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Richard Stephens

Publications and source records attributed to Richard Stephens.

26 records · Page 2Linked to original sources
PubMed2004

The analysis, interpretation, and presentation of quality of life data.

All too often in clinical trials the assessment of quality of life is seen as a bolt-on study. Consequently insufficient consideration is often given to its design, collection, analysis and presentation, and its impact on the trial results and on clinical practice is minimal. In many trials quality of life is a key endpoint, and it is vital that quality of life expertise is involved as soon as possible in the design. Setting a priori quality of life hypotheses will focus the decisions regarding which questionnaire to use, when to administer it, the sample size required, and the primary analyses. Nevertheless quality of life data are complex, and require much skill in determining how to deal with multi-dimensional and longitudinal data, much of which is often missing. There are no agreed standard ways of analysing and presenting quality of life data, but there are guidelines, which if followed, will add transparency to the way results have been calculated. Understanding the impact of treatments on their quality of life is vital to patients, and it is up to us, as statisticians and trialists, to present the data as clearly as we can.

Data Interpretation, Statistical↗
PubMed2003

Endothelial cells preparing to die by apoptosis initiate a program of transcriptome and glycome regulation.

The protein-based changes that underlie the cell biology of apoptosis have been extensively studied. In contrast, mRNA- and polysaccharide-based changes have received relatively little attention. We have combined transcriptome and glycome analyses to show that apoptotic endothelial cell cultures undergo programmed changes to RNA transcript abundance and cell surface polysaccharide profiles. Although a few of the transcriptome changes were protective, most appeared to prepare cells for apoptosis by decreasing the reception and transduction of pro-survival signals, increasing pro-death signals, increasing abundance of apoptotic machinery, inhibiting cellular proliferation, recruiting phagocytes to regions of cell death, and promoting phagocytosis. Additional transcriptomal changes appeared to alter the synthesis and modification of cell surface glycosaminoglycans. The resultant reduced abundance of sulphated cell surface glycosaminoglycans may further promote cell death by inhibiting the presentation of extracellular matrix-tethered survival factors to their receptors on dying cells. We propose that the transcriptome and glycome regulation presented here synergize with previously described protein-based changes to guide the apoptotic program.

Apoptosis↗
PubMed2003

The Orientation of Social Support measure.

In this study we proposed and tested the theory that behavior is affected by the orientation of the members of one's social network. We collected data from 98 women (some drug users) with the Orientation of Social Support (OSS) scale and two other widely used measures: the Social Support Questionnaire (SSQ), and the Multidimensional Scale of Perceived Social Support (MSPSS). Drug use was measured with the Addiction Severity Index (ASI). Pairwise correlations showed that the OSS had no correlation with the SSQ or the MSPSS. Subjects' ASI scores were regressed on the three measures of support. The only variable that entered stepwise regression was the OSS scale. This study confirmed our theory that it is important to examine the orientation of and not just the extent of social support. The paper provides the questionnaire and the scoring procedures for measurement of extent of peer pressure.

Adult↗
PubMed2003

The neuropsychology of heading and head trauma in Association Football (soccer): a review.

Association Football (soccer) is the most popular and widespread sport in the world. A significant proportion of the injuries suffered in football are head injuries involving trauma to the brain. In normal play, head trauma frequently arises from collisions, but some researchers have claimed that it also may arise as a consequence of heading the ball. Although assessments based on biomechanical analyses are equivocal on the potential for brain injury due to football heading, a growing literature seems to support the claim that neuropsychological impairment results from general football play and football heading in particular. However, this review suggests a distinction is required between the neuropsychological effects of concussive and subconcussive head trauma and that all of the neuropsychological studies conducted so far suffer from methodological problems. At best, a few of these studies may be regarded as exploratory. The review concludes that presently, although there is exploratory evidence of subclinical neuropsychological impairment as a consequence of football-related concussions, there is no reliable and certainly no definitive evidence that such impairment occurs as a result of general football play or normal football heading. The neuropsychological consequences of football-related subconcussive effects await confirmatory investigation.

Alcoholism↗
PubMed2002

Microarray analysis of insulin and insulin-like growth factor-1 (IGF-1) receptor signaling reveals the selective up-regulation of the mitogen heparin-binding EGF-like growth factor by IGF-1.

Insulin and insulin-like growth factor-1 (IGF-1) act through highly homologous receptors that engage similar intracellular signaling pathways, yet these hormones serve largely distinct physiological roles in the control of metabolism and growth, respectively. In an attempt to uncover the molecular mechanisms underlying their divergent functions, we compared insulin receptor (IR) and IGF-1 receptor (IGF-1R) regulation of gene expression by microarray analysis, using 3T3-L1 cells expressing either TrkC/IR or TrkC/IGF-1R chimeric receptors to ensure the highly selective activation of each receptor tyrosine kinase. Following stimulation of the chimeric receptors for 4 h, we detected 11 genes to be differentially regulated, of which 10 were up-regulated to a greater extent by the IGF-1R. These included genes involved in adhesion, transcription, transport, and proliferation. The expression of mRNA encoding heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen, was markedly increased by IGF-1R but not IR activation. This effect was dependent on MAPK, but not phosphatidylinositol 3-kinase, and did not require an autocrine loop through the epidermal growth factor receptor. HB-EGF mitogenic activity was detectable in the medium of 3T3-L1 preadipocytes expressing activated IGF-1R but not IR, indicating that the transcriptional response is accompanied by a parallel increase in mature HB-EGF protein. The differential abilities of the IR and IGF-1R tyrosine kinases to stimulate the synthesis and release of a growth factor may provide, at least in part, an explanation for the greater role of the IGF-1R in the control of cellular proliferation.

3T3 Cells↗
PubMed2002

A human TAPBP (TAPASIN)-related gene, TAPBP-R.

TAPASIN, a V-C1 (variable-constant) immunoglobulin superfamily (IgSF) molecule that links MHC class I molecules to the transporter associated with antigen processing (TAP) in the endoplasmic reticulum (ER) is encoded by the TAPBP gene, located near to the MHC at 6p21.3. A related gene was identified at chromosome position 12p13.3 between the CD27 and VAMP1 genes near a group of MHC-paralogous loci. The gene, which we have called TAPBP-R (R for related), also encodes a member of the IgSF, TAPASIN-R. Its putative product contains similar structural motifs to TAPASIN, with some marked differences, especially in the V domain, transmembrane and cytoplasmic regions. By using the mouse ortholog to screen tissue, we revealed that the TAPBP-R gene was broadly expressed. Sub-cellular localization showed that the bulk of TAPASIN-R is located within the ER but biotinylation experiments were consistent with some expression at thecell surface. TAPASIN-R lacks an obvious ER retention signal. The function of TAPASIN-R will be of interest in regards to the evolution of the immune system as well as antigen processing.

Amino Acid Motifs↗
PubMed2002

Analysis of substitution test performance using eye movement and video data.

Substitution tests continue to enjoy widespread popularity in applied neuropsychology. Though highly sensitive, these tests lack specificity, and substitution test decrements are often reported in terms that bear little relation to cognitive or other psychological theory. Objectives were to quantify, using eye movement/video analysis, subitem performance elements for the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol Test (DST); to assess the relative contribution of each of these to standard WAIS-R DST performance in a group; and to assess whether wearing the eye-movement measuring equipment interfered with test performance.

Adult↗