The role of osteoarthritis regulated microRNAs in skeletal development pathways

PhDCellular changes occur during osteoarthritis (OA), which lead to an alteration in phenotype of the resident cartilage cell, the chondrocyte, and subsequent destruction of the tissue. Many of these changes are unknown. I hypothesise these changes may be due in part to microRNAs (miRNAs), small non-coding RNAs that regulate the expression of a discrete repertoire of genes through base-specific interactions within the target genes 3’untranslated region. A previous screen in our laboratory has identified a number of miRNAs differentially expressed in OA cartilage. The objectives of this study were; (1) to investigate the genetic association of the most extensively studied cartilage miRNA (miR-140), and its targets, with OA, and (2) to assess the function of other, differentially expressed, and less well studied miRNAs, in development signalling pathways, namely miR-125b and miR-324-5p, but focusing on miR-324-5p. Here I identified; (1) SNPs within the miR-140 locus and a predicted, OA-associated, miR-140 target, that may affect function; and (2) miR-125b and miR-324-5p as regulators of Hedgehog (Hh) signalling, likely to play a role in skeletal development. miR-324-5p regulates Hh signalling in human and mouse, yet the mechanism appears unconserved. In humans, miR-324-5p targets SMO and GLI1. Using Stable Isotope Labelling with Amino acids in Cell culture (SILAC) mass spectrometry and whole-genome microarrays, I identified novel miR-324-5p targets, and validated Glypican1 (Gpc1) as a direct target of miR-324-5p and a regulator of Hh signalling in mouse. In addition to regulation of Hh, miR-324-5p regulates Wnt signalling, in which it forms a negative feedback loop. Together, this body of work demonstrates how miRNAs, their targets and their function can be linked in their expression and association with OA.Nuffield Foundation and the Oliver Bird Rheumatism Programm

The Influence of Rater Training, Scale Format, and Rating Justification on the Quality of Performance Ratings by Three Rater Sources

The primary focus of the present study was to examine systematically the influence of rater training, scale format, and rating justification on the quality (i.e., convergent and discriminant validity, halo, leniency) of ratings exhibited by three rater sources (i.e., self, peer, observer). Ninety-one undergraduate students participated in a videotaped role play exercise and returned at a later time to take part in a three-hour rating session. These individuals provided self- and peer ratings. Forty-five advanced undergraduate students participated in a similar rating session and provided observer ratings. Convergent validity, discriminant validity, and halo were tested with the multitrait-multimethod analysis of variance (MTMM ANOVA) approach. To assess the influence of training, scale format, and rating justification on the quality of performance ratings, each experimental condition was treated as a MTMM design and separate ANOVAs were calculated. A 2 (Training) x 2 (Format) x 2 (Justification) x 3 (Rater Sources) x 4 (Dimensions) ANOVA was computed to test the effects of the experimental conditions on the leniency of performance ratings across rater sources. Mixed support was found for the ability of these variables to influence the quality of performance ratings given by the three rater sources. Specifically, training and the use of the behavioral checklist increased discriminant validity and reduced halo, while raters who had to justify their performance ratings exhibited lower discriminant validity than raters who did not have to justify their ratings. With respect to leniency, the level of ratings across the three rater sources was affected by the variables of interest. Training and the use of the behavioral checklist helped to reduce leniency in self-ratings in those situations when raters had to justify their performance ratings. These results lend support for the use of training and the behavioral checklist to improve the overall quality of performance ratings given by different rater sources. However, future research should assess what specific training program content is needed to improve convergent validity when the behavioral checklist is used. In addition, research must be conducted to identify which rater sources provide high-quality ratings on which performance dimensions if a multiple-method approach to the assessment of job performance is desire

EDUCATIONAL PROGRAMS TO ADDRESS THE ECONOMIC ADJUSTMENTS FACING TOBACCO FARMERS AND RURAL COMMUNITIES

This paper discusses the context within which educational programs tailored to tobacco producers and related rural communities have developed. Discussion is expanded by examining current program approaches employed by various organizations. Many of these organizations have a manual stake in helping producers in tobacco communities develop their management capacity. A range of initiatives aimed at facilitating economic adjustment is compared, including the major issues addressed and expected outcomes. Many of the initiatives have made useful contributions; however, gaps and limitations remain. These are considered as future educational efforts and issues are discussed.educational programs, tobacco producers, Community/Rural/Urban Development,

Antiretroviral Non-Adherence is Associated With a Retrieval Profile of Deficits in Verbal Episodic Memory.

