Development and testing of galvanic anodes for cathodic protection

Aquest treball resumeix els resultats obtinguts en un projecte de recerca dut a terme en el nostre laboratori i relacionat amb l'assaig electroquímic dels ànodes de sacrifici emprats en protecció catòdica, així com en el desenvolupament de nous ànodes d'alumini -Al- lliures d'indi -In- i de mercuri -Hg. Les aportacions més importants han estat fetes en els aspectes següents: 1. Mecanisme de corrosió durant els assaigs electroquímics. 1.1. Al. Assaig electroquímic d'ànodes de sacrifici de Al. 1.2. Mg. Mecanisme de dissolució dels ànodes de sacrifici de Mg durant l'assaig electroquímic. 1.3. Zn. L'impedància electroquímica com a eina d'assaig dels ànodes de sacrifici de Zn aplicats per projecció tèrmica sobre el formigó. 2. Augment de l'eficiència electroquímica dels ànodes de Mg mitjançant el tractament tèrmic i el control de la seva microestructura. 3. Disseny i desenvolupament de nous ànodes de Al sense In ni Hg. Aquests nous ànodes de Al-Zn-Mg-Li són proposats com una alternativa als actualment en ús. El sistema Al-Mg-Zn ha estat escollit a causa de la presència de precipitats en la matriu de l'alumini, que poden ser capaços de trencar la pel·lícula passiva, però mantenen una alta eficiència electroquímica.This paper summarizes the results obtained in the research project carried out in our laboratory related to the testing of sacrificial anodes used in cathodic protection (CP) systems and the development of new In/Hg-free aluminium-alloy anodes. The main contributions are in the following subjects: 1. Corrosion mechanism during electrochemical testing. 1.1. Al. Electrochemical testing of Al sacrificial anodes. 1.2. Mg. Dissolution mechanism of Mg sacrificial anodes under electrochemical testing. 1.3. Zn. EIS testing of thermal spray Zn anodes for concrete applications. 2. Improving the efficiency of Mg sacrificial anodes by microstructure control and heat treatments. 3. Design and development of new Al-alloy anodes In/Hg free. The evaluation of an Al-Zn-Mg-Li alloy as a potential candidate for Al-sacrificial anode was studied. The Al-Zn-Mg system was particularly selected due to the presence of precipitates in _-Al matrix which are capable of breaking down passive films whilst presenting good electrochemical efficiencies. The effect of Li additions on superficial activation of the anode by means of precipitation of AlLi type compounds was also examined

Un análisis comparativo de las características de las microempresas en España

A pesar del creciente interés y de la atención prestada a las microempresas por parte de las administraciones públicas, se echan en falta investigaciones empíricas sobre este tema en España. En el presente trabajo se examinan las principales características de este segmento empresarial en España y se comparan con las de varios países de la Unión Europea a partir de múltiples fuentes de datos. Los resultados indican que el elevado peso de las microempresas en España en sectores como la construcción, el comercio, la hostelería y los transportes parece responder a la falta de oportunidades de empleo asalariado adecuado. Los resultados también muestran que el nivel de formación de los empresarios-directivos de microempresas es inferior al que se observa en la UE e incluso es menor al de los parados en los mencionados sectores. Para finalizar, se discuten las implicaciones que se derivan de los resultados obtenidos y se presentan orientaciones para futuras investigaciones

Serum miR-181b-5p predicts ascites onset in patients with compensated cirrhosis

Betabloqueantes; MicroARN; Hipertensión portalBetablocadors; MicroRNAs; Hipertensió portalBeta-blockers; MicroRNAs; Portal hypertensionBackground & Aims Treatment with non-selective beta-blockers (NSBBs) reduces the risk of ascites, which is the most common decompensating event in cirrhosis. This study aimed to assess the ability of a serum microRNA (miRNA) signature to predict ascites formation and the hemodynamic response to NSBBs in compensated cirrhosis. Methods Serum levels of miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p were analyzed in patients with compensated cirrhosis (N = 105). Hepatic venous pressure gradient (HVPG) was measured at baseline, after intravenous propranolol, and 1 year after randomization to NSBBs (n = 52) or placebo (n = 53) (PREDESCI trial). miRNAs were analyzed at baseline and at 1 year. Results Nineteen patients (18%) developed ascites, of whom 17 developed ascites after 1 year. miR-181b-5p levels at 1 year, but not at baseline, were higher in patients that developed ascites. The AUC of miR-181b-5p at 1 year to predict ascites was 0.7 (95% CI 0.59–0.78). miR-429 levels were lower at baseline in acute HVPG responders to NSBBs (AUC 0.65; 95% CI, 0.53–0.76), but levels at baseline and at 1 year were not associated with the HVPG response to NSBBs at 1 year. Conclusions Serum miR-181b-5p is a promising non-invasive biomarker to identify patients with compensated cirrhosis at risk of ascites development.Supported by grants from the Ministerio de Ciencia e Innovación and Instituto de Salud Carlos III (SAF 2017-86343-R awarded to A.A., PI20/01302 to A.A., PI18/01901 to R.B., CIBEREHD-16PI03 and PI20/00220 to J.G.S.). A.G.G.P is the recipient of a grant from Ministerio de Ciencia e Innovación and Instituto de Salud Carlos III (Contrato Rio Hortega CM18/00091). Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD) is funded by the Instituto de Salud Carlos III with grants cofinanced by the European Development Regional Fund “A way to achieve Europe” (EDRF). Supported in part by a grant from Gilead Sciences (GLD19/00045)

Noninvasive predictors of clinically significant portal hypertension in NASH cirrhosis: Validation of ANTICIPATE models and development of a lab-based model

Noninvasive predictors; Portal hypertension; CirrhosisPredictores no invasivos; Hipertensión portal; CirrosisPredictors no invasius; Hipertensió portal; CirrosiClinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg, identifies patients with compensated cirrhosis at a high risk of decompensation. However, HVPG is an invasive and nuanced method. The ANTICIPATE models, which include liver stiffness measurements by transient elastography (TE) and platelet count ± body mass index, are robust noninvasive surrogates of CSPH but required external validation in patients with nonalcoholic steatohepatitis (NASH) cirrhosis. Additionally, TE is not widely available worldwide. The aims of the study were: (1) to externally validate the ANTICIPATE models using baseline data from patients with compensated NASH cirrhosis screened/enrolled in a multicenter international randomized controlled trial; and (2) to develop and externally validate a model using only laboratory values. Regarding aim 1, both ANTICIPATE models showed good calibration and discrimination (area under the curve [AUC] > 0.8) in our cohort (n = 222). Regarding aim 2, a new lab-based model using the Fibrosis-4 index (FIB-4 [age, aspartate aminotransferase, alanine aminotransferase, platelet count]) plus serum albumin was developed. The discrimination in the training cohort (n = 309) was good (AUC of 0.78 [95% confidence interval [CI]:0.72–0.83]). It was then externally validated in a separate cohort of 245 patients with compensated NASH cirrhosis (AUC of 0.8 [95% CI: 0.75–0.86]). Given the difference in the prevalence of CSPH between training (74%) and validation (39%) cohorts, the model required an update of the baseline risk to achieve a good calibration. The updated model was named FIB4+. In conclusion, both ANTICIPATE models performed well in predicting the presence of CSPH in NASH cirrhosis. A model using FIB-4 plus albumin (FIB4+) can be used to predict CSPH where TE is not available.Supported by the Yale Liver Center, National Institutes of Health (P30 DK34989)

Liver steatosis induces portal hypertension regardless of fibrosis in patients with NAFLD: A proof of concept case report

Esteatosi hepàtica; Hipertensió portalLiver steatosis; Portal hypertensionEsteatosis hepática; Hipertensión portalNo financial support was received for data analysis or writing assistance. JRE is a PhD student at Universitat Autònoma de Barcelona, Spain. JMP reports having received consulting fees from Boehringer Ingelheim, MSD and Novo Nordisk. He has received speaking fees from Gilead, Intercept, and Novo Nordisk, and travel expenses from Gilead, Rubió, Pfizer, Astellas, MSD, CUBICIN, and Novo Nordisk. He has received educational and research support from Madrigal, Gilead, Pfizer, Astellas, Accelerate, Novartis, Abbvie, ViiV, and MSD. Funds from European Commission/EFPIA IMI2 853966-2, IMI2 777377, H2020 847989, and ISCIII PI19/01898 (PI22/01770). JG has received consulting fees from Boehringer Ingelheim, speaking fees from Echosens and travel expenses from Gilead and Abbie. Funds from ISCIII PI18/00947 and PI21/00691. All other authors: nothing to disclose

Effects of Albumin on Survival after a Hepatic Encephalopathy Episode: Randomized Double-Blind Trial and Meta-Analysis

