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In this paper, we combine the Early Science radio continuum data from the MeerKAT International GHz Tiered Extragalactic Exploration (MIGHTEE) Survey, with optical and near-infrared data and release the cross-matched catalogues. The radio data used in this work covers 0.86 deg2 of the COSMOS field, reaches a thermal noise of 1.7  μ Jy beam−1 and contains 6102 radio components. We visually inspect and cross-match the radio sample with optical and near-infrared data from the Hyper Suprime-Cam (HSC) and UltraVISTA surveys. This allows the properties of active galactic nuclei and star-forming populations of galaxies to be probed out to z ≈ 5. Additionally, we use the likelihood ratio method to automatically cross-match the radio and optical catalogues and compare this to the visually cross-matched catalogue. We find that 94 per cent of our radio source catalogue can be matched with this method, with a reliability of 95 per cent. We proceed to show that visual classification will still remain an essential process for the cross-matching of complex and extended radio sources. In the near future, the MIGHTEE survey will be expanded in area to cover a total of ∼20 deg2; thus the combination of automated and visual identification will be critical. We compare the redshift distribution of SFG and AGN to the SKADS and T-RECS simulations and find more AGN than predicted at z ∼ 1. [ABSTRACT FROM AUTHOR]

We present deep 1.4 GHz source counts from ∼5 deg2 of the continuum Early Science data release of the MeerKAT International Gigahertz Tiered Extragalactic Exploration survey down to S 1.4GHz ∼15 |$\mu$| Jy. Using observations over two extragalactic fields (COSMOS and XMM-LSS), we provide a comprehensive investigation into correcting the incompleteness of the raw source counts within the survey to understand the true underlying source count population. We use a variety of simulations that account for: errors in source detection and characterization, clustering, and variations in the assumed source model used to simulate sources within the field and characterize source count incompleteness. We present these deep source count distributions and use them to investigate the contribution of extragalactic sources to the sky background temperature at 1.4 GHz using a relatively large sky area. We then use the wealth of ancillary data covering a subset of the COSMOS field to investigate the specific contributions from both active galactic nuclei (AGN) and star-forming galaxies (SFGs) to the source counts and sky background temperature. We find, similar to previous deep studies, that we are unable to reconcile the sky temperature observed by the ARCADE 2 experiment. We show that AGN provide the majority contribution to the sky temperature contribution from radio sources, but the relative contribution of SFGs rises sharply below 1 mJy, reaching an approximate 15–25 per cent contribution to the total sky background temperature (Tb ∼100 mK) at ∼15 |$\mu$| Jy. [ABSTRACT FROM AUTHOR]

MIGHTEE is a galaxy evolution survey using simultaneous radio continuum, spectropolarimetry, and spectral line observations from the South African MeerKAT telescope. When complete, the survey will image ∼20 deg2 over the COSMOS, E-CDFS, ELAIS-S1, and XMM- Newton Large Scale Structure field (XMM-LSS) extragalactic deep fields with a central frequency of 1284 MHz. These were selected based on the extensive multiwavelength data sets from numerous existing and forthcoming observational campaigns. Here, we describe and validate the data processing strategy for the total intensity continuum aspect of MIGHTEE, using a single deep pointing in COSMOS (1.6 deg2) and a three-pointing mosaic in XMM-LSS (3.5 deg2). The processing includes the correction of direction-dependent effects, and results in thermal noise levels below 2  |$\mathrm{\mu }$| Jy beam−1 in both fields, limited in the central regions by classical confusion at ∼8 arcsec angular resolution, and meeting the survey specifications. We also produce images at ∼5 arcsec resolution that are ∼3 times shallower. The resulting image products form the basis of the Early Science continuum data release for MIGHTEE. From these images we extract catalogues containing 9896 and 20 274 radio components in COSMOS and XMM-LSS, respectively. We also process a close-packed mosaic of 14 additional pointings in COSMOS and use these in conjunction with the Early Science pointing to investigate methods for primary beam correction of broad-band radio images, an analysis that is of relevance to all full-band MeerKAT continuum observations, and wide-field interferometric imaging in general. A public release of the MIGHTEE Early Science continuum data products accompanies this article. [ABSTRACT FROM AUTHOR]

High vaccine wastage can serve as a critical barrier to achieving the gains of vaccination, especially in a country like Nigeria, where data on vaccine wastage are sparsely available. We determined the country-wide vaccine wastage rates and their determinants through a mixed-methods study conducted across 576 health facilities (primary and secondary) in 24 states in Nigeria. We collected facility-based immunization records from June 2018 to May 2019, in addition to healthcare workers' interviews and observations of fixed and outreach sessions. The results show that open-vial wastage ranged from 21.2% (95% CI: 20.2%, 22.2%) for the pentavalent vaccine to 72.6% (95% CI: 71.5%, 73.6%) for BCG. Open-vial wastage rates for BCG, measles, and yellow fever vaccines were higher during outreach sessions, with rates of 76.2%, 64.3%, and 65.2%, respectively. For the outreach and fixed sessions, PCV and Penta had the least wastages of 22.0% for fixed sessions and 20.4% for outreach sessions. This study identified vaccine presentation (liquid vs. lyophilized vaccines), vial size (4 dose vs. 5 dose vs. 10 dose vs. 20 dose), RI service delivery strategies (fixed vs. outreach sessions), number of children vaccinated, and human resources (healthcare workers position/cadre) as key determinants of vaccine wastages in Nigeria.

Background: Sustaining independence is important for older people, but there is insufficient guidance about which community health and care services to implement., Objectives: To synthesise evidence of the effectiveness of community services to sustain independence for older people grouped according to their intervention components, and to examine if frailty moderates the effect., Review Design: Systematic review and network meta-analysis., Eligibility Criteria: Studies: Randomised controlled trials or cluster-randomised controlled trials. Participants: Older people (mean age 65+) living at home. Interventions: community-based complex interventions for sustaining independence. Comparators: usual care, placebo or another complex intervention., Main Outcomes: Living at home, instrumental activities of daily living, personal activities of daily living, care-home placement and service/economic outcomes at 1 year., Data Sources: We searched MEDLINE (1946-), Embase (1947-), CINAHL (1972-), PsycINFO (1806-), CENTRAL and trial registries from inception to August 2021, without restrictions, and scanned reference lists., Review Methods: Interventions were coded, summarised and grouped. Study populations were classified by frailty. A random-effects network meta-analysis was used. We assessed trial-result risk of bias (Cochrane RoB 2), network meta-analysis inconsistency and certainty of evidence (Grading of Recommendations Assessment, Development and Evaluation for network meta-analysis)., Results: We included 129 studies (74,946 participants). Nineteen intervention components, including 'multifactorial-action' (multidomain assessment and management/individualised care planning), were identified in 63 combinations. The following results were of low certainty unless otherwise stated. For living at home, compared to no intervention/placebo, evidence favoured: multifactorial-action and review with medication-review (odds ratio 1.22, 95% confidence interval 0.93 to 1.59; moderate certainty) multifactorial-action with medication-review (odds ratio 2.55, 95% confidence interval 0.61 to 10.60) cognitive training, medication-review, nutrition and exercise (odds ratio 1.93, 95% confidence interval 0.79 to 4.77) and activities of daily living training, nutrition and exercise (odds ratio 1.79, 95% confidence interval 0.67 to 4.76). Four intervention combinations may reduce living at home. For instrumental activities of daily living, evidence favoured multifactorial-action and review with medication-review (standardised mean difference 0.11, 95% confidence interval 0.00 to 0.21; moderate certainty). Two interventions may reduce instrumental activities of daily living. For personal activities of daily living, evidence favoured exercise, multifactorial-action and review with medication-review and self-management (standardised mean difference 0.16, 95% confidence interval -0.51 to 0.82). For homecare recipients, evidence favoured the addition of multifactorial-action and review with medication-review (standardised mean difference 0.60, 95% confidence interval 0.32 to 0.88). Care-home placement and service/economic findings were inconclusive., Limitations: High risk of bias in most results and imprecise estimates meant that most evidence was low or very low certainty. Few studies contributed to each comparison, impeding evaluation of inconsistency and frailty. Studies were diverse; findings may not apply to all contexts., Conclusions: Findings for the many intervention combinations evaluated were largely small and uncertain. However, the combinations most likely to sustain independence include multifactorial-action, medication-review and ongoing review of patients. Some combinations may reduce independence., Future Work: Further research is required to explore mechanisms of action and interaction with context. Different methods for evidence synthesis may illuminate further., Study Registration: This study is registered as PROSPERO CRD42019162195., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128862) and is published in full in Health Technology Assessment ; Vol. 28, No. 48. See the NIHR Funding and Awards website for further award information.

Androgen excess is a hallmark feature of polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility. Clinical and preclinical evidence links developmental or chronic exposure to hyperandrogenism with programming and evoking the reproductive and metabolic traits of PCOS. While critical androgen targets remain to be determined, central GABAergic neurons are postulated to be involved. Here, we tested the hypothesis that androgen signaling in GABAergic neurons is critical in PCOS pathogenesis in 2 well-characterized hyperandrogenic mouse models of PCOS. Using cre-lox transgenics, GABA-specific androgen receptor knockout (GABARKO) mice were generated and exposed to either acute prenatal androgen excess (PNA) or chronic peripubertal androgen excess (PPA). Females were phenotyped for reproductive and metabolic features associated with each model and brains of PNA mice were assessed for elevated GABAergic input to gonadotropin-releasing hormone (GnRH) neurons. Reproductive and metabolic dysfunction induced by PPA, including acyclicity, absence of corpora lutea, obesity, adipocyte hypertrophy, and impaired glucose homeostasis, was not different between GABARKO and wild-type (WT) mice. In PNA mice, acyclicity remained in GABARKO mice while ovarian morphology and luteinizing hormone secretion was not significantly impacted by PNA or genotype. However, PNA predictably increased the density of putative GABAergic synapses to GnRH neurons in adult WT mice, and this PNA-induced plasticity was absent in GABARKO mice. Together, these findings suggest that while direct androgen signaling in GABA neurons is largely not required for the development of PCOS-like traits in androgenized models of PCOS, developmental programming of GnRH neuron innervation is dependent upon androgen signaling in GABA neurons., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Frailty is a suggested consequence of ageing, but with a variety of different definitions the understanding of what it means to be frail is challenging. There is a common belief that frailty results in a reduction of physical functioning and ability and therefore is likely to significantly affect a person's quality of life. The aim of this study was to explore the understanding of older people about the meaning of frailty and the potential consequences of being classified as frail., Methods: This paper forms a secondary analysis of a process evaluation of a complex intervention that was embedded within the individually randomised Home-based Extended Rehabilitation of Older people (HERO) trial. A maximum variation, purposive sampling strategy sought to recruit participants with a wide range of characteristics. Data collection included observations of the delivery of the intervention, documentary analysis and semi-structured interviews with participants. Thematic analysis was used to make sense of the observational and interview data, adopting both inductive and deductive approaches., Results: Ninety three HERO trial participants were sampled for the process evaluation with a total of 60 observational home visits and 35 interviews were undertaken. There was a wide range in perceptions about what it meant to be classified as frail with no clear understanding from our participants. However, there was a negative attitude towards frailty with it being considered something that needed to be avoided where possible. Frailty was seen as part of a negative decline that people struggled to associate with. There was discussion about frailty being temporary and that it could be reduced or avoided with sufficient physical exercise and activity., Conclusion: Our study provides insight into how older people perceive and understand the concept of frailty. Frailty is a concept that is difficult for patients to understand, with most associating the term with an extreme degree of physical and cognitive decline. Having a label of being "frail" was deemed to be negative and something to be avoided, suggesting the term needs to be used cautiously., Trial Registration: ISRCTN 13927531. Registered on April 19, 2017., (© 2024. The Author(s).)

