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Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin. Inhibition of Mucorales fungi by allicin in solution and by allicin vapor was demonstrated. Mathematical modeling showed that the efficacy of allicin vapor is comparable to direct contact with the commercially available antifungal agent amphotericin B (ampB). Furthermore, the study revealed a synergistic interaction between allicin and the non-volatile ampB. The toxicity of allicin solution to human cell lines was evaluated and it was found that the half maximal effective concentration (EC50) of allicin was 25–72 times higher in the cell lines as compared to the fungal spores. Fungal allicin sensitivity depends on the spore concentration, as demonstrated in a drop test. This study shows the potential of allicin, a sulfur-containing defense compound from garlic, to combat zygomycete fungi. The findings underscore allicin's promise for applications in infections of the nasopharynx via inhalation, suggesting a novel therapeutic avenue against challenging fungal infections. [ABSTRACT FROM AUTHOR]

β3-Adrenoceptors mediate several functions in rodents that could be beneficial for the treatment of obesity and type 2 diabetes. This includes promotion of insulin release from the pancreas, cellular glucose uptake, lipolysis, and thermogenesis in brown adipose tissue. In combination, they lead to a reduction of body weight in several rodent models including ob/ob mice and Zucker diabetic fatty rats. These findings stimulated drug development programs in various pharmaceutical companies, and at least nine β3-adrenoceptor agonists have been tested in clinical trials. However, all of these projects were discontinued due to the lack of clinically relevant changes in body weight. Following a concise historical account of discoveries leading to such drug development programs we discuss species differences that explain why β3-adrenoceptors are not a meaningful drug target for the treatment of obesity and type 2 diabetes in humans. [ABSTRACT FROM AUTHOR]

Knowledge of who infected whom during an outbreak of an infectious disease is important to determine risk factors for transmission and to design effective control measures. Both whole-genome sequencing of pathogens and epidemiological data provide useful information about the transmission events and underlying processes. Existing models to infer transmission trees usually assume that the pathogen is introduced only once from outside into the population of interest. However, this is not always true. For instance, SARS-CoV-2 is suggested to be introduced multiple times in mink farms in the Netherlands from the SARS-CoV-2 pandemic among humans. Here, we developed a Bayesian inference method combining whole-genome sequencing data and epidemiological data, allowing for multiple introductions of the pathogen in the population. Our method does not a priori split the outbreak into multiple phylogenetic clusters, nor does it break the dependency between the processes of mutation, within-host dynamics, transmission, and observation. We implemented our method as an additional feature in the R-package phybreak. On simulated data, our method correctly identifies the number of introductions, with an accuracy depending on the proportion of all observed cases that are introductions. Moreover, when a single introduction was simulated, our method produced similar estimates of parameters and transmission trees as the existing package. When applied to data from a SARS-CoV-2 outbreak in Dutch mink farms, the method provides strong evidence for independent introductions of the pathogen at 13 farms, infecting a total of 63 farms. Using the new feature of the phybreak package, transmission routes of a more complex class of infectious disease outbreaks can be inferred which will aid infection control in future outbreaks. Author summary: Information about transmission routes is essential to design effective control measures for infectious disease outbreaks. A key question is whether outbreaks are caused by single imported index cases, or by multiple introductions. We introduce the concept of a 'history host' in a Bayesian model for simultaneous inference of phylogenetic and transmission trees. This artificial host—representing a source population—merges transmission trees by acting as the infector of all index cases, creating one large transmission tree. We applied the model to data from a SARS-CoV2 outbreak among mink farms in the Netherlands. We conclude that introductions from humans were an important factor in the outbreak, which implies that culling of infected farms alone was insufficient to prevent newly infected farms. [ABSTRACT FROM AUTHOR]

Background: Worldwide, gastric cancer is a leading cause of cancer incidence and mortality. This study aims to devise and validate a scoring system based on readily available clinical data to predict the risk of gastric cancer in a large Chinese population. Methods: We included a total of 6,209,697 subjects aged between 18 and 70 years who have received upper digestive endoscopy in Hong Kong from 1997 to 2018. A binary logistic regression model was constructed to examine the predictors of gastric cancer in a derivation cohort (n = 4,347,224), followed by model evaluation in a validation cohort (n = 1,862,473). The algorithm's discriminatory ability was evaluated as the area under the curve (AUC) of the mathematically constructed receiver operating characteristic (ROC) curve. Results: Age, male gender, history of Helicobacter pylori infection, use of proton pump inhibitors, non‐use of aspirin, non‐steroidal anti‐inflammatory drugs (NSAIDs), and statins were significantly associated with gastric cancer. A scoring of ≤8 was designated as "average risk (AR)". Scores at 9 or above were assigned as "high risk (HR)". The prevalence of gastric cancer was 1.81% and 0.096%, respectively, for the HR and LR groups. The AUC for the risk score in the validation cohort was 0.834, implying an excellent fit of the model. Conclusions: This study has validated a simple, accurate, and easy‐to‐use scoring algorithm which has a high discriminatory capability to predict gastric cancer. The score could be adopted to risk stratify subjects suspected as having gastric cancer, thus allowing prioritized upper digestive tract investigation. [ABSTRACT FROM AUTHOR]

Background: Poor medication adherence is a major barrier to HIV control among youth living with HIV (Y-PLWH). The PEERNaija application (app) is an adapted smartphone app grounded in social cognitive and contigency management theories and designed to harness peer-based social incentives and conditional financial incentives to promote medication adherence. The app delivers a multifaceted medication adherence intervention including (1) peer-based social incentives, (2) financial incentives, (3) virtual peer social support, and (4) early clinic-based outreach for non-adherent Y-PLWH. A pilot trial of the app will be conducted in Nigeria, Africa's most populous country with the 4th largest HIV epidemic, and home to 10% of the world's four million Y-PLWH. Methods: In this randomized controlled trial, we will compare implementation outcomes (feasibility, acceptability, appropriateness measured via validated scales, enrollment and application installation rates, feedback surveys and focus group discussions with participants, and back-end application data), and preliminary efficacy (in improving medication adherence and viral suppression) of the PEERNaija app at 6 months. Participants in Arm 1 (PEERNaija) will receive daily medication reminders, peer-based social incentives, and virtual peer social support. Participants in Arm 2 (PEERNaija +) will additionally receive a conditional financial incentive based on their adherence performance. Eligibility for Y-PLWH includes (1) being aged 14–29 years, (2) being on ART, (3) owning a smartphone, (4) being willing to download an app, and (5) being able to read simple text in English. Discussion: This study will serve as the basis for a larger intervention trial evaluating the PEERNaija app (and the integration of mHealth, incentive, and peer-support-based strategies) to improve HIV outcomes in a critically important region of the world for Y-PLWH. Trial registration: ClinicalTrials.gov. NCT04930198. First submitted date: May 25, 2021. Study start: August 1, 2021, https://clinicaltrials.gov/. Protocol version: January 21, 2022. [ABSTRACT FROM AUTHOR]

The article presents a study which assessed how the bioenergetics of scattering layer forays by a model predator vary across biomes using an interdisciplinary approach. Topics discussed include archival tagging and geolocation, dive extraction and classification of layer prey, and construction of light attenuation profiles from the archival depth-light series data.

Benign conditions of the lower urinary tract, including benign prostatic hyperplasia, overactive bladder syndrome, and stress urinary incontinence, are frequent in the general population. Despite their benign nature, they have major adverse effects on the quality of life of the afflicted patients and their partners. Despite major progress in the diagnosis and treatment of these conditions, improved understanding and management of these patients remain substantial medical needs. This editorial discusses some recent high-quality articles published in the Journal of Clinical Medicine on the understanding of the epidemiology, pathophysiology, diagnostic, and treatment of benign diseases of the lower urinary tract tissues such as the bladder and prostate. [ABSTRACT FROM AUTHOR]

This paper covers considerations in using criterion measures based on administrative data. We begin with a conceptual framework for understanding and evaluating administrative criterion measures as "objective" rather than (ratings-based) assessments of job performance. We then describe the associated advantages (e.g., availability) and disadvantages (e.g., contamination) of using administrative data for criterion-related validation purposes. Best practices in the use of administrative data for validation purposes, including procedures for (a) handling missing data, (b) performing data checks, and (c) reporting detailed decision rules so future researchers can replicate the analyses are also described. Finally, we discuss "modern data management" approaches for improving administrative data for supporting organizational decision-making. [ABSTRACT FROM AUTHOR]

First, CRC screening meets the vast majority, if not all, criteria of screening proposed by Wilson and Jungner (WHO), which remains a widely recognized standard. Keywords: cancer; colorectal; screening EN cancer colorectal screening 1 3 3 10/31/23 20231001 NES 231001 Worldwide, the incidence of colorectal cancer (CRC) increased substantially in various countries, which could be attributed to the rising rate of lifestyle, metabolic, and environmental risk factors due to globalization, urbanization and westernization.[[1]] Nevertheless, the value of population-based, CRC screening has been challenged by recent evidence.[3] It was opined that CRC screening may offer limited value at the population level, mainly due to its modest impact on decreased CRC mortality based on findings from the NordICC trial, the first pragmatic, randomised controlled trial of colonoscopy screening.[4] According to the landmark study, which included data from 84,585 healthy subjects aged 55-64 years recruited from three European countries between 2009 and 2014, the risk ratio (0.90, 95% confidence interval [CI] 0.64-1.16) and absolute risk reduction (-0.03, 95% CI -0.11-0.05) of mortality from CRC were not statistically significant. By all means, it is inappropriate to recommend CRC screening for all clinical consultations, but a large proportion of the population would benefit from screening, especially those with risk factors such as smoking and a family history of CRC. [Extracted from the article]

Precipitation events have been predicted and observed to become fewer, but larger, as the atmosphere warms. Water-limited ecosystems are especially sensitive to changes in water cycling, yet evidence suggests that productivity may either increase or decrease in response to precipitation intensification. Interactions among climate, soil properties, and vegetation type may explain different responses, but this is difficult to experimentally test over large spatial scales. Simulation modeling may reveal the mechanisms through which climate, soils, and vegetation interact to affect plant growth. We use an individual-based plant ecohydrological model to simulate the effects of 25%, 50%, and 100% increases in precipitation event sizes on water cycling and shrub, grass, and forb biomass in 200 shrub-steppe sites spanning 651,000 km2 of the Intermountain West, USA. Simulations did not change annual precipitation amounts and were performed for 0, 3, and 5 °C warming. Larger precipitation events decreased evaporation and 'pushed' water into shrub root zones in arid and semi-arid sites, but 'pushed' water below shrub root zones in mesic sites resulting in increased shrub biomass in arid and semi-arid, but not mesic, sites. Positive effects of precipitation intensification on shrub growth partially counteracted negative effects of warming. Grasses and forbs showed no consistent response to precipitation intensification. Results indicate that increased precipitation intensity creates a competitive advantage for shrubs in arid and semi-arid sites. This advantage results in greater shrub relative abundance and suggests that precipitation intensification contributes to woody plant encroachment observed globally in arid and semi-arid ecosystems. [ABSTRACT FROM AUTHOR]

Portland cement-based grouts used for radioactive waste immobilisation contain a Ca- and Si-rich binder phase, known as calcium–silicate–hydrate (C–S–H). Depending on the blend of cement used, the Ca/Si ratio can vary considerably. A range of C–S–H minerals with Ca/Si ratios from 0.6 to 1.6 were synthesised and contacted with aqueous U(VI) at 0.5 mM and 10 mM concentrations. Solid-state 29Si MAS-NMR spectroscopy was applied to probe the Si coordination environment in U(VI)-contacted C–S–H minerals and, in conjunction with U LIII-edge X-ray absorption spectroscopy analysis, inferences of the fate of U(VI) in these systems were made. At moderate or high Ca/Si ratios, uranophane-type uranyl silicates or Ca-uranates dominated, while at the lowest Ca/Si ratios, the formation of a Ca-bearing uranyl silicate mineral, similar to haiweeite (Ca[(UO2)2Si5O12(OH)2]·3H2O) or Ca-bearing weeksite (Ca2(UO2)2Si6O15·10H2O) was identified. This study highlights the influence of Ca/Si ratio on uranyl sequestration, of interest in the development of post-closure safety models for U-bearing radioactive waste disposal. [ABSTRACT FROM AUTHOR]

Motivation We face an increasing flood of genetic sequence data, from diverse sources, requiring rapid computational analysis. Rapid analysis can be achieved by sampling a subset of positions in each sequence. Previous sequence-sampling methods, such as minimizers, syncmers and minimally overlapping words, were developed by heuristic intuition, and are not optimal. Results We present a sequence-sampling approach that provably optimizes sensitivity for a whole class of sequence comparison methods, for randomly evolving sequences. It is likely near-optimal for a wide range of alignment-based and alignment-free analyses. For real biological DNA, it increases specificity by avoiding simple repeats. Our approach generalizes universal hitting sets (which guarantee to sample a sequence at least once) and polar sets (which guarantee to sample a sequence at most once). This helps us understand how to do rapid sequence analysis as accurately as possible. Availability and implementation Source code is freely available at https://gitlab.com/mcfrith/noverlap. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Simple Summary: There is a scarcity of economic analysis on the use of non-invasive biomarkers to inform policy-making with respect to their application in population-based colorectal cancer (CRC) screening programs. The objective of this study is to conduct a comparative cost-effectiveness analysis on using M3CRC (m3 + Fn + Ch + Bc + FIT) as a primary test for population-based screening, when compared with FIT and colonoscopy. The study can provide economic analysis regarding the use of non-invasive biomarkers in population-based CRC screening programs. This study aimed to examine the cost-effectiveness of fecal biomarker M3 panel compared to fecal immunochemical test (FIT) and colonoscopy in an Asian population. In a hypothetical population of 100,000 persons aged 50 years who received FIT yearly, M3 biomarker yearly, or colonoscopy every 10 years until the age of 75 years. Participants with positive FOBT or a result of "high risk" identified using the M3 biomarker are offered colonoscopy. We assumed surveillance colonoscopy is repeated every 3 years, and examined the treatment cost. A comparison of various outcome measures was conducted using Markov modelling. The incremental cost-effectiveness ratio (ICER) of FIT, M3 biomarker, and colonoscopy was USD108,176, USD133,485 and USD159,596, respectively. Comparing with FIT, the use of M3 biomarker could lead to significantly smaller total loss of cancer-related life-years (2783 vs. 5279); a higher number of CRC cases prevented (1622 vs. 146), a higher proportion of CRC cases prevented (50.2% vs. 4.5%), more life-years saved (2852 vs. 339), and cheaper total costs per life-year saved (USD212,553 vs. 773,894). The total costs per life-year saved is more affordable than that achieved by colonoscopy as a primary screening tool (USD212,553 vs. USD236,909). The findings show that M3 biomarkers may be more cost-effective than colonoscopy. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) pandemic has induced a significant global concern on mental health. However few studies have measured the ability of individuals to "withstand setbacks, adapt positively, and bounce back from adversity" on a global scale. We aimed to examine the level of resilience, its determinants, and its association with maladaptive coping behaviours during the pandemic. Methods: The Association of Pacific Rim Universities (APRU) conducted a global survey involving 26 countries by online, self-administered questionnaire (October 2020-December 2021). It was piloted-tested and validated by an expert panel of epidemiologists and primary care professionals. We collected data on socio-demographics, socioeconomic status, clinical information, lifestyle habits, and resilience levels measured by the Brief Resilience Scale (BRS) among adults aged ≥ 18 years. We examined factors associated with low resilience level, and evaluated whether low resilience was correlated with engagement of maladaptive coping behaviours. Results: From 1,762 surveys, the prevalence of low resilience level (BRS score 1.00–2.99) was 36.4% (America/Europe) and 24.1% (Asia Pacific). Young age (18–29 years; adjusted odds ratio [aOR] = 0.31–0.58 in older age groups), female gender (aOR = 1.72, 95% C.I. = 1.34–2.20), poorer financial situation in the past 6 months (aOR = 2.32, 95% C.I. = 1.62–3.34), the presence of one (aOR = 1.56, 95% C.I. = 1.19–2.04) and more than two (aOR = 2.32, 95% C.I. = 1.59–3.39) medical conditions were associated with low resilience level. Individuals with low resilience were significantly more likely to consume substantially more alcohol than usual (aOR = 3.84, 95% C.I. = 1.62–9.08), take considerably more drugs (aOR = 12.1, 95% C.I. = 2.72–54.3), buy supplements believed to be good for treating COVID-19 (aOR = 3.34, 95% C.I. = 1.56–7.16), exercise less than before the pandemic (aOR = 1.76, 95% C.I. = 1.09–2.85), consume more unhealthy food than before the pandemic (aOR = 2.84, 95% C.I. = 1.72–4.67), self-isolate to stay away from others to avoid infection (aOR = 1.83, 95% C.I. = 1.09–3.08), have an excessive urge to disinfect hands for avoidance of disease (aOR = 3.08, 95% C.I. = 1.90–4.99) and transmission (aOR = 2.54, 95% C.I. = 1.57–4.10). Conclusions: We found an association between low resilience and maladaptive coping behaviours in the COVID-19 pandemic. The risk factors identified for low resilience in this study were also conditions known to be related to globalization-related economic and social inequalities. Our findings could inform design of population-based, resilience-enhancing intervention programmes. [ABSTRACT FROM AUTHOR]

A proportion of Babesia rossi infections in dogs are classified as complicated and one of the most lethal complications is acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Most dogs that die succumb within 24 hours of presentation. The pulmonary pathology caused by B. rossi in dogs has not been described. The aim of this study was to provide a thorough macroscopic, histological and immunohistochemical description of the lung changes seen in dogs naturally infected with B. rossi that succumbed to the infection. Death was invariably accompanied by alveolar oedema. Histopathology showed acute interstitial pneumonia characterised by alveolar oedema and haemorrhages, with increased numbers of mononuclear leucocytes in alveolar walls and lumens. Intra-alveolar polymerised fibrin aggregates were observed in just over half the infected cases. Immunohistochemistry showed increased numbers of MAC387- and CD204-reactive monocyte-macrophages in alveolar walls and lumens, and increased CD3-reactive T-lymphocytes in alveolar walls, compared with controls. These histological features overlap to some extent (but far from perfectly) with the histological pattern of lung injury referred to as the exudative stage of diffuse alveolar damage (DAD) as is quite commonly reported in ALI/ARDS. [ABSTRACT FROM AUTHOR]

Background Lung cancer is the leading cause of cancer mortality globally. Early detection through risk-based screening can markedly improve prognosis. However, most risk models were developed in North American cohorts of smokers, whereas less is known about risk profiles for never-smokers, which represent a growing proportion of lung cancers, particularly in Asian populations. Methods Based on the China Kadoorie Biobank, a population-based prospective cohort of 512 639 adults with up to 12 years of follow-up, we built Asian Lung Cancer Absolute Risk Models (ALARM) for lung cancer mortality using flexible parametric survival models, separately for never and ever-smokers, accounting for competing risks of mortality. Model performance was evaluated in a 25% hold-out test set using the time-dependent area under the curve and by comparing model-predicted and observed risks for calibration. Results Predictors assessed in the never-smoker lung cancer mortality model were demographics, body mass index, lung function, history of emphysema or bronchitis, personal or family history of cancer, passive smoking, and indoor air pollution. The ever-smoker model additionally assessed smoking history. The 5-year areas under the curve in the test set were 0.77 (95% confidence interval = 0.73 to 0.80) and 0.81 (95% confidence interval = 0.79 to 0.84) for ALARM-never-smokers and ALARM-ever smokers, respectively. The maximum 5-year risk for never and ever-smokers was 2.6% and 12.7%, respectively. Conclusions This study is among the first to develop risk models specifically for Asian populations separately for never and ever-smokers. Our models accurately identify Asians at high risk of lung cancer death and may identify those with risks exceeding common eligibility thresholds who may benefit from screening. [ABSTRACT FROM AUTHOR]

Background: A new nationwide screening strategy was implemented in Germany in January 2020. No data are available for women referred to certified dysplasia units for secondary clarification after primary diagnosis by a local physician. We therefore investigated combined testing with Papanicolaou smears and high-risk human papillomavirus (hrHPV) and compared the data with the final histological findings. Methods: Between January 2015 and October 2020, all referred women who underwent colposcopy of the uterine cervix in our certified dysplasia unit were included. Cytology findings were classified using the Munich III nomenclature. Results: A total of 3588 colposcopies were performed in 3118 women, along with Pap smear and hrHPV co-testing, followed by histology. Women with Pap II-p (ASC-US) and a positive hrHPV co-test had a 22.4% risk for cervical intraepithelial neoplasia (CIN) 3/high-grade squamous intraepithelial lesion (HSIL). The risk of CIN 3/HSIL was 83.8% in women with Pap IVa-p (HSIL) and a positive hrHPV co-test. A positive hrHPV co-test increased the risk for HSIL+ (OR 5.942; 95% CI, 4.617 to 7.649; p < 0.001) as compared to a negative hrHPV co-test. Conclusions: The accuracy of Pap smears is comparable with the screening results. A positive hrHPV test increases the risk for HSIL+ fivefold. Colposcopy is necessary to diagnose HSIL+ correctly. [ABSTRACT FROM AUTHOR]

Background: Quantification of acquisition routes of antibiotic resistant bacteria (ARB) is pivotal for understanding transmission dynamics and designing cost-effective interventions. Different methods have been used to quantify the importance of transmission routes, such as relative risks, odds ratios (OR), genomic comparisons and basic reproduction numbers. We systematically reviewed reported estimates on acquisition routes' contributions of ARB in humans, animals, water and the environment and assessed the methods used to quantify the importance of transmission routes.Methods: PubMed and EMBASE were searched, resulting in 6054 articles published up until January 1st, 2019. Full text screening was performed on 525 articles and 277 are included.Results: We extracted 718 estimates with S. aureus (n = 273), E. coli (n = 157) and Enterobacteriaceae (n = 99) being studied most frequently. Most estimates were derived from statistical methods (n = 560), mainly expressed as risks (n = 246) and ORs (n = 239), followed by genetic comparisons (n = 85), modelling (n = 62) and dosage of ARB ingested (n = 17). Transmission routes analysed most frequently were occupational exposure (n = 157), travelling (n = 110) and contacts with carriers (n = 83). Studies were mostly performed in the United States (n = 142), the Netherlands (n = 87) and Germany (n = 60). Comparison of methods was not possible as studies using different methods to estimate the same route were lacking. Due to study heterogeneity not all estimates by the same method could be pooled.Conclusion: Despite an abundance of published data the relative importance of transmission routes of ARB has not been accurately quantified. Links between exposure and acquisition are often present, but the frequency of exposure is missing, which disables estimation of transmission routes' importance. To create effective policies reducing ARB, estimates of transmission should be weighed by the frequency of exposure occurrence. [ABSTRACT FROM AUTHOR]

Background: Clinical trials investigating acetabular fractures are heterogeneous in their investigated outcomes and their corresponding measurements. Standardization may facilitate comparability and pooling of research results, which would lead to an increase in knowledge about the optimal treatment of acetabular fractures, resulting in long-term evidence-based treatment decisions and improvements in patient care. The aim of this systematic review is to identify the reported outcomes and their measurements from studies on treatments for acetabular fractures to develop a core outcome set which contains the most relevant outcome measures to be included in future studies. Methods: Studies published in English and German including patients aged 16 years and older, with a surgically treated acetabular fracture, will be included. Studies with nonsurgical treatment, pathologic fractures, polytraumatized patients, and patients younger than 16 years of age will be excluded because other outcomes may be of interest in these cases. Any prospective and retrospective study will be included. Systematic reviews will be excluded, but their included studies will be screened for eligibility. The literature will be searched on MEDLINE, CENTRAL, Web of Science, ClinicalTrials.gov, and WHO ICTRP. Risk of selective reporting of outcomes will be assessed using the Outcome Reporting Bias in Trials classification system. Heterogeneously defined outcomes that measure the same outcome will be grouped and subsequently categorized into outcome domains using the taxonomy of the Core Outcome Measures in Effectiveness Trials Initiative. Discussion: It is expected that a high number of studies will be included, and many outcomes will be identified using different definitions and measurement instruments. A limitation of this systematic review is that only previously investigated outcomes will be detected, thus disregarding potentially relevant outcomes. Systematic review registration: PROSPERO CRD42022357644 [ABSTRACT FROM AUTHOR]

Infections caused by antibiotic-resistant bacteria have become more prevalent during past decades. Yet, it is unknown whether such infections occur in addition to infections with antibiotic-susceptible bacteria, thereby increasing the incidence of infections, or whether they replace such infections, leaving the total incidence unaffected. Observational longitudinal studies cannot separate both mechanisms. Using plasmid-based beta-lactam resistant E. coli as example we applied mathematical modelling to investigate whether seven biological mechanisms would lead to replacement or addition of infections. We use a mathematical neutral null model of individuals colonized with susceptible and/or resistant E. coli, with two mechanisms implying a fitness cost, i.e., increased clearance and decreased growth of resistant strains, and five mechanisms benefitting resistance, i.e., 1) increased virulence, 2) increased transmission, 3) decreased clearance of resistant strains, 4) increased rate of horizontal plasmid transfer, and 5) increased clearance of susceptible E. coli due to antibiotics. Each mechanism is modelled separately to estimate addition to or replacement of antibiotic-susceptible infections. Fitness costs cause resistant strains to die out if other strain characteristics are maintained equal. Under the assumptions tested, increased virulence is the only mechanism that increases the total number of infections. Other benefits of resistance lead to replacement of susceptible infections without changing the total number of infections. As there is no biological evidence that plasmid-based beta-lactam resistance increases virulence, these findings suggest that the burden of disease is determined by attributable effects of resistance rather than by an increase in the number of infections. Author summary: Infections with antibiotic-resistant bacteria (ARB) are considered a major global problem. To estimate the burden of antibiotic resistance, one should know whether, at a population level, infections with ARB replace infections with non-ARB (scenario labelled replacement) or whether infections with ARB occur on top of infections with non-ARB (scenario labelled addition). With replacement, only the additional burden of infections with ARB compared to infections with a non-ARB should be attributed to antibiotic resistance. With addition, the total burden associated with infections with ARB should be ascribed to antibiotic resistance. Using E. coli as example, we developed a mathematical model to investigate whether seven biological characteristics of ARB, each linked to either fitness costs or benefits, cause replacement or addition. A fitness cost causes resistant bacteria to die out if other characteristics are the same as for susceptible bacteria. Only increased virulence of ARB increases the total number of infections, while other benefits of resistance lead to replacement. As there is no biological evidence that the type of resistance in E. coli we studied increases virulence, these findings suggest that the burden of ARB is determined by attributable effects of resistance rather than by an increase in infections. [ABSTRACT FROM AUTHOR]

Many marine algae are strong accumulators of halogens. Commercial iodine production started by burning seaweeds in the 19th century. The high iodine content of certain seaweeds has potential pharmaceutical and nutritional applications. While the metabolism of iodine in brown algae is linked to oxidative metabolism, with iodide serving the function of an inorganic antioxidant protecting the cell and thallus surface against reactive oxygen species with implications for atmospheric and marine chemistry, rather little is known about the regulation and homoeostasis of other halogens in seaweeds in general and the ecological and biological role of marine algal halogenated metabolites (except for organohalogen secondary metabolites). The present review covers these areas, including the significance of seaweed-derived halogens and of halogens in general in the context of human diet and physiology. Furthermore, the understanding of interactions between halogenated compound production by algae and the environment, including anthropogenic impacts, effects on the ozone layer and global climate change, is reviewed together with the production of halogenated natural products by seaweeds and the potential of seaweeds as bioindicators for halogen radionuclides. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common disabling disease worldwide, with no effective and safe disease-modifying drugs (DMOAD) in the market. However, studies suggest that drugs, such as liraglutide, which possess strong potential in decreasing low-grade systemic inflammation may be effective in treating OA. Therefore, the aim of this study was to examine the anti-inflammatory, analgesic, and anti-degradative effects in OA using in vitro and in vivo experiments. The results showed that intra-articular injection of liraglutide alleviated pain-related behavior in in vivo sodium monoiodoacetate OA mouse model, which was probably driven by the GLP-1R-mediated anti-inflammatory activity of liraglutide. Moreover, liraglutide treatment significantly decreased IL-6, PGE2 and nitric oxide secretion, and the expression of inflammatory genes in vitro in chondrocytes and macrophages in a dose-dependent manner. Additionally, liraglutide shifted polarized macrophage phenotype in vitro from the pro-inflammatory M1 phenotype to the M2 anti-inflammatory phenotype. Furthermore, liraglutide exerted anti-catabolic activity by significantly decreasing the activities of metalloproteinases and aggrecanases, a family of catabolic enzymes involved in cartilage breakdown in vitro. Overall, the findings of this study showed that liraglutide ameliorated OA-associated pain, possess anti-inflammatory and analgesic properties, and could constitute a novel therapeutic candidate for OA treatment. [ABSTRACT FROM AUTHOR]

Portland cement based grouts used for radioactive waste immobilization contain high replacement levels of supplementary cementitious materials, including blast‐furnace slag and fly ash. The minerals formed upon hydration of these cements may have capacity for binding actinide elements present in radioactive waste. In this work, the minerals ettringite (Ca6Al2(SO4)3(OH)12·26H2O) and hydrotalcite (Mg6Al2(OH)16CO3·4H2O) were selected to investigate the importance of minor cement hydrate phases in sequestering and immobilizing UVI from radioactive waste streams. U LIII‐edge X‐ray absorption spectroscopy (XAS) was used to probe the UVI coordination environment in contact with these minerals. For the first time, solid‐state 27Al magic angle spinning nuclear magnetic resonance (MAS‐NMR) spectroscopy was applied to probe the Al coordination environment in these UVI‐contacted minerals and make inferences on the UVI coordination, in conjunction with the X‐ray spectroscopy analyses. The U LIII‐edge XAS analysis of the UVI‐contacted ettringite phases found them to be similar (>∼70%) to the uranyl oxyhydroxides present in a mixed becquerelite/metaschoepite mineral. Fitting of the EXAFS region, in combination with 27Al NMR analysis, indicated that a disordered Ca‐ or Al‐bearing UVI secondary phase also formed. For the UVI‐contacted hydrotalcite phases, the XAS and 27Al NMR data were interpreted as being similar to uranyl carbonate, that was likely Mg‐containing. [ABSTRACT FROM AUTHOR]

Background: Electronic medical records systems (EMRs) adoption in healthcare to facilitate work processes have become common in many countries. Although EMRs are associated with quality patient care, patient safety, and cost reduction, their adoption rates are comparatively low. Understanding factors associated with the use of the implemented EMRs are critical for advancing successful implementations and scale-up sustainable initiatives. The aim of this study was to explore end users' perceptions and experiences on factors facilitating and hindering EMRs use in healthcare facilities in Kenya, a low- and middle-income country.Methods: Two focus group discussions were conducted with EMRs users (n = 20) each representing a healthcare facility determined by the performance of the EMRs implementation. Content analysis was performed on the transcribed data and relevant themes derived.Results: Six thematic categories for both facilitators and barriers emerged, and these related to (1) system functionalities; (2) training; (3) technical support; (4) human factors; (5) infrastructure, and (6) EMRs operation mode. The identified facilitators included: easiness of use and learning of the system complemented by EMRs upgrades, efficiency of EMRs in patient data management, responsive information technology (IT) and collegial support, and user training. The identified barriers included: frequent power blackouts, inadequate computers, retrospective data entry EMRs operation mode, lack of continuous training on system upgrades, and delayed IT support.Conclusions: Users generally believed that the EMRs improved the work process, with multiple factors identified as facilitators and barriers to their use. Most users perceived system functionalities and training as motivators to EMRs use, while infrastructural issues posed as the greatest barrier. No specific EMRs use facilitators and/or barriers could be attributed to facility performance levels. Continuous evaluations are necessary to assess improvements of the identified factors as well as determine emerging issues. [ABSTRACT FROM AUTHOR]

Sleep and wakefulness are not simple, homogenous all-or-none states but represent a spectrum of substates, distinguished by behavior, levels of arousal, and brain activity at the local and global levels. Until now, the role of the hypothalamic circuitry in sleep-wake control was studied primarily with respect to its contribution to rapid state transitions. In contrast, whether the hypothalamus modulates within-state dynamics (state "quality") and the functional significance thereof remains unexplored. Here, we show that photoactivation of inhibitory neurons in the lateral preoptic area (LPO) of the hypothalamus of adult male and female laboratory mice does not merely trigger awakening from sleep, but the resulting awake state is also characterized by an activated electroencephalogram (EEG) pattern, suggesting increased levels of arousal. This was associated with a faster build-up of sleep pressure, as reflected in higher EEG slow-wave activity (SWA) during subsequent sleep. In contrast, photoinhibition of inhibitory LPO neurons did not result in changes in vigilance states but was associated with persistently increased EEG SWA during spontaneous sleep. These findings suggest a role of the LPO in regulating arousal levels, which we propose as a key variable shaping the daily architecture of sleep-wake states. [ABSTRACT FROM AUTHOR]

We show that there are one-loop IR singularities arising from UV/IR mixing in noncommutative SU(N) Yang–Mills theory defined by means of the θ -exact Seiberg–Witten map. This is in spite of the fact that there are no ordinary U(1) gauge fields in the theory and this is at variance with the noncommutative U(N) case, where the two-point part of the effective action involving the ordinary SU(N) fields do not suffer from those one-loop IR singularities. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare two different techniques of performing one-level spondylodesis for thoracolumbar burst fractures using either an autologous iliac crest bone graft (ICBG) or a porous tantalum fusion implant (PTFI). In a prospective nonrandomized study, 44 patients (20 women, 24 men; average age 43.1 ± 13.2 years) suffering from severe thoracolumbar burst fractures were treated with combined anterior–posterior stabilization. An ICBG was used in 21 cases, and a PTFI was used in the other 23 cases. A two-year clinical and radiographic follow-up was carried out. There were no statistically significant differences in age, sex, localization/classification of the fracture, or visual analog scale (VAS) before injury between the two groups. All 44 patients were followed up for an average period of 533 days (range 173–1567). The sagittal spinal profile was restored by an average of 11.1° (ICBG) vs. 14.3° (PTFI) (monosegmental Cobb angle). Loss of correction until the last follow-up tended to be higher in the patients treated with ICBG than in those treated with PTFI (mean: 2.8° vs. 1.6°). Furthermore, significantly better restoration of the sagittal profile was obtained with the PTFI than with the iliac bone graft at the long-term follow-up (mean: ICBG 7.8°, PTFI 12.3°; p < 0.005). Short-segment posterior instrumentation combined with anterior one-level spondylodesis using either an ICBG or a PTFI resulted in sufficient correction of posttraumatic segmental kyphosis. PTFI might be a good alternative for autologous bone grafting and prevent donor site morbidities. [ABSTRACT FROM AUTHOR]

Pseudogenes have been classified as functionless and their annotation is an ongoing problem. The Adh6-ps1—a mouse pseudogene belonging to the alcohol dehydrogenase gene complex (Adh) was analyzed to review the conservation, homology, expression, and interactions and identify any role it plays in disease phenotypes using bioinformatics databases. Results showed that Adh6-ps1 have 2 transcripts (processed and unprocessed) which may have emerged from a transposition and duplication event, respectively, and that induced inversions (Uox gene, In(3)11Rk) involving gene complexes associated with Adh6-ps1 have been implicated in a diverse range of diseases. Adh6-ps1 is highly conserved in vertebrates particularly rodents and expressed in the liver. The top 5 MirRNA targets were Mir455, Mir511, Mir1903, Mir361, and Mir669o markers. While much is unknown about Mir1903 and Mir669o, the silencing of Mir455 and Mir511 is linked with hepatocellular carcinoma (HCC), and Mir361 is implicated in endometrial cancers. Given the identified MirRNA interactions with Adh6-ps1 and its expression in HCC and reproductive systems, it may well have a role in tumorigenesis and disease phenotypes. Nonetheless, further studies are required to establish these facts to add to the growing efforts to understand pseudogenes and their potential involvement in disease conditions. [ABSTRACT FROM AUTHOR]

Operative treatment of ruptured pubic symphysis by plating is often accompanied by complications. Trans-obturator cable fixation might be a more reliable technique; however, have not yet been tested for stabilization of ruptured pubic symphysis. This study compares symphyseal trans-obturator cable fixation versus plating through biomechanical testing and evaluates safety in a cadaver experiment. APC type II injuries were generated in synthetic pelvic models and subsequently separated into three different groups. The anterior pelvic ring was fixed using a four-hole steel plate in Group A, a stainless steel cable in Group B, and a titan band in Group C. Biomechanical testing was conducted by a single-leg-stance model using a material testing machine under physiological load levels. A cadaver study was carried out to analyze the trans-obturator surgical approach. Peak-to-peak displacement, total displacement, plastic deformation and stiffness revealed a tendency for higher stability for trans-obturator cable/band fixation but no statistical difference to plating was detected. The cadaver study revealed a safe zone for cable passage with sufficient distance to the obturator canal. Trans-obturator cable fixation has the potential to become an alternative for symphyseal fixation with less complications. [ABSTRACT FROM AUTHOR]

Gastrointestinal symptoms (GIS) are common in kidney transplant candidates and recipients and may be worsened by HIV. Objective: To determine the frequency and severity of GIS in HIV-positive kidney transplant recipients from HIV-positive donors, and those waiting to receive one. A GIS rating scale (GSRS) was completed by 76 participants at baseline and at 6 months. GIS frequency was defined as having at least one symptom (GSRS > 1). Severity was indicated by the GSRS score. Transplant candidates: GIS frequency was 88.9% and 86.3% at baseline and 6 months respectively. Indigestion was the most frequent (79.6% and 66.7% at baseline and 6 months), and severe GIS (GSRS 2.3). Women reported global mean (p = 0.030) severity significantly more than men. Transplant recipients: GIS frequency was 95.2% and 76.2% at baseline and 6 months respectively. At both assessment points, indigestion occurred most frequently (85.7% and 61.9% respectively). Highest GSRS was reported for indigestion at baseline (2.33) and at 6 months (1.33). Waist circumference (WC) was positively associated with the severity of constipation GSRS. GIS are common in both groups, especially indigestions. WC in transplant recipients should be monitored. [ABSTRACT FROM AUTHOR]

Objective To assess the validity of embedded measures of performance validity, the effort index (EI) and effort scale (ES) of the repeatable battery for the assessment of neuropsychological status (RBANS), in Veterans with seizures; to compare the frequency of failure on the test of memory malingering (TOMM) in patients with epileptic versus psychogenic nonepileptic seizures (PNES). Methods Seizure diagnosis was established for 309 participants in epilepsy monitoring units using conventional diagnostic criteria who completed both the TOMM and RBANS. The criterion for performance invalidity was failure on any trial of the TOMM. We examined multiple EI and ES cutoffs to establish optimal sensitivity and specificity. Results An RBANS EI cutoff score of greater than three was optimal with specificity of.98, sensitivity of.19, and positive Likelihood Ratio of 10 but was not useful when below this cutoff. Confidence intervals indicate the need for confirmation of a failed EI with another performance validity test (PVT). No ES cutoff had sufficient specificity for clinical use. Invalid TOMM performance but not invalid RBANS performance was significantly more common in persons with PNES than in persons with epileptic seizures. Conclusions In Veterans undergoing seizure monitoring, the RBANS EI was useful as a screen when positive that requires confirmation with another PVT. The RBANS ES was not useful. Invalid performance on the TOMM was more common in persons with PNES than in persons with epileptic seizures. [ABSTRACT FROM AUTHOR]

Background: Tandem repeats are highly mutable and contribute to the development of human disease by a variety of mechanisms. It is difficult to predict which tandem repeats may cause a disease. One hypothesis is that changeable tandem repeats are the source of genetic diseases, because disease-causing repeats are polymorphic in healthy individuals. However, it is not clear whether disease-causing repeats are more polymorphic than other repeats. Methods: We performed a genome-wide survey of the millions of human tandem repeats using publicly available long read genome sequencing data from 21 humans. We measured tandem repeat copy number changes using tandem-genotypes. Length variation of known disease-associated repeats was compared to other repeat loci. Results: We found that known Mendelian disease-causing or disease-associated repeats, especially CAG and 5′UTR GGC repeats, are relatively long and polymorphic in the general population. We also show that repeat lengths of two disease-causing tandem repeats, in ATXN3 and GLS, are correlated with near-by GWAS SNP genotypes. Conclusions: We provide a catalog of polymorphic tandem repeats across a variety of repeat unit lengths and sequences, from long read sequencing data. This method especially if used in genome wide association study, may indicate possible new candidates of pathogenic or biologically important tandem repeats in human genomes. [ABSTRACT FROM AUTHOR]

Pseudogenes have been classified as functionless and their annotation is an ongoing problem. The Adh6-ps1-a mouse pseudogene belonging to the alcohol dehydrogenase gene complex (Adh) was analyzed to review the conservation, homology, expression and interactions, and identify any role it plays in disease phenotypes using bioinformatics databases. Results showed that Adh6-ps1 have 2 transcripts (processed and unprocessed) which may have emerged from a transposition and duplication event, respectively, and that induced inversions (Uox gene, In(3)11Rk) involving gene complexes associated with Adh6-ps1 have been implicated in a diverse range of diseases. Adh6-ps1 is highly conserved in vertebrates particularly rodents, and expressed in the liver. The top 5 MirRNA targets identified are Mir455, Mir511, Mir1903, Mir361, and Mir669o markers. While much is unknown about Mir1903 and Mir669o, the silencing of Mir455 and Mir511 is linked with hepatocellular carcinoma (HCC), and Mir361 is implicated in endometrial cancers. Given the identified MirRNA interactions with Adh6-ps1 and their expression in cancer phenotypes, and Adh6-ps1 associations with induced inversions, it may well have a role in tumorigenesis and disease phenotypes. Nonetheless, further studies are required to establish these facts to add to the growing efforts to understand pseudogenes and their potential involvement in disease conditions. [ABSTRACT FROM AUTHOR]

As the atmosphere warms, precipitation events become larger, but less frequent. Yet, there is fundamental disagreement about how increased precipitation intensity will affect vegetation. Walter's two‐layer hypothesis and experiments testing it have demonstrated that precipitation intensity can increase woody plant growth. Observational studies have found the opposite pattern. Not only are the patterns contradictory, but inference is largely limited to grasslands and savannas. We tested the effects of increased precipitation intensity in a shrub‐steppe ecosystem that receives >30% of its precipitation as snow. We used 11 (8 × 8 m) shelters to collect and redeposit rain and snow as larger, more intense events. Total annual precipitation was the same in all plots, but each plot received different precipitation event sizes ranging from 1 to 18 mm. Over three growing seasons, larger precipitation event sizes increased soil water availability, sagebrush (Artemisia tridentata) stem radius, and canopy greenness, decreased new root growth in shallow soils, and had no effect on herbaceous plant cover. Thus, we found that increased precipitation intensity can increase soil water availability and woody plant growth in a cold semiarid system. Assuming that stem growth is positively correlated with shrub reproduction, establishment and spread, results suggest that increasing precipitation intensity may have contributed to the woody plant encroachment observed around the world in the past 50 yr. Further, continuing increases in precipitation intensity caused by atmospheric warming are likely to continue to contribute to shrub encroachment in the future. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a growing concern for health systems, but the epidemiology of sepsis is poorly characterised. We evaluated sepsis recording across primary care electronic records, hospital episodes and mortality registrations. Methods and findings: Cohort study including 378 general practices in England from Clinical Practice Research Datalink (CPRD) GOLD database from 2002–2017 with 36,209,676 patient-years of follow-up with linked Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality registrations. Incident sepsis episodes were identified for each source. Concurrent records from different sources were identified and age-standardised and age-specific incidence rates compared. Logistic regression analysis evaluated associations of gender, age-group, fifth of deprivation and period of diagnosis with concurrent sepsis recording. There were 20,206 first episodes of sepsis from primary care, 20,278 from HES and 13,972 from ONS. There were 4,117 (20%) first HES sepsis events and 2,438 (17%) mortality records concurrent with incident primary care sepsis records within 30 days. Concurrent HES and primary care records of sepsis within 30 days before or after first diagnosis were higher at younger or older ages and for patients with the most recent period of diagnosis. Those diagnosed during 2007:2011 were less likely to have a concurrent HES record given CPRD compared to those diagnosed during 2012–2017 (odd ratio 0.65, 95% confidence interval 0.60–0.70). At age 85 and older, primary care incidence was 5.22 per 1,000 patient years (95% CI 1.75–11.97) in men and 3.55 (0.87–9.58) in women which increased to 10.09 (4.86–18.51) for men and 7.22 (2.96–14.72) for women after inclusion of all three sources. Conclusion: Explicit recording of 'sepsis' is inconsistent across healthcare sectors with a high proportion of non-concurrent records. Incidence estimates are higher when linked data are analysed. [ABSTRACT FROM AUTHOR]

Motivation Analysis of genetic sequences is usually based on finding similar parts of sequences, e.g. DNA reads and/or genomes. For big data, this is typically done via 'seeds': simple similarities (e.g. exact matches) that can be found quickly. For huge data, sparse seeding is useful, where we only consider seeds at a subset of positions in a sequence. Results Here, we study a simple sparse-seeding method: using seeds at positions of certain 'words' (e.g. ac, at, gc or gt). Sensitivity is maximized by using words with minimal overlaps. That is because, in a random sequence, minimally overlapping words are anti-clumped. We provide evidence that this is often superior to acclaimed 'minimizer' sparse-seeding methods. Our approach can be unified with design of inexact (spaced and subset) seeds, further boosting sensitivity. Thus, we present a promising approach to sequence similarity search, with open questions on how to optimize it. Availability and implementation Software to design and test minimally overlapping words is freely available at https://gitlab.com/mcfrith/noverlap. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Background: Plague is a re-emerging flea-borne infectious disease of global importance and in recent years, Zambia has periodically experienced increased incidence of outbreaks of this disease. However, there are currently no studies in the country that provide a quantitative assessment of the ability of the disease to spread during these outbreaks. This limits our understanding of the epidemiology of the disease especially for planning and implementing quantifiable and cost-effective control measures. To fill this gap, the basic reproduction number, R0, for bubonic plague was estimated in this study, using data from the 2015 Nyimba district outbreak, in the Eastern province of Zambia. R0 is the average number of secondary infections arising from a single infectious individual during their infectious period in an entirely susceptible population. Methodology/Principal findings: Secondary epidemic data for the most recent 2015 Nyimba district bubonic plague outbreak in Zambia was analyzed. R0 was estimated as a function of the average epidemic doubling time based on the initial exponential growth rate of the outbreak and the average infectious period for bubonic plague. R0 was estimated to range between 1.5599 [95% CI: 1.382–1.7378] and 1.9332 [95% CI: 1.6366–2.2297], with average of 1.7465 [95% CI: 1.5093–1.9838]. Further, an SIR deterministic mathematical model was derived for this infection and this estimated R0 to be between 1.4 to 1.5, which was within the range estimated above. Conclusions/Significance: This estimated R0 for bubonic plague is an indication that each bubonic plague case can typically give rise to almost two new cases during these outbreaks. This R0 estimate can now be used to quantitatively analyze and plan measurable interventions against future plague outbreaks in Zambia. Author summary: Bubonic plague is a historically important and neglected bacterial infectious disease that has claimed more than 170 million lives from multiple devastating epidemics especially during mediaeval and earlier times. Despite a recorded decline in the disease for much of the 21st century, incidence has begun to sharply rise again mainly in developing nations including Zambia which recently recorded a five-fold increase in recorded cases by the turn of the century. For developing and resource strained nations like Zambia, such major public health challenges need to be addressed with the most cost-effective, efficient, and sustainable approaches appropriate to the region. This firstly requires developing a sufficient and comprehensive epidemiological understanding of the disease. This study therefore estimated the basic reproduction number (R0) for bubonic plague which is an estimate of the average number of secondary infections expected to arise from a single infectious individual during their infectious period assuming the entire population is susceptible to the infection. Based on data from the Nyimba district bubonic plague outbreak in Zambia, we estimated R0 for the infection to range between 1.5599 to 1.9332 which shows that each infectious individual with bubonic plague can potentially infect up to two other individuals during their infectious period. We also observed that this R0 estimate was comparable to that previously estimated for large medieval bubonic plague epidemics. Estimating this important epidemiological parameter for bubonic plague greatly enhances existing knowledge of the epidemiology and transmission dynamics of the infection in Zambia and creates prospects for better management of the disease through informed planning. [ABSTRACT FROM AUTHOR]

The article offers information on the exponential increase of plastic burial in mangrove sediments as a major plastic sink. It mentions the sequestration of plastics in sediments as considered the ultimate sink of marine plastic pollution that would justify unexpectedly low loads found in surface waters. It discusses the global plastic production increase, confirming mangrove sediments as long-term sinks for plastics since 1950.

Objective: To investigate contemporary patient expectations and experiences of antibiotic prescribing in England. Background: Primary care providers' compliance with patient influences has been identified as a motivation for antibiotic‐prescribing behaviour. Since 2013, there have been concerted efforts to publicize and address the growing threat of antimicrobial resistance. A fresh qualitative insight into patient expectations and experiences is needed. Design: Qualitative study using semi‐structured interviews. Setting and participants: Two English regions, one an urban metropolitan area and the other a town in rural England. Patients who recently consulted for infections were recruited. The information power approach was used to determine the number of participants, yielding a sample of 31 participants. Main measures: Thematic analysis was carried out to analyse the interview data. Results: Five themes were identified: beliefs, expectations, experiences of taking antibiotic, experience of antimicrobial resistance and side‐effects, and experiences of consultations. The accounts reflected improved public knowledge: antibiotics were perceived to be much‐needed medicines that should be prescribed when appropriate. The data showed that patients formed expectations of expectations, trying to read the prescribers' intentions and reflect on the dependency between what prescribers and patients wanted. Patient experiences featured as nuanced and detailed with knowledge of AMR and side‐effects of antibiotics in the context of positive consultation experiences. Conclusions: The study highlighted complex interplays between adherence to antibiotics and consuming antibiotics in reflexive, informed ways. Ensuring that present and future patients are informed about potential benefits and harms of antibiotic use will contribute to future antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Background: In our clinic, a substantial number of patients present with transtibial residual limb pain of no specific somatic origin. Silicone liner induced tissue compression may reduce blood flow, possibly causing residual limb pain. Thus, as a first step we investigated if the liner itself has an effect on transcutaneous oxygen pressure (TcPO2). Methods: Persons with unilateral transtibial amputation and residual limb pain of unknown origin were included. Medical history, including residual limb pain, was recorded, and the SF-36 administered. Resting TcPO2 levels were measured in the supine position and without a liner at 0, 10, 20 and 30 minutes using two sensors: one placed in the Transverse plane over the tip of the Tibia End (= TTE), the other placed in the Sagittal plane, distally over the Peroneal Compartment (= SPC). Measurements were repeated with specially prepared liners avoiding additional pressure due to sensor placement. Statistical analyses were performed using SPSS. Results: Twenty persons (9 women, 11 men) with a mean age of 68.65 years (range 47–86 years) participated. The transtibial amputation occurred on average 43 months prior to study entry (range 3–119 months). With liner wear, both sensors measured TcPO2 levels that were significantly lower than those measured without a liner (TTE: p < 0.001; SPC: p = 0.002) after 10, 20 and 30 minutes. No significant differences were found between TcPO2 levels over time between the sensors. There were no significant associations between TcPO2 levels and pain, smoking status, age, duration of daily liner use, mobility level, and revision history. Conclusion: Resting TcPO2 levels decreased significantly while wearing a liner alone, without a prosthetic socket. Further studies are required to investigate the effect of liner wear on exercise TcPO2 levels. [ABSTRACT FROM AUTHOR]

The article discusses mandates for mask use in public during the coronavirus disease 2019 pandemic, by global shortage of commercial supplies, have led to widespread use of homemade masks. Topics include measurement setup has inexpensive and built and operated by nonexperts, allowing for rapid evaluation of mask performance during speech, and sneezing; and the term "face mask" governs a wide range of protective equipment with the primary function of reducing the transmission of particles.

The follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) are malignant and benign thyroid neoplasms, respectively. MicroRNA (miRNA) expressions have been touted as an indicator for prognostic outcome in thyroid cancer. The study objective was to explore genes suppressed by miRNA-21-3p and miRNA-21-5p for potential therapeutic insights. Differentially expressed genes and their functional enrichment were obtained from 25 FTA and 27 FTC gene microarray dataset GSE82208 using R and Bioconductor tools. The miRNA target sites were obtained from miR-TarBase database. A unique gene list of differentially expressed FTC and FTA were entered into miR-TarBase database to obtain target genes for both miRNA-21-3p and miRNA-21-5p. The result showed that miRNA-21-3p and miRNA-21-5p downregulated TIMP3, MAT2A, TGFBR2, and PLAT gene in FTC and FTA leading to significant expression of acute phase-response to metallothionein, metal ions, and unfolded protein response (UPR). The computational analysis suggests that the suppression of miRNA-21-3p and miRNA-21-5p could be an intervention strategy for therapeutically targeting FTC and FTA treatments. [ABSTRACT FROM AUTHOR]

Many predator species make regular excursions from near-surface waters to the twilight (200 to 1,000 m) and midnight (1,000 to 3,000m) zones of the deep pelagic ocean. While the occurrence of significant vertical movements into the deep ocean has evolved independently across taxonomic groups, the functional role(s) and ecological significance of these movements remain poorly understood. Here, we integrate results from satellite tagging efforts with model predictions of deep prey layers in the North Atlantic Ocean to determine whether prey distributions are correlated with vertical habitat use across 12 species of predators. Using 3D movement data for 344 individuals who traversed nearly 1.5 million km of pelagic ocean in >42,000 d, we found that nearly every tagged predator frequented the twilight zone and many made regular trips to the midnight zone. Using a predictive model, we found clear alignment of predator depth use with the expected location of deep pelagic prey for at least half of the predator species. We compared high-resolution predator data with shipboard acoustics and selected representative matches that highlight the opportunities and challenges in the analysis and synthesis of these data. While not all observed behavior was consistent with estimated prey availability at depth, our results suggest that deep pelagic biomass likely has high ecological value for a suite of commercially important predators in the open ocean. Careful consideration of the disruption to ecosystem services provided by pelagic food webs is needed before the potential costs and benefits of proceeding with extractive activities in the deep ocean can be evaluated. [ABSTRACT FROM AUTHOR]

ThTi2O6 derived compounds with the brannerite structure were designed, synthesised, and characterised with the aim of stabilising incorporation of U5+ or U6+, at dilute concentration. Appropriate charge compensation was targeted by co-substitution of Gd3+, Ca2+, Al3+, or Cr3+, on the Th or Ti site. U L3 edge X-ray Absorption Near Edge Spectroscopy (XANES) and High Energy Resolution Fluorescence Detected U M4 edge XANES evidenced U5+ as the major oxidation state in all compounds, with a minor fraction of U6+ (2–13%). The balance of X-ray and Raman spectroscopy data support uranate, rather than uranyl, as the dominant U6+ speciation in the reported brannerites. It is considered that the U6+ concentration was limited by unfavourable electrostatic repulsion arising from substitution in the octahedral Th or Ti sites, which share two or three edges, respectively, with neighbouring polyhedra in the brannerite structure. [ABSTRACT FROM AUTHOR]

Background: Randomized clinical trials have demonstrated efficacy and safety of erenumab. The aim of this study is to evaluate the effectiveness and safety of erenumab in a real-world setting in French patients with migraine associated with extreme unmet needs. Methods: This is a one year-prospective real-word study with enrolment of all consecutive adult patients included in the FHU InovPain registry who participated in a compassionate erenumab use program. Results: Of 144 patients included, 140 patients (82.1% female / mean age of 50.9 ± 11.4) received at least one dose of erenumab and were concerned by effectiveness and safety assessment. All patients had failed 11 oral preventive treatments. Most of them suffered from chronic migraine (88.6%) and presented a medication overuse (90.7%) at baseline. Thirty-eight (27.1%) discontinued treatment during the 12-month follow-up, with 22 (15.7%), 11 (7.9%) and 5 (3.6%) patients before 3, 6 or 9 months of treatment. The proportion of ≥ 50% responders at M3, M6, M9 and M12 was 74/140 (52.9%), 69/118 (58.5%), 61/107 (57.0%) and 60/102 (58.8%) respectively. At M3, the rate of reversion from chronic migraine to episodic migraine was 57.3% and the rate of transition from medication overuse to non-overuse was 46.5%. For monthly migraine days, the median (IQR) was 18.0 (13.0–26.0), 9.0 (5.0–17.0), 7.5 (5.0–14.0), 8.0 (5.0–12.5) and 8.0 (5.0–12.0) at M0, M3, M6, M9 and M12 respectively. For HIT-6 score, the median (IQR) was 68.0 (63.8–73.3), 60.0 (54.0–65.0), 60.0 (50.3–53.0), 59.0 (50.0–63.0) and 58.0 (50.0–62.9) at M0, M3, M6, M9 and M12 respectively. Fifty-three (37.9%) patients reported at least one of the following adverse events: cutaneous erythema and/or pain at the injection site for 42 (30%) patients, constipation for 22 (15.7%) patients, muscle spasm for 2 (1.4%) patients, alopecia for one (0.7%) patient and blood pressure increase in one (0.7%) patient. There was no serious adverse event. One female patient became pregnant after 5 months of exposure to erenumab with a safe evolution after treatment discontinuation. Conclusion: This first French real-world study related to migraine prevention with CGRP-mAbs confirms effectiveness and safety of erenumab in patients with extreme unmet needs. [ABSTRACT FROM AUTHOR]

Background: Efforts to reduce unnecessary antibiotic prescribing have coincided with increasing awareness of sepsis. We aimed to estimate the probability of sepsis following infection consultations in primary care when antibiotics were or were not prescribed.Methods and Findings: We conducted a cohort study including all registered patients at 706 general practices in the United Kingdom Clinical Practice Research Datalink, with 66.2 million person-years of follow-up from 2002 to 2017. There were 35,244 first episodes of sepsis (17,886, 51%, female; median age 71 years, interquartile range 57-82 years). Consultations for respiratory tract infection (RTI), skin or urinary tract infection (UTI), and antibiotic prescriptions were exposures. A Bayesian decision tree was used to estimate the probability (95% uncertainty intervals [UIs]) of sepsis following an infection consultation. Age, gender, and frailty were evaluated as association modifiers. The probability of sepsis was lower if an antibiotic was prescribed, but the number of antibiotic prescriptions required to prevent one episode of sepsis (number needed to treat [NNT]) decreased with age. At 0-4 years old, the NNT was 29,773 (95% UI 18,458-71,091) in boys and 27,014 (16,739-65,709) in girls; over 85 years old, NNT was 262 (236-293) in men and 385 (352-421) in women. Frailty was associated with greater risk of sepsis and lower NNT. For severely frail patients aged 55-64 years, the NNT was 247 (156-459) in men and 343 (234-556) in women. At all ages, the probability of sepsis was greatest for UTI, followed by skin infection, followed by RTI. At 65-74 years, the NNT following RTI was 1,257 (1,112-1,434) in men and 2,278 (1,966-2,686) in women; the NNT following skin infection was 503 (398-646) in men and 784 (602-1,051) in women; following UTI, the NNT was 121 (102-145) in men and 284 (241-342) in women. NNT values were generally smaller for the period from 2014 to 2017, when sepsis was diagnosed more frequently. Lack of random allocation to antibiotic therapy might have biased estimates; patients may sometimes experience sepsis or receive antibiotic prescriptions without these being recorded in primary care; recording of sepsis has increased over the study period.Conclusions: These stratified estimates of risk help to identify groups in which antibiotic prescribing may be more safely reduced. Risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following UTIs. [ABSTRACT FROM AUTHOR]

Frail older people have an inherent risk of polypharmacy due to the need to treat multiple comorbidities, thus leading to various negative effects on their health due to the adverse actions from the drugs. This issue was discussed from a person-centered perspective, highlighting the category of frail older adults who are at a higher risk. Appropriate medication reconciliation in this population with useful prescribing tools (Beers and START/STOPP criteria) to minimize polypharmacy and to provide alternative prescriptive intervention could go alongside primary care to reduce the extent of frailty and polypharmacy. Reducing delayed referrals and extended hospitalization with electronic health record systems and using the signs of frailty from the Electronic Frailty Index (EFI) to predict polypharmacy for frail older persons are preventative approaches that proactively respond to frailty associated with the risk of polypharmacy. [ABSTRACT FROM AUTHOR]

The binary manganese–rhodium (Mn–Rh) phase diagram was reinvestigated from 5 to 90 at.% Rh with focus on determining the transition temperature between the ordered γ′-Mn3Rh and the γ-Mn phase as well as the transition temperature between of the tetragonal and cubic MnRh phase and phase boundaries, applying XRD, DTA and SEM including EDX. A reassessment of the Mn–Rh phase diagram based on obtained and literature data is given. Furthermore, the phase equilibria of the ternary bismuth–manganese–rhodium (Bi–Mn–Rh) system were experimentally investigated, focusing on the possible existence of new ferromagnetic phases. Isothermal sections at 330 °C and 600 °C were studied applying powder XRD and EDX. The corresponding phase diagram was established based on these results. No additional ferromagnetic phase was found in the ternary system. [ABSTRACT FROM AUTHOR]

The Arctic Ocean is an early warning system for indicators and effects of climate change. We use a novel combination of experimental and time-series data on effects of ocean warming and acidification on the commercially important Northeast Arctic cod (Gadus morhua) to incorporate these physiological processes into the recruitment model of the fish population. By running an ecological-economic optimization model, we investigate how the interaction of ocean warming, acidification and fishing pressure affects the sustainability of the fishery in terms of ecological, economic, social and consumer-related indicators, ranging from present day conditions up to future climate change scenarios. We find that near-term climate change will benefit the fishery, but under likely future warming and acidification this large fishery is at risk of collapse by the end of the century, even with the best adaptation effort in terms of reduced fishing pressure. [ABSTRACT FROM AUTHOR]

Contrast gain control is the systematic adjustment of neuronal gain in response to the contrast of sensory input. It is widely observed in sensory cortical areas and has been proposed to be a canonical neuronal computation. Here, we investigated whether shunting inhibition from parvalbumin-positive interneurons—a mechanism involved in gain control in visual cortex—also underlies contrast gain control in auditory cortex. First, we performed extracellular recordings in the auditory cortex of anesthetized male mice and optogenetically manipulated the activity of parvalbumin-positive interneurons while varying the contrast of the sensory input. We found that both activation and suppression of parvalbumin interneuron activity altered the overall gain of cortical neurons. However, despite these changes in overall gain, we found that manipulating parvalbumin interneuron activity did not alter the strength of contrast gain control in auditory cortex. Furthermore, parvalbumin-positive interneurons did not show increases in activity in response to high-contrast stimulation, which would be expected if they drive contrast gain control. Finally, we performed in vivo whole-cell recordings in auditory cortical neurons during high- and low-contrast stimulation and found that no increase in membrane conductance was observed during high-contrast stimulation. Taken together, these findings indicate that while parvalbumin-positive interneuron activity modulates the overall gain of auditory cortical responses, other mechanisms are primarily responsible for contrast gain control in this cortical area. NEW & NOTEWORTHY We investigated whether contrast gain control is mediated by shunting inhibition from parvalbumin-positive interneurons in auditory cortex. We performed extracellular and intracellular recordings in mouse auditory cortex while presenting sensory stimuli with varying contrasts and manipulated parvalbumin-positive interneuron activity using optogenetics. We show that while parvalbumin-positive interneuron activity modulates the gain of cortical responses, this activity is not the primary mechanism for contrast gain control in auditory cortex. [ABSTRACT FROM AUTHOR]