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Purpose To examine differences between genders in exposure to psychosocial and ergonomic factors at work and in work-related health, according to different work organization models. Methods The study population included a sample of 9749 (women: 37.1%) and 10,374 (women: 39.9%) employees who participated in the 2010 and 2015 European Working Conditions Surveys, respectively. Multiple Correspondence Analysis was applied to work characteristics reported by workers to estimate principal components, followed by Hierarchical Clustering on principal components to identify clusters of work organization models. Gender differences in exposure to work hazards and health outcomes were assessed through Poisson robust regression. Differences of PRs across organizational models were tested through interaction between gender and type of work organization. Results Three organizational models were identified in 2010, including lean production, Tayloristic production, and a “reflexive production” model, whereas in 2015, a “simple” or traditional model was also found. In 2010, women employed in companies adopting the Tayloristic or the lean production models were more likely than men to be exposed to unfavourable psychosocial and physical work factors, and to report musculoskeletal pain, compared to those belonging to reflexive production. In 2015, a significantly higher female/male ratio persisted in lean production for exposure to high job strain and for carrying/moving heavy loads, whereas gender differences in Tayloristic and traditional production were quite similar to those of reflexive production. Conclusions Our results suggest that employment in workplaces characterized by lower monotony, repetitiveness, and production constraints may contribute to reduce exposure to job strain among working women.

Background: Testicular germ cell tumors (TGCT), histologically classified as seminomas and nonseminomas, are believed to arise from primordial gonocytes, with the maturation process blocked when they are subjected to DNA methylation reprogramming. SNPs in DNA methylation machinery and folate-dependent one-carbon metabolism genes have been postulated to influence the proper establishment of DNA methylation. Methods: In this pathway-focused investigation, we evaluated the association between 273 selected tag SNPs from 28 DNA methylation–related genes and TGCT risk. We carried out association analysis at individual SNP and gene-based level using summary statistics from the Genome Wide Association Study meta-analysis recently conducted by the international Testicular Cancer Consortium on 10,156 TGCT cases and 179,683 controls. Results: In individual SNP analyses, seven SNPs, four mapping within MTHFR, were associated with TGCT risk after correction for multiple testing (q ≤ 0.05). Queries of public databases showed that three of these SNPs were associated with MTHFR changes in enzymatic activity (rs1801133) or expression level in testis tissue (rs12121543, rs1476413). Gene-based analyses revealed MTHFR (q = 8.4 × 10–4), methyl-CpG–binding protein 2 (MECP2; q = 2 × 10–3), and ZBTB4 (q = 0.03) as the top TGCT-associated genes. Stratifying by tumor histology, four MTHFR SNPs were associated with seminoma. In gene-based analysis MTHFR was associated with risk of seminoma (q = 2.8 × 10–4), but not with nonseminomatous tumors (q = 0.22). Conclusions: Genetic variants within MTHFR, potentially having an impact on the DNA methylation pattern, are associated with TGCT risk. Impact: This finding suggests that TGCT pathogenesis could be associated with the folate cycle status, and this relation could be partly due to hereditary factors.

Background: Many studies have shown that socioeconomic position (SEP) is associated with the incidence of malignant tumors at different sites. This study aims to estimate the association between educational level (as proxy for SEP) and cancer incidence and to understand whether the observed associations might be partially explained by lifestyle behaviors. Methods: The analyses were performed on data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, globally and by sex. We used Cox proportional hazards models together with mediation analysis to disentangle the total effect (TE) of educational level [measured through the Relative Index of Inequality (RII)] on cancer incidence into pure direct (PDE) and total indirect (TIE) effect, unexplained and explained by mediators, respectively. PDE and TIE were then combined to compute the proportions mediated (PM). Results: After an average of 14 years of follow-up, 52,422 malignant tumors were ascertained. Low educated participants showed higher risk of developing stomach, lung, kidney (in women), and bladder (in men) cancers, and, conversely, lower risk of melanoma and breast cancer (in post-menopausal women), when compared with more educated participants. Mediation analyses showed that portions of the TE of RII on cancer could be explained by site-specific related lifestyle behaviors for stomach, lung, and breast (in women). Conclusions: Cancer incidence in Europe is determined at least in part by a socioeconomically stratified distribution of risk factors. Impact: These observational findings support policies to reduce cancer occurrence by altering mediators, such as lifestyle behaviors, particularly focusing on underprivileged strata of the population.

Summary Background In many European countries, human papillomavirus (HPV) vaccine uptake among girls has remained below target levels, supporting the scope for vaccination of boys. We aimed to investigate if sex-neutral HPV vaccination can be considered cost-effective compared with girls-only vaccination at uptake levels equal to those among girls and under tender-based vaccination costs achieved throughout Europe. Methods We investigated the cost-effectiveness of sex-neutral HPV vaccination in European tender-based settings. We applied a Bayesian synthesis framework for health economic evaluation to 11 countries (Austria, Belgium, Croatia, Estonia, Italy, Latvia, the Netherlands, Poland, Slovenia, Spain, and Sweden), accommodating country-specific information on key epidemiological and economic parameters, and on current HPV vaccination programmes. We used projections from three independently developed HPV transmission models to tailor region-specific herd effects. The main outcome measures in the comparison of sex-neutral with girls-only vaccination were cancer cases prevented and incremental cost-effectiveness ratios (ICERs), defined as the cost in international dollars (I$) per life-year gained. Findings The total number of cancer cases to be prevented by vaccinating girls at currently realised vaccine uptake varied from 318 (95% CI 197–405) per cohort of 200 000 preadolescents (100 000 girls plus 100 000 boys) in Croatia (under 20% uptake of the 9-valent vaccine) to 1904 (1741–2101) in Estonia (under 70% uptake of the 9-valent vaccine). Vaccinating boys at equal coverage increased these respective numbers by 168 (95% CI 121–213) in Croatia and 467 (391–587) in Estonia. Sex-neutral vaccination was likely to be cost-effective, with ICERs of sex-neutral compared with girls-only vaccination varying from I$4300 per life-year gained in Latvia (95% credibility interval 3450–5160; 40% uptake) to I$25 720 per life-year gained in Spain (21 380–30 330; 80% uptake). At uniform 80% uptake, a favourable cost-effectiveness profile was retained for most of the countries investigated (Austria, Belgium, Italy, Latvia, the Netherlands, Slovenia, Spain, and Sweden). Interpretation Sex-neutral HPV vaccination is economically attractive in European tender-based settings. However, tendering mechanisms need to ensure that vaccination of boys will remain cost-effective at high vaccine uptake rates. Funding European Commission 7th Framework Programme and WHO.

International variations in the prevalence of HPV infection derive from differences in sexual behaviors, which are also a key factor of the basic reproductive number (R0 ) of HPV infection in different populations. R0 affects the strength of herd protection and hence the impact of a vaccination program. Similar vaccination programs may therefore generate different levels of impact depending upon the population's pre-vaccination HPV prevalence. We used IARC's transmission model to estimate (i) the overall effectiveness of vaccination versus no vaccination in women aged 15-34 years measured as percent prevalence reduction (%PR) of HPV16 and (ii) the corresponding herd protection in populations with gender-equal or traditional sexual behavior and with different levels of sexual activity, corresponding to pre-vaccination HPV16 prevalence from 1 to 8% as observed worldwide. Between populations with different levels of gender-equal sexual activity, the highest difference in %PR under girls-only vaccination is observed at 40% coverage (91%PR vs. 48%PR for 1% and 8% pre-vaccination prevalence, respectively). HPV16 elimination is obtained with 55 and 97% coverage, respectively. To achieve desirable levels of HPV16 prevalence after vaccination, different levels of coverage are required in populations with different levels of pre-vaccination HPV16 prevalence, for example, in populations with gender-equal sexual behavior a decrease to 1/1000 HPV16 from pre-vaccination prevalence of 1 and 8% would require coverages of 37 and 96%, respectively. In traditional populations, corresponding coverages would need to be 28 and 93%, respectively. In conclusion, pre-vaccination HPV prevalence strongly influences herd immunity and helps predict the overall effectiveness of HPV vaccination.

Background Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination. Methods We searched MEDLINE and Embase for transmission-dynamic modelling studies published between Jan 1, 2009, and April 28, 2015, that predicted the population-level impact of vaccination on HPV 6, 11, 16, and 18 infections in high-income countries. We contacted authors to determine whether they were willing to produce new predictions for standardised scenarios. Strategies investigated were girls-only vaccination and girls and boys vaccination at age 12 years. Base-case vaccine characteristics were 100% efficacy and lifetime protection. We did sensitivity analyses by varying vaccination coverage, vaccine efficacy, and duration of protection. For all scenarios we pooled model predictions of relative reductions in HPV prevalence (RRprev) over time after vaccination and summarised results using the median and 10th and 90th percentiles (80% uncertainty intervals [UI]). Findings 16 of 19 eligible models from ten high-income countries provided predictions. Under base-case assumptions, 40% vaccination coverage and girls-only vaccination, the RRprev of HPV 16 among women and men was 0·53 (80% UI 0·46–0·68) and 0·36 (0·28–0·61), respectively, after 70 years. With 80% girls-only vaccination coverage, the RRprev of HPV 16 among women and men was 0·93 (0·90–1·00) and 0·83 (0·75–1·00), respectively. Vaccinating boys in addition to girls increased the RRprev of HPV 16 among women and men by 0·18 (0·13–0·32) and 0·35 (0·27–0·39) for 40% coverage, and 0·07 (0·00–0·10) and 0·16 (0·01–0·25) for 80% coverage, respectively. The RRprev were greater for HPV 6, 11, and 18 than for HPV 16 for all scenarios investigated. Finally at 80% coverage, most models predicted that girls and boys vaccination would eliminate HPV 6, 11, 16, and 18, with a median RRprev of 1·00 for women and men for all four HPV types. Variability in pooled findings was low, but increased with lower vaccination coverage and shorter vaccine protection (from lifetime to 20 years). Interpretation Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time. Funding Canadian Institutes of Health Research.

International variations in the prevalence of HPV infection derive from differences in sexual behaviors, which are also a key factor of the basic reproductive number (R0) of HPV infection in different populations. R 0 affects the strength of herd protection and hence the impact of a vaccination program. Similar vaccination programs may therefore generate different levels of impact depending upon the population's pre‐vaccination HPV prevalence. We used IARC's transmission model to estimate (i) the overall effectiveness of vaccination versus no vaccination in women aged 15–34 years measured as percent prevalence reduction (%PR) of HPV16 and (ii) the corresponding herd protection in populations with gender‐equal or traditional sexual behavior and with different levels of sexual activity, corresponding to pre‐vaccination HPV16 prevalence from 1 to 8% as observed worldwide. Between populations with different levels of gender‐equal sexual activity, the highest difference in %PR under girls‐only vaccination is observed at 40% coverage (91%PR vs. 48%PR for 1% and 8% pre‐vaccination prevalence, respectively). HPV16 elimination is obtained with 55 and 97% coverage, respectively. To achieve desirable levels of HPV16 prevalence after vaccination, different levels of coverage are required in populations with different levels of pre‐vaccination HPV16 prevalence, for example, in populations with gender‐equal sexual behavior a decrease to 1/1000 HPV16 from pre‐vaccination prevalence of 1 and 8% would require coverages of 37 and 96%, respectively. In traditional populations, corresponding coverages would need to be 28 and 93%, respectively. In conclusion, pre‐vaccination HPV prevalence strongly influences herd immunity and helps predict the overall effectiveness of HPV vaccination., What's new? Differences in sexual activity from one population to another account for up to a ten‐fold difference in HPV prevalence, which in turn affects cervical‐cancer risk. How do these factors impact the effectiveness of HPV‐vaccination programs? In this epidemiological study, the authors found that, in countries where sexual behavior is based on traditional norms and HPV prevalence remains low, an early introduction of HPV vaccination will anticipate any increase of HPV prevalence among young women due to the liberalization of social attitudes.

Summary The level of coverage and type-specific vaccine efficacy necessary to reduce or eliminate carcinogenic human papillomavirus (HPV) is chiefly determined by their propensity to persist. Therefore, HPV-16 infection and related cancers are the most difficult to eliminate through vaccination., Background Human papillomavirus (HPV) vaccination is still not reaching many high-risk populations. HPV16/18 vaccines offer cross-protection against other types, for example, HPV45. Both direct vaccine efficacy and indirect herd protection contribute to vaccination effectiveness. Methods We used a dynamic transmission model, calibrated to cervical screening data from Italy, to estimate vaccination effectiveness against HPV16 and HPV45 infection, assuming for HPV45 either 95% or lower cross-protection. Results Basic reproductive number was smaller (2.1 vs 4.0) and hence vaccine effectiveness and herd protection stronger for HPV45 than for HPV16. The largest difference in the reduction of infection prevalence in women

Human papillomavirus (HPV) vaccination of a birth cohort of girls in the 9-13 age range is recommended as a priority, but decreases in HPV vaccine cost may make catch-up of a few additional cohorts more attractive not only in high-income countries. We assessed the reduction in HPV16 and 18 infections that could be achieved in a medium- (Poland) and a low-income (Guinea) country by adding one-time catch-up of 12- to 19-year-old girls to the vaccination of 11-year-old girls. According to our ad hoc adapted dynamic model of HPV infection transmission, the addition of catch-up was estimated to bring forward the 50% reduction of HPV16/18 prevalence due to vaccination in women ≤35 by as much as 5 years. Catch-up of 12- to 15-year olds reduced the cumulative probability of HPV16/18 infections by age 35 in the relevant cohorts by about 30% in both countries. Catch-up of 16- to 19-year-old girls added little. Regardless of the chosen catch-up strategy, 16 to 20% of HPV16/18 prevention from vaccination was attributable to herd immunity. Assuming a sufficiently low vaccine cost, the addition of a catch-up round is, therefore, worth considering in medium/low-income countries to extend vaccine benefits to less young adolescent girls whose future access to cervical screening is uncertain.

Introduction. The area of Casale Monferrato (north west Italy) is affected by high levels of environmental asbestos pollution from an Eternit asbestos cement (AC) plant active from 1906 to 1986. We...

Early vaccination may prevent infections in populations undergoing age-specific changes in sexual activity., Human papillomavirus (HPV) prevalence varies widely worldwide. We used a transmission model to show links between age-specific sexual patterns and HPV vaccination effectiveness. We considered rural India and the United States as examples of 2 heterosexual populations with traditional age-specific sexual behavior and gender-similar age-specific sexual behavior, respectively. We simulated these populations by using age-specific rates of sexual activity and age differences between sexual partners and found that transitions from traditional to gender-similar sexual behavior in women

Background: Cervical cancer is the most common female cancer in Rwanda that, in 2011, became the first African country to implement a national vaccination programme against human papillomavirus (HPV). Methods: To provide a robust baseline for future evaluations of vaccine effectiveness, cervical cell specimens were obtained from 2508 women aged 18-69 years from the general population in Kigali, Rwanda, during 2013/14. 20 % of women were HIV-positive. Samples were used for liquid-based cytology and HPV testing (44 types) with GP5+/6+ PCR. Results: HPV prevalence was 34 %, being highest (54 %) in women ≤19 years and decreasing to 20 % at age ≥50. Prevalence of high risk (HR) HPV and cytological abnormalities was 22 and 11 % respectively (including 2 % with high-grade squamous intraepithelial lesions, HSIL) decreasing with age. Age-standardised prevalence of HR HPV was 22 % (or 19 % among HIV-negative women), and HPV16 was the most common type. Prevalence of HPV and cytological abnormalities were significantly higher in HIV-positive than HIV-negative women, and the difference increased with age. Other significant risk factors for HPV positivity in multivariate analyses were high lifetime number of sexual partners, receiving cash for sex, and being a farmer. 40 % of women with HSIL were infected with HPV16/18 and there was no significant difference between HIV-positive and HIV-negative women. Conclusions: This study confirms Rwanda to be a setting of high prevalence of HPV and cervical disease that is worsened by HIV. These data will serve as a robust baseline for future evaluations of HPV vaccine programme effectiveness., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Decreasing human papillomavirus (HPV) vaccine prices makes scaling up of vaccination programs attractive for countries that initially targeted 1 or a few birth cohorts of girls and/or achieved low coverage. This article aims to compare the impact of alternative HPV vaccination strategies, using data from Sweden, a high-income country that has experienced vaccine price changes. Methods Using an HPV transmission model, we compared the existing vaccination program to alternatives, accounting for a 1-time catch-up vaccination of 22-26-year-old women, with or without routine vaccination of school-age boys, and for a 1-time catch-up vaccination of males aged 13-26 years. We also assessed the resilience of vaccination alternatives to coverage reduction. Results On the basis of an HPV16/18 prevalence of 12% before the HPV vaccine era, extended catch-up vaccination for females and males yielded relative reductions in the HPV prevalence of 49.4% and 55.6%, respectively, during the first 10 years after the start of each vaccination strategy, whereas the existing program yielded a relative reduction of 38.6% during the same period. The increased prevalence reduction due to catch-up vaccination continued for about 30 years. As compared to female-only routine and extended catch-up vaccination, routine vaccination of males with or without catch-up was, respectively, 12.6-fold and 7.2-fold more resilient to coverage reduction. Conclusions Vaccination strategies based on catch-up vaccination of females and males are effective for accelerating HPV prevalence reduction. Inclusion of routine male vaccination improves the resilience of vaccination programs.

