Disulfide-activated protein kinase G I alpha regulates cardiac diastolic relaxation and fine-tunes the Frank-Starling response

British Heart Foundation, European Research Council (ERC Advanced award), Medical Research Council and the Department of Health via the NIHR cBRC award to Guy’s & St Thomas’ NHS Foundation Trust. Part supported by the NIHR University College London Hospitals Biomedical Research Centre

Unexpected Role of α-Fetoprotein in Spermatogenesis

BACKGROUND: Heat shock severely affects sperm production (spermatogenesis) and results in a rapid loss of haploid germ cells, or in other words, sperm formation (spermiogenesis) is inhibited. However, the mechanisms behind the effects of heat shock on spermatogenesis are obscure. METHODOLOGY/PRINCIPAL FINDINGS: To identify the inhibitory factor of spermiogenesis, experimental cryptorchid (EC) mice were used in this study. Here we show that α-fetoprotein (AFP) is specifically expressed in the testes of EC mice by proteome analysis. AFP was also specifically localized spermatocytes by immunohistochemical analysis and was secreted into the circulation system of EC mice by immunoblot analysis. Since spermatogenesis of an advanced mammal cannot be reproduced with in vitro, we performed the microinjection of AFP into the seminiferous tubules of normal mice to determine whether AFP inhibits spermiogenesis in vivo. AFP was directly responsible for the block in spermiogenesis of normal mice. To investigate whether AFP inhibits cell differentiation in other models, using EC mice we performed a partial hepatectomy (PH) that triggers a rapid regenerative response in the remnant liver tissue. We also found that liver regeneration is inhibited in EC mice with PH. The result suggests that AFP released into the blood of EC mice regulates liver regeneration by inhibiting the cell division of hepatocytes. CONCLUSIONS/SIGNIFICANCE: AFP is a well-known cancer-specific marker, but AFP has no known function in healthy human beings. Our findings indicate that AFP expressed under EC conditions plays a role as a regulatory factor in spermatogenesis and in hepatic generation

Diagnostic scope in out-of-hours primary care services in eight European countries: an observational study

Background: In previous years, out- of-hours primary care has been organised in large-scale organisations in many countries. This may have lowered the threshold for many patients to present health problems at nights and during the weekend. Comparisons of out-of-hours care between countries require internationally comparable figures on symptoms and diagnoses, which were not available. This study aimed to describe the symptoms and diagnoses in out-of-hours primary care services in regions in eight European countries. Methods: We conducted a retrospective observational study based on medical records from out-of-hours primary care services in Belgium, Denmark, Germany, the Netherlands, Norway, Slovenia, Spain, and Switzerland. We aimed to include data on 1000 initial contacts from up to three organisations per country. Excluded were contacts with an administrative reason. The International Classification for Primary Care (ICPC) was used to categorise symptoms and diagnoses. In two countries (Slovenia and Spain) ICD10 codes were translated into ICPC codes. Results: The age distribution of patients showed a high consistency across countries, while the percentage of males varied from 33.7% to 48.3%. The ICPC categories that were used most frequently concerned: chapter A 'general and unspecified symptoms' (mean 13.2%), chapter R 'respiratory' (mean 20.4%), chapter L 'musculoskeletal' (mean 15.0%), chapter S 'skin' (mean 12.5%), and chapter D 'digestive' (mean 11.6%). So, relatively high numbers of patients presenting with infectious diseases or acute pain related syndromes. This was largely consistent across age groups, but in some age groups chapter H ('ear problems'), chapter L ('musculoskeletal') and chapter K ('cardiovascular') were frequently used. Acute life-threatening problems had a low incidence. Conclusions: This international study suggested a highly similar diagnostic scope in out-of-hours primary care services. The incidence rates of acute life-threatening health problems were low in all countries

A community-integrated home based depression intervention for older African Americans: descripton of the Beat the Blues randomized trial and intervention costs

ABSTRACT: BACKGROUND: Primary care is the principle setting for depression treatment; yet many older African Americans in the United States fail to report depressive symptoms or receive the recommended standard of care. Older African Americans are at high risk for depression due to elevated rates of chronic illness, disability and socioeconomic distress. There is an urgent need to develop and test new depression treatments that resonate with minority populations that are hard-to-reach and underserved and to evaluate their cost and cost-effectiveness. METHODS/DESIGN: Beat the Blues (BTB) is a single-blind parallel randomized trial to assess efficacy of a non-pharmacological intervention to reduce depressive symptoms and improve quality of life in 208 African Americans 55+ years old. It involves a collaboration with a senior center whose care management staff screen for depressive symptoms (telephone or in-person) using the Patient Health Questionnaire (PHQ-9). Individuals screened positive (PHQ-9 ≥ 5) on two separate occasions over 2 weeks are referred to local mental health resources and BTB. Interested and eligible participants who consent receive a baseline home interview and then are randomly assigned to receive BTB immediately or 4 months later (wait-list control). All participants are interviewed at 4 (main study endpoint) and 8 months at home by assessors masked to study assignment. Licensed senior center social workers trained in BTB meet with participants at home for up to 10 sessions over 4 months to assess care needs, make referrals/linkages, provide depression education, instruct in stress reduction techniques, and use behavioral activation to identify goals and steps to achieve them. Key outcomes include reduced depressive symptoms (primary), reduced anxiety and functional disability, improved quality of life, and enhanced depression knowledge and behavioral activation (secondary). Fidelity is enhanced through procedure manuals and staff training and monitored by face-to-face supervision and review of taped sessions. Cost and cost effectiveness is being evaluated. DISCUSSION: BTB is designed to bridge gaps in mental health service access and treatments for older African Americans. Treatment components are tailored to specific care needs, depression knowledge, preference for stress reduction techniques, and personal activity goals. Total costs are $584.64/4 months; or$146.16 per participant/per month. TRIAL REGISTRATION: ClinicalTrials.gov #NCT00511680

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

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV