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Sessions of Acupuncture and Nutritional Therapy Evaluation for Atrial Fibrillation (Santé-AF): a feasibility study

Atrial fibrillation (AF) is the most common arrhythmia globally, associated with increased risk of stroke, debilitating symptoms and a decrease in health-related quality of life (HRQoL). Current treatments for AF may not provide symptomatic relief, and are associated with risks and adverse responses that may decrease HRQoL. A systematic review was conducted, revealing a small amount of low-quality evidence demonstrating positive effects of complementary therapies for symptoms and HRQoL in AF. This suggests that a large-scale trial would be justified to investigate whether complementary therapies may improve symptoms and/or HRQoL in AF. To decrease the uncertainty associated with a future trial, a feasibility study was carried out. Thirty participants were recruited to a three-arm parallel-group pragmatic randomised controlled trial of acupuncture and nutritional therapy compared with usual care. Seven feasibility objectives (comprising a total 10 domains) were investigated quantitatively and qualitatively, including participants’ willingness to take part, appropriateness of eligibility criteria, participant retention, and acceptability of interventions and study assessments. Additional parameters were investigated relating to practitioners, and the effect of the COVID-19 pandemic. The study used a convergent mixed methods design to understand not only whether, but why, objectives and domains were (in)feasible. A future large-scale trial was found to be feasible. Of the 10 feasibility domains, six were feasible without modification, one required process-related modifications to achieve feasibility, and one was re-analysed to correct participant error, thus achieving feasibility. Two domains were abandoned as inappropriate/unviable but did not affect feasibility. Recommendations made to improve feasibility across all domains included changes in eligibility criteria to reflect real-world populations, and changes in study assessments to attenuate participant burden. The study also proposed an extension to pragmatic trials methodology – the inclusion of nested case studies/series – to give a fuller representation of the effects of complementary therapies

How did the guppy Y chromosome evolve?

The sex chromosome pairs of many species do not undergo genetic recombination, unlike the autosomes. It has been proposed that the suppressed recombination results from natural selection favouring close linkage between sex-determining genes and mutations on this chromosome with advantages in one sex, but disadvantages in the other (these are called sexually antagonistic mutations). No example of such selection leading to suppressed recombination has been described, but populations of the guppy display sexually antagonistic mutations (affecting male coloration), and would be expected to evolve suppressed recombination. In extant close relatives of the guppy, the Y chromosomes have suppressed recombination, and have lost all the genes present on the X (this is called genetic degeneration). However, the guppy Y occasionally recombines with its X, despite carrying sexually antagonistic mutations. We describe evidence that a new Y evolved recently in the guppy, from an X chromosome like that in these relatives, replacing the old, degenerated Y, and explaining why the guppy pair still recombine. The male coloration factors probably arose after the new Y evolved, and have already evolved expression that is confined to males, a different way to avoid the conflict between the sexes

Has recombination changed during the recent evolution of the guppy Y chromosome?

Genome sequencing and genetic mapping of molecular markers have demonstrated nearly complete Y-linkage across much of the guppy (Poecilia reticulata) XY chromosome pair. Predominant Y-linkage of factors controlling visible male-specific coloration traits also suggested that these polymorphisms are sexually antagonistic (SA). However, occasional exchanges with the X are detected, and recombination patterns also appear to differ between natural guppy populations, suggesting ongoing evolution of recombination suppression under selection created by partially sex-linked SA polymorphisms. We used molecular markers to directly estimate genetic maps in sires from four guppy populations. The maps are very similar, suggesting that their crossover patterns have not recently changed. Our maps are consistent with population genomic results showing that variants within the terminal 5 Mb of the 26.5 Mb sex chromosome, chromosome 12, are most clearly associated with the maleness factor, albeit incompletely. We also confirmed occasional crossovers proximal to the male-determining region, defining a second, rarely recombining, pseudo-autosomal region, PAR2. This fish species may therefore have no completely male-specific region (MSY) more extensive than the male-determining factor. The positions of the few crossover events suggest a location for the male-determining factor within a physically small repetitive region. A sex-reversed XX male had few crossovers in PAR2, suggesting that this region’s low crossover rate depends on the phenotypic, not the genetic, sex. Thus, rare individuals whose phenotypic and genetic sexes differ, and/or occasional PAR2 crossovers in males can explain the failure to detect fully Y-linked variants

Developmental appropriateness of kindergarten programs and academic outcomes in first grade

This study explored the relationship between the developmental appropriateness of kindergarten classroom instruction and first-grade report card grade overall averages and averages in reading, language, spelling, math, science, and social studies. The interactive roles that gender, SES, and kindergarten classroom type play in children’s later achievement were also examined. The sample consisted of166first-grade children who hadattended kindergarten classrooms with teaching practices identified as predominately developmentally appropriate or developmentally inappropriate. Findings indicated that firstgraders from more appropriate kindergarten classrooms had higher reading averages than children from less appropriate kindergarten classrooms. Females had higher overall and subject area averages than males. Significant interaction effects indicated that high SES children from less appropriate kindergarten classrooms hadhigheroverall averages and higher averages in all subjects except reading, when compared with low SES children from less appropriate classrooms. Low SES children from more appropriate kindergarten classrooms had higher overall averages and higher averages in all subjects except reading when comparedwith low SES children from less appropriate kindergarten classrooms. No significant differences were found between high and low SES children from more appropriate kindergarten classrooms. © 1993 Taylor & Francis Group, LLC

Analysis of Nkx3.1:Cre-driven Erk5 deletion reveals a profound spinal deformity which is linked to increased osteoclast activity

Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcinogenesis. Nkx3.1-mediated Cre expression is a useful strategy to genetically manipulate the mouse prostate. While grossly normal at birth, we observed an unexpected phenotype of spinal protrusion in Nkx3.1:Cre;Erk5fl/fl (Erk5fl/fl) mice by ~6–8 weeks of age. X-ray, histological and micro CT (µCT) analyses showed that 100% of male and female Erk5fl/fl mice had a severely deformed curved thoracic spine, with an associated loss of trabecular bone volume. Although sex-specific differences were observed, histomorphometry measurements revealed that both bone resorption and bone formation parameters were increased in male Erk5fl/fl mice compared to wild type (WT) littermates. Osteopenia occurs where the rate of bone resorption exceeds that of bone formation, so we investigated the role of the osteoclast compartment. We found that treatment of RANKL-stimulated primary bone marrow-derived macrophage (BMDM) cultures with small molecule ERK5 pathway inhibitors increased osteoclast numbers. Furthermore, osteoclast numbers and expression of osteoclast marker genes were increased in parallel with reduced Erk5 expression in cultures generated from Erk5fl/fl mice compared to WT mice. Collectively, these results reveal a novel role for Erk5 during bone maturation and homeostasis in vivo

Feminist Scholarship on International Law in the 1990s and today: An Inter-Generational Conversation

The world of international relations and law is constantly changing. There is a risk of the systematic undermining of international organisations and law over the next years. Feminist approaches to international law will need to adapt accordingly, to ensure that they continue to challenge inequalities, and serve as an important and critical voice in international law. This article seeks to tell the story of feminist perspectives on international law from the early 1990s till today through a discussion between three generations of feminist international legal scholars: Hilary Charlesworth, who, with her colleagues, contributed to the area in the immediate post-Cold War years, Gina Heathcote, who over the past decade has published extensively on feminist perspectives on the use of force and collective security, and Emily Jones, an early career scholar working on feminist approaches to international law. The conversation, which began as a Skype discussion, considers both the ways in which feminist approaches to international law have changed over the past two decades, as well as the ways in which they have been shaped by global politics, before turning to consider the future for feminist approaches to international law. The impact of feminist approaches to international law has been considerable. However, it seems that feminist approaches still lack legitimacy and credibility in many mainstream circles, remaining on the disciplinary periphery. Charlesworth, Heathcote and Jones discuss potential ways in which to manage some of these tensions, noting both the importance of ‘speaking to ourselves’ (Charlesworth in Feminist perspectives on contemporary International Law: Between resistance and compliance? Hart, Oxford, pp. 17–32, 2011) as a creative and nurturing space, as well as the need to be seen as a more credible voice in the mainstream. They note the need, too, for further feminist work beyond the realms of sexual violence and women’s representation. While the great amount of work in this area is, indeed, foundational, having achieved many important legal and political outcomes, feminist approaches should now develop beyond these areas. Doing so will not only propel this area of scholarship in new and exciting directions, but it might help feminist scholarship gain further traction by avoiding categorisation only under the umbrella of “women’s issues” and thus ready dismissal as just another specialist area of international law in the era of fragmentation

The changing health needs of the UK population

The demographics of the UK population are changing and so is the need for health care. In this Health Policy, we explore the current health of the population, the changing health needs, and future threats to health. Relative to other high-income countries, the UK is lagging on many health outcomes, such as life expectancy and infant mortality, and there is a growing burden of mental illness. Successes exist, such as the striking improvements in oral health, but inequalities in health persist as well. The growth of the ageing population relative to the working-age population, the rise of multimorbidity, and persistent health inequalities, particularly for preventable illness, are all issues that the National Health Service (NHS) will face in the years to come. Meeting the challenges of the future will require an increased focus on health promotion and disease prevention, involving a more concerted effort to understand and tackle the multiple social, environmental, and economic factors that lie at the heart of health inequalities. The immediate priority of the NHS will be to mitigate the wider and long-term health consequences of the COVID-19 pandemic, but it must also strengthen its resilience to reduce the impact of other threats to health, such as the UK leaving the EU, climate change, and antimicrobial resistance

Effective Population Size and the Efficacy of Selection on the X Chromosomes of Two Closely Related Drosophila Species

The prevalence of natural selection relative to genetic drift is of central interest in evolutionary biology. Depending on the distribution of fitness effects of new mutations, the importance of these evolutionary forces may differ in species with different effective population sizes. Here, we survey population genetic variation at 105 orthologous X-linked protein coding regions in Drosophila melanogaster and its sister species D. simulans, two closely related species with distinct demographic histories. We observe significantly higher levels of polymorphism and evidence for stronger selection on codon usage bias in D. simulans, consistent with a larger historical effective population size on average for this species. Despite these differences, we estimate that <10% of newly arising nonsynonymous mutations have deleterious fitness effects in the nearly neutral range (i.e., −10 < Nes < 0) in both species. The inferred distributions of fitness effects and demographic models translate into surprisingly high estimates of the fraction of “adaptive” protein divergence in both species (∼85–90%). Despite evidence for different demographic histories, differences in population size have apparently played little role in the dynamics of protein evolution in these two species, and estimates of the adaptive fraction (α) of protein divergence in both species remain high even if we account for recent 10-fold growth. Furthermore, although several recent studies have noted strong signatures of recurrent adaptive protein evolution at genes involved in immunity, reproduction, sexual conflict, and intragenomic conflict, our finding of high levels of adaptive protein divergence at randomly chosen proteins (with respect to function) suggests that many other factors likely contribute to the adaptive protein divergence signature in Drosophila

Auriculotherapy to reduce anxiety and pain in nursing professionals: a randomized clinical trial

Objetivos: avaliar a efetividade do protocolo auricular para redução de ansiedade, dor (APPA) e melhoria de qualidade de vida em equipe de Enfermagem de um hospital. Método: ensaio clínico randomizado com amostra inicial de 180 profissionais divididos em 4 grupos Controle (G1), Semente (G2), Agulha (G3) e Fita Adesiva (G4). Os instrumentos de avaliação foram o Inventário de Ansiedade Traço-Estado, Escala Visual Analógica de dor e instrumento de Qualidade de Vida, aplicados no início, depois de cinco e 10 sessões (cinco semanas). Na análise utilizou-se a estatística descritiva, a análise de variância (ANOVA) e o Índice d de Cohen. Resultados: houve diferença estatística (p < 0,05) para a ansiedade segundo ANOVA de medidas repetidas, com melhores resultados para o G3 na última avaliação (índice d de Cohen 1,08/17% de redução). Houve redução de 36% no G3, 24% no G2 para a dor e 13% de aumento no nível mental de qualidade de vida para o G3, embora sem diferenças estatísticas. Conclusão: o protocolo APPA reduziu os níveis de ansiedade em equipe de enfermagem depois de 10 sessões. Mas, sugerem-se mais estudos com novas populações e em diferentes contextos para que os resultados se confirmem. RBR-5pc43m.Objetivos: evaluar la efectividad del protocolo auricular para reducción de ansiedad, dolor (APPA) y mejoría de calidad de vida, en equipo de enfermería de un hospital. Método: ensayo clínico aleatorizado con muestra inicial de 180 profesionales divididos en 4 grupos: Control (G1), Semilla (G2), Aguja (G3) y Cinta Adhesiva (G4). Los instrumentos de evaluación fueron el Inventario de Ansiedad Rasgo-Estado, la Escala Visual Analógica de Dolor y el instrumento de Calidad de Vida, aplicados en el inicio, y después de cinco y 10 sesiones (cinco semanas). En el análisis se utilizó la estadística descriptiva, la análisis de variancia (ANOVA) y el Índice d de Cohen. Resultados: hubo diferencia estadística (p < 0,05) para la ansiedad según ANOVA de medidas repetidas, con mejores resultados para el G3 en la última evaluación (índice d de Cohen 1,08/17% de reducción). Hubo reducción de 36% en el G3, 24% en el G2 para el dolor y 13% de aumento en el nivel mental de calidad de vida para el G3, a pesar de que sin diferencias estadísticas. Conclusión: el protocolo APPA redujo los niveles de ansiedad en el equipo de enfermería después de 10 sesiones. Se sugiere realizar más estudios con nuevas poblaciones y en diferentes contextos para que los resultados puedan ser confirmados. RBR-5pc43m.RESUMEN Objectives: to evaluate the effectiveness of the auricular protocol (APPA) in reducing pain and anxiety and improving the quality of life of the nursing staff of a hospital. Method: randomized clinical trial with an initial sample of 180 professionals divided into 4 groups Control (G1), Seed (G2), Needle (G3) and Tape (G4). The evaluation instruments were the State-Trait Anxiety Inventory, Pain Visual Analog Scale and Quality of Life instrument, applied at the start and after five and 10 sessions (five weeks). Descriptive statistics, analysis of variance (ANOVA) and Cohen's d Index were used in the analysis. Results: there was a statistical difference (p < 0.05) for anxiety according to the repeated measures ANOVA, with better results for the G3 in the final assessment (Cohen's d index 1.08/17% reduction). There was a reduction of pain of 36% in G3 and 24% in G2 and a 13% increase in the mental aspect of quality of life for the G3, although without statistical significance. Conclusion: the APPA protocol reduced the anxiety levels of nursing staff after 10 sessions. Further studies are, however, suggested with new populations and in different contexts so that the results can be confirmed. RBR-5pc43m