David Francis - US grants

The objective of this proposal is to investigate new methodologies for the early detection and identification of reading disabled children. Current approaches to the identification of reading disabilities suffer from statistical and theoretical shortcomings which result in high rates of misclassification. In addition, such approaches, which compare indices of presumed ability potential and actual attainment, preclude early detection of reading disabilities. We propose a skill-based approach based on the growth of requisite precursor abilities underlying successful reading rather than attainment of designated levels of performance. Analysis of individual growth curves yields a quantification of learning that can form the basis for designating children at risk for reading difficulties, and provide an alternative to definitions based on ability potential/achievement discrepancies. To accomplish these objectives, we propose to study the development of precursors of reading and spelling in a broad based sample of kindergarten, first, and second grade children. We propose to use a modified longitudinal time-sequential design with N=900 children studied for one to three years and to assess the utility of using growth rates of reading and spelling precursors and related skills as predictors of growth and attainment in reading and spelling. Three specific aims are proposed addressing (a) reading precursors; (b) predictive utility; and (c) identification. We predict that: 1. Reading Precursors: Kindergarten children will differ in their growth and development of precursor skills, viz. orthographic and phonological awareness, and visual-motor integration. 2. Predictive Utility: The rate of development of the precursors will positively relate to the rate of development and the level of attainment of reading and spelling skill. In turn, individual growth rates in reading and spelling skills will predict performance on standardized tests of reading and spelling, and in-class performance. 3. Identification: The use of growth rates for skills and precursors will (1) allow for earlier identification of children at risk for poor academic outcomes and (2) lead to more stable predictions regarding future academic performance.

9814102 Francis The Strategies for Teacher Excellence Promoting Student Success (STEPSS) Local Systemic Change project involves the Visalia Unified School District (CA), California State University - Fresno, and Fresno Pacific University. The project focuses on the implementation of mathematics education reform initiatives at the K-6 levels. Approximately 900 teachers and administrators are involved in this project. The design and implementation model for this project includes successful components from the California Department of Education's NSF-funded Math Matters project, the San Joaquin Valley Mathematics Project, and Visalia Unified's own staff development initiatives. Project teachers will be supported as they implement Creative Publication's MathLand mathematics program. The project is dedicated to strengthening the mathematics content background of the K-6 project teachers. The project serves a very needy student population. This includes 24,000 K-12 students and covers 200 square miles in the San Joaquin Valley of central California. Approximately fifty percent of the district's students live in poverty. A promising and unique aspect of this project is the involvement of pre- and inservice teachers. The project will create at least two pre-service mathematics laboratory sites (linked to Fresno Pacific University and California State University - Fresno, respectively). The labs will be organized to provide pre- and inservice teachers with awareness and knowledge of all of the NSF-funded elementary and middle school curriculum projects. Project pre- and inservice teachers will have access to the NSF curriculum materials and have experiences with them involving and related to mathematics content and pedagogy.

data collection methodology /evaluation; statistics /biometry

The objective of Project I (Measurement) is to develop and evaluate instruments used to measure oracy and literacy in Spanish and English in English-language learners. We propose a five-year study of 1600 children in grades K-3 who are English-language learners. Primary data collection will occur in the first two years. In subsequent years, efforts will be devoted to hypothesis-oriented analyses of the first two years of data collection, and the analysis of measurement-related hypotheses based on data collected in Project II (Development) of this program project. A cross-sectional design is proposed over t he same age range studied longitudinally in Project II (Development). The data collection scheme in Project I (Measurement) will allow efficient development of new tests and initial estimation of item parameters and test properties using a pool of subjects that span the age and ability range of Project II, but requiring only one year of primary data collection. This approach of superimposing a cross-sectional design over a longitudinal design allows us to assess potential effects of repeat testing (so called practice effects) in the longitudinal study. More importantly, Project I will permit identification of appropriate basal and ceiling rules for all tests, allow reduction in administrative time for all tests, thoroughly evaluate the psychometric properties of all tests without comprising domain coverage, and test specific hypotheses about the inter-relationship of the various constructs in English-language learners. Three specific aims are proposed: 1) language proficiency addresses the psychometric properties and construct validity of tests used to measure oracy, literacy, and literacy-related skills in English and Spanish in English language learners; 2) literacy-related skills addresses the nature of the constructs that underlie development of language and literacy skills in English and Spanish, and their interrelationships; 3) psychometric characteristics provides for instrument development and refinement through systematic evaluations of the reliability and validity of measures of oracy and literacy used across the program project. Altogether, Project 1 is central to the goals of the research program, providing tools and a hypothesis-oriented evaluation of these tools essential to the Projects II-V. In addition, Project I highly responsive to the overall goals of the RFA, responding to the call for improve measurement strategies and normative development studies of English-language learners.

The development and literacy skills in children who speak Spanish is a major problem for our society. The most pressing issue for research in this area is the language in the literacy development of English-language learning. The objective of this program project application is to identify the factors and conditions under which children who speak Spanish develop proficient literacy skills in English and Spanish. The central theme is that there is substantial variability in the development of literacy skills among English-language. Multiple factors and conditions at levels involving the child, teacher, and the context in which the child develops (school, family, community) account for this variability. In order to explain this variability, these factor and conditions must by language in literacy skill development. To address this objective and central theme, we propose a core longitudinal study from K-G3 of 1,440 children in 144 classrooms in schools from 3 geographic regions: urban Texas, border Texas, and urban California. These children will be selected from classroom representative of one of 4 language program models; (1) English language immersion; (2) early exit; (3) late exit; and (4) dual language. Five projects are proposed: 1) Project I (Measurement) addresses the development and evaluation of instruments for measuring oral language proficiency, literacy skills, and literacy-related skills in English and Spanish; 2) Project II (Development) proposes a 4-year longitudinal study (K-G3) of the growth of oral language proficiency, literacy skills, and literacy-related skills; 3) Project III (Instruction) provides for systematic observations of classroom instructional practices; Project IV (Intervention) evaluates the efficacy of early interventions for high risk English-language learners. Two Cores support the 5 projects: Core A (Administrative Core); and Core B (Data Management, Computer, and Statistics). Projects II-IV are based on the same core longitudinal sample and utilize the measures developed in Project I (Measurement). This synergistic, multi-site study addresses the primary focus of the RFA by systematically evaluating "the condition under which English-language reading and writing skills are most efficiently and productively developed in children whose first language is Spanish."

This award provides support for purchase of several instruments used in analysis of plants and microbes. The equipment includes a 16 capillary DNA sequencer, PCR machines, a liquid robotic handler, and necessary software. The instrumentation has the increased throughput capacity needed for several ongoing research projects of faculty and students at the OSU campus in Wooster, and at nearby Hiram College. The instruments will be placed in the Molecular and Cellular Imaging Center (MCIC), a multi-disciplinary core facility on the campus. Research programs expected to use the instruments include studies of variation in tomato fruit morphology, studies of the molecular basis of interactions between oomycete fungi and their plant hosts, molecular studies of quantitative variation in plant resistance to disease and abiotic stress, and high throughput genotyping and sequencing of microbial genomes. In addition to its role in research, the equipment will be integrated into a broad range of ongoing outreach and training activities for which the MCIC is currently a focal point. Graduate students, postdoctoral fellows, faculty and technical staff from more than 28 laboratories in ten different departments use the facility for studies related to their thesis work or research. In addition, undergraduate students from private, state, community, and minority colleges participate in summer research programs on the Wooster campus . These students will have access to training and use of the requested instrumentation. The MCIC hosts frequent tours for high school students and teachers, K-12 students, as well as area residents to provide a greater understanding of plant, animal and microbial research and to engage the broader community in science-related activities .

ABSTRACT NOT PROVIDED

0-11 years old; Achievement; Achievement Attainment; Address; Affect; Aptitude; Child; Child Youth; Children (0-21); Classification; Cognitive; Comprehension; Confidence Intervals; Data; Development; Disabled Persons; Disabled Population; Early Intervention; Early Intervention (Education); Exhibits; Handicapped; History; Human, Child; Incidence; Individual; Individual Differences; Instruction; Intercept; Intervention; Intervention Strategies; Intervention Studies; Investigation; Learning; Learning Disabilities; Learning disability; Longitudinal Studies; Measurement; Measures; Modeling; Monitor; Nature; Numbers; Outcome; People with Disabilities; Performance; Persons with Disabilities; Population; Rate; Reader; Reading; Reading Disabilities; Reading disability; Recording of previous events; Relative; Relative (related person); Research; Risk; SUBGP; Sampling; Schools; Sensitivity and Specificity; Severities; Students; Subgroup; Systematics; Testing; Texas; Time; Validity and Reliability; Vocabulary; Vocabulary Words; base; children; disability; disabled; disabled people; improved; interventional strategy; long-term study; neuroimaging; remediation; response; skills; youngster

