Road tunnel risk-based safety design methodology by GU@LARP Quantum risk model

The ALARP concept is used in different countries for different sectors of activity where a risk assessment or measure is requested. In this paper a model is developed based upon ALARP principle for tunnel risk-based design in case of fire accident scenarios. In Italy, ALARP risk acceptability and tolerability criteria have been adopted then the compliance with them has to be verified in order to guarantee a minimum-sufficient level of safety. The quantum of risk coupled with any design scenario is defined and modelled and the consequent individual quantum of risk coupled with the single exposed unit in the scenario is defined too. The methodologies for the identification of the requested design scenario, in number and type, are outlined. The scenarios are described in a shape suitable as INPUTS in the thermo-dynamical numerical simulations for fire generation and exposed units evacuation. The expected OUTPUTS of the numerical simulation are the estimations of the number of the fatalities (N) coupled with the single specific scenarios. In parallel with the above physical deterministic scenario simulations, a conceptual and operational procedure has been also established for the scenarios probabilities assessment. Merging the resulting data of both the above separate models, the risk quanta Gu@larp model is finally established. A case study is developed considering scenarios related to a virtual limit tunnel to support the description of the model itself, properties, advantages and perspectives

Oxidative Stress in Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it still remains an orphan of adequate therapies. This review highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive oxygen species generators, including those produced in the gastrointestinal tract, contribute to the lipotoxic hepatic (and extrahepatic) damage by fatty acids and a great variety of their biologically active metabolites in a “multiple parallel-hit model”. This leads to inflammation and fibrogenesis and contributes to NAFLD progression. The alterations of the oxidant/antioxidant balance affect also metabolism-related organelles, leading to lipid peroxidation, mitochondrial dysfunction, and endoplasmic reticulum stress. This OS-induced damage is at least partially counteracted by the physiological antioxidant response. Therefore, modulation of this defense system emerges as an interesting target to prevent NAFLD development and progression. For instance, probiotics, prebiotics, diet, and fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. The OS and its counter-regulation are under the influence of individual genetic and epigenetic factors as well. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors, coupled with new OS biomarkers, will likely assist in noninvasive diagnosis and monitoring of NAFLD progression and in further personalizing treatments

Reversibility of Central Nervous System Adverse Events in Course of Art

The purpose of this study is to evaluate the frequency of central nervous system adverse events (CNS-AE) on dolutegravir (DTG) and non-DTG containing ART, and their reversibility, in the observational prospective SCOLTA cohort. Factors associated with CNS-AE were estimated using a Cox proportional-hazards model. 4939 people living with HIV (PLWH) were enrolled in DTG (n = 1179) and non-DTG (n = 3760) cohorts. Sixty-six SNC-AE leading to ART discontinuation were reported, 39/1179 (3.3%) in DTG and 27/3760 (0.7%) in non-DTG cohort. PLWH naive to ART, with higher CD4 + T count and with psychiatric disorders were more likely to develop a CNS-AE. The risk was lower in non-DTG than DTG-cohort (aHR 0.33, 95% CI 0.19-0.55, p < 0.0001). One-year follow-up was available for 63/66 PLWH with CNS-AE. AE resolution was reported in 35/39 and 23/24 cases in DTG and non-DTG cohorts, respectively. The probability of AE reversibility was not different based on ART class, sex, ethnicity, CDC stage, or baseline psychiatric disorder. At the same time, a lower rate of event resolution was found in PLWH older than 50 years (p = 0.017). In conclusion, CNS-AE leading to ART discontinuation was more frequent in DTG than non-DTG treated PLWH. Most CNS-AE resolved after ART switch, similarly in both DTG and non-DTG cohorts

Growing old with antiretroviral therapy or elderly people in antiretroviral therapy: two different profiles of comorbidity?

