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With new pre-exposure prophylaxis (PrEP) modalities for HIV prevention becoming available, understanding how adolescent girls and young women (AGYW) navigate through PrEP options is essential, including factors underlying their choice. Through 16 focus group discussions (FGDs) and 52 in-depth interviews (IDIs) from REACH, an open-label crossover study in which AGYW were allocated 1:1 (between 06 February 2019 and 18 March 2020) to receive oral PrEP for six months and the dapivirine ring for six months, in a randomized sequence, followed by a 6-month period where either product (or neither) could be chosen, we explored decision-making process and product choice, using a mixed inductive-deductive analytical approach. Key themes included the desire to remain HIV-negative and weighing product attributes through experiential learning. Product triability appeared important in informing product choice as individual circumstances changed or assuaging side effects with a given product. Approved biomedical prevention innovations may also benefit from hands-on experience to help with adoption and use during real-world implementation. Furthermore, support from trusted providers will remain critical as AGYW contemplate navigating through PrEP options and choice.

BackgroundPost-stroke depression (PSD) is a frequent problem in stroke patients, affecting their rehabilitation process and functional outcomes. Several studies have investigated the relationship between PSD and functional outcomes, but the results have been inconsistent.ObjectiveThis systematic review of non-experimental studies aims to investigate the prevalence of post-stroke depression and the association between post-stroke depression and functional outcomes.MethodA search of PubMed, MEDLINE, Web of Science, and CINAHL Plus with Full Text was carried out from inception until January 2024. The literature was screened using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with relevant papers included. We extracted data from non-experimental studies that examined associations between PSD and functional outcomes. The Joanna Briggs Institute for systematic reviews was used for critical appraisal.ResultsTwenty-one studies met the study criteria, including sixteen cohort studies, four cross-sectional studies, and one case-control study. PSD prevalences ranged from 12.2% to 32.2% in the first two weeks, 17.9 to 35.5% in the first month, and 10.4% to 32.0% in the third month following a stroke. Functional outcomes were evaluated in four domains: degree of dependence, basic activity of daily living, instrumental activity of daily living, and physical and cognitive function. Significant associations between PSD and functional outcomes were identified after controlling potential factors such as age, comorbidities, and stroke severity. PSD had negative associations with functional outcomes in all four measure domains from one month to five years after a stroke. Depression treatment showed positive results on functional outcomes in stroke patients.ConclusionPSD prevalence was high in the first three months after stroke. PSD is significantly associated with poor functional outcomes. PSD assessment and management should be performed on a frequent basis in the early stages of stroke to achieve the best possible functional recovery.

Selective serotonin re-uptake inhibitors (SSRI) widely used in the treatment of depression, anxiety, obsessive compulsive disorder, fibromyalgia, and migraine are among the most heavily prescribed drug class in the United States (US). Along with an overall rise in SSRI use, these medications are increasingly used by pregnant individuals and recent preclinical and clinical studies have indicated that SSRIs may increase the prevalence of congenital abnormalities and birth defects of the craniofacial region. Our group has developed pre-clinical models of study, including those that mimic the clinical use of SSRI in mice. Here we designed a study to interrogate a commonly prescribed SSRI drug, Citalopram, for its effects on craniofacial and dental development when introduced in utero. Pre-natal exposure to a clinically relevant dose of citalopram resulted in changes in craniofacial form identified by an increase in endocast volume in SSRI exposed postnatal day 15 mouse pups. More specifically, cranial length and synchondrosis length increased in SSRI exposed pups as compared to control pups of the same age. Additionally, growth center (synchondrosis) height and width and palate length and width decreased in SSRI exposed pups as compared to control un-exposed pups. Effects of SSRI on the molars was minimal. Craniofacial growth and development continue to be an area of interest in the investigation of in utero pharmaceutical drug exposure. Altogether these data indicate that prenatal SSRI exposure affects craniofacial form in multiple tissues and specifically at growth sites and centers of the skull.

Colorectal cancer (CRC) is the third most common malignancy cause of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) promotes cancer metastasis and a tumour-based Glasgow EMT score was associated with adverse clinical features and poor prognosis. In this study, the impact of using the established five tumour-based EMT markers consisting of E-cadherin (E-cad), β-catenin (β-cat), Snail, Zeb-1, and Fascin in combination with the stromal periostin (PN) on the prediction of CRC patients' prognosis were invesigated. Formalin-fixed paraffin-embedded tissues of 202 CRC patients were studies the expressions of E-cad, β-cat, Snail, Zeb-1, Fascin, and PN by immunohistochemistry. Individually, cytoplasmic Fascin (Fc), cytoplasmic Snail (Sc), nuclear Snail (Sn), stromal Snail (Ss), and stromal PN (Ps) were significantly associated with reduced survival. A combination of Ps with Fc, Fs, and Sn was observed in 2 patterns including combined Fc, Fs, and Ps (FcFsPs) and Fc, Sn, and Ps (FcSnPs). These combinations enhanced the prognostic power compared to individual EMT markers and were independent prognostic markers. As the previously established scoring method required five markers and stringent criteria, its clinical use might be limited. Therefore, using these novel combined prognostic markers, either FcFsPs or FcSnPs, may be useful in predicting CRC patient outcomes.

Basic foot care is a real need of people experiencing homelessness. To improve access to foot health for this group, three services structured to provide healthcare support for people experiencing homelessness collaborated in metropolitan Melbourne, Australia: an established nurse-led Homeless Persons Program (HPP), a specialty community health podiatry clinic servicing people experiencing homelessness, and a charity supporting disadvantaged communities providing free socks, foot first aid kits and second-hand footwear for distribution by nurses and podiatrists of participating services. This paper outlines the implementation and evaluation of this collaboration. A four stage implementation approach was used, addressing: 1. Who needs to do what differently? 2. What are the barriers and enablers that need to be addressed? 3. Which intervention components could overcome the modifiable barriers and enhance the enablers? 4. How can the changes be measured? The evaluation prospectively collected information about how HPP nurses referred adults to podiatry, and whether the referred individuals accessed the podiatry clinic, the outcomes of the podiatry visit, and how many received footwear, socks and foot first aid kits provided by the non-profit organisation. Over 1st June 2019 and 31st December 2020, 52 individuals were identified as adults who could potentially benefit from podiatry by the HPP nurses, of which 33 accessed podiatry. Those who did not visit the podiatry clinic were more likely to be born outside of Australia, live in more precarious housing (crisis accommodation and rough sleeping), have slightly more predisposing factors for homelessness, but have fewer medical, psychological and cognitive conditions. A structured approach including processes, education, regular, outreach to youth refuges and formal outcome monitoring enabled foot health care access in people experiencing homelessness. Further research is needed to ascertain how to support participants at risk of foot problems to access podiatry before their foot health issue reaches crisis point.

ObjectiveReproducible diagnoses of endometrial hyperplasia (EH) remains challenging and has potential implications for patient management. This systematic review aimed to identify pathologist-specific factors associated with interobserver variation in the diagnosis and reporting of EH.MethodsThree electronic databases, namely MEDLINE, Embase and Web of Science, were searched from 1st January 2000 to 25th March 2023, using relevant key words and subject headings. Eligible studies reported on pathologist-specific factors or working practices influencing interobserver variation in the diagnosis of EH, using either the World Health Organisation (WHO) 2014 or 2020 classification or the endometrioid intraepithelial neoplasia (EIN) classification system. Quality assessment was undertaken using the QUADAS-2 tool, and findings were narratively synthesised.ResultsEight studies were identified. Interobserver variation was shown to be significant even amongst specialist gynaecological pathologists in most studies. Few studies investigated pathologist-specific characteristics, but pathologists were shown to have different diagnostic styles, with some more likely to under-diagnose and others likely to over-diagnose EH. Some novel working practices were identified, such as grading the "degree" of nuclear atypia and the incorporation of objective methods of diagnosis such as semi-automated quantitative image analysis/deep learning models.ConclusionsThis review highlighted the impact of pathologist-specific factors and working practices in the accurate diagnosis of EH, although few studies have been conducted. Further research is warranted in the development of more objective criteria that could improve reproducibility in EH diagnostic reporting, as well as determining the applicability of novel methods such as grading the degree of nuclear atypia in clinical settings.

