A comparison of the effectiveness of two methods of teaching reading vocabulary in grade two

Thesis (M.A.)--Boston University, 1950

Adolescent Experiences with Self-Asphyxial Behaviors and Problematic Drinking in Emerging Adulthood

Self-asphyxial behavior to achieve a euphoric high (The Choking Game; TCG), occurs most often during early adolescence. Participants in TCG often engage in other risky behaviors. This study investigated the relationship between prior experience with TCG and problematic drinking behaviors in emerging adulthood. Emerging adults, 18 to 25 years old (N = 1248), 56% female, and 78% Caucasian completed an online survey regarding knowledge of and prior engagement in TCG and current drinking behaviors. Participants who personally engaged in TCG during childhood/adolescence or were familiar with TCG reported significantly more problematic drinking behaviors during emerging adulthood. Those present when others engaged in TCG but resisted participation themselves reported significantly less current problematic drinking behaviors than those who participated, but significantly more current problematic drinking behaviors than those never present. Emerging adults with increased social familiarity with TCG during adolescence endorsed greater problematic drinking behaviors. Results suggest resistance skills may generalize across time/activities

Novel statistical approaches for non-normal censored immunological data: analysis of cytokine and gene expression data

Background: For several immune-mediated diseases, immunological analysis will become more complex in the future with datasets in which cytokine and gene expression data play a major role. These data have certain characteristics that require sophisticated statistical analysis such as strategies for non-normal distribution and censoring. Additionally, complex and multiple immunological relationships need to be adjusted for potential confounding and interaction effects. Objective: We aimed to introduce and apply different methods for statistical analysis of non-normal censored cytokine and gene expression data. Furthermore, we assessed the performance and accuracy of a novel regression approach in order to allow adjusting for covariates and potential confounding. Methods: For non-normally distributed censored data traditional means such as the Kaplan-Meier method or the generalized Wilcoxon test are described. In order to adjust for covariates the novel approach named Tobit regression on ranks was introduced. Its performance and accuracy for analysis of non-normal censored cytokine/gene expression data was evaluated by a simulation study and a statistical experiment applying permutation and bootstrapping. Results: If adjustment for covariates is not necessary traditional statistical methods are adequate for non-normal censored data. Comparable with these and appropriate if additional adjustment is required, Tobit regression on ranks is a valid method. Its power, type-I error rate and accuracy were comparable to the classical Tobit regression. Conclusion: Non-normally distributed censored immunological data require appropriate statistical methods. Tobit regression on ranks meets these requirements and can be used for adjustment for covariates and potential confounding in large and complex immunological datasets

Malonyl coenzymeA decarboxylase regulates lipid and glucose metabolism in human skeletal muscle

Objective: malonyl coenzyme A (CoA) decarboxylase (MCD) is a key enzyme responsible for malonyl-CoA turnover and functions in the control of the balance between lipid and glucose metabolism. We utilized RNA interference (siRNA)-based gene silencing to determine the direct role of MCD on metabolic responses in primary human skeletal muscle. Research design and methods: we used siRNA to silence MCD gene expression in cultured human myotubes from healthy volunteers (seven male and seven female) with no known metabolic disorders. Thereafter, we determined lipid and glucose metabolism and signal transduction under basal and insulin-stimulated conditions. Results: RNA interference-based silencing of MCD expression (75% reduction) increased malonyl-CoA levels twofold and shifted substrate utilization from lipid to glucose oxidation. RNA interference-based depletion of MCD reduced basal palmitate oxidation. In parallel with this reduction, palmitate uptake was decreased under basal (40%) and insulin-stimulated (49%) conditions compared with myotubes transfected with a scrambled sequence. MCD silencing increased basal and insulin-mediated glucose oxidation 1.4- and 2.6-fold, respectively, compared with myotubes transfected with a scrambled sequence. In addition, glucose transport and cell-surface GLUT4 content was increased. In contrast, insulin action on IRS-1 tyrosine phosphorylation, tyrosine-associated phosphatidylinositol (PI) 3-kinase activity, Akt, and glycogen synthase kinase (GSK) phosphorylation was unaltered between myotubes transfected with siRNA against MCD versus a scrambled sequence. Conclusions: these results provide evidence that MCD silencing suppresses lipid uptake and enhances glucose uptake in primary human myotubes. In conclusion, MCD expression plays a key reciprocal role in the balance between lipid and glucose metabolism

Ras-p53 genomic cooperativity as a model to investigate mechanisms of innate immune regulation in gastrointestinal cancers

Despite increasingly thorough mechanistic understanding of the dominant genetic drivers of gastrointestinal (GI) tumorigenesis (e.g., Ras/Raf, TP53, etc.), only a small proportion of these molecular alterations are therapeutically actionable. In an attempt to address this therapeutic impasse, our group has proposed an innovative extreme outlier model to identify novel cooperative molecular vulnerabilities in high-risk GI cancers which dictate prognosis, correlate with distinct patterns of metastasis, and define therapeutic sensitivity or resistance. Our model also proposes comprehensive investigation of their downstream transcriptomic, immunomic, metabolic, or upstream epigenomic cellular consequences to reveal novel therapeutic targets in previously “undruggable” tumors with high-risk genomic features. Leveraging this methodology, our and others’ data reveal that the genomic cooperativity between Ras and p53 alterations is not only prognostically relevant in GI malignancy, but may also represent the incipient molecular events that initiate and sustain innate immunoregulatory signaling networks within the GI tumor microenvironment, driving T-cell exclusion and therapeutic resistance in these cancers. As such, deciphering the unique transcriptional programs encoded by Ras-p53 cooperativity that promote innate immune trafficking and chronic inflammatory tumor-stromal-immune crosstalk may uncover immunologic vulnerabilities that could be exploited to develop novel therapeutic strategies for these difficult-to-treat malignancies

Papers in Australian linguistics No. 15 : Australian Aboriginal lexicography

The past f if teen years have seen major developments in the description and analysis of Australian Aboriginal languages. A large number of descriptive grammars have been published (see Walsh (1979: 8-10) for a partial listing) and several theoretical topics have been discussed in detail, for example , casemarking and ergativity (see papers in Topic B and Topic D of Dixon 1 976, Dixon 1979, Blake 1977 and Silverstein 1981). In addition, some excellent surveys of the f ield have appeared: Blake 1 981, Dixon 1 980 , Yallop 1 982. During this time , lexicography and dictionary production has lagged behind the s tudy of phonological and grammatical issues. In a seminal article on lexicography in Aboriginal Australia , O'Grady 197 1 discussed and evaluated work completed and research in progress for the period 1 780 to 1 968. In an appendix, he gave a summary listing of forty-nine unpublished dictionaries representing thirty-nine different Austral ian languages . A mere four of those have been published in the intervening fif teen years. Admittedly , several vocabularies and d ictionaries not known to O' Grady have appeared recently (for example Coate and Elkin 1975, Hansen and Hansen 1977 and Heath 1982 ) , however , the number of published dictionaries is small compared to the number of available grammars . In addition, no dictionary of an Aus tralian language published to date could be describ�d as truly comprehensive (cf. La ughlin 1 975 or Young and Morgan 1980 for indigenous languages elsewhere in the world ). This situation is set to change in the near future. There are a number of projects currently underway which will see the preparation and publication over the next few years of large comprehensive bilingual dictionaries for a range of Australian languages. Several scholars working on dictionary projects were present at the annual conference of the Australian Linguistic Society held at the Australian National University in 1981. In informal discussions I raised the idea of our getting together to exchange ideas and share experiences . To this end I convened a workshop on Australian Aboriginal lexicography which was held in conjuction with the ALS annual conference at the Univers ity of Sydney in August 1982. Eight papers were presented at the workshop which was attended by thirty-five linguists , many of whom had begun or were about to begin dictionary preparation. All the presentations , with the exception of one by R.M.W. Dixon on the Dyirbal dictionary-thesaurus , were written up and appear in this volume

BMPR2 expression is suppressed by signaling through the estrogen receptor

<p>Abstract</p> <p>Background</p> <p>Studies in multiple organ systems have shown cross-talk between signaling through the bone morphogenetic protein receptor type 2 (BMPR2) and estrogen pathways. In humans, pulmonary arterial hypertension (PAH) has a female predominance, and is associated with decreased BMPR2 expression. The goal of this study was to determine if estrogens suppress BMPR2 expression.</p> <p>Methods</p> <p>A variety of techniques were utilized across several model platforms to evaluate the relationship between estrogens and BMPR2 gene expression. We used quantitative RT-PCR, gel mobility shift, and luciferase activity assays in human samples, live mice, and cell culture.</p> <p>Results</p> <p>BMPR2 expression is reduced in lymphocytes from female patients compared with male patients, and in whole lungs from female mice compared with male mice. There is an evolutionarily conserved estrogen receptor binding site in the BMPR2 promoter, which binds estrogen receptor by gel-shift assay. Increased exogenous estrogen decreases BMPR2 expression in cell culture, particularly when induced to proliferate. Transfection of increasing quantities of estrogen receptor alpha correlates strongly with decreasing expression of BMPR2.</p> <p>Conclusions</p> <p>BMPR2 gene expression is reduced in females compared to males in live humans and in mice, likely through direct estrogen receptor alpha binding to the BMPR2 promoter. This reduced BMPR2 expression may contribute to the increased prevalence of PAH in females.</p

Racial and ethnic differences and COVID-19 pandemic-related changes in drug overdose deaths in North Carolina

Purpose To examine racial/ethnic differences and COVID-19 pandemic-related changes in key characteristics of drug overdose deaths in North Carolina. Methods We used North Carolina State Unintentional Drug Overdose Reporting System (NC-SUDORS) data to describe specific drug-involvement, bystander presence, and naloxone administration for drug overdose deaths by race/ethnicity during pre-COVID-19 (May 2019–February 2020) and COVID-19 periods (March 2020–December 2020). Results For all racial/ethnic groups, drug overdose death rates and the percentage with fentanyl and alcohol involvement increased from the pre-COVID-19 to COVID-19 period, with fentanyl involvement highest among American Indian/Alaska Native (82.2%) and Hispanic (81.4%) individuals and alcohol involvement highest among Hispanic individuals (41.2%) during the COVID-19 period. Cocaine involvement remained high among Black non-Hispanic individuals (60.2%) and increased among American Indian/Alaska Native individuals (50.6%). There was an increase in the percentage of deaths with a bystander present from the pre-COVID-19 to COVID-19 period for all racial/ethnic groups, with more than half having a bystander present during the COVID-19 period. There was a decrease in the percentage with naloxone administered for most racial/ethnic groups, with the lowest percentage among Black non-Hispanic individuals (22.7%). Conclusions Efforts to address increasing inequities in drug overdose deaths, including expanded community naloxone access, are needed