a. Objectives Core B plays the role of the traditional Data Coordinating Center in multi-site clinical trials research. As such, Core B was designed to provide support to Cores A and C and Projects 1-4 in three broadly defined areas - Data Acquisition, Data Management and Communications, and Data Analysis. The specific objectives of Core B are to (a) facilitate acquisition of data and project specific data for Projects 1-4, (b) develop tools and procedures for ensuring and monitoring the accuracy and confidentiality of all collected data, (c) develop tools and procedures to aid the Principal Investigator, the Executive Committee, and the Scientific Advisory Board in providing scientific oversight and administration of the Program Project, (d) facilitate communication and sharing of data among investigators through state of the art computer networking, and (e) provide statistical support to investigators in the evaluation of Project 1-4 hypotheses.

Project 1: Classification and Definition of Learning Disabilities Based on Response to Instruction Models. The objective of Project 1 (Classification) is to systematically evaluate a set of classification and measurement issues that affect the identification of students as learning disabled (LD) in response to instruction (RTI) models. We propose three specific aims organized around the classification, measurement, and identification of LD. Specific Aim 1 (Assessment and Identification) addresses the development of an assessment battery that permits the identification of poor readers in the older grades. To implement RTI models, it must be possible to screen a school population, identify students at-risk for disability status, and monitor their progress. In Year 1, we propose a study of 800 students followed from the end of Grade 5 - beginning of Grade 6 in an effort to (a) identify the incidence and types of reading problems involving accuracy, fluency, and comprehension in a sample initially selected on the basis of poor performance on a comprehension test;(b) evaluate the stability of these types;and (c) determine whether abbreviated assessments at ah individual or group level can reliably identify poor readers in middle school. Specific Aim 2 (Reliability of RTI Models) addresses the nature and reliability of different criteria for identifying inadequate responders in different assessment domains (accuracy, fluency) and criteria (intercept, slope, absolute criteria). By utilizing the assessment data used to evaluate outcomes in Projects 2 (Early Intervention) and 3 (Remediation) at the beginning and end of intervention, and more frequent progress monitoring assessments from these Projects, we will define the number of students that meet different RTI criteria, examine overlap, and manipulate the effect of different cut points. Specific Aim 3 (External Validity of RTI Models) addresses the validity of classifications that emerge under Aim 2 using cognitive assessments obtained before and after Tier III interventions in Project 2 (Early Intervention) and Project 3 (Remediation). In addition, we will use the functional neuroimaging data from Project 4 (MSI) to further evaluate the external validity of RTI classifications based on variables not used to define the groups. RTI criteria will be compared to criteria generated by other proposed classification, including IQ-discrepancy, low achievement, and individual difference models. Altogether, we propose a thorough investigation of classification and definition issues involving LD and RTI that reflects our 25 year history of research on these issues and is integrated with the other projects and cores in the Texas Center for Learning Disabilities.

