Burst Testing of Triaxial Braided Composite Tubes

Applications using triaxial braided composites are limited by the materials transverse strength which is determined by the delamination capacity of unconstrained, free-edge tows. However, structural applications such as cylindrical tubes can be designed to minimize free edge effects and thus the strength with and without edge stresses is relevant to the design process. The transverse strength of triaxial braided composites without edge effects was determined by internally pressurizing tubes. In the absence of edge effects, the axial and transverse strength were comparable. In addition, notched specimens, which minimize the effect of unconstrained tow ends, were tested in a variety of geometries. Although the commonly tested notch geometries exhibited similar axial and transverse net section failure strength, significant dependence on notch configuration was observed. In the absence of unconstrained tows, failure ensues as a result of bias tow rotation, splitting, and fracture at cross-over regions

CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

BACKGROUND: Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. METHODS AND FINDINGS: Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30-0.40) for counts <200 cells/µl, 0.81 (0.71-0.92) for counts 200 to <350 cells/µl, 0.74 (0.66-0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. CONCLUSIONS: Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl

Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques.

International audienceThe mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4(+) T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure

Btk regulates macrophage polarization in response to lipopolysaccharide

Bacterial Lipopolysaccharide (LPS) is a strong inducer of inflammation and does so by inducing polarization of macrophages to the classic inflammatory M1 population. Given the role of Btk as a critical signal transducer downstream of TLR4, we investigated its role in M1/M2 induction. In Btk deficient (Btk (−\−)) mice we observed markedly reduced recruitment of M1 macrophages following intraperitoneal administration of LPS. Ex vivo analysis demonstrated an impaired ability of Btk(−/−) macrophages to polarize into M1 macrophages, instead showing enhanced induction of immunosuppressive M2-associated markers in response to M1 polarizing stimuli, a finding accompanied by reduced phosphorylation of STAT1 and enhanced STAT6 phosphorylation. In addition to STAT activation, M1 and M2 polarizing signals modulate the expression of inflammatory genes via differential activation of transcription factors and regulatory proteins, including NF-κB and SHIP1. In keeping with a critical role for Btk in macrophage polarization, we observed reduced levels of NF-κB p65 and Akt phosphorylation, as well as reduced induction of the M1 associated marker iNOS in Btk(−/−) macrophages in response to M1 polarizing stimuli. Additionally enhanced expression of SHIP1, a key negative regulator of macrophage polarisation, was observed in Btk(−/−) macrophages in response to M2 polarizing stimuli. Employing classic models of allergic M2 inflammation, treatment of Btk (−/−) mice with either Schistosoma mansoni eggs or chitin resulted in increased recruitment of M2 macrophages and induction of M2-associated genes. This demonstrates an enhanced M2 skew in the absence of Btk, thus promoting the development of allergic inflammation

Outcomes in antiretroviral-naive HIV-infected patients initiating therapy with TDF/FTC plus either atazanavir/r or another third recommended drug

POSTER PRESENTATIONInternational audienceN.

Does rapid HIV disease progression prior to combination antiretroviral therapy hinder optimal CD4 + T-cell recovery once HIV-1 suppression is achieved?

Objective: This article compares trends in CD4+ T-cell recovery and proportions achieving optimal restoration (>=500 cells/µl) after viral suppression following combination antiretroviral therapy (cART) initiation between rapid and nonrapid progressors. Methods: We included HIV-1 seroconverters achieving viral suppression within 6 months of cART. Rapid progressors were individuals experiencing at least one CD4+ less than 200 cells/µl within 12 months of seroconverters before cART. We used piecewise linear mixed models and logistic regression for optimal restoration. Results: Of 4024 individuals, 294 (7.3%) were classified as rapid progressors. At the same CD4+ T-cell count at cART start (baseline), rapid progressors experienced faster CD4+ T-cell increases than nonrapid progressors in first month [difference (95% confidence interval) in mean increase/month (square root scale): 1.82 (1.61; 2.04)], which reversed to slightly slower increases in months 1–18 [-0.05 (-0.06; -0.03)] and no significant differences in 18–60 months [-0.003 (-0.01; 0.01)]. Percentage achieving optimal restoration was significantly lower for rapid progressors than nonrapid progressors at months 12 (29.2 vs. 62.5%) and 36 (47.1 vs. 72.4%) but not at month 60 (70.4 vs. 71.8%). These differences disappeared after adjusting for baseline CD4+ T-cell count: odds ratio (95% confidence interval) 0.86 (0.61; 1.20), 0.90 (0.38; 2.17) and 1.56 (0.55; 4.46) at months 12, 36 and 60, respectively. Conclusion: Among people on suppressive antiretroviral therapy, rapid progressors experience faster initial increases of CD4+ T-cell counts than nonrapid progressors, but are less likely to achieve optimal restoration during the first 36 months after cART, mainly because of lower CD4+ T-cell counts at cART initiation

Modelos de endemicidad a lo largo de un gradiente altitudinal en Sierra Nevada (España) y Lefka Ori (Creta, Grecia)

Aim: High mountains in the Mediterranean region of Europe are particularly rich in endemic vascular plants. We aimed to compare the altitudinal patterns of vascular plant species richness and the proportion of endemic species in two Mediterranean region: Lefka Ori on the island of Crete (Greece) and Sierra Nevada on the Iberian peninsula. Location: Sierra Nevada, Granada (Spain); Lefka Ori, Crete (Greece). Methods: Data from standardised permanent plots settings on summit sites (comprising eight plot sectors, covering the upeermost 10 altitudinal metres) of different elevations were used (GLORIA Multi-Summit approach; www.gloria.ac.at). Species numbers, rates of endemic species, and soils temperature were compared by means of ANCOVA and linear regression. Results: The two regions, though climatically similar, showed strikingly different patterns: In Sierra Nevada, the proportion of endemic vascular plants (species restricted to Sierra Nevada) showed a stepwise increase from the lowest to the highest summit. In contrast, the proportion of endemic species restricted to Crete was not significantly different between the four summits in Lefka Ori. In both regions the observed trends were largely consistent with the altitudinal distribution of the endemic species obtained from standard floras. Main conclusions: The geographic positions of the two regions, i.e. island versus mainland and the higher elevation of Sierra Nevada are suggested to be the primary causes of the observed differences. The high degree of endemism in the cold environments of Mediterranean mountains’ upper bioclimatic zones indicates a pronounced vulnerability to the impacts of climate change. A continued and intensified species monitoring in the mountains around the Mediterranean basin, therefore, should be considered as a priority research task.Objetivo: Las zonas de alta montaña en la región mediterránea europea son particularmente ricas en plantas vasculares endémicas. Nuestro objetivo es comparar los modelos altitudinales para la riqueza de plantas vasculares y la proporción de endemismos en dos regiones mediterráneas: Lefka Ori en la isla de Creta (Grecia) y Sierra Nevada en la Península Ibérica. Localización: Sierra Nevada, Granada (España); Lefka Ori, Creta (Grecia). Método: Los datos proceden de un muestreo estandarizado en varias cimas situadas a diferentes altitudes (GLORIA Multi-Summit approach; www.gloria.ac.at). El número de especies, tasas de endemicidad, y temperatura del suelo se compararon por medio de ANCOVA y regresión lineal. Resultados: Las dos regiones objeto de análisis, aunque similares climáticamente, muestran patrones llamativamente diferentes: en Sierra Nevada, la proporción de plantas vasculares endémicas (especies restringidas a Sierra Nevada) muestra un incremento gradual desde la cima más baja a la más alta. En contraste, la proporción de endemismos restringidos a Creta no fue significativamente diferente entre las cuatro cimas de Lefka Ori. Las tendencias observadas en ambas regiones fueron en gran parte consistentes con la distribución de las especies endémicas obtenida de las floras para cada región. Conclusiones principales: La posición geográfica de ambas regiones, por ejemplo. isla frente a continente, y la mayor elevación de Sierra Nevada se sugieren como las principales causas de las diferencias observadas. El alto grado de endemicidad en los ambientes fríos de las zonas bioclimáticas superiores de las montañas mediterráneas evidencia una marcada vulnerabilidad a los impactos del cambio climático. Por lo tanto, el seguimiento continuado e intensivo de las especies de montaña alrededor de la cuenca mediterránea, debería considerarse como una tarea investigadora prioritaria.He set up of the permanent plots and data collection was supported by the FP-5 project GLORIA-Europe (2001-2003) No EVK2-2000-00056 of the European Commission

Recent HIV-1 Infection Contributes to the Viral Diffusion over the French Territory with a Recent Increasing Frequency

To analyse the contribution of primary human immunodeficiency virus type 1 (HIV-1) infection (PHI) to the French viral epidemic. sequences included 987 PHI from the French ANRS PRIMO cohort between 1999 and 2010 and were analysed using a population-based phylogenetic approach. Clinical features, risk factors, sexual behaviour and drug resistance for clustered and nonclustered transmission events were ascertained.Viruses from 125 (12.7%) of PHI cosegregated into 56 transmission chains, with increasing frequency during the last years (10.2% before 2006 versus 15.2% of clusters in 2006–2010, p = 0.02). The mean number of patients per cluster was 2.44. Compared to unique PHI, clusters involved more often men, infected through homosexual intercourse, of young age, with a high number of casual sexual partnerships and frequent previous HIV serological tests. Resistant strains were found in 16.0% and 11.1% of clusters and unique PHI, respectively (p = 0.11). Overall, 34% (n = 19) clusters included patients followed in French regions far apart, involving 13 clusters with at least one Parisian patient.PHIs are a significant source of onward transmission, especially in the MSM population. Recently infected people contribute to the spread of the viral epidemic throughout the French territory. Survey of transmitted drug resistance and behavioural characteristics of patients involved into clustered PHI may help to guide prevention and treatment interventions