Cross border critical infrastructure. A new approach for the protection evaluation

The work proposes an operational model for the management of cross-border transport critical infrastructures. Particular focus is given to road and rail network. The main goal is to develop a Decision Support System (DSS) for the management of relevant events that may have impacts on the two countries. The SICt project - Resilience of cross-border Critical Infrastructures is part of the Interreg VA Italy-Switzerland 2014-2020. The project area includes Regione Lombardia (Italy) and Canton Ticino (Switzerland) and has been divided into two areas. The study area where the hazards (events) of both anthropic and natural origin are analyzed. Critical scenarios on critical infrastructure are also evaluated. The impact area is a larger area in which the effects, after the total or partial interruptions of a critical infrastructure in the study area, are evaluated. Specifically, the work illustrates the different operational phases of the proposed model. The first one is the analysis of anthropic and natural hazards related to the study area: road and rail accidents, rail failures, intense rainfall events, floods, landslides, debris flow, etc... The second phase concerns the detailed analysis aimed at managing the events, with particular reference to the first responders' intervention models and the emergency and traffic management plans. This phase also includes the implementation of a monitoring network and an IT platform, used to share data and information about critical infrastructures. The third phase is the test and validation of the IT platform implemented

Tenofovir renal safety in HIV-infected patients: results from the SCOLTA project

Objective: To evaluate the prevalence and incidence of nephrotoxicity in HIV-infected patients enrolled in the SCOLTA Project tenofovir cohort and to identify possible risk factors. Design: The SCOLTA Project is a prospective, observational, multicenter study involving 25 infectious disease departments in Italy created to assess the incidence of severe adverse events in patients receiving new antiretroviral drugs. Patients: The SCOLTA Project tenofovir cohort includes a total of 754 HIV infected patients. Results: Data including grade IIeIV creatinine elevations according to ACTG scale were available in 354 patients, 237 (67%) males with a mean age of 40.1 ± 7.6 years enrolled in the SCOLTA Project tenofovir cohort. During a mean follow up of 19.5 ± 11.5 months creatinine elevations were reported in 9/354 (2.5%) patients, all males. Mean duration of tenofovir therapy at the event was 9.5 ± 5 months. The overall incidence was 1.6 (95% CI 1.5e1.7) per 100 person-years (p-y) and 0.5 (95% CI 0.4e0.6) p-y for grade III. No grade IV creatinine elevations were reported. Patients with nephrotoxicity were older and more frequently male, HCV infected, in CDC stage C and their CD4 cell count was significantly lower than those without nephrotoxicity. No significant difference was found between tenofovir co-administered antiretroviral drugs. Conclusions: Both prevalence and incidence of nephrotoxicity were low in patients receiving tenofovir in a non-selected clinical setting. Renal injury in patients receiving tenofovir seems associated with the presence of co-morbidities and with advanced HIV infection

Follicular helper T cell signature of replicative exhaustion, apoptosis, and senescence in common variable immunodeficiency

Common variable immunodeficiency (CVID) is the most frequent primary antibody deficiency whereby follicular helper T (Tfh) cells fail to establish productive responses with B cells in germinal centers. Here, we analyzed the frequency, phenotype, transcriptome, and function of circulating Tfh (cTfh) cells in CVID patients displaying autoimmunity as an additional phenotype. A group of patients showed a high frequency of cTfh1 cells and a prominent expression of PD-1 and ICOS as well as a cTfh mRNA signature consistent with highly activated, but exhausted, senescent, and apoptotic cells. Plasmatic CXCL13 levels were elevated in this group and positively correlated with cTfh1 cell frequency and PD-1 levels. Monoallelic variants in RTEL1, a telomere length- and DNA repair-related gene, were identified in four patients belonging to this group. Their blood lymphocytes showed shortened telomeres, while their cTfh were more prone to apoptosis. These data point toward a novel pathogenetic mechanism in CVID, whereby alterations in DNA repair and telomere elongation might predispose to antibody deficiency. A Th1, highly activated but exhausted and apoptotic cTfh phenotype was associated with this form of CVID

The instruments used by the Italian centres for cognitive disorders and dementia to diagnose mild cognitive impairment (MCI)

Aims: The purpose of this study was to examine the tools used in Italy to diagnose mild cognitive impairment (MCI). Methods: In collaboration with the Luigi Amaducci Research Consortium, the Italian Network of Alzheimer Evaluation Units prepared a questionnaire to describe how MCI is diagnosed in the Italian Centres for cognitive disorders and dementia (CCDD). Results: Most of the ninety-two CCDDs participating in the survey were located in hospitals (54.7%); large percentages were coordinated by neurologists (50.8%) and geriatricians (44.6%). Almost all (98.5%) used the Mini Mental State Examination to diagnose MCI; the Clock Drawing Test was also frequently used (83.9%). Other neuropsychological, imaging and biomarker tests were utilized less frequently and a wide diversity in the instruments used was noted. Conclusions: According to the results, diagnoses of MCI are based on a multitude of instruments, with major differences in the clinical assessment of geriatricians and neurologists. Standardized testing protocols, validated instruments and cut-off points need to be identified and adopted by the CCDDs for assessing MCI

Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy: Collaborative Analysis of Cohorts of HIV-1-Infected Patients

Background: The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods: We analyzed data on 20,379 treatment-naive HIV-1- infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results: Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count 350 cells/μL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions: Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART