EDOS: 20 Years or Level 0 Processing for Terra

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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

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Daily temperature data from the Foothills Climate Array Mesonet, Canadian Rocky Mountains, 2005-2010

Near-surface air temperatures were monitored from 2005 to 2010 in a mesoscale network of 230 sites in the foothills of the Rocky Mountains in southwestern Alberta, Canada. The monitoring network covers a range of elevations from 890 to 2880 m above sea level and an area of about 18 000 km², sampling a variety of topographic settings and surface environments with an average spatial density of one station per 78 km². This paper presents the multiyear temperature dataset from this study, with minimum, maximum, and mean daily temperature data. In this paper, we describe the quality control and processing methods used to clean and filter the data and assess its accuracy. Overall data coverage for the study period is 91 %. We introduce a weather-system-dependent gap-filling technique to estimate the missing 9 % of data. Monthly and seasonal distributions of minimum, maximum, and mean daily temperature lapse rates are shown for the region

Near-surface atmospheric humidity data from a mesoscale meteorological network in the foothills of the Canadian Rocky Mountains, 2005-2010

Hourly near-surface relative humidity and temperature were monitored from 2005 to 2010 in a mesoscale network of 232 sites in the foothills of the Rocky Mountains in southwestern Alberta, Canada. The monitoring network covers a range of elevations from 890 to 2880 m above sea level and an area of about 18 000 km², sampling a variety of topographic settings and surface environments with an average spatial density of one station per 78 km². Having been combined with air pressure measurements from Calgary International Airport and adjusted for the site elevation, the hourly data form the basis of estimates of daily mean specific humidity, vapour pressure, and relative humidity at each site. Overall data coverage for the study period is 89 %. This paper describes the processing methods used to quality control and gap fill the data. Inverse-distance weighting techniques are used to estimate the missing 11 % of data, based on neighbourhood values of daily mean specific humidity. We also report monthly mean lapse rates of specific and relative humidity. Plots of seasonal and spatial humidity patterns in the region illustrate the relations between humidity variables and temperature, elevation, and longitude

Using assessment to individualize early mathematics instruction.

Accumulating evidence suggests that assessment-informed personalized instruction, tailored to students' individual skills and abilities, is more effective than more one-size-fits-all approaches. In this study, we evaluate the efficacy of Individualizing Student Instruction in Mathematics (ISI-Math) compared to Reading (ISI-Reading) where classrooms were randomly assigned to ISI-Math or ISI-Reading. The literature on child characteristics X instruction or skill X treatment interaction effects point to the complexities of tailoring instruction for individual students who present with constellations of skills. Second graders received mathematics instruction in small flexible learning groups based on their assessed learning needs. Results of the study (n=32 teachers, 370 students) revealed significant treatment effects on standardized mathematics assessments. With effect sizes (d) of 0.41-0.60, we show that we can significantly improve 2nd graders' mathematics achievement, including for children living in poverty, by using assessment data to individualize the mathematics instruction they receive. The instructional regime, ISI-Math, was implemented by regular classroom teachers and it led to about a 4-month achievement advantage on standardized mathematics tests when compared to students in control classrooms. These results were realized within one school year. Moreover, treatment effects were the same regardless of school-level poverty and students' gender, initial mathematics or vocabulary scores

Using assessment to individualize early mathematics instruction.

Accumulating evidence suggests that assessment-informed personalized instruction, tailored to students' individual skills and abilities, is more effective than more one-size-fits-all approaches. In this study, we evaluate the efficacy of Individualizing Student Instruction in Mathematics (ISI-Math) compared to Reading (ISI-Reading) where classrooms were randomly assigned to ISI-Math or ISI-Reading. The literature on child characteristics X instruction or skill X treatment interaction effects point to the complexities of tailoring instruction for individual students who present with constellations of skills. Second graders received mathematics instruction in small flexible learning groups based on their assessed learning needs. Results of the study (n=32 teachers, 370 students) revealed significant treatment effects on standardized mathematics assessments. With effect sizes (d) of 0.41-0.60, we show that we can significantly improve 2nd graders' mathematics achievement, including for children living in poverty, by using assessment data to individualize the mathematics instruction they receive. The instructional regime, ISI-Math, was implemented by regular classroom teachers and it led to about a 4-month achievement advantage on standardized mathematics tests when compared to students in control classrooms. These results were realized within one school year. Moreover, treatment effects were the same regardless of school-level poverty and students' gender, initial mathematics or vocabulary scores