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Background Ovarian and tubal cancers are lethal gynaecological cancers, with over 50% of the patients diagnosed at advanced stage. Trial design Randomised controlled trial involving 27 primary care trusts adjacent to 13 trial centres based at NHS Trusts in England, Wales and Northern Ireland. Methods Participants Postmenopausal average-risk women, aged 50–74, with intact ovaries and no previous ovarian or current non-ovarian cancer. Interventions One of two annual screening strategies: (1) multimodal screening (MMS) using a longitudinal CA125 algorithm with repeat CA125 testing and transvaginal scan (TVS) as second line test (2) ultrasound screening (USS) using TVS alone with repeat scan to confirm any abnormality. The control (C) group had no screening. Follow-up was through linkage to national registries, postal follow-up questionnaires and direct communication with trial centres and participants. Objective To assess comprehensively risks and benefits of ovarian cancer screening in the general population. Outcome Primary outcome was death due to ovarian or tubal cancer as assigned by an independent outcomes review committee. Secondary outcomes included incidence and stage at diagnosis of ovarian and tubal cancer, compliance, performance characteristics, harms and cost-effectiveness of the two screening strategies and a bioresource for future research. Randomisation The trial management system confirmed eligibility and randomly allocated participants using computer-generated random numbers to MMS, USS and C groups in a 1:1:2 ratio. Blinding Investigators and participants were unblinded and outcomes review committee was masked to randomisation group. Analyses Primary analyses were by intention to screen, comparing separately MMS and USS with C using the Versatile test. Results Recruitment 1,243,282 women were invited and 205,090 attended for recruitment between April 2001 and September 2005. Randomised 202,638 women: 50,640 MMS, 50,639 USS and 101,359 C group. Numbers analysed for primary outcome 202,562 (>99.9%): 50,625 (>99.9%) MMS, 50,623 (>99.9%) USS, and 101,314 (>99.9%) C group. Outcome Women in MMS and USS groups underwent 345,570 and 327,775 annual screens between randomisation and 31 December 2011. At median follow-up of 16.3 (IQR 15.1–17.3) years, 2055 women developed ovarian or tubal cancer: 522 (1.0% of 50,625) MMS, 517 (1.0% of 50,623) USS, and 1016 (1.0% of 101314) in C group. Compared to the C group, in the MMS group, the incidence of Stage I/II disease was 39.2% (95% CI 16.1 to 66.9) higher and stage III/IV 10.2% (95% CI –21.3 to 2.4) lower. There was no difference in stage in the USS group. 1206 women died of the disease: 296 (0.6%) MMS, 291 (0.6%) USS, and 619 (0.6%) C group. There was no significant reduction in ovarian and tubal cancer deaths in either MMS (p = 0.580) or USS (p = 0.360) groups compared to the C group. Overall compliance with annual screening episode was 80.8% (345,570/420,047) in the MMS and 78.0% (327,775/420,047) in the USS group. For ovarian and tubal cancers diagnosed within one year of the last test in a screening episode, in the MMS group, the sensitivity, specificity and positive predictive values were 83.8% (95% CI 78.7 to 88.1), 99.8% (95% CI 99.8 to 99.9), and 28.8% (95% CI 25.5 to 32.2) and in the USS group, 72.2% (95% CI 65.9 to 78.0), 99.5% (95% CI 99.5 to 99.5), and 9.1% (95% CI 7.8 to 10.5) respectively. The final within-trial cost-effectiveness analysis was not undertaken as there was no mortality reduction. A bioresource (UKCTOCS Longitudinal Women’s Cohort) of longitudinal outcome data and over 0.5 million serum samples including serial annual samples in women in the MMS group was established and to date has been used in many new studies, mainly focused on early detection of cancer. Harms Both screening tests (venepuncture and TVS) were associated with minor complications with low (8.6/100,000 screens MMS; 18.6/100,000 screens USS) complication rates. Screening itself did not cause anxiety unless more intense repeat testing was required following abnormal screens. In the MMS group, for each screen-detected ovarian or tubal cancer, an additional 2.3 (489 false positives; 212 cancers) women in the MMS group had unnecessary false-positive (benign adnexal pathology or normal adnexa) surgery. Overall, 14 (489/345,572 annual screens) underwent unnecessary surgery per 10,000 screens. In the USS group, for each screen-detected ovarian or tubal cancer, an additional 10 (1630 false positives; 164 cancers) underwent unnecessary false-positive surgery. Overall, 50 (1630/327,775 annual screens) women underwent unnecessary surgery per 10,000 screens. Conclusions Population screening for ovarian and tubal cancer for average-risk women using these strategies should not be undertaken. Decreased incidence of Stage III/IV cancers during multimodal screening did not translate to mortality reduction. Researchers should be cautious about using early stage as a surrogate outcome in screening trials. Meanwhile the bioresource provides a unique opportunity to evaluate early cancer detection tests. Funding Long-term follow-up UKCTOCS (2015–2020) – National Institute for Health and Care Research (NIHR HTA grant 16/46/01), Cancer Research UK, and The Eve Appeal. UKCTOCS (2001–2014) – Medical Research Council (MRC) (G9901012/G0801228), Cancer Research UK (C1479/A2884), and the UK Department of Health, with additional support from The Eve Appeal. Researchers at UCL were supported by the NIHR UCL Hospitals Biomedical Research Centre and by MRC Clinical Trials Unit at UCL core funding (MR_UU_12023).

The practice of ovarian stimulation for IVF is undergoing a fundamental re-evaluation as recent data begin to successfully challenge the traditional paradigm that ovarian stimulation should be aimed at the retrieval of as many oocytes as possible, in the belief that this will increase pregnancy rates. An opposing view is that live birth rate should not be the only end-point in evaluating the success of IVF treatment and that equal emphasis should be placed on safety and affordability. The International Society for Mild Approaches in Assisted Reproduction (ISMAAR) committee has carried out an up-to-date literature search, with the evidence being graded according to the University of Oxford's Centre for Evidence-Based Medicine. The recommendations were formulated taking into account the quality of evidence on the efficacy, risk and cost of each intervention. ISMAAR recommends adopting a mild approach to ovarian stimulation in all clinical settings as an increasing body of evidence suggests that mild stimulation is as effective as conventional stimulation, while being safer and less expensive. Mild ovarian stimulation could replace conventional stimulation, thus making IVF safer and more accessible worldwide.

Forest bathing is based upon a Japanese practice known as Shinrin–Yoku and is a nature-based therapy involving mindful walks through ancient woodland to reduce stress and anxiety. One proposed mechanism behind the effectiveness of Forest bathing is based on the potential mental and physical health benefits of the natural volatile organic compounds (NVOCs) that fill the forest understory. Surprisingly little is known about the concentrations and diversity of plant NVOCs in ambient air particularly in the UK and this study aims to increase that knowledge. Air samples were collected in July 2022 in a UK forest and compared with samples from a walled garden environment. The samples were collected over a 2 h time period and analysed using GC-MS and showed clear differences in the chemical composition of the air. This study revealed NVOCs including limonene, carvone, terpenes, terpenoids and sesquiterpenoids were present within a UK forest but were either not present or present at little to low levels in the control setting of a walled garden. This study also found that the typical 2 h duration of a Forest bathing session was a long enough sampling period to detect these NVOCs, indicating that Forest bathers could benefit from exposure to NVOCs.

The home and personal care (HPC) industry generally relies on initial cultivation and subsequent biochemical testing for the identification of microorganisms in contaminated products. This process is slow (several days for growth), labour intensive, and misses organisms which fail to revive from the harsh environment of preserved consumer products. Since manufacturing within the HPC industry is high-throughput, the process of identification of microbial contamination could benefit from the multiple cultivation-independent methodologies that have developed for the detection and analysis of microbes. We describe a novel workflow starting with automated DNA extraction directly from a HPC product, and subsequently applying metagenomic methodologies for species and strain-level identification of bacteria. The workflow was validated by application to a historic microbial contamination of a general-purpose cleaner (GPC). A single strain of Pseudomonas oleovorans was detected metagenomically within the product. The metagenome mirrored that of a contaminant isolated in parallel by a traditional cultivation-based approach. Using a dilution series of the incident sample, we also provide evidence to show that the workflow enables detection of contaminant organisms down to 100 CFU/ml of product. To our knowledge, this is the first validated example of metagenomics analysis providing confirmatory evidence of a traditionally isolated contaminant organism, in a HPC product.

The obsidian mirror associated with the Elizabethan polymath and magus John Dee (1527–1608/1609) has been an object of fascination for centuries. The mirror, however, has a deeper history as an Aztec artefact brought to Europe soon after the Spanish conquest. The authors present the results of new geochemical analysis, and explore its history and changing cultural context to provide insights into its meaning during a period in which entirely new world views were emerging. The biography of the mirror demonstrates how a complex cultural history underpins an iconic object. The study highlights the value of new compositional analyses of museum objects for the reinterpretation of historically significant material culture.

Research question How many oocytes or embryos are needed to optimize the live birth rate (LBR) per cycle and cumulative LBR (CLBR) following mild stimulation IVF (MS-IVF) in women with uncompromised ovarian reserve? Design Retrospective analysis of a 4-year database of five fertility centres. The study population included women with normal/high ovarian reserve, who underwent autologous MS-IVF (daily ≤150 IU gonadotrophin) with fresh and subsequent frozen embryo transfer(s) (FET) from surplus embryos. Only the first cycle of each patient was included. Cycles with >150 IU daily average of gonadotrophin were excluded. ‘Freeze-all embryo' (FAE) cycles were analysed separately. Results A total of 862 consecutive cycles fulfilled the inclusion criteria; 592 were eligible for fresh embryo transfer, 239 had non-elective 'freeze-all' cycles. Median age (25–75th percentile) of women who had fresh embryo transfer was 35 (32–37) years, median antral follicle count 19 (14–28) and anti-Mullerian hormone 19.2 (13–28.9) pmol/l. LBR/fresh cycle and CLBR inclusive of FAE cycles in the Conclusion Nine oocytes, or four embryos, can optimize fresh transfer cycle LBR in MS-IVF. The CLBR are optimized with 12 oocytes, or nine embryos in predicted normal responders, while safeguarding against OHSS.

Right-sided diaphragmatic injury is an uncommon sequelae from blunt trauma and may be associated with other severe thoracoabdominal injuries. This injury can be easily missed on initial assessment and a high index of suspicion and clinical judgment is required. Recently, we treated a 25-year-old male inflicted with a right-sided diaphragmatic injury after a left-sided transhumeral amputation sustained from an overturned motor vehicle collision with thoracoscopic exploration and reapproximation.

BACKGROUND Mild ovarian stimulation has emerged as an alternative to conventional IVF with the advantages of being more patient-friendly and less expensive. Inadequate data on pregnancy outcomes and concerns about the cycle cancellation rate (CCR) have prevented mild, or low-dose, IVF from gaining wide acceptance. OBJECTIVE AND RATIONALE To evaluate parallel-group randomised controlled trials (RCTs) on IVF where comparisons were made between a mild (≤150 IU daily dose) and conventional stimulation in terms of clinical outcomes and cost-effectiveness in patients described as poor, normal and non-polycystic ovary syndrome (PCOS) hyper-responders to IVF. SEARCH METHODS Searches with no language restrictions were performed using Medline, Embase, Cochrane central, Pre-Medicine from January 1990 until April 2020, using pre-specified search terms. References of included studies were hand-searched as well as advance access articles to key journals. Only parallel-group RCTs that used ≤150 IU daily dose of gonadotrophin as mild-dose IVF (MD-IVF) and compared with a higher conventional dose (CD-IVF) were included. Studies were grouped under poor, normal or hyper-responders as described by the authors in their inclusion criteria. Women with PCOS were excluded in the hyper-responder group. The risk of bias was assessed as per Cochrane Handbook for the included studies. The quality of evidence (QoE) was assessed according to the GRADE system. PRISMA guidance was followed for review methodology. OUTCOMES A total of 31 RCTs were included in the analysis: 15 in the poor, 14 in the normal and 2 in the hyper-responder group. Live birth rates (LBRs) per randomisation were similar following use of MD-IVF in poor (relative risk (RR) 0.91 (CI 0.68, 1.22)), normal (RR 0.88 (CI 0.69, 1.12)) and hyper-responders (RR 0.98 (CI 0.79, 1.22)) when compared to CD-IVF. QoE was moderate. Cumulative LBRs (5 RCTs, n = 2037) also were similar in all three patient types (RR 0.96 (CI 0.86 1.07) (moderate QoE). Risk of ovarian hyperstimulation syndrome was significantly less with MD-IVF than CD-IVF in both normal (RR 0.22 (CI 0.10, 0.50)) and hyper-responders (RR 0.47 (CI 0.31, 0.72)), with moderate QoE. The CCRs were comparable in poor (RR 1.33 (CI 0.96, 1.85)) and hyper-responders (RR 1.31 (CI 0.98, 1.77)) but increased with MD-IVF among normal responders (RR 2.08 (CI 1.38, 3.14)); all low to very low QoE. Although fewer oocytes were retrieved and fewer embryos created with MD-IVF, the proportion of high-grade embryos was similar in all three population types (low QoE). Compared to CD-IVF, MD-IVF was associated with less gonadotrophin use and lower cost. WIDER IMPLICATIONS This updated review provides reassurance on using MD-IVF not only for the LBR per cycle but also for the cumulative LBR, with moderate QoE. With risks identified with ‘freeze-all’ strategies, it may be time to recommend mild-dose ovarian stimulation for IVF for all categories of women i.e. hyper, poor and normal responders to IVF.

We examine the relationship between parental ethnic identity and the test scores of ethnic minority children. We use standard survey measures of the strength of parental identity alongside validated cognitive test scores in a rich British cohort study. We show that children whose mothers report either an adoption or an active rejection of the majority identity tend to score lower in cognitive tests at age 7, compared with those children whose mothers report neutral feelings about the majority identity. We find no consistent differences in test scores according to mothers’ minority identity. Our findings provide no support for education or citizenship policies that promote the adoption of the majority identity or discourage the maintenance of separate identities in ethnic minority communities.

Mild ovarian stimulation is a treatment option for poor responders in IVF treatment. Our updated review evaluated mild IVF solely from randomized controlled trials (RCTs) that used genuine low-dose gonadotrophin (≤150 IU daily) alone or in combination with oral medications, comparing it with conventional-dose (>150 IU/ daily) IVF for poor responders. Electronic searches on MEDLINE, Embase, The Cochrane Central Register of Controlled Trials and PreMEDLINE, and hand searches from 2002 up to 31 January 2019, identified 14 RCTs, which were compiled with the above inclusion criteria. The risk of bias (ROB) and quality of evidence (QOE) were assessed as per Cochrane Collaboration. Meta-analyses found no difference in live birth rate (four RCTs, n = 1057, RR 0.91, CI 0.66 to 1.25) (moderate QOE), ongoing pregnancy rate (six RCTs, n = 1782, RR 1.01, CI 0.86 to 1.20) (moderate-high QOE) and cycle cancellation rates (14 RCTs, n = 2746, RR 1.38, CI 0.99 to 1.92) (low QOE). Fewer oocytes and embryos were obtained from mild IVF; however, the number and proportion of high-grade embryos were similar. Mild IVF resulted in reduced gonadotrophin use and cost. The inference remained unchanged when smaller studies with ROB were excluded, or whether gonadotrophin alone or combination with oral medication was used. The evidence of equal efficacy from a pooled population, which was adequately powered for live birth, supported a mild IVF strategy for poor responders in preference to more expensive conventional IVF. Although clinical heterogeneity remained a limiting factor, it increased the generalizability of the findings.

Objective Estrogen is a well‐established risk factor for various cancers. It causes endometrial proliferation, which is assessed routinely as endometrial thickness (ET) using transvaginal ultrasound (TVS). Only one previous study, restricted to endometrial and breast cancer, has considered ET and the risk of non‐endometrial cancer. The aim of this study was to explore the association between baseline and serial ET measurements and nine non‐endometrial hormone‐sensitive cancers, in postmenopausal women, using contemporary statistical methodology that attempts to minimize the biases typical of endogenous serial data. Methods This was a cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). In the ultrasound arm of UKCTOCS, 50639 postmenopausal women, aged 50–74, underwent annual TVS examination, of whom 38 105 had a valid ET measurement, no prior hysterectomy and complete covariate data, and were included in this study. All women were followed up through linkage to national cancer registries. The effect of ET on the risk of six estrogen‐dependent cancers (breast, ovarian, colorectal, bladder, lung and pancreatic) was assessed using joint models for longitudinal biomarker and time‐to‐event data, and Cox models were used to assess the association between baseline ET measurement and these six cancers in addition to liver cancer, gastric cancer and non‐Hodgkin's lymphoma (NHL). All models were adjusted for current hormone‐replacement therapy (HRT) use, body mass index, age at last menstrual period, parity and oral contraceptive pill use. Results The 38 105 included women had a combined total of 267 567 (median, 8; interquartile range, 5–9) valid ET measurements. During a combined total of 407 838 (median, 10.9) years of follow‐up, 1398 breast, 351 endometrial, 381 lung, 495 colorectal, 222 ovarian, 94 pancreatic, 79 bladder, 62 gastric, 38 liver cancers and 52 NHLs were registered. Using joint models, a doubling of ET increased significantly the risk of breast (hazard ratio (HR), 1.21; 95% CI, 1.09–1.36; P = 0.001), ovarian (HR, 1.39; 95% CI, 1.06–1.82; P = 0.018) and lung (HR, 1.25; 95% CI, 1.02–1.54; P = 0.036) cancers. There were no statistically significant associations between ET and the remaining six cancers. Conclusion Postmenopausal women with high/increasing ET on TVS are at increased risk of breast, ovarian and lung cancer. It is important that clinicians are aware of these risks, as TVS is a common investigation. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Small‐scale fisheries are an important livelihood and primary protein source for coastal communities in many of the poorest regions in the world, yet many are overfished and thus require effective and scalable management solutions. Positive ecological and socioeconomic responses to management typically lag behind immediate costs borne by fishers from fishing pressure reductions necessary for fisheries recovery. These short‐term costs challenge the long‐term success of these interventions. However, social marketing may increase perceptions of management benefits before ecological and socioeconomic benefits are fully realized, driving new social norms and ultimately long‐term sustainable behavior change. By conducting underwater visual surveys to quantify ecological conditions and by conducting household surveys with community members to quantify their perceptions of management support and socioeconomic conditions, we assessed the impact of a standardized small‐scale fisheries management intervention that was implemented across 41 sites in Brazil, Indonesia, and the Philippines. The intervention combines TURF reserves (community‐based territorial use rights for fishing coupled with no‐take marine reserves) with locally tailored social‐marketing behavior change campaigns. Leveraging data across 22 indicators and 4 survey types, along with data from 3 control sites, we found that ecological and socioeconomic impacts varied and that communities supported the intervention and were already changing their fishing practices. These results suggest that communities were developing new social norms and fishing more sustainably before long‐term ecological and socioeconomic benefits of fisheries management materialized., Article impact statement: Moving from overfishing to sustainability, behavior change campaigns can be used to transition fisheries from near‐term losses to long‐term gains.

Sphingosines are antimicrobial lipids that form part of the innate barrier to skin colonisation by microbes. Sphingosine deficiencies can result in increased epithelial infections by bacteria including Staphylococcus aureus. Recent studies have focused on the potential use of sphingosines as novel therapeutic agents, but there have been no investigations into sphingosine resistance or its potential mechanisms. We used RNA-Seq to identify the common D-sphingosine transcriptomic response of the transient skin coloniser S. aureus and the dominant skin coloniser S. epidermidis. A common D-sphingosine stimulon was identified that included downregulation of the SaeSR two-component system (TCS) regulon and upregulation of both the VraSR TCS and CtsR stress regulons. We show that the PstSCAB phosphate transporter, and VraSR offer intrinsic resistance to D-sphingosine. Further, we demonstrate increased sphingosine resistance in these staphylococci evolves readily through mutations in genes encoding the FarE-FarR efflux/regulator proteins. The ease of selecting mutants with resistance to sphingosine may impact upon staphylococcal colonisation of skin where the lipid is present and have implications with topical therapeutic applications.

The NSLS-II network and computing infrastructure has been significantly updated recently. The re-IP process in 2020-2021 enabled the NSLS-II network to be routable to the rest of the BNL campus. Then, standardization of the operating systems and deployment procedures helped to deliver a consistent environment to workstations and servers used by all NSLS-II beamlines. In particular, the RedHat Enterprise Linux 8 was deployed to 700+ machines using the RedHat Satellite infrastructure management product, and all critical services (IOCs, databases, etc.) were migrated to the new OS. NFS users’ home directories are consistent across all of the machines, which eliminates the need for the individual configuration of the user environment on each host. The standard suite of software packages is available to the beamline staff and users, which includes the system packages (deployed via RPM) as well as the conda environments for data acquisition and analysis. Security measures were implemented to comply with the industry standards, which include multi-factor authentication (using Duo), secure screen lock for the beamline machines, and advanced access control to the experimental data that is stored in shared central storage available on all hosts. These major enhancements facilitated sharing the experimental data (currently for a number of selected beamlines, with a plan to extend it to the whole facility in the nearest future) with the users via an externally facing JupyterHub instance - https://jupyter.nsls2.bnl.gov. The beamlines keep using the Bluesky data acquisition framework to orchestrate their experiments, and the new infrastructure enabled them to use a next-generation data access library called tiled.

