Workgroup Report: Biomonitoring Study Design, Interpretation, and Communication—Lessons Learned and Path Forward

Human biomonitoring investigations have provided data on a wide array of chemicals in blood and urine and in other tissues and fluids such as hair and human milk. These data have prompted questions such as a) What is the relationship between levels of environmental chemicals in humans and external exposures? b) What is the baseline or “background” level against which individual levels should be compared? and c) How can internal levels be used to draw conclusions about individual and/or population health? An interdisciplinary panel was convened for a 1-day workshop in November 2004 with the charge of focusing on three specific aspects of biomonitoring: characteristics of scientifically robust biomonitoring studies, interpretation of human biomonitoring data for potential risks to human health, and communication of results, uncertainties, and limitations of biomonitoring studies. In this report we describe the recommendations of the panel

Family Income Gradients in the Health and Health Care Access of US Children

This study sought to examine the shape and magnitude of family income gradients in US children’s health, access to care, and use of services. We analyzed cross-sectional data from the 2003 National Survey of Children’s Health, a telephone survey of 102,353 parents of children aged 0–17 years. Associations between family income [Below 100% Federal Poverty Level (FPL), 100–199% FPL, 200–299% FPL, 300–399% FPL, 400% FPL or Greater] and a set of 32 health and health care indicators were examined using linear polynomial testing and multivariate logistic regression. The percentage of children in better health increased with family income for 15 health outcomes. In multivariate logistic regression models that controlled for health insurance coverage and socio-demographic confounders, odds ratios >2 comparing the lowest to the highest income groups were noted for health conditions across both physical and developmental domains (diabetes, headaches, ear infections, learning disabilities, behavior/conduct problems, speech problems). Parent-reported global child health status, activity limitation, and oral health status showed steeper gradients than specific chronic and acute conditions. Ten measures of health care access and utilization were associated with family income in multivariate logistic regression models. Income gradients are pervasive across many health indicators at an early age. Social and health policy interventions are needed to address the multitude of factors that can affect children’s health and initiate disparities in development

Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer

The present study investigated the interaction between c-erbB2 overexpression and the response to first-line endocrine therapy in patients with advanced breast cancer. The primary tumours of 241 patients who were treated at first relapse with endocrine therapy were assessed for overexpression of c-erbB2 by immunohistochemistry. c-erbB2 was overexpressed in 76 (32%) of primary breast cancers and did not correlate with any other prognostic factor. The overall response to treatment and time to progression were significantly lower in patients with c-erbB2-positive tumours compared to those that were c-erbB2-negative (38% vs 56%, P = 0.02; and 4.1 months vs 8.7 months, P < 0.001, respectively). In multivariate analysis, c-erbB2 status was the most significant predictive factor for a short time to progression (P = 0.0009). In patients with ER-positive primary tumours treated at relapse with tamoxifen (n = 170), overexpression of c-erbB2 was associated with a significantly shorter time to progression (5.5 months vs 11.2 months, P < 0.001). In conclusion, overexpression of c-erbB2 in the primary tumour is an independent marker of relative resistance to first-line endocrine therapy in patients with advanced breast cancer. In patients with ER-positive primary tumours, the overexpression of c-erbB2 defines a subgroup less likely to respond to endocrine therapy. © 1999 Cancer Research Campaig

Psychopathic Traits of Dutch Adolescents in Residential Care: Identifying Subgroups

The present study examined whether a sample of 214 (52.8% male, M age = 15.76, SD = 1.29) institutionalized adolescents could be classified into subgroups based on psychopathic traits. Confirmatory Factor Analyses revealed a relationship between the subscales of the Youth Psychopathic traits Inventory (YPI) and the three latent constructs of the original model on which it is based. Latent Class Analyses showed that adolescents showing psychopathic traits could be classified into three subgroups. The first group showed low scores on the grandiose/manipulative dimension, the callous/unemotional dimension, and the impulsive/irresponsible dimension (normal group). The second group scored moderate on the grandiose/manipulative dimension and the callous/unemotional dimension and high on the impulsive/irresponsible dimension (impulsive, non-psychopathic-like group). The third group scored high on all three dimensions (psychopathy-like group). The findings revealed that the impulsive, non-psychopathic like group scored significantly higher on internalizing problem behavior compared to the normal group, while the psychopathy-like and the impulsive, non-psychopathic-like group both scored higher on externalizing problem behavior compared to the normal group. Based on a self-report delinquency measure, it appeared that the psychopathy-like group had the highest delinquency rates, except for vandalism. Both the impulsive and psychopathy-like group had the highest scores on the use of soft drugs

Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis

Background Naltrexone is an opioid antagonist used in many different conditions, both licensed and unlicensed. It is used at widely varying doses from 3 - 250 mg. The aim of this review was to evaluate the safety of oral naltrexone by examining the risk of serious adverse events (SAEs) in randomised controlled trials (RCTs) of naltrexone compared to placebo. Methods A systematic search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, other databases and clinical trials registries was undertaken up to March 2018. Parallel placebo-controlled RCTs longer than 4 weeks published after 1/1/2001, of oral naltrexone at any dose were selected. Any condition and age group were included, excluding only studies for opioid or ex-opioid users, due to possible opioid/opioid antagonist interactions. The systematic review used the guidance of the Cochrane Handbook throughout. Numerical data was independently extracted by two people and cross-checked. Risk of bias was assessed with the Cochrane Risk of Bias Tool. Meta-analyses were performed using Stata 15 and R, using random and fixed effects models throughout. Results Eighty-nine RCTs with 11194 participants were found, studying alcohol use disorders, various psychiatric disorders, impulse control disorders, other addictions, obesity, Crohn’s disease, fibromyalgia and cancers. Twenty-six studies (4,960 participants) recorded SAEs occurring by arm of study. There was no evidence of increased risk of SAEs for naltrexone compared to placebo, relative risk (RR) 0.84 (95% CI: 0.66 to 1.06). Sensitivity analyses pooling risk differences supported this conclusion (RD = -0.01 (-0.02, 0.00)) and subgroup analyses showed that results were consistent across different doses and disease groups. The quality of evidence for this outcome was judged high using the GRADE criteria. Conclusions Naltrexone does not appear to increase the risk of SAEs over placebo. These findings confirm the safety of naltrexone when used in licensed indications and encourage investments to undertake efficacy studies in unlicensed indications

Thirty years of Biology & Philosophy: philosophy of which biology?

Which domains of biology do philosophers of biology primarily study? The fact that philosophy of biology has been dominated by an interest for evolutionary biology is widely admitted, but it has not been strictly demonstrated. Here I analyse the topics of all the papers published in Biology & Philosophy, just as the journal celebrates its thirtieth anniversary. I then compare the distribution of biological topics in Biology & Philosophy with that of the scientific journal Proceedings of the National Academy of Science of the USA, focusing on the recent period 2003-2015. This comparison reveals a significant mismatch between the distributions of these topics. I examine plausible explanations for that mismatch. Finally, I argue that many biological topics underrepresented in philosophy of biology raise important philosophical issues and should therefore play a more central role in future philosophy of biology

ANCA-associated vasculitis.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients