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The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex serves to connect the nuclear envelope and the cytoskeleton, influencing cellular processes such as nuclear arrangement, architecture, and mechanotransduction. The role LINC plays in mechanotransduction pathways in bone progenitor cells has been well studied; however, the mechanisms by which LINC complexes govern in vivo bone formation remain less clear. To bridge this knowledge gap, we established a murine model disrupting LINC using transgenic Prx-Cre mice and floxed Tg(CAG-LacZ/EGFP-KASH2) mice. Prx-Cre mice express the Cre recombinase enzyme controlled by the paired-related homeobox gene-1 promoter (Prrx1), a pivotal regulator of skeletal development. Prx-Cre animals have been widely used in the bone field to target bone progenitor cells. Tg(CAG-LacZ/EGFP-KASH2) mice carry a lox-stop-lox flanked LacZ gene allowing for the overexpression of an EGFP-KASH2 fusion protein via cre recombinase mediated deletion of the LacZ cassette. This disrupts endogenous Nesprin-Sun binding in a dominant negative manner disconnecting nesprin from the nuclear envelope. By combining these lines, we generated a Prrx1(+) cell-specific LINC disruption model to study its impact on the developing skeleton and subsequently exercise-induced bone accrual. The findings presented here indicate Prx-driven LINC disruption (PDLD) cells exhibit no change in osteogenic and adipogenic potential compared to controls in vitro nor are there bone quality changes when compared to in sedentary animals at 8 weeks. While PDLD animals displayed increased voluntary running activity andPrrx1(+) cell-specific LINC disruption abolished the exercise-induced increases in osteoid volume and surface after a 6-week exercise intervention, no other changes in bone microarchitecture or mechanical properties were found.

There are few studies comparing proportion, frequency, mortality and mortality rate following antimicrobial-resistant (AMR) infections between tertiary-care hospitals (TCHs) and secondary-care hospitals (SCHs) in low and middle-income countries (LMICs) to inform intervention strategies. The aim of this study is to demonstrate the utility of an offline tool to generate AMR reports and data for a secondary data analysis. We conducted a secondary-data analysis on a retrospective, multicentre data of hospitalised patients in Thailand. Routinely collected microbiology and hospital admission data of 2012 to 2015, from 15 TCHs and 34 SCHs were analysed using the AMASS v2.0 (www.amass.website). We then compared the burden of AMR bloodstream infections (BSI) between those TCHs and SCHs. Of 19,665 patients with AMR BSI caused by pathogens under evaluation, 10,858 (55.2%) and 8,807 (44.8%) were classified as community-origin and hospital-origin BSI, respectively. The burden of AMR BSI was considerably different between TCHs and SCHs, particularly of hospital-origin AMR BSI. The frequencies of hospital-origin AMR BSI per 100,000 patient-days at risk in TCHs were about twice that in SCHs for most pathogens under evaluation (for carbapenem-resistant Acinetobacter baumannii [CRAB]: 18.6 vs. 7.0, incidence rate ratio 2.77; 95%CI 1.72-4.43, p0.20). Due to the higher frequencies, all-cause in-hospital mortality rates following hospital-origin AMR BSI per 100,000 patient-days at risk were considerably higher in TCHs for most pathogens (for CRAB: 10.2 vs. 3.6,mortality rate ratio 2.77; 95%CI 1.71 to 4.48, p

Recent national trends in the United States indicate a significant increase in childhood obesity, a major public health concern with documented physical and mental comorbidities and sociodemographic disparities. We aimed to estimate the prevalence of obesity and severe obesity among youth in New York City (NYC) before the COVID-19 pandemic and examine time trends overall and by key characteristics. We included all valid height and weight measurements of kindergarten through 8th grade public school students aged 5 to 15 from school years 2011-12 through 2019-20 (N = 1,370,890 unique students; 5,254,058 observations). Obesity and severe obesity were determined using age- and sex-specific body mass index percentiles based on the Centers for Disease Control and Prevention growth charts. Analyses were performed using multivariate logistic regression models with repeated cross-sectional observations weighted to represent the student population for each year and clustered by student and school. Among youth attending public elementary and middle schools in NYC, we estimate that 20.9% and 6.4% had obesity and severe obesity, respectively, in 2019-20. While consistent declines in prevalence were observed overall from 2011-12 to 2019-20 (2.8% relative decrease in obesity and 0.2% in severe obesity, p

[This corrects the article DOI: 10.1371/journal.pone.0204509.].

BackgroundLittle is known about diagnostic and antibiotic use practices in low and middle-income countries (LMICs) before and during COVID-19 pandemic. This information is crucial for monitoring and evaluation of diagnostic and antimicrobial stewardships in healthcare facilities.MethodsWe linked and analyzed routine databases of hospital admission, microbiology laboratory and drug dispensing of Indonesian National Referral Hospital from 2019 to 2020. Patients were classified as COVID-19 cases if their SARS-CoV-2 RT-PCR result were positive. Blood culture (BC) practices and time to discontinuation of parenteral antibiotics among inpatients who received a parenteral antibiotic for at least four consecutive days were used to assess diagnostic and antibiotic use practices, respectively. Fine and Grey subdistribution hazard model was used.ResultsOf 1,311 COVID-19 and 58,917 non-COVID-19 inpatients, 333 (25.4%) and 18,837 (32.0%) received a parenteral antibiotic for at least four consecutive days. Proportion of patients having BC taken within ±1 calendar day of parenteral antibiotics being started was higher in COVID-19 than in non-COVID-19 patients (21.0% [70/333] vs. 18.7% [3,529/18,837]; pConclusionsRoutine electronic data could be used to inform diagnostic and antibiotic use practices in LMICs. In Indonesia, the proportion of timely blood culture is low in both COVID-19 and non-COVID-19 patients, and duration of parenteral antibiotics is longer in COVID-19 patients. Improving diagnostic and antimicrobial stewardship is critically needed.

IntroductionThere is a pressing need for transitional care that prepares rural dwelling medical patients to identify and respond to the signs of worsening health conditions. An evidence-based warning signs intervention has the potential to address this need. While the intervention is predominantly delivered by nurses, other healthcare providers may be required to deliver it in rural communities where human health resources are typically limited. Understanding the perspectives of other healthcare providers likely to be involved in delivering the intervention is a necessary first step to avert consequences of low acceptability, such as poor intervention implementation, uptake, and effectiveness. This study examined and compared nurses' and other healthcare providers' perceived acceptability of an evidence-based warning signs intervention proposed for rural transitional care.MethodsA cross-sectional design was used. The convenience sample included 45 nurses and 32 other healthcare providers (e.g., physical and occupational therapists, physicians) who self-identified as delivering transitional care to patients in rural Ontario, Canada. In an online survey, participants were presented with a description of the warning signs intervention and completed established measures of intervention acceptability. The measures captured 10 intervention acceptability attributes (effectiveness, appropriateness, risk, convenience, relevance, applicability, usefulness, frequency of current use, likelihood of future use, and confidence in ability to deliver the intervention). Ratings ≥ 2 indicated acceptability. Data analysis included descriptive statistics, independent samples t-tests, as well as effect sizes to quantify the magnitude of any differences in acceptability ratings between nurses and other healthcare providers.ResultsNurses and other healthcare providers rated all intervention attributes > 2, except the attributes of convenience and frequency of current use. Differences between the two groups were found for only three attributes: nurses' ratings were significantly higher than other healthcare providers on perceived applicability, frequency of current use, and the likelihood of future use of the intervention (all p's < .007; effect sizes .58 - .68, respectively).DiscussionThe results indicate that both participant groups had positive perspectives of the intervention on most of the attributes and suggest that initiatives to enhance the convenience of the intervention's implementation are warranted to support its widespread adoption in rural transitional care. However, the results also suggest that other healthcare providers may be less receptive to the intervention in practice. Future research is needed to explore and mitigate the possible reasons for low ratings on perceived convenience and frequency of current use of the intervention, as well as the between group differences on perceived applicability, frequency of current use, and the likelihood of future use of the intervention.ConclusionsThe intervention represents a tenable option for rural transitional care in Ontario, Canada, and possibly other jurisdictions emphasizing transitional care.

There is a growing interest in low dose radiation (LDR) to counteract neurodegeneration. However, LDR effects on normal brain have not been completely explored yet. Recent analyses showed that LDR exposure to normal brain tissue causes expression level changes of different proteins including neurodegeneration-associated proteins. We assessed the proteomic changes occurring in radiated vs. sham normal swine brains. Due to its involvement in various neurodegenerative processes, including those associated with cognitive changes after high dose radiation exposure, we focused on the hippocampus first. We observed significant proteomic changes in the hippocampus of radiated vs. sham swine after LDR (1.79Gy). Mass spectrometry results showed 190 up-regulated and 120 down-regulated proteins after LDR. Western blotting analyses confirmed increased levels of TPM1, TPM4, PCP4 and NPY (all proteins decreased in various neurodegenerative processes, with NPY and PCP4 known to be neuroprotective) in radiated vs. sham swine. These data support the use of LDR as a potential beneficial tool to interfere with neurodegenerative processes and perhaps other brain-related disorders, including behavioral disorders.

Candida albicans is a commensal yeast that has important impacts on host metabolism and immune function, and can establish life-threatening infections in immunocompromised individuals. Previously, C. albicans colonization has been shown to contribute to the progression and severity of alcoholic liver disease. However, relatively little is known about how C. albicans responds to changing environmental conditions in the GI tract of individuals with alcohol use disorder, namely repeated exposure to ethanol. In this study, we repeatedly exposed C. albicans to high concentrations (10% vol/vol) of ethanol-a concentration that can be observed in the upper GI tract of humans following consumption of alcohol. Following this repeated exposure protocol, ethanol small colony (Esc) variants of C. albicans isolated from these populations exhibited increased ethanol tolerance, altered transcriptional responses to ethanol, and cross-resistance/tolerance to the frontline antifungal fluconazole. These Esc strains exhibited chromosomal copy number variations and carried polymorphisms in genes previously associated with the acquisition of fluconazole resistance during human infection. This study identifies a selective pressure that can result in evolution of fluconazole tolerance and resistance without previous exposure to the drug.

Male contraceptive options and infertility treatments are limited, and almost all innovation has been limited to updates to medically assisted reproduction protocols and methods. To accelerate the development of drugs that can either improve or inhibit fertility, we established a small molecule library as a toolbox for assay development and screening campaigns using human spermatozoa. We have profiled all compounds in the Sperm Toolbox in several automated high-throughput assays that measure stimulation or inhibition of sperm motility or the acrosome reaction. We have assayed motility under non-capacitating and capacitating conditions to distinguish between pathways operating under these different physiological states. We also assayed cell viability to ensure any effects on sperm function are specific. A key advantage of our studies is that all compounds are assayed together in the same experimental conditions, which allows quantitative comparisons of their effects in complementary functional assays. We have combined the resulting datasets to generate fingerprints of the Sperm Toolbox compounds on sperm function. The data are included in an on-line R-based app for convenient querying.

FITNESSGRAM® is the most widely used criterion-referenced tool to assess/report on student health-related fitness across the US. Potential weight-related biases with the two most common tests of musculoskeletal fitness-the trunk extension and Back-Saver Sit-and-Reach (sit-and-reach)-have been hypothesized, though have not been studied. To determine the association between musculoskeletal fitness test performance and weight status, we use data from 571,133 New York City public school 4th-12th grade students (85% non-White; 75% qualified for free or reduced-price meals) with valid/complete 2017-18 FITNESSGRAM® data. Adjusted logistic mixed effects models with a random effect for school examined the association between weight status and whether a student was in the Healthy Fitness Zone (HFZ; met sex- and age-specific criterion-referenced standards) for the trunk extension and sit-and-reach. Compared to students with normal weight, the odds of being in the HFZ for trunk extension were lower for students with underweight (OR = 0.77; 95% CI: 0.741, 0.795) and higher for students with overweight (OR = 1.10; 95% CI: 1.081, 1.122) and obesity (OR = 1.11; 95% CI: 1.090, 1.13). The odds of being in the HFZ for sit-and-reach were lower for students with underweight OR = 0.85; 95% CI: 0.826, 0.878), overweight (OR = 0.83; 95% CI: 0.819, 0.844) and obesity (OR = 0.65; 95% CI: 0.641, 0.661). Students with overweight and obesity perform better on the trunk extension, yet worse on the sit-and-reach, compared to students with normal weight. Teachers, administrators, and researchers should be aware of the relationship of BMI with student performance in these assessments.

Standardized physical fitness monitoring provides a more accurate proxy for youth health when compared with physical activity. Little is known about the utilization of broad-scale individual-level youth physical fitness testing to explore health disparities. We examined longitudinal trends in population-level fitness for 4th-12th grade New York City youth during 2006/7-2016/17 (average n = 510,293 per year). Analyses were performed in 2019. The primary outcome was whether or not youth achieved sex-/age-specific performance levels (called the Healthy Fitness Zone) on the aerobic capacity, muscular strength and muscular endurance tests using the NYC FITNESSGRAM. The Cooper Institute's most recent Healthy Fitness Zone criteria were applied to all tests and years. Prevalence estimates were weighted, accounted for school clustering, adjusted for student-level sociodemographics, and run by sociodemographic subgroups and year. The overall prevalence for meeting 3 Healthy Fitness Zones increased from 15.5% (95%CI: 13.9%-17.0%) in 2006/7 to 23.3% (95%CI: 22.2%-24.4%) in 2016/17 for students in grades 4-12. Fitness for all student groups increased over time, although Hispanic and non-Hispanic black girls consistently had the lowest prevalence of meeting 3 Healthy Fitness Zones as compared to all other race/sex subgroups. Also, 9th-12th graders had a lower prevalence of meeting 3 Healthy Fitness Zones as compared to 4th-8th graders. Given forecasted sharp increases in cardiovascular disease prevalence, routine youth fitness surveillance using standardized, criterion referenced methods can identify important fitness disparities and inform interventions.

BackgroundMass administrations of antimalarial drugs (MDA) have reduced the incidence and prevalence of P. falciparum infections in a trial in the Greater Mekong Subregion. Here we assess the impact of the MDA on P. vivax infections.MethodsBetween May 2013 and July 2017, four villages in each Myanmar, Vietnam, Cambodia and Lao PDR were selected based on high prevalence of P. falciparum infections. Eight of the 16 villages were randomly assigned to receive MDA consisting of three-monthly rounds of three-day courses of dihydroartemisinin-piperaquine and, except in Cambodia, a single low-dose of primaquine. Cross-sectional surveys were conducted at quarterly intervals to detect Plasmodium infections using ultrasensitive qPCR. The difference in the cumulative incidence between the groups was assessed through a discrete time survival approach, the difference in prevalence through a difference-in-difference analysis, and the difference in the number of participants with a recurrence of P. vivax infection through a mixed-effect logistic regression.Results3,790 (86%) residents in the intervention villages participated in at least one MDA round, of whom 2,520 (57%) participated in three rounds. The prevalence of P. vivax infections fell from 9.31% to 0.89% at month 3 but rebounded by six months to 5.81%. There was no evidence that the intervention reduced the cumulative incidence of P.vivax infections (95% confidence interval [CI] Odds ratio (OR): 0.29 to 1.36). Similarly, there was no evidence of MDA related reduction in the number of participants with at least one recurrent infection (OR: 0.34; 95% CI: 0.08 to 1.42).ConclusionMDA with schizontocidal drugs had a lasting effect on P. falciparum infections but only a transient effect on the prevalence of P. vivax infections. Radical cure with an 8-aminoquinoline will be needed for the rapid elimination of vivax malaria.

Microtubules are polymeric filaments, constructed of α-β tubulin heterodimers that underlie critical subcellular structures in eukaryotic organisms. Four homologous proteins (γ-, δ-, ε- and ζ-tubulin) additionally contribute to specialized microtubule functions. Although there is an immense volume of publicly available data pertaining to tubulins, it is difficult to assimilate all potentially relevant information across diverse organisms, isotypes, and categories of data. We previously assembled an extensive web-based catalogue of published missense mutations to tubulins with >1,500 entries that each document a specific substitution to a discrete tubulin, the species where the mutation was described and the associated phenotype with hyperlinks to the amino acid sequence and citation(s) for research. This report describes a significant update and expansion of our online resource (TubulinDB.bio.uci.edu) to nearly 18,000 entries. It now encompasses a cross-referenced catalog of post-translational modifications (PTMs) to tubulin drawn from public datasets, primary literature, and predictive algorithms. In addition, tubulin protein structures were used to define local interactions with bound ligands (GTP, GDP and diverse microtubule-targeting agents) and amino acids at the intradimer interface, within the microtubule lattice and with associated proteins. To effectively cross-reference these datasets, we established a universal tubulin numbering system to map entries into a common framework that accommodates specific insertions and deletions to tubulins. Indexing and cross-referencing permitted us to discern previously unappreciated patterns. We describe previously unlinked observations of loss of PTM sites in the context of cancer cells and tubulinopathies. Similarly, we expanded the set of clinical substitutions that may compromise MAP or microtubule-motor interactions by collecting tubulin missense mutations that alter amino acids at the interface with dynein and doublecortin. By expanding the database as a curated resource, we hope to relate model organism data to clinical findings of pathogenic tubulin variants. Ultimately, we aim to aid researchers in hypothesis generation and design of studies to dissect tubulin function.

IntroductionVoluntary medical male circumcision (VMMC) clients are required to attend multiple post-operative follow-up visits in South Africa. However, with demonstrated VMMC safety, stretched clinic staff in SA may conduct more than 400,000 unnecessary reviews for males without complications, annually. Embedded into a randomized controlled trial (RCT) to test safety of two-way, text-based (2wT) follow-up as compared to routine in-person visits among adult clients, the objective of this study was to compare 2wT and routine post-VMMC care costs in rural and urban South African settings.MethodsActivity-based costing (ABC) estimated the costs of post-VMMC care, including counselling, follow-ups, and tracing in $US dollars. Transportation for VMMC and follow-up was provided for rural clients in outreach settings but not for urban clients in static sites. Data were collected from National Department of Health VMMC forms, RCT databases, and time-and-motion surveys. Sensitivity analysis presents different follow-up scenarios. We hypothesized that 2wT would save per-client costs overall, with higher savings in rural settings.ResultsVMMC program costs were estimated from 1,084 RCT clients: 537 in routine care and 547 in 2wT. On average, 2wT saved $3.56 per client as compared to routine care. By location, 2wT saved $7.73 per rural client and increased urban costs by $0.59 per client. 2wT would save $2.16 and $7.02 in follow-up program costs if men attended one or two post-VMMC visits, respectively.ConclusionQuality 2wT follow-up care reduces overall post-VMMC care costs by supporting most men to heal at home while triaging clients with potential complications to timely, in-person care. 2wT saves more in rural areas where 2wT offsets transportation costs. Minimal additional 2wT costs in urban areas reflect high care quality and client engagement, a worthy investment for improved VMMC service delivery. 2wT scale-up in South Africa could significantly reduce overall VMMC costs while maintaining service quality.

BackgroundHealthcare services regularly receive patient feedback, most of which is positive. Empirical studies suggest that health services can use positive feedback to create patient benefit. Our aim was to map all available empirical evidence for how positive patient feedback creates change in healthcare settings.MethodsEmpirical studies in English were systematically identified through database searches (ACM Digital Library, AMED, ASSIA, CINAHL, MEDLINE and PsycINFO), forwards and backwards citation, and expert consultation. We summarise the characteristics of included studies and the feedback they consider, present a thematic synthesis of qualitative findings, and provide narrative summaries of quantitative findings.Results68 papers were included, describing research conducted across six continents, with qualitative (n = 51), quantitative (n = 10), and mixed (n = 7) methods. Only two studies were interventional. The most common settings were hospitals (n = 27) and community healthcare (n = 19). The most common recipients were nurses (n = 29). Most outcomes described were desirable. These were categorised as (a) short-term emotional change for healthcare workers (including feeling motivated and improved psychological wellbeing); (b) work-home interactional change for healthcare workers (such as improved home-life relationships); (c) work-related change for healthcare workers (such as improved performance and staff retention). Some undesirable outcomes were described, including envy when not receiving positive feedback. The impact of feedback may be moderated by characteristics of particular healthcare roles, such as night shift workers having less interaction time with patients. Some factors moderating the change created by feedback are modifiable.ConclusionFurther interventional research is required to assess the effectiveness and cost-effectiveness of receiving positive feedback in creating specific forms of change such as increases in staff retention. Healthcare managers may wish to use positive feedback more regularly, and to address barriers to staff receiving feedback.

IntroductionPeople living with frailty risk adverse outcomes following even minor illnesses. Admission to hospital or the intensive care unit is associated with potentially burdensome interventions and poor outcomes. Decision-making during an emergency is fraught with complexity and potential for conflict between patients, carers and clinicians. Advance care planning is a process of shared decision-making which aims to ensure patients are treated in line with their wishes. However, planning for future care is challenging and those living with frailty are rarely given the opportunity to discuss their preferences. The aim of the ProsPECT (Prospective Planning for Escalation of Care and Treatment) study was to explore perspectives on planning for treatment escalation in the context of frailty. We spoke to people living with frailty, their carers and clinicians across primary and secondary care.MethodsIn-depth online or telephone interviews and online focus groups. The topic guide explored frailty, acute decision-making and planning for the future. Data were thematically analysed using the Framework Method. Preliminary findings were presented to a sample of study participants for feedback in two online workshops.ResultsWe spoke to 44 participants (9 patients, 11 carers and 24 clinicians). Four main themes were identified: frailty is absent from treatment escalation discussions, planning for an uncertain future, escalation in an acute crisis is 'the path of least resistance', and approaches to facilitating treatment escalation planning in frailty.ConclusionBarriers to treatment escalation planning include a lack of shared understanding of frailty and uncertainty about the future. Emergency decision-making is focussed on survival or risk aversion and patient preferences are rarely considered. To improve planning discussions, we recommend frailty training for non-specialist clinicians, multi-disciplinary support, collaborative working between patients, carers and clinicians as well as broader public engagement.

Many Canadian-trained geriatricians from the subspecialty's first decade of existence continue to practice today. The objective of this study was to examine the experiences and perspectives of the earliest cohort of geriatricians in Canada. Using qualitative description method, we conducted semi-structured interviews to explore participants' experiences in training and practice. We included geriatricians who trained in Canada between 1980-1989 and were in active clinical practice as of October 2021. Each transcript was coded independently by two investigators. Thematic analysis was used to develop key themes. Fourteen participants (43% female, mean years in practice 35.9) described their choice to enter geriatric medicine, their training process, the roles of a geriatrician, challenges facing the profession and advice for trainees. Two themes were developed from the data: (i) advocacy for the older adult and (ii) geriatrics as "the road less taken". Advocacy was described as the "core mission" of a geriatrician. Participants discussed the importance of advocacy in clinical practice, education, research and disseminating geriatric principles in the health system and society. "The road less taken" reflected the challenges participants faced during training, which led to relatively few geriatricians for the growing number of older adults in Canada. Despite these challenges, participants described rewarding careers and encouraged trainees to consider the profession.

[This corrects the article DOI: 10.1371/journal.pone.0254131.].

Although both the analysis of regional culture and urbanisation are long-standing preoccupations in geography, few studies have considered the relationship between the two, the former traditionally being a topic in cultural geography, while the latter is usually interpreted and analysed as a process in economic geography. Taking evidence from the 1851-1911 censuses of England and Wales, this article analyses individual migration paths to identify stable regions of human interaction by applying a sophisticated community-detection algorithm. By accurately mapping the regions within which the majority of migration occurred between 1851 and 1911 and arguing that the stability of these geographies is evidence of more than just mutable communities but rather of persistent regional cultures, this article responds to previous studies that have sought to identify the cultural provinces of England and Wales. Indeed, by demonstrating that the regions bear a striking resemblance to those that have long been hypothesised as being distinct cultural provinces of England and Wales, this article empirically corroborates their existence. In order to further demonstrate that the regions constitute cultural provinces, this paper incorporates these boundaries into a spatial interaction model (SIM). The results of the SIM not only shows that the boundaries between the regions limited the number of migrants that crossed them-over and above that explained by control variables-and therefore represented the boundaries of cultural provinces, demarcating discrete regions of human interaction-but that such boundaries disproportionately restricted rural-urban migrants, thereby slowing the pace at which England and Wales urbanised. This paper therefore demonstrates that urbanisation should not only be interpreted as only an economic phenomenon, but a cultural one also, and that if urbanisation is to be fully understood, individuals' attachment to place as a component of their identity, ought to be formally incorporated into models of migration.

