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Self-medication of pain with alcohol is prevalent, and expectancies for alcohol analgesia (EAA) likely influence pain relief and alcohol consumption. Hazardous alcohol use has been associated with greater delay discounting rates; however, little is known about the relationship between delay discounting and EAA. Therefore, the present study examined sex differences in associations between delay discounting and EAA. Healthy drinkers without chronic pain (N = 53) completed measures of EAA, alcohol use, and alcohol outcome expectancies. A five-trial adjusting-delay discounting task (DDT) for monetary outcomes was also administered. Regression analyses revealed that sex moderated the relationship between delay discounting and EAA. Steeper delay discounting rates were associated with weaker EAA among men when adjusting for average alcohol consumption. Among women, nonsignificant associations between delay discounting rates and EAA were observed. These findings provide initial evidence of sex differences in associations between delay discounting and EAA. The directionality of these associations was unexpected and may have implications for patterns of self-medication with alcohol. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Binge-eating disorder (BED) is associated with overweight/obesity, physical inactivity, and disturbances in affective functioning. While research suggests that physical activity (PA) may have beneficial effects on BED symptoms, little is known about the daily correlates of PA. As a first step in understanding the processes linking PA and binge eating, this study examined associations between PA (i.e., self-reported time engaged in moderate-to-vigorous PA), affective functioning (i.e., positive and negative affect, body satisfaction, emotion regulation), and eating-related cognitions and behaviors (i.e., craving, overeating, loss of control eating) measured via ecological momentary assessment (EMA). Adults with BED (N = 91) completed a seven-day EMA protocol during which they completed repeated measures of these variables. Results indicated individuals who reported greater time engaged in PA over the EMA protocol evidenced higher positive affect and body satisfaction, and lower overeating (between-subjects effects). No significant within-subjects effects were observed. Findings demonstrate that individual differences in PA levels were related to more adaptive affective functioning and eating regulation in daily life. Results highlight the relevance of PA in BED, and the need for future studies to identify the timescale of these relationships using objective measurements of PA.

Cervical myelopathy is a clinical syndrome caused by compression of the spinal cord between the levels of the C1 and T1 vertebrae. Its clinical presentation can mimic many other degenerative and neurological pathologies, making diagnosis challenging. Diagnosis is confirmed with appropriate imaging studies carefully correlated with history and physical examination. Treatment options are focused on decompression of the spinal canal from an anterior, posterior, or combined anterior and posterior surgical approach depending on the location of compression and patient factors. Outcomes are favorable if treatment is performed prior to severe symptom onset.

Anti–SARS-CoV-2 antibodies have been used in health care and clinical settings to prevent and treat COVID-19. The National Institutes of Health convened a virtual summit on 15 June 2021 to summarize existing knowledge and to identify key unanswered scientific questions to catalyze future development of these antibodies., As the fourth wave of the SARS-CoV-2 pandemic encircles the globe, there remains an urgent challenge to identify safe and effective treatment and prevention strategies that can be implemented in a range of health care and clinical settings. Substantial advances have been made in the use of anti–SARS-CoV-2 antibodies to mitigate the morbidity and mortality associated with COVID-19. On 15 June 2021, the National Institutes of Health, in collaboration with the U.S. Food and Drug Administration, convened a virtual summit to summarize existing knowledge on anti–SARS-CoV-2 antibodies and to identify key unanswered scientific questions to further catalyze the clinical development and implementation of antibodies.

Objective:To describe the cumulative seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies during the coronavirus disease 2019 (COVID-19) pandemic among employees of a large pediatric healthcare system.Design, setting, and participants:Prospective observational cohort study open to adult employees at the Children’s Hospital of Philadelphia, conducted April 20–December 17, 2020.Methods:Employees were recruited starting with high-risk exposure groups, utilizing e-mails, flyers, and announcements at virtual town hall meetings. At baseline, 1 month, 2 months, and 6 months, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity.Results:In total, 1,740 employees were enrolled. At 6 months, the cumulative seroprevalence was 5.3%, which was below estimated community point seroprevalence. Seroprevalence was 5.8% among employees who provided direct care and was 3.4% among employees who did not perform direct patient care. Most participants who were seropositive at baseline remained positive at follow-up assessments. In a post hoc analysis, direct patient care (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.03–3.68), Black race (HR, 2.70; 95% CI, 1.24–5.87), and exposure to a confirmed case in a nonhealthcare setting (HR, 4.32; 95% CI, 2.71–6.88) were associated with statistically significant increased risk for seropositivity.Conclusions:Employee SARS-CoV-2 seroprevalence rates remained below the point-prevalence rates of the surrounding community. Provision of direct patient care, Black race, and exposure to a confirmed case in a nonhealthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID-19 waves or other epidemics.

Many nations are pursuing the rollout of SARS-CoV-2 vaccines as an exit strategy from unprecedented COVID-19-related restrictions. However, the success of this strategy relies critically on the duration of protective immunity resulting from both natural infection and vaccination. SARS-CoV-2 infection elicits an adaptive immune response against a large breadth of viral epitopes, although the duration of the response varies with age and disease severity. Current evidence from case studies and large observational studies suggests that, consistent with research on other common respiratory viruses, a protective immunological response lasts for approximately 5-12 months from primary infection, with reinfection being more likely given an insufficiently robust primary humoral response. Markers of humoral and cell-mediated immune memory can persist over many months, and might help to mitigate against severe disease upon reinfection. Emerging data, including evidence of breakthrough infections, suggest that vaccine effectiveness might be reduced significantly against emerging variants of concern, and hence secondary vaccines will need to be developed to maintain population-level protective immunity. Nonetheless, other interventions will also be required, with further outbreaks likely to occur due to antigenic drift, selective pressures for novel variants, and global population mobility.

BACKGROUND: In the absence of randomised head-to-head trials, we conducted a population-adjusted indirect treatment comparison (PA-ITC) of phase III trial data to evaluate the relative efficacy and safety of maintenance olaparib and bevacizumab alone and in combination in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation (BRCAm). METHODS: An unanchored PA-ITC was performed on investigator-assessed progression-free survival (PFS) data. Individual patient data from SOLO1 (olaparib versus placebo) and from BRCA-mutated patients in PAOLA-1/ENGOT-ov25 (olaparib plus bevacizumab versus placebo plus bevacizumab) were pooled. Each arm of PAOLA-1 was weighted so that key baseline patient characteristics were similar to the SOLO1 cohort. Analyses were performed in patients with complete baseline data. Weighted Cox regression analysis was used to estimate the comparative efficacy of different maintenance therapy strategies, supplemented by weighted Kaplan-Meier analyses. RESULTS: Data from SOLO1 patients (olaparib, n = 254; placebo, n = 126) were compared with data from BRCA-mutated PAOLA-1 patients (olaparib plus bevacizumab, n = 151; placebo plus bevacizumab, n = 71). Adding bevacizumab to olaparib was associated with a numerical improvement in PFS compared with olaparib alone (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.45-1.09). Statistically significant improvements in PFS were seen with olaparib alone versus placebo plus bevacizumab (HR 0.48; 95% CI 0.30-0.75), olaparib plus bevacizumab versus placebo (0.23; 0.14-0.34), and placebo plus bevacizumab versus placebo (0.65; 0.43-0.95). CONCLUSIONS: Results of this hypothesis-generating PA-ITC analysis support the use of maintenance olaparib alone or with bevacizumab in patients with newly diagnosed, advanced ovarian cancer and a BRCAm. ispartof: EUROPEAN JOURNAL OF CANCER vol:157 pages:415-423 ispartof: location:England status: published

Background and Purpose: Conventional magnetic resonance imaging (MRI) poses challenges in quantitative analysis because voxel intensity values lack physical meaning. While intensity standardization methods exist, their effects on head and neck MRI have not been investigated. We developed a workflow based on healthy tissue region of interest (ROI) analysis to determine intensity consistency within a patient cohort. Through this workflow, we systematically evaluated intensity standardization methods for MRI of head and neck cancer (HNC) patients. Materials and Methods: Two HNC cohorts (30 patients total) were retrospectively analyzed. One cohort was imaged with heterogenous acquisition parameters (HET cohort), whereas the other was imaged with homogenous acquisition parameters (HOM cohort). The standard deviation of cohort-level normalized mean intensity (SD NMIc), a metric of intensity consistency, was calculated across ROIs to determine the effect of five intensity standardization methods on T2-weighted images. For each cohort, a Friedman test followed by a post-hoc Bonferroni-corrected Wilcoxon signed-rank test was conducted to compare SD NMIc among methods. Results: Consistency (SD NMIc across ROIs) between unstandardized images was substantially more impaired in the HET cohort (0.29 ± 0.08) than in the HOM cohort (0.15 ± 0.03). Consequently, corrected p-values for intensity standardization methods with lower SD NMIc compared to unstandardized images were significant in the HET cohort (p 0.05). In both cohorts, differences between methods were often minimal and nonsignificant. Conclusions: Our findings stress the importance of intensity standardization, either through the utilization of uniform acquisition parameters or specific intensity standardization methods, and the need for testing intensity consistency before performing quantitative analysis of HNC MRI.

We explored the associations among perceived stress, depressive symptoms, loneliness, and social support during the COVID-19 pandemic; and differences in perceived stress, depressive symptoms, and social support prior to the pandemic and during the pandemic among pregnant Black women. A sample of 33 pregnant Black women who participated in the Biosocial Impact on Black Births (BIBB) and were still pregnant in May–June 2020 were invited to complete an online survey about their experiences during the pandemic. Fifteen women responded very much or somewhat to experiencing stress and anxiety because of the COVID-19 pandemic. Eight women had CES-D scores ≥23, which have been correlated with depression diagnosis. Women who reported higher levels of loneliness during the COVID-19 pandemic also reported higher levels of perceived stress and depressive symptoms and lower levels of social support during the pandemic. Women who reported lower levels of social support during the pandemic also reported higher levels of perceived stress and depressive symptoms during the pandemic. There were no changes in perceived stress, depressive symptoms, or social support prior to the pandemic and during the pandemic. Clinicians should assess for signs of loneliness and depressive symptoms for pregnant women and offer recommendations for therapy and support groups.

Coupled aerothermoelastic simulations are required for the accurate simulation of many high-speed flow problems. Hence, the multidisciplinary analysis of such problems is the main focus of the curr...

It has been suggested that aging and inflammation play key roles in the development of delirium. In the present study, we investigated the differences of the DNAm patterns in the TNF gene between patients with delirium and without. The data and samples derived from previous and ongoing cohort studies were analyzed. DNAm levels of the TNF gene were analyzed using the Illumina EPIC array genome-wide method and pyrosequencing method. Correlations between age and DNAm levels of each CpG were calculated. Several CpG in the TNF gene in blood showed negative correlation between their DNAm and age in delirium cases both with the EPIC array and by the pyrosequencing method. However, there was no CpG that had significant correlation between their DNAm and age regardless of delirium status among buccal samples. On the other hand, among peripheral blood mononuclear cells samples, it was found that several CpG showed negative correlation between their DNAm and age in delirium cases. The evidence of DNAm change in the TNF gene among delirious subjects was demonstrated.

Background Many patients with American College of Cardiology/American Heart Association Stage D (advanced) heart failure are discharged home on chronic intravenous inotropic support (CIIS) as bridge to surgical therapy or as palliative therapy. This study analyzed the clinical trajectory of patients with advanced heart failure who were on home CIIS. Methods We conducted a single-institution, retrospective cohort study of patients on CIIS between 2010 and 2016 (n = 373), stratified by indication for initiation of inotropic support. Study outcomes were time from initiation of CIIS to cessation of therapy, time to death for patients who did not receive surgical therapy and rates of involvement with palliative care. Results Overall, patients received CIIS therapy for an average of 5.9 months (standard deviation [SD] 7.3). Patients on CIIS as palliative therapy died in an average of 6.2 months (SD 6.6) from the time of initiation of CIIS, and those on CIIS as bridge therapy who did not ultimately receive surgical therapy died after an average of 8.6 months (SD 9.3). Patients who received CIIS as bridge therapy were significantly less likely to receive palliative-care consultation than those on inotropes as palliative therapy, whether or not they underwent surgery. Conclusions In this large cohort of patients with advanced HF, patients who on CIIS as palliative therapy survived for 6.2 months, on average, with wide variation among patients. Patients who were on CIIS as bridge therapy but did not ultimately receive surgical therapy received less palliative care despite the high mortality rate in this subgroup.

SUMMARYElectroconvulsive therapy (ECT) for depression is a controversial treatment with highly polarised views about the balance between therapeutic benefits and adverse effects. Studies investigating whether ECT is more effective than a placebo treatment started in the 1950s, with the most important randomised controlled trials carried out about four decades ago in which ECT was compared with sham ECT (SECT) involving anaesthesia but no electrically induced seizure. Subsequently the data have been pooled in a number of meta-analyses which have found that ECT is an effective treatment. However, a recent review of the quality of the SECT-controlled studies, and the meta-analyses based on them, concludes that their quality is too poor to allow assessment of the efficacy of ECT and that, given its risks (permanent memory loss and death), the use of ECT should be suspended. This commentary critically discusses the methodology of this review and its conclusions.

Background Cognitive complications persist in persons with HIV (PWH) during suppressive antiretroviral therapy (ART). Low levels of HIV during ART could contribute to these complications. In this study, we measured cerebrospinal fluid (CSF) HIV using a single copy assay (SCA) to investigate a possible relationship between low level HIV and cognition.Design/Methods: SCA data were analyzed from three consecutive paired CSF-plasma specimens collected over a mean of 456 days from 96 participants on suppressive ART. Using mixed models, the presence of CSF HIV by SCA as a risk factor for worse neurocognitive performance was examined. Results At baseline on the SCA, 45.8% of participants had detectable plasma HIV RNA (median 8 copies/milliliter (ml), interquartile range (IQR) = 3-17 among detectable values), and 17.7% had detectable CSF HIV RNA (median CSF concentration= 3 copies/ml, interquartile range= 2-13 among detectable values). The frequency of CSF HIV RNA detection declined over time in CSF (p=0.018) with a trend toward decline in plasma (p=0.064). Detectable CSF HIV RNA during the study was associated with worse performance in the domains of recall (p=0.014) and motor (p=0.040), and a trend with worse overall global performance (p=0.078). Integrase inhibitor use, while very infrequent in this cohort, was associated with better performance in two domains. Conclusions Low-level CSF HIV RNA declines with time but is associated with worse cognitive performance in two domains. Additional research is needed to better understand the relationship between HIV RNA persistence during long-term ART and central nervous system complications in PWH.

This paper explores the potential economic gains of allowing additional flexibility in gear choice, within rights-based management programs. A case study of US west coast sablefish (Anoplopoma fimbria) provides an example of a commercially important species where gear-switching is currently occurring within the individual fishing quota (IFQ) program, allowing us to isolate the economic potential of gear flexibility along two important margins: size and quality. We conduct a hedonic price analysis of ex-vessel prices using panel fish ticket data and linear mixed-effect econometric models to examine the influences of gear, size, condition, fishing sector, port group, landing month, and year on the price of sablefish. We generate a counter-factual scenario that represents the IFQ fishery where the use of fixed gear is prohibited by predicting what the size composition of catch would have been if the sablefish had been caught with trawl gear. We find that the flexibility of targeting sablefish with fixed gear between 2011 and 2016 generated an annual mean 10.45% increase in total revenue, or US$1.17 million, compared with the trawl-only scenario. These results show sablefish value increases through implementing gear flexibility, which contributes to a broader conversation of allocative efficiency.

Introduction: The aims of this study were to investigate the potential impact of age, sex and body mass index (BMI) upon the incidence of arrhythmias pre- and post- diving, and to identify the prevalence of left ventricular hypertrophy (LVH) in older recreational divers. Methods: Divers aged ≥ 40 years participating in group dive trips had ECG rhythm and echocardiograph recordings before and after diving. Arrhythmias were confirmed by an experienced human reader. LVH was identified by two-dimensional echocardiography. Weighted (0.5 fractional) values were used to account for participation by seven divers in 14 trips. Results: Seventy-seven divers undertook 84 dive trips and recorded 677 dives. Among divers with no pre-trip arrhythmias (n = 55), we observed that 6.5 (12%) recorded post-trip arrhythmias and the median increase was 1.0 arrhythmia. In divers with pre-trip arrhythmias, 14.5 had a median of 1.0 fewer post-trip arrhythmias, 2.0 had no change and 5.5 had a median of 16.0 greater. Age, but neither sex nor BMI, was associated with change in the number of arrhythmias before and after dive trips (P = 0.02). The relative risk for experiencing a change in the frequency of arrhythmias after a diver trip, was 2.1 for each additional 10 years of age (95% CI 1.1, 4.0). Of the 60 divers with imaging of their heart, five had left ventricular hypertrophy. Conclusions: We observed a higher than expected prevalence of arrhythmias. Divers with pre-trip arrhythmias tended to be older than divers without pre-trip arrhythmias (P = 0.02). The prevalence of LVH in our cohort was one quarter of that found post-mortem in scuba fatalities.

BackgroundMost dementia algorithms are unsuitable for population-level assessment and planning as they are designed for use in the clinical setting. A predictive risk algorithm to estimate 5-year dementia risk in the community setting was developed.MethodsThe Dementia Population Risk Tool (DemPoRT) was derived using Ontario respondents to the Canadian Community Health Survey (survey years 2001 to 2012). Five-year incidence of physician-diagnosed dementia was ascertained by individual linkage to administrative healthcare databases and using a validated case ascertainment definition with follow-up to March 2017. Sex-specific proportional hazards regression models considering competing risk of death were developed using self-reported risk factors including information on socio-demographic characteristics, general and chronic health conditions, health behaviours and physical function.ResultsAmong 75 460 respondents included in the combined derivation and validation cohorts, there were 8448 cases of incident dementia in 348 677 person-years of follow-up (5-year cumulative incidence, men: 0.044, 95% CI: 0.042 to 0.047; women: 0.057, 95% CI: 0.055 to 0.060). The final full models each include 90 df (65 main effects and 25 interactions) and 28 predictors (8 continuous). The DemPoRT algorithm is discriminating (C-statistic in validation data: men 0.83 (95% CI: 0.81 to 0.85); women 0.83 (95% CI: 0.81 to 0.85)) and well-calibrated in a wide range of subgroups including behavioural risk exposure categories, socio-demographic groups and by diabetes and hypertension status.ConclusionsThis algorithm will support the development and evaluation of population-level dementia prevention strategies, support decision-making for population health and can be used by individuals or their clinicians for individual risk assessment.

Introduction Advanced breast cancer (aBC) remains incurable and the quest for more effective systemic anticancer agents continues. Promising results have led to the FDA approval of three antibody-drug conjugates (ADCs) and two immune checkpoint inhibitors (ICIs) to date for patients with aBC. Areas covered With the anticipated emergence of newer ADCs and ICIs for patients with several subtypes of breast cancer, and given their potential synergy, their use in combination is of clinical interest. In this article, we review the use of ADCs and ICIs in patients with breast cancer, assess the scientific rationale for their combination, and provide an overview of ongoing trials and some early efficacy and safety results of such dual therapy. Expert opinion Improvement in the medicinal chemistry of next-generation ADCs, their rational combination with ICIs and other agents, and the development of multiparametric immune biomarkers could help to significantly improve the outlook for patients with refractory aBC.

Background The World Health Organization previously set goals of controlling morbidity due to schistosomiasis by 2020 and attaining elimination as a public health problem (EPHP) by 2025 (now adjusted to 2030 in the new neglected tropical diseases roadmap). As these milestones are reached, it is important that programs reassess their treatment strategies to either maintain these goals or progress from morbidity control to EPHP and ultimately to interruption of transmission. In this study, we consider different mass drug administration (MDA) strategies to maintain the goals. Methods We used 2 independently developed, individual-based stochastic models of schistosomiasis transmission to assess the optimal treatment strategy of a multiyear program to maintain the morbidity control and the EPHP goals. Results We found that, in moderate-prevalence settings, once the morbidity control and EPHP goals are reached it may be possible to maintain the goals using less frequent MDAs than those that are required to achieve the goals. On the other hand, in some high-transmission settings, if control efforts are reduced after achieving the goals, particularly the morbidity control goal, there is a high chance of recrudescence. Conclusions To reduce the risk of recrudescence after the goals are achieved, programs have to re-evaluate their strategies and decide to either maintain these goals with reduced efforts where feasible or continue with at least the same efforts required to reach the goals.

The total number of children in the U.S. foster care system exceeds 428,000. Previous research indicates that when social workers and legal professionals work together, children and their families benefit significantly. Parents who effectively engage in the child welfare system are more likely to benefit from services and reunify with their children. The present study employed a phenomenological approach to explore how a parent representation pilot, which paired social workers with public defenders to better represent the needs of families in the child welfare system, was experienced by legal professionals. Judges and family court attorneys (n = 9) found the program to be helpful in reunifying families. Public defenders were able to leverage the social worker’s skills and experience to facilitate more positive outcomes, while reducing case burden. Challenges were also identified and included a lack of interdisciplinary training, potential overlap in ethical responsibilities, and role confusion. Structured intervention programs that encourage collaboration between social workers and legal professionals may improve case outcomes for indigent families involved in the child welfare system. It is advised that social work undertake a formal multidisciplinary approach in support of public defenders, which may serve to encourage positive case outcomes.

The design and evaluation of control programs for soil-transmitted helminths (STHs) is based on surveillance data recording measurements of egg counts in the stool of infected individuals, which underpin estimates of the prevalence and average intensity of infection. There is considerable uncertainty around these measurements and their interpretation. The uncertainty is composed of several sources of measurement error and the limit of detection of fecal smear tests on the one hand, and key assumptions on STH biology on the other hand, including assumptions on the aggregation of worms within hosts and on the impact of density-dependent influences on worm reproduction. Using 2 independently developed models of STH transmission we show how different aspects of STH biology and human behavior impact on STH surveillance and control programs and how accounting for uncertainty can help to develop optimal and sustainable control strategies to meet the World Health Organization (WHO) morbidity target for STHs.

Calls for biodiversity conservation practice to be more evidence based are growing, and we agree evidence use in conservation practice needs improvement. However, evidence-based conservation will not be realized without improved access to evidence. In medicine, unlike in conservation, a well-established and well-funded layer of intermediary individuals and organizations engage with medical practitioners, synthesize primary research relevant to decision making, and make evidence easily accessible. These intermediaries prepare targeted evidence summaries and distribute them to practitioners faced with time-sensitive and value-laden decisions. To be effective, these intermediaries, who we refer to as evidence bridges, should identify research topics based on the priorities of practitioners; synthesize evidence; prepare and distribute easy-to-find and easy-to-use evidence summaries; and develop and maintain networks of connections with researchers and practitioners. Based on a review of the literature regarding evidence intermediaries in conservation and environmental management, as well as an anonymous questionnaire searching for such organizations, we found few intermediaries that met all these criteria. Few evidence bridges that do exist are unable to reach most conservation practitioners, which include resource managers in government and industry, conservation organizations, and farmers and other private landowners. We argue that the lack of evidence bridges from research to practitioners contributes to evidence complacency and limits the use of evidence in conservation action. Nevertheless, several existing organizations help reduce the gap between evidence and practice and could serve as a foundation for building additional components of evidence bridges in conservation. Although evidence bridges need expertise in research and evidence synthesis, they also require expertise in identifying and communicating with the community of practitioners most in need of clear and concise syntheses of evidence. Article Impact Statement: Evidence-based conservation will not be realized without improved access to evidence. We call for intermediary evidence bridges.Vinculación entre la Investigación y la Práctica en la Conservación Resumen Cada vez existen más peticiones para que las prácticas de conservación de la biodiversidad estén más basadas en evidencias, además de que apoyamos la idea de que el uso de evidencias en la práctica de la conservación necesita mejorar. Sin embargo, la conservación basada en la evidencia no se logrará sin un acceso mejorado a las evidencias. En la medicina, no como en la conservación, un estrato bien establecido y financiado de individuos y organizaciones intermediarias interactúan con los médicos, sintetizan las investigaciones primarias relevantes para la toma de decisiones y hacen que las evidencias sean de fácil acceso. Estos intermediarios preparan resúmenes de evidencias específicas y los distribuyen a los médicos que enfrentan decisiones urgentes y muy valiosas. Para que sean efectivos, estos intermediarios, a quienes nos referimos como puentes de evidencias, deben poder identificar los temas de estudio con base en las prioridades de los practicantes, sintetizar evidencias, preparar y distribuir resúmenes fáciles de encontrar y fáciles de usar, y desarrollar y mantener redes de conexiones con los investigadores y los practicantes. Con base en una revisión de la literatura correspondiente a los intermediarios de evidencias en la conservación y el manejo ambiental, así como en un cuestionario anónimo que busca a dichas organizaciones, encontramos a pocos intermediarios que cumplieran con estos criterios. Los pocos puentes de evidencias que existen no son capaces de llegar a la mayoría de los practicantes de la conservación, los cuales incluyen a los gestores de recursos en el gobierno y en la industria, a las organizaciones de conservación y a los agricultores y otros terratenientes privados. Argumentamos que la falta de puentes de evidencia entre los investigadores y los practicantes contribuye a la indulgencia de evidencias y limita el uso de evidencias en las acciones de conservación. Sin embargo, varias organizaciones existentes ayudan a reducir la brecha entre la evidencia y la práctica y podrían funcionar como base para la construcción de componentes adicionales para los puentes de evidencia en la conservación. Aunque los puentes de evidencias necesitan experiencia con la investigación y con la síntesis de evidencias, también requieren experiencia con la identificación de y comunicación con la comunidad de practicantes que más necesitan una síntesis clara y concisa de la evidencia.对于生物多样性保护实践应更加注重证据的呼声已越来越高, 我们也同意在保护实践中需要改进证据的使用。然而, 如果不能获取更好的证据, 也将无从实现基于证据的保护。与保护领域不同的是, 在医学领域中, 由已确立并资金充足的中介人或中介组织与医务人员合作, 来整合与决策相关的第一手研究资料, 从而使这些研究证据更易于获取。这些中介机构会准备有针对性的证据摘要, 并将其分发给需要进行较强时效性、主观性决策的医务人员。为了提高效率, 中介机构 (我们称之为“证据桥梁”) 应根据医务人员的优先排序来确定研究课题、整合证据、准备和分发易获得且易使用的证据摘要, 并发展和保持研究者与医务工作者的联系网络。基于对保护及环境管理领域证据中介研究的文献调研, 以及此类机构的匿名问卷搜索, 我们发现很少有中介能达到全部标准。现有的少量证据桥梁无法影响到大多数包括政府和行业的资源管理人员、保护组织、农民及其他私人土地所有者在内的保护实践者。我们认为, 缺乏从研究到实践者的证据桥梁会导致“证据自满”, 并限制保护行动中的证据使用。尽管如此, 已有的一些组织能帮助缩小证据与实践之间的差距, 并可作为建立保护证据桥梁额外组成部分的基础。建立证据桥梁不仅要有研究和证据整合的专门知识, 还要有识别出最需要清晰简明的整合证据的实践者群体并与之沟通的专门知识。 【翻译: 胡怡思; 审校: 聂永刚】.

Virtual meetings are now a core construct of how business operations are conducted during the coronavirus pandemic. There has been a sharp increase in the use of video and interactive meetings to assure business continuity while maintaining the community's safety and workforce. Additionally, technology has given rise to businesses re-evaluating how outcomes can be reached today and in the future. Our ability to conduct high quality, interactive virtual meetings is essential. Virtual meetings offer many advantages, such as decreasing travel costs, and expand the definition of reaching a more diverse audience while incorporating technology to stay connected. The benefits extend to meetings beyond the organizations' confines where care occurs, to professional events, conferences, regulatory visits, and other virtual meetings. In response to the novel coronavirus, the American Nurse Credentialing Center now uses this technology to meet the site visit requirement to achieve Magnet designation. This article discusses how to conduct effective virtual meetings, how organizations can best prepare for a Magnet® virtual site visit, and the critical lessons learned to assist nurse leaders in conducting effective Magnet virtual site visits.

Objective The purpose of this study was to evaluate the relationship between treatment escalation and spinal manipulation in a retrospective cohort of people diagnosed with musculoskeletal disorders of the cervical spine. Methods We used retrospective analysis of insurance claims data (2012-2018) from a single Fortune 500 company. After isolating the first episode of care, we categorized 58 147 claims into 7951 unique patient episodes. Treatment escalation included claims where imaging, injection, emergency room, or surgery was present. Modified Poisson regression was used to determine the relative risk of treatment escalation comparing recipients vs nonrecipients of spinal manipulation, adjusted for age, sex, episode duration, and risk scores. Results The sample was 55% women, with a mean age of 44 years (range, 18-103). Treatment escalation was present in 42% of episodes overall: 2448 (46%) associated with other care and 876 (26%) associated with spinal manipulation. The estimated risk of any treatment escalation was 2.38 times higher in those who received other care than in those who received spinal manipulation (95% confidence interval, 2.22-2.55, P = .001). Conclusion Among episodes of care associated with neck pain diagnoses, those associated with other care had twice the risk of any treatment escalation compared with those associated with spinal manipulation. In the United States, over 90% of spinal manipulation is provided by doctors of chiropractic; therefore, these findings are relevant and should be considered in addressing solutions for neck pain. Additional research investigating the factors influencing treatment escalation is necessary to moderate the use of high-cost and guideline-incongruent procedures in people with neck pain.

Candida albicans is a common human fungal pathogen that was first described in the 1930s and is currently one of the major causes of invasive fungal infections, especially in immunocompromised patients. Since its first identification and association with disease, C. albicans has been the subject of intense research investigations. In this review, we focus on the trailblazing women who made instrumental discoveries about some of the key research questions that we are still working on answering today. We highlight five major areas of C. albicans research: morphogenesis, drug resistance, polymicrobial interactions, in vivo pathogenesis, and host immune responses. In each section, we discuss early findings by women researchers as well as current, cutting-edge research being performed by women leaders in the field. In many cases, some of the “common knowledge” in C. albicans biology was first described by women, and we hope to re-emphasize their contributions to the work that is still being carried out today.

Acute occlusion of the posterior sagittal sinus may lead to dramatic increase in intracranial pressure (ICP), refractory to standard treatment. Hybrid vascular bypass of cranial venous outflow into the internal jugular vein (IJV) has seldom been described for this in recent neurosurgical literature. To describe creation of a novel vascular bypass shunt from the superior sagittal sinus (SSS) to internal jugular vein (IJV) utilizing a covered stent-Dacron graft construct for control of refractory ICP. We illustrate a patient with refractory ICP increases after acute sinus ligation that was performed to halt torrential bleeding from intraoperative injury. A temporary shunt was created that successfully controlled ICP. From the promising results of the temporary shunt, we utilized a prosthetic hybrid bypass graft to function as a shunt from the sagittal sinus to IJV. Yet the associated anticoagulation led to complications and a poor outcome. Rapid and sustained ICP reduction can be expected after sagittal sinus-to-jugular bypass shunt placement in acute sinus occlusion. Details of the surgical technique are described. Heparin anticoagulation, while imperative, is also associated with worrisome complications. Acute occlusion of posterior third of sagittal sinus carries a very malignant clinical course. Intractable intracranial hypertension from acute sinus occlusion may be effectively treated with a SSS-IJV bypass shunt. A covered stent construct provides an effective vascular bypass conduit. However, the anticoagulation risk can lead to fatal outcomes. The neurosurgeon must always strive for primary repair of an injured sinus.

Food manufacturers are required to obtain scientific and technical evidence that a control measure or combination of control measures is capable of reducing a significant hazard to an acceptable level that does not pose a public health risk under normal conditions of distribution and storage. A validation study provides evidence that a control measure is capable of controlling the identified hazard under a worst-case scenario for process and product parameters tested. It also defines the critical parameters that must be controlled, monitored, and verified during processing. This review document is intended as guidance for the food industry to support appropriate validation studies, and aims to limit methodological discrepancies in validation studies that can occur among food safety professionals, consultants, and third-party laboratories. The document describes product and process factors that are essential when designing a validation study, and gives selection criteria for identifying an appropriate target pathogen or surrogate organism for a food product and process validation. Guidance is provided for approaches to evaluate available microbiological data for the target pathogen or surrogate organism in the product type of interest that can serve as part of the weight of evidence to support a validation study. The document intends to help food manufacturers, processors, and food safety professionals to better understand, plan, and perform validation studies by offering an overview of the choices and key technical elements of a validation plan, the necessary preparations including assembling the validation team and establishing prerequisite programs, and the elements of a validation report.

Deep learning is becoming increasingly popular and available to new users, particularly in the medical field. Deep learning image segmentation, outcome analysis, and generators rely on presentation of Digital Imaging and Communications in Medicine (DICOM) images and often radiation therapy (RT) structures as masks. Although the technology to convert DICOM images and RT structures into other data types exists, no purpose-built Python module for converting NumPy arrays into RT structures exists. The 2 most popular deep learning libraries, Tensorflow and PyTorch, are both implemented within Python, and we believe a set of tools built in Python for manipulating DICOM images and RT structures would be useful and could save medical researchers large amounts of time and effort during the preprocessing and prediction steps. Our module provides intuitive methods for rapid data curation of RT-structure files by identifying unique region of interest (ROI) names and ROI structure locations and allowing multiple ROI names to represent the same structure. It is also capable of converting DICOM images and RT structures into NumPy arrays and SimpleITK Images, the most commonly used formats for image analysis and inputs into deep learning architectures and radiomic feature calculations. Furthermore, the tool provides a simple method for creating a DICOM RT-structure from predicted NumPy arrays, which are commonly the output of semantic segmentation deep learning models. Accessing DicomRTTool via the public Github project invites open collaboration, and the deployment of our module in PyPi ensures painless distribution and installation. We believe our tool will be increasingly useful as deep learning in medicine progresses.

BACKGROUND AND AIMS. Epstein-Barr Virus (EBV)-associated Gastric Carcinoma (EBVaGC) is the most common EBV-associated cancer and accounts for ~10% of all gastric cancers (GC). Epstein-Barr virus Nuclear Antigen 1 (EBNA1), which is critical for the replication and maintenance of the EBV latent genome, is consistently expressed in all EBVaGC tumors. We previously developed small molecule inhibitors of EBNA1. In this study, we investigated the efficacy and selectivity of an EBNA1 inhibitor in cell-based and animal xenograft models of EBV-positive and EBV-negative gastric carcinoma. METHODS. We tested the potency of an EBNA1 inhibitor, VK-1727, in vitro and in xenograft studies, using EBV-positive (SNU-719 and YCCEL1) and EBV-negative (AGS and MKN74) GC cell lines. After treatment, we analyzed cell viability, proliferation, and RNA expression of EBV genes by RT-qPCR. RESULTS. Treatment with VK-1727 selectively inhibits cell cycle progression and proliferation in vitro. In animal studies, treatment with an EBNA1 inhibitor resulted in a significant dose-dependent decrease in tumor growth in EBVaGC xenograft models, but not in EBV-negative GC xenograft studies. Gene expression analysis revealed that short term treatment in cell culture tended towards viral gene activation, while long-term treatment in animal xenografts showed a significant decrease in viral gene expression. CONCLUSIONS. EBNA1 inhibitors are potent and selective inhibitors of cell growth in tissue culture and animal models of EBV-positive GC. Long-term treatment with EBNA1 inhibitors may lead to loss of EBV in mouse xenografts. These results suggest that pharmacological targeting of EBNA1 may be an effective strategy to treat patients with EBVaGC.

To adequately address health disparities, underserved populations must be recruited for biomedical research. Particularly, Black women have been insufficiently included in biomedical research for reasons beyond those of participant preference. Researchers can and should be taking responsibility to ensure rigorous methods are employed to appropriately recruit Black women and enable meaningful implications of their results. The objective of this paper is to identify and describe innovative community-based strategies for successful recruitment of Black women in research. Three studies are referenced to exemplify recruitment methods and demonstrate promising recruitment results in sample size and screening-to-enrollment ratio.

Relapse susceptibility in women with substance use disorders (SUDs) has been linked to the estrogen, 17β-estradiol (E2). Our previous findings in female rats suggest that the influence of E2 on cocaine seeking can be localized to the prelimbic prefrontal cortex (PrL-PFC). Here, we investigated the receptor mechanisms through which E2 regulates the reinstatement of extinguished cocaine seeking. Sexually mature female rats underwent intravenous cocaine self-administration (0.5 mg/inf; 14 × 2 h daily) and extinction, and then were ovariectomized before reinstatement testing. E2 (10 µg/kg, i.p.) alone did not reinstate cocaine seeking, but it potentiated reinstatement when combined with an otherwise subthreshold priming dose of cocaine. A similar effect was observed following intra-PrL-PFC microinfusions of E2 and by systemic or intra-PrL-PFC administration of the estrogen receptor (ER)β agonist, DPN, but not agonists at ERα or the G-protein-coupled ER1 (GPER1). By contrast, E2-potentiated reinstatement was prevented by intra-PrL-PFC microinfusions of the ERβ antagonist, MPP, or the GPER1 antagonist, G15, but not an ERα antagonist. Whole-cell recordings in PrL-PFC layer (L)5/6 pyramidal neurons revealed that E2 decreases the frequency, but not amplitude, of GABA(A)-dependent miniature IPSCs (mIPSC). As was the case with E2-potentiated reinstatement, E2 reductions in mIPSC frequency were prevented by ERβ and GPER1, but not ERα, antagonists and mimicked by ERβ, but not GPER1, agonists. Altogether, the findings suggest that E2 activates ERβ and GPER1 in the PrL-PFC to attenuate the GABA-mediated constraint of key outputs that mediate cocaine seeking.

