Exercise for people with a fragility fracture of the pelvis or lower limb: A systematic review of interventions evaluated in clinical trials and reporting quality

Background. To aid design of exercise trials for people with pelvic and lower limb fragility fractures a systematic review was conducted to identify what types of exercise and mobility outcomes have been assessed, investigate intervention reporting quality, and evaluate risk of bias in published trials. Methods. Systematic searches of electronic databases (CENTRAL, MEDLINE, EMBASE, PEDro) 1996-2019 were conducted to identify randomised controlled trials of exercise for pelvic or lower limb fragility fractures. Two reviewers independently screened titles and abstracts. One reviewer extracted data, a second verified. Two reviewers independently assessed risk of bias. Intervention reporting quality was based on TIDieR, assessed by one reviewer and verified by a second. Narrative synthesis was undertaken. Registration. PROSPERO CRD42017060905. Results. Searches identified 37 trials including 3564 participants, median sample size 81(IQR 48-124), participants aged 81 years (IQR 79-82) and 76%(2536/3356) female. All trials focussed on people with hip fracture except one on ankle fracture. Exercise types focussed on resistance exercise in 14 trials, weight bearing exercise in 5 trials, 13 varied dose of sessions with health professionals, and 2 trials each focussed on treadmill gait training, timing of weight bearing or aerobic exercise. 30/37(81%) of trials reported adequate sequence generation, 25/37(68%) sufficient allocation concealment. 10/37(27%) trials lacked outcome assessor blinding. Of 65 exercise interventions, reporting was clear for 33(51%) in terms of when started, 61(94%) for where delivered, 49(75%) for who delivered, 47(72%) for group or individual, 29(45%) for duration, 46(71%) for session frequency, 8(12%) for full prescription details to enable the exercises to be reproduced, 32(49%) clearly reported tailoring or modification, and 23(35%) reported exercise adherence. Subjectively assessed mobility was assessed in 22/37(59%) studies and 29/37(78%) used an objective measure. Conclusions. All trials focussed on hip fracture, apart from one ankle fracture trial. Research into pelvic and other lower limb fragility fractures is indicated. A range of exercise types were investigated but to date deficiencies in intervention reporting hamper reproducibility. Adoption of TIDieR and CERT guidelines should improve intervention reporting as use increases. Trials would be improved by consistent blinded outcome assessor use and with consensus on which mobility outcomes should be assessed

Cortico-amygdalar connectivity and externalizing/internalizing behavior in children with neurodevelopmental disorders

Background: Externalizing and internalizing behaviors contribute to clinical impairment in children with neurodevelopmental disorders (NDDs). Although associations between externalizing or internalizing behaviors and cortico-amygdalar connectivity have been found in clinical and non-clinical pediatric samples, no previous study has examined whether similar shared associations are present across children with different NDDs. Methods: Multi-modal neuroimaging and behavioral data from the Province of Ontario Neurodevelopmental Disorders (POND) Network were used. POND participants aged 6–18 years with a primary diagnosis of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or obsessive–compulsive disorder (OCD), as well as typically developing children (TDC) with T1-weighted, resting-state fMRI or diffusion weighted imaging (DWI) and parent-report Child Behavioral Checklist (CBCL) data available, were analyzed (total n = 346). Associations between externalizing or internalizing behavior and cortico-amygdalar structural and functional connectivity indices were examined using linear regressions, controlling for age, gender, and image-modality specific covariates. Behavior-by-diagnosis interaction effects were also examined. Results: No significant linear associations (or diagnosis-by-behavior interaction effects) were found between CBCL-measured externalizing or internalizing behaviors and any of the connectivity indices examined. Post-hoc bootstrapping analyses indicated stability and reliability of these null results. Conclusions: The current study provides evidence towards an absence of a shared linear relationship between internalizing or externalizing behaviors and cortico-amygdalar connectivity properties across a transdiagnostic sample of children with different primary NDD diagnoses and TDC. Different methodological approaches, including incorporation of multi-dimensional behavioral data (e.g., task-based fMRI) or clustering approaches may be needed to clarify complex brain-behavior relationships relevant to externalizing/internalizing behaviors in heterogeneous clinical NDD populations

TRAIL inhibits oxidative stress in human aortic endothelial cells exposed to pro-inflammatory stimuli

Studies suggest that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has vasoprotective potential, as low levels of TRAIL cause accelerated vascular calcification, whereas exogenous TRAIL administration exhibits anti-atherosclerotic activity. The mechanism of TRAIL-mediated vasoprotection remains unclear. We studied the effects of TRAIL (100 ng/ml) on human aortic endothelial cells (HAECs) exposed to pro-atherogenic conditions; (a) oscillatory shear stress (±10 dynes/cm2) using the ibidi µ-slide fluidic system; (b) pro-inflammatory injury, that is, tumor necrosis factor alpha (TNF-α, 100 ng/ml) and hyperglycemia (30 mM d-glucose). End-points examined included inflammatory gene expression and reactive oxygen species (ROS) formation. TRAIL shifted the net gene expression toward an antioxidant phenotype in HAECs exposed to oscillatory shear stress. TRAIL significantly reduced ROS formation in HAECs exposed to both TNF-α and hyperglycemia. Therefore, TRAIL appears to confer atheroprotective effects on the endothelium, at least in part, by reducing oxidative stress

Quantification of the effect of in-utero events on lifetime resilience in dairy cows

Currently, the dairy industry is facing many challenges that could affect its sustainability, including climate change and public perception of the industry. As a result, interest is increasing in the concept of identifying resilient animals, those with a long productive lifespan, good reproductive performance and milk yield. There is much evidence that events in utero, i.e., the Developmental Origins of Health and Disease (DOHaD), alter life-course health of offspring and we hypothesized that these could alter resilience in calves, where resilience is identified using lifetime data. The aim of this study was to quantify lifetime resilience scores (LRS) using an existing scoring system based on longevity with secondary corrections for age at first calving and calving interval and to quantify the effects of in-utero events on the LRS using 2 data sets. The first was a large data set of cattle in 83 farms in Great Britain born from 2006 to 2015 and the second was a smaller, more granular data set of cattle born between 2003 and 2015 in the Langhill research herd at Scotland's Rural College. Events during dam's pregnancy included health events (lameness, mastitis, use of an antibiotic or anti-inflammatory medication), the impact of heat stress as measured by temperature-humidity index and perturbations in milk yield and quality (somatic cell count, percentage fat, percentage protein and fat:protein ratio). Daughters born to dams that experienced higher temperature-humidity indexes while they were in-utero during the first and third trimesters of pregnancy had lower LRS. Daughter LRS scores were also lower where milk yields or median fat percentages in the first trimester were low, and when milk yields were high in the third trimester. Dam LRS was positively associated with LRS of their offspring, however, as parity of the dam increased, LRS of their calves decreased. Similarly, in the Langhill herd, dams of a higher parity produced calves with lower LRS. Additionally, dams which recorded a high max locomotion score in the third trimester of pregnancy were negatively associated with lower calf LRS in the Langhill herd. Our results suggest that events that occur during pregnancy have lifelong consequences for the calf's lifetime performance. However, experience of higher temperature-humidity indexes, higher dam LRS scores and mothers in higher parities explained a relatively small proportion of variation in offspring LRS, which suggests that other factors play a substantial role in determining calf LRS scores. While 'big data' can contain a considerable amount of noise, similar findings between the 2 data sets indicate it is likely these findings are real.</p

Reproducible protocols for metagenomic analysis of human faecal phageomes

peer-reviewedAll sequence data used in the analyses were deposited in the Sequence read Archive (SRA) (http://www.ncbi.nlm.nih.gov/sra) under BioProject PRJNA407341. Sample IDs, meta data and corresponding accession numbers are summarised in Additional file 2: Table S2. All raw count tables, 16S taxonomic assignments, BLAST top hits for viral contigs and R code used for the analysis are available at (https://figshare.com/s/71163558b4f78e3e7ed6).Background Recent studies have demonstrated that the human gut is populated by complex, highly individual and stable communities of viruses, the majority of which are bacteriophages. While disease-specific alterations in the gut phageome have been observed in IBD, AIDS and acute malnutrition, the human gut phageome remains poorly characterised. One important obstacle in metagenomic studies of the human gut phageome is a high level of discrepancy between results obtained by different research groups. This is often due to the use of different protocols for enriching virus-like particles, nucleic acid purification and sequencing. The goal of the present study is to develop a relatively simple, reproducible and cost-efficient protocol for the extraction of viral nucleic acids from human faecal samples, suitable for high-throughput studies. We also analyse the effect of certain potential confounding factors, such as storage conditions, repeated freeze-thaw cycles, and operator bias on the resultant phageome profile. Additionally, spiking of faecal samples with an exogenous phage standard was employed to quantitatively analyse phageomes following metagenomic sequencing. Comparative analysis of phageome profiles to bacteriome profiles was also performed following 16S rRNA amplicon sequencing. Results Faecal phageome profiles exhibit an overall greater individual specificity when compared to bacteriome profiles. The phageome and bacteriome both exhibited moderate change when stored at + 4 °C or room temperature. Phageome profiles were less impacted by multiple freeze-thaw cycles than bacteriome profiles, but there was a greater chance for operator effect in phageome processing. The successful spiking of faecal samples with exogenous bacteriophage demonstrated large variations in the total viral load between individual samples. Conclusions The faecal phageome sequencing protocol developed in this study provides a valuable additional view of the human gut microbiota that is complementary to 16S amplicon sequencing and/or metagenomic sequencing of total faecal DNA. The protocol was optimised for several confounding factors that are encountered while processing faecal samples, to reduce discrepancies observed within and between research groups studying the human gut phageome. Rapid storage, limited freeze-thaw cycling and spiking of faecal samples with an exogenous phage standard are recommended for optimum results

Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.

Control of liver fluke infections remains a significant challenge in the livestock sector due to widespread distribution of drug resistant parasite populations. In particular, increasing prevalence and economic losses due to infection with Fasciola hepatica is a direct result of drug resistance to the gold standard flukicide, triclabendazole. Sustainable control of this significant zoonotic pathogen, therefore, urgently requires the identification of new anthelmintics. Plants represent a source of molecules with potential flukicidal effects and, amongst their secondary metabolites, the diterpenoid abietic acids can be isolated in large quantities. In this study, nineteen (19) chemically modified abietic acid analogues (MC_X) were first evaluated for their anthelmintic activities against F. hepatica newly excysted juveniles (NEJs, from the laboratory-derived Italian strain); from this, 6 analogues were secondly evaluated for their anthelmintic activities against adult wild strain flukes. One analogue, MC010, was progressed further against 8-week immature- and 12-week mature Italian strain flukes. Here, MC010 demonstrated moderate activity against both of these intra-mammalian fluke stages (with an adult fluke EC50 = 12.97 µM at 72 h post culture). Overt mammalian cell toxicity of MC010 was inferred from the Madin-Darby bovine kidney (MDBK) cell line (CC50 = 17.52 µM at 24 h post culture) and demonstrated that medicinal chemistry improvements are necessary before abietic acid analogues could be considered as potential anthelmintics against liver fluke pathogen

Efficient Methods for Natural Language Processing: A Survey

Recent work in natural language processing (NLP) has yielded appealing results from scaling model parameters and training data; however, using only scale to improve performance means that resource consumption also grows. Such resources include data, time, storage, or energy, all of which are naturally limited and unevenly distributed. This motivates research into efficient methods that require fewer resources to achieve similar results. This survey synthesizes and relates current methods and findings in efficient NLP. We aim to provide both guidance for conducting NLP under limited resources, and point towards promising research directions for developing more efficient methods.Comment: Accepted at TACL, pre publication versio

Sepsis: when a simple infection becomes deadly

The immune system plays a crucial role in maintaining a healthy body by working around the clock to recognize and respond to infection. Inflammation is part of the immune system’s protective response to an infection. The inflammatory response is incredibly powerful, so much so that it can damage the body’s cells if it is not tightly controlled. Sometimes, inflammation affects the whole body—this is called sepsis. The powerful and complex mechanisms in place to wipe out the infection can cause serious damage to healthy cells and tissues. Uncontrolled inflammation can cause irreversible damage to the body’s organs, such as the kidneys, eventually causing organs to shut down. If sepsis is not treated rapidly, it can lead to death. In this article, we describe the symptoms and diagnosis of sepsis and some of the current research being performed to better understand this dangerous process

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries