eXtreme Adaptive Optics Planet Imager: overview and status

As adaptive optics (AO) matures, it becomes possible to envision AO systems oriented towards specific important scientific goals rather than general-purpose systems. One such goal for the next decade is the direct imaging detection of extrasolar planets. An "extreme" adaptive optics (ExAO) system optimized for extrasolar planet detection will have very high actuator counts and rapid update rates - designed for observations of bright stars - and will require exquisite internal calibration at the nanometer level. In addition to extrasolar planet detection, such a system will be capable of characterizing dust disks around young or mature stars, outflows from evolved stars, and high Strehl ratio imaging even at visible wavelengths. The NSF Center for Adaptive Optics has carried out a detailed conceptual design study for such an instrument, dubbed the eXtreme Adaptive Optics Planet Imager or XAOPI. XAOPI is a 4096-actuator AO system, notionally for the Keck telescope, capable of achieving contrast ratios >10^7 at angular separations of 0.2-1". ExAO system performance analysis is quite different than conventional AO systems - the spatial and temporal frequency content of wavefront error sources is as critical as their magnitude. We present here an overview of the XAOPI project, and an error budget highlighting the key areas determining achievable contrast. The most challenging requirement is for residual static errors to be less than 2 nm over the controlled range of spatial frequencies. If this can be achieved, direct imaging of extrasolar planets will be feasible within this decade

Os saberes a ensinar e para ensinar matemática e suas relações com o ensino industrial brasileiro

Disponível em: http://revistas.upel.edu.ve/index.php/paradigma/article/view/6907/0Este trabalho é parte de uma pesquisa de doutorado que se preocupa em investigar o ensino de matemática no Liceu e na Escola Industrial de Florianópolis no período de 1937 a 1961. O objetivo é identificar os saberes a ensinar e para ensinar nos cursos do Liceu Industrial e da Escola Industrial de Florianópolis e quais as principais mudanças no ensino de Mat emática destas instituições de ensino industrial. Foram utilizados como referenciais teóricos Chervel (1990) sobre história das disciplinas escolares, Julia (2001) sobre cultura escolar , Hofstetter & Valente (2017) a respeito dos saberes a ensinar , Hofstet ter et al . (2017) na definição dos experts e Cellard (2008) para a análise documental . Percebeu - se que o ensino de Matemática era voltado para cálculos básicos, pois o enfoque era formar o aluno para a indústria, apesar de se intensificar o ensino de Álgeb ra e Trigonometria no início dos anos de 1940. Palavras - chave: Ensino Industrial. História da Educação Matemática. Experts . Saberes a ensinar. Saberes para ensinar

eXtreme Adaptive Optics Planet Imager: overview and status

As adaptive optics (AO) matures, it becomes possible to envision AO systems oriented towards specific important scientific goals rather than general-purpose systems. One such goal for the next decade is the direct imaging detection of extrasolar planets. An "extreme" adaptive optics (ExAO) system optimized for extrasolar planet detection will have very high actuator counts and rapid update rates - designed for observations of bright stars - and will require exquisite internal calibration at the nanometer level. In addition to extrasolar planet detection, such a system will be capable of characterizing dust disks around young or mature stars, outflows from evolved stars, and high Strehl ratio imaging even at visible wavelengths. The NSF Center for Adaptive Optics has carried out a detailed conceptual design study for such an instrument, dubbed the eXtreme Adaptive Optics Planet Imager or XAOPI. XAOPI is a 4096-actuator AO system, notionally for the Keck telescope, capable of achieving contrast ratios >10^7 at angular separations of 0.2-1". ExAO system performance analysis is quite different than conventional AO systems - the spatial and temporal frequency content of wavefront error sources is as critical as their magnitude. We present here an overview of the XAOPI project, and an error budget highlighting the key areas determining achievable contrast. The most challenging requirement is for residual static errors to be less than 2 nm over the controlled range of spatial frequencies. If this can be achieved, direct imaging of extrasolar planets will be feasible within this decade

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570