"I can't be dealing with this brain fog":A workplace focus group study investigating factors underpinning the menopausal experience for NHS staff

OBJECTIVES: Multiple studies highlight that individuals undergoing menopause are not receiving sufficient support at work. An improved menopausal experience in the workplace has been found to be associated with increased job satisfaction, increased economic participation and reduced absenteeism. This work was undertaken to explore the impact of menopause on the working lives of NHS staff working in Wales, with specific emphasis on their experience of menopausal symptoms and management strategies in the workplace.STUDY DESIGN: This was a qualitative study using semi-structured focus groups and thematic analysis. 14 women working in the NHS in Wales attended four focus groups, lasting up to 1.5 h. Stem questions focused on participants' positive and negative experiences in the workplace, and their receipt of support. Transcripts were analysed using the framework approach.RESULTS: Three major themes were identified: experiences of menopausal symptoms and symptom management, the impact of menopause on work and the impact of work on the menopause. Menopause symptom experience in the workplace was multifaceted and varied, depending on factors such as ongoing or past symptom experience, expectations, social support and effectiveness of management strategies. Inconsistent information was highlighted as a reason why some participants felt confused both about the symptoms that they could attribute to the menopause and the management strategies available to them. A variety of symptom management strategies had been used by participants, including hormone replacement therapy, flexible working hours, working from home, changes to uniform, peer support and lifestyle changes, with varying levels of success. Some women were reticent to ask for support at work even though they felt the workplace response was likely to be supportive. Almost all the women felt that they had to persuade their GP to prescribe HRT and felt that their doctors were too reticent in prescribing this treatment.CONCLUSIONS: Employers have a key role in supporting their staff experiencing menopausal symptoms, and such support has the potential to reduce sickness absence and boost retention. Based on the findings we recommend creating an open culture to break down taboos; protected time for peer support around shared experiences and effective symptom management techniques; and maximising the impact of non-menopause-specific policies such as flexible working to help all staff manage fatigue and become more productive in their roles.</p

Staff – Student Partnerships in Teaching and Learning: Hearing from the students themselves!

Building on the success of last year’s student-led keynote session, students from the universities of Bath, Nottingham Trent and Sheffield Hallam, who have been working with staff on a wide range of teaching and learning projects, will describe aspects of their work, its outcomes and the personal benefits for them of engaging with staff in this way. This session is likely to be of interest to all delegates as it sheds light on the value and potential of staff-student partnerships, but particularly for those who are interested in exploring ways in which they too might take this strategic agenda forward for the benefit of all students

Developing a population data science approach to assess increased risk of COVID-19 associated with attending large sporting events.

Objectives To design and test a method to assess whether test events were associated with an increase in risk of confirmed COVID-19, in order to inform policy on the safe re-introduction of spectator events following decreasing incidence of COVID-19 and relaxing of restrictions. Approach We designed a cohort study to measure relative risk of confirmed COVID-19 in those attending two large sporting events in South Wales during May-June 2021. First, we linked ticketing information to records on the Welsh Demographic Service (WDS) and identified NHS numbers for attendees. We then linked attendees to routine SARS-CoV-2 test data to calculate incidence rates in people attending each event for a fourteen days period following the event.  We selected a comparison cohort from WDS for each event, individually matched by age band, gender and locality of residence. Risk ratios were then computed for the two events. Results We successfully assigned NHS numbers to 91% and 84% of people attending the two events, respectively. Other identifiers were available for the remainder. Only a small number of attendees (1) than event 2 (<1), which did include pre-event testing. Conclusions We demonstrate the potential for data linkage to inform COVID-19 policy regarding sporting events. At that point in the epidemic, there was no evidence that attending large sporting events increased risk of COVID-19. However, these events took place between epidemic waves when background incidence and testing rate was low

Family cluster of three cases of monkeypox imported from Nigeria to the United Kingdom, May 2021

Monkeypox is a rare viral zoonotic disease. The causing virus belongs to the Orthopoxvirus genus that includes variola virus (the cause of smallpox), vaccinia virus (used in the smallpox vaccine), and cowpox virus. There are two distinct clades of monkeypox virus—Central African and West African. The first human cases were identified in the Democratic Republic of Congo in 1970 [1]. Outside of Africa, cases of human monkeypox infections have been documented in four countries: four cases the United Kingdom (UK) in 2018/2019, one case in Israel in 2018 and one case in Singapore in 2019 [2], 47 cases in the United States (US) in 2003 and one in 2021 [3]. We report on a family cluster of three recent cases of monkeypox in the UK associated with travel from Nigeria

Planck intermediate results X. Physics of the hot gas in the Coma cluster

We present an analysis of Planck satellite data on the Coma cluster observed via the Sunyaev-Zeldovich effect. Thanks to its great sensitivity, Planck is able, for the first time, to detect SZ emission up to r ≈ 3 × R500. We test previously proposed spherically symmetric models for the pressure distribution in clusters against the azimuthally averaged data. In particular, we find that the Arnaud et al. (2010, A&A, 517, A92) "universal" pressure profile does not fit Coma, and that their pressure profile for merging systems provides a reasonable fit to the data only at r R500 than the mean pressure profile predicted by the simulations used to constrain the models. The Planck image shows significant local steepening of the y profile in two regions about half a degree to the west and to the south-east of the cluster centre. These features are consistent with the presence of shock fronts at these radii, and indeed the western feature was previously noticed in the ROSAT PSPC mosaic as well as in the radio. Using Plancky profiles extracted from corresponding sectors we find pressure jumps of 4.9-0.2+0.4 and 5.0-0.1+1.3 in the west and south-east, respectively. Assuming Rankine-Hugoniot pressure jump conditions, we deduce that the shock waves should propagate with Mach number Mw = 2.03-0.04+0.09 and Mse = 2.05-0.02+0.25 in the west and south-east, respectively. Finally, we find that the y and radio-synchrotron signals are quasi-linearly correlated on Mpc scales, with small intrinsic scatter. This implies either that the energy density of cosmic-ray electrons is relatively constant throughout the cluster, or that the magnetic fields fall off much more slowly with radius than previously thought. © 2013 ESO

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

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