Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited.
To estimate population-based MIS-C ...incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years.
This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020.
Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years).
Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections.
In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median interquartile range age, 8 4-13 years; 133 53.6% male; 96 persons 38.7% were Hispanic or Latino; 75 persons 30.2% were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio aIRR, 9.26 95% CI, 6.15-13.93), Hispanic or Latino persons (aIRR, 8.92 95% CI, 6.00-13.26), and Asian or Pacific Islander (aIRR, 2.94 95% CI, 1.49-5.82) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 95% CI, 3.68-8.60), Hispanic or Latino (aIRR, 4.26 95% CI, 2.85-6.38), and Asian or Pacific Islander persons (aIRR, 2.88 95% CI, 1.42-5.83) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 95% CI, 3.7-6.6 children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 95% CI, 4.8-8.3 children per 1 000 000 person-months).
In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.
Secure patient portals are widely available, and patients use them to view their electronic health records, including their clinical notes. We conducted experiments asking them to cogenerate notes ...with their clinicians, an intervention called OurNotes.
This study aims to assess patient and provider experiences and attitudes after 12 months of a pilot intervention.
Before scheduled primary care visits, patients were asked to submit a word-constrained, unstructured interval history and an agenda for what they would like to discuss at the visit. Using site-specific methods, their providers were invited to incorporate the submissions into notes documenting the visits. Sites served urban, suburban, and rural patients in primary care practices in 4 academic health centers in Boston (Massachusetts), Lebanon (New Hampshire), Denver (Colorado), and Seattle (Washington). Each practice offered electronic access to visit notes (open notes) to its patients for several years. A mixed methods evaluation used tracking data and electronic survey responses from patients and clinicians. Participants were 174 providers and 1962 patients who submitted at least 1 previsit form. We asked providers about the usefulness of the submissions, effects on workflow, and ideas for the future. We asked patients about difficulties and benefits of providing the requested information and ideas for future improvements.
Forms were submitted before 9.15% (5365/58,652) eligible visits, and 43.7% (76/174) providers and 26.76% (525/1962) patients responded to the postintervention evaluation surveys; 74 providers and 321 patients remembered receiving and completing the forms and answered the survey questions. Most clinicians thought interim patient histories (69/74, 93%) and patient agendas (72/74, 97%) as good ideas, 70% (52/74) usually or always incorporated them into visit notes, 54% (40/74) reported no change in visit length, and 35% (26/74) thought they saved time. Their most common suggestions related to improving notifications when patient forms were received, making it easier to find the form and insert it into the note, and educating patients about how best to prepare their submissions. Patient respondents were generally well educated, most found the history (259/321, 80.7%) and agenda (286/321, 89.1%) questions not difficult to answer; more than 92.2% (296/321) thought sending answers before the visit a good idea; 68.8% (221/321) thought the questions helped them prepare for the visit. Common suggestions by patients included learning to write better answers and wanting to know that their submissions were read by their clinicians. At the end of the pilot, all participating providers chose to continue the OurNotes previsit form, and sites considered expanding the intervention to more clinicians and adapting it for telemedicine visits.
OurNotes interests patients, and providers experience it as a positive intervention. Participation by patients, care partners, clinicians, and electronic health record experts will facilitate further development.
The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is ...of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants.
Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and ...diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.
Ice sheet numerical modeling is an important tool to estimate the dynamic contribution of the Antarctic ice sheet to sea level rise over the coming centuries. The influence of initial conditions on ...ice sheet model simulations, however, is still unclear. To better understand this influence, an initial state intercomparison exercise (initMIP) has been developed to compare, evaluate, and improve initialization procedures and estimate their impact on century-scale simulations. initMIP is the first set of experiments of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6), which is the primary Coupled Model Intercomparison Project Phase 6 (CMIP6) activity focusing on the Greenland and Antarctic ice sheets. Following initMIP-Greenland, initMIP-Antarctica has been designed to explore uncertainties associated with model initialization and spin-up and to evaluate the impact of changes in external forcings. Starting from the state of the Antarctic ice sheet at the end of the initialization procedure, three forward experiments are each run for 100 years: a control run, a run with a surface mass balance anomaly, and a run with a basal melting anomaly beneath floating ice. This study presents the results of initMIP-Antarctica from 25 simulations performed by 16 international modeling groups. The submitted results use different initial conditions and initialization methods, as well as ice flow model parameters and reference external forcings. We find a good agreement among model responses to the surface mass balance anomaly but large variations in responses to the basal melting anomaly. These variations can be attributed to differences in the extent of ice shelves and their upstream tributaries, the numerical treatment of grounding line, and the initial ocean conditions applied, suggesting that ongoing efforts to better represent ice shelves in continental-scale models should continue.
Plasmodium vivax is the most widespread human malaria geographically; however, no effective vaccine exists. Red blood cell invasion by the P. vivax merozoite depends on an interaction between the ...Duffy antigen receptor for chemokines (DARC) and region II of the parasite's Duffy-binding protein (PvDBP_RII). Naturally acquired binding-inhibitory antibodies against this interaction associate with clinical immunity, but it is unknown whether these responses can be induced by human vaccination.
Safety and immunogenicity of replication-deficient chimpanzee adenovirus serotype 63 (ChAd63) and modified vaccinia virus Ankara (MVA) viral vectored vaccines targeting PvDBP_RII (Salvador I strain) were assessed in an open-label dose-escalation phase Ia study in 24 healthy UK adults. Vaccines were delivered by the intramuscular route in a ChAd63-MVA heterologous prime-boost regimen using an 8-week interval.
Both vaccines were well tolerated and demonstrated a favorable safety profile in malaria-naive adults. PvDBP_RII-specific ex-vivo IFN-γ T cell, antibody-secreting cell, memory B cell, and serum IgG responses were observed after the MVA boost immunization. Vaccine-induced antibodies inhibited the binding of vaccine homologous and heterologous variants of recombinant PvDBP_RII to the DARC receptor, with median 50% binding-inhibition titers greater than 1:100.
We have demonstrated for the first time to our knowledge that strain-transcending antibodies can be induced against the PvDBP_RII antigen by vaccination in humans. These vaccine candidates warrant further clinical evaluation of efficacy against the blood-stage P. vivax parasite.
Clinicaltrials.gov NCT01816113.
Support was provided by the UK Medical Research Council, UK National Institute of Health Research Oxford Biomedical Research Centre, and the Wellcome Trust.
Abstract
Radial velocity (RV) surveys have discovered giant exoplanets on au-scale orbits with a broad distribution of eccentricities. Those with the most eccentric orbits are valuable laboratories ...for testing theories of high-eccentricity migration. However, few such exoplanets transit their host stars, thus removing the ability to apply constraints on formation from their bulk internal compositions. We report the discovery of Kepler-1704 b, a transiting 4.15
M
J
giant planet on a 988.88 day orbit with an extreme eccentricity of
0.921
−
0.015
+
0.010
. Our decade-long RV baseline from the Keck I telescope allows us to measure the orbit and bulk heavy-element composition of Kepler-1704 b and place limits on the existence of undiscovered companions. A failed hot Jupiter, Kepler-1704 b was likely excited to high eccentricity by scattering events that possibly began during its gas accretion phase. Its final periastron distance was too large to allow for tidal circularization, so now it orbits its host from distances spanning 0.16–3.9 au. The maximum difference in planetary equilibrium temperature resulting from this elongated orbit is over 700 K. A simulation of the thermal phase curve of Kepler-1704 b during periastron passage demonstrates that it is a remarkable target for atmospheric characterization from the James Webb Space Telescope, which could potentially also measure the planet’s rotational period as the hot spot from periastron rotates in and out of view. Continued characterization of the Kepler-1704 system promises to refine theories explaining the formation of hot Jupiters and cool giant planets like those in the solar system.
Drift tube ion mobility spectrometry coupled with mass spectrometry (DTIMS-MS) is increasingly implemented in high throughput omics workflows, and new informatics approaches are necessary for ...processing the associated data. To automatically extract arrival times for molecules measured by DTIMS at multiple electric fields and compute their associated collisional cross sections (CCS), we created the PNNL Ion Mobility Cross Section Extractor (PIXiE). The primary application presented for this algorithm is the extraction of data that can then be used to create a reference library of experimental CCS values for use in high throughput omics analyses.
We demonstrate the utility of this approach by automatically extracting arrival times and calculating the associated CCSs for a set of endogenous metabolites and xenobiotics. The PIXiE-generated CCS values were within error of those calculated using commercially available instrument vendor software.
PIXiE is an open-source tool, freely available on Github. The documentation, source code of the software, and a GUI can be found at https://github.com/PNNL-Comp-Mass-Spec/PIXiE and the source code of the backend workflow library used by PIXiE can be found at https://github.com/PNNL-Comp-Mass-Spec/IMS-Informed-Library .
erin.baker@pnnl.gov or thomas.metz@pnnl.gov.
Supplementary data are available at Bioinformatics online.
Long-distance terrestrial migrations are imperiled globally. We determined both round-trip migration distances (straight-line measurements between migratory end points) and total annual movement (sum ...of the distances between successive relocations over a year) for a suite of large mammals that had potential for long-distance movements to test which species displayed the longest of both. We found that caribou likely do exhibit the longest terrestrial migrations on the planet, but, over the course of a year, gray wolves move the most. Our results were consistent with the trophic-level based hypothesis that predators would move more than their prey. Herbivores in low productivity environments moved more than herbivores in more productive habitats. We also found that larger members of the same guild moved less than smaller members, supporting the 'gastro-centric' hypothesis. A better understanding of migration and movements of large mammals should aid in their conservation by helping delineate conservation area boundaries and determine priority corridors for protection to preserve connectivity. The magnitude of the migrations and movements we documented should also provide guidance on the scale of conservation efforts required and assist conservation planning across agency and even national boundaries.
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