Biomedical subjects
Publications and source records attributed to C Phillips.
Y chromosome haplotype data was collected for 155 Irish males residing in the Republic of Ireland. Eleven short tandem repeat (STR) markers: DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439 were analysed and the allele and haplotype frequencies calculated. This Irish data is presented here and was found to be less diverse when compared with the neighbouring UK population.
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We describe a case of post-operative bleeding after a posterior fascial defect repair. This was refractive to exploration and vaginal packing so laparotomy would have been necessary. Superselective cannulation demonstrated bleeding from a branch of the anterior pudendal artery which had crossed the midline making identification difficult during vaginal exploration. The bleeding vessel was embolised using a mixture of PVA300 and Spongistan gel foam and the bleeding ceased. The use of embolisation in the peri-operative phase is discussed.
Previously reported Y chromosome STR haplotype databases for three UK population groups, plus additionally analysed samples, have been scrutinised for the presence of non-standard (intermediate, null and duplicated) alleles. These alleles have been characterised by sequencing, some showing changes in the repeat structure, and the frequencies reported. Mutation rates for each of the 13 STRs have been calculated when analysis of father-son pairs has been possible. An example illustrating the use of non-standard alleles in a large family tree is outlined.
Single case study and evidence-based practice With the current emphasis upon evidence-based medicine in statutory health care provision in the UK, mental health nursing is challenged to justify its approaches. Psychological theories, once taken for granted in mental health nursing, are now being challenged by new definitions of evidence. In this paper the authors focus upon the use of individual case study. The discussion questions the validity of applying the hierarchies of evidence proposed by evidence-based medicine to mental health nursing theory and practice. The role of case study as the prime source of evidence is argued and is justified in mental health nursing research and practice.
Eleven Y chromosome short tandem repeat markers: DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439, have been typed in the three main UK population groups: Caucasians, Afro-Caribbeans and South Asians. Existing PCR reactions were adapted to incorporate DYS437, DYS438 and DYS439. The observed 11 loci haplotypes and the individual allele frequencies for each locus are presented. Distinct differences for most markers were observed between the population groups studied.
The development of new methodologies for high-throughput SNP analysis is one of the most stimulating areas in genetic research. Here, we describe a rapid and robust assay to simultaneously genotype 17 mitochondrial DNA (mtDNA) coding region SNPs by minisequencing using SNaPshot. SNaPshot is a methodology based on a single base extension of an unlabeled oligonucleotide with labeled dideoxy terminators. The set of SNPs implemented in this multiplexed SNaPshot reaction allow us to allocate common mitochondrial West Eurasian haplotypes into their corresponding branch in the mtDNA skeleton, with special focus on those haplogroups lacking unambiguous diagnostic positions in the first and second hypervariable regions (HVS-I/II; by far, the most common segments analyzed by sequencing). Particularly interesting is the set of SNPs that subdivide haplogroup H; the most frequent haplogroup in Europe (40-50%) and one of the most poorly characterized phylogenetically in the HVS-I/II region. In addition, the polymorphic positions selected for this multiplex reaction increase considerably the discrimination power of current mitochondrial analysis in the forensic field and can also be used as a rapid