Measurements of Differential Reflectivity in Snowstorms and Warm Season Stratiform Systems

The organized behavior of differential radar reflectivity (ZDR) is documented in the cold regions of a wide variety of stratiform precipitation types occurring in both winter and summer. The radar targets and attendant cloud microphysical conditions are interpreted within the context of measurements of ice crystal types in laboratory diffusion chambers in which humidity and temperature are both stringently controlled. The overriding operational interest here is in the identification of regions prone to icing hazards with long horizontal paths. Two predominant regimes are identified: category A, which is typified by moderate reflectivity (from 10 to 30 dBZ) and modest +ZDR values (from 0 to +3 dB) in which both supercooled water and dendritic ice crystals (and oriented aggregates of ice crystals) are present at a mean temperature of −13°C, and category B, which is typified by small reflectivity (from −10 to +10 dBZ) and the largest +ZDR values (from +3 to +7 dB), in which supercooled water is dilute or absent and both flat-plate and dendritic crystals are likely. The predominant positive values for ZDR in many case studies suggest that the role of an electric field on ice particle orientation is small in comparison with gravity. The absence of robust +ZDR signatures in the trailing stratiform regions of vigorous summer squall lines may be due both to the infusion of noncrystalline ice particles (i.e., graupel and rimed aggregates) from the leading deep convection and to the effects of the stronger electric fields expected in these situations. These polarimetric measurements and their interpretations underscore the need for the accurate calibration of ZDR.United States. Federal Aviation Administration (Air Force Contract FA8721-05-C-0002

A Functional Variant in MicroRNA-146a Promoter Modulates Its Expression and Confers Disease Risk for Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong genetic predisposition, characterized by an upregulated type I interferon pathway. MicroRNAs are important regulators of immune homeostasis, and aberrant microRNA expression has been demonstrated in patients with autoimmune diseases. We recently identified miR-146a as a negative regulator of the interferon pathway and linked the abnormal activation of this pathway to the underexpression of miR-146a in SLE patients. To explore why the expression of miR-146a is reduced in SLE patients, we conducted short parallel sequencing of potentially regulatory regions of miR-146a and identified a novel genetic variant (rs57095329) in the promoter region exhibiting evidence for association with SLE that was replicated independently in 7,182 Asians (Pmeta = 2.74×10−8, odds ratio = 1.29 [1.18–1.40]). The risk-associated G allele was linked to reduced expression of miR-146a in the peripheral blood leukocytes of the controls. Combined functional assays showed that the risk-associated G allele reduced the protein-binding affinity and activity of the promoter compared with those of the promoter containing the protective A allele. Transcription factor Ets-1, encoded by the lupus-susceptibility gene ETS1, identified in recent genome-wide association studies, binds near this variant. The manipulation of Ets-1 levels strongly affected miR-146a promoter activity in vitro; and the knockdown of Ets-1, mimicking its reduced expression in SLE, directly impaired the induction of miR-146a. We also observed additive effects of the risk alleles of miR-146a and ETS1. Our data identified and confirmed an association between a functional promoter variant of miR-146a and SLE. This risk allele had decreased binding to transcription factor Ets-1, contributing to reduced levels of miR-146a in SLE patients

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

Aircraft in situ validation of hydrometeors and icing conditions inferred by ground-based NEXRAD polarimetric radar

MIT Lincoln Laboratory is tasked by the U.S. Federal Aviation Administration to investigate the use of the NEXRAD polarimetric radars* for the remote sensing of icing conditions hazardous to aircraft. A critical aspect of the investigation concerns validation that has relied upon commercial airline icing pilot reports and a dedicated campaign of in situ flights in winter storms. During the month of February in 2012 and 2013, the Convair-580 aircraft operated by the National Research Council of Canada was used for in situ validation of snowstorm characteristics under simultaneous observation by NEXRAD radars in Cleveland, Ohio and Buffalo, New York. The most anisotropic and easily distinguished winter targets to dual pol radar are ice crystals. Accordingly, laboratory diffusion chamber measurements in a tightly-controlled parameter space of temperature and humidity provide the linkage between shape and the expectation for the presence/absence of water saturation conditions necessary for icing hazard in situ. In agreement with the laboratory measurements pertaining to dendritic and hexagonal flat plate crystals, the aircraft measurements have verified the presence of supercooled water in mainly low concentrations coincident with regions showing layered anomalies of positive differential reflectivity (ZDR) by ground-based radar, otherwise known as +ZDR \u2018bright bands\u2019. Extreme values of ZDR (up to +8 dB) have also been found to be coincident with hexagonal flat plate crystals and intermittent supercooled water, also consistent with laboratory measurements. The icing conditions found with the anisotropic description are considered non-classical (condensation/collision-coalescence) and require the ascent of air and availability of ice nuclei. A modest ascent rate (<1 m/s) is needed for preservation of the anisotropic ice crystal shapes, making them identifiable to dual-pol radar. In the other limit of strong ascent (several m/s and greater), a vigorous riming process is present leading to graupel and hail, and with attendant radar reflectivity of 30 dBZ and greater. These rimed hydrometeors are also readily verified by dual pol hydrometeor classification and in situ aircraft measurements. For the intermediate level of ascent speed, snow can become rimed, diluting its anisotropy, and presents a challenge to unambiguous detection of an icing condition by dual pol radar. This challenge is under current study.Peer reviewed: YesNRC publication: Ye