Search

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or Long COVID) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIHs REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

BackgroundWith large volumes of longitudinal data in electronic medical records from diverse patients, primary care is primed for disruption by artificial intelligence (AI) technology. With AI applications in primary care still at an early stage in Canada and most countries, there is a unique opportunity to engage key stakeholders in exploring how AI would be used and what implementation would look like.ObjectiveTo identify the barriers that patients, providers, and health leaders perceive in relation to implementing AI in primary care and strategies to overcome them.Design12 virtual deliberative dialogues. Dialogue data were thematically analyzed using a combination of rapid ethnographic assessment and interpretive description techniques.SettingVirtual sessions.ParticipantsParticipants from eight provinces in Canada, including 22 primary care service users, 21 interprofessional providers, and 5 health system leaders.ResultsThe barriers that emerged from the deliberative dialogue sessions were grouped into four themes: (1) system and data readiness, (2) the potential for bias and inequity, (3) the regulation of AI and big data, and (4) the importance of people as technology enablers. Strategies to overcome the barriers in each of these themes were highlighted, where participatory co-design and iterative implementation were voiced most strongly by participants.LimitationsOnly five health system leaders were included in the study and no self-identifying Indigenous people. This is a limitation as both groups may have provided unique perspectives to the study objective.ConclusionsThese findings provide insight into the barriers and facilitators associated with implementing AI in primary care settings from different perspectives. This will be vital as decisions regarding the future of AI in this space is shaped.

BackgroundNowadays, metabolic syndrome has become a major health threat, and affects over one billion people globally. It also plays a great role in the growth of diseases like type 2 diabetes, coronary diseases, stroke, and other chronicity. It increases the risk of cardiovascular disorder and stroke by three to ten times and diabetic mellitus by ten times. The prevalence of metabolic syndrome is increasing globally as a result of epidemiological shift. Low and middle-income countries are facing an increasing burden of metabolic syndrome. There is a need for concerted efforts to modify behavioral risk factors that significantly contribute to the prevalence of the syndrome. This can be done by developing and implementing appropriate interventions that can bring behavior change after testing for effectiveness, feasibility, and acceptability. Thus, this study aims to develop and test the effectiveness, feasibility and acceptability of an education intervention promoting healthy lifestyle to reduce risk factors for metabolic syndrome, among office workers in Ethiopia.Methods and analysisThis randomized controlled trial will be implemented with 226 bank employees (age ≥18 years) with metabolic syndrome from government and private banks in Bahir Dar City, Ethiopia. Participants will be randomized to intervention (education) and control (general health advice) groups. The intervention group will be given one-on -one base education about healthy diets, physical exercise, stress management, avoidance of harmful alcohol consumption and smoking cessation by experts on health promotion. Text messages will be sent every two weeks and reading materials will also be provided. Additionally, a review meeting will be held at the 3rd and 6th month of the intervention. The primary outcomes of interest will be change in metabolic parameters (obesity levels, blood pressure, fasting blood glucose, total cholesterol, high density lipoprotein, low density lipoprotein, and triglycerides). Secondary outcomes will be knowledge, attitudes and practice of the participants towards lifestyle and cardiovascular risk factors, feasibility, acceptability, implementation fidelity, and cost-effectiveness of the intervention. Data will be collected at three time points: at baseline, at the 6th month of the intervention and at the end of the intervention (9 months). Generalized linear mixed models will be utilized to compare the desired outcome between the trial arms, after accounting for baseline variations. Cost-benefit analysis and a qualitative process evaluation of the intervention will also be conducted.DiscussionThis randomized control trial study will provide information on the effectiveness, feasibility, and acceptability of an education intervention promoting healthy lifestyle to reduce risk factors for metabolic syndrome, among office workers in Ethiopia, where the burden of metabolic syndrome is high among office workers.Clinical trial registrationThis trial has been prospectively registered at the Australian New Zealand Clinical Trials Registry: ACTRN12623000409673p.

IntroductionThe World Health Organization (WHO) called for the expansion of all nursing roles, including advanced practice nurses (APNs), nurse practitioners (NPs) and clinical nurse specialists (CNSs). A clearer understanding of the impact of these roles will inform global priorities for advanced practice nursing education, research, and policy.ObjectiveTo identify gaps in advanced practice nursing research globally.Materials and methodsA review of systematic reviews was conducted. We searched CINAHL, Embase, Global Health, Healthstar, PubMed, Medline, Cochrane Library, DARE, Joanna Briggs Institute EBP, and Web of Science from January 2011 onwards, with no restrictions on jurisdiction or language. Grey literature and hand searches of reference lists were undertaken. Review quality was assessed using the Critical Appraisal Skills Program (CASP). Study selection, data extraction and CASP assessments were done independently by two reviewers. We extracted study characteristics, country and outcome data. Data were summarized using narrative synthesis.ResultsWe screened 5840 articles and retained 117 systematic reviews, representing 38 countries. Most CASP criteria were met. However, study selection by two reviewers was done inconsistently and language and geographical restrictions were applied. We found highly consistent evidence that APN, NP and CNS care was equal or superior to the comparator (e.g., physicians) for 29 indicator categories across a wide range of clinical settings, patient populations and acuity levels. Mixed findings were noted for quality of life, consultations, costs, emergency room visits, and health care service delivery where some studies favoured the control groups. No indicator consistently favoured the control group. There is emerging research related to Artificial Intelligence (AI).ConclusionThere is a large body of advanced practice nursing research globally, but several WHO regions are underrepresented. Identified research gaps include AI, interprofessional team functioning, workload, and patients and families as partners in healthcare.Prospero registration numberCRD42021278532.

IntroductionSerological surveys of the prevalence of SARS-CoV-2 are instrumental to understanding the course of the COVID-19 epidemic. We evaluate the seroprevalence of SARS-CoV-2 among young adult Finnish females residing in 25 communities all over Finland from 2020 until 2022.MethodsBetween 1st March 2020 and 30th June 2022, 3589 blood samples were collected from 3583 women born in 1992-95 when aged 25 or 28 years old attending the follow-up of an ongoing population-based trial of cervical screening strategies. The crude and population standardized SARS-CoV-2 seroprevalence was measured using nucleocapsid (induced by infection) and spike wild-type (WT) protein (induced both by infection and by vaccination) antigens over time and stratified by place of residence (inside or outside the Helsinki metropolitan region).ResultsDuring 2020 (before vaccinations), spike-WT and nucleocapsid IgG antibodies followed each other closely, at very low levels (ConclusionsLow SARS-CoV-2 infection-related seroprevalence during 2020-2021 suggest a comparatively successful infection control. Antibodies to the SARS-CoV-2 WT spike protein became extremely common among young women by the end of 2021, in line with the high uptake of SARS-CoV-2 vaccination. Finally, the rapid increase of seroprevalences to the SARS-CoV-2 nucleocapsid protein during the first and second quartile of 2022, imply a high incidence of infections with SARS-CoV-2 variants able to escape vaccine-induced protection.

BackgroundSince the early 2000s, there have been marked trends in adolescent health and wellbeing indicators across Europe, North America and Australia. In particular, there have been substantial declines in youth drinking. We know little about how these trends are underpinned by co-occurring indicators within individuals. This paper aims to analyse change over time in how indicators cluster within individuals and differences in these patterns between five countries with different trends in youth drinking.MethodsWe analysed four waves of repeat cross-sectional survey data from 15-year-olds in England (n = 5942), Italy (n = 5234), the Netherlands (n = 5408), Hungary (n = 5274), and Finland (n = 7446), which were included in the Health Behaviours in School-aged Children (HBSC) study between 2001/02 and 2013/14. We defined clusters of individuals using multigroup latent class analyses which accounts for change over time. The class indicators included health behaviours, attitudes, wellbeing and relationships. We modelled associations between class membership, sex, and family affluence over time.ResultsWe identified four classes in all countries: Overall unhealthy, Overall healthy, Moderately healthy and Substance abstainers with behaviour risk indicators. The proportion of adolescents in the Overall unhealthy class declined between 2001/02 and 2013/14 by between 22.8 percentage points (pp) in England and 3.2pp in Italy. The extent to which indicators of health and wellbeing changed as linked clusters differed across countries, but changes in alcohol consumption, smoking, drug use and sexual activity were typically concurrent. Adolescents with low family affluence were more likely to be in the Overall unhealthy class in all years.ConclusionsImprovements in indicators of adolescent health and well-being are due mainly to concurrent declines in drinking, smoking, sexual activity, and cannabis use, but these declines are not consistently associated with improvements in other domains. They have also not led to reductions in inequalities in indicators of health and well-being.

Forest ecosystems store large amounts of carbon and can be important sources, or sinks, of the atmospheric carbon dioxide that is contributing to global warming. Understanding the carbon storage potential of different forests and their response to management and disturbance events are fundamental to developing policies and scenarios to partially offset greenhouse gas emissions. Projections of live tree carbon accumulation are handled differently in different models, with inconsistent results. We developed growth-and-yield style models to predict stand-level live tree carbon density as a function of stand age in all vegetation types of the coastal Pacific region, US (California, Oregon, and Washington), from 7,523 national forest inventory plots. We incorporated site productivity and stockability within the Chapman-Richards equation and tested whether intensively managed private forests behaved differently from less managed public forests. We found that the best models incorporated stockability in the equation term controlling stand carrying capacity, and site productivity in the equation terms controlling the growth rate and shape of the curve. RMSEs ranged from 10 to 137 Mg C/ha for different vegetation types. There was not a significant effect of ownership over the standard industrial rotation length (~50 yrs) for the productive Douglas-fir/western hemlock zone, indicating that differences in stockability and productivity captured much of the variation attributed to management intensity. Our models suggest that doubling the rotation length on these intensively managed lands from 35 to 70 years would result in 2.35 times more live tree carbon stored on the landscape. These findings are at odds with some studies that have projected higher carbon densities with stand age for the same vegetation types, and have not found an increase in yields (on an annual basis) with longer rotations. We suspect that differences are primarily due to the application of yield curves developed from fully-stocked, undisturbed, single-species, "normal" stands without accounting for the substantial proportion of forests that don't meet those assumptions. The carbon accumulation curves developed here can be applied directly in growth-and-yield style projection models, and used to validate the predictions of ecophysiological, cohort, or single-tree style models being used to project carbon futures for forests in the region. Our approach may prove useful for developing robust models in other forest types.

Emerging technologies focused on the detection and quantification of circulating tumor DNA (ctDNA) in blood show extensive potential for managing patient treatment decisions, informing risk of recurrence, and predicting response to therapy. Currently available tissue-informed approaches are often limited by the need for additional sequencing of normal tissue or peripheral mononuclear cells to identify non-tumor-derived alterations while tissue-naïve approaches are often limited in sensitivity. Here we present the analytical validation for a novel ctDNA monitoring assay, FoundationOne®Tracker. The assay utilizes somatic alterations from comprehensive genomic profiling (CGP) of tumor tissue. A novel algorithm identifies monitorable alterations with a high probability of being somatic and computationally filters non-tumor-derived alterations such as germline or clonal hematopoiesis variants without the need for sequencing of additional samples. Monitorable alterations identified from tissue CGP are then quantified in blood using a multiplex polymerase chain reaction assay based on the validated SignateraTM assay. The analytical specificity of the plasma workflow is shown to be 99.6% at the sample level. Analytical sensitivity is shown to be >97.3% at ≥5 mean tumor molecules per mL of plasma (MTM/mL) when tested with the most conservative configuration using only two monitorable alterations. The assay also demonstrates high analytical accuracy when compared to liquid biopsy-based CGP as well as high qualitative (measured 100% PPA) and quantitative precision (

BackgroundAccurate estimates of the COVID-19 pandemic's indirect impacts are crucial, especially in low- and middle-income countries. This study aims to update estimates of excess maternal deaths in Brazil during the first two years of the COVID-19 pandemic.MethodsThis was an exploratory mixed ecological study using the counterfactual approach. The observed maternal deaths were gathered from the Mortality Information System (SIM) for the period between March 2015 and February 2022. Expected deaths from March 2020 to February 2022 were estimated using quasipoisson generalized additive models, considering quadrimester, age group, and their interaction as predictor variables. Analyses were performed in R version 4.1.2, RStudio, version 2023.03.1+446 and carried out with support from the "mgcv" and "plot_model" libraries.ResultsA total of 5,040 maternal deaths were reported, with varying excess mortality across regions and age groups, resulting in 69% excess maternal mortality throughout Brazil during the first two years of the pandemic. The Southeast region had 50% excess mortality throughout the first two years and 76% excess in the second year. The North region had 69% excess mortality, increasing in the second year, particularly among women aged 20-34. The Northeast region showed 80% excess mortality, with a significant increase in the second year, especially among women aged 35-49. The Central-West region had 75% excess mortality, higher in the second year and statistically significant among women aged 35-49. The South region showed 117% excess mortality, reaching 203% in the second year among women aged 20-34, but no excess mortality in the 10-19 age category.ConclusionsOver two years, Brazil saw a significant impact on maternal excess deaths, regardless of region and pandemic year. The highest peak occurred between March and June 2021, emphasizing the importance of timely and effective epidemic responses to prevent avoidable deaths and prepare for new crises.

Patients with diabetic foot ulcers have poor adherence to treatment recommendations. However, the most effective way to support adherence in this population is unknown. This study aimed to assess the preliminary effectiveness of a motivation communication training programme for healthcare professionals working with these patients, using theory and evidence-based strategies.A proof-of-concept study using a non-randomised, controlled before-and-after design. Six podiatrists took part in the motivation communication training programme. Pre-training, observation was undertaken to examine the communication style currently used by podiatrists in routine consultations. Patients' (n = 25) perceptions of podiatrist autonomy support, self-determination for limiting weight-bearing activity and average daily step count were also assessed. Post training, observations and patient measures were repeated with a different group of patients (n = 24). Observations indicated that podiatrists exhibited a more need-supportive communication style (e.g., taking time to understand patients' perspectives) after undergoing the training programme. Patients in the post-training group reported higher levels of autonomy support, while self-determination to limit weight-bearing activity remained unchanged. Although the post-training group had a lower average daily step count, the difference was not statistically significant. This is the first study to investigate implementation of motivation communication strategies in routine consultations with patients with diabetic foot ulcers. Results suggest that training can enhance healthcare professionals' motivation communication skills with potential for addressing adherence issues, however, a larger cluster randomised controlled trial is necessary to confirm this.

Eutrophic conditions in estuaries are a globally important stressor to coastal ecosystems and have been suggested as a driver of coastal salt marsh loss. Potential mechanisms in marshes include disturbance caused by macroalgae accumulations, enhanced soil sulfide levels linked to high labile carbon inputs, accelerated decomposition, and declines in belowground biomass that contribute to edge instability, erosion, and slumping. However, results of fertilization studies have been mixed, and it is unclear the extent to which local environmental conditions, such as soil composition and nutrient profiles, help shape the response of salt marshes to nutrient exposure. In this study, we characterized belowground productivity and decomposition, organic matter mineralization rates, soil respiration, microbial biomass, soil humification, carbon and nitrogen inventories, nitrogen isotope ratios, and porewater profiles at high and low marsh elevations across eight marshes in four estuaries in California and New York that have strong contrasts in nutrient inputs. The higher nutrient load marshes were characterized by faster carbon turnover, with higher belowground production and decomposition and greater carbon dioxide efflux than lower nutrient load marshes. These patterns were robust across marshes of the Atlantic and Pacific coasts that varied in plant species composition, soil flooding patterns, and soil texture. Although impacts of eutrophic conditions on carbon cycling appeared clear, it was ambiguous whether high nutrient loads are causing negative effects on long-term marsh sustainability in terms of studied metrics. While high nutrient exposure marshes had high rates of decomposition and soil respiration rates, high nutrient exposure was also associated with increased belowground production, and reduced levels of sulfides, which should lead to greater marsh sustainability. While this study does not resolve the extent to which nutrient loads are negatively affecting these salt marshes, we do highlight functional differences between Atlantic and Pacific wetlands which may be useful for understanding coastal marsh health and integrity.

Two mRNA vaccines (BNT162b2 and mRNA-1273) against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) are globally authorized as a two-dose regimen. Understanding the magnitude and duration of protective immune responses is vital to curbing the pandemic. We enrolled 461 high-risk health services workers at the University of California, Los Angeles (UCLA) and first responders in the Los Angeles County Fire Department (LACoFD) to assess the humoral responses in previously infected (PI) and infection naïve (NPI) individuals to mRNA-based vaccines (BNT162b2/Pfizer- BioNTech or mRNA-1273/Moderna). A chemiluminescent microparticle immunoassay was used to detect antibodies against SARS-CoV-2 Spike in vaccinees prior to (n = 21) and following each vaccine dose (n = 246 following dose 1 and n = 315 following dose 2), and at days 31-60 (n = 110) and 61-90 (n = 190) following completion of the 2-dose series. Both vaccines induced robust antibody responses in all immunocompetent individuals. Previously infected individuals achieved higher median peak titers (p = 0.002) and had a slower rate of decay (p = 0.047) than infection-naïve individuals. mRNA-1273 vaccinated infection-naïve individuals demonstrated modestly higher titers following each dose (p = 0.005 and p = 0.029, respectively) and slower rates of antibody decay (p = 0.003) than those who received BNT162b2. A subset of previously infected individuals (25%) required both doses in order to reach peak antibody titers. The biologic significance of the differences between previously infected individuals and between the mRNA-1273 and BNT162b2 vaccines remains uncertain, but may have important implications for booster strategies.

Glottal insufficiency due to vocal fold paralysis, paresis, or atrophy often leads to degraded voice quality. One of the primary surgical intervention procedures to treat glottal insufficiency is medialization laryngoplasty, in which an implant is inserted through a lateral window on the thyroid cartilage to medialize the vocal folds. While the goal of medialization is to modify the vocal fold structure to restore normal phonation, few studies have attempted to quantify such structural changes of the vocal folds. The goal of this study is to quantify the three-dimensional structural changes of the vocal folds due to implant insertion in medialization laryngoplasty, and evaluate its potential effect on voice production. Medialization laryngoplasty were performed in excised human larynges using implants of different stiffness. Magnetic resonance images of the larynges were obtained with and without implant insertion. The results showed that implant insertion significantly changed the original body-cover structure of the vocal folds, with the implant taking over the large space used to be occupied by the original body layer and the vocal fold being stretched into a thin layer wrapped around the implant. The medial-lateral dimension of the vocal fold was significantly reduced from about 4 mm to 1 mm, and the vocal fold was stretched in the coronal plane by about 70%. It is hypothesized that use of implants with stiffness comparable to that of the vocal folds is beneficial because the degree of medialization can be adjusted without much negative effects on phonation frequency, phonation threshold pressure, or vibration amplitude.

Self-control underlies goal-directed behaviour in humans and other animals. Delayed gratification - a measure of self-control - requires the ability to tolerate delays and/or invest more effort to obtain a reward of higher value over one of lower value, such as food or mates. Social context, in particular, the presence of competitors, may influence delayed gratification. We adapted the 'rotating-tray' paradigm, where subjects need to forgo an immediate, lower-quality (i.e. less preferred) reward for a delayed, higher-quality (i.e. more preferred) one, to test social influences on delayed gratification in two corvid species: New Caledonian crows and Eurasian jays. We compared choices for immediate vs. delayed rewards while alone, in the presence of a competitive conspecific and in the presence of a non-competitive conspecific. We predicted that, given the increased risk of losing a reward with a competitor present, both species would similarly, flexibly alter their choices in the presence of a conspecific compared to when alone. We found that species differed: jays were more likely to select the immediate, less preferred reward than the crows. We also found that jays were more likely to select the immediate, less preferred reward when a competitor or non-competitor was present than when alone, or when a competitor was present compared to a non-competitor, while the crows selected the delayed, highly preferred reward irrespective of social presence. We discuss our findings in relation to species differences in socio-ecological factors related to adult sociality and food-caching (storing). New Caledonian crows are more socially tolerant and moderate cachers, while Eurasian jays are highly territorial and intense cachers that may have evolved under the social context of cache pilfering and cache protection strategies. Therefore, flexibility (or inflexibility) in delay of gratification under different social contexts may relate to the species' social tolerance and related risk of competition.

BackgroundPeople with radiographic evidence for pulmonary tuberculosis (TB), but negative sputum cultures, have increased risk of developing culture-positive TB. Recent expansion of X-ray screening is leading to increased identification of this group. We set out to synthesise the evidence for treatment to prevent progression to culture-positive disease.MethodsWe conducted a systematic review and meta-analysis. We searched for prospective trials evaluating the efficacy of TB regimens against placebo, observation, or alternative regimens, for the treatment of adults and children with radiographic evidence of TB but culture-negative respiratory samples. Databases were searched up to 18 Oct 2022. Study quality was assessed using ROB 2·0 and ROBINS-I. The primary outcome was progression to culture-positive TB. Meta-analysis with a random effects model was conducted to estimate pooled efficacy. This study was registered with PROSPERO (CRD42021248486).FindingsWe included 13 trials (32,568 individuals) conducted between 1955 and 2018. Radiographic and bacteriological criteria for inclusion varied. 19·1% to 57·9% of participants with active x-ray changes and no treatment progressed to culture-positive disease. Progression was reduced with any treatment (6 studies, risk ratio [RR] 0·27, 95%CI 0·13-0·56), although multi-drug TB treatment (RR 0·11, 95%CI 0·05-0·23) was significantly more effective than isoniazid treatment (RR 0·63, 95%CI 0·35-1·13) (p = 0·0002).InterpretationMulti-drug regimens were associated with significantly reduced risk of progression to TB disease for individuals with radiographically apparent, but culture-negative TB. However, most studies were old, conducted prior to the HIV epidemic and with outdated regimens. New clinical trials are required to identify the optimal treatment approach.

Mesoscale oceanographic features, including eddies, have the potential to alter productivity and other biogeochemical rates in the ocean. Here, we examine the microbiome of a cyclonic, Gulf Stream frontal eddy, with a distinct origin and environmental parameters compared to surrounding waters, in order to better understand the processes dominating microbial community assembly in the dynamic coastal ocean. Our microbiome-based approach identified the eddy as distinct from the surround Gulf Stream waters. The eddy-associated microbial community occupied a larger area than identified by temperature and salinity alone, increasing the predicted extent of eddy-associated biogeochemical processes. While the eddy formed on the continental shelf, after two weeks both environmental parameters and microbiome composition of the eddy were most similar to the Gulf Stream, suggesting the effect of environmental filtering on community assembly or physical mixing with adjacent Gulf Stream waters. In spite of the potential for eddy-driven upwelling to introduce nutrients and stimulate primary production, eddy surface waters exhibit lower chlorophyll a along with a distinct and less even microbial community, compared to the Gulf Stream. At the population level, the eddy microbiome exhibited differences among the cyanobacteria (e.g. lower Trichodesmium and higher Prochlorococcus) and in the heterotrophic alpha Proteobacteria (e.g. lower relative abundances of specific SAR11 phylotypes) versus the Gulf Stream. However, better delineation of the relative roles of processes driving eddy community assembly will likely require following the eddy and surrounding waters since inception. Additionally, sampling throughout the water column could better clarify the contribution of these mesoscale features to primary production and carbon export in the oceans.

The person-centered care movement has influenced hospitals to make patient and family engagement (PE) an explicit commitment in their strategic plans. This is often reflected in mission, vision, and value (MVV) statements, which are organizational artifacts intended to influence the attitudes, beliefs, and actions of hospital teams and employees because of their saliency in organizational documents and communications. Previous research has found that organizational goals for PE, like those articulated in MVV statements, can lead to effective and meaningful PE. However, a deeper understanding of how and under which circumstances MVV statements encourage and promote PE practices is needed. A scoping review was conducted to understand the connection between hospital PE goals (such as MVV statements) and PE processes and practices. The research question was: what is known about how hospital MVV statements relate to PE processes and activities? Following Arksey and O'Malley's scoping review approach, 27 articles were identified as relevant to the research question. These articles revealed five strategies that help realize hospital PE goals: communicating organizational goals; aligning documents that convey organizational goals; aligning organizational processes to support PE; providing employees with resources and support; and motivating and empowering employees to integrate PE into their work. We discuss the implications of misalignment between hospital goals and practices, which reduce team and individual motivation toward hospital PE goals.

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson's Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients.

Background Non-medical health-related social needs (social needs) are major contributors to worse health outcomes and may have an adverse impact on cardiovascular risk factors and cardiovascular disease. The present study evaluated the effect of a closed-loop community-based pathway in reducing social needs among Black men in a lifestyle change program. Methods Black men (n = 70) from a large Midwestern city participated in Black Impact, a 24-week community-based team lifestyle change single-arm pilot trial adapted from the Diabetes Prevention Program and American Heart Association’s (AHA) Check, Change, Control Blood Pressure Self-Management Program, which incorporates AHA’s Life’s Simple 7 (LS7) framework. Participants were screened using the Centers for Medicare and Medicaid Services (CMS) Accountable Health Communities Health-Related Social Needs Screening Tool. Participants with affirmative responses were referred to a community hub pathway to address social needs. The primary outcome for this analysis is change in social needs based on the CMS social needs survey at 12 and 24 weeks using mixed effect logistic regressions with random intercepts for each participant. Change in a LS7 score (range 0–14) from baseline to 12 and 24 weeks was evaluated using a linear mixed-effects model stratified by baseline social needs. Results Among 70 participants, the mean age of participants was 52 ±10.5 years. The men were sociodemographically diverse, with annual income ranging from Conclusions The Black Impact lifestyle change single-arm pilot program showed that a referral to a closed-loop community-based hub reduced social needs in Black men. We found no association of social needs with baseline or change in LS7 scores. Further evaluation of community-based strategies to advance the attainment of LS7 and address social needs among Black men in larger trials is warranted.