DESCRIPTION (provided by applicant): The discovery and development of a vaccine candidate that elicits a broad-spectrum protection against diverse influenza subtypes, also termed a universal vaccine, is needed to prevent or limit the spread of influenza viruses with pandemic potential in pigs and humans. Some progress has recently been made in generating a universal vaccine, such as M2e and virus-like-particle vaccines. Perhaps the most significant progress is the discovery of CR6261, F10, and 12D1 antibodies apparently targeting viral fusion machinery largely constituted by HA2, rather than the receptor-binding site in HA1. CR6261 and F10 bind to conformational epitopes within the conserved A helix of HA2 likely presented in the context of the adjoining region, while 12D1 binds to a linear eptiope within the long CD helix of HA2. However, such antibodies are infrequently induced either by immunization with influenza vaccines or through natural infection, suggesting that their epitope(s) are temporary and short-lived, or are spatially restricted in exposure. The goal of this R15 project is to identify immunogens that elicit a broadly neutralizing antibody response targeting both the A helix and the CD helix of HA2. This will be achieved by modifying the HA2 protein to allow exposure of the A helix as well as the CD helix with its adjoining region in a native context that will preserve a unique set of broadly neutralizing epitopes represented by CR6261/F10/12D1. Specifically, we will generate the fusion intermediates that present these conserved targets to the immune system as they exist after low pH triggering, but prior to fusogenic structure formation. We plan to utilize the virus-like-particle (VLP) platform as a technical basis to produce our innovative fusion-active vaccine. Another goal in this application is to evaluate the efficacy of M2e vaccine in a pig model and determine whether it induces protective immunity, or an adverse immune response as was demonstrated in a previous study. This R15 project will be accomplished by: Aim 1, To prepare, characterize, and purify H1N1 fusion-active and M2e immunogens, and Aim 2, To evaluate selected immunogens and vaccination strategies in a pig model for their ability to elicit protective immune responses against different subtypes of influenza A virus. This project will be approached by an interdisciplinary team that consists of David Francis (Co-PI, Pig model), Radhey Kaushik (Co-PI, swine immunology), Feng Li (Investigator, influenza virology) and two swine influenza consultants (Weijun Ma and Mahesh Khatri). PUBLIC HEALTH RELEVANCE: Influenza remains a significant cause of morbidity and mortality worldwide with the potential to cause pandemics. The vaccine is by far the most effective means of preventing influenza infection;however, rapid genetic drift and reassortment associated with viral surface glycoproteins often render vaccine less effective particularly against virus strains not closely related to vaccine strains, which has been highlighted in 2009 swine influenza H1N1 pandemic. Thus, the development of new vaccine strategies eliciting potent and broadly cross-protective antibodies is urgently needed, and has been viewed as a global public health priority. The goal of the proposed research is to identify immunogens that will elicit a broadly neutralizing antibody response in a pig model against different subtypes of influenza viruses. If successful, the immunogens studied in this project will provide critical insight to develop a universal influenza vaccine that can used to prevent or limit the spread of influenza viruses with pandemic potential in both pigs and humans.

The objectives of Core C are to (a) facilitate acquisition of data and project specific data for Projects 1-4, (b) develop tools and procedures for ensuring and monitoring the accuracy and confidentiality of all collected data, (c) develop tools and procedures to aid the Principal Investigator, the Executive Committee, and the Scientific Advisory Board in providing scientific oversight and administration of the Texas Center for Learning Disabilities, (d) facilitate communication and sharing of data among investigators through state of the art computer networking, (e) provide statistical analysis of Project 1-4 hypotheses, and (f) collaborate with investigators in the conceptualization of and to conduct cross-project, integrative analyses from the current projects, as well as those that might involve data from the current projects and data collected in the prior award. Dr. David Francis, an experienced methodologist, is the Core Director. He will supervise all activities of Core C, working closely with other experienced methodologists (Stuebing, Cirino, Roberts) to establish data bases, supervise quality control, and perform statistical analyses. The resources of the Texas Institute for Measurement, Evaluation, and Statistics (TIMES) are extensive and will be available to the Center. The Core has the capacity for sophisticated data management and complex statistical analysis, with an established track record in this area. All of the project publications reflect usage of Core C for data management and analysis over the past 5 years.

Most existing methodologies of functional data analysis are limited to data structured in one domain, such as time. Two-way structured functional data are indexed by two functional domains, such as space and time, and each domain has its own notion of regularity, such as smoothness or sparsity. Fully considering the two-way structure of the data will lead to more accurate analysis results. Recent work by the lead PI on two-way regularization has provided some preliminary results and a good starting point for investigating new methodology of dimension reduction, feature extraction, regression and classification for two-way functional data. This research team plans to further develop the methodology for two-way functional data in several important directions:(a) Develop a Reproducing Kernel Hilbert Space theory for two-way regularized singular value decomposition (SVD); (b) Develop novel dimension reduction methods for data that are indexed by general domains such as manifolds; (c) Develop dimension reduction methods that effectively analyze discrete two-way functional data; (d) Develop two-way regularization methods for solving the magnetoencephalography (MEG) inverse problem; (e) Develop new classifiers for diagnosis of mental disorders using dynamic MEG images as predictors; (f) Develop robust methods that are resistant to outliers. The success of the research will add a new dimension to functional data analysis and significantly enrich the field.

