments and industries have tended to consider the problem of trust as merely a matter of informing consumers on risks. In this article, we argue that the food sector better addresses the problem of trust from the perspective (...) of the trustworthiness of the food sector itself. This broad idea for changing the focus of trust is the assumption that if you want to be trusted, you should be trustworthy. To provide a clear understanding of what being trustworthy means within the food sector, we elaborate on both the concept of trust and of responsibility. In this way we show that policy focused on enhancing transparency and providing information to consumers is crucial, but not sufficient for dealing with the problem of consumer trust in the current agri-food context. (shrink)