Ethnic differences in SARS-CoV-2 vaccine hesitancy in United Kingdom healthcare workers: Results from the UK-REACH prospective nationwide cohort study

Background: In most countries, healthcare workers (HCWs) represent a priority group for vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) due to their elevated risk of COVID-19 and potential contribution to nosocomial SARS-CoV-2 transmission. Concerns have been raised that HCWs from ethnic minority groups are more likely to be vaccine hesitant (defined by the World Health Organisation as refusing or delaying a vaccination) than those of White ethnicity, but there are limited data on SARS-CoV-2 vaccine hesitancy and its predictors in UK HCWs. Methods: Nationwide prospective cohort study and qualitative study in a multi-ethnic cohort of clinical and non-clinical UK HCWs. We analysed ethnic differences in SARS-CoV-2 vaccine hesitancy adjusting for demographics, vaccine trust, and perceived risk of COVID-19. We explored reasons for hesitancy in qualitative data using a framework analysis. Findings: 11,584 HCWs were included in the cohort analysis. 23% (2704) reported vaccine hesitancy. Compared to White British HCWs (21.3% hesitant), HCWs from Black Caribbean (54.2%), Mixed White and Black Caribbean (38.1%), Black African (34.4%), Chinese (33.1%), Pakistani (30.4%), and White Other (28.7%) ethnic groups were significantly more likely to be hesitant. In adjusted analysis, Black Caribbean (aOR 3.37, 95% CI 2.11 - 5.37), Black African (aOR 2.05, 95% CI 1.49 - 2.82), White Other ethnic groups (aOR 1.48, 95% CI 1.19 - 1.84) were significantly more likely to be hesitant. Other independent predictors of hesitancy were younger age, female sex, higher score on a COVID-19 conspiracy beliefs scale, lower trust in employer, lack of influenza vaccine uptake in the previous season, previous COVID-19, and pregnancy. Qualitative data from 99 participants identified the following contributors to hesitancy: lack of trust in government and employers, safety concerns due to the speed of vaccine development, lack of ethnic diversity in vaccine studies, and confusing and conflicting information. Participants felt uptake in ethnic minority communities might be improved through inclusive communication, involving HCWs in the vaccine rollout, and promoting vaccination through trusted networks. Interpretation: Despite increased risk of COVID-19, HCWs from some ethnic minority groups are more likely to be vaccine hesitant than their White British colleagues. Strategies to build trust and dispel myths surrounding the COVID-19 vaccine in these communities are urgently required. Emphasis should be placed on the safety and benefit of SARS-CoV-2 vaccination in pregnancy and in those with previous COVID-19. Public health communications should be inclusive, non-stigmatising and utilise trusted networks

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Ovarian Activity and Oestrous Signs among Group-Housed, Lactating Sows: Influence of Behaviour, Environment and Production

Animal welfare concerns require the development of housing systems that allow the animals to express their natural behaviour. One example of this is the group-housing system for lactating sows. The present study aimed at exploring ovarian activity in such a system. Thirty-eight sows farrowing individually outdoors during spring and summer, and indoors during autumn and winter, and group-housed in groups of four during weeks 3–7 of the lactation period, were monitored regarding reproductive functions, behaviour and production during their first to fourth lactation period. Average ovulation frequency during lactation was 47%. Only 50% of these ovulating cases were accompanied by a standing oestrus. Lactational ovulation frequency was higher in later parities (p < 0.001). Ovulation frequency was higher (p < 0.05) during winter (74%) and spring (69%), than during summer (10%) and autumn (23%). Occurrence of lactational ovulation was associated with some aspects of suckling behaviour and also with litter weight gain (p < 0.05). Forty-nine per cent of the lactational ovulations occurred during the seventh week of lactation. Timing of ovulation seemed positively (p = 0.08) associated with weight loss during lactation. Compared with the sows that were anoestrus during lactation, oestradiol-17β values were higher (p < 0.05) only in the week before occurrence of lactational ovulation. Weaning-to-oestrous interval was prolonged (p < 0.05) among the sows that ovulated during lactation. The present study identifies several factors influencing ovarian activity among group-housed sows, thereby providing tools for the control of lactational ovulation in group-housing systems

Investigation of the obscuring circumnuclear torus in the active galaxy Mrk231

Here we report on observations of powerful hydroxyl (OH) line emissions that trace the obscuring material within the circumnuclear environment of the galaxy Markarian 231. The hydroxyl (mega)-maser emission shows the characteristics of a rotating, dusty, molecular torus (or thick disk) located between 30 and 100 pc from the central engine. We now have a clear view of the physical conditions, the kinematics and the spatial structure of this material on intermediate size scales, confirming the main tenets of unification models.Comment: 10 pages, including 3 Figures, published in Nature Vol 421 2003; the published pdf--file and higher quality images are available at http://www.astro.rug.nl/~hrkloeck/np/pubmrk231.htm

A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.

Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression-based biomarkers facilitating such tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice. We show that transcriptional profiling of purified CD8(+) T cells, which avoids the confounding influences of unseparated cells, identifies two distinct subject subgroups predicting long-term prognosis in two autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium-sized and small blood vessels, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction. We show that the subset of genes defining the poor prognostic group is enriched for genes involved in the interleukin-7 receptor (IL-7R) pathway and T cell receptor (TCR) signaling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8(+) T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest new potential therapeutic targets in autoimmunity

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Discriminating lymphomas and reactive lymphadenopathy in lymph node biopsies by gene expression profiling

<p>Abstract</p> <p>Background</p> <p>Diagnostic accuracy of lymphoma, a heterogeneous cancer, is essential for patient management. Several ancillary tests including immunophenotyping, and sometimes cytogenetics and PCR are required to aid histological diagnosis. In this proof of principle study, gene expression microarray was evaluated as a single platform test in the differential diagnosis of common lymphoma subtypes and reactive lymphadenopathy (RL) in lymph node biopsies.</p> <p>Methods</p> <p>116 lymph node biopsies diagnosed as RL, classical Hodgkin lymphoma (cHL), diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL) were assayed by mRNA microarray. Three supervised classification strategies (global multi-class, local binary-class and global binary-class classifications) using diagonal linear discriminant analysis was performed on training sets of array data and the classification error rates calculated by leave one out cross-validation. The independent error rate was then evaluated by testing the identified gene classifiers on an independent (test) set of array data.</p> <p>Results</p> <p>The binary classifications provided prediction accuracies, between a subtype of interest and the remaining samples, of 88.5%, 82.8%, 82.8% and 80.0% for FL, cHL, DLBCL, and RL respectively. Identified gene classifiers include LIM domain only-2 (<it>LMO2</it>), Chemokine (C-C motif) ligand 22 (<it>CCL22</it>) and Cyclin-dependent kinase inhibitor-3 (<it>CDK3</it>) specifically for FL, cHL and DLBCL subtypes respectively.</p> <p>Conclusions</p> <p>This study highlights the ability of gene expression profiling to distinguish lymphoma from reactive conditions and classify the major subtypes of lymphoma in a diagnostic setting. A cost-effective single platform "mini-chip" assay could, in principle, be developed to aid the quick diagnosis of lymph node biopsies with the potential to incorporate other pathological entities into such an assay.</p