Socioeconomic inequalities in pregnancy outcome associated with Down syndrome: a population-based study.

OBJECTIVE: To investigate socioeconomic inequalities in outcome of pregnancy associated with Down syndrome (DS) compared with other congenital anomalies screened for during pregnancy. DESIGN AND SETTING: Retrospective population-based registry study (East Midlands & South Yorkshire in England). PARTICIPANTS: All registered cases of DS and nine selected congenital anomalies with poor prognostic outcome (the UK Fetal Anomaly Screening Programme (FASP)9) with an end of pregnancy date between 1 January 1998 and 31 December 2007. MAIN OUTCOME MEASURES: Poisson regression models were used to explore outcome measures, including socioeconomic variation in rates of anomaly; antenatal detection; pregnancy outcome; live birth incidence and neonatal mortality. Deprivation was measured using the Index of Multiple Deprivation 2004 at super output area level. RESULTS: There were 1151 cases of DS and 1572 cases of the nine severe anomalies combined. The overall rate of antenatal detection was 57% for DS, which decreased with increasing deprivation (rate ratio comparing the most deprived tenth with the least deprived: 0.76 (0.60 to 0.97)). Antenatal detection rates were considerably higher for FASP9 anomalies (86%), with no evidence of a trend with deprivation (0.99 95% CI (0.84 to 1.17)). The termination of pregnancy rate following antenatal diagnosis was higher for DS (86%) than the FASP9 anomalies (70%). Both groups showed wide socioeconomic variation in the termination of pregnancy rate (rate ratio: DS: 0.76 (0.58 to 0.99); FASP9 anomalies: 0.80 (0.65 to 0.97)). Consequently, socioeconomic inequalities in live birth and neonatal mortality rates associated with these anomalies arise that were not observed in utero. CONCLUSIONS: Socioeconomic inequalities exist in the antenatal detection of DS, and subsequent termination rates are much higher for DS than other anomalies. Termination rates for all anomalies are lower in more deprived areas leading to wide socioeconomic inequalities in live born infants with a congenital anomaly, particularly DS, and subsequent neonatal mortality

Indigenous Peoples' Rights in Data: a contribution toward Indigenous Research Sovereignty

Indigenous Peoples' right to sovereignty forms the foundation for advocacy and actions toward greater Indigenous self-determination and control across a range of domains that impact Indigenous Peoples' communities and cultures. Declarations for sovereignty are rising throughout Indigenous communities and across diverse fields, including Network Sovereignty, Food Sovereignty, Energy Sovereignty, and Data Sovereignty. Indigenous Research Sovereignty draws in the sovereignty discourse of these initiatives to consider their applications to the broader research ecosystem. Our exploration of Indigenous Research Sovereignty, or Indigenous self-determination in the context of research activities, has been focused on the relationship between Indigenous Data Sovereignty and efforts to describe Indigenous Peoples' Rights in data

Measurement of Epstein-Barr virus DNA load using a novel quantification standard containing two EBV DNA targets and SYBR Green I dye

<p>Abstract</p> <p>Background</p> <p>Reactivation of Epstein-Barr virus (EBV) infection may cause serious, life-threatening complications in immunocompromised individuals. EBV DNA is often detected in EBV-associated disease states, with viral load believed to be a reflection of virus activity. Two separate real-time quantitative polymerase chain reaction (QPCR) assays using SYBR Green I dye and a single quantification standard containing two EBV genes, Epstein-Barr nuclear antigen-1 (EBNA-1) and BamHI fragment H rightward open reading frame-1 (BHRF-1), were developed to detect and measure absolute EBV DNA load in patients with various EBV-associated diseases. EBV DNA loads and viral capsid antigen (VCA) IgG antibody titres were also quantified on a population sample.</p> <p>Results</p> <p>EBV DNA was measurable in ethylenediaminetetraacetic acid (EDTA) whole blood, peripheral blood mononuclear cells (PBMCs), plasma and cerebrospinal fluid (CSF) samples. EBV DNA loads were detectable from 8.0 × 10²to 1.3 × 10⁸copies/ml in post-transplant lymphoproliferative disease (n = 5), 1.5 × 10³to 2.0 × 10⁵copies/ml in infectious mononucleosis (n = 7), 7.5 × 10⁴to 1.1 × 10⁵copies/ml in EBV-associated haemophagocytic syndrome (n = 1), 2.0 × 10²to 5.6 × 10³copies/ml in HIV-infected patients (n = 12), and 2.0 × 10²to 9.1 × 10⁴copies/ml in the population sample (n = 218). EBNA-1 and BHRF-1 DNA were detected in 11.0% and 21.6% of the population sample respectively. There was a modest correlation between VCA IgG antibody titre and BHRF-1 DNA load (rho = 0.13, p = 0.05) but not EBNA-1 DNA load (rho = 0.11, p = 0.11).</p> <p>Conclusion</p> <p>Two sensitive and specific real-time PCR assays using SYBR Green I dye and a single quantification standard containing two EBV DNA targets, were developed for the detection and measurement of EBV DNA load in a variety of clinical samples. These assays have application in the investigation of EBV-related illnesses in immunocompromised individuals.</p

Indigenous Peoples' Rights in Data: a contribution toward Indigenous Research Sovereignty

Indigenous Peoples' right to sovereignty forms the foundation for advocacy and actions toward greater Indigenous self-determination and control across a range of domains that impact Indigenous Peoples' communities and cultures. Declarations for sovereignty are rising throughout Indigenous communities and across diverse fields, including Network Sovereignty, Food Sovereignty, Energy Sovereignty, and Data Sovereignty. Indigenous Research Sovereignty draws in the sovereignty discourse of these initiatives to consider their applications to the broader research ecosystem. Our exploration of Indigenous Research Sovereignty, or Indigenous self-determination in the context of research activities, has been focused on the relationship between Indigenous Data Sovereignty and efforts to describe Indigenous Peoples' Rights in data

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

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&lt;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&lt;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&lt;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 &gt;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

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Disrupting Colonial Narratives: (Re)claiming Autonomy and (Re)affirming Traditional Family Structures through Story in the Teme-augaming

Land displacement, theft, and erasure have been key drivers in undermining the political, economic, cultural, linguistic, ancestral, and family formations of First Nations people in Canada. Nation rebuilding is the cornerstone of all sovereignty efforts and is a necessary component of improving the social and political conditions that impact health and wellness. Exercising sovereignty is tightly linked to the autonomous assertion of land and resource rights. Discrimination through the Crown’s self-imposed position as the natural owner of all land and resources across the country is evidenced by a continued failure to recognize the many ways that First Nations self-identify. This inadequacy overlooks First Nations’ inherent rights to self-determination while advancing colonial ideologies. This paper presents a thread of qualitative research findings from a project that included an Indigenous storywork method with one First Nations’ Elder and grandmother, kookum. Within the context of her-story and traditional knowledge mobilization, this work challenges the colonially defined territorial boundaries of the hereditary family clan structures across the Temagami region in Northeastern Ontario, Canada. Kookum’s story demonstrates how colonial policies and practices undermine hereditary conceptions of traditional family identity and led to the misguided and unauthorized theft of the Friday family territories. The reconstruction of identity damages hereditary forms of governance and impairs traditional and familial connection to land, culture, language, and traditions, and is 1) incompatible with self-determination; 2) maintains and perpetuates colonialism; 3) hinders genuine reconciliation; and 4) furthers health and socio-economic inequities for First Nations people. Le déplacement, le vol et l’effacement des terres ont été les principaux facteurs qui ont miné les formations politiques, économiques, culturelles, linguistiques, ancestrales et familiales des peuples des Premières nations du Canada. La reconstruction de la nation est la pierre angulaire de tous les efforts de souveraineté et constitue un élément nécessaire à l’amélioration des conditions sociales et politiques qui ont un impact sur la santé et le bien-être. L’exercice de la souveraineté est étroitement lié à l’affirmation autonome des droits à la terre et aux ressources. La discrimination qui découle de la position que la Couronne s’est imposée en tant que propriétaire naturel de toutes les terres et ressources du pays est attestée par l’incapacité persistante de reconnaître les nombreuses façons dont les Premières nations s’identifient. Cette inadéquation néglige les droits inhérents des Premières nations à l’autodétermination tout en faisant progresser les idéologies coloniales. Cet article présente les résultats d’une recherche qualitative menée dans le cadre d’un projet incluant une méthode de travail narrative indigène avec une aînée et grand-mère des Premières Nations, kookum. Dans le contexte de la mobilisation de son histoire et de son savoir traditionnel, ce travail remet en question les frontières territoriales définies par la colonisation des structures claniques familiales héréditaires dans la région de Temagami, dans le nord-est de l’Ontario, au Canada. L’histoire de kookum montre comment les politiques et les pratiques coloniales ont sapé les conceptions héréditaires de l’identité familiale traditionnelle et conduit au vol malavisé et non autorisé des territoires de la famille Friday. La reconstruction de l’identité porte atteinte aux formes héréditaires de gouvernance et compromet les liens traditionnels et familiaux avec la terre, la culture, la langue et les traditions, ce qui est 1) incompatible avec l’autodétermination ; 2) maintient et perpétue le colonialisme ; 3) fait obstacle à une véritable réconciliation ; et 4) aggrave les inégalités sanitaires et socio-économiques pour les peuples des Premières nations