We investigate whether using various VMA trading rules would improve investment performance due to the flexibility of VMA trading rules and the aid of Heatmap Visualization. Previously, investors frequently chose the best performance derived from limited VMA trading rules. However, our new design, which can display all results using Heatmap Visualization, shows that the NASDAQ100 index outperforms the DJ30 index and that weekly data outperforms daily data when measured by annualized return. These findings may be useful to those who trade index ETFs tracking the DJ30 and NASDAQ100 indices, as well as investors making investment decisions, and may contribute to the existing literature by evaluating the outcomes of VMA trading rules and providing insights for index ETF investors using a heatmap matrix, which is rarely explored and presented in the relevant literature.

As global awareness, science, and policy interventions for plastic escalate, institutions around the world are seeking preventative strategies. Central to this is the need for precise global time series of plastic pollution with which we can assess whether implemented policies are effective, but at present we lack these data. To address this need, we used previously published and new data on floating ocean plastics (n = 11,777 stations) to create a global time-series that estimates the average counts and mass of small plastics in the ocean surface layer from 1979 to 2019. Today's global abundance is estimated at approximately 82-358 trillion plastic particles weighing 1.1-4.9 million tonnes. We observed no clear detectable trend until 1990, a fluctuating but stagnant trend from then until 2005, and a rapid increase until the present. This observed acceleration of plastic densities in the world's oceans, also reported for beaches around the globe, demands urgent international policy interventions.

Large-bodied temnospondyl amphibians were the dominant predators in non-marine aquatic ecosystems from the Carboniferous to the Middle Triassic. In the Permian-aged lower Beaufort Group of the main Karoo Basin, South Africa, temnospondyls are represented exclusively by the family Rhinesuchidae and are well represented by body fossils, whereas trace fossils are scarce. Accordingly, most interpretations of the behaviour of this family are based on skeletal morphology and histological data. Here we document the sedimentology and palaeontology of a late Permian palaeosurface situated immediately below the palaeoshoreline of the Ecca Sea (transition from the Ecca Group to the Beaufort Group) near the town of Estcourt in KwaZulu-Natal Province. The surface preserves numerous ichnofossils, including tetrapod footprints and fish swim-trails, but most striking are seven body impressions and associated swim trails that we attribute to a medium-sized (~1.9 m long) rhinesuchid temnospondyl. These provide valuable insight into the behaviour of these animals. The sinuous shape of some of the traces suggest that the tracemaker swam with continuous sub-undulatory propulsion of the tail.

BackgroundDepression is common amongst patients receiving haemodialysis (HD). Assessment and intervention when faced with language and cultural barriers is challenging. To support clinician decisions, we conducted a cross-sectional study to assess the use of culturally adapted and translated versions of commonly-used depression screening questionnaires with South Asian patients receiving HD in England.MethodsPatients completed adapted versions of the Patient Health Questionnaire (PHQ-9), the Centre for Epidemiological Studies Depression Scale Revised (CESD-R), and the Beck Depression Inventory II (BDI-II). All questionnaires were available in Gujarati, Punjabi, Urdu, and Bengali. A comparative sample of white-Europeans completed the questionnaires in English. The research was based across 9 National Health Service (NHS) Trusts in England. Structural validity of translated questionnaires was assessed using confirmatory factor analysis. Diagnostic accuracy was explored in a subgroup of South Asians against ICD-10 categories using the Clinical Interview Schedule Revised (CIS-R) with receiver operating curve (ROC) analysis.Results229 South Asian and 120 white-European HD patients participated. A single latent depression factor largely accounted for the correlations between items of the PHQ-9, CESD-R and BDI-II. Issues with measurement equivalence implied that scores on the translations may not be comparable with the English language versions. Against CIS-R based ICD-10 diagnosis of depression, sensitivity was modest across scales (50-66.7%). Specificity was higher (81.3-93.8%). Alternative screening cut-offs did not improve positive predictive values.ConclusionsCulturally adapted translations of depression screening questionnaires are useful to explore symptom endorsement amongst South Asian patients. However, data indicate that standard cut-off scores may not be appropriate to classify symptom severity. Use of the CIS-R algorithms for optimal case identification requires further exploration in this setting. Strategies to encourage recruitment of under-represented groups in renal research are also warranted, especially for in-depth discussions related to psychological care needs.

Antibiotic resistance threatens provision of healthcare and livestock production worldwide with predicted negative socioeconomic impact. Antibiotic stewardship can be considered of importance to people living in rural communities, many of which depend on agriculture as a source of food and income and rely on antibiotics to control infectious diseases in livestock. Consequently, there is a need for clarity of the structure of antibiotic value chains to understand the complexity of antibiotic production and distribution in community settings as this will facilitate the development of effective policies and interventions. We used a value chain approach to investigate how relationships, behaviours, and influences are established during antibiotic distribution. Interviews were conducted with key informants (n = 17), value chain stakeholders (n = 22), and livestock keeping households (n = 36) in Kolkata, and two rural sites in West Bengal, India. Value chain mapping and an assessment of power dynamics, using manifest content analysis, were conducted to investigate antibiotic distribution and identify entry points for antibiotic stewardship. The flow of antibiotics from manufacturer to stockists is described and mapped and two local level maps showing distribution to final consumers presented. The maps illustrate that antibiotic distribution occurred through numerous formal and informal routes, many of which circumvent antibiotic use legislation. This was partly due to limited institutional power of the public sector to govern value chain activities. A 'veterinary service lacuna' existed resulting in livestock keepers having higher reliance on private and informal providers, who often lacked legal mandates to prescribe and dispense antibiotics. The illegitimacy of many antibiotic prescribers blocked access to formal training who instead relied on mimicking the behaviour of more experienced prescribers-who also lacked access to stewardship guidelines. We argue that limited institutional power to enforce existing antibiotic legislation and guide antibiotic usage and major gaps in livestock healthcare services make attempts to curb informal prescribing unsustainable. Alternative options could include addressing public sector deficits, with respect to both healthcare services and antibiotic provision, and by providing resources such as locally relevant antibiotic guidelines to all antibiotic prescribers. In addition, legitimacy of informal prescribers could be revised, which may allow formation of associations or groups to incentivise good antibiotic practices.

BackgroundThe amplification of GTP cyclohydrolase 1 (pfgch1) in Plasmodium falciparum has been linked to the upregulation of the pfdhfr and pfdhps genes associated with resistance to the antimalarial drug sulfadoxine-pyrimethamine. During the 1990s and 2000s, sulfadoxine-pyrimethamine was withdrawn from use as first-line treatment in southeast Asia due to clinical drug resistance. This study assessed the temporal and geographic changes in the prevalence of pfdhfr and pfdhps gene mutations and pfgch1 amplification a decade after sulfadoxine-pyrimethamine had no longer been widely used.MethodsA total of 536 P. falciparum isolates collected from clinical trials in Thailand, Cambodia, and Lao PDR between 2008 and 2018 were assayed. Single nucleotide polymorphisms of the pfdhfr and pfdhps genes were analyzed using nested PCR and Sanger sequencing. Gene copy number variations of pfgch1 were investigated using real-time polymerase chain reaction assay.ResultsSequences of the pfdhfr and pfdhps genes were obtained from 96% (517/536) and 91% (486/536) of the samples, respectively. There were 59 distinct haplotypes, including single to octuple mutations. The two major haplotypes observed included IRNI-AGEAA (25%) and IRNL-SGKGA (19%). The sextuple mutation IRNL-SGKGA increased markedly over time in several study sites, including Pailin, Preah Vihear, Ratanakiri, and Ubon Ratchathani, whereas IRNI-AGEAA decreased over time in Preah Vihear, Champasak, and Ubon Ratchathani. Octuple mutations were first observed in west Cambodia in 2011 and subsequently in northeast Cambodia, as well as in southern Laos by 2018. Amplification of the pfgch1 gene increased over time across the region, particularly in northeast Thailand close to the border with Laos and Cambodia.ConclusionDespite the fact that SP therapy was discontinued in Thailand, Cambodia, and Laos decades ago, parasites retained the pfdhfr and pfdhps mutations. Numerous haplotypes were found to be prevalent among the parasites. Frequent monitoring of pfdhfr and pfdhps in these areas is required due to the relatively rapid evolution of mutation patterns.

Surgical specialties account for a high proportion of antimicrobial use in hospitals, and misuse has been widely reported resulting in unnecessary patient harm and antimicrobial resistance. We aimed to synthesize qualitative studies on surgical antimicrobial prescribing behavior, in hospital settings, to explain how and why contextual factors act and interact to influence practice. Stakeholder engagement was integrated throughout to ensure consideration of varying interpretive repertoires and that the findings were clinically meaningful. The meta-ethnography followed the seven phases outlined by Noblit and Hare. Eight databases were systematically searched without date restrictions. Supplementary searches were performed including forwards and backwards citation chasing and contacting first authors of included papers to highlight further work. Following screening, 14 papers were included in the meta-ethnography. Repeated reading of this work enabled identification of 48 concepts and subsequently eight overarching concepts: hierarchy; fear drives action; deprioritized; convention trumps evidence; complex judgments; discontinuity of care; team dynamics; and practice environment. The overarching concepts interacted to varying degrees but there was no consensus among stakeholders regarding an order of importance. Further abstraction of the overarching concepts led to the development of a conceptual model and a line-of-argument synthesis, which posits that social and structural mediators influence individual complex antimicrobial judgements and currently skew practice towards increased and unnecessary antimicrobial use. Crucially, our model provides insights into how we might 'tip the balance' towards more evidence-based antimicrobial use. Currently, healthcare workers deploy antimicrobials across the surgical pathway as a safety net to allay fears, reduce uncertainty and risk, and to mitigate against personal blame. Our synthesis indicates that prescribing is unlikely to change until the social and structural mediators driving practice are addressed. Furthermore, it suggests that research specifically exploring the context for effective and sustainable quality improvement stewardship initiatives in surgery is now urgent.

The levels of psychological distress and burnout among healthcare staff are high, with negative implications for patient care. A growing body of evidence indicates that workplace programmes based on Acceptance and Commitment Therapy (ACT) are effective for improving employees’ general psychological health. However, there is a paucity of research examining the specific psychological and/or behavioural processes through which workplace ACT programmes transmit their beneficial effects. The aim of this randomised controlled trial was to investigate the outcomes and putative processes of change in a 4-session ACT training programme designed to reduce psychological distress among healthcare staff (n = 98). Ninety-eight employees of a healthcare organisation were randomly allocated to the ACT intervention or to a waiting list control group. Study measures were administered on four occasions (baseline, mid-intervention, post-intervention, and follow-up) over a three-month evaluation period. Results showed that the ACT intervention led to a significant decrease in symptoms of psychological distress and a less pronounced reduction in burnout. These effects were mediated primarily via an improvement in mindfulness skills and values-based behaviour and moderated by participants’ initial levels of distress. At four-week post-intervention, 48% of participants who received the ACT intervention showed reliable improvements in psychological distress, with just under half of the aforementioned improvements (46.15%) meeting criteria for clinically significant change. The results advance ACT as an effective stress management intervention for healthcare staff. The findings should be confirmed in a large scale randomised controlled trial with longer follow-up and cost-effectiveness analyses.

Objective This study describes how the School Vision Program (SVP) operates in NYC Public Schools, and how it has expanded to provide screening, follow-up, eye exams, and even glasses to more students in recent years. Methods Using administrative data from the SVP, we analyze a population sample of all public-school students with non-missing demographic variables in grades Pre-K through 12, focusing on the most recent year of data, 2018–19. We tabulate rates of screening and other results across students by grade and student characteristics, highlighting the expansion of SVP in community schools beginning in 2015–16. Results The SVP screens about 87% of students in Pre-K through 1st Grade each school year. Of the 22% of screened students who failed the screening in 2018–19, 69% received follow-up efforts, and 39% completed eye exams. Among students with completed eye exams, 13% of students in Pre-K through 1st grade were diagnosed with amblyopia, and 70% needed glasses. Less advantaged students in terms of race, ethnicity, and socioeconomic status were less likely to pass vision screenings and less likely to receive eye exams after failing the screening. The SVP’s expansion to all grades in community schools and its provision of eye exams and glasses increased the rate of eye exams to 90% of students with a failed vision screening and distributed glasses to over 22,000 students in grades Pre-K to 12 in 2018–19. Conclusion The expansion of SVP services in community schools suggests large potential benefits from school districts connecting students who fail vision screenings directly to eye doctors. Otherwise, low rates of follow-up eye exams in younger grades can lead to unidentified and unmet need for vision services in older grades, especially among disadvantaged students.

BackgroundPrescription Drug Monitoring Programs (PDMPs) are electronic databases that track controlled substance prescriptions in a state. They are underused tools in preventing opioid abuse. Most PDMP education research measures changes in knowledge or confidence rather than behavior.ObjectiveTo evaluate the impact of online case-based training on healthcare provider use of the Maryland (USA) PDMP.MethodsWe used e-mail distribution lists to recruit providers to complete a brief educational module. Using a pre-training and post-training survey in the module, we measured self-reported PDMP use patterns and perceived PDMP value in specific clinical situations and compared pre- and post-training responses. Within the module, we presented three fictional pain cases and asked participants how they would manage each, both before, and then after presenting prescription drug history simulating a PDMP report. We measured changes in the fictional case treatment plans before and after seeing prescription history. Finally, we measured and compared how often each participant accessed the Maryland PDMP database before and after completing the educational module. We used multivariate logistic regression to measure the effect of the intervention on actual PDMP use frequency.ResultsOne hundred and fifty participants enrolled and completed the training module, and we successfully retrieved real-world PDMP use data of 137 of them. Participants' decisions to prescribe opioids changed significantly after reviewing PDMP data in each of the fictional cases provided in the module. In the months following the training, the rate of PDMP use increased by a median of four use-cases per month among providers in practice for less than 20 years (p = 0.039) and two use-cases per month among infrequent opioid prescribers (p = 0.014).ConclusionA brief online case-based educational intervention was associated with a significant increase in the rate of PDMP use among infrequent opioid prescribers and those in practice less than 20 years.

Despite many innovative ideas generated in response to COVID-19, few studies have examined community preferences for these ideas. Our study aimed to determine university community members' preferences for three novel ideas identified through a crowdsourcing open call at the University of North Carolina (UNC) for making campus safer in the pandemic, as compared to existing (i.e. pre-COVID-19) resources. An online survey was conducted from March 30, 2021 -May 6, 2021. Survey participants included UNC students, staff, faculty, and others. The online survey was distributed using UNC's mass email listserv and research directory, departmental listservs, and student text groups. Collected data included participant demographics, COVID-19 prevention behaviors, preferences for finalist ideas vs. existing resources in three domains (graduate student supports, campus tours, and online learning), and interest in volunteering with finalist teams. In total 437 survey responses were received from 228 (52%) staff, 119 (27%) students, 78 (18%) faculty, and 12 (3%) others. Most participants were older than age 30 years (309; 71%), women (332, 78%), and white (363, 83.1%). Five participants (1%) were gender minorities, 66 (15%) identified as racial/ethnic minorities, and 46 (10%) had a disability. Most participants preferred the finalist idea for a virtual campus tour of UNC's lesser-known history compared to the existing campus tour (52.2% vs. 16.0%). For graduate student supports, 41.4% of participants indicated no preference between the finalist idea and existing supports; for online learning resources, the existing resource was preferred compared to the finalist idea (41.6% vs. 30.4%). Most participants agreed that finalists' ideas would have a positive impact on campus safety during COVID-19 (81.2%, 79.6%, and 79.2% for finalist ideas 1, 2 and 3 respectively). 61 (14.1%) participants indicated interest in volunteering with finalist teams. Together these findings contribute to the development and implementation of community-engaged crowdsourced campus safety interventions during COVID-19.

Myeloperoxidase (MPO), oxidative stress (OS), and endoplasmic reticulum (ER) stress are increased in the lungs of rat pups raised in hyperoxia, an established model of bronchopulmonary dysplasia (BPD). However, the relationship between OS, MPO, and ER stress has not been examined in hyperoxia rat pups. We treated Sprague-Dawley rat pups with tunicamycin or hyperoxia to determine this relationship. ER stress was detected using immunofluorescence, transcriptomic, proteomic, and electron microscopic analyses. Immunofluorescence observed increased ER stress in the lungs of hyperoxic rat BPD and human BPD. Proteomic and morphometric studies showed that tunicamycin directly increased ER stress of rat lungs and decreased lung complexity with a BPD phenotype. Previously, we showed that hyperoxia initiates a cycle of destruction that we hypothesized starts from increasing OS through MPO accumulation and then increases ER stress to cause BPD. To inhibit ER stress, we used tauroursodeoxycholic acid (TUDCA), a molecular chaperone. To break the cycle of destruction and reduce OS and MPO, we used N-acetyl-lysyltyrosylcysteine amide (KYC). The fact that TUDCA improved lung complexity in tunicamycin- and hyperoxia-treated rat pups supports the idea that ER stress plays a causal role in BPD. Additional support comes from data showing TUDCA decreased lung myeloid cells and MPO levels in the lungs of tunicamycin- and hyperoxia-treated rat pups. These data link OS and MPO to ER stress in the mechanisms mediating BPD. KYC's inhibition of ER stress in the tunicamycin-treated rat pup's lung provides additional support for the idea that MPO-induced ER stress plays a causal role in the BPD phenotype. ER stress appears to expand our proposed cycle of destruction. Our results suggest ER stress evolves from OS and MPO to increase neonatal lung injury and impair growth and development. The encouraging effect of TUDCA indicates that this compound has the potential for treating BPD.

Earlier, we proposed the "mechanosome" concept as a testable model for understanding how mechanical stimuli detected by cell surface adhesion molecules are transmitted to modulate gene expression inside cells. Here, for the first time we document a putative mechanosome involving Src, Pyk2 and MBD2 in MLO-Y4 osteocytes with high spatial resolution using FRET-FLIM. Src-Pyk2 complexes were concentrated at the periphery of focal adhesions and the peri-nuclear region. Pyk2-MBD2 complexes were located primarily in the nucleus and peri-nuclear region. Lifetime measurements indicated that Src and MBD2 did not interact directly. Finally, mechanical stimulation by fluid flow induced apparent accumulation of Src-Pyk2 protein complexes in the peri-nuclear/nuclear region, consistent with the proposed behavior of a mechanosome in response to a mechanical stimulus.

Anthropogenic impacts are increasingly affecting the world's oceans. Networks of marine protected areas (MPAs) provide an option for increasing the ecological and economic benefits often provided by single MPAs. It is vital to empirically assess the effects of MPA networks and to prioritize the monitoring data necessary to explain those effects. We summarize the types of MPA networks based on their intended management outcomes and illustrate a framework for evaluating whether a connectivity network is providing an outcome greater than the sum of individual MPA effects. We use an analysis of an MPA network in Hawai'i to compare networked MPAs to non-networked MPAs to demonstrate results consistent with a network effect. We assert that planning processes for MPA networks should identify their intended outcomes while also employing coupled field monitoring-simulation modeling approaches, a powerful way to prioritize the most relevant monitoring data for empirically assessing MPA network performance.

The demand for food will outpace productivity of conventional agriculture due to projected growth of the human population, concomitant with shrinkage of arable land, increasing scarcity of freshwater, and a rapidly changing climate. While aquaponics has potential to sustainably supplement food production with minimal environmental impact, there is a need to better characterize the complex interplay between the various components (fish, plant, microbiome) of these systems to optimize scale up and productivity. Here, we investigated how the commonly-implemented practice of continued microbial community transfer from pre-existing systems might promote or impede productivity of aquaponics. Specifically, we monitored plant growth phenotypes, water chemistry, and microbiome composition of rhizospheres, biofilters, and fish feces over 61-days of lettuce (Lactuca sativa var. crispa) growth in nitrogen-limited aquaponic systems inoculated with bacteria that were either commercially sourced or originating from a pre-existing aquaponic system. Lettuce above- and below-ground growth were significantly reduced across replicates treated with a pre-existing aquaponic system inoculum when compared to replicates treated with a commercial inoculum. Reduced productivity was associated with enrichment in specific bacterial genera in plant roots, including Pseudomonas, following inoculum transfer from pre-existing systems. Increased productivity was associated with enrichment of nitrogen-fixing Rahnella in roots of plants treated with the commercial inoculum. Thus, we show that inoculation from a pre-existing system, rather than from a commercial inoculum, is associated with lower yields. Further work will be necessary to test the putative mechanisms involved.

Coastal wetlands are experiencing accelerated rates of fragmentation and degradation due to sea-level rise, sediment deficits, subsidence, and salt-water intrusion. This reduces their ability to provide ecosystem benefits, such as wave attenuation, habitat for migratory birds, and a sink for carbon and nitrogen cycles. A deteriorated back barrier wetland in New Jersey, USA was nourished through thin layer placement (TLP) of dredged sediment in 2016. A field investigation was conducted in 2019 using a cone penetrometer (CPT) to quantify the establishment of soil strength post sediment nourishment compared to adjacent reference sites in conjunction with traditional wetland performance measures. Results show that the nourished area exhibited weaker strengths than the reference sites, suggesting the root system of the vegetation is still establishing. The belowground biomass measurements correlated to the CPT strength measurements, demonstrating that shear strength measured from the cone penetrometer could serve as a surrogate to monitor wetland vegetation trajectories. In addition, heavily trafficked areas underwent compaction from heavy equipment loads, inhibiting the development of vegetation and highlighting how sensitive wetlands are to anthropogenic disturbances. As the need for more expansive wetland restoration projects grow, the CPT can provide rapid high-resolution measurements across large areas supplying government and management agencies with vital establishment trajectories.

The Neotropical invasive plant Chromolaena odorata R.M. King and H. Robinson (Asteraceae) is a serious weed in West and Central Africa and two biological control agents that have been introduced into West Africa to help reduce its impacts on agriculture and biodiversity, have established. The stem-galling fly, Cecidochares connexa (Macquart) (Diptera: Tephritidae), has spread widely across West Africa since its release in only Côte d'Ivoire, occurring in six countries. This study aimed to investigate whether the gall fly had spread further across West Africa and into Central Africa. Here, we surveyed C. odorata for C. connexa galls in Cameroon between October 2018 and October 2020, along roadsides, on farms, residential areas, and abandoned plots, encompassing various vegetation types. Additional surveys were conducted across four countries (Ghana, Togo, Benin Republic and Nigeria) in West Africa that we considered the probable pathway for the spread of the gall fly into Central Africa. Cecidochares connexa was present at five of the six locations surveyed in Cameroon, albeit in varying abundance. In Africa, these findings represent the first-ever report of C. connexa outside of West Africa. In West Africa, we recorded significant expansion in the geographic range of C. connexa, as reflected in the absent-present record of C. connexa in two locations in Nigeria and one in Ghana, as well as its occurrence in all locations surveyed in Benin Republic and Togo. Clearly, Ghana, Togo, Benin Republic and Nigeria served as the dispersal pathway of C. connexa from the release sites in Côte d'Ivoire into Cameroon, covering over 2,300 km. Following the spread and establishment of C. connexa into Cameroon, we anticipate that it will continue to spread further into other parts of Central Africa which are climatically suitable. Cecidochares connexa is currently the only biological control agent for C. odorata in Central Africa. Given that it has significantly reduced populations of C. odorata in other countries where it has established, it is expected to have a similar impact in Central Africa.

BackgroundMalawi has halved the neonatal mortality rate between 1990-2018, however, is not on track to achieve the Sustainable Development Goal 12 per 1,000 live births. Despite a high facility birth rate (91%), mother-newborn dyads may not remain in facilities long enough to receive recommended care and quality of care improvements are needed to reach global targets. Physical access and distance to health facilities remain barriers to quality postnatal care.MethodsUsing data We used individual data from the 2015-16 Malawi Demographic and Health Survey and facility data from the 2013-14 Malawi Service Provision Assessment, linking households to all health facilities within specified distances and travel times. We calculated service readiness scores for facilities to measure their capacity to provide birth/newborn care services. We fitted multi-level regression models to evaluate the association between the service readiness and appropriate newborn care (receiving at least five of six interventions).ResultsHouseholds with recent births (n = 6010) linked to a median of two birth facilities within 5-10 km and one facility within a two-hour walk. The maximum service environment scores for linked facilities median was 77.5 for facilities within 5-10 km and 75.5 for facilities within a two-hour walk. While linking to one or more facilities within 5-10km or a two-hour walk was not associated with appropriate newborn care, higher levels of service readiness in nearby facilities was associated with an increased risk of appropriate newborn care.ConclusionsWomen's choice of nearby facilities and quality facilities is limited. High quality newborn care is sub-optimal despite high coverage of facility birth and some newborn care interventions. While we did not find proximity to more facilities was associated with increased risk of appropriate care, high levels of service readiness was, showing facility birth and improved access to well-prepared facilities are important for improving newborn care.

Students often bring laptops to university classes, however, they do not limit their laptop use to class-related activity. Off-task laptop use occurs frequently in university classrooms and this use negatively impacts learning. The present study addresses whether potential benefits of class-related laptop use might mitigate the costs of off-task laptop activity. We used tracking software to monitor both class-related and off-task laptop use by undergraduate students enrolled in an introductory psychology course, and we observed how types of laptop use related to course performance. We found a positive correlation between class-related use and exam scores that was driven by viewing lecture slides during class. We also found a negative correlation between off-task laptop use and exam scores, but class-related activities did not predict an increase in off-task use. Thus, for students who constrain their laptop use to class-related activity, the benefits outweigh the costs. While a laptop may be beneficial for some, it is unclear which students are able to constrain themselves to class-related activities and whether the benefits of class-related laptop use obtained by slide viewing could be achieved by other means. Thus, students and educators should carefully consider the costs and benefits of laptop use in the classroom.

Horseshoes influence how horses' hooves interact with different ground surfaces, during the impact, loading and push-off phases of a stride cycle. Consequently, they impact on the biomechanics of horses' proximal limb segments and upper body. By implication, different shoe and surface combinations could drive changes in the magnitude and stability of movement patterns in horse-jockey dyads. This study aimed to quantify centre of mass (COM) displacements in horse-jockey dyads galloping on turf and artificial tracks in four shoeing conditions: 1) aluminium; 2) barefoot; 3) GluShu; and 4) steel. Thirteen retired racehorses and two jockeys at the British Racing School were recruited for this intervention study. Tri-axial acceleration data were collected close to the COM for the horse (girth) and jockey (kidney-belt), using iPhones (Apple Inc.) equipped with an iOS app (SensorLog, sample rate = 50 Hz). Shoe-surface combinations were tested in a randomized order and horse-jockey pairings remained constant. Tri-axial acceleration data from gallop runs were filtered using bandpass Butterworth filters with cut-off frequencies of 15 Hz and 1 Hz, then integrated for displacement using Matlab. Peak displacement was assessed in both directions (positive 'maxima', negative 'minima') along the cranio-caudal (CC, positive = forwards), medio-lateral (ML, positive = right) and dorso-ventral (DV, positive = up) axes for all strides with frequency ≥2 Hz (mean = 2.06 Hz). Linear mixed-models determined whether surfaces, shoes or shoe-surface interactions (fixed factors) significantly affected the displacement patterns observed, with day, run and horse-jockey pairs included as random factors; significance was set at p

Our laboratory has demonstrated that captopril, an angiotensin converting enzyme inhibitor, mitigates hematopoietic injury following total body irradiation in mice. Improved survival in mice is correlated with improved recovery of mature blood cells and bone marrow, reduction of radiation-induced inflammation, and suppression of radiation coagulopathy. Here we investigated the effects of captopril treatment against radiation injuries in the Göttingen mini pig model of Hematopoietic-Acute Radiation Syndrome (H-ARS). Minipigs were given captopril orally (0.96 mg/kg) twice daily for 12 days following total body irradiation (60Co 1.79 Gy, 0.42-0.48 Gy/min). Blood was drawn over a time course following irradiation, and tissue samples were collected at euthanasia (32-35 days post-irradiation). We observed improved survival with captopril treatment, with survival rates of 62.5% in vehicle treated and 87.5% in captopril treated group. Additionally, captopril significantly improved recovery of peripheral blood mononuclear cells, and a trend toward improvement in recovery of red blood cells and platelets. Captopril significantly reduced radiation-induced expression of cytokines erythropoietin and granulocyte-macrophage colony-stimulating factor and suppressed radiation-induced acute-phase inflammatory response cytokine serum amyloid protein A. Using quantitative-RT-PCR to monitor bone marrow recovery, we observed significant suppression of radiation-induced expression of redox stress genes and improved hematopoietic cytokine expression. Our findings suggest that captopril activities in the Göttingen minipig model of hematopoietic-acute radiation syndrome reflect findings in the murine model.

FITNESSGRAM® is the most widely used criterion-referenced tool to assess/report on student health-related fitness across the US. Potential weight-related biases with the two most common tests of musculoskeletal fitness–the trunk extension and Back-Saver Sit-and-Reach (sit-and-reach)—have been hypothesized, though have not been studied. To determine the association between musculoskeletal fitness test performance and weight status, we use data from 571,133 New York City public school 4th-12th grade students (85% non-White; 75% qualified for free or reduced-price meals) with valid/complete 2017–18 FITNESSGRAM® data. Adjusted logistic mixed effects models with a random effect for school examined the association between weight status and whether a student was in the Healthy Fitness Zone (HFZ; met sex- and age-specific criterion-referenced standards) for the trunk extension and sit-and-reach. Compared to students with normal weight, the odds of being in the HFZ for trunk extension were lower for students with underweight (OR = 0.77; 95% CI: 0.741, 0.795) and higher for students with overweight (OR = 1.10; 95% CI: 1.081, 1.122) and obesity (OR = 1.11; 95% CI: 1.090, 1.13). The odds of being in the HFZ for sit-and-reach were lower for students with underweight OR = 0.85; 95% CI: 0.826, 0.878), overweight (OR = 0.83; 95% CI: 0.819, 0.844) and obesity (OR = 0.65; 95% CI: 0.641, 0.661). Students with overweight and obesity perform better on the trunk extension, yet worse on the sit-and-reach, compared to students with normal weight. Teachers, administrators, and researchers should be aware of the relationship of BMI with student performance in these assessments.

We tested the hypothesis that the brain uses a variance-based weighting of multisensory cues to estimate head rotation to perceive which way is up. The hypothesis predicts that the known bias in perceived vertical, which occurs when the visual environment is rotated in a vertical-plane, will be reduced by the addition of visual noise. Ten healthy participants sat head-fixed in front of a vertical screen presenting an annulus filled with coloured dots, which could rotate clockwise or counter-clockwise at six angular velocities (1, 2, 4, 6, 8, 16°/s) and with six levels of noise (0, 25, 50, 60, 75, 80%). Participants were required to keep a central bar vertical by rotating a hand-held dial. Continuous adjustments of the bar were required to counteract low-amplitude low-frequency noise that was added to the bar's angular position. During visual rotation, the bias in verticality perception increased over time to reach an asymptotic value. Increases in visual rotation velocity significantly increased this bias, while the addition of visual noise significantly reduced it, but did not affect perception of visual rotation velocity. The biasing phenomena were reproduced by a model that uses a multisensory variance-weighted estimate of head rotation velocity combined with a gravito-inertial acceleration signal (GIA) from the vestibular otoliths. The time-dependent asymptotic behaviour depends on internal feedback loops that act to pull the brain's estimate of gravity direction towards the GIA signal. The model's prediction of our experimental data furthers our understanding of the neural processes underlying human verticality perception.

Mercury (Hg) and selenium (Se) are contaminants of concern for fish in the Upper Colorado River Basin (UCRB). We explored Hg and Se in fish tissues (2,324 individuals) collected over 50 years (1962-2011) from the UCRB. Samples include native and non-native fish collected from lotic waterbodies spanning 7 major tributaries to the Colorado River. There was little variation of total mercury (THg) in fish assemblages basin-wide and only 13% (272/1959) of individual fish samples exceeded the fish health benchmark (0.27 μg THg/g ww). Most THg exceedances were observed in the White-Yampa tributary whereas the San Juan had the lowest mean THg concentration. Risks associated with THg are species specific with exceedances dominated by Colorado Pikeminnow (mean = 0.38 and standard error ± 0.08 μg THg/g ww) and Roundtail Chub (0.24 ± 0.06 μg THg/g ww). For Se, 48% (827/1720) of all individuals exceeded the fish health benchmark (5.1 μg Se/g dw). The Gunnison river had the most individual exceedances of the Se benchmark (74%) whereas the Dirty Devil had the fewest. We identified that species of management concern accumulate THg and Se to levels above risk thresholds and that fishes of the White-Yampa (THg) and Gunnison (Se) rivers are at the greatest risk in the UCRB.

Whole genome sequencing (WGS) has been used routinely by Public Health England (PHE) for identification, surveillance and monitoring of resistance determinants in referred Salmonella isolates since 2015. We report the first identified case of extended-spectrum-β-lactamase (ESBL) Salmonella enterica serovar Paratyphi A (S. Paratyphi A) isolated from a traveller returning to England from Bangladesh in November 2017. The isolate (440915) was resistant to ciprofloxacin and harboured both the mobile element ISEcp9 -blaCTX-M-15-hp-tnpA and blaTEM-191, associated with ESBL production. Phenotypic resistance was subsequently confirmed by Antimicrobial Susceptibility Testing (AST). S. Paratyphi A 440915 harboured an IncI1 plasmid previously reported to encode ESBL elements in Enterobacteriaceae and recently described in a S. Typhi isolate from Bangladesh. Results from this study indicate the importance of monitoring imported drug resistance for typhoidal salmonellae as ceftriaxone is the first line antibiotic treatment for complicated enteric fever in England. We conclude that WGS provides a rapid, accurate method for surveillance of drug resistance genes in Salmonella, leading to the first reported case of ESBL producing S. Paratyphi A and continues to inform the national treatment guidelines for management of enteric fever.

Standardized physical fitness monitoring provides a more accurate proxy for youth health when compared with physical activity. Little is known about the utilization of broad-scale individual-level youth physical fitness testing to explore health disparities. We examined longitudinal trends in population-level fitness for 4th-12th grade New York City youth during 2006/7-2016/17 (average n = 510,293 per year). Analyses were performed in 2019. The primary outcome was whether or not youth achieved sex-/age-specific performance levels (called the Healthy Fitness Zone) on the aerobic capacity, muscular strength and muscular endurance tests using the NYC FITNESSGRAM. The Cooper Institute's most recent Healthy Fitness Zone criteria were applied to all tests and years. Prevalence estimates were weighted, accounted for school clustering, adjusted for student-level sociodemographics, and run by sociodemographic subgroups and year. The overall prevalence for meeting 3 Healthy Fitness Zones increased from 15.5% (95%CI: 13.9%-17.0%) in 2006/7 to 23.3% (95%CI: 22.2%-24.4%) in 2016/17 for students in grades 4-12. Fitness for all student groups increased over time, although Hispanic and non-Hispanic black girls consistently had the lowest prevalence of meeting 3 Healthy Fitness Zones as compared to all other race/sex subgroups. Also, 9th-12th graders had a lower prevalence of meeting 3 Healthy Fitness Zones as compared to 4th-8th graders. Given forecasted sharp increases in cardiovascular disease prevalence, routine youth fitness surveillance using standardized, criterion referenced methods can identify important fitness disparities and inform interventions.

BACKGROUND:Health systems routinely implement changes to the design of electronic health records (EHRs). Physician behavior may vary in response and methods to identify this variation could help to inform future interventions. The objective of this study was to phenotype primary care physician practice patterns and evaluate associations with response to an EHR nudge for influenza vaccination. METHODS AND FINDINGS:During the 2016-2017 influenza season, 3 primary care practices at Penn Medicine implemented an active choice intervention in the EHR that prompted medical assistants to template influenza vaccination orders for physicians to review during the visit. We used latent class analysis to identify physician phenotypes based on 9 demographic, training, and practice pattern variables, which were obtained from the EHR and publicly available sources. A quasi-experimental approach was used to evaluate response to the intervention relative to control practices over time in each of the physician phenotype groups. For each physician latent class, a generalized linear model with logit link was fit to the binary outcome of influenza vaccination at the patient visit level. The sample comprised 45,410 patients with a mean (SD) age of 58.7 (16.3) years, 67.1% were white, and 22.1% were black. The sample comprised 56 physicians with mean (SD) of 24.6 (10.2) years of experience and 53.6% were male. The model segmented physicians into groups that had higher (n = 41) and lower (n = 15) clinical workloads. Physicians in the higher clinical workload group had a mean (SD) of 818.8 (429.1) patient encounters, 11.6 (4.7) patient appointments per day, and 4.0 (1.1) days per week in clinic. Physicians in the lower clinical workload group had a mean (SD) of 343.7 (129.0) patient encounters, 8.0 (2.8) patient appointments per day, and 3.1 (1.2) days per week in clinic. Among the higher clinical workload group, the EHR nudge was associated with a significant increase in influenza vaccination (adjusted difference-in-difference in percentage points, 7.9; 95% CI, 0.4-9.0; P = .01). Among the lower clinical workload group, the EHR nudge was not associated with a significant difference in influenza vaccination rates (adjusted difference-in-difference in percentage points, -1.0; 95% CI, -5.3-5.8; P = .90). CONCLUSIONS:A model-based approach categorized physician practice patterns into higher and lower clinical workload groups. The higher clinical workload group was associated with a significant response to an EHR nudge for influenza vaccination.

Occult hepatitis B infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in the liver or serum in the absence of detectable HBV surface antigen (HBsAg). OBI poses a risk for the development of cirrhosis and hepatocellular carcinoma. The prevalence of OBI in Kenya is unknown, thus a study was undertaken to determine the prevalence and molecular characterization of OBI in Kenyan populations at high risk of HBV infection. Sera from two Nairobi cohorts, 99 male sex workers, primarily having sex with men (MSM-SW), and 13 non-MSM men having HIV-positive partners, as well as 65 HBsAg-negative patients presenting with jaundice at Kenyan medical facilities, were tested for HBV serological markers, including HBV DNA by real-time PCR. Positive DNA samples were sequenced and MSM-SW patients were further tested for hepatitis C virus (HCV) infection. Of the 166 HBsAg-negative samples tested, 31 (18.7%; 95% confidence interval [CI] 13.5-25.3) were HBV DNA positive (i.e., occult), the majority (20/31; 64.5%) of which were HBV core protein antibody positive. HCV infection was not observed in the MSM-SW participants, although the prevalence of HBsAg positivity was 10.1% (10/99; 95% CI 5.6-17.6). HBV genotype A was predominant among study cases, including both HBsAg-positive and OBI participants, although the data suggests a non-African network transmission source among MSM-SW. The high prevalence of HBV infection among MSM-SW in Kenya suggests that screening programmes be instituted among high-risk cohorts to facilitate preventative measures, such as vaccination, and establish entry to treatment and linkage to care.

BACKGROUND:Hepatitis C virus (HCV) genotype 6 is the commonest cause of chronic hepatitis C infection in much of southeast Asia, but data on the effectiveness of direct-acting antiviral agents (DAAs) against this genotype are limited. We conducted a retrospective cohort study of patients attending the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam, to define the effectiveness of DAAs in the treatment of chronic HCV genotype 6 in actual practice. METHODS:We included all patients with genotype 6 infections attending our hospital between March 2016 and October 2017 who received treatment with sofosbuvir-based DAA treatment regimens, and compared their responses with those with genotype 1 infections. RESULTS:1758 patients (1148 genotype 6, 65.4%; 610 genotype 1, 34.6%) were analyzed. The majority of patients (1480, 84.2%) received sofosbuvir/ledipasvir (SOF/LDV) ± ribavirin (RBV); 278 (15.8%) received sofosbuvir/Daclatasvir (SOF/DCV) ± RBV. The median age of the patients was 57 years, (interquartile range (IQR) 46-64 years) The baseline HCV viral load (log IU/ml) was significantly higher in patients infected with genotype 6 compared with those infected with genotype 1 (6.8, 5.3-6.6 versus 6.3, 5.3-6.5 log10 IU/ml, p =