This paper examines inequalities in the match between student and degree quality using linked administrative data from schools, universities and tax authorities. We analyse two measures of match at the university-subject level: undergraduate enrollment qualifications, and graduate earnings. We find for both that disadvantaged students match to lower quality degrees across the entire distribution of achievement, in a setting with uniform fees and a generous financial aid system. While there are negligible gender gaps in academic match, high-attaining women systematically undermatch in terms of expected earnings, driven by subject choice. These inequalities in match are largest among the most undermatched.

Ovarian cancer is most commonly diagnosed at an advanced stage (3 or 4) and remains the deadliest gynecologic malignancy. When diagnosed at stage 1, a survival rate of greater than 90% has been demonstrated, compared with a 5-year survival rate of 27% and 13% for stage 3 and stage 4 disease, respectively. Despite international efforts to identify robust screening methods and increase early-stage detection, to date no evidence that screening saves lives has been presented. The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is a randomized controlled trial that demonstrated no evidence associated with screening for ovarian cancer and reduction in ovarian cancer-related deaths at primary analysis but requires further follow-up. This secondary analysis of the UKCTOCS randomized controlled trial aimed to provide a follow-up and report on the long-term mortality effects of ovarian cancer screening. The UKCTOCS is a multicenter randomized trial of 202,638 women aged 50 to 74 years assigned to 2 annual screening groups (multimodal screening [MMS] vs ultrasound screening [USS]). Women in the United Kingdom were recruited from 13 National Health Service (NHS) centers and randomized to MMS, USS, or no screening in a 1:1:2 ratio. Annual screening in the MMS group involved serum CA125 measurements used in conjunction with the risk of ovarian cancer (ROCA) calculation to guide follow-up involving either no additional screening, repeat CA125 ROCA in 3 months, or transvaginal USS as a second test. Annual screening in the USS group involved transvaginal ultrasound with follow-up involving either continuation of annual screening, repeat in 3 months, or requiring a scan with a senior ultrasonographer within 6 weeks. The primary study outcome was death due to ovarian cancer or tubal cancer. A total of 202,638 women were randomized between April 2001 and September 2005, with screening concluding in December 2011 and follow-up continuing until June 2020. The final analysis cohort consisted of 202,562 women, 50,625 in the MMS group, 50,623 in the USS group, and 101,314 in the no screening group. Compliance with screening was 81% in the MMS group versus 78% in the USS group, with a median of 8 annual screens per participant. The median follow-up was 16.3 years (interquartile range, 15.1–17.3). A total of 2055 participants were diagnosed with ovarian or tubal cancer. At 9.5 years after screening, there was a 47.2% (95% confidence interval, 19.7–81.1) greater incidence of stage 1 disease and a 24.5% (-41.8 to -2.0) lower incidence of stage IV disease in the MMS group compared with the no screening group. Overall, a 39.2% (95% confidence interval, 16.1–66.9) greater incidence of stage I or II disease and a 10.2% (-21.3 to 2.4) lower incidence of stage III or IV disease was observed in the MMS group compared with the no screening group. At follow-up conclusion, 1206 women had died of ovarian cancer (296/50,625 [0.6%] in the MMS group, 291/50,623 [0.6%] in the USS group, 619/101,314 [0.6%] in the no screening group) with no significant difference between the MMS (P = 0.58) and USS (P = 0.36) groups compared with the no screening group. The results of this large-scale ovarian cancer screening trial demonstrate that, on long-term follow-up, while the screening strategies defined here resulted in a greater likelihood of diagnosing early stage disease, neither MMS nor USS resulted in a significant reduction in deaths from ovarian or tubal cancer.

Objective There are widespread efforts to increase symptom awareness of ‘pelvic/abdominal pain, increased abdominal size/bloating, difficulty eating/feeling full and urinary frequency/urgency’ in an attempt to diagnose ovarian cancer earlier. Long-term survival of women with these symptoms adjusted for known prognostic factors is yet to be determined. This study explored the association of symptoms, routes and interval to diagnosis and long-term survival in a population-based cohort of postmenopausal women diagnosed with invasive epithelial tubo-ovarian cancer (iEOC) in the ‘no screen’ (control) UKCTOCS arm. Methods Of 101,299 women in the control arm, 574 were confirmed on outcome review to have iEOC between randomisation (2001–2005) and 31 December 2014. Data was extracted from medical notes and electronic records. A multivariable model was fitted for individual symptoms, time interval from symptom onset to diagnosis, route to diagnosis, speciality, morphological Type, age at diagnosis, year of diagnosis (period effect), stage, primary treatment, and residual disease. Results Women presenting with symptoms listed in the NICE guidelines (HR1.48, 95%CI1.16–1.89, p = 0.001) or the modified Goff Index (HR1·68, 95%CI1·32–2.13, p, Highlights • This study explored the association of symptoms of ovarian cancer, interval and route to diagnosis with survival. • Focus on ‘high alert’ symptoms: pelvic/abdominal pain, increase abdominal size/bloating and difficulty eating/feeling full • The ovarian cancer ‘high alert’ symptom complexes identify postmenopausal women with a significantly poorer prognosis. • The study could not however exclude the possibility of better outcomes in those who are aware and acted on these symptoms.

