Background & Aims Subtle inter-patient genetic variation and environmental factors combine to determine disease progression in non-alcoholic fatty liver disease (NAFLD). Carriage of the PNPLA3 ...rs738409 c.444C >G minor allele (encoding the I148M variant) has been robustly associated with advanced NAFLD. Although most hepatocellular carcinoma (HCC) is related to chronic viral hepatitis or alcoholic liver disease, the incidence of NAFLD-related HCC is increasing. We examined whether rs738409 C >G was associated with HCC-risk in patients with NAFLD. Methods PNPLA3 rs738409 genotype was determined by allelic discrimination in 100 European Caucasians with NAFLD-related HCC and 275 controls with histologically characterised NAFLD. Results Genotype frequencies were significantly different between NAFLD-HCC cases (CC = 28, CG = 43, GG = 29) and NAFLD-controls (CC = 125, CG = 117, GG = 33) ( p = 0.0001). In multivariate analysis adjusted for age, gender, diabetes, BMI, and presence of cirrhosis, carriage of each copy of the rs738409 minor (G) allele conferred an additive risk for HCC (adjusted OR 2.26 95% CI 1.23–4.14, p = 0.0082), with GG homozygotes exhibiting a 5-fold 1.47–17.29, p = 0.01 increased risk over CC. When compared to the UK general population (1958 British Birth Cohort, n = 1476), the risk-effect was more pronounced (GC vs. CC: unadjusted OR 2.52 1.55–4.10, p = 0.0002; GG vs. CC: OR 12.19 6.89–21.58, p <0.0001). Conclusions Carriage of the PNPLA3 rs738409 C >G polymorphism is not only associated with greater risk of progressive steatohepatitis and fibrosis but also of HCC. If validated, these findings suggest that PNPLA3 genotyping has the potential to contribute to multi-factorial patient-risk stratification, identifying those to whom HCC surveillance may be targeted.
Sorafenib (S), a multitargeted tyrosine kinase inhibitor, is the standard of care for first-line systemic treatment of advanced hepatocellular carcinoma (HCC). Everolimus (E) is a potent inhibitor of ...mTOR, a pathway frequently activated in HCC. Preclinical data suggest that the combination S + E has additive effects compared with single-agent S.
Patients with unresectable or metastatic HCC and Child-Pugh ≤7 liver dysfunction were randomized to receive daily S 800 mg alone or with E 5 mg until progression or unacceptable toxicity. The primary end point was progression-free survival at 12 weeks (PFS12). The secondary end points included response rate, PFS, time to progression (TTP), overall survival (OS), duration of disease stabilization (DDS), safety, and quality-of-life (QoL) assessments.
A total of 106 patients were randomized: 46 patients received S and 60 patients received S + E. Ninety-three patients were assessable for the primary end point and 105 patients for the safety analysis. The PFS12 rate was 70% 95% confidence interval (CI) 54–83 and 68% (95% CI 53–81) in patients randomized to S and S + E, respectively. The RECIST (mRECIST) response rate was 0% (23%) in the S arm and 10% (35%) in the S + E arm. Median PFS (6.6 versus 5.7 months), TTP (7.6 versus 6.3 months), DDS (6.7 versus 6.7 months), and OS (10 versus 12 months) were similar in the S and S + E arms, respectively. Grade 3/4 adverse events occurred in 72% and 86% of patients in arm S and arm S + E, respectively. Patients had similar QoL scores over time, except for a greater worsening in physical well-being and mood in the arm S + E.
No evidence was found that S + E improves the efficacy compared with S alone. Combining 5 mg E with full-dose S is feasible, but more toxic than S alone. Further testing of this drug combination in molecularly unselected HCCs appears unwarranted.
NCT01005199.
Gasification of biomass can be used for obtaining hydrogen reducing the total greenhouse gases emissions due the fixation of CO2 during photosynthetic processes. The kind of raw materials is an ...important variable since has a great influence on the energy balance and environmental impacts. Wastes from forestry are considered as the most appropriate raw materials since they do not compete for land. The aim of this work is to determine the environmental feasibility of four Spanish lignocellulosic wastes (vine and almond pruning and forest waste coming from pine and eucalyptus plantation) for the production of hydrogen through gasification. LCA methodology was applied using global warming potential, acidification, eutrophication and the gross energy necessary for the production of 1 Nm3 of hydrogen as impact categories. As expected, the use of biomass instead of natural gas leads to the reduction of CO2 emissions. Regarding to the different feedstocks, biomass coming from forestry is more environmental-friendly since does not need cropping procedures. Finally, the distribution of environmental charges between pruning wastes and fruits (grape and almond) and the use of obtained by-products have a great influence, reducing the environmental impacts.
► Gasification of several biomass feedstocks has been evaluated by LCA methodology. ► Biomass coming from eucalyptus presents the best environmental performance. ► Recovery and use of non-converted methane clearly reduce environmental impacts. ► Allocation of cultivation charges reduces CO2 credit increasing GHG emissions.
Summary
In order to accurately assess the burden of hepatitis C (HCV) and develop effective interventions, we must understand the magnitude and trends of mortality related to the disease. In the ...United States, HCV‐related mortality is continuously increasing. We have no comparable data for Switzerland and other European countries, although a modelling study predicted a similar increase. We analysed time trends (1 January 1995‐31 December 2014) in HCV‐specific mortality rates in the Swiss general population using the death registry of the Swiss Federal Statistical Office (SFSO). We compared HCV‐related mortality to HIV‐related and hepatitis B (HBV)‐related mortality. To determine potential under‐reporting in HCV‐related mortality, we probabilistically linked the SFSO data to persons who died in the Swiss Hepatitis C Cohort Study (SCCS). SFSO data showed that HCV‐related mortality more than doubled between 1995 and 2003, but has since stabilized at ~2.5/100 000 person‐years. Since 2000, HCV‐related mortality has been higher than HIV‐related mortality and was about fivefold higher in 2014. HBV‐related mortality remained low at ~0.5/100 000 person‐years. Of 4556 persons in the SCCS, 421 have died and 86.2% could be linked to the death registry. According to the SCCS, 133 deaths were HCV‐related. HCV was not mentioned on the SFSO death certificate of 45% of these (n = 60/133). In conclusion, HCV‐related mortality remained constant, possibly because quality of care was high, or because of under‐reporting or because mortality has not yet increased. However, HCV‐related mortality is now much higher than HIV‐ and HBV‐related mortality, and under‐reporting was common.
Summary
It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular ‘nurse cell’, not only a key cell in the testis, but indeed one of the most amazing ...cells in the vertebrate body. In this review, we begin by examining the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery. Biochemistry and molecular biology then changed all of biological sciences, including our understanding of the functions of Sertoli cells. Immunology and stem cell biology were not even topics of science in 1865, but they have now become major issues in our appreciation of Sertoli cell's role in spermatogenesis. We end with the universal importance and plasticity of function by comparing Sertoli cells in fish, amphibians, and mammals. In these various classes of vertebrates, Sertoli cells have quite different modes of proliferation and epithelial maintenance, cystic vs. tubular formation, yet accomplish essentially the same function but in strikingly different ways.