IntroductionIn low-resource settings, midwives are the first contact for women with preeclampsia and lead the coordination of care. Unfavourable preeclampsia outcomes create a burden for women, families, and the health system. It is therefore important to understand the unique context of midwives' practice and the complex factors that influence the delivery of maternal healthcare.AimThis qualitative study explored the perspectives of key stakeholders in a tertiary hospital in Ghana regarding the facilitators and barriers influencing midwives' provision of preeclampsia care using a socioecological model.MethodsSemi-structured interviews were conducted with 42 participants comprising senior managers (n = 7) and hospital midwives (n = 35) in 2021. Thematic analysis used Braun and Clarke's six-step method, and the findings were organised within four levels of the socioecological model: individual, interpersonal, organisational, and public policy.ResultsTwo main themes were identified: 1) Facilitators of preeclampsia management, and 2) Barriers to preeclampsia management. Facilitators were identified at three levels (individual, interpersonal, and organisational) and included midwives' knowledge of preeclampsia; midwives' self-efficacy; midwives' skillset to enhance preeclampsia care; collaborative practice; and strategies for preeclampsia care quality improvement. At the individual level, the barriers were inadequate pre-service preparation, lack of evidence-based midwifery care, and colleagues' work attitudes. Hierarchical decision-making and staff views of women's risk perceptions were identified as barriers at the interpersonal level. At the organisational level, the barriers were: scarce resources and staff shortages, and a lack of midwifery-specific guidelines. Two barriers were identified within the public policy level: the high cost of preeclampsia care and issues with the referral system.ConclusionMulti-faceted factors play a significant role in midwives' management of preeclampsia. Hence context-specific multi-level interventions have the potential to improve the quality-of-care women in Ghana receive.

Males are around three times more likely to possess an autism diagnosis than females. For years this was explained by accounts that considered the male gender more compatible with the autistic phenotype. However, new research suggests that a lack of understanding and recognition of the female autistic phenotype, and a predisposition to associate males with autistic traits, could lead to structural inequalities that hinder the identification of autistic females. To explore how autism and gender are more widely perceived, the present study tested implicit and explicit associations between autism and binary gender using the Implicit Association Test (IAT) and the Autism Quotient (AQ) presented alongside a male or female vignette. A significant association was found on the IAT, identifying an implicit bias towards males and autistic traits. The vignette AQ pairing also revealed some specific items perceived as explicitly male traits, while only reverse-scored items were perceived as female. These findings suggest that current perceptions and even metrics of autism are skewed towards males, which may hinder the identification and understanding of the female autistic phenotype.

The lack of information regarding biodiversity status hampers designing and implementing conservation strategies and achieving future targets. Northern Pakistan consists of a unique ecoregion mosaic which supports a myriad of environmental niches for anuran diversity in comparison to the deserts and xeric shrublands throughout the rest of the country. In order to study the niche suitability, species overlap and distribution patterns in Pakistan, we collected observational data for nine anuran species across several distinct ecoregions by surveying 87 randomly selected locations from 2016 to 2018 in Rawalpindi District and Islamabad Capital Territory. Our model showed that the precipitation of the warmest and coldest quarter, distance to rivers and vegetation were the greatest drivers of anuran distribution, expectedly indicating that the presence of humid forests and proximity to waterways greatly influences the habitable range of anurans in Pakistan. Sympatric overlap between species occurred at significantly higher density in tropical and subtropical coniferous forests than in other ecoregion types. We found species such as Minervarya spp., Hoplobatrachus tigerinus and Euphlyctis spp. preferred the lowlands in proximal, central and southern parts of the study area proximal to urban settlements, with little vegetation and higher average temperatures. Duttaphrynus bengalensis and D. stomaticus had scattered distributions throughout the study area with no clear preference for elevation. Sphaerotheca pashchima was patchily distributed in the midwestern extent of the study area as well as the foothills to the north. Microhyla nilphamariensis was widely distributed throughout the study area with a preference for both lowlands and montane terrain. Endemic frogs (Nanorana vicina and Allopaa hazarensis) were observed only in locations with higher elevations, higher density of streams and lower average temperatures as compared to the other seven species sampled. It is recommended to provide legal protection to amphibians of Pakistan, especially endemic species, through revision in the existing wildlife laws. We suggest studying the effectiveness of existing amphibian tunnels and corridors or designing new ones tailored to the needs of our species to prevent their local extinction due to ongoing or proposed urban development which might affect their dispersal and colonization.

BackgroundEarly intervention alcohol and drug (AOD) programs for disadvantaged young people have the potential to substantially decrease the need for future intervention, however there is little research about how young people use these programs or the substance use and other outcomes of such programs. This paper uses data from an Australian AOD early intervention program, The Street Universities, to: describe young people's participation; examine changes in substance use and wellbeing over 90 days; and assess which young people are most positively impacted.MethodsData come from a prospective study of new attendees, measuring retention in and attendance patterns in an 'engagement' program focussed on arts and lifestyle activities (n = 95), and a routine service dataset collected from seven years of therapeutic intervention (n = 3,893), measuring substance dependence (SDS), psychological distress (K10) and quality of life (EQoL).ResultsAnalysis reveals that young people were retained in the program at high proportion (63% at six months) and more than half of these returned at a frequency of weekly or more often. Young people participating in the therapeutic component of the program reported significant improvements in all key wellbeing indicators with SDS, K10 and EQoL scores significantly improving (at p < .001). These improvements occurred rapidly, within the first 30 days, and were maintained over the 90 day study period. Moreover, young people with the highest SDS and K10 scores and lowest quality of life at baseline experienced the most positive changes.ConclusionAligning engagement program with therapeutic intervention can provide comprehensive support to disadvantaged young people, producing substantial improvements in AOD use, distress and wellbeing.

BackgroundChoose to Move (CTM), an effective health-promoting intervention for older adults, was scaled-up across British Columbia, Canada. Adaptations that enable implementation at scale may lead to 'voltage drop'-diminished positive effects of the intervention. For CTM Phase 3 we assessed: i. implementation; ii. impact on physical activity, mobility, social isolation, loneliness and health-related quality of life (impact outcomes); iii. whether intervention effects were maintained; iv) voltage drop, compared with previous CTM phases.MethodsWe conducted a type 2 hybrid effectiveness-implementation pre-post study of CTM; older adult participants (n = 1012; mean age 72.9, SD = 6.3 years; 80.6% female) were recruited by community delivery partners. We assessed CTM implementation indicators and impact outcomes via survey at 0 (baseline), 3 (mid-intervention), 6 (end-intervention) and 18 (12-month follow-up) months. We fitted mixed-effects models to describe change in impact outcomes in younger (60-74 years) and older (≥ 75 years) participants. We quantified voltage drop as percent of effect size (change from baseline to 3- and 6-months) retained in Phase 3 compared with Phases 1-2.ResultsAdaptation did not compromise fidelity of CTM Phase 3 as program components were delivered as intended. PA increased during the first 3 months in younger (+1 days/week) and older (+0.9 days/week) participants (pConclusionBenefits of health-promoting interventions-like CTM-can be retained when implemented at broad scale. Diminished social isolation in Phase 3 reflects how CTM was adapted to enhance opportunities for older adults to socially connect. Thus, although intervention effects may be reduced at scale-up, voltage drop is not inevitable.

BackgroundMeasurement of SARS-CoV-2 antibody seropositivity is important to accurately understand exposure to infection and/or vaccination in specific populations. This study aimed to estimate the serologic response to SARS-CoV-2 virus infection and vaccination in children in Calgary, Alberta over a two-year period.MethodsChildren with or without prior SARS-CoV-2 infections, were enrolled in Calgary, Canada in 2020. Venous blood was sampled 4 times from July 2020 to April 2022 for SARS-CoV-2 nucleocapsid and spike antibodies. Demographic and clinical information was obtained including SARS-CoV-2 testing results and vaccination records.Results1035 children were enrolled and 88.9% completed all 4 visits; median age 9 years (IQR: 5,13); 519 (50.1%) female; and 815 (78.7%) Caucasian. Before enrolment, 118 (11.4%) had confirmed or probable SARS-CoV-2. By April 2022, 39.5% of previously uninfected participants had a SARS-CoV-2 infection. Nucleocapsid antibody seropositivity declined to 16.4% of all infected children after more than 200 days post diagnosis. Spike antibodies remained elevated in 93.6% of unvaccinated infected children after more than 200 days post diagnosis. By April 2022, 408 (95.6%) children 12 years and older had received 2 or more vaccine doses, and 241 (61.6%) 5 to 11 year-old children had received 2 vaccine doses. At that time, all 685 vaccinated children had spike antibodies, compared with 94/176 (53.4%) of unvaccinated children.ConclusionsIn our population, after the first peak of Omicron variant infections and introduction of COVID-19 vaccines for children, all vaccinated children, but just over one-half of unvaccinated children, had SARS-CoV-2 spike antibodies indicating infection and/or vaccination, highlighting the benefit of vaccination. It is not yet known whether a high proportion of seropositivity at the present time predicts sustained population-level protection against future SARS-CoV-2 transmission, infection or severe COVID-19 outcomes in children.

BackgroundResearch efforts in Rwanda to improve sexual and reproductive health and rights (SRHR) are increasing; however, comprehensive literature reviews on SRHR are limited. This scoping review examines individual and contextual factors shaping knowledge, attitudes, and practices in the domains of: 1) family planning, 2) abortion care, and 3) other SRHR in Rwanda. Recognizing that individual, community, and societal factors influence RH, this review is guided by Bronfenbrenner's Ecological Systems Theory.MethodsEligible studies were conducted in Rwanda, included males and/or females of any age, and were published within the past 20 years. Studies reporting views of only healthcare or other professionals were excluded.ResultsThirty-six studies were included. The majority addressed individual and contextual considerations. At the individual level, studies explored knowledge about SRHR problems while at the interpersonal level, the support and attitudes of men and community members for adolescent SRHR were investigated. In terms of healthcare organization, maternal health practices, increased access to family planning programs, and the need for sexually transmitted infection programs was explored. At the social and cultural level, researchers investigated beliefs and traditional gender roles. Regarding public health policy, studies mentioned promoting and increasing funding for SRHR and reducing gender inequities.ConclusionOur findings can inform SRHR research programs, public health campaigns, and policy advances in Rwanda.

BackgroundHuman papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the US, responsible for cervical cancer and increased risk of Human Immunodeficiency Virus (HIV) acquisition. Despite an effective HPV vaccine, women's HPV vaccination coverage and rates remain far below desired levels. This study aimed to evaluate HPV knowledge, attitudes, and vaccination practices as well as factors associated with HPV vaccination among women of reproductive age living in Miami, Florida, a Southern US city with a high incidence of STIs and low HPV vaccination coverage.MethodsFrom April to June 2022, 100 HIV-negative, cisgender, sexually active women aged 18-45 years were recruited from the Miami community. Participants completed validated questionnaires using REDCap© electronic surveys, assessing socio-demographics and sexual behaviors; HPV knowledge, screening, vaccination practices; barriers and motivators to HPV vaccination. A cumulative HPV knowledge score (HPV score) was generated. Factors associated with HPV vaccination were analyzed by Chi-square, Fisher's exact test, studentized t-test, and multivariate logistic regression (MLR).ResultsA total of 100 participants were enrolled, and 84 who knew their vaccination status were included in the analysis. Of these, 43 reported receiving at least 1 HPV vaccine dose (vaccinated group) and 41 reported never being vaccinated (unvaccinated group). Mean age was 24.7 (SD 4.03) years for the vaccinated group and 31.4 (SD 8.33) for the unvaccinated group. Mean HPV score was 18.9/29 (SD 6.05) for the vaccinated group and 9.1/29 (SD 8.82) for the unvaccinated group. Amongst vaccinated participants, 76.74% reported a history of HPV/Pap smear screening vs 87.80% in the unvaccinated group. Barriers to HPV vaccination included: 14.6% low-risk perception, 29.3% healthcare barriers, and 46.3% vaccine hesitancy and personal beliefs. Motivators t HPV vaccination included: risk perception and vaccine beliefs (71.42%), healthcare-related (60.71%) and social motivators (55.95%). In the first MLR, one-point increases in HPV score were significantly associated with higher odds of HPV vaccination until an HPV score of 16, and a one-year increase in age was associated with a 16% lower odds of HPV vaccination (aOR = 0.84, 95% CI [0.72, 0.99]; p = 0.035). Contraception use was also associated with HPV vaccination (aOR 8.36 (95% CI [1.41, 49.62]; p = 0.020). Race, ethnicity, college education status, and number of sexual partners were not significant predictors of HPV vaccination. In the second MLR evaluating vaccination motivators as predictors of HPV vaccination, we found that individuals who were motivated by healthcare had 3.03 (95% CI [1.02, 9.00]; p = 0.046) times the odds of HPV vaccination compared to individuals without healthcare-related motivators.ConclusionFindings suggest suboptimal HPV knowledge and low vaccination rates among women of reproductive age. Public health efforts should focus on increasing basic HPV knowledge among women with little-to-no HPV knowledge to increase vaccine uptake.

BackgroundWith large volumes of longitudinal data in electronic medical records from diverse patients, primary care is primed for disruption by artificial intelligence (AI) technology. With AI applications in primary care still at an early stage in Canada and most countries, there is a unique opportunity to engage key stakeholders in exploring how AI would be used and what implementation would look like.ObjectiveTo identify the barriers that patients, providers, and health leaders perceive in relation to implementing AI in primary care and strategies to overcome them.Design12 virtual deliberative dialogues. Dialogue data were thematically analyzed using a combination of rapid ethnographic assessment and interpretive description techniques.SettingVirtual sessions.ParticipantsParticipants from eight provinces in Canada, including 22 primary care service users, 21 interprofessional providers, and 5 health system leaders.ResultsThe barriers that emerged from the deliberative dialogue sessions were grouped into four themes: (1) system and data readiness, (2) the potential for bias and inequity, (3) the regulation of AI and big data, and (4) the importance of people as technology enablers. Strategies to overcome the barriers in each of these themes were highlighted, where participatory co-design and iterative implementation were voiced most strongly by participants.LimitationsOnly five health system leaders were included in the study and no self-identifying Indigenous people. This is a limitation as both groups may have provided unique perspectives to the study objective.ConclusionsThese findings provide insight into the barriers and facilitators associated with implementing AI in primary care settings from different perspectives. This will be vital as decisions regarding the future of AI in this space is shaped.

Introduction In recent years, there has been increasing awareness of the lack of diversity among clinical trial participants. Equitable representation is key when testing novel therapeutic and non-therapeutic interventions to ensure safety and efficacy across populations. Unfortunately, in the United States (US), racial and ethnic minority populations continue to be underrepresented in clinical trials compared to their White counterparts. Methods Two webinars in a four-part series, titled “Health Equity through Diversity,” were held to discuss solutions for advancing health equity through diversifying clinical trials and addressing medical mistrust in communities. Each webinar was 1.5 hours long, beginning with panelist discussions followed by breakout rooms where moderators led discussions related to health equity and scribes recorded each room’s conversations. The diverse groups of panelists included community members, civic representatives, clinician-scientists, and biopharmaceutical representatives. Scribe notes from discussions were collected and thematically analyzed to uncover the central themes. Results The first two webinars were attended by 242 and 205 individuals, respectively. The attendees represented 25 US states, four countries outside the US, and shared various backgrounds including community members, clinician/researchers, government organizations, biotechnology/biopharmaceutical professionals, and others. Barriers to clinical trial participation are broadly grouped into the themes of access, awareness, discrimination and racism, and workforce diversity. Participants noted that innovative, community-engaged, co-designed solutions are essential. Conclusions Despite racial and ethnic minority groups making up nearly half of the US population, underrepresentation in clinical trials remains a critical challenge. The community engaged co-developed solutions detailed in this report to address access, awareness, discrimination and racism, and workforce diversity are critical to advancing clinical trial diversity.

As replications of individual studies are resource intensive, techniques for predicting the replicability are required. We introduce the repliCATS (Collaborative Assessments for Trustworthy Science) process, a new method for eliciting expert predictions about the replicability of research. This process is a structured expert elicitation approach based on a modified Delphi technique applied to the evaluation of research claims in social and behavioural sciences. The utility of processes to predict replicability is their capacity to test scientific claims without the costs of full replication. Experimental data supports the validity of this process, with a validation study producing a classification accuracy of 84% and an Area Under the Curve of 0.94, meeting or exceeding the accuracy of other techniques used to predict replicability. The repliCATS process provides other benefits. It is highly scalable, able to be deployed for both rapid assessment of small numbers of claims, and assessment of high volumes of claims over an extended period through an online elicitation platform, having been used to assess 3000 research claims over an 18 month period. It is available to be implemented in a range of ways and we describe one such implementation. An important advantage of the repliCATS process is that it collects qualitative data that has the potential to provide insight in understanding the limits of generalizability of scientific claims. The primary limitation of the repliCATS process is its reliance on human-derived predictions with consequent costs in terms of participant fatigue although careful design can minimise these costs. The repliCATS process has potential applications in alternative peer review and in the allocation of effort for replication studies.

IntroductionIn 2020, the World Health Organization called for the expansion and greater recognition of all nursing roles, including advanced practice nurses (APNs), to better meet patient care needs. As defined by the International Council of Nurses (ICN), the two most common APN roles include nurse practitioners (NPs) and clinical nurse specialists (CNSs). They help ensure care to communities as well as patients and families with acute, chronic or complex conditions. Moreover, APNs support providers to deliver high quality care and improve access to services. Currently, there is much variability in the use of advanced practice nursing roles globally. A clearer understanding of the roles that are in place across the globe, and how they are being used will support greater role harmonization, and inform global priorities for advanced practice nursing education, research, and policy reform.ObjectiveTo identify current gaps in advanced practice nursing research globally.Materials and methodsThis review of systematic reviews will provide a description of the current state of the research, including gaps, on advanced practice nursing globally. We will include reviews that examine APNs, NPs or CNSs using recognized role definitions. We will search the CINAHL, EMBASE, Global Health, HealthStar, PubMed, Medline, Cochrane Library Database of Systematic Reviews and Controlled Trials Register, Database of Abstracts of Reviews of Effects, Joanna Briggs Institute, and Web of Science electronic databases for reviews published from January 2011 onwards, with no restrictions on jurisdiction or language. We will search the grey literature and hand search the reference lists of all relevant reviews to identify additional studies. We will extract country, patient, provider, health system, educational, and policy/scope of practice data. We will assess the quality of each included review using the CASP criteria, and summarize their findings. This review of systematic reviews protocol was developed following the PRISMA-P recommendations.Prospero registration numberCRD42021278532.

BackgroundTheoretically, behavioural activation may have a valuable role to play in the treatment of depression among young people with emerging/early psychosis, however we lack trial evidence concerning its acceptability and feasibility. This study will establish the feasibility of clinician-delivered behavioural activation as an adjunct to standard care for this population. We aim to train and support clinicians in delivering behavioural activation to improve depressive symptoms in young people with early/emerging psychosis. Our objectives are to: Establish the number of young people with early/emerging psychosis with clinically meaningful depression symptoms.Establish the proportion of clinicians that complete the behavioural activation training and are deemed to be competent.Determine the proportion of eligible participants approached who agree to consent to the research.Determine the proportion of participants that complete baseline measures, complete behavioural activation treatment (attending for at least fifteen minutes in a minimum of eight sessions), and complete follow-up measures (immediately post-intervention and at 3 months follow-up).Establish clinicians' fidelity to treatment (by recording randomly selected treatment sessions and completing a fidelity checklist).Calculate preliminary efficacy of behavioural activation against primary and secondary outcomes.Explore participants' experiences of facilitating behavioural activation (clinicians) and receiving behavioural activation (young people with emerging/early psychosis).MethodThis is a pilot controlled clinical trial with a two-arm parallel-group study. Approximately 60 young people with emerging/early psychosis will be randomly allocated to either behavioural activation treatment plus standard care or standard care alone. The primary outcome: depressive symptoms; and secondary outcomes: negative symptoms, overall psychiatric symptoms, medication side effects and functioning, will be assessed at baseline, post-intervention and at 3-months follow-up. The protocol is registered with the Australian New Zealand Clinical Trials Registry (reference number: ACTRN12622000756729).DiscussionThe findings will inform the design of a full-scale randomised controlled trial.

Sample preparation is critical to biological electron microscopy (EM), and there have been continuous efforts on optimizing the procedures to best preserve structures of interest in the sample. However, a quantitative characterization of the morphological changes associated with each step in EM sample preparation is currently lacking. Using correlative EM and superresolution microscopy (SRM), we have examined the effects of different drying methods as well as osmium tetroxide (OsO4) post-fixation on cell morphology during scanning electron microscopy (SEM) sample preparation. Here, SRM images of the sample acquired under hydrated conditions were used as a baseline for evaluating morphological changes as the sample went through SEM sample processing. We found that both chemical drying and critical point drying lead to a mild cellular boundary retraction of ~60 nm. Post-fixation by OsO4 causes at least 40 nm additional boundary retraction. We also found that coating coverslips with adhesion molecules such as fibronectin prior to cell plating helps reduce cell distortion from OsO4 post-fixation. These quantitative measurements offer useful information for identifying causes of cell distortions in SEM sample preparation and improving current procedures.

Early analyses revealed that dark web marketplaces (DWMs) started offering COVID-19 related products (e.g., masks and COVID-19 tests) as soon as the COVID-19 pandemic started, when these goods were in shortage in the traditional economy. Here, we broaden the scope and depth of previous investigations by considering how DWMs responded to an ongoing pandemic after the initial shock. Our dataset contains listings from 194 DWMs collected until July 2021. We start by focusing on vaccines. We find 248 listings offering approved vaccines, like Pfizer/BioNTech and AstraZeneca, as well as vendors offering fabricated proofs of vaccination and COVID-19 passports. Then, we consider COVID-19 related products. We show that, as the regular economy has become able to satisfy the demand of these goods, DWMs have decreased their offer. Next, we analyse the profile of vendors of COVID-19 related products and vaccines. We find that most of them are specialized in a single type of listings and are willing to ship worldwide. Finally, we consider a broader set of listings mentioning COVID-19, in order to assess the general impact of the pandemic on the broader activity of DWMs. Among 10,330 such listings, we show that recreational drugs are the most affected among traditional DWMs product, with COVID-19 mentions steadily increasing since March 2020. We anticipate that our results will be of interest to researchers, practitioners, and law enforcement agencies focused on the study and safeguard of public health.

BackgroundWomen with Severe Mental Illness (SMI) may have more complex pregnancies and pregnancy outcomes that require different care and management, but this has not been extensively studied. The aim of this study was to explore associations between SMI and adverse maternal and infant outcomes in the state of Victoria, Australia.MethodsOur sample included all reported live singleton births in Victoria 2009-2016 (N = 595 792). Associations between SMI and adverse pregnancy outcomes were explored using Odds Ratios (OR), adjusted for sociodemographic and lifestyle factors, and co-morbidities, including any other mental illness.ResultsOf all singleton births, 2046 (0.34%) were to a mother diagnosed with a SMI. We found evidence of an association between SMI and a range of adverse maternal and infant outcomes. Compared to women without SMI, women with a SMI had higher adjusted odds of being admitted to a High Dependency Unit or Intensive Care Unit (aOR 1.83, 1.37-2.43), having gestational diabetes mellitus (1.57, 1.34-1.84), undergoing an unplanned caesarean section (1.17, 1.02-1.33), induction of labour (1.17, 1.05-1.30) and postpartum haemorrhage (1.15, 1.03-1.29). Newborns of women with SMI had higher adjusted odds of being admitted to Special Care Nursery (aOR 1.61, 1.43-1.80), a low Apgar score at 5 minutes (1.50, 1.19-1.90), preterm birth (1.40, 1.20-1.63), and low birthweight (1.26, 1.06-1.49).ConclusionWomen with SMI are at higher risk for a range of adverse maternal and infant outcomes and are a population that may benefit from targeted early identification and enhanced antenatal care.

Improving outcomes for people undergoing major surgery, specifically reducing perioperative morbidity and mortality remains a global health challenge. Prehabilitation involves the active preparation of patients prior to surgery, including support to tackle risk behaviours that mediate and undermine physical and mental health and wellbeing. The majority of prehabilitation interventions are delivered in person, however many patients express a preference for remotely-delivered interventions that provide them with tailored support and the flexibility. Digital prehabilitation interventions offer scalability and have the potential to benefit perioperative healthcare systems, however there is a lack of robustly developed and evaluated digital programmes for use in routine clinical care. We aim to systematically develop and test the feasibility of an evidence and theory-informed multibehavioural digital prehabilitation intervention 'iPREPWELL' designed to prepare patients for major surgery. The intervention will be developed with reference to the Behaviour Change Wheel, COM-B model, and the Theoretical Domains Framework. Codesign methodology will be used to develop a patient intervention and accompanying training intervention for healthcare professionals. Training will be designed to enable healthcare professionals to promote, support and facilitate delivery of the intervention as part of routine clinical care. Patients preparing for major surgery and healthcare professionals involved with their clinical care from two UK National Health Service centres will be recruited to stage 1 (systematic development) and stage 2 (feasibility testing of the intervention). Participants recruited at stage 1 will be asked to complete a COM-B questionnaire and to take part in a qualitative interview study and co-design workshops. Participants recruited at stage 2 (up to twenty healthcare professionals and forty participants) will be asked to take part in a single group intervention study where the primary outcomes will include feasibility, acceptability, and fidelity of intervention delivery, receipt, and enactment. Healthcare professionals will be trained to promote and support use of the intervention by patients, and the training intervention will be evaluated qualitatively and quantitatively. The multifaceted and systematically developed intervention will be the first of its kind and will provide a foundation for further refinement prior to formal efficacy testing.

An increase in telomere shortening in gestational tissues has been proposed as a mechanism involved in the timing for the initiation of parturition. An increase in very short telomeres with increasing gestational age has been observed in mice; this study sought to explore this phenomenon in human pregnancies. Specifically, this study addressed the hypothesis that prior to labor, the quantity of very short telomeres (

Background The COVID-19 pandemic has exceeded 6 million known disease-related deaths and there is evidence of an increase in maternal deaths, especially in low- and middle-income countries. We aimed to estimate excess maternal deaths in Brazil and its macroregions as well as their trajectories in the first 15 months of the COVID-19 epidemic. Methods This study evaluated maternal deaths from the Mortality Information System of the Ministry of Health, with excess deaths being assessed between March 2020 and May 2021 by quasi-Poisson generalized additive models adjusted for overdispersion. Observed deaths were compared to deaths expected without the pandemic, accompanied by 95% confidence intervals according to region, age group, and trimester of occurrence. Analyses were conducted in R version 3.6.1 and RStudio version 1.2.1335. Results There were 3,291 notified maternal deaths during the study period, resulting in a 70% excess of deaths regardless of region, while in the North, Northeast, South and Southeast regions, excess deaths occurred regardless of age group. Excess deaths occurred in the March-May 2021 trimester regardless of region and age group. Excess deaths were observed in the Southeast region for the 25-36-year-old age group regardless of the trimester assessed, and in the North, Central-West and South regions, the only period in which excess deaths were not observed was September-November 2020. Excess deaths regardless of trimester were observed in the 37-49-year-old age group in the North region, and the South region displayed explosive behavior from March-May 2021, with a 375% excess of deaths. Conclusions Excess maternal deaths, with geographically heterogenous trajectories and consistently high patterns at the time of the epidemic’s greatest impact, reflect not only the previous effect of socioeconomic inequalities and of limited access to maternal health services, but most of all the precarious management of Brazil’s health crisis.

Tinnitus is a common, functionally disabling condition of often unknown etiology. Neuroimaging research to better understand tinnitus is emerging but remains limited in scope. Voxel-based physiology (VBP) studies detect tinnitus-associated pathophysiology by group-wise contrast (tinnitus vs controls) of resting-state indices of hemodynamics, metabolism, and neurovascular coupling. Voxel-based morphometry (VBM) detects tinnitus-associated neurodegeneration by group-wise contrast of structural MRI. Both VBP and VBM studies routinely report results as atlas-referenced coordinates, suitable for coordinate-based meta-analysis (CBMA). Here, 17 resting-state VBP and 8 VBM reports of tinnitus-associated regional alterations were meta-analyzed using activation likelihood estimation (ALE). Acknowledging the need for data-driven insights, ALEs were performed at two levels of statistical rigor: corrected for multiple comparisons and uncorrected. The corrected ALE applied cluster-level inference thresholding by intensity (z-score > 1.96; p < 0.05) followed by family-wise error correction for multiple comparisons (p < .05, 1000 permutations) and fail-safe correction for missing data. The corrected analysis identified one significant cluster comprising five foci in the posterior cingulate gyrus and precuneus, that is, not within the primary or secondary auditory cortices. The uncorrected ALE identified additional regions within auditory and cognitive processing networks. Taken together, tinnitus is likely a dysfunction of regions spanning multiple canonical networks that may serve to increase individuals’ interoceptive awareness of the tinnitus sound, decrease capacity to switch cognitive sets, and prevent behavioral and cognitive attention to other stimuli. It is noteworthy that the most robust tinnitus-related abnormalities are not in the auditory system, contradicting collective findings of task-activation literature in tinnitus.

BackgroundSome mother-to-child transmission (MTCT) studies suggest that allelic variations of Fc gamma receptors (FcγR) play a role in infant HIV-1 acquisition, but findings are inconsistent. To address the limitations of previous studies, the present study investigates the association between perinatal HIV-1 transmission and FcγR variability in three cohorts of South African infants born to women living with HIV-1.MethodsThis nested case-control study combines FCGR genotypic data from three perinatal cohorts at two hospitals in Johannesburg, South Africa. Children with perinatally-acquired HIV-1 (cases, n = 395) were compared to HIV-1-exposed uninfected children (controls, n = 312). All study participants were black South Africans and received nevirapine for prevention of MTCT. Functional variants were genotyped using a multiplex ligation-dependent probe amplification assay, and their representation compared between groups using logistic regression analyses.ResultsFCGR3A gene duplication associated with HIV-1 acquisition (OR = 10.27; 95% CI 2.00-52.65; P = 0.005) as did the FcγRIIb-232TT genotype even after adjusting for FCGR3A copy number and FCGR3B genotype (AOR = 1.72; 95%CI 1.07-2.76; P = 0.024). The association between FcγRIIb-232TT genotype and HIV-1 acquisition was further strengthened (AOR = 2.28; 95%CI 1.11-4.69; P = 0.024) if adjusted separately for FCGR2C c.134-96C>T. Homozygous FcγRIIIb-HNA1a did not significantly associate with HIV-1 acquisition in a univariate model (OR = 1.42; 95%CI 0.94-2.16; P = 0.098) but attained significance after adjustment for FCGR3A copy number and FCGR2B genotype (AOR = 1.55; 95%CI 1.01-2.38; P = 0.044). Both FcγRIIb-232TT (AOR = 1.83; 95%CI 1.13-2.97; P = 0.014) and homozygous FcγRIIIb-HNA1a (AOR = 1.66; 95%CI 1.07-2.57; P = 0.025) retained significance when birthweight and breastfeeding were added to the model. The common FCGR2A and FCGR3A polymorphisms did not associate with HIV-1 acquisition.ConclusionsCollectively, our findings suggest that the FcγRIIb-232TT genotype exerts a controlling influence on infant susceptibility to HIV-1 infection. We also show a role for less studied variants-FCGR3A duplication and homozygous HNA1a. These findings provide additional insight into a role for FcγRs in HIV-1 infection in children.

A variety of antibiotics are ubiquitous in all freshwater ecosystems that receive wastewater. A wide variety of antibiotics have been developed to kill problematic bacteria and fungi through targeted application, and their use has contributed significantly to public health and livestock management. Unfortunately, a substantial fraction of the antibiotics applied to humans, pets and livestock end up in wastewater, and ultimately many of these chemicals enter freshwater ecosystems. The effect of adding chemicals that are intentionally designed to kill microbes, on freshwater microbial communities remains poorly understood. There are reasons to be concerned, as microbes play an essential role in nutrient uptake, carbon fixation and denitrification in freshwater ecosystems. Chemicals that reduce or alter freshwater microbial communities might reduce their capacity to degrade the excess nutrients and organic matter that characterize wastewater. We performed a laboratory experiment in which we exposed microbial community from unexposed stream sediments to three commonly detected antibiotics found in urban wastewater and urban streams (sulfamethoxazole, danofloxacin, and erythromycin). We assessed how the form and concentration of inorganic nitrogen, microbial carbon, and nitrogen cycling processes changed in response to environmentally relevant doses (10 μg/L) of each of these antibiotics individually and in combination. We expected to find that all antibiotics suppressed rates of microbial mineralization and nitrogen transformations and we anticipated that this suppression of microbial activity would be greatest in the combined treatment. Contrary to our expectations we measured few significant changes in microbially mediated functions in response to our experimental antibiotic dosing. We found no difference in functional gene abundance of key nitrogen cycling genes nosZ, mcrA, nirK, and amoA genes, and we measured no treatment effects on NO3- uptake or N2O, N2, CH4, CO2 production over the course of our seven-day experiment. In the mixture treatment, we measured significant increases in NH4+ concentrations over the first 24 hours of the experiment, which were indistinguishable from controls within six hours. Our results suggest remarkable community resistance to pressure antibiotic exposure poses on naïve stream sediments.

