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R Warner

Publications and source records attributed to R Warner.

At least 19 recordsLinked to original sources
PubMed2006

Estimation of the relative risk of developing clinical scrapie: the role of prion protein (PrP) genotype and selection bias.

Prion protein (PrP) genotype data from statutory confirmed cases and from three non-case datasets have been used to calculate the odds ratio (or) for the development of clinical scrapie for an individual sheep of a given PrP genotype, compared with one possessing the "wild-type" ARQ/ARQ genotype. Logistic regression has been used to estimate the ors, and a multiple-test procedure has been used to evaluate the statistical significance of each comparison. The results are similar to those observed in other studies: the VRQ/VRQ genotype has or point estimates greater than 20; the ARQ/VRQ and ARH/VRQ genotypes have or point estimates between 5 and 20; AHQ/VRQ between 0.03 and 0.1; ARR/VRQ 0.4 and 0.5; all the other PrP genotypes, excluding ARR/ARR, ARR/ARH and AHQ/ARH for which no clinical cases have been recorded have or point estimates of less than 0.3. The estimates derived from each dataset are comparable, but not identical. This can be explained by plausible biases inherent in the sampling of the non-case populations.

Abattoirs↗
PubMed2005

Frequencies of PrP genotypes in 38 breeds of sheep sampled in the National Scrapie Plan for Great Britain.

Between October 2001 and January 2003 the prion protein (PrP) genotypes of over 250,000 sheep were determined through the operation of the National Scrapie Plan (NSP); the results for 38 breeds were analysed to provide an estimate of the underlying PrP genotype distribution of the British sheep population. Although there was marked variability among the genotype profiles of the different breeds, several trends emerged. A comparison of the allele frequencies demonstrated that the breeds could be grouped into three categories: breeds dominated by ARR and ARQ in which the frequency of ARR exceeded the frequency of ARQ; breeds dominated by ARR and ARQ in which the frequency of ARQ exceeded the frequency of ARR; and breeds with significant levels of either AHQ, ARH or VRQ. Hill breeds were more likely to have a lower proportion of animals at low risk of scrapie (NSP type 1) and a higher proportion of animals at an intermediate risk of scrapie (NSP type 3) than other breeds. Most breeds had a small proportion of animals at high risk of scrapie (NSP type 5). The frequency of ARR/VRQ (NSP type 4) was variable.

Animals↗
PubMed2005

PrP genotypes of rare breeds of sheep in Great Britain.

In total 31,669 blood samples were collected from 1187 flocks of 27 rare breeds of sheep in the UK, and their genotype profiles at the prion protein locus were determined. The frequencies of the five alleles varied widely among the breeds and some had only two of the alleles and others had all five; the average was three. The average allele frequencies across all 27 breeds were 49.7 per cent for ARR, 4.4 per cent for AHQ, 2.7 per cent for ARH, 37.4 per cent for ARQ and 5.8 per cent for VRQ. The highest frequencies for each allele were 90.7 per cent for ARR in the Leicester Longwool, 24.7 per cent for AHQ in the Hebridean, 68.7 per cent for ARH in the Manx Loghtan, 98.7 per cent for ARQ in the North Ronaldsay and 28.4 per cent for VRQ in the Boreray. All 27 breeds had the ARR allele, 21 had AHQ, 11 had ARH, 26 had ARQ and 20 had VRQ.

Alleles↗
PubMed2001

Effects of exposure to event 176 Bacillus thuringiensis corn pollen on monarch and black swallowtail caterpillars under field conditions.

The widespread planting of corn genetically modified to produce Bacillus thuringiensis endotoxin has led to speculation that pollen from these fields might adversely affect nearby nontarget lepidopterans. A previous study of Bt corn engineered with Monsanto event 810 failed to detect an effect of pollen exposure on the black swallowtail, Papilio polyxenes, in either the field or the laboratory. Here, we report results of a field study investigating the impact of exposure to pollen from a Bt corn hybrid containing Novartis event 176 on two species of Lepidoptera, black swallowtails and monarch butterflies, Danaus plexippus. Nearly half of the 600 monarch larvae died within the first 24 h; this and subsequent mortality was not associated with proximity to Bt corn and may have been due in part to predation. Survivorship of black swallowtails was much higher than that of the monarchs and was also independent of proximity to the transgenic corn. However, despite five rainfall events that removed much of the pollen from the leaves of their host plants during the experiment, we observed a significant reduction in growth rates of black swallowtail larvae that was likely caused by pollen exposure. These results suggest that Bt corn incorporating event 176 can have adverse sublethal effects on black swallowtails in the field and underscore the importance of event selection in reducing environmental impacts of transgenic plants.

Animals↗
PubMed2001

The prevention of schizophrenia: what interventions are safe and effective?

Obstetric complications appear to increase the risk of developing schizophrenia, and post-World War II improvements in obstetric care may have contributed to a decline in the incidence of the illness in the developed world. Educating providers and consumers of psychiatric and obstetric services about the risk of obstetric complications in increasing the risk of schizophrenia could bring about a further small decrease in the incidence of the illness, safely and at low cost. On the other hand, attempts to prevent the occurrence of schizophrenia by treating people who manifest high-risk indicators prior to the development of the illness have a low probability of success and a high probability of unintended negative consequences. Early intervention with people who have developed the full schizophrenia syndrome is likely to have few negative effects and may yield benefits, although it is not yet clear that it will.

Female↗
PubMed2001

Subjective and objective dimensions of quality of life in psychiatric patients: a factor analytical approach: The South Verona Outcome Project 4.

BACKGROUND: Both subjective and objective information is necessary to assess quality of life (QOL). AIMS: To explore the role of subjective and objective QOL dimensions and their cross-sectional and longitudinal predictors. METHOD: The relationship between QOL, as measured by the Lancashire Quality of Life Profile (LQL), and demographic variables, diagnosis, psychopathology, disability, functioning, affect balance, self-esteem, service use and service satisfaction was investigated at two points in time, using factor analysis and multiple regression techniques. RESULTS: One subjective and two objective LQL factors with strong face validity were identified. Cross-sectional predictors of the subjective factor were primarily subjective measures; longitudinally, few predictors of this factor were identified. The cross-sectional and longitudinal predictors of the objective factors were primarily demographic and observer-rated measures. CONCLUSIONS: Subjective and objective data are distinct types of information. Objective measures may be more suitable in detecting treatment effects. Subjective information is necessary to complete the QOL picture and to enhance the interpretation of objective data.

Adolescent↗
PubMed2000

Inhibition of farnesyltransferase with A-176120, a novel and potent farnesyl pyrophosphate analogue.

Farnesylation of Ras is required for its transforming activity in human cancer and the reaction is catalysed by the enzyme farnesyltransferase. Recently, we discovered a novel chemical series of potent farnesyl pyrophosphate (FPP) analogues which selectively inhibited farnesyltransferase. Our most potent compound to date in this series, A-176120, selectively inhibited farnesyltransferase activity (IC(50) 1.2+/-0.3 nM) over the closely related enzymes geranylgeranyltransferase I (GGTaseI) (IC(50) 423+/-1.8 nM), geranylgeranyltransferase II (GGTaseII) (IC(50) 3000 nM) and squalene synthase (SSase) (IC(50)>10000 nM). A-176120 inhibited ras processing in H-ras-transformed NIH3T3 cells and HCT116 K-ras-mutated cells (ED(50) 1.6 and 0.5 microM, respectively). The anti-angiogenic potential of A-176120 was demonstrated by a decrease in Ras processing, cell proliferation and capillary structure formation of human umbilical vein endothelial cells (HUVEC), and a decrease in the secretion of vascular endothelial growth factor (VEGF) from HCT116 cells. In vivo, A-176120 reduced H-ras NIH3T3 tumour growth and extended the lifespan of nude mice inoculated with H- or K-ras-transformed NIH3T3 cells. A-176120 also had an additive effect in combination with cyclophosphamide in nude mice inoculated with K-ras NIH3T3 transformed cells. Overall, our results demonstrate that A-176120 is a potent FPP mimetic with both antitumour and anti-angiogenic properties.

Alkyl and Aryl Transferases↗
PubMed2000

Validation of cardiologists' decisions to initiate reperfusion therapy for acute myocardial infarction with electrocardiograms viewed on liquid crystal displays of cellular telephones.

BACKGROUND: The transmission of 12-lead electrocardiograms from remote locations to hand-held computers of cardiologists is now possible with the development of wireless technology and computer software. This investigation determined whether the cardiologist's decisions regarding reperfusion therapy for patients with symptoms suggestive of an acute myocardial infarction are the same when given electrocardiograms displayed on a cellular telephone as on a standard paper recording. METHODS: Cardiologists were given 20 electrocardiograms of patients with acute chest pain suggestive of acute myocardial infarction to test the diagnostic reliability of the Nokia 9000i cellular telephone liquid crystal display (LCD) screen. The cardiologists made their decision to initiate or not initiate reperfusion therapy for the patients after viewing their electrocardiograms displayed on both 5-mm and 1-mm formatted grids and twice on traditional printout electrocardiograms. The control level of intraobserver agreement between the responses from the 2 sets of paper display electrocardiograms was compared with the experimental level of intraobserver agreement between the 1-mm LCD electrocardiograms and both sets of paper display electrocardiograms to determine whether the viewing medium affected the cardiologist's decisions. The 1-mm and 5-mm LCD screen electrocardiograms were compared to determine if the grid size affected the cardiologist's decisions. RESULTS: Ninety-three percent of the 2 sets of paper-guided decisions were in agreement. When comparing the 1-mm LCD-guided decisions with both sets of paper-guided decisions, 94% and 89% of the decisions, respectively, were in agreement. The differences between the control and experimental degrees of intraobserver agreement of 1% and 4% were not statistically significant (P1 =.81, P2 =.29). Ninety-one percent of the 1-mm LCD-guided decisions were in agreement with the 5-mm LCD-guided decisions. CONCLUSIONS: Cardiologists' decisions did not vary significantly when viewing either traditional paper electrocardiograms or LCD screen electrocardiograms. Even though there was not a significant difference in the cardiologists' decisions when they viewed electrocardiograms displayed on both the 1-mm and 5-mm grid, it is recommended that the 1-mm grid be used for clinical implementation of the LCD screen.

Computer Terminals↗
PubMed1999

Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy.

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.

Alkyl and Aryl Transferases↗
PubMed1999

Retinal function as a marker for cell membrane omega-3 fatty acid depletion in schizophrenia: a pilot study.

BACKGROUND: There is a growing body of evidence that abnormalities of the cell membrane, particularly depletion of n-3 essential fatty acids (EFA), are found in patients suffering from schizophrenia. These fatty acids particularly Docosohexaenoic acid (DHA) are found in particularly high concentrations in the photoreceptor cells of the retina and abnormalities of light sensitivity have been reported in patients with schizophrenia. Animal studies have demonstrated that reduced EFA levels are associated with changes in the electrophysiological response of the retina to light as measured by the electroretinogram (ERG). METHODS: We measured the ERG of 9 patients with schizophrenia and 9 age and sex matched control subjects. All but one of the patients was medicated. RESULTS: Schizophrenic subjects had significantly reduced a-wave amplitudes on the ERG when compared with control subjects and the a-wave amplitude was independent of the dose of antipsychotic agents being taken. The a-wave of the ERG is thought to reflect activity of the photoreceptor cells. CONCLUSIONS: These findings support the hypothesis that patients with schizophrenia have abnormalities of photoreceptor function, which may be a result of reduced levels of n-3 EFA in the cell membrane.

Adaptation, Ocular↗
PubMed1999

Potent and orally bioavailable noncysteine-containing inhibitors of protein farnesyltransferase.

Potent and orally bioavailable nonthiol-containing inhibitors of protein farnesyltransferase are described. Oral bioavailability was achieved by replacement of the pyridyl ether moiety of 1 with a 2-substituted furan ether to give 4. Potency was regained with 2,5-disubstituted furan ethers while maintaining the bioavailability inherent in 4. p-Chlorophenylfuran ether 24 is 0.7 nM in vitro (FTase) and is 32% bioavailable in the mouse, 30% bioavailable in rats, and 21% bioavailable in dogs.

Alkyl and Aryl Transferases↗
PubMed1999

Potent inhibitors of protein farnesyltransferase: heteroarenes as cysteine replacements.

Synthesis and biological evaluation of heteroarenes as reduced cysteine replacements are described. Of the heteroaryl groups examined with respect to FT inhibitor FTI-276 (1), pyridyl was the replacement found to be most effective. Substitutions at C4 of the pyridyl moiety did not affect the in vitro activity. Compound 9a was found to have moderate in vivo bioavailability.

3T3 Cells↗
PubMed1999

The emics and etics of quality of life assessment.

BACKGROUND: Among quality of life (QOL) researchers there is a debate over the value of subjective measures, because subjective ratings of different areas of people's lives often bear little relation to their objective life circumstances. Anthropological theory can illuminate this debate, since cultural anthropologists grapple with a similar issue--the difference between emics and etics. Emic data, in anthropology, deal with distinctions that are real and significant to natives of the culture, while etic statements depend on distinctions judged appropriate by scientific observers. CONCLUSIONS: The study of emics and etics suggests the following conclusions for QOL researchers. Subjective and objective appraisals are different kinds of data, both of which can be collected from subjects. Both are valuable, but it may be necessary to override subjective data to develop a predictive model. Objective circumstances do not reliably predict subjective evaluations of those circumstances or vice versa, particularly in evaluating change over time. The combination of subjective and objective measures, however, can lead more directly to service improvements that are sensitive to consumers' needs.

Anthropology↗
PubMed1999

An evaluation of the impact of clubhouse membership on quality of life and treatment utilization.

A group of clubhouse users matched with similar patients (not clubhouse users) in a neighbouring area were compared in terms of quality of life (Lancashire Quality of Life Profile), service utilization and treatment costs over a two year period. The clubhouse group achieved a reasonable employment status and good social relationships, and advantages in subjective well-being favoured the clubhouse group. Over two years the pattern of service utilization and costs also favoured the clubhouse group. When the two groups were disaggregated for employment status the group with least treatment utilization and lowest costs was the employed clubhouse group.

Adolescent↗