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Thomas Kyd: A Dramatist Restored by Brian Vickers Princeton University Press, [pounds sterling]35, pp. 400 The biggest blockbuster hit of the Elizabethan theatre was not by William Shakespeare or Christopher [...]

The article discusses the importance of the publication of a collected edition of William Shakespeare's plays named "First Folio" in 1623. Topics include Shakespeare's plays that have not survived without the book such as "Macbeth" and "Julius Caesar," the impact of the book on Shakespeare's reputation as a playwright and the collaboration of Shakespeare's fellow actors and friends such as John Heminge and Henry Condell to publish the book as a homage to Shakespeare's literary works.

This review focuses on screens to assess everything from mood and substance use to pain and cognition. It also offers an algorithm to aid with clinical decision making. Many screening [...]

Background: Chronic vomiting is a common and, at times, frustrating clinical presentation in our canine patients. Vomiting is considered ‘chronic’ in cases that have gone on for over three to four weeks and the clinical presentation in these cases can vary widely. Given that the list of potential differentials is extensive, a careful and methodical approach to these cases is paramount to successful management. Aim of the article: This article considers an approach to achieving a diagnosis in the chronically vomiting patient, providing readers with the necessary diagnostic toolkit. It also discusses appropriate management strategies to consider in these cases.

Emma Smith discusses the effect of the current staffing crisis on low-risk birth environments, and explores how the challenges that they face may be overcome

Why we must treat decarbonization policies as an experiment and put in place measures now to evaluate what works best.

Many LGBTQ adults have ongoing relationships with their parents that are ambivalent, typified by both solidarity (e.g., frequent contact, emotional or financial exchange) as well as conflict (e.g., parents’ heterosexism and cissexism). Yet, why LGBTQ people remain in—rather than end—their ambivalent intergenerational ties is under explored. We analyze qualitative in-depth interview data with 76 LGBTQ adults to answer this question. We find that LGBTQ adult children deploy narratives that privilege intergenerational solidarity over strain—what we call “solidarity rationales”— to explain why they remain in their ambivalent intergenerational ties. Four solidarity rationales were identified: 1) closeness and love, 2) parental growth, 3) the unique parent-child role, and 4) the importance of parental resources. Identifying LGBTQ adults’ solidarity rationales pulls back the curtain on the compulsory social forces driving persistent intergenerational relationships. This study also advances our thinking about how socially marginalized people cope with complex social ties that include interpersonal discrimination and stigma.

Author: Emma Smith Publisher: Oxford University Press Price: [pounds sterling]20 Released: Out now Within Shakespeare's First Folio Emma Smith has provided a fascinating insight into the history of the First [...]

Background. Mobility limitations represent the third most prevalent cause of disability, affecting more than 1.9 million community-dwelling Canadians. Walking aids are often prescribed to reduce the impacts of mobility impairments. There are limited data on walking aids since 2004. Objective. The objectives of this study were to investigate the prevalence of walking aid use in Canada and to explore demographic characteristics among users of walking aids. Design. The design used was a secondary analysis of a cross-sectional national survey. Methods. Data were obtained from the 2012 Canadian Survey on Disability from community-dwelling individuals who were 15 years old or older, had a self-identified activity limitation, and indicated that they used at least 1 walking aid (cane/walking stick/crutches or walker). Prevalence estimates were calculated as weighted frequencies. Analytic variables included walking aid type, sex, age, province/territory of residence, and main cause of activity limitation. Results. Approximately 1,125,000 community-dwelling individuals who were 15 years old or older used walking aids, representing 4.1% of the Canadian population. Of these individuals, 962,290 used canes/walking sticks/crutches, and 465,340 used a walker. Users of walking aids were predominantly female, with a mean age of 68 years. Limitations. Self-reported results reflect only the perceptions of individuals living in Canadian communities. Analyses excluded individuals in residential or long-term care settings and individuals living on First Nations reserves. Conclusions. Since 2004, there has been a 2% increase in the prevalence of walking aid use by the Canadian population, which is likely related to the aging of the population. The high prevalence of walking aid use highlights the need for better use of existing resources to ensure that individuals are receiving the correct devices. Results of this study suggest a need to evaluate the impact of device use to better understand how resources should be allocated for prescription and maintenance of walking aids and training of users., According to the 2012 Canadian Survey on Disability (CSD), 13.7% of the population experience some form of disability. (1) Mobility limitations represent the third leading cause of disability in Canada, [...]

High-throughput experimentation (HTE) has the potential to improve our understanding of organic chemistry by systematically interrogating reactivity across diverse chemical spaces. Notable bottlenecks include few publicly available large-scale datasets and the need for facile interpretation of these data’s hidden chemical insights. Here we report the development of a high-throughput experimentation analyser, a robust and statistically rigorous framework, which is applicable to any HTE dataset regardless of size, scope or target reaction outcome, which yields interpretable correlations between starting material(s), reagents and outcomes. We improve the HTE data landscape with the disclosure of 39,000+ previously proprietary HTE reactions that cover a breadth of chemistry, including cross-coupling reactions and chiral salt resolutions. The high-throughput experimentation analyser was validated on cross-coupling and hydrogenation datasets, showcasing the elucidation of statistically significant hidden relationships between reaction components and outcomes, as well as highlighting areas of dataset bias and the specific reaction spaces that necessitate further investigation.

High throughput and rapid biological evaluation of small molecules is an essential factor in drug discovery and development. Direct-to-biology (D2B), whereby compound purification is foregone, has emerged as a viable technique in time efficient screening, specifically for PROTAC design and biological evaluation. However, one notable limitation is the prerequisite of high yielding reactions to ensure the desired compound is indeed the compound responsible for biological activity. Herein, we report a machine learning based yield-assay deconfounder capable of deconvoluting low yield from low potency to identify false negatives. We validated this approach by identifying promising SARS-CoV-2 main protease inhibitors with nanomolar activity that rivaled potency observed from the standard D2B workflow. Furthermore, we show how our framework can be utilized in a broad, in silicoscreen to produce compounds of similar potency as a D2B assay.

A photocatalytic methodology for the single step synthesis of γ-ketoacids from α-ketoacids has been developed. This method employs maleic anhydrides as traceless synthetic equivalents of acrylic acids, achieving a selective cross-coupling via a dual decarboxylative strategy, where molecular CO2is released as the only waste byproduct. The method has also been expanded to incorporate a highly regioselective, 3-component coupling with various alcohols to access functionalized γ-ketoesters.

History In Portable Magic: A History of Books and Their Readers (Knopf, $28, 9781524749095), Oxford University Shakespeare studies professor Emma Smith offers a lively and engaging survey of the history [...]

ABSTRACTUsing a quasi-experimental design with no control groups, this pilot study aimed to test the effectiveness of a universal mental health promotion program for elementary school students in an underserved United States-Mexico border community. A total of eighty-five fifth and sixth grade students participated in this program and completed the emotional domain of the Self-Efficacy Questionnaire for Children before and after the intervention. Preliminary program benefits were identified among students who perceived low emotional self-efficacy prior to program participation. The program satisfaction rate was over 60%. About 70% of the participants expressed both confidence and competence in using calming tools for future stressful events. This study supports the use of occupational- and activity-based programs in public elementary schools that serve predominantly Hispanic students from low socioeconomic households. Implications for future occupational therapy practice and research are discussed.

The blockade of the CD154-CD40 pathway with anti-CD154 monoclonal antibody has been a promising immunomodulatory approach to prevent allograft rejection. However, clinical trials of immunoglobulin G1 antibodies targeting this pathway revealed thrombogenic properties, which were subsequently shown to be mediated by crystallizable fragment (Fc)-gamma receptor IIa–dependent platelet activation. To prevent thromboembolic complications, an immunoglobulin G4 anti-CD154 monoclonal antibody, TNX-1500, which retains the fragment antigen binding region of ruplizumab (humanized 5c8, BG9588), was modified by protein engineering to decrease Fc binding to Fc-gamma receptor IIa while retaining certain other effector functions and pharmacokinetics comparable with natural antibodies. Here, we report that TNX-1500 treatment is not associated with platelet activation in vitro and consistently inhibits kidney allograft rejection in vivo without clinical or histologic evidence of prothrombotic phenomena. We conclude that TNX-1500 retains efficacy similar to that of 5c8 to prevent kidney allograft rejection while avoiding previously identified pathway-associated thromboembolic complications.

Background. Mobility impairments are the third leading cause of disability for community-dwelling Canadians. Wheelchairs and scooters help compensate for these challenges. There are limited data within the last decade estimating the prevalence of wheelchair and scooter use in Canada. Objective. The aims of this study were: (1) to estimate the prevalence of wheelchair and scooter use in Canada and (2) to explore relevant demographic characteristics of wheelchair and scooter users. Design. This study was a secondary analysis of a cross-sectional national survey. Methods. The Canadian Survey on Disability (2012) collected data on wheelchair and scooter use from community-dwelling individuals aged 15 years and over with a self-identified activity limitation on the National Household Survey. Prevalence estimates were calculated as weighted frequencies, with cross-tabulations to determine the number of wheelchair and scooter users in Canada, by province, and demographic characteristics (ie, age, sex) and bootstrapping to estimate the variance of all point estimates. Results. There were approximately 288,800 community-dwelling wheelchair and scooter users aged 15 years and over, representing 1.0% of the Canadian population. The sample included 197,560 manual wheelchair users, 42,360 powered wheelchair users, and 108,550 scooter users. Wheelchair and scooter users were predominantly women, with a mean age of 65 years. Approximately 50,620 individuals used a combination of 2 different types of devices. Limitations. The results are representative of individuals living in the community in Canada and exclude individuals in residential or group-based settings; estimates do not represent the true population prevalence. Conclusion. This analysis is the first in more than 10 years to provide a prevalence estimate and description of wheelchair and scooter users in Canada. Since 2004, there has been an increase in the proportion of the population who use wheelchairs and scooters, likely related to an aging Canadian population. These new prevalence data have potential to inform policy, research, and clinical practice., According to the Canadian Survey on Disability (CSD) (2012), 13.7% of the Canadian population experience some form of disability. (1) Mobility impairment affects 7.2% of the population (1.9 million people) [...]

ABSTRACTOccupational therapy, people, and assistive technology have a longstanding relationship. Occupational therapists have the broadest scope of allied health practice across the breadth of assistive products and advisory services. This commentary revisits key foundations of occupational therapy and assistive technology practice. It then examines the recent recommendations made within the inaugural WHO/UNICEF Global Report on Assistive Technology. Drawing on international exemplars of diverse practice and leadership linked to each of the report’s Recommendations, this article demonstrates core roles for occupational therapists as leaders and change agents in delivering on the imperatives identified for assistive technology and assistive technology users globally.

Shakespeare in a Divided America by James Shapiro Faber, 20 [pounds sterling], pp. 310 Shakespeare's single explicit reference to America is found in The Comedy of Errors. The two Dromios [...]

Background: Over half the population (51%) of England and Wales is female, most of whom will experience menopause, either as a result of endocrine ageing or medical treatment. Aim: The project aimed to undertake a review of the literature to determine the level of knowledge about menopause that healthcare students are exposed to, and to highlight why it is important for them to have an understanding of this subject both for their own clinical practice and for supporting colleagues in the workplace. Method: A literature review was conducted by the project team. Findings: There is a lack of education for healthcare students, who will go on to care for those affected by menopause, and will also work with colleagues experiencing menopause. Conclusion: Educational programmes should include menopause as a component, which will allow for a breaking down of barriers on a subject that is still generally considered taboo. Recommendations: A national audit should be conducted on menopause coverage in UK pre-registration nursing. The addition of menopause to the Liverpool John Moores University pre-registration nursing curriculum is also recommended based on agreed competencies.

