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Biomedical subjects

Paul Smith

Publications and source records attributed to Paul Smith.

At least 55 records · Page 3Linked to original sources
PubMed2004

Follicular lymphoma international prognostic index.

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs < or = 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs > or = 120 g/L), number of nodal areas (> 4 vs < or = 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk (> or = 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.

Adult↗
PubMed2004

Polymorphism in wild-type p53 modulates response to chemotherapy in vitro and in vivo.

A single-nucleotide polymorphism (SNP) in exon 4 results in expression of either arginine (72R) or proline (72P) at codon 72 of p53. We demonstrate that the in vitro response of cells exposed to anticancer agents is strongly influenced by this SNP in wild-type p53. In inducible systems and in cells expressing the endogenous protein, expression of 72P wild-type p53 results in a predominant G1 arrest, with only a minor apoptosis, at drug concentrations causing extensive apoptosis in cells expressing the 72R wild-type variant. The superior apoptosis-inducing activity of the 72R form correlates with more efficient induction of specific apoptosis-associated genes, and is maximal in the presence of serine 46 (S46). In vivo, the outcome of chemo-radiotherapy of squamous carcinomas is more favourable in cancers retaining a wild-type 72R allele, such cases having higher response rates and longer survival than those with wild-type 72P. Together, these results reveal that this SNP is an important determinant of response to anticancer agents in cells expressing wild-type p53. Analysis of complete p53 genotype (mutation and SNP) merits detailed investigation as a simple means for prediction of treatment response and survival in clinical oncology.

Antineoplastic Agents↗
PubMed2004

Matt finish.

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Efficiency, Organizational↗
PubMed2004

Growing pains.

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Decision Making, Organizational↗
PubMed2004

Missing link.

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Black People↗
PubMed2004

Air apparent.

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England↗
PubMed2004

Robotic grid loading system for a transmission electron microscope.

The design, construction, and testing of a robotic grid loading system for a transmission electron microscope is presented. The system, when integrated with automated data collection software, has the potential to carry out large scale multi-grid experiments, as required, for example, by 2D protein crystallization screening trials. We present a detailed description of the system that utilizes a 6 axis articulate robotic arm to load microscope grids into a specimen holder and then load the holder into the microscope. Grids are stored in trays with a capacity of 96 that are based on the format of a standard 96-well microtiter plate. The system has been integrated with an FEI Tecnai microscope and does not require any modification to the microscope and only minor modifications to the specimen holder. Preliminary results regarding cycle time, failure rates, positioning accuracy and a 96 grid screening experiment are presented.

Automation↗
PubMed2004

Caffeine lowers perceptual response and increases power output during high-intensity cycling.

The aim of this study was to determine the effects of caffeine ingestion on a 'preloaded' protocol that involved cycling for 2 min at a constant rate of 100% maximal power output immediately followed by a 1-min 'all-out' effort. Eleven male cyclists completed a ramp test to measure maximal power output. On two other occasions, the participants ingested caffeine (5 mg. kg(-1)) or placebo in a randomized, double-blind procedure. All tests were conducted on the participants' own bicycles using a Kingcycle test rig. Ratings of perceived exertion (RPE; 6-20 Borg scale) were lower in the caffeine trial by approximately 1 RPE point at 30, 60 and 120 s during the constant rate phase of the preloaded test (P <0.05). The mean power output during the all-out effort was increased following caffeine ingestion compared with placebo (794+/-164 vs 750+/-163 W; P=0.05). Blood lactate concentration 4, 5 and 6 min after exercise was also significantly higher by approximately 1 mmol. l(-1) in the caffeine trial (P <0.05). These results suggest that high-intensity cycling performance can be increased following moderate caffeine ingestion and that this improvement may be related to a reduction in RPE and an elevation in blood lactate concentration.

Adult↗
PubMed2004

Mechanically braked Wingate powers: agreement between SRM, corrected and conventional methods of measurement.

In this study, we assessed the agreement between the powers recorded during a 30 s upper-body Wingate test using three different methods. Fifty-six men completed a single test on a Monark 814E mechanically braked ergometer fitted with a Schoberer Rad Messtechnik (SRM) powermeter. A commercial software package (Wingate test kit version 2.21, Cranlea, UK) was used to calculate conventional and corrected (with accelerative forces) values of power based on a resistive load (5% body mass) and flywheel velocity. The SRM calculated powers based on torque (measured at the crank arm) and crank rate. Values for peak 1 and 5 s power and mean 30 s power were measured. No significant differences (P >0.05) were found between the three methods for 30 s power values. However, the corrected values for peak 1 and 5 s power were 36 and 23% higher (P <0.05) respectively than those for the conventional method, and 27 and 16% higher (P <0.05) respectively than those for the SRM method. The conventional and SRM values for peak 1 and 5 s power were similar (P >0.05). Power values recorded using each method were influenced by sample time (P <0.05). Our results suggest that these three measures of power are similar when sampled over 30 s, but discrepancies occur when the sample time is reduced to either 1 or 5 s.

Anaerobic Threshold↗
PubMed2004

Two-stage grafting of flexor tendons: results after mobilisation by controlled early active movement.

We present the results of two-stage flexor tendon grafting to the hand followed by early active mobilisation. Twenty-six digits from 22 patients were assessed over a 10-year period between 1991 and 2001. Using the LaSalle and Strickland assessment for surgical outcome, we found that 20 digits (77%) achieved excellent or good results. Two ruptured (8%) and one developed adhesions (4%). We think that our results are achieved through meticulous attention to surgical technique with the use of mid-lateral incisions for surgical access, strong bony fixation of the graft that allows a good interface between tendon and distal phalanx, and a closely supervised early active mobilisation regimen after the repair.

Adolescent↗
PubMed2004

Layered motion segmentation and depth ordering by tracking edges.

This paper presents a new Bayesian framework for motion segmentation--dividing a frame from an image sequence into layers representing different moving objects--by tracking edges between frames. Edges are found using the Canny edge detector, and the Expectation-Maximization algorithm is then used to fit motion models to these edges and also to calculate the probabilities of the edges obeying each motion model. The edges are also used to segment the image into regions of similar color. The most likely labeling for these regions is then calculated by using the edge probabilities, in association with a Markov Random Field-style prior. The identification of the relative depth ordering of the different motion layers is also determined, as an integral part of the process. An efficient implementation of this framework is presented for segmenting two motions (foreground and background) using two frames. It is then demonstrated how, by tracking the edges into further frames, the probabilities may be accumulated to provide an even more accurate and robust estimate, and segment an entire sequence. Further extensions are then presented to address the segmentation of more than two motions. Here, a hierarchical method of initializing the Expectation-Maximization algorithm is described, and it is demonstrated that the Minimum Description Length principle may be used to automatically select the best number of motion layers. The results from over 30 sequences (demonstrating both two and three motions) are presented and discussed.

Algorithms↗
PubMed2004

Interaction between a G-patch protein and a spliceosomal DEXD/H-box ATPase that is critical for splicing.

Prp2 is an RNA-dependent ATPase that activates the spliceosome before the first transesterification reaction of pre-mRNA splicing. Prp2 has extensive homology throughout the helicase domain characteristic of DEXD/H-box helicases and a conserved carboxyl-terminal domain also found in the spliceosomal helicases Prp16, Prp22, and Prp43. Despite the extensive homology shared by these helicases, each has a distinct, sequential role in splicing; thus, uncovering the determinants of specificity becomes crucial to the understanding of Prp2 and the other DEAH-splicing helicases. Mutations in an 11-mer near the C-terminal end of Prp2 eliminate its spliceosome binding and splicing activity. Here we show that a helicase-associated protein interacts with this domain and that this interaction contributes to the splicing process. First, a genome-wide yeast two-hybrid screen using Prp2 as bait identified Spp2, which contained a motif with glycine residues found in a number of RNA binding proteins. SPP2 was originally isolated as a genetic suppressor of a prp2 mutant. In a reciprocal screen, Spp2 specifically pulled out the C-terminal half of Prp2. Mutations in the Prp2 C-terminal 11-mer that disrupted function or spliceosome binding also disrupted Spp2 interaction. A screen of randomly mutagenized SPP2 clones identified an Spp2 protein with a mutation in the G patch that could restore interaction with Prp2 and enhanced splicing in a prp2 mutant strain. The study identifies a potential mechanism for Prp2 specificity mediated through a unique interaction with Spp2 and elucidates a role for a helicase-associated protein in the binding of a DEXD/H-box protein to the spliceosome.