Preservatives play an essentially role in ensuring that cosmetic formulations remain safe for use via control of microbial contamination. Commonly used preservatives include organic acids, alcohols and phenols and these play an essential role in controlling the growth of bacteria, fungi and moulds in substrates that can potentially act as a rich food source for microbial contaminants. Whilst the activity of these compounds is clear, both in vitro and in formulation, little information exists on the potential impact that common preservative systems, in full formulation, have on the skin’s resident microbiome. Dysbiosis of the skin’s microbiome has been associated with a number of cosmetic conditions but there currently are no in vivo studies investigating the potential for preservative ingredients, when included in personal care formulations under normal use conditions, to impact the cutaneous microbiome. Here we present an analysis of four in vivo studies that examine the impact of different preservation systems in full formulation, in different products formats, with varying durations of application. This work demonstrates that despite the antimicrobial efficacy of the preservatives in vitro, the skin microbiome is not impacted by preservative containing products in vivo.

OBJECTIVE To investigate the association between hysterectomy with conservation of one or both adnexa and ovarian and tubal cancer. DESIGN Prospective cohort study. SETTING Thirteen NHS Trusts in England, Wales and Northern Ireland. POPULATION A total of 202 506 postmenopausal women recruited between 2001 and 2005 to the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and followed up until 31 December 2014. METHODS Multiple sources (questionnaires, hospital notes, Hospital Episodes Statistics, national cancer/death registries, ultrasound reports) were used to obtain accurate data on hysterectomy (with conservation of one or both adnexa) and outcomes censored at bilateral oophorectomy, death, ovarian/tubal cancer diagnosis, loss to follow up or 31 December 2014. Cox proportional hazards regression models were used to assess the association. MAIN OUTCOME MEASURES Invasive epithelial ovarian and tubal cancer (WHO 2014) on independent outcome review. RESULTS Hysterectomy with conservation of one or both adnexa was reported in 41 912 (20.7%; 41 912/202 506) women. Median follow up was 11.1 years (interquartile range 9.96-12.04), totalling >2.17 million woman-years. Among women who had undergone hysterectomy, 0.55% (231/41 912) were diagnosed with ovarian/tubal cancer, compared with 0.59% (945/160 594) of those with intact uterus. Multivariable analysis showed no evidence of an association between hysterectomy and invasive epithelial ovarian/tubal cancer (hazard ratio 0.98, 95% CI 0.85-1.13, P = 0.765). CONCLUSIONS This large cohort study provides further independent validation that hysterectomy is not associated with alteration of invasive epithelial ovarian and tubal cancer risk. These data are important both for clinical counselling and for refining risk prediction models. TWEETABLE ABSTRACT Hysterectomy does not alter risk of invasive epithelial ovarian and tubal cancer.

The Burkholderia cepacia complex (Bcc) is a closely related group of bacteria, composed of at least 20 different species, the accurate identification of which is essential in the context of infectious diseases. In industry, they can contaminate non-food products, including home and personal care products and cosmetics. The Bcc are problematic contaminants due to their ubiquitous presence and intrinsic antimicrobial resistance, which enables them to occasionally overcome preservation systems in non-sterile products. Burkholderia lata and Burkholderia contaminans are amongst the Bcc bacteria encountered most frequently as industrial contaminants, but their identification is not straightforward. Both species were historically established as a part of a group known collectively as taxon K, based upon analysis of the recA gene and multilocus sequence typing (MLST). Here, we deploy a straightforward genomics-based workflow for accurate Bcc classification using average nucleotide identity (ANI) and core-gene analysis. The workflow was used to examine a panel of 23 Burkholderia taxon K industrial strains, which, based on MLST, comprised 13 B. lata, 4 B. contaminans and 6 unclassified Bcc strains. Our genomic identification showed that the B. contaminans strains retained their classification, whilst the remaining strains were reclassified as Burkholderia aenigmatica sp. nov. Incorrect taxonomic identification of industrial contaminants is a problematic issue. Application and testing of our genomic workflow allowed the correct classification of 23 Bcc industrial strains, and also indicated that B. aenigmatica sp. nov. may have greater importance than B. lata as a contaminant species. Our study illustrates how the non-food manufacturing industry can harness whole-genome sequencing to better understand antimicrobial-resistant bacteria affecting their products.

