A new long-term lifetime distribution induced by a latent complementary risk framework

In this paper, we proposed a new three-parameter long-term lifetime distribution induced by a latent complementary risk framework with decreasing, increasing and unimodal hazard function, the long-term complementary exponential geometric distribution. The new distribution arises from latent competing risk scenarios, where the lifetime associated scenario, with a particular risk, is not observable, rather we observe only the maximum lifetime value among all risks, and the presence of long-term survival. The properties of the proposed distribution are discussed, including its probability density function and explicit algebraic formulas for its reliability, hazard and quantile functions and order statistics. The parameter estimation is based on the usual maximum-likelihood approach. A simulation study assesses the performance of the estimation procedure. We compare the new distribution with its particular cases, as well as with the long-term Weibull distribution on three real data sets, observing its potential and competitiveness in comparison with some usual long-term lifetime distributions.

Mayaro Virus Infection in Amazonia: A Multimodel Inference Approach to Risk Factor Assessment

Background: Arboviral diseases are major global public health threats. Yet, our understanding of infection risk factors is, with a few exceptions, considerably limited. A crucial shortcoming is the widespread use of analytical methods generally not suited for observational data - particularly null hypothesis-testing (NHT) and step-wise regression (SWR). Using Mayaro virus (MAYV) as a case study, here we compare information theory-based multimodel inference (MMI) with conventional analyses for arboviral infection risk factor assessment. Methodology/Principal Findings: A cross-sectional survey of anti-MAYV antibodies revealed 44% prevalence (n = 270 subjects) in a central Amazon rural settlement. NHT suggested that residents of village-like household clusters and those using closed toilet/latrines were at higher risk, while living in non-village-like areas, using bednets, and owning fowl, pigs or dogs were protective. The "minimum adequate" SWR model retained only residence area and bednet use. Using MMI, we identified relevant covariates, quantified their relative importance, and estimated effect-sizes (beta +/- SE) on which to base inference. Residence area (beta(Village) = 2.93 +/- 0.41; beta(Upland) = -0.56 +/- 0.33, beta(Riverbanks) = -2.37 +/- 0.55) and bednet use (beta = -0.95 +/- 0.28) were the most important factors, followed by crop-plot ownership (beta = 0.39 +/- 0.22) and regular use of a closed toilet/latrine (beta = 0.19 +/- 0.13); domestic animals had insignificant protective effects and were relatively unimportant. The SWR model ranked fifth among the 128 models in the final MMI set. Conclusions/Significance: Our analyses illustrate how MMI can enhance inference on infection risk factors when compared with NHT or SWR. MMI indicates that forest crop-plot workers are likely exposed to typical MAYV cycles maintained by diurnal, forest dwelling vectors; however, MAYV might also be circulating in nocturnal, domestic-peridomestic cycles in village-like areas. This suggests either a vector shift (synanthropic mosquitoes vectoring MAYV) or a habitat/habits shift (classical MAYV vectors adapting to densely populated landscapes and nocturnal biting); any such ecological/adaptive novelty could increase the likelihood of MAYV emergence in Amazonia.

Tecniche investigative ed aspetti criminologici nelle indagini giudiziarie relative ai suicidi ed alle morti equivoche. L'autopsia psicologica

La ricerca è strutturata in due sezioni: nella prima, dopo una premessa storica sul suicidio ed una lettura dei relativi dati statistici italiani integrata dall’analisi delle principali teorie sociologiche e dei principali aspetti psicopatologici e di psicologia clinica, vengono esaminati i risultati forniti da numerosi studi scientifici sul tema complementare delle morti equivoche, con particolare riferimento alle categorie a rischio rappresentate da anziani, carcerati, piloti di aerei, soggetti dediti a pratiche di asfissia autoerotica o roulette russa, istigatori delle forze di polizia e suicida stradali. Successivamente sono esaminati gli aspetti investigativi e medico-legali in tema di suicidi e morti equivoche con particolare riferimento alla tecnica dell’autopsia psicologica analizzandone le origini ed evoluzioni, il suo ambito di utilizzo ed i relativi aspetti metodologici. Nella seconda sezione del lavoro il tema dei suicidi e delle morti equivoche viene approfondito grazie all’apporto di professionisti di discipline diverse esperti in materia di autopsia psicologica ed indagini giudiziarie. A questi è stata presentata, con l’utilizzo della tecnica qualitativa “Dephi, una iniziale ipotesi di protocollo di autopsia psicologica, con le relative modalità applicative, al fine di procedere ad una sua revisione ed adattamento alle esigenze operative italiane grazie alle specifiche esperienze professionali e multidisciplinari maturate dagli esperti. I dati raccolti hanno permesso di giungere alla formulazione di un protocollo di autopsia psicologica, basato sulla elaborazione di domande generali, specifiche e conclusive, a risposta aperta, che possono esser formulate, secondo le modalità previste, alle persone affettivamente significative per la vittima nei confronti della quale si intende procedere con tale strumento investigativo.