PurposePoint-of-care ultrasound (POCUS) is a sensitive, safe, and efficient tool used in many clinical settings and is an essential part of medical education in the United States. Numerous studies present improved diagnostic performances and positive clinical outcomes among POCUS users. However, others stress the degree to which the modality is user-dependent, rendering high-quality POCUS training necessary in medical education. In this study, the authors aimed to investigate the potential of an artificial intelligence (AI) based quality indicator tool as a teaching device for cardiac POCUS performance.MethodsThe authors integrated the quality indicator tool into the pre-clinical cardiac ultrasound course for 4th-year medical students and analyzed their performances. The analysis included 60 students who were assigned to one of two groups as follows: the intervention group using the AI-based quality indicator tool and the control group. Quality indicator users utilized the tool during both the course and the final test. At the end of the course, the authors tested the standard echocardiographic views, and an experienced clinician blindly graded the recorded clips. Results were analyzed and compared between the groups.ResultsThe results showed an advantage in quality indictor users' median overall scores (P = 0.002) with a relative risk of 2.3 (95% CI: 1.10, 4.93, P = 0.03) for obtaining correct cardiac views. In addition, quality indicator users also had a statistically significant advantage in the overall image quality in various cardiac views.ConclusionsThe AI-based quality indicator improved cardiac ultrasound performances among medical students who were trained with it compared to the control group, even in cardiac views in which the indicator was inactive. Performance scores, as well as image quality, were better in the AI-based group. Such tools can potentially enhance ultrasound training, warranting the expansion of the application to more views and prompting further studies on long-term learning effects.

ObjectivesWhile previous research has utilized remote delivery of yoga interventions, no research has specifically interrogated the effectiveness of remote yoga intervention delivery. In this secondary analysis of weight-maintenance trial data, we examined participant perceptions of essential yoga properties across in-person and remote formats, hypothesizing that perceptions would not differ following remote delivery.Methods24 women with overweight or obesity (34.6±4.1 kg/m2, 48.2±9.9 years) received a 12-week Iyengar yoga intervention (2x/week) following a 3-month behavioral weight loss program. Of 23 participants who completed follow-up questionnaires, 12 received the planned in-person intervention and 11 received a remote intervention (delivered live) due to the COVID-19 pandemic. The Essential Properties of Yoga Questionnaire (EPYQ) was completed online by participants and by the instructors to measure the perceptions of the relative emphasis placed on the essential components of the yoga intervention via 14 subscales. Linear regression models were used to compare perceptions of each EPYQ dimension across in-person and remote delivery methods, as well as between participants and instructors, independent of delivery method.Results13 of the 14 subscales did not differ between delivery modalities (p>0.05). Participants perceived more individual attention within in-person yoga (p = 0.003). For both delivery methods, instructors perceived breathwork, restorative postures, and body locks to be incorporated to a lesser degree compared to participants (β = -1.28, p = 0.003; β = -1.57, p = 0.019; β = -1.39, p = 0.036; respectively). No other significant differences across the participant and instructor scores were observed.ConclusionsFindings provide preliminary support for the use of live remote delivery of yoga, effectively communicating most essential yoga properties when compared to in-person classes. However, participants perceived more individual attention with in-person versus remote delivery; thus, future remote-based yoga interventions may benefit from providing additional individualized feedback.

[This corrects the article DOI: 10.1371/journal.pone.0261768.].

BackgroundSocial care is vital to quality of life for people with young onset dementia and their families. Yet care is hugely variable, frequently lacking and poorly coordinated. We aim to establish current practice in English social care for people with young onset dementia and co-produce evidence-based recommendations and resources for improvement.Methods and analysisIn Work-Package 1, we will gather qualitative data from 25 people with young onset dementia and/or main supporters residing in England. We will ask them about their experiences of social care (broadly defined, including independent and voluntary sector provision) and suggestions for improvement. In Work-Package 2, we will conduct a short on-line survey with a wide range of staff with a role in adult social care in England. We will find out about current awareness, knowledge and practice and suggestions for improvements. Quantitative and qualitative analysis will provide a picture of current practice. In Work-Package 3, we will use convergence analysis to synthesise the findings from Work-Packages 1 and 2 and present the findings to a stakeholder workshop, to identify feasible priorities for improvement. We will establish what is already known about good practice relating to these key priorities using a scoping review and interviews with professionals. This knowledge will then feed into the co-production of resources and recommendations with key stakeholders to improve social care for people with young onset dementia and their families.DiscussionThis study seeks to address a gap in our understanding of social care provision for people with young onset dementia and develop recommendations and practical resources for improvements. The findings will help people with young onset dementia and supporters to receive higher quality social care.Trial registrationStudy registration number: ISRCTN10653250.

Climate change imposes physiological constraints on organisms particularly through changing thermoregulatory requirements. Bergmann's and Allen's rules suggest that body size and the size of thermoregulatory structures differ between warm and cold locations, where body size decreases with temperature and thermoregulatory structures increase. However, phenotypic plastic responses to malnutrition during development can result in the same patterns while lacking fitness benefits. The Gulf of Maine (GOM), located at the southern end of the Labrador current, is warming faster than most of the world's oceans, and many of the marine species that occupy these waters exist at the southern edge of their distributions including Atlantic puffins (Fratercula arctica; hereafter "puffin"). Monitoring of puffins in the GOM, at Machias Seal Island (MSI), has continued annually since 1995. We asked whether changes in adult puffin body size and the proportional size of bill to body have changed with observed rapid ocean warming. We found that the size of fledgling puffins is negatively related to sea surface temperature anomalies (warm conditions = small fledgers), adult puffin size is related to fledgling size (small fledgers = small adults), and adult puffins have decreased in size in recent years in response to malnutrition during development. We found an increase in the proportional size of bill to wing chord, likely in response to some mix of malnutrition during development and increasing air temperatures. Although studies have assessed clinal variation in seabird morphology with temperature, this is the first study addressing changes in seabird morphology in relation to ocean warming. Our results suggest that puffins nesting in the GOM have morphological plasticity that may help them acclimate to ocean warming.

Invasive species present a worldwide concern as competition and pathogen reservoirs for native species. Specifically, the invasive social wasp, Vespula pensylvanica, is native to western North America and has become naturalized in Hawaii, where it exerts pressures on native arthropod communities as a competitor and predator. As invasive species may alter the microbial and disease ecology of their introduced ranges, there is a need to understand the microbiomes and virology of social wasps. We used 16S rRNA gene sequencing to characterize the microbiome of V. pensylvanica samples pooled by colony across two geographically distinct ranges and found that wasps generally associate with taxa within the bacterial genera Fructobacillus, Fructilactobacillus, Lactococcus, Leuconostoc, and Zymobacter, and likely associate with environmentally-acquired bacteria. Furthermore, V. pensylvanica harbors-and in some cases were dominated by-many endosymbionts including Wolbachia, Sodalis, Arsenophonus, and Rickettsia, and were found to contain bee-associated taxa, likely due to scavenging on or predation upon honey bees. Next, we used reverse-transcriptase quantitative PCR to assay colony-level infection intensity for Moku virus (family: Iflaviridae), a recently-described disease that is known to infect multiple Hymenopteran species. While Moku virus was prevalent and in high titer, it did not associate with microbial diversity, indicating that the microbiome may not directly interact with Moku virus in V. pensylvanica in meaningful ways. Collectively, our results suggest that the invasive social wasp V. pensylvanica associates with a simple microbiome, may be infected with putative endosymbionts, likely acquires bacterial taxa from the environment and diet, and is often infected with Moku virus. Our results suggest that V. pensylvanica, like other invasive social insects, has the potential to act as a reservoir for bacteria pathogenic to other pollinators, though this requires experimental demonstration.

Glioma is recognized to be a highly heterogeneous CNS malignancy, whose diverse cellular composition and cellular interactions have not been well characterized. To gain new clinical- and biological-insights into the genetically-bifurcated IDH1 mutant (mt) vs wildtype (wt) forms of glioma, we integrated data from protein, genomic and MR imaging from 20 treatment-naïve glioma cases and 16 recurrent GBM cases. Multiplexed immunofluorescence (MxIF) was used to generate single cell data for 43 protein markers representing all cancer hallmarks, Genomic sequencing (exome and RNA (normal and tumor) and magnetic resonance imaging (MRI) quantitative features (protocols were T1-post, FLAIR and ADC) from whole tumor, peritumoral edema and enhancing core vs equivalent normal region were also collected from patients. Based on MxIF analysis, 85,767 cells (glioma cases) and 56,304 cells (GBM cases) were used to generate cell-level data for 24 biomarkers. K-means clustering was used to generate 7 distinct groups of cells with divergent biomarker profiles and deconvolution was used to assign RNA data into three classes. Spatial and molecular heterogeneity metrics were generated for the cell data. All features were compared between IDH mt and IDHwt patients and were finally combined to provide a holistic/integrated comparison. Protein expression by hallmark was generally lower in the IDHmt vs wt patients. Molecular and spatial heterogeneity scores for angiogenesis and cell invasion also differed between IDHmt and wt gliomas irrespective of prior treatment and tumor grade; these differences also persisted in the MR imaging features of peritumoral edema and contrast enhancement volumes. A coherent picture of enhanced angiogenesis in IDHwt tumors was derived from multiple platforms (genomic, proteomic and imaging) and scales from individual proteins to cell clusters and heterogeneity, as well as bulk tumor RNA and imaging features. Longer overall survival for IDH1mt glioma patients may reflect mutation-driven alterations in cellular, molecular, and spatial heterogeneity which manifest in discernable radiological manifestations.

Though physical activity (PA) is recommended during pregnancy, it remains unclear how occupational physical activity (OPA) and sedentary behavior (SB) contribute to activity patterns and health during pregnancy. The purpose of this secondary analysis was to determine if OPA pattern is a determinant of all-day PA and evaluate associations with pregnancy/infant health outcomes. Data was from two prospective cohorts with study visits each trimester: MoM Health (Pittsburgh, PA; n = 120) and PRAMS (Iowa City, Iowa; n = 20). Using employment status/job hours (self-reported in demographic questionnaires) and OPA from the Pregnancy Physical Activity Questionnaire, latent class analysis identified three groups: sitting (n = 61), part-time mixed (n = 9), and active (n = 29). A fourth group included non-working participants (n = 32). Device-based PA (ActiGraph GT3X), SB (activPAL3 micro), and blood pressure were measured each trimester. Glucose screening test, gestational age, gestational weight gain, adverse pregnancy outcomes (APOs: gestational hypertension, preeclampsia, eclampsia, gestational diabetes, intrauterine growth restriction, and preterm birth), and infant outcomes (length, weight, and sex) were abstracted from medical records. Associations between groups with APOs and pregnancy/infant health were calculated using linear/logistic regression with adjustment for age, pre-pregnancy BMI, education, and race. Self-reported participant characteristics were similar across groups, except education which was higher in the sitting versus other groups. All-day device-based PA differed across groups; for example, the sitting group had the highest SB across trimester (all p0.09). Compared to the non-working group, the risk of any APO was non-significantly higher in the sitting (OR = 2.27, 95%CI = 0.63-8.18) and active groups (OR = 2.40, 95%CI = 0.66-9.75), though not the part-time mixed (OR = 0.86, 95%CI = 0.08-9.1). OPA pattern is a determinant of all-day PA during pregnancy. Future studies with larger samples should examine associations between pregnancy OPA patterns and pregnancy/infant health.

Individuals with sickle cell disease are increasingly surviving into adulthood, many of whom have interest in future biological parenthood. Reproductive health knowledge is low among adolescent and young adult males and their caregivers. Their understanding of these topics is needed to optimize their reproductive health outcomes. As such, through collaboration with a community advisory board (adolescents and young adults with sickle cell disease and mothers of adolescent and young adult males with sickle cell disease) and digital design team, we developed a web-based sickle cell disease-focused reproductive health program entitled FUTURES to address these knowledge gaps. For phase I of this two phase feasibility and acceptability study, adolescent and young adult males and their caregivers will complete a pre- and post-program reproductive health knowledge and attitudes questionnaire to assess change in knowledge. In phase II, after learning about fertility testing as part of the FUTURES curriculum, adolescent and young adult male participants are given the option to pursue testing. The two-phase study aims to: 1) develop and test the feasibility, acceptability, and efficacy of a reproductive health web-based educational program at increasing reproductive health knowledge in male adolescent and young adult males with sickle cell disease and their caregivers, and 2) assess feasibility of fertility testing. The long-term goal is to improve reproductive and psychosocial outcomes among adolescent and young adult males with sickle cell disease.

Long-term datasets can reveal otherwise undetectable ecological trends, illuminating the historical context of contemporary ecosystem states. We used two decades (1997-2019) of scientific trawling data from a subtidal, benthic site in Puget Sound, Washington, USA to test for gradual trends and sudden shifts in total sea star abundance across 11 species. We specifically assessed whether this community responded to the sea star wasting disease (SSWD) epizootic, which began in 2013. We sampled at depths of 10, 25, 50 and 70 m near Port Madison, WA, and obtained long-term water temperature data. To account for species-level differences in SSWD susceptibility, we divided our sea star abundance data into two categories, depending on the extent to which the species is susceptible to SSWD, then conducted parallel analyses for high-susceptibility and moderate-susceptibility species. The abundance of high-susceptibility sea stars declined in 2014 across depths. In contrast, the abundance of moderate-susceptibility species trended downward throughout the years at the deepest depths- 50 and 70 m-and suddenly declined in 2006 across depths. Water temperature was positively correlated with the abundance of moderate-susceptibility species, and uncorrelated with high-susceptibility sea star abundance. The reported emergence of SSWD in Washington State in the summer of 2014 provides a plausible explanation for the subsequent decline in abundance of high-susceptibility species. However, no long-term stressors or mortality events affecting sea stars were reported in Washington State prior to these years, leaving the declines we observed in moderate-susceptibility species preceding the 2013-2015 SSWD epizootic unexplained. These results suggest that the subtidal sea star community in Port Madison is dynamic, and emphasizes the value of long-term datasets for evaluating patterns of change.

ObjectiveThe objective of this exploratory study was to assess the potential impacts of two different continuous positive airway pressure (CPAP) devices on preterm infant head shape and circumference.Study designTwenty infants born at ResultsAt baseline, average total birthweight of infants was 1021 grams (SD = 227 grams), average gestational age was 26.9 weeks (SD = 1.80), mean CI was 79.7 cm (SD = 5.95), and HC was 10.2 cm (SD = 0.92). Days on CPAP ranged from 16 to 63 days, with an average of 40.7 (SD = 13.6) days. Neither CI nor HC differed by device type; however, the Fisher-Paykel device was associated with slightly greater HC growth rate.ConclusionCPAP devices and the pressures they apply plausibly contribute to preterm infant cranial molding over time, with the greatest potential impact on infants who require CPAP support for longer periods; however, these findings must be validated in larger cohorts. Additionally, positioning practices should be further examined to determine how they may contribute to or prevent the development of cranial molding deformity.

ObjectiveTo date no research has examined the potential influence of acute stress symptoms (ASD) on subsequent development of post-traumatic stress disorder (PTSD) symptoms in stroke survivors. Our objective was to examine whether acute stress symptoms measured 1-2 weeks post-stroke predicted the presence of post-traumatic stress symptoms measured 6-12 weeks later.DesignProspective within-groups study.MethodsFifty four participants who completed a measure of acute stress disorder at 1-2 weeks following stroke (time 1) and 31 of these participants completed a measure of posttraumatic stress disorder 6-12 weeks later (time 2). Participants also completed measures of stroke severity, functional impairment, cognitive impairment, depression, anxiety, pre-morbid intelligence and pain across both time points.ResultsSome 22% met the criteria for ASD at baseline and of those, 62.5% went on to meet the criteria for PTSD at follow-up. Meanwhile two of the seven participants (28.6%) who met the criteria for PTSD at Time 2, did not meet the ASD criteria at Time 1 (so that PTSD developed subsequently). A hierarchical multiple regression analysis indicated that the presence of acute stress symptoms at baseline was predictive of post-traumatic stress symptoms at follow-up (R2 = .26, p < .01). Less severe stroke was correlated with higher levels of post-traumatic stress symptoms at Time 2 (rho = .42, p < .01).ConclusionsThe results highlight the importance of early assessment and identification of acute stress symptoms in stroke survivors as a risk factor for subsequent PTSD. Both ASD and PTSD were prevalent and the presence of both disorders should be assessed.

Many workplaces offer health and wellbeing initiatives to their staff as recommended by international and national health organisations. Despite their potential, the influence of these initiatives on health behaviour appears limited and evaluations of their effectiveness are rare. In this research, we propose evaluating the effectiveness of an established behaviour change intervention in a new workplace context. The intervention, 'mental contrasting plus implementation intentions', supports staff in achieving their health and wellbeing goals by encouraging them to compare the future with the present and to develop a plan for overcoming anticipated obstacles. We conducted a systematic review that identified only three trials of this intervention in workplaces and all of them were conducted within healthcare organisations. Our research will be the first to evaluate the effectiveness of mental contrasting outside a solely healthcare context. We propose including staff from 60 organisations, 30 in the intervention and 30 in a waitlisted control group. The findings will contribute to a better understanding of how to empower and support staff to improve their health and wellbeing. Trial registration: ISRCTN17828539.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024.

Rising rates of depression among adolescents raise many questions about the role of depressive symptoms in academic outcomes for college students and their roommates. In the current longitudinal study, we follow previously unacquainted roommate dyads over their first year in college (N = 245 dyads). We examine the role of depressive symptoms of incoming students and their roommates on their GPAs and class withdrawals (provided by university registrars) at the end of the Fall and Spring semesters. We test contagion between the roommates on both academic outcomes and depressive symptoms over time. Finally, we examine the moderating role of relationship closeness. Whereas students' own initial levels of depressive symptoms predicted their own lower GPA and more course withdrawals, they did not directly predict the academic outcomes of their roommates. For roommates who form close relationships, there was evidence of contagion of both GPAs and depressive symptoms at the end of Fall and Spring semesters. Finally, a longitudinal path model showed that as depressive symptoms spread from the student to their roommate, the roommate's GPA decreased. The current work sheds light on a common college experience with implications for the role of interventions to increase the academic and mental health of college students.

For a single species, human kinship organization is both remarkably diverse and strikingly organized. Kinship terminology is the structured vocabulary used to classify, refer to, and address relatives and family. Diversity in kinship terminology has been analyzed by anthropologists for over 150 years, although recurrent patterning across cultures remains incompletely explained. Despite the wealth of kinship data in the anthropological record, comparative studies of kinship terminology are hindered by data accessibility. Here we present Kinbank, a new database of 210,903 kinterms from a global sample of 1,229 spoken languages. Using open-access and transparent data provenance, Kinbank offers an extensible resource for kinship terminology, enabling researchers to explore the rich diversity of human family organization and to test longstanding hypotheses about the origins and drivers of recurrent patterns. We illustrate our contribution with two examples. We demonstrate strong gender bias in the phonological structure of parent terms across 1,022 languages, and we show that there is no evidence for a coevolutionary relationship between cross-cousin marriage and bifurcate-merging terminology in Bantu languages. Analysing kinship data is notoriously challenging; Kinbank aims to eliminate data accessibility issues from that challenge and provide a platform to build an interdisciplinary understanding of kinship.

BackgroundGiven the high rates of both HIV and unintended pregnancies in sub-Saharan Africa, the SCHIELD program aims to develop a multipurpose technology implant for HIV and pregnancy prevention. An end-user evaluation was undertaken with young women and health care providers to assess preferences for modifiable implant attributes to improve future adoption and rollout.MethodsFocus group discussions were conducted with potential women end users, and health care providers experienced in implant insertion or removal participated in in-depth interviews. All participants were recruited from Harare, Zimbabwe, or Soshanguve, South Africa. The purposively stratified sampled women were either implant experienced or implant naïve and were categorized into three groups: nulliparous, postpartum, or engaged in transactional sex. Topics covered included duration (six months to three years), biodegradability, removability, and independent rod retrievability (per indication). Data were analyzed using Dedoose software and summarized into emerging themes.ResultsParticipants identified three key areas that could facilitate rollout, uptake, and adherence of an implant for HIV and pregnancy prevention. First, discreetness was the most salient topic and was associated with implant characteristics such as anatomical location, flexibility, and biodegradability. Second, the ability to independently retrieve the HIV or pregnancy prevention component was preferred, as life circumstances may change and was favored by all participants, except for young women in Soshanguve. Third, there is a need for proper counseling, sensitization, provider training, and health campaigns to facilitate rollout of a 2-in-1 implant.ConclusionsA 2-in-1 implant was seen as highly desirable by most young women and health care providers. Participants discussed potential concerns and barriers to uptake of a biodegradable implant with dual HIV prevention and contraceptive properties, identifying key implant attributes that product developers can modify while still in preclinical stages.

Endothelial cells synthesize biochemical signals to coordinate a response to insults, resolve inflammation and restore barrier integrity. Vascular cells release a variety of vasoactive bioactive lipid metabolites during the inflammatory response and produce pro-resolving mediators (e.g., Lipoxin A4, LXA4) in cooperation with leukocytes and platelets to bring a halt to inflammation. Aspirin, used in a variety of cardiovascular and pro-thrombotic disorders (e.g., atherosclerosis, angina, preeclampsia), potently inhibits proinflammatory eicosanoid formation. Moreover, aspirin stimulates the synthesis of pro-resolving lipid mediators (SPM), so-called Aspirin-Triggered Lipoxins (ATL). We demonstrate that cytokines stimulated a time- and dose-dependent increase in PGI2 (6-ketoPGF1α) and PGE2 formation that is blocked by aspirin. Eicosanoid production was caused by cytokine-induced expression of cyclooxygenase-2 (COX-2). We also detected increased production of pro-resolving LXA4 in cytokine-stimulated endothelial cells. The R-enantiomer of LXA4, 15-epi-LXA4, was enhanced by aspirin, but only in the presence of cytokine challenge, indicating dependence on COX-2 expression. In contrast to previous reports, we detected arachidonate 5-lipoxygenase (ALOX5) mRNA expression and its cognate protein (5-lipoxygenase, 5-LOX), suggesting that endothelial cells possess the enzymatic machinery necessary to synthesize both pro-inflammatory and pro-resolving lipid mediators independent of added leukocytes or platelets. Finally, we observed that, endothelial cells produced LTB4 in the absence of leukocytes. These results indicate that endothelial cells produce both pro-inflammatory and pro-resolving lipid mediators in the absence of other cell types and aspirin exerts pleiotropic actions influencing both COX and LOX pathways.

Differential scanning calorimetry (DSC) can indicate changes in structure and/or concentration of the most abundant proteins in a biological sample via heat denaturation curves (HDCs). In blood serum for example, HDC changes result from either concentration changes or altered thermal stabilities for 7-10 proteins and has previously been shown capable of differentiating between sick and healthy human subjects. Here, we compare HDCs and proteomic profiles of 50 patients experiencing joint-inflammatory symptoms, 27 of which were clinically diagnosed with rheumatoid arthritis (RA). The HDC of all 50 subjects appeared significantly different from expected healthy curves, but comparison of additional differences between the RA and the non-RA subjects allowed more specific understanding of RA samples. We used mass spectrometry (MS) to investigate the reasons behind the additional HDC changes observed in RA patients. The HDC differences do not appear to be directly related to differences in the concentrations of abundant serum proteins. Rather, the differences can be attributed to modified thermal stability of some fraction of the human serum albumin (HSA) proteins in the sample. By quantifying differences in the frequency of artificially induced post translational modifications (PTMs), we found that HSA in RA subjects had a much lower surface accessibility, indicating potential ligand or protein binding partners in certain regions that could explain the shift in HSA melting temperature in the RA HDCs. Several low abundance proteins were found to have significant changes in concentration in RA subjects and could be involved in or related to binding of HSA. Certain amino acid sites clusters were found to be less accessible in RA subjects, suggesting changes in HSA structure that may be related to changes in protein-protein interactions. These results all support a change in behavior of HSA which may give insight into mechanisms of RA pathology.

Corporations across sectors engage in the conduct, sponsorship, and dissemination of scientific research. Industry sponsorship of research, however, is associated with research agendas, outcomes, and conclusions that are favourable to the sponsor. The legalization of cannabis in Canada provides a useful case study to understand the nature and extent of the nascent cannabis industry's involvement in the production of scientific evidence as well as broader impacts on equity-oriented research agendas. We conducted a cross-sectional, descriptive, meta-research study to describe the characteristics of research that reports funding from, or author conflicts of interest with, Canadian cannabis companies. From May to August 2021, we sampled licensed, prominent Canadian cannabis companies, identified their subsidiaries, and searched each company name in the PubMed conflict of interest statement search interface. Authors of included articles disclosed research support from, or conflicts of interest with, Canadian cannabis companies. We included 156 articles: 82% included at least one author with a conflict of interest and 1/3 reported study support from a Canadian cannabis company. More than half of the sampled articles were not cannabis focused, however, a cannabis company was listed amongst other biomedical companies in the author disclosure statement. For articles with a cannabis focus, prevalent topics included cannabis as a treatment for a range of conditions (15/72, 21%), particularly chronic pain (6/72, 8%); as a tool in harm reduction related to other substance use (10/72, 14%); product safety (10/72, 14%); and preclinical animal studies (6/72, 8%). Demographics were underreported in empirical studies with human participants, but most included adults (76/84, 90%) and, where reported, predominantly white (32/39, 82%) and male (49/83, 59%) participants. The cannabis company-funded studies included people who used drugs (37%) and people prescribed medical cannabis (22%). Canadian cannabis companies may be analogous to peer industries such as pharmaceuticals, alcohol, tobacco, and food in the following three ways: sponsoring research related to product development, expanding indications of use, and supporting key opinion leaders. Given the recent legalization of cannabis in Canada, there is ample opportunity to create a policy climate that can mitigate the harms of criminalization as well as impacts of the "funding effect" on research integrity, research agendas, and the evidence base available for decision-making, while promoting high-priority and equity-oriented independent research.

Questionable authorship practices in scientific publishing are detrimental to research quality and management. The existing literature dealing with the prevalence, and perceptions, of such practices has focused on the medical sciences, and on experienced researchers. In contrast, this study investigated how younger researchers (PhD students) from across the faculties view fair authorship attribution, their experience with granting guest authorships to more powerful researchers and their reasons for doing so. Data for the study were collected in a survey of European PhD students. The final dataset included 1,336 participants from five European countries (Denmark, Hungary, Ireland, Portugal, and Switzerland) representing all major disciplines. Approximately three in ten reported that they had granted at least one guest authorship to "a person in power". Half of these indicated that they had done so because they had been told to do so by the person in power. Participants from the medical, natural and technical sciences were much more likely to state that they had granted a guest authorship than those from other faculties. We identified four general views about what is sufficient for co-authorship. There were two dominant views. The first (inclusive view) considered a broad range of contributions to merit co-authorship. The second (strongly writing-oriented) emphasised that co-authors must have written a piece of the manuscript text. The inclusive view dominated in the natural, technical, and medical sciences. Participants from other faculties were more evenly distributed between the inclusive and writing oriented view. Those with an inclusive view were most likely to indicate that they have granted a guest authorship. According to the experiences of our participants, questionable authorship practices are prevalent among early-career researchers, and they appear to be reinforced through a combination of coercive power relations and dominant norms in some research cultures, particularly in the natural, technical, and medical sciences.

Comparing two Australian regions, Western Australia (WA) and South Australia (SA), this research investigates official noncompliance datasets of recreational blue swimmer crab (Portunus armatus) fishing between 2009 and 2019. These recreational fisheries in both jurisdictions are license-free and therefore participating fisher information is limited. Analyses provide a glimpse at the (noncompliant) fisher population profiles against the application of management strategies. The data provide (1) an evidence-base to optimize regulatory strategies by balancing education and enforcement activities with recreational fisher enjoyment. The results of this research enable application within and beyond these fisheries and jurisdictions; and (2) drawing from the criminology discipline, deterrence theory offers insight to enhance compliance tools. Further, it shows the importance of a multi-disciplinary approach to assessing compliance and identifies some practical approaches to data collection that can be readily undertaken to assist with more detailed analysis and enhance compliance strategies.

IntroductionCardiac arrest is the leading cause of natural death in the United States, and most surviving patients suffer from neurological dysfunction. Although this is recognized as a problem, there have been very few changes to the cardiopulmonary resuscitation (CPR) procedure. Tourniquets have been recognized for their ability to increase truncal blood pressure and have been shown to improve CPR outcomes in animal models. However, the relationship between tourniquet application and blood pressure elevation has not been adequately explored in healthy human adults.ObjectivesThe objective of this study is to demonstrate that bilateral, non-invasive, peripheral vascular occlusion in the thighs results in an increased proximal systolic blood pressure ≥ 10 mmHg.MethodsThis is a single-center, non-blinded clinical trial. Volunteers will be screened for eligibility at least 24 hours before the day of the trial. On the day of the trial, volunteers will undergo an informed consent process. If they choose to participate in the trial after informed consent, their baseline blood pressure will be measured. Volunteers will then have a Combat Application Tourniquet (CAT) applied to each thigh, and the windlasses will be tightened by IRB-approved personnel. Once no pulse can be felt in the lower extremity, blood pressure will be measured in the arm. This will be replicated three times, and the tourniquets will be loosened between trials to allow the volunteers to rest. Any complications that arise during the trial will be handled by the physician that is present.AnalysisChanges in systolic blood pressure and diastolic blood pressure will be analyzed using a Shapiro-Wilk test. Then, a one-way repeated measures analysis of variance (ANOVA) will be performed with a Holm-Sidak post-hoc test to determine the mean differences. The significance level will be set to 5% for statistical significance.Registry and registration numberClinicaltrials.gov, NCT05324306.

Patterns in within-day hive weight data from two independent datasets in Arizona and California were modeled using piecewise regression, and analyzed with respect to honey bee colony behavior and landscape effects. The regression analysis yielded information on the start and finish of a colonys daily activity cycle, hive weight change at night, hive weight loss due to departing foragers and weight gain due to returning foragers. Assumptions about the meaning of the timing and size of the morning weight changes were tested in a third study by delaying the forager departure times from one to three hours using screen entrance gates. A regression of planned vs. observed departure delays showed that the initial hive weight loss around dawn was largely due to foragers. In a similar experiment in Australia, hive weight loss due to departing foragers in the morning was correlated with net bee traffic (difference between the number of departing bees and the number of arriving bees) and from those data the payload of the arriving bees was estimated to be 0.02 g. The piecewise regression approach was then used to analyze a fifth study involving hives with and without access to natural forage. The analysis showed that, during a commercial pollination event, hives with previous access to forage had a significantly higher rate of weight gain as the foragers returned in the afternoon, and, in the weeks after the pollination event, a significantly higher rate of weight loss in the morning, as foragers departed. This combination of continuous weight data and piecewise regression proved effective in detecting treatment differences in foraging activity that other methods failed to detect.

Protected areas (PAs) are often considered the most important biodiversity conservation areas in national plans, but PAs often do not represent national-scale biodiversity. We evaluate the current conservation status of plant biodiversity within current existing PAs, and identify potential additional PAs for South Korea. We modeled species ranges for 2,297 plant species using Multivariate Adaptive Regression Splines and compared the level of mean range representation in South Korea's existing PAs, which comprise 5.7% of the country's mainland area, with an equal-area alternative PA strategy selected with the reserve algorithm Marxan. We also used Marxan to model two additional conservation scenarios that add lands to approach the Aichi Biodiversity Target objectives (17% of the country). Existing PAs in South Korea contain an average of 6.3% of each plant species' range, compared to 5.9% in the modeled equal-area alternative. However, existing PAs primarily represent a high percentage of the ranges for high-elevation and small range size species. The additional PAs scenario that adds lands to the existing PAs covers 14,587.55 km2, and would improve overall plant range representation to a mean of 16.8% of every species' range. The other additional PAs scenario, which selects new PAs from all lands and covers 13,197.35 km2, would improve overall plant range representation to a mean of 13.5%. Even though the additional PAs that includes existing PAs represents higher percentages of species' ranges, it is missing many biodiversity hotspots in non-mountainous areas and the additional PAs without locking in the existing PAs represent almost all species' ranges evenly, including low-elevation ones with larger ranges. Some priority conservation areas we identified are expansions of, or near, existing PAs, especially in northeastern and southern South Korea. However, lowland coastal areas and areas surrounding the capital city, Seoul, are also critical for biodiversity conservation in South Korea.

BackgroundAssays have been developed for cross-sectional HIV incidence estimation using plasma samples. Large scale surveillance programs are planned using dried blood spot (DBS) specimens for incidence assessment. However, limited information exists on the performance of HIV cross-sectional incidence assays using DBS.MethodsThe assays evaluated were: Maxim HIV-1 Limiting Antigen Avidity EIA (LAg-Avidity), Sedia HIV-1 BED-Capture EIA (BED-CEIA), and CDC modified BioRad HIV-1/2 Plus O Avidity-based Assay (CDC-BioRad Avidity) using pre-determined cutoff values. 100 matched HIV-1 positive plasma and DBS samples, with known duration of infection, from the Consortium for the Evaluation and Performance of HIV Incidence Assays repository were tested. All assays were run in duplicate. To examine the degree of variability within and between results for each sample type, both categorical and continuous results were analyzed. Associations were assessed with Bland Altman, R2 values and Cohen's kappa coefficient (ĸ).ResultsIntra-assay variability using the same sample type was similar for all assays (R2 0.96 to 1.00). The R2 values comparing DBS and plasma results for LAg-Avidity, BED-CEIA, and CDC-BioRad Avidity were 0.96, 0.94, and 0.84, respectively. The concordance and ĸ values between DBS and plasma for all three assays were >87% and >0.64, respectively. The Bland-Altman analysis showed significant differences between plasma and DBS samples. For all three assays, a higher number of samples were classified as recent infections using DBS samples.ConclusionsDBS and plasma sample results were highly correlated. However, when compared to plasma, each assay performed somewhat differently in DBS at the lower and higher ends of the dynamic range. DBS samples were more likely to be classified as recently infected by all three assays, which may lead to overestimation of incidence in surveys using performance criteria derived for plasma samples.

A large family of prototoxin-like molecules endogenous to mammals, Ly6 proteins have been implicated in the regulation of cell signaling processes across multiple species. Previous work has shown that certain members of the Ly6 family are expressed in the brain and target nicotinic acetylcholine receptor and potassium channel function. Structural similarities between Ly6 proteins and alpha-neurotoxins suggest the possibility of additional ionotropic receptor targets. Here, we investigated the possibility of lypd2 as a novel regulator of AMPA receptor (AMPAR) function. In particular, we focused on potential interactions with the Q/R isoforms of the GluR2 subunit, which have profound impacts on AMPAR permeability to calcium during neuronal stimulation. We find that although lypd2 and GluR2 share overlapping expression patterns in the mouse hippocampus, there was no interaction between lypd2 and either GluR2Q or GluR2R isoform. These results underscore the importance of continuing to investigate novel targets for Ly6 interaction and regulation.

The Covid-19 pandemic has been recognised to affect families’ socio-emotional well-being. Collecting the views of families in diverse socio-economic contexts can contribute to understanding their specific needs and resources in relation to the Covid-19 pandemic. The overarching objective of the current research was to explore the views and experiences of families in relation to the Covid-19 pandemic, who were living in the Republic of Ireland, including in areas designated as disadvantaged. In Study 1, the objective was to explore changes, difficulties, and concerns experienced by parents of children up to six years old during the pandemic, and related associations with socio-demographic characteristics. Data were collected from 168 parents/carers via an online questionnaire, and examined using conceptual content analysis. The most frequently identified experiences related to restrictions, social isolation, negative impacts on parents’ emotional and psychological well-being, negative impacts on children’s emotional well-being and development, concerns with physical health, uncertainty about the future, and positive changes regarding family time and activities. Associations were found with parents’ age and work situation, and family’s income and composition. In Study 2, the objective was to explore the views of children, parents, and service providers about the impact of the Covid-19 pandemic on families’ life, and relevant supports. Data were collected from 50 children aged between eight and 17 years old, 17 parents, and 20 service providers through focus group discussions, and examined using thematic analysis. The participants reported experiences related to challenges with online education, uncertainty regarding children’s education, food poverty, and children’s socio-emotional health. The findings of both studies reinforced the importance of implementing measures to promote parents’ and children’s socio-emotional well-being, combat educational inequalities, and ensure economic and employment security.

Background'Engager' is an innovative 'through-the-gate' complex care intervention for male prison-leavers with common mental health problems. In parallel to the randomised-controlled trial of Engager (Trial registration number: ISRCTN11707331), a set of process evaluation analyses were undertaken. This paper reports on the depth multiple case study analysis part of the process evaluation, exploring how a sub-sample of prison-leavers engaged and responded to the intervention offer of one-to-one support during their re-integration into the community.MethodsTo understand intervention delivery and what response it elicited in individuals, we used a realist-informed qualitative multiple 'case' studies approach. We scrutinised how intervention component delivery lead to outcomes by examining underlying causal pathways or 'mechanisms' that promoted or hindered progress towards personal outcomes. 'Cases' (n = 24) were prison-leavers from the intervention arm of the trial. We collected practitioner activity logs and conducted semi-structured interviews with prison-leavers and Engager/other service practitioners. We mapped data for each case against the intervention logic model and then used Bhaskar's (2016) 'DREIC' analytic process to categorise cases according to extent of intervention delivery, outcomes evidenced, and contributing factors behind engagement or disengagement and progress achieved.ResultsThere were variations in the dose and session focus of the intervention delivery, and how different participants responded. Participants sustaining long-term engagement and sustained change reached a state of 'crises but coping'. We found evidence that several components of the intervention were key to achieving this: trusting relationships, therapeutic work delivered well and over time; and an in-depth shared understanding of needs, concerns, and goals between the practitioner and participants. Those who disengaged were in one of the following states: 'Crises and chaos', 'Resigned acceptance', 'Honeymoon' or 'Wilful withdrawal'.ConclusionsWe demonstrate that the 'implementability' of an intervention can be explained by examining the delivery of core intervention components in relation to the responses elicited in the participants. Core delivery mechanisms often had to be 'triggered' numerous times to produce sustained change. The improvements achieved, sustained, and valued by participants were not always reflected in the quantitative measures recorded in the RCT. The compatibility between the practitioner, participant and setting were continually at risk of being undermined by implementation failure as well as changing external circumstances and participants' own weaknesses.Trial registration numberISRCTN11707331, Wales Research Ethics Committee, Registered 02-04-2016-Retrospectively registered https://doi.org/10.1186/ISRCTN11707331.

To reorient food systems to ensure they deliver healthy diets that protect against multiple forms of malnutrition and diet-related disease and safeguard the environment, ecosystems, and natural resources, there is a need for better governance and accountability. However, decision-makers are often in the dark on how to navigate their food systems to achieve these multiple outcomes. Even where there is sufficient data to describe various elements, drivers, and outcomes of food systems, there is a lack of tools to assess how food systems are performing. This paper presents a diagnostic methodology for 39 indicators representing food supply, food environments, nutrition outcomes, and environmental outcomes that offer cutoffs to assess performance of national food systems. For each indicator, thresholds are presented for unlikely, potential, or likely challenge areas. This information can be used to generate actions and decisions on where and how to intervene in food systems to improve human and planetary health. A global assessment and two country case studies-Greece and Tanzania-illustrate how the diagnostics could spur decision options available to countries.

Background Left ventricular assist device (LVAD) implantation significantly impacts on a recipient’s symptoms and quality of life. Capturing their experiences and post implant journey is an important part of clinical practice, research and device design evolution. Patient reported outcome measures (PROMs) are a useful tool for capturing that experience. However, patient reported outcome measures need to reflect recipients’ experiences. Discussions with a patient partner group found that none of the frequently used cardiology PROMs captured their unique experiences. Aims To capture the experiences and important issues for LVAD recipients. Develop a conceptual map of domains and items that should be reflected in patient reported outcomes. Methods Group concept mapping (GCM) web-based software was used to remotely capture and structure recipients’ experiences across a wide geographical area. GCM is a semi-quantitative mixed method consisting of 3 stages: item generation, item sorting and rating (importance, relevance and frequency). Patient partners were involved in all aspects of the study design and development. Results 18 LVAD recipients consented to take part. 101 statements were generated and multi-dimensional scaling, and hierarchical cluster analysis identified 9 clusters. Cluster themes included: Activities, Partner/family support, Travel, Mental wellbeing, Equipment and clothing, Physical and cognitive limitations, LVAD Restrictions, LVAD Challenges and positive impact of the LVAD (LVAD Positives). LVAD Positives were scored highest across all the rating variables, e.g., frequency (2.85), relevance (2.44) and importance (2.21). Other domains rated high for importance included physical and cognitive limitations (2.19), LVAD restrictions (2.11), Partner/family support (2.02), and Equipment and clothing (2.01). Conclusion Online GCM software facilitated the inclusion of geographically dispersed recipients and provided useful insights into the experiences of LVAD recipients. The conceptual framework identifies important domains and items that should be prioritised and included in patient reported outcomes in future research, LVAD design evolution, and clinical practice.

Stigmatizing attitudes toward children with psychopathology represent a barrier to treatment and well-being, yet almost no research has investigated what contributes to these attitudes. This study examines the effects of medication treatment and genetic etiology on stigmatizing attitudes toward a relatively new and controversial disorder-Disruptive Mood Dysregulation Disorder (DMDD). Participants (159 parents, 225 non-parents) completed a vignette study on Amazon's Mechanical Turk (MTurk) in which a child displayed behaviors consistent with DMDD. The child was described as either taking psychiatric medication or not, and the vignette described the child's condition as either genetic or did not mention etiology. Participants who were parents reported greater stigma when the etiology (genetic prime vs. no prime) matched the perceived appropriate treatment (medication vs. no medication). Among parents, a child treated with medication who had a genetic disorder, and a child who was not treated with medication and for whom genetic etiology was not primed, were most stigmatized. No differences emerged among non-parents. These findings highlight the importance of considering multiple factors (parental status, congruence between treatment and perceived disorder etiology) when investigating mental health stigma and underscore the need to further investigate such nuances to inform anti-stigma interventions.

The COVID-19 pandemic brought widespread attention to an “infodemic” of potential health misinformation. This claim has not been assessed based on evidence. We evaluated if health misinformation became more common during the pandemic. We gathered about 325 million posts sharing URLs from Twitter and Facebook during the beginning of the pandemic (March 8-May 1, 2020) compared to the same period in 2019. We relied on source credibility as an accepted proxy for misinformation across this database. Human annotators also coded a subsample of 3000 posts with URLs for misinformation. Posts about COVID-19 were 0.37 times as likely to link to “not credible” sources and 1.13 times more likely to link to “more credible” sources than prior to the pandemic. Posts linking to “not credible” sources were 3.67 times more likely to include misinformation compared to posts from “more credible” sources. Thus, during the earliest stages of the pandemic, when claims of an infodemic emerged, social media contained proportionally less misinformation than expected based on the prior year. Our results suggest that widespread health misinformation is not unique to COVID-19. Rather, it is a systemic feature of online health communication that can adversely impact public health behaviors and must therefore be addressed.

The threat to public health posed by drug-resistant bacteria is rapidly increasing, as some of healthcare’s most potent antibiotics are becoming obsolete. Approximately two-thirds of the world’s antibiotics are derived from natural products produced by Streptomyces encoded biosynthetic gene clusters. Thus, to identify novel gene clusters, we sequenced the genomes of four bioactive Streptomyces strains isolated from the soil in San Diego County and used Bacterial Cytological Profiling adapted for agar plate culturing in order to examine the mechanisms of bacterial inhibition exhibited by these strains. In the four strains, we identified 104 biosynthetic gene clusters. Some of these clusters were predicted to produce previously studied antibiotics; however, the known mechanisms of these molecules could not fully account for the antibacterial activity exhibited by the strains, suggesting that novel clusters might encode antibiotics. When assessed for their ability to inhibit the growth of clinically isolated pathogens, three Streptomyces strains demonstrated activity against methicillin-resistant Staphylococcus aureus. Additionally, due to the utility of bacteriophages for genetically manipulating bacterial strains via transduction, we also isolated four new phages (BartholomewSD, IceWarrior, Shawty, and TrvxScott) against S. platensis. A genomic analysis of our phages revealed nearly 200 uncharacterized proteins, including a new site-specific serine integrase that could prove to be a useful genetic tool. Sequence analysis of the Streptomyces strains identified CRISPR-Cas systems and specific spacer sequences that allowed us to predict phage host ranges. Ultimately, this study identified Streptomyces strains with the potential to produce novel chemical matter as well as integrase-encoding phages that could potentially be used to manipulate these strains.

Many childhood cancer survivors desire biological children but are at risk for infertility after treatment. One option for mitigating risk is the use of fertility preservation prior to gonadotoxic therapy. Adolescents and emerging adults may rely on their parents to help them decide whether to use fertility preservation. While this is often a collaborative process, it is currently unknown how parents can optimally support adolescents and emerging adults through this decision. To address this gap, we developed a family-centered, psychoeducational intervention to prompt adolescents and emerging adults to reflect on their future parenthood goals and attitudes towards fertility preservation, as well as to prompt their parents (or other caregivers) to reflect on their own and their child's perspectives on the topic. In this randomized controlled trial, families will be randomized to either the standard of care control group (fertility consult) or the intervention group. After their fertility consult, adolescents and emerging adults and parents in the intervention group will complete a fertility preservation values clarification tool and then participate in a guided conversation about their responses and the fertility preservation decision. The primary expected outcome of this study is that participation in the intervention will increase the use of fertility preservation. The secondary expected outcome is an improvement in decision quality. Chi-square analyses and t-tests will evaluate primary and secondary outcomes. The goal of this intervention is to optimize family-centered fertility preservation decision-making in the context of a new cancer diagnosis to help male adolescents and emerging adults achieve their future parenthood goals.

The generation of surrogate potential energy functions (PEF) that are orders of magnitude faster to compute but as accurate as the underlying training data from high-level electronic structure methods is one of the most promising applications of fitting procedures in chemistry. In previous work, we have shown that transition state force fields (TSFFs), fitted to the functional form of MM3* force fields using the quantum guided molecular mechanics (Q2MM) method, provide an accurate description of transition states that can be used for stereoselectivity predictions of small molecule reactions. Here, we demonstrate the applicability of the method for fit TSFFs to the well-established Amber force field, which could be used for molecular dynamics studies of enzyme reaction. As a case study, the fitting of a TSFF to the second hydride transfer in Pseudomonas mevalonii 3-hydroxy-3-methylglutaryl coenzyme A reductase (PmHMGR) is used. The differences and similarities to fitting of small molecule TSFFs are discussed.

Antibiotic resistance is a worldwide problem that is increasing largely due to the misuse of antibiotics in human health and agriculture. This situation is further exacerbated by a dearth of new antibiotic development, the focus of pharmaceutical companies having shifted to more lucrative treatments for chronic conditions such as elevated blood pressure. To conserve the efficacy of the current crop of antibiotics, it is vital that they are used appropriately by individuals. Effective education may be a means to achieve such appropriate use. This paper reports on a large-scale, mixed methods study, which employed a survey and oral questionnaires, undertaken with senior secondary Omani students. The study explored students' understanding of antibiotic resistance as well as their attitudes to the issue of antibiotic resistance. The study findings indicated that, although some students had a reasonably clear understanding of antibiotic resistance, many had serious misconceptions that could result in misuse of antibiotics. The article concludes with suggestions for amending secondary school pedagogy in Oman to address the misconceptions.

We investigated the cumulative effects of predation by piscivorous colonial waterbirds on the survival of multiple salmonid (Oncorhynchus spp.) populations listed under the U.S. Endangered Species Act (ESA) and determined what proportion of all sources of fish mortality (1 -survival) were due to birds in the Columbia River basin, USA. Anadromous juvenile salmonids (smolts) were exposed to predation by Caspian terns (Hydroprogne caspia), double-crested cormorants (Nannopterum auritum), California gulls (Larus californicus), and ring-billed gulls (L. delawarensis), birds known to consume both live and dead fish. Avian consumption and survival probabilities (proportion of available fish consumed or alive) were estimated for steelhead trout (O. mykiss), yearling Chinook salmon (O. tshawytscha), sub-yearling Chinook salmon, and sockeye salmon (O. nerka) during out-migration from the lower Snake River to the Pacific Ocean during an 11-year study period (2008-2018). Results indicated that probabilities of avian consumption varied greatly across salmonid populations, bird species, colony location, river reach, and year. Cumulative consumption probabilities (consumption by birds from all colonies combined) were consistently the highest for steelhead, with annual estimates ranging from 0.22 (95% credible interval = 0.20-0.26) to 0.51 (0.43-0.60) of available smolts. The cumulative effects of avian consumption were significantly lower for yearling and sub-yearling Chinook salmon, with consumption probabilities ranging annually from 0.04 (0.02-0.07) to 0.10 (0.07-0.15) and from 0.06 (0.3-0.09) to 0.15 (0.10-0.23), respectively. Avian consumption probabilities for sockeye salmon smolts was generally higher than for Chinook salmon smolts, but lower than for steelhead smolts, ranging annually from 0.08 (0.03-0.22) to 0.25 (0.14-0.44). Although annual consumption probabilities for birds from certain colonies were more than 0.20 of available smolts, probabilities from other colonies were less than 0.01 of available smolts, indicating that not all colonies of birds posed a substantial risk to smolt mortality. Consumption probabilities were lowest for small colonies and for colonies located a considerable distance from the Snake and Columbia rivers. Total mortality attributed to avian consumption was relatively small for Chinook salmon (less than 10%) but was the single greatest source of mortality for steelhead (greater than 50%) in all years evaluated. Results suggest that the potential benefits to salmonid populations of managing birds to reduce smolt mortality would vary widely depending on the salmonid population, the species of bird, and the size and location of the breeding colony.

The association between COVID-19 symptoms and antibody responses against SARS-CoV-2 is poorly characterized. We analyzed antibody levels in individuals with known SARS-CoV-2 infection to identify potential antibody-symptom associations. Convalescent plasma from 216 SARS-CoV-2 RNA+ individuals with symptomatology information were tested for the presence of IgG to the spike S1 subunit (Euroimmun ELISA), IgG to receptor binding domain (RBD, CoronaCHEK rapid test), and for IgG, IgA, and IgM to nucleocapsid (N, Bio-Rad ELISA). Logistic regression was used to estimate the odds of having a COVID-19 symptom from the antibody response, adjusting for sex and age. Cough strongly associated with antibodies against S1 (adjusted odds ratio [aOR] = 5.33; 95% CI from 1.51 to 18.86) and RBD (aOR = 4.36; CI 1.49, 12.78). In contrast, sore throat significantly associated with the absence of antibodies to S1 and N (aOR = 0.25; CI 0.08, 0.80 and aOR = 0.31; 0.11, 0.91). Similarly, lack of symptoms associated with the absence of antibodies to N and RBD (aOR = 0.16; CI 0.03, 0.97 and aOR = 0.16; CI 0.03, 1.01). Cough appeared to be correlated with a seropositive result, suggesting that SARS-CoV-2 infected individuals exhibiting lower respiratory symptoms generate a robust antibody response. Conversely, those without symptoms or limited to a sore throat while infected with SARS-CoV-2 were likely to lack a detectable antibody response. These findings strongly support the notion that severity of infection correlates with robust antibody response.

BackgroundThere is encouraging evidence that interdisciplinary teams of Health and Social Care Professionals (HSCPs) can enhance patient care in the Emergency Department (ED), especially for older adults with complex needs. However, no formal process evaluations of implementations of ED-based HSCP interventions are available. The study aimed to evaluate the development and delivery of a HSCP team intervention for older adults in the ED of a large Irish teaching hospital.MethodsUsing the Medical Research Council (MRC) Framework for process evaluations, we investigated implementation and delivery, mechanisms of impact, and contextual influences on implementation by analysing the HSCP team's activity notes and participant recruitment logs, and by carrying out six interviews and four focus groups with 26 participants (HSCP team members, ED doctors and nurses, hospital staff). Qualitative insights were analysed thematically.ResultsThe implementation process had three phases (pre-implementation, piloting, and delivery), with the first two described as pivotal to optimise care procedures and build positive stakeholders' involvement. The team's motivation and proactive communication were key to promote acceptability and integration in the ED (Theme 1); also, their specialised skills and interdisciplinary approach enhanced patient and staff's ED experience (Theme 2). The investment and collaboration of multiple stakeholders were described as essential contextual enablers of implementation (Theme 4). Delivering the intervention within a randomised controlled trial fostered credibility but caused frustration among patients and staff (Theme 3).DiscussionThis process evaluation is the first to provide in-depth and practical insights on the complexities of developing and delivering an ED-based HSCP team intervention for older adults. Our findings highlight the importance of establishing a team of HSCPs with a strong interdisciplinary ethos to ensure buy-in and integration in the ED processes. Also, actively involving relevant stakeholders is key to facilitate implementation.Trial registrationClinicalTrials.gov, NCT03739515; registered on 12th November 2018.

Understanding how to source agricultural raw materials sustainably is challenging in today's globalized food system given the variety of issues to be considered and the multitude of suggested indicators for representing these issues. Furthermore, stakeholders in the global food system both impact these issues and are themselves vulnerable to these issues, an important duality that is often implied but not explicitly described. The attention given to these issues and conceptual frameworks varies greatly--depending largely on the stakeholder perspective--as does the set of indicators developed to measure them. To better structure these complex relationships and assess any gaps, we collate a comprehensive list of sustainability issues and a database of sustainability indicators to represent them. To assure a breadth of inclusion, the issues are pulled from the following three perspectives: major global sustainability assessments, sustainability communications from global food companies, and conceptual frameworks of sustainable livelihoods from academic publications. These terms are integrated across perspectives using a common vocabulary, classified by their relevance to impacts and vulnerabilities, and categorized into groups by economic, environmental, physical, human, social, and political characteristics. These issues are then associated with over 2,000 sustainability indicators gathered from existing sources. A gap analysis is then performed to determine if particular issues and issue groups are over or underrepresented. This process results in 44 "integrated" issues--24 impact issues and 36 vulnerability issues--that are composed of 318 "component" issues. The gap analysis shows that although every integrated issue is mentioned at least 40% of the time across perspectives, no issue is mentioned more than 70% of the time. A few issues infrequently mentioned across perspectives also have relatively few indicators available to fully represent them. Issues in the impact framework generally have fewer gaps than those in the vulnerability framework.

Background Hepatic and biliary diseases are prevalent worldwide, but the majority of people lack access to diagnostic medical imaging for their assessment. The liver and gallbladder are readily amenable to sonographic examination, and ultrasound is a portable, cost-effective imaging modality suitable for use in rural and underserved areas. However, the deployment of ultrasound in these settings is limited by the lack of experienced sonographers to perform the exam. In this study, we tested an asynchronous telediagnostic system for right upper quadrant abdominal ultrasound examination operated by individuals without prior ultrasound experience to facilitate deployment of ultrasound to rural and underserved areas. Methods The teleultrasound system utilized in this study employs volume sweep imaging and a telemedicine app installed on a tablet which connects to an ultrasound machine. Volume sweep imaging is an ultrasound technique in which an individual scans the target region utilizing preset ultrasound sweeps demarcated by easily recognized external body landmarks. The sweeps are saved as video clips for later interpretation by an experienced radiologist. Teleultrasound scans from a Peruvian clinic obtained by individuals without prior ultrasound experience were sent to the United States for remote interpretation and quality assessment. Standard of care comparison was made to a same-day ultrasound examination performed by a radiologist. Results Individuals without prior ultrasound experience scanned 144 subjects. Image quality was rated “poor” on 36.8% of exams, “acceptable” on 38.9% of exams, and “excellent” on 24.3% of exams. Among telemedicine exams of “acceptable” or “excellent” image quality (n = 91), greater than 80% of the liver and gallbladder were visualized in the majority of cases. In this group, there was 95% agreement between standard of care and teleultrasound on whether an exam was normal or abnormal, with a Cohen’s kappa of 0.84 (95% CI 0.7–0.98, p Conclusion This asynchronous telediagnostic system allows individuals without prior ultrasound experience to effectively scan the liver, gallbladder, and right kidney with a high degree of agreement with standard of care ultrasound. This system can be deployed to improve access to diagnostic imaging in low-resource areas.

[This corrects the article DOI: 10.1371/journal.pone.0228725.].

Intimate and sexual relationships provide opportunity for emotional and sexual fulfillment. In consensually non-monogamous (CNM) relationships, needs are dispersed among multiple partners. Using Self-Determination Theory (SDT) and dyadic data from 56 CNM partnerships (112 individuals), we tested how sexual motives and need fulfillment were linked to relational outcomes. We drew from models of need fulfillment to explore how sexual motives with a second partner were associated with satisfaction in the primary relationship. In a cross-sectional and daily experience study we demonstrated that self-determined reasons for sex were positively associated with sexual satisfaction and indirectly linked through sexual need fulfillment. Self-determined reasons for sex predicted need fulfillment for both partners at a three-month follow up. The association between sexual motives and need fulfillment was stronger on days when participants engaged in sex with an additional partner, though this was not related to satisfaction in the primary relationship. Implications for need fulfillment are discussed.