455 research outputs found

    Mapping infiltration in an urbanizing mixed-land-use watershed with multi-temporal satellite imagery

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    Digital soil mapping (DSM) is a field of soil science that aims to improve traditional soil maps by producing higher resolution predictive maps of soil properties using spatial environmental data. DSM has historically relied primarily on static environmental covariates—such as slope gradient, slope aspect, and other topographic variables derived from digital terrain models—for predicting static soil properties, like soil texture. Advancements in satellite imagery and statistical modeling improve the accuracy of digital soil maps by incorporating multi-temporal data that can capture landscape-scale change over relatively short periods of time. Adding these dynamic environmental covariates may be especially useful for spatial prediction of dynamic soil properties, like infiltration rate, that are strongly affected by phenomenon that satellite imagery can detect, like land use that changes rapidly due to human activity. Infiltration strongly impacts soil health and hydrologic characteristics in a watershed. Understanding infiltration for sustainable land management is vital for making best management decisions in urbanizing environments like the West Run Watershed in Morgantown, West Virginia. We hypothesized that infiltration could be predicted at a higher accuracy and a finer spatiotemporal scale using digital soil mapping techniques than is currently provided by the current official soil data and maps produced by the National Cooperative Soil Survey. Spatial predictions of infiltration rate were produced for the West Run watershed using both static and dynamic environmental covariates as inputs into multiple linear regression (MLR) and random forest (RF) models, each of which were made using 10-fold cross validation. Training and independent validation sampling locations were selected using a conditioned Latin hypercube sampling scheme and observed saturated hydraulic conductivity of the soil surface was collected using automated dual-head infiltrometers. The MLR and RF models had R 2 of 0.302 and 0.201, respectively. Validation sampling was stratified by the predicted infiltration values of the MLR model. Validation R 2 values for the MLR and RF models were 0.080 and 0.103. The results from this study will benefit the development of a dynamic soil survey and will improve hydrologic models in this and potentially other mixed-land-use watersheds

    Evaluating Communication and Collaboration Among Healthcare Students

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    The purpose of this pilot study was to determine if the Interprofessional Collaborator Assessment Rubric (ICAR): Communication and Collaboration Dimensions would demonstrate good inter-rater reliability and be a useful and efficient tool to evaluate professional communication and collaboration between occupational therapy (OT) and physician assistant (PA) students. An additional aim of this study was to assess students’ thoughts, perceptions, and perceived value regarding these types of interprofessional opportunities. A sequential explanatory mixed methods design was used. An interclass correlation coefficient (ICC) examined the inter-rater reliability of the instrument for both faculty raters (n = 7) and standardized patient (SP) raters (n =5). Qualitative data was gathered from focus groups to assess the utility of the ICAR: Communication and Collaboration. Quantitative and qualitative data were also gathered from a convenience sample of student participants (n =19) to investigate the perceived value of this interprofessional experience. Quantitative data revealed that there was moderate inter-rater reliability for four out of five of the subscales. Three themes emerged from the rater and student focus groups. Students found the interprofessional education (IPE) opportunity to be valuable. They also felt that it enhanced their understanding of the OT/PA profession, as well as their comfort and ability to collaborate and communicate with other professionals. The results of this study suggest that the ICAR: Communication and Collaboration Dimensions has the potential to maintain inter-rater reliability among healthcare students. The results of this study also indicate that healthcare students view IPE events as being highly valuable and beneficial

    Investigating the effects of irrational and rational self-statements on motor-skill and hazard-perception performance

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    Rational Emotive Behavior Therapy (REBT) is a psychotherapeutic approach based on the premise that when faced with adversity irrational beliefs determine unhealthy negative emotions and maladaptive behaviors, whereas rational beliefs lead to healthy and adaptive alternatives. The detrimental effects of irrational beliefs on psychological health are established, however less is known about the deleterious effects on human behavior and performance. In the present study we examined the effects of irrational and rational self-statements on motor-skill performance (Experiment 1), performance effectiveness, and efficiency during a modified hazard perception task, and task persistence during a breath-holding task (Experiment 2). Using a repeated measures counter balanced design, two cohorts of 35 undergraduate university students were recruited for Experiment 1 and 2, each participating in no self-statement, irrational, and rational self-statement conditions. Data indicated no differences in motor-skill and task performance, performance efficiency, task persistence, mental effort, and pre-performance anxiety between irrational and rational self-statement conditions. In contrast to previous research the findings provide insight into a juxtaposition that irrational beliefs hinder psychological health, yet may help performance, highlighting important distinctions in factual and practical rationality that have been overlooked within the extant literature. The findings have important practical implications for practitioners that may look to REBT to enhance the psychological health and performance for individuals who operate in high performance contexts. Further, the short and long-term effects of irrational and rational beliefs on performance and psychological health warrants greater investigation

    PAR1 Agonists Stimulate APC-Like Endothelial Cytoprotection and Confer Resistance to Thromboinflammatory Injury

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    Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated protein C (APC) is protective in several animal models of disease, and APC has been used clinically in severe sepsis and wound healing. Clinical use of APC, however, is limited by its immunogenicity and its anticoagulant activity. We show that a class of small molecules termed “parmodulins” that act at the cytosolic face of PAR1 stimulates APC-like cytoprotective signaling in endothelium. Parmodulins block thrombin generation in response to inflammatory mediators and inhibit platelet accumulation on endothelium cultured under flow. Evaluation of the antithrombotic mechanism showed that parmodulins induce cytoprotective signaling through Gβγ, activating a PI3K/Akt pathway and eliciting a genetic program that includes suppression of NF-κB–mediated transcriptional activation and up-regulation of select cytoprotective transcripts. STC1 is among the up-regulated transcripts, and knockdown of stanniocalin-1 blocks the protective effects of both parmodulins and APC. Induction of this signaling pathway in vivo protects against thromboinflammatory injury in blood vessels. Small-molecule activation of endothelial cytoprotection through PAR1 represents an approach for treatment of thromboinflammatory disease and provides proof-of-principle for the strategy of targeting the cytoplasmic surface of GPCRs to achieve pathway selective signaling

    Does testosterone mediate the relationship between vitamin D and prostate cancer progression? A systematic review and meta-analysis

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    PURPOSE: Observational studies and randomized controlled trials (RCTs) have shown an association between vitamin D levels and prostate cancer progression. However, evidence of direct causality is sparse and studies have not examined biological mechanisms, which can provide information on plausibility and strengthen the evidence for causality. METHODS: We used the World Cancer Research Fund International/University of Bristol two-stage framework for mechanistic systematic reviews. In stage one, both text mining of published literature and expert opinion identified testosterone as a plausible biological mechanism. In stage two, we performed a systematic review and meta-analysis to assess the evidence from both human and animal studies examining the effect of vitamin D on testosterone, and testosterone on advanced prostate cancer (diagnostic Gleason score of ≥ 8, development of metastasis) or prostate cancer-specific mortality. RESULTS: A meta-analysis of ten human RCTs showed evidence of an effect of vitamin D on total testosterone (standardised mean difference (SMD) = 0.133, 95% CI =  − 0.003–0.269, I(2) = 0.0%, p = 0.056). Five human RCTs showed evidence of an effect of vitamin D on free testosterone (SMD = 0.173, 95% CI =  − 0.104–0.450, I(2) = 52.4%, p = 0.220). Three human cohort studies of testosterone on advanced prostate cancer or prostate cancer-specific mortality provided inconsistent results. In one study, higher levels of calculated free testosterone were positively associated with advanced prostate cancer or prostate cancer-specific mortality. In contrast, higher levels of dihydrotestosterone were associated with lowering prostate cancer-specific mortality in another study. No animal studies met the study eligibility criteria. CONCLUSION: There is some evidence that vitamin D increases levels of total and free testosterone, although the effect of testosterone levels within the normal range on prostate cancer progression is unclear. The role of testosterone as a mechanism between vitamin D and prostate cancer progression remains inconclusive. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10552-022-01591-w

    Cadaveric Simulation of Endoscopic Endonasal Procedures: Analysis of Droplet Splatter Patterns During the COVID-19 Pandemic

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    Objective The primary mode of viral transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is thought to occur through the spread of respiratory droplets. The objective of this study was to investigate droplet and splatter patterns resulting from common endoscopic endonasal procedures. Study Design Cadaver simulation series. Setting Dedicated surgical laboratory. Subjects and Methods After instilling cadaver head specimens (n = 2) with fluorescein solution, endoscopic endonasal procedures were systematically performed to evaluate the quantity, size, and distance of droplets and splatter following each experimental condition. Results There were no observable fluorescein droplets or splatter noted in the measured surgical field in any direction after nasal endoscopy, septoplasty with microdebrider-assisted turbinoplasty, cold-steel functional endoscopic sinus surgery (FESS), and all experimental conditions using an ultrasonic aspirator. Limited droplet spread was noted with microdebrider FESS (2 droplets, <1 mm in size, within 10 cm), drilling of the sphenoid rostrum with a diamond burr (8, <1 mm, 12 cm), and drilling of the frontal beak with a cutting burr (5, <1 mm, 9 cm); however, the use of concurrent suction while drilling resulted in no droplets or splatter. The control condition of external activation of the drill resulted in gross contamination (11, 2 cm, 13 cm). Conclusion Our results indicate that there is very little droplet generation from routine rhinologic procedures. The droplet generation from drilling was mitigated with the use of concurrent suction. Extreme caution should be used to avoid activating powered instrumentation outside of the nasal cavity, which was found to cause droplet contamination

    Could Reducing Body Fatness Reduce the Risk of Aggressive Prostate Cancer via the Insulin Signalling Pathway? A Systematic Review of the Mechanistic Pathway

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    Excess body weight is thought to increase the risk of aggressive prostate cancer (PCa), although the biological mechanism is currently unclear. Body fatness is positively associated with a diminished cellular response to insulin and biomarkers of insulin signalling have been positively associated with PCa risk. We carried out a two-pronged systematic review of (a) the effect of reducing body fatness on insulin biomarker levels and (b) the effect of insulin biomarkers on PCa risk, to determine whether a reduction in body fatness could reduce PCa risk via effects on the insulin signalling pathway. We identified seven eligible randomised controlled trials of interventions designed to reduce body fatness which measured insulin biomarkers as an outcome, and six eligible prospective observational studies of insulin biomarkers and PCa risk. We found some evidence that a reduction in body fatness improved insulin sensitivity although our confidence in this evidence was low based on GRADE (Grading of Recommendations, Assessment, Development and Evaluations). We were unable to reach any conclusions on the effect of insulin sensitivity on PCa risk from the few studies included in our systematic review. A reduction in body fatness may reduce PCa risk via insulin signalling, but more high-quality evidence is needed before any conclusions can be reached regarding PCa

    Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses

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    Certain bacteria use a type III secretion system (TTSS) to deliver effector proteins that interfere with cell function into host cells. While transcription of genes encoding TTSS components has been demonstrated, studies to date have failed to identify TTSS effector proteins in Bordetella pertussis. Here we present the first evidence of a functionally active TTSS in B. pertussis. Three known TTSS effectors, Bsp22, BopN, and BopD, were identified as TTSS substrates in B. pertussis 12743. We found expression of Bsp22 in a significant proportion of clinical isolates but not in common laboratory-adapted strains of B. pertussis. We generated a TTSS mutant of B. pertussis 12743 and showed that it induced significantly lower respiratory tract colonization in mice than the wild-type bacteria. Respiratory infection of mice with the mutant bacteria induced significantly greater innate proinflammatory cytokine production in the lungs soon after challenge, and this correlated with significantly higher antigen-specific interleukin-17, gamma interferon, and immunoglobulin G responses later in infection. Our findings suggest that the TTSS subverts innate and adaptive immune responses during infection of the lungs and may be a functionally important virulence factor for B. pertussis infection of humans.Instituto de Biotecnologia y Biologia Molecula

    Prognostic value of test(s) for O6-methylguanine–DNA methyltransferase (MGMT) promoter methylation for predicting overall survival in people with glioblastoma treated with temozolomide

