A forward dynamics simulation study of increasing load on the anterior cruciate ligament of the knee, for young women performing recreational drop jump activities.

Anterior Cruciate Ligament (ACL) injuries are among the most common injuries incurred by both recreational and professional athletes. ACL injuries often occur during popular contact sports like basketball, football, volleyball and baseball, and non-contact activities like aerobics, jogging and running. Non-contact actions like jumping, sprinting and sidecutting that involve sudden or rapid changes in motion may lead to ACL injuries. At the instance of an injury, the knee joint muscles and ligaments typically undergo extremely high loads. The ACL, which is an integral part of the knee joint undergo high strain rates and rapid energy absorption, and consequently get injured. As has been shown by others, ACL injury is related to a number of dynamic variables of the knee joint. An important observation made in recent years is that recreational (also professional) female athletes have higher incidences of noncontact ACL injuries than males 33, 35. The primary focus of this study was to determine effects of several dynamic variables, associated with both knee and ACL, during normal recreational drop-jump activities performed by young female athletes. Subjects recruited were eleven young adult female recreational athletes who felt comfortable participating in the drop-jump activities, from heights of 30, 40 and 50 cm. Using a simulation environment to recreate the trials, changes in ACL load and strain were observed along with several dynamic variables related to ACL load and strain, among which the three most important were, 1. knee flexion, 2. knee valgus (abduction) which may be accompanied by increased internal rotation, and, 3. flexor to extensor muscle recruitment ratios, i.e., the co-contraction of flexor and extensor muscles. Observations from the above simulations formed the basis of the final step involving forward dynamic simulation, where the knee joint was subject to higher valgus by decreasing the distance between the knees (medial translation). Significant changes to ACL load and strain were seen in the added medial translation simulations compared to the simulations from the original jumps. Mean fiber strain for the additional valgus simulation increased from 8.82 ± 0.08 % to 11.82 ± 0.04 % for the right ACL and from 8.18 ± 0.08 % to 11.34 ± 0.06 % for the left. Mean ACL tensile force increased from 1058.19 ± 2.04 N to 1102.19 ± 1.86 N for the right ACL and from 1056.77 ± 12.36 N to 1099.99 ± 2.02 N for the left. Average peak (from eleven subjects) ACL tensile force increased from 1165.36 ± 123.83 N to 1197.07 ± 129.11 N for the right ACL and from 1160.64 ± 121.32 N to 1193.11 ± 130.16 N for the left

Noncompact Symmetries in String Theory

Noncompact groups, similar to those that appeared in various supergravity theories in the 1970's, have been turning up in recent studies of string theory. First it was discovered that moduli spaces of toroidal compactification are given by noncompact groups modded out by their maximal compact subgroups and discrete duality groups. Then it was found that many other moduli spaces have analogous descriptions. More recently, noncompact group symmetries have turned up in effective actions used to study string cosmology and other classical configurations. This paper explores these noncompact groups in the case of toroidal compactification both from the viewpoint of low-energy effective field theory, using the method of dimensional reduction, and from the viewpoint of the string theory world sheet. The conclusion is that all these symmetries are intimately related. In particular, we find that Chern--Simons terms in the three-form field strength $H_{\mu\nu\rho}$ play a crucial role.Comment: 40 pages, phyzzx, CALT-68-179

Differential prefrontal and subcortical circuitry engagement during encoding of semantically related words in patients with late‐life depression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109350/1/gps4165.pd

Evidence for social learning in a family living lizard

This work was funded by the Australian Research Council (DP130102998 to MW and RB). DWAN was supported by an ARC DECRA (DE150101774) and UNSW VC Fellowship. JR was supported by the Natural Sciences and Engineering Research Council of Canada, and Macquarie University.Social learning is widespread among family living species, particularly mammals and birds with relatively high levels of social complexity and overt social interaction. However, the occurrence of social learning has never been documented in lizards with kin-based sociality, which have less obvious social interactions. We tested for social learning in Australian tree skinks (Egernia striolata), a species that commonly lives in family groups in the wild, using a two-step foraging task. Lizards were randomly allocated to either a social learning treatment or a control group and presented first with an instrumental task requiring the displacement of a lid, followed by an association task, consisting of two dishes with different colored lids. Prior to each task, lizards in the social learning treatment observed a trained demonstrator extract a food reward while the control also viewed a conspecific, but in the absence of the foraging task. The social learning treatment and control group solved the instrumental task at similar rates, but in the association task lizards in the social learning treatment made fewer errors and reached our learning criterion sooner. To the best of our knowledge, we present the first evidence for social learning in a lizard with kin-based sociality.Publisher PDFPeer reviewe

Variability in COVID-19 in-hospital mortality rates between national health service trusts and regions in England: A national observational study for the Getting It Right First Time Programme

Background A key first step in optimising COVID-19 patient outcomes during future case-surges is to learn from the experience within individual hospitals during the early stages of the pandemic. The aim of this study was to investigate the extent of variation in COVID-19 outcomes between National Health Service (NHS) hospital trusts and regions in England using data from March–July 2020. Methods This was a retrospective observational study using the Hospital Episode Statistics administrative dataset. Patients aged ≥ 18 years who had a diagnosis of COVID-19 during a hospital stay in England that was completed between March 1st and July 31st, 2020 were included. In-hospital mortality was the primary outcome of interest. In secondary analysis, critical care admission, length of stay and mortality within 30 days of discharge were also investigated. Multilevel logistic regression was used to adjust for covariates. Findings There were 86,356 patients with a confirmed diagnosis of COVID-19 included in the study, of whom 22,944 (26.6%) died in hospital with COVID-19 as the primary cause of death. After adjusting for covariates, the extent of the variation in-hospital mortality rates between hospital trusts and regions was relatively modest. Trusts with the largest baseline number of beds and a greater proportion of patients admitted to critical care had the lowest in-hospital mortality rates. Interpretation There is little evidence of clustering of deaths within hospital trusts. There may be opportunities to learn from the experience of individual trusts to help prepare hospitals for future case-surges

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Effects of Chronic Calorie Restriction or Dietary Resveratrol Supplementation on Insulin Sensitivity Markers in a Primate, Microcebus murinus

The prevalence of diabetes and hyperinsulinemia increases with age, inducing metabolic failure and limiting lifespan. Calorie restriction (CR) without malnutrition delays the aging process, but its long-term application to humans seems difficult. Resveratrol (RSV), a dietary polyphenol, appears to be a promising CR mimetic that can be easily administered in humans. In this work, we hypothesized that both CR and RSV impact insulin sensitivity in a non-human primate compared to standard-fed control (CTL) animals. Four- to five-year-old male grey mouse lemurs (Microcebus murinus) were assigned to three dietary groups: a CTL group, a CR group receiving 30% fewer calories than the CTL and a RSV group receiving the CTL diet supplemented with RSV (200 mg·day−1·kg−1). Insulin sensitivity and glycemia were assessed using an oral glucose tolerance test (OGTT) and the homeostasis model assessment of insulin resistance (HOMA-IR index) evaluation after 21 or 33 months of chronic treatment. Resting metabolic rate was also measured to assess the potential relationships between this energy expenditure parameter and insulin sensitivity markers. No differences were found after a 21-month period of treatment, except for lower glucose levels 30 min after glucose loading in CR animals. After 33 months, CR and RSV decreased glycemia after the oral glucose loading without decreasing fasting blood insulin. A general effect of treatment was observed on the HOMA-IR index, with an 81% reduction in CR animals and 53% in RSV animals after 33 months of treatment compared to CTL. Chronic CR and dietary supplementation with RSV affected insulin sensitivity by improving the glucose tolerance of animals without disturbing their baseline insulin secretion. These results suggest that both CR and RSV have beneficial effects on metabolic alterations, although these effects are different in amplitude between the two anti-aging treatments and potentially rely on different metabolic changes