Obesity dependent metabolic signatures associated with nonalcoholic fatty liver disease progression

Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLCMS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual’s level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values = 0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention

Implementation of an extended ZINB model in the study of low levels of natural gastrointestinal nematode infections in adult sheep

Background: In this study, two traits related with resistance to gastrointestinal nematodes (GIN) were measured in 529 adult sheep: faecal egg count (FEC) and activity of immunoglobulin A in plasma (IgA). In dry years, FEC can be very low in semi-extensive systems, such as the one studied here, which makes identifying animals that are resistant or susceptible to infection a difficult task. A zero inflated negative binomial model (ZINB) model was used to calculate the extent of zero inflation for FEC; the model was extended to include information from the IgA responses. Results: In this dataset, 64 % of animals had zero FEC while the ZINB model suggested that 38 % of sheep had not been recently infected with GIN. Therefore 26 % of sheep were predicted to be infected animals with egg counts that were zero or below the detection limit and likely to be relatively resistant to nematode infection. IgA activities of all animals were then used to decide which of the sheep with zero egg counts had been exposed and which sheep had not been recently exposed. Animals with zero FEC and high IgA activity were considered resistant while animals with zero FEC and low IgA activity were considered as not recently infected. For the animals considered as exposed to the infection, the correlations among the studied traits were estimated, and the influence of these traits on the discrimination between unexposed and infected animals was assessed. Conclusions: The model presented here improved the detection of infected animals with zero FEC. The correlations calculated here will be useful in the development of a reliable index of GIN resistance that could be of assistance for the study of host resistance in studies based on natural infection, especially in adult sheep, and also the design of breeding programs aimed at increasing resistance to parasites

The development of a resource-efficient photovoltaic system

This paper presents the measures taken in the demonstration of the photovoltaic case study developed within the European project ‘Towards zero waste in industrial networks’ (Zerowin), integrating the D4R (Design for recycling, repair, refurbishment and reuse) criteria at both system and industrial network level. The demonstration is divided into three phases. The first phase concerns the development of a D4R photovoltaic concept, the second phase focused on the development of a specific component of photovoltaic systems and the third phase was the demonstration of the D4R design in two complete photovoltaic systems (grid-connected and stand-alone). This paper includes a description of the installed photovoltaic systems, including a brief summary at component level of the lithium ion battery system and the D4R power conditioning system developed for the pilot installations. Additionally, industrial symbioses within the network associated with the photovoltaic systems and the production model for the network are described

Curie temperature enhancement of electron doped Sr2_2FeMoO6_6 perovskites studied by photoemission spectroscopy

We report here on the electronic structure of electron-doped half-metallic ferromagnetic perovskites such Sr$_{2-x}$La$_x$FeMoO$_6$ ($x$=0-0.6) as obtained from high-resolved valence-band photoemission spectroscopy (PES). By comparing the PES spectra with band structure calculations, a distinctive peak at the Fermi level (E$_F$) with predominantly (Fe+Mo) t$_{2g}^\downarrow$ character has been evidenced for all samples, irrespectively of the $x$ values investigated. Moreover, we show that the electron doping due to the La substitution provides selectively delocalized carriers to the t$_{2g}^\downarrow$ metallic spin channel. Consequently, a gradual rising of the density of states at the E$_F$ has been observed as a function of the La doping. By changing the incoming photon energy we have shown that electron doping mainly rises the density of states of Mo parentage. These findings provide fundamental clues for understanding the origin of ferromagnetism in these oxides and shall be of relevance for tailoring oxides having still higher T$_C$

The IFMIF-EVEDA accelerator beam dump design

The IFMIF-EVEDA accelerator will be a 9 MeV, 125 mA cw deuteron accelerator prototype for verifying the validity of the 40 MeV accelerator design for IFMIF. A beam dump designed for maximum power of 1.12 MW will be used to stop the beam at the accelerator exit. The conceptual design for the IFMIF-EVEDA accelerator beam dump is based on a conical beam stop made of OFE copper. The cooling system uses an axial high velocity flow of water pressurized up to 3.4 × 105 Pa to avoid boiling. The design has been shown to be compliant with ASME mechanical design rules under nominal full power conditions. A sensitivity analysis has been performed to take into account the possible margin on the beam properties at the beam dump entrance. This analysis together with the study of the maintenance issues and the mounting and dismounting operations has led to the complete design definition

Autologous stem cell transplantation may be curative for patients with follicular lymphoma with early therapy failure without the need for immunotherapy

Objective/Background: Patients with follicular lymphoma (FL) with early therapy failure (ETF) within 2 years of frontline therapy have poor overall survival (OS). We recently reported the results of autologous stem cell transplantation (ASCT) in patients from the Grupo Español de Linfomas y Trasplantes de Médula Ósea (GELTAMO) registry treated with rituximab prior to ASCT and with ETF after first-line immunochemotherapy, leading to 81% 5-year OS since ASCT. We explored whether ASCT is also an effective option in the pre-rituximab era—that is, in patients treated in induction and rescued only with chemotherapy. Methods: ETF was defined as relapse/progression within 2 years of starting first-line therapy. We identified two groups: the ETF cohort (n = 87) and the non-ETF cohort (n = 47 patients receiving ASCT but not experiencing ETF following first-line therapy). Results: There was a significant difference in 5-year progression-free survival between the ETF and non-ETF cohorts (43% vs. 57%, respectively; p = .048). Nevertheless, in patients with ETF with an interval from first relapse after primary treatment to ASCT of <1 year, no differences were observed in 5-year progression-free survival (48% vs. 66%, respectively; p = .44) or in 5-year OS (69% vs. 77%, p = .4). Patients in the ETF cohort transplanted in complete remission showed a plateau in the OS curves, at 56%, beyond 13.7 years of follow-up. Conclusion: ASCT may be a curative option for ETF in patients who respond to rescue chemotherapy, without the need for immunotherapy or other therapies, and should be considered as an early consolidation, especially in patients with difficult access to rituximab

Prolonged survival of patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation: the GELTAMO experience

Abstract OBJECTIVES: Angioimmunoblastic T-cell lymphoma (AIL) is a rare lymphoma with a poor prognosis and no standard treatment. Here, we report our experiences with 19 patients treated with high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) within the GELTAMO co-operative group between 1992 and 2004. METHODS: The median age at transplantation was 46 yr. Fifteen patients underwent the procedure as front-line therapy and four patients as salvage therapy. Most patients received peripheral stem cells (90%) coupled with BEAM or BEAC as conditioning regimen (79%). RESULTS: A 79% of patients achieved complete response, 5% partial response and 16% failed the procedure. After a median follow-up of 25 months, eight patients died (seven of progressive disease and secondary neoplasia), while actuarial overall survival and progression-free survival at 3 yr was 60% and 55%. Prognostic factors associated with a poor outcome included bone marrow involvement, transplantation in refractory disease state, attributing more than one factor of the age-adjusted-International Prognostic Index, Pretransplant peripheral T-cell lymphoma (PTCL) Score or Prognostic Index for PTCL. CONCLUSIONS: More than half of the patients with AIL that display unfavourable prognostic factors at diagnosis or relapse would be expected to be alive and disease-free after 3 yr when treated with HDC/ASCT. Patients who are transplanted in a refractory disease state do not benefit from this procedure

Un nuevo grupo de manos paleolíticas pintadas en el sur de la Península Ibérica. La cueva de las Estrellas (Castellar de la Frontera, Cádiz)

Presentamos en este trabajo la revisión de las manifestaciones de arte rupestre conservadas en una estación localizada en la comunidad autónoma de Andalucía, conocida en la literatura precedente como cueva de Las Estrellas (Castellar de la Frontera, Cádiz). Se trata de un abrigo rocoso de grandes dimensiones, abierto al aire libre, en el que ya se había constatado, en los primeros años del presente siglo, la presencia de diversas pictografías de estilo esquemático. Durante una visita reciente al enclave se ha advertido, además, la existencia de un importante conjunto figurativo de cronología paleolítica que incluye representaciones de fauna y una pequeña serie de improntas de manos en negativo. Este artículo aborda el análisis genérico de las grafías catalogadas hasta el momento en la cavidad, atendiendo con especial detalle al conjunto de las citadas huellas de manos paleolíticas, que han sido documentadas usando tecnología digital 3d. De igual modo, se tendrán en cuenta su contextualización en el arte paleolítico andaluz y una primera aproximación cronológica a este interesante y variado complejo figurativo

As múltiplas funções da agricultura familiar: um estudo no assentamento Monte Alegre, região de Araraquara (SP).

A partir da emergência da ideia de sustentabilidade, a agricultura adquiriu novas conotações, associadas não apenas ao aspecto produtivo, mas também à conservação dos recursos naturais e dos territórios rurais, em um reconhecimento de sua multifuncionalidade. Com base nesta noção, que valoriza as funções socioambientais desempenhadas pelas famílias rurais e pelas agriculturas praticadas, o presente artigo analisa um assentamento rural no estado de São Paulo, buscando identificar quais são e de que forma se expressam as funções para além da produção neste território particular. Por meio de uma metodologia de cunho quali-quantitativo, observou-se que, no assentamento em foco, a agricultura encerra em si questões de coesão territorial, manutenção da segurança alimentar, conservação da agrobiodiversidade e de fomento a outras atividades produtivas, sendo o elemento central da reconstrução de um modo de vida rural neste ambiente