Standard reference sequences for submission of HLA genotyping for the 18th International HLA and Immunogenetics Workshop

The International human leukocyte antigen (HLA) and Immunogenetics Workshops (IHIWs) have fostered international collaborations of researchers and experts in the fields of HLA, histocompatibility and immunology. These IHIW collaborations have comprised many projects focused on achieving a variety of specific goals. The international and collaborative nature of these projects necessitates the collection and analysis of complex data generated in multiple laboratories, often using multiple methods of acquisition. Collection and storage of these data in a consistent way adds value to IHIW projects, which can be extended to future work. DNA-based genotyping data, especially HLA genotyping data, can be transmitted in the form of a Histoimmunogenetics Markup Language (HML) document. HML facilitates clear communication of a genotype and supporting metadata, such as, sequencing platform, laboratory assays, consensus sequence, and interpretation. Sequence information can be reported relative to known reference sequences, which add meaning and context to genotypes. Selecting the correct reference sequence for a given allele sequence is nuanced, and guidelines have emerged through collaborative community efforts such as Data Standards Hackathons. Here, we describe the guidelines established for the selection of reference sequences to be used in transmission of HLA (and MICA/MICB) genotyping data for the 18th IHIW.Transplantation and autoimmunit

Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children

Background In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ò100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age

Extracorporeal Membrane Oxygenation Characteristics and Outcomes in Children and Adolescents With COVID-19 or Multisystem Inflammatory Syndrome Admitted to U.S. ICUs

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. Design: Case series of patients from the Overcoming COVID-19 public health surveillance registry. SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final cohort included 2,733 patients with MIS-C (n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 (n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. Conclusions: ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge

Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire: an expert assessment

As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%–85% of permafrost carbon release can still be avoided if human emissions are actively reduced

Momentum scale calibration of the LHCb spectrometer

For accurate determination of particle masses accurate knowledge of the momentum scale of the detectors is crucial. The procedure used to calibrate the momentum scale of the LHCb spectrometer is described and illustrated using the performance obtained with an integrated luminosity of 1.6 fb-1 collected during 2016 in pp running. The procedure uses large samples of J/ψ → μ + μ - and B+ → J/ψ K + decays and leads to a relative accuracy of 3 × 10-4 on the momentum scale

Curvature-bias corrections using a pseudomass method

Momentum measurements for very high momentum charged particles, such as muons from electroweak vector boson decays, are particularly susceptible to charge-dependent curvature biases that arise from misalignments of tracking detectors. Low momentum charged particles used in alignment procedures have limited sensitivity to coherent displacements of such detectors, and therefore are unable to fully constrain these misalignments to the precision necessary for studies of electroweak physics. Additional approaches are therefore required to understand and correct for these effects. In this paper the curvature biases present at the LHCb detector are studied using the pseudomass method in proton-proton collision data recorded at centre of mass energy √(s)=13 TeV during 2016, 2017 and 2018. The biases are determined using Z→μ + μ - decays in intervals defined by the data-taking period, magnet polarity and muon direction. Correcting for these biases, which are typically at the 10-4 GeV-1 level, improves the Z→μ + μ - mass resolution by roughly 18% and eliminates several pathological trends in the kinematic-dependence of the mean dimuon invariant mass

Standard reference sequences for submission of HLA

The International human leukocyte antigen (HLA) and Immunogenetics Workshops (IHIWs) have fostered international collaborations of researchers and experts in the fields of HLA, histocompatibility and immunology. These IHIW collaborations have comprised many projects focused on achieving a variety of specific goals. The international and collaborative nature of these projects necessitates the collection and analysis of complex data generated in multiple laboratories, often using multiple methods of acquisition. Collection and storage of these data in a consistent way adds value to IHIW projects, which can be extended to future work. DNA-based genotyping data, especially HLA genotyping data, can be transmitted in the form of a Histoimmunogenetics Markup Language (HML) document. HML facilitates clear communication of a genotype and supporting metadata, such as, sequencing platform, laboratory assays, consensus sequence, and interpretation. Sequence information can be reported relative to known reference sequences, which add meaning and context to genotypes. Selecting the correct reference sequence for a given allele sequence is nuanced, and guidelines have emerged through collaborative community efforts such as Data Standards Hackathons. Here, we describe the guidelines established for the selection of reference sequences to be used in transmission of HLA (and MICA/MICB) genotyping data for the 18th IHIW.Transplantation and autoimmunit