HIV-associated deficits in verbal episodic memory are commonly associated with antiretroviral non-adherence; however, the specific aspects of memory functioning (e.g., encoding, consolidation, or retrieval) that underlie this established relationship are not well understood. This study evaluated verbal memory profiles of 202 HIV+ participants who underwent a 30-day electronic monitoring of antiretroviral adherence. At the group level, non-adherence was significantly associated with lower scores on immediate and delayed passage recall and word list learning. Retention and recognition of passages and word lists were not related to adherence. Participants were then classified as having either a normal verbal memory profile, a "subcortical" retrieval profile (i.e., impaired free recall with relatively spared recognition), or a "cortical" encoding profile (e.g., cued recall intrusions) based on the Massman et al. ( 1990 ) algorithm for the California Verbal Learning Test. HIV+ participants with a classic retrieval deficit had significantly greater odds of being non-adherent than participants with a normal or encoding profile. These findings suggest that adherence to prescribed antiretroviral regimens may be particularly vulnerable to disruption in HIV+ individuals due to deficits in the complex process of efficiently accessing verbal episodic information with minimal cues. A stronger relationship between non-adherence and passage (vs. word list) recall was also found and may reflect the importance of contextual features in remembering to take medications. Targeted interventions for enhancing and supporting episodic memory retrieval processes may improve antiretroviral adherence and overall health outcomes among persons living with HIV

An examination of Van Dijk's analysis of prejudice in news discourse

LD2668 .R4 SPCH 1989 W66Master of ArtsCommunication Studie

The effect of flares on total solar irradiance

Flares are powerful energy releases occurring in stellar atmospheres. Solar flares, the most intense energy bursts in the solar system, are however hardly noticeable in the total solar luminosity. Consequently, the total amount of energy they radiate 1) remains largely unknown and 2) has been overlooked as a potential contributor to variations in the Total Solar Irradiance (TSI), i.e. the total solar flux received at Earth. Here, we report on the detection of the flare signal in the TSI even for moderate flares. We find that the total energy radiated by flares exceeds the soft X-ray emission by two orders of magnitude, with an important contribution in the visible domain. These results have implications for the physics of flares and the variability of our star.Comment: accepted in Nature Physic

Neurocognitive impairment is associated with lower health literacy among persons living with HIV infection.

This study sought to determine the effects of HIV-associated neurocognitive disorders (HAND) on health literacy, which encompasses the ability to access, understand, appraise, and apply health-related information. Participants included 56 HIV seropositive individuals, 24 of whom met Frascati criteria for HAND, and 24 seronegative subjects who were comparable on age, education, ethnicity, and oral word reading. Each participant was administered a brief battery of well-validated measures of health literacy, including the Expanded Numeracy Scale (ENS), Newest Vital Sign (NVS), Rapid Estimate of Adult Literacy in Medicine (REALM), and Brief Health Literacy Screen (BHLS). Results revealed significant omnibus differences on the ENS and NVS, which were driven by poorer performance in the HAND group. There were no significant differences on the REALM or the BHLS by HAND status. Among individuals with HAND, lower scores on the NVS were associated with greater severity of neurocognitive dysfunction (e.g., working memory and verbal fluency) and self-reported dependence in activities of daily living. These preliminary findings suggest that HAND hinders both fundamental (i.e., basic knowledge, such as numeracy) and critical (i.e., comprehension and application of healthcare information) health literacy capacities, and therefore may be an important factor in the prevalence of health illiteracy. Health literacy-focused intervention may play an important role in the treatment and health trajectories among persons living with HIV infection