Spatial organisation of expanding bacterial colonies is affected by contact-dependent growth inhibition

Identifying how microbes are able to manipulate, survive and thrive in complex multispecies communities has expanded our understanding of how microbial ecosystems impact human health and the environment. The ability of bacteria to negatively affect neighbours, through explicit toxin delivery systems, provides them with an opportunity to manipulate the composition of growing microbial communities. Contact-dependent inhibition (CDI) systems (a Type Vb secretion system) are a distinct subset of competition systems whose contribution to shaping the development of spatially-structured bacterial communities are yet to be fully understood. Here we compare the impact of different CDI systems, at both the single cell and population level, to determine the key drivers of CDI-mediated competition within spatially-structured bacterial populations. Through an iterative approach using both an Escherichia coli experimental system and computational modelling, we show that CDI systems have subtle and system-specific effects at the single cell level, generating single cell wide boundaries between CDI-expressing inhibitor cells and their neighbouring targets. Despite the subtle effects of CDI at a single cell level, CDI systems greatly diminished the ability of susceptible targets to expand their range during colony growth. The inoculum density of the population, together with the CDI system-specific variables of the speed of inhibition after contact and biological cost of CDI, strongly affects CDI-mediated competition. In contrast, the magnitude of the toxin-induced growth retardation of target cells only weakly impacts the composition of the population. Our work reveals how distinct CDI systems can differentially affect the composition and spatial arrangement of bacterial populations

Sprint performance and propulsion asymmetries on an ergometer in trained high- and low-point wheelchair rugby players

The purpose of this study was to examine the propulsion asymmetries of wheelchair athletes whilst sprinting on an instrumented, dual-roller ergometer system. Eighteen experienced wheelchair rugby players (8 low-point (LP) (class ≤1.5) and 10 high-point (HP) (class ≥2.0)) performed a 15s sprint in their sports wheelchair on the instrumented ergometer. Asymmetry was defined as the difference in distance and power output (PO) between left and right sides when the best side reached 28m. Propulsion techniques were quantified based on torque and velocity data. HP players covered an average 3m further than the LP players (P=0.002) and achieved faster sprint times than LP players (6.95 ± 0.89 vs. 8.03 ± 0.68 s, P=0.005) and at the time the best player finished (5.96 s). Higher peak PO’s (667 ± 108 vs. 357 ± 78 W, P=0.0001) and greater peak speeds were also evident were for HP players (4.80 ± 0.71 vs. 4.09 ± 0.45 m·s-1, P=0.011). Greater asymmetries were found in HP players for distance (1.86 ± 1.43 vs. 0.70 ± 0.65 m, P=0.016), absolute peak PO (P=0.049) and speed (0.35 ± 0.25 vs. 0.11 ± 0.10 m·s-1, P=0.009). Although HP players had faster sprint times over 28m (achieved by a higher PO), high standard deviations show the heterogeneity within the two groups (e.g. some LP players were better than HP players). Quantification of asymmetries is not only important for classifiers but also for sports practitioners wishing to improve performance as they could be addressed through training and/or wheelchair configuration

Measuring handrim wheelchair propulsion in the lab: a critical analysis of stationary ergometers

There are many ways to simulate handrim wheelchair propulsion in the laboratory. Ideally, these would be able to, at least mechanically, simulate field conditions. This narrative review provides an overview of the lab-based equipment used in published research and critically assesses their ability to simulate and measure wheelchair propulsion performance. A close connection to the field can only be achieved if the instrument can adequately simulate frictional losses and inertia of real-life handrim wheelchair propulsion, while maintaining the ergonomic properties of the wheelchair-user interface. Lab-based testing is either performed on a treadmill or a wheelchair ergometer (WCE). For this study WCEs were divided into three categories: roller, flywheel, and integrated ergometers. In general, treadmills are mechanically realistic, but cannot simulate air drag and acceleration tasks cannot be performed; roller ergometers allow the use of the personal wheelchair, but calibration can be troublesome; flywheel ergometers can be built with commerciallyavailable parts, but inertia is fixed and the personal wheelchair cannot be used; integrated ergometers do not employ the personal wheelchair, but are suited for the implementation of different simulation models and detailed measurements. Lab-based equipment is heterogeneous and there appears to be little consensus on how to simulate field conditions

Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial)

Contains fulltext : 69534.pdf (publisher's version ) (Open Access)BACKGROUND: With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction.The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. METHODS/DESIGN: The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. DISCUSSION: The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease. TRIAL REGISTRATION: Nederlands Trial Register NTR1150

Psychosocial determinants of sustained maternal functional impairment: longitudinal findings from a pregnancy-birth cohort study in rural Pakistan

Function is an important marker of health throughout the life course, however, in low-and-middle-income-countries, little is known about the burden of functional impairment as women transition from pregnancy to the first year post-partum. Leveraging longitudinal data from 960 women participating in the Share Child Cohort in Pakistan, this study sought to (1) characterize functional trajectories over time among women in their perinatal period and (2) assess predictors of chronic poor functioning following childbirth. We used a group-based trajectory modeling approach to examine maternal patterns of function from the third trimester of pregnancy through 12 months post-partum. Three trajectory groups were found: persistently well-functioning (51% of women), poor functioning with recovery (39% of women), and chronically poor functioning (10% of women). When compared to mothers in the highest functioning group, psychosocial characteristics (e.g., depression, stress, and serious life events) were significantly associated with sustained poor functioning one-year following child-birth. Mothers living in nuclear households were more likely to experience chronic poor functioning. Higher education independently predicted maternal function recovery, even when controlling for psychosocial characteristics. Education, above and beyond socio-economic assets, appears to play an important protective role in maternal functional trajectories following childbirth. Public health implications related to maternal function and perinatal mental health are discussed

Association of HLA-DRB1 amino acid residues with giant cell arteritis: genetic association study, meta-analysis and geo-epidemiological investigation

Introduction: Giant cell arteritis (GCA) is an autoimmune disease commonest in Northern Europe and Scandinavia. Previous studies report various associations with HLA-DRB1*04 and HLA-DRB1*01; HLA-DRB1 alleles show a gradient in population prevalence within Europe. Our aims were (1) to determine which amino acid residues within HLA-DRB1 best explained HLA-DRB1 allele susceptibility and protective effects in GCA, seen in UK data combined in meta-analysis with previously published data, and (2) to determine whether the incidence of GCA in different countries is associated with the population prevalence of the HLA-DRB1 alleles that we identified in our meta-analysis. Methods: GCA patients from the UK GCA Consortium were genotyped by using single-strand oligonucleotide polymerization, allele-specific polymerase chain reaction, and direct sequencing. Meta-analysis was used to compare and combine our results with published data, and public databases were used to identify amino acid residues that may explain observed susceptibility/protective effects. Finally, we determined the relationship of HLA-DRB1*04 population carrier frequency and latitude to GCA incidence reported in different countries. Results: In our UK data (225 cases and 1378 controls), HLA-DRB1*04 carriage was associated with GCA susceptibility (odds ratio (OR) = 2.69, P = 1.5×10 −11 ), but HLA-DRB1*01 was protective (adjusted OR = 0.55, P = 0.0046). In meta-analysis combined with 14 published studies (an additional 691 cases and 4038 controls), protective effects were seen from HLA-DR2, which comprises HLA-DRB1*15 and HLA-DRB1*16 (OR = 0.65, P = 8.2×10 −6 ) and possibly from HLA-DRB1*01 (OR = 0.73, P = 0.037). GCA incidence (n = 17 countries) was associated with population HLA-DRB1*04 allele frequency (P = 0.008; adjusted R 2 = 0.51 on univariable analysis, adjusted R 2 = 0.62 after also including latitude); latitude also made an independent contribution. Conclusions: We confirm that HLA-DRB1*04 is a GCA susceptibility allele. The susceptibility data are best explained by amino acid risk residues V, H, and H at positions 11, 13, and 33, contrary to previous suggestions of amino acids in the second hypervariable region. Worldwide, GCA incidence was independently associated both with population frequency of HLA-DRB1*04 and with latitude itself. We conclude that variation in population HLA-DRB1*04 frequency may partly explain variations in GCA incidence and that HLA-DRB1*04 may warrant investigation as a potential prognostic or predictive biomarker