Understanding Emerging Environmental Health Concerns and Environmental Public Health-Tracking Priorities Among State and Local Professionals in Colorado.

CONTEXT: Colorado is experiencing dramatic changes related to population growth, climate change, and expanded industrial activity. Local and state public health professionals are trying to address a growing array of unique public health issues with stagnant or limited resources. OBJECTIVES: To understand, through perspectives from local and state public health professionals, the alignment of contemporary environmental and community health issues with state and local capacity and state environmental public health-tracking priorities. DESIGN: During 2014-2015, we conducted semistructured interviews which informed the development of a statewide survey of Colorado's professionals from public health, emergency management, forestry, and transportation. SETTING: This work took place in Colorado. PARTICIPANTS: Fifteen professionals from public (n = 9), academic (n = 4), and private (n = 2) sectors were interviewed. Forty-seven professionals, representing 34 counties and 40 public agencies, completed the 25-minute online survey. MAIN OUTCOME MEASURES: Environmental and community health concerns; contributing factors to environmental concerns; strengths and limitations of capacity to respond to issues; and frequency of community engagement activities. RESULTS: Top environmental health concerns were indoor air pollution (eg, radon), outdoor air pollution, and waste management. Transportation, extreme weather (eg, wildfires), and oil and gas development were most frequently reported as major contributing factors to concerns. Obesity, physical inactivity, and mental illness were the top community health concerns. To remain prepared for emerging challenges, professionals cited a need for more spatiotemporal-refined data related to their top concerns in the environmental public health-tracking database, and support from local, state, and federal agencies, in addition to personnel and funding. To address concerns, participants reported frequently working with government officials, advisory committees, and media outlets. CONCLUSIONS: This project illuminates opportunities to strengthen connections between the state's environmental public health-tracking priorities and local-level capacity related to professionals' top concerns. It also suggests reinforcing and broadening partnerships to improve data infrastructure and inform environmental public health priorities.

Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees.

A novel Protocol Ethics Tool Kit ('Ethics Tool Kit') has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval.

Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.

Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.