The management of myeloma in the elderly is shifting its focus towards reducing the risk of under-treating fit patients and the risk of over-treating frail patients. Frailty assessment is required in this patient group in order to individualise treatment decisions. In addition to the proven prognostic values of the International Myeloma Working Group (IMWG) frailty score and the revised Myeloma Co-morbidity Index (R-MCI), a new easy-to-use frailty-based risk profile score (high-risk (i.e. frail), medium risk (i.e. intermediate-fitness) and low-risk (i.e. fit)) named Myeloma Risk Profile (MRP) was shown to be predictive of survival in the clinical trial setting. In this retrospective real-world study, we set out to evaluate the frailty characteristics and clinical outcomes according to the different MRP scoring algorithm categories (frail vs. intermediate vs fit), in a high risk cohort of elderly newly diagnosed myeloma patients treated with the fixed-duration triplet therapy VCD (bortezomib with cyclophosphamide and dexamethasone). Clinical outcomes included: reason for treatment discontinuation, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Out of 100 patients, 62 were frail, 27 were intermediate and 11 were fit, according to MRP scores. To enable meaningful comparisons between comparable numbers, subgroups analyses for ORR, OS, PFS, and AEs focused on frail (n = 62) versus intermediate or fit (n = 38) patients. The proportion of patients in each subgroup who were able to complete the planned course of treatment was (frail: 43.5% vs. intermediate or fit: 55.3%). A higher proportion in the frail subgroup discontinued therapy due to progressive disease (19.4% vs. 2.6%). Discontinuation due to toxicity was comparable across subgroups (14.5% vs. 15.8%), ORR in the total cohort was 75%, and this was comparable between subgroups (frail: 74.2% vs. intermediate or fit: 76.3%). There was a trend for a shorter median OS in the frail subgroup but without a statistical significance: (frail vs. intermediate or fit): (46 months vs. not reached, HR: 1.94, 95% CI 0.89–4.2, p = 0.094). There was no difference in median PFS between subgroups: (frail vs. intermediate or fit): (11.8 vs. 9.9 months, HR: 0.99, 95% CI: 0.61–1.61, P = 0.982). This cohort demonstrated a higher incidence rate of AEs in frail patients compared to those in the intermediate or fit group: patients with at least one any grade toxicity (85.5% vs. 71.1%), patients with at least one ≥G3 AE (37.1% vs. 21.1%). In conclusion, our study is to the first to evaluate clinical outcomes according to MRP in a high risk real-world cohort of patients treated exclusively with the proteasome inhibitor-based VCD therapy. Our study demonstrated a trend for worse OS in addition to worse AE outcomes in the frail group, but no difference in PFS with this fixed-duration therapy. MRP is an easy-to-use tool in clinical practice; its prognostic value was validated in the real-world in a large cohort of patients from the Danish Registry. Further evaluation of MRP in the real-world when continuous therapies are used, can further support the generalisability of its prognostic value in elderly myeloma patients.

The use of surgical-type face masks has become increasingly common during the COVID-19 pandemic. Recent findings suggest that it is harder to categorise the facial expressions of masked faces, than of unmasked faces. To date, studies of the effects of mask-wearing on emotion recognition have used categorisation paradigms: authors have presented facial expression stimuli and examined participants' ability to attach the correct label (e.g., happiness, disgust). While the ability to categorise particular expressions is important, this approach overlooks the fact that expression intensity is also informative during social interaction. For example, when predicting an interactant's future behaviour, it is useful to know whether they are slightly fearful or terrified, contented or very happy, slightly annoyed or angry. Moreover, because categorisation paradigms force observers to pick a single label to describe their percept, any additional dimensionality within observers' interpretation is lost. In the present study, we adopted a complementary emotion-intensity rating paradigm to study the effects of mask-wearing on expression interpretation. In an online experiment with 120 participants (82 female), we investigated how the presence of face masks affects the perceived emotional profile of prototypical expressions of happiness, sadness, anger, fear, disgust, and surprise. For each of these facial expressions, we measured the perceived intensity of all six emotions. We found that the perceived intensity of intended emotions (i.e., the emotion that the actor intended to convey) was reduced by the presence of a mask for all expressions except for anger. Additionally, when viewing all expressions except surprise, masks increased the perceived intensity of non-intended emotions (i.e., emotions that the actor did not intend to convey). Intensity ratings were unaffected by presentation duration (500ms vs 3000ms), or attitudes towards mask wearing. These findings shed light on the ambiguity that arises when interpreting the facial expressions of masked faces.

We estimated excess mortality in Medicare recipients in the United States with probable and confirmed Covid-19 infections in the general community and amongst residents of long-term care (LTC) facilities. We considered 28,389,098 Medicare and dual-eligible recipients from one year before February 29, 2020 through September 30, 2020, with mortality followed through November 30th, 2020. Probable and confirmed Covid-19 diagnoses, presumably mostly symptomatic, were determined from ICD-10 codes. We developed a Risk Stratification Index (RSI) mortality model which was applied prospectively to establish baseline mortality risk. Excess deaths attributable to Covid-19 were estimated by comparing actual-to-expected deaths based on historical (2017-2019) comparisons and in closely matched concurrent (2020) cohorts with and without Covid-19. Overall, 677,100 (2.4%) beneficiaries had confirmed Covid-19 and 2,917,604 (10.3%) had probable Covid-19. A total of 472,329 confirmed cases were community living and 204,771 were in LTC. Mortality following a probable or confirmed diagnosis in the community increased from an expected incidence of about 4.0% to actual incidence of 7.5%. In long-term care facilities, the corresponding increase was from 20.3% to 24.6%. The absolute increase was therefore similar at 3-4% in the community and in LTC residents. The percentage increase was far greater in the community (89.5%) than among patients in chronic care facilities (21.1%) who had higher baseline risk of mortality. The LTC population without probable or confirmed Covid-19 diagnoses experienced 38,932 excess deaths (34.8%) compared to historical estimates. Limitations in access to Covid-19 testing and disease under-reporting in LTC patients probably were important factors, although social isolation and disruption in usual care presumably also contributed. Remarkably, there were 31,360 (5.4%) fewer deaths than expected in community dwellers without probable or confirmed Covid-19 diagnoses. Disruptions to the healthcare system and avoided medical care were thus apparently offset by other factors, representing overall benefit. The Covid-19 pandemic had marked effects on mortality, but the effects were highly context-dependent.

BackgroundOpioid-induced respiratory depression driven by ligand binding to mu-opioid receptors is a leading cause of opioid-related fatalities. Buprenorphine, a partial agonist, binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects. The authors examined whether sustained buprenorphine plasma concentrations similar to those achieved with some extended-release injections used to treat opioid use disorder could reduce the frequency and magnitude of fentanyl-induced respiratory depression.MethodsIn this two-period crossover, single-centre study, 14 healthy volunteers (single-blind, randomized) and eight opioid-tolerant patients taking daily opioid doses ≥90 mg oral morphine equivalents (open-label) received continuous intravenous buprenorphine or placebo for 360 minutes, targeting buprenorphine plasma concentrations of 0.2 or 0.5 ng/mL in healthy volunteers and 1.0, 2.0 or 5.0 ng/mL in opioid-tolerant patients. Upon reaching target concentrations, participants received up to four escalating intravenous doses of fentanyl. The primary endpoint was change in isohypercapnic minute ventilation (VE). Additionally, occurrence of apnea was recorded.ResultsFentanyl-induced changes in VE were smaller at higher buprenorphine plasma concentrations. In healthy volunteers, at target buprenorphine concentration of 0.5 ng/mL, the first and second fentanyl boluses reduced VE by [LSmean (95% CI)] 26% (13-40%) and 47% (37-59%) compared to 51% (38-64%) and 79% (69-89%) during placebo infusion (p = 0.001 and < .001, respectively). Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection. In opioid-tolerant patients, fentanyl reduced VE up to 49% (21-76%) during buprenorphine infusion (all concentration groups combined) versus up to 100% (68-132%) during placebo infusion (p = 0.006). In opioid-tolerant patients, the risk of experiencing apnea requiring verbal stimulation following fentanyl boluses was lower with buprenorphine than with placebo (odds ratio: 0.07; 95% CI: 0.0 to 0.3; p = 0.001).InterpretationResults from this proof-of-principle study provide the first clinical evidence that high sustained plasma concentrations of buprenorphine may protect against respiratory depression induced by potent opioids like fentanyl.

The rapid emergence of antimicrobial resistance (AMR) is a major concern for wildlife and ecosystem health globally. Genetic determinants of AMR have become indicators of anthropogenic pollution due to their greater association with humans and rarer presence in environments less affected by humans. The objective of this study was to determine the distribution and frequency of the class 1 integron, a genetic determinant of AMR, in both the faecal microbiome and in Escherichia coli isolated from neonates of three pinniped species. Australian sea lion (Neophoca cinerea), Australian fur seal (Arctocephalus pusillus doriferus) and long-nosed fur seal (Arctocephalus forsteri) pups from eight breeding colonies along the Southern Australian coast were sampled between 2016-2019. DNA from faecal samples (n = 309) and from E. coli (n = 795) isolated from 884 faecal samples were analysed for class 1 integrons using PCRs targeting the conserved integrase gene (intI) and the gene cassette array. Class 1 integrons were detected in A. p. doriferus and N. cinerea pups sampled at seven of the eight breeding colonies investigated in 4.85% of faecal samples (n = 15) and 4.52% of E. coli isolates (n = 36). Integrons were not detected in any A. forsteri samples. DNA sequencing of the class 1 integron gene cassette array identified diverse genes conferring resistance to four antibiotic classes. The relationship between class 1 integron carriage and the concentration of five trace elements and heavy metals was also investigated, finding no significant association. The results of this study add to the growing evidence of the extent to which antimicrobial resistant bacteria are polluting the marine environment. As AMR determinants are frequently associated with bacterial pathogens, their occurrence suggests that these pinniped species are vulnerable to potential health risks. The implications for individual and population health as a consequence of AMR carriage is a critical component of ongoing health investigations.