Household food security is associated with infant feeding practices in rural Bangladesh.

Although household food security (HHFS) has been shown to affect diet, nutrition, and health of adults and also learning in children, no study has examined associations with infant feeding practices (IFP). We studied 1343 infants born between May 2002 and December 2003 in the Maternal and Infant Nutrition Intervention in Matlab study to investigate the effect of HHFS on IFP in rural Bangladesh. We measured HHFS using a previously developed 11-item scale. Cumulative and current infant feeding scales were created from monthly infant feeding data for the age groups of 1-3, 1-6, 1-9, and 1-12 mo based on comparison to infant feeding recommendations. We used lagged, dynamic, and difference longitudinal regression models adjusting for various infant and maternal variables to examine the association between HHFS and changes in IFP, and Cox proportional hazards models to examine the influence of HHFS on the duration of breast-feeding and the time of introduction of complementary foods. Better HHFS status was associated with poor IFP during 3-6 mo but was associated with better IFP during 6-9 and 9-12 mo of age. Although better HHFS was not associated with the time of introduction of complementary foods, it was associated with the type of complementary foods given to the infants. Intervention programs to support proper IFP should target mothers in food-secure households when their babies are 3-6 mo old and also mothers in food-insecure households during the 2nd half of infancy. Our results provide strong evidence that HHFS influences IFP in rural Bangladesh

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; FundRef: http://dx.doi.org/10.13039/501100002927Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff

Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Abstract: Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating

Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups

IntroductionWhile complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.MethodsWe therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.ResultsWe show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.ConclusionIn conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted

Single-cell multi-omics analysis of the immune response in COVID-19

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255Funder: University College London, Birkbeck MRC Doctoral Training ProgrammeFunder: The Jikei University School of MedicineFunder: Action Medical Research (GN2779)Funder: NIHR Clinical Lectureship (CL-2017-01-004)Funder: NIHR (ACF-2018-01-004) and the BMA FoundationFunder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194)Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944)Funder: Barbour FoundationFunder: ERC Consolidator and EU MRG-Grammar awardsFunder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002)Funder: European Molecular Biology Laboratory (EMBL)Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Simulations and components for novel fast wave microwave amplifiers and sources

A three dimensional parameterised model of an X-band 2nd harmonic gyro-travelling wave amplifier (gyro-TWA) with a helically corrugated interaction region has been created and optimised in the Particle-in-Cell code MAGIC-3D, to achieve an output power and saturated efficiency of ~1.0MW and ~27% respectively at 9.4GHz. This numerical model has been benchmarked to an experiment [Bratman, 2000] which demonstrated an output power and saturated efficiency of ~1.1MW and ~29% respectively at 9.4GHz, for similar input parameters. The numerical model has been coded in the Cartesian co-ordinate system which offers greater numerical stability over previous models, and has been shown to accurately and consistently reproduce results comparable to the experimental measurements. The good agreement between the simulation data and the experimental measurements naturally present the numerical model as a suitable benchmark tool to investigate potential efficiency and bandwidth enhancement of the amplifier, achieved through parameter profiling of the microwave circuit. The model predicts that a helical down taper of length 14cm to an output mean radius (r0) and corrugation amplitude (l) of ~11.3mm and ~1.8mm respectively i.e. ~80% of the original helical waveguide's r0 and l values, positioned 4cm before the end of the original uniform helical interaction region of the amplifier, could increase both the saturated efficiency of the amplifier by ~2.5% at 10.0GHz, from ~28.6% to ~31.1% and its bandwidth by 800MHz, from 1.8GHz to 2.6GHz. In addition, an X-band Marie-type mode converter has been simulated and fabricated which effectively converts from the fundamental mode in rectangular waveguide to the cylindrical TE01 mode with minimal reflections, over an optimised 2.0GHz bandwidth. This converter has been used to test a Penning cathode mesh with the experimental measurements confirming that the mesh transmitted an RF signal in the TE01 mode without reflection or mode conversion.A three dimensional parameterised model of an X-band 2nd harmonic gyro-travelling wave amplifier (gyro-TWA) with a helically corrugated interaction region has been created and optimised in the Particle-in-Cell code MAGIC-3D, to achieve an output power and saturated efficiency of ~1.0MW and ~27% respectively at 9.4GHz. This numerical model has been benchmarked to an experiment [Bratman, 2000] which demonstrated an output power and saturated efficiency of ~1.1MW and ~29% respectively at 9.4GHz, for similar input parameters. The numerical model has been coded in the Cartesian co-ordinate system which offers greater numerical stability over previous models, and has been shown to accurately and consistently reproduce results comparable to the experimental measurements. The good agreement between the simulation data and the experimental measurements naturally present the numerical model as a suitable benchmark tool to investigate potential efficiency and bandwidth enhancement of the amplifier, achieved through parameter profiling of the microwave circuit. The model predicts that a helical down taper of length 14cm to an output mean radius (r0) and corrugation amplitude (l) of ~11.3mm and ~1.8mm respectively i.e. ~80% of the original helical waveguide's r0 and l values, positioned 4cm before the end of the original uniform helical interaction region of the amplifier, could increase both the saturated efficiency of the amplifier by ~2.5% at 10.0GHz, from ~28.6% to ~31.1% and its bandwidth by 800MHz, from 1.8GHz to 2.6GHz. In addition, an X-band Marie-type mode converter has been simulated and fabricated which effectively converts from the fundamental mode in rectangular waveguide to the cylindrical TE01 mode with minimal reflections, over an optimised 2.0GHz bandwidth. This converter has been used to test a Penning cathode mesh with the experimental measurements confirming that the mesh transmitted an RF signal in the TE01 mode without reflection or mode conversion

From the Catalog to the Book on the Shelf: Building a Mapping Application for Vufind

At Yale University Library (YUL), recorded reference transactions revealed that after finding a book in the catalog patrons had difficulty knowing how to use the call number to find the book on the shelf. The Library created a mobile service to help locate the call number in the library stacks. From any call number of a book in Sterling Memorial Library at YUL, a map will be displayed which highlights that call number’s general area on a floor in the stacks. YUL introduced the mapping application in Yufind, a catalog in place at Yale since 2008 which is based on Vufind