Faculty Bibliography

INTRODUCTION/BACKGROUND:POP biomonitoring programs are useful for exposure assessment, to analyze patterns, and to evaluate policies. However, population-representative surveys are scarce and heterogeneous. Reports on time trends in representative samples using the same methods are rare. OBJECTIVES/OBJECTIVE:To analyze the distribution of serum concentrations of 19 POPs in the general population of Barcelona city in 2006, and to compare it with the distribution in 2002. METHODS:231 participants in the Barcelona Health Survey were interviewed face-to-face, gave blood, and underwent a physical exam. Density plots ("POP Geoffrey Rose curves") were used to represent the full population distribution of each compound. RESULTS:Eight POPs were each detected in >80% of the study subjects: p,p'-DDT, p,p'-DDE, PCB congeners 118, 138, 153 and 180, HCB and β-HCH. The minimum number of POPs detected in one person was 5, and 72% of the population accumulated ≥ 10 compounds. p,p'-DDE and HCB showed the highest concentrations (median=219 and 109 ng/g lipid, respectively). Concentrations decreased by 34-56% from 2002 to 2006. The decrease was similar in women and men, and in all age groups/birth cohorts. It was larger with increasing BMI; for p,p'-DDT, HCB and β-HCH the decrease in obese individuals was 31-44 percentage points larger than in subjects with normal weight. The distribution of POP concentrations was always switched towards higher values in women than men. POP levels also differed significantly by age, body mass index, weight gain, birth place and social class, but not by parity and breastfeeding. The two younger cohorts had a higher DDT/DDE ratio than the oldest cohort. CONCLUSION/CONCLUSIONS:Although human POP contamination remains common in the city of Barcelona, concentrations decreased significantly in 4years. Our approach suggests innovative ways to conceive, analyze and present results for other monitoring programs.

Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change, susceptibility and clinical outcomes are used as proxies for investigating interactions between external and/or endogenous agents and body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as the STrengthening Reporting of OBservational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology -Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE statement implementing nine existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendations.

Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change, susceptibility and clinical outcomes are used as proxies for investigating interactions between external and / or endogenous agents and body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as the STrengthening Reporting of OBservational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology - Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE statement implementing nine existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendations.

Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change, susceptibility and clinical outcomes are used as proxies for investigating the interactions between external and/or endogenous agents and the body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as the STrenghtening Reporting of Observational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology - Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE Statement implementing 9 existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendations.

Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change susceptibility and clinical outcomes are used as proxies for investigating the interactions between external and/or endogenous agents and body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as the STrengthening Reporting of OBservational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology -Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE statement implementing 9 existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendations.

BACKGROUND:Numerous studies analyzed concentrations of persistent organic pollutants (POPs) in human samples, and in many types of foods; however, food consumption is less commonly included in studies on the determinants of POP concentrations in humans, and these approaches are rarely integrated with surveys of food intake to estimate the amount and safety of human POP intake from food. OBJECTIVE:To analyze the main characteristics and findings of all studies conducted in Spain that quantitatively assessed the influence of diet on human concentrations of POPs. METHODS:Studies published until December 2010 (with no other time restrictions) were identified through Medline/PubMed, ISI-Thomson, ScienceDirect, and SciELO databases. RESULTS:We identified 25 papers, from 19 different studies. Twelve papers were published in 2009-2010. All studies but one were based on subgroups not representative of the general population, and over half were limited to women. Serum was the most used biological matrix, while p,p'-DDE, HCB and PCBs were the most frequently analyzed compounds. Food intakes were measured with heterogeneous food frequency questionnaires. The most consistent association was between fish consumption and PCBs and HCB, followed by dairy products and PCBs. A few studies observed a relationship between meat and some POPs, whilst intake of vegetables, fruits and cereals was rarely related to POP levels. Only 3 studies did not find any relationship between dietary habits and POP concentrations. CONCLUSIONS:In spite of methodological heterogeneity, the studies were able to quantify to what extent consumption of foods from animal origin (fish, milk, dairy products and meat) is related to higher body concentrations of POPs. As in a few other countries, in Spain food consumption is increasingly analyzed as a major determinant of human POP intake.

Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change, susceptibility, and clinical outcomes are used as proxies for investigating the interactions between external and/or endogenous agents and the body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as STrengthening Reporting of Observational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology-Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE Statement implementing 9 existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendations.

BACKGROUND:More clinically meaningful diagnostic tests are needed in exocrine pancreatic cancer (EPC). K-ras mutations are the most frequently acquired genetic alteration in EPC. We analysed the diagnostic utility of detecting K-ras mutations through a systematic analysis of the literature. METHODS:We searched PubMed using suitable medical subject headings and text words. Original research articles that evaluated the diagnostic accuracy of detecting K-ras mutations for diagnosis of EPC were selected. Two investigators independently extracted data from each study regarding the methodology used, the methodological quality of the study, the diagnostic accuracy reported and the authors' conclusions about clinical applicability of the test. Combined estimates for the sensitivity and specificity of K-ras were determined using bivariate meta-analysis; heterogeneity was explored using meta-regression. RESULTS:We assessed 34 studies from 30 published articles. The research reports were prone to numerous methodological biases and often lacked vital information for assessing external validity. The sensitivity of detecting K-ras status ranged from 0% through 100%, and the specificity from 58% through 100%. Diagnostic accuracy was highest when cytohistological samples were used: sensitivity and specificity were 76·5% (66·7-84·2) and 91·8% (87·6-94·1), respectively. Studies conducted in a clinically relevant population observed lower accuracy than case-control designs (68·4% vs. 82·7%). CONCLUSIONS:Because of the numerous methodological limitations of studies, the utility of analysing K-ras mutations for the diagnosis of EPC remains unknown. Flaws in diagnostic biomarkers with well-established biological properties, as K-ras, become even more relevant when the promises of 'personalized medicine' are pondered.

Observational studies of human health and disease (basic, clinical and epidemiological) are vulnerable to methodological problems -such as selection bias and confounding- that make causal inferences problematic. Gene-disease associations are no exception, as they are commonly investigated using observational designs. A rich body of knowledge exists in medicine and epidemiology on the assessment of causal relationships involving personal and environmental causes of disease; it includes seminal causal criteria developed by Austin Bradford Hill and more recently applied directed acyclic graphs (DAGs). However, such knowledge has seldom been applied to assess causal relationships in clinical genetics and genomics, even in studies aimed at making inferences relevant for human health. Conversely, incorporating genetic causal knowledge into clinical and epidemiological causal reasoning is still a largely unexplored area.As the contribution of genetics to the understanding of disease aetiology becomes more important, causal assessment of genetic and genomic evidence becomes fundamental. The method we develop in this paper provides a simple and rigorous first step towards this goal. The present paper is an example of integrative research, i.e., research that integrates knowledge, data, methods, techniques, and reasoning from multiple disciplines, approaches and levels of analysis to generate knowledge that no discipline alone may achieve.