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ObjectivesWe aimed to estimate the fraction of deaths from ovarian cancer attributable to asbestos exposure in Lombardy Region, Italy, using a novel approach that exploits the fact that ovarian cancer asbestos exposure is associated with pleural cancer and other risk factors for breast cancer.MethodsThis ecological study is based on the Italian National Institute of Statistics mortality data. We formulate a trivariate Bayesian joint disease model to estimate the attributable fraction (AF) and the number of ovarian cancer deaths attributable to asbestos exposure from the geographic distribution of ovarian, pleural and breast cancer mortality at the municipality level from 2000 to 2018. Expected deaths and standardised mortality ratios were calculated using regional rates.ResultsWe found shared dependencies between ovarian and pleural cancer, which capture risk factors common to the two diseases (asbestos exposure), and a spatially structured clustering component shared between ovarian and breast cancer, capturing other risk factors. Based on 10 462 ovarian cancer deaths, we estimated that 574 (95% credibility interval 388–819) were attributable to asbestos (AF 5.5%; 95% credibility interval 3.7–7.8). AF reaches 34%–47% in some municipalities with known heavy asbestos pollution.ConclusionsThe impact of asbestos on ovarian cancer occurrence can be relevant, particularly in areas with high asbestos exposure. Estimating attributable cases was possible only by using advanced Bayesian modelling to consider other risk factors for ovarian cancer. These findings are instrumental in tailoring public health surveillance programmes and implementing compensation and prevention policies.

We analyzed Sardinian registry data to assess time trends in incidence rates (IRs) of type 1 diabetes during the period 1989-2009 (2,371 case subjects 0-14 years of age). Poisson regression models were used to estimate the effects of sex, age, period of diagnosis, and birth cohorts. IR was 44.8 cases/100,000 person-years (95% CI 43.1-46.7). The annual increase was 2.12% (1.45-2.80; test for linear trend, P < 0.001). For boys, the increasing trend was evident up to 5 years of age and for girls up to 8 years of age. Compared with the 1989-1994 birth cohort, the relative risk increased from 0.78 (0.61-1.10) in 1974-1979 to 1.62 (1.18-2.23) in 2004-2009. The increase over period was less striking, with a tendency to regress in more recent years. The best-fitting model for boys included age and a linear time trend, and for girls age and nonlinear effects of calendar period and birth cohort. In conclusion, incidence increased over time, and the increase tended to level off in more recent years by calendar period but not by birth cohort, with some evidence of a stronger increase among girls than boys. Should the increase be attributable to the effects of some perinatal environmental factor, this would mean that such a factor has started affecting females before males., The most striking feature of type 1 diabetes epidemiology is the evidence of large geographical variation in disease risk (1-3). Sardinia has the second-highest incidence rates ORs) in the world [...]

OBJECTIVE--The aim of this study was to assess in an 11-year survival follow-up of a population-based cohort of type 2 diabetes the predictive role of World Health Organization-defined metabolic syndrome, [...]

J Epidemiol Community Health 2004;58:199-207. doi: 10.1136/jech.2003.014928 Study objective: To evaluate the independent and mutual effects of neighbourhood deprivation and of individual socioeconomic conditions on mortality and to assess the [...]

OBJECTIVE--Data on the incidence of end-stage renal disease (ESRD) and chronic renal failure from population-based studies in Caucasian type 2 diabetic patients are lacking. To provide such data, a population-based [...]

OBJECTIVE--The first sign of diabetic nephropathy is microalbuminuria, but its predictive role of progression to overt nephropathy in type 2 diabetes has not yet been clarified. The aims of this [...]

It is essential to measure within-country differences in housing costs in order to evaluate costs of living, assessing and comparing poverty levels, quantifying salaries and disposable income of families and finally for designing housing policies at local level. To the authors knowledge, no studies have yet been carried out on the computation of Space Price Indexes for Housing Rents (SPIHRs). In this article we computed preliminary estimates of sub-national SPIHRs by using hedonic regression model, which is an extension of the Country Product Dummy method, for all the Italian regions. The hedonic regression is generally used to obtain multilateral spatial indexes, thus allowing us to obtain multilateral SPIHRs for the Italian regions. The estimates have been done using 2017 data from the Real Estate Market Observatory which is a part of the Italian Agency of Revenue and Tax. This data source is the most comprehensive source of information on Italian houses price rents with a wide geographical coverage, including data for each Italian municipality. The obtained results show significant differences across the Italian regions, thus highlighting the importance of calculating SPIHR in Italy on a regular basis and the need to continue researches in this field.

In this study, the authors evaluated the risk of respiratory cancer related to environmental pollutants among a population that resided near a sewage plant in Prato, Italy. Subjects included lung cancer deaths (1987-1996) and incident cases of lung and laryngeal cancers (1987-1994) among residents of Prato. The authors used the mortality or incidence rates for the entire population of Prato (by gender and by 5-yr age group) to calculate the expected cases in each census unit. Data were analyzed and adjusted for an index of social deprivation (Stone test). Among males, the excess risk of lung cancer mortality decreased as distance from the plant increased for 2 time periods (1987-1996 [p = .008] and 1990-1996 [p = .030]) and for lung cancer incidence during 1987-1994 (p = .011). Similar results were obtained when sewage plant workers were excluded from the analysis. A similar, but not statistically significant, trend was observed among female incident lung cancer cases, as well as among male incident laryngeal cancer cases. Despite methodological limitations common to geographic studies, the results were consistent with those previously published on mortality excesses for lung cancer among plant workers under study. The role of environmental pollutants as a risk for respiratory cancer must be further clarified with additional epidemiological studies and an environmental monitoring program., EXCESS CANCERS of the central nervous system, kidney, larynx, and stomach have been reported among sewage plant workers or in persons who live near municipal wastewater treatment plants. (1-4) Studies [...]

For decades, child growth monitoring has been performed by measuring anthropometric indicators and comparing them against universal standards. Since the 1970s various efforts have been made to expand the focus from anthropometric indicators and include broader contextual and structural factors that influence children’s growth. However, those efforts have so far not led to changes in the dimensions that are taken into account in child growth monitoring. In this paper we introduce the Capability Approach asan evaluative framework for growth monitoring of children under five years old. Applying the CA helps focusing on what children are able to achieve by analyzing their available resources (endowments), as well as the mechanisms that could enhance or restrict their access to those resources (conversion factors). In addition, children’s growth could be assessed alongside the caregivers’ capabilities that children rely on to achieve their full growth potential. We present a child growth evaluation framework as well as a matrix, which has different categories of dimensions that interact with each other and ultimately shape children’s growth. The framework is a flexible tool, and is thus broad enough to accommodate contextual differences.

Study design:Observational prospective population-based incidence study.Objectives:The main objective of this study was to assess the incidence of traumatic spinal cord injuries (TSCIs) and incidence rates, in order to provide estimates by age, gender, characteristics and cause.Setting:This study was conducted at acute-care spinal cord injury (SCI) hospitals and SCI centers from 11 Italian regions, between 1 October 2013 and 30 September 2014.Methods:Data of all consecutive patients with acute TSCI who met the inclusion criteria were obtained through case reporting by clinicians. The data were collected into a web database. Incidence rates and incidence rate ratios were calculated and stratified by age, gender, cause, level and completeness.Results:From 50% of the entire population of Italy, 445 new cases of TSCI were included. The crude incidence rate of TSCI was 14.7 cases per million per year (95% CI: 13.4–16.4); the overall male to female ratio was 4:1 and the mean age was 54. Complete information was available in 85% of the sample and revealed tetraplegia in 58% and incomplete lesion in 67% of cases. The leading cause of TSCI was falls (40.9%) followed by road traffic accidents (33.5%). The leading cause was falls for patients over 55 and road traffic accidents for patients under 55.Conclusion:The changing trend of TSCI epidemiology concerns the increase in the average age of TSCI people and the increase of both cervical and incomplete lesions. The etiology shows the primacy of falls over road traffic accidents and suggests the need for a change in prevention policies.