Background In persons living with HIV (PLWH), the burden of non-communicable chronic diseases increased over time, because of aging associated with chronic inflammation, systemic immune activation, and long-term exposure to the combination antiretroviral therapy (ART). Methods To explore the association of chronological age, age at first ART, and exposure to ART with non-communicable chronic diseases, we performed a cross-sectional analysis to evaluate the prevalence of comorbidities in patients enrolled in the SCOLTA Project, stratified by groups of chronological age (50-59 and 60-69 years) and by years of antiretroviral treatment (ART, <= 3 or > 3 years). Results In 1394 subjects (23.8% women), mean age at enrollment was 57.4 (SD 6.5) years, and at first ART 45.3 (SD 10.7). Men were older than women both at enrollment (57.6 vs 56.8, p = 0.06) and at first ART (45.8 vs 43.6, p = 0.0009). ART duration was longer in women (13.1 vs 11.7 years, p = 0.01). The age- and sex-adjusted rate ratios (aRRs, and 95% confidence interval, CI) showed that longer ART exposure was associated with dyslipidemia (aRR 1.35, 95% CI 1.20-1.52), hypertension (aRR 1.52, 95% CI 1.22-1.89), liver disease (aRR 1.78, 95% CI 1.32-2.41), osteopenia/osteoporosis (aRR 2.88, 95% CI 1.65-5.03) and multimorbidity (aRR 1.36, 95% CI 1.21-1.54). These findings were confirmed in strata of age, adjusting for sex. Conclusions Our data suggest that longer ART exposure was associated with increased risk of dyslipidemia, hypertension, and osteopenia/osteoporosis, hence the presence of multimorbidity, possibly due to the exposition to more toxic antiretrovirals. We observed different comorbidities, according to ART exposure and age

Roadmap on thermoelectricity

The increasing energy demand and the ever more pressing need for clean technologies of energy conversion pose one of the most urgent and complicated issues of our age. Thermoelectricity, namely the direct conversion of waste heat into electricity, is a promising technique based on a long-standing physical phenomenon, which still has not fully developed its potential, mainly due to the low efficiency of the process. In order to improve the thermoelectric performance, a huge effort is being made by physicists, materials scientists and engineers, with the primary aims of better understanding the fundamental issues ruling the improvement of the thermoelectric figure of merit, and finally building the most efficient thermoelectric devices. In this Roadmap an overview is given about the most recent experimental and computational results obtained within the Italian research community on the optimization of composition and morphology of some thermoelectric materials, as well as on the design of thermoelectric and hybrid thermoelectric/photovoltaic devices

Prevalence of hepatic steatosis in patients with type 2 diabetes and response to glucose-lowering treatments. A multicenter retrospective study in Italian specialist care

Type 2 diabetes (T2D) is a risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD), which is becoming the commonest cause of chronic liver disease worldwide. We estimated MAFLD prevalence among patients with T2D using the hepatic steatosis index (HSI) and validated it against liver ultrasound. We also examined whether glucose-lowering medications (GLM) beneficially affected HSI

Similar effectiveness of dapagliflozin and GLP-1 receptor agonists concerning combined endpoints in routine clinical practice: A multicentre retrospective study

Aims According to cardiovascular outcome trials, some sodium-glucose contransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are recommended for secondary cardiovascular prevention in type 2 diabetes (T2D). In this real-world study, we compared the simultaneous reductions in HbA1c, body weight and systolic blood pressure after initiation of dapagliflozin or GLP-1RA as second or a more advanced line of therapy. Materials and methods DARWIN-T2D was a retrospective multi-centre study conducted at diabetes specialist clinics in Italy that compared T2D patients who initiated dapagliflozin or GLP-1RA (exenatide once weekly or liraglutide). Data were collected at baseline and at the first follow-up visit after 3 to 12 months. The primary endpoint was the proportion of patients achieving a simultaneous reduction in HbA1c, body weight and systolic blood pressure. To reduce confounding, we used multivariable adjustment (MVA) or propensity score matching (PSM). Results Totals of 473 patients initiating dapagliflozin and 336 patients initiating GLP-1RA were included. The two groups differed in age, diabetes duration, HbA1c, weight and concomitant medications. The median follow-up was 6 months in both groups. Using MVA or PSM, the primary endpoint was observed in 30% to 32% of patients, with no difference between groups. Simultaneous reduction of HbA1c, BP and SBP by specific threshold, as well as achievement of final goals, did not differ between groups. GLP-1RA reduced HbA1c by 0.3% more than the reduction achieved with dapagliflozin. Conclusion In routine specialist care, initiation of dapagliflozin can be as effective as initiation of a GLP-1RA for attainment of combined risk factor goals

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation