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COMMA recommends that the PROMIS-Sexual Function and Satisfaction: Vaginal Discomfort with sexual activity be used to measure “pain with sex,” the Day-to-Day Impact of Vaginal Aging Questionnaire to measure “distress, bother or interference of genitourinary symptoms” and that all trials should report adverse events in study participants, which is a requirement of Good Clinical Practice.

The COMMA (Core Outcomes in Menopause) recommends that the Hot Flash Related Daily Interference Scale be used to measure distress, bother, or interference of vasomotor symptoms and to capture impact on sleep. Additionally, all trials should report adverse events in study participants, which is a requirement of Good Clinical Practice.

New tick species are appearing in the UK, which can transmit diseases to animals and humans. These new species pose a greater threat because they can carry and transmit diseases that were previously uncommon or absent in the UK. Factors such as climate change, increased international animal movements, and changes in land use contribute to the increasing geographical range of these ticks. The Hyalomma tick, usually found in Mediterranean and Balkan countries, Africa, India, Iran, and Pakistan, is particularly notable among the emerging tick species in the UK. These ticks can spread a variety of diseases, including equine diseases and a serious viral disease called Crimean-Congo haemorrhagic fever (CCHF) that can infect humans. The risk of new tick species establishing themselves in the UK depends on factors such as the environment, the availability of animal species to feed on, and the effectiveness of disease spread. Ongoing monitoring is crucial as tick distribution in the UK is shifting, and tick numbers are increasing. The Tick Surveillance Scheme (TSS) collects data on tick species found on horses in the UK, and awareness of the risks of equine piroplasmosis and Hyalomma ticks is necessary. While new tick species may not be able to overwinter and become fully established in the UK at present, the situation must be continuously reviewed. The Department for Environment, Food and Rural Affairs (Defra) collaborates with equine industry stakeholders to prevent equine diseases and promote high welfare standards. Equine [Extracted from the article]

Purpose: This study aims to examine the association between mandatory corporate social responsibility (CSR) regulations (CSR mandate) and social disclosures (SOCDS) in India. It also investigates whether CSR committees mediate the relationship between CSR mandate and SOCDS. Furthermore, this paper explores how business group (BG) affiliation moderates CSR committee quality and SOCDS. Design/methodology/approach: This study uses a data set of 5,345 observations from the Bombay stock exchange (BSE)-listed firms over 10 years (2011–2020) to examine the research questions. Baron and Kenny’s (1986) three-step model is estimated to examine the mediating role of CSR committees on the relationship between CSR mandate and SOCDS. Findings: The study reveals that the CSR mandate positively impacts SOCDS in India due to coercive pressures. CSR committees mediate this relationship, with higher CSR committee quality leading to increased SOCDS. Furthermore, the authors report that SOCDS in India is positively related to CSR committee quality, and this relationship is stronger for BG firms. Finally, the supplementary analysis reveals that promoting CSR committee quality enhances firms’ likelihood of meeting CSR mandatory spending and actual CSR spending in India. Originality/value: This research contributes to the academic literature by shedding light on the intricate dynamics of CSR mandates, CSR committees and SOCDS in emerging economies. Notably, the authors identify the previously unexplored mediation role of CSR committees in the link between CSR mandates and SOCDS. The creation of a composite index that measures complementary CSR committee attributes allows us to undertake a novel assessment of CSR committee quality. An examination of the moderating influence of BG affiliation documents the importance of CSR committee quality, particularly in governance, for enhancing SOCDS transparency within BG firms.

