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Concerns have been expressed about a worldwide retreat from liberal democracy and a turn toward more authoritarian forms of government. Along with that concern has come surprise: when the cold war ended, it was widely believed that a new historical era was dawning during which alternatives to Western liberalism would wither away. Influential psychological theories also assume that freedom and autonomy are powerful human needs—needs that are thwarted by dictatorships. However, a number of theoretical perspectives and programs of research in psychology lead to the conclusion that in certain circumstances, turns toward authoritarian forms of government and restrictive societies are not only explicable, but also predictable. Fromm's analysis of why people might want to escape from freedom, Baumeister's work on escape-from-self mechanisms, and Schwartz's review of the literature on choice overload all provide ways of understanding why in turbulent times, members of free countries might intentionally seek out—and perhaps even ecstatically embrace—authoritarian forms of government.

OBJECTIVES: This study aimed to test the effect of a 30-minute nap versus a 2-hour nap opportunity taken during a simulated night shift on performance, fatigue, sleepiness, mood, and sleep at the end of shift and during post-night shift recovery. METHODS: We conducted a randomized crossover trial of three nap conditions (30-minute, 2-hour, and no-nap) during 12-hour simulated night shifts. We tested for differences in performance, fatigue, sleepiness, mood, and sleep during in-lab and at-home recovery. Performance was measured with the Brief Psychomotor Vigilance Test (PVT-B). Subjective ratings were assessed with single-item surveys. RESULTS: Twenty-eight individuals consented to participate [mean age 24.4 (standard deviation 7.2) years; 53.6% female; 85.7% Emergency Medical Services clinicians]. PVT-B false starts at the end of the 12-hour night shift (at 07:00 hours) and at the start of in-lab recovery (08:00 hours) were lower following the 2-hour nap versus other conditions (P0.05). Sleepiness, fatigue, and some mood states were lower at most hourly assessments during the in-lab recovery period following the 2-hour nap condition compared to the other conditions. Sleep during recovery did not differ by duration of night shift nap. CONCLUSIONS: A 2-hour nap opportunity versus a 30-minute or no-nap opportunity is beneficial for performance, alertness, and mood post-night shift. No differences were detected in sleep during recovery.

PurposeDescribe real-life practice and outcomes in the management of post-stroke upper limb spasticity with botulinum toxin A (BoNT-A) in Asian settings.MethodsSubgroup analysis of a prospective, observational study (NCT01020500) of adult patients (≥18 years) with post-stroke upper limb spasticity presenting for routine spasticity management, including treatment with BoNT-A. The primary outcome was goal attainment as assessed using goal-attainment scaling (GAS). Patients baseline clinical characteristics and BoNT-A injection parameters are also described.ResultsOverall, 51 patients from Asia were enrolled. Rates of comorbid cognitive and emotional problems were relatively low. Patients tended to have more severe distal limb spasticity and to prioritize active over passive function goals. Most (94.1%) patients in the subgroup were treated with abobotulinumtoxinA. For these patients, the median total dose was 500 units, and the most frequently injected muscles were the biceps brachii (83.3%), flexor carpi radialis (72.9%), and flexor digitorum profundus (66.7%). Overall, 74.5% achieved their primary goal and the mean GAS T score after one treatment cycle was 56.0 ± 13.0, with a change from baseline of 20.9 ± 14.3 (p

Abstract Many polymer-based medical devices are sterilized by gamma irradiation. To reduce the use of cobalt-60 gamma-ray sources, transition from gamma ray to alternative irradiation technologies was proposed, namely electron beam (e-beam) and X-ray. A major impediment for such a transition is the knowledge gap in material compatibility with the different radiation sources. In this study, multi-layer films consisting of ethylene vinyl acetate (EVA) and ethylene vinyl alcohol (EVOH) components were irradiated to target doses of 30, 45, and 60 kGy by gamma-ray, e-beam, and X-ray sources. Effects of irradiation were evaluated on 12 material properties, and statistical comparisons between gamma irradiation and alternative technologies were conducted using the two one-sided t-test (or “equivalence test”) and classic t-test. Melting temperature and UV absorbance below 300 nm showed dose dependencies, while other investigated properties such as discoloration and mechanical durability did not change with dose up to 60 kGy. Based on these results, there is no material compatibility issue associated with the transition from gamma to e-beam or to X-ray as source of sterilization radiation of the studied multi-layer film.

In the polymeric material industry, thermosets and related composites have played a substantial role in the production of rubber and plastics. One important subset of these is thermoset composites with carbon reinforcement. The incorporation of carbon fillers and fibers gives polymeric materials improved electrical and mechanical properties, among other benefits. However, the covalently crosslinked network of thermosets presents significant challenges for recycling and reprocessing because of its intractable nature. The introduction of vitrimer materials opens a new avenue to produce biodegradable and recyclable thermosets. Carbon-reinforced vitrimer composites are pursued for high-performance, long-lasting materials with attractive physical properties, the ability to be recycled and processed, and other features that respond uniquely to stimuli. The development of carbon-reinforced vitrimer composites over the last few years is summarized in this article. First, an overview of vitrimers and the methods used to prepare carbon fiber-reinforced vitrimer composites is provided. Because of the vitrimer nature of such composites, reprocessing, healing, and recycling are viable ways to greatly extend their service life; these approaches are thoroughly explained and summarized. The conclusion is our prediction for developing carbon-based vitrimer composites.

Abstract The protein kinase Mechanistic Target of Rapamycin (mTOR) in Complex 1 (mTORC1) is regulated in part by the Ras‐related GTP‐binding proteins (Rag GTPases). Rag GTPases form a heterodimeric complex consisting of either RagA or RagB associated with either RagC or RagD and act to localize mTORC1 to the lysosomal membrane. Until recently, RagA and RagB were thought to be functionally redundant, as were RagC and RagD. However, recent research suggests that the various isoforms differentially activate mTORC1. Here, the mRNA expression and protein abundance of the Rag GTPases was compared across male rat skeletal muscle, heart, liver, kidney, and brain. Whereas mRNA expression of RagA was higher than RagB in nearly all tissues studied, RagB protein abundance was higher than RagA in all tissues besides skeletal muscle. RagC mRNA expression was more abundant or equal to RagD mRNA, and RagD protein was more abundant than RagC protein in all tissues. Moreover, the proportion of RagB in the short isoform was greater than the long in liver, whereas the opposite was true in brain. These results serve to further elucidate Rag GTPase expression and offer potential explanations for the differential responses to amino acids that are observed in different tissues.

Abstract Bioconversion using insects is a promising strategy to convert organic waste (catering leftovers, harvest waste, food processing byproducts, etc.) into biomass that can be used for multiple applications, turned into high added-value products, and address environmental, societal and economic concerns. Due to its ability to feed on a tremendous variety of organic wastes, the black soldier fly (Hermetia illucens) has recently emerged as a promising insect for bioconversion of organic wastes on an industrial scale. A growing number of studies have highlighted the pivotal role of the gut microbiota in the performance and health of this insect species. This review aims to provide a critical overview of current knowledge regarding the functional diversity of the gut microbiota of H. illucens, highlighting its importance for bioconversion, food safety and the development of new biotechnological tools. After providing an overview of the different strategies that have been used to outline the microbial communities of H. illucens, we discuss the diversity of these gut microbes and the beneficial services they can provide to their insect host. Emphasis is placed on technical strategies and aspects of host biology that require special attention in the near future of research. We also argue that the singular digestive capabilities and complex gut microbiota of H. illucens make this insect species a valuable model for addressing fundamental questions regarding the interactions that insects have evolved with microorganisms. By proposing new avenues of research, this review aims to stimulate research on the microbiota of a promising insect to address the challenges of bioconversion, but also fundamental questions regarding bacterial symbiosis in insects.

Background: Magnetic resonance imaging (MRI) underestimation of prostate cancer extent complicates the definition of focal treatment margins. Objective: To validate focal treatment margins produced by an artificial intelligence (AI) model. Design, setting, and participants: Testing was conducted retrospectively in an independent dataset of 50 consecutive patients who had radical prostatectomy for intermediate-risk cancer. An AI deep learning model incorporated multimodal imaging and biopsy data to produce three-dimensional cancer estimation maps and margins. AI margins were compared with conventional MRI regions of interest (ROIs), 10-mm margins around ROIs, and hemigland margins. The AI model also furnished predictions of negative surgical margin probability, which were assessed for accuracy. Outcome measurements and statistical analysis: Comparing AI with conventional margins, sensitivity was evaluated using Wilcoxon signed-rank tests and negative margin rates using chi-square tests. Predicted versus observed negative margin probability was assessed using linear regression. Clinically significant prostate cancer (International Society of Urological Pathology grade ≥2) delineated on whole-mount histopathology served as ground truth. Results and limitations: The mean sensitivity for cancer-bearing voxels was higher for AI margins (97%) than for conventional ROIs (37%, p

This review article critically examines the pivotal role of chromatin organization in gene regulation, cellular differentiation, disease progression and aging. It explores the dynamic between the euchromatin and heterochromatin, coded by a complex array of histone modifications that orchestrate essential cellular processes. We discuss the pathological impacts of chromatin state misregulation, particularly in cancer and accelerated aging conditions such as progeroid syndromes, and highlight the innovative role of epigenetic therapies and artificial intelligence (AI) in comprehending and harnessing the histone code toward personalized medicine. In the context of aging, this review explores the use of AI and advanced machine learning (ML) algorithms to parse vast biological datasets, leading to the development of predictive models for epigenetic modifications and providing a framework for understanding complex regulatory mechanisms, such as those governing cell identity genes. It supports innovative platforms like CEFCIG for high-accuracy predictions and tools like GridGO for tailored ChIP-Seq analysis, which are vital for deciphering the epigenetic landscape. The review also casts a vision on the prospects of AI and ML in oncology, particularly in the personalization of cancer therapy, including early diagnostics and treatment optimization for diseases like head and neck and colorectal cancers by harnessing computational methods, AI advancements and integrated clinical data for a transformative impact on healthcare outcomes.

Abstract Background Partial gland ablation (PGA) is a new option for treatment of prostate cancer (PCa). Cryotherapy, an early method of PGA, has had favorable evaluations, but few studies have employed a strict protocol using biopsy endpoints in men with clinically significant prostate cancer (csPCa). Methods 143 men with unilateral csPCa were enrolled in a prospective, observational trial of outpatient PGA‐cryotherapy. Treatment was a 2‐cycle freeze of the affected prostate part. Participants were evaluated with MRI‐guided biopsy (MRGB) at baseline and at 6 months and 18 months after treatment. Absence of csPCa upon MRGB was the primary endpoint; quality‐of‐life at baseline and at 6 months after treatment was assessed by EPIC‐CP questionnaires in the domains of urinary and sexual function. Results Of the 143 participants, 136 (95%) completed MRGB at 6 months after treatment. In 103/136 (76%), the biopsy revealed no csPCa. Of the 103, 71 subsequently had an 18‐month comprehensive biopsy; of the 71 with 18‐month biopsies, 46 (65%) were found to have no csPCa. MRI lesions became undetectable in 96/130 (74%); declines in median serum PSA levels (6.9 to 2.5 ng/mL), PSA density (0.15 to 0.07), and prostate volume (42 to 34cc) were observed (all p

The majority of epigenetic epidemiology studies to date have generated genome-wide profiles from bulk tissues (e.g., whole blood) however these are vulnerable to confounding from variation in cellular composition. Proxies for cellular composition can be mathematically derived from the bulk tissue profiles using a deconvolution algorithm; however, there is no method to assess the validity of these estimates for a dataset where the true cellular proportions are unknown. In this study, we describe, validate and characterize a sample level accuracy metric for derived cellular heterogeneity variables. The CETYGO score captures the deviation between a sample’s DNA methylation profile and its expected profile given the estimated cellular proportions and cell type reference profiles. We demonstrate that the CETYGO score consistently distinguishes inaccurate and incomplete deconvolutions when applied to reconstructed whole blood profiles. By applying our novel metric to >6,300 empirical whole blood profiles, we find that estimating accurate cellular composition is influenced by both technical and biological variation. In particular, we show that when using a common reference panel for whole blood, less accurate estimates are generated for females, neonates, older individuals and smokers. Our results highlight the utility of a metric to assess the accuracy of cellular deconvolution, and describe how it can enhance studies of DNA methylation that are reliant on statistical proxies for cellular heterogeneity. To facilitate incorporating our methodology into existing pipelines, we have made it freely available as an R package (https://github.com/ds420/CETYGO).

Abstract The increase in bedrock channel width and the decline in bedrock channel slope with increasing drainage area are fundamental characteristics of mountainous landscapes. Compared with slope, little is known about controls on steady‐state bedrock channel width. We model steady‐state bedrock channel width by iteratively solving models for bed and bank erosion by impacting bedload, using measurable physical parameters, including uplift rate, water discharge, sediment supply, grain size, rock strength, and bank angle. The results indicate that width is largely controlled by sediment flux, rather than water discharge. The commonly used width‐discharge scaling relation is an artifact of the covariance of sediment flux and water discharge. Scaling up from cross‐section to drainage basin scales, our model reproduces the width‐drainage area scaling relation and suggests that the scaling exponent is largely controlled by the downstream change in the fraction of total sediment supply transported as bedload.

