Prevalence of strong bottom currents in the greater Agulhas system

Deep current meter data and output from two high-resolution global ocean circulation models are used to determine the prevalence and location of strong bottom currents in the greater Agulhas Current system. The two models and current meter data are remarkably consistent, showing that benthic storms, with bottom currents greater than 0.2 m s(-1), occur throughout the Agulhas retroflection region south of Africa more than 20% of the time. Furthermore, beneath the mean Agulhas Current core and the retroflection front, bottom currents exceed 0.2 m s(-1) more than 50% of the time, while away from strong surface currents, bottom currents rarely exceed 0.2 m s(-1). Implications for sediment transport are discussed and the results are compared to atmospheric storms. Benthic storms of this strength (0.2 m s(-1)) are comparable to a 9 m s(-1) (Beaufort 5) windstorm, but scaling shows that benthic storms may be less effective at lifting and transporting sediment than dust storms

Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE‐SPECT ESUS Trial

Risk factors; Secondary prevention; Stroke predictorsFactores de riesgo; Prevención secundaria; Predictores de accidentes cerebrovascularesFactors de risc; Prevenció secundària; Predictors d'accidents cerebrovascularsBackground We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE‐SPECT ESUS (Randomized, Double‐Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow‐up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83–2.82]), creatinine clearance <50 mL/min (HR, 1.69 [95% CI, 1.23–2.32]), male sex (HR, 1.60 [95% CI, 1.27–2.02]), and CHA2DS2‐VASc ≥4 (HR, 1.55 [95% CI, 1.15–2.08] and HR, 1.66 [95% CI, 1.21–2.26] for scores of 4 and ≥5, respectively) versus CHA2DS2‐VASc of 2 to 3, were independent predictors for recurrent stroke. Conclusions In RE‐SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high‐risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS.This study was supported by Boehringer Ingelheim

Chromosome 10q26-driven age-related macular degeneration is associated with reduced levels of HTRA1 in human retinal pigment epithelium

Genome-wide association studies have identified the chromosome 10q26 (Chr10) locus, which contains the age-related maculopathy susceptibility 2 (ARMS2) and high temperature requirement A serine peptidase 1 (HTRA1) genes, as the strongest genetic risk factor for age-related macular degeneration (AMD) [L.G. Fritsche et al., Annu. Rev. Genomics Hum. Genet. 15, 151–171, (2014)]. To date, it has been difficult to assign causality to any specific single nucleotide polymorphism (SNP), haplotype, or gene within this region because of high linkage disequilibrium among the disease-associated variants [J. Jakobsdottir et al. Am. J. Hum. Genet. 77, 389–407 (2005); A. Rivera et al. Hum. Mol. Genet. 14, 3227–3236 (2005)]. Here, we show that HTRA1 messenger RNA (mRNA) is reduced in retinal pigment epithelium (RPE) but not in neural retina or choroid tissues derived from human donors with homozygous risk at the 10q26 locus. This tissue-specific decrease is mediated by the presence of a noncoding, cis-regulatory element overlapping the ARMS2 intron, which contains a potential Lhx2 transcription factor binding site that is disrupted by risk variant rs36212733. HtrA1 protein increases with age in the RPE–Bruch’s membrane (BM) interface in Chr10 nonrisk donors but fails to increase in donors with homozygous risk at the 10q26 locus. We propose that HtrA1, an extracellular chaperone and serine protease, functions to maintain the optimal integrity of the RPE–BM interface during the aging process and that reduced expression of HTRA1 mRNA and protein in Chr10 risk donors impairs this protective function, leading to increased risk of AMD pathogenesis. HtrA1 augmentation, not inhibition, in high-risk patients should be considered as a potential therapy for AMD

Risperidone Treatment of Autistic Disorder: Longer-Term Benefits and Blinded Discontinuation After 6 Months