It's amazing that it only became illegal to discriminate against people identifying as lesbian, gay or bisexual in the workplace in 2003, The property industry's own landmark moment came in [...]

Background: Neuroinflammatory processes have been hypothesized to play a role in the pathogenesis of psychiatric and neurological diseases. Studies on this topic often rely on analysis of inflammatory biomarkers in peripheral blood. Unfortunately, the extent to which these peripheral markers reflect inflammatory processes in the central nervous system (CNS) is unclear. Methods: We performed a systematic review and found 29 studies examining the association between inflammatory marker levels in blood and cerebrospinal (CSF) samples. We performed a random effects meta-analysis of 21 studies (pooled n= 1679 paired samples) that reported the correlation of inflammatory markers in paired blood-CSF samples. Results: A qualitative review revealed moderate to high quality of included studies with the majority of studies reporting no significant correlation of inflammatory markers between paired blood-CSF. Meta-analyses revealed a significant low pooled correlation between peripheral and CSF biomarkers (r= 0.21). Meta-analyses of individual cytokines revealed a significant pooled correlation for IL-6 (r= 0.26) and TNFα (r= 0.3) after excluding outlier studies, but not for other cytokines. Sensitivity analyses showed that correlations were highest among participants with a median age above 50 (r= 0.46) and among autoimmune disorder patients (r= 0.35). Conclusion: This systematic review and meta-analysis revealed poor correlation between peripheral and central inflammatory markers in paired blood-CSF samples, with increased correlations in certain study populations. Based on the current findings, peripheral inflammatory markers are a poor reflection of the neuroinflammatory profile.

The article analyzes the film "Iago." Particular focus is given the content of the film where it mentions that film takes Othello as its source of stimulation. The author discusses about the character Iago played by Nicolas Vaporidis and mentions that Iago joins a long list of William Shakespeare-inspired Italian films.

Background: Pancreatitis can be challenging from a diagnostic and management point of view in both canine and feline patients. Aim of the article: This article considers the differences in anatomy and pathophysiology between dogs and cats and discusses a practical approach to these cases in the clinic. It also highlights when it's appropriate to manage these cases the same way, as well as the critical times when clinicians should remember that cats aren't just small dogs.

Background: Thigh muscle mass and cross-sectional area (CSA) are useful indexes of sarcopenia and the response to treatment in older patients. Current criterion methods are computed tomography (CT) and magnetic resonance imaging. Objective: The objective was to compare thigh muscle mass estimated by dual-energy X-ray absorptiometry (DXA), a less expensive and more accessible method, with thigh muscle CSA determined by CT in a group of elderly patients recovering from hip fracture. Design: Midthigh muscle CSA (in [cm.sup.2]) was assessed from a 1-ram CT slice and midthigh muscle mass (g) from a 1.3-cm DXA slice in 30 patients (24 women) aged 81 [+ or -] 8 y during 12 mo of follow-up. Fat-to-lean soft tissue ratios were calculated with each technique to permit direct comparison of a variable in the same units. Results: Baseline midthigh muscle CSA was highly correlated with midthigh muscle mass (r = 0.86, P < 0.001) such that DXA predicted CT-determined CSA with an SEE of 10 [cm.sup.2] (an error of [approximately equal to] 12% of the mean CSA value). CT- and DXA-determined ratios of midthigh fat to lean mass were similarly related (intraclass correlation coefficient = 0.87, P < 0.001 ). When data were expressed as the changes from baseline to follow-up, CT and DXA changes were weakly correlated (intraclass correlation coefficient = 0.51, P = 0.019). Conclusions: Assessment of sarcopenia by DXA midthigh slice is a potential low-radiation, accessible alternative to CT scanning of older patients. The errors inherent in this technique indicate, however, that it should be applied to groups of patients rather than to individuals or to evaluate the response to interventions. KEY WORDS Sarcopenia, midthigh muscle mass, dual-energy X-ray absorptiometry, hip fracture, frail elders

Since its emergence in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of cases and continues to circulate globally. To establish a novel SARS-CoV-2 human challenge model that enables controlled investigation of pathogenesis, correlates of protection and efficacy testing of forthcoming interventions, 36 volunteers aged 18–29 years without evidence of previous infection or vaccination were inoculated with 10 TCID50of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally in an open-label, non-randomized study (ClinicalTrials.gov identifier NCT04865237; funder, UK Vaccine Taskforce). After inoculation, participants were housed in a high-containment quarantine unit, with 24-hour close medical monitoring and full access to higher-level clinical care. The study’s primary objective was to identify an inoculum dose that induced well-tolerated infection in more than 50% of participants, with secondary objectives to assess virus and symptom kinetics during infection. All pre-specified primary and secondary objectives were met. Two participants were excluded from the per-protocol analysis owing to seroconversion between screening and inoculation, identified post hoc. Eighteen (~53%) participants became infected, with viral load (VL) rising steeply and peaking at ~5 days after inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log10copies per milliliter (median, 95% confidence interval (8.41, 9.53)). Viable virus was recoverable from the nose up to ~10 days after inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected participants, beginning 2–4 days after inoculation, whereas two (11%) participants remained asymptomatic (no reportable symptoms). Anosmia or dysosmia developed more slowly in 15 (83%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs present even in asymptomatic infection. All infected individuals developed serum spike-specific IgG and neutralizing antibodies. Results from lateral flow tests were strongly associated with viable virus, and modeling showed that twice-weekly rapid antigen tests could diagnose infection before 70–80% of viable virus had been generated. Thus, with detailed characterization and safety analysis of this first SARS-CoV-2 human challenge study in young adults, viral kinetics over the course of primary infection with SARS-CoV-2 were established, with implications for public health recommendations and strategies to affect SARS-CoV-2 transmission. Future studies will identify the immune factors associated with protection in those participants who did not develop infection or symptoms and define the effect of prior immunity and viral variation on clinical outcome.

The article reviews the play "Henry IV, Parts 1 and 2" adapted and directed by Robert Icke, starring Ian McKellen as Falstaff, performed at the Noel Coward Theatre in London until June 22, 2024, before touring.

The article discusses that gay couple Rob Stow and Jeremy Evans became licensed foster parents with Child and Family Services (CFS) in Michigan at the time when CFS was the only private agency that would license gay couples for foster care. In 2010, gay marriage was also not legal in Michigan, which meant very few options for gay couples looking to adopt jointly.

Initial characterization of autoimmune rheumatic disease through clinical assessment and investigation including serological measurements offers a vital opportunity to personalize treatment regimens, contributes to accurate prognosis and optimizes outcomes. Disease monitoring using serological tests as biomarkers also contributes to earlier recognition of disease relapse or remission and allows appropriate titration of medication. All rheumatic diseases have typical antibody associations and understanding how to request tests appropriately and thereafter analyse them forms an important part of disease management. In this article, we introduce the standard tests available in the UK and a pragmatic approach to testing in inpatient and outpatient environments.

Purpose: This paper aims to explore how enforced forms of social isolation arising from the first COVID-19 lockdown influenced experiences of problem substance use, relapse and coping strategies for recovery in individuals engaging with harm reduction recovery services. Design/methodology/approach: A qualitative semi-structured interview design was adopted for this research. Seven participants were recruited from a harm reduction recovery organisation. During their initial interview, participants volunteered information regarding their experience of the first lockdown due to emerging concerns of the COVID-19 pandemic. Participants completed a second semi-structured interview at the end of the first lockdown regarding their experience of enforced isolation during this time. Findings: Three themes identified from the analysis were isolation resulting in hindered human capabilities; adjusting to a new normal: an individual experience; and unexpected benefits to recovery resulting from isolation. While some participants reported boredom, loneliness and relapse events, others reported that the national response to the virus did not adversely affect them as they had already adjusted to living in a state of anxiety, isolation and uncertainty. These findings illuminate negative, neutral and positive aspects of substance use recovery throughout the COVID-19 lockdown as well as highlighting the complex and individualised role that social connectedness plays in relapse occurrence. Originality/value: Participants reported differences in how they were affected by the pandemic, leading to theoretical implications for the effect of social isolation on recovery. For this reason, individuals with a history of dependency should be considered potentially vulnerable to the effects of enforced isolation and should be supported accordingly.

Documentation of patterns and long-term trends in mortality in young people, which reflect huge changes in demographic and social determinants of adolescent health, enables identification of global investment priorities for this age group. We aimed to analyse data on the number of deaths, years of life lost, and mortality rates by sex and age group in people aged 10–24 years in 204 countries and territories from 1950 to 2019 by use of estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social behaviors and communication. In rodents and humans, prenatal exposure to antiepileptic valproic acid is associated with an increased risk for autistic-like characteristics. One potential treatment is oxytocin, a prosocial neuropeptide that can be delivered intranasally. However, the sex-specific effects of valproic acid exposure and intranasal oxytocin treatment on behavior have not been fully explored. Pregnant Long Evans rats were administered valproic acid (500 mg/kg) or saline midday on gestational day 12, and after weaning, male and female pups were assigned to control (saline–saline), valproic acid–saline, or valproic acid–oxytocin groups. Oxytocin (0.8 IU/kg) or saline was delivered intranasally 30–60 min before tests for anxiety-like behaviors (elevated plus maze), social interactions (sociability) and sociosexual behaviors (partner preference, 50 kHz vocalizations and scent marking). Prenatal exposure to valproic acid resulted in sex-specific differences in behavior. When compared to controls, valproic acid males showed enhanced anxiety-like behaviors in adolescence and fewer scent marks in adulthood, while valproic acid females showed reduced sexual (partner) preference as adults. Intranasal oxytocin was anxiolytic for valproic acid males, but moderately anxiogenic for valproic acid females, and in both sexes it surprisingly impaired social interactions in the sociability test. Furthermore, intranasal oxytocin failed to improve sociosexual deficits in valproic acid rats. These findings highlight the importance of conducting preclinical studies in both sexes, and suggest that oxytocin may be an effective treatment in animal models with heightened anxiety-like behaviors.

There is growing concern that the social and physical distancing measures implemented in response to the Covid-19 pandemic may negatively impact health in other areas, via both decreased physical activity and increased social isolation. Here, we investigated whether increased engagement with digital social tools may help mitigate effects of enforced isolation on physical activity and mood, in a naturalistic study of at-risk individuals. Passively sensed smartphone app use and actigraphy data were collected from a group of psychiatric outpatients before and during imposition of strict Covid-19 lockdown measures. Data were analysed using Gaussian graphical models: a form of network analysis which gives insight into the predictive relationships between measures across timepoints. Within-individuals, we found evidence of a positive predictive path between digital social engagement, general smartphone use, and physical activity—selectively under lockdown conditions (N= 127 individual users, M= 6201 daily observations). Further, we observed a positive relationship between social media use and total daily steps across individuals during (but not prior to) lockdown. Although there are important limitations on the validity of drawing causal conclusions from observational data, a plausible explanation for our findings is that, during lockdown, individuals use their smartphones to access social support, which may help guard against negative effects of in-person social deprivation and other pandemic-related stress. Importantly, passive monitoring of smartphone app usage is low burden and non-intrusive. Given appropriate consent, this could help identify people who are failing to engage in usual patterns of digital social interaction, providing a route to early intervention.

'The globalization of the yuan seems remorseless and unstoppable,' pronounced The Economist in April 2014. Indeed, use of the Chinese yuan, or renminbi, in global payments would double between then [...]