David Hammond - US grants

Various neurodegenerative and developmental disorders of unknown etiology characteristically affect specific neural systems. These diseases have been hypothesized to involve defects in trophic interactions that are essential for maintaining the connectivity of a particular system. In order to study the role of trophic influences in the development and maintenance of cholinergic innervation of cortex, and to provide insight into the selective vulnerability of cholinergic neuronal networks in neurologic disease, the experiments outlined in this proposal will employ clonal cell lines and rotation-mediated culture methods to study the trophic interactions between cholinergic neurons of the septal region of the basal forebrain and their target cells in the hippocampus. In preliminary studies, cell lines expression specific cholinergic and neuronal characteristics, including choline acetyltransferase and neurofilament expression, neurite formation, and the ability to aggregate in rotation-mediated culture, have been derived from septal cells using somatic cell fusion techniques. Recently, clonal cell lines have also been derived from hippocampal target areas. In preparation for studies employing these lines in conjunction with the rotation-mediated culture system, the target-specific influences of primary hippocampal cells on primary septal cholinergic cells in that culture system will be further characterized. Studies will be performed to extend the initial observation that mouse embryonic hippocampal cells, in contrast to nontarget cerebellar cells, enhance septal cholinergic cell survival and fiber proliferation in reaggregate cultures, and promote the formation of synaptic contacts by septal cholinergic cells with identified target cell populations. The hybrid cell lines will be further characterize with respect to the expression of additional cholinergic markers. The capacity to respond to target-specific influences on fiber proliferation and synapse formation and maintenance will be assessed, as will responsiveness to nerve growth factor (NGF). Permanent cell lines have also been derived from hippocampal target areas. These will be characterized and screened for the expression of either NGF- or non-NGF-mediated trophic effects on both primary septal cholinergic neurons and cholinergic cell lines. If any of the hippocampal cell lines exhibit facilitory effects that are not attributable to NGF, the relevant macromolecule(s) will localized to a particular subcellular fraction. The active fraction will be employed to prepare specific antibodies, and through iterative immunization techniques, the relevant macromolecule(s) will be isolated and partially characterized. These studies will provide a clearer understanding of the factors involved in the formation and maintenance of specific connections between basal forebrain cholinergic neurons and their cortical targets, and important insights into the possible causes of neuronal loss and dysfunction in disorders affecting this central cholinergic system.

The primary goal of Project 2 is to build the evidence base in the area of tobacco packaging and labeling policies (Article 11 of the FCTC), in low, middle, and high income countries. Project 2 will complement the survey data described in Project 1 by collecting information directly from tobacco packages and by conducting experimental studies in

DESCRIPTION (provided by applicant): Excess body weight is a risk factor for a range of chronic diseases. Currently, more than two thirds of US adults are obese or overweight, with increasing rates of childhood obesity. The medical costs of overweight and obesity have been estimated at $169 billion per year, and even modest population-level reductions in calorie intake of 100 calories per day could save as much as $58 billion. Increasing calorie intake outside the home at fast-food and other restaurants has contributed to the rise in obesity. In 2013, the US will become the first country in the world to implement federal regulations requiring nutritional labeling on menus. The regulations mandate that calorie amounts appear on menus next to the price and that additional nutrient information be made available at the point-of-sale. The regulations will apply to chains of 20 or more restaurants, which account for the vast majority of restaurant visits in the US. The federal menu labeling regulations will establish a new international precedent and are among the most significant policy interventions in nutrition education since mandated nutrition information on pre-packaged foods. Six US states and several cities have already implemented similar policies. The primary objective of the current study is to examine the population level impact of nutritional information on menus on dietary patterns using a pre-post quasi- experimental design in which baseline and follow-up measures will be conducted in the US and Canada, which will serve as the control group given that no regulations have been implemented or are planned. The study will consist of nationally representative phone surveys at pre and post, and face-to-face exit surveys of restaurant patrons at pre and post. First, population-based telephone surveys will be conducted with representative samples of 1,000 participants in both jurisdictions before and after the implementation of the federal menu regulations, scheduled for late 2012, early 2013. Exit surveys will also be conducted with 1,000 participants before and after implementation in each of four paired cities: Seattle-Vancouver, and Chicago- Toronto. Seattle is among the US jurisdictions that have previously implemented menu labeling regulations. Exit Surveys will be conducted with patrons of 5 full service and 5 fast-food restaurants at two locations in each city. The representative phone surveys and Exit Surveys will be conducted during the same period (before and 12 months after implementation) using parallel measures to assess the extent to which the data from Exit Surveys can be generalized to the population level. Note that baseline data collection has already been conducted: funding is requested for follow-up data collection only. Overall, the current study has the potential to make important contributions to the evidence base on nutritional labeling and to evaluate a novel policy measure for preventing obesity. The study will help to establish whether requiring nutritional information on restaurant menus modifies intake, including whether the effects may differ among sub-populations.

PROEJCT SUMMARY/ABSTRACT The global nicotine market is rapidly evolving due to the emergence of vaporized nicotine products (VNPs). Regulators are considering a range of policies to minimize youth uptake of VNPs, particularly with regards to restrictions on forms of promotion and product attributes that may enhance appeal among youth. The current project seeks to increase the understanding of the factors that predict VNP uptake among youth and to examine policy measures that may prevent uptake among non-smokers. Specific aims include: 1) to examine international variations in VNP uptake among youth in the US, Canada, and England; 2) to estimate the influence of policy measures on consumer demand for VNPs among youth, using methods from the fields of marketing (discrete choice experiments) and economics (auction experiments); and, 3) to develop the methodological framework for policy evaluation and pre-market testing of nicotine products. Prospective cohort surveys will be conducted at baseline and 12-month follow-up among youth (aged 14 to 18) in three countries: the US (n=9,000), Canada (n=9,000), and England (n=9,000). Participants will be recruited through Neilsen's consumer panel, using the same methodology across the three countries. Quotas will be used to recruit equal proportions of ?never? smokers and ?experimental? smokers in each country. After completing baseline survey measures, participants will be randomized to one of the following: 1) a discrete choice experiment, 2) an auction experiment, or 3) a ?no experiment? control condition. The discrete choice experiment and auction experiments will be used to assess the overall level of VNP demand for each participant, as well as to test how promotion and product attributes affect VNP demand. Due to the number of attributes that will be tested, the project will be conducted in two sequential studies, with separate cohorts used in each study. Study 1 (n=4,500 in each country) will examine the influence of five product attributes: product type, nicotine level, flavor, brand, and price. A separate cohort will be recruited using the same methods for Study 2 (n=4,500 in each country), which will examine the influence of three promotional attributes? advertisements, modified risk claims on packaging, and health warnings?in the context of price and product type. Analyses will consist of the following: 1) tests between countries to examine differences in VNP uptake between baseline and follow-up; 2) analysis of the discrete choice and auction experiments at baseline to estimate the effect of product and promotional attributes on consumer demand; 3) tests to examine which of the baseline measures is best able to predict individual-level VNP uptake at 12-month follow-up: measures of susceptibility assessed in the ?no experiment? control group, or aggregate measures of demand from the discrete choice and auction studies. Overall, the proposed project would be the first to directly compare differences in VNP uptake among youth across countries. The project also has the potential to advance the methodological framework for predicting youth uptake and estimating the efficacy of policy measures prior to their implementation.