CAUSAL INFERENCE WITH A CONTINUOUS TREATMENT AND OUTCOME: ALTERNATIVE ESTIMATORS FOR PARAMETRIC DOSE-RESPONSE FUNCTIONS WITH APPLICATIONS.

Causal inference with a continuous treatment is a relatively under-explored problem. In this dissertation, we adopt the potential outcomes framework. Potential outcomes are responses that would be seen for a unit under all possible treatments. In an observational study where the treatment is continuous, the potential outcomes are an uncountably infinite set indexed by treatment dose. We parameterize this unobservable set as a linear combination of a finite number of basis functions whose coefficients vary across units. This leads to new techniques for estimating the population average dose-response function (ADRF). Some techniques require a model for the treatment assignment given covariates, some require a model for predicting the potential outcomes from covariates, and some require both. We develop these techniques using a framework of estimating functions, compare them to existing methods for continuous treatments, and simulate their performance in a population where the ADRF is linear and the models for the treatment and/or outcomes may be misspecified. We also extend the comparisons to a data set of lottery winners in Massachusetts. Next, we describe the methods and functions in the R package causaldrf using data from the National Medical Expenditure Survey (NMES) and Infant Health and Development Program (IHDP) as examples. Additionally, we analyze the National Growth and Health Study (NGHS) data set and deal with the issue of missing data. Lastly, we discuss future research goals and possible extensions.

IMPROMPTU: FROM PUBLISHER'S IMPULSE TO AN ESTABLISHED SMALL­ SCALE GENRE IN PIANO LITERATURE

The word 'impromptu' began to appear in music literature in the early 19th century, specifically as title for a relatively short composition written for solo piano. The first impromptus appear to have been named so by the publishers. However, the composers themselves soon embraced the title to indicate, for the most part, fairly short character pieces. Impromptus do not follow any specific structural pattern, although many are cast in ternary form. The formal design ranges from strict compound ternary in the early impromptus to through-composed and variation forms. The peak of impromptu's popularity undoubtedly came during the middle and late19th century. However, they are still being composed today, albeit much less frequently. Although there have been many variants of impromptus in relation to formal design and harmonic language over the years, the essence of impromptu remains the same: it is still a short character piece with a general feeling of spontaneity. Overall, impromptus may be categorized into several different groups: some appear as part of a larger cycle, such as Dvorak's G minor Impromptu from his Piano Pieces, B. 110; many others use an element of an additional genre that enhances the character ofthe impromptu, such as Liszt's Valse-Impromptu and Antonio Bibalo's Tango Impromptu; yet another group consists of works based on opera themes, such as Liszt's Impromptu Brillant sur des themes de Rossini et Spontini and Czerny's Impromptus et variations sur Oberon, Op. 134. My recording project includes well-known impromptus, such as Schubert's Op. 142 and the four by Chopin, as well as lesser known works that have not been performed or recorded often. There are four impromptus that have been recorded here for the first time, including those written by Leopold Godowsky, Antonio Bibalo, Altin Volaj, and Nikolay Mazhara. I personally requested the two last named composers to contribute impromptus to this project. My selection represents works by twenty composers and reflects the different types of impromptus that have been encountered through almost three hundred years of the genre's existence, from approximately 1817 (VoriSek) to 2008 (Volaj and Mazhara).

Improving the Timeliness and Response to an Aerosolizedanthrax Attack in the Metropolitan Washington, D.C. Region

Our research was conducted to improve the timeliness, coordination, and communication during the detection, investigation and decision-making phases of the response to an aerosolized anthrax attack in the metropolitan Washington, DC, area with the goal of reducing casualties. Our research gathered information of the current response protocols through an extensive literature review and interviews with relevant officials and experts in order to identify potential problems that may exist in various steps of the detection, investigation, and response. Interviewing officials from private and government sector agencies allowed the development of a set of models of interactions and a communication network to identify discrepancies and redundancies that would elongate the delay time in initiating a public health response. In addition, we created a computer simulation designed to model an aerosol spread using weather patterns and population density to identify an estimated population of infected individuals within a target region depending on the virulence and dimensions of the weaponized spores. We developed conceptual models in order to design recommendations that would be presented to our collaborating contacts and agencies that would use such policy and analysis interventions to improve upon the overall response to an aerosolized anthrax attack, primarily through changes to emergency protocol functions and suggestions of technological detection and monitoring response to an aerosolized anthrax attack.

A Study of pH Manipulation on Tumor Proliferation and the CTL Response

Adoptive Cell Transfer (ACT) Therapy is a cancer treatment that enhances and utilizes the body’s own immune system. However, this treatment has had limited success in clinical trials. We hypothesized that this is due to the immunosuppressive, acidic microenvironment of cancer tumors. We tested the effects of acidic, neutral, and basic environments in vitro on cytotoxic T lymphocyte (CTL) survival, activation, migration and killing ability and on cancer cell survival. We found that CTLs have most optimum survival, activation, and migration in a neutral environment, while the optimal extracellular conditions for EG-7 lymphoma are slightly acidic and B16-OVA melanoma survives best in physiological conditions. Future research should further study the killing ability of T cells in the three different environments and look to move to in vivo experiments.

Genome Wide Association Studies of Phagocytosis and the Cellular Immune Response in Drosophila melanogaster.

Phagocytosis of bacteria by specialized blood cells, known as hemocytes, is a vital component of Drosophila cellular immunity. To identify novel genes that mediate the cellular response to bacteria, we conducted three separate genetic screens using the Drosophila Genetic Reference Panel (DGRP). Adult DGRP lines were tested for the ability of their hemocytes to phagocytose the Gram-positive bacteria Staphylococcus aureus or the Gram-negative bacteria Escherichia coli. The DGRP lines were also screened for the ability of their hemocytes to clear S. aureus infection through the process of phagosome maturation. Genome-wide association analyses were performed to identify potentially relevant single nucleotide polymorphisms (SNPs) associated with the cellular immune phenotypes. The S. aureus phagosome maturation screen identified SNPs near or in 528 candidate genes, many of which have no known role in immunity. Three genes, dpr10, fred, and CG42673, were identified whose loss-of-function in blood cells significantly impaired the innate immune response to S. aureus. The DGRP S. aureus screens identified variants in the gene, Ataxin 2 Binding Protein-1 (A2bp1) as important for the cellular immune response to S. aureus. A2bp1 belongs to the highly conserved Fox-1 family of RNA-binding proteins. Genetic studies revealed that A2bp1 transcript levels must be tightly controlled for hemocytes to successfully phagocytose S. aureus. The transcriptome of infected and uninfected hemocytes from wild type and A2bp1 mutant flies was analyzed and it was found that A2bp1 negatively regulates the expression of the Immunoglobulin-superfamily member Down syndrome adhesion molecule 4 (Dscam4). Silencing of A2bp1 and Dscam4 in hemocytes rescues the fly’s immune response to S. aureus indicating that Dscam4 negatively regulates S. aureus phagocytosis. Overall, we present an examination of the cellular immune response to bacteria with the aim of identifying and characterizing roles for novel mediators of innate immunity in Drosophila. By screening panel of lines in which all genetic variants are known, we successfully identified a large set of candidate genes that could provide a basis for future studies of Drosophila cellular immunity. Finally, we describe a novel, immune-specific role for the highly conserved Fox-1 family member, A2bp1.

Multi-Scale Dynamic Study of Secondary Impact During Drop Testing of Surface Mount Packages

This dissertation focuses on design challenges caused by secondary impacts to printed wiring assemblies (PWAs) within hand-held electronics due to accidental drop or impact loading. The continuing increase of functionality, miniaturization and affordability has resulted in a decrease in the size and weight of handheld electronic products. As a result, PWAs have become thinner and the clearances between surrounding structures have decreased. The resulting increase in flexibility of the PWAs in combination with the reduced clearances requires new design rules to minimize and survive possible internal collisions impacts between PWAs and surrounding structures. Such collisions are being termed ‘secondary impact’ in this study. The effect of secondary impact on board-level drop reliability of printed wiring boards (PWBs) assembled with MEMS microphone components, is investigated using a combination of testing, response and stress analysis, and damage modeling. The response analysis is conducted using a combination of numerical finite element modeling and simplified analytic models for additional parametric sensitivity studies.

An exploration of parent ivolvement in Response to Intervention (RTI) in Title I schools

Research demonstrates that parental involvement positively impacts student achievement and enhances targeted instruction. Notably, however, little research currently exists on how schools involve parents in Response to Intervention (RTI), a framework for implementing targeted, tiered, research-based instruction. The purpose of this study was to interview selected parents, teachers, RTI specialists, and principals in three Title I elementary schools in one school district, plus one district-level administrator, in order to examine how elementary schools currently involve parents in RTI prereferral interventions, and to understand the factors that might facilitate or challenge such parent involvement. I employed a comparative case study qualitative design with each elementary school as the main unit of analysis. I conducted individual, in-depth interviews that lasted approximately 45-60 minutes with a total of 33 participants across the three school sites, including 11 parents, 12 teachers, and six RTI specialists, three principals, and one district-level administrator. I also analyzed documents related to RTI processes that are available through websites and participants. I used Strauss and Corbin’s (1998) three-step scheme for thematic/grounded theory analysis, and Atlas.ti as the electronic tool for management and analysis. Analyses of the data revealed that personnel across the sites largely agreed on how they explain RTI to parents and notify parents of student progress. Parents mostly disagreed with these accounts, stating instead that they learn about RTI and their child’s progress by approaching teachers or their own children with questions, or by examining report cards and student work that comes home. Personnel and parents cited various challenges for involving parents in RTI. However, they all also agreed that teachers are accessible and willing to reach out to parents, and that teachers already face considerable workloads. It appears that no district- or school-wide plan guides parent involvement practices in RTI at any of the three schools. Finally, I present a discussion of findings; implications for teachers, RTI implementation leaders, and Title school leaders; study limitations; and possibilities for future research.