Implementing systematic review techniques in chemical risk assessment: challenges, opportunities and recommendations

Systematic review (SR) is a rigorous, protocol-driven approach designed to minimise error and bias when summarising the body of research evidence relevant to a specific scientific question. Taking as a comparator the use of SR in synthesising research in healthcare, we argue that SR methods could also pave the way for a “step change” in the transparency, objectivity and communication of chemical risk assessments (CRA) in Europe and elsewhere. We suggest that current controversies around the safety of certain chemicals are partly due to limitations in current CRA procedures which have contributed to ambiguity about the health risks posed by these substances. We present an overview of how SR methods can be applied to the assessment of risks from chemicals, and indicate how challenges in adapting SR methods from healthcare research to the CRA context might be overcome. Regarding the latter, we report the outcomes from a workshop exploring how to increase uptake of SR methods, attended by experts representing a wide range of fields related to chemical toxicology, risk analysis and SR. Priorities which were identified include: the conduct of CRA-focused prototype SRs; the development of a recognised standard of reporting and conduct for SRs in toxicology and CRA; and establishing a network to facilitate research, communication and training in SR methods. We see this paper as a milestone in the creation of a research climate that fosters communication between experts in CRA and SR and facilitates wider uptake of SR methods into CRA.

Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers

Background and aims: Virgin olive oil (VOO) and nuts are basic components of the Mediterranean diet, a heart-healthy dietary pattern. Nuts have well known cholesterol lowering effects, while evidence is unclear for VOO. We designed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40% of the fat in the background diet with VOO, walnuts or almonds. Methods and Results: After a 4 week run-in period with a healthy diet, eligible candidates were randomized into three diet sequences in a crossover design, with a common background diet enriched with VOO, walnuts or almonds, lasting 4 weeks each. Outcomes were changes of serum lipids and oxidation and inflammation markers, measured by standard methods. Plasma fatty acids were determined by gas chromatography to assess compliance. In 18 participants completing the study (9 women, mean age 56 y, BMI 25.7 kg/m(2)), LDL-cholesterol was reduced from baseline by 7.3%, 10.8% and 13.4% after the VOO, walnut and almond diets, respectively (P = 0.001, Friedman test). Total cholesterol and LDL/HDL ratios decreased in parallel. LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets. No changes of other lipid fractions, oxidation analytes or inflammatory biomarkers were observed. Plasma fatty acid changes after each diet sequence supported good compliance.

Review of the literature on credit risk modeling : development of the past 10 years

This paper traces the developments of credit risk modeling in the past 10 years. Our work can be divided into two parts: selecting articles and summarizing results. On the one hand, by constructing an ordered logit model on historical Journal of Economic Literature (JEL) codes of articles about credit risk modeling, we sort out articles which are the most related to our topic. The result indicates that the JEL codes have become the standard to classify researches in credit risk modeling. On the other hand, comparing with the classical review Altman and Saunders(1998), we observe some important changes of research methods of credit risk. The main finding is that current focuses on credit risk modeling have moved from static individual-level models to dynamic portfolio models.

Biomarkers of extracellular matrix metabolism (MMP-9 and TIMP-1) and risk of stroke, myocardial infarction and cause-specific mortality : cohort study

Objective: Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective. Design: The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991–1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163). Results: Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03–1.19; and 1.11, 1.02–1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09–1.37; and 1.18, 1.04–1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample. Conclusion: In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.

The trade-off between incentives and endogenous risk

Standard models of moral hazard predict a negative relationship between risk and incentives, but the empirical work has not confirmed this prediction. In this paper, we propose a model with adverse selection followed by moral hazard, where effort and the degree of risk aversion are private information of an agent who can control the mean and the variance of profits. For a given contract, more risk-averse agents suppIy more effort in risk reduction. If the marginal utility of incentives decreases with risk aversion, more risk-averse agents prefer lower-incentive contractsj thus, in the optimal contract, incentives are positively correlated with endogenous risk. In contrast, if risk aversion is high enough, the possibility of reduction in risk makes the marginal utility of incentives increasing in risk aversion and, in this case, risk and incentives are negatively related.

Asset pricing when risk sharing is limited by default: a theoretical framework

We study the asset pricing implications of an endowment economy when agents can default on contracts that would leave them otherwise worse off. We specialize and extend the environment studied by Kocherlakota (1995) and Kehoe and Levine (1993) to make it comparable to standard studies of asset pricillg. We completely charactize efficient allocations for several special cases. We illtroduce a competitive equilibrium with complete markets alld with elldogellous solvency constraints. These solvellcy constraints are such as to prevent default -at the cost of reduced risk sharing. We show a version of the classical welfare theorems for this equilibrium definition. We characterize the pricing kernel, alld compare it with the one for economies without participation constraints : interest rates are lower and risk premia can be bigger depending on the covariance of the idiosyncratic and aggregate shocks. Quantitative examples show that for reasonable parameter values the relevant marginal rates of substitution fali within the Hansen-Jagannathan bounds.

The role of consumer's risk aversion on price rigidity

This paper aims at contributing to the research agenda on the sources of price stickiness, showing that the adoption of nominal price rigidity may be an optimal firms' reaction to the consumers' behavior, even if firms have no adjustment costs. With regular broadly accepted assumptions on economic agents behavior, we show that firms' competition can lead to the adoption of sticky prices as an (sub-game perfect) equilibrium strategy. We introduce the concept of a consumption centers model economy in which there are several complete markets. Moreover, we weaken some traditional assumptions used in standard monetary policy models, by assuming that households have imperfect information about the ineflicient time-varying cost shocks faced by the firms, e.g. the ones regarding to inefficient equilibrium output leveIs under fiexible prices. Moreover, the timing of events are assumed in such a way that, at every period, consumers have access to the actual prices prevailing in the market only after choosing a particular consumption center. Since such choices under uncertainty may decrease the expected utilities of risk averse consumers, competitive firms adopt some degree of price stickiness in order to minimize the price uncertainty and fi attract more customers fi.'

Wrong-way risk in stock swaps : measuring counterparty credit risk and CVA

Uma forma interessante para uma companhia que pretende assumir uma posição comprada em suas próprias ações ou lançar futuramente um programa de recompra de ações, mas sem precisar dispor de caixa ou ter que contratar um empréstimo, ou então se protegendo de uma eventual alta no preço das ações, é através da contratação de um swap de ações. Neste swap, a companhia fica ativa na variação de sua própria ação enquanto paga uma taxa de juros pré ou pós-fixada. Contudo, este tipo de swap apresenta risco wrong-way, ou seja, existe uma dependência positiva entre a ação subjacente do swap e a probabilidade de default da companhia, o que precisa ser considerado por um banco ao precificar este tipo de swap. Neste trabalho propomos um modelo para incorporar a dependência entre probabilidades de default e a exposição à contraparte no cálculo do CVA para este tipo de swap. Utilizamos um processo de Cox para modelar o instante de ocorrência de default, dado que a intensidade estocástica de default segue um modelo do tipo CIR, e assumindo que o fator aleatório presente na ação subjacente e que o fator aleatório presente na intensidade de default são dados conjuntamente por uma distribuição normal padrão bivariada. Analisamos o impacto no CVA da incorporação do riscowrong-way para este tipo de swap com diferentes contrapartes, e para diferentes prazos de vencimento e níveis de correlação.

Assessment of risk factors for low bone mineral density in Brazilian postmenopausal women

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparison between 100-g glucose tolerance test and two other screening tests for gestational diabetes: combined fasting glucose with risk factors and 50-g glucose tolerance test

CONTEXTO E OBJETIVO: A falta de consenso sobre os protocolos de rastreamento e diagnóstico do diabetes gestacional, associada às dificuldades na realização do teste oral simplificado do diabete gestacional (o teste de tolerância a 100 g de glicose, considerado padrão-ouro) justificam a comparação com alternativas. O objetivo deste trabalho é comparar o teste padrão-ouro a dois testes de rastreamento: associação de glicemia de jejum e fatores de risco (GJ + FR) e o teste oral simplificado de tolerância a 50 g de glicose (TTG 50 g), com o teste de tolerância a 100 g de glicose (TTG 100 g). TIPO DE ESTUDO E LOCAL: Estudo de coorte longitudinal, prospectivo, realizado no Serviço de Ginecologia e Obstetrícia do Hospital Universitário da Universidade Federal de Mato Grosso do Sul. MÉTODOS: 341 gestantes foram submetidas aos três testes. Calcularam-se os índices de sensibilidade (S), especificidade (E), valores preditivos (VPP e VPN), razões de probabilidade (RPP e RPN) e resultados falsos (FP e FN), positivos e negativos da associação GJ + FR e do TTG 50 g em relação ao TTG 100 g. Compararam-se as médias das glicemias de uma hora pós-sobrecarga (1hPS) com 50 e 100 g. Na análise estatística, empregou-se o teste t de Student, com limite de significância de 5%. RESULTADOS: A associação GJ + FR encaminhou mais gestantes (53,9%) para a confirmação diagnóstica que o TTG 50 g (14,4%). Os dois testes foram equivalentes nos índices de S (86,4 e 76,9%), VPN (98,7 e 98,9%), RPN (0,3 e 0,27) e FN (15,4 e 23,1%). As médias das glicemias 1hPS foram semelhantes, 106,8 mg/dl para o TTG 50 g e 107,5 mg/dl para o TTG 100 g. CONCLUSÕES: Os resultados da eficiência diagnóstica associados à simplicidade, praticabilidade e custo referendaram a associação GJ + FR como o mais adequado para o rastreamento. A equivalência das glicemias de 1hPS permitiram a proposição de um novo protocolo de rastreamento e diagnóstico do diabete gestacional, com menores custo e desconforto.

