Robert J. McMahon - US grants

The major purpose of the proposed project is to implement and evaluate a developmentally-based prevention and promotive intervention program for use with normally-adjusted and behaviorally at-risk second and third grade children. The specific preventive intervention program is a revised version of the PATHS/ (Providing Alternative Thinking Strategies) Curriculum for Children. Based on a theoretical development approach (Affective- Behavioral-Cognitive-Developmental or ABCD Model), which focuses on the importance of integrating emotional, cognitive, and linguistic functions for optimum maturation, it is hypothesized that PATHS will be shown to be an affective program for both (1) promoting personal competence and adaptive capacities in normally- adjusted children, and (2) preventing the development of serious behavioral disorders in children who are presently "at risk." In order to assess the effectiveness of PATHS as both a promotive and prevention intervention program, the present project will utilize a pre-post-followup training design to separately compare intervention and control groups of a total of 300 normally-adjusted and 150 behaviorally at-risk children ages 8-9. Following training, the intervention children's regular classroom teachers will implement PATHS in 6 normal and 10 special classrooms. Matched control groups will receive regular classroom instruction from their untrained teachers in separate, but otherwise equivalent, classrooms. Posttesting and three followup assessments will be conducted over the next four years to evaluate long-term promotive and preventive effects. Pre, post, and followup testing will involve multiple-method, multiple measure assessment consisting of a battery of behavioral, affective-social cognitive, problem-solving, personality, and cognitive-academic measures. Data will be collected from the children, teachers, parents and school files. Based on the hypothesis that self-control, emotional understanding, social cognition, and interpersonal problem-solving skills are critical factors in both behavioral change and social-cognitive growth, a second major purpose of the present project will involve examining the reciprocal, causal relationships between affective, social-cognitive, behavioral, and cognitive-academic domains in normally-adjusted and behaviorally a-risk children. This second objective will involve two different types of statistical analyses: (1) Analyses of pretest prior to intervention, and (2) process analyses will be performed to investigate how improvements in self- control, emotional-social understanding, and problem-solving resulting from the intervention are related to changes in self- esteem and behavior.

This Presidential Young Investigator Award given in the Organic Dynamics Program provides support for the research of Dr. Robert McMahon at the University of Wisconsin/Madison. The focus of the research is the generation, isolation, chacterization and reactivity of reactive intermediates. The common experimental approach will be matrix isolation spectroscopy. The systems to be studied are intramolecular hydrogen migration in carbenes, nitrenes and 16-electron coordinatively unsaturated organometallic species and the chemistry of reactive carbon species such as carbene, carbyne and atomic carbon. In the latter system, the bond-shifting automerization of acetylenic carbenes will be studied in the context of polymerization of diacetylenes to polydiacetylene, soliton migration in conducting polymers and linear carbon structures as applied to carbon fiber technology.

This grant from the Organic Dynamics Program supports the work of Dr. Robert J. McMahon at the University of Wisconsin, Madison. The investigation will focus on molecular rearrangements of reactive molecular species and will result in an improved understanding of the fundamental processes by which chemical reactions occur. The experiments that will be carried out by Dr. McMahon will involve a systematic study of intramolecular hydrogen migration in electron deficient organic intermediates and isolobal, organometallic analogs. Low-temperature matrix isolation techniques will be employed to establish rearrangement pathways and to characterize intermediate species by spectroscopic methods. Experiments will be designed to probe the roles of spin-multiplicity, orientation, distance, and thermodynamic driving force for the rearrangements.

The mechanistic basis underlying intramolecular hydrogen migration reactions in reactive organic and organometallic intermediates will be studied. Low-temperature matrix isolation spectroscopy, low- temperature NMR spectroscopy, and time-resolved absorption spectroscopy will be used to establish rearrangement pathways and to characterize the reactive species. Organic carbenes, organic nitrenes, and certain coordinately unsaturated 16-electron organometallic intermediates comprise an isolobal class of electron-deficient reactive intermediates that will be studied. In the organometallic studies, low-temperature NMR will be used to follow the chemistry of reactive allyl hydride intermediates and the involvement of these species in alkene isomerization processes. Iron, Osmium, and Ruthenium metal atoms will be incorporated in the organometallic intermediates. In particular, studies will be directed to allylic C-H and beta C-H insertion reactions. In the organic studies, experiments will focus on direct observation of hydrogen migration reactions of carbenes and 1,4-biradicals by time-resolved spectroscopy. %%% This grant from the Organic Dynamics Program supports the work of Professor Robert J. McMahon at the University of Wisconsin. The details of how hydrogen atoms migrate in reactive electron- deficient organic and organometallic intermediates by intramolecular processes will be studied. These elusive intermediates will be studied at low temperatures by various spectroscopic methods in order to characterize the intermediates and individual steps in the overall reaction. The reactive intermediates that will be studied include carbenes (divalent carbon species), nitrenes (monovalent nitrogen species), and organometallic intermediates that have 16 electrons rather than the stable 18-electron complement about the metal atom. Iron, Osmium, and Ruthenium metal atoms will be incorporated in the organometallic intermediates.

This project consists of the continued implementation and evaluation of a developmentally based, long-term, comprehensive intervention designed to prevent conduct disorder and social maladaptation in adolescence and adulthood. The hypothesis will be tested that such an intervention will lead to proximal improvements in child behavior and family ecology and, in turn, that these changes will lead to the long-term prevention of conduct disorder. The project is being carried out at four sites (Durham, NC/Duke; Nashville, TN/vanderbilt; rural Pennsylvania/Penn State, and Seattle, WA/U. of Washington). Two successive cohorts of children who will be followed over twelve years have already been identified, and a third cohort will have been identified prior to the start of the next grant period. Kindergarten-age children who are at high-risk for conduct disorder are randomly assigned to an intervention (child n = 480) or control (child n = 480) group. The intervention attempts to promote children's compliant behavior, social-cognitive skills, peer relations, and academic success; to promote parents' and teachers' skills in child behavioral management; to assist teachers in promoting children's social competence; and to develop coordination between families and schools. This multi-system program is designed to provide intensive intervention for two year periods at two developmentally important transition points (school entry and the transition to middle school), and to provide less intensive criterion-based intervention, classroom-based tutoring and home visiting during the middle elementary school years. The effects of intervention will be evaluated in multiple theoretically based ways. In addition, a representatively selected normative group of children in the control schools will be followed to provide normative comparisons for the intervention group, as well as to further investigate risk factors in the development of conduct disorder. Analyses of data comparing the first cohort of high-risk children and their families to the normative children and their families confirm the assumptions of the developmental model of conduct disorder on which this proposal is based. In the proposed three year grant period, intervention will focus on elementary school intervention and the developmental transition that occurs with entrance into middle school (for the first cohort). Further preventive intervention and evaluation is planned to complete the transition to middle school and early adolescence for all cohorts in a subsequent grant period.

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This research focuses on identifying, characterizing and examining the reactivity of organic molecules that occur in interstellar space. Species known, or likely to exist in interstellar space will be generated in low temperature matrices in the laboratory and characterized by a variety of spectroscopy techniques. Laboratory results will be correlated with radioastronomical searches to identify new species in interstellar clouds, and the carriers of diffuse interstellar bands. The research will introduce graduate and postdoctoral students to low-temperature matrix-isolation techniques, spectroscopic characterization of the isolated species, and a unique interdisciplinary application of these techniques. With this Renewal award, the Organic and Macromolecular Chemistry Program supports the research of Professor Robert McMahon of the Department of Chemistry at the University of Wisconsin. Professor McMahon's research will address questions regarding the nature and chemistry of the reactive, organic fragments known, or postulated to exist in interstellar space. Intermediates thought to be present in interstellar space will be prepared in the laboratory, spectroscopically fingerprinted, and the spectral data compared with radioastronomical data to establish their presence in interstellar clouds and diffuse interstellar bands, and to identify other species present. Professor McMahon's educational activities will include the training of graduate and postdoctoral students.

DESCRIPTION (provided by applicant): This proposal is to complete the evaluation of a developmentally based, long-term, comprehensive intervention designed to prevent serious antisocial behavior and related adolescent problems. The project is being carried out at four sites (Durham, NC/Duke University; Nashville, TN/Vanderbilt University; rural Pennsylvania/Pennsylvania State University; and Seattle, WA/University of Washington). The screening procedure of Fast Track identified three successive cohorts of high-risk children in kindergarten by their early conduct problems at home and school. These children were randomly assigned by school to an intervention or control group. Intervention began in first grade with high-risk children, their adult caretakers, and their teachers based on a developmental model that specified six areas of risk and protective factors: parenting, child problem-solving and emotional coping skills, peer relations, classroom atmosphere, academic achievement, and home-school relations. It was continued in adolescence with an emphasis on protection from deviant peer influence; promoting positive identity, goals, and aspirations; and academic and vocational skill development. Analyses indicate the intervention has led to significant improvements in the hypothesized risk and protective factors and reductions in conduct problem behavior over the elementary school years. The primary aims of this proposal are: 1) to complete the assessments in the last 2 years of high school and the 2 years immediately after high school in order to evaluate intervention effects on mental health, crime, substance abuse, education and employment, and the use of community services; 2) to determine whether characteristics of the participant sample moderated the effects of the intervention; 3) to understand factors that mediate successful preventive intervention; 4) to identify factors influencing participation and the relation between dosage and outcome; 5) to continue to test the developmental model of early and late-starting conduct problems with the normative and high-risk samples; 6) to continue to develop innovative methods for analyzing data from prevention trials; and 7) to provide data for an economic study of the impact of Fast Track on professional service utilization. The data collection plan calls for completion of annual parent and youth assessments at the end of 11th (cohort 3) and 12th grades (cohorts 2 and 3); a phone interview 1 year after the end of high school; and a face-to-face interview at age 20 that will provide a final assessment of mental health status, conduct problem behavior, substance use, educational progress, and employment status at the end of the teenage years (all cohorts).

Professor Robert J. McMahon, of the Department of Chemistry at the University of Wisconsin - Madison, is supported by the Organic and Macromolecular Chemistry Program for his studies directed toward the elucidation of the identity, structure, properties, and reactivity of organic molecules that occur in interstellar space. A combination of experimental and computational investigations are focused on organic species that are either known to or are likely to exist in the interstellar medium. These organic species will be generated in the laboratory, and their molecular structure investigated by infrared, ultraviolet/visible, electron spin resonance, and microwave spectrometry. In order to address the question of the existence of cyclic, aromatic species in interstellar space, as well as the mechanisms for their formation from acyclic molecules whose existence has been demonstrated, the fundamental chemical mechanisms by which open-chain organic molecules undergo ring closure will be investigated. Additional studies will attempt to detect aromatic species and their precursors in the interstellar medium through a combination of laboratory rotational spectroscopy and subsequent radio-astronomical searches.

The origin of the so-called "diffuse interstellar bands" has been described as one of the fundamental problems in modern astronomy and molecular spectroscopy. At the present time, it is not known with certainty whether cyclic species displaying the unusual stabilization known as aromaticity exist in interstellar space and, if so, how these species can be formed from the acyclic molecules that are known to exist there. With the support of the Organic and Macromolecular Chemistry Program, Professor Robert J. McMahon, of the Department of Chemistry at the University of Wisconsin - Madison, is carrying out a combination of experimental and calculational studies designed to address these questions. By preparing acyclic precursors to aromatic species and examining their structure and reactivity, Professor McMahon explores the fundamental reaction chemistry which could occur in interstellar space. By probing these species with a variety of spectroscopic techniques, he both elucidates their structures and provides spectroscopic "signatures" which may be sought in the interstellar medium, providing evidence for the existence (or absence) of these species.

