Development of a model for integrated care at the end of life in advanced dementia: A whole systems UK-wide approach

yesBackground: The prevalence of dementia is rising worldwide and many people will die with the disease. Symptoms towards the end of life may be inadequately managed and informal and professional carers poorly supported. There are few evidence-based interventions to improve end-of-life care in advanced dementia. Aim: To develop an integrated, whole systems, evidence-based intervention that is pragmatic and feasible to improve end-of-life care for people with advanced dementia and support those close to them. Design: A realist-based approach in which qualitative and quantitative data assisted the development of statements. These were incorporated into the RAND/UCLA appropriateness method to achieve consensus on intervention components. Components were mapped to underlying theory of whole systems change and the intervention described in a detailed manual. Setting/participants: Data were collected from people with dementia, carers and health and social care professionals in England, from expert opinion and existing literature. Professional stakeholders in all four countries of the United Kingdom contributed to the RAND/UCLA appropriateness method process. Results: A total of 29 statements were agreed and mapped to individual, group, organisational and economic/political levels of healthcare systems. The resulting main intervention components are as follows: (1) influencing local service organisation through facilitation of integrated multi-disciplinary care, (2) providing training and support for formal and informal carers and (3) influencing local healthcare commissioning and priorities of service providers. Conclusion: Use of in-depth data, consensus methods and theoretical understanding of the intervention components produced an evidence-based intervention for further testing in end-of-life care in advanced dementia

Pharmacological characterization of recombinant human neuronal nicotinic acetylcholine receptors

ABSTRACT Human neuronal nicotinic acetylcholine receptors (nAChRs) h␣2␤2, h␣2␤4, h␣3␤2, h␣3␤4, h␣4␤2, h␣4␤4 and h␣7 were expressed in Xenopus oocytes and tested for their sensitivities to the nicotinic agonists acetylcholine (ACh), nicotine, cytisine (CYT) and 1,1-dimethyl-4-phenylpiperazinium (DMPP) and the nAChR. antagonists mecamylamine (MEC), d-tubocurarine and dihydro-␤-erythroidine. CYT was the least efficacious agonist at hnAChRs containing ␤2 subunits, but it displayed significant activity at h␣2␤4, h␣3␤4, h␣4␤4 and h␣7 nAChRs. ACh was one of the most efficacious agonists at all hnAChRs, except at h␣3␤2, where DMPP was markedly more efficacious than ACh. ACh was among the least potent agonists at all hnAChRs. The rank order of potency displayed by h␣3␤2 and h␣3␤4 nAChRs (DMPPϷCYTϷnicotineϾACh and DMPP Ͼ CYTϷnicotineϾACh, respectively), differs from that reported for their rat homolog

Fueling the female athlete: auditing her representation in studies of acute carbohydrate intake for exercise

Purpose The aim of this audit was to assess the representation of female athletes within the literature that has led to current guidelines for carbohydrate (CHO) intake in the acute periods surrounding exercise and the quality of this research. Methods We conducted a standardized audit of research assessing CHO loading protocols, CHO mouth rinse, and CHO intake before, during, and after exercise. Results A total of 937 studies were identified in this audit. There were a total of 11,202 participants across these studies, with only 11% being women. Most studies involved male-only cohorts (79%), with a mere 38 studies (4%) involving female-only cohorts and 14 studies (2%) including a methodological design for comparison of sex-based responses. The frequent use of incorrect terminology surrounding menstrual status and the failure of most studies (69%) to provide sufficient information on the menstrual status of participants suggests incomplete understanding and concern for female-specific considerations among researchers. Of the 197 studies that included women, only 13 (7%) provided evidence of acceptable methodological control of ovarian hormones, and no study met all best-practice recommendations. Of these 13 studies, only half also provided sufficient information regarding the athletic caliber of participants. The topics that received such scrutiny were CHO loading protocols and CHO intake during exercise. Conclusions The literature that underpins the current guidelines for CHO intake in the acute periods around exercise is lacking in high-quality research that can contribute knowledge specific to the female athlete and sex-based differences. New research that considers ovarian hormones and sex-based differences is needed to ensure that the recommendations for acute CHO fueling provided to female athletes are evidence based

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Female athlete health domains:A supplement to the International Olympic Committee consensus statement on methods for recording and reporting epidemiological data on injury and illness in sport

The IOC made recommendations for recording and reporting epidemiological data on injuries and illness in sports in 2020, but with little, if any, focus on female athletes. Therefore, the aims of this supplement to the IOC consensus statement are to (i) propose a taxonomy for categorisation of female athlete health problems across the lifespan; (ii) make recommendations for data capture to inform consistent recording and reporting of symptoms, injuries, illnesses and other health outcomes in sports injury epidemiology and (iii) make recommendations for specifications when applying the Strengthening the Reporting of Observational Studies in Epidemiology-Sport Injury and Illness Surveillance (STROBE-SIIS) to female athlete health data. In May 2021, five researchers and clinicians with expertise in sports medicine, epidemiology and female athlete health convened to form a consensus working group, which identified key themes. Twenty additional experts were invited and an iterative process involving all authors was then used to extend the IOC consensus statement, to include issues which affect female athletes. Ten domains of female health for categorising health problems according to biological, life stage or environmental factors that affect females in sport were identified: menstrual and gynaecological health; preconception and assisted reproduction; pregnancy; postpartum; menopause; breast health; pelvic floor health; breast feeding, parenting and caregiving; mental health and sport environments. This paper extends the IOC consensus statement to include 10 domains of female health, which may affect female athletes across the lifespan, from adolescence through young adulthood, to mid-age and older age. Our recommendations for data capture relating to female athlete population characteristics, and injuries, illnesses and other health consequences, will improve the quality of epidemiological studies, to inform better injury and illness prevention strategies

Wolves in the Wolds: Late Capitalism, the English Eerie, and the Wyrd Case of ‘Old Stinker’ the Hull Werewolf

In this article, I depart from the earlier opinions of Emily Gerard, Sabine Baring-Gould, and others, who explained the disappearance of the werewolf in folklore as following the extinction of the wolf. I argue instead that British literature is distinctive in representing a history of werewolf sightings in places in Britain where there were once wolves. I draw on the idea of absence, manifestations of the English eerie, and the turbulence of England in the era of late capitalism to illuminate my analysis of the representation of contemporary werewolf sightingsPeer reviewe

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease