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Objective: To examine the impact that participation in 2019 coronavirus disease (COVID-19) vaccination clinics had on students’ self-assessed ability to vaccinate and secondarily, to examine the impact these experiences had on student perspectives of pharmacist engagement in public health. Methods: Student pharmacists who volunteered in COVID-19 vaccination clinics were invited to complete an anonymous, electronic survey consisting of items pertaining to their self-assessed ability to vaccinate and attitudes towards pharmacist engagement in public health in a retrospective pre/post-experience. Results: Students indicated that the experiences were valuable, participation increased their comfort level with vaccination, and they were better prepared to engage in vaccination following engagement. Additionally, student attitudes toward pharmacist engagement in public health improved after engagement. Conclusion: Participation in COVID-19 vaccination clinics had a positive effect on students’ self-efficacy toward vaccination and their attitudes toward pharmacist engagement in public health. Similar opportunities should be promoted to student-pharmacists to facilitate their professional development.

Purpose The aim of this research is to gain an insight into the attitudes that therapists, both qualified and trainee, have towards the use of artificial intelligence (AI)/machine therapy in therapeutic practice. The paper also aims to gain an insight into attitudes towards machine therapy and the potential of developing a therapeutic alliance with a machine therapist. Design/methodology/approach A short questionnaire was developed to gauge therapists and trainee therapists’ attitudes towards machine therapy. The questionnaire included a scenario for participants to read and then respond to questions on the therapeutic alliance using questions based upon those asked on the working alliance short inventory scale. At the end of the questionnaire, there was also the opportunity for participants to respond to an open-ended question. Findings It is evident from the responses that there is a clear reservation about the use of AI technology within the therapeutic setting. In spite of this reticence, many participants recognised the potential and are open to the possibilities this technology can bring. It was notable that the therapists largest concern was about the potential to create a strong bond with a machine therapist. Originality/value This paper presents findings on therapists’ attitudes towards AI use within therapeutic practice and machine therapy. Whilst limited in scope, it provides a yardstick for considering the way that attitudes towards these emerging technologies might change in the future.

Academics and journalists alike have written extensively on how Bridgerton () has portrayed BIPOC characters and history in the Regency era. Few writers however have attempted to analyse these questions with both academic and non-academic readers in mind. This article is a self-reflection, based analysis of how the conversation around Bridgerton has evolved over the three years since it was first released.

State-of-the-art radio observatories produce large amounts of data which can be used to study the properties of radio galaxies. However, with this rapid increase in data volume, it has become unrealistic to manually process all of the incoming data, which in turn led to the development of automated approaches for data processing tasks, such as morphological classification. Deep learning plays a crucial role in this automation process and it has been shown that convolutional neural networks (CNNs) can deliver good performance in the morphological classification of radio galaxies. This paper investigates two adaptations to the application of these CNNs for radio galaxy classification. The first adaptation consists of using principal component analysis (PCA) during preprocessing to align the galaxies' principal components with the axes of the coordinate system, which will normalize the orientation of the galaxies. This adaptation led to a significant improvement in the classification accuracy of the CNNs and decreased the average time required to train the models. The second adaptation consists of guiding the CNN to look for specific features within the samples in an attempt to utilize domain knowledge to improve the training process. It was found that this adaptation generally leads to a stabler training process and in certain instances reduced overfitting within the network, as well as the number of epochs required for training., 20 pages, 17 figures, this is a pre-copyedited, author-produced PDF of an article accepted for publication in the Monthly Notices of the Royal Astronomical Society

Children who experience a severe burn injury not only require acute medical care but may also need ongoing rehabilitation. To mitigate the potential long-term consequences of scarring and the impact of scarring on their everyday lives, children may be expected to use a variety of time-consuming and multi-component non-invasive scar treatments (such as pressure garments and silicone gels). These treatments may pose unique challenges for children and their caregivers. With limited research previously addressing how Australian children navigate the use of scar treatments at home, this study aimed to develop a grounded theory of children and their caregivers’ engagement with non-invasive burn scar treatments. Using a constructivist grounded theory approach, interviews were completed with 20 caregivers and 7 children, and a theory of children and their caregivers becoming experts in the use of non-invasive burn scar treatments was developed. Through persistence and flexibility, they continued to develop expertise. Engaging with scar treatments was an evolving process over time for children with burns and their caregivers. Theoretical categories identified included ‘making it work’, ‘finding the balance’ and ‘seeking reassurance’ and highlighted the remarkable strengths and adaptability of children and their caregivers. Through trial and error, children and their caregivers developed their own unique strategies for engaging with scar treatments. These insightful results may inform the development of interventions to support children and their caregivers’ day-to-day engagement with non-invasive burn scar treatments and guide health professionals recommending these treatments.