Food safety and zoonotic enteric pathogens: sources, risk factors and transmission routes of human salmonellosis and campylobacteriosis

Salmonella and Campylobacter are common causes of human gastroenteritis. Their epidemiology is complex and a multi-tiered approach to control is needed, taking into account the different reservoirs, pathways and risk factors. In this thesis, trends in human gastroenteritis and food-borne outbreak notifications in Italy were explored. Moreover, the improved sensitivity of two recently-implemented regional surveillance systems in Lombardy and Piedmont was evidenced, providing a basis for improving notification at the national level. Trends in human Salmonella serovars were explored: serovars Enteritidis and Infantis decreased, Typhimurium remained stable and 4,[5],12:i:-, Derby and Napoli increased, suggesting that sources of infection have changed over time. Attribution analysis identified pigs as the main source of human salmonellosis in Italy, accounting for 43–60% of infections, followed by Gallus gallus (18–34%). Attributions to pigs and Gallus gallus showed increasing and decreasing trends, respectively. Potential bias and sampling issues related to the use of non-local/non-recent multilocus sequence typing (MLST) data in Campylobacter jejuni/coli source attribution using the Asymmetric Island (AI) model were investigated. As MLST data become increasingly dissimilar with increasing geographical/temporal distance, attributions to sources not sampled close to human cases can be underestimated. A combined case-control and source attribution analysis was developed to investigate risk factors for human Campylobacter jejuni/coli infection of chicken, ruminant, environmental, pet and exotic origin in The Netherlands. Most infections (~87%) were attributed to chicken and cattle. Individuals infected from different reservoirs had different associated risk factors: chicken consumption increased the risk for chicken-attributed infections; animal contact, barbecuing, tripe consumption, and never/seldom chicken consumption increased that for ruminant-attributed infections; game consumption and attending swimming pools increased that for environment-attributed infections; and dog ownership increased that for environment- and pet-attributed infections. Person-to-person contacts around holiday periods were risk factors for infections with exotic strains, putatively introduced by returning travellers.

Analisi e riprogettazione del processo di ict risk management: un caso applicativo in Telecom Italia

Questo lavoro di tesi muove da tematiche relative alla sicurezza IT e risulta dagli otto mesi di lavoro all’interno della funzione Technical Security di Telecom Italia Information Technology. Il compito primario di questa unità di business è ridurre il rischio informatico dei sistemi di Telecom Italia per mezzo dell’attuazione del processo di ICT Risk Management, che coinvolge l’intera organizzazione ed è stato oggetto di una riprogettazione nel corso del 2012. Per estendere tale processo a tutti i sistemi informatici, nello specifico a quelli caratterizzati da non conformità, all’inizio del 2013 è stato avviato il Programma Strutturato di Sicurezza, un aggregato di quattro progetti dalla durata triennale particolarmente articolato e complesso. La pianificazione di tale Programma ha visto coinvolto, tra gli altri, il team di cui ho fatto parte, che ha collaborato con Telecom Italia assolvendo alcune delle funzioni di supporto tipiche dei Project Management Office (PMO).

La linea guida api - risk based inspection: Definizione delle frequenze di rilascio e ottimazione delle visite ispettive

La stima della frequenza di accadimento di eventi incidentali di tipo random da linee e apparecchiature è in generale effettuata sulla base delle informazioni presenti in banche dati specializzate. I dati presenti in tali banche contengono informazioni relative ad eventi incidentali avvenuti in varie tipologie di installazioni, che spaziano dagli impianti chimici a quelli petrolchimici. Alcune di queste banche dati risultano anche piuttosto datate, poiché fanno riferimento ad incidenti verificatisi ormai molto addietro negli anni. Ne segue che i valori relativi alle frequenze di perdita forniti dalle banche dati risultano molto conservativi. Per ovviare a tale limite e tenere in conto il progresso tecnico, la linea guida API Recommended Pratice 581, pubblicata nel 2000 e successivamente aggiornata nel 2008, ha introdotto un criterio per determinare frequenze di perdita specializzate alla realtà propria impiantistica, mediante l’ausilio di coefficienti correttivi che considerano il meccanismo di guasto del componente, il sistema di gestione della sicurezza e l’efficacia dell’attività ispettiva. Il presente lavoro di tesi ha lo scopo di mettere in evidenza l’evoluzione dell’approccio di valutazione delle frequenze di perdita da tubazione. Esso è articolato come descritto nel seguito. Il Capitolo 1 ha carattere introduttivo. Nel Capitolo 2 è affrontato lo studio delle frequenze di perdita reperibili nelle banche dati generaliste. Nel Capitolo 3 sono illustrati due approcci, uno qualitativo ed uno quantitativo, che permettono di determinare le linee che presentano priorità più alta per essere sottoposte all’attività ispettiva. Il Capitolo 4 è dedicato alla descrizione della guida API Recomended Practice 581. L’applicazione ad un caso di studio dei criteri di selezione delle linee illustrati nel Capitolo 3 e la definizione delle caratteristiche dell’attività ispettiva secondo la linea guida API Recomended Practice 581 sono illustrati nel Capitolo 5. Infine nel Capitolo 6 sono rese esplicite le considerazioni conclusive dello studio effettuato.

Hypoxia aggravates non-alcoholic steatohepatitis in mice lacking hepatocellular PTEN

The metabolic disorders that predispose patients to NASH (non-alcoholic steatohepatitis) include insulin resistance and obesity. Repeated hypoxic events, such as occur in obstructive sleep apnoea syndrome, have been designated as a risk factor in the progression of liver disease in such patients, but the mechanism is unclear, in particular the role of hypoxia. Therefore we studied the influence of hypoxia on the development and progression of steatohepatitis in an experimental mouse model. Mice with a hepatocellular-specific deficiency in the Pten (phosphatase and tensin homologue deleted on chromosome 10) gene, a tumour suppressor, were exposed to a 10% O2 (hypoxic) or 21% O2 (control) atmosphere for 7 days. Haematocrit, AST (aspartate aminotransferase), glucose, triacylglycerols (triglycerides) and insulin tolerance were measured in blood. Histological lesions were quantified. Expression of genes involved in lipogenesis and mitochondrial beta-oxidation, as well as FOXO1 (forkhead box O1), hepcidin and CYP2E1 (cytochrome P450 2E1), were analysed by quantitative PCR. In the animals exposed to hypoxia, the haematocrit increased (60+/-3% compared with 50+/-2% in controls; P<0.01) and the ratio of liver weight/body weight increased (5.4+/-0.2% compared with 4.7+/-0.3% in the controls; P<0.01). Furthermore, in animals exposed to hypoxia, steatosis was more pronounced (P<0.01), and the NAS [NAFLD (non-alcoholic fatty liver disease) activity score] (8.3+/-2.4 compared with 2.3+/-10.7 in controls; P<0.01), serum AST, triacylglycerols and glucose were higher. Insulin sensitivity decreased in mice exposed to hypoxia relative to controls. The expression of the lipogenic genes SREBP-1c (sterol-regulatory-element-binding protein-1c), PPAR-gamma (peroxisome-proliferator-activated receptor-gamma), ACC1 (acetyl-CoA carboxylase 1) and ACC2 (acetyl-CoA carboxylase 2) increased significantly in mice exposed to hypoxia, whereas mitochondria beta-oxidation genes [PPAR-alpha (peroxisome-proliferator-activated receptor-alpha) and CPT-1 (carnitine palmitoyltransferase-1)] decreased significantly. In conclusion, the findings of the present study demonstrate that hypoxia alone aggravates and accelerates the progression of NASH by up-regulating the expression of lipogenic genes, by down-regulating genes involved in lipid metabolism and by decreasing insulin sensitivity.

A multifactorial analysis of obesity as CVD risk factor: use of neural network based methods in a nutrigenetics context

Obesity is a multifactorial trait, which comprises an independent risk factor for cardiovascular disease (CVD). The aim of the current work is to study the complex etiology beneath obesity and identify genetic variations and/or factors related to nutrition that contribute to its variability. To this end, a set of more than 2300 white subjects who participated in a nutrigenetics study was used. For each subject a total of 63 factors describing genetic variants related to CVD (24 in total), gender, and nutrition (38 in total), e.g. average daily intake in calories and cholesterol, were measured. Each subject was categorized according to body mass index (BMI) as normal (BMI ≤ 25) or overweight (BMI > 25). Two artificial neural network (ANN) based methods were designed and used towards the analysis of the available data. These corresponded to i) a multi-layer feed-forward ANN combined with a parameter decreasing method (PDM-ANN), and ii) a multi-layer feed-forward ANN trained by a hybrid method (GA-ANN) which combines genetic algorithms and the popular back-propagation training algorithm.