Focal therapy of prostate cancer (PCa) is currently of great interest, but a metric of success. other than biopsy, is not yet available. In a patient with a repeatedly negative MRI and negative systematic biopsies, a scan employing the radioisotope 68Ga-PSMA-11 PET/CT identified a PSMA-avid hotspot in the prostate. PSMA-guided biopsy confirmed the diagnosis of a clinically-significant PCa. Following ablation of the lesion with high-intensity focused ultrasound (HIFU), the PSMA-avid lesion disappeared and targeted biopsy confirmed a fibrotic scar with no residual cancer. PSMA imaging may have a role in guiding diagnosis, focal ablation, and follow-up of men with PCa.

Objective: Quail production is ranked as an important alternative animal protein source in Cameroon. One of the main constraints of this production is the quality of feed, which lacks pro¬tein that is regularly supplied by fish meal. To avoid disagreements due to the constant shortage of fish meal, alternative protein sources are needed, and among them are crickets (Acheta domes¬ticus). The goal of this study was to find out how well Japanese quails could be raised if fish meal was replaced with cricket meal. Materials and Methods: A total of 192, 4-week-old quails were divided into 12 similar sets of 8 females and 8 males. The Four experimental diets (T00, T15, T30, and T45) were all formulated based on the level (0%, 15%, 30%, and 45%, respectively) of fish meal substitution with cricket meal in the basal diet (crude protein: 20.18% and ME: 3,013.78 kcal/kg) and randomly assigned to three sets in a completely randomized design consisting of four treatments each repeated three times. Growth, carcass, and some reproduction parameters were collected. The data were analyzed using one-way analysis of variance and the Duncan test, with a significance level of 5%. Results: Cricket meal diets increased body weight in males (204.32 ± 5.69 gm for T45) and regard¬less of the sex (226.72 ± 29.45 gm for T30) compared to 184.17 ± 3.11 gm and 214.55 ± 32.77 gm for the control group, respectively. In females, substitution at 30% increased body weight (253.80 ± 6.48 gm), while 45% induced a reduction (216.67 ± 6.49 gm) when compared to the control group value (244.92 ± 6.07 gm). Carcass yield and the proportion of different parts were not significantly affected by the experimental diets. Liver proportions were significantly higher at 15% and 35% cricket meal incorporation compared to 45%. First songs and egg laying were recorded at 7 weeks with T15, which also led to improved egg laying performance compared to the other treatments. Ovaries were poorly developed in the T45 females compared to the other treatments. Conclusions: Cricket flour might be a good candidate as a locally available protein source to sub¬stitute fish meal in the Japanese quail's diet at the finisher and reproductive stages, and the level of 30% seems to be more efficient. [J Adv Vet Anim Res 2022; 9(2.000): 310-322]

The COVID-19 pandemic has underscored the lack of resources and oversight that hinders medical care for incarcerated people in the United States. The US Supreme Court has held that “deliberate indifference” to “serious medical needs” violates the Constitution. But this legal standard does not assure the consistent provision of health care services. This leads the United States to fall behind European nations that define universal standards of care grounded in principles of human rights and the ideal of equivalence that incarcerated and non-incarcerated people are entitled to the same health care. In this paper, we review a diverse legal and policy literature and undertake a conceptual analysis of policy issues related to the standard of care in correctional health; we then describe a framework for moving incrementally closer toward a universal standard. The expansion of Medicaid funding and benefits to corrections facilities, alongside a system of comprehensive and enforceable external oversight, would meaningfully raise the standard of care. Although these changes on their own will not resolve all of the thorny health problems posed by mass incarceration, they present a tangible opportunity to move closer to the human rights ideal.

Consumption of a diet rich in saturated fatty acids and carbohydrates contributes to the accumulation of fat in the liver and development of non-alcoholic steatohepatitis (NASH). Herein we investigated the hypothesis that short-term consumption of a high fat/sucrose Western diet (WD) alters the genomic and translatomic profile of the liver in association with changes in signaling through the protein kinase mTORC1, and that such alterations contribute to development of NAFLD. The results identify a plethora of mRNAs that exhibit altered expression and/or translation in the liver of rats consuming a WD compared to a CD. In particular, consumption of a WD altered the abundance and ribosome association of mRNAs involved in lipid and fatty acid metabolism, as well as those involved in glucose metabolism and insulin signaling. Hepatic mTORC1 signaling was enhanced when rats were fasted overnight and then refed in the morning; however, this effect was blunted in rats fed a WD as compared to a CD. Despite similar plasma insulin concentrations, fatty acid content was elevated in the liver of rats fed a WD as compared to a CD. We found that feeding had a significant positive effect on ribosome occupancy of 49 mRNAs associated with hepatic steatosis (e.g., LIPE, LPL), but this effect was blunted in the liver of rats fed a WD. In many cases, changes in ribosome association were independent of alterations in mRNA abundance, suggesting a critical role for diet-induced changes in mRNA translation in the expression of proteins encoded by those mRNAs. Overall, the findings demonstrate that short-term consumption of a WD impacts hepatic gene expression by altering the abundance of many mRNAs, but also causes wide-spread variation in mRNA translation that potentially contribute to development of hepatic steatosis.

This is an editorial on low energy nuclear astrophysics and sterile neutrinos as dark matter. First, the symmetric cosmic microwave background radiation and the the symmetric evolution of the Universe are editorialized. Then, low energy astrophysics with the evolution of the Sun, supernovae, and the Galaxy’s rotation are editorialized. In the final section, sterile neutrinos as dark matter is editorialized.

Abstract Background Attacks on health care in armed conflict, including those on health workers, facilities, patients and transports, represent serious violations of human rights and international humanitarian law. Information about these incidents and their characteristics are available in myriad forms: as published research or commentary, investigative reports, and within online data collection initiatives. We review the research on attacks on health to understand what data they rely on, what subjects they cover and what gaps exist in order to develop a research agenda going forward. Methods and findings This study utilizes a systematic review of peer-reviewed to identify and understand relevant data about attacks on health in situations of conflict. We identified 1479 papers published before January 1, 2020 using systematic and hand-searching and chose 45 articles for review that matched our inclusion criteria. We extracted data on geographical and conflict foci, methodology, objectives and major themes. Among the included articles, 26 focused on assessment of evidence of attacks, 15 on analyzing their impacts, three on the legal and human rights principles and one on the methods of documentation. We analyzed article data to answer questions about where and when attacks occur and are investigated, what types of attacks occur, who is perpetrating them, and how and why they are studied. We synthesized cross-cutting themes on the impacts of these attacks, mitigation efforts, and gaps in existing data. Conclusion Recognizing limitations in the review, we find there have been comparatively few studies over the past four decades but the literature is growing. To deepen the discussions of the scope of attacks and to enable cross-context comparisons, documentation of attacks on health must be enhanced to make the data more consistent, more thorough, more accessible, include diverse perspectives, and clarify taxonomy. As the research on attacks on health expands, practical questions on how the data is utilized for advocacy, protection and accountability must be prioritized.

Summary: Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. Findings: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17–1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81–1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92–1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82–1·15]; p=0·69), smoking status (interaction 1·68 [0·41–6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89–4·82; p=0·025) were not associated with cardiovascular risk. Interpretation: We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. Funding: National Institute for Health Research Health Technology Assessment Programme.

Gamma-ray irradiation, using the cobalt-60 isotope, is the most common radiation modality used for medical device and biopharmaceutical products sterilization. Although X-ray and electron-beam (e-beam) sterilization technologies are mature and have been in use for decades, impediments remain to switching to these sterilization modalities because of lack of data on the resulting radiation effects for the associated polymers, as well as a lack of education for manufacturers and regulators on the viability of these sterilization alternatives. For this study, the compatibility of ethylene vinyl acetate (EVA) multilayer films with different ionizing radiation sterilization (X-ray, e-beam, and gamma irradiation) is determined by measuring chemical and physical film properties using high performance liquid chromatography, differential scanning calorimetry, Fourier-Transform InfraRed spectroscopy (FTIR), surface energy measurement, and electron spin resonance techniques. The results indicate that the three irradiation modalities induce no differences in thermal properties in the investigated dose range. Gamma and X-Ray irradiations generate the same level of reactive species in the EVA multilayer film, whereas e-beam generates a reduced quantity of reactive species.

Abstract Background There is an emerging body of evidence that links exposure to shift work to cardiovascular disease (CVD). The risk of coronary events, such as myocardial infarction, is greater among night shift workers compared to day workers. There is reason to believe that repeated exposure to shift work, especially night shift work, creates alterations in normal circadian patterns of blood pressure (BP) and heart rate variability (HRV) and that these alterations contribute to increased risk of CVD. Recent data suggest that allowing shift workers to nap during night shifts may help to normalize BP and HRV patterns and, over time, reduce the risk of CVD. The risk of CVD related to shift work is elevated for emergency medical services (EMS) shift workers due in part to long-duration shifts, frequent use of night shifts, and a high prevalence of multiple jobs. Methods We will use a randomized crossover trial study design with three study conditions. The targeted population is comprised of EMS clinician shift workers, and our goal enrollment is 35 total participants with an estimated 10 of the 35 enrolled not completing the study protocol or classified as lost to attrition. All three conditions will involve continuous monitoring over 72 h and will begin with a 36-h at-home period, followed by 24 total hours in the lab (including a 12-h simulated night shift), ending with 12 h at home. The key difference between the three conditions is the intra-shift nap. Condition 1 will involve a simulated 12-h night shift with total sleep deprivation. Condition 2 will involve a simulated 12-h night shift and a 30-min nap opportunity. Condition 3 will involve a simulated 12-h night shift with a 2-h nap opportunity. Our primary outcomes of interest include blunted BP dipping and reduced HRV as measured by the standard deviation of the inter-beat intervals of normal sinus beats. Non-dipping status will be defined as sleep hours BP dip of less than 10%. Discussion Our study will address two indicators of cardiovascular health and determine if shorter or longer duration naps during night shifts have a clinically meaningful impact. Trial registration ClinicalTrials.gov NCT04469803 . Registered on 9 July 2020

Summary: Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for PC, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9 × 10−7 and GAB2, p = 2.0 × 10−6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 0.94–1.36); whereas decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04–1.50). These results suggest that germline genetics may help inform and individualize the decision of AS—or the intensity of monitoring on AS—versus treatment for the initial management of patients with low-risk PC.

Abstract Background When a child undergoes hematopoietic cell transplantation (HCT), the impact extends to the entire family, including siblings. Assessment of the quality of life (QoL) of siblings is challenged by their general lack of availability for regular assessment by clinical providers. Thus, the use of parent proxy reporting may be useful. Our aim was to describe the QoL of siblings of HCT survivors, as reported by their parents, as well as to identify parent and family factors associated with lower sibling QoL. Methods A cross-sectional study was utilized to assess parent-reported QoL of the HCT recipient’s sibling (Short Form (SF)-10 Health Survey for Children and the Pediatric Symptom Checklist (PSC)-17). Parent QoL was assessed using the SF-12. Multivariable linear regression was used to explore hypothesized predictors of sibling QoL, including parent QoL, family impact/function (Impact on Family Scale, Family Adaptability and Cohesion Evaluation Scales, IV, and a question asking about financial problems) while adjusting for demographic and HCT characteristics. Results Ninety-seven siblings (55% males) with a mean age of 12 years (standard deviation [SD] 4 years) were assessed, representing HCT survivors, who were an average of 5 years (SD 4 years) post-HCT. Neither sibling psychosocial (mean 49.84, SD 10.70, p = 0.87) nor physical health scores (mean 51.54, SD 8.42, p = 0.08) differed from norms. Parent proxies reported behavioral/emotional problems (PSC-17 total score > 15) in 24% of siblings. While parental ratings of their own physical health (SF-12 were higher than norms (mean 53.04, SD 8.17, p = 0.0005), mental health scores were lower (mean 45.48, SD 10.45, p

Background Hundreds of thousands of people have been killed during the Syrian civil war and millions more displaced along with an unconscionable amount of destroyed civilian infrastructure.Methods We aggregate attack data from Airwars, Physicians for Human Rights and the Safeguarding Health in Conflict Coalition/Insecurity Insight to provide a summary of attacks against civilian infrastructure during the years 2012–2018. Specifically, we explore relationships between date of attack, governorate, perpetrator and weapon for 2689 attacks against five civilian infrastructure classes: healthcare, private, public, school and unknown. Multiple correspondence analysis (MCA) via squared cosine distance, k-means clustering of the MCA row coordinates, binomial lasso classification and Cramer’s V coefficients are used to produce and investigate these correlations.Results Frequencies and proportions of attacks against the civilian infrastructure classes by year, governorate, perpetrator and weapon are presented. MCA results identify variation along the first two dimensions for the variables year, governorate, perpetrator and healthcare infrastructure in four topics of interest: (1) Syrian government attacks against healthcare infrastructure, (2) US-led Coalition offensives in Raqqa in 2017, (3) Russian violence in Aleppo in 2016 and (4) airstrikes on non-healthcare infrastructure. These topics of interest are supported by results of the k-means clustering, binomial lasso classification and Cramer’s V coefficients.Discussion Findings suggest that violence against healthcare infrastructure correlates strongly with specific perpetrators. We hope that the results of this study provide researchers with valuable data and insights that can be used in future analyses to better understand the Syrian conflict.

We investigated the effects of mirror visual feedback (MVF), with reference to using a glass wall or a covered mirror, on the reduction of spatial neglect for patients with stroke. A total of 21 subacute patients with left spatial neglect after right-hemispheric stroke were randomly assigned to 3 groups: MVF, sham 1 (viewing the hemiparetic arm through the transparent glass during bilateral arm movement) and sham 2 (using a covered mirror). The 3-week treatment program for all groups consisted of 12 sessions of movement tasks for the hemiparetic arm graded according to the severity of arm impairments. Blinded assessments were administered at pre/post and a three-week follow-up. The results showed that there was no significant advantage for MVF than sham 1; however, MVF was more beneficial than sham 2, as shown by the line crossing (p = 0.022). Improvement in discriminating the left-gap figures on the left and right side of the page in the Gap Detection Test was greater in MVF than using the covered mirror (p = 0.013; p = 0.010), showing a slight advantage of MVF in alleviating allocentric symptoms. Our study confirms that MVF was superior to using a covered mirror as a method for reducing spatial neglect and in alleviating its allocentric symptoms, but no significant advantage over bilateral arm movement through transparent glass was found. Further research in comparing their therapeutic effects is warranted.

We review the cosmic microwave background (CMBR) estimate of ordinary matter, dark matter and dark energy in the universe. Then, we review the cosmological electroweak (EWPT) and quantum chromodynamics (QCDPT) phase transitions. During both the EWPT and QCDPT, bubbles form and collide, producing magnetic fields. We review dark matter produced during the EWPT and the estimate of dark matter via galaxy rotation.

Bullying has been recognized as a phenomenon that detrimentally affects the lives of many, and researchers continue to explore its various influences and correlates. We examined the relationship between the global belief in a just world (BJW; a person’s tendency to believe that life is fair and people get what they deserve) and reactions to bullying. Although BJW is undergirded by a justice motive, and although previous research found that global BJW is associated with more negative explicit attitudes toward bullying in the abstract, we hypothesized that strong global BJW beliefs would instead predict more tolerance and less condemnation when participants were presented with specific behaviors that could be construed as bullying. In two vignette-based experiments, global BJW (but not personal BJW), predicted less negative reactions to bullying, and did so regardless of whether the behavior was explicitly labeled as being a case of bullying. Implications of these results are discussed.

Event-related desynchronization (ERD), as a proxy for mirror neuron activity, has been used as a neurophysiological marker for motor execution after mirror visual feedback (MVF). Using EEG, this study investigated ERD upon the immediate effects of single-session MVF in unimanual arm movements compared with the ERD effects occurring without a mirror, in two groups: stroke patients with left hemiplegia and their healthy counterparts. During EEG recordings, each group performed one session of mirror therapy training in three task conditions: with a mirror, with no mirror, and with a covered mirror. An asymmetry index was calculated from the subtraction of the event-related spectrum perturbations between the C3 and C4 electrodes located over the sensorimotor cortices contralateral and ipsilateral to the moved arm. Results of the effect of task versus group in contralateral and ipsilateral motor areas showed that there was a significant effect of task condition at the contralateral motor area in the high beta band (17–35 Hz) at C3. High beta ERD showed that the suppression was greater over the contralateral hemisphere than it was over the ipsilateral hemisphere in both study groups. The magnitude of low beta (12–16 Hz) ERD in patients with stroke was more suppressed in contralesional C3 under the no mirror compared to that of the covered mirror and similarly more suppressed in ipsilesional C4 ERD under the no mirror compared to that of the mirror condition. The correlation analysis revealed that the magnitude of ERSP power correlated significantly with arm severity in the low and high beta bands in patients with stroke, and a higher asymmetry index in the low beta band was associated with higher arm functioning under the no-mirror condition. There was a shift in sensorimotor ERD toward the contralateral hemisphere as induced by MVF accompanying unimanual movement in both stroke patients and healthy controls. The use of ERD in the low beta band as a neurophysiological marker to indicate the relationships between the amount of MVF-induced ERD attenuation and motor severity, and the outcome indicator for improving stroke patients’ neuroplasticity in clinical trials using MVF are warranted to be explored in the future.

Abstract Background Humanitarian health care organizations and health workers working in contexts of armed or violent conflict experience challenges in fulfilling ethical obligations and humanitarian principles. To better understand the types of challenges experienced in these contexts, we conducted a systematic literature review. Methods A broad search strategy was developed for English language publications available in PubMed, Ovid/EMBASE, and Scopus. The search relied upon three key concept blocks: conflict settings, humanitarian or relief organizations, and non-clinical or non-military ethics. To be included, publications had to (1) refer implicitly or explicitly to ethics and/or humanitarian principle(s), (2) relate to non-military relief work in active conflict or conflict-affected settings, (3) relate to organizational mission and/or delivery of services, and (4) relate to events after 1900. Records were qualitatively analyzed using an emergent thematic analysis approach that mapped challenges onto recognized ethical obligations and humanitarian principles. Results A total of 66 out of a possible 2077 retrieved records met inclusion criteria. The most frequently noted ethical challenges for organizations working in conflict settings were (1) providing the highest attainable quality of care, (2) protecting workers, and (3) minimizing unintended harms. The humanitarian principle most frequently noted as challenging to uphold was neutrality (the duty that humanitarian actors must not take sides in a conflict). Ethical challenges and humanitarian principles were commonly co-coded. For example, the challenge of providing the highest attainable quality of care frequently intersected with the humanitarian principle of humanity. Conclusions By categorizing the types of ethical challenges experienced by humanitarian care organizations, this review can help organizations anticipate issues that might arise in conflict settings. The identified relationships between ethical challenges and humanitarian principles suggests that frameworks and guidance for ethical decision-making, if adapted for conflict settings, could support organizational capacity to fulfill ethical and humanitarian commitments.

Abstract Background There has been a steady increase in the number of studies aiming to identify DNA methylation differences associated with complex phenotypes. Many of the challenges of epigenetic epidemiology regarding study design and interpretation have been discussed in detail, however there are analytical concerns that are outstanding and require further exploration. In this study we seek to address three analytical issues. First, we quantify the multiple testing burden and propose a standard statistical significance threshold for identifying DNA methylation sites that are associated with an outcome. Second, we establish whether linear regression, the chosen statistical tool for the majority of studies, is appropriate and whether it is biased by the underlying distribution of DNA methylation data. Finally, we assess the sample size required for adequately powered DNA methylation association studies. Results We quantified DNA methylation in the Understanding Society cohort (n = 1175), a large population based study, using the Illumina EPIC array to assess the statistical properties of DNA methylation association analyses. By simulating null DNA methylation studies, we generated the distribution of p-values expected by chance and calculated the 5% family-wise error for EPIC array studies to be 9 × 10− 8. Next, we tested whether the assumptions of linear regression are violated by DNA methylation data and found that the majority of sites do not satisfy the assumption of normal residuals. Nevertheless, we found no evidence that this bias influences analyses by increasing the likelihood of affected sites to be false positives. Finally, we performed power calculations for EPIC based DNA methylation studies, demonstrating that existing studies with data on ~ 1000 samples are adequately powered to detect small differences at the majority of sites. Conclusion We propose that a significance threshold of P

Abstract Most variants associated with complex phenotypes in genome-wide association studies (GWAS) do not directly index coding changes affecting protein structure. Instead they are hypothesized to influence gene regulation, with common variants associated with disease being enriched in regulatory domains including enhancers and regions of open chromatin. There is interest, therefore, in using epigenomic annotation data to identify the specific regulatory mechanisms involved and prioritize risk variants. We quantified lysine H3K27 acetylation (H3K27ac) - a robust mark of active enhancers and promoters that is strongly correlated with gene expression and transcription factor binding – across the genome in entorhinal cortex samples using chromatin immunoprecipitation followed by highly parallel sequencing (ChIP-seq). H3K27ac peaks were called using high quality reads combined across all samples and formed the basis of partitioned heritability analysis using LD score regression along with publicly-available GWAS results for seven psychiatric and neurodegenerative traits. Heritability for all seven brain traits was significantly enriched in these H3K27ac peaks (enrichment ranging from 1.09–2.13) compared to regions of the genome containing other active regulatory and functional elements across multiple cell types and tissues. The strongest enrichments were for amyotrophic lateral sclerosis (ALS) (enrichment = 2.19; 95% CI = 2.12–2.27), autism (enrichment = 2.11; 95% CI = 2.05–2.16) and major depressive disorder (enrichment = 2.04; 95% CI = 1.92–2.16). Much lower enrichments were observed for 14 non-brain disorders, although we identified enrichment in cortical H3K27ac domains for body mass index (enrichment = 1.16; 95% CI = 1.13–1.19), ever smoked (enrichment = 2.07; 95% CI = 2.04–2.10), HDL (enrichment = 1.53; 95% CI = 1.45–1.62) and trigylcerides (enrichment = 1.33; 95% CI = 1.24–1.42). These results indicate that risk alleles for brain disorders are preferentially located in regions of regulatory/enhancer function in the cortex, further supporting the hypothesis that genetic variants for these phenotypes influence gene regulation in the brain.

Background. Pain in the shoulder joint is a topical problem of modern traumatology and orthopedics. One of the most common causes of pain arising in the anterior shoulder is instability of the tendon of the long biceps head (SDHB). Purpose. To analyze the frequency of concomitant damage to the rotator and bicipital elements of the rotatorbicipital complex with instability of the tendon of the long biceps head. Material and methods. The article presents the results of a prospective and retrospective analysis of 66 patients over the period from 2004 to 2018. Of these, 51% were men (77.3%), 15 - women (22.7%). The age varied from 19 to 77 years old, the average age was 47.3 ± 15.9 years. The patients were examined according to the algorithm developed by the authors, which is used in everyday practice. Results and conclusions. The figures of descriptive statistics and the statistical analysis carried out using the association coefficient of D. Yul indicate a direct, strong, statistically significant relationship between the damage to the rotator apparatus and the tendon of the long biceps head. The developed algorithm for the diagnosis of traumatic injuries of RBC is simple and highly effective in making a diagnosis in patients with instability of the tendon of the long biceps head.

We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.

PurposeDeveloping large-scale datasets with research-quality annotations is challenging due to the high cost of refining clinically generated markup into high precision annotations. We evaluated the direct use of a large dataset with only clinically generated annotations in development of high-performance segmentation models for small research-quality challenge datasets.Materials and methodsWe used a large retrospective dataset from our institution comprised of 1,620 clinically generated segmentations, and two challenge datasets (PROMISE12: 50 patients, ProstateX-2: 99 patients). We trained a 3D U-Net convolutional neural network (CNN) segmentation model using our entire dataset, and used that model as a template to train models on the challenge datasets. We also trained versions of the template model using ablated proportions of our dataset, and evaluated the relative benefit of those templates for the final models. Finally, we trained a version of the template model using an out-of-domain brain cancer dataset, and evaluated the relevant benefit of that template for the final models. We used five-fold cross-validation (CV) for all training and evaluation across our entire dataset.ResultsOur model achieves state-of-the-art performance on our large dataset (mean overall Dice 0.916, average Hausdorff distance 0.135 across CV folds). Using this model as a pre-trained template for refining on two external datasets significantly enhanced performance (30% and 49% enhancement in Dice scores respectively). Mean overall Dice and mean average Hausdorff distance were 0.912 and 0.15 for the ProstateX-2 dataset, and 0.852 and 0.581 for the PROMISE12 dataset. Using even small quantities of data to train the template enhanced performance, with significant improvements using 5% or more of the data.ConclusionWe trained a state-of-the-art model using unrefined clinical prostate annotations and found that its use as a template model significantly improved performance in other prostate segmentation tasks, even when trained with only 5% of the original dataset.

Distal radius fracture (DRF) is one of the most common fractures of the elderly. The higher the degree of joint surface destruction, and the more adverse factors are involved, the more challenging proper treatment becomes. In this regard, osteoporosis as underlying systemic disease, chondropathy or degeneration of adjacent wrist bones as well as incompliance significantly impair the success of the chosen primary therapy. Wrist hemiarthroplasty has already been reported as primary or secondary procedure for DRFs. In this case report, we present a patient with a severely comminuted DRF including posttraumatic degeneration of the lunate as well as manifest osteoporosis. Wrist hemiarthroplasty using the ReMotion radius component in combination with proximal row carpectomy was performed as secondary surgery. This procedure proved to be a viable treatment option in terms of achieving low pain levels, high range of motion values and stable osteointegration over a course of 6.5 follow-up years.

Escherichia coli strains carrying Shiga toxins 1 and 2 (stx1 and stx2), intimin (eae), and hemolysin (ehxA) production genes were found in grass shoot, rhizosphere soil, and stable manure samples from a small-scale cattle farm located at the center of Netherlands, using cultivation-dependent and -independent microbiological detection techniques. Pasture land with grazing heifers in the first year of sampling in 2014 and without grazing cattle in 2015 was physically separated from the stable that housed rose calves during both years. Manure from the stable was applied to pasture via injection into soil once per year in early spring. Among a variety of 35 phylogenetic distinctly related E. coli strains, one large group consisting of 21 closely resembling E. coli O150:H2 (18), O98:H21 (2), and O84:H2 (1) strains, all belonging to phylogenetic group B1 and carrying all screened virulence traits, was found present on grass shoots (10), rhizosphere soil (3), and stable manure (8) in 2014, but not anymore in 2015 when grazing heifers were absent. Presence and absence of these strains, obtained via enrichments, were confirmed via molecular detection using PCR-NALFIA in all ecosystems in both years. We propose that this group of Shiga toxin-producing E. coli phylogenetic group B1 strains was originally introduced via stable manure injection into the pasture. Upon grazing, these potential pathogens proliferated in the intestinal track systems of the heifers resulting in defecation with higher loads of the STEC strain onto the grass cover. The STEC strain was further smeared over the field via the hooves of the heifers resulting in augmentation of the potential pathogen in the pasture in 2014, whereas in 2015, in the absence of heifers, no augmentation occurred and only a more diverse group of potentially mild virulent E. coli phylogenetic group A and B1 strains, indigenous to pasture plants, remained present. Via this model, it was postulated that human pathogens can circulate between plants and farm animals, using the plant as an alternative ecosystem. These data indicate that grazed pasture must be considered as a potential carrier of human pathogenic E. coli strains and possibly also of other pathogens.

A salient objective feature of the social environment in which people find themselves is group size. Knowledge of group size is highly relevant to behavioural scientists given that humans spend considerable time in social settings and the number of others influences much of human behaviour. What size of group do people actually look for and encounter in everyday life? Here we report four survey studies and one experience-sampling study (total N = 4,398) which provide evidence for the predominance of the dyad in daily life. Relative to larger group sizes, dyads are most common across a wide range of activities (e.g., conversations, projects, holidays, movies, sports, bars) obtained from three time moments (past activities, present, and future activities), sampling both mixed-sex and same-sex groups, with three different methodological approaches (retrospective reports, real-time data capture, and preference measures) in the United States and the Netherlands. We offer four mechanisms that may help explain this finding: reciprocity, coordination, social exclusion, and reproduction. The present findings advance our understanding of how individuals organize themselves in everyday life.

We estimate the production of Za bosons, with a as the component of a Z vector boson, via p-p collisions using previous work on J/Ψ,Ψ2S production in p-p collisions, with the new aspect being the creation of Za bosons via quark interactions. We then estimate the production of Za bosons via Pb-Pb collisions using modification factors from previous publications.

Reputation and punishment are two distinct mechanisms that facilitate cooperation among strangers. However, empirical research on their effectiveness is mainly limited to relatively small groups and does not address how they enhance cooperation in relatively larger groups. We address this gap in the literature by testing hypotheses from competing perspectives about the extent to which reputation-based partner choice and punishment enhance cooperation in both small and large groups. Prior work recognizes that an increase in group size is accompanied by a change in the incentive structure, which determines whether the temptation (extra benefit for each person from non-cooperation over cooperation, regardless of others’ choices) or gain (extra benefit for each person from full cooperation over full non-cooperation) remains constant or varies with group size. Thus, we first test how group size affects cooperation when temptation or gain increases with group size (Study 1), and then move on to testing predictions on the effectiveness of reputation and punishment across different group sizes (Study 2). In Study 1 (N = 820), we randomly assigned participants to play an online one-shot public goods game in groups of 4, 20, or 40, while keeping the marginal group return or marginal per capita return fixed across groups, in which case the temptation or gain increased with group size. In Study 2 (N = 1,132), we further compared a public goods situation involving a punishment or reputation mechanism with an anonymous situation across group sizes, while the marginal group return was fixed across groups. Overall, we found that when temptation increased with group size, 20-person groups cooperated significantly less than 4-person groups in one-shot interactions, and that this effect was explained by lower expectation of others’ cooperation, less perceived collective efficacy, and greater perceived conflict. However, 40-person and 4-person groups did not vary in one-shot cooperation. Importantly, reputation-based partner choice and punishment invariably promoted one-shot cooperation in groups of different sizes. These findings suggest no simple effect of group size on cooperation and underscore the utility of reputation and punishment in fostering cooperation (at least in one-shot interactions) regardless of the size of groups.

On Saturday, October 27, 2018, a man with anti-Semitic motivations entered Tree of Life synagogue in the Squirrel Hill section of Pittsburgh, Pennsylvania; he had an AR-15 semi-automatic rifle and three handguns, opening fire upon worshippers. Eventually 11 civilians died at the scene and eight people sustained non-fatal injuries, including five police officers. Each person injured but alive at the scene received care at one of three local level-one trauma centers. The injured had wounds often seen in war-settings, with the signature of high velocity weaponry. We describe the scene response, specific elements of our hospital plans, the overall out-of-hospital preparedness in Pittsburgh, and the lessons learned.

The current standardized scheme for interpreting MRI requires a high level of expertise and exhibits a significant degree of inter-reader and intra-reader variability. An automated prostate cancer (PCa) classification can improve the ability of MRI to assess the spectrum of PCa. The purpose of the study was to evaluate the performance of a texture-based deep learning model (Textured-DL) for differentiating between clinically significant PCa (csPCa) and non-csPCa and to compare the Textured-DL with Prostate Imaging Reporting and Data System (PI-RADS)-based classification (PI-RADS-CLA), where a threshold of PI-RADS ≥ 4, representing highly suspicious lesions for csPCa, was applied. The study cohort included 402 patients (60% (n = 239) of patients for training, 10% (n = 42) for validation, and 30% (n = 121) for testing) with 3T multiparametric MRI matched with whole-mount histopathology after radical prostatectomy. For a given suspicious prostate lesion, the volumetric patches of T2-Weighted MRI and apparent diffusion coefficient images were cropped and used as the input to Textured-DL, consisting of a 3D gray-level co-occurrence matrix extractor and a CNN. PI-RADS-CLA by an expert reader served as a baseline to compare classification performance with Textured-DL in differentiating csPCa from non-csPCa. Sensitivity and specificity comparisons were performed using Mcnemar’s test. Bootstrapping with 1000 samples was performed to estimate the 95% confidence interval (CI) for AUC. CIs of sensitivity and specificity were calculated by the Wald method. The Textured-DL model achieved an AUC of 0.85 (CI [0.79, 0.91]), which was significantly higher than the PI-RADS-CLA (AUC of 0.73 (CI [0.65, 0.80]); p < 0.05) for PCa classification, and the specificity was significantly different between Textured-DL and PI-RADS-CLA (0.70 (CI [0.59, 0.82]) vs. 0.47 (CI [0.35, 0.59]); p < 0.05). In sub-analyses, Textured-DL demonstrated significantly higher specificities in the peripheral zone (PZ) and solitary tumor lesions compared to the PI-RADS-CLA (0.78 (CI [0.66, 0.90]) vs. 0.42 (CI [0.28, 0.57]); 0.75 (CI [0.54, 0.96]) vs. 0.38 [0.14, 0.61]; all p values < 0.05). Moreover, Textured-DL demonstrated a high negative predictive value of 92% while maintaining a high positive predictive value of 58% among the lesions with a PI-RADS score of 3. In conclusion, the Textured-DL model was superior to the PI-RADS-CLA in the classification of PCa. In addition, Textured-DL demonstrated superior performance in the specificities for the peripheral zone and solitary tumors compared with PI-RADS-based risk assessment.

Prostate specific membrane antigen (PSMA) scanning is a sensitive method of prostate cancer detection. In a 71 y.o. man with a PSA of 49 (6%F), 4 negative MRI studies and 6 negative biopsies over an 8 year interval, a 68Ga-PSMA PET/CT scan showed a PSMA-avid spot in the prostate. Using image fusion technology, the lesion was target-biopsied and Gleason 3 + 4 = 7 (cancer core length of 12 mm) was identified. This case may herald a new application for PSMA scanning and prostate cancer imaging.

Abstract We estimate differential rapidity cross sections for J/Ψ, Ψ(2S), Y(1S), Y(2S), and Y(3S) production via Pb-Pb collisions at proton-proton energy ≡ s pp $$ \sqrt{s_{pp}} $$ = 5.02 TeV. For the Ψ(2S) and Y(3S) states we use the mixed heavy quark hyrid theory and compare the cross section to the standard model. This is an extension of previous work on heavy quark state production via Cu-Cu and Au-Au collisions at s pp $$ \sqrt{s_{pp}} $$ = 200 GeV.

Abstract This study was to evaluate the effectiveness of oral hygiene care in improving oral health- and health-related quality of life (OHRQoL and HRQoL) among patients receiving outpatient stroke rehabilitation. Subjects were randomized to: (1) a conventional oral hygiene care programme (COHCP) comprising a manual toothbrush, and oral hygiene instruction, or (2) an advanced oral hygiene care programme (AOHCP) comprising a powered toothbrush, 0.2% chlorhexidine mouthrinse, and oral hygiene instruction. The interventional period lasted for 3 months, followed by a 3-month observational period. HRQoL was assessed by SF-12, and OHRQoL was assessed by Oral Health Impact Profile-14 (OHIP-14), General Oral Health Assessment Index (GOHAI), and Oral Health Transitional Scale (OHTS). Participants in AOHCP group had significantly better OHRQoL at the end of clinical trial as assessed by OHTS (p

Abstract Ecosystem engineers transform habitats in ways that facilitate a diversity of species; however, few investigations have isolated short‐term effects of engineers from the longer‐term legacy effects of their engineered structures. We investigated how initial presence of net‐spinning caddisflies (Hydropsychidae) and their structures that provide and modify habitat differentially influence benthic community colonization in a headwater stream by conducting an in situ experiment that included three treatments: (1) initial engineering organism with its habitat modification structure occupied (hereafter caddisfly); (2) initial habitat modification structure alone (hereafter silk); and (3) a control with the initial absence of both engineer and habitat modification structure (hereafter control). Total invertebrate colonization density and biomass was higher in caddisfly and silk treatments compared to controls (~25% and 35%, respectively). However, finer‐scale patterns of taxonomy revealed that density for one of the taxa, Chironomidae, was ~19% higher in caddisfly compared to silk treatments. Additionally, conspecific biomass was higher by an average of 50% in silk treatments compared to controls; however, no differences in Hydropsyche sp. biomass were detected between caddisfly treatments and controls, indicating initially abandoned silk structures elevated conspecific biomass. These findings suggest that the positive effects of the habitat modification structures that were occupied for the entirety of the experiment may outweigh any potential negative impacts from the engineer, which is known to be territorial. Importantly, these results reveal that the initial presence of the engineer itself may be important in maintaining the ecological significance of habitat modifications. Furthermore, the habitat modifications that were initially abandoned (silk) had similar positive effects on conspecific biomass compared to caddisfly treatments, suggesting legacy effects of these engineering structures may have pertinent intraspecific feedbacks of the same magnitude to that of occupied habitat modifications. Elucidating how engineers and their habitat modifications differentially facilitate organisms will allow for a clearer mechanistic understanding of the extent to which animal engineers and their actions influence aspects of community organization such as colonization.

Immunotherapeutic treatments in head and neck cancer clinical trials include cancer vaccines targeting foreign viral antigens or mutational neoantigens derived from cancer-expressed proteins. Anti-tumor immune responses place cancer cells under selective pressure to lose or downregulate target antigens; therefore, vaccination against virus- or host- “driver” oncogenes are proposed as a strategy to overcome immune escape. Herein, we demonstrate the impact of immunogenic viral antigens on anti-tumor response and immune editing in MOC2-E6E7, a syngeneic murine oral cancer cell line expressing HPV-16 E6 and E7 oncoproteins. Using orthotopic syngeneic models, we observed in vivo tumor growth kinetics of MOC2-E6E7 is delayed in immunocompetent mice compared to parental MOC2 tumors. In contrast, tumor growth remained similar in Rag1-/- mice lacking adaptive immunity. MOC2-E6E7 tumors demonstrated an “inflamed” or immune-activated tumor microenvironment and greater infiltration of CD8+ T cells compared to MOC2. By real-time PCR, we detected downregulation of E6 and E7 genes in MOC2-E6E7 tumors only in immunocompetent mice, suggesting the loss of ectopic viral antigen expression due to immune editing. We then assessed the efficacy of a biomaterials-based mesoporous silica rod (MSR) cancer vaccine targeting HPV-16 E7 in our model. Vaccination induced robust infiltration of antigen-specific CD8+ T cells, which led to tumor growth delay and modestly prolonged survival in MOC2-E6E7 tumors. Increased efficacy was seen in a separate head and neck cancer tumor model, mEER, which obligately expresses E7 antigen. Collectively, our data highlight the need for both immunogenicity and ‘driver’ status of target antigens to be considered in cancer vaccine design.

Background: Irritable bowel syndrome with diarrhea (IBS-D) is a prevalent gastrointestinal (GI) disorder with a varied presentation, often overlapping with other GI and non-GI disorders. Eluxadoline is a locally active mixed µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist approved for the treatment of IBS-D in adults. As IBS-D is a heterogeneous disease, factors such as patient demographics, symptom severity, and symptom pattern history can potentially inform treatment selection. Methods: Here, we report additional prospectively planned analyses of two large double-blind, placebo-controlled studies (IBS-3001 and IBS-3002) enrolling patients meeting Rome III criteria for IBS-D. Patients were randomized 1:1:1 to receive placebo or eluxadoline 75 mg or 100 mg twice daily. Efficacy (abdominal pain, stool consistency, and composite, simultaneous improvement in both) and safety were assessed for prospectively defined patient subgroups stratified by age, sex, race, presence of comorbidities, and baseline disease characteristics. Results: Across all age, sex, race, comorbidity, and disease characteristic subgroups, a greater proportion of patients were composite responders with both eluxadoline doses as compared with placebo, including patients with a history of depression or a history of gastroesophageal reflux disease. Among patients aged ⩾65 years, a greater proportion of patients receiving eluxadoline 75 mg were composite, abdominal pain, and stool consistency responders compared with those receiving 100 mg. The proportion of patients with at least one adverse event was slightly higher in patients aged ⩾65 years and also in female patients. Conclusions: This analysis suggests that eluxadoline is effective in treating IBS-D across a range of commonly encountered patient types. In contrast to the overall population, patients aged ⩾65 years demonstrated a greater proportion of responders at the lower approved 75 mg eluxadoline dose.