Pathways of ocean heat towards Pine Island and Thwaites grounding lines

In the Amundsen Sea, modified Circumpolar Deep Water (mCDW) intrudes into ice shelf cavities, causing high ice shelf melting near the ice sheet grounding lines, accelerating ice flow, and controlling the pace of future Antarctic contributions to global sea level. The pathways of mCDW towards grounding lines are crucial as they directly control the heat reaching the ice. A realistic representation of mCDW circulation, however, remains challenging due to the sparsity of in-situ observations and the difficulty of ocean models to reproduce the available observations. In this study, we use an unprecedentedly high-resolution (200 m horizontal and 10 m vertical grid spacing) ocean model that resolves shelf-sea and sub-ice-shelf environments in qualitative agreement with existing observations during austral summer conditions. We demonstrate that the waters reaching the Pine Island and Thwaites grounding lines follow specific, topographically-constrained routes, all passing through a relatively small area located around 104°W and 74.3°S. The temporal and spatial variabilities of ice shelf melt rates are dominantly controlled by the sub-ice shelf ocean current. Our findings highlight the importance of accurate and high-resolution ocean bathymetry and subglacial topography for determining mCDW pathways and ice shelf melt rates

Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing

No abstract available

A Variant of Fibroblast Growth Factor Receptor 2 (Fgfr2) Regulates Left-Right Asymmetry in Zebrafish

Many organs in vertebrates are left-right asymmetrical located. For example, liver is at the right side and stomach is at the left side in human. Fibroblast growth factor (Fgf) signaling is important for left-right asymmetry. To investigate the roles of Fgfr2 signaling in zebrafish left-right asymmetry, we used splicing blocking morpholinos to specifically block the splicing of fgfr2b and fgfr2c variants, respectively. We found that the relative position of the liver and the pancreas were disrupted in fgfr2c morphants. Furthermore, the left-right asymmetry of the heart became random. Expression pattern of the laterality controlling genes, spaw and pitx2c, also became random in the morphants. Furthermore, lefty1 was not expressed in the posterior notochord, indicating that the molecular midline barrier had been disrupted. It was also not expressed in the brain diencephalon. Kupffer's vesicle (KV) size became smaller in fgfr2c morphants. Furthermore, KV cilia were shorter in fgfr2c morphants. We conclude that the fgfr2c isoform plays an important role in the left-right asymmetry during zebrafish development

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Ensino superior e pesquisa em Educação Física: Mapeamento nas universidades argentinas e primeiras considerações

Este escrito remite a los avances del proyecto de investigación “Formación superior y Educación Física: prácticas, saberes y discursos”, situado en el Departamento en Ciencias Sociales y Educación de la Universidad Nacional Pedagógica, que postula como objetivo general interpelar los discursos, prácticas y saberes que se reproducen en las formaciones (de grado y posgrado) e investigaciones en la Educación Física universitaria. Se trata de una investigación mixta organizada en dos partes: un rastreo de la estructura de la profesionalización en Argentina y luego un análisis de sus discursos y prácticas, esto es, de su ejecución. A un año calendario desde el inicio del trabajo se ha cumplimentado la primera parte, habiendo rastreado y mapeado las formaciones de grado y posgrado (públicas y privadas) en la Educación Física universitaria argentina, los proyectos de investigación acreditados dirigidos por profesionales del campo y las revistas especializadas que reúnen a la comunidad de conocimiento. En los avances es factible identificar la desigual distribución territorial del crecimiento académico de la Educación Física universitaria argentina, así como dimensionar las conquistas regionales en contextos institucionales diversos y la necesidad de leerlas en clave federal.This article refers to the progress of the research project “Formación superior y Educación Física: prácticas, saberes y discursos” (“Higher Education and Physical Education: Practices, Knowledge, and Discourses”), located in the Department of Social Sciences and Education a the National Pedagogical University (UNIPE). The general objective of the project is to question the discourses, practices, and knowledge reproduced in undergraduate and postgraduate training and research in university-level Physical Education. It is a mixed- methods research organized in two parts: a survey of the professionalization structure in Argentina, followed by an analysis of its discourses and practices, i.e., its implementation. One calendar year into the project, the first part has been completed, involving the tracking and mapping of undergraduate and postgraduate programs (both public and private) in Argentine university-level Physical Education. The project also identified accredited research projects led by professionals in the field and specialized journals that bring together the knowledge community. In the progress made, it is possible to identify the unequal territorial distribution of academic growth in Argentine university-level Physical Education, as well as to assess regional achievements in various institutional contexts and the need to interpret them from a federal perspective.Este artigo refere-se ao andamento do projeto de pesquisa “Formação superior e Educação Física: práticas, saberes e discursos”, localizado no Departamento de Ciências Sociais e Educação da Universidade Pedagógica Nacional, que postula como objetivo geral questionar os discursos, práticas e saberes que se reproduzem na formação (graduação e pós- graduação) e na pesquisa em Educação Física universitária. É uma investigação mista organizada em duas partes: um traçado da estrutura da profissionalização na Argentina e depois uma análise de seus discursos e práticas, ou seja, sua execução. Um ano civil desde o início do trabalho, a primeira parte foi concluída, tendo rastreado e mapeado a formação de graduação e pós-graduação (pública e privada) em Educação Física universitária argentina, os projetos de pesquisa credenciados dirigidos por profissionais da área e especialistas revistas que reúnem a comunidade de conhecimento. Nos avanços é viável identificar a distribuição territorial desigual do crescimento acadêmico da Educação Física universitária argentina, bem como medir as conquistas regionais em diversos contextos institucionais e a necessidade de lê-las em chave federal.Fil: Galak, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Humanidades y Ciencias Sociales. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales; ArgentinaFil: Ribero, Ivana Verónica. Universidad Pedagogica Nacional.; ArgentinaFil: Ruiz, Mariel Alejandra. Universidad Nacional de Luján; ArgentinaFil: Bertolotto, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Humanidades y Ciencias Sociales. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales; ArgentinaFil: Tita, Analia Veronica. Universidad Provincial de Cordoba.; ArgentinaFil: Nakayama, Lilia. Universidad Provincial de Cordoba. Facultad de Educacion Fisica.; ArgentinaFil: Dupuy, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Humanidades y Ciencias Sociales. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales; Argentin

Pathways of ocean heat towards Pine Island and Thwaites grounding lines

In the Amundsen Sea, modified Circumpolar Deep Water (mCDW) intrudes into ice shelf cavities, causing high ice shelf melting near the ice sheet grounding lines, accelerating ice flow, and controlling the pace of future Antarctic contributions to global sea level. The pathways of mCDW towards grounding lines are crucial as they directly control the heat reaching the ice. A realistic representation of mCDW circulation, however, remains challenging due to the sparsity of in-situ observations and the difficulty of ocean models to reproduce the available observations. In this study, we use an unprecedentedly high-resolution (200 m horizontal and 10 m vertical grid spacing) ocean model that resolves shelf-sea and sub-ice-shelf environments in qualitative agreement with existing observations during austral summer conditions. We demonstrate that the waters reaching the Pine Island and Thwaites grounding lines follow specific, topographically-constrained routes, all passing through a relatively small area located around 104 degrees W and 74.3 degrees S. The temporal and spatial variabilities of ice shelf melt rates are dominantly controlled by the sub-ice shelf ocean current. Our findings highlight the importance of accurate and high-resolution ocean bathymetry and subglacial topography for determining mCDW pathways and ice shelf melt rates