Purpose To evaluate the effectiveness of a school-based comprehensive sexual health curriculum (FLASH) on high-school students’ sexual behavior and related outcomes. Methods A cohort of 1,597 9th and 10th grade students representing 20 schools from two regions in the U.S. (Midwest and South) were enrolled and completed the baseline survey. Following baseline, the 20 schools were randomly assigned to receive FLASH (n = 10 schools, five per region) or a knowledge-based sexual health curriculum (n = 10 schools, five per region). Follow-up surveys were administered at 3 months and 12 months after the instruction period. Results There were no statistically significant differences between conditions for the overall sample on rates of vaginal sex in the past 3 months or the rates of vaginal sex without a condom or other birth control. In supplementary subgroup analyses of students who were not sexually experienced at baseline, FLASH showed a statistically significant protective impact at the 3-month follow-up on vaginal sex without a condom or birth control (p = .04). FLASH also showed statistically significant gains in psychosocial outcomes, such as refusal and condom use self-efficacy, attitudes toward birth control and condoms, and perceived norms. Conclusions FLASH demonstrated consistent short-term and long-term impacts on key behavioral determinants. It also showed a significant impact on vaginal sex without a condom or other birth control for the subgroup of students who were not sexually experienced at baseline. Behavioral impacts were not evident for the entire study population.

Caring for terminally ill patients can be emotionally burdensome. Previous research has demonstrated that caregiving is associated with anxiety and depression. Research on caregivers of terminally ill patients is limited by retrospective studies with small samples. This study aimed to (1) describe religiosity, religious coping, and depressive symptoms in caregivers of persons with amyotrophic lateral sclerosis or advanced cancer; (2) examine the relationship between religiosity and depressive symptoms in caregivers of persons with amyotrophic lateral sclerosis or advanced cancer; (3) examine the relationship between religious coping and depressive symptoms in caregivers of persons with amyotrophic lateral sclerosis or advanced cancer. A descriptive exploratory design was used to analyze data from a larger 5-year National Institutes of Health-funded multisite randomized controlled trial (the TAILORED study). Nearly half of the caregivers screened positive for depressive symptoms, and negative religious coping was associated with higher depressive symptoms (P < .001). Spouse caregivers reported higher depressive symptoms than nonspouse caregivers. Many caregivers experienced depression, which was mitigated by positive religious coping.

In pharmacy education, we are experiencing the “new normal” after an “inflection point” along with a host of other overused phrases Yet, without doubt, there is pressing need to reconsider what was once standard operating procedure When an inflection point is viewed as opportunity, it sparks a strategic boom Indeed, the confluence of threats and opportunities caused—or revealed—by the COVID-19 pandemic is setting the stage for an acceleration of change in professional education In this paper, we investigate the motivations and approaches to accelerate needed change in pharmacy education Though prompted by the demand for rapid restructuring in response to the COVID-19 pandemic, these ideas transcend any one driver We argue that now is the time to disrupt current practices through innovation leading to new educational models and present sample solutions We consider academic, social, technological, economic, and political (ASTEP) forces driving the imperative to educational change

Purpose This study investigated deep learning models for automatic segmentation to support the development of daily online dose optimization strategies, eliminating the need for internal target volume expansions and thereby reducing toxicity events of intensity modulated radiation therapy for cervical cancer. Methods and Materials The cervix-uterus, vagina, parametrium, bladder, rectum, sigmoid, femoral heads, kidneys, spinal cord, and bowel bag were delineated on 408 computed tomography (CT) scans from patients treated at MD Anderson Cancer Center (n = 214), Polyclinique Bordeaux Nord Aquitaine (n = 30), and enrolled in a Medical Image Computing & Computer Assisted Intervention challenge (n = 3). The data were divided into 255 training, 61 validation, 62 internal test, and 30 external test CT scans. Two models were investigated: the 2-dimensional (2D) DeepLabV3+ (Google) and 3-dimensional (3D) Unet in RayStation (RaySearch Laboratories). Three intensity modulated radiation therapy plans were generated on each CT of the internal and external test sets using either the manual, 2D model, or 3D model segmentations. The dose constraints followed the External beam radiochemotherapy and MRI based adaptive BRAchytherapy in locally advanced CErvical cancer (EMBRACE) II protocol, with reduced margins of 5 and 3 mm for the target and nodal planning target volume. Geometric discrepancies between the manual and predicted contours were assessed using the Dice similarity coefficient (DSC), distance-to-agreement, and Hausdorff distance. Dosimetric discrepancies between the manual and model doses were assessed using clinical indices on the manual contours and the gamma index. Interobserver variability was assessed for the cervix-uterus, parametrium, and vagina for the definition of the primary clinical target volume (CTVT) on the external test set. Results Average DSCs across all organs were 0.67 to 0.96, 0.71 to 0.97, and 0.42 to 0.92 for the 2D model and 0.66 to 0.96, 0.70 to 0.97, and 0.37 to 0.93 for the 3D model on the validation, internal, and external test sets. Average DSCs of the CTVT were 0.88 and 0.81 for the 2D model and 0.87 and 0.82 for the 3D model on the internal and external test sets. Interobserver variability of the CTVT corresponded to a mean (range) DSC of 0.85 (0.77-0.90) on the external test set. On the internal test set, the doses from the 2D and 3D model contours provided a CTVT V42.75 Gy >98% for 98% and 91% of the CT scans, respectively. On the external test set, these percentages were increased to 100% and 93% for the 2D and 3D models, respectively. Conclusions The investigated models provided auto-segmentation of the cervix anatomy with similar performances on 2 institutional data sets and reasonable dosimetric accuracies using small planning target volume margins, paving the way to automatic online dose optimization for advanced adaptive radiation therapy strategies.

IntroductionAsian immigrants to the U.S. smoke at higher rates than U.S.-born Asians. However, few programs exist to help these immigrants quit and little is known about their real-world effectiveness. The Centers for Disease Control and Prevention funded the Asian Smokers' Quitline to serve Chinese, Korean, and Vietnamese immigrants nationwide. This study examines service utilization and outcomes from the first 7 years of the program.MethodsFrom August 2012 to July 2019, the Asian Smokers' Quitline enrolled 14,073 Chinese-, Korean-, and Vietnamese-speaking smokers. Service utilization rates and cessation outcomes were compared with those of an earlier trial (conducted 2004-2008) that demonstrated the efficacy of an Asian-language telephone counseling protocol. Data were analyzed in 2019.ResultsAsian Smokers' Quitline participants came from all 50 states and the District of Columbia. The main referral sources were Asian-language newspapers (37.2%), family and friends (16.4%), healthcare providers (11.9%), and radio (11.9%). Overall, 37.6% were uninsured, 38.8% had chronic health conditions, and 15.4% had mental health conditions. Compared with participants in the earlier trial, Quitline participants received 1 fewer counseling session (3.8 vs 4.9, p14,000 Asian-language-speaking smokers across the U.S. in its first 7 years. This quitline could serve as a model for delivering other behavioral services to geographically dispersed linguistic minority populations.

PURPOSE OF REVIEW: Healthcare provider burnout is a real phenomenon. The rates of burnout are on the rise. Burnout-associated suicide amongst physicians represents a real "public health crisis." This article discusses the drivers of burnout and offers some strategies to mitigate burnout and improve well-being. RECENT FINDINGS: Measures of burnout such as stress, micro, and macro-aggression in the workplace have a psychological impact on staff. Additionally, a measurable economic price is exacted when an organization fails to address the lack of well-being burnout represents. SUMMARY: As healthcare providers struggle to survive and deal with the complex new set of problems and obstacles that the COVID-19 pandemic, the National economic crisis, and the increasing regulatory obligations have summoned forth, professional burnout rates have risen drastically. With good leadership, developing comprehensive programs to identify, track, and treat burnout symptoms and improve well-being in the work environment can result in greater work satisfaction and save resources.

Aberrations in the stress response are associated with posttraumatic stress disorder (PTSD) symptom development, maintenance, and severity. Gamma-aminobutyric acid (GABA), the brain’s primary inhibitory neurotransmitter, may play a key role in stress recovery. In this preliminary study, we examined whether plasma GABA levels differed between women with PTSD and trauma-exposed healthy controls. Thirty participants provided plasma samples during two phases of the menstrual cycle: the early follicular phase and the mid-luteal phase. During each phase, blood was drawn after 45 min of rest, and after mild and moderately stressful psychophysiological tasks. Plasma GABA levels were measured using HPLC-mass spectrometry (LC-MS/MS). In analyses using PTSD diagnosis as a categorical group variable, women with and without a diagnosis of PTSD did not differ in plasma GABA levels (ps > .18). However, in analyses examining PTSD symptom severity as a continuous variable, there was a trend-level positive association between more severe PTSD symptoms and higher plasma GABA levels across the four blood draws (p = .06). In analyses examining DSM-IV PTSD symptom clusters separately, dysphoria symptoms were positively and significantly associated with plasma GABA levels (p = .03). Similarly, there was a trend-level positive association between avoidance cluster symptoms and plasma GABA levels (p = .06). Plasma GABA levels were not modulated by experimentally induced stress or menstrual cycle phase. Dysregulation in GABA may be a neurobiological marker and/or potential treatment target for women with PTSD symptom profiles characterized by prominent dysphoria and avoidance cluster symptoms.

Gastroschisis occurs in one of 2000 births with survival rates partially contingent on intestinal complications and time to establishing feeding. Enhancements in prenatal imaging have given better insight into postnatal outcomes. The goal of this study was to examine the gastroschisis patient population at a single children's hospital in the modern era and to use prenatal ultrasound (US) to develop new prenatal prognostic indicators.We performed a retrospective review of gastroschisis patients at a quaternary-care referral children's hospital from 2010 through 2018. We recorded demographics, prenatal data and imaging, early postnatal data, operative data, and patient outcomes. We compared patients within our cohort born with complex gastroschisis (bowel atresia/perforation) to uncomplicated gastroschisis patients. Second trimester and third trimester prenatal US were evaluated for changes in amniotic fluid level, amount of external bowel, bowel dilatation, and bowel wall edema to identify prognostic indicators of the status of the bowel at birth. For categorical variables, chi-square tests were used to assess for significance. Univariate and multivariable analyses were used to assess significance between categorical and continuous variables using medians and interquartile ranges or means.A total of 134 patients were included in the study: complex (n = 24), uncomplicated (n = 110). Compared with uncomplicated gastroschisis, complex patients required longer median days to feeding initiation (44 versus 10; P 0.001), full feeding (80 versus 23; P 0.001), length of stay (83 versus 33; P 0.001), and total parenteral nutrition at discharge (P = 0.004). Full US data were available on 81% of patients, and partial data were identified on 19%. Prenatal US analysis showed significantly more complex patients had polyhydramnios on third trimester US (23.5%-4.3%; P = 0.018). US analysis showed these additional factors to be most associated with complex gastroschisis: large amount of external bowel on third trimester US, increase in bowel edema on third trimester US, and increase in external bowel dilation on third trimester US. Multivariable logistic regression analyses revealed amniotic fluid on third trimester US to be the most significant predictor of complex gastroschisis (P = 0.01). Polyhydramnios in combination with two-thirds of the other US factors had both sensitivity and positive predictive value for predicting complex gastroschisis of 75%. Patients with two or less of these positive US factors had high specificity (96.8%) and negative predictive value (87.5%), suggesting uncomplicated disease. There were no differences in perioperative or long-term complications in the complex group when compared with the group with uncomplicated gastroschisis.Polyhydramnios on third trimester prenatal US on babies with gastroschisis can predict complex gastroschisis at birth, whereas the absence of markers on prenatal US can suggest uncomplicated disease. Complex gastroschisis is associated with increased time to feeds and length of stay.

Excess energy intake by spectators at a sporting event (i.e., a tailgate) might cause acute negative health effects. However, limited data exist regarding the effects of overeating and alcohol consumption on lipid metabolism and the potential to gain intrahepatic triacylglycerols (IHTG). We tested the hypothesis that overconsumption of food and alcohol would significantly increase both hepatic de novo lipogenesis (DNL) and IHTG.Eighteen males (mean ± SD, age: 31.4 ± 7.3 years, BMI: 32.1 ± 5.9 kg/mSubjects consumed 5087 ± 149 kcal (191 ± 25% excess of total daily energy needs including 171 ± 24 g alcohol), which increased plasma insulin, glucose, TG, and decreased NEFA (ANOVA p ≤ 0.003 for all). Both DNL and TRL-TG increased (p 0.001), while IHTG did not change in the group as a whole (p = 0.229). Individual subject data revealed remarkably differing responses for IHTG (nine increased, five decreased, one did not change). Despite maintaining equal breath alcohol levels, subjects with IHTG elevations exhibited higher DNL, consumed 90% less alcohol (p = 0.048), tended to consume more carbohydrates, and exhibited lower whole-body fat oxidation (not significant) compared to those whose IHTG was reduced.This study demonstrates that acute excess energy intake may have differing effects on an individual's DNL and IHTG, and dietary carbohydrate may influence DNL more than alcohol.

Which management actions work best to prevent or halt overfishing and to rebuild depleted populations? A comprehensive evaluation of multiple, co-occurring management actions on the sustainability status of marine populations has been lacking. Here we compiled detailed management histories for 288 assessed fisheries from around the world (accounting for 45% of those with formal stock assessments) and used hierarchical time-series analyses to estimate effects of different management interventions on trends in stock status. Rebuilding plans, applied less commonly than other management measures (implemented at some point historically for 43% of stocks), rapidly lowered fishing pressure towards target levels and emerged as the most important factor enabling overfished populations to recover. Additionally, the ratification of international fishing agreements, and harvest control rules specifying how catch limits should vary with population biomass, helped to reduce overfishing and rebuild biomass. Notably, we found that benefits of management actions are cumulative—as more are implemented, stock status improves and predicted long-term catches increase. Thus, a broad suite of management measures at local, national and international levels appears to be key to sustaining fish populations and food production. Wise management is critical to sustaining fisheries. This study finds that rebuilding plans, ratification of international agreements and harvest control rules yield strong benefits and that these are cumulative.

Diabetic dyslipidemia, a common pattern of lipid abnormalities associated with diabetes, is characterized by hyperglycemia, elevated serum levels of triglycerides and low-density lipoprotein (LDL)-cholesterol, and reduced serum levels of high-density lipoprotein (HDL)-cholesterol. These lipid abnormalities make diabetes an independent risk-factor for the development of cardiovascular disease. Two mouse models of diabetes were used in the present study: 1) streptozotocin (STZ)-induced insulin-deficient male Swiss Webster mice (a model of T1DM), and 2) male diet-induced obese (DIO) mice rendered insulin-resistant by maintenance on a high-fat diet for 30 weeks (a model of T2DM). Both models were then treated with MA-[D-Leu-4]-OB3 by oral gavage for 14 or 17 days. At the end of the test period, the mice were exsanguinated by cardiac puncture; serum was prepared from the whole blood and analyzed by ELISA for total-, HDL-, LDL/VLDL-cholesterol, and triglyceride content. In mouse models of both T1DM and T2DM, MA-[D-Leu-4]-OB3 significantly (P

Background Stereotactic body radiation therapy (SBRT) is increasingly used for patients with recurrent and or metastatic tumors. Sarcomas are generally considered not sensitive to radiotherapy and SBRT may allow for increased biological effectiveness. We report intermediate outcomes and toxicity for pediatric, adolescent, and young adult patients treated with SBRT to sites of recurrent and or metastatic sarcoma. Procedure We queried an Institutional Review Board-approved registry of patients treated with SBRT for metastases from pediatric sarcomas. Patients age 29 and below were assessed for local control, survival, and toxicity. Results Thirty-one patients with a total of 88 lesions met eligibility criteria. Median patient age was 17.9 years at treatment. Sixteen patients were treated with SBRT to >1 site of disease. The median dose was 30 Gy in 5 fractions. The median follow-up time was 7.4 months (range: 0.2 to 31.4 mo). Patients were heavily pretreated with systemic therapy. In 57 lesions with >3 months of radiographic follow-up, the 6-month and 12-month local control rates were 88.3%±4.5% and 83.4%±5.5%, respectively. Radiographic local failures were rare (6/57 in-field, 4/57 marginal). Only 1/88 treated lesions was associated with a radiation-related high-grade toxicity; late grade 3 intestinal obstruction in a re-irradiated field while on concurrent therapy (gemcitabine and docetaxel). No acute grade ≥3 toxicity was observed. Conclusions SBRT was well tolerated in the majority of patients with favorable local control outcomes. Additional studies will be required to determine the optimal SBRT dose and fractionation, treatment volume, and appropriate concurrent therapies.

A variety of crowdfunding sites, such as HomeFundIt, provide competitive options for perspective homebuyers to obtain the necessary funds required for their down payment. Although other options exi...

Background Quantitative cardiovascular magnetic resonance T1-mapping is increasingly used for myocardial tissue characterization. However, the lack of standardization limits direct comparability between centers and wider roll-out for clinical use or trials. Purpose To develop a quality assurance (QA) program assuring standardized T1 measurements for clinical use. Methods MR phantoms manufactured in 2013 were distributed, including ShMOLLI T1-mapping and reference T1 and T2 protocols. We first studied the T1 and T2 dependency on temperature and phantom aging using phantom datasets from a single site over 4 years. Based on this, we developed a multiparametric QA model, which was then applied to 78 scans from 28 other multi-national sites. Results T1 temperature sensitivity followed a second-order polynomial to baseline T1 values (R2 > 0.996). Some phantoms showed aging effects, where T1 drifted up to 49% over 40 months. The correlation model based on reference T1 and T2, developed on 1004 dedicated phantom scans, predicted ShMOLLI-T1 with high consistency (coefficient of variation 1.54%), and was robust to temperature variations and phantom aging. Using the 95% confidence interval of the correlation model residuals as the tolerance range, we analyzed 390 ShMOLLI T1-maps and confirmed accurate sequence deployment in 90%(70/78) of QA scans across 28 multiple centers, and categorized the rest with specific remedial actions. Conclusions The proposed phantom QA for T1-mapping can assure correct method implementation and protocol adherence, and is robust to temperature variation and phantom aging. This QA program circumvents the need of frequent phantom replacements, and can be readily deployed in multicenter trials., Highlights • CMR T1 correlated with reference T1 and T2; this derives the QA model for T1-map. • The proposed QA model is robust to temperature variations and phantom aging. • This QA method requires no frequent phantom replacements. • The T1-map QA program can be readily deployed in multicenter trials.

Objective Hemodialysis access-related hand dysfunction is a common clinical feature of patients with chronic kidney disease (CKD) after arteriovenous fistula (AVF) placement. The heterogeneity in symptoms and the lack of a predictive association with changes in hemodynamic alterations precipitated by the AVF suggest that other factors are involved in the mechanisms responsible for causing hand and limb dysfunction postoperatively. To the best of our knowledge, no suitable animal models have provided a platform for performing preclinical experiments designed to elucidate the biologic drivers of access-related hand dysfunction. Therefore, our objective was to develop a novel murine AVF model that could be used to study dialysis access-related limb dysfunction. Methods Male 8-week-old C57BL/6J mice (n = 15/group) were exposed to either an adenine-supplemented diet to induce CKD or casein-based chow (control). Four weeks after the diet intervention, the mice were randomly assigned to receive an iliac AVF (n = 10/group) or sham surgery (n = 5/group) on the left hindlimb. The mice were sacrificed 2 weeks after surgery, and AVF specimens and hindlimb skeletal muscles were collected for further analysis. Results Before AVF or sham surgery, the glomerular filtration rates were significantly reduced and the blood urea nitrogen levels were significantly elevated in the CKD groups compared with the controls (P < .05). AVF surgery was associated with an ∼80% patency rate among the survivors (four control and three CKD mice died postoperatively). Patency was verified by changes in hemodynamics using Doppler ultrasound imaging and altered histologic morphology. Compared with sham surgery, AVF surgery reduced ipsilateral hindlimb perfusion to the tibialis anterior muscle (20%-40%) and paw (40%-50%), which remained stable until euthanasia. Analysis of gastrocnemius muscle mitochondrial respiratory function uncovered a significant decrease (40%-50%) in mitochondrial function in the AVF mice. No changes were found in the muscle mass, myofiber cross-sectional area, or centrally nucleated fiber proportion in the extensor digitorum longus and soleus muscles between the sham and AVF mice. Conclusions The results from the present study have demonstrated that iliac AVF formation is a practical animal model that facilitates examination of hemodialysis access-related limb dysfunction. AVF surgery produced the expected hemodynamic changes, and evaluation of the limb muscle revealed a substantial mitochondrial impairment that was present without changes in muscle size., Clinical Relevance Autogenous arteriovenous fistula creation remains the preferred vascular access option for patients requiring chronic hemodialysis therapy. However, access-related hand dysfunction (ARHD) remains highly prevalent in this population. Clinical management of the disability is difficult because of symptom heterogeneity and limited treatment options. Additionally, the current preclinical models do not adequately replicate the pathologic condition to allow for investigation of underlying mechanisms and to test new therapies. Therefore, medical progress has been marginal. In the present study, we have outlined a novel murine model to study ARHD and described the associated mitochondrial impairments, providing a unique tool for preclinical therapeutic development., Visual abstract

Along the U.S. West Coast, sustainable manage­ment has rebuilt fish stocks, providing an oppor­tunity to supply nutrient-rich food to adjacent coastal communities where food insecurity and diet-based diseases are common. However, the market has not successfully supplied locally sourced seafood to nutritionally vulnerable people. Rather, a few organizations make this connection on a limited scale. We used a “positive deviant” approach to learn how these organizations’ efforts developed, how they overcame challenges, and what conditions enabled their interventions. We found that organizations in these positive deviant cases provided fish from a wide variety of species and sources, and distributed them through different channels to a diversity of end consumers. A key factor facilitating success was the ability to negotiate a price point that was both profitable and reasonable for organizations supplying nutritionally vulnerable or low-income consumers. Further­more, securing access to grants overcame initial costs of establishing new supply channels. All cases highlighted the importance of individual cham­pi­ons who encouraged development and cultural connections between the initiative and the nearby community. Organizations overcame key chal­lenges by establishing regulations governing these new channels and either using partnerships or vertically integrating to reduce costs associated with processing and transport. Oftentimes training and education were also critical to instruct workers on how to process unfamiliar fish and to increase consumer awareness of local fish and how to pre­pare them. These lessons illuminate pathways to improve the contribution of local seafood to the healthy food system.