Two-way structured functional data arise in various disciplines, including medicine, social sciences, earth sciences, economics, and business. But few existing methodologies fully take into account the two-way structure of this type of functional data. The novel statistical methods developed in this research will provide valuable tools for efficient use of such data. They will provide better understanding of scientific, social and economic phenomena and make more accurate predictions. In particular, the two-way reguarlized SVD provides a new analysis of variance method for analyzing high throughput bioinformatics data and for discovering interactions among biomarkers and clinical variables that are associated with a disease phenotype. The new MEG inverse solvers will facilitate noninvasive presurgical mapping of functional areas of the brain. The new classifiers will help diagonosis and assessment of mental diseases using dynamic MEG images. The proposed activities involve training of Ph.D. students who participate in the proposed projects and mentoring of the female, junior statistician P.I. in a psychology department. Research results will be disseminated through collaborative work, academic presentations, and journal publications. Web pages will be created to enable quick access to user-friendly and accessible software implementations of new methods as well as technical reports and relevant references.

PROJECT SUMMARY Unilateral vocal fold paralysis (UVFP) is a debilitating condition with major health and quality of life implications. It is caused by injury to the recurrent laryngeal nerve and is iatrogenic in 50% of cases, most commonly from thyroidectomy or anterior cervical disc fusion surgeries. Rates of these procedures have increased several fold in the last few decades, which when combined with other surgical, traumatic, and other etiologies puts a correspondingly increased proportion of patients at risk for this condition. The quality of life consequences for patients with UVFP-associated voice disturbances are worse than those with asthma, acute coronary syndrome and depression. From a health perspective, 60% of UVFP patients suffer from dysphagia (23% among these have aspiration), and 75% have breathing difficulties. The basic tenet of treatment is to recapitulate the laryngeal sphincter to permit vocal fold closure thereby improving voice and swallowing, reducing aspiration risk, and normalizing respiration. Treatment algorithms vary widely based on timing and type of intervention. However, significant practice variation exists with advocates of each touting their advantages; however, no standard measure exists to compare their relative effectiveness at relieving symptoms related to all domains of laryngeal function (e.g. voice, swallowing, breathing). Lack of a standard composite measure of UVFP-attributable disability is a barrier to quantifying patient disability, tracking symptom improvement, and comparing treatment effectiveness. To date, objective measures (e.g. acoustics) have not consistently correlated with symptomatic improvement. Therefore, patient reported outcome measures (PROM) assessing quality of life and disability are arguably most relevant and should be used to optimize our treatment algorithms. No PROM currently evaluates all aspects of laryngeal function; instead their scope is limited to voice or swallowing, and none assess laryngeal- associated respiratory dysfunction. Such deficiencies in clinically applicable measures have limited our ability to comprehensively assess patient response to interventions aimed at treating UVFP. This proposal describes a career development plan that will enable me to develop expertise in outcome measure development methodology, systematic reviews and meta-analysis, and surgical comparative effectiveness research techniques. The research specific aims are: a) to systematically review the literature on PROMs related to voice, swallowing, and breathing, evaluating their construct and analyzing adequacy of psychometric development; b) to rigorously develop a PROM to assess UVFP-attributable disability using classical test theory principles and to perform principal component analysis to determine its latent dimension structure and scoring; and c) validate the PROM by: performing confirmatory factor analysis and assessing test-retest reliability, alternate administration/form reliability, concurrent criterion-related validity, and construct validity including longitudinal responsiveness to time and intervention. The career development plan integrates: a) advanced coursework and individualized mentor-directed instruction in outcome measure development methodology, systematic review/meta-analysis, and surgical comparative effectiveness techniques, b) participation in local/national seminars and conferences to advance expertise in qualitative and quantitative aspects in development of PROMs in addition to conduct of systematic reviews/meta-analysis and surgical trials, c) a multidisciplinary mentored research experience, and d) a highly supportive research environment. This environment includes the Center for Surgical Quality and Outcomes Research, an AHRQ-funded Evidence-based Practice Center, a NIH-funded Clinical Translation Science Award, a top-ranked Peabody School of Education, a Masters in Public Health program, and the state-of-the- art Bill Wilkerson Center for Otolaryngology and Communication Sciences. Overall, this career development award will advance my career in comparative effectiveness research by providing education in outcome measure development methodology and will yield a rigorously developed and psychometrically valid PROM that comprehensively assesses UVFP-attributable disability. Importantly, this award provides critical support to seamlessly transition toward future independently funded studies that use the newly created PROM to compare UVFP interventions, track recovery, prognosticate, and better tailor management algorithms to minimize UVFP-attributable disability.

A Wilson, Core C (Data Management and Statistics) Summary The objectives of Core C are to (a) facilitate acquisition of shared data and project specific data for Projects 1- 5, (b) develop tools and procedures for ensuring and monitoring the accuracy and confidentiality of all collected data, (c) develop tools and procedures to aid the Principal Investigator, the Executive Committee, and the Scientific Advisory Committee in providing scientific oversight and administration of the Texas Center for Learning Disabilities (TCLD), (d) facilitate communication and sharing of data among investigators through state of the art computer networking and HIPAA Compliant shared, distributed workspaces, and data movement (e) provide statistical analysis and/or support to Projects 1-5, and (f) to collaborate with investigators in the conceptualization and execution of cross-project, integrative analyses from the current projects, including synergistic activities that might incorporate data collected in the prior TCLD awards. These objectives are organized into three specific aims targeting: (1) Data Acquisition; (2) Data Management; and (3) Data Analysis. Through these aims Core C seeks to enhance the scientific rigor and reproducibility of research throughout the center by providing investigators access to sustainable, cost effective, cutting-edge intellectual and technical resources, prioritizing quality control, scientific integrity, and productivity, and promoting advanced statistical approaches to individual study aims and interdisciplinary, cross-project synergies. Dr. David Francis, an experienced methodologist, is the Core Director. He will supervise all activities of Core C, working closely with other experienced methodologists (Taylor, Roberts, Cirino) to establish databases, supervise quality control, and perform statistical analyses. The resources of the Texas Institute for Measurement, Evaluation, and Statistics (TIMES) are extensive and will be available to the Center. The Core has the capacity for efficient, high quality data acquisition, sophisticated data management, and complex statistical analysis, with an established track record in all three areas. The project publications that involve data listed in the current progress reports reflect usage of Core C for data management and analysis over the past 5 years.

The overarching theme of Project 1 (Integration) is integration, with the following objectives: (a) to continue research on the classification and identification of children with learning disabilities (LDs) using statistical simulation and real data (b) to extend this work to English learners (Els), and (c) to expand the use of meta- analysis and extend previous syntheses to co-morbid disabilities and to Els. The activities integrate research across projects, approaches, frameworks, settings, and populations. With this overarching purpose of Integration and these stated objectives, Project 1 has three specific aims. Specific Aim 1 (Classification and Identification) addresses the challenges inherent in the identification and classification of LDs, targeting a historical mismatch permeating the literature between approach (dimensional) and framework (categorical). Project 1 seeks to investigate the inherent nature of LDs as either dimensional or non-dimensional while moving beyond current approaches to identification to develop and evaluate new approaches that overcome the known problems with existing approaches. Aim 1 draws on simulated data and actual data from Projects 2- 4 in the prior and current awards, and Projects 1 (Classification) and 3 (Remediation) from the first award. New methods include (a) latent variable models appropriate for categorical and dimensional frameworks, and (b) a reframing of RTI in terms of expected magnitude of response to instruction, consistent with a dimensional view of LDs. We expect to find support for our reconceptualization of RTI in terms of expected magnitude of response that is consistent with ideas from personalized medicine as applied to student learning and instruction. In addition, application of these methods to a large sample of Els will address fundamental questions of how to identify LDs in Els with persistent academic difficulties. Specific Aim 2 (External Validity of Identification Methods) addresses the validity of the identification and classification methods developed and tested under Aim 1. Using data collected under Projects 2 (Attention), 4 (Neuroimaging), and 5 (Epigenetics), we will compare children from Project 3 (Intervention) identified using different methods under Aim 1 on measures of attention, written expression, math, and other domains, including measures of neural response and epigenetics. We will also work with Project 4 (Neuroimaging) to develop a measure of neural specificity to use in external validation of identifications and to characterize RTI. Specific Aim 3 (Synthesis) continues and expands our work on empirical synthesis from the previous five years. We propose to undertake meta-analytic work addressing (a) the history of LD identification drawing on our prior 100 year review (Scammacca, et al., 2016), (b) predictors of intervention response in comorbid disabilities; (c) cognitive similarities and differences between comorbid and singular disabilities, including multiple academic domains with and without ADD/ADHD; (d) expand previous meta-analyses on identification to synthesize the literature on identification of disabilities in children who are Els; and (e) to update the Grigorenko (2005) synthesis of the LD-genetics literature.

Project Summary/Abstract Unilateral vocal fold paralysis is a debilitating condition that is increasing in prevalence due to proliferation of surgeries that may manipulate the recurrent laryngeal nerve (e.g., thyroidectomy, anterior cervical spine surgery). It has substantial quality of life and health consequences related to dysphonia, dysphagia (with aspiration in some circumstances) and dyspnea. Optimizing management and treatment of this condition has been hindered by lack of a rigorously developed outcome that can measure the degree of disability and track improvement in comparative effectiveness trials. Objective physiological measures do not consistently correspond with patient-reported improvement in function. Therefore, functional recovery needs to be patient-centered; thus patient-reported outcome (PRO) measures are the ideal outcome for this purpose. Unfortunately, current PRO measures are psychometrically inadequate for this purpose. To fill this void, the proposed investigation will finalize the development and validate a unilateral vocal fold paralysis-specific PRO measure that assesses disability related to all aspects of laryngeal dysfunction. Leveraging extensive systematic review of currently available PRO measures and qualitative interviews with UVFP patients and clinicians who routinely treat this population. An item bank was created using patient input, translated into Spanish, and is actively being refined and winnowed based cognitive interviews with both English- and Spanish- speaking UVFP patients. The resultant items will comprise the novel PRO measure, which requires further development and validation. The present investigation creates an online interface that will allow the administration of the novel PRO measure to a diverse, nationwide sample of patients with UVFP in both English and Spanish. It will enable rigorous evaluation of the PRO measure's test-retest reliability, alternative form reliability (online and paper), construct validity, responsiveness to change, and will provide critical data to establish the minimal important difference in scores needed to perform power calculations. The deliverable from this research program will be a patient- centered outcome that can be seamlessly applied as the primary endpoint in planned clinical trials comparing current standard of care and novel treatments for UVFP to optimize care of patients.

Project Summary/Abstract This proposal will generate evidence to reduce the overdiagnosis of thyroid cancer in the United States. Overdiagnosis is the identification of a disease that, had it not been detected, would be unlikely to cause symptoms or death during a patient?s lifetime. Overdiagnosis has significant consequences, such as overtreatment with associated side effects and complications, patient anxiety, and increased healthcare costs. Despite a three-fold increase in thyroid cancer diagnoses since the late 1980s, the mortality rate remains stable. Small papillary thyroid cancers, which are rarely lethal, are responsible for virtually the entire increase in incidence. However, it is not safe to assume that all small thyroid cancers are overdiagnosed; some small thyroid cancers can be aggressive and do need treatment. Effective methods are urgently needed to understand the key factors contributing to thyroid cancer overdiagnosis, so that directed solutions can be developed and implemented to reduce overdiagnosis. We propose the innovative use of systems engineering and simulation modeling to address this knowledge gap and provide a nuanced understanding of the natural history of thyroid tumors. We will use our model to identify the effect of reducing referrals for and use of thyroid imaging on overdiagnosis; the effect of changing the size threshold for biopsy on overdiagnosis; and the downstream impact of reducing overdiagnosis on harms and benefits of treatment. This approach also accounts for differential use and improved precision of ultrasound over time. Our goal is to create and validate a simulation model that quantifies overdiagnosis in thyroid cancer. We will engage stakeholders at all stages of development, from model conception to validation, to elicit clinical guidance and inform our model inputs, outcomes, and dissemination strategies. Our research team comprises an industrial-systems engineer with expertise in cancer modeling, as well as experts in thyroid cancer, cancer epidemiology, health services research, and communication. The multidisciplinary team is highly qualified to complete the three specific aims: (1) Develop and validate a simulation model to quantify overdiagnosis of thyroid cancer in the US; (2) Identify healthcare utilization patterns (e.g., provider encounters and referral decisions) that expose patients to increased thyroid imaging, biopsies, and the overdiagnosis of thyroid cancer; (3) Engage key stakeholders throughout the duration of the project to ensure that the model has face validity, and that the output can be applied to questions important to both clinicians and policy makers. The proposed research aligns with the National Cancer Institute?s mission to help people live longer and healthier lives. Results from this innovative model will help to inform clinical practice guidelines and referral practice recommendations to improve the quality of health care, while reducing inappropriate testing, to minimize overdiagnosis and overtreatment.