THE ANALYSIS OF THE ADDITIVE MIXED MODEL FOR CLASSES OF NON ORTHOGONAL DESIGNS

Tests for fixed and random effects can be difficult to derive for nonorthogonal designs with mixed models. However, extensions of the intrablock and inter-block analyses of Balanced Incomplete Block Designs can often be obtained. Here we derive the extensions for the broad class of Group Divisible Designs. Decompositions of the design space are used to develop exact tests for fixed and random effects in the additive mixed model with random block effects. Conditions on the design which permit the standard use of the intra-block and inter-block test statistics are given. Important subclasses of Group Divisible Designs include Equireplicate Variance Balanced Block Designs and Group Divisible Partially Balanced Incomplete Block Designs with Two Associate Classes. These two subclasses are also examined. An example from the literature of an experiment on fruit trees is used to illustrate the methods

The Zuni Kidney Project

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Gene methylation biomarkers in sputum as a classifier for lung cancer risk

CT screening for lung cancer reduces mortality, but will cost Medicare ∼2 billion dollars due in part to high false positive rates. Molecular biomarkers could augment current risk stratification used to select smokers for screening. Gene methylation in sputum reflects lung field cancerization that remains in lung cancer patients post-resection. This population was used in conjunction with cancer-free smokers to evaluate classification accuracy of a validated eight-gene methylation panel in sputum for cancer risk. Sputum from resected lung cancer patients (n=487) and smokers from Lovelace (n=1380) and PLuSS (n=718) cohorts was studied for methylation of an 8-gene panel. Area under a receiver operating characteristic curve was calculated to assess the prediction performance in logistic regressions with different sets of variables. The prevalence for methylation of all genes was significantly increased in the ECOG-ACRIN patients compared to cancer-free smokers as evident by elevated odds ratios that ranged from 1.6 to 8.9. The gene methylation panel showed lung cancer prediction accuracy of 82–86% and with addition of clinical variables improved to 87–90%. With sensitivity at 95%, specificity increased from 25% to 54% comparing clinical variables alone to their inclusion with methylation. The addition of methylation biomarkers to clinical variables would reduce false positive screens by ruling out one-third of smokers eligible for CT screening and could increase cancer detection rates through expanding risk assessment criteria

Implication of a Chromosome 15q15.2 Locus in Regulating UBR1 and Predisposing Smokers to MGMT Methylation in Lung

O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that protects cells from carcinogenic effects of alkylating agents; however, MGMT is silenced by promoter hypermethylation during carcinogenesis. A single nucleotide polymorphism (SNP) in an enhancer in the MGMT promoter was previously identified to be highly significantly associated with risk for MGMT methylation in lung cancer and sputum from smokers. To further genetic investigations, a genome-wide association and replication study was conducted in two smoker cohorts to identify novel loci for MGMT methylation in sputum that were independent of the MGMT enhancer polymorphism. Two novel trans-acting loci (15q15.2 and 17q24.3) that were identified acted together with the enhancer SNP to empower risk prediction for MGMT methylation. We found that the predisposition to MGMT methylation arising from the 15q15.2 locus involved regulation of the ubiquitin protein ligase E3 component UBR1. UBR1 attenuation reduced turnover of MGMT protein and increased repair of O6-methylguanine in nitrosomethylurea-treated human bronchial epithelial cells (HBEC), while also reducing MGMT promoter activity and abolishing MGMT induction. Overall, our results substantiate reduced gene transcription as a major mechanism for predisposition to MGMT methylation in the lungs of smokers, and support the importance of UBR1 in regulating MGMT homeostasis and DNA repair of alkylated DNA adducts in cells

Two-step mixed model approach to analyzing differential alternative RNA splicing.

Changes in gene expression can correlate with poor disease outcomes in two ways: through changes in relative transcript levels or through alternative RNA splicing leading to changes in relative abundance of individual transcript isoforms. The objective of this research is to develop new statistical methods in detecting and analyzing both differentially expressed and spliced isoforms, which appropriately account for the dependence between isoforms and multiple testing corrections for the multi-dimensional structure of at both the gene- and isoform- level. We developed a linear mixed effects model-based approach for analyzing the complex alternative RNA splicing regulation patterns detected by whole-transcriptome RNA-sequencing technologies. This approach thoroughly characterizes and differentiates three types of genes related to alternative RNA splicing events with distinct differential expression/splicing patterns. We applied the concept of appropriately controlling for the gene-level overall false discovery rate (OFDR) in this multi-dimensional alternative RNA splicing analysis utilizing a two-step hierarchical hypothesis testing framework. In the initial screening test we identify genes that have differentially expressed or spliced isoforms; in the subsequent confirmatory testing stage we examine only the isoforms for genes that have passed the screening tests. Comparisons with other methods through application to a whole transcriptome RNA-Seq study of adenoid cystic carcinoma and extensive simulation studies have demonstrated the advantages and improved performances of our method. Our proposed method appropriately controls the gene-level OFDR, maintains statistical power, and is flexible to incorporate advanced experimental designs

