Mouse p53-deficient cancer models as platforms for obtaining genomic predictors of human cancer clinical outcomes

Mutations in the TP53 gene are very common in human cancers, and are associated with poor clinical outcome. Transgenic mouse models lacking the Trp53 gene or that express mutant Trp53 transgenes produce tumours with malignant features in many organs. We previously showed the transcriptome of a p53-deficient mouse skin carcinoma model to be similar to those of human cancers with TP53 mutations and associated with poor clinical outcomes. This report shows that much of the 682-gene signature of this murine skin carcinoma transcriptome is also present in breast and lung cancer mouse models in which p53 is inhibited. Further, we report validated gene-expression-based tests for predicting the clinical outcome of human breast and lung adenocarcinoma. It was found that human patients with cancer could be stratified based on the similarity of their transcriptome with the mouse skin carcinoma 682-gene signature. The results also provide new targets for the treatment of p53-defective tumours.

Assessing the suitability of student interactions from Moodle data logs as predictors of cross-curricular competencies

In the past decades, online learning has transformed the educational landscape with the emergence of new ways to learn. This fact, together with recent changes in educational policy in Europe aiming to facilitate the incorporation of graduate students to the labor market, has provoked a shift on the delivery of instruction and on the role played by teachers and students, stressing the need for development of both basic and cross-curricular competencies. In parallel, the last years have witnessed the emergence of new educational disciplines that can take advantage of the information retrieved by technology-based online education in order to improve instruction, such as learning analytics. This study explores the applicability of learning analytics for prediction of development of two cross-curricular competencies – teamwork and commitment – based on the analysis of Moodle interaction data logs in a Master’s Degree program at Universidad a Distancia de Madrid (UDIMA) where the students were education professionals. The results from the study question the suitability of a general interaction-based approach and show no relation between online activity indicators and teamwork and commitment acquisition. The discussion of results includes multiple recommendations for further research on this topic.

Dissociation of response conflict, attentional selection, and expectancy with functional magnetic resonance imaging

Two different attentional networks have been associated with visuospatial attention and conflict resolution. In most situations either one of the two networks is active or both are increased in activity together. By using functional magnetic resonance imaging and a flanker task, we show conditions in which one network (anterior attention system) is increased in activity whereas the other (visuospatial attention system) is reduced, showing that attentional conflict and selection are separate aspects of attention. Further, we distinguish between neural systems involved in different forms of conflict. Specifically, we dissociate patterns of activity in the basal ganglia and insula cortex during simple violations in expectancies (i.e., sudden changes in the frequency of an event) from patterns of activity in the anterior attention system specifically correlated with response conflict as evidenced by longer response latencies and more errors. These data provide a systems-level approach in understanding integrated attentional networks.

Patterns and Predictors of Stability and Change in Representations of Romantic Relationships in Adolescence and Young Adulthood

Research on the stability of attachment representations across the lifespan has led to two alternative perspectives: the prototype and revisionist perspectives (Fraley, 2002). The prototype perspective posits that there is a stable factor underlying fluctuations in representations and the revisionist perspective argues that there is no inherently stable factor. The current study employed a latent trait-state model to investigate these alternative models of stability and change in representations of romantic relationships in adolescence and young adulthood. The study also sought to identify individual characteristics and relationship experiences that are associated with changes in representations. In a sample of 200 participants, representations were assessed by interview and self-report over seven measurement occasions between ages 15 and 23. Results were consistent with the prototype perspective emphasizing that a stable, latent factor exerts a consistent influence over the lifespan. In addition to a stable component, representations incorporated a component that varies over time. Findings showed that this fluctuating component of representations was associated with internalizing and externalizing symptomatology as well as experiences of support and negative interaction in relationships.

General mental ability as moderator of personality traits as predictors of early career success

In this paper, we examine the effects of general mental ability (GMA) and the personality traits defined in the big five model on extrinsic and intrinsic indicators of career success, in a sample of 130 graduates who were in the early stages of their careers. Results from hierarchical regression analyses indicated that GMA does not predict any of the success indicators. In contrast, the combination of GMA and three of the Big Five Personality traits, conscientiousness, neuroticism, and openness, is significantly associated with greater early career success and has incremental predictive validity.

The adaptive response of humans to exercise: Impact of exercise intensity, fibre-type specific responses and molecular patterns of response

In an attempt to improve the current understanding of the adaptive response to exercise in humans, this dissertation performed a series of studies designed to examine the impact of training intensity and mode on aerobic capacity and performance, fibre-type specific adaptations to training, and individual patterns of response across molecular, morphological and genetic factors. Project #1 determined that training intensity, session dose, baseline VO2max and total training volume do not influence the magnitude of change in VO2max by performing a meta-regression, and meta-analysis of 28 different studies. The intensity of training had no effect on the magnitude of increase in maximal oxygen uptake in young healthy participants, but similar adaptations were achieved with lower training doses following high intensity training. Project # 2 determined the acute molecular response, and training-induced adaptations in aerobic performance, aerobic capacity and muscle phenotype following high-intensity interval training (HIT) or endurance exercise (END). The acute molecular response (fibre recruitment and signal activation) and training-induced adaptations in aerobic capacity, aerobic performance, and muscle phenotype were similar following HIT and END. Project # 3 examined the impact of baseline muscle morphology and molecular characteristics on the training response, and if muscle adaptations are coordinated. The muscle phenotype of individuals who experience the largest improvements (high responders) were lower before training for some muscle characteristics and molecular adaptations were coordinated within individual participants. Project # 4 examined the impact of 2 different intensities of HIT on the expression of nuclear and mitochondrial encoded genes targeted by PGC-1α. A systematic upregulation of nuclear and mitochondrial encoded genes was not present in the early recovery period following acute HIT, but the expression of mitochondrial genes were coordinated at an individual level. Collectively, results from the current dissertation contribute to our understanding of the molecular mechanisms influencing skeletal muscle and whole-body adaptive responses to acute exercise and training in humans.

Predictors of Nasal Obstruction: Quantification and Assessment Using Multiple Grading Scales

Objective. To evaluate the association between nasal obstruction and (1) demographic factors, (2) medical history, (3) physical tests, and (4) nasal exam findings. Study Design. CASE SERIES: Methods. Chart review at a tertiary medical center. Results. Two hundred-forty consecutive patients (52.1 ± 17.5 years old, with a Nasal Obstruction Symptom Evaluation (NOSE) score of 32.0 ± 24.1) were included. Demographic factors and inferior turbinate sizes were not associated with NOSE score or Nasal Obstruction Visual Analog Scale (NO-VAS). A significant association was found between higher NOSE score on univariate analysis and positive history of nasal trauma (p = 0.0136), allergic rhinitis (p < 0.0001), use of nasal steroids (p = 0.0108), higher grade of external nasal deformity (p = 0.0149), higher internal nasal septal deviation grade (p = 0.0024), and narrow internal nasal valve angle (p < 0.0001). Multivariate analysis identified the following as independent predictors of high NOSE score: NO-VAS: ≥50 (Odds Ratio (OR) = 17.6 (95% CI 5.83-61.6), p < 0.0001), external nasal deformity: grades 2-4 (OR = 4.63 (95% CI 1.14-19.9), p = 0.0339), and allergic rhinitis: yes (OR = 5.5 (95% CI 1.77-18.7), p = 0.0041). Conclusion. Allergic rhinitis, NO-VAS score ≥ 50, and external nasal deformity (grades 2-4) were statistically significant independent predictors of high NOSE scores on multivariate analysis. Inferior turbinate size was not associated with NOSE scores or NO-VAS.

Movable-bed laboratory experiments comparing radiation stress and energy flux factor as predictors of longshore transport rate /

"April 1981."

A feasibility study of response techniques for discharge of hazardous chemicals that disperse through the water column /

Prepared for the U.S. Coast Guard, Office of Research and Development, Washington, D.C. under contract no. DOT-CG-51122-A.

A feasibility study of response techniques for discharges of hazardous chemicals that sink /

Includes bibliographical references.