Study design: Review by the spinal cord outcomes partnership endeavor (SCOPE), which is a broadbased international consortium of scientists and clinical researchers representing academic institutions, industry, government agencies, not-for-profit organizations and foundations. Objectives: Assessment of current and evolving tools for evaluating human spinal cord injury (SCI) outcomes for both clinical diagnosis and clinical research studies. Methods: a framework for the appraisal of evidence of metric properties was used to examine outcome tools or tests for accuracy, sensitivity, reliability and validity for human SCI. Results: Imaging, neurological, functional, autonomic, sexual health, bladder/bowel, pain and psychosocial tools were evaluated. Several specific tools for human SCI studies have or are being developed to allow the more accurate determination for a clinically meaningful benefit (improvement in functional outcome or quality of life) being achieved as a result of a therapeutic intervention. Conclusion: Significant progress has been made, but further validation studies are required to identify the most appropriate tools for specific targets in a human SCI study or clinical trial.

A commentary on this article appears in this issue on page 1331.

ObjectivesLong-term studies of oil spill responders are urgently needed as oil spills continue to occur. To this end, we established the prospective Deepwater Horizon (DWH) Oil Spill Coast Guard Cohort study.MethodsDWH oil spill responders (n=8696) and non-responders (n=44 823) who were members of the US Coast Guard (20 April–17 December 2010) were included. This cohort uses both prospective, objective health data from military medical encounters and cross-sectional survey data. Here, we describe the cohort, present adjusted prevalence ratios (PRs) estimating cross-sectional associations between crude oil exposure (none, low/medium, high) and acute physical symptoms, and present adjusted relative risks (RRs) based on longitudinal medical encounter data (2010–2012) for responders/non-responders and responders exposed/not exposed to crude oil.ResultsResponders and non-responders in this large cohort (n=53 519) have similar characteristics. Crude oil exposure was reported by >50% of responders. We found statistically significant associations for crude oil exposure with coughing (PRhigh=1.78), shortness of breath (PRhigh=2.30), wheezing (PRhigh=2.32), headaches (PRhigh=1.46), light-headedness/dizziness (PRhigh=1.96), skin rash/itching (PRhigh=1.87), diarrhoea (PRhigh=1.76), stomach pain (PRhigh=1.67), nausea/vomiting (PRhigh=1.48) and painful/burning urination (PRhigh=2.89) during deployment. Longitudinal analyses revealed that responders had elevated RRs for dermal conditions (RR=1.09), as did oil-exposed responders for chronic respiratory conditions (RR=1.32), asthma (RR=1.83) and dermal conditions (RR=1.21).ConclusionsWe found positive associations between crude oil exposure and various acute physical symptoms among responders, as well as longer term health effects. This cohort is well positioned to evaluate both short-term and long-term effects of oil spill exposures using both self-reported and clinical health data.

Background Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. Methods DNA was extracted from whole blood from male AHS pesticide applicators (n=695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Results Ever having an HPEE (n=142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; p<0.01) and for the mean across CpGs (chr11:67,351,099, 67,351,124-145; p<0.01). In stratified analyses, elevated GSTP1 promoter DNAm associated with HPEE was more pronounced among applicators >59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction <0.01); HPEE was associated with reduced MGMT promoter DNAm at CpG2 (chr10:131,265,803; p=0.03), CpG3 (chr10:131,265,810; p=0.05), and the mean across CpGs (chr10:131,265,796-810; p=0.03) among applicators >59 years and reduced LINE-1 DNAm (p=0.05) among applicators with ≤16.56 ng/mL plasma folate. Conclusions Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer.

