Reality Versus Grant Application Research "Plans".

This article describes the implementation of the American Indian mHealth Smoking Dependence Study focusing on the differences between what was written in the grant application compared to what happened in reality. The study was designed to evaluate a multicomponent intervention involving 256 participants randomly assigned to one of 15 groups. Participants received either a minimal or an intense level of four intervention components: (1) nicotine replacement therapy, (2) precessation counseling, (3) cessation counseling, and (4) mHealth text messaging. The project team met via biweekly webinars as well as one to two in-person meetings per year throughout the study. The project team openly shared progress and challenges and collaborated to find proactive solutions to address challenges as compared to what was planned in the original grant application. The project team used multiple strategies to overcome unanticipated intervention issues: (1) cell phone challenges, (2) making difficult staffing decisions, (3) survey lessons, (4) nicotine replacement therapy, (5) mHealth text messages, (6) motivational interviewing counseling sessions, and (7) use of e-cigarettes. Smoking cessation studies should be designed based on the grant plans. However, on the ground reality issues needed to be addressed to assure the scientific rigor and innovativeness of this study.

Evidence for a second messenger function of dUTP during Bax mediated apoptosis of yeast and mammalian cells.

The identification of novel anti-apoptotic sequences has lead to new insights into the mechanisms involved in regulating different forms of programmed cell death. For example, the anti-apoptotic function of free radical scavenging proteins supports the pro-apoptotic function of Reactive Oxygen Species (ROS). Using yeast as a model of eukaryotic mitochondrial apoptosis, we show that a cDNA corresponding to the mitochondrial variant of the human DUT gene (DUT-M) encoding the deoxyuridine triphosphatase (dUTPase) enzyme can prevent apoptosis in yeast in response to internal (Bax expression) and to exogenous (H(2)O(2) and cadmium) stresses. Of interest, cell death was not prevented under culture conditions modeling chronological aging, suggesting that DUT-M only protects dividing cells. The anti-apoptotic function of DUT-M was confirmed by demonstrating that an increase in dUTPase protein levels is sufficient to confer increased resistance to H(2)O(2) in cultured C2C12 mouse skeletal myoblasts. Given that the function of dUTPase is to decrease the levels of dUTP, our results strongly support an emerging role for dUTP as a pro-apoptotic second messenger in the same vein as ROS and ceramide.

A randomized trial to reduce smoking among American Indians in South Dakota: The walking forward study.

BACKGROUND: Lung cancer is an important public health issue, particularly among American Indians (AIs). The reported decline in tobacco use for most racial/ethnic groups is not observed among AIs. This project was designed to address the research question, "Why don't more Northern Plains American Indians alter tobacco use behaviors known to increase the risk of cancer?" METHODS: Guided by the Theory of Planned Behavior, a multi-component intervention study was implemented. Adult AIs, age 18 years or older and currently smoking, were enrolled. Eligible subjects were randomized to one of 15 groups and exposed to either a MINIMAL or an INTENSE level of 4 intervention components. The intervention was delivered face-to-face or via telephone by Patient Navigators (PN). The primary outcome was self-reported abstinence from smoking verified by carbon monoxide measurement. RESULTS: At 18 months post-quit date, 88% of those who were still in the study were abstinent. This included 6% of all participants who enrolled in the study (14/254) and 13% of those who made it to the quit date (14/108). No intervention groups were found to have significant proportions of participants who were abstinent from smoking at the quit date (visit 5) or primary outcome visit (18 months post-quit date, visit 11), but use of pharmacologic support for abstinence was found to be an effective strategy for individuals who continued participation throughout the study. Those who remained in the study received more visits and were more likely to be abstinent. CONCLUSIONS: Use of NRT increased the odds of not smoking, as assessed at the 18-month follow-up visit, but no other interventions were found to significantly contribute to abstinence from smoking. Although the intervention protocol included numerous points of contact between CRRs and participants (11 visits) loss to follow-up was extensive with only 16/254 remaining enrolled. Additional research is needed to improve understanding of factors that influence enrollment and retention in smoking cessation interventions for AI and other populations.

Linking growth, survival, and heterogeneity through vitality.

We model the cross-stage effect of juvenile growth on future cohort survival with vitality, a single stochastic measure of an organism's survival capacity that results in death when it reaches 0. In this construct, the distribution of vitality at the end of a growth treatment stage, which is a measure of survival capacity heterogeneity, determines a cohort's susceptibility to starvation in a subsequent challenge stage. The model predicts that the treatment-stage duration and mass gain determine the mean and variance of the initial vitality distribution of the challenge stage, which in turn determine the effect of a challenge-stage stressor on survival. Studies linking the effect of juvenile growth on time to starvation for chinook salmon and yellow perch are compared to model predictions. The feasibility of predicting survival and heterogeneity in overwintering fish populations from first-year growth is considered. Some limitations and potential extensions of the model to other scenarios are discussed.

Dynamic plantar pressure parameters associated with static arch height index during gait.

BACKGROUND: Although extreme values of arch height have been associated with increased risk for overuse injury, knowledge is limited regarding the association between arch height and plantar pressure distributions during gait. The primary purpose of this study was to explore which plantar pressure measurements during gait were associated with static arch height and arch height index. METHODS: Static arch height, arch height index, and dynamic plantar pressure distributions were collected for 1000 subjects (566 males, 434 females, 30.6 [SD 8.0] years, 171.1 [SD 9.3]cm, 76.9 [SD 14.7]kg). A hierarchical regression analysis was performed to determine the most parsimonious set of plantar pressure parameters associated with arch height. The predicted values were used to calculate dynamic arch height index. Correlation and residual analysis were performed to assess the association between statically and dynamically determined arch height indices. FINDINGS: A 5-variable model (F = 296.6; P < 0.001) was able to describe the relationship between static arch height and the dynamic foot during gait (R =0 .77 [95% CI = 0.75-0.80]). The correlation between the static and dynamically determined arch height indices was r = 0.60 (95% CI = 0.53, 0.63), with a mean residual of 0.000 (SD 0.015). INTERPRETATION: A multivariate model generated by plantar parameters during gait was able to predict 60% of the variability in static arch height. This model consisted of variables that appear to be clinically plausible and inform the association between static arch height and dynamic foot posture. Future researchers should address the association between statically and dynamically determined AHI values with lower extremity overuse injuries.