Study Abroad Increases Risk for Sexual Assault in Female Undergraduates: A Preliminary Report

Since 2007, more than 250,000 American students have studied abroad annually for a semester or more. While there are obvious benefits associated with study abroad programs, personal risks (including interpersonal victimization such as sexual and physical assault) occurring during the experience have been anecdotally reported but not systematically assessed. This study is the first to investigate the possibility of increased risk for sexual assault in female undergraduates while abroad. Two hundred eighteen female undergraduates completed a modified version of the Sexual Experiences Survey (SES: Koss et al., 2007) about their sexual experiences abroad and on campus. Findings indicate increased risk for sexual assault while abroad relative to on-campus rates, particularly in non-English speaking countries. Study abroad programs should consider educating students about increased risk and develop response protocols when sexual assaults happen while abroad.

Estimating loss to follow-up in HIV-infected patients on antiretroviral therapy: the effect of the competing risk of death in Zambia and Switzerland

Background Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland. Methods and Findings HIV-infected patients aged ≥18 years who started ART 2004–2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ≥350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naïve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up. Conclusions In ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings.

Learned irrelevance and associative learning is attenuated in individuals at risk for psychosis but not in asymptomatic first-degree relatives of schizophrenia patients: translational state markers of psychosis?

Learned irrelevance (LIrr) refers to a form of selective learning that develops as a result of prior noncorrelated exposures of the predicted and predictor stimuli. In learning situations that depend on the associative link between the predicted and predictor stimuli, LIrr is expressed as a retardation of learning. It represents a form of modulation of learning by selective attention. Given the relevance of selective attention impairment to both positive and cognitive schizophrenia symptoms, the question remains whether LIrr impairment represents a state (relating to symptom manifestation) or trait (relating to schizophrenia endophenotypes) marker of human psychosis. We examined this by evaluating the expression of LIrr in an associative learning paradigm in (1) asymptomatic first-degree relatives of schizophrenia patients (SZ-relatives) and in (2) individuals exhibiting prodromal signs of psychosis ("ultrahigh risk" [UHR] patients) in each case relative to demographically matched healthy control subjects. There was no evidence for aberrant LIrr in SZ-relatives, but LIrr as well as associative learning were attenuated in UHR patients. It is concluded that LIrr deficiency in conjunction with a learning impairment might be a useful state marker predictive of psychotic state but a relatively weak link to a potential schizophrenia endophenotype.

Decreasing frequency of plasma exchange complications in patients treated for thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 1996 to 2011

Plasma exchange (PEX) treatment for patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) has risk for major complications.

Mapping the increasing risk of human alveolar echinococcosis in Limburg, The Netherlands

The parasite Echinococcus multilocularis was first detected in The Netherlands in 1996 and repeated studies have shown that the parasite subsequently spread in the local population of foxes in the province of Limburg. It was not possible to quantify the human risk of alveolar echinococcosis because no relationship between the amount of parasite eggs in the environment and the probability of infection in humans was known. Here, we used the spread of the parasite in The Netherlands as a predictor, together with recently published historical records of the epidemiology of alveolar echinococcosis in Switzerland, to achieve a relative quantification of the risk. Based on these analyses, the human risk in Limburg was simulated and up to three human cases are predicted by 2018. We conclude that the epidemiology of alveolar echinococcosis in The Netherlands might have changed from a period of negligible risk in the past to a period of increasing risk in the forthcoming years.

Risk attribution of Campylobacter infection by age group using exposure modelling

Knowledge on the relative importance of alternative sources of human campylobacteriosis is important in order to implement effective disease prevention measures. The objective of this study was to assess the relative importance of three key exposure pathways (travelling abroad, poultry meat, pet contact) for different patient age groups in Switzerland. With a stochastic exposure model data on Campylobacter incidence for the years 2002-2007 were linked with data for the three exposure pathways and the results of a case-control study. Mean values for the population attributable fractions (PAF) over all age groups and years were 27% (95% CI 17-39) for poultry consumption, 27% (95% CI 22-32) for travelling abroad, 8% (95% CI 6-9) for pet contact and 39% (95% CI 25-50) for other risk factors. This model provided robust results when using data available for Switzerland, but the uncertainties remained high. The output of the model could be improved if more accurate input data are available to estimate the infection rate per exposure. In particular, the relatively high proportion of cases attributed to 'other risk factors' requires further attention.

Predictors of surgical, general and follow-up complications in lumbar spinal stenosis relative to patient age as emerged from the Spine Tango Registry

Published opinions regarding the outcomes and complications in older patients have a broad spectrum and there is a disagreement whether surgery in older patients entails a higher risk. Therefore this study examines the risk of surgery for lumbar spinal stenosis relative to age in the pooled data set of the Spine Tango registry.