1,642 research outputs found

    SBV Regularity for Genuinely Nonlinear, Strictly Hyperbolic Systems of Conservation Laws in one space dimension

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    We prove that if tu(t)BV(R)t \mapsto u(t) \in \mathrm {BV}(\R) is the entropy solution to a N×NN \times N strictly hyperbolic system of conservation laws with genuinely nonlinear characteristic fields ut+f(u)x=0, u_t + f(u)_x = 0, then up to a countable set of times {tn}nN\{t_n\}_{n \in \mathbb N} the function u(t)u(t) is in SBV\mathrm {SBV}, i.e. its distributional derivative uxu_x is a measure with no Cantorian part. The proof is based on the decomposition of ux(t)u_x(t) into waves belonging to the characteristic families u(t)=i=1Nvi(t)r~i(t),vi(t)M(R), r~i(t)RN, u(t) = \sum_{i=1}^N v_i(t) \tilde r_i(t), \quad v_i(t) \in \mathcal M(\R), \ \tilde r_i(t) \in \mathrm R^N, and the balance of the continuous/jump part of the measures viv_i in regions bounded by characteristics. To this aim, a new interaction measure \mu_{i,\jump} is introduced, controlling the creation of atoms in the measure vi(t)v_i(t). The main argument of the proof is that for all tt where the Cantorian part of viv_i is not 0, either the Glimm functional has a downward jump, or there is a cancellation of waves or the measure μi,jump\mu_{i,\mathrm{jump}} is positive

    A draft map of the mouse pluripotent stem cell spatial proteome.

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    Knowledge of the subcellular distribution of proteins is vital for understanding cellular mechanisms. Capturing the subcellular proteome in a single experiment has proven challenging, with studies focusing on specific compartments or assigning proteins to subcellular niches with low resolution and/or accuracy. Here we introduce hyperLOPIT, a method that couples extensive fractionation, quantitative high-resolution accurate mass spectrometry with multivariate data analysis. We apply hyperLOPIT to a pluripotent stem cell population whose subcellular proteome has not been extensively studied. We provide localization data on over 5,000 proteins with unprecedented spatial resolution to reveal the organization of organelles, sub-organellar compartments, protein complexes, functional networks and steady-state dynamics of proteins and unexpected subcellular locations. The method paves the way for characterizing the impact of post-transcriptional and post-translational modification on protein location and studies involving proteome-level locational changes on cellular perturbation. An interactive open-source resource is presented that enables exploration of these data.The authors thank Andreas Hühmer, Philip Remes, Jesse Canterbury and Graeme McAlister of Thermo Fisher Scientific, San Jose, CA, USA, for their advice regarding operation of the Orbitrap Fusion. We also thank Mike Deery for assistance with checking sample integrity on the mass spectrometers in the Cambridge Centre for Proteomics on equipment purchased via a Wellcome Trust grant (099135/Z/12/Z ), and Brian Hendrich of the Wellcome Trust-MRC Stem Cell Institute in Cambridge and Sean Munro of the MRC Laboratory of Molecular Biology in Cambridge for insightful comments about the data. AC was supported by BBSRC grant (BB/D526088/1). C.M.M. and L.G. were supported by European Union 7th Framework Program (PRIMEXS project, grant agreement number 262067), L.M.B was supported by a BBSRC Tools and Resources Development Fund (Award BB/K00137X/1), and P.C.H. was supported by an ERC Advanced Investigator grant to A.M.A. A.G. was funded through the Alexander S. Onassis Public Benefit Foundation, the Foundation for Education and European Culture (IPEP) and the Embiricos Trust Scholarship of Jesus College Cambridge. T.H. was supported by Commonwealth Split Site PhD Scholarship. T.N. was supported by an ERASMUS Placement scholarshipThis is the final version of the article. It was first available from NPG via http://dx.doi.org/10.1038/ncomms999

    Clinical and cost-effectiveness of contingency management for cannabis use in early psychosis: the CIRCLE randomised clinical trial

