Generation of H₂ on Board Lng Vessels for Consumption in the Propulsion System

[Abstract] At present, LNG vessels without reliquefaction plants consume the BOG (boil-off gas) in their engines and the excess is burned in the gas combustion unit without recovering any of its energy content. Excess BOG energy could be captured to produce H₂, a fuel with high energy density and zero emissions, through the installation of a reforming plant. Such H₂ production would, in turn, require on-board storage for its subsequent consumption in the propulsion plant when navigating in areas with stringent anti-pollution regulations, thus reducing CO₂ and SOₓ emissions. This paper presents a review of the different H₂ storage systems and the methods of burning it in propulsion engines, to demonstrate the energetic viability thereof on board LNG vessels. Following the analysis, it is identified that a pressurised and cooled H₂ storage system is the best suited to an LNG vessel due to its simplicity and the fact that it does not pose a safety hazard. There are a number of methods for consuming the H₂ generated in the DF engines that comprise the propulsión plant, but the use of a mixture of 70% CH₄-30% H₂ is the most suitable as it does not require any modifications to the injection system. Installation of an on-board reforming plant and H₂ storage system generates sufficient H₂ to allow for almost 3 days’ autonomy with a mixture of 70%CH₄-30%H₂. This reduces the engine consumption of CH₄ by 11.38%,thus demonstrating that the system is not only energy-efficient, but lends greater versatility to the vessel

Chapter The Rise of Glutaminase in End-Stage Liver Diseases

Applied optic

The Role of Nrf2 Signaling in PPARβ/δ-Mediated Vascular Protection against Hyperglycemia-Induced Oxidative Stress

Hyperglycemia induces oxidative stress and plays a substantial role in the progression of vascular diseases. Here, we demonstrated the potentiality of peroxisome proliferator-activated receptor (PPAR)β/δ activation in attenuating high glucose-induced oxidative stress in endothelial cells and diabetic rats, pointing to the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2). HUVECs exposed to high glucose showed increased levels of reactive oxygen species (ROS) and upregulated NOX-2, NOX-4, Nrf2, and NQO-1 effects that were significantly reversed by the PPARβ/δ agonists GW0742 and L165041. Both PPARβ/δ agonists, in a concentration-dependent manner, induced transcriptional and protein upregulation of heme oxygenase-1 (HO-1) under low- and high-glucose conditions. All effects of PPARβ/δ agonists were reversed by either pharmacological inhibition or siRNA-based downregulation of PPARβ/δ. These in vitro findings were confirmed in diabetic rats treated with GW0742. In conclusion, PPARβ/δ activation confers vascular protection against hyperglycemia-induced oxidative stress by suppressing NOX-2 and NOX-4 expression plus a direct induction of HO-1; with the subsequent downregulation of the Nrf2 pathway. Thus, PPARβ/δ activation could be of interest to prevent the progression of diabetic vascular complications.This work was supported by Grants from Ministerio de Economía y Competitividad and Fondo Europeo de Desar- rollo Regional (FEDER) (SAF2010-22066-C02-01, SAF2010-22066-C02-02, SAF2011-28150, SAF2014-55523- R), Junta de Andalucía (Proyecto de excelencia, P12-CTS- 2722), and Instituto de Salud Carlos III (RIC RD12/0042/ 0011), Spain

A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH

BACKGROUND Management of nonalcoholic steatohepatitis (NASH) is an unmet clinical need. Lanifibranor is a pan-PPAR (peroxisome proliferator–activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis of NASH. METHODS In this phase 2b, double-blind, randomized, placebo-controlled trial, patients with noncirrhotic, highly active NASH were randomly assigned in a 1:1:1 ratio to receive 1200 mg or 800 mg of lanifibranor or placebo once daily for 24 weeks. The pri- mary end point was a decrease of at least 2 points in the SAF-A score (the activity part of the Steatosis, Activity, Fibrosis [SAF] scoring system that incorporates scores for ballooning and inflammation) without worsening of fibrosis; SAF-A scores range from 0 to 4, with higher scores indicating more-severe disease activity. Secondary end points included resolution of NASH and regression of fibrosis. RESULTS A total of 247 patients underwent randomization, of whom 103 (42%) had type 2 diabetes mellitus and 188 (76%) had significant (moderate) or advanced fibrosis. The percentage of patients who had a decrease of at least 2 points in the SAF-A score without worsening of fibrosis was significantly higher among those who received the 1200-mg dose, but not among those who received the 800-mg dose, of lanifibranor than among those who received placebo (1200-mg dose vs. placebo, 55% vs.33%, P = 0.007; 800-mg dose vs. placebo, 48% vs. 33%, P = 0.07). The results favored both the 1200-mg and 800-mg doses of lanifibranor over placebo for resolution of NASH without worsening of fibrosis (49% and 39%, respectively, vs. 22%), improvement in fibrosis stage of at least 1 without worsening of NASH (48% and 34%, respectively, vs. 29%), and resolution of NASH plus improvement in fibrosis stage of at least 1 (35% and 25%, respectively, vs. 9%). Liver enzyme levels decreased and the levels of the majority of lipid, inflammatory, and fibrosis biomarkers improved in the lanifibranor groups. The dropout rate for adverse events was less than 5% and was similar across the trial groups. Diarrhea, nausea, peripheral edema, anemia, and weight gain occurred more frequently with lanifibranor than with placebo. CONCLUSIONS In this phase 2b trial involving patients with active NASH, the percentage of patients who had a decrease of at least 2 points in the SAF-A score without worsening of fibrosis was significantly higher with the 1200-mg dose of lanifibranor than with placebo. These findings support further assessment of lanifibranor in phase 3 trials. (Funded by Inventiva Pharma; NATIVE ClinicalTrials.gov number, NCT0300807

Analysis and Modelling of the Structural Components of the Elbow Joint

A recent application of computer simulation is its use for the human body, which resembles a mechanism that is complemented by torques in the joints that are caused by the action of muscles and tendons. Among others, the application can be used to provide training in surgical procedures or to learn how the body works. Some of the other applications are to make a biped walk upright, to build robots that are designed on the human body or to make prostheses or robot arms to perform specific tasks. One of the uses of simulation is to optimise the movement of the human body by examining which muscles are activated and which should or should not be activated in order to improve a person?s movements. This work presents a model of the elbow joint, and by analysing the constraint equations using classic methods we go on to model the bones, muscles and tendons as well as the logic linked to the force developed by them when faced with a specific movement. To do this, we analyse the reference bibliography and the software available to perform the validation

Captación de participantes en el programa experimental de prescripción de estupefacientes en Andalucía (PEPSA)

ResumenEsta nota tiene como finalidad describir los pasos seguidos en el proceso de captación de los participantes en el ensayo andaluz de prescripción de heroína intravenosa. El programa experimental de prescripción de estupefacientes en Andalucía (PEPSA) compara el tratamiento de heroína respecto a la metadona oral, en la mejoría de la salud física y mental y la integración social. Dada las características de la población diana (usuarios de heroína por vía intravenosa en situación de exclusión social para quienes no han sido efectivos los tratamientos disponibles), se planificó un abordaje específico para acercar dichas personas al estudio. Tras una investigación previa sobre la distribución de la población diana en la ciudad de Granada, se dividió ésta en 3 zonas. Se acudía a los principales centros de reunión (plazas, comedores sociales, dispensarios de metadona) y se concretaba una cita con un médico del PEPSA. El trabajo apoyado en iguales ha sido una herramienta fundamental en este proceso de captación, y ha facilitado el acercamiento a la población diana. Asimismo, este trabajo ha permitido entablar contacto con usuarios de drogas que no acceden a los servicios sociosanitarios, por lo que la labor del equipo de captación también ha sido educar en la reducción de daños y ofrecer alternativas sociales y sanitarias más allá del ensayo.AbstractIn this field note we describe the steps followed in the process of recruiting participants for the experimental drug prescription program in Andalusia (PEPSA). This trial is a comparative, randomized, open study of the difference between intravenous heroin treatment and oral methadone for socially excluded, opiate-dependent patients, in whom other available treatments have been unsuccessful. Because this is a hidden and hard-to-reach population, a specific approach was planned to put as many patients as possible in touch with the program. A previous study of the target population’s distribution in the City of Granada was performed and the city was divided into three areas. Potential participants were interviewed in squares, soup kitchens and methadone dispensaries by outreach workers and peers, who suggested they make an appointment with a PEPSA physician. Peer-driven intervention was a crucial instrument in this recruitment procedure, allowing greater access to the target population. Furthermore, this approach allowed contact with drug users who do not attend health and social services. The work of the outreach team involved educating these users in harm reduction and offering them health and social alternatives beyond the clinical trial

European 'NAFLD Preparedness Index' - Is Europe ready to meet the challenge of fatty liver disease?

Background & Aims: Non-alcoholic fatty liver disease (NAFLD), which is closely associated with obesity, metabolic syndrome, and diabetes, is a highly prevalent emerging condition that can be optimally managed through a multidisciplinary patient centred approach. National preparedness to address NAFLD is essential to ensure that health systems can deliver effective care. We present a NAFLD Preparedness Index for Europe. Methods: In June 2019, data were extracted by expert groups from 29 countries to complete a 41-item questionnaire about NAFLD. Questions were classified into 4 categories: policies/civil society (9 questions), guidelines (16 questions), epidemiology (4 questions), and care management (12 questions). Based on the responses, national preparedness for each indicator was classified into low, middle, or high-levels. We then applied a multiple correspondence analysis to obtain a standardised preparedness score for each country ranging from 0 to 100. Results: The analysis estimated a summary factor that explained 71.3% of the variation in the dataset. No countries were found to have yet attained a high-level of preparedness. Currently, the UK (75.5) scored best, although falling within the mid level preparedness band, followed by Spain (56.2), and Denmark (43.4), whereas Luxembourg and Ireland were the lowest scoring countries with a score of 4.9. Only Spain scored highly in the epidemiology indicator category, whereas the UK was the only country that scored highly for care management. Conclusions: The NAFLD Preparedness Index indicates substantial variation between countries’ readiness to address NAFLD. Notably, even those countries that score relatively highly exhibit deficiencies in key domains, suggesting that structural changes are needed to optimise NAFLD management and ensure effective public health approaches are in place. Lay summary: Non-alcoholic fatty liver disease (NAFLD), which is closely associated with obesity, metabolic syndrome, and diabetes, is a highly prevalent condition that can be optimally managed through a multidisciplinary patient-centred approach. National preparedness to address NAFLD is essential to allow for effective public health measures aimed at preventing disease while also ensuring that health systems can deliver effective care to affected populations. This study defined preparedness as having adequate policies and civil society engagement, guidelines, epidemiology, and care management. NAFLD preparedness was found to be deficient in all 29 countries studied, with great variation among the countries and the 4 categories studied

Cost of non-alcoholic steatohepatitis in Europe and the USA: the GAIN study

Background & Aims: Non-alcoholic steatohepatitis (NASH) leads to cirrhosis and is associated with a substantial socioeco- nomic burden, which, coupled with rising prevalence, is a growing public health challenge. However, there are few real-world data available describing the impact of NASH. Methods: The Global Assessment of the Impact of NASH (GAIN) study is a prevalence-based burden of illness study across Europe (France, Germany, Italy, Spain, and the UK) and the USA. Physicians provided demographic, clinical, and economic patient information via an online survey. In total, 3,754 patients found to have NASH on liver biopsy were stratified by fibrosis score and by biomarkers as either early or advanced fibrosis. Per-patient costs were estimated using national unit price data and extrapolated to the population level to calculate the economic burden. Of the patients, 767 (20%) provided information on indirect costs and health-related quality of life using the EuroQOL 5-D (EQ-5D; n = 749) and Chronic Liver Disease Ques- tionnaire – Non-Alcoholic Fatty Liver Disease (CLDQ-NAFLD) (n = 723). Results: Mean EQ-5D and CLDQ-NAFLD index scores were 0.75 and 4.9, respectively. For 2018, the mean total annual per patient cost of NASH was V2,763, V4,917, and V5,509 for direct medical, direct non-medical, and indirect costs, respectively. National per-patient cost was highest in the USA and lowest in France. Costs increased with fibrosis and decompensation, driven by hospitalisation and comorbidities. Indirect costs were driven by work loss. Conclusions: The GAIN study provides real-world data on the direct medical, direct non-medical, and indirect costs asso- ciated with NASH, including patient-reported outcomes in Europe and the USA, showing a substantial burden on health services and individuals

The European NAFLD Registry: A real-world longitudinal cohort study of nonalcoholic fatty liver disease

Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive liver disease that is closely associated with obesity, type 2 diabetes, hypertension and dyslipidaemia, represents an increasing global public health challenge. There is significant variability in the disease course: the majority exhibit only fat accumulation in the liver but a significant minority develop a necroinflammatory form of the disease (non-alcoholic steatohepatitis, NASH) that may progress to cirrhosis and hepatocellular carcinoma. At present our understanding of pathogenesis, disease natural history and long-term outcomes remain incomplete. There is a need for large, well characterised patient cohorts that may be used to address these knowledge gaps and to support the development of better biomarkers and novel therapies. The European NAFLD Registry is an international, prospectively recruited observational cohort study that aims to establish a large, highly-phenotyped patient cohort and linked bioresource. Here we describe the infrastructure, data management and monitoring plans, and the standard operating procedures implemented to ensure the timely and systematic collection of high-quality data and samples. Already recruiting subjects at secondary/tertiary care centres across Europe, the Registry is supporting the European Union IMI2-funded LITMUS ‘Liver Investigation: Testing Marker Utility in Steatohepatitis’ consortium, which is a major international effort to robustly validate biomarkers that diagnose, risk stratify and/or monitor NAFLD progression and liver fibrosis stage. The European NAFLD Registry has the demonstrable capacity to support research and biomarker development at scale and pace.EFPIAEPoS (Elucidating Pathways of Steatohepatitis) consortium - Horizon 2020 Framework Program of the European Union 634413European Association for the Study of the LiverFLIP consortium - Framework Program 7 of the European Union 241762LITMUS (Liver Investigation: Testing Biomarker Utility in Steatohepatitis) consortium - European Union Innovative Medicines Initiative 2 (IMI2) Joint Undertaking from the Horizon 2020 Framework Program of European Union 77737