Background: Human milk is a complex source of nutrition and other bioactives that protects infants from disease, holding a lifetime of beneficial effects. The field of metabolomics provides a robust platform through which we can better understand human milk at a level rarely examined. Research Aim: To Identify, describe, synthesize, and critically analyze the literature within the past 5 years related to the human milk metabolome. Methods: We conducted a scoping literature review and quality analysis of the recent science reflecting untargeted metabolomic approaches to examining human milk. We searched six databases using the terms “breast milk,” “metabolome,” “metabolite,” and “human milk,” Out of more than 1,069 abstracts, we screened and identified 22 articles that met our inclusion criteria. Results: We extracted data related to the study author, geographic location, research design, analyses, platform used, and results. We also extracted data related to human milk research activities, including collection protocol, infant/maternal considerations, and time. Selected studies focused on a variety of phenotypes, including maternal and infant disease. Investigators used varying approaches to evaluate the metabolome, and differing milk collection protocols were observed. Conclusion: The human milk metabolome is informed by many factors—which may contribute to infant health outcomes—that have resulted in disparate milk metabolomic profiles. Standardized milk collection and storage procedures should be implemented to minimize degradation. Investigators may use our findings to develop research questions that test a targeted metabolomic approach.

Estimated heritability of educational attainment (EA) varies widely, from 23% to 80%, with growing evidence suggesting the degree to which genetic variation contributes to individual differences in EA is highly dependent upon situational factors. We aimed to decompose EA into influences attributable to genetic propensity and to environmental context and their interplay, while considering influences of rearing household economic status (HES) and sex. We use the Project Talent Twin and Sibling Study, drawn from the population-representative cohort of high school students assessed in 1960 and followed through 2014, to ages 68−72. Data from 3552 twins and siblings from 1741 families were analyzed using multilevel regression and multiple group structural equation models. Individuals from less-advantaged backgrounds had lower EA and less variation. Genetic variance accounted for 51% of the total variance, but within women and men, 40% and 58% of the total variance respectively. Men had stable genetic variance on EA across all HES strata, whereas high HES women showed the same level of genetic influence as men, and lower HES women had constrained genetic influence on EA. Unexpectedly, middle HES women showed the largest constraints in genetic influence on EA. Shared family environment appears to make an outsized contribution to greater variability for women in this middle stratum and whether they pursue more EA. Implications are that without considering early life opportunity, genetic studies on education may mischaracterize sex differences because education reflects different degrees of genetic and environmental influences for women and men.

Pathogen infection causes a stereotyped state of sickness that involves neuronally orchestrated behavioural and physiological changes1,2. On infection, immune cells release a ‘storm’ of cytokines and other mediators, many of which are detected by neurons3,4; yet, the responding neural circuits and neuro–immune interaction mechanisms that evoke sickness behaviour during naturalistic infections remain unclear. Over-the-counter medications such as aspirin and ibuprofen are widely used to alleviate sickness and act by blocking prostaglandin E2 (PGE2) synthesis5. A leading model is that PGE2 crosses the blood–brain barrier and directly engages hypothalamic neurons2. Here, using genetic tools that broadly cover a peripheral sensory neuron atlas, we instead identified a small population of PGE2-detecting glossopharyngeal sensory neurons (petrosal GABRA1 neurons) that are essential for influenza-induced sickness behaviour in mice. Ablating petrosal GABRA1 neurons or targeted knockout of PGE2 receptor 3 (EP3) in these neurons eliminates influenza-induced decreases in food intake, water intake and mobility during early-stage infection and improves survival. Genetically guided anatomical mapping revealed that petrosal GABRA1 neurons project to mucosal regions of the nasopharynx with increased expression of cyclooxygenase-2 after infection, and also display a specific axonal targeting pattern in the brainstem. Together, these findings reveal a primary airway-to-brain sensory pathway that detects locally produced prostaglandins and mediates systemic sickness responses to respiratory virus infection.

Specific ion effects govern myriad biological phenomena, including protein-ligand interactions and enzyme activity. Despite recent advances, detailed understanding of the role of ion hydrophobicity in specific ion effects, and the intersection with hydrotropic effects, remains elusive. Short chain fatty acid sodium salts are simple amphiphiles which play an integral role in our gastrointestinal health. We hypothesise that increasing a fatty acid's hydrophobicity will manifest stronger salting-out behaviour.Here we study the effect of these amphiphiles on an exemplar thermoresponsive polymer brush system, conserving the carboxylate anion identity while varying anion hydrophobicity via the carbon chain length. Ellipsometry and quartz crystal microbalance with dissipation monitoring were used to characterise the thermoresponse and viscoelasticity of the brush, respectively, whilst neutron reflectometry was used to reveal the internal structure of the brush. Diffusion-ordered nuclear magnetic resonance spectroscopy and computational investigations provide insight into polymer-ion interactions.Surface sensitive techniques unveiled a non-monotonic trend in salting-out ability with increasing anion hydrophobicity, revealing the bundle-like morphology of the ion-collapsed system. An intersection between ion-specific and hydrotropic effects was observed both experimentally and computationally; trending from good anti-hydrotrope towards hydrotropic behaviour with increasing anion hydrophobicity, accompanying a change in hydrophobic hydration.

