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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.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are common in Far North Queensland (FNQ) and their incidence is increasing. Decolonisation regimens that include topical mupirocin are recommended in Australian guidelines to reduce recurrent infection. Mupirocin resistance was identified in 3,932/15,851 (24.8%) methicillin-sensitive Staphylococcus aureus (MSSA) isolates and in 533/5,134 (10.4%) MRSA isolates from FNQ between 1997 and 2016. Factors associated with mupirocin resistance in multivariate analysis were an MSSA isolate, age < 40 years, rural residence and female gender. These data support the use of mupirocin in MRSA decolonisation in FNQ, although addressing the underlying social determinants of health that drive the incidence of S. aureus infections remain a priority for local healthcare provision.

Effective management of freshwater fish habitat is essential to supporting healthy aquatic ecosystems and sustainable fisheries. In Canada, recent changes to the Fisheries Act enhanced the protection of fish habitat, but application of those provisions relies on sound scientific evidence. We employed collaborative research prioritization methods to identify scientific research questions that, if addressed, would significantly advance the management of freshwater fish habitat in Canada. This list was generated by a diverse group of freshwater fish experts, including substantial contributions from practitioners who administer provisions of the Fisheries Act. The research questions generated in this study identify priority topics for future research, while highlighting issues that could be addressed with different funding models. As a result, this study should support evidence-based management of Canada’s aquatic resources by identifying scientific knowledge gaps faced by practitioners, and suggesting mechanisms to address them. Given the important contribution of Canadian freshwater systems to global ecosystem values, and the similar scientific challenges facing fish habitat managers in other jurisdictions, this study is likely to have broad applicability.

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.

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.

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.

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.

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.