Albúmina; Assaig clínic; MetanàlisiAlbumin; Clinical trial; Meta-analysisAlbúmina; Ensayo clínico; MetaanálisisNo therapies have been proven to increase survival after a hepatic encephalopathy (HE) episode. We hypothesize that two doses of albumin could improve 90-day survival rates after a HE episode. Methods: (1) A randomized double-blind, placebo-controlled trial (BETA) was conducted in 12 hospitals. The effect of albumin (1.5 g/kg at baseline and 1 g/kg on day 3) on 90-day survival rates after a HE episode grade II or higher was evaluated. (2) A meta-analysis of individual patient’s data for survival including two clinical trials (BETA and ALFAE) was performed. Results: In total, 82 patients were included. Albumin failed to increase the 90-day transplant-free survival (91.9% vs. 80.5%, p = 0.3). A competing risk analysis was performed, observing a 90-day cumulative incidence of death of 9% in the albumin group vs. 20% in the placebo (p = 0.1). The meta-analysis showed a benefit in the albumin group, with a lower rate of clinical events (death or liver transplant) than patients in the placebo (HR, 0.44; 95% CI, 0.21–0.82), when analyzed by a competing risk analysis (90-days mortality rate of 11% in the albumin group vs. 30% in the placebo, p = 0.02). Conclusions: Repeated doses of albumin might be beneficial for patient’s survival as an add-on therapy after an HE episode, but an adequately powered trial is needed.This work was supported by grants ICI14/00352 and PI/18/00947 from Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union (ERDF/ESF, “Investing in your future”—Una manera de hacer Europa). MVC and MST are both recipients of Juan Rodes grants from ISCIII. JG is a recipient of a research intensification grant from the ISCIII. CIBERehd is supported by ISCIII. ACS is a recipient of the Rio Hortega grant from ISCIII. The work was independent of all funding

Platform trials to overcome major shortcomings of traditional clinical trials in non-alcoholic steatohepatitis? Pros and cons

Non-alcoholic steatohepatitis; Drug development; Non-invasive biomarkersEsteatohepatitis no alcohólica; Desarrollo de fármacos; Biomarcadores no invasivosEsteatohepatitis no alcohòlica; Desenvolupament de medicaments; Biomarcadors no invasiusNon-alcoholic fatty liver disease is a condition that affects 25% of the population. Non-alcoholic steatohepatitis (NASH) is a progressive form of the disease that can lead to severe complications such as cirrhosis and hepatocellular carcinoma. Despite its high prevalence, no drugs are currently approved for the treatment of NASH. The drug development pipeline in NASH is very active, yet most assets do not progress to phase III trials and those that do reach phase III often fail to achieve the endpoints necessary for approval by regulatory agencies. Amongst other reasons, the methodological and operational features of traditional clinical trials in NASH might impede optimal drug development. In this regard, platform trials might be an attractive complement or alternative to conventional clinical trials. Platform trials use a master protocol which enables evaluation of multiple investigational medicinal products concurrently or sequentially with a single, shared control arm. Through Bayesian interim analyses, these trials allow for early exit of drugs from the trial based on success or futility, while providing participants better chances of receiving active compounds through adaptive randomisation. Overall, platform trials represent an alternative for patients, pharmaceutical companies, and clinicians in the quest to accelerate the approval of pharmacologic treatments for NASH.EU-PEARL has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966-2. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and Children’s Tumor Foundation, Global Alliance for TB Drug Development Non-profit Organisation, Springworks Therapeutics Inc

Duration of the acute hepatic encephalopathy episode determines survival in cirrhotic patients

Altres ajuts: MST is a recipient of a Río Hortega grant from Instituto de Salud Carlos III, Spain. JG is a recipient of a Research Intensification grant from Instituto de Salud Carlos III, Spain. MVC is a recipient of a scholarship grant for study extension abroad, sponsored by the Spanish Association for the Study of the Liver. CIBERehd is supported by Instituto de Salud Carlos III, Spain.Episodes of hepatic encephalopathy (HE) have been related to low survival rate. However, the relation between its clinical evolution and mortality has not been assessed. A retrospective analysis of 245 cirrhotic patients admitted for an acute episode of HE (⩾grade 2) or who developed an HE episode after an upper gastrointestinal bleeding (UGIB) event was performed to assess the relation between time in HE and transplant-free survival. Median (IQR) time in HE was 48 h (24-96 h) in the whole cohort. Patients who presented a longer time in HE (>48 h; n = 89) exhibited a lower transplant-free survival at 28 days (67.2% versus 88.9%, p 48 h, when comparing patients according to baseline HE grade (2 versus ⩾3) or model for end-stage liver disease (MELD) function (⩽15 versus >15). Time in HE was also an independent risk factor for mortality at each time point, hazard ratio (HR) (95 CI%) 28 days 2.59 (1.39-4.84); 90 days 1.98 (1.28-3.1) and 365 days 1.5 (1.08-2.19). The duration of the acute HE episode determines survival in cirrhotic patients independently of liver function and baseline HE grade