Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of locum GPs in antibiotic prescribing and stewardship: a mixed-methods study

Background Most antibiotics are prescribed in primary care. Locum or sessional GPs (locums) are perceived as contributing to higher prescribing and may face barriers to engaging with antimicrobial stewardship (AMS). Aim To identify how locums’ antibiotic prescribing compares with other general practice prescribers, and how they perceive their role in antibiotic prescribing and AMS. Design and setting Mixed-methods study in primary care. Method Data on antibiotic prescribing, diagnoses, and patient and prescriber characteristics were extracted from The Health Improvement Network database. A mixed-effects logistic model was used to compare locums’ and other prescribers’ antibiotic prescribing for conditions that do not usually benefit from antibiotics. Nineteen semi-structured telephone interviews were conducted with locums in England and analysed thematically. Results Locums accounted for 11% of consultations analysed. They prescribed antibiotics more often than other GPs and nurse prescribers for acute cough, sore throat, asthma and chronic obstructive pulmonary disease exacerbations, and acute bronchitis. The number of patients receiving antibiotics for these conditions was 4% higher (on absolute scale) when consulting with locums compared with when they consulted with other GPs. Four themes capture the perceived influences on prescribing antibiotics and AMS: antibiotic prescribing as a complex but individual issue, nature and patterns of locum work, relationships between practices and locums, and professional isolation. Conclusion Locums contribute to higher antibiotic prescribing compared with their peers. They experience challenges but also opportunities for contributing to AMS, which should be better addressed. With an increasing proportion of locums in general practice, they have an important role in antibiotic optimisation and AMS.
Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice

Chronic liver diseases are multifactorial and the need to develop effective therapies is high. Recent studies have shown the potential of ameliorating liver disease progression through protection of the liver endothelium. Polyamine spermidine (SPD) is a caloric restriction mimetic with autophagy-enhancing properties capable of prolonging lifespan and with a proven beneficial effect in cardiovascular disease in mice and humans. We evaluated the use of dietary supplementation with SPD in two models of liver disease (CCl4 and CDAAH diet). We analyzed the effect of SPD on endothelial dysfunction in vitro and in vivo. C57BL/6J mice were supplemented with SPD in the drinking water prior and concomitantly with CCl4 and CDAAH treatments. Endothelial autophagy deficient (Atg7endo) mice were also evaluated. Liver tissue was used to evaluate the impact of SPD prophylaxis on liver damage, endothelial dysfunction, oxidative stress, mitochondrial status, inflammation and liver fibrosis. SPD improved the endothelial response to oxidative injury in vitro and improved the liver endothelial phenotype and protected against liver injury in vivo. SPD reduced the overall liver oxidative stress and improved mitochondrial fitness. The absence of benefits in the Atg7endo mice suggests an autophagy-dependent effect of SPD. This study suggests SPD diet supplementation in early phases of disease protects the liver endothelium from oxidative stress and may be an attractive approach to modify the chronic liver disease course and halt fibrosis progression.
Weibull-Fréchet random path length model for avalanche gain and noise in photodiodes

A four-parameter Weibull-Fréchet (WF) distribution function has been introduced in the random path length (RPL) model for nonlocal modelling of soft-threshold ionisation in semiconductors. The WF function has been demonstrated to be capable of reproducing the realistic probability distribution function (PDF) of electron and hole ionisation path lengths extracted from full band Monte Carlo (FBMC) transport simulations of bulk GaAs. The electron-initiated multiplication in GaAs avalanche photodiodes (APDs) calculated by the WF-RPL model is in excellent agreement with the results from FBMC. The predicted excess noise factor is closer to that of FBMC as compared to the hard threshold RPL model. The advantage of this improved RPL model as a tool for predicting the PDF of electron and hole ionisation path lengths in AlAs0.56Sb0. 44 from the experimentally measured avalanche gain and noise has been analysed. The electron ionisation path length PDF of AlAs0.56Sb0. 44 has a unique feature of two decay rates with a narrow full width at half maximum and a long tail. The extremely low hole ionisation coefficient in AlAs0.56Sb0. 44 is found with a PDF of ionisation path length spanning over 50 µm at an electric field of 600 kVcm−1, supporting the very low hole feedback ionisation in AlAs0.56Sb0. 44 APDs. The combination of the detailed and peaked electron’s ionisation path length PDF and of the broad hole’s ionisation path length PDF is responsible for the extremely low avalanche noise in the 1.55 µm thick AlAs0.56Sb0. 44 APDs.
The mediterranean diet: Healthy and sustainable dietary pattern in the time of Sars-Cov-2

COVID-19, first reported in Wuhan, China in December 2019 quickly spread worldwide leading to serious health, social and economic consequences. A crucial role in the pathogenesis of severe disease has been attributed to the inflammatory status, that in more severe cases may evolve in an overproduction of pro-inflammatory cytokines (“cytokine storm)” and fatal outcome. Non-communicable diseases, nutritional disorders and advanced age, conditions associated with a low-grade systemic inflammation and immune function alterations, have been identified as major risks for severe COVID-19. General recommendations for fighting COVID-19 highlighted the paramount importance of adopting a healthy plant-based dietary pattern and healthy lifestyle. The Mediterranean dietary pattern is considered as one of the healthiest dietary patterns, and its benefits are supported by a large body of evidence. Furthermore, it is considered as a sustainable lifestyle model. The aim of this research was to update the multiple benefits of the Mediterranean dietary pattern on physical and mental health, focusing on the effects that it may have in combating COVID-19. The potential effects and mechanisms of action of the main bioactive components of Mediterranean diet were also analyzed. Considering its effects in modulating inflammation and oxidative stress and supporting the immune system, the Mediterranean dietary pattern may be considered the most promising dietary approach to combat COVID-19.
One-Stage Multilevel Surgery for Treatment of Obstructive Sleep Apnea Syndrome

We report the results of one-stage multilevel upper airway surgery for patients who could not tolerate continuous positive airway pressure (CPAP). Patients treated with multilevel surgery at a University Hospital in 2015–2019 were identified from a prospectively maintained database. The inclusion criteria were aged 18–70 years, body mass index (BMI) < 35 kg/m2, apnea–hypopnea index (AHI) > 20, and lingual tonsil hypertrophy grade 3 or 4. Drug-induced sleep endoscopy was performed before surgery in all patients. Multilevel surgery was performed in one stage and included expansion sphincter pharyngoplasty (ESP), coblation tongue base reduction (CTBR), and partial epiglottectomy (PE) as required. The outcome measures were postoperative AHI, time percentage oxygen saturation < 90%, and Epworth Sleepiness Scale (ESS) score. A total of 24 patients were included: median age 49.1 years, average BMI 27.26 kg/m2, and 90% men. Ten patients received ESP plus CTBR plus PE, eight received ESP plus CTBR, and six received ESP plus PE. The mean preoperative AHI was 33.01 at baseline and improved to 17.7 ± 13 after surgery (p < 0.05). The ESS score decreased from 11 ± 5.11 to 7.9 ± 4.94 (p < 0.05). The surgical success rate according to Sher’s criteria was 82.3%. The median follow-up was 23.3 months (range 12–36). These findings suggest that multilevel surgery is a safe and successful treatment of OSAHS.
fcfdr: an R package to leverage continuous and binary functional genomic data in GWAS

Genome-wide association studies (GWAS) are limited in power to detect associations that exceed the stringent genome-wide significance threshold. This limitation can be alleviated by leveraging relevant auxiliary data, such as functional genomic data. Frameworks utilising the conditional false discovery rate have been developed for this purpose, and have been shown to increase power for GWAS discovery whilst controlling the false discovery rate. However, the methods are currently only applicable for continuous auxiliary data and cannot be used to leverage auxiliary data with a binary representation, such as whether SNPs are synonymous or non-synonymous, or whether they reside in regions of the genome with specific activity states. We describe an extension to the cFDR framework for binary auxiliary data, called “Binary cFDR”. We demonstrate FDR control of our method using detailed simulations, and show that Binary cFDR performs better than a comparator method in terms of sensitivity and FDR control. We introduce an all-encompassing user-oriented CRAN R package (https://annahutch.github.io/fcfdr/; https://cran.r-project.org/web/packages/fcfdr/index.html) and demonstrate its utility in an application to type 1 diabetes, where we identify additional genetic associations. Our all-encompassing R package, fcfdr, serves as a comprehensive toolkit to unite GWAS and functional genomic data in order to increase statistical power to detect genetic associations.
Statistics on Jupiter’s Current Sheet With Juno Data: Geometry, Magnetic Fields and Energetic Particles

Jupiter’s magnetosphere contains a current sheet of huge size near its equator. The current sheet not only mediates the global mass and energy cycles of Jupiter’s magnetosphere, but also provides a site for many localized dynamic processes, such as reconnection and wave‐particle interaction. To correctly evaluate its role in these processes, a statistical description of the current sheet is required. To this end, here we conduct statistics on Jupiter’s current sheet, by using four‐year Juno data obtained in the 20–100 Jupiter radius, 0–6 local time magnetosphere. The statistics show the thickness of the current sheet is comparable with the gyro‐radius of ions dominating the plasma pressure. Magnetic fields in the current sheet decrease in power‐law with increasing radial distances. At given energy, the flux of energetic electrons and protons increases with decreasing radial distances. On the other hand, at given radial distances, the flux decreases in power‐law with increasing energy. The flux also varies with the distances to the current sheet center. The corresponding relationship can be described by a Gaussian function peaking at the current sheet center. In addition, the statistics show the flux of oxygen‐ and sulfur‐group ions is comparable with the flux of protons at the same energy and radial distances, indicating the non‐negligible role of heavy ions in the current sheet dynamics. From these results, a statistical model is constructed, providing us with a starting point of understanding the dynamics of the whole Jupiter’s magnetosphere.
A Systematic Review of Studies on Genotoxicity and Related Biomarkers in Populations Exposed to Pesticides in Mexico

In agricultural activities, pest control is essential, and the most effective method is the use of chemical agents that also represent an important source of exposure to potentially toxic compounds. Pesticides constitute a heterogeneous group of compounds designed specifically to control different pests. Besides measuring their levels or that of their metabolites in air, plasma, serum, blood, urine, etc., some studies reported increased DNA damage levels after occupational or environmental pesticides exposure, evidenced by several cytogenetic biomarkers such as chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei frequency (MN) together with other nuclear abnormalities (NA), alkaline comet assay, but also changes in oxidative stress parameters and miRNA levels. Single or combined, these techniques have also been used in genotoxic biomonitoring studies of workers occupationally exposed to pesticides in Mexico. Despite being a country with great agricultural activity and reported excessive pesticide use, genotoxic studies have been relatively few and, in some cases, contradictory. A review was made of the studies available (published until the end of 2020 on PubMed, Web of Science, Redalyc and Scielo, both in English and Spanish) in the scientific literature that evaluated occupational exposure of human samples to pesticides assessed with DNA damage and related biomarkers in Mexico.
Predictors and long-term prognosis of early and late recurrence for patients undergoing hepatic resection of hepatocellular carcinoma: a large-scale multicenter study

Background Recurrence is common among patients undergoing hepatic resection for hepatocellular carcinoma (HCC), which greatly limits long-term survival. We aimed to identify predictors and long-term prognosis of early and late recurrence after HCC resection. Methods Multicenter data of patients who underwent HCC resection between 2002 and 2016 were analyzed. Recurrence was divided into early (≤2 years) and late recurrence (>2 years after surgery). Predictors of early and late recurrence, and prognostic factors of post-recurrence survival (PRS) were identified by univariate and multivariate analyses. Results Among 1,426 patients, 554 (38.8%) and 348 (24.4%) developed early and late recurrence, respectively. Independent predictors associated with early recurrence included preoperative alpha-fetoprotein level >400 µg/L, resection margin <1 cm, and tumor size >5.0 cm, multiplicity, macrovascular and microvascular invasion, and satellites of the initial tumor at the first diagnosis of HCC; independent predictors associated with late recurrence included male, cirrhosis, and tumor size >5.0 cm, multiplicity, macrovascular and microvascular invasion, and satellites of the initial tumor. Patients with early recurrence had a lower likelihood of undergoing potentially curative treatments for recurrence (37.2% vs. 48.0%, P<0.001) and a worse median PRS (13.5 vs. 36.6 months, P<0.001) vs. patients who had late recurrence. Multivariate analysis revealed that early recurrence and irregular postoperative surveillance were independently associated with worse PRS [hazard ratio (HR) =1.250, 95% CI: 1.016–1.538, P=0.035; and HR =1.983, 95% CI: 1.677–2.345, P<0.001]. Conclusions Predictors associated with early and late recurrence after curative resection for patients with HCC were generally same, although several did differ. Patients with late recurrence had better long-term survival than patients with early recurrence.
Genetic Variation in ABCC4 and CFTR and Acute Pancreatitis during Treatment of Pediatric Acute Lymphoblastic Leukemia

Background: Acute pancreatitis (AP) is a serious, mechanistically not entirely resolved side effect of L-asparaginase-containing treatment for acute lymphoblastic leukemia (ALL). To find new candidate variations for AP, we conducted a genome-wide association study (GWAS). Methods: In all, 1,004,623 single-nucleotide variants (SNVs) were analyzed in 51 pediatric ALL patients with AP (cases) and 1388 patients without AP (controls). Replication used independent patients. Results: The top-ranked SNV (rs4148513) was located within the ABCC4 gene (odds ratio (OR) 84.1; p = 1.04 × 10−14). Independent replication of our 20 top SNVs was not supportive of initial results, partly because rare variants were neither present in cases nor present in controls. However, results of combined analysis (GWAS and replication cohorts) remained significant (e.g., rs4148513; OR = 47.2; p = 7.31 × 10−9). Subsequently, we sequenced the entire ABCC4 gene and its close relative, the cystic fibrosis associated CFTR gene, a strong AP candidate gene, in 48 cases and 47 controls. Six AP-associated variants in ABCC4 and one variant in CFTR were detected. Replication confirmed the six ABCC4 variants but not the CFTR variant. Conclusions: Genetic variation within the ABCC4 gene was associated with AP during the treatment of ALL. No association of AP with CFTR was observed. Larger international studies are necessary to more conclusively assess the risk of rare clinical phenotypes.
Decentralized uniform finite‐time stabilization of large‐scale nonlinear networks by small‐gain theorems

We solve the problem of decentralized uniform finite‐time stabilization for a large‐scale network of nonlinear systems in triangular form which are not feedback linearizable and whose input–output maps are not invertible. For this, we provide a new recursive design to satisfy the conditions of a certain modification of the small‐gain theorems for the case of the uniform finite‐time stability of large‐scale networks. In the general case, we consider the general triangular form systems whose input–output links are surjections only. In addition, we consider the special case of the triangular form systems with polynomial integrators, which is also needed as the first step of the proof of our main result. In the latter case, the design becomes constructive, the decentralized stabilizers can be designed explicitly, and this is demonstrated by examples.
Epidemiology of Malnutrition among Children with Cerebral Palsy in Low- and Middle-Income Countries: Findings from the Global LMIC CP Register

Background: This study aimed to describe the epidemiology of malnutrition among children with cerebral palsy (CP) in low- and middle-income countries (LMICs). Methods: Data from children with confirmed CP aged <18 years registered into the Global LMIC CP Register (GLM CPR) from Bangladesh, Indonesia, Nepal, and Ghana were included. Anthropometric measurements were collected, and nutritional status was determined following the WHO guidelines. Descriptive statistics and adjusted logistic regression were used to describe the nutritional status and identify predictors of malnutrition. Results: Between January 2015 and December 2020, 3619 children with CP were registered into the GLM CPR (median age at assessment: 7.0 years, 39% female). Overall, 72–98% of children from Bangladesh, Indonesia, Nepal, and Ghana had at least one form of undernutrition. The adjusted analysis showed, older age, low maternal education, spastic tri/quadriplegia, and Gross Motor Functional Classification System (GMFCS) levels III–V were significant predictors of underweight and stunting among children with CP in Bangladesh. In Nepal, female children, GMFCS III–V had higher odds of underweight and stunting. In Ghana, low maternal education was significantly associated with underweight, whereas older age and the presence of associated impairments were the significant predictors of stunting among children with CP. Having a GMFCS of III–V increased the odds of being underweight among children in Indonesia; however, no predictors were identified for stunting, as nearly all children with CP registered from Indonesia were stunted. Conclusion: Most children with CP in GLM CPR had undernutrition. Maternal education and moderate-to-severe motor impairment (GMFCS III–V) were significant predictors. Practical nutrition education to mothers/caregivers and management guidelines according to the motor severity using local resources could improve the nutritional outcome of children with CP in LMICs.
Evaluation of Greenhouse Gas Emissions from Reservoirs: A Review

In order to evaluate the greenhouse gas (GHG) emissions from a reservoir or from several reservoirs in a country or a climatic zone, simpler or more complex models based on measurements and analyses of emissions presented in the literature were developed, which take into account one or more reservoir-specific parameters. The application of the models in the assessment of GHG emissions from a multipurpose reservoir gave values that are more or less close to the average values reported in the literature for the temperate zone reservoirs. This is explained by the fact that some models only consider emissions caused by impoundment and not degassing, spillway emissions, and downstream emissions, or those that use different calculation periods. The only model that calculates GHG emissions over the life cycle that occur pre-impoundment, post-impoundment, from unrelated anthropogenic sources and due to the reservoir construction is the model used by the G-res tool. In addition, this tool is best suited for multipurpose reservoirs because it allocates GHG emissions for each use, thus facilitating the correct reporting of emissions. The G-res tool used to calculate GHG emissions from the Stânca-Costești Multipurpose Reservoir shows that this is a sink of GHG with a net emission of −5 g CO2eq/m2/yr (without taking into account the emissions due to dam construction).
Meta-Analysis of the Association between Asbestos Exposure and Esophageal Cancer

Background: We conducted a meta-analysis to quantitatively assess the association between asbestos exposure and esophageal cancer. Methods: We systematically collected articles from three electronic databases and calculated the pooled standardized mortality rate (SMR) from the meta-analysis. Subgroup analysis according to the type of asbestos exposure, follow-up years, sample size, industry classification, sex, and high-dose exposure was conducted. Results: From 242 studies, 34 cohort studies were included in our meta-analysis. Pooled SMR was positively associated with asbestos exposure and esophageal cancer (pooled SMR = 1.28; 95% confidence interval (CI) 1.19–1.38, p < 0.00001). In the subgroup analysis, (1) chrysolite, (2) four groups with follow-up over ten years, (3) the textile industry and shipyard, (4) both male and female, and (5) eight studies on highest asbestos exposure, all the subgroups showed significantly increased pooled SMRs. Conclusion: Asbestos exposure was significantly and positively associated with esophageal cancer, especially chrysolite. Considering the long latency period, we suggest that patients should be followed up for cancer, including esophageal cancer, for over ten years.
Introducing coordination in hand position analysis during a steering wheel-based tracking task using fuzzy sets

Abstract This paper describes a new approach to analyse the way both hands are placed in relation to the steering wheel. The study is based on a 2D-tracking task, in which the stimulus is a steering wheel angle signal recorded while driving on 7 road geometries in real situations at 30 km/h. Hand movements are measured using a 3D-motion capture system. Data analysis is based on the segmentation of the hand angular position using 8 fuzzy angle windows (labelled as approximately 0°, approximately 45°, etc.), when the hand rests on the steering wheel, one window, else. To obtain information about the coordination aspect, 9 × 9 bivariate windows are considered for each time sample (recorded at 25 Hz); then, the average membership values are computed for each individual driving situation. The individual membership value sets related to the road geometries are studied via Correspondence Analysis, allowing to displaying both the inter- and intra-individual differences and the most discriminating bivariate windows. The methodology with 9 × 9 windows is more complex but implies less information loss than alternative ones e.g. when the two hands are separately analysed, which constitutes 9 + 9 windows and contains no information about the coordination aspect.