Background During trials that span decades, new evidence including progress in statistical methodology, may require revision of original assumptions. An example is the continued use of a constant-effect approach to analyse the mortality reduction which is often delayed in cancer-screening trials. The latter led us to re-examine our approach for the upcoming primary mortality analysis (2020) of long-term follow-up of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (LTFU UKCTOCS), having initially (2014) used the proportional hazards (PH) Cox model. Methods We wrote to 12 experts in statistics/epidemiology/screening trials, setting out current evidence, the importance of pre-specification, our previous mortality analysis (2014) and three possible choices for the follow-up analysis (2020) of the mortality outcome: (A) all data (2001–2020) using the Cox model (2014), (B) new data (2015–2020) only and (C) all data (2001–2020) using a test that allows for delayed effects. Results Of 11 respondents, eight supported changing the 2014 approach to allow for a potential delayed effect (option C), suggesting various tests while three favoured retaining the Cox model (option A). Consequently, we opted for the Versatile test introduced in 2016 which maintains good power for early, constant or delayed effects. We retained the Royston-Parmar model to estimate absolute differences in disease-specific mortality at 5, 10, 15 and 18 years. Conclusions The decision to alter the follow-up analysis for the primary outcome on the basis of new evidence and using new statistical methodology for long-term follow-up is novel and has implications beyond UKCTOCS. There is an urgent need for consensus building on how best to design, test, estimate and report mortality outcomes from long-term randomised cancer screening trials. Trial registration ISRCTN22488978. Registered on 6 April 2000.

The volume and value of fish catches by Indonesia's small-scale fisheries have declined significantly since national government restrictions on travel and social distancing were imposed in response to the COVID-19 pandemic. Using a digital data collection system (OurFish), that records purchases by fish traders from small-scale fishers, data was collected across 82 coastal communities in Southeast Sulawesi. We found that the number of active fishers and traders declined by more than 90% after the onset of the pandemic and the average weight of catch per fishing trip increased across fishers. Although the average price per kilogram of fish declined after the pandemic began, fishers that were able to maintain fishing had on average higher catches and therefore daily catch value was maintained. High value fisheries that usually enter export supply chains were more negatively impacted compared with lower value species that are commonly sold to local markets. We interviewed 185 small scale fishers and fish traders across 20 of the 82 communities in Southeast Sulawesi province, recording the perceived level of impact on local fisheries and the fish trade, causes of this impact and proposed coping strategies. Over 50% of both fishers and fish traders believed low demand for fish from traders and a decline in the price received for fish were disrupting their lives. Approximately 75% of both male and female fishers are coping by continuing to fish, highlighting that there were few alternative livelihoods available at the time of the interviews. Our results provide key insights into the vulnerability of small-scale fishing communities to impacts of the COVID-19 pandemic.

Background There is a trend to increasing use of routinely collected health data to ascertain outcome measures in trials. We report on the completeness and accuracy of national ovarian cancer and death registration in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Methods Of the 202,638 participants, 202,632 were successfully linked and followed through national cancer and death registries of Northern Ireland, Wales and England. Women with registrations of any of 19 pre-defined ICD-10 codes suggestive of tubo-ovarian cancer or notification of ovarian/tubal/peritoneal cancer from hospital episode statistics or trial sites were identified. Copies of hospital and primary care notes were retrieved and reviewed by an independent outcomes review committee. National registration of site and cause of death as ovarian/tubal/peritoneal cancer (C56/C57/C48) obtained up to 3 months after trial censorship was compared to that assigned by outcomes review (reference standard). Results Outcome review was undertaken in 3110 women on whom notification was received between 2001 and 2014. Ovarian cancer was confirmed in 1324 of whom 1125 had a relevant cancer registration. Sensitivity and specificity of ovarian/tubal/peritoneal cancer registration were 85.0% (1125/1324; 95% CI 83.7–86.2%) and 94.0% (1679/1786; 95% CI 93.2–94.8%), respectively. Of 2041 death registrations reviewed, 681 were confirmed to have a tubo-ovarian cancer of whom 605 had relevant death registration. Sensitivity and specificity were 88.8% (605/681; 95% CI 86.4–91.2%) and 96.7% (1482/1533, 95% CI 95.8–97.6%), respectively. When multiple electronic health record sources were considered, sensitivity for cancer site increased to 91.1% (1206/1324, 95% CI 89.4–92.5%) and for cause of death 94.0% (640/681, 95% CI 91.9–95.5%). Of 1232 with cancer registration, 8.7% (107/1232) were wrongly designated as ovarian/tubal/peritoneal cancers by the registry and 4.0% (47/1172) of confirmed tubo-ovarian cancers were mis-registered. In 656 with death registrations, 7.8% (51/656) were wrongly assigned as due to ovarian/tubal/peritoneal cancers while 6.2% (40/645) of confirmed tubo-ovarian cancer deaths were mis-registered. Conclusion Follow-up of trial participants for tubo-ovarian cancer using national registry data will result in incomplete ascertainment, particularly of the site due in part to the latency of registration. This can be reduced by using other routinely collected data such as hospital episode statistics. Central adjudication by experts though resource intensive adds value by improving the accuracy of diagnoses. Trial registration ISRCTN: ISRCTN22488978. Registered on 6 April 2000

This article addresses Rachmaninoff’s activities in Paris, both a musical capital of the world and unrivalled cultural centre of the Russian emigration until 1940. It looks at the small number of concerts performed by the pianist there and places them in the context of the French press. It attempts to understand his ambiguous personal relationship to the city, the activity of his publishing company “TAIR”, and finally assesses the extent of the composer’s charitable endeavours for the Russian community. The article concludes Rachmaninoff was of monumental significance for the “Russian” Paris. В статье освещается деятельность Рахманинова в Париже, который до 1940 года являлся не только одной из мировых музыкальных столиц, но и культурным центром русской эмиграции. Обращается внимание на незначительное количество концертов, которые дал там пианист, и то место, которое они заняли во французской прессе. Предпринимается попытка понять неоднозначное отношение Рахманинова к Парижу, рассказывается о его издательском предприятии «Таир» и, наконец, оценивается благотворительная деятельность Рахманинова в отношении русской диаспоры. Делается вывод об огромном значении Рахманинова для «русского» Парижа. Париз је једна од водећих престоница музичког света. Између 1925. и 1940. био је и интелектуални, културни и политички центар руске емиграције. Било би изненађујуће да Сергеј Рахмањинов није провео неко време у том граду. И заиста, између 1928. и 1939. тамо је одржао дванаест клавирских реситала и два концерта с оркестром. Релативно мали број концерата које је Рахмањинов имао у Паризу сугерише да је француска публика била навикнута на другачију, егзотичнију руску музику, препуну блиставих пејзажа, костима, плесача виртуозних скокова и боја. Томе у прилог иде и приметан вакуум који је око Рахмањинова начинила француска штампа од краја двадесетих до почетка четрдесетих година. Његов шездесети рођендан и четрдесетогодишњицу његове музичке каријере 1933. године, који су у руским круговима у Паризу прослављени с великом помпом, није забележио ниједан од популарних, а ни музичких часописа Француске. Сам Рахмањинов би најрадије изабрао живот на селу. Међутим, бракови обеју кћерки чврсто су га били везали за Француску, а посебно за Париз. Тамо је покренуо издавачку кућу „Tair“. Рахмањинов, као и чланови његове породице, писци из руске дијаспоре и колеге музичари били су укључени у тај подухват. Издавачку кућу је користио да помогне Русима, објављујући њихова дела. Рахмањиновљев однос према Паризу био је амбивалентан. С једне стране, он је живот у Паризу сматрао добрим. С друге стране, у писмима је град називао „уклетим“, „ужурбаним и скупим“, а говорио је и да рђаво делује на његово здравље и да га је „растргао га на комаде“. Иако су добротворни концерти били уобичајена појава у Рахмањиновљевој каријери, та добротворна димензија била је посебно важна у Паризу. Помагао је руске студенте, добротворне организације за помоћ емигрантима, цркве и образовне установе, попут Института Светог Сергија. Ако Рахмањинов није оставио готово никаквог трага у музичкој историји Париза, то је за „руски“ Париз међуратног доба несумњиво имао огроман значај. В основу статьи положен доклад шотландского музыковеда Стюарта Кэмпбелла (1949–2018), прочитанный на конференции Русский Париж между двух мировых войн (Москва, Дом русского зарубежья имени Александра Солженицына, 3 декабря 2013 года). Статья и приложение к ней подготовлены к публикации С. Г. Зверевой и Г. Л. Лапшиновым.

Objectives: Chronic ventilator dependency in cervical tetraplegia is associated with substantial morbidity. When non-invasive weaning methods have failed the primary surgical treatment is diaphragm...

Background: There is a trend to increasing use of routinely collected health data to ascertain outcome measures in trials. We report on completeness and accuracy of national ovarian cancer and death registration in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).Methods: Of the 202638 participants, 202632 were successfully linked and followed through national cancer and death registries of Northern Ireland, Wales and England. Women with registrations of any of 19 pre-defined ICD-10 codes suggestive of tubo-ovarian cancer or notification of ovarian/tubal/peritoneal cancer from hospital episode statistics or trial sites were identified. Copies of hospital and primary care notes were retrieved and reviewed by an independent outcomes review committee. National registration of site and cause of death as ovarian/tubal/peritoneal cancer (C56/C57/C48) obtained up to three months after trial censorship was compared to that assigned by outcomes review (reference standard).Results: Outcome review was undertaken in 3110 women on whom notification was received between 2001 and 2014. Ovarian cancer was confirmed in 1324 of whom 1125 had a relevant cancer registration. Sensitivity and specificity of ovarian/tubal/peritoneal cancer registration was 85.0%(1125/1324; 95%CI 83.7%-86.2%) and 94.0%(1679/1786; 95%CI93.2%-94.8%), respectively. Of 2041 death registrations reviewed, 681 were confirmed to have a tubo-ovarian cancer of whom 605 had relevant death registration. Sensitivity and specificity was 88.8%(605/681; 95%CI86.4%-91.2%) and 96.7%(1482/1533; 95%CI95.8%-97.6%%) respectively. When multiple electronic health record sources were considered, sensitivity for cancer site increased to 91.1%(1206/1324; 95%CI89.4%-92.5%) and for cause of death 94.0%(640/681; 95%CI91.9%-95.5%).Of 1232 with cancer registration, 8.7%(107/1232) were wrongly designated as ovarian/tubal/peritoneal cancers by the registry and 4.0%(47/1172) of confirmed tubo-ovarian cancers were mis-registered. In 656 with death registrations, 7.8%(51/656) were wrongly assigned as ovarian/tubal/peritoneal cancers whilst 6.2%(40/645) of confirmed tubo-ovarian cancer deaths were mis-registered.Conclusion: Follow-up of trial participants for tubo-ovarian cancer using national registry data will result in incomplete ascertainment particularly of site due in part to the latency of registration. This can be reduced by using other routinely collected data such as hospital episode statistics. Central adjudication by experts though resource intensive adds value by improving accuracy of diagnoses. Trial registration: ISRCTN22488978, date of trial registration: 6/4/2000