ObjectiveTo systematically review the literature describing children and young people (CYP) admissions to paediatric general wards because of primary mental health (MH) reasons, particularly in MH crisis.DesignPubMed, Embase, PsycINFO, Web of Science and Google Scholar were searched, with no restriction on country or language. We addressed five search questions to inform: trends and/or the number of admissions, the risk factors for adverse care, the experiences of CYP, families/carers and healthcare professionals (HCPs) and the evidence of interventions aimed at improving the care during admissions.Two reviewers independently assessed the relevance of abstracts identified, extracted data and undertook quality assessment. This review was registered with PROSPERO (CRD42022350655).ResultsThirty-two studies met the inclusion criteria. Eighteen addressed trends and/or numbers/proportions of admissions, 12 provided data about the views/experiences of HCPs, two provided data about CYP’s experiences and four explored improving care. We were unable to identify studies examining risk factors for harm during admissions, but studies did report the length of stay in general paediatric/adult settings while waiting for specialised care, which could be considered a risk factor while caring for this group.ConclusionsMH admissions to children’s wards are a long-standing issue and are increasing. CYP will continue to need to be admitted in crisis, with paediatric wards a common location while waiting for assessment. For services to be delivered effectively and for CYP and their families/carers to feel supported and HCPs to feel confident, we need to facilitate more integrated physical and MH pathways of care.PROSPERO registration numberCRD42022350655.

The article in Horse & Hound features letters from readers expressing their opinions on various aspects of the equestrian world. One reader discusses the importance of published timetables in eventing for amateur riders, highlighting the challenges they face in scheduling their activities. Another reader expresses concern over the treatment of horses at auctions, emphasizing the need for compassion towards all animals. Additionally, a heartfelt tribute is paid to a friend who recently passed away, reminiscing about their shared love for riding and the countryside. The article also includes a touching message from an elderly relative remembering the achievements of their nephew in the equestrian world. [Extracted from the article]

AimsFOCUS4 was a phase II/III umbrella trial, recruiting patients with advanced or metastatic colorectal cancer, between 2014 and 2020. Molecular profiling of patients’ formalin-fixed, paraffin-embedded tumour blocks was undertaken at two centralised biomarker laboratories (Leeds and Cardiff), and the results fed directly to the Medical Research Council Clinical Trials Unit, and used for subsequent randomisation. Here the laboratories discuss their experiences.MethodsFollowing successful tumour content assessment, blocks were sectioned for DNA extraction and immunohistochemistry (IHC). Pyrosequencing was initially used to determine tumour mutation status (KRAS, NRAS, BRAF and PIK3CA), then from 2018 onwards, next-generation sequencing was employed to allow the inclusion of TP53. Protein expression of MLH1, MSH2, MSH6, PMS2 and pTEN was determined by IHC. An interlaboratory comparison programme was initiated, allowing sample exchanges, to ensure continued assay robustness.Results1291 tumour samples were successfully analysed. Assay failure rates were very low; 1.9%–3.3% for DNA sequencing and 0.9%–1.3% for IHC. Concordance rates of >98% were seen for the interlaboratory comparisons, where a result was obtained by both laboratories.ConclusionsPractical and logistical problems were identified, including poor sample quality and difficulties with sample anonymisation. The often last-minute receipt of a sample for testing and a lack of integration with National Health Service mutation analysis services were challenging. The laboratories benefitted from both pretrial validations and interlaboratory comparisons, resulting in robust assay development and provided confidence during the implementation of new sequencing technologies. We conclude that our centralised approach to biomarker testing in FOCUS4 was effective and successful.

The directly dated RRMarch2021age model (Roberts et al., 2021) for the ∼293 m long composite core from Chew Bahir, southern Ethiopia, has provided a valuable chronology for long-term climate changes in northeastern Africa. However, the age model has limitations on shorter time scales (less than 1–2 precession cycles), especially in the time range <20 kyr BP (kiloyears before present or thousand years before 1950) and between ∼155 and 428 kyr BP. To address those constraints we developed a partially orbitally tuned age model. A comparison with the ODP Site 967 record of the wetness index from the eastern Mediterranean, 3300 km away but connected to the Ethiopian plateau via the River Nile, suggests that the partially orbitally tuned age model offers some advantages compared to the exclusively directly dated age model, with the limitation of the reduced significance of (cross) spectral analysis results of tuned age models in cause-effect studies. The availability of this more detailed age model is a prerequisite for further detailed spatiotemporal correlations of climate variability and its potential impact on the exchange of different populations of Homo sapiensin the region.