Acknowledgements: This work was supported by CDC Environmental Public Health Tracking and Asthma grants awarded to NMDOH Environmental Health Epidemiology Bureau

SPOR KULÜPLERİNDE SPOR YAPAN VE SPOR YAPMAYAN ORTAÖĞRETİM ÖĞRENCİLERİNİN ATILGANLIK DÜZEYLERİNİN KARŞILAŞTIRILMASI Adı ve Soyadı: Cemil YILDIRIM Danışman adı : Tayfun AMMAN Kabul tarihi : 20.02.2004 Program : Spor Yöneticiliği Anabilim Dalı : Beden Eğitimi ve Spor Araştırmanın amacı, bir spor kulübünde lisanslı olarak spor yapan ve spor yapmayan ortaöğretim öğrencilerinin atılganlık düzeylerini karşılaştırmaktır. 2002 - 2003 eğitim öğretim yılında gerçekleştirilen çalışma, ilişkisel tarama modeline uygun bir şekilde dizayn edilmiştir. Örneklemini Anadolu yakasından seçilen üç ilçenin sınırları içinde bulunan üç özel, altı resmi okuldan seçilen 142'si lisanslı olarak spor yapan, 198'i de spor yapmayan 340 öğrenciden oluşmuştur. Veri toplam aracı olarak "Rathus Atılganlık Envanteri" ve "Bireyi Tanıma Çizelgesi" kullanılmıştır. Verilerin toplanmasından sonra istatiksel çözümlemeler yapılmış ve bunun içinde SPSS 11,0 programı kullanılmıştır. Araştırmanın sonunda şu sonuçlar elde edilmiştir: Lisanslı olarak spor yapan öğrencilerin atılganlık puanı ortalamaları, spor yapmayan öğrencilerin atılganlık puanı ortalamalarından yüksektir. Bu farklılık p<0.001 düzeyinde anlamlıdır. Yine lisanslı olarak spor yapan erkek öğrencilerin atılganlık puanı ortalamaları, spor yapmayan erkek öğrencilerin atılganlık puanı ortalamalarından yüksektir. Bu farklılık p<0.001 düzeyinde anlamlıdır. Bir başka sonuçta, lisanslı olarak spor yapan kız öğrencilerin atılganlık puanı ortalamaları, spor yapmayan kız öğrencilerin atılganlık puanı ortalamalarından yüksektir. Bu farklılık p<0.001 düzeyinde anlamlıdır. Lisanslı olarak spor yapan kız öğrencilerin atılganlık puanı ortalamaları, lisanslı olarak spor yapan erkek öğrencilerin atılganlık puanı ortalamalarından yüksektir. Bu farklılık p<0.05 düzeyinde anlamlıdır. Yine lisanslı olarak spor yapan öğrencilerin bir hafta içinde yaptıkları sporun süresi ile atılganlık düzeyi puanları arasında anlamlı bir farklılık bulunmuştur, buna göre haftada beş gün spor yapan grubun atılganlık puanları, haftada bir gün spor yapan grubun atılganlık puanlarından daha yüksektir, diğer gruplar arasında anlamlı bir farklılık bulunmamıştır. Diğer değişkeler açısından ise istatiksel olarak bir farklılık bulunamamıştır. THE COMPRASİON AMONG ASSERTİVENSS LEVELS OF SECONDARY STUDENTS WHO ENGAGE IN SPORT OR DON'T ENGOPE IN SPORT IN SPORT CLUBS Summary The aim of this research is to compare the assertiveness levels of the secondary school students who carry out any kind of sport in sport clubs, or don't..Some of them have licenses whereas others don t have licenses. The study, which was made in 2002-2003 Academic Year, was designed in an appropriate way of the correlational method. The sample consists totally 340 students,198 of them licensed , and 142 of them don t license. These students were chosen from three private schools and 6 government schools located in three different borders in Anatolian Region of İstanbul, ın Turkey. In oreder to collect data, Rathus assertiveness ınventory and personal ınformation sheet have been used as a tool. After collecting data,statistical analyses were done and in order to achieve this the programme of SPSS 11.0 was used. At the end of the this research, those results have been obtained. The average points of assertiveness of the licensed students are higher than the average points of asssertiveness of the unlicensed students. This diffrentation is meaningful at the level of p….Again, the average of assertiveness points of the licensed male students is higher than the average of assertiveness points of the male students who do not do sports. This differetiation is meaningful at the level of p<0.001. Another result is that the avarage of assertiveness points of the female students who are licensed to do sports is higher than the avarage of assertiveness points of female students. Who do not do sports. This differentiation is meaningful at the level of p<0.001. The avarage of assertiveness points of female students is higher than the avarage of assertiveness points of male students. This differintation is meaningful at the level of p<0.005. Again, there is a significant diferences between those who make exercises at five days of a week and a day a week among licenced students. It hasn't been found a diffarence statistically by means of other variables