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    Cannabis is the most commonly used illicit substance amongst people with psychosis. Continued cannabis use following the onset of psychosis is associated with poorer functional and clinical outcomes. However, finding effective ways of intervening has been very challenging. We examined the clinical and cost-effectiveness of adjunctive contingency management (CM), which involves incentives for abstinence from cannabis use, in people with a recent diagnosis of psychosis. CIRCLE was a pragmatic multi-centre randomised controlled trial. Participants were recruited via Early Intervention in Psychosis (EIP) services across the Midlands and South East of England. They had had at least one episode of clinically diagnosed psychosis (affective or non-affective); were aged 18 to 36; reported cannabis use in at least 12 out of the previous 24 weeks; and were not currently receiving treatment for cannabis misuse, or subject to a legal requirement for cannabis testing. Participants were randomised via a secure web-based service 1:1 to either an experimental arm, involving 12 weeks of CM plus a six-session psychoeducation package, or a control arm receiving the psychoeducation package only. The total potential voucher reward in the CM intervention was £240. The primary outcome was time to acute psychiatric care, operationalised as admission to an acute mental health service (including community alternatives to admission). Primary outcome data were collected from patient records at 18 months post-consent by assessors masked to allocation. The trial was registered with the ISRCTN registry, number ISRCTN33576045. Five hundred fifty-one participants were recruited between June 2012 and April 2016. Primary outcome data were obtained for 272 (98%) in the CM (experimental) group and 259 (95%) in the control group. There was no statistically significant difference in time to acute psychiatric care (the primary outcome) (HR 1.03, 95% CI 0.76, 1.40) between groups. By 18 months, 90 (33%) of participants in the CM group, and 85 (30%) of the control groups had been admitted at least once to an acute psychiatric service. Amongst those who had experienced an acute psychiatric admission, the median time to admission was 196 days (IQR 82, 364) in the CM group and 245 days (IQR 99, 382) in the control group. Cost-effectiveness analyses suggest that there is an 81% likelihood that the intervention was cost-effective, mainly resulting from higher mean inpatient costs for the control group compared with the CM group; however, the cost difference between groups was not statistically significant. There were 58 adverse events, 27 in the CM group and 31 in the control group. Overall, these results suggest that CM is not an effective intervention for improving the time to acute psychiatric admission or reducing cannabis use in psychosis, at least at the level of voucher reward offered

    An overview on the approximation of boundary Riemann problems through physical viscosity

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    This note aims at providing an overview of some recent results concerning the viscous approximation of so-called boundary Riemann problems for nonlinear systems of conservation laws in small total variation regimes. \ua9 2016, Sociedade Brasileira de Matem\ue1tica

    Social capital: a roadmap of theoretical and empirical contributions and limitations

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    The general idea of social capital is that relationships matter. In this sense, the trust, cooperation and reciprocity involved in these relationships can have a positive impact on the wealth of society by reducing transaction costs, facilitating collective actions, and lowering opportunistic behavior. This work sheds light on the different theoretical and empirical problems that a scholar is likely to face in dealing with social capital research and analysis. We propose a critical roadmap of the social capital theories and applications for a general audience, nonusers included, with particular attention to the works of political and social economists. We provide a critical debate on the different definitions and measures produced, the theoretical frameworks developed, and the empirical techniques adopted so far in the analysis of the impact of social capital on socio-economic outcomes. We turn to the limitations of these techniques and suggest some basic strategies to reduce the magnitude of these limitations

    Crisis resolution teams for people experiencing mental health crises: the CORE mixed-methods research programme including two RCTs

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    Background Crisis resolution teams (CRTs) seek to avert hospital admissions by providing intensive home treatment for people experiencing a mental health crisis. The CRT model has not been highly specified. CRT care is often experienced as ending abruptly and relapse rates following CRT discharge are high. Aims The aims of CORE (Crisis resolution team Optimisation and RElapse prevention) workstream 1 were to specify a model of best practice for CRTs, develop a measure to assess adherence to this model and evaluate service improvement resources to help CRTs implement the model with high fidelity. The aim of CORE workstream 2 was to evaluate a peer-provided self-management programme aimed at reducing relapse following CRT support. Methods Workstream 1 was based on a systematic review, national CRT manager survey and stakeholder qualitative interviews to develop a CRT fidelity scale through a concept mapping process with stakeholders (n = 68). This was piloted in CRTs nationwide (n = 75). A CRT service improvement programme (SIP) was then developed and evaluated in a cluster randomised trial: 15 CRTs received the SIP over 1 year; 10 teams acted as controls. The primary outcome was service user satisfaction. Secondary outcomes included CRT model fidelity, catchment area inpatient admission rates and staff well-being. Workstream 2 was a peer-provided self-management programme that was developed through an iterative process of systematic literature reviewing, stakeholder consultation and preliminary testing. This intervention was evaluated in a randomised controlled trial: 221 participants recruited from CRTs received the intervention and 220 did not. The primary outcome was re-admission to acute care at 1 year of follow-up. Secondary outcomes included time to re-admission and number of days in acute care over 1 year of follow-up and symptoms and personal recovery measured at 4 and 18 months’ follow-up. Results Workstream 1 – a 39-item CRT fidelity scale demonstrated acceptability, face validity and promising inter-rater reliability. CRT implementation in England was highly variable. The SIP trial did not produce a positive result for patient satisfaction [median Client Satisfaction Questionnaire score of 28 in both groups at follow-up; coefficient 0.97, 95% confidence interval (CI) –1.02 to 2.97]. The programme achieved modest increases in model fidelity. Intervention teams achieved lower inpatient admission rates and less inpatient bed use. Qualitative evaluation suggested that the programme was generally well received. Workstream 2 – the trial yielded a statistically significant result for the primary outcome, in which rates of re-admission to acute care over 1 year of follow-up were lower in the intervention group than in the control group (odds ratio 0.66, 95% CI 0.43 to 0.99; p = 0.044). Time to re-admission was lower and satisfaction with care was greater in the intervention group at 4 months’ follow-up. There were no other significant differences between groups in the secondary outcomes. Limitations Limitations in workstream 1 included uncertainty regarding the representativeness of the sample for the primary outcome and lack of blinding for assessment. In workstream 2, the limitations included the complexity of the intervention, preventing clarity about which were effective elements. Conclusions The CRT SIP did not achieve all its aims but showed potential promise as a means to increase CRT model fidelity and reduce inpatient service use. The peer-provided self-management intervention is an effective means to reduce relapse rates for people leaving CRT care. Study registration The randomised controlled trials were registered as Current Controlled Trials ISRCTN47185233 and ISRCTN01027104. The systematic reviews were registered as PROSPERO CRD42013006415 and CRD42017043048. Funding The National Institute for Health Research Programme Grants for Applied Research programme

    Impact of the Covid-19 pandemic on perinatal mental health (Riseup-PPD-COVID-19): protocol for an international prospective cohort study

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    Background: Corona Virus Disease 19 (COVID-19) is a new pandemic, declared a public health emergency by the World Health Organization, which could have negative consequences for pregnant and postpartum women. The scarce evidence published to date suggests that perinatal mental health has deteriorated since the COVID-19 outbreak. However, the few studies published so far have some limitations, such as a cross-sectional design and the omission of important factors for the understanding of perinatal mental health, including governmental restriction measures and healthcare practices implemented at the maternity hospitals. Within the Riseup-PPD COST Action, a study is underway to assess the impact of COVID-19 in perinatal mental health. The primary objectives are to (1) evaluate changes in perinatal mental health outcomes; and (2) determine the risk and protective factors for perinatal mental health during the COVID-19 pandemic. Additionally, we will compare the results between the countries participating in the study. Methods: This is an international prospective cohort study, with a baseline and three follow-up assessments over a six-month period. It is being carried out in 11 European countries (Albania, Bulgaria, Cyprus, France, Greece, Israel, Malta, Portugal, Spain, Turkey, and the United Kingdom), Argentina, Brazil and Chile. The sample consists of adult pregnant and postpartum women (with infants up to 6 months of age). The assessment includes measures on COVID-19 epidemiology and public health measures (Oxford COVID-19 Government Response Tracker dataset), Coronavirus Perinatal Experiences (COPE questionnaires), psychological distress (BSI-18), depression (EPDS), anxiety (GAD-7) and post-traumatic stress symptoms (PTSD checklist for DSM-V). Discussion: This study will provide important information for understanding the impact of the COVID-19 pandemic on perinatal mental health and well-being, including the identification of potential risk and protective factors by implementing predictive models using machine learning techniques. The findings will help policymakers develop suitable guidelines and prevention strategies for perinatal mental health and contribute to designing tailored mental health interventions. Trial registration: ClinicalTrials.gov Identifier: NCT04595123.The project is part of the COST Action Riseup-PPD CA 18138 and was supported by COST under COST Action Riseup-PPD CA18138; also, by the Spanish Ministry of Health, the Institute of Health Carlos III, and the European Regional Development Fund «Una manera de hacer Europa» by the Prevention and Health Promotion Research Network ‘redIAPP’ (RD16/0007). Raquel Costa is supported by the FSE and FCT under an individual Post-Doctoral Grant SFRH/BPD/117597/2016. Rena Bina and Drorit Levy received funding from the Bar-Ilan Dangoor Centre for Personalized Medicine, Israel. Ana Mesquita is supported from the Portuguese Foundation for Science and Technology (FCT) and from EU through the European Social Fund and from the Human Potential Operational Program - IF/00750/2015. Ana Osório received financial support from CAPES/Proex no. 0653/2018 and CAPES/PrInt grant no. 88887.310343/2018-00.The funders of the study had no role in the study design or the writing the protocol. The corresponding author had final responsibility for the decision to submit for publication

    Confounding conventional wisdom: political not principled differences in the transatlantic regulatory relationship

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    The transatlantic complaints over hormone-treated beef and genetically modified organisms before the World Trade Organisation (WTO) seem to confirm two separate but related conventional wisdoms about the transatlantic economic relationship: that it is highly conflictual and that many of the conflicts are rooted in profoundly different approaches to regulation. This article argues that neither of the two conventional wisdoms is accurate. Rather, it contends that they are products of two, compounding analytical shortcomings: one methodological, one empirical. The methodological shortcoming takes the form of an implicit selection bias. While WTO complaints are high profile they are rare and extreme examples; it is, therefore, unsound to generalise from them to the regulatory relationship as a whole. The empirical shortcoming has to do with neither the beef hormones nor the GMO dispute demonstrating what it is purported to. The article thus serves as a cautionary tale about the dangers of relying on obvious cases and the need to question whether evidence really does support a prevailing popular narrative
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