Fracture imaging within a granitic rock aquifer using multiple-offset single-hole and cross-hole GPR reflection data

The sparsely spaced highly permeable fractures of the granitic rock aquifer at Stang-er-Brune (Brittany, France) form a well-connected fracture network of high permeability but unknown geometry. Previous work based on optical and acoustic logging together with single-hole and cross-hole flowmeter data acquired in 3 neighbouring boreholes (70-100 m deep) has identified the most important permeable fractures crossing the boreholes and their hydraulic connections. To constrain possible flow paths by estimating the geometries of known and previously unknown fractures, we have acquired, processed and interpreted multifold, single- and cross-hole GPR data using 100 and 250 MHz antennas. The GPR data processing scheme consisting of timezero corrections, scaling, bandpass filtering and F-X deconvolution, eigenvector filtering, muting, pre-stack Kirchhoff depth migration and stacking was used to differentiate fluid-filled fracture reflections from source generated noise. The final stacked and pre-stack depth-migrated GPR sections provide high-resolution images of individual fractures (dipping 30-90°) in the surroundings (2-20 m for the 100 MHz antennas; 2-12 m for the 250 MHz antennas) of each borehole in a 2D plane projection that are of superior quality to those obtained from single-offset sections. Most fractures previously identified from hydraulic testing can be correlated to reflections in the single-hole data. Several previously unknown major near vertical fractures have also been identified away from the boreholes.

Reduction of plasma alanine aminotransferase during vigabatrin treatment.

In 9 drug-resistant patients with partial seizures treated with vigabatrin, gamma-vinyl GABA (VGB), alanine aminotransaminase (ALAT) activity in plasma was significantly reduced. Comparison of in vitro with in vivo measurements led us to conclude that this reduction is mainly an in vivo phenomenon, perhaps due to cross-enzyme inhibition. The assessment of two biological variables linked with ALAT, glucose and alanine levels under fasting conditions, failed to show any significant metabolic alterations. VGB is an effective drug for partial epilepsy. Our observations do not suggest that reduced ALAT activity is of clinical concern.

Treatment of hepatitis C in HCV mono-infected and in HIV-HCV co-infected patients: an open-labelled comparison study.

BACKGROUND/AIMS: Treatment of chronic HCV infection has become a priority in HIV+ patients, given the faster progression to end-stage liver disease. The primary endpoint of this study was to evaluate and compare antiviral efficacy of Peginterferon alpha 2a plus ribavirin in HIV-HCV co-infected and HCV mono-infected patients, and to examine whether 6 months of therapy would have the same efficacy in HIV patients with favourable genotypes 2 and 3 as in mono-infected patients, to minimise HCV-therapy-related toxicities. Secondary endpoints were to evaluate predictors of sustained virological response (SVR) and frequency of side-effects. METHODS: Patients with genotypes 1 and 4 were treated for 48 weeks with Pegasys 180 microg/week plus Copegus 1000-1200 mg/day according to body weight; patients with genotypes 2 and 3 for 24 weeks with Pegasys 180 microg/week plus Copegus 800 mg/day. RESULTS: 132 patients were enrolled in the study: 85 HCV mono-infected (38: genotypes 1 and 4; 47: genotypes 2 and 3), 47 HIV-HCV co-infected patients (23: genotypes 1 and 4; 24: genotypes 2 and 3). In an intention-to-treat analysis, SVR for genotypes 1 and 4 was observed in 58% of HCV mono-infected and in 13% of HIV-HCV co-infected patients (P = 0.001). For genotypes 2 and 3, SVR was observed in 70% of HCV mono-infected and in 67% of HIV-HCV co-infected patients (P = 0.973). Undetectable HCV-RNA at week 4 had a positive predictive value for SVR for mono-infected patients with genotypes 1 and 4 of 0.78 (95% CI: 0.54-0.93) and of 0.81 (95% CI: 0.64-0.92) for genotypes 2 and 3. For co-infected patients with genotypes 2 and 3, the positive predictive value of SVR of undetectable HCV-RNA at week 4 was 0.76 (95%CI, 0.50-0.93). Study not completed by 22 patients (36%): genotypes 1 and 4 and by 12 patients (17%): genotypes 2 and 3. CONCLUSION: Genotypes 2 or 3 predict the likelihood of SVR in HCV mono-infected and in HIV-HCV co-infected patients. A 6-month treatment with Peginterferon alpha 2a plus ribavirin has the same efficacy in HIV-HCV co-infected patients with genotypes 2 and 3 as in mono-infected patients. HCV-RNA negativity at 4 weeks has a positive predictive value for SVR. Aggressive treatment of adverse effects to avoid dose reduction, consent withdrawal or drop-out is crucial to increase the rate of SVR, especially when duration of treatment is 48 weeks. Sixty-one percent of HIV-HCV co-infected patients with genotypes 1 and 4 did not complete the study against 4% with genotypes 2 and 3.

