193 research outputs found

    Causation in Toxic Torts: Burdens of Proof, Standards of Persuasion, and Statistical Evidence

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    Critique [of Asians, Jews, and the Legacy of Midas by Alan Spector]

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    In reading Alan Spector\u27s paper, I was reminded of British sociologist Christie Davies\u27 cross-national analysis of ethnic jokes. In it, she argues that majority members of a society stereotype others in order to reduce their own anxiety about social position. Davies found that such jokes tend to fall into either one of two catagories [categories]. The first and most common type of ethnic joke addresses those groups who live below one\u27s own station in life.[1] By referring to them, one can elevate his/her own status and hence feel a bit more secure. A second type of joke ridicules groups who appear to be especially successful. By showing overachieving groups in a negative light, the average member of society can feel a bit better about his/her own lack of achievement. The superachievers are depicted as so inhuman, immoral, work-driven or tight-fisted that their acccomplishments[accomplishments] are pointless. Spector\u27s paper draws important parallels between the experience of Asians and Jews, two groups most often depicted as negative successes in popular stereotypes

    When Certainty Dissolves into Probability: A Legal Vision of Toxic Causation for the Post-Genomic Era

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    Proof of causation in toxic torts has presented persistent problems for the legal system, because the probabilities that science can know fit poorly with the demands for particularistic proof imposed by the law’s deterministic model of causation. Some scholars have hoped that genomic and molecular information will at last provide scientific certainty—definitive, individualized proof of toxic causation. This Article argues that the opposite is true. Scientific research will increasingly elucidate the ways in which environmental exposures and human genes interact to produce disease, but this deeper knowledge will extend rather than resolve the problem of causal indeterminacy in toxic torts. Genomic and molecular understanding, instead of sounding the death knell for proposals to reform toxic tort causation law, will strengthen the argument for those reforms. This Article proposes a probabilistic causal contribution model to replace the model of deterministic causation in toxic torts, building on earlier scholarly proposals and the creativity of a handful of courts. The Article explores how the model would work and argues that it is superior to present doctrine when assessed against the goals of the tort system

    Systematic review and meta-analysis of the pharmacokinetics of benznidazole in the treatment of Chagas disease

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    Chagas disease is a neglected parasitic illness affecting approximately 8 million people, predominantly in Latin America. Benznidazole is the drug of choice for treatment, although its availability has been limited. A paucity of knowledge of the pharmacokinetic properties of this drug has contributed to its limited availability in several jurisdictions. The objective of this study was to conduct a systematic literature review and a Bayesian meta-analysis of pharmacokinetic studies to improve estimates of the basic pharmacokinetic properties of benznidazole. A systematic search of the Embase, Medline, LILACS, and SciELO (Scientific Electronic Library Online) databases was conducted. Eligible studies reported patient-level data from single-100-mg-dose pharmacokinetic evaluations of benznidazole in adults or otherwise provided data relevant to the estimation of pharmacokinetic parameters which could be derived from such studies. A Bayesian hierarchical model was used for analysis. Secondary data (i.e., data from studies that did not include patient-level, single-100-mg-dose data) were used for the generation of empirical priors for the Bayesian analysis. The systematic search identified nine studies for inclusion. Nine pharmacokinetic parameters were estimated, including the area under the concentration-time curve (AUC), the maximum concentration of drug in plasma (Cmax), the time to Cmax, the elimination rate constant (kel), the absorption rate constant (Ka), the absorption and elimination half-lives, the apparent oral clearance, and the apparent oral volume of distribution. The results showed consistency across studies. AUC and Cmax were 51.31 mg · h/liter (95% credible interval [CrI], 45.01, 60.28 mg · h/liter) and 2.19 mg/liter (95% CrI, 2.06, 2.33 mg/liter), respectively. Ka and kel were 1.16 h-1 (95% CrI, 0.59, 1.76 h-1) and 0.052 h-1 (95% CrI, 0.045, 0.059 h-1), respectively, with the corresponding absorption and elimination half-lives being 0.60 h (95% CrI, 0.38, 1.11 h) and 13.27 h (95% CrI, 11.79, 15.42 h), respectively. The oral clearance and volume of distribution were 2.04 liters/h (95% CrI, 1.77, 2.32 liters/h) and 39.19 liters (95% CrI, 36.58, 42.17 liters), respectively. A Bayesian meta-analysis was used to improve the estimates of the standard pharmacokinetic parameters of benznidazole. These data can inform clinicians and policy makers as access to this drug increases.Fil: Wiens, Matthew O.. University of British Columbia; CanadáFil: Kanters, Steve. Precision Global Health;Fil: Mills, Edward. Mc Master University; CanadáFil: Peregrina Lucano, Alejandro A.. Universidad de Guadalajara; MéxicoFil: Gold, Silvia. Fundación Mundo Sano; ArgentinaFil: Ayers, Dieter. Precision Global Health;Fil: Ferrero, Luis. Fundación Mundo Sano; ArgentinaFil: Krolewiecki, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentin

    Non-Fasting High-Density Lipoprotein Is Associated With White Matter Microstructure in Healthy Older Adults

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    A growing body of evidence indicates that biomarkers of cardiovascular risk may be related to cerebral health. However, little is known about the role that non-fasting lipoproteins play in assessing age-related declines in a cerebral biomarker sensitive to vascular compromise, white matter (WM) microstructure. High-density lipoprotein cholesterol (HDL-C) is atheroprotective and low-density lipoprotein cholesterol (LDL-C) is a major atherogenic lipoprotein. This study explored the relationships between non-fasting levels of cholesterol and WM microstructure in healthy older adults. A voxelwise and region of interest approach was used to determine the relationship between cholesterol and fractional anisotropy (FA). Participants included 87 older adults between the ages of 59 and 77 (mean age = 65.5 years, SD = 3.9). Results indicated that higher HDL-C was associated with higher FA in diffuse regions of the brain when controlling for age, sex, and body mass index (BMI). HDL-C was also positively associated with FA in the corpus callosum and fornix. No relationship was observed between LDL-C and FA. Findings suggest that a modifiable lifestyle variable associated with cardiovascular health may help to preserve cerebral WM

    Non-fasting High-Density Lipoprotein Is Associated With White Matter Microstructure in Healthy Older Adults

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    A growing body of evidence indicates that biomarkers of cardiovascular risk may be related to cerebral health. However, little is known about the role that non-fasting lipoproteins play in assessing age-related declines in a cerebral biomarker sensitive to vascular compromise, white matter (WM) microstructure. High-density lipoprotein cholesterol (HDL-C) is atheroprotective and low-density lipoprotein cholesterol (LDL-C) is a major atherogenic lipoprotein. This study explored the relationships between non-fasting levels of cholesterol and WM microstructure in healthy older adults. A voxelwise and region of interest approach was used to determine the relationship between cholesterol and fractional anisotropy (FA). Participants included 87 older adults between the ages of 59 and 77 (mean age = 65.5 years, SD = 3.9). Results indicated that higher HDL-C was associated with higher FA in diffuse regions of the brain when controlling for age, sex, and body mass index (BMI). HDL-C was also positively associated with FA in the corpus callosum and fornix. No relationship was observed between LDL-C and FA. Findings suggest that a modifiable lifestyle variable associated with cardiovascular health may help to preserve cerebral WM

    Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents ( Update 2016)

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    Background: Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. Methods: Asystematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. Results: The consensus group recommended that invasive diagnostic testing for Hpylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. Conclusions: The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child

    When a birth cohort grows up: challenges and opportunities in longitudinal developmental origins of health and disease (DOHaD) research

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    High-quality evidence from prospective longitudinal studies in humans is essential to testing hypotheses related to the developmental origins of health and disease. In this paper, the authors draw upon their own experiences leading birth cohorts with longitudinal follow-up into adulthood to describe specific challenges and lessons learned. Challenges are substantial and grow over time. Long-term funding is essential for study operations and critical to retaining study staff, who develop relationships with participants and hold important institutional knowledge and technical skill sets. To maintain contact, we recommend that cohorts apply multiple strategies for tracking and obtain as much high-quality contact information as possible before the child's 18th birthday. To maximize engagement, we suggest that cohorts offer flexibility in visit timing, length, location, frequency, and type. Data collection may entail multiple modalities, even at a single collection timepoint, including measures that are self-reported, research-measured, and administrative with a mix of remote and in-person collection. Many topics highly relevant for adolescent and young adult health and well-being are considered to be private in nature, and their assessment requires sensitivity. To motivate ongoing participation, cohorts must work to understand participant barriers and motivators, share scientific findings, and provide appropriate compensation for participation. It is essential for cohorts to strive for broad representation including individuals from higher risk populations, not only among the participants but also the staff. Successful longitudinal follow-up of a study population ultimately requires flexibility, adaptability, appropriate incentives, and opportunities for feedback from participants
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