Despite more than half a century of hominin fossil discoveries in eastern Africa, the regional environmental context of hominin evolution and dispersal is not well established due to the lack of continuous palaeoenvironmental records from one of the proven habitats of early human populations, particularly for the Pleistocene epoch. Here we present a 620,000-year environmental record from Chew Bahir, southern Ethiopia, which is proximal to key fossil sites. Our record documents the potential influence of different episodes of climatic variability on hominin biological and cultural transformation. The appearance of high anatomical diversity in hominin groups coincides with long-lasting and relatively stable humid conditions from ~620,000 to 275,000 years bp(episodes 1–6), interrupted by several abrupt and extreme hydroclimate perturbations. A pattern of pronounced climatic cyclicity transformed habitats during episodes 7–9 (~275,000–60,000 years bp), a crucial phase encompassing the gradual transition from Acheulean to Middle Stone Age technologies, the emergence of Homo sapiensin eastern Africa and key human social and cultural innovations. Those accumulative innovations plus the alignment of humid pulses between northeastern Africa and the eastern Mediterranean during high-frequency climate oscillations of episodes 10–12 (~60,000–10,000 years bp) could have facilitated the global dispersal of H. sapiens.

This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. Placebo‐controlled, parallel group, double‐blind, randomized two‐by‐two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category‐specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between‐group difference in the short physical performance battery (SPPB) score over 12‐month follow‐up by repeated‐measures mixed models. Results were combined with existing systematic reviews using random‐effects meta‐analysis to derive summary estimates of treatment efficacy. We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n= 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n= 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P< 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect −0.1 points (95%CI −1.2 to 1.0), P= 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect −0.4 kg (95%CI −1.1 to 0.3), P= 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n= 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n= 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P= 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI −1.0 to 1.1), P= 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect −0.3 kg (95%CI −1.0 to 0.4), P= 0.47]. Meta‐analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between‐group difference −0.1 points (95%CI −0.4 to 0.2)]. Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta‐analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.

Abstract Objectives To identify which type of smoke alarm is most likely to remain working in local authority inner city housing, and to identify an alarm tolerated in households with [...]

Most women who use injectable contraceptives such as Norplant will not lose bone after menopause compared to women who do not use injectable contraceptives, according to a study of 31 women. Hormone replacement therapy can increase bone density in women who have used injectable contraceptives.

Objective: It has been suggested that the primary focus of the pathological process in schizophrenia is on the limbic system, and there have been several postmortem reports of changes in the histological structure or volume of the hippocampus, as well as a larger number of MRI reports of volume reductions. There are conflicting findings, however, with both techniques. Method: The authors conducted a study of the gross and subfield structure and cellular composition of the hippocampus in postmortem brains from 30 patients with DSM-IV-diagnosed schizophrenia (13 women, 17 men) and 29 comparison subjects with no psychopathology (14 women, 15 men). Stereological sampling procedures were applied to 25-[micro]m-thick coronal paraffin sections taken at 5-mm intervals throughout the formalin-fixed hippocampus. Subfields were defined as the dentate fascia, the hilus (CA4), an amalgamation of the CA2 and CA3 subfields, the CA1 subfield, and the subiculum. Volumes, cell densities, and cell numbers of the subfields were assessed microscopically, and the volume of the hippocampus was estimated from both photographs and histological slides of the coronal slices. Results: As assessed from histologically stained slides, the volumes of the hippocampus and its subfields did not differ between patients and comparison subjects. Left-sided reduction in hippocampal volumes estimated from photographs, which may have included parahippocampal tissue, was not confirmed on histological examination. No significant differences were observed between patients and comparison subjects in the cellular composition of the hippocampus. Conclusions: These findings do not support a primary alteration of the hippocampus in schizophrenia.

Purpose: This paper aims to examine the relationship between board gender diversity and private firm performance. Design/methodology/approach: The authors test the association between board gender diversity and private firm performance by estimating pooled multivariate regressions using an unbalanced panel data set of 115,253 firm-year observations. Findings: The authors find that younger, less busy and local women directors enhance private firm performance. Firms with 40% or more women directors report triple the economic benefits compared to boards with at least 20% women directors. Considering firm size, women directors significantly increase small firm profitability, and the effect is more pronounced for high-risk firms. Greater board gender diversity enhances small firm performance as the monitoring role of women directors benefits the firm even in the presence of busy men directors. Consistent with the agency theory framework, the authors find that women directors improve small firm profitability in the presence of agency costs. Research limitations/implications: Due to the lack of availability of data about private firms, many factors are not directly observable. The analysis uses accounting-based performance measures that may be subject to managerial discretion. Nevertheless, the authors report highly significant results using cash-based performance measures that substantiate the overall findings. Practical implications: The results of the present study point to the need for private firms to increase board gender diversity and consider women director busyness, age, nationality and firm size when making board director appointments. Originality/value: This study adds to the scarce existent literature investigating private firms. The results contribute to the understanding of gender-diverse boards as well as the attributes of women directors that enhance private firm performance.

Sarcopenia is the age‐related loss of muscle mass, strength, and function. Epigenetic processes such as DNA methylation, which integrate both genetic and environmental exposures, have been suggested to contribute to the development of sarcopenia. This study aimed to determine whether differences in the muscle methylome are associated with sarcopenia and its component measures: grip strength, appendicular lean mass index (ALMi), and gait speed. Using the Infinium Human MethylationEPIC BeadChip, we measured DNA methylation in vastus lateralismuscle biopsies of 83 male participants (12 with sarcopenia) with a mean (standard deviation) age of 75.7 (3.6) years from the Hertfordshire Sarcopenia Study (HSS) and Hertfordshire Sarcopenia Study extension (HSSe) and examined associations with sarcopenia and its components. Pathway, histone mark, and transcription factor enrichment of the differentially methylated CpGs (dmCpGs) were determined, and sodium bisulfite pyrosequencing was used to validate the sarcopenia‐associated dmCpGs. Human primary myoblasts (n= 6) isolated from vastus lateralismuscle biopsies from male individuals from HSSe were treated with the EZH2 inhibitor GSK343 to assess how perturbations in epigenetic processes may impact myoblast differentiation and fusion, measured by PAX7 and MYHC immunocytochemistry, and mitochondrial bioenergetics determined using the Seahorse XF96. Sarcopenia was associated with differential methylation at 176 dmCpGs (false discovery rate ≤ 0.05) and 141 differentially methylated regions (Stouffer ≤ 0.05). The sarcopenia‐associated dmCpGs were enriched in genes associated with myotube fusion (P= 1.40E‐03), oxidative phosphorylation (P= 2.78E‐02), and voltage‐gated calcium channels (P= 1.59E‐04). ALMi was associated with 71 dmCpGs, grip strength with 49 dmCpGs, and gait speed with 23 dmCpGs (false discovery rate ≤ 0.05). There was significant overlap between the dmCpGs associated with sarcopenia and ALMi (P= 3.4E‐35), sarcopenia and gait speed (P= 4.78E‐03), and sarcopenia and grip strength (P= 7.55E‐06). There was also an over‐representation of the sarcopenia, ALMi, grip strength, and gait speed‐associated dmCpGs with sites of H3K27 trimethylation (all P≤ 0.05) and amongst EZH2 target genes (all P≤ 0.05). Furthermore, treatment of human primary myoblasts with the EZH2 inhibitor GSK343 inhibitor led to an increase in PAX7 expression (P≤ 0.05), decreased myotube fusion (P= 0.043), and an increase in ATP production (P= 0.008), with alterations in the DNA methylation of genes involved in oxidative phosphorylation and myogenesis. These findings show that differences in the muscle methylome are associated with sarcopenia and individual measures of muscle mass, strength, and function in older individuals. This suggests that changes in the epigenetic regulation of genes may contribute to impaired muscle function in later life.

The Australian High Court ruled in Hill v. Van Erp that solicitors can be held liable to third parties for negligently executing a will. Although solicitors owe a duty foremost to their clients, the court recognized that with wills solicitors are also responsible for transferring property as the client wishes. The beneficiary in Hill had a reasonable expectation of receiving from the estate and the court agreed she should be compensated.

In the early 1940s, on the publication of Richard Titmuss's Birth, poverty and wealth,[1] newspapers reported 'Poor folks' babies stand less chance' and 'Babies beware of poor parents.' Titmuss's work [...]

Objectives - To study the resuscitation preferences, choice of decision-maker, views on the seeking of patients' wishes and determinants of these of elderly hospital in-patients. Design - Questionnaire administered on admission and prior to discharge. Setting - Two acute geriatric medicine units (Southampton and Poole). Participants - Two hundred and fourteen consecutive consenting mentally competent patients admitted to hospital as emergencies. Results - Resuscitation was wanted by 60%, particularly married and functionally independent patients and those who had not already considered it. Not wanting resuscitation was associated with lack of social contacts. Sixty-seven per cent welcomed enquiry about their preferences and 78% wanted participation in decisions, 43% as sole decision-maker. Wishing to choose oneself was associated with not wanting resuscitation, prior knowledge of it, and lack of a spouse. Patients' opinions remained stable during their admission. Conclusions - Discussion of resuscitation is practical on hospital admission without causing distress and the views expressed endure through the period of hospitalisation. Elderly patients' attitudes depend partly on personal health and social circumstances. This may assist doctors when patients are unable to participate themselves.

The reasons for acute hospital admissions among people with Parkinson’s disease are well documented. However, understanding of crises that are managed in the community is comparatively lacking. Most existing literature on the causes of crisis for people with Parkinson’s disease (PwP) uses hospital data and excludes the individual’s own perspective on the crisis trigger and the impact of the crisis on their care needs. To identify the causes and impact of crises in both community and hospital settings, from a patient and carer perspective. A total of 550 UK-based PwP and carers completed a survey on (a) their own personal experiences of crisis, and (b) their general awareness of potential crisis triggers for PwP. In addition to well-recognised causes of crisis such as falls, events less widely associated with crisis were identified, including difficulties with activities of daily living and carer absence. The less-recognised crisis triggers tended to be managed more frequently in the community. Many of these community-based crises had a greater impact on care needs than the better-known causes of crisis that more frequently required hospital care. PwP and carer responses indicated a good general knowledge of potential crisis triggers. PwP were more aware of mental health issues and carers were more aware of cognitive impairment and issues with medications. These findings could improve care of Parkinson’s by increasing understanding of crisis events from the patient and carer perspective, identifying under-recognised crisis triggers, and informing strategies for best recording symptoms from PwP and carers.

High treatment burden is associated with poor adherence, wasted resources, poor quality of life and poor health outcomes. Identifying factors that impact treatment burden in Parkinson’s disease can offer insights into strategies to mitigate them. To explore the experiences of treatment burden among people with Parkinson’s disease (PwP) and their caregivers. A systematic review of studies published from year 2006 was conducted. Qualitative and mixed-method studies with a qualitative component that relate to usual care in Parkinson’s disease were included. Quantitative studies and grey literature were excluded. Data synthesis was conducted using framework synthesis. 1757 articles were screened, and 39 articles included. Understanding treatment burden in PwP and caregivers was not the primary aim in any of the included studies. The main issues of treatment burden in Parkinson’s disease are: 1) work and challenges of taking medication; 2) healthcare provider obstacles including lack of patient-centered care, poor patient-provider relationships, lack of care coordination, inflexible organizational structures, lack of access to services and issues in care home or hospital settings; and 3) learning about health and challenges with information provision. The treatment burden led to physical and mental exhaustion of self-care and limitations on the role and social activities of PwP and caregivers. There are potential strategies to improve the treatment burden in Parkinson’s disease at an individual level such as patient-centered approach to care, and at system level by improving access and care coordination between services. Future research is needed to determine the modifiable factors of treatment burden in Parkinson’s disease.

Introduction Postmenopausal oestrogen deficiency is a major cause of bone loss in older women. A reduction in bone density also accompanies oestrogen deficiency from other causes in younger women. This [...]

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