The selective migration of young graduates : which of them return to their rural home region and which do not?

This paper addresses the migration behaviours of young university graduates from a rural region in Switzerland. Based on a questionnaire survey, it compares graduates' current place of residence (i.e. whether or not they returned to their home region) with characteristics related to their socio-familial, migration and professional trajectories. The propensity to return varies not only according to labour market variables (employment opportunities), but also to other factors, some of which have even more influence than job opportunities. The graduates' life course position (kind of household), their partners' characteristics (level of education and home region) and their family background (socio-economic status and history of migration) all play a central role. On the whole, results show that migration appears as a selective and complex process embedded in the life course of graduates.

Co-trimoxazole prophylaxis is associated with reduced risk of incident tuberculosis in participants in the Swiss HIV Cohort Study.

Co-trimoxazole reduces mortality in HIV-infected adults with tuberculosis (TB), and in vitro data suggest potential antimycobacterial activity of co-trimoxazole. We aimed to evaluate whether prophylaxis with co-trimoxazole is associated with a decreased risk of incident TB in Swiss HIV Cohort Study (SHCS) participants. We determined the incidence of TB per 1,000 person-years from January 1992 to December 2012. Rates were analyzed separately in participants with current or no previous antiretroviral treatment (ART) using Poisson regression adjusted for CD4 cell count, sex, region of origin, injection drug use, and age. A total of 13,431 cohort participants contributed 107,549 person-years of follow-up: 182 patients had incident TB-132 (73%) before and 50 (27%) after ART initiation. The multivariable incidence rate ratios for cumulative co-trimoxazole exposure per year for persons with no previous ART and current ART were 0.70 (95% confidence interval [CI], 0.55 to 0.89) and 0.87 (95% CI, 0.74 to 1.0), respectively. Co-trimoxazole may prevent the development of TB among HIV-positive persons, especially among those with no previous ART.

Genetics for clinicians: from candidate genes to whole genome scans (technological advances).

Human genetics has progressed at an unprecedented pace during the past 10 years. DNA microarrays currently allow screening of the entire human genome with high level of coverage and we are now entering the era of high-throughput sequencing. These remarkable technical advances are influencing the way medical research is conducted and have boosted our understanding of the structure of the human genome as well as of disease biology. In this context, it is crucial for clinicians to understand the main concepts and limitations of modern genetics. This review will describe key concepts in genetics, including the different types of genetic markers in the human genome, review current methods to detect DNA variation, describe major online public databases in genetics, explain key concepts in statistical genetics and finally present commonly used study designs in clinical and epidemiological research. This review will therefore concentrate on human genetic variation analysis.

Repeated Double-Poling Sprint Training in Hypoxia by Competitive Cross-country Skiers.

PURPOSE: Repeated-sprint training in hypoxia (RSH) was recently shown to improve repeated-sprint ability (RSA) in cycling. This phenomenon is likely to reflect fiber type-dependent, compensatory vasodilation, and therefore, our hypothesis was that RSH is even more beneficial for activities involving upper body muscles, such as double poling during cross-country skiing. METHODS: In a double-blinded fashion, 17 competitive cross-country skiers performed six sessions of repeated sprints (each consisting of four sets of five 10-s sprints, with 20-s intervals of recovery) either in normoxia (RSN, 300 m; FiO2, 20.9%; n = 8) or normobaric hypoxia (RSH, 3000 m; FiO2, 13.8 %; n = 9). Before (pre) and after (post) training, performance was evaluated with an RSA test (10-s all-out sprints-20-s recovery, until peak power output declined by 30%) and a simulated team sprint (team sprint, 3 × 3-min all-out with 3-min rest) on a double-poling ergometer. Triceps brachii oxygenation was measured by near-infrared spectroscopy. RESULTS: From pretraining to posttraining, peak power output in the RSA was increased (P < 0.01) to the same extent (29% ± 13% vs 26% ± 18%, nonsignificant) in RSH and in RSN whereas the number of sprints performed was enhanced in RSH (10.9 ± 5.2 vs 17.1 ± 6.8, P < 0.01) but not in RSN (11.6 ± 5.3 vs 11.7 ± 4.3, nonsignificant). In addition, the amplitude in total hemoglobin variations during sprints throughout RSA rose more in RSH (P < 0.01). Similarly, the average power output during all team sprints improved by 11% ± 9% in RSH and 15% ± 7% in RSN. CONCLUSIONS: Our findings reveal greater improvement in the performance of repeated double-poling sprints, together with larger variations in the perfusion of upper body muscles in RSH compared with those in RSN.

MGMT promoter methylation in malignant gliomas.

The O(6)-methylguanine-DNA methyltransferase (MGMT) gene is located at chromosome 10q26 and codes for a DNA repair enzyme that--if active--can counteract the effects of alkylating chemotherapy. Malignant gliomas often have the MGMT gene inactivated due to aberrant methylation of its promoter region. The assessment of the MGMT promoter methylation status has become of clinical relevance as a molecular marker associated with response to alkylating chemotherapy and prolonged survival of glioblastoma patients. MGMT promoter methylation testing is also on the merge of being used as a marker for patient selection within clinical trials, e.g., the current CENTRIC trial that is specifically focusing on patients with MGMT promoter-methylated glioblastomas. In anaplastic gliomas, MGMT promoter methylation is a favorable prognostic marker independent of the type of therapy, i.e., radio- or chemotherapy. This occurrence might be associated with the high incidence of other prognostically favorable molecular markers in these tumors, such as IDH1 mutation, 1p/19q deletion or yet to be identified novel aberrations. A variety of different methods are being used to assess MGMT promoter methylation in clinical samples, which may give rise to inter-laboratory variations in test results. Immunohistochemical determination of MGMT protein expression has not proven reliable for diagnostic purposes. This brief review article aims to summarize the main aspects of MGMT promoter methylation testing in contemporary neuro-oncology, in particular its value as a clinically useful molecular marker, putting it into the context of other molecular markers of clinical use in gliomas of adult patients.

Efficacy of clarithromycin versus that of clindamycin for single-dose prophylaxis of experimental streptococcal endocarditis.

Clarithromycin is compared with clindamycin for single-dose prophylaxis of streptococcal endocarditis in rats. Human-like kinetics of the two antibiotics prevented endocarditis in animals challenged with both small and large amounts of bacterial inocula. Clarithromycin was marginally superior to clindamycin against small amounts of inocula. Clarithromycin may be considered for endocarditis chemoprophylaxis in human.

Characterization of the role of AKAP-Lbc/p38 complex in the hypertrophic response of the heart

In response to chronic stress the heart undergoes an adverse remodeling process associated with cardiomyocyte hypertrophy, increased cellular apoptosis and fibrosis, which ultimately causes cardiac dysfunction and heart failure. Increasing evidence suggest the role of scaffolding and anchoring proteins in coordinating different signaling pathways that mediate the hypertrophic response of the heart. In this context, the family of Α-kinase anchoring proteins (AKAPs) emerged as important regulators of the cardiac function. During my thesis work I have conducted two independent projects, both of them aiming at elucidating the role of AKAPs in the heart. It has been shown that AKAP-Lbc, an anchoring protein that possesses an intrinsic Rho- specific exchange factor activity, organizes a signaling complex that links AKAP-Lbc- dependent activation of RhoA with the mitogen activated protein kinase (MAPK) p38. The first aim of my thesis was to study the role of this novel transduction pathway in the context of cardiac hypertrophy. Here we show that transgenic mice overexpressing in cardiomyocytes a competitor fragment of AKAP-Lbc, which specifically disrupts endogenous AKAP-Lbc / p38 complexes, developed early dilated cardiomyopathy in response to two weeks of transverse aortic constriction (TAC) as compared to controls. Interestingly, inhibition of the AKAP-Lbc / p38 transduction pathway significantly reduced the hypertrophic growth of single cardiomyocytes induced by pressure overload. Therefore, it appears that the AKAP- Lbc / p38 complex is crucially involved in the regulation of stress-induced cardiomyocyte hypertrophy and that disruption of this signaling pathway is detrimental for the heart under conditions of sustained hemodynamic stress. Secondly, in order to identify new AKAPs involved in the regulation of cardiac function, we followed a proteomic approach which allowed us to characterize AKAP2 as a major AKAP in the heart. Importantly, here we show that AKAP2 interacts with several proteins known to be involved in the control of gene transcription, such as the nuclear receptor coactivator 3 (NCoA3) or the ATP-dependent SWI/SNF chromatin remodeling complex. Thus, we propose AKAP2 as a novel mediator of cardiac gene expression through its interaction with these transcriptional regulators.

Medical and legal professionals' attitudes towards confidentiality and disclosure of clinical information in forensic settings: a survey using case vignettes.

OBJECTIVE: When potentially dangerous patients reveal criminal fantasies to their therapists, the latter must decide whether this information has to be transmitted to a third person in order to protect potential victims. We were interested in how medical and legal professionals handle such situations in the context of prison medicine and forensic evaluations. We aimed to explore the motives behind their actions and to compare these professional groups. METHOD: A mail survey was conducted among medical and legal professionals using five fictitious case vignettes. For each vignette, participants were asked to answer questions exploring what the professional should do in the situation and to explain their justification for the chosen response. RESULTS: A total of 147 questionnaires were analysed. Agreement between participants varied from one scenario to another. Overall, legal professionals tended to disclose information to a third party more easily than medical professionals, the latter tending to privilege confidentiality and patient autonomy over security. Perception of potential danger in a given situation was not consistently associated with actions. CONCLUSION: Professionals' opinions and attitudes regarding the confidentiality of potentially dangerous patients differ widely and appear to be subjectively determined. Shared discussions about clinical situations could enhance knowledge and competencies and reduce differences between professional groups.