Shear design of circular concrete sections using the eurocode 2 truss model

The introduction of the Eurocodes for concrete design will alter the way that shear is approached for concrete structures. BS EN 1992-1-1 has adopted the variable angle truss model for shear, a more theoretically consistent approach than that used in BS 8110-1. The model is confidently applied to rectangular sections, but its applicability to irregular sections is less clear. In particular, the behaviour of circular concrete sections is not well defined. This paper is intended to satisfy a requirement for design guidance on this topic that has been recognised by key BSI Committees. Using both experimental and theoretical data, the Eurocode variable angle truss model for shear design is assessed and extended to circular columns

Aetiology, Risk Factors, and Biomarkers in Systemic Sclerosis with Interstitial Lung Disease

Systemic sclerosis (SSc) is a complex, multi-organ, autoimmune disease. Lung fibrosis occurs in ~80% of patients with SSc; 25-30% develop progressive interstitial lung disease (ILD). The pathogenesis of fibrosis in SSc associated ILD (SSc-ILD) involves cellular injury, activation/differentiation of mesenchymal cells and morphological/biological changes in epithelial/endothelial cells. Risk factors for progressive SSc-ILD include older age, male sex, lung involvement on baseline high-resolution computed tomography, reduced diffusing capacity for carbon monoxide and reduced forced vital capacity. SSc-ILD is characterized by genetic risk architecture distinct from that associated with idiopathic pulmonary fibrosis (IPF). Presence of anti-Scl-70 antibodies and absence of anti-centromere antibodies indicate increased likelihood of progressive ILD. Elevated levels of serum Krebs von den Lungen-6 (KL6) and CRP are associated with SSc-ILD severity, although whether KL6 independently predicts SSc-ILD progression remains controversial. A promising prognostic indicator is serum chemokine (C-C motif) ligand 18. SSc-ILD shares similarities with IPF, although clear differences exist. Histologically, a non-specific interstitial pneumonia pattern is commonly observed in SSc-ILD, whereas IPF is defined by usual interstitial pneumonia. The course of SSc-ILD is variable, ranging from minor, stable disease to a progressive course, while all IPF patients experience progression of disease. Although appropriately treated SSc-ILD patients have better chances of stabilization and survival, a relentlessly progressive course, akin to IPF, is seen in a minority. Better understanding of cellular and molecular pathogenesis, genetic risk and distinctive features of SSc-ILD, and identification of robust prognostic biomarkers are needed for optimal disease management. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Systematic analysis of the literature in search of defining systemic sclerosis subsets

OBJECTIVE: Systemic sclerosis (SSc) is a multisystem disease with heterogeneity in presentation and prognosis. An international collaboration to develop new SSc subset criteria is underway. Our objectives were to identify systems of SSc subset classification and synthesize novel concepts to inform development of new criteria. METHODS: Medline, Cochrane MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Web of Science were searched from their inceptions to December 2019 for studies related to SSc subclassification, limited to humans and without language or sample size restrictions. RESULTS: Of 5686 citations, 102 studies reported original data on SSc subsets. Subset classification systems relied on extent of skin involvement and/or SSc-specific autoantibodies (n = 61), nailfold capillary patterns (n = 29), and molecular, genomic, and cellular patterns (n = 12). While some systems of subset classification confer prognostic value for clinical phenotype, severity, and mortality, only subsetting by gene expression signatures in tissue samples has been associated with response to therapy. CONCLUSION: Subsetting on extent of skin involvement remains important. Novel disease attributes including SSc-specific autoantibodies, nailfold capillary patterns, and tissue gene expression signatures have been proposed as innovative means of SSc subsetting

Derivation and External Validation of a Prediction Rule for Five-Year Mortality in Patients With Early Diffuse Cutaneous Systemic Sclerosis

OBJECTIVE: Although diffuse cutaneous systemic sclerosis (dcSSc) is associated with a reduction in life expectancy, there are no validated prognostic models for determining 5-year mortality in patients with dcSSc. The objective of this study was to derive and validate a rule for predicting 5-year mortality in patients with early dcSSc. METHODS: We studied an inception cohort of 388 US Caucasian patients with early dcSSc (<2 years from the appearance of the first symptom). Predefined baseline variables were analyzed in a stepwise logistic regression model in order to identify factors independently associated with 5-year all-cause mortality. We rounded the beta weights to the nearest integer and summed the points assigned to each variable in order to stratify patients into low-risk (<0 points), moderate-risk (1-2 points), and high-risk (≥3 points) groups. We then applied this rule to an external validation cohort of 144 Caucasian patients with early dcSSc from the Royal Free Hospital cohort and compared stratum-specific 5-year mortality. RESULTS: Six independent predictors (rounded beta weight) comprised the model: age at first visit (points allotted: -1, 0, or 1), male sex (points allotted: 0 or 1), tendon friction rubs (points allotted: 0 or 1), gastrointestinal involvement (points allotted: 0 or 1), RNA polymerase III antibodies (points allotted: 0 or 1), and anemia (points allotted: 0 or 1). The 3-level risk stratification model performed well, with no significant differences between the US derivation cohort and the UK validation cohort. CONCLUSION: We derived and externally validated, in US and UK cohorts, an easy-to-use 6-variable prediction rule that assigns low-risk, moderate-risk, and high-risk categories for 5-year mortality in patients with early dcSSc. Only history, physical examination, and basic laboratory assessments are required

Safety and efficacy of abatacept in early diffuse cutaneous systemic sclerosis (ASSET): open-label extension of a phase 2, double-blind randomised trial

Background: Abatacept was well tolerated by patients with early diffuse cutaneous systemic sclerosis in a phase 2, double-blind randomised trial, with potential efficacy at 12 months. We report here the results of an open-label extension for 6 months. / Methods: Patients (aged ≥18 years) with diffuse cutaneous systemic sclerosis of less than 3 years' duration from their first non-Raynaud's symptom were enrolled into the ASSET trial (A Study of Subcutaneous Abatacept to Treat Diffuse Cutaneous Systemic Sclerosis), which is a double-blind trial at 22 sites in Canada, the UK, and the USA. After completion of 12 months of treatment with either abatacept or placebo, patients received a further 6 months of abatacept (125 mg subcutaneous every week) in an open-label extension. The primary endpoint of the double-blind trial was modified Rodnan Skin Score (mRSS) at 12 months, which was reassessed at 18 months in the open-label extension. The primary analysis included all participants who completed the double-blind trial and received at least one dose of open-label treatment (modified intention to treat). This trial is registered with ClinicalTrials.gov, NCT02161406. / Findings: Between Sept 22, 2014, and March 15, 2017, 88 participants were randomly allocated in the double-blind trial either abatacept (n=44) or placebo (44); 32 patients from each treatment group completed the 6-month open-label extension. Among patients assigned abatacept, a mean improvement from baseline in mRSS was noted at 12 months (−6·6 [SD 6·4]), with further improvement seen during the open-label extension period (−9·8 [8·1] at month 18). Participants assigned placebo had a mean improvement from baseline in mRSS at 12 months (−3·7 [SD 7·6]), with a further improvement at month 18 (−6·3 [9·3]). Infections during the open-label extension phase occurred in nine patients in the placebo–abatacept group (12 adverse events, one serious adverse event) and in 11 patients in the abatacept–abatacept group (14 adverse events, one serious adverse event). Two deaths occurred during the 12-month double-blind period in the abatacept group, which were related to scleroderma renal crisis; no deaths were recorded during the open-label extension. / Interpretation: During the 6-month open-label extension, no new safety signals for abatacept were identified in the treatment of diffuse cutaneous systemic sclerosis. Clinically meaningful improvements in mRSS and other outcome measures were observed in both the abatacept and placebo groups when patients transitioned to open-label treatment. These data support further studies of abatacept in diffuse cutaneous systemic sclerosis. / Funding: Bristol-Myers Squibb and National Institutes of Health

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

Hygienic characteristics of radishes grown in soil contaminated with Stenotrophomonas maltophilia

Background: Stenotrophomonas maltophilia is a plant growth-promoter. This bacterium is also implicated in human diseases. Thus, after the use of this bacterium in agriculture, the safety of the final products has to be verified. Due to the ubiquitous presence of S. maltophilia in soil, in this study a massive contamination was simulated to evaluate the growth and safety of Raphanus sativus L.. Results: Different inoculums and soil treatment conditions were tested. Soils were analysed weekly and the radishes at harvest for their microbial loads and presence/persistence of S. maltophilia LMG 6606. The concentration of the bacterium added in the different trials decreased during the first week, but increased thereafter and determined a significant increase of growth parameters of radishes. Conclusions: The addition of S. maltophilia LMG 6606 to non-autoclaved soil enhanced the productivity of radishes. The bacterium did not internalize in the hypocotyls, but colonized the external surface ensuring the safety of the products. Thus, a sanitizing bath of hypocotyls before consumption is necessary