multimodal choice model for e mobility scenarios

Abstract The paper focuses on the definition, calibration and testing of a simulation model that is able to represent multimodal choice behaviours for electric vehicles. Taking into account the interchange between public transport and electric private mobility, the model estimates the parking demand at the Park & Ride sites equipped with charging stations. The model is based on a data-driven approach, in which mainly Floating Car Data and open data of public transport have derived the explanatory variables. Specifically, a machine learning method (Random Forest) has been used to calibrate and test the model in the real case of the metropolitan area of Rome (Italy). We first perform a stability analysis, letting the parameters of the model vary. We then carry out a sensitivity analysis on the variables that can affect the user propensity to adopt the Park & Ride. Finally, we profile and test an incentive policy to boost the choice of Park & Ride. Results suggest that the model succeeds in simulating Park & Ride by electric vehicles and, therefore, it can be extremely valuable for planning financial support to the multimodal travel choice and forecasting vehicle-to-grid scenarios

Is the Oxidant/Antioxidant Status Altered in CADASIL Patients?

The altered aggregation of proteins in non-native conformation is associated with endoplasmic reticulum derangements, mitochondrial dysfunction and excessive production of reactive oxygen species. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary systemic vasculopathy, caused by NOTCH3 mutations within the receptor extracellular domain, that lead to abnormal accumulation of the mutated protein in the vascular wall. NOTCH3 misfolding could cause free radicals increase also in CADASIL. Aim of the study was to verify whether CADASIL patients have increased oxidative stress compared to unrelated healthy controls. We enrolled 15 CADASIL patients and 16 gender- and age-matched healthy controls with comparable cardiovascular risk factor. Blood and plasma reduced and total aminothiols (homocysteine, cysteine, glutathione, cysteinylglycine) were measured by HPLC and plasma 3- nitrotyrosine by ELISA. Only plasma reduced cysteine (Pr-Cys) and blood reduced glutathione (Br-GSH) concentrations differed between groups: in CADASIL patients Br-GSH levels were higher (p = 0.019) and Pr-Cys lower (p = 0.010) than in controls. No correlation was found between Br-GSH and Pr-Cys either in CADASIL patients (rho 0.25, P=0.36) or in controls (rho -0.15, P=0.44). Conversely, 3- nitrotyrosine values were similar in CADASIL and healthy subjects (p = 0.82). The high levels of antioxidant molecules and low levels of oxidant mediators found in our CADASIL population might either be expression of an effective protective action against free radical formation at an early stage of clinical symptoms or they could suggest that oxidative stress is not directly involved in the pathogenesis of CADASIL

Hypofractionated postoperative helical tomotherapy in prostate cancer: a mono-institutional report of toxicity and clinical outcomes

Purpose: This is a mono-institutional study of acute and late toxicities and early biochemical control of a retrospective series of 75 prostate cancer patients treated with moderate postoperative hypofractionation delivered by helical tomotherapy (HT).Patients and methods: From April 2013 to June 2017, 75 patients received adjuvant (n=37) or salvage (n=38) treatment, delivering to prostate bed a total dose of 63.8 Gy (equivalent dose in 2-Gy fraction..67.4 Gy) using 2.2 Gy fractions. Whole-pelvis irradiation was performed in 63% of cases (median dose, 49.3 Gy; range, 48-55.1 Gy). Concurrent hormonal therapy was administered in 46% of cases. Common Terminology Criteria for Adverse Events (version 4.0) was adopted for acute and late genitourinary (GU) and gastrointestinal (GI) toxicity evaluations. Biochemical progression was defined as PSA level increase of >= 0.2 or more above the postoperative radiotherapy (RT) nadir.Results: Acute GU toxicities were as follows: G1 in 46% and G2 in 4%, detecting no G >= 3 events. For GI toxicity, we recorded G1 in 36% and G2 in 18%. With a median follow-up of 30 months (range, 12-58 months), we found late toxicity G2 GI in 6.6% and G >= 2 GU in 5.3%, including two patients who underwent surgical incontinence correction. Acute toxicity and diabetes were found to be predictive of late GI >= 2 toxicity (P=0.04 and P=0.0019). Actuarial 2- and 3-year biochemical recurrence-free survivals were 88% and 73%, respectively, for the entire population.Conclusion: In our experience, moderate hypofractionated postoperative RT with HT was feasible and safe, with reports of low incidence of toxicity and promising biochemical control rates

The APOGEE-2 Survey of the Orion Star Forming Complex: I. Target Selection and Validation with early observations

The Orion Star Forming Complex (OSFC) is a central target for the APOGEE-2 Young Cluster Survey. Existing membership catalogs span limited portions of the OSFC, reflecting the difficulty of selecting targets homogeneously across this extended, highly structured region. We have used data from wide field photometric surveys to produce a less biased parent sample of young stellar objects (YSOs) with infrared (IR) excesses indicative of warm circumstellar material or photometric variability at optical wavelengths across the full 420 square degrees extent of the OSFC. When restricted to YSO candidates with H < 12.4, to ensure S/N ~100 for a six visit source, this uniformly selected sample includes 1307 IR excess sources selected using criteria vetted by Koenig & Liesawitz and 990 optical variables identified in the Pan-STARRS1 3$\pi$ survey: 319 sources exhibit both optical variability and evidence of circumstellar disks through IR excess. Objects from this uniformly selected sample received the highest priority for targeting, but required fewer than half of the fibers on each APOGEE-2 plate. We fill the remaining fibers with previously confirmed and new color-magnitude selected candidate OSFC members. Radial velocity measurements from APOGEE-1 and new APOGEE-2 observations taken in the survey's first year indicate that ~90% of the uniformly selected targets have radial velocities consistent with Orion membership.The APOGEE-2 Orion survey will include >1100 bona fide YSOs whose uniform selection function will provide a robust sample for comparative analyses of the stellar populations and properties across all sub-regions of Orion.Comment: Accepted for publication in ApJ

Can the Multidimensional Prognostic Index (MPI) be a predictive instrument for mortality in older adult liver transplant candidates?

PurposeThe most recent guidelines recommend that selection of liver transplant recipient patients be guided by a multidimensional approach that includes frailty assessment. Different scales have been developed to identify frail patients and determine their prognosis, but the data on older adult candidates are still inconclusive. The aim of this study was to compare the accuracy of the Liver Frailty Index (LFI) and the Multidimensional Prognostic Index (MPI) as predictors of mortality in a cohort of older people patients being evaluated for liver transplantation.MethodsThis retrospective study was conducted on 68 patients > 70 years being followed at the University Hospital of Padua in 2018. Clinical information on each patient, Model For End-Stage Liver Disease (MELD), Body Mass Index (BMI), Activities of Daily Living (ADL), Mini Nutritional Assessment (MNA), LFI, MPI, and date-of-death, were recorded. The observational period was 3 years.ResultsWe studied 68 individuals (25 women), with a mean age 72.21 & PLUSMN; 1.64 years. Twenty-five (36.2%) patients died during the observational period. ROC curve analysis showed both MPI and LFI to be good predictors of mortality (AUC 0.7, p = 0.007, and AUC 0.689, p = 0.015, respectively). MELD (HR 1.99, p = 0.001), BMI (HR 2.34, p = 0.001), and poor ADL (HR 3.34, p = 0.04) were risk factors for mortality in these patients, while male sex (HR 0.1, p = 0.01) and high MNA scores (HR 0.57, p = 0.01) were protective factors.ConclusionOur study confirmed the prognostic value of MPI in older adult patients awaiting liver transplantation. In this cohort, good nutritional status and male sex were protective factors, while high MELD and BMI scores and poor functional status were risk factors.Key summary pointsAimThe aim of this study was to compare the accuracy of the Liver Frailty Index (LFI) and the Multidimensional Prognostic Index (MPI) as predictors of mortality in a cohort of older adult patients being evaluated for liver transplantationFindingsOn the 68 patients studied, ROC curve analysis showed that MPI was similar or slightly better than LFI as predictor of mortality (AUC 0.7, p=0.007, and AUC 0.689, p=0.015, respectively).MessageIn older people patients listed for liver transplantation, MPI is as good a prognostic tool as LFI for predicting mortality

Road traffic pollution and childhood leukemia: a nationwide case-control study in Italy

Background The association of childhood leukemia with traffic pollution was considered in a number of studies from 1989 onwards, with results not entirely consistent and little information regarding subtypes. Aim of the study We used the data of the Italian SETIL case-control on childhood leukemia to explore the risk by leukemia subtypes associated to exposure to vehicular traffic. Methods We included in the analyses 648 cases of childhood leukemia (565 Acute lymphoblastic–ALL and 80 Acute non lymphoblastic-AnLL) and 980 controls. Information on traffic exposure was collected from questionnaire interviews and from the geocoding of house addresses, for all periods of life of the children. Results We observed an increase in risk for AnLL, and at a lower extent for ALL, with indicators of exposure to traffic pollutants. In particular, the risk was associated to the report of closeness of the house to traffic lights and to the passage of trucks (OR: 1.76; 95% CI 1.03–3.01 for ALL and 6.35; 95% CI 2.59–15.6 for AnLL). The association was shown also in the analyses limited to AML and in the stratified analyses and in respect to the house in different period of life. Conclusions Results from the SETIL study provide some support to the association of traffic related exposure and risk for AnLL, but at a lesser extent for ALL. Our conclusion highlights the need for leukemia type specific analyses in future studies. Results support the need of controlling exposure from traffic pollution, even if knowledge is not complete

Rol de la alineación de la prótesis y las calcificaciones heterotópicas en la artroplastia total de tobillo

Introducción: El objetivo principal fue evaluar la relación entre la formación de calcificaciones heterotópicas y los parámetros de alineación de la prótesis. Materiales y Métodos: La población estaba formada por 31 pacientes. Se evaluaron variables radiográficas de alineación, como ángulos alfa y beta, centro de rotación astragalino y el porcentaje de cobertura posterior de la tibia en el posoperatorio inmediato y a los 2 años. Las variables de evaluación clínica fueron: la escala analógica visual y la escala de la AOFAS, y el cuestionario SF-36 para evaluar la calidad de vida al final del seguimiento. Resultados: La etiología más frecuente de la artrosis fue la postraumática (67,7%). En el posoperatorio inmediato, el ángulo alfa promedio fue de 88,7° (rango 82-92,6; DE ± 2,61); el ángulo beta, de 84,46° (rango 78,62-91,40; DE ± 3,59). La alineación del componente tibial en el plano frontal fue neutra en 25 pacientes (80,6%), en valgo en 6 (19,4%) y en varo (0%). A los 2 años de seguimiento, el 96% tenía calcificaciones heterotópicas. Mejoraron los puntajes en la escala de la AOFAS (preoperatorio/posoperatorio: 31,90/80,94) y en la escala analógica visual (preoperatorio/posoperatorio: 8,7/1,97) (p <0,05). Conclusiones: No se halló una relación entre calcificaciones heterotópicas y peores resultados funcionales ni de dolor, excepto en los parámetros de calidad de vida (SF-36), como el rol físico, la limitación emocional y la percepción de la salud general, que empeoraron a medida que aumentó el grado de calcificaciones alrededor de la prótesis

Are complications after repairing acute Achilles tendon ruptures related to the surgical approach or the patient’s comorbidities?*

Objective: Analyze the postoperative complications after repairing acute Achilles tendon rupture and compare them according to the surgical approach (open surgery (OS) or minimally invasive surgery (MIS)) and the patient’s comorbidities. Methods: A retrospective analytical study including 154 consecutive patients with an acute Achilles tendon rupture submitted to surgery and divided into OS and MIS cohorts. The following relevant comorbidities were analyzed: obesity, diabetes mellitus, smoking, dyslipidemia, gout, chronic corticosteroid use, connective tissue pathologies, transplant history, cancer treatment patients, and postoperative complications. Results: Seventy-eight patients (50.6%) were treated surgically with an OS technique and 76 (49.4%) with an MIS approach. Twenty patients (13%) had postoperative complications between the two cohorts (OS 11.5%; MIS 14.5%; p = 0.588). No statistically significant difference was found in the logistic regression of the risk of the surgical approaches and complications. Obesity had a significant statistical difference when complications and comorbidities were compared. Conclusions: Patients with obesity have a higher risk of developing postoperative complications with both OS and MIS techniques. No relationship was found between the type of surgical approach and a higher percentage of postoperative complications in treating acute Achilles tendon rupture

