John Hughes - US grants

This is an application for an ADAMHA RSDA (Level 1). While the candidate has published experimental work and obtained research funding, a full clinical load as a staff physician and little formal training in research techniques have hampered his development as a research scientist. This RSDA will help the candidate become a full-time researcher by relieving him of his clinical duties and providing research training and experience. The specific aim of the RSDA will be to provide the candidate with a working knowledge of a variety of methodologies and concepts applicable to research on smoking as a dependence process. The main site for the training and research experience will be the Departments of Psychiatry and Psychology at the University of Minnesota. Both departments have several investigators in drug dependence and have a long history of research in the area. The sponsor will be Roy W. Pickens, Ph.D., a Professor in both departments who has extensive experience in training and research in drug dependence. The training will consist of 1) didactic course work, primarily in behavioral pharmacology, drug abuse and tactics of scientific research, 2) collaboration with faculty in ongoing research projects and 3) participation in the existing NIDA training program in drug dependence. In addition, off-site training will occur at the NIDA Addiction Research Center (supervised by Jack Henningfield, Ph.D.) and the Addiction Research Unit of the Institute of Psychiatry in London (supervised by M.A.H. Russell, M.D.). The research experience will consist of participation in 17 studies in 4 areas in which the candidate has aleady begun working: 1) nicotine self-administration, 2) measurement of smoking behavior, 3) tobacco withdrawal, and 4) use of nicotine gum in smokers. With these studies, the candidate will learn a variety of research strategies (from laboratory psychophysiology to clinical studies in physicians' offices). Most of the studies (14 of 17) will be funded from 5 existing NIDA and NCI grants. Evaluation of the RSDA will be by a team of local advisors. In addition, an established investigator will visit the institution annually to review the career development of the candidate. This RSDA will provide the time, training and research experience necessary for the candidate to develop a full-time research career in smoking as a dependence process.

Nicotine gum has been recently approved as a prescription drug to help smokers stop smoking. Despite both theoretical and clinical evidence that a substantial proportion of patients will persist in chronic use of the gum, a study of the self-administration properties of the gum has not been performed. In the first study of this proposal, the patterns of self-administration of nicotine gum will be determined among smokers seen in a general medical practice who follow FDA-approved guidelines for gum use. This study will use a double-blind placebo-controlled design to determine the incidence of chronic use of gum after the prescribed period and the relationship between chronic use and behavioral factors (e.g., history of abuse of other drugs. A second set of studies will test whether factors that control the self-administration of other drugs of abuse also control self-administration of nicotine gum. The factors to be studied are (1) dose (1 vs. 2 vs. 4 mg gum), (2) response cost (free vs. half price vs. full price gum), (3) schedule of self-administration (i.e., ad-lib vs. fixed times), and (4) duration of exposure (1 vs. 2 vs. 3 mo.). The studies proposed will provide the first experimental determination of how nicotine gum is actually used, the incidence of chronic use of the gum, and factors that can be used to identify smokers at increased risk of chronic use (Study 1), as well as prescription practices that can be used to reduce chronic use of nicotine gum (Studies 2-5).

This study will test whether abstinent smokers who experience intense withdrawal are more likely to relapse to smoking than abstinent smokers who experience little withdrawal. Most smokers who quit on their own relapse in the first two weeks. Whether this is due to aversive withdrawal symptoms (e.g. irritability) is unknown because prior studies have had several major flaws; e.g., retrospective designs, nongeneralizable samples and unvalidated, self-report measures of withdrawal. We have experimentally documented several physiological signs and observable behaviors that reliably occur upon cessation of smoking and have the characteristics of classical withdrawal syndromes. We now propose to prospectively test the ability of these withdrawal variables to predict relapse in self-quitters. 1000 smokers who are about to quit on their own will name a reliable observer to rate their withdrawal behavior. These observer ratings plus weight, heart rate, and self-reported symptoms will be recorded prior to and 2, 14 and 30 days after subject quit. One year later, salivary cotinine will verify whether smokers have relapsed. We will test the hypothesis that among smokers who quit for 2 days, those with more intense withdrawal are more likely to relapse by one year follow-up. The results of this study will be a crucial, direct test of the nicotine dependence theory of smoking. The results will also encourage or discourage the development of smoking treatments designed to combat withdrawal symptoms.

Vanadium is considered by many to be the most difficult element to characterize geochemically because of its low crustal abundance and its existence in three valence states under geologic conditions. Vanadium minerals are typically poorly-crystallized, and its isolation of samples suitable for crystal structure studies has historically proved difficult; thus, our knowledge of the crystal-chemical behavior of vanadium has not kept pace with other mineral groups. The research proposed will produce crystal structure solutions or refinements of several vanadium minerals and related minerals. The first will be the lead apatites, the second brackebuschite and gamagarite, and the final portion of the project will be the determination of the crystal structure of ziesite, a high-temperature vanadium mineral.

Over 90% of Americans drink caffeinated beverages daily. Caffeine appears to fulfill several criteria for a drug of dependence; i.e., it can produce: 1) adverse effects (e.g. arrythymias, insomnia, etc.), 2) physical dependence (e.g. withdrawal symptoms of headache and fatigue), and 3) behavioral effects that might be rewarding (e.g. decreased fatigue and improved performance). However, whether caffeine fulfills the most crucial criteria for dependence potential - ability to serve as a reinforcer - is debatable. For example, whether coffee drinkers will consistently self-administer caffeinated coffee in preference to decaffeinated coffee has only begun to be studied. The ability of a drug to function as a reinforcer is highly dependent on pharmacological, environmental and behavioral conditions. This application proposes six parametric studies to determine conditions under which caffeine will serve as a reinforcer. We will test dose (25, 50, 100, & 150 mg), present history of drug use (heavy users, light users & abstainers), vehicle (coffee, non-coffee beverage & capsules), instructions (told beverage does or does not contain caffeine), fatigue (after normal sleep vs. after sleep deprivation) and method of testing (concurrent access vs. exclusive choice tests). These studies will help NIDA deliver rational public information about whether coffee drinking is a drug dependence. They will also help devise treatments for those who need to abstain from caffeine but have difficulty doing so. Finally, the studies will test whether commonalities across forms of substance abuse can be extended to coffee drinking.

The calcium phosphate apatites are found in igneous, metamorphic, and sedimentary rocks. Interest among geologists in these minerals has increased in recent years, especially as indicators of geologic environment. Recent investigations by the P.I.'s indicate that many aspects of the crystal structures of natural apatites are not well understood. The studies proposed are intended to elucidate the crystal structures of natural apatites. They will emphasize naturally-occurring apatites, whose chemistry falls within ranges of interest to geologists, and the resultant data will complement that already available in the published literature. The proposed research should be important to geologists who use thermodynamics, partitioning, diffusion and annealing properties of apatite minerals to gain insight into geologic processes.

Laboratory studies will develop methods to examine the reinforcing and discriminative effects of alcohol, caffeine and nicotine in humans, examine the effects of nicotine administration in smokers and nonsmokers, further characterize caffeine and nicotine withdrawal, describe the effects of combining stimulants (e.g. cocaine) and sedatives (e.g. alcohol) and test the effects of drugs on learning, performance and social interaction. Laboratory studies will also examine the influence of environmental, pharmacological, organismic (e.g. behavioral history and genetics) and procedural variables on the reinforcing, discriminative, and direct effects of drugs. Epidemiological studies will longitudinally study the process of smoking cessation in self-quitters, examine the prevalence of DSM-III-R defined caffeine and nicotine disorders, and test the association of nicotine dependence with past and present psychiatric disorders. Treatment studies will test new nicotine replacement and non-nicotine pharmacological treatments for nicotine dependence, as well as behavioral treatments for cocaine and nicotine dependence. Continued funding of the candidate will help develop the Human Behavioral Pharmacology Laboratory and allow the applicant to select only administrative, clinical and teaching activities that are consistent with his career goals and growth of the laboratory.