Risk factors relating to helminth infections in cows during the peripartum

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Prevalence of trachoma in a population of the upper Rio Negro basin and risk factors for active disease

Purpose: To determine the prevalence of trachoma in Sao Gabriel da Cachoeira (SGC), the only urban community of the upper Rio Negro Basin of the Amazon state in Brazil, near the Colombian border, and to investigate the risk factors associated with the active forms of the disease. Methods: A total of 1702 people (440 children up to 9 years and 1069 adults aged 15 years and above) were examined. The sample was selected from a probabilistic household sampling procedure based on census data and a previous study of trachoma prevalence in Sao Gabriel da Cachoeira. A two-stage probabilistic household cluster sample was drawn. Household units were randomly selected within each cluster. A variety of socioeconomic and hygiene variables were studied in order to determine the risk factors for active trachoma in a household. Results: The total prevalence of trachoma was 8.9%. Prevalence of active trachoma (TF and/or TI) in children aged 1-9 years was 11.1% and trachomatous trichiasis in adults aged 15 years and above was 0.19%. Trachomatous scarring reached a peak of 22.4% for subjects between 50 to 60 years of age. Corneal opacity occurred in subjects aged 50 years and older with a prevalence of 2.0%. No sex effect was found on the overall prevalence of trachoma in SGC. Risk factors associated with active trachoma were mainly related to poor socioeconomic indicators. Conclusions: Despite the ubiquitous presence of water, the analysis of the risk factors associated with the active forms of the disease supports the idea that a low personal standard of hygiene and not water availability per se, is the key factor associated with trachoma. Copyright © 2008 Informa Healthcare USA, Inc.

Prevalence of enamel white spots and risk factors in children up to 36 months old

The aim of this study was to determine the prevalence of enamel white spots and the quality of oral hygiene in children up to 36 months old, in municipalities with different fluoride levels in the water supply, analyzing the contribution of several variables. After approval of the Ethics Committee, the parents signed an informed consent form and were interviewed about their educational level, economic classification of the family, nursing habits, use of toothpaste, access to dental service and other information. The children were clinically examined using the same codes and criteria established by the WHO (World Health Organization) and ADA (American Dental Association). The data were processed and analyzed with the Epi-info software program, version 3.2, and Microsoft Excel. Fisher's exact test (p<0.05) was applied to assess the association among the variables. The enamel white spot prevalence was 30.8% and the age group, duration of the bedtime milk feeding habit, age of initial practice of oral hygiene and presence of caries lesions with cavitation were considered statistically significant with regard to enamel white spot prevalence (p < 0.05). No association was found between oral hygiene quality and the study variables. © 2009 Sociedade Brasileira de Pesquisa Odontológica.

Risk-adjusted poverty in Argentina: measurement and determinants

Includes bibliography

Atrophic gastritis: Risk factor for esophageal squamous cell carcinoma in a Latin-American population

AIM: To study the association between atrophic gastritis (AG) and esophageal squamous cell carcinoma (ESCC) in a Latin-America population. METHODS: A case-control study was performed at two reference Brazilian hospitals including patients diagnosed with advanced ESCC and dyspeptic patients who had been subjected to upper gastrointestinal endoscopy, with biopsies of the gastric antrum and body. All cases with ESCC were reviewed by a single pathologist, who applied standard criteria for the diagnosis of mucosal atrophy, intestinal metaplasia, and dysplasia, all classified as AG. The data on the patients' age, sex, smoking status, and alcohol consumption were collected from clinical records, and any missing information was completed by telephone interview. The association between AG and ESCC was assessed by means of univariate and multiple conditional logistic regressions. RESULTS: Most patients were male, and the median age was 59 years (range: 37-79 years) in both the ESCC and control groups. Univariate analysis showed that an intake of ethanol greater than 32 g/d was an independent risk factor that increased the odds of ESCC 7.57 times (P = 0.014); upon multiple analysis, alcohol intake of ethanol greater than 32 g/d exhibited a risk of 4.54 (P = 0.081), as adjusted for AG and smoking. Smoking was shown to be an independent risk factor that increased the odds of ESCC 14.55 times (P = 0.011) for individuals who smoked 0 to 51 packs/year and 21.40 times (P = 0.006) for those who smoked more than 51 packs/year. Upon multiple analyses, those who smoked up to 51 packs/year exhibited a risk of 7.85 (P = 0.058), and those who smoked more than 51 packs/year had a risk 11.57 times higher (P = 0.04), as adjusted for AG and alcohol consumption. AG proved to be a risk factor that increased the odds of ESCC 5.33 times (95%CI: 1.55-18.30, P = 0.008) according to the results of univariate conditional logistic regression. CONCLUSION: There was an association by univariate conditional logistic regression between AG and ECSS in this sample of Latin-American population. © 2013 Baishideng.