Objective: Risperidone is effective for short-term treatment of aggression, temper outbursts, and self-injurious behavior in children with autism. Because these behaviors may be chronic, there is a need to establish the efficacy and safety of longer-term treatment with this agent. Method: The authors conducted a multisite, two-part study of risperidone in children ages 5 to 17 years with autism accompanied by severe tantrums, aggression, and/or self-injurious behavior who showed a positive response in an earlier 8-week trial. Part I consisted of 4-month open-label treatment with risperidone, starting at the established optimal dose; part II was an 8-week randomized, double-blind, placebo-substitution study of risperidone withdrawal. Primary outcome measures were the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression improvement scale. Results: Part I included 63 children. The mean risperidone dose was 1.96 mg/day at entry and remained stable over 16 weeks of open treatment. The change on the Aberrant Behavior Checklist irritability subscale was small and clinically insignificant. Reasons for discontinuation of part I included loss of efficacy (N=5) and adverse effects (N=1). The subjects gained an average of 5.1 kg. Part II included 32 patients. The relapse rates were 62.5% for gradual placebo substitution and 12.5% for continued risperidone; this difference was statistically significant. Conclusions: Risperidone showed persistent efficacy and good tolerability for intermediate-length treatment of children with autism characterized by tantrums, aggression, and/or self-injurious behavior. Discontinuation after 6 months was associated with a rapid return of disruptive and aggressive behavior in most subjects

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Global perspectives on observing ocean boundary current systems

Ocean boundary current systems are key components of the climate system, are home to highly productive ecosystems, and have numerous societal impacts. Establishment of a global network of boundary current observing systems is a critical part of ongoing development of the Global Ocean Observing System. The characteristics of boundary current systems are reviewed, focusing on scientific and societal motivations for sustained observing. Techniques currently used to observe boundary current systems are reviewed, followed by a census of the current state of boundary current observing systems globally. The next steps in the development of boundary current observing systems are considered, leading to several specific recommendations.Fil: Todd, Robert E.. Woods Hole Oceanographic Institution; Estados UnidosFil: Chavez, Francisco. Monterey Bay Aquarium Research Institute; Estados UnidosFil: Clayton, Sophie. Old Dominion University; Estados UnidosFil: Cravatte, Sophie E.. Centre National de la Recherche Scientifique. Institut de Recherche pour le Développement; Francia. Universite de Toulouse; FranciaFil: Goes, Marlos P.. University of Miami; Estados UnidosFil: Graco, Michelle I.. Instituto del Mar del Peru; PerúFil: Lin, Xiaopei. Ocean University of China; ChinaFil: Sprintall, Janet. University of California; Estados UnidosFil: Zilberman, Nathalie V.. University of California; Estados UnidosFil: Archer, Matthew. California Institute of Technology; Estados UnidosFil: Arístegui, Javier. Universidad de Las Palmas de Gran Canaria; EspañaFil: Balmaseda, Magdalena A.. European Centre for Medium-Range Weather Forecasts; Reino UnidoFil: Bane, John M.. University of North Carolina; Estados UnidosFil: Baringer, Molly O.. Atlantic Oceanographic and Meteorological Laboratory ; Estados UnidosFil: Barth, John A.. State University of Oregon; Estados UnidosFil: Beal, Lisa M.. University of Miami; Estados UnidosFil: Brandt, Peter. Geomar-Helmholtz Centre for Ocean Research Kiel; AlemaniaFil: Calil, Paulo H.. Universidade Federal do Rio Grande; BrasilFil: Campos, Edmo. Universidade de Sao Paulo; BrasilFil: Centurioni, Luca R.. University of California; Estados UnidosFil: Chidichimo, María Paz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval; ArgentinaFil: Cirano, Mauro. Universidade Federal do Rio de Janeiro; BrasilFil: Cronin, Meghan F.. National Oceanic and Atmospheric Administration. Pacific Marine Environmental Laboratory; Estados UnidosFil: Curchitser, Enrique N.. Rutgers University; Estados UnidosFil: Davis, Russ E.. University of California; Estados UnidosFil: Dengler, Marcus. Geomar-Helmholtz Centre for Ocean Research Kiel; AlemaniaFil: DeYoung, Brad. Memorial University of Newfoundland; CanadáFil: Dong, Shenfu. University of Miami; Estados UnidosFil: Escribano, Ruben. Universidad de Concepción; ChileFil: Fassbender, Andrea J.. Monterey Bay Aquarium Research Institute; Estados Unido

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy