Development of an optimized methodology for tensile testing of carbon steels in hydrogen environment

The study was performed at OCAS, the Steel Research Centre of ArcelorMittal for the Industry market. The major aim of this research was to obtain an optimized tensile testing methodology with in-situ H-charging to reveal the hydrogen embrittlement in various high strength steels. The second aim of this study has been the mechanical characterization of the hydrogen effect on hight strength carbon steels with varying microstructure, i.e. ferrite-martensite and ferrite-bainite grades. The optimal parameters for H-charging - which influence the tensile test results (sample geometry type of electrolyte, charging methods effect of steel type, etc.) - were defined and applied to Slow Strain Rate testing, Incremental Step Loading and Constant Load Testing. To better understand the initiation and propagation of cracks during tensile testing with in-situ H-charging, and to make the correlation with crystallographic orientation, some materials have been analyzed in the SEM in combination with the EBSD technique. The introduction of a notch on the tensile samples permits to reach a significantly improved reproducibility of the results. Comparing the various steel grades reveals that Dual Phase (ferrite-martensite) steels are more sensitive to hydrogen induced cracking than the FB (ferritic-bainitic) ones. This higher sensitivity to hydrogen was found back in the reduced failure times, increased creep rates and enhanced crack initiation (SEM) for the Dual Phase steels in comparison with the FB steels.

Genotype-level interactions determine the degree of reduction of leaf rust on wheat by seed application of beneficial Pseudomonas spp.

Some bacteria have the capacity to reduce incidence and severity of plant diseases either by inhibiting the pathogen or by modulating the resistance response of the plant. Plants dispose of different resistance mechanisms that are influenced by the biotic and abiotic environment. The present experiments explored the effects of biocontrol strains of Pseudomonas fluorescens on the resistance of wheat varieties against brown rust disease caused by Puccinia triticina. Root inoculation with biocontrol pseudomonads reduced the disease severity on the leaves. The plant response depended on the genotype of both the microbes and the wheat varieties, suggesting a straight interaction at the molecular level.

Withdrawal, "serosorting" and "strategic positioning": use of risk reduction strategies with casual sex partners in men who have sex with men (MSM) in Switzerland, 2007

Introduction: 1) Withdrawal before ejaculation, "serosorting" (to choose a partner of same serostatus) and "strategic positioning" (only insertive vs. only receptive role in anal sex according to serostatus) are known to be used by MSM as alternatives to condom use. 2) Despite their questionable levels of effectiveness they are collectively labelled as "risk reduction strategies" (RRS). Objectives: The aim of this study is to estimate the prevalence and factors related to RRS in men who report unprotected anal intercourse (UAI) with occasional partners in the last 12 months. Methods: 1) In 2007, a module on RRS was included in a repeated national survey conducted among readers of gay newspapers, members of gay organizations and visitors of gay websites (N=2953). 2) Using an anonymous self-completed questionnaire, participants were asked whether, with the aim of avoiding HIV infection, RRS were used with occasional partners. Analysis: 1) Prevalences were calculated in participants who reported UAI with occasional partners in the last 12 months (n=416). 2) A logistic regression was performed, using "at least one RRS" as dependent variable. Number of partners in the last 12 months, HIV-status and usual socio-demographic characteristics were used as independent factors. Result : 1) 70% (292/416) of the participants reporting UAI used at least one RRS when they had unprotected sex with casual partners in the last 12 months (Table 1). 2) Withrawal before ejaculation was the most frequently reported strategy, followed by serosorting and strategic positioning (Table 1). 3) Participants who reported at least one RRS were more likely to be over 30 years and to belong to a gay organisation. HIV-positive and non-tested participants were less likely to report RRS than HIV-negative participants (Table 2). Conclusions: 1) The majority of MSM who reported UAI in the last 12 months tried to reduce risk of HIV transmission by using specific strategies (withdrawal, serosorting, strategic positioning). It is not known, however, to what extent the use of these strategies was systematic. 2) It is necessary to provide MSM with balanced information on these strategies and their respective level of effectiveness. 3) It is important to monitor the use of RRS in HIV behavioural surveillance surveys in MSM.

Paclitaxel-eluting biodegradable synthetic vascular prostheses: a step towards reduction of neointima formation?