The mechanisms by which fluoride produces its toxic effects are still not clear. Therefore, we conducted a cross-sectional study to evaluate the fluoride-induced toxicity on randomly selected sheep with skeletal fluorosis resident near the large non-ferrous metallurgy Portoscuso-Portovesme industrial estate and the Carbonia and Gonnessa towns (control district) with respect to animals from a remote site without industrial settlements, on Sardinia Island, Italy. We measured the prevalence of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) adducts, a biomarker of oxidative stress and lipid peroxidation, in the soft organs of the study animals using the 32P-postlabelling assay. Then, we analysed the association between M1dG adducts and sheep-farm localization. In addition, cadmium and lead levels were measured in the same matrices by mass spectrometry. The histopathology analysis showed that the sheep resident near the industrial site and in the control district presented typical manifestations of fluorosis. The statistical analyses using log-normal regression models indicated that there was a significant association between exocyclic DNA adducts and skeletal fluorosis. The mean ratios, adjusted for age, of renal and hepatic M1dG for the sheep with fluorosis were 5.09, 95% C.I. 1.67–15.53 and 2.04, 95% C.I. 0.91–4.57, p= 0.009 and p= 0.078, respectively. After stratification for sheep-farm localization, the renal and hepatic levels of M1dG adducts were significantly higher in the sheep resident near the industrial estate as compared to controls. Intermediate amounts of DNA damage were observed in the kidney of the sheep living in the control district. As expected, the levels of cadmium and lead were significantly increased in the sheep with fluorosis as compared to controls. Also, the concentrations of heavy metals were driven from the distance of the sheep-farms to the industrial site. Our results broaden knowledge about the role of exocyclic DNA adducts in the etiology of skeletal fluorosis. Fluoride generated from the non-ferrous metallurgy complexes may increase the intracellular amounts of oxidative stress and ROS within the soft organs. A continuous attack to DNA may contribute to the general decline of cellular functions, ranging from disturbance of DNA metabolism, triggering cell-cycle arrest and apoptosis, to inducing necrosis and cellular degenerative changes.

Quality monitoring has great relevance in stroke care. The Project “How to guarantee adherence to effective interventions in stroke care” aimed to estimate adherence to acute-phase guidelines in stroke care in Italy. A prospective observational study was performed in 27 hospitals of 13 Italian Regions. Adherence to 15 process indicators was evaluated, comparing also stroke units (SU) with conventional wards. An overall score of care, defined as the sum of achieved indicators, was calculated. A multilevel hierarchical model described performance at patient, hospital and regional level. Overall, 484 consecutive stroke patients (mean age, 73.4 years; 52.7 % males) were included. Total score ranged from 2 to 15 (mean 8.5 ± 2.4). SU patients were more often evaluated with the National Institutes of Health Stroke Scale (NIHSS) within 24 h, had more frequently an assessment of pre- and post-stroke disability, and a CT scan the same or the day after admission. Regional-hospital- and patient-level variability explained, respectively, 25, 34, and 41 % of total score variance. In multivariate models, patients >80 years vs. younger showed a change in total score of −0.45 (95 % CI −0.79 to −0.12), and those with NIHSS ≥14 vs. ≤5 of −0.92 (95 % CI −1.53 to −0.30). A negative change means a worse adjusted average adherence to process indicators. SU admission increased total score of 1.55 (95 % CI 0.52–2.58). Our data confirm the need of quality monitoring in stroke care. Although SU patients showed a better adherence to quality indicators, overall compliance was unsatisfactory.

Data regarding the use of Interferon-gamma release assays (IGRAs) for tuberculosis diagnosis are accumulating. We systematically searched PubMed, EMBASE and Cochrane and performed pooled estimates of sensitivity and specificity of QuantiFERON-TB Gold In Tube (QFT-G-IT) and T-SPOT. TB compared to tuberculin skin test (TST). For studies assessing sensitivity, children had to have active tuberculosis. Specificity data were derived from children classified as non-infected. Eleven studies were included in the sensitivity analysis for TST, 10 for QFT-G-IT, and 9 for T-SPOT.TB. Eight studies were included in specificity analysis for TST, 8 for QFT-G-IT, and 7 for T-SPOT.TB. Pooled QFT-G-IT sensitivity was 0.79 (95%CI:0.70–0.89) pooled T-SPOT.TB sensitivity was 0.74 (95%CI:0.59–0.90) and pooled TST sensitivity was 0.82 (95%CI:0.72–0.93). Pooled QFT-G-IT and T-SPOT.TB specificities were 0.95 (95%CI:0.93–0.97) and 0.96 (95%CI:0.93–1.00), respectively. Pooled TST specificity was significantly lower 0.83 (95%CI:0.74–0.92). IGRA performance in children showed no better sensitivity than TST, but higher specificity.

