The relative compliance of energy-storing tendons may be due to the helical fibril arrangement of their fascicles

T.S. acknowledges funding for this work from the EPSRC through grant no. EP/L017997/1

Measurement of Exercise Tolerance before Surgery (METS) study: a protocol for an international multicentre prospective cohort study of cardiopulmonary exercise testing prior to major non-cardiac surgery

Introduction: Preoperative functional capacity is considered an important risk factor for cardiovascular and other complications of major non-cardiac surgery. Nonetheless, the usual approach for estimating preoperative functional capacity, namely doctors’ subjective assessment, may not accurately predict postoperative morbidity or mortality. 3 possible alternatives are cardiopulmonary exercise testing; the Duke Activity Status Index, a standardised questionnaire for estimating functional capacity; and the serum concentration of N-terminal pro-B-type natriuretic peptide (NT pro-BNP), a biomarker for heart failure and cardiac ischaemia.Methods and analysis: The Measurement of Exercise Tolerance before Surgery (METS) Study is a multicentre prospective cohort study of patients undergoing major elective non-cardiac surgery at 25 participating study sites in Australia, Canada, New Zealand and the UK. We aim to recruit 1723 participants. Prior to surgery, participants undergo symptom-limited cardiopulmonary exercise testing on a cycle ergometer, complete the Duke Activity Status Index questionnaire, undergo blood sampling to measure serum NT pro-BNP concentration and have their functional capacity subjectively assessed by their responsible doctors. Participants are followed for 1?year after surgery to assess vital status, postoperative complications and general health utilities. The primary outcome is all-cause death or non-fatal myocardial infarction within 30?days after surgery, and the secondary outcome is all-cause death within 1?year after surgery. Both receiver-operating-characteristic curve methods and risk reclassification table methods will be used to compare the prognostic accuracy of preoperative subjective assessment, peak oxygen consumption during cardiopulmonary exercise testing, Duke Activity Status Index scores and serum NT pro-BNP concentration.Ethics and dissemination: The METS Study has received research ethics board approval at all sites. Participant recruitment began in March 2013, and 1-year follow-up is expected to finish in 2016. Publication of the results of the METS Study is anticipated to occur in 2017.<br/

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120

Balancing influence between actors in healthcare decision making

<p>Abstract</p> <p>Background</p> <p>Healthcare costs in most developed countries are not clearly linked to better patient and public health outcomes, but are rather associated with service delivery orientation. In the U.S. this has resulted in large variation in healthcare availability and use, increased cost, reduced employer participation in health insurance programs, and reduced overall population health outcomes. Recent U.S. healthcare reform legislation addresses only some of these issues. Other countries face similar healthcare issues.</p> <p>Discussion</p> <p>A major goal of healthcare is to enhance patient health outcomes. This objective is not realized in many countries because incentives and structures are currently not aligned for maximizing population health. The misalignment occurs because of the competing interests between "actors" in healthcare. In a simplified model these are individuals motivated to enhance their own health; enterprises (including a mix of nonprofit, for profit and government providers, payers, and suppliers, etc.) motivated by profit, political, organizational and other forces; and government which often acts in the conflicting roles of a healthcare payer and provider in addition to its role as the representative and protector of the people. An imbalance exists between the actors, due to the resources and information control of the enterprise and government actors relative to the individual and the public. Failure to use effective preventive interventions is perhaps the best example of the misalignment of incentives. We consider the current Pareto efficient balance between the actors in relation to the Pareto frontier, and show that a significant change in the healthcare market requires major changes in the utilities of the enterprise and government actors.</p> <p>Summary</p> <p>A variety of actions are necessary for maximizing population health within the constraints of available resources and the current balance between the actors. These actions include improved transparency of all aspects of medical decision making, greater involvement of patients in shared medical decision making, greater oversight of guideline development and coverage decisions, limitations on direct to consumer advertising, and the need for an enhanced role of the government as the public advocate.</p

Phytotoxic Effects of (±)-Catechin In vitro, in Soil, and in the Field

BACKGROUND: Exploring the residence time of allelochemicals released by plants into different soils, episodic exposure of plants to allelochemicals, and the effects of allelochemicals in the field has the potential to improve our understanding of interactions among plants. METHODOLOGY/PRINCIPAL FINDINGS: We conducted experiments in India and the USA to understand the dynamics of soil concentrations and phytotoxicity of (+/-)-catechin, an allelopathic compound exuded from the roots of Centaurea maculosa, to other plants in vitro and in soil. Experiments with single and pulsed applications into soil were conducted in the field. Experimental application of (+/-)-catechin to soils always resulted in concentrations that were far lower than the amounts added but within the range of reported natural soil concentrations. Pulses replenished (+/-)-catechin levels in soils, but consistently at concentrations much lower than were applied, and even pulsed concentrations declined rapidly. Different natural soils varied substantially in the retention of (+/-)-catechin after application but consistent rapid decreases in concentrations over time suggested that applied experimental concentrations may overestimate concentrations necessary for phytotoxicity by over an order of magnitude. (+/-)-Catechin was not phytotoxic to Bambusa arundinacea in natural Indian soil in a single pulse, but soil concentrations at the time of planting seeds were either undetectable or very low. However, a single dose of (+/-)-catechin suppressed the growth of bamboo in sand, in soil mixed with organic matter, and Koeleria macrantha in soils from Montana and Romania, and in field applications at 40 microg l(-1). Multiple pulses of (+/-)-catechin were inhibitory at very low concentrations in Indian soil. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that (+/-)-catechin is highly dynamic in natural soils, but is phytotoxic well below natural concentrations measured in some soils and applied at low concentrations in the field. However, there is substantial conditionality in the effects of the allelochemical

Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals

The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17β-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17β-Estradiol, 17α-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds—tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p′-DDT, p,p′-DDE, endosulfan, chlomequat chloride, and ethanol—varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods

The bashful and the boastful : prestigious leaders and social change in Mesolithic Societies

The creation and maintenance of influential leaders and authorities is one of the key themes of archaeological and historical enquiry. However the social dynamics of authorities and leaders in the Mesolithic remains a largely unexplored area of study. The role and influence of authorities can be remarkably different in different situations yet they exist in all societies and in almost all social contexts from playgrounds to parliaments. Here we explore the literature on the dynamics of authority creation, maintenance and contestation in egalitarian societies, and discuss the implications for our interpretation and understanding of the formation of authorities and leaders and changing social relationships within the Mesolithic

Recurrent Connections Aid Occluded Object Recognition by Discounting Occluders

Recurrent connections in the visual cortex are thought to aid object recognition when part of the stimulus is occluded. Here we investigate if and how recurrent connections in artificial neural networks similarly aid object recognition. We systematically test and compare architectures comprised of bottom-up (B), lateral (L) and top-down (T) connections. Performance is evaluated on a novel stereoscopic occluded object recognition dataset. The task consists of recognizing one target digit occluded by multiple occluder digits in a pseudo-3D environment. We find that recurrent models perform significantly better than their feedforward counterparts, which were matched in parametric complexity. Furthermore, we analyze how the network's representation of the stimuli evolves over time due to recurrent connections. We show that the recurrent connections tend to move the network's representation of an occluded digit towards its un-occluded version. Our results suggest that both the brain and artificial neural networks can exploit recurrent connectivity to aid occluded object recognition.Comment: 13 pages, 5 figures, accepted at the 28th International Conference on Artificial Neural Networks, published in Springer Lecture Notes in Computer Science vol 1172

Anatomical heterogeneity of tendon: Fascicular and interfascicular tendon compartments have distinct proteomic composition

This study was funded by the BBSRC (BB/K008412/1)

Evidence for Enhanced Mutualism Hypothesis: Solidago canadensis Plants from Regular Soils Perform Better

The important roles of plant-soil microbe interactions have been documented in exotic plant invasion, but we know very little about how soil mutualists enhance this process (i.e. enhanced mutualism hypothesis). To test this hypothesis we conducted two greenhouse experiments with Solidago canadensis (hereafter Solidago), an invasive forb from North America, and Stipa bungeana (hereafter Stipa), a native Chinese grass. In a germination experiment, we found soil microbes from the rhizospheres of Solidago and Stipa exhibited much stronger facilitative effects on emergence of Solidago than that of Stipa. In a growth and competition experiment, we found that soil microbes strongly facilitated Solidago to outgrow Stipa, and greatly increased the competitive effects of Solidago on Stipa but decreased the competitive effects of Stipa on Solidago. These findings from two experiments suggest that in situ soil microbes enhance the recruitment potential of Solidago and its ability to outcompete native plants, thereby providing strong evidence for the enhanced mutualism hypothesis. On the other hand, to some extent this outperformance of Solidago in the presence of soil microbes seems to be unbeneficial to control its rapid expansion, particularly in some ranges where this enhanced mutualism dominates over other mechanisms