Current guidelines recommend extubation only if a patient is not receiving vasopressor therapy or is receiving minimal doses of vasopressors. However, recent data indicate that extubation of patients receiving higher vasopressor doses may be safe. This study was undertaken to examine practices regarding extubation of patients receiving vasopressor therapy reported by clinician respondents to a survey by the Michigan Health and Hospital Association Keystone Center. One-third of respondents indicated that they would extubate a patient receiving vasopressors, and one-quarter indicated that it depended on the agent used, but more than half reported that their unit did not have a vasopressor use protocol or they did not know whether it did. Practices regarding extubation of patients receiving vasopressor therapy differed significantly by unit type and by role as a direct care provider. These data indicate that patient and clinician factors may drive practice patterns. Additional research to inform guidelines and local protocols is warranted.

Bronchodilator responsiveness (BDR) in obstructive lung disease varies over time and may be associated with distinct clinical features.Is consistent BDR over time (always present) differentially associated with obstructive lung disease features relative to inconsistent (sometimes present) or never (never present) BDR in tobacco-exposed people with or without COPD?We retrospectively analyzed data from 2,269 tobacco-exposed participants in the Subpopulations and Intermediate Outcome Measures in COPD Study with or without COPD. We used various BDR definitions: change of ≥ 200 mL and ≥ 12% in FEVBoth consistent and inconsistent ATS-BDR were associated with asthma history and greater small airways disease (%parametric response mapping functional small airways disease) relative to never ATS-BDR in participants with GOLD stage 0 disease and the entire cohort. We observed similar findings using FEVDemonstration of BDR, even once, describes an obstructive lung disease phenotype with a history of asthma and greater small airways disease. Consistent demonstration of BDR indicated a high risk of lung function decline over time in the entire cohort and was associated with higher risk of progression to COPD in patients with GOLD stage 0 disease.

Purpose The positive addiction recovery website (https://positiveaddictionrecovery.com) has been created following a successful pilot study of a programme of work known as positive addiction recovery therapy (PART). The aim of the website is to disseminate PART to an online audience, extending its reach to a larger population. The purpose of this study is to explain the process of creating this online resource and to conduct a user evaluation to understand how well received the website is likely to be to its target audience. Design/methodology/approach An implementation framework cognisant of positive computing, positive technology, contemporary understanding of human–computer interaction and knowledge acquired from the delivery of eHealth interventions from the past decade was used to create the website. To understand user opinion of the resultant website, data were collected using the mobile application ratings scale user version. Findings By adopting a tailored implementation framework, with appropriate determinant factors of wellbeing and evidenced theoretical input, a website resource was created that users considered engaging and informative. The findings also suggest that participants appreciated the importance of intended behavioural change, having interacted with the interventions on the website. Originality/value To the best of the authors’ knowledge, the website is the first online version of PART, a new programme of work aimed at people in addiction recovery.

Aims To evaluate the extent of left atrial (LA) fibrosis in patients with a recent stroke without atrial fibrillation and controls without established cardiovascular disease. Methods and results This prospectively designed study used cardiac magnetic resonance to detect LA late gadolinium enhancement as a proxy for LA fibrosis. Between 2019 and 2021, we consecutively included 100 patients free of atrial fibrillation with recent ischaemic stroke ( Conclusion LA fibrosis was more extensive in patients with stroke than in age- and sex-matched controls. A similar extent of LA fibrosis was observed in patients with stroke of undetermined aetiology and stroke classified as attributable to large- or small-vessel disease. Our findings suggest that LA structural abnormality is more frequent in patients with stroke than in controls independent of aetiological classification.

AimsTo test whether usual outpatient cardiac rehabilitation (CR) supplemented by a cognitive-behavioural therapy (CBT) intervention may reduce anxiety and depression compared with usual CR.Methods and resultsIn this multicentre randomized controlled trial, 147 cardiac patients (67% men, mean age 54 years, 92% with coronary artery disease) with psychological distress defined as a hospital anxiety and depression scale (HADS) anxiety or depression score ≥8 were randomized to five sessions of group CBT plus usual CR (intervention, n = 74) or CR alone (control, n = 73). Patients with severe distress or a psychiatric diagnosis were excluded. The intervention was delivered by cardiac nurses with CBT training and supervised by a psychologist. A reference, non-randomized group (background, n = 41) of consecutive patients without psychological distress receiving usual CR was included to explore the effect of time on HADS score. The primary outcome, total HADS score after 3 months, improved more in the intervention than in the control group [the mean total HADS score improved by 8.0 (standard deviation 5.6) vs. 4.1 (standard deviation 7.8), P < 0.001]. Significant between-group differences were maintained after 6 months. Compared with the control group, the intervention group also had greater adherence to CR (P = 0.003), more improvement in the heart-related quality of life (HeartQoL) at 6 months (P < 0.01), and a significant reduction in cardiac readmissions at 12 months (P < 0.01). The background group had no significant change in HADS score over time.ConclusionBrief CBT provided by cardiac nurses in relation to CR reduced anxiety and depression scores, improved HeartQoL and adherence to CR, and reduced cardiovascular readmissions. The programme is simple and may be implemented by CR nurses.

Structural characterisation of thermoresponsive polymer brushes in binary DMSO–water mixtures reveals both LCST and UCST behaviour.

Sacubitril/valsartan (Sac/Val) improves left ventricular ejection fraction (LVEF) in heart failure (HF) with reduced ejection fraction regardless of previous treatments. Improvements in LVEF may change eligibility for primary implantable cardioverter-defibrillator (ICD) placement. Awaiting LVEF improvement may expose patients to potential risks for arrhythmic complications.The authors sought to develop a model predicting LVEF change after Sac/Val therapy.A total of 416 persons with HF and LVEF of 35% were included in this analysis. Following initiation of Sac/Val, echocardiographic parameters were measured serially for 1 year. A machine learning algorithm was implemented to develop a risk model for predicting the persistence of LVEF of 35% after 1 year and was validated in a separate group of study participants.Baseline LVEF, left ventricular mass index, HF duration, age, N-terminal pro-B-type natriuretic peptide concentration at baseline and change by day 14, and body mass index were the most significant factors for identifying lack of LVEF improvement to ≥35% after 1 year. In the training and validation cohorts, the areas under the model curve for predicting lack of LVEF improvement were 0.92 and 0.86, respectively. Three categories of likelihood for LVEF of 35% after 1 year of Sac/Val treatment were developed based on the model predictions: 3.8%, 30.1%, and 83.7%. During follow-up, arrhythmia event rates were 0.9%, 2.9%, and 6.7% in these groups, respectively.Many persons with HF with reduced ejection fraction eligible for ICD insertion experience an increase in LVEF to ≥35% after treatment with Sac/Val. Early identification of those less likely to improve their LVEF might allow for more refined selection of primary ICD candidates. (Effects of Sacubitril/Valsartan Therapy on biomarkers, Myocardial Remodeling, and Outcomes [PROVE-HF]; NCT02887183).

This work provides examples of Weinreich's Identity Structure Analysis (ISA), Nomothetic Analyses of 3 groups of teachers. The groups were formed in response to ratings of the teachers as good, average or weaker by their Principals. The analyses indicate that ISA nomothetics may hold potential for differentiating among good, average and weaker teachers. Summaries of the analyses close the work. They present possible paths for the provision of group-specific Professional Development which speaks to the potential for improvements in teacher identity. The article was received: 17. 09. 2022., revised: 06. 10. 2022., accepted: 07. 10. 2022.

The incidence of women entering into pregnancy with BMI indicating overweight or obesity is rising with concurrent increases in adverse complications such as gestational diabetes. Although several studies have examined the compositional changes to the microbiome across BMI classifications, there has been no investigation regarding changes in microbial function during pregnancy.A total of 105 gastrointestinal microbiome biospecimens were used in this analysis. Biospecimens were sequenced by using the Illumina NovaSeq 6000 shotgun metagenomics platform.Findings indicate an enrichment in microbiota from the phylum Firmicutes across all pregravid BMI groups with a decrease in α diversity in groups with BMI indicating obesity or overweight compared with a group with BMI indicating normal weight (p = 0.02). More specifically, women with BMI indicating obesity or overweight had enrichment in Bifidobacterium bifidum and B. adolescentis. Women with BMI25 kg/mOur analysis suggests that there are differences in microbial composition and function between BMI groups. Future research should consider how these changes contribute to specific clinical outcomes during pregnancy.

Purpose This study aims to evaluate a novel mobile therapeutic videogame for adolescents with anxiety disorders (ADs), combining elements of cognitive-behavioural therapy and attention-bias modification, in terms of both its therapeutic efficacy over a controlled intervention and two-month follow-up, as well as the extent and implications of self-directed play. Design/methodology/approach A within-groups design with two parallel conditions [clinical anxiety (N = 16) and subclinical/at-risk (N = 15)] were measured on both self-reported anxiety and threat-detection bias (TDB) across three timepoints (pre- and post-intervention and two-month follow-up). Findings Significant reductions were observed in both self-reported state and trait anxiety and TDB over the course of the two-week intervention, which were maintained at follow-up. Engagement in self-directed play during the follow-up period significantly predicted outcomes at two-month follow-up for clinical participants. Originality/value To the best of the authors’ knowledge, this paper represents the first of its kind to evaluate a mobile therapeutic game designed with and solely for adolescents with ADs. This study also represents the first of its kind to examine the extent and implications of self-directed play for outcomes.