Summary: Chimera is a Bioconductor package that organizes, annotates, analyses and validates fusions reported by different fusion detection tools; current implementation can deal with output from bellerophontes, chimeraScan, deFuse, fusionCatcher, FusionFinder, FusionHunter, FusionMap, mapSplice, Rsubread, tophat-fusion and STAR. The core of Chimera is a fusion data structure that can store fusion events detected with any of the aforementioned tools. Fusions are then easily manipulated with standard R functions or through the set of functionalities specifically developed in Chimera with the aim of supporting the user in managing fusions and discriminating false-positive results. Availability and implementation: Chimera is implemented as a Bioconductor package in R. The package and the vignette can be downloaded at bioconductor.org. Contact: raffaele.calogero@unito.it Supplementary information: Supplementary data are available at Bioinformatics online.

Objectives The Bhutanese Screening Programme recommends a Pap smear every 3 years for women aged 25–65 years, and coverage ranges from 20% to 60%, being especially challenging in rural settings. The ‘REACH-Bhutan’ study was conducted to assess the feasibility and outcomes of a novel approach to cervical cancer screening in rural Bhutan. Design Cross-sectional, population-based study of cervical cancer screening based on the careHPV test on self-collected samples. Setting Women were recruited in rural primary healthcare centres, that is, Basic Health Units (BHU), across Bhutan. Participants Overall, 3648 women aged 30–60 were invited from 15 BHUs differing in accessibility, size and ethnic composition of the population. Interventions Participants provided a self-collected cervicovaginal sample and were interviewed. Samples were tested using careHPV in Thimphu (the Bhutanese capital) referral laboratory. Main outcome measures Screening participation by geographic area, centre, age and travelling time. Previous screening history and careHPV positivity by selected characteristics of the participants. Results In April/May 2016, 2590 women (median age: 41) were enrolled. Study participation was 71% and significantly heterogeneous by BHU (range: 31%–96%). Participation decreased with increase in age (81% in women aged 30–39 years; 59% in ≥50 years) and travelling time (90% in women living 6 hours away). 50% of participants reported no previous screening, with the proportion of never-screened women varying significantly by BHU (range: 2%–72%). 265 women (10%; 95% CI 9% to 11%) were careHPV positive, with a significant variation by BHU (range: 5%–19%) and number of sexual partners (prevalence ratio for ≥3 vs 0–1, 1.55; 95% CI 1.05 to 2.27). Conclusions Community-based cervical cancer screening by testing self-collected samples for human papillomavirus (HPV) can achieve high coverage in rural Bhutan. However, solutions to bring self-collection, HPV testing and precancer treatment closer to the remotest villages are needed.

Background The decrease in human papillomavirus (HPV) vaccine prices may allow upscale already started vaccination programmes but the advantages of different options are unclear. Methods Using a mathematical model of HPV16 and 18 transmission and data on vaccination coverage from Italy, we compared 3 options to upscale an already started programme targeting 11-year old girls (coverage 65%): a) coverage improvement (from 65% to 90%); b) addition of 11-year-old boys (coverage 65%); or c) 1-year catch-up of older girls (coverage 50%). Results The reduction of cervical HPV16/18 infection as compared to no vaccination (i.e. effectiveness against HPV16/18) increased from 76% to 98% with coverage improvement in girls and to 90% with the addition of boys. With higher coverage in girls, HPV16/18 infection cumulative probability by age 35 decreased from 25% to 8% with a 38% increase in vaccine number. The addition of boys decreased the cumulative probability to 18% with a 100% increase in the number of vaccinees. For any coverage in girls, the number of vaccinees to prevent 1 woman from being infected by HPV16/18 by age 35 was 1.5, whereas it was 2.7 for the addition of boys. Catch-up of older girls only moved forward the vaccination effectiveness by 2–5 years. Conclusions Increasing vaccination coverage among girls is the most effective option for decreasing HPV16/18. If not achievable, vaccinating boys is justifiable if vaccine cost has at least halved, because this option would almost double the number of vaccinees.

Background. Gene fusions arising from chromosomal translocations have been implicated in cancer. RNA-seq has the potential to discover such rearrangements generating functional proteins (chimera/fusion). Recently, many methods for chimeras detection have been published. However, specificity and sensitivity of those tools were not extensively investigated in a comparative way.Results. We tested eight fusion-detection tools (FusionHunter, FusionMap, FusionFinder, MapSplice, deFuse, Bellerophontes, ChimeraScan, and TopHat-fusion) to detect fusion events using synthetic and real datasets encompassing chimeras. The comparison analysis run only on synthetic data could generate misleading results since we found no counterpart on real dataset. Furthermore, most tools report a very high number of false positive chimeras. In particular, the most sensitive tool, ChimeraScan, reports a large number of false positives that we were able to significantly reduce by devising and applying two filters to remove fusions not supported by fusion junction-spanning reads or encompassing large intronic regions.Conclusions. The discordant results obtained using synthetic and real datasets suggest that synthetic datasets encompassing fusion events may not fully catch the complexity of RNA-seq experiment. Moreover, fusion detection tools are still limited in sensitivity or specificity; thus, there is space for further improvement in the fusion-finder algorithms.

Summary: RRE allows the extraction of non-coding regions surrounding a coding sequence [i.e. gene upstream region, 5′-untranslated region (5′-UTR), introns, 3′-UTR, downstream region] from annotated genomic datasets available at NCBI. Availability: RRE parser and web-based interface are accessible at http://www.bioinformatica.unito.it/bioinformatics/rre/rre.html

Human papillomavirus (HPV) vaccination of a birth cohort of girls in the 9-13 age range is recommended as a priority, but decreases in HPV vaccine cost may make catch-up of a few additional cohorts more attractive not only in high-income countries. We assessed the reduction in HPV16 and 18 infections that could be achieved in a medium- (Poland) and a low-income (Guinea) country by adding one-time catch-up of 12- to 19-year-old girls to the vaccination of 11-year-old girls. According to our ad hoc adapted dynamic model of HPV infection transmission, the addition of catch-up was estimated to bring forward the 50% reduction of HPV16/18 prevalence due to vaccination in women ≤35 by as much as 5 years. Catch-up of 12- to 15-year olds reduced the cumulative probability of HPV16/18 infections by age 35 in the relevant cohorts by about 30% in both countries. Catch-up of 16- to 19-year-old girls added little. Regardless of the chosen catch-up strategy, 16 to 20% of HPV16/18 prevention from vaccination was attributable to herd immunity. Assuming a sufficiently low vaccine cost, the addition of a catch-up round is, therefore, worth considering in medium/low-income countries to extend vaccine benefits to less young adolescent girls whose future access to cervical screening is uncertain.

It is important for clinicians to understand which are the clinical signs, the patient characteristics and the procedures that are related with the occurrence of hypertrophic burn scars in order to carry out a possible prognostic assessment. Providing clinicians with an easy-to- use tool for predicting the risk of pathological scars. A total of 703 patients with 2440 anatomical burn sites who were admitted to the Department of Plastic and Reconstructive Surgery, Burn Center of the Traumatological Hospital in Torino between January 1994 and May 2006 were included in the analysis. A Bayesian network (BN) model was implemented. The probability of developing a hypertrophic scar was evaluated on a number of scenarios. The error rate of the BN model was assessed internally and it was equal to 24·83%. While classical statistical method as logistic models can infer only which variables are related to the final outcome, the BN approach displays a set of relationships between the final outcome (scar type) and the explanatory covariates (patient's age and gender, burn surface area, full-thickness burn surface area, burn anatomical area and wound-healing time; burn treatment options such as advanced dressings, type of surgical approach, number of surgical procedures, type of skin graft, excision and coverage timing). A web-based interface to handle the BN model was developed on the website www.pubchild.org (burns header). Clinicians who registered at the website could submit their data in order to get from the BN model the predicted probability of observing a pathological scar type.

Background Several studies have examined the effects of sample selection on the exposure–outcome association estimates in cohort studies, but the reasons why this selection may induce bias have not been fully explored. Aims To investigate how sample selection of the web-based NINFEA birth cohort may change the confounding patterns present in the source population. Methods The characteristics of the NINFEA participants (n=1105) were compared with those of the wider source population—the Piedmont Birth Registry (PBR)—(n=36 092), and the association of two exposures (parity and educational level) with two outcomes (low birth weight and birth by caesarean section), while controlling for other risk factors, was studied. Specifically the associations among measured risk factors within each dataset were examined and the exposure–outcome estimates compared in terms of relative ORs. Results The associations of educational level with the other risk factors (alcohol consumption, folic acid intake, maternal age, pregnancy weight gain, previous miscarriages) partly differed between PBR and NINFEA. This was not observed for parity. Overall, the exposure–outcome estimates derived from NINFEA only differed moderately from those obtained in PBR, with relative ORs ranging between 0.74 and 1.03. Conclusions Sample selection in cohort studies may alter the confounding patterns originally present in the general population. However, this does not necessarily introduce selection bias in the exposure–outcome estimates, as sample selection may reduce some of the residual confounding present in the general population.

The investigation of distribution, determinants and transmission of infectious diseases is largely based on the development of mathematical models of ecological nature suitable to capture the dynamics of infectious diseases epidemiology. In this paper the essential aspects of the dynamic models of infection transmission are described. These models are increasingly being adopted to investigate and control epidemic and endemic infections, but also cancers of infectious aetiology.

In recent years, cost-effectiveness analysis has become a frequent component of randomized clinical trials. In statistical terms, the major efforts addressed the method for estimating the Incremental Cost Effectiveness Ratio (ICER) and its confidence interval both with parametric and non-parametric methods. The goal of the present work is to briefly present the main non-parametric methods, based on a bootstrap approach. The methods which have been considered were applied to the data of a randomized clinical trial comparing two alternative approaches to treat hepatocellular carcinoma. The example shows that the application of different methods leads to significantly different confidence intervals' estimates, with consequences on the interpretation of the study results.

OBJECTIVE—Hyperglycemia is a common condition in hospitalized patients. The aim of this study was to investigate the relationships between glycemia upon admission and mortality in a heterogeneous group of adult patients. RESEARCH DESIGN AND METHODS—The 3-year records released from a general hospital were associated with a plasma glucose dataset of its general laboratory. A matched case-control study was implemented (3,338 case-control subject pairs). All-patient refined diagnosis–related groups and the relative risk of death were the matching criteria. A multivariate conditional logistic regression model was used to evaluate the associations between death and glycemia. RESULTS—Higher in-hospital mortality was associated with hyperglycemia or hypoglycemia, whereas lower risk was observed for values between 78 and 101 mg/dl. CONCLUSIONS—Our data confirm the relation between glycemia upon admission and mortality and suggest that slightly increased or decreased plasma glucose can be linked with increased mortality risk.

Background RNA-seq has the potential to discover genes created by chromosomal rearrangements. Fusion genes, also known as "chimeras", are formed by the breakage and re-joining of two different chromosomes. It is known that chimeras have been implicated in the development of cancer. Few publications in the past showed the presence of fusion events also in normal tissue, but with very limited overlaps between their results. More recently, two fusion genes in normal tissues were detected using both RNA-seq and protein data. Due to heterogeneous results in identifying chimeras in normal tissue, we decided to evaluate the efficacy of state of the art fusion finders in detecting chimeras in RNA-seq data from normal tissues. Results We compared the performance of six fusion-finder tools: FusionHunter, FusionMap, FusionFinder, MapSplice, deFuse and TopHat-fusion. To evaluate the sensitivity we used a synthetic dataset of fusion-products, called positive dataset; in these experiments FusionMap, FusionFinder, MapSplice, and TopHat-fusion are able to detect more than 78% of fusion genes. All tools were error prone with high variability among the tools, identifying some fusion genes not present in the synthetic dataset. To better investigate the false discovery chimera detection rate, synthetic datasets free of fusion-products, called negative datasets, were used. The negative datasets have different read lengths and quality scores, which allow detecting dependency of the tools on both these features. FusionMap, FusionFinder, mapSplice, deFuse and TopHat-fusion were error-prone. Only FusionHunter results were free of false positive. FusionMap gave the best compromise in terms of specificity in the negative dataset and of sensitivity in the positive dataset. Conclusions We have observed a dependency of the tools on read length, quality score and on the number of reads supporting each chimera. Thus, it is important to carefully select the software on the basis of the structure of the RNA-seq data under analysis. Furthermore, the sensitivity of chimera detection tools does not seem to be sufficient to provide results consistent with those obtained in normal tissues on the basis of fusion events extracted from published data.