The role of statistical significance testing in public law and health risk assessment

Following a fundamental statement made in 2016 by the American Statistical Associations and broad and consistent changes in data analysis and interpretation methodology in public health and other sciences, statistical significance/null hypothesis testing is being increasingly criticized and abandoned in the reporting and interpretation of the results of biomedical research. This shift in favor of a more comprehensive and non-dichotomous approach in the assessment of causal relationships may have a major impact on human health risk assessment. It is interesting to see, however, that authoritative opinions by the Supreme Court of the United States and European regulatory agencies have somehow anticipated this tide of criticism of statistical significance testing, thus providing additional support to its demise. Current methodological evidence further warrants abandoning this approach in both the biomedical and public law contexts, in favor of a more comprehensive and flexible method of assessing the effects of toxicological exposure on human and environmental health

TBA type equations and tropical curves

The Joyce integrable system and the corresponding Bridgeland\u2013Toledano-Laredo connections are fundamental objects associated with suitable abelian categories or, more generally, with a class of continuous families of stability data. We offer an overview of some of our work, mostly joint with M. Garcia Fernandez, focusing on equations of TBA type as a useful tool in the analysis of these objects and their deformations, and as a means to establish a connection with tropical geometry. \ua9 2016 World Scientific Publishing Company

Selenium and Other Trace Elements in the Etiology of Parkinson's Disease: A Systematic Review and Meta-Analysis of Case-Control Studies

Background: Parkinson's disease (PD) is the most common neurodegenerative disease after Alzheimer's dementia. Whereas the exact etiology of PD remains unknown, risk of developing PD seems to be related to a combination of genetic and environmental factors. This also includes abnormal exposure to trace elements of nutritional and toxicological interest. Objectives: In this systematic review and meta-Analysis, we summarized the results of case-control studies comparing levels of selenium, copper, iron, and zinc in PD patients and controls in either blood (whole blood, serum/plasma) or cerebrospinal fluid (CSF). Methods: We performed a systematic PubMed search selecting studies reporting trace element levels in different specimens of patients and controls. We performed a meta-Analysis using a random-effect model to compute the weighted mean differences (WMD) and corresponding 95% CI of selenium, copper, iron, and zinc levels in the blood or CSF of patients and their matched controls. Results: We retrieved 56 papers reporting data for selenium (cases/controls: 588/721), copper (2,190/2,522), iron (2,956/3,469), and zinc (1,798/1,913) contents in CSF and blood. Cases showed considerably higher levels of selenium in CSF compared with controls (+51.6%; WMD 5.49; 95% CI 2.82 to 8.15), while levels in serum were similar (-0.2%; WMD-0.22; 95% CI-8.05 to 7.62). For copper, cases showed slightly higher levels in CSF and slightly lower concentrations in serum (+4.5%; WMD 1.87; 95% CI-3.59 to 7.33, and-4.5%; WMD-42.79; 95% CI-134.35 to 48.76, respectively). A slight increase was also found for CSF iron-levels (+9.5%; WMD 9.92; 1.23 to 18.61), while levels were-decreased in serum/plasma (-5.7%; WMD-58.19; 95% CI-106.49 to-9.89) and whole blood (-10.8%; WMD-95.69; 95% CI-157.73 to-33.65). Conversely, for zinc cases exhibited lower levels both in CSF (-10.8%; WMD-7.34; 95% CI-14.82 to 0.14) and serum/plasma (-7.5%; WMD-79.93; 95% CI-143.80 to-16.06). A longer duration of the disease tends to be associated with overall lower trace element levels in either CSF or blood. Conclusions: Due to the study findings and the greater relevance of the CSF compartment compared with the circulating peripheral ones, this meta-Analysis suggests that overexposure in the central nervous system to selenium, and possibly to copper and iron, may be a risk factor of the disease, while zinc might have a protective-effect

Dietary cadmium intake and risk of cutaneous melanoma: a population-based case-control study in Northern Italy

BACKGROUND AND AIM. Cadmium is a toxic heavy metal for humans, and its environmental exposure has been linked to many adverse health effects, including cancer, atherosclerosis and diabetes. In particular, recent findings suggest that cadmium may increase risk of cutaneous melanoma, possibly through the promotion of the malignant transformation of melanoma cells through aberrant DNA methylation and by inducing gene expression dysregulation. Since in non-occupational exposed and non-smoking subjects dietary exposure is the major source of cadmium exposure, we aimed to assess melanoma risk in relation to dietary cadmium intake. METHODS. We recruited 380 newly-diagnosed incident cases of cutaneous melanoma and 719 sex- and age-matched population controls in four North Italian provinces (Parma, Reggio Emilia, Modena, and Bologna) of Emilia-Romagna Region. We estimated their dietary habits using a semi-quantitative food frequency questionnaire and we evaluated melanoma risk by computing the odds ratio (OR) and its 95% confidence interval (CI) according to quintile distribution of cadmium intake. We used a conditional logistic regression model to compute ORs, matching by sex, age and province of residence, and adjusting also for phototype, non-alcoholic energy intake, body mass index, and Italian Mediterranean Diet Index. Also a spline regression model was used in order to evaluated possible dose-response relation. RESULTS: Median cadmium intake was 5.81 µg/day (interquartile range 4.46-7.59) in cases, and 5.63 µg/day (4.46-7.34) in controls. OR of melanoma associated with 1-unit increase in cadmium intake was 1.11 (95% CI 1.00-1.24). Melanoma risk increased with increasing quintile of cadmium exposure, with ORs of 1.55 (95% CI 0.99-2.42), 1.54 (95% CI 0.99-2-40), 1.75 (95% CI 1.12-2.75), and 1.65 (95% CI 1.05-2.61) from second to highest quintile compared to lowest quintile. Sex-stratified analysis showed substantially comparable results and a generally higher risk in women, with continuous ORs of 1.10 (95% CI 0.93-1-29), and 1.15 (95% CI 0.99-1.33) in men and women, respectively. Spline regression analysis showed a non-linear risk increase, with possible plateau at 5-6 µg/day of cadmium intake. Slightly higher risk estimates in women and older subjects were detected. CONCLUSIONS: Our results seem to point out a positive association between dietary cadmium exposure and melanoma risk in the study population. Such association started to occur at a level of exposure lower than the tolerable intake established for food safety by international authorities

Selenium and other trace elements in the etiology of Parkinson’s disease: a systematic review and meta-analysis of case-control studies

.INTRODUCTION Parkinson’s disease (PD) is a neurodegenerative illness recognised as the most common neurological disorder after Alzheimer’s dementia. Whereas the exact PD etiology remains unknown, risk of developing PD seems to be related to an interrelation of genetic and environmental factors, including also altered exposure to trace elements. In this systematic review and meta-analysis, we updated and summarized the results of epidemiologic case-control studies comparing levels of selenium, copper, iron and zinc in PD patients with healthy subjects in either blood (as whole blood, serum or plasma) and cerebrospinal fluid (CSF). MATERIALS AND METHODS We performed a systematic PubMed search and we included in our assessment only studies reporting demographic and disease-related characteristics, as well as trace element levels in different specimens (whole blood, serum/plasma and CSF). We then performed a meta-analysis of mean differences of trace element levels between cases and controls, using a random-effect model computing the weighted mean differences (WMD) and corresponding 95% confidence intervals (CI) to assess the association between serum/plasma, whole blood, CSF and selenium, copper, iron and zinc with Parkinson’s disease. RESULTS We retrieved 55 papers reporting data for selenium (588 cases and 721 controls), copper (2190 and 2522), iron (2843 and 3434), and zinc (1798 and 1913). Cases showed higher levels of selenium in CSF compared with controls (WMD=5.49; 95%CI 2.82 to 8.15), while levels in serum were similar (WMD=-0.22; -8.05 to 7.62). For copper cases showed higher levels in CSF and lower in serum compared to controls (WMD=1.87; -3.59 to 7.33, and -42.79, -134.35 to 48.76 respectively). Same results were found for iron in CSF (WMD=6.54; -1.97 to 15.04) and in serum/plasma (WMD=-58.19; -106.49 to -9.89 and whole blood (WMD=-95.69; 157.73 to -33.65). On the converse, cases had lower levels of zinc both in CSF (WMD=-7.34; -14.82 to 0.14) and serum/plasma (WMD=-79.93; -143.80 to -16.06). CONCLUSIONS Results of this systematic review and meta-analysis suggests that overexposure to environmental selenium, copper and iron may be risk factors for PD onset or progression. Alternatively, some variation in levels of these trace elements may occur as a consequence of the disease. Considering the burden of PD in the world population, further investigation of trace element exposure in this disease is therefore warranted, especially to plan possible prevention measures

Dietary cadmium exposure and risk of melanoma: an Italian population-based case-control study

Background and aim. The heavy metal cadmium could be highly toxic to humans, and its environmental exposure has been linked to many adverse health effects, such as atherosclerosis, diabetes, and cancer, including melanoma. Although the underlying mechanisms need yet to be clearly identified, recent findings suggested that cadmium can specifically promote the malignant transformation of melanoma cells through the aberrant DNA methylation inducing dysregulation of specific gene expression. Since in the non-occupationally exposed population, in addition to smoking, food intake is the major source of cadmium exposure, we aimed at assessing the risk of cutaneous melanoma in relation to dietary cadmium intake. Methods. Using a population-based study design, we recruited 380 incident cases of newly-diagnosed melanoma and 719 sex- and age-matched controls in the Emilia-Romagna Region, Northern Italy. We evaluated their dietary habits through a semi-quantitative food frequency questionnaire and we computed the odds ratio (OR) and its 95% confidence interval (CI) for melanoma according to quintile distribution of cadmium intake, using a conditional logistic regression model, matching by sex, age and province of residence, and adjusting also for phototype, non-alcoholic energy intake, body mass index, and Italian Mediterranean Diet Index. Results: Median intake of cadmium was 5.81 µg/day (interquartile range 4.46-7.59) in cases, and 5.63 µg/day (4.46-7.34) in controls. OR of melanoma associated with 1-unit increase in cadmium intake was 1.11 (95% CI 1.00-1.24). Melanoma risk increased with increasing quintile of cadmium exposure, with ORs of 1.55 (95% CI 0.99-2.42), 1.54 (95% CI 0.99-2-40), 1.75 (95% CI 1.12-2.75), and 1.65 (95% CI 1.05-2.61) in the second to the highest quintile compared to the lowest quintile. Sex-stratified analysis showed substantially comparable results and a generally higher risk in female population, with continuous ORs of 1.10 (95% CI 0.93-1-29), and 1.15 (95% CI 0.99-1.33) in men and women, respectively. Conclusions: Our results suggest a positive association between cadmium exposure through diet and risk of cutaneous melanoma in a Northern Italy population. Such association started to occur at a level of exposure lower than the tolerable intake established by the World Health Organization, and considered to be safe for humans

Upper critical field in {Ba1−x_{1-x}Kx_xBiO3_3}: magnetotransport versus magnetotunneling

Elastic tunneling is used as a powerful direct tool to determine the upper critical field $H_{c2}(T)$ in the high-$T_c$ oxide Ba$_{1-x}$K$_x$BiO$_3$. The temperature dependence of $H_{c2}$ inferred from the tunneling follows the Werthamer-Helfand-Hohenberg prediction for type-II superconductors. A comparison will be made with resistively determined critical field data.Comment: 4 pages incl. 5 figure