Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design

Background TNK-S2B, an innovative, randomized, seamless phase II/III trial of tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow enrollment before regulatory approval of use of phase II patients in phase III

Routing of western Canadian Plains runoff during the 8.2 ka cold event

The collapse of the Laurentide Ice Sheet over Hudson Bay ∼8.47 ka allowed the rapid drainage of glacial Lake Agassiz into the Labrador Sea, an event identified as causing a reduction in Atlantic meridional overturning circulation (AMOC) and the 8.2 ka cold event. Atmosphere-ocean models simulations based on this forcing, however, fail to reproduce several characteristics of this event, particularly its duration. Here we use planktonic foraminifera U/Ca records to document the routing of western Canadian Plains runoff that accompanied ice-sheet collapse. Geochemical modeling of the ∼7 nmol/mol increase in U/Ca at the opening of Hudson Bay indicates an increase in freshwater discharge of 0.13 ± 0.03 Sverdrups (106 m3 s−1) from routing, a sufficient magnitude to cause an AMOC reduction. We suggest that this routing event suppressed AMOC strength for several centuries after the drainage of Lake Agassiz, explaining multi-centennial climate anomalies associated with the 8.2 ka cold event

Antiretroviral Drug Use in a Cohort of HIV-Uninfected Women in the United States: HIV Prevention Trials Network 064

Antiretroviral (ARV) drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009–2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2%) of 1,806 participants: 27/181 (15%) in Baltimore, MD and 12/179 (7%) in Bronx, NY. The ARV drugs detected included different combinations of non-nucleoside reverse transcriptase inhibitors and protease inhibitors (1–4 drugs/sample). These data were analyzed in the context of self-reported data on ARV drug use. None of the 39 women who had ARV drugs detected reported ARV drug use at any study visit. Further research is needed to evaluate ARV drug use by HIV-uninfected individuals

Search for Neutral Higgs Bosons in Events with Multiple Bottom Quarks at the Tevatron

The combination of searches performed by the CDF and D0 collaborations at the Fermilab Tevatron Collider for neutral Higgs bosons produced in association with b quarks is reported. The data, corresponding to 2.6 fb-1 of integrated luminosity at CDF and 5.2 fb-1 at D0, have been collected in final states containing three or more b jets. Upper limits are set on the cross section multiplied by the branching ratio varying between 44 pb and 0.7 pb in the Higgs boson mass range 90 to 300 GeV, assuming production of a narrow scalar boson. Significant enhancements to the production of Higgs bosons can be found in theories beyond the standard model, for example in supersymmetry. The results are interpreted as upper limits in the parameter space of the minimal supersymmetric standard model in a benchmark scenario favoring this decay mode.Comment: 10 pages, 2 figure

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model

Nothing New in the (North) East? Interpreting the Rhetoric and Reality of Japanese Corporate Governance

Japan finally seems to be pulling itself out of its lost decade (and a half) of economic stagnation. Some grudgingly or triumphantly attribute this to micro-economic reforms, freeing up arthritic markets, although there is also evidence that macro-economic policy failures have been a major cause of poor performance since the 1990s. Many point to overlapping transformations in corporate governance, broadly defined to cover relationships among managers and employees as well as between firms and outside shareholders, creditors, and other stakeholders. These relationships are in flux, with moves arguably favouring shareholders and more market-driven control mechanisms. It has certainly been a found decade for law reform in Japan, particularly in corporate law, with a plethora of legislative amendments commencing around 1993 and culminating in the enactment of a consolidated Company Law in 2005. This modernisation project, particularly since 2001, is reportedly aimed at (i) securing better corporate governance, (ii) bringing the law into line with a highly-developed information society, (iii) liberalising fundraising measures, (iv) bringing corporate law into line with the internationalization of corporate activity, and (v) modernizing terms and consolidating corporate law. Because the suite of revisions has moved away from strict mandatory rules set out originally in Japan\u27s Commercial Code of 1899, modeled primarily on German law, another growing perception is that Japanese corporate law and practice is or will soon be converging significantly on US models. However, assessments remain divided as to whether these moves in corporate governance and capitalism more generally in Japan amount to a new paradigm or regime shift . Focusing primarily on quite influential commentary in English, Part I of this paper outlines two pairs of views. It concludes that the most plausible assessment is of significant but gradual transformation towards a more market-driven approach, evident also in other advanced political economies. Drawing more generally from these often virulently divided views, Part II sets out five ways forward through the proliferating literature and source material on corporate governance in Japan. Particular care must be taken in: (i) selecting the temporal timeframe, (ii) selecting countries to compare, (iii) balancing black-letter law and broader socio-economic context, (iv) reflecting on and disclosing normative preferences, and (v) giving weight to processes as well as outcomes, when assessing change in Japan - and any other country\u27s governance system. Part III ends with a call for further research particularly on law- and policy-producing processes, rather than mainly outcomes. It also outlines the usefulness of this analytical framework for analysing the broader field of Corporate Social Responsibility, now emerging as the next major area of debate and transformation in Japan - as elsewhere

Addendum:Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways

No abstract available

Kepler Planet-Detection Mission: Introduction and First Results

The Kepler mission was designed to determine the frequency of Earth-sized planets in and near the habitable zone of Sun-like stars. The habitable zone is the region where planetary temperatures are suitable for water to exist on a planet’s surface. During the first 6 weeks of observations, Kepler monitored 156,000 stars, and five new exoplanets with sizes between 0.37 and 1.6 Jupiter radii and orbital periods from 3.2 to 4.9 days were discovered. The density of the Neptune-sized Kepler-4b is similar to that of Neptune and GJ 436b, even though the irradiation level is 800,000 times higher. Kepler-7b is one of the lowest-density planets (~0.17 gram per cubic centimeter) yet detected. Kepler-5b, -6b, and -8b confirm the existence of planets with densities lower than those predicted for gas giant planets

Informing the development of Australia's national eating disorders research and translation strategy : a rapid review methodology

Background Eating disorders (EDs) are highly complex mental illnesses associated with significant medical complications. There are currently knowledge gaps in research relating to the epidemiology, aetiology, treatment, burden, and outcomes of eating disorders. To clearly identify and begin addressing the major deficits in the scientific, medical, and clinical understanding of these mental illnesses, the Australian Government Department of Health in 2019 funded the InsideOut Institute (IOI) to develop the Australian Eating Disorder Research and Translation Strategy, the primary aim of which was to identify priorities and targets for building research capacity and outputs. A series of rapid reviews (RR) were conducted to map the current state of knowledge, identify evidence gaps, and inform development of the national research strategy. Published peer-reviewed literature on DSM-5 listed EDs, across eight knowledge domains was reviewed: (1) population, prevalence, disease burden, Quality of Life in Western developed countries; (2) risk factors; (3) co-occurring conditions and medical complications; (4) screening and diagnosis; (5) prevention and early intervention; (6) psychotherapies and relapse prevention; (7) models of care; (8) pharmacotherapies, alternative and adjunctive therapies; and (9) outcomes (including mortality). While RRs are systematic in nature, they are distinct from systematic reviews in their aim to gather evidence in a timely manner to support decision-making on urgent or high-priority health concerns at the national level. Results Three medical science databases were searched as the primary source of literature for the RRs: Science Direct, PubMed and OVID (Medline). The search was completed on 31st May 2021 (spanning January 2009-May 2021). At writing, a total of 1,320 articles met eligibility criteria and were included in the final review. Conclusions For each RR, the evidence has been organised to review the knowledge area and identify gaps for further research and investment. The series of RRs (published separately within the current series) are designed to support the development of research and translation practice in the field of EDs. They highlight areas for investment and investigation, and provide researchers, service planners and providers, and research funders rapid access to quality current evidence, which has been synthesised and organised to assist decision-making