Obesity is a significant public health concern across the globe. Research investigating epigenetic mechanisms related to obesity and obesity-associated conditions has identified differences that may contribute to cellular dysregulation that accelerates the development of disease. However, few studies include Black women, who experience the highest incidence of obesity and early onset of cardiometabolic disorders.The association of BMI with epigenome-wide DNA methylation (DNAm) was examined using the 850K Illumina EPIC BeadChip in two Black populations (Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure [InterGEN], n = 239; and The Genetic Epidemiology Network of Arteriopathy [GENOA] study, n = 961) using linear mixed-effects regression models adjusted for batch effects, cell type heterogeneity, population stratification, and confounding factors.Cross-sectional analysis of the InterGEN discovery cohort identified 28 DNAm sites significantly associated with BMI, 24 of which had not been previously reported. Of these, 17 were replicated using the GENOA study. In addition, a meta-analysis, including both the InterGEN and GENOA cohorts, identified 658 DNAm sites associated with BMI with false discovery rate 0.05. In a meta-analysis of Black women, we identified 628 DNAm sites significantly associated with BMI. Using a more stringent significance threshold of Bonferroni-corrected p value 0.05, 65 and 61 DNAm sites associated with BMI were identified from the combined sex and female-only meta-analyses, respectively.This study suggests that BMI is associated with differences in DNAm among women that can be identified with DNA extracted from salivary (discovery) and peripheral blood (replication) samples among Black populations across two cohorts.

Although sacubitril/valsartan (Sac/Val) is indicated for the treatment of heart failure with reduced ejection fraction (HFrEF), gaps in care continue to exist for those with newer onset HFrEF vs those with longer durations of disease.We categorized 794 persons with HFrEF (EF of ≤40%) according to a HF duration of less than 12 months, 12-24 months, 24-60 months, and more than60 months. After the initiation of Sac/Val, concentrations of N-terminal pro-B type natriuretic peptide, high sensitivity cardiac troponin T, and soluble ST2 were measured, and Kansas City Cardiomyopathy Questionnaire 23 scores were obtained serially from baseline to 12 months. The left ventricular ejection fraction was measured by echocardiography. Significant decreases in the concentrations of N-terminal pro-B type natriuretic peptide, high sensitivity cardiac troponin T, and soluble ST2 were observed regardless of HF duration (P.001). Comparable gains in Kansas City Cardiomyopathy Questionnaire 23 scores were achieved in all HF duration categories. Moreover, consistent reverse cardiac remodeling in all HF duration categories occurred, with the absolute left ventricular ejection fraction improvement by 12 months across HF duration groups of 12.2%, 6.9%, 8.5%, and 8.6% for HF duration of less than 12 months, 12-24 months, 24-60 months, and more than 60 months, respectively.The initiation of Sac/Val decreases prognostic biomarkers, improves health status, and reverses cardiac remodeling processes, regardless of HF duration.We categorized 794 persons with heart failure owing to a low ejection fraction according to disease duration into 4 groups: less than 12 months, 12-24 months, 24-60 months, and more than 60 months. After the initiation of sacubitril/valsartan (Entresto), we found that regardless of the duration of heart failure significant improvements occurred in cardiac biomarkers, patients felt better with improved health status and on testing with cardiac ultrasound examination, improvement in heart size, and function occurred. These results suggest that, regardless of heart failure duration, patients with a reduced ejection fraction would benefit from use of sacubitril/valsartan for their care.

BACKGROUND: ACE2 is a key enzyme in the renin-angiotensin system (RAS) capable of balancing the RAS by metabolizing angiotensin II (AngII). First described in cardiac tissue, abundance of ACE2 is highest in the kidney, and it is also expressed in several extrarenal tissues. Previously, we reported an association between enhanced susceptibility to hypertension and elevated renal AngII levels in global ACE2-knockout mice. METHODS: To examine the effect of ACE2 expressed in the kidney, relative to extrarenal expression, on the development of hypertension, we used a kidney crosstransplantation strategy with ACE2-KO and WT mice. In this model, both native kidneys are removed and renal function is provided entirely by the transplanted kidney, such that four experimental groups with restricted ACE2 expression are generated: WT→WT (WT), KO→WT (KidneyKO), WT→KO (SystemicKO), and KO→KO (TotalKO). Additionally, we used nanoscale mass spectrometry–based proteomics to identify ACE2 fragments in early glomerular filtrate of mice. RESULTS: Although significant differences in BP were not detected, a major finding of our study is that shed or soluble ACE2 (sACE2) was present in urine of KidneyKO mice that lack renal ACE2 expression. Detection of sACE2 in the urine of KidneyKO mice during AngII-mediated hypertension suggests that sACE2 originating from extrarenal tissues can reach the kidney and be excreted in urine. To confirm glomerular filtration of ACE2, we used micropuncture and nanoscale proteomics to detect peptides derived from ACE2 in the Bowman’s space. CONCLUSIONS: Our findings suggest that both systemic and renal tissues may contribute to sACE2 in urine, identifying the kidney as a major site for ACE2 actions. Moreover, filtration of sACE2 into the lumen of the nephron may contribute to the pathophysiology of kidney diseases characterized by disruption of the glomerular filtration barrier.

Patients with gynecologic malignancies may have varied responses to COVID-19 infection. We aimed to describe clinical courses, treatment changes, and short-term clinical outcomes for gynecologic oncology patients with concurrent COVID-19 in the United States.The Society of Gynecologic Oncology COVID-19 and Gynecologic Cancer Registry was created to capture clinical courses of gynecologic oncology patients with COVID-19. Logistic regression models were employed to evaluate factors for an association with hospitalization and death, respectively, within 30 days of COVID-19 diagnosis.Data were available for 348 patients across 7 institutions. At COVID-19 diagnosis, 125 patients (36%) had active malignancy. Delay (n = 88) or discontinuation (n = 10) of treatment due to COVID-19 infection occurred in 28% with those on chemotherapy (53/88) or recently receiving surgery (32/88) most frequently delayed. In addition to age, performance status, diabetes, and specific COVID symptoms, both non-White race (adjusted odds ratio (aOR) = 3.93, 95% CI 2.06-7.50) and active malignancy (aOR = 2.34, 95% CI 1.30-4.20) were associated with an increased odds of hospitalization. Eight percent of hospitalized patients (8/101) died of COVID-19 complications and 5% (17/348) of the entire cohort died within 30 days after diagnosis.Gynecologic oncology patients diagnosed with COVID-19 are at risk for hospitalization, delay of anti-cancer treatments, and death. One in 20 gynecologic oncology patients with COVID-19 died within 30 days after diagnosis. Racial disparities exist in patient hospitalizations for COVID-19, a surrogate of disease severity. Additional studies are needed to determine long-term outcomes and the impact of race.

Purpose The purpose of this study resolved to evidence worldwide studies addressing the effects of the global COVID-19 pandemic on higher education (HE) academic staff. Particularly in relation to wellbeing and pedagogical role, as part of a parallel study exploring the impact of COVID-19 on academics’ pastoral role. Design/methodology/approach The systematized review identified eight relevant studies that shed light on the impacts of the COVID-19 pandemic on university academics’ well-being. Findings The review highlights the paucity of research in this area, with no studies, at the time of the review, considering how academics responded to a broadening of their pastoral role amidst an evolving academic landscape, and how are universities supporting them. Research limitations/implications Firstly, only eight relevant studies were included, affecting generalisability of results owing to uneven distribution between geographic regions. Secondly, participants across the eight studies accounted for less than 0.05% of a population of 6 million university academics worldwide (Price, 2011). Thirdly, most of the studies used cross-sectional design, limiting assessment of the longer-term impact of an evolving HE landscape. Practical implications The findings of this systematized review can be placed in the context of illuminating research deficits within a shifting HE landscape. Specifically, no studies that the authors are aware of have investigated how academics are responding to a broadening of their pastoral role amidst an evolving academic landscape, and how are universities supporting them. Originality/value In providing pastoral support to students, the mental well-being of academics is frequently ignored (Urbina-Garcia, 2020). The provision of well-being support by university management for academics appears to be “limited to non-existent” (Hughes et al., 2018, p. 49). Critically, the Coronavirus pandemic appears to have both accelerated and precipitated a step-change to pastoral care within the HE teaching ecosystem. The impact of a broadening pastoral role on academics' well-being has yet to be fully realized and understood. The authors have subsequently conducted an empirical study to address this embryonic area of research.

This study employs a state-level model of recovery and a comprehensive set of tax- and expenditure-related variables to explore the effect that the states’ fiscal policy decisions had on their recoveries after the Great Recession in the United States. In addition, we combine those findings with our resistance results from two earlier studies to identify the structural and fiscal-policy factors that consistently strengthened or weakened the states’ economic resilience entering, during, and exiting that recession. Although our analysis indicates that resistance and recovery are distinctly different economic resilience phenomena, states that avoided sales and corporate income taxes, and that committed a greater share of their resources to public welfare expenditures, fared better than others throughout. This knowledge may aid state governments’ fiscal policy decision making as they prepare for future recessionary shocks.

A prospective study and its long-term extension examined whether weekly treatment of patients with primary immunodeficiencies (PIDs) with a 16.5% subcutaneous immunoglobulin (SCIg; cutaquig®) confers acceptable efficacy, safety, and tolerability over a follow-up of up to 238 weeks (>4 years). Seventy-five patients received 4462 infusions during up to 70 weeks of follow-up in the main study and 27 patients received 2777 infusions during up to 168 weeks of follow-up in the extension. In the main study, there were no serious bacterial infections (SBIs), and the annual rate of other infections was 3.3 (95% CI 2.4, 4.5). One SBI was recorded in the extension, for an SBI rate of 0.02 (upper 99% CI 0.19). The annual rate of all infections over the duration of the extension study was 2.2 (95% CI 1.2, 3.9). Only 15.0% (1085) of 7239 infusions were associated with infusion site reactions (ISRs), leaving 85.0% (6153) of infusions without reactions. The majority of ISRs were mild and transient. ISR incidence decreased over time, from 36.9% to 16% during the main study and from 9% to 2.3% during the extension. The incidence of related systemic adverse events was 14.7% in the main study and 7.4% in the extension. In conclusion, this prospective, long-term study with cutaquig showed maintained efficacy and low rates of local and systemic adverse reactions in PID patients over up to 238 weeks of follow-up.