The role of Interferon-gamma release assays (IGRAs) for immunologic diagnosis of tuberculosis in children is under debate. We carried out a narrative review on the studies on IGRAs in paediatric populations. A literature search was conducted using multiple keywords and standardized terminology in Medline, EMBASE and Cochrane databases, up to January 27th, 2011. Study quality was assessed using the MOOSE checklist and results of relevant studies were summarized. Sixty-seven paediatric studies (study population ranging from 14 to 5,244 children) were identified. Non-commercial ELISPOT assay (by means of ESAT-6 and CFP-10 antigens) had been carried out in 11 studies. QuantiFERON-TB Gold (QFT-G), QuantiFERON-TB Gold In-tube (QFT-G-IT), and T-SPOT.TB assays had been performed in 10, 44 and 18 studies, respectively. Most studies reported higher specificity of IGRA than tuberculin skin test (TST), but interpretation of the results is complicated by the fact that a gold standard for the diagnosis of latent TB is lacking. The reported sensitivity for active TB ranged from 51–93% for QFT-G/QFT-G-IT and 40–100% for ELISPOT assays, suggesting that a negative IGRA result may not exclude tuberculosis. Combining TST and IGRA results increased the diagnostic sensitivity. Rates of indeterminate results largely varied (0 to 35%). Most of the studies on young (< 5 years) or immune-compromised children reported a proportion of indeterminate results exceeding 4%. Agreement among TST and IGRA, assessed by the k statistics, ranged from -0.03 to 0.87. Higher rates of discordance were reported in BCG-vaccinated than in non-BCG-vaccinated children. Studies on children <5 years and immunocompromised children reported conflicting results, as did studies on serial IGRA determinations. Despite the large amount of literature data, the role of IGRA in the pediatric population is still unclear, especially in young children. Combined use of TST/IGRA may increase diagnostic sensitivity but interpretation of discordant results remains a challenging issue.

The possibility that daily sessions of music-guided slow breathing may reduce 24-h ambulatory blood pressure (ABP), and predictors of efficacy were explored in a randomized, placebo-controlled trial with parallel design.

Abstract: Generalized additive models (GAMs) have become the standard tool for the analysis of short-term effects of air pollution on human health. Usually, the confounding effect of seasonality and long-term trend is described by flexible parametric or non-parametric functions of calendar time. Two different modeling strategies, i.e. GAM with penalized regression splines and GAM with regression splines, were compared by means of a simulation study, addressing attention to the inference on air pollutant effect. Simulation results indicated that GAM with regression splines provides negligibly biased estimates of air pollutant effect and it is robust to misspecification of the degrees of freedom of the spline. GAM with penalized regression splines requires a certain amount of undersmoothing in order to reduce the bias of the estimates and to improve the coverage of confidence intervals. These findings agree with asymptotic results developed in the context of partially splined models. [Copyright &y& Elsevier]

Mortality during sustained periods of hot weather is generally regarded as being in excess of what would be predicted from smooth temperature-mortality gradients estimated using standard time-series regression models. However, the evidence for an effect of continuous days of exceptional heat (“heat wave effect”) is indirect. In addition, because some interventions may be triggered only during forecasted heat waves, it would be helpful to know what fraction of all heat-related deaths falls during these specific periods and what fraction occurs throughout the remainder of the summer.

Although studies have documented increased mortality during heat waves, little information is available on the subgroups most susceptible to these effects. We evaluated the effects of summertime high temperature on daily mortality among population subgroups defined by demographic characteristics, socioeconomic status, and episodes of hospitalization for various conditions during the preceding 2 years.

Recently, instrumental variables methods have been used to address non-compliance in randomized experiments. Complicating such analyses is often the presence of missing data. The standard model for missing data, missing at random (MAR), has some unattractive features in this context. In this paper we compare MAR-based estimates of the complier average causal effect (CACE) with an estimator based on an alternative, nonignorable model for the missing data process, developed by Frangakis and Rubin (1999, Biometrika, 86, 365-379). We also introduce a new missing data model that, like the Frangakis-Rubin model, is specially suited for models with instrumental variables, but makes different substantive assumptions. We analyze these issues in the context of a randomized trial of breast self-examination (BSE). In the study two methods of teaching BSE, consisting of either mailed information about BSE (the standard treatment) or the attendance of a course involving theoretical and practical sessions (the new treatment), were compared with the aim of assessing whether teaching programs could increase BSE practice and improve examination skills. The study was affected by the two sources of bias mentioned above: only 55% of women assigned to receive the new treatment complied with their assignment and 35% of the women did not respond to the post-test questionnaire. Comparing the causal estimand of the new treatment using the MAR, Frangakis-Rubin, and our new approach, the results suggest that for these data the MAR assumption appears least plausible, and that the new model appears most plausible among the three choices.

This paper continues work presented in Böhning et al. (2002b, Annals of the Institute of Statistical Mathematics54, 827–839, henceforth BMSRB) where a class of non‐iterative estimators of the variance of the heterogeneity distribution for the standardized mortality ratio was discussed. Here, these estimators are further investigated by means of a simulation study. In addition, iterative estimators including the Clayton–Kaldor procedure as well as the pseudo‐maximum‐likelihood (PML) approach are added in the comparison. Among all candidates, the PML estimator often has the smallest mean square error, followed by the non‐iterative estimator where the weights are proportional to the external expected counts. This confirms the theoretical result in BMSRB in which an asymptotic efficiency could be proved for this estimator (in the class of non‐iterative estimators considered). Surprisingly, the Clayton–Kaldor iterative estimator (often recommended and used by practitioners) performed poorly with respect to the MSE. Given the widespread use of these estimators in disease mapping, medical surveillance, meta‐analysis and other areas of public health, the results of this study might be of considerable interest.

Health care workers are at risk of acquiring transmissible diseases. Controversial results have been reported about HCV. The aims of the present study are to assess the prevalence of HCV in health care workers in Pistoia General Hospital (central Italy) and to compare prevalence with other groups, particularly with a sample of the general population. Serum samples collected from 511 health care employees engaged in direct clinical task and 222 clerical and nurse school attendees have been tested by ELISA and confirmed by RIBA. Total seroprevalence was 3.8%: 4.7% in the first group; 1.8% in the second group. The data showed a slight increase in prevalence by age and not by length of stay in the health care workers' group. Comparison of HCV prevalence with blood donors from the province of Pistoia and the general population from Sersale (Catanzaro, southern Italy), restricted to under-40 subjects, indicates an increasing trend in this order: Blood donors, general population, clerical and nursing school attendees, health care workers' group with the highest value (3.4%). A cohort study is needed to evaluate pattern of HCV seroconversion.

The space-time variation of disease risk, considering the closeness and availability of care units, is studied by a hierarchical Bayesian model in a gravitational formulation. The pattern of mortality for Hodgkin's lymphoma over the last twenty-five years in the Tuscany region and the evaluation of the consequences of distance from the nearest radiation-therapy center are described. Results show a decrease in mortality for Hodgkin's lymphoma and the attraction exercised by each care units.

Non-parametric maximum likelihood estimators of relative risk have been proposed as an alternative to empirical Bayes or full Bayes approaches to disease mapping. They have the advantage of being relatively simple, the EM algorithm assures convergence and area classification is straightforward. However, they do not take into account spatial autocorrelation and have higher mean square error when the true underlying risk pattern is strongly spatially structured. Furthermore, the EM algorithm is sensible to starting values and could converge to local maxima. We review the transitional generalized linear models and propose a transitional non-parametric maximum pseudo-likelihood estimator for disease mapping. The usual kernel likelihood of the mixture models is replaced by the conditional density of the observed response for a single area given the values observed in adjacent areas. The estimation of the parameters is based on the EM algorithm, appropriately modified to handle the problem of local maxima and to estimate the number of components of the mixture. A simulation study shows that the transitional non-parametric maximum pseudo-likelihood estimator performs similarly to full Bayes estimators. [Copyright &y& Elsevier]

Abstract: This study aimed to verify the efficacy of a strategy for science learning acquisition based on contextual, metacognitive and sociocultural perspectives, strongly linked to the paradigm of conceptual change. The teaching model we adopted is based on co-operation for the realization of scientific experiences, and included direct observation, pair or group work, individual written reports and confrontation through discussion by the whole class. The experiment also aimed at verifying the efficacy of our learning strategy on the acquisition of skills such as debating, prediction, description, narrative structure and basic cognitive linguistic competence (the capacity to activate periphrastic, inferential, logical, critical, evaluative and aesthetic-poetic reasoning during the reading of a passage). Our sample consisted of 79 pupils, aged 7 to 10 years: the experimental group (18 boys and 22 girls) and the control group (19 boys and 20 girls). The result show that the children belonging to the experimental group, unlike those from the control group, were able to give reasons why the scientific phenomena they studied occurred and were better to explain these newly acquired concepts, producing spontaneously a large amount of metaphors and analogies, while they tried to understand, record and discuss what they had observed.

In this paper we consider estimating heterogeneity variance with the DerSimonian-Laird (DSL) estimator as typically used in meta-analysis. In its general form the DSL estimator requires inverse population-averaged study-specific variances as weights, in which case the estimator is unbiased. It has become common practice, however, to use estimates of the study-specific variances instead of their population-averaged versions. This can lead to considerable bias. Simulations illustrate these findings.