Neddylation inhibition ameliorates steatosis in NAFLD by boosting hepatic fatty acid oxidation via the DEPTOR-mTOR axis

Objective: Neddylation is a druggable and reversible ubiquitin-like post-translational modification upregulated in many diseases, including liver fibrosis, hepatocellular carcinoma, and more recently, non-alcoholic fatty liver disease (NAFLD). Herein, we propose to address the effects of neddylation inhibition and the underlying mechanisms in pre-clinical models of NAFLD. Methods: Hepatic neddylation measured by immunohistochemical analysis and NEDD8 serum levels measured by ELISA assay were evaluated in NAFLD clinical and pre-clinical samples. The effects of neddylation inhibition by using a pharmacological small inhibitor, MLN4924, or molecular approaches were assessed in isolated mouse hepatocytes and pre-clinical mouse models of diet-induced NAFLD, male adult C57BL/6 mice, and the AlfpCre transgenic mice infected with AAV-DIO-shNedd8. Results: Neddylation inhibition reduced lipid accumulation in oleic acid-stimulated mouse primary hepatocytes and ameliorated liver steatosis, preventing lipid peroxidation and inflammation in the mouse models of diet-induced NAFLD. Under these conditions, increased Deptor levels and the concomitant repression of mTOR signaling were associated with augmented fatty acid oxidation and reduced lipid content. Moreover, Deptor silencing in isolated mouse hepatocytes abolished the anti-steatotic effects mediated by neddylation inhibition. Finally, serum NEDD8 levels correlated with hepatic neddylation during the disease progression in the clinical and pre-clinical models. Conclusions: Overall, the upregulation of Deptor, driven by neddylation inhibition, is proposed as a novel effective target and therapeutic approach to tackle NAFLDThis work was supported by grants from Gobierno Vasco-Departamento de Salud 2013111114 (to M.L.M.-C), ELKARTEK 2016, Departamento de Industria del Gobierno Vasco (to M.L.M−C), Ministerio de Ciencia, Innovación y Universidades MICINN: SAF2017-87301-R, and RTI2018-096759-A-100 integrado en el Plan Estatal de Investigación Científica y Técnica y Innovación, cofinanciado con Fondos FEDER (to M.L.M− T.C.D respectively); MCIU/AEI/FEDER, UE (RTI2018-095134-B-100) (to P.A.), AECC Bizkaia (M.S-M); Asociación Española contra el Cáncer (T.C.D), Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M, J.M.B., M.A.A., J.J.G.M.), La Caixa Foundation Program (to M.L.M and J.M.B.), 2018 BBVA Foundation Grants for Scientific Research Teams (to M.L.M.-C.), Ayudas para apoyar grupos de investigación del sistema Universitario Vasco IT971-16 (P.A.). MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico (to LV), the European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- “Liver Investigation: Testing Marker Utility in Steatohepatitis” (to LV), Fondazione IRCCS Ca’ Granda “Liver BIBLE” PR-0391, Fondazione IRCCS Ca’ Granda core COVID-19 Biobank (RC100017A) (to LV). This research was funded by the CIBERehd (EHD15PI05/2016) and “Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III”, Spain (PI16/00598 and PI19/00819, co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”); Spanish Ministry of Economy, Industry and Competitiveness (SAF2016-75197-R); “Junta de Castilla y Leon” (SA063P17); AECC Scientific Foundation (2017/2020), Spain; “Centro Internacional sobre el Envejecimiento” (OLD-HEPAMARKER, 0348_CIE_6_E), Spain; University of Salamanca Foundation, Spain (PC-TCUE18-20_051), and Fundació Marato TV3 (Ref. 201916–31), Spain. RB acknowledges BFU2017-84653-P (MINECO/FEDER, EU), SEV-2016-0644 (Severo Ochoa Excellence Program), 765445-EU (UbiCODE Program), SAF2017-90900-REDT (UBIRed Program), and IT1165-19 (Basque Country Government). Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644)S