Share tables (ST) are tables or stations in school cafeterias where students can return unopened foods and beverages, providing an opportunity to access these items at no cost. Currently, research suggests that milk is among the most wasted items in breakfast and lunch programs in the United States. Share tables present a simple solution for reducing milk waste, but research is needed to understand the microbial spoilage potential of milk in ST. To this end, uninoculated milk cartons and milk cartons inoculated with 2 to 3 log 10 (cfu/mL) Pseudomonas poae, a fast-growing psychrotroph, was exposed to ambient temperature during winter (mean temperature = 20.3°C) and summer (23.1°C) for 125 min, repeated over 5 d (the length of a school week). Microbial counts in the inoculated milk cartons increased linearly, exceeding the spoilage threshold of 6.0 log 10 (cfu/mL) after d 3 and after d 4 in the winter and summer season trials, respectively. In the winter trial, the microbial counts for uninoculated milk cartons never exceeded the lower limit of detection, 2.31 log 10 (cfu/mL), and in the summer trials, microbial counts never reached the spoilage threshold, indicating that initial contamination is a driving factor of microbial milk spoilage. Regardless of sharing status or seasonality, the greatest changes in counts for inoculated milk cartons occurred during overnight refrigeration, ranging from 0.56 to 1.4 log 10 (cfu/mL), while during the share table ranged from no observable change up to 0.29 log 10 (cfu/mL), emphasizing that school nutrition personnel should focus efforts on tightly controlling refrigeration temperatures and returning milk to refrigeration as soon as possible. A previously developed model for school cafeteria share tables was adapted to understand the typical residence time of milk in a simulated cafeteria with an ambient temperature share table for the summer and winter seasons over 1,000 wk. Milk was predicted to have a very short mean residence time (85 min) regardless of sharing status or season, with 99.8% of milk consumed, discarded, or donated within the first 2 d. As a result, only 3 out of 451,410 and 6 out of 451,410 simulated milks spoiled in the winter and summer seasons, respectively. The data generated here can be used to inform science-based decision-making for including milk in share tables, or applied to any system where one might have to accept short-term unrefrigerated storage of milk to meet a waste reduction or food security goal., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Objective: To synthesise evidence of the effectiveness of community based complex interventions, grouped according to their intervention components, to sustain independence for older people., Design: Systematic review and network meta-analysis., Data Sources: Medline, Embase, CINAHL, PsycINFO, CENTRAL, clinicaltrials.gov, and International Clinical Trials Registry Platform from inception to 9 August 2021 and reference lists of included studies., Eligibility Criteria: Randomised controlled trials or cluster randomised controlled trials with ≥24 weeks' follow-up studying community based complex interventions for sustaining independence in older people (mean age ≥65 years) living at home, with usual care, placebo, or another complex intervention as comparators., Main Outcomes: Living at home, activities of daily living (personal/instrumental), care home placement, and service/economic outcomes at 12 months., Data Synthesis: Interventions were grouped according to a specifically developed typology. Random effects network meta-analysis estimated comparative effects; Cochrane's revised tool (RoB 2) structured risk of bias assessment. Grading of recommendations assessment, development and evaluation (GRADE) network meta-analysis structured certainty assessment., Results: The review included 129 studies (74 946 participants). Nineteen intervention components, including "multifactorial action from individualised care planning" (a process of multidomain assessment and management leading to tailored actions), were identified in 63 combinations. For living at home, compared with no intervention/placebo, evidence favoured multifactorial action from individualised care planning including medication review and regular follow-ups (routine review) (odds ratio 1.22, 95% confidence interval 0.93 to 1.59; moderate certainty); multifactorial action from individualised care planning including medication review without regular follow-ups (2.55, 0.61 to 10.60; low certainty); combined cognitive training, medication review, nutritional support, and exercise (1.93, 0.79 to 4.77; low certainty); and combined activities of daily living training, nutritional support, and exercise (1.79, 0.67 to 4.76; low certainty). Risk screening or the addition of education and self-management strategies to multifactorial action from individualised care planning and routine review with medication review may reduce odds of living at home. For instrumental activities of daily living, evidence favoured multifactorial action from individualised care planning and routine review with medication review (standardised mean difference 0.11, 95% confidence interval 0.00 to 0.21; moderate certainty). Two interventions may reduce instrumental activities of daily living: combined activities of daily living training, aids, and exercise; and combined activities of daily living training, aids, education, exercise, and multifactorial action from individualised care planning and routine review with medication review and self-management strategies. For personal activities of daily living, evidence favoured combined exercise, multifactorial action from individualised care planning, and routine review with medication review and self-management strategies (0.16, -0.51 to 0.82; low certainty). For homecare recipients, evidence favoured addition of multifactorial action from individualised care planning and routine review with medication review (0.60, 0.32 to 0.88; low certainty). High risk of bias and imprecise estimates meant that most evidence was low or very low certainty. Few studies contributed to each comparison, impeding evaluation of inconsistency and frailty., Conclusions: The intervention most likely to sustain independence is individualised care planning including medicines optimisation and regular follow-up reviews resulting in multifactorial action. Homecare recipients may particularly benefit from this intervention. Unexpectedly, some combinations may reduce independence. Further research is needed to investigate which combinations of interventions work best for different participants and contexts., Registration: PROSPERO CRD42019162195., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: AC, TC, JE, AF, JGl, MJ, NL, and