In this paper the situation of extra population heterogeneity in the standardized mortality ratio is discussed from the point-of-view of an analysis of variance. First, some simple non-iterative ways are provided to estimate the variance of the heterogeneity distribution without estimating the heterogeneity distribution itself. Next, a wider class of linear unbiased estimators is introduced and their properties investigated. Consistency is shown for a wide sub-class of estimators charactererized by the fact that the associated linear weights are within some positive, finite bounds. Furthermore, it is shown that an efficient estimator is often provided when the weights are proportional to the expected counts.

Prebiotics such as fructans, and probiotics such as Lactobacilli or Bifidobacteria, or a combination of prebiotics and probiotics (synbiotics) are thought to be protective against colon cancer. Therefore, we studied whether the prebiotic inulin enriched with oligofructose (Raftilose-Synergy1®, briefly, Synergy1, 10% of the diet), probiotics [Bifidobacterium lactis (Bb12) and Lactobacillus rhamnosus (LGG), each at 5×108 c.f.u./g diet] or synbiotics (a combination of the two) protect rats against azoxymethane (AOM)-induced colon cancer. Male F344 rats were divided into: Controls; PRE, which were fed a diet containing Synergy1; PRO, fed a diet containing LGG and Bb12; PREPRO, fed a diet containing Synergy1, LGG and BB12. Ten days after beginning the diets, rats were treated with AOM (15 mg/kg s.c. two times); dietary treatments were continued for the entire experiment. Thirty-one weeks after AOM, rats treated with Synergy1 (PRE and PREPRO groups) had a significantly lower (P < 0.001) number of tumours (adenomas and cancers) than rats without Synergy1 (colorectal tumours/rat were 1.9 ± 1.7, 1.1 ± 1.1, 2.2 ± 1.4 and 0.9 ± 1.2 in Controls, PRE, PRO and PREPRO groups, respectively, means ± SD). A slight, not significant effect of probiotics in reducing malignant tumours was also observed (P = 0.079). Caecal short-chain fatty acids (SCFA) were higher (P < 0.001) in the groups treated with Synergy1. Apoptosis was increased in the normal mucosa of the PRO group, while no variation was observed in the tumours. Colonic proliferation was lower in the PRE group as compared with Controls. Glutathione S-transferase placental enzyme pi type expression, and to a lesser extent, inducible NO synthase were depressed in the tumours from rats in the PRE and PREPRO groups. Cycloxygenase-2 expression was increased in the tumours of control rats but not in those from PRE, PRO or PREPRO rats. In conclusion, prebiotic administration in the diet decreases AOM-induced carcinogenesis in rats.

We investigated whether polyphenolic extracts from black tea, green tea or red wine affect azoxymethane (AOM)-induced intestinal carcinogenesis. Male F344 rats were treated 10 times (1 week apart) with AOM (7.4 mg/kg, s.c.) and then allocated into groups receiving black tea, green tea or red wine extracts mixed in the diet at a dose of 50 mg/kg body weight for 16 weeks. In the rats treated with black tea or wine extracts, there were significantly fewer colorectal tumours than in controls (the mean ± SE number of tumours/rat was 2.54 ± 1.6 in controls, 1.54 ± 1.4 in the black tea group, 3.2 ± 1.9 in the green tea group and 1.63 ± 1.6 in the wine extract group). Significantly fewer rats in the black tea and wine extract groups had adenomas than in controls (86%, 59%, 90% and 50% of rats in the control, black tea, green tea and wine extract groups, respectively, had adenomas). The tumours from the black tea group and, to a lesser extent, those from the wine group, had a significantly greater apoptotic index than tumours in controls (mean ± SE apoptotic index: 2.92 ± 0.25, 4.13 ± 0.46, 2.88 ± 0.30 and 3.72 ± 0.46 in controls, black tea, green tea or wine extract groups, respectively). In contrast, the apoptotic index of the normal mucosa did not vary among groups. These data indicate that black tea and wine extracts, but not green tea extracts, can protect against AOM-induced colon carcinogenesis by a mechanism probably involving increased apoptosis in tumours.