Breastfeeding has been linked with increased forced vital capacity (FVC) in children but not in older adolescents. Our aim was to investigate the effects of breastfeeding duration and infant weight gain on FVC in both developmental periods.In a birth cohort, information on breastfeeding duration was collected at 1 and 2 yrs; spirometric tests were conducted at 10 and 18 yrs. To estimate the effect of breastfeeding duration on FVC at 18 yrs of age, we used linear models; to analyse repeated FVC measurements at 10 and 18 yrs of age, we used linear mixed models. Links between breastfeeding, infant weight gain and FVC at 10 and 18 yrs of age were analysed through path analyses.Among 808 breastfed children, 49% were breastfed for o4 months. At 18 yrs of age the augmenting effect of breastfeeding on FVC was reduced with increased height. Linear mixed models identified that breastfeeding duration was associated with increased FVC. Path analysis suggested a direct effect of breastfeeding on FVC at 10 yrs of age, but an indirect effect at 18 yrs of age via FVC at 10 yrs of age. Although inversely related to breastfeeding, a higher weight gain in infants led to taller adolescents and, in turn, resulted in increased FVC.In conclusion, a longer duration of breastfeeding contributes to lung health in childhood and adolescence.

In a Columbia, South Carolina-based case-control study, we developed a healthy lifestyle index from five modifiable lifestyle factors (smoking, alcohol intake, physical activity, diet, and body mass index), and examined the association between this lifestyle index and the risk of colorectal adenomatous polyps (adenoma). Participants were recruited from a local endoscopy center and completed questionnaires related to lifestyle behaviors prior to colonoscopy. We scored responses on each of five lifestyle factors as unhealthy (0 point) or healthy (1 point) based on current evidence and recommendations. We added the five scores to produce a combined lifestyle index for each participant ranging from 0 (least healthy) to 5 (healthiest), which was dichotomized into unhealthy (0–2) and healthy (3–5) lifestyle scores. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for adenoma with adjustment for multiple covariates. We identified 47 adenoma cases and 91 controls. In the main analyses, there was a statistically nonsignificant inverse association between the dichotomous (OR 0.54; 95% CI 0.22, 1.29) and continuous (OR 0.75; 95%CI 0.51, 1.10) lifestyle index and adenoma. Odds of adenoma were significantly modified by the use of non-steroidal anti-inflammatory drugs (NSAIDs) (pinteraction=0.04). For participants who reported no use of NSAIDs, those in the healthy lifestyle category had a 72% reduction in odds of adenoma as compared to those in the unhealthy category (OR 0.28; 95%CI 0.08, 0.98), whereas a one-unit increase in the index significantly reduced odds of adenoma by 53% (OR 0.47; 95% CI 0.26, 0.88). Although these findings should be interpreted cautiously given our small sample size, our results suggest that higher scores from this index are associated with reduced odds of adenomas, especially in nonusers of NSAIDs. Lifestyle interventions are required to test this approach as a strategy to prevent colorectal adenomatous polyps.

Clock genes are expressed in a self-perpetuating, circadian pattern in virtually every tissue including the human gastrointestinal tract. They coordinate cellular processes critical for tumor development, including cell proliferation, DNA damage response and apoptosis. Circadian rhythm disturbances have been associated with an increased risk for colon cancer and other cancers. This mechanism has not been elucidated, yet may involve dysregulation of the ‘period’ (PER) clock genes, which have tumor suppressor properties. A variable number tandem repeat (VNTR) in the PERIOD3 (PER3) gene has been associated with sleep disorders, differences in diurnal hormone secretion, and increased premenopausal breast cancer risk. Susceptibility related to PER3 has not been examined in conjunction with adenomatous polyps. This exploratory case-control study was the first to test the hypothesis that the 5-repeat PER3 VNTR sequence is associated with increased odds of adenoma formation. Information on demographics, medical history, occupation and lifestyle was collected prior to colonoscopy. Cases (n=49) were individuals with at least one histopathologically confirmed adenoma. Controls (n=97) included patients with normal findings or hyperplastic polyps not requiring enhanced surveillance. Unconditional multiple logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), after adjusting for potential confounding. Adenomas were detected in 34% of participants. Cases were more likely to possess the 5-repeat PER3 genotype relative to controls (4/5 OR, 2.1; 95% CI, 0.9–4.8; 5/5 OR, 5.1; 95% CI, 1.4–18.1; 4/5+5/5 OR, 2.5; 95% CI, 1.7–5.4). Examination of the Oncomine microarray database indicated lower PERIOD gene expression in adenomas relative to adjacent normal tissue. Results suggest a need for follow-up in a larger sample.

Results from the present study suggested strong relationships between oil and oil dispersant exposures and acute respiratory symptoms among disaster responders. Future prospective studies will be needed to confirm these findings.