RRi had financial support from the NIHR Health Technology Assessment Programme for the submitted work; MB had financial support from the PhD Graduate Teaching Fund at the University of Liverpool for the submitted work; DA declares payment made to her employer, University of Leeds Library, from the Academic Unit for Ageing and Stroke Research, Bradford Institute for Health Research, for services that included contributions to the submitted work; TC, AC, and AF received research funding from NIHR Programme Grants for Applied Research; AC and AF also received research funding from NIHR HSDR Programme; AC also received research funding from Health Data Research UK, NIHR ARC Yorkshire and Humber, NIHR Leeds BRC, and Dunhill Medical Trust; AF also declares NIHR Senior Investigator award, National Institute for Health (USA) payment for panel membership in 2021 and 2022, and University of Leeds Governor representative on the Governors Board of Bradford Teaching Hospitals NHS Foundation Trust; MB and MP received NIHR pre-doctoral fellowship funding; RB is supported by matched funding awarded to the NIHR Applied Research Collaboration (West Midlands) and is a member of the data monitoring committee for the Predict and Prevent AECOPD Trial and College of Experts, Versus Arthritis; AC is a member of NIHR HTA Commissioned Research Funding Committee and Dunhill Medical Trust Research Grants Committee; RRi received personal payments for training courses provided in-house to universities (Leeds, Aberdeen, Exeter, LSHTM) and other organisations (Roche), has received personal payments from the BMJ and BMJ Medicine as their statistical editor, is a co-convenor of the Cochrane Prognosis Methods Group and on the Editorial Board of Diagnostic and Prognostic Research, and Research Synthesis Methods, but receives no income for these roles, receives personal payment for being the external examiner of the MSc Medical Statistics, London School of Hygiene and Tropical Medicine, was previously an external examiner for the MSc Medical Statistics at University of Leicester, has written two textbooks for which he receives royalties from sales (Prognosis Research in Healthcare, and Individual Participant Data Meta-analysis), is a lead editor on an upcoming book (Cochrane Handbook for Prognosis Reviews, Wiley, 2025), for which he will receive royalties from sales, has received consulting fees for a training course on IPD meta-analysis from Roche in 2018, the NIHR HTA grant paid for travel to Leeds for one meeting, and is a member of the NIHR Doctoral Research Fellowships grant panel, and a member of the MRC Better Methods Better Research grant panel—for the latter, he receives an attendance fee; MH declares NIHR Academic Clinical Fellowship; OT declares NIHR Academic Clinical Lectureship and Dunhill Medical Trust Doctoral Research Fellowship RTF107/0117; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite growing efforts to improve access to vaccination, millions of children, especially in developing countries, have not received a single dose of diphtheria, tetanus, and pertussis (DTP) vaccine. Consequently, they are often called zero-dose children (ZDC). With limited health resources, prioritising communities for rapid and mass zero-dose catch-up vaccination in missed communities to avert epidemic outbreaks is complicated by unreliable denominators used to compute vaccination coverages. Incorporating other indicators of access and utilisation of vaccination services can help with identifying and ranking missed communities based on the likelihood of finding ZDC. We described the process of generating a scoring method to rank health areas in Cameroon based on their likelihood of containing ZDC., Methods: We used geospatial analysis to compute and aggregate health area characteristics, including hard-to-reach (HTR) areas (defined as areas of settlement above a one- (for urban areas) or 15-kilometre radius (for rural areas) beyond a vaccinating health facility), amount of area covered by slums and new area settlement, and percentage of children unvaccinated for DTP-1. We attributed a weight based on the ability to limit accessibility or utilisation of vaccination services to each characteristic and computed the score as a weighted average of health area characteristics. The health area score ranged from 0 to 1, with higher scores representing a higher likelihood of containing ZDC. We stratified the analysis by rural and urban health areas., Results: We observed substantial district and regional variations in health area scores, with hotspots health areas (administrative level 4) observed in the Far North (0.83), North (0.81), Adamawa (0.80), East (0.75), and South West (0.67) regions. The Adamawa region had the highest percentage of health areas with the highest score (78%), followed by the East (50%), West (48%), and North (46%) regions. For most regions (Far North, South, South West, Littoral, West, and North West), DTP-1 contributed the most to the score. However, HTR settlement areas within a health area contributed substantially to the overall score in the East, North, and Adamawa regions., Conclusions: We found substantial variations in health area scores with hotspots in the Far North, North, Adamawa, East, and South West regions. Although DTP-1 could be used as an indicator to identify health areas with ZDC for most communities, HTR settlement area was a valuable indicator in ranking priority health areas in the East, North, and Adamawa regions, further emphasising the need to consider other indicators before prioritisation., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

Cooking-related literacy and attitudes may play important roles in preventing and reducing diet-related chronic diseases and nutrition disparities. People living alone are an under-researched but growing population who face above average food insecurity rates. This study's objectives were to 1) test how cooking self-efficacy and attitude are stratified demographically among a sample of people living alone, focusing on variations across gender, age, and food security, and 2) examine how cooking self-efficacy and attitude are associated with two indicators of cooking behavior - cooking frequency and convenience orientation. We draw from a cross-sectional survey analysis of 493 adults living alone in Illinois, USA with validated measures for cooking self-efficacy, attitude, frequency, convenience orientation, and demographic characteristics. Hierarchical linear regression models were used to examine demographic factors explaining variation in self-efficacy and attitude, with attention to interactions between gender, food insecurity, and age. Poisson and OLS linear regression models were used to examine associations between self-efficacy and attitude and cooking frequency and convenience orientation. We find cooking-related self-efficacy and attitude showed strong but distinct associations with cooking frequency and convenience orientation. Overall, food insecure groups had lower self-efficacy than those who were food secure; however, food insecure women had higher self-efficacy than men in similar positions, apart from older-adult women who held particularly low efficacy. Cooking attitudes varied in small ways, notably with food insecure younger and older women possessing more negative cooking attitudes than middle-aged women. This research highlights the importance of understanding the cooking-related orientations of single-living people, while demonstrating that this group's ability to prevent and manage food insecurity is not uniform. These results can inform targeted interventions around food and nutrition insecurity, cooking attitudes, and self-efficacy among single-living populations., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To report our experience using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2)., Study Design and Setting: Two reviewers independently applied RoB 2 to results of interest in a large systematic review of complex interventions and reached consensus. We recorded the time taken, and noted and discussed our difficulties using the tool, and the resolutions we adopted. We explored the time taken with regression analysis and summarized our experience of implementing the tool., Results: We assessed risk of bias in 860 results of interest in 113 studies. Staff resource averaged 358 minutes per study (SD 183). Number of results (β = 22) and reports (β = 14) per study and experience of the team (β = -6) significantly affected assessment time. To implement the tool consistently, we developed cut points for missingness and considerations of balance regarding missingness, assumed some concerns with intervention deviations unless otherwise prevented or investigated, some concerns with measurements from unblinded self-reporting participants, and judged low risk of selection for certain dichotomous outcomes despite the absence of an analysis plan., Conclusion: The RoB 2 tool and guidance are useful but resource-intensive and challenging to implement. Critical appraisal tools and reporting guidelines should detail risk of bias implementation. Improved guidance focusing on implementation could assist reviewers., Competing Interests: Declaration of Competing Interest Andrew Clegg declares funding through the NIHR HTA programme, NIHR Programme Grants for Applied Research, NIHR HS&DR programme, NIHR Applied Research Collaboration Yorkshire & Humber, and Health Data Research UK; Anne Forster declares NIHR Senior Investigator Award 2017-present, NIHR Programme Grant 10% of salary, NIHR HS&DR grant 8% of salary, HTA grant 5% of salary, National Institute for Health (USA) payment for panel membership 2021, 2022, participation in Programme Steering Committees for NIHR 202,339 Improving the lives of stroke survivors with data, and NIHR202020 Research Title Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (multimorbidity)-The PERFORM trial, University of Leeds Governor representative on the Governors Board of Bradford Teaching Hospitals NHS Foundation Trust, member of HSDR Researcher-Led panel, member of NIHR Doctoral Fellowship Panel member of Policy Research Unit assessment panel. Other authors declare no potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Immunohistochemical visualization of progesterone receptor (PR)-expressing cells in the brain is a powerful technique to investigate the role of progesterone in the neuroendocrine regulation of fertility. A major obstacle to the immunohistochemical visualization of progesterone-sensitive cells in the rodent brain has been the discontinuation of the commercially produced A0098 rabbit polyclonal PR antibody by DAKO. To address the unavailability of this widely used PR antibody, we optimized and evaluated 4 alternative commercial PR antibodies and found that each lacked the specificity and/or sensitivity to immunohistochemically label PR-expressing cells in paraformaldehyde-fixed female mouse brain sections. As a result, we developed and validated a new custom RC269 PR antibody, directed against the same 533-547 amino acid sequence of the human PR as the discontinued A0098 DAKO PR antibody. Immunohistochemical application of the RC269 PR antibody on paraformaldehyde-fixed mouse brain sections resulted in nuclear PR labeling that was highly distinguishable from background, specific to its antigen, highly regulated by estradiol, matched the known distribution of PR protein expression in the female mouse hypothalamus, and nearly identical to that of the discontinued A0098 DAKO PR antibody. In summary, the RC269 PR antibody is a specific and sensitive antibody to immunohistochemically visualize PR-expressing cells in the mouse brain., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Chemical communication by females remains poorly understood, with most attention focused on female advertisement of sexual receptivity to males or mother-offspring communication. However, in social species, scents are likely to be important for mediating competition and cooperation between females determining individual reproductive success. Here, we explore chemical signaling by female laboratory rats ( Rattus norvegicus ) to test i) whether females target their deployment of scent information differentially according to their sexual receptivity and the genetic identity of both female and male conspecifics signaling in the local environment and ii) whether females are attracted to gain the same or different information from female scents compared to males. Consistent with targeting of scent information to colony members of similar genetic background, female rats increased scent marking in response to scents from females of the same strain. Females also suppressed scent marking in response to male scent from a genetically foreign strain while sexually receptive. Proteomic analysis of female scent deposits revealed a complex protein profile, contributed from several sources but dominated by clitoral gland secretion. In particular, female scent marks contained a series of clitoral-derived hydrolases and proteolytically truncated major urinary proteins (MUPs). Manipulated blends of clitoral secretion and urine from estrus females were strongly attractive to both sexes, while voided urine alone stimulated no interest. Our study reveals that information about female receptive status is shared between females as well as with males, while clitoral secretions containing a complex set of truncated MUPs and other proteins play a key role in female communication.

Introduction: Polycystic ovary syndrome (PCOS) is the most common infertility disorder worldwide, typically characterised by high circulating androgen levels, oligo- or anovulation, and polycystic ovarian morphology. Sexual dysfunction, including decreased sexual desire and increased sexual dissatisfaction, is also reported by women with PCOS. The origins of these sexual difficulties remain largely unidentified. To investigate potential biological origins of sexual dysfunction in PCOS patients, we asked whether the well-characterized, prenatally androgenized (PNA) mouse model of PCOS exhibits modified sex behaviours and whether central brain circuits associated with female sex behaviour are differentially regulated. As a male equivalent of PCOS is reported in the brothers of women with PCOS, we also investigated the impact of maternal androgen excess on the sex behaviour of male siblings., Methods: Adult male and female offspring of dams exposed to dihydrotestosterone (PNAM/PNAF) or an oil vehicle (VEH) from gestational days 16 to 18 were tested for a suite of sex-specific behaviours., Results: PNAM showed a reduction in their mounting capabilities, however, most of PNAM where able to reach ejaculation by the end of the test similar to the VEH control males. In contrast, PNAF exhibited a significant impairment in the female-typical sexual behaviour, lordosis. Interestingly, while neuronal activation was largely similar between PNAF and VEH females, impaired lordosis behaviour in PNAF was unexpectedly associated with decreased neuronal activation in the dorsomedial hypothalamic nucleus (DMH)., Conclusion: Taken together, these data link prenatal androgen exposure that drives a PCOS-like phenotype with altered sexual behaviours in both sexes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Donaldson, Prescott, Ruddenklau, Campbell and Desroziers.)

Background: Although there have been recent efforts to improve access to Canadian national parks, many remain not fully accessible to people with disabilities. Winter conditions, in particular, present challenges that limit their participation in outdoor activities., Objective: This study aimed to develop a novel method to assess park access during winter, which will inform recommendations for national park standards to meet the needs of all park visitors (regardless of ability) during winter conditions., Methods: A larger participatory mixed methods research project exploring park access was adapted. A 3-phase approach has already been proposed to achieve the study objectives. In the first phase, a scoping review of the existing accessibility standards will be conducted. In the second phase, objective audits of trails and features in 6 parks, 3 in western Canada and 3 in eastern Canada, will be conducted, as well as mobile interviews with 24 various participants in each region regarding their experiences of and recommendations for improving the park's accessibility. In the final phase, a Delphi participatory consensus development process will be used, based on the data gathered in the first 2 phases, to prioritize recommendations for standards. This paper will focus on the second phase of the study, specifically on whether the in-person winter mobile interviews (ie, walking and wheeling interviews) with people who have a wide range of disabilities while visiting 3 parks in 2 provinces were modified. Changes were made to accommodate the extreme winter weather conditions in Quebec while using safe and informative data collection methods., Results: In Quebec, one park, where winter conditions are safer, has been assessed in person (n=4). Web-based interviews were used to facilitate the assessment of other winter and summer conditions in two other parks (n=8). Winter and web-based interviews were completed in April 2022. Data are currently being collected and analyzed, and results will be completed by December 2022., Conclusions: We expect that adapting the protocol to gather further information on winter conditions and access to parks will provide high-quality and rich data to better inform park access standards. This participatory mixed methods research will inform the development of park standards that consider the accessibility needs of all people., International Registered Report Identifier (irrid): DERR1-10.2196/38715., (©Mike Prescott, Stéphanie Gamache, W Ben Mortenson, Krista L Best, Marie Grandisson, Mir Abolfazl Mostafavi, Delphine Labbé, Ernesto Morales, Atiya Mahmood, Jaimie Borisoff, Bonita Sawatzky, William C Miller, Laura Yvonne Bulk, Julie M Robillard, François Routhier. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 07.10.2022.)

Objective: We conducted an intersectional analysis to explore how demographic characteristics and mobility device use were associated with psychological distress (depression and anxiety) and confidence negotiating physical and social environments., Design: Cross-sectional data were collected using the Hospital Anxiety and Depression Scale, modified Wheelchair Use Confidence Scale, and self-reported functional independence scale., Participants: The sample included 105 participants. Primary mobility devices used included mobility scooters (27%), power wheelchairs (26%), manual wheelchairs (25%), walkers (11%), and cane or crutch (12%). The mean age of participants was 58 yrs, 53% were female, and 52% lived alone and were functionally independent with the use of assistive technology., Results: We were able to explain between 39% and 65% of the variance (adjusted R2) in the dependent variables with parsimonious regression models. Age was an independent predictor of all outcomes. Women were less confident negotiating the physical environment, and walker use was associated with depression and lower confidence negotiating physical environments, but increased confidence negotiating social environments., Conclusions: Age is associated with psychosocial outcomes for assistive device users, and those who use walkers may experience increased challenges with depression and negotiating the physical environment. Pending confirmatory research, the findings may have important implications for targeted interventions related to device provision., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lower limb exoskeletons are a recent intervention promoted to improve gait disorders. Available research has focused on clinical outcomes; however, little is known about therapists' experiences using the device in practice., Purpose: We explored the implementation of an exoskeleton at a tertiary rehabilitation center., Method: In this longitudinal qualitative study we conducted semi-structured interviews with 10 therapists. One group of therapists was formally trained using the device, whereas the other group only had clinical exposure to the device. The interviews were transcribed, coded, and analyzed for themes., Results: Three main themes emerged: (1) A steep learning curve described challenges in learning to use the exoskeleton. (2) One step at a time illustrated the complex process of incorporating the exoskeleton in daily work. (3) Not a magic bullet revealed the tensions using this emergent technology in practice., Conclusion: The exoskeleton represents one of the most complicated and labor-intensive interventions provided by therapists. Implementation requires substantial resources, raising questions regarding its efficacy and cost-effectiveness relative to other approaches. Until more evidence becomes available around the use and effectiveness of this rapidly evolving technology, therapists must contend with a high degree of uncertainty.IMPLICATIONS FOR REHABILITATIONUsing a lower limb exoskeleton may reduce physical demands on therapists in high-intensity rehabilitation programs that involve repetitive, effortful movements.However, a number of potential barriers to implementing the exoskeleton into practice need to be taken into consideration, including calibration time, intensive training required to become qualified to administer the intervention, the cost of the device, and comfort and safety of the device affecting user acceptance and uptake.Therapists also need to manage patient expectations related to outcomes related to use of exoskeletons.

Polycystic ovary syndrome (PCOS) is associated with androgen excess and, frequently, hyperactive pulsatile luteinizing hormone (LH) secretion. Although the origins of PCOS are unclear, evidence from pre-clinical models implicates androgen signalling in the brain in the development of PCOS pathophysiology. Chronic exposure of female mice to dihydrotestosterone (DHT) from 3 weeks of age drives both reproductive and metabolic impairments that are ameliorated by selective androgen receptor (AR) loss from the brain. This suggests centrally driven mechanisms in hyperandrogen-mediated PCOS-like pathophysiology that remain to be defined. Acute prenatal DHT exposure can also model the hyperandrogenism of PCOS, and this is accompanied by increased LH pulse frequency and increased GABAergic innervation of gonadotrophin-releasing hormone (GnRH) neurons. We aimed to determine the impact of chronic exposure of female mice to DHT, which models the hyperandrogenism of PCOS, on pulsatile LH secretion and putative GABAergic input to GnRH neurons. To do this, GnRH-green fluorescent protein (GFP) female mice received either DHT or blank capsules for 90 days from postnatal day 21 (n = 6 or 7 per group). Serial tail-tip blood sampling was used to measure LH dynamics and perfusion-fixed brains were collected and immunolabelled for vesicular GABA transporter (VGAT) to assess putative GABAergic terminals associated with GFP-labelled GnRH neurons. As expected, chronic DHT resulted in acyclicity and significantly increased body weight. However, no differences in LH pulse frequency or the density of VGAT appositions to GnRH neurons were identified between ovary-intact DHT-treated females and controls. Chronic DHT exposure significantly increased the number of AR expressing cells in the hypothalamus, whereas oestrogen receptor α-expressing neuron number was unchanged. Therefore, although chronic DHT exposure from 3 weeks of age increases AR expressing neurons in the brain, the GnRH neuronal network changes and hyperactive LH secretion associated with prenatal androgen excess are not evident. These findings suggest that unique central mechanisms are involved in the reproductive impairments driven by exposure to androgen excess at different developmental stages., (© 2022 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Background: Canada's national parks are world-renowned. However, despite recent attempts to improve access, many are not accessible to people with disabilities. With the advent of provincial and federal legislation, standards are being developed to assist with the design and management of parks., Objective: The overarching objective of this study is to inform accessibility standards for federal parks that meet the needs of all park visitors, regardless of ability. The specific objectives of this study are to identify park accessibility standards that exist internationally, identify the accessibility challenges that people with disabilities face in park environments, and prioritize and recommend accessibility standards for national parks., Methods: A 3-phase approach will be used to achieve the study objectives. In the first phase, a scoping review of the existing accessibility standards will be conducted. The second phase will include objective audits of trails and features in 6 parks, 3 in western Canada and 3 in eastern Canada, as well as mobile interviews with 24 diverse participants in each region regarding their experiences of and recommendations for improving the park's accessibility. In the final phase, a Delphi participatory consensus development process will be used, based on the data gathered in the first 2 phases, to prioritize recommendations for standards., Results: We expect to find gaps in existing standards that do not account for the diverse range of accessibility requirements that people with disabilities have for visiting parks. We also expect to find that existing standards, on their own, may not be enough to ensure equitable access to all the experiences and amenities that parks have to offer. Development of subsequent guidelines and best practices may be necessary to address complex scenarios for which standards may not be the best approach to ensuring accessibility., Conclusions: The participatory and mixed methods approaches used in this study will provide rich insights for developing accessible park standards that consider the diverse needs of people with disabilities. The findings will also support the development or enhancement of park standards at all levels of government., International Registered Report Identifier (irrid): DERR1-10.2196/33611., (©Mike Prescott, François Routhier, Delphine Labbé, Marie Grandisson, Atiya Mahmood, Ernesto Morales, Krista L Best, Mir Abolfazl Mostafavi, Jaimie Borisoff, Stéphanie Gamache, Bonita Sawatzky, William C Miller, Laura Yvonne Bulk, Julie M Robillard, Hailey-Thomas Jenkins, Kishore Seetharaman, W Ben Mortenson. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 31.03.2022.)

