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.

Health effects of human T-lymphotropic virus type I (HTLV-I) in a Jamaican cohort

BACKGROUND: Other than adult T-cell leukaemia (ATL) and HTLV-I associated myelopathy (HAM), the health effects of infection with human T-lymphotropic virus type I (HTLV-I) are not well defined. METHOD: A cohort of 201 confirmed HTLV-I seropositive Jamaican food service workers and 225 seronegative controls of similar age and sex from the same population was examined. A health questionnaire, physical examination, and laboratory tests were performed at enrollment into the cohort in 1987-1988. RESULTS: One of 201 HTLV-I seropositives, but no controls were diagnosed with HAM, for a prevalence of 0.5 percent (95 percent confidence interval) (CI) 0.01-2.7 percent); no cases of ATL were diagnosed. While there was no difference in current symptoms, the HTLV-I seropositive group was more likely to report a past medical history of hepatitis or jaundice (OR = 3.49, 95 percent CI: 0.93-13.08), malaria (OR = 2.13, 95 percent CI: 0.96-4.73), and dengue fever (OR = 1.37, 95 percent CI 0.82-2.29); however, these differences were of borderline statistical significance. Low income HTLV-I seropositive women had lower body weight (P , 0.01) and body mass index (P < 0.009) than their seronegative counterparts; similar differences were seen in the smaller male group. A trend toward higher prevalence of severe anaemia (haemoglobin < 10 g/dl) (12.6 percent verus 7.7 percent, P < 0.105) and a significantly lower prevalence of eosinophilia (1.0 percent verus 6.3 percent, P < 0.004) was seen among HTLV-I seropositives are asymptomatic, HAM may be diagnosed in approximately 0.5 percent of carriers. Chronic HTLV-I infection may also subtle effects on body mass and haematological parameters.(AU)

A case-control study of risk factors for seropositivity to human T-lymphotropic virus type I (HTLV-I) in Jamaica

BACKGROUND: We investigated behavioural and environmental risk factors for seropositivity to human T-lymphotropic virus type I (HTLV-I). METHODS: A nested case-control study of 201 HTLV-I seropositive subjects and 225 age and sex matched seronegative controls was performed using questionaire data from the enrollment visit of a cohort study in 1987-1988. HTLV-I serostatus was confirmed using enzyme-linked imunosorbent assay (ELISA) and Western blot. RESULTS: Among women, the number of lifetime sexual partners (P < 0.05, chi 2 trend) and the number of different men fathering a child by the woman (P < 0.06, chi 2 trend) were associated with HTLV-I seropositivity. Use by the female subject of an intrauterine device (IUD) was associated with an increased risk of seropositivity (odds ratio (OR) = 2.67, 95 percent confidence interval (CI): 1.13-6.23); condom use was rare in this population. Among male subjects, a larger number of lifetime sexual partners was also associated with HTLV-I seropositivity (P < 0.05, chi 2 trend). No association was found between HTLV-I seropositivity and educational attainment, income, or occupation. Having been breastfed as a child or receipt of a blood transfusion had elevated but imprecise OR due to very high and low prevalence of the risk factors, respectively. Several variables relating to insect or animal exposure showed no association with HTLV-I seropositivity. CONCLUSIONS: These data confirm that heterosexual intercourse is a major route of HTLV-I transmission, but do not support suggestions of insect or environmental vectors.(AU)

Risk factors and cofactors for human T-cell lymphotropic virus type 1 (HTLV-1) - associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica

Human T-cell lymphotrophic virus type 1 (HTLV-1) has been etiologically associated with a neurologic syndrome called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as with adult T-cell leukemia/lymphoma. The authors sought to quantify the risk in Jamaica of HAM/TSP associated with HTLV-1 infection and cofactors associated with this disease among infected individuals. Between 1988 and 1989, prevalent and incident HAM/TSP patients and controls with other neurologic diseases were enrolled in a retrospective study. A second control group was composed of HTLV-1-seropositive, asymptomatic carriers in Jamaica, ascertained in a separate study conducted in 1988. Although HTLV-1 seropositivity was not a component of the case definition for HAM/TSP, all 43 HAM/TSP patients were HTLV-1 seropsitive compared with two (4.0 percent) of the controls with other neurologic diseases. Given HTLV-1 seropositivity, one cofactor associated with the risk of HAM/TSP was young age at initial heterosexual intercourse (odds ratio = 4.00, 95 percent confidence interval 1.29-12.46 for individuals aged ó15; odds ratio = 4.26, 95 percent confidence interval 1.41-12.90 for individuals aged 16-17 years at initial intercourse). Among individuals who reported this early age at initial sexual intercourse, an increased risk of HAM/TSP was associated with having reported more than five lifetime sexual partners (odds ratio = 2.88, 95 percent confidence interval 0.90-8.70). Neither an early age at initial sexual intercourse nor the number of lifetime sexual partners was a risk factor for adult T-cell leukemia/lymphoma. These data support the hypothesis that HAM/TSP is associated with sexually acquired HTLV-1 infection, whereas adult T-cell leukemia/lymphoma is not. (AU)

Sibling adult T-cell leukemia/lymphoma and clustering of human T-Cell lymphotropic virus type I infection in a Jamaican family

BACKGROUND:- Human T-cell lymphotropic virus type I (HTLV-I) infection is endemic in Jamaica, with an estimated crude seroprevalence of 5percent. Adult T-cell lymphoma/Leukemia (ATL), a disease caused by HTLV-I, has an incidence of 1-2/100,000 in the Jamiacan population. Familial ATL has not previously been reported from Jamaica. METHODS:- Hospital records and histologic specimens of the two cases were reviewed. HTLV-I infection was confirmed by antibody testing and by polymerase chain reaction on paraffin-embedded tissue,where serum was unavailable. Family members identified by the patient's parents. After giving informed consent, family members were asked to complete an interviewer-administered questionnaire and to agree to phlebotomy. RESULTS:- ATL developed 10 years apart in two siblings from a Jamaican family at age 16 and 24 years. A study of 19 members of their extended family, including both parents, 2 grandparents, and 3 siblings, revealed an overall HTLV-I seroprevalence of 17 percent. This compared with 75 percent among parents and sibling living in the same household as the patients (AU)

Sibling ATL and familial clustering of HTLV-1 infection in a Jamaican family - abstract

Two siblings from a Jamaican family developed adult T-cell leukaemia/lymphoma (ATL) in 1979 and 1989 respectively. The latter was HTLV-1 seropositive. Our aims were, to study the seroprevalence of HTLV-1 in the household of the index cases and among relatives living in the same parish, to identify any relative with HTLV-1 associated diseases (ATL and HAM/TSP) and the presence of risk factors for acquiring HTLV-1 infection. Eighteen (18) family members including two parents, 2 grandmothers, 3 siblings, 7 uncles and 4 aunts of the index cases were studied. The medical records of the first sibling were reviewed. Both parents and 2 of the siblings' studies live in the same house as the index cases. Results of the enzyme-linked immunoabsorbent assay (ELISA) testing are shown on the pedigree. Four members of the index cases' household were antibody (Ab) positive, whereas no family member outside the household was Ab positive. The sero status of the first case of ATL is unknown as she died in 1979. HTLV-1 Ab positive and Ab negative subjects had a similar mean age 34 and 38 years respectively. Neither group reported sexual contact with prostitutes or male homosexual activity. Among 18 healthy family members, no significant lymphadenopathy or neurological abnormality was detected. The high rate of HTLV-1 seropositivity among the family in the affected household (3/4 - 75) and the family overall (3/18 = 17 per cent) of the index cases were significantly greater than the general population (5 per cent). These findings support the theory that transmission is likely to take place horizontally, by sexual contact (husband to wife) and vertically (mother to child). The persistent Ab seronegativity of the 12 year-old child in the affected household is noteworthy, and the presence of other markers of HTLV-1 infection is being investigated (AU)