The Wrangell volcanic field (WVF) defines the northeastern- most expression of late Cenozoic volcanic activity associated wit plate convergence in southern Alaska. The primary goals of this research are: identification and characterization of mantle and crustal reservoirs responsible for WVF volcanism; quantification of the relative roles of these reservoirs in the evolution of WVF mafic silicic products; and evaluation of the relationships between magmatic evolution, mantle-crust interactions, and lithospheric structure and composition in the WVF as a model for understanding continental arc processes. In order to achieve these goals, combined field, petrographic, mineral chemistry, elemental (including REE), and isotopic (Sr, Nd, Pb) studies of eruptive products from three major WVF volcanic centers, Mount Drum, Mount Churchill, and Skookum Creek, are planned.

The fundamental crystal chemical behavior of REEs in minerals is not well understood. Among those minerals whose atomic arrangements are unknown or poorly characterized are the most common REE-bearing minerals, including 1) bastnaesite, the most abundant REE-bearing ore mineral, and its associated REE fluorcarbonates; 2) the common REE (PO4) "dimorphs", moazite and xenotime, and 3) high-Si monazite, of particular interest because substituent Si may play an important role in controlling the REE chemistry of monazites. Preliminary to this submission an extensive effort has been undertaken to obtain high quality specimens of these minerals in order to undertake high-precision crystal structure analysis of the phases. Preliminary film studies attest to the high quality of the crystals and ultimately assure success in the crystal structure studies. The results of these studies will help to elucidate the crystal chemical behavior of the REEs in the most common REE-bearing minerals.

9403194 Hughes This award provides 50 % of the funding necessary to acquire a new x-ray powder diffractometer that will be installed and operated in the Department of Geology at Miami University (Ohio). The University is committed to providing the remaining 50% of the cost of acquiring this instrument system. The new x-ray powder diffractometer will replace an outmoded 1970 instrument and will be the only such instrument on the Miami campus. The diffractometer system will be used in research projects that include : 1) structural studies of minerals, 2) studies of disorder in intermetallic alloys and their hydrides, 3) studies of minerals in the low-temperature weathering environment, 4) studies of the source and transport of carbonate sediments , and 5) investigations of clay minerals related to their use in potassium-argon and rubidium-strontium dating methods. The diffractometer will also be used in graduate and undergraduate teaching. ***

Over 85% of alcoholics smoke, most are heavy smokers and many die of smoking-related illnesses. Despite the recent interest of both patients and clinicians, experimental studies of treatment for smoking cessation among alcoholics are lacking. A post-hoc finding in an earlier study of ours suggests recovering alcoholic smokers are more dependent on and are especially benefitted by nicotine replacement therapy. We propose to prospectively test this finding by randomly assigning recovering alcoholics to group behavior therapy plus either nicotine or placebo transdermal patches in a double-blind manner. 200 Ss at two sites (VT & MN) will receive daily patches and weekly group therapy for 12 was. Biochemically verified smoking abstinence and observer- and self-ratings of nicotine withdrawal and craving will be obtained. These results with recovering alcoholics will be compared with those from smokers drawn from the general population who were tested with the exact same patch and protocol in an earlier study. We will also compare desire for alcohol and confidence in not relapsing back to drinking between our recovering alcoholics who are abstinent from smoking with a group of recovering alcoholic smokers who are not trying to stop smoking. Post-hoc analyses will be used to estimate the optimal timing pose-drinking for smoking cessation to occur. This trial will provide initial information on whether 1) transdermal nicotine plus group behavior therapy is an effective treatment for smoking cessation in recovering alcoholics, 2) recovering alcoholics are less likely to stop smoking in a smoking cessation program than smokers in the general population, 3) stopping smoking increases desire to drink alcohol or decreases confidence in not relapsing to alcohol, and 4) it is better to attempt smoking cessation soon after or long after achieving sobriety. Positive results would encourage recovering alcoholics to enter and their counselors to provide smoking cessation treatment.

APPLICANT'S ABSTRACT: This application is to renew a Research Scientist Development Award, Level 2 (K02) from NIDA. The goal of this RSDA is to free the applicant from clinical and administrative duties so he can conduct and acquire training in laboratory, treatment and epidemiological studies on nicotine and caffeine. Despite increasing public and governmental concerns around nicotine and caffeine use and dependence, to our knowledge, this is the only NIDA-funded RSDA that focuses on nicotine or caffeine. In the first 4 yrs of the prior KO2, the applicant published 108 articles, including articles in NEJM, JAMA and JPET, fostered growth of the University of Vermont, Human Behavioral Pharmacology Laboratory (HBPL), mentored several undergraduate graduate, post- graduate and medical students and several physicians served as a resource to the University of Vermont, the State of VT, NIDA and other federal agencies, the general public and the media on drug abuse matters, especially policy issues about nicotine and caffeine use. In the renewal the applicant proposes laboratory studies to test the conditions that control the reinforcing and subjective effects of nicotine and caffeine, nicotine and caffeine withdrawal, and the effect of nicotine and caffeine on the use of other drugs of abuse; treatment studies to test new nicotine and nonnicotine therapies for nicotine dependence both in the general population and in alcohol/drug abusers; and epidemiological studies to examine the utility of DSM/WHO generic criteria for drug dependence/abuse when applied to nicotine and caffeine. In addition, the applicant will continue collaboration with Drs. Bickel and Higgins in studies of alcohol, benzodiazepine, cocaine and opioid use/dependence.

9627222 Hughes This study will characterize the nature of chemical substitutions by precise diffraction data. The project involves three tasks: incorporation of REE in titanite, high-precision single crystal and Rietveld studies of LaNi5-ySny hydrides, and REE in naturally-occurring perovskite phases. Of particular interest in titanite is the accommodation of REE's and the concomitant charge-balancing substitution for the Ca+2 ( REE+3 exchange. Intermetallic compounds such as LaNi5 doped with varying amounts of Sn, are under intense multi-disciplinary investigation for use as hybrid hosts for H fuels and electrodes in high-performance batteries. High-precision crystal structure studies investigate the disorder in the phase as SN substitutes for Ni. Rietveld analysis of the atomic arrangements will be undertaken to overcome the pervasive twinning in perovskites that mitigates against solution/refinement by single crystal methods.

The major aim of this study was to determine whether one's past history of smoking or alcoholism is associated with a different response to nicotine. We tested this by exposing never, ex and current smokers to nicotine via nicotine gum and by exposing current smokers with and without a history of alcoholism to nicotine.

The subjective effects and degree of seeking or avoiding of nicotine will be compared among neversmokers (NS), ex-smokers (ES), current smokers (CS), and current smokers with a history of alcohol dependence. During a three-day exposure period, subjects receive three doses each day of either 0 mg, 2 mg or 4 mg nicotine gum in a double-blind, randomized crossover. Subjects provide subjective ratings (euphoria, liking, etc.) after each dose. On the fourth day, subjects (Ss) choose among the three types of gum to which they were exposed previously. Saliva samples will be analyzed in the GCRC Biochemistry Core Laboratory for levels of nicotine and cotinine.

9804768
Hughes
Site assignment of atoms in crystals with multiply-occupied atomic sites can be determined uniquely using the bond valence method. We find that site assignments in which the weighted calculated valence sums are closest to the weighted formal valences yield excellent agreement with the chemical analysis. For any crystal, the method requires structure data and electron count for the sites in question; furthermore, if chemical analyses are available, these data may be incorporated into the method. The method minimizes the sum of squares of the difference between observed and calculated bond valence sums and observed and calculated electron occupancy by varying the fractional site occupancy for each potential substituent; terms for modeling chemical analyses can also be added, and the optimum solution is calculated by minimizing valence energy. Granted funds will be used to evaluate the model itself and test it extensively on mineral examples. Furthermore, because the student supported by the requested funds is returning to science after a disabling stroke, an important outcome of the research will be observations of enabling science to the disabled.

DESCRIPTION: (Applicant's Abstract) Despite many years of education, social pressure, physician advice and effective treatments, the average smoker tries to quit only once every three years; thus, interventions to prompt smoking cessation are needed. This application tests whether a behavioral instruction program plus nicotine gum will induce a large and durable reduction in smoking and whether this will serve as a success experience and thereby prompt a quit attempt. Smokers who do not plan to quit smoking in the next month will be randomly assigned to one of four groups: non-specific therapy + brief advice to quit, a behavioral instructional program to reduce smoking + brief advice to quit, behavioral instructions to reduce + advice + placebo gum, or behavioral instructions to reduce + advice + nicotine gum. To increase generalizability, treatment will be delivered via written materials and five telephone contacts. Our major hypothesis is that both behavioral instructions to reduce and nicotine gum will each increase quit attempts over the ensuing 12 months. We will also test whether increased self-efficacy or the magnitude and duration of reduced smoking mediate any increase in quit attempts. Finally, we will monitor the safety of concurrent use of gum and cigarettes. The present application is not designed to test reduced smoking as a treatment for cessation among smokers trying to quit (i.e., "gradual reduction"). It also is not a test of reduced smoking as a goal in itself (i.e., "harm reduction"). Rather, the application focuses on using reduced smoking to prompt cessation. Current public health strategies discourage reduced smoking. If we show reduced smoking prompts quit attempts, it will suggest reconsideration of reduced smoking as an intermediary step toward quitting smoking.

DESCRIPTION: (Applicant's Abstract) Cigarette substitutes (CS) have been and continue to be developed. Although advertised for smokers concerned about secondhand smoke, many smokers may see these as safer cigarettes and alternatives to cessation. We will determine a) by whom, why and how such substitutes are used, b) whether CS use undermines motivation to stop smoking, and c) whether CS use (+/- cigarette use) produces less nicotine and toxin exposure than cigarettes. One survey and two experimental studies will examine the newest CS: Eclipse. We will survey 400 Eclipse users to determine their characteristics (e.g., level of nicotine dependence), reasons for purchase (e.g., to decrease risks of smoking), pattern of use (e.g., along with vs instead of cigarettes), etc. These users will be compared to 400 smokers who have not used Eclipse to determine who is attracted to CSs. Both groups will be followed for one year to determine whether the incidence of attempts to stop smoking is less in CS users than nonusers. Study 2 will enter 60 smokers interested in using a CS to an A-B-A design of smoking their normal cigarette for 3 weeks, followed by using Eclipse for 12 weeks, followed by a return-to-baseline for 3 weeks. The major dependent variables will be CS and cigarette use, cotinine, CO, SCN, withdrawal symptoms, product ratings, adverse events and vital signs. Whether or not Eclipse itself becomes a commonly used product, CSs are very likely to be marketed in the near future. We believe it imperative to begin studying these substitutes so that, unlike low-tar/low nicotine cigarettes, we will know whether their introduction is good or bad for public health.

Introdurtion and Objectives. Image-based rendering (IBR) is a relatively new computer graphics technique in which multiple images (either computer-generated or photographs) of a scene are modified and combined to produce an image representing a novel view of the scene. The resulting images often have great detail but are sometimes incorrect, partly because of the lack of an underlying geometric model. Traditional graphics, by contrast, uses geometric and lighting models to generate correct views of a scene from an arbitrary view-point; but because of modeling costs, they often lack detail.
An ideal geometric model would have both the complete geometry of the object plus a BRDF (bidirectional reflectance distribution function) at every point on the surface to describe how light interacts with the object, allowing computation of any view of the object under any lighting conditions. A simple approximation to this ideal is a geometric model with a single color; texture maps improve this approximation by mapping an image onto the geometry. This project is to devlop a new modeling paradigm, based on IBR, that extends this idea further by adding an approximation to the BRDF at every point on the surface.
This new modeling paradigm improves upon the efficiency of generating and storing image-based rendering models by combining them with geometric model information, thus bridging the gap between the two methods. The intent is to construct geometric models which are visually complex and geometrically faithful, but avoid the overhead of geometrically modeled surface detail.
Just as important as developing an underlying model is the ability to use real-world objects to create the models. Many of today's complicated geometric models were captured, using a laser scan or a 3D digitizer, from physical objects. One goal of this research is a similar mechanism for capturing and rendering objects or scenes with complex visual properties.

Methods. The two disciplines to be merged are image-based rendering and geometric modeling. The project will use the lumigraph for IBR, partly because it already incorporates a limited geometric model, and will use a manifold-based models for the geometric component. The lumigraph is a very general method for capturing the behavior of light as it leaves an object. Manifold-based geometry supports construction of arbitrary-topology surfaces by blending small surface pieces. The result of combining a lumigraph with a manifold is a geometric model that has information about how light rays are emitted from it.
With this structure, any local constancy in emitted light along the surface is easily recognized, leading to considerable data-compression advantages. Thus, in addition to an interesting geometric model, this structure allows for efficient storage of IBR datasets. This same local-constancy can be used as a guide to goodness-of-fit of the surface to the actual geometry of the object being modeled. Each of these operations requires a homogeneous representation of the underlying geometry - one in which all of the points can be treated equally, rather than, for example, the division of the points into the vertices, edges, and faces of polyhedra, or the abutting patches of B-spline models. The manifold structure provides exactly this homogeneity.

Impact. Many image-based rendering approaches use some knowledge of geometry, usually depth. The addition of explicit geometry object has two potential benefits; a richer modeling type, in which global lumigraph-like data is attached to a geometric foundation, and a means for explicitly exploring the relationship between geometry and the compression of data gathered from images.
The resulting models will be useful in multiple applications, particularly those in which high image quality is essential, but where explicit modeling is impossible. These include special-effects production and educational applications (e.g., on-line medical models), as well as possible applications in reverse engineering and architectural lighting simulation.

DESCRIPTION: (Applicant's Abstract) This Research Scientist Award (K05) will a) generate research on interventions for smokers who are and are not currently interested in quitting and b) assist professional (e.g. SRNT) and governmental (e.g. WHO) organizations interested in tobacco control. The applicant's past research contributions include description of the nicotine withdrawal syndrome, psychiatric comorbidity, the role of expectancies in nicotine effects and caffeine reinforcement and dependence in humans. In the last K02, the applicant averaged 17.2 papers/yr of which he was first author on 12.2/yr and of which 6.2/yr were empirical studies. He founded the Human Behavioral Pharmacology Laboratory (HBPL) at UVM and cofounded the Society for Research on Nicotine and Tobacco (SRNT). This K05 will examine interventions for smokers not interested in quitting: i.e., reduced smoking, using Eclipse, and offering free samples of NRT to use during smoking restrictions or during "test quits." The K05 will also investigate interventions for smokers currently interested in quitting. i.e, it will compare gradual vs abrupt, group vs individual and patient-vs expert-chosen interventions and interventions for treatment-resistant smokers. The K05 will include assisting other drug abuse researchers at UVM. The applicant will continue to mentor 4-6 students/yr and to explore new disciplines (e.g., diagnostic nosology) and methodologies (e.g. Markov models, IVR technologies). This would be the first NIDA K05 to focus on nicotine dependence.

0003201
Hughes

This grant provides partial support for a single crystal x-ray diffractometer with a CCD detector, to be housed in the X-ray crystallography laboratory at Miami University, Ohio. The PIs, John M. Hughes, John Rakovan, and Hailiang Dong, are all from the Department of Geology. The group includes a mid-career researcher with extensive single-crystal x-ray experience, and two early-career researchers with expertise in emerging areas of the Earth Sciences (mineral surface structure and biomineralization). Miami University students will be extensively involved in the studies to be undertaken.

The addition of the CCD-detector diffractometer at Miami University will allow the investigation of samples that were previously too small for characterization through x-ray structure analysis. The instrument will be used to investigate material properties of natural materials such as apatite, tourmaline, clay minerals, and biominerals. The studies are of importance in the studies of environmental mineralogy, medical mineralogy, earth science, and the formation of minerals by organisms. The facility will also by used by other researchers on a time-available basis. The instrument will be housed in a newly renovated room in Hughes Hall on the Miami campus, and will complement the existing powder x-ray diffraction equipment, atomic force microscope, and single-crystal x-ray cameras. In addition to support from the Earth Sciences Instrumentation and Facilities Program (EAR/IF), matching funds are provided by the State of Ohio and Miami University.

***

This proposal will improve techniques used by the fifteen SuperDARN radars to determine in real-time the critical frequency and layer height at the ionospheric reflection point. These observations will be made over large geographical regions that are currently sparsely sampled by ionosondes. This effort represents a new use of the SuperDARN system in "sounding mode." This new mode of operation has been developed and implemented by the PI at the Kodiak radar. The sounding mode exploits the pause time (~10 sec) during the normal azimuth scan mode, making use of ground reflections to determine the skip distance of rays at various frequencies. By determining how the skip distance varies with frequency, it will be possible to find the maximum useable frequency as a function of ground range. The PI's main goals involve six distinct research activities: (1) modification of current SuperDARN software to include angle-of-arrival (AOA) information in the real-time data stream; (2) use of sounding mode data to determine real-time ionospheric critical frequencies and layer heights; (3) use of critical frequency determinations to observe, track, and study the dynamics of large-scale high latitude ionospheric density irregularities; (4) distribution of SuperDARN real-time foF2 values and virtual heights to the space weather community via the internet; (5) continued development of the SuperDARN sounding mode technique; and (6) use of sounding mode data to optimize the operating frequency at each SuperDARN radar.

The auroras are characterized not only be a variety of active optical emissions, but by a wide variety of radio emissions as well. The relationship between different optical features and different radio features, however, is poorly understood. Wave phenomena in the auroral regions play an important role in the energy flow between the magnetosphere and the ionosphere. In order to understand the relationships between optical and radio phenomena in the auroral region it is necessary to monitor the region with a variety of instruments. This project will utilize data from optical imaging instruments, radar backscatter from auroral features, and plasma wave, electric field, magnetic field and particle measurements from satellites crossing the auroral regions. Satellites which will be used in the study include the defense department DMSP satellites, NASA's FAST, WIND, POLAR, SAMPEX, and IMAGE satellites, and the European CLUSTER mission. A ground-based radio imaging system will be used to locate the regions producing auroral Medium Frequency (MF) radio emissions. The investigation will also contribute to studies of the timing and location of magnetic substorm onsets. The radio imaging instruments will be deployed at existing facilities in Alaska and Greenland. The data will be made available to all researchers, including those using the Alaska and Greenland facilities. The research project will also be integrated with educational activities being carried out by the three collaborating institutions (Dartmouth College, Siena College, and the Univ. of Alaska). In particular the educational effort at Dartmouth will include a focus toward the Dartmouth Women-in Science-Program (WISP). Students will be involved with both the engineering aspects of the new instrumentation as well as the analysis of the resulting scientific data.

Apatite, Ca10(PO4)6(F,OH,Cl)2, can accommodate numerous substituents, including many radionuclides of environmental concern (90Sr, 90Y, REE, U and Th). Scores of studies have focused on the crystal chemistry of substituents in apatite; surprisingly, however, little is known about the mechanisms of incorporation and the structural response of apatite to U and Th, despite the fact that the presence of these elements in this mineral has been used in geochronologic and petrogenetic studies for decades. This two-part study focuses on fundamental mineralogical and geochemical aspects of U and Th incorporation in apatite and implications for apatite as a solid nuclear-waste form and a metal sequestration agent.
Interest in apatite as a potential solid waste form for radionuclides is based on: 1) its high affinity for elements of environmental concern; 2) its thermal annealing properties; and 3) its relatively low solubility in most surface environments. Fundamental to our understanding of radionuclide retention and release are crystal chemical parameters such as site preference, oxidation state, and structural distortions/symmetry-breaking created by substituents such as U and Th; surprisingly, the crystal chemistry of their substitution in apatite is unknown. Part I of this study is to determine these structural parameters in a variety of natural and synthetic apatites with substituent U and Th. This will be accomplished through complementary use of crystal synthesis, single crystal X-ray diffraction, and X-ray absorption spectroscopy.
Part II of this study focuses on the role of precursor calcium phosphate phases on the uptake of U, Th and other metals and the fate of these contaminants through structural transformations in these sequestered states. Use of apatite formation in contaminated sediments (sometimes called phosphate-induced metal stabilization, PIMS) is a new and promising method for metal sequestration (including radionuclides) and environmental remediation. Numerous experimental studies of apatite formation under the temperature and pH conditions found in sediments and soils indicate the formation of precursor phases such as OCP (octacalcium phosphate) and brushite is essential to the process. This fundamental aspect of apatite formation under surface conditions has not been addressed in the context of metal sequestration and fate. This has critical bearing on the effective use of apatite for metal immobilization and our understanding of the role of phosphate in the global geochemical cycling of heavy metals. Part II of the study will be accomplished through a combination of 1) low-temperature synthesis in the presence of U, Th and other metals with in situ (time-resolved synchrotron X-ray diffraction) and 2) ex situ chemical and structural analyses including Rietveld structure analysis and X-ray absorption spectroscopy.
This work has broad environmental implications (heavy-metal and radionuclide sequestration) that are of immense importance to a society that generates radioactive waste. The research will include the participation and education of undergraduate and graduate students, as well as support the ongoing research of a Postdoctoral Fellow at Miami University.

The Kodiak Super Dual Auroral Radar Network (SuperDARN) is an international project of scientific radars used for studies of the high-latitude auroral environment. The radar detects echoes from irregularities of the ionospheric plasma, which are generated in abundance in the high-latitude regions. These plasma irregularities also scatter the signals of other radars and interfere with their normal operation. Auroral clutter is a major problem in high-latitude regions. This project would lead to the installation of direct digital synthesizers on each element of the radar transmitters. This will enable the formation and transmission of a beam pattern that can be designed to suit either experimental aims or environmental conditions. The experiments will determine whether or not it is possible to mitigate the effect of the auroral plasma on radar reception, as well as enable the discrimination of signals different from the background ionospheric scatter.

The Super Dual Auroral Radar Network, or SuperDARN, is an international collaborative experiment for observations of plasma convection in the Earth's ionosphere. By observing ionospheric plasma motion, a multitude of geophysical processes can be studied. These processes range from E-region plasma instabilities, to the relationships between auroral luminosity and electric fields, to the global-scale convective response to changes in the solar wind and interplanetary magnetic field. Each of these areas of study contributes to the overall goals of space physics: developing an understanding of the coupling of energy from the solar wind into Earth's upper atmosphere and its effects on man or manmade systems. Currently, SuperDARN covers nearly 15 hours of local time in the northern hemisphere, and close to 12 hours in the southern hemisphere. As the network has grown and demonstrated its potential, the number of scientist working with SuperDARN data has increased annually as has the number of scientifically significant publications. Addressing many of the goals, however, requires larger-scale coverage. Specifically, the continuous monitoring of convective flows requires radar observations that circumscribe the magnetic poles. The radar proposed for South Pole Station, along with the other new radars currently being proposed by our international collaborators for other locations on the Antarctic continent, will achieve this goal in the southern hemisphere.
Under the proposed program, the HF radar will be constructed Amundsen-Scott South Pole station. Data from the radar will be used, in conjunction with data from the rest of the SuperDARN network and the wealth of other space physics instruments in Antarctica, to study a variety of topics, including: responses of global convection to solar wind and IMF changes, plasma entry into, and exit from, the polar cap, and the accompanying response of the magnetotail, magnetospheric cusp response to changes in the solar wind, the motions of plasma patches through the polar cap, mesospheric winds, and thermospheric gravity waves. In addition, by establishing global-scale coverage in the southern hemisphere, the radar will help addressing questions about geomagnetic conjugacy, and the differences caused by the asymmetry of solar illumination. There are two main areas of broader impact in this proposal. First, as an international network of radars, SuperDARN fosters collaboration among member nations. There are currently eight nations that support SuperDARN work in Antarctica. It plays an important role in space physics research programs in each of these nations. The international cooperative scientific effort fostered under this program will have broad societal impacts. Another broader impact aspect of this proposal is its contribution to the education of the next generation of space physics scientists. Over the lifetime of the program, it will contribute to the education of a number of students and postdoctoral fellows.

DESCRIPTION (provided by applicant): This revised competing continuation tests whether a gradual reduction treatment we found effective for smokers not interested in quitting in our prior grant period will also be effective as a treatment for smokers who are trying to quit. Most treatment guidelines, reviews and tobacco control programs recommend abrupt cessation over gradual cessation yet many smokers prefer to quit gradually. Although recent work suggests gradual cessation may be effective, the five experimental studies of gradual vs. abrupt cessation have produced inconsistent results and had methodological problems such as small sample sizes. We hypothesize gradual cessation is more efficacious than abrupt cessation when aided by nicotine replacement. We will randomize 750 smokers to receive gradual cessation counseling (aided by pre-cessation nicotine lozenge) vs. abrupt cessation counseling vs. no counseling prior to the quit date. The first two conditions will receive 60 min of phone counseling prior to the quit date. After the quit date, all three conditions will receive nicotine lozenge for cessation and one 10 min counseling phone call. Our major outcome will be 6-month prolonged abstinence. We also hypothesize that significant adverse events are not greater when using lozenge with gradual cessation than with abrupt cessation. Prior to the trial, pilot work will include focus groups, a small survey, development of treatment manuals, recruitment strategies and mediator measures and a pilot rehearsal of the final protocol. This revision adds procedures to increase and verify treatment fidelity and decreases the number of differences between the two active treatment groups. If we find gradual cessation produces higher quit rates than abrupt cessation, this would suggest cessation services should encourage gradual cessation. If we find abrupt cessation is superior to gradual cessation, this would be the most comprehensive verification of the current practice of recommending abrupt cessation for all smokers. If we find gradual and abrupt cessation produce similar outcomes and if gradual cessation counseling is better than no counseling, this would suggest gradual cessation should be offered to those who request it. This study will be the first large, systematic test of gradual vs. abrupt cessation.

DESCRIPTION (provided by applicant): This competing continuation of a Senior Scientist Award (K05) will allow the applicant to conduct research on cessation and reduction of tobacco and marijuana use and on new methods to treat nicotine and cannabis dependence. The K05 would allow the PI to continue leadership roles in organizations interested in tobacco research and tobacco control and to continue science education activities such as mentoring and teaching. The applicant's past research contributions include description of the nicotine withdrawal syndrome, psychiatric co-morbidity with nicotine dependence, abuse liability of nicotine replacement, the role of expectancies in nicotine effects, caffeine reinforcement and dependence, and harm reduction approaches to nicotine dependence. The applicant founded the Human Behavioral Pharmacology Laboratory at the University of Vermont (UVM) and co-founded the Society for Research on Nicotine and Tobacco and the Association for the Treatment of Tobacco Use and Dependence. In the prior K05, the applicant averaged 13 published papers/yr of which he was first author on 9/yr and of which 7/yr were empirical studies. UVM has several resources to aid the applicant to learn new disciplines and methods; e.g. UVM currently has 25 NIH grants on drug abuse across 13 Pis. This continuation proposes tobacco studies to a) compare the efficacy of NRT-assisted abrupt vs gradual cessation, b) test a cannabinoid antagonist for smoking cessation, c) test a computer mediated clinical decision support system to help clinicians treat tobacco dependence, d) describe why the large majority of smokers do not seek free treatment and e) comprehensively review the world literature on the nicotine withdrawal syndrome. The continuation proposes a new line of research on marijuana to f) describe the natural history of attempts to stop or reduce marijuana use, g) determine if the marijuana withdrawal syndrome is due to THC deprivation, h) directly compare the clinical significance of marijuana and tobacco withdrawal syndromes, i) describe marijuana withdrawal in treatment seekers and j) describe marijuana withdrawal in adolescent marijuana users. The continuation will also include collaborating with other drug abuse researchers at UVM and elsewhere. The applicant will continue to mentor 4-6 students/yr and to be actively engaged in media and policy initiatives.

DESCRIPTION (provided by applicant): The purpose of this grant is to discover the most important attitudes and beliefs (i.e., internal barriers) that prevent smokers from seeking treatment; e.g., beliefs that seeking treatment is a sign of weakness or that treatments do not work. Such knowledge could be used to devise media and other interventions to increase treatment seeking among smokers. Several behavioral and pharmacological treatments for smoking cessation have been well validated; however, even when external barriers such as awareness, cost and availability are minimized, few smokers trying to quit access treatment. We hypothesize certain beliefs and attitudes of smokers are internal barriers to seeking treatment. Studies have examined internal barriers to attempting to quit smoking and to succeeding in quitting smoking; however, few have examined internal barriers to seeking treatment per se. We will focus on the use of telephone help line treatments as this is the most commonly used psychosocial treatment for smoking cessation and is free of most external barriers; e.g., high cost and low availability. Study 3 is our main validity test of whether internal barriers are important. Studies 1A and 1B will generate a list of possible internal barriers to use in Study 3. Study 1A will interview 16 smoking cessation/drug dependence experts on why smokers/drug abusers do not seek treatment even when external barriers are minimized. Study 1B will ask 80 smokers who have recently tried to stop smoking and were aware of an available phone quit line to volunteer reasons they did or did not use this treatment. Study 2 will select barriers to be used in Study 3. We will administer barrier items from Studies 1A and 1B to 400 recent quit attempters to examine understandability and response bias. We will conduct an exploratory factor analysis in 200 of these smokers to derive a set of factors that covers the breadth of internal barriers followed by a confirmatory factor analysis in the other 200 smokers. We will also conduct tests of test-retest reliability, content validity, concurrent validity and discriminant validity. Study 3 will be a test of predictive validity; i.e. a test of whether our internal barrier factors prospectively predict use of a help line. We will recruit 560 smokers who plan to quit in the next 30 days, inform them of a free phone help line and ask them our barrier items. They will be re-contacted 2 months later to determine which of our internal barrier factors best predict calling the help line. To assess generalizability, we will also determine if our factors also predict use of other smoking cessation treatments. Our results will suggest messages for media campaigns and for clinicians to use to motivate smokers to access proven treatments.

The overall goal of this project is to continue the operations of the Kodiak SuperDARN Radar.
The Super Dual Auroral Radar Network, or SuperDARN, is an international collaborative
experiment for observations of plasma motions in Earth's upper atmosphere. By observing ionospheric plasma motions, a multitude of geophysical processes can be studied. These
processes range from E-region plasma instabilities, to the relationships between auroral
luminosity and electric fields, to the global-scale convective response to changes in the solar
wind and interplanetary magnetic field. Each of these areas of study contributes to the overall
goals of space physics: developing an understanding of the coupling of energy from the solar
wind into Earth's upper atmosphere and its effects on man or manmade systems. The Kodiak radar is particularly well suited for studies of he general areas to be addressed are convection observations, substorm processes, dayside transients, reconnection features at the cusp, mesospheric winds observed in meteor scatter, gravity waves, and thermosphere-ionosphere interactions, and these will be supported by this award.

The SuperDARN network comprises nine radars in the northern hemisphere, and seven radars in
the southern hemisphere, each operated independently by the member institutions, and supported
by the national agencies in their countries of residence. As is the nature of such networks, data from the SuperDARN network are used in such a wide variety of studies by such a wide range of scientists that it is prohibitive to produce a comprehensive list of the topics.

