Macroscopic cellular automata for groundwater modelling: A first approach

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Telerilevamento di aree archeologiche mediante dati iperspettrali MIVIS

The aim of this study is to examine the relationship between physical parameters and the spatial distribution of buried archaeological structures, using data acquired by the airborne hyperspectral sensor MIVIS in the visible, near infrared and thermal infrared wavelengths. The study areas are the territories of Halaesa, an important city in the Hellenistic-Roman period, and the Punic city of Mozia in Sicily. The influence of buried structures on thermal-radiative behaviour has been investigated using three parameters: Normalized Difference Vegetation Index (NDVI), thermal inertia, and Thermal Balanced Gradient. These techniques are shown to be particularly effective in identifying surface phenomena caused by structures present in the top soil. Multicriterial analysis has been carried out to investigate the possible presence of buried linear structures, which are linked to these parameters. Results show good agreement with the distribution of known structures and archaeological sites identified by survey

The TM6SF2 E167K genetic variant induces lipid biosynthesis and reduces apolipoprotein B secretion in human hepatic 3D spheroids

There is a high unmet need for developing treatments for nonalcoholic fatty liver disease (NAFLD), for which there are no approved drugs today. Here, we used a human in vitro disease model to understand mechanisms linked to genetic risk variants associated with NAFLD. The model is based on 3D spheroids from primary human hepatocytes from five different donors. Across these donors, we observed highly reproducible differences in the extent of steatosis induction, demonstrating that inter-donor variability is reflected in the in vitro model. Importantly, our data indicates that the genetic variant TM6SF2 E167K, previously associated with increased risk for NAFLD, induces increased hepatocyte fat content by reducing APOB particle secretion. Finally, differences in gene expression pathways involved in cholesterol, fatty acid and glucose metabolism between wild type and TM6SF2 E167K mutation carriers (N = 125) were confirmed in the in vitro model. Our data suggest that the 3D in vitro spheroids can be used to investigate the mechanisms underlying the association of human genetic variants associated with NAFLD. This model may also be suitable to discover new treatments against NAFLD

Final results from the Betaseron (interferon β-1b) Pregnancy Registry: a prospective observational study of birth defects and pregnancy-related adverse events

ObjectiveWomen with multiple sclerosis are often diagnosed and treated during their reproductive years. Limited data are available on the safety of treatment during pregnancy. The Betaseron Pregnancy Registry prospectively monitored women exposed to interferon β-1b (IFNβ-1b) during pregnancy to estimate the rates of birth defects, spontaneous abortions (SABs) and other negative outcomes in this population.DesignFrom 2006 to 2011, this observational registry enrolled women exposed prior to conception or during pregnancy (but prior to or without abnormalities on prenatal screening). Follow-up continued from enrolment through the 4-month paediatric visit.SettingPatients in the USA who met these criteria were enrolled in the registry.ResultsThe registry enrolled 99 pregnant women; 3 were lost to follow-up. The earliest exposure to IFNβ-1b occurred during the first trimester for 95 pregnancies and in the third trimester for 1 pregnancy. There were 99 birth outcomes (3 twins), including 86 (86.9%) live births, 11 (11.1%) SABs and 2 (2%) stillbirths. Birth defects were reported in five (5.1%) cases. Rates of birth defects and SAB were not significantly different from population comparators. No developmental concerns were identified at the 4-month paediatric visit.ConclusionsThe small sample size limits the ability to draw definitive conclusions; however, there was no pattern to suggest increased negative outcomes with IFNβ-1b.Clinical trials registration numberNCT00317564

Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNB-1b trial

OBJECTIVE: To examine the effects of interferon beta (IFNβ)-1b on all-cause mortality over 21 years in the cohort of 372 patients who participated in the pivotal randomized clinical trial (RCT), retaining (in the analysis) the original randomized treatment-assignments. METHODS: For this randomized long-term cohort study, the primary outcome, defined before data collection, was the comparison of all-cause mortality between the IFNβ-1b 250 μg and placebo groups from the time of randomization through the entire 21-year follow-up interval (intention-to-treat, log-rank test for Kaplan-Meier survival curves). All other survival outcomes were secondary. RESULTS: After a median of 21.1 years from RCT enrollment, 98.4%(366 of 372) of patients were identified, and, of these, 81 deaths were recorded (22.1% [81 of 366]). Patients originally randomly assigned to IFNβ-1b 250 μg showed a significant reduction in all-cause mortality over the 21-year period compared with placebo (p = 0.0173), with a hazard ratio of 0.532 (95% confidence interval 0.314-0.902). The hazard rate of death at long-term follow-up by Kaplan-Meier estimates was reduced by 46.8% among IFNβ-1b 250 μg-treated patients (46.0% among IFNβ-1b 50 μg-treated patients) compared with placebo. Baseline variables did not influence the observed treatment effect. CONCLUSIONS: There was a significant survival advantage in this cohort of patients receiving early IFNβ-1b treatment at either dose compared with placebo. Near-complete ascertainment, together with confirmatory findings from both active treatment groups, strengthens the evidence for an IFNβ-1b benefit on all-cause mortality. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that early treatment with IFNβ-1b is associated with prolonged survival in initially treatment-naive patients with relapsing-remitting multiple sclerosis

Macroscopic Cellular Automata for groundwater modelling: a first approach

A groundwater model representing two-dimensional flow in unconfined aquifers is presented. The model is based on the paradigm of macroscopic cellular automata, that represents dynamical systems which are discrete in space and time, operate on a uniform regular lattice and are characterised by local interactions. Physically based equations are implemented to simulate the flow of water between adjacent cells. The model was validated against solutions of simple problems in both steady state and transient state conditions including analytical solutions and simulations performed with the MODFLOW-2000 model. The developed code is simple enough to facilitate its integration into other models such as land-surface models. The good performance without detriment to accuracy makes the model adequate to perform long simulation time analysi