Efficient Inferential Methods in Regression Models with Change Points or High Dimensional Covariates.

We present a fast approach for estimating change-point(s) in the broken-stick model efficiently in both cross-sectional and longitudinal settings. Our method, based on local smoothing in a shrinking neighborhood of each change-point, is shown via simulations to be computationally more viable than existing methods that rely on search procedures. The proposed estimates are shown to have root-n-consistency and asymptotic normality. As our motivating application, we study the MBHMS cohort data to describe patterns of change in log estradiol levels around the final menstrual period, for which a two change-points broken-stick model is a good fit. Though there has been a considerable work done on studying the effects of coarse and fine ambient particles, how the constituent pollutants affect cardiovascular functioning is not clearly understood. We propose using multivariate adaptive elastic-net to capture these effects in an autoregressive model for time series data. Because of the large number of highly correlated pollutants, a reliable method must take into account the high dimensionality as well as multicollinearity issues. This is accomplished by using adaptive elastic-net which deals effectively with the correlated nature of the data. Furthermore, the selection consistency and asymptotic normality properties allow us to provide meaningful statistical inference. As our motivating example, we study the effects of multiple pollutants on several cardiovascular end-points in a rat-study based in Dearborn, Michigan, conducted by the GLACIER. Finally, we look at problems where there are several covariates and some of the covariates have a simple linear effect while some have a broken-stick effect. We are looking at two separate but similar types of problems: one where we have several covariates each with possibly a broken-stick effect but with only a single change-point and the other where the broken-stick effect is exhibited in a single covariate but the number of change-points is unknown. In both settings we strive for a parsimonious yet accurate model, which necessitates an effective variable selection procedure. In a sparse setting, we illustrate the difficulty in using the popular variable selection methods and propose post local-smoothing thresholded ridge regression as an effective variable selection method.PhDBiostatisticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113538/1/ritob_1.pd

Accretion of Chaplygin gas upon black holes: Formation of faster outflowing winds

We study the accretion of modified Chaplygin gas upon different types of black hole. Modified Chaplygin gas is one of the best candidates for a combined model of dark matter and dark energy. In addition, from a field theoretical point of view the modified Chaplygin gas model is equivalent to that of a scalar field having a self-interacting potential. We formulate the equations related to both spherical accretion and disc accretion, and respective winds. The corresponding numerical solutions of the flow, particularly of velocity, are presented and are analyzed. We show that the accretion-wind system of modified Chaplygin gas dramatically alters the wind solutions, producing faster winds, upon changes in physical parameters, while accretion solutions qualitatively remain unaffected. This implies that modified Chaplygin gas is more prone to produce outflow which is the natural consequence of the dark energy into the system.Comment: 21 pages including 7 figures; published in Classical and Quantum Gravit

Friedreich's Ataxia – A Clinical Diagnosis

Friedreich's ataxia (FA) is an autosomal recessive spinocerebellar degenerative disease characterized by hyperexpansion of GAA triplets in Frataxin gene. The hallmark of this disorder is ataxic gait, areflexia, Babinski's sign and positive Romberg test. We report a 9 year old child who presented with all these features and was diagnosed with FA on the basis of these clinical features. There are few case reports of FA where the diagnosis was made so earl

Fast Estimation of Regression Parameters in a Broken-Stick Model for Longitudinal Data

<p>Estimation of change-point locations in the broken-stick model has significant applications in modeling important biological phenomena. In this article, we present a computationally economical likelihood-based approach for estimating change-point(s) efficiently in both cross-sectional and longitudinal settings. Our method, based on local smoothing in a shrinking neighborhood of each change-point, is shown via simulations to be computationally more viable than existing methods that rely on search procedures, with dramatic gains in the multiple change-point case. The proposed estimates are shown to have <math><msqrt><mi>n</mi></msqrt></math>-consistency and asymptotic normality—in particular, they are asymptotically efficient in the cross-sectional setting—allowing us to provide meaningful statistical inference. As our primary and motivating (longitudinal) application, we study the Michigan Bone Health and Metabolism Study cohort data to describe patterns of change in log  estradiol levels, before and after the final menstrual period, for which a two change-point broken-stick model appears to be a good fit. We also illustrate our method on a plant growth dataset in the cross-sectional setting. Supplementary materials for this article are available online.</p

Zwitterionic Nanogels and Microgels: An Overview on Their Synthesis and Applications

Zwitterionic polymers by virtue of their unique chemical and physical attributes have attracted researchers in recent years. The simultaneous presence of positive and negative charges in the same repeat unit renders them of various interesting properties such as superhydrophilicity, which has significantly broadened their scope for being used in different applications. Among polyzwitterions of different architectures, micro- and/or nano-gels have started receiving attention only until recently. These 3D cross-linked colloidal structures show peculiar characteristics in context to their solution properties, which are attributable either to the comonomers present or the presence of different electrolytes and biological specimens. In this review, a concise yet detailed account is provided of the different synthetic techniques and application domains of zwitterion-based micro- and/or nanogels that have been explored in recent years. Here, the focus is kept solely on the “polybetaines,” which have garnered maximum research interest and remain the extensively studied polyzwitterions in literature. While their vast application potential in the biomedical sector is being detailed here, some other areas of scope such as using them as microreactors for the synthesis of metal nanoparticles or making smart membranes for water-treatment are discussed in this minireview as well

Efficacy of Adjuvant 5-Fluorouracil Therapy for Patients with EMAST-Positive Stage II/III Colorectal Cancer

Elevated Microsatellite Alterations at Selected Tetranucleotide repeats (EMAST) is a genetic signature found in up to 60% of colorectal cancers (CRCs) that is caused by somatic dysfunction of the DNA mismatch repair (MMR) protein hMSH3. We have previously shown in vitro that recognition of 5-fluorouracil (5-FU) within DNA and subsequent cytotoxicity was most effective when both hMutSα (hMSH2-hMSH6 heterodimer) and hMutSβ (hMSH2-hMSH3 heterodimer) MMR complexes were present, compared to hMutSα > hMutSβ alone. We tested if patients with EMAST CRCs (hMutSβ defective) had diminished response to adjuvant 5-FU chemotherapy, paralleling in vitro findings. We analyzed 230 patients with stage II/III sporadic colorectal cancers for which we had 5-FU treatment and survival data. Archival DNA was analyzed for EMAST (>2 of 5 markers mutated among UT5037, D8S321, D9S242, D20S82, D20S85 tetranucleotide loci). Kaplan-Meier survival curves were generated and multivariate analysis was used to determine contribution to risk. We identified 102 (44%) EMAST cancers. Ninety-four patients (41%) received adjuvant 5-FU chemotherapy, and median follow-up for all patients was 51 months. Patients with EMAST CRCs demonstrated improved survival with adjuvant 5FU to the same extent as patients with non-EMAST CRCs (P<0.05). We observed no difference in survival between patients with stage II/III EMAST and non-EMAST cancers (P = 0.36). There is improved survival for stage II/III CRC patients after adjuvant 5-FU-based chemotherapy regardless of EMAST status. The loss of contribution of hMSH3 for 5-FU cytotoxicity may not adversely affect patient outcome, contrasting patients whose tumors completely lack DNA MMR function (MSI-H).This work was supported by the United States Public Health Service (DK067287 and CA162147) and the A. Alfred Taubman Medical Research Institute of the University of Michigan