DESCRIPTION (provided by applicant): This competing continuation of a Senior Scientist Award (K05) will allow the applicant to conduct research on cessation and reduction of tobacco and marijuana use and on new methods to treat nicotine and cannabis dependence. The K05 would allow the PI to continue leadership roles in organizations interested in tobacco research and tobacco control and to continue science education activities such as mentoring and teaching. The applicant's past research contributions include description of the nicotine withdrawal syndrome, psychiatric co-morbidity with nicotine dependence, abuse liability of nicotine replacement, the role of expectancies in nicotine effects, caffeine reinforcement and dependence, and harm reduction approaches to nicotine dependence. The applicant founded the Human Behavioral Pharmacology Laboratory at the University of Vermont (UVM) and co-founded the Society for Research on Nicotine and Tobacco and the Association for the Treatment of Tobacco Use and Dependence. In the prior K05, the applicant averaged 13 published papers/yr of which he was first author on 9/yr and of which 7/yr were empirical studies. UVM has several resources to aid the applicant to learn new disciplines and methods; e.g. UVM currently has 25 NIH grants on drug abuse across 13 Pis. This continuation proposes tobacco studies to a) compare the efficacy of NRT-assisted abrupt vs gradual cessation, b) test a cannabinoid antagonist for smoking cessation, c) test a computer mediated clinical decision support system to help clinicians treat tobacco dependence, d) describe why the large majority of smokers do not seek free treatment and e) comprehensively review the world literature on the nicotine withdrawal syndrome. The continuation proposes a new line of research on marijuana to f) describe the natural history of attempts to stop or reduce marijuana use, g) determine if the marijuana withdrawal syndrome is due to THC deprivation, h) directly compare the clinical significance of marijuana and tobacco withdrawal syndromes, i) describe marijuana withdrawal in treatment seekers and j) describe marijuana withdrawal in adolescent marijuana users. The continuation will also include collaborating with other drug abuse researchers at UVM and elsewhere. The applicant will continue to mentor 4-6 students/yr and to be actively engaged in media and policy initiatives.

DESCRIPTION (provided by applicant): Smoking cessation can be enhanced either by increasing the success of quit attempts or by increasing in the number of quit attempts. Although many studies have determined the variables that influence remaining abstinent after a quit attempt, few have examined the variables that influence the onset of a quit attempt. The current application tests two facets of a model of the processes that lead to a quit attempt. First, we test whether certain environmental cues (e.g., a request from a child to quit smoking or exposure to a smoking-related health message) increase the probability of a quit attempt in the near future. We also examine whether such cues predict attempts over and above the predictive ability of cognitive factors such as self-efficacy and perceived social norms and whether these cognitive factors interact to make cues more powerful predictors. Second, we test whether planning behaviors (e.g. seeking information about treatment) and setting a quit date are common and increase the probability of a quit attempt. We also provide a more rigorous replication test of prior findings that spontaneous, unplanned quit attempts are more successful than delayed, planned quit attempts. In a pilot study, we will develop measures of external cues and planning activities. The main study is a non-treatment, prospective, natural history study. In this study, we will recruit 200 adult daily smokers who are interested in quitting in the next 6 months. They will call an Interactive Voice Recording (IVR) system daily and complete mailed or internet questionnaires weekly for 6 months. Our prior work has shown that we can obtain such daily and weekly reports for 6 months with little missing data. The daily IVR will record tobacco use/abstinence, intentions to quit, external cues and planning behaviors. The weekly questionnaires will measure cognitive variables and other outcomes (e.g. other drug use). Data analysis will use multilevel models designed to accommodate many repeated measures over time within participants. The results of this study will a) help develop a model of the causes of smoking cessation attempts, b) guide development of media and individual interventions to motivate smokers to make a quit attempt, and c) provide a more rigorous test of whether spontaneous, impulsive quit attempts should be encouraged rather than delayed, planned quit attempts. PUBLIC HEALTH RELEVANCE: Despite many public health efforts, most smokers do not try to quit in a given year and, despite significant public health efforts, the number of smokers who try to quit each year has not increased in the last 15 yrs. We propose a study to better understand how smokers decide to quit smoking;e.g., what cues prompt them to try to quit and how much they plan out their quit attempts. The study will also test a recent finding that smokers who make a spontaneous, unplanned quit attempt do better than those who delay and plan out their quit attempt. The study will have smokers call in information daily or weekly about cigs/day, exposure to cues to stop smoking, their intentions to quit, their actual quit attempts, etc for 6 months. The results of this study will a) help develop media and individual interventions to motivate smokers to make a quit attempt, and b) help decide if smokers should be encouraged to quit spontaneously or wait and plan out their quit attempts.

Computers are becoming essential in all disciplines. Researchers in the social sciences rely on the availability of large data repositories and the general availability of data over the Web. Researchers in the humanities are increasingly looking to analyze the growing number of electronic corpora. Workers in all fields are making use of new ways to publish data and of to interact with colleagues and others using electronic media. Moreover, more and more jobs and companies are relying on the understanding and processing of information. Modern companies as diverse as Google, WalMart, Amazon, and Goldman Sachs all owe their success in large part to their ability to evaluate and act on available information. It is estimated that in the next ten years, over twelve million people in the U.S. workforce will consider programming their primary job, which is far more than the current or near-term number of computer science majors. To address these needs, to better prepare students for careers involving information processing, to prepare
tomorrow?s researchers in the humanities and social sciences, and to prepare tomorrow?s workers for an information-based world, computer science needs to reach out beyond its traditional audience and even beyond the sciences. This project focuses on disciplines that have traditionally
been neglected by computer scientists, harnessing the growing revolution in applying computing to social artifacts. Second, it will result in a novel, application-driven, on-demand presentation of computing material, coming to topics like machine-learning and data-mining very early, rather than late, in the curriculum. Third, the development of a curriculum arranged in concentric rings of growing commitment, where a student who stops early will still get a meaningful education. It will provide the proper foundation for the growing use of computing and cyberinfrastructure in the humanities and social sciences. It will ultimately train such students have been relegated to with the tools to make their own non-trivial contributions to cyberinfrastructure. It will result in more women and minorities, groups traditionally underrepresented in computing, working with and using computation and cyberinfrastructure. Finally, it will enable students to wed their deep social and humanistic insights to tools that can enable them to build wonderful inventions that have the power to greatly enrich society.

This project is a three-way collaboration between PIs at Dartmouth, Embry-Riddle and Siena College. In a previous grant the team examined LF, MF, and HF radio emissions at several high latitude observatories. The instrumentation utilized interferometry to provide direction finding information in order to locate the source region of the observed emissions. This proposal will use the existing radio interferometers and spectrum analyzers in conjunction with riometers, magnetometers, all-sky cameras, photometers, ISR and SuperDARN radars to investigate the relationship of the radio emissions to substorms and to energetic particle precipitation. The project will concentrate on the least well understood form of auroral emission, what is known as an MF-burst. There are two primary goals: (1) to determine the generation mechanism of MF-bursts and (2) to determine the relationship of the MF-bursts to auroral acceleration processes and substorm phenomena.

The project includes research opportunities for both graduate and undergraduate students. The data will be made publicly available and is likely to be useful to researchers involved with the Canadian e-Pop satellite mission and the NASA THEMIS mission.

DESCRIPTION (provided by applicant): The major aim of this study is to provide a detailed understanding of attempts to stop or reduce marijuana use that can be used to develop better behavioral treatments for marijuana dependence. The application will provide a prospective description of attempts by dependent adult marijuana users to stop or reduce their marijuana use in a real-world setting. Although prospective, natural history studies describing attempts to stop or reduce alcohol, heroin and tobacco use have proved useful, we know of no such study among adult marijuana users. A pilot study will develop measures and assess compliance with our procedures. The main study will recruit 200 daily, adult marijuana smokers who plan to quit or reduce in the near future. Participants will call an Interactive Voice Recording (IVR) system daily for 3 months to report marijuana use, intentions to change marijuana use, quit/reduction attempts, and events that might increase or decrease the probability of initiating a quit/reduction attempt or the success of an attempt. Participants will be called weekly to obtain more detailed measures such as other drug use, self-efficacy, psychiatric/medical symptoms, and treatment seeking. Phone follow-ups at 4, 5 and 6 months will track marijuana and other drug use and dependence/abuse. PUBLIC HEALTH RELEVANCE: Knowing what motivates marijuana users to try to stop or reduce, and knowing which strategies for stopping marijuana use are successful, can help develop treatments for marijuana dependence. For example, if stopping tobacco when trying to stop marijuana decreases the chance of stopping marijuana, then smoking cessation should be done after stopping marijuana. Or if reducing marijuana often leads to cessation, then convincing those not interested in quitting marijuana to first try reducing may be helpful.

0922961
Druschel

This MRI proposal seeks funding to acquire materials characterization equipment. Requested are a wavelength-dispersive spectrometer (WDS), and energy-dispersive spectrometer (EDS), and an electron-backscatter-diffraction unit (EBSD) to be added to an existing electron microscope. In addition, the PIs are requesting an x-ray diffractometer (XRD), and x-ray fluorescence spectrometer (XRF), a Raman spectrometer, and an optical microscope with digital imaging capabilities. Instrumentation will be put to use in NSF, EPA, USDA, NOAA, DoD, DOE and other agency-funded research. Major research areas involve understanding mineralogical controls on nutrient availability and mobility in watersheds, characterizing microbial-mineral and water interactions in watersheds and the critical zone, characterizing mixed phase materials such as zeolites and other microporous mineral matrices, understanding mineral distributions at mining sites, and physicochemical condition control by mineralogical microstructure. The fundamental research to be undertaken here will advance the state of knowledge for how mineralogical surfaces impact contaminant and natural compound movement and distribution in groundwaters, watersheds and in the critical zone. The studies will server as a foundation for education and training for environmental science and engineering. Equipment will be incorporated into classes and workshops. The equipment will be placed in recently-renovated existing laboratory space within the Department of Geology. The PIs will comprise the management team and will arrange training and administer day-to-day usage. Funded researchers will be charged a small fee to use the instrumentation. Online scheduling software will be used to solicit instrument use. The EDS will upgrade an existing EM, which is administered by a full-time technician.

***

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).

The project seeks continued support of investigations of the polar mesosphere, thermosphere, and ionosphere over Sondrestromfjord through coordinated optical and radar observations. Airglow emissions are measured by a spectrometer and an interferometer and combined with observations by the incoherent scatter radar at Sondrestrom to provide information on the energetics, dynamics, and thermodynamics over the region. The specific questions to be addressed are: 1. What are the effects of geomagnetic storms on the E-region's O/N2 (atomic oxygen to molecular nitrogen) ratio and on thermosphere dynamics and how do these lead to variations in the E-region composition? 2. What are the effects of intense auroral electric fields and the subsequent Joule heating on the thermodynamics of the ionosphere? 3. To what extent are perturbations to planetary and gravity waves observed in the polar mesosphere associated with stratospheric warming events? The O/N2 abundance measurements will make contributions to understanding of thermospheric circulation and its solar and geomagnetic drivers. The investigations focused on Joule heating will augment information on auroral energy inputs. The planetary and gravity wave investigation will contribute to a more quantitative understanding of the energetic coupling between the stratosphere and the mesosphere/lower thermosphere region. A particular interest is the energy transport mechanism responsible for the mesopause cooling that precedes stratospheric warmings by about two days, including the role of planetary and gravity waves in the stratospheric warming events. The broader impacts of the project include the involvement of graduate and undergraduate students and a postdoctoral researcher and the generation of an extensive database of optical and radar data.

With this award, co-funded by the Division of Chemistry and the Major Research Instrumentation (MRI) program , Professor Rory Waterman and colleagues Randall Headrick and John Hughes from University of Vermont & State Agricultural College will acquire a single-crystal X-ray diffractometer with low-temperature capabilities to be used in chemistry, geology and material science projects. The proposal is aimed at enhancing research training and education at all levels, especially in areas of study such as phosphaalkane synthesis, use of phthalocyanines for organic electronics and discotic liquid crystals, apatite OH-F-Cl ternary systems in geology, as well as studies of oxidation-reduction reactions of organotransition metal complexes and polycyclic heterocycles.

An X-ray diffractometer allows accurate and precise measurements of the full three dimensional structure of a molecule, including bond distances and angles, and provides accurate information about the spatial arrangement of a molecule relative to neighboring molecules. The studies described here will impact a number of areas, including organic and inorganic chemistry, materials chemistry and geology. This instrument will be an integral part of teaching as well as research.

DESCRIPTION (provided by applicant): Recent animal research indicates acute nicotine increases the reinforcing effects of other rewards; however, chronic use of nicotine recruits an opponent process that counteracts the acute effects of nicotine and decreases sensitivity to rewards. When nicotine is discontinued in animals, this opponent process persists and the resultant decreased sensitivity to rewards may be a cause of nicotine withdrawal symptoms such as depression and a cause of relapse back to smoking. Although this animal model is widely cited, whether decreased reward sensitivity occurs when smokers stop smoking is unclear. The investigators propose an experimental test that focuses on whether abstinent smokers a) are less sensitive to monetary rewards during an operant task and/or b) report anhedonia (less pleasure from rewards) and apathy (less motivation to seek rewards). The investigators will recruit 120 current smokers who plan to quit smoking for good to smoke their usual amount for one week and then will abstain for 4 weeks. To insure an adequate number of continuously abstinent smokers and to decrease selection bias, they will use monetary contingencies to encourage abstinence. The investigators anticipate this will produce > 70 smokers who remain abstinent for all 4 weeks. To assist in interpretation of results, they will also recruit a comparison group of 70 long-abstinent former smokers to be measured on the same schedule. The investigators will measure reward sensitivity three times each week using a) progressive ratio (PR) responding for monetary rewards and b) self-report measures of anhedonia and apathy scales. If reward sensitivity changes with abstinence, secondary aims will be to determine a) its magnitude, incidence and time course; b) whether it exhibits the time course expected of a withdrawal effect, c) whether reward sensitivity becomes similar to the level among long-abstinent smokers and c) whether decreased reward sensitivity could be the basis for much of withdrawal discomfort. The results of this study will be an important translational test of the leading animal model of nicotine withdrawal. If decreased reward sensitivity is found, this would suggest revisions in clinical descriptions of nicotine withdrawal, new targets for behavioral and pharmacological interventions and new treatments for smoking cessation (e.g., increased exposure to rewarding events). If reward sensitivity does not change with abstinence, then (given the adequacy of the investigators' test) this would suggest a widely cited animal model of abstinence effects may not be generalizable to human attempts to stop smoking.

DESCRIPTION (provided by applicant): Despite tobacco control interventions, the incidence of quitting among US adult smokers has not increased in the last decade. One new method to increase quit attempts is to have smokers reduce their cigs/day. We and others have shown that reduction aided by NRT can increase quit attempts and later abstinence among smokers not ready to quit. Because half of smokers are reluctant to use NRT for a non-cessation reason, we now propose to test whether reduction not aided by NRT can be effective. Another new method to increase quit attempts is motivational counseling. Although some studies have found motivational interviewing prompts quit attempts, this treatment is intensive (median time = 1.7 hours) and thus not practical in many settings. We previously found implementation of the USPHS Guidelines 5 Rs motivational intervention via three 15 min phone calls can provide a large increase in quitting (OR = 6.3). However, that study employed a no treatment control group~ thus, we propose to test for efficacy using a more clinically-relevant usual care control condition. We will proactively call adult, daily smokers to recruit 850 smokers who do not plan to quit in the next month and randomize them to a) reduction counseling without the aid of NRT, b) counseling guided by the USPHS 5 R's, or c) usual care. The first two conditions will be delivered via brief counseling calls at study onset and then 2 and 4 weeks later (total = 35 min). The usual care condition will consist of a brief (< 5 min) 2 As intervention and three newsletters providing information on quitting sent at these same times. Our major hypothesis is that the incidence of quit attempts over the 6 months of the study will be greater in both the reduction and the 5 Rs conditions than in the usual care condition. A secondary hypothesis is that the increase in quit attempts will lead to increased abstinence. Another secondary hypothesis is that beneficial effects of both treatments will be mediated by increases in self-efficacy and intentions to quit. A final hypothesis is that decreases in cigs/day and nicotine dependence will mediate the efficacy of the reduction treatment but not the 5 Rs treatment and, conversely, that a shift in decisional balance will mediate the efficacy of the 5 Rs treatment but not of the reduction treatment. If our two interventions are effective, this would encourage quitlines, healthcare organizations and clinicians to offer these time-limited interventions to ambivalent smokers. Also, having an action-oriented intervention (reduction) and a cognitive-oriented intervention (5 Rs) could increase the acceptability of these interventions to different types of smokers. Finally, prior studies have been interpreted to indicate that reducing cigs/day will increase later quitting~ however, all prior studies that have shown this included NRT to aid reduction~ thus, it may be that pretreatment, not reduction is the cause of any increase quitting in prior studies. A study showing that reduction without the aid of NRT increases later quitting would be the first direct test to indicate reduction per se aids later quitting. PUBLIC HEALTH RELEVANCE: New methods to prompt smokers to quit could have a significant public health impact. In a prior study, we found that, helping such smokers to reduce the number of cigarettes/day by counseling plus nicotine replacement therapy (NRT), or motivating them with brief discussions over the phone, both dramatically increased later quitting compared to no treatment. We now propose to re-test these treatments for three reasons: a) because most smokers are not willing to use NRT, we wish to see if reduction without using NRT is effective, b) we wish to test if our reduction and motivational treatments are better than current usual care and c) we wished to conduct a more rigorous experimental test.

DESCRIPTION (provided by applicant): Over-the-counter nicotine replacement therapy (OTC NRT) is, by far, the most common treatment for smoking cessation in the US. Over 80% of those using NRT will lapse and return to smoking. One possible reason for this high rate of treatment failure is that smokers are instructed to stop medication when they lapse (in contrast to recommendations to increase medication dose when heroin users lapse). Recent indirect evidence suggests that, in fact, a lapse is the most important time to continue NRT. We propose a randomized controlled trial of continued NRT post-lapse vs. stopping NRT post- lapse. Smokers who want to quit will receive, counseling, stop abruptly and begin NRT. All psychosocial treatment will occur via phone and medications via mail. Instructions and rationales for continuing or stopping NRT during a lapse episode will be delivered via written material, Interactive Voice Response (IVR) phone messages and reinforced during phone counseling. We will enter 1000 smokers and anticipate observing 580 lapses while using NRT. We hypothesize our intervention to continue NRT use upon a lapse will increase 6 month point prevalent abstinence with an OR of 2.0. We will also examine compliance with instructions and possible behavioral mechanisms of efficacy (e.g. does continued NRT reduce nicotine reward from cigarettes) as well as the incidence of serious adverse events when participants are concurrently smoking and using NRT after a lapse. This study will be the first direct experimental test of whether continuing NRT after a relapse increases abstinence and is safe. Positive results would suggest the package instructions for NRT, treatment guidelines and training programs should change to explicitly encourage smokers to continue NRT treatment after a lapse.

Apatite, Ca10(PO4)6(OH,F,Cl)2, is the tenth most abundant mineral on Earth and one with fundamental importance in geology, materials science, medicine, dentistry, pollutant mitigation, and as the foundation of the Earth's phosphorus cycle; indeed, all hard tissue of the human body except small parts of the inner ear are made of apatite. All of these applications of apatite require understanding of the atomic arrangement of the mineral. Despite the extensive multidisciplinary literature on apatite crystal chemistry, the atomic arrangements of members of the (OH,F,Cl) binary and ternary systems are not well understood and our current knowledge is full of inconsistencies that must be resolved; apatite is one of the rare minerals for which the atomic arrangement of the solid solutions cannot be predicted from the end-member arrangements.

Mixing of the end-member atomic arrangements suggests, for example, that binary members of the system must undergo symmetry breaking, possess immiscibility gaps, incorporate essential vacancies with an unknown method of charge balance, and/or possess anion positions that are not currently recognized. This multi-faceted proposed study will couple mineral synthesis and detailed compositional characterization with single-crystal X-ray structure analysis and Magic-Angle-Spinning Nuclear Magnetic Resonance spectroscopic studies in order to elucidate the nature of solid solution among and between the OH, F, Cl ternary apatites, and provide a better fundamental understanding of anionic substitution and phase behavior. The results of this study will have applications in the fields of geology, materials science, medicine, and dentistry. A proof-of-concept study demonstrates that miscibility along the F-Cl join is achieved by the creation of at least four anion sites in the F-Cl anion column, and confirms the efficacy of the proposed synthesis and analysis methods.

DESCRIPTION (provided by applicant): A relatively new approach to spatial modeling is the copula-based approach, which has thus far been applied only to geostatistical data, i.e., data observed over a continuous spatial domain. The chief advantage of copula-based modeling is modularity. The dependence structure and the marginal distributions can be modeled separately and then joined by way of the probability integral transform. This approach can, in principle, allow copula-based areal models to overcome many of the problems associated with the most commonly used areal models. Specifically, we expect copula-based areal models (1) to be flexible and intuitive, (2) to permit positive spatial dependence for all types of data, (3) to be ow dimensional, (4) to permit efficient computation (so that large datasets can be handled), and (5) to provide reliable spatial regression inference (because spatial confounding is impossible). In this project, we will develop various copula models for areal data, and we will develop approaches to frequentist and Bayesian inference for the models. The performance of the copula models will be compared to one another and to existing areal models by way of an extensive simulation study and application to current SEER data for HPV-related cancers. We will also implement R software for fitting the copula models to data. The new routines (and thorough documentation) will be added to existing R package ngspatial, which is freely available from the Comprehensive R Archive Network.

? DESCRIPTION (provided by applicant): Electronic cigarettes (e-cigarettes) are the fastest growing harm reduction product. Many e-cigarette users obtain nicotine blood levels from e-cigarettes that are much higher than those from nicotine replacement products and, in some studies, similar to that for tobacco cigarette users. Given this, one would expect abrupt cessation of e-cigarettes to produce withdrawal symptoms but this has not been tested. We propose to recruit 120 long-term e- cigarette-only users. Participants will enter a within-participants study with random, balanced order of assignment to four conditions: a) their own e-cigarettes, b) a new nicotine e-cigarette, c) the non-nicotine (i.e. placebo) version of the new e-cigarette, and d) no use of any e-cigarettes. The use of nicotine or non-nicotine new e-cigarettes will be double-blind. Participants will be instructed to abstain from tobacco and nicotine products during the study. Each condition will last 5 days with a 2 day washout between conditions. To encourage compliance we will use an escalating payment system with bonuses that has resulted in high compliance rates in our prior studies. Participants will monitor symptoms of nicotine withdrawal daily via an Interactive Voice Response system. They will also attend 3 lab visits/week to provide carbon monoxide and cotinine samples to determine compliance payments, and to complete longer surveys, a cognitive task and a task to measure increased motivation to use e-cigarettes. We will test the effect of abstinence (own e-cigarette vs no e-cigarette) and its pharmacological specificity (new nicotine e-cigarette vs new non-nicotine e-cigarette). Our results will help determine a) the addiction potential of e-cigarettes, b) whether labeling should warn purchasers of e-cigarettes that abrupt cessation can induce withdrawal, and c) whether withdrawal problems should be included in risk/benefit assessments of e-cigarettes.

Galaxy clusters are enormous reservoirs of galaxies, hot gas and mysterious "dark" matter. The hot gas produces a signal at millimeter wavelengths. The most massive clusters produce the strongest signals. Such signals can be detected from clusters anywhere in the universe. The team used millimeter observations from a space mission to identify massive cluster candidates. They will obtain follow-up observations to confirm the cluster identifications. The clusters will be used to test models of how structures form in the universe. They will also be used to constrain cosmological parameters. Senior team members will train junior team members. The team will develop material in Spanish and present it in Spanish in Illinois schools. The team will also engage with underrepresented minorities in South Africa.

The team will conduct follow-up observations of candidate galaxy clusters discovered through the Sunyaev-Zeldovich (SZ) effect. Their extensive imaging and spectroscopy with ground-based facilities will yield confirmed clusters. These are expected to be at high redshift and have high SZ-determined masses. The team will use the clusters to (1) test the Lambda Cold Dark Matter model for structure formation in the universe and (2) improve constraints on cosmological parameters from galaxy cluster counts.