A Non-Parametric Maximum Likelihood approach to the estimation of relative risks in the context of disease mapping is discussed and a NPML approximation to conditional autoregressive models is proposed. NPML estimates have been compared to other proposed solutions (Maximum Likelihood via Monte Carlo Scoring, Hierarchical Bayesian models) using real examples. Overall, the NPML autoregressive estimates (with weighted term) were closer to the Bayesian estimates. The exchangeable NPML model ranked immediately after, even if it implied a greater shrinkage, while the truncated auto-Poisson showed inadequate for disease mapping. The coefficients of the autoregressive term for the different mixtures have clear interpretations: in the breast cancer example, the larger cities in the region showed high rates and very low correlation with the neighbouring areas, while the less populated rural areas with low rates were strongly positively correlated each other. This pattern is expected since breast cancer is strongly correlated with parity and age at first birth, and the female population of the rural areas experienced a decline in fertility much later than those living in the larger cities. The leukemia example highlighted the failure of the Poisson-Gamma model and other general overdispersion tests to detect high risk areas under specific conditions. The NPML approach in Aitkin is very general, simple and flexible. However the user should be warned against the possibility of local maxima and the difficulty in detecting the optimal number of components. Special software (such as CAMAN or DismapWin) had been developed and should be recommended mainly to not experienced users. Copyright © 2000 John Wiley & Sons, Ltd.

In psychiatry, the assessment of outcome, to be relevant for clinical practice, should be multidimensional. This demands suitable statistical tools both to represent and to analyse the complex relationships between variables. This paper aims to provide guidelines for selecting graphical displays of multidimensional data that enable better capturing of the relationships between variables and summarize information available for individual cases as well as for groups of patients. Multivariate graphical techniques such as Chernoff faces, stars, parallel co‐ordinates and Andrews plots are applied to a set of data drawn from the South Verona Outcome Project, a naturalistic study based on a multidimensional model for the assessment of outcomes, routinely conducted at the Institute of Psychiatry of the University of Verona, Italy. The assessment includes global functioning, psychopathology, social disability, subjective quality of life, and satisfaction with services, number of service contacts and days of hospitalization.

The new silicon tracker layout (V4) is presented. The system aspects of the construction are discussed together with the expected tracking performance. Because of the high radiation environment in which the detectors will operate, particular care has been devoted to the study of the characteristics of heavily irradiated detectors.

Summary: In mapping geographical variation of risk or occurrence of disease in tract count data, information from the neighbouring areas is used to improve the estimate for a given area. However such information is incomplete for those areas at the region boundary and ignoring this could lead to a distortion of the estimates (edge-effect). We present a general approach to compensate for edge effects under a hierarchical Bayesian model. In our model the out-of-the-border areas are regarded as having missing values of the number of events but known population at risk. Two algorithms for the imputation of missing data and estimation of relative risks are applied: doubly stochastic EM and Chained Data Augmentation. Results on simulated data as well as a real example on mortality for gastric cancer in Tuscany (Italy) 1981–88 are discussed.

Background: Histopathologic association between melanocytic nevus and melanoma has been reported in approximately 10% to more than 50% of melanoma cases. Whether melanomas in contiguity with a nevus have a different natural history and pathogenesis from melanomas without a nevus is still to be determined. Objective: The present study was undertaken to clarify whether melanocytic nevus-associated melanomas (MN[+]) have a different risk factor profile from cases without histopathologic evidence of melanocytic nevus association (MN[-]). Methods: The study population consisted of 131 invasive melanoma cases with a thickness of 4.00 mm or less and 174 control cases without melanomas. The whole series was evaluated for the following risk factors: phenotypic traits; the number of common, atypical, and congenital nevus-like nevi; and freckling and history of sunburns. Melanoma cases were revised for the presence of associated melanocytic nevi. The analysis of risk factors was performed by a case-control approach comparing cases, classified by histologic association with nevus, to the group of controls. Possible differences in risk factor distribution between MN(+) cases and MN(-) cases were evaluated with a polychotomous logistic regression model and a likelihood ratio test for heterogeneity. Results: Histopathologic association between melanocytic nevus and melanoma was found in 27 cases (20.6%). Phenotypic traits were shown to be more powerful predictors of risk for MN(-) than for MN(+) cases (blond/red hair; odds ratio, 7.4 and 1.2, respectively; likelihood ratio test for heterogeneity, 4.13; P < .05). Conversely, history of frequent sunburn was a risk factor only in MN(+) cases (more than 5 sunburns; odds ratio, 6.7; 95% confidence interval, 1.3-33.7), but not in MN(-) cases (odds ratio, 1.2; 95% confidence interval, 0.3-4.0; likelihood ratio test for heterogeneity, 4.2; P < .05). Where melanocytic nevi are concerned, an increased number of common nevi was a predictor of melanoma risk in both MN(+) and MN(-) cases, but with a different magnitude of risk, higher for MN(+) cases (number of common nevi, 10-30; odds ratio, 14.4 and 4.7, respectively; likelihood ratio test for heterogeneity, 3.7; P = .055). Conclusion: This study showed that, although MN(+) and MN(-) melanomas share many risk factors, there is a different strength of association between the 2 groups. The effect of a history of sunburn as a predictor of risk was found only for nevus-associated melanomas, suggesting a possible role of sunburns in the neoplastic transformation of nevi. (J Am Acad Dermatol 1999;40:549-57.)

Study objective: We sought to assess the effect of nitrates on prehospital mortality among patients with acute pulmonary edema (APE). Methods: The study involved a retrospective evaluation of the records of prehospital outcome in 640 patients with APE rescued by the mobile CCU (MCCU) of Florence, Italy, between January 1980 and December 1991. The MCCU serves an urban environment with a population of 400,000 in a 102-sq km area. In the years 1980 through 1983, patients were treated with oxygen, morphine, furosemide, digoxin, nitrates, aminophylline, or dopamine, according to the attending physician's judgment. From 1984 through 1991, new guidelines for the use of intravenous nitrates, based on differential treatment according to blood pressure, were in use. Results: Overall prehospital mortality rate for APE in all patients was 7.8% (50 of of 640 patients). Mortality after 1984 was significantly lower than before (5.3% versus 13%, P<.01). Nitrates were effective in reducing mortality, even in hypotensive patients. Multivariate analysis showed that outcome was significantly affected by two clinical features (dyspnea and low blood pressure), treatment with nitrates, and calendar period effects (before/after 1984). Conclusion: Our findings suggest that the use of intravenous nitrates improves short-term prognosis in APE. [Bertini G, Giglioi C, Biggeri A, Margheri M, Simonetti I, Sica ML, Russo L, Gensini G: Intravenous nitrates in the prehospital management of acute pulmonary edema. Ann Emerg Med October 1997;30:493-499.]

AbstractWe studied whether repeated boluses of sucrose or diets containing carbohydrates with a variable glycemic index (GI) affect intestinal carcinogenesis in rats. Male F344 rats were treated twice (1 wk apart) with 15 mg/kg sc azoxymethane (AOM) and then divided into four experimental dietary groups with different carbohydrate composition and administration schedules: the sucrose group was fed 44% (wt/wt) sucrose (GI = 65), the bolus group was fed sucrose as carbohydrate and 43 boluses of sucrose (10–15 g/kg) at various time intervals, the pasta group was fed pasta [77% (wt/wt) cooked pasta, GI = 557, and the glucose group wasfed44% (wt/wt) glucose (GI = 97). All nutrients, including carbohydrates, were provided in similar amount to the different groups. The experiment was terminated between Day 230 and Day 245 after AOM administration. At this time the pasta group had significantly higher cecal short‐chain fatty acids than the other groups. Intestinal adenomas and cancers occurred with the same frequency in the bolus, sucrose, and glucose groups. On the contrary, we observed a significant decrease (p = 0.03) in the cumulative incidence of intestinal adenomas, but not adenocarcinomas, in the pasta group compared with the sucrose group (intestinal adenoma incidence in the pasta group was 31% compared with 63% in the sucrose group, 46% in the bolus group, and 37% in the glucose group). In conclusion, these results do not support the hypothesis that sucrose boluses or carbohydrates with a high GI stimulate colon carcinogenesis, but they indicate that foods such as pasta may exert a protective effect.

Summary: Empirical Bayes estimates have been advocated as an improvement for mapping rare diseases or health events aggregated in small areas. In particular different parametric approaches have been proposed for dealing with non-normal data, assuming that disease occurrencies follow non-homogeneous Poisson law, whose parameters are treated as random variables. This paper shows how to conduct a complete Empirical Bayes analysis under an exchangeable model in the context of Geographical Epidemiology. Three different approaches for defining confidence limits obtained using a parametric bootstrap are compared: method 1 relies only on the first and second moment of the bootstrapped posterior distributions; method 2 computes the centiles of the bootstrapped posteriors; method 3 equates to α the average of the probabilities derived from the estimated bootstrapped cumulative posterior distributions. The simple Poisson-Gamma formulation was used to model mortality data on Larynx Cancer in the Local Health Units of Tuscany (1980–82 males). Two areas of significant elevated risk are identified.