Two commonly used methods for cyanotoxin analysis are enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Each method has its advantages and disadvantages, and discrepancies are commonly observed between the two methods due to various factors including the ELISA antibody cross-reacting to different cyanotoxin congeners. However, reliable cyanotoxin monitoring methods and accurate interpretation of results are needed for water utilities to guide recreational water planning and drinking water treatment operations. In this study, we explored an innovative "effective concentration-equivalent concentration" (EC-EQ) approach to improve the interpretation of ELISA results and the comparison to LC-MS/MS results. The precision of ELISA results was first improved by reporting the sample ECs and EQs derived from their ELISA dose curves. Concentrations of each cyanotoxin as measured by LC-MS/MS were then combined with their respective ELISA cross-reactivities to calculate their theoretical ELISA responses. Finally, instead of comparing the results from the two methods directly, the equivalent concentration based on one single reference cyanotoxin was used for reporting and comparison. This integrated mass balance-based approach provides a more reliable interpretation of results by considering the reactivity differences between toxins as well as their mixture effects. This approach has been successfully applied to microcystin (one main group of cyanotoxins) standard mixtures and cyanobacterial bloom samples to interpret and compare their ELISA and LC-MS/MS detection results. The study provides guidance to utilities on how to obtain more accurate cyanotoxin monitoring results and better understand the discrepancy between the two methods.

Doses of sacubitril/valsartan (Sac/Val) achieved in clinical trials of heart failure with reduced ejection fraction (HFrEF) are often not reached in clinical practice.The purpose of this study was to investigate associations among Sac/Val doses and changes in prognostic biomarkers, health status, and cardiac remodeling among individuals with HFrEF through 12 months of treatment with Sac/Val administered per usual care.A total of 794 persons with HFrEF (ejection fraction [EF] ≤40%) were categorized according to average daily doses of Sac/Val divided into tertiles. Change from baseline to 12 months in biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin T, soluble ST2, atrial natriuretic peptide, urinary cyclic guanosine monophosphate), Kansas City Cardiomyopathy Questionnaire-23 scores, and parameters of cardiac reverse remodeling (left ventricular EF, indexed left atrial and ventricular volumes, and E/e') were assessed.The average daily dose was 112 mg in Tertile 1 (low dose), 342 mg in Tertile 2 (moderate dose), and 379 mg in Tertile 3 (high dose). Similar changes in prognostic biomarkers were observed in all dose tertiles. Gains in Kansas City Cardiomyopathy Questionnaire-23 scores were comparable regardless of dose category. Consistent reverse cardiac remodeling in all dose categories occurred; the median absolute left ventricular EF improvement across HF dose groups was 9.3%, 8.7%, and 10.2%, for low, moderate, and high doses, respectively; similar improvements in left atrial and ventricular volumes and E/e' were also observed across dose categories.Among patients with HFrEF, similar improvement in prognostic biomarkers, health status, and cardiac remodeling were observed across various Sac/Val doses. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183.

The carefully curated, small-scale world of literary manuscripts in institutions such as The British Library is far removed from the vast scale of government archives where documents are measured by the kilometers of shelf space they offer. The sheer scale of the surviving archives can mean that thousands of records remain in sacks for centuries, unsorted and unlisted. We might assume that the life-records gathered together for a figure such as Geoffrey Chaucer are fairly complete and that there are unlikely to be significant new documents. The discovery of the new Chaucer–Chaumpaigne documents presented in this issue demonstrates that there is more to be found among the vast collections of medieval legal material at The National Archives. Here we present two approaches to researching these complicated collections and demonstrate their potential for uncovering new life-records, literary and otherwise. In doing so, we present minor new life-records for Chaucer, Gower, and Skelton from recently accessioned material.

This article reviews the surviving evidence for the life of Cecily Chaumpaigne in light of the new discoveries relating to the litigation against her and Chaucer. Her father, William, had been a well-to-do merchant who was not simply a street baker but a dealer in corn. Her mother, Agnes, was aspirational and ambitious, and married after William’s death the wealthy saddler William Pickerel, who had been Edward III’s saddler. Cecily’s eldest brother, Robert, was a valet in the royal household at the same time as Chaucer was an esquire there. He also sought unsuccessfully to take over the saddlery business of his stepfather and mother, but quickly ran into financial difficulties. Much of our understanding of Chaumpaigne is defined by the surviving information about her family, but some facts are clear. She came from a well-to-do, perhaps even prosperous background. At the time of Staundon’s threatened prosecution, she was a mature woman in her early thirties and apparently still single.

Rationale: Individuals with Chronic Obstructive Pulmonary Disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. Objectives:...