Adenosine Triphosphatases↗
PubMed2004

Processing bias for sexual material: the emotional stroop and sexual offenders.

As part of an ongoing research project we examined information-processing biases in forensic and nonforensic participants (n = 10 sex offenders, n = 10 violent offenders, n = 10 nonviolent offenders, and n = 13 undergraduates). A computerised version of the Stroop task demonstrated that offenders convicted of both sexual and violent offences were significantly slower than undergraduates to color-name words relating to sexual offending (with sex offenders demonstrating the greatest interference bias). Furthermore, processing bias was also evident for aggression words in violent offenders and violent sexual offenders but not in non-violent sexual offenders. Specifically, paedophiles convicted of indecent assault presented different response profiles compared to heterosexual rapists. These findings suggest that tests that assess information processing bias for salient material may also prove useful as an assessment tool within forensic populations.

Adult↗
PubMed2004

Identification of surface morphologic changes in the mitral valve leaflets and chordae tendineae of dogs with myxomatous degeneration.

OBJECTIVE: To describe structural changes in the left atrioventricular (mitral) valve complex of dogs with endocardiosis by use of scanning electron microscopy. ANIMALS: 5 clinically normal dogs and 4 dogs with mitral valve endocardiosis. PROCEDURE: The mitral valve complex from each dog was fixed and prepared for examination via scanning electron microscopy. Findings in valves from clinically normal and affected dogs were compared to identify surface changes associated with endocardiosis. RESULTS: Compared with findings in valves from clinically normal dogs, endocardiosis-affected mitral valve complexes had several morphologic abnormalities. Tissue swelling on the edge of valve leaflets, chordae tendineae, and the chordal-papillary muscle junction was evident. Damage to the valve complex endothelium was unevenly distributed; in some areas, denudation of endothelial cells had exposed the basement membrane or subendothelial valve collagen matrix. This damage was most noticeable on the leaflet edges and extended more to the ventricular aspect of the valve than the atrial side. Cell loss also extended to the chordae tendineae but was less apparent at the chordal-papillary muscle junction. The remaining endothelial cells on affected valves were arranged in less-ordered rows and had more plasmalemmal microappendages, compared with cells on unaffected valves. CONCLUSIONS AND CLINICAL RELEVANCE: Morphologic changes associated with mitral valve endocardiosis in dogs were similar to those observed in humans with mitral valve prolapse. In dogs with mitral valve endocardiosis, gross changes in the valve complex may affect hemodynamics in the heart; alterations in the leaflet and chordal endothelium may contribute to pathogenesis of this disease.

Animals↗
PubMed2004

Effects of a stress-management program on injury and stress of competitive gymnasts.

20 competitive gymnasts (17 girls, 3 boys; mean age, 14.4 +/- 3.4 yr.) were recruited from two clubs in Auckland, New Zealand. Gymnasts, who had competed at a national or international level, were divided into two groups to examine the effects of a longitudinal stress-management program on injury and stress. Those in the stress-management group took part in 12 1-hr. sessions over 24 weeks, while the control group took part in a placebo program of anthropometric measurements and lectures on nutrition. All participants completed the Life Experiences Survey and Athletic Experiences Survey at baseline, 3 mo., 6 mo. (end of intervention), and 9 mo. (3 mo. after completion of intervention). Injury data were collected prospectively by weekly self-report over the 9-mo. study. Repeated-measures analyses of covariance with age and, where applicable, the baseline measure of the dependent variable entered as covariates, indicated no significant group or group by time effects for the scores on the two surveys, or injury scores. However, given the small sample, the statistical power of the study to detect even large effects was low. Therefore, rather than concluding that the stress-management program had no effect on training hours lost to injury or on stress, upper limits were placed on the magnitude of any effects that might exist. Further research using larger samples is recommended.

Adaptation, Psychological↗
PubMed2003

Must try harder.

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Academies and Institutes↗