Prenatal exposure to excess androgens is associated with the development of polycystic ovary syndrome (PCOS). In prenatally androgenised (PNA) mice, a model of PCOS, progesterone receptor (PR) protein expression is reduced in arcuate nucleus (ARC) GABA neurons. This suggests a mechanism for PCOS-related impaired steroid hormone feedback and implicates androgen excess with respect to inducing transcriptional repression of the PR-encoding gene Pgr in the ARC. However, the androgen sensitivity of ARC neurons and the relative gene expression of PRs over development and following prenatal androgen exposure remain unknown. Here, we used a quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) of microdissected ARC to determine the relative androgen receptor (Ar) and progesterone receptor (Pgr) gene expression in PNA and control mice at five developmental timepoints. In a two-way analysis of variance, none of the genes examined showed expression changes with a statistically significant interaction between treatment and age, although PgrA showed a borderline interaction. For all genes, there was a statistically significant main effect of age on expression levels, reflecting a general increase in expression with increasing age, regardless of treatment. For PgrB and Ar, there was a statistically significant main effect of treatment, indicating a change in expression following PNA (increased for PgrB and decreased for Ar), regardless of age. For PgrA, there was a borderline main effect of treatment, suggesting a possible change in expression following PNA, regardless of age. PgrAB gene expression changes showed no significant main effect of treatment. We additionally examined androgen and progesterone responsiveness specifically in P60 ARC GABA neurons using RNAScope® (Advanced Cell Diagnostics, Inc.) in situ hybridization. This analysis revealed that Pgr and Ar were expressed in the majority of ARC GABA neurons in normal adult females. However, our RNAScope® analysis did not show significant changes in Pgr or Ar expression within ARC GABA neurons following PNA. Lastly, because GABA drive to gonadotropin-releasing hormone neurons is increased in PNA, we hypothesised that PNA mice would show increased expression of glutamic acid decarboxylase (GAD), the rate-limiting enzyme in GABA production. However, the RT-qPCR showed that the expression of GAD encoding genes (Gad1 and Gad2) was unchanged in adult PNA mice compared to controls. Our findings indicate that PNA treatment can impact Pgr and Ar mRNA expression in adulthood. This may reflect altered circulating steroid hormones in PNA mice or PNA-induced epigenetic changes in the regulation of Pgr and Ar gene expression in ARC neurons., (© 2021 British Society for Neuroendocrinology.)

Background: The majority of older people (> 65 years) in hospital have frailty and are at increased risk of readmission or death following discharge home. In the UK, following acute hospitalisation, around one third of older people with frailty are referred on for rehabilitation, termed 'intermediate care' services. Although this rehabilitation can reduce early readmission to hospital (< 30 days), recipients often do not feel ready to leave the service on discharge, suggesting possible incomplete recovery. Limited evidence suggests extended rehabilitation is of benefit in several conditions and there is preliminary evidence that progressive physical exercise can improve mobility and function for older people with frailty, and slow progression to disability. Our aim is to evaluate the effectiveness of the Home-based Older People's Exercise (HOPE) programme as extended rehabilitation for older people with frailty discharged home from hospital or intermediate care services after acute illness or injury., Methods: A multi-centre individually randomised controlled trial, to evaluate the clinical and cost-effectiveness of the HOPE programme. This individualised, graded and progressive 24-week exercise programme is delivered by NHS physiotherapy teams to people aged 65 and older with frailty, identified using the Clinical Frailty Scale, following discharge from acute hospitalisation and linked intermediate care rehabilitation pathways. The primary outcome is physical health-related quality of life, measured using the physical component summary score of the modified Short Form 36- item health questionnaire (SF36) at 12 months. Secondary outcomes include self-reported physical and mental health, functional independence, death, hospitalisations, care home admissions. Plans include health economic analyses and an embedded process evaluation., Discussion: This trial seeks to determine if extended rehabilitation, via the HOPE programme, can improve physical health-related quality of life for older people with frailty following acute hospitalisation. Results will improve awareness of the rehabilitation needs of older people with frailty, and provide evidence on the clinical and cost-effectiveness of the targeted exercise intervention. There is potential for considerable benefit for health and social care services through widespread implementation of trial findings if clinical and cost-effectiveness is demonstrated., Trial Registration: ISRCTN 13927531 . Registered on April 19, 2017., (© 2021. The Author(s).)