The effects of irradiation on the biological and biomechanical properties of an acellular porcine superflexor tendon graft for cruciate ligament repair

Acellular xenogeneic tissues have the potential to provide ‘off‐the‐shelf’ grafts for anterior cruciate ligament (ACL) repair. To ensure that such grafts are sterile following packaging, it is desirable to use terminal sterilization methods. Here, the effects of gamma and electron beam irradiation on the biological and biomechanical properties of a previously developed acellular porcine superflexor tendon (pSFT) were investigated. Irradiation following treatment with peracetic acid was compared to peracetic acid treatment alone and the stability of grafts following long‐term storage assessed. Irradiation did not affect total collagen content or biocompatibility (determined using a contact cytotoxicity assay) of the grafts, but slightly increased the amount of denatured collagen in and decreased the thermal denaturation temperature of the tissue in a dose dependant fashion. Biomechanical properties of the grafts were altered by irradiation (reduced ultimate tensile strength and Young's modulus, increased failure strain), but remained superior to reported properties of the native human ACL. Long term storage at 4°C had no negative effects on the grafts. Of all the conditions tested, a dose of minimum 25 kGy of gamma irradiation had least effect on the grafts, suggesting that this dose produces a biocompatible pSFT graft with adequate mechanical properties for ACL repair

Tumour invasiveness, the local and systemic environment and the basis of staging systems in colorectal cancer

background: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. methods: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR). A 5-year CSS was examined. results: A total of 331 patients were included. Increasing T stage was associated with colonic primary, N stage, poor differentiation, margin involvement and venous invasion (P<0.05). T stage was significantly associated with KM grade (P=0.001), Immunoscore (P=0.016), TSP (P=0.006), tumour budding (P<0.001), and elevated mGPS and NLR (both P<0.05). In patients with T3 cancer, N stage stratified survival from 88 to 64%, whereas Immunoscore and budding stratified survival from 100 to 70% and from 91 to 56%, respectively. The Glasgow Microenvironment Score, a score based on KM grade and TSP, stratified survival from 93 to 58%. conclusions: Although associated with increasing T stage, local and systemic tumour environment characteristics, and in particular Immunoscore, budding, TSP and mGPS, are stage-independent determinants of survival and may be utilised in the staging of patients with primary operable colorectal cancer

Does landscape-scale conservation management enhance the provision of ecosystem services?

Biodiversity conservation approaches are increasingly being implemented at the landscape-scale to support the maintenance of metapopulations and metacommunities. However, the impact of such interventions on the provision of ecosystem services is less well defined. Here we examine the potential impacts of landscape-scale conservation initiatives on ecosystem services, through analysis of five case study areas in England and Wales. The provision of multiple ecosystem services was projected according to current management plans and compared with a baseline scenario. Multicriteria analysis indicated that in most cases landscape-scale approaches lead to an overall increase in service provision. Consistent increases were projected in carbon storage, recreation and aesthetic value, as well as biodiversity value. However, most study areas provided evidence of trade-offs, particularly between provisioning services and other types of service. Results differed markedly between study areas, highlighting the importance of local context. These results suggest that landscape-scale conservation approaches are likely to be effective in increasing ecosystem service provision, but also indicate that associated costs can be significant, particularly in lowland areas

Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed. METHODS: Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm. Mean height-for-age, weight-for-age and weight-for-height z scores were compared between treatment arms. RESULTS: No significant differences in mean height-for-age, weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms, nor was there a significant reduction in prevalence of stunting, wasting or underweight between arms. CONCLUSIONS: Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia. This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status

Quantifying habitual levels of physical activity according to impact in older people: accelerometry protocol for the VIBE study

Physical activity (PA) may need to produce high impacts to be osteogenic. The aim of this study was to identify threshold(s) for defining high impact PA for future analyses in the VIBE (Vertical Impact and Bone in the Elderly) study, based on home recordings with triaxial accelerometers. Recordings were obtained from 19 Master Athlete Cohort (MAC; mean 67.6 years) and 15 Hertfordshire Cohort Study (HCS; mean 77.7 years) participants. Data cleaning protocols were developed to exclude artifacts. Accelerations expressed in g units were categorized into three bands selected from the distribution of positive Y-axis peak accelerations. Data were available for 6.6 and 4.4 days from MAC and HCS participants respectively, with approximately 14 hr recording daily. Three-fold more 0.5–1.0g impacts were observed in MAC versus HCS, 20-fold more 1.0–1.5g impacts, and 140-fold more impacts ≥ 1.5g. Our analysis protocol successfully distinguishes PA levels in active and sedentary older individuals

Impacts of household sources on air pollution at village and regional scales in India

Approximately 3 billion people worldwide cook with solid fuels, such as wood, charcoal, and agricultural residues. These fuels, also used for residential heating, are often combusted in inefficient devices, producing carbonaceous emissions. Between 2.6 and 3.8 million premature deaths occur as a result of exposure to fine particulate matter from the resulting household air pollution (Health Effects Institute, 2018a; World Health Organization, 2018). Household air pollution also contributes to ambient air pollution; the magnitude of this contribution is uncertain. Here, we simulate the distribution of the two major health-damaging outdoor air pollutants (PM2:5 and O3) using state-of-thescience emissions databases and atmospheric chemical transport models to estimate the impact of household combustion on ambient air quality in India. The present study focuses on New Delhi and the SOMAARTH Demographic, Development, and Environmental Surveillance Site (DDESS) in the Palwal District of Haryana, located about 80 km south of New Delhi. The DDESS covers an approximate population of 200 000 within 52 villages. The emissions inventory used in the present study was prepared based on a national inventory in India (Sharma et al., 2015, 2016), an updated residential sector inventory prepared at the University of Illinois, updated cookstove emissions factors from Fleming et al. (2018b), and PM2:5 speciation from cooking fires from Jayarathne et al. (2018). Simulation of regional air quality was carried out using the US Environmental Protection Agency Community Multiscale Air Quality modeling system (CMAQ) in conjunction with the Weather Research and Forecasting modeling system (WRF) to simulate the meteorological inputs for CMAQ, and the global chemical transport model GEOS-Chem to generate concentrations on the boundary of the computational domain. Comparisons between observed and simulated O3 and PM2:5 levels are carried out to assess overall airborne levels and to estimate the contribution of household cooking emissions

Coalescent-based genome analyses resolve the early branches of the euarchontoglires

Despite numerous large-scale phylogenomic studies, certain parts of the mammalian tree are extraordinarily difficult to resolve. We used the coding regions from 19 completely sequenced genomes to study the relationships within the super-clade Euarchontoglires (Primates, Rodentia, Lagomorpha, Dermoptera and Scandentia) because the placement of Scandentia within this clade is controversial. The difficulty in resolving this issue is due to the short time spans between the early divergences of Euarchontoglires, which may cause incongruent gene trees. The conflict in the data can be depicted by network analyses and the contentious relationships are best reconstructed by coalescent-based analyses. This method is expected to be superior to analyses of concatenated data in reconstructing a species tree from numerous gene trees. The total concatenated dataset used to study the relationships in this group comprises 5,875 protein-coding genes (9,799,170 nucleotides) from all orders except Dermoptera (flying lemurs). Reconstruction of the species tree from 1,006 gene trees using coalescent models placed Scandentia as sister group to the primates, which is in agreement with maximum likelihood analyses of concatenated nucleotide sequence data. Additionally, both analytical approaches favoured the Tarsier to be sister taxon to Anthropoidea, thus belonging to the Haplorrhine clade. When divergence times are short such as in radiations over periods of a few million years, even genome scale analyses struggle to resolve phylogenetic relationships. On these short branches processes such as incomplete lineage sorting and possibly hybridization occur and make it preferable to base phylogenomic analyses on coalescent methods

A Massive S-duality in 4 dimensions

We reduce the Type IIA supergravity theory with a generalized Scherk-Schwarz ansatz that exploits the scaling symmetry of the dilaton, the metric and the NS 2-form field. The resulting theory is a new massive, gauged supergravity theory in four dimensions with a massive 2-form field and a massive 1-form field. We show that this theory is S-dual to a theory with a massive vector field and a massive 2-form field, which are dual to the massive 2-form and 1-form fields in the original theory, respectively. The S-dual theory is shown to arise from a Scherk-Schwarz reduction of the heterotic theory. Hence we establish a massive, S-duality type relation between the IIA theory and the heterotic theory in four dimensions. We also show that the Lagrangian for the new four dimensional theory can be put in the most general form of a D=4, N=4 gauged Lagrangian found by Schon and Weidner, in which (part of) the SL(2) group has been gauged.Comment: 20 pages, references adde