Repeated Measures Mixture Modeling with Applications to Neuroscience

In some neurological postmortem brain tissue studies, repeated measures are observed. These observations are taken on the same experimental subject and are therefore correlated within the subject. Furthermore, each observation can be viewed as coming from one of a pre-specified number of populations where each population corresponds to a possible type of neurons. In this dissertation, we propose several mixture models with two components to model such repeated data. In the first model, we include subject-specific random effects in the component distributions to account for the within-subject correlation present in the data. The mixture components are generalized linear models with random effects, while the mixing proportions are governed by a logistic regression. In the second proposed model, the mixture components are generalized linear models, while the component-indicator variables are modeled by a multivariate Bernoulli distribution that depends on covariates. The within-subject observations are taken to be correlated through the latent component indicator random variables. As a special case of the second model, we focus on multivariate Bernoulli mixtures of normals, where the component-indicator variables are modeled by logistic regressions with random effects, and the mixture components are linear regressions. The third proposed model combines the first and second models, so that the within-subject correlation is built into the model not only through the component distributions, but also through the latent component indicator variables. The focus again is on a special case of the third model, where the mixture components are linear regressions with random effects while the mixing proportions are logistic regressions with another group of random effects. For each model, model fitting procedures, based on MCMC methods for sampling from the posterior distribution of the parameters, are developed. The second and third model are used to compare schizophrenic and control subjects with regard to the somal volumes of deep layer 3 pyramidal cells in the auditory association cortex. As a preliminary analysis, we start by employing classic mixture models and mixtures-of-experts to analyze such data neglecting the within-subject correlation. We also provide a discussion of the statistical and computational issues concerning estimation of classic Poisson mixtures

Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1-98 trial

Endocrine therapy for breast cancer may affect cognition. The purpose of this study was to examine whether cognitive function improves after cessation of adjuvant endocrine therapy. Change in cognitive function was assessed in 100 postmenopausal breast cancer patients in the BIG 1-98 trial, who were randomized to receive 5years of adjuvant tamoxifen or letrozole alone or in sequence. Cognitive function was evaluated by computerized tests during the fifth year of trial treatment (Y5) and 1year after treatment completion (Y6). Cognitive test scores were standardized according to age-specific norms and the change assessed using the Wilcoxon signed-rank test. There was significant improvement in the composite cognitive function score from Y5 to Y6 (median of change=0.22, effect size=0.53, P<0.0001). This improvement was consistent in women taking either tamoxifen or letrozole at Y5 (P=0.0006 and P=0.0002, respectively). For postmenopausal patients who received either adjuvant letrozole or tamoxifen alone or in sequence, cognitive function improved after cessation of treatmen

Key technologies research on of soil-structure interaction base story isolated structure response in 3D seismic zone

The development of karst in Karst area leads to poor stability of stratum. If earthquake occurs, the area will produce destructive disaster. In order to improve the stability capacity of the grassroots in the region, this study investigates the seismic response of inter-story isolation structures considering soil-structure interaction (SSI) in three-dimensional earthquakes. A model of the inter-story isolation structure incorporating SSI was developed, and one-dimensional, two-dimensional, and three-dimensional ground motions were applied to compare the seismic response under different input conditions. A three-dimensional isolation system was introduced and compared with traditional horizontal isolation structures to address excessive tensile and compressive stresses on the isolation structure during three-dimensional ground motion. The results demonstrate that the seismic response to three-dimensional earthquakes surpasses one-dimensional and two-dimensional inputs. Furthermore, adding a three-dimensional isolation structure effectively isolates vertical ground motion and reduces structural seismic response. Moreover, it minimizes soil stresses on the foundation compared to traditional horizontal isolation structure, enhancing foundation stability. This study will provide theoretical value and practical guidance for the research on key technology of SSI base story isolation structure response in Karst Plateau 3D Seismic zone

Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX

Introduction: The prognostic significance of p53 protein expression in early breast cancer remains uncertain, with some but not all studies finding an association with poorer outcomes. Estrogen receptor (ER) expression is both a positive prognostic marker and predictive of response to endocrine therapies. The relationship between these biomarkers is unknown. Methods: We constructed tissue microarrays (TMAs) from available pathological material from 1113 patients participating in two randomized clinical trials comparing endocrine therapy alone versus chemo-endocrine therapy in node-negative breast cancer. Expression of p53 defined as >10% positive nuclei was analyzed together with prior immunohistochemical assays of ER performed at central pathological review of whole tumor sections. Results: ER was present (i.e. >1% positive tumor cell nuclei) in 80.1% (880/1092). p53 expression was significantly more frequent when ER was absent, 125/212 (59%) than when ER was present, 171/880 (19%), p <0.0001. A significant qualitative interaction was observed such that p53 expression was associated with better disease-free survival (DFS) and overall survival (OS) among patients whose tumors did not express ER, but worse DFS and OS among patients whose tumors expressed ER. The interaction remained significant after allowance for pathologic variables, and treatment. Similar effects were seen when luminal and non-luminal intrinsic subtypes were compared. Conclusions: Interpretation of the prognostic significance of p53 expression requires knowledge of concurrent expression of ER. The reason for the interaction between p53 and ER is unknown but may reflect qualitatively different p53 mutations underlying the p53 expression in tumors with or without ER expression. Trial registration Current Controlled Trials ACTRN12607000037404 (Trial VIII) and ACTRN12607000029493 (Trial IX)

Independent Prognostic Significance of Monosomy 17 and Impact of Karyotype Complexity in Monosomal Karyotype/Complex Karyotype Acute Myeloid Leukemia: Results from Four ECOG-ACRIN Prospective Therapeutic Trials

The presence of a monosomal karyotype (MK+) and/or a complex karyotype (CK+) identifies subcategories of AML with poor prognosis. The prognostic significance of the most common monosomies (monosomy 5, monosomy 7, and monosomy 17) within MK+/CK+ AML is not well defined. We analyzed data from 1,592 AML patients age 17–93 years enrolled on ECOG-ACRIN therapeutic trials. The majority of MK+ patients (182/195; 93%) were MK+/CK+ with 87% (158/182) having ≥5 clonal abnormalities (CK≥ 5). MK+ patients with karyotype complexity ≤4 had a median overall survival (OS) of 0.4y compared to 1.0y for MK- with complexity ≤4 (p < 0.001), whereas no OS difference was seen in MK+ vs. MK- patients with CK≥ 5 (p = 0.82). Monosomy 5 (93%; 50/54) typically occurred within a highly complex karyotype and had no impact on OS (0.4y; p = 0.95). Monosomy 7 demonstrated no impact on OS in patients with CK≥ 5 (p = 0.39) or CK ≤ 4 (p = 0.44). Monosomy 17 appeared in 43% (68/158) of CK≥ 5 patients and demonstrated statistically significant worse OS (0.4y) compared to CK≥ 5 patients without monosomy 17 (0.5y; p = 0.012). Our data suggest that the prognostic impact of MK+ is limited to those with less complex karyotypes and that monosomy 17 may independently predict for worse survival in patients with AML

Chiral phosphoric acid and its applications of asymmetric catalytic hydrogenation

As an excellent representative of organic small molecular catalysts, chiral phosphoric acid played an important role in asymmetric catalytic hydrogenation. According to the skeleton of chiral phosphoric acid, the development and applications of chiral phosphoric acid were summarized. The applications of chiral phosphoric acid in asymmetric catalytic hydrogenation were introduced according to three kinds of hydrogen source systems used in chiral phosphoric acid catalytic reaction. It was found that chiral phosphoric acid has high activity and excellent selectivity. Chiral products with excellent yields and enantioselectivities were obtained in most reactions

Methods and technologies for high quality medical ultrasound imaging

Using Pulse-echo Technique, ultrasound imaging is considered to be Noninvasive, Portable, Real-time, and Cost Effective, which makes it a most popular diagnostic imaging modality in the world. Based on Sonix RP, an advanced experimental ultrasound scanner, the project Objective is to develop and implement new methods and technologies for high quality medical ultrasound imaging, especially in the area of Speckle Reduction. [5th Award

Identification of a Natural Hybrid between Castanopsis sclerophylla and Castanopsis tibetana (Fagaceae) Based on Chloroplast and Nuclear DNA Sequences

Castanopsis &times; kuchugouzhui Huang et Y. T. Chang was recorded in Flora Reipublicae Popularis Sinicae (FRPS) as a hybrid species on Yuelushan mountain, but it is treated as a hybrid between Castanopsis sclerophylla (Lindl.) Schott. and Castanopsis tibetana Hance in Flora of China. After a thorough investigation on Yuelushan mountain, we found a population of C. sclerophylla and one individual of C. &times; kuchugouzhui, but no living individual of C. tibetana. We collected C. &times; kuchugouzhui, and we sampled 42 individuals of C. sclerophylla from Yuelushan and Xiushui and 43 individuals of C. tibetana from Liangyeshan and Xiushui. We used chloroplast DNA sequences and 29 nuclear microsatellite markers to investigate if C. &times; kuchugouzhui is a natural hybrid between C. sclerophylla and C. tibetana. The chloroplast haplotype analysis showed that C. &times; kuchugouzhui shared haplotype H2 with C. sclerophylla on Yuelushan. The STRUCTURE analysis identified two distinct genetic pools that corresponded well to C. sclerophylla and C. tibetana, revealing the genetic admixture of C. &times; kuchugouzhui. Furthermore, the NewHybrids analysis suggested that C. &times; kuchugouzhui is an F2 hybrid between C. sclerophylla and C. tibetana. Our results confirm that C. &times; kuchugouzhui recorded in FRPS is a rare hybrid between C. sclerophylla and C. tibetana