Abstract
Even though the simulations used to describe the failure of laminates are becoming more and more predictive, complex testing under multiaxial loadings is still required to validate the ...design of structural parts in a wide range of industrial domains. It is thus essential to assess the actual boundary conditions to allow for an objective comparison between testing and calculations, in particular since the structural tests are complex and often leads to buckling. Therefore, accurate estimation of force and moment fluxes applied to the specimen is critical. In this context, stereo digital image correlation (SDIC) has proven to be an important measurement tool and provides very well‐resolved surface displacement fields, but the exploitation of such measurements to calculate fluxes remains problematic when testing composites. The first objective of this study is both to reduce the uncertainty associated with fluxes determination on a complex test and to simplify the extraction process with respect to existing procedures. The second objective is to make this methodology robust to geometrically non‐linear deformations. In this paper, we propose a new methodology that extracts minimal boundary conditions in the form of 3D mechanically admissible displacements fields. The approach developed uses a finite element SDIC (FE‐SDIC) method regularized by means of mechanical behaviour admissibility equations. Results show that the new methodology outputs much more accurate fluxes than classical data generated from multiple differentiations of the displacement fields. Excellent noise robustness is obtained and quantified. Numerical predictions have been satisfactorily compared with experimental data from one structural‐scale composite specimen under complex testing.
The water gas shift reaction is an essential process to adjust the CO/H2 ratio in the industrial production of hydrogen. FeCr catalysts have been widely used in this reaction at high temperature but ...have environmental and safety concerns related to chromium content. In this work, the replacement of chromium by molybdenum in magnetite-based catalysts is studied. The materials were prepared by oxidation–precipitation and wet impregnation and they were characterized using X-ray powder diffraction, X-ray fluorescence, transmission electron microscopy, and temperature programmed reduction. Specific surface areas of samples were also measured. The results obtained indicate that molybdenum increases thermal stability of the magnetite active phase and prevents metallic iron formation during the reaction. The oxidation–precipitation method allows obtaining the material directly in the active phase and molybdenum is incorporated into magnetite lattice.
Abstract Even though the simulations used to predict failure are becoming increasingly predictive, complex multiaxial loading tests are still required to validate the design of structural components ...in a wide range of industries. Large specimen testing often requires two different scales. A global Far Field to obtain boundary conditions and a local Near Field to evaluate strain gradients around discontinuities such as bolts, notches… The main goal of this study is to provide a continuous displacement over the whole specimen surface integrating data from multiple cameras. In this paper, we propose a new methodology that generates 3D displacements determined by finite‐element stereo digital image correlation in the Near Field and in the Far Field using a unique fractal speckle pattern and an off‐line determined texture . The displacements are obtained in the same coordinate system and on the same mesh. Satisfactory data fusion from both Near Field and Far Field images of a biaxial test on a notched laminate composite was obtained with a refined mesh at the notch tip. This methodology can be applied to any tests requiring multiple camera systems and will support the use of the finite‐element digital image correlation framework as an experimental‐numerical efficient technique.
Abstract Background Hand hygiene is a major means for preventing healthcare-associated infections. One critical point in understanding poor compliance is the lack of relevant markers used to ...systematically monitor practices. Methods We analyzed hand hygiene compliance and associated factors with a radio-frequency identification (RFID)-based real time continuous automated monitoring system in a 17 single bedroom infectious disease ward. Heath care workers (HCW) were tracked while performing routine care during 171 days. A multilevel multivariate logistics model was used for data analysis. The main outcome measures were hand disinfection before entering the bedroom (outside used) and before entering the patient zone, defined as the zone surrounding the patient’s bed (inside/bedside used). Variables analyzed included healthcare workers’ characteristics and behavior, patients, room layouts, path chains and duration of healthcare worker paths. Findings 4,629 paths with initial hand hygiene opportunities when entering the care zone were selected, of which 763 (16.5%), 285 (6.1%), and 3581 (77.4%) were associated with outside use, inside/bedside use and no use respectively. Hand hygiene is caregiver-dependent. The shorter the HCW path duration, the worse the bedside hand hygiene. Bedside hand hygiene is improved when one or two extra healthcare workers are present in the room. Interpretation Hand hygiene compliance at the bedside, as analyzed using the continuous monitoring system, depended upon the healthcare worker’s occupation and personal behavior, number of HCWs, time spent in the room, and potentially the dispenser location. Meal tray distribution was also a possible factor in the case of failure to disinfect hands.
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