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    BACKGROUND: Glioblastoma is an aggressive form of brain cancer. Approximately five in 100 people with glioblastoma survive for five years past diagnosis. Glioblastomas that have a particular modification to their DNA (called methylation) in a particular region (the O(6)‐methylguanine–DNA methyltransferase (MGMT) promoter) respond better to treatment with chemotherapy using a drug called temozolomide. OBJECTIVES: To determine which method for assessing MGMT methylation status best predicts overall survival in people diagnosed with glioblastoma who are treated with temozolomide. SEARCH METHODS: We searched MEDLINE, Embase, BIOSIS, Web of Science Conference Proceedings Citation Index to December 2018, and examined reference lists. For economic evaluation studies, we additionally searched NHS Economic Evaluation Database (EED) up to December 2014. SELECTION CRITERIA: Eligible studies were longitudinal (cohort) studies of adults with diagnosed glioblastoma treated with temozolomide with/without radiotherapy/surgery. Studies had to have related MGMT status in tumour tissue (assessed by one or more method) with overall survival and presented results as hazard ratios or with sufficient information (e.g. Kaplan‐Meier curves) for us to estimate hazard ratios. We focused mainly on studies comparing two or more methods, and listed brief details of articles that examined a single method of measuring MGMT promoter methylation. We also sought economic evaluations conducted alongside trials, modelling studies and cost analysis. DATA COLLECTION AND ANALYSIS: Two review authors independently undertook all steps of the identification and data extraction process for multiple‐method studies. We assessed risk of bias and applicability using our own modified and extended version of the QUality In Prognosis Studies (QUIPS) tool. We compared different techniques, exact promoter regions (5'‐cytosine‐phosphate‐guanine‐3' (CpG) sites) and thresholds for interpretation within studies by examining hazard ratios. We performed meta‐analyses for comparisons of the three most commonly examined methods (immunohistochemistry (IHC), methylation‐specific polymerase chain reaction (MSP) and pyrosequencing (PSQ)), with ratios of hazard ratios (RHR), using an imputed value of the correlation between results based on the same individuals. MAIN RESULTS: We included 32 independent cohorts involving 3474 people that compared two or more methods. We found evidence that MSP (CpG sites 76 to 80 and 84 to 87) is more prognostic than IHC for MGMT protein at varying thresholds (RHR 1.31, 95% confidence interval (CI) 1.01 to 1.71). We also found evidence that PSQ is more prognostic than IHC for MGMT protein at various thresholds (RHR 1.36, 95% CI 1.01 to 1.84). The data suggest that PSQ (mainly at CpG sites 74 to 78, using various thresholds) is slightly more prognostic than MSP at sites 76 to 80 and 84 to 87 (RHR 1.14, 95% CI 0.87 to 1.48). Many variants of PSQ have been compared, although we did not see any strong and consistent messages from the results. Targeting multiple CpG sites is likely to be more prognostic than targeting just one. In addition, we identified and summarised 190 articles describing a single method for measuring MGMT promoter methylation status. AUTHORS' CONCLUSIONS: PSQ and MSP appear more prognostic for overall survival than IHC. Strong evidence is not available to draw conclusions with confidence about the best CpG sites or thresholds for quantitative methods. MSP has been studied mainly for CpG sites 76 to 80 and 84 to 87 and PSQ at CpG sites ranging from 72 to 95. A threshold of 9% for CpG sites 74 to 78 performed better than higher thresholds of 28% or 29% in two of three good‐quality studies making such comparisons

    Radiotherapy exposure directly damages the uterus and causes pregnancy loss

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    Female cancer survivors are significantly more likely to experience infertility than the general population. It is well established that chemotherapy and radiotherapy can damage the ovary and compromise fertility, yet the ability of cancer treatments to induce uterine damage, and the underlying mechanisms, have been understudied. Here, we show that in mice total-body γ-irradiation (TBI) induced extensive DNA damage and apoptosis in uterine cells. We then transferred healthy donor embryos into ovariectomized adolescent female mice that were previously exposed to TBI to study the impacts of radiotherapy on the uterus independent from effects to ovarian endocrine function. Following TBI, embryo attachment and implantation were unaffected, but fetal resorption was evident at midgestation in 100% of dams, suggesting failed placental development. Consistent with this hypothesis, TBI impaired the decidual response in mice and primary human endometrial stromal cells. TBI also caused uterine artery endothelial dysfunction, likely preventing adequate blood vessel remodeling in early pregnancy. Notably, when pro-apoptotic protein Puma-deficient (Puma-/-) mice were exposed to TBI, apoptosis within the uterus was prevented, and decidualization, vascular function, and pregnancy were restored, identifying PUMA-mediated apoptosis as a key mechanism. Collectively, these data show that TBI damages the uterus and compromises pregnancy success, suggesting that optimal fertility preservation during radiotherapy may require protection of both the ovaries and uterus. In this regard, inhibition of PUMA may represent a potential fertility preservation strategy.</p
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