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The UK began delivering its COVID-19 vaccination programme on 8 December 2020, with health and social care workers (H&SCWs) given high priority for vaccination. Despite well-documented occupational exposure risks, however, there is evidence of lower uptake among some H&SCW groups. We used a mixed-methods approach-involving an online cross-sectional survey and semi-structured interviews-to gain insight into COVID-19 vaccination beliefs, attitudes, and behaviours amongst H&SCWs in the UK by socio-demographic and employment variables. 1917 people were surveyed- 1656 healthcare workers (HCWs) and 261 social care workers (SCWs). Twenty participants were interviewed. Workplace factors contributed to vaccination access and uptake. SCWs were more likely to not be offered COVID-19 vaccination than HCWs (OR:1.453, 95%CI: 1.244-1.696). SCWs specifically reported uncertainties around how to access COVID-19 vaccination. Participants who indicated stronger agreement with the statement 'I would recommend my organisation as a place to work' were more likely to have been offered COVID-19 vaccination (OR:1.285, 95%CI: 1.056-1.563). Those who agreed more strongly with the statement 'I feel/felt under pressure from my employer to get a COVID-19 vaccine' were more likely to have declined vaccination (OR:1.751, 95%CI: 1.271-2.413). Interviewees that experienced employer pressure to get vaccinated felt this exacerbated their vaccine concerns and increased distrust. In comparison to White British and White Irish participants, Black African and Mixed Black African participants were more likely to not be offered (OR:2.011, 95%CI: 1.026-3.943) and more likely to have declined COVID-19 vaccination (OR:5.550, 95%CI: 2.294-13.428). Reasons for declining vaccination among Black African participants included distrust in COVID-19 vaccination, healthcare providers, and policymakers. H&SCW employers are in a pivotal position to facilitate COVID-19 vaccination access, by ensuring staff are aware of how to get vaccinated and promoting a workplace environment in which vaccination decisions are informed and voluntary.

•Maternal vaccine information seeking behaviour is common during pregnancy.•Trust in health care professionals is key for satisfaction with information.•Develops the Psychosocial Determinates of Vaccine Information Seeking Behaviour Scale. Information search and processing is critical to the vaccine decision-making process. However, the role of drivers of information satisfaction and search is not fully understood. Here, we investigated the predictive potential of psychosocial characteristics related to satisfaction with information and additional information-seeking about the pertussis vaccine currently recommended during pregnancy. Cross-sectional online questionnaire study. A UK based sample of 314 women who had given birth during the previous six months was recruited to participate. The questionnaire included measures of the psycho-social predictors: trust, coping strategies, attitude towards vaccine information-seeking behaviour and risk perception of vaccination during pregnancy, and measures of two outcome variables: satisfaction with information received from a health care professional and whether participants engaged in vaccine information-seeking behaviour. Trust in health care professionals, a perceived behavioural control of own vaccine information-seeking behaviour, and an engaged problem-focused strategy for coping with stress were significant predictors of satisfaction with official information given by a health care professional. 40% of women sought out additional information about vaccination however, none of the psychosocial factors measured significantly predicted the behaviour. We found that high trust in health care professionals, a perceived ability to seek out accurate information about vaccines and actively focusing on problems as a means of coping with stress, drives satisfaction in official vaccine information. We also developed measures of these variables that could be used in further research.

BackgroundThe UK began delivering its COVID-19 vaccination programme on 8 December 2020, with health and social care workers (H&SCWs) given high priority for vaccination. Despite well-documented occupational exposure risks, however, there is evidence of lower uptake among some H&SCW groups.MethodsWe used a mixed-methods approach-involving an online cross-sectional survey and semi-structured interviews-to gain insight into COVID-19 vaccination beliefs, attitudes, and behaviours amongst H&SCWs in the UK by socio-demographic and employment variables. 1917 people were surveyed- 1656 healthcare workers (HCWs) and 261 social care workers (SCWs). Twenty participants were interviewed.FindingsWorkplace factors contributed to vaccination access and uptake. SCWs were more likely to not be offered COVID-19 vaccination than HCWs (OR:1.453, 95%CI: 1.244-1.696). SCWs specifically reported uncertainties around how to access COVID-19 vaccination. Participants who indicated stronger agreement with the statement 'I would recommend my organisation as a place to work' were more likely to have been offered COVID-19 vaccination (OR:1.285, 95%CI: 1.056-1.563). Those who agreed more strongly with the statement 'I feel/felt under pressure from my employer to get a COVID-19 vaccine' were more likely to have declined vaccination (OR:1.751, 95%CI: 1.271-2.413). Interviewees that experienced employer pressure to get vaccinated felt this exacerbated their vaccine concerns and increased distrust. In comparison to White British and White Irish participants, Black African and Mixed Black African participants were more likely to not be offered (OR:2.011, 95%CI: 1.026-3.943) and more likely to have declined COVID-19 vaccination (OR:5.550, 95%CI: 2.294-13.428). Reasons for declining vaccination among Black African participants included distrust in COVID-19 vaccination, healthcare providers, and policymakers.ConclusionH&SCW employers are in a pivotal position to facilitate COVID-19 vaccination access, by ensuring staff are aware of how to get vaccinated and promoting a workplace environment in which vaccination decisions are informed and voluntary.

Today we often hear of a \"crisis in middle management\" - too many managers, too little quality. Perhaps organizations are partially to blame - for bending over backwards to cater to these managers' psychological needs

Previous analyses of the International Subarachnoid Aneurysm Trial (ISAT) cohort have reported on the risks of recurrent subarachnoid haemorrhage and death or dependency for a minimum of 5 years and up to a maximum of 14 years after treatment of a ruptured intracranial aneurysm with either neurosurgical clipping or endovascular coiling. At 1 year there was a 7% absolute and a 24% relative risk reduction of death and dependency in the coiling group compared with the clipping group, but the medium-term results showed the increased need for re-treatment of the target aneurysm in the patients given coiling. We report the long-term follow-up of patients in this UK cohort. In ISAT, patients were randomly allocated to either neurosurgical clipping or endovascular coiling after a subarachnoid haemorrhage, assuming treatment equipoise, between Sept 12, 1994, and May 1, 2002. We followed up 1644 patients in 22 UK neurosurgical centres for death and clinical outcomes for 10·0–18·5 years. We assessed dependency as self-reported modified Rankin scale score obtained through yearly questionnaires. Data for recurrent aneurysms and rebleeding events were collected from questionnaires and from hospital and general practitioner records. The Office for National Statistics supplied data on deaths. This study is registered, number ISRCTN49866681. At 10 years, 674 (83%) of 809 patients allocated endovascular coiling and 657 (79%) of 835 patients allocated neurosurgical clipping were alive (odds ratio [OR] 1·35, 95% CI 1·06–1·73). Of 1003 individuals who returned a questionnaire at 10 years, 435 (82%) patients treated with endovascular coiling and 370 (78%) patients treated with neurosurgical clipping were independent (modified Rankin scale score 0–2; OR 1·25; 95% CI 0·92–1·71). Patients in the endovascular treatment group were more likely to be alive and independent at 10 years than were patients in the neurosurgery group (OR 1·34, 95% CI 1·07–1·67). 33 patients had a recurrent subarachnoid haemorrhage more than 1 year after their initial haemorrhage (17 from the target aneurysm). Although rates of increased dependency alone did not differ between groups, the probability of death or dependency was significantly greater in the neurosurgical group than in the endovascular group. Rebleeding was more likely after endovascular coiling than after neurosurgical clipping, but the risk was small and the probability of disability-free survival was significantly greater in the endovascular group than in the neurosurgical group at 10 years. UK Medical Research Council.

First described in 1983, Barth syndrome (BTHS) is widely regarded as a rare X-linked genetic disease characterised by cardiomyopathy (CM), skeletal myopathy, growth delay, neutropenia and increased urinary excretion of 3-methylglutaconic acid (3-MGCA). Fewer than 200 living males are known worldwide, but evidence is accumulating that the disorder is substantially under-diagnosed. Clinical features include variable combinations of the following wide spectrum: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), endocardial fibroelastosis (EFE), left ventricular non-compaction (LVNC), ventricular arrhythmia, sudden cardiac death, prolonged QTc interval, delayed motor milestones, proximal myopathy, lethargy and fatigue, neutropenia (absent to severe; persistent, intermittent or perfectly cyclical), compensatory monocytosis, recurrent bacterial infection, hypoglycaemia, lactic acidosis, growth and pubertal delay, feeding problems, failure to thrive, episodic diarrhoea, characteristic facies, and X-linked family history. Historically regarded as a cardiac disease, BTHS is now considered a multi-system disorder which may be first seen by many different specialists or generalists. Phenotypic breadth and variability present a major challenge to the diagnostician: some children with BTHS have never been neutropenic, whereas others lack increased 3-MGCA and a minority has occult or absent CM. Furthermore, BTHS was first described in 2010 as an unrecognised cause of fetal death. Disabling mutations or deletions of the tafazzin ( TAZ ) gene, located at Xq28, cause the disorder by reducing remodeling of cardiolipin, a principal phospholipid of the inner mitochondrial membrane. A definitive biochemical test, based on detecting abnormal ratios of different cardiolipin species, was first described in 2008. Key areas of differential diagnosis include metabolic and viral cardiomyopathies, mitochondrial diseases, and many causes of neutropenia and recurrent male miscarriage and stillbirth. Cardiolipin testing and TAZ sequencing now provide relatively rapid diagnostic testing, both prospectively and retrospectively, from a range of fresh or stored tissues, blood or neonatal bloodspots. TAZ sequencing also allows female carrier detection and antenatal screening. Management of BTHS includes medical therapy of CM, cardiac transplantation (in 14% of patients), antibiotic prophylaxis and granulocyte colony-stimulating factor (G-CSF) therapy. Multidisciplinary teams/clinics are essential for minimising hospital attendances and allowing many more individuals with BTHS to live into adulthood.

Breeding for Fusarium head blight (FHB) resistance in durum wheat is complicated by the quantitative trait expression and narrow genetic diversity of available resources. High-density mapping of the FHB resistance quantitative trait loci (QTL), evaluation of their co-localization with plant height and maturity QTL and the interaction among the identified QTL are the objectives of this study. Two doubled haploid (DH) populations, one developed from crosses between Triticum turgidum ssp. durum lines DT707 and DT696 and the other between T. turgidum ssp. durum cv. Strongfield and T. turgidum ssp. carthlicum cv. Blackbird were genotyped using the 90K Infinium iSelect chip and evaluated phenotypically at multiple field FHB nurseries over years. A moderate broad-sense heritability indicated a genotype-by-environment interaction for the expression of FHB resistance in both populations. Resistance QTL were identified for the DT707 × DT696 population on chromosomes 1B, 2B, 5A (two loci) and 7A and for the Strongfield × Blackbird population on chromosomes 1A, 2A, 2B, 3A, 6A, 6B and 7B with the QTL on chromosome 1A and those on chromosome 5A being more consistently expressed over environments. FHB resistance co-located with plant height and maturity QTL on chromosome 5A and with a maturity QTL on chromosome 7A for the DT707 × DT696 population. Resistance also co-located with plant height QTL on chromosomes 2A and 3A and with maturity QTL on chromosomes 1A and 7B for the Strongfield × Blackbird population. Additive × additive interactions were identified, for example between the two FHB resistance QTL on chromosome 5A for the DT707 × DT696 population and the FHB resistance QTL on chromosomes 1A and 7B for the Strongfield × Blackbird population. Application of the Single Nucleotide Polymorphic (SNP) markers associated with FHB resistance QTL identified in this study will accelerate combining genes from the two populations.

Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. In this high incidence population, daily tenofovir–emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.

Optogenetic actuators have revolutionized the resolution at which biological processes can be controlled. In plants, deployment of optogenetics is challenging due to the need for these light-responsive systems to function in the context of horticultural light environments. Furthermore, many available optogenetic actuators are based on plant photoreceptors that might crosstalk with endogenous signaling processes, while others depend on exogenously supplied cofactors. To overcome such challenges, we have developed Highlighter, a synthetic, light-gated gene expression system tailored for in planta function. Highlighter is based on the photoswitchable CcaS-CcaR system from cyanobacteria and is repurposed for plants as a fully genetically encoded system. Analysis of a re-engineered CcaS in Escherichia coli demonstrated green/red photoswitching with phytochromobilin, a chromophore endogenous to plants, but also revealed a blue light response likely derived from a flavin-binding LOV-like domain. We deployed Highlighter in transiently transformed Nicotiana benthamiana for optogenetic control of fluorescent protein expression. Using light to guide differential fluorescent protein expression in nuclei of neighboring cells, we demonstrate unprecedented spatiotemporal control of target gene expression. We implemented the system to demonstrate optogenetic control over plant immunity and pigment production through modulation of the spectral composition of broadband visible (white) light. Highlighter is a step forward for optogenetics in plants and a technology for high-resolution gene induction that will advance fundamental plant biology and provide new opportunities for crop improvement.

Breeding for solid-stemmed durum (Triticum turgidum L. var durum) and common wheat (Triticum aestivum L.) cultivars is one strategy to minimize yield losses caused by the wheat stem sawfly (Cephus cinctus Norton). Major stem-solidness QTL have been localized to the long arm of chromosome 3B in both wheat species, but it is unclear if these QTL span a common genetic interval. In this study, we have improved the resolution of the QTL on chromosome 3B in a durum (Kofa/W9262-260D3) and common wheat (Lillian/Vesper) mapping population. Coincident QTL (LOD = 94-127, R2 = 78-92%) were localized near the telomere of chromosome 3BL in both mapping populations, which we designate SSt1. We further examined the SSt1 interval by using available consensus maps for durum and common wheat and compared genetic to physical intervals by anchoring markers to the current version of the wild emmer wheat (WEW) reference sequence. These results suggest that the SSt1 interval spans a physical distance of 1.6 Mb in WEW (positions 833.4-835.0 Mb). In addition, minor QTL were identified on chromosomes 2A, 2D, 4A, and 5A that were found to synergistically enhance expression of SSt1 to increase stem-solidness. These results suggest that developing new wheat cultivars with improved stem-solidness is possible by combining SSt1 with favorable alleles at minor loci within both wheat species.