The 'At-risk mental state' for psychosis in adolescents : clinical presentation, transition and remission.

Despite increased efforts over the last decade to prospectively identify individuals at ultra-high risk of developing a psychotic illness, limited attention has been specifically directed towards adolescent populations (<18 years). In order to evaluate how those under 18 fulfilling the operationalised criteria for an At-Risk Mental State (ARMS) present and fare over time, we conducted an observational study. Participants (N = 30) generally reported a high degree of functional disability and frequent and distressing perceptual disturbance, mainly in the form of auditory hallucinations. Seventy percent (21/30) were found to fulfil the criteria for a co-morbid ICD-10 listed mental health disorder, with mood (affective; 13/30) disorders being most prevalent. Overall transition rates to psychosis were low at 24 months follow-up (2/28; 7.1 %) whilst many participants demonstrated a significant reduction in psychotic-like symptoms. The generalisation of these findings may be limited due to the small sample size and require replication in a larger sample

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

&lt;b&gt;Background&lt;/b&gt; Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods and findings&lt;/b&gt; The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems

Researchers’ attitudes to the 3Rs - An upturned hierarchy?

Animal use in biomedical research is generally justified by its potential benefits to the health of humans, or other animals, or the environment. However, ethical acceptability also requires scientists to limit harm to animals in their research. Training in laboratory animal science (LAS) helps scientists to do this by promoting best practice and the 3Rs. This study evaluated scientists’ awareness and application of the 3Rs, and their approach to other ethical issues in animal research. It was based on an online survey of participants in LAS courses held in eight venues in four European countries: Portugal (Porto, Braga), Germany (Munich, Heidelberg), Switzerland (Basel, Lausanne, Zurich), and Denmark (Copenhagen). The survey questions were designed to assess general attitudes to animal use in biomedical research, Replacement alternatives, Reduction and Refinement conflicts, and harm-benefit analysis. The survey was conducted twice: immediately before the course (‘BC’, N = 310) and as a follow-up six months after the course (‘AC’, N = 127). While courses do appear to raise awareness of the 3Rs, they had no measurable effect on the existing low level of belief that animal experimentation can be fully replaced by non-animal methods. Most researchers acknowledged ethical issues with their work and reported that they discussed these with their peers. The level of an animal’s welfare, and especially the prevention of pain, was regarded as the most pressing ethical issue, and as more important than the number of animals used or the use of animals as such. Refinement was considered more feasible than Replacement, as well as more urgent, and was also favoured over Reduction. Respondents in the survey reversed the ‘hierarchy’ of the 3Rs proposed by their architects, Russell and Burch, prioritizing Refinement over Reduction, and Reduction over Replacement. This ordering may conflict with the expectations of the public and regulators.</div

Search for time-dependent B0s - B0s-bar oscillations using a vertex charge dipole technique

We report a search for B0s - B0s-bar oscillations using a sample of 400,000 hadronic Z0 decays collected by the SLD experiment. The analysis takes advantage of the electron beam polarization as well as information from the hemisphere opposite that of the reconstructed B decay to tag the B production flavor. The excellent resolution provided by the pixel CCD vertex detector is exploited to cleanly reconstruct both B and cascade D decay vertices, and tag the B decay flavor from the charge difference between them. We exclude the following values of the B0s - B0s-bar oscillation frequency: Delta m_s < 4.9 ps-1 and 7.9 < Delta m_s < 10.3 ps-1 at the 95% confidence level.Comment: 18 pages, 3 figures, replaced by version accepted for publication in Phys.Rev.D; results differ slightly from first versio

The effective rate of influenza reassortment is limited during human infection

We characterise the evolutionary dynamics of influenza infection described by viral sequence data collected from two challenge studies conducted in human hosts. Viral sequence data were collected at regular intervals from infected hosts. Changes in the sequence data observed across time show that the within-host evolution of the virus was driven by the reversion of variants acquired during previous passaging of the virus. Treatment of some patients with oseltamivir on the first day of infection did not lead to the emergence of drug resistance variants in patients. Using an evolutionary model, we inferred the effective rate of reassortment between viral segments, measuring the extent to which randomly chosen viruses within the host exchange genetic material. We find strong evidence that the rate of effective reassortment is low, such that genetic associations between polymorphic loci in different segments are preserved during the course of an infection in a manner not compatible with epistasis. Combining our evidence with that of previous studies we suggest that spatial heterogeneity in the viral population may reduce the extent to which reassortment is observed. Our results do not contradict previous findings of high rates of viral reassortment in vitro and in small animal studies, but indicate that in human hosts the effective rate of reassortment may be substantially more limited.CJRI is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 101239/Z/13/Z) and received support from the National Science Foundation Research Coordination Network on Infectious Disease Evolution Across Scales. KK, ASL, CWW, and MTM were funded by NIGMS U54-GM111274, the MIDAS Center for Inference and Dynamics of Infectious Disease. ASL acknowledges support from the MSTP training grant number T32 GM007171. GJDS was supported by the Duke-NUS Signature Research Programme funded by the Ministry of Health, Singapore and by contract HHSN272201400006C from the National Institute of Allergy and Infectious Disease, National Institutes of Health, Department of Health and Human Services, USA. DEW, RAH, XL, AR, TBS, SRD and also the influenza whole genome sequencing were supported with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract HHSN272200900007C. GSG was funded by the Defense Advanced Research Projects Agency under grant number DARPA-N66001-07-C-2024. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Evolution Across Scales. KK, ASL, CWW, and MTM were funded by NIGMS U54- GM111274, the MIDAS Center for Inference and Dynamics of Infectious Disease. DEW, RAH, XL, AR, TBS, and SRD were supported with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract HHSN272200900007C. GSG was funded by the Defense Advanced Research Projects Agency under grant number DARPA-N66001-07-C-2024. This work was performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

The Ly6 Protein Coiled Is Required for Septate Junction and Blood Brain Barrier Organisation in Drosophila

Background: Genetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes. Methodology/Principal Findings: In this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component. Conclusion/Significance: We discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose tha

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

A microscale protein NMR sample screening pipeline

As part of efforts to develop improved methods for NMR protein sample preparation and structure determination, the Northeast Structural Genomics Consortium (NESG) has implemented an NMR screening pipeline for protein target selection, construct optimization, and buffer optimization, incorporating efficient microscale NMR screening of proteins using a micro-cryoprobe. The process is feasible because the newest generation probe requires only small amounts of protein, typically 30–200 μg in 8–35 μl volume. Extensive automation has been made possible by the combination of database tools, mechanization of key process steps, and the use of a micro-cryoprobe that gives excellent data while requiring little optimization and manual setup. In this perspective, we describe the overall process used by the NESG for screening NMR samples as part of a sample optimization process, assessing optimal construct design and solution conditions, as well as for determining protein rotational correlation times in order to assess protein oligomerization states. Database infrastructure has been developed to allow for flexible implementation of new screening protocols and harvesting of the resulting output. The NESG micro NMR screening pipeline has also been used for detergent screening of membrane proteins. Descriptions of the individual steps in the NESG NMR sample design, production, and screening pipeline are presented in the format of a standard operating procedure