BACKGROUND: Clinical small-caliber vascular prostheses are unsatisfactory. Reasons for failure are early thrombosis and late intimal hyperplasia. We thus prepared biodegradable small-caliber vascular prostheses using electrospun polycaprolactone (PCL) with slow-releasing paclitaxel (PTX), an antiproliferative drug. METHODS AND RESULTS: PCL solutions containing PTX were used to prepare nonwoven nanofibre-based 2-mm ID prostheses. Mechanical morphological properties and drug loading, distribution, and release were studied in vitro. Infrarenal abdominal aortic replacement was carried out with nondrug-loaded and drug-loaded prostheses in 18 rats and followed for 6 months. Patency, stenosis, tissue reaction, and drug effect on endothelialization, vascular remodeling, and neointima formation were studied in vivo. In vitro prostheses showed controlled morphology mimicking extracellular matrix with mechanical properties similar to those of native vessels. PTX-loaded grafts with suitable mechanical properties and controlled drug-release were obtained by factorial design. In vivo, both groups showed 100% patency, no stenosis, and no aneurysmal dilatation. Endothelial coverage and cell ingrowth were significantly reduced at 3 weeks and delayed at 12 and 24 weeks in PTX grafts, but as envisioned, neointima formation was significantly reduced in these grafts at 12 weeks and delayed at 6 months. CONCLUSIONS: Biodegradable, electrospun, nanofibre, polycaprolactone prostheses are promising because in vitro they maintain their mechanical properties (regardless of PTX loading), and in vivo show good patency, reendothelialize, and remodel with autologous cells. PTX loading delays endothelialization and cellular ingrowth. Conversely, it reduces neointima formation until the end point of our study and thus may be an interesting option for small caliber vascular grafts.

Reactive Nitrogen and Oxygen Intermediates in Patients with Cutaneous Leishmaniasis

The metabolisms of reactive nitrogen and oxygen intermediates (RNI and ROI) in patients with cutaneous leishmaniasis (CL) were investigated and compared with those of healthy subjects. To determine RNI metabolism, nitrite plus nitrate concentrations were measured spectrophotometrically. Nitrite concentration in plasma was determined directly by the Griess method. Nitrate levels in plasma were measured after reduction into nitrite by using copper-cadmium-zinc. ROI metabolism was evaluated by measuring erythrocyte superoxide dismutase, catalase and glutathione peroxidase activities. Plasma nitrite plus nitrate levels and erythrocyte superoxide dismutase activity were higher in the patient group than healthy subjects (p<0.01). In contrast, erythrocyte catalase and glutathione peroxidase activities were lower (p<0.05, p<0.01, respectively). ROI metabolism was altered in relation to hydrogen peroxide elevation in patients with CL. These alterations in ROI enable nitric oxide (NO) to amplify its leishmanicidal effect. The determination of ROI and RNI in patients with CL may be a useful tool to evaluate effector mechanisms of NO and clinical manifestations.

Effect of changes in the deuterium content of drinking water on the hydrogen isotope ratio of urinary steroids in the context of sports drug testing.

The hydrogen isotope ratio (HIR) of body water and, therefore, of all endogenously synthesized compounds in humans, is mainly affected by the HIR of ingested drinking water. As a consequence, the entire organism and all of its synthesized substrates will reflect alterations in the isotope ratio of drinking water, which depends on the duration of exposure. To investigate the effect of this change on endogenous urinary steroids relevant to doping-control analysis the hydrogen isotope composition of potable water was suddenly enriched from -50 to 200 0/00 and maintained at this level for two weeks for two individuals. The steroids under investigation were 5β-pregnane-3α,20α-diol, 5α-androst-16-en-3α-ol, 3α-hydroxy-5α-androstan-17-one (ANDRO), 3α-hydroxy-5β-androstan-17-one (ETIO), 5α-androstane-3α,17β-diol, and 5β-androstane-3α,17β-diol (excreted as glucuronides) and ETIO, ANDRO and 3β-hydroxyandrost-5-en-17-one (excreted as sulfates). The HIR of body water was estimated by determination of the HIR of total native urine, to trace the induced changes. The hydrogen in steroids is partly derived from the total amount of body water and cholesterol-enrichment could be calculated by use of these data. Although the sum of changes in the isotopic composition of body water was 150 0/00, shifts of approximately 30 0/00 were observed for urinary steroids. Parallel enrichment in their HIR was observed for most of the steroids, and none of the differences between the HIR of individual steroids was elevated beyond recently established thresholds. This finding is important to sports drug testing because it supports the intended use of this novel and complementary methodology even in cases where athletes have drunk water of different HIR, a plausible and, presumably, inevitable scenario while traveling.

Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study.

BACKGROUND: A growing number of case reports have described tenofovir (TDF)-related proximal renal tubulopathy and impaired calculated glomerular filtration rates (cGFR). We assessed TDF-associated changes in cGFR in a large observational HIV cohort. METHODS: We compared treatment-naive patients or patients with treatment interruptions > or = 12 months starting either a TDF-based combination antiretroviral therapy (cART) (n = 363) or a TDF-sparing regime (n = 715). The predefined primary endpoint was the time to a 10 ml/min reduction in cGFR, based on the Cockcroft-Gault equation, confirmed by a follow-up measurement at least 1 month later. In sensitivity analyses, secondary endpoints including calculations based on the modified diet in renal disease (MDRD) formula were considered. Endpoints were modelled using pre-specified covariates in a multiple Cox proportional hazards model. RESULTS: Two-year event-free probabilities were 0.65 (95% confidence interval [CI] 0.58-0.72) and 0.80 (95% CI 0.76-0.83) for patients starting TDF-containing or TDF-sparing cART, respectively. In the multiple Cox model, diabetes mellitus (hazard ratio [HR] = 2.34 [95% CI 1.24-4.42]), higher baseline cGFR (HR = 1.03 [95% CI 1.02-1.04] by 10 ml/min), TDF use (HR = 1.84 [95% CI 1.35-2.51]) and boosted protease inhibitor use (HR = 1.71 [95% CI 1.30-2.24]) significantly increased the risk for reaching the primary endpoint. Sensitivity analyses showed high consistency. CONCLUSION: There is consistent evidence for a significant reduction in cGFR associated with TDF use in HIV-infected patients. Our findings call for a strict monitoring of renal function in long-term TDF users with tests that distinguish between glomerular dysfunction and proximal renal tubulopathy, a known adverse effect of TDF.

Transcriptional control of the hydrogen cyanide biosynthetic genes hcnABC by the anaerobic regulator ANR and the quorum-sensing regulators LasR and RhlR in Pseudomonas aeruginosa.

Virulence factors of Pseudomonas aeruginosa include hydrogen cyanide (HCN). This secondary metabolite is maximally produced at low oxygen tension and high cell densities during the transition from exponential to stationary growth phase. The hcnABC genes encoding HCN synthase were identified on a genomic fragment complementing an HCN-deficient mutant of P. aeruginosa PAO1. The hcnA promoter was found to be controlled by the FNR-like anaerobic regulator ANR and by the quorum-sensing regulators LasR and RhlR. Primer extension analysis revealed two transcription starts, T1 and T2, separated by 29 bp. Their function was confirmed by transcriptional lacZ fusions. The promoter sequence displayed an FNR/ANR box at -42.5 bp upstream of T2 and a lux box centered around -42.5 bp upstream of T1. Expression of the hcn genes was completely abolished when this lux box was deleted or inactivated by two point mutations in conserved nucleotides. The lux box was recognized by both LasR [activated by N-(oxododecanoyl)-homoserine lactone] and RhlR (activated by N-butanoyl-homoserine lactone), as shown by expression experiments performed in quorum-sensing-defective P. aeruginosa mutants and in the N-acyl-homoserine lactone-negative heterologous host P. fluorescens CHA0. A second, less conserved lux box lying 160 bp upstream of T1 seems to account for enhanced quorum-sensing-dependent expression. Without LasR and RhlR, ANR could not activate the hcn promoter. Together, these data indicate that expression of the hcn promoter from T1 can occur under quorum-sensing control alone. Enhanced expression from T2 appears to rely on a synergistic action between LasR, RhlR, and ANR.

Liver kidney microsomes type 1 antibodies are associated with 80% reduction of the CYP2D6 activity in patients with chronic hepatitis C

Introduction Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease CYP2D6 activity in vitro. We investigated whether LKM-1 antibodies might reduce CYP2D6 activity also in vivo.Materials and Methods All patients with chronic hepatitis C and LKM-1 antibodies enrolled in the Swiss Hepatitis C Cohort Study (SCCS) were assessed: ten were eligible and fi tted to patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specifi c substrate using the dextromethorphan/dextrorphan (DEM/DOR) metabolic ratio to classify patients into four activity phenotypes (i.e. ultrarapid, extensive, intermediate and poor metabolizers). The concordance between phenotype based on DEM/DOR ratio and phenotype expected from genotype was examined in LKM-1 positive and negative patients. Groups were compared with respect to the DEM/DOR metabolic ratio.Results All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with CYP2D6 genotype in most LKM-negative patients, whereas only three (30%) LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was six-fold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, p = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies.Conclusion In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies in the setting of new protease inhibitor therapies

Elaboració de membranes de fibra buida modificades amb nanopartícules metàl·liques per aplicacions catalítiques

Investigación producida a partir de una estancia en la Université Paul Sabatier, Toulouse III - CNRS, entre 2007 y 2009. Durante los últimos años la investigación centrada en nuevos materiales de tamaño nanoscòpico (nanopartículas, quantum dots, nanotubos de carbono,...) ha experimentado un crecimiento considerable debido a las especiales propiedades de los "nanoobjetos" con respecto a magnetismo, catálisis, conductividad eléctrica, etc ... Sin embargo, hoy en día todavía existen pocas aplicaciones de las nanopartículas en temas medioambientales. Uno de los motivos de esta situación es la posible toxicidad de los nanoobjetos, pero existe también una dificultad tecnológica dado que las nanopartículas tienden a agregarse y es muy difícil manipularlas sin que pierdan sus propiedades especiales. Así, aunque la preparación de materiales catalíticos nanoestructurados es muy interesante, es necesario definir nuevas estrategias para prepararlos. Este proyecto de investigación tiene como objetivo principal la preparación de nuevas membranas catalíticas con nanopartículas metálicas en el interior para aplicaciones de tratamiento de agua. La innovación principal de este proyecto consiste en que las nanopartículas no son introducidas en la matriz polimérica una vez preformadas sino que se hacen crecer en el interior de la matriz polimérica mediante una síntesis intermatricial. El único requisito es que la matriz polimérica contenga grupos funcionales capaces de interaccionar con los precursores de las nanopartículas. Una vez finalizado el proyecto se puede afirmar que se han logrado parte de los objetivos planteados inicialmente. Concreamente ha quedado demostrado que se pueden sintetizar nanopartículas metálicas de metales nobles (platino y paladio) en membranas de fibra hueca de micro- y ultrafiltración siguiendo dos metodologías diferentes: modificación fotoquímica de polímeros y deposición de multicapas de polielectrolitos. Los nuevos materiales son efectivos en la catálisis de reducción de un compuesto modelo (4-nitrofenol con borohidruro de sodio) y, en general, los resultados han sido satisfactorios. Sin embargo, se ha puesto de manifiesto que el uso de un reactivo que genera hidrógeno gas en contacto con la solución acuosa dificulta enormemente la implementación de la reacción catalítica al ser el medio de la membrana una matriz porosa. Así, como conclusión principal se puede decir que se han encontrado las limitaciones de esta aproximación y se sugieren dos posibilidades de continuidad: la utilización de las membranas sintetizadas en contactores gas-líquido o bien el estudio y optimización del sistema de membrana en configuración de membranas planas, un objetivo más asequible dada su menor complejidad. Esta investigación se ha realizado en el seno del “Laboratoire de Génie Chimique” de Toulouse y del Departamento de Química de la Michigan State University y ha sido posible gracias a un proyecto financiado por la “Agence National pour la Recherce” y al programa PERMEANT entre el CNRS y la NSF.

Reduction in catheter-related bloodstream infections in critically ill patients through a multiple system intervention.

Els catéters venosos centrals són necessaris per al maneig del pacient crític però poden ser l´origen d´una bacteriemia. Aquest estudi prospectiu de cohort té com a objectiu determinar la utilitat de l´aplicació d´unes mesures bàsiques de prevenció per disminuir la incidència de bacteriemia associada a catéter. Els resultats de l´estudi confirmen que l´aplicació d´aquest sistema d´intervenció múltiple basat en l´evidencia redueix de forma significativa les bacteriemies associades a catéter a la nostra UCI.

Seeds of hope: Assessing the effect of development aid on the reduction of child mortality

The Millennium Declaration (2000) set as one of its targets a substantial reduction in child mortality. This paper studies whether the massive increase in development aid can account for part of the reduction in child mortality observed in developing countries since the year 2000. To do so, we analyze a panel of more than 130 developing countries over the 2000-2008 period. We use the time trend evolution of aid to identify an exogenous source of variation. Total aid has had no statistically significant effect on child mortality. However, a disaggregate analysis identifies certain sectors of aid that have had a significant impact. The effects have been larger in high mortality countries, including Sub-Saharan Africa. Projections based on our estimates strongly support the concern that most countries in that region will miss the Millennium Goals target on child mortality.

Reduction theorems for operators on the cones of monotone functions

For a quasilinear operator on the semiaxis a reduction theorem is proved on the cones of monotone functions in Lp - Lq setting for 0 < q < ∞, 1<= p < ∞. The case 0 < p < 1 is also studied for operators with additional properties. In particular, we obtain critera for three-weight inequalities for the Hardy-type operators with Oinarov' kernel on monotone functions in the case 0 < q < p <= 1.