RATIONALE: Individuals with chronic obstructive pulmonary disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. OBJECTIVES: Examine the impact of depressive symptoms compared with FEV(1)% on COPD morbidity. METHODS: Using longitudinal data from individuals with COPD in the Subpopulations and Intermediate Outcome Measures in COPD Study, longitudinal growth analysis was performed to assess COPD morbidity by assessing differences in baseline 6-minute walk distance and patient reported outcomes (PROs) and their rate of change over time explained by depressive symptoms or lung function, as measured by Hospital Anxiety and Depression Scale or FEV(1)% respectively. PROs consisted of in-person completion of St. George's Respiratory Questionnaire, COPD Assessment Test, Functional Assessment of Chronic Illness Therapy Fatigue, and Modified Medical Research Council Dyspnea Scale measures. RESULTS: Of the individuals analyzed (n = 1,830), 43% were female, 81% Caucasian with mean ± SD age of 65.1 ± 8.1, and 52.7 ± 27.5 pack-years smoking. Mean ± SD FEV(1)% was 60.9 ± 23.0% and 20% had clinically significant depressive symptoms. Adjusted models showed higher Hospital Anxiety and Depression Scale scores and lower FEV(1)% each were associated with worse PROs at baseline (P ⩽ 0.001). Depression accounted for more baseline variance in St. George's Respiratory Questionnaire, COPD Assessment Test, and Functional Assessment of Chronic Illness Therapy Fatigue than FEV(1)%, explaining 30–67% of heterogeneity. FEV(1)% accounted for more baseline variance in Modified Medical Research Council Dyspnea Scale and 6-minute walk distance than depression, explaining 16–32% of heterogeneity. Depressive symptoms accounted for 3–17% variance in change over time in PROs. In contrast, FEV(1)% accounted for 1–4% variance over time in PROs. CONCLUSIONS: Depression is more strongly associated with many PROs at baseline and their change over time compared with FEV(1)%. Recognizing and incorporating the impact of depressive symptoms into individualized care may improve COPD outcomes.

Newly emerging infectious diseases (EIDs), like the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, are becoming increasingly common. Due to geographic, political, social, behavioral, and genomic differences, some populations are more vulnerable to infectious disease spread than others. The purpose of this article is to present a framework for research and practice response to emergent infectious diseases that addresses multiple transdisciplinary actions to limit exposure or mitigate adverse outcomes for individuals and communities. Recent experience with new strains of emergent infectious diseases reinforces the importance of intervening at multiple levels, from genomics to political messaging to create multipronged, transdisciplinary interventions to contain the threat. In particular, incorporation of genomics into public health nursing practice of infectious diseases management can enhance existing regional-, community-, and individual-level health promotion and protection efforts, thus impacting long-term health outcomes.

Elucidating the mechanism of action of an antifungal or cytotoxic compound is a time-consuming process. Yeast chemogenomic profiling provides a compelling solution to the problem but is experimentally complex. Here, we demonstrate the use of a highly simplified yeast chemical genetic assay comprising just 89 yeast deletion strains, each diagnostic for a specific mechanism of action. We use the assay to investigate the mechanism of action of two antifungal chalcone compounds, trans-chalcone and 4'-hydroxychalcone, and narrow down the mechanism to transcriptional stress. Crucially, the assay eliminates mechanisms of action such as topoisomerase I inhibition and membrane disruption that have been suggested for related chalcone compounds. We propose this simplified assay as a useful tool to rapidly identify common off-target mechanisms.

Mutations enhancing the kinase activity of LRRK2 cause Parkinson’s disease (PD) and therapies that reduce LRRK2 kinase activity are being tested in clinical trials. Numerous rare variants of unknown clinical significance have been reported, but how the vast majority impact on LRRK2 function is unknown. Here, we investigate 100 LRRK2 variants linked to PD, including previously described pathogenic mutations. We identify 23 LRRK2 variants that robustly stimulate kinase activity, including variants within the N-terminal non-catalytic regions [ARM (E334K, A419V), ANK(R767H), LRR (R1067Q, R1325Q)], as well as variants predicted to destabilise the ROC:CORB interface [ROC (A1442P, V1447M), CORA (R1628P) CORB (S1761R, L1795F)] and COR:COR dimer interface [CORB (R1728H/L)]. Most activating variants decrease LRRK2 biomarker site phosphorylation (pSer935/pSer955/pSer973), consistent with the notion that the active kinase conformation blocks their phosphorylation. We conclude that the impact of variants on kinase activity is best evaluated by deploying a cellular assay of LRRK2-dependent Rab10 substrate phosphorylation, compared to a biochemical kinase assay, as only a minority of activating variants [CORB (Y1699C, R1728H/L, S1761R) and kinase (G2019S, I2020T, T2031S)], enhance in vitro kinase activity of immunoprecipitated LRRK2. Twelve variants including several that activate LRRK2 and have been linked to PD, suppressed microtubule association in the presence of a Type I kinase inhibitor [ARM(M712V), LRR(R1320S), ROC (A1442P, K1468E, S1508R), CORA(A1589S), CORB (Y1699C, R1728H/L) and WD40(R2143M, S2350I, G2385R)]. Our findings will stimulate work to better understand the mechanisms by which variants impact biology and provide rationale for variant carrier inclusion or exclusion in ongoing and future LRRK2 inhibitor clinical trials.