An Exploration of Ethical Issues in Research in Children’s Health and the Environment

The consideration of ethical issues relating to pediatric environmental health is a recent phenomenon. Discussions of biomedical ethics, research on children, and environmental health research have a longer history. In the late 1990s, researchers at the Kennedy Krieger Institute in Baltimore, Maryland, undertook a study to compare the effectiveness of several methods of reducing lead risk in housing. In a preliminary finding in the case of Grimes v. Kennedy Krieger Institute, Inc., a Maryland court questioned the ethics of performing research on children when there is no prospect of direct benefit to those children and whether parents can consent to such research. This case dramatically raised the profile of ethical issues among the pediatric environmental health research community. To broaden the discussion of these issues and in response to the Kennedy-Krieger case, the Children’s Environmental Health Network held a working meeting on 5 and 6 March 2004 to explore this topic. The articles in this mini-monograph were prepared by the authors as a result of the workshop and represent their opinions. This article is an introduction to the workshop and a summary of the articles to follow

Review of: Ailing in Place: Environmental Inequities and Health Disparities in Appalachia

The Journal of Appalachian Health is committed to reviewing published media that relate to contemporary concepts affecting the health of Appalachia. The Appalachian environmental inequities and the health disparities we face have a direct effect on our experience of illness. Dr. Jerome Paulson reviews the book Ailing in Place: Environmental Inequities and Health Disparities in Appalachia

School Siting Near Industrial Chemical Facilities: Findings from the U.S. Chemical Safety Board\u27s Investigation of the West Fertilizer Explosion.

BACKGROUND: The U.S. Chemical Safety and Hazard Investigation Board (CSB) investigated the April 17, 2013 explosion at the West Fertilizer Company (WFC) that resulted in 15 fatalities, more than 260 injuries and damage to more than 150 buildings. Among these structures were four nearby school buildings cumulatively housing children in grades K-12, a nursing care facility and an apartment complex. The incident occurred during the evening when school was not in session, which reduced the number of injuries. OBJECTIVES: The goal of this paper is to illustrate the consequences of siting schools near facilities that store or use hazardous chemicals, and highlight the need for additional regulations to prevent future siting of schools near these facilities. DISCUSSION: This paper summarizes the findings of the CSB\u27s investigation related to the damaged school buildings and the lack of regulation surrounding the siting of schools near facilities that store hazardous chemicals. CONCLUSIONS: In light of the current lack of federal authority for oversight of land use near educational institutions, state and local governments should take a proactive role in promulgating state regulations that prohibit the siting of public receptors, such as buildings occupied by children, near facilities that store hazardous chemicals

Public Health Stops at the School House Door.

In the United States, all children of appropriate age are required to attend school, and many parents send their children to child care. Many school and day care buildings have been found to have environmental health problems that impact children’s health and diminish their ability to learn. No federal agency has the capacity or authority to identify, track, or remediate these problems. A recent meeting, coordinated by Healthy Schools Network, Inc., has developed a set of recommendations to begin to deal with the issue of environmental health problems in schools

Condensed Mitotic Chromosome Structure at Nanometer Resolution Using PALM and EGFP- Histones

Photoactivated localization microscopy (PALM) and related fluorescent biological imaging methods are capable of providing very high spatial resolutions (up to 20 nm). Two major demands limit its widespread use on biological samples: requirements for photoactivatable/photoconvertible fluorescent molecules, which are sometimes difficult to incorporate, and high background signals from autofluorescence or fluorophores in adjacent focal planes in three-dimensional imaging which reduces PALM resolution significantly. We present here a high-resolution PALM method utilizing conventional EGFP as the photoconvertible fluorophore, improved algorithms to deal with high levels of biological background noise, and apply this to imaging higher order chromatin structure. We found that the emission wavelength of EGFP is efficiently converted from green to red when exposed to blue light in the presence of reduced riboflavin. The photon yield of red-converted EGFP using riboflavin is comparable to other bright photoconvertible fluorescent proteins that allow <20 nm resolution. We further found that image pre-processing using a combination of denoising and deconvolution of the raw PALM images substantially improved the spatial resolution of the reconstruction from noisy images. Performing PALM on Drosophila mitotic chromosomes labeled with H2AvD-EGFP, a histone H2A variant, revealed filamentous components of ∼70 nm. This is the first observation of fine chromatin filaments specific for one histone variant at a resolution approximating that of conventional electron microscope images (10–30 nm). As demonstrated by modeling and experiments on a challenging specimen, the techniques described here facilitate super-resolution fluorescent imaging with common biological samples

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Public Health Stops at the School House Door.

In the United States, all children of appropriate age are required to attend school, and many parents send their children to child care. Many school and day care buildings have been found to have environmental health problems that impact children’s health and diminish their ability to learn. No federal agency has the capacity or authority to identify, track, or remediate these problems. A recent meeting, coordinated by Healthy Schools Network, Inc., has developed a set of recommendations to begin to deal with the issue of environmental health problems in schools