With this renewal award, the Organic and Organic and Macromolecular Chemistry Program and the Galactic Astronomy Program supports the work of Professor Robert J. McMahon of the Department of Chemistry at the University of Wisconsin, Madison, WI. The research will extend the PI's studies of the synthesis and characterization of reactive organic molecules that may be present in the interstellar medium (ISM). The PI will synthesize carbon chain species and hydrogen deficient aromatics, characterize them by matrix isolation and ESR spectroscopy combined with quantum chemical calculations, and study their photochemistry. Since the diffuse interstellar bands, absorptions in the near-IR to near-UV, are often hypothesized to arise from either carbon chain molecules or aromatics in the diffuse ISM, these studies will aid in establishing the identity of the specific molecules responsible for these bands.

These investigations of energetic molecules, which include strong partnerships with laboratory astrophysicists, are expected provide important fundamental information that will increase our understanding of interstellar molecules and of the dynamics of such species as reactive intermediates.

With this Renewal Award, the Chemical Structure, Dynamics, and Mechanisms Program continues to support Professor Robert J. McMahon of the University of Wisconsin-Madison in a project involving investigations of fundamental issues in structural and mechanistic organic chemistry of relevance to astrochemistry. The project will explore the structure, reactivity, and spectroscopy of carbon-rich molecules that are hypothesized to play a role in the chemistry of interstellar clouds, protoplanetary nebulae, circumstellar shells, and the atmosphere of Titan. The PI and his students and collaborators will generate these energetic species, determine their spectroscopic properties, investigate their thermal and photochemical reactivity and attempt to detect them as constituents of interstellar space. This interdisciplinary program will utilize the techniques of synthetic organic chemistry, molecular spectroscopy, quantum chemistry and observational astronomy to obtain a deeper understanding of the organic chemistry occurring in interstellar space.

This project, which cuts across numerous disciplines including fundamental organic chemistry, astrochemistry and combustion chemistry, will train graduate and undergraduate students in the techniques of organic synthesis, matrix isolation, and molecular spectroscopy.

In this project funded by the Chemical Structure, Dynamics & Mechanism B Program of the Chemistry Division, Professor Robert J. McMahon of the Department of Chemistry at the University of Wisconsin-Madison will investigate the behavior of organic compounds under harsh conditions of temperature, pressure, or radiation. These conditions, which are similar to the conditions found in flames (combustion) or in space, cause the degradation of organic compounds and generate a complex mixture of highly reactive products. The proposed research will explore the chemical properties and chemical reactions of these reactive molecules. This research provides a foundation for understanding two very different problems: one involving combustion and another involving the chemistry of space. Combustion of organic fuels is central to our nation's energy supply and national economy. A fundamental understanding of combustion offers the possibility of enhancing the energy efficiency of fuel combustion and minimizing pollutants (soot) that arise from incomplete combustion. In interstellar space, it is now known that hundreds of different organic compounds exist throughout the galaxy in environments that are harsh because they are so hot (near stars) or because they are so cold (far from stars). Studying these environments is a crucial step in understanding the distribution of organic material in the universe and identifying molecules that could be precursors to life. Professor McMahon and his coworkers will also continue their engagement in a variety of science education and outreach activities.

The fundamental chemical studies proposed herein would not have been possible only a few years ago. Tremendous advances in both experimental and computational techniques now permit the analysis and interpretation of the experimental spectra obtained from complex mixtures of reactive species. Direct studies of these species are challenging because these molecules typically exhibit high reactivity. Nevertheless, it is the reaction chemistry of these ephemeral intermediates that governs the chemical behavior of the system. In combustion chemistry, the determination of accurate equilibrium structures of reactive intermediates will provide important benchmarks for prototypical molecules, and theory can be further used to establish thermodynamic parameters that are important for modeling. In astrochemistry, the Atacama Large Millimeter / sub-millimeter Array (ALMA), an astronomical interferometer of radio telescopes in the Atacama Desert of northern Chile completed in 2013, is generating a deluge of new radio-astronomical data. These data can be interpreted only by comparison with laboratory spectra of the type that will be obtained through the proposed studies.

Children with oppositional defiant disorder (ODD) are at significantly increased risk for a host of negative outcomes in later childhood, adolescence, and adulthood. These outcomes can include delinquency, early and risky sexual behavior, poor academic and occupational adjustment, poor interpersonal relations, and increased risk for various mental disorders. Effective treatment for ODD has typically been based on a social learning-based ¿parent management training¿ (PMT) model. Despite strong evidence for PMT, it is not effective with all children, with up to one third failing to show reliable and sustained improvement. Having limited prosocial emotions (e.g., lack of guilt and empathy, callous use of others) appears to be one factor that mitigates the effects of traditional PMT. Children with ODD with limited prosocial emotions present with more severe conduct problems and have poorer behavioral outcomes. It is therefore important to develop empirically based methods to enhance the efficacy of ¿traditional¿ PMT for those children with ODD and limited prosocial emotions. Recent meta-analytic research indicates that one key component of successful family based intervention approaches involves teaching parents skills related to emotional communication. Given evidence that children with ODD with limited prosocial emotions have deficits in the awareness/recognition of emotion and in empathy, incorporating an emotion-focused intervention (which has not been a focus of PMT) into traditional PMT should enhance outcomes for these children. Consistent with the aims of the R34 mechanism, the primary goal of this application is to develop and test the feasibility of a brief emotion-coaching (EC) intervention in combination with an evidence-based PMT program, Helping the Noncompliant Child (HNC; Forehand & McMahon, 1981; McMahon & Forehand, 2003), for use with clinic-referred children with ODD who have limited prosocial emotions. The Specific Aims are to: 1) develop and refine an empirically based combined HNC-EC parenting intervention to reduce CP in children with ODD and limited prosocial emotions; and 2) assess the viability of a later clinical trial by a) pilot testing the newly developed HNC-EC intervention compared to HNC alone with mothers and their 3-7 year-old children who have been referred for treatment of significant levels of oppositional behavior (and who also have limited prosocial emotions) in a community mental health center setting, and b) establishing the treatment feasibility (family and therapist-level feasibility, treatment fidelity, participant satisfaction) and research feasibility of the HNC-EC intervention compared to HNC alone. While pilot studies should not be used to estimate effect sizes, (Kraemer et al., 2006; Sherrill et al., 2009), we will explore trends in the data to facilitate consideration of possible designs for later statistical modeling in a larger trial. Promising findings would form the basis of a research proposal for a randomized clinical outcome study comparing HNC alone and in combination with an EC intervention for children with ODD and limited prosocial emotions. Should this combined intervention (which is focused on improving outcomes in this hard-to-treat population) prove to be effective, it will be one of the first interventions targeting known developmental mechanisms related to limited prosocial emotions in children. Given the increased likelihood that children with an early onset of CP and limited prosocial emotions are at increased likelihood of multiple negative outcomes extending into adulthood, at extraordinary social and economic cost, improving response rates to PMT (which is a low-cost, low-restrictiveness intervention) will have substantial public health impact.

? DESCRIPTION (provided by applicant): Although prevention scientists have documented effective interventions to prevent adult substance abuse, antisocial behavior, and risky sexual behavior, these interventions have not been applied to optimize return on investment and thus have not yet been fully embraced by communities. This application proposes to map the relations between early risk profiles (and preventive intervention) and adult health and financial outcomes. Past studies have estimated these relations with regression coefficients that satisfy scholars but provide insufficient information to enable practitioners and policy makers to target children for intervention by age and risk profile. The proposed studies will identify the government service outcomes and financial costs associated with various risk profiles by age and the likely return on investment for the Fast Track intervention, which has been documented to prevent antisocial behavior and substance use problems. We propose interviews and administrative data collection at ages 30-34 with participants in each of two ongoing longitudinal studies that have followed children with detailed measurement of risk factors from kindergarten into adulthood, the Child Development Project (n=585, retention=90%) and the Fast Track randomized controlled trial (n=1199, retention=81%). We will pursue three aims: 1) Model the relation between early risk and adult health outcomes at different levels, qualities, and ages of risk, to identify optimal intervention timing and targets; 2) Map the relation between risk profile and adult service utilization and ultimate public costs in adulthood, to monetize the possible returns on prevention investment; and 3) Evaluate the impact of the Fast Track intervention on adult health and financial outcomes, by subgroups. The findings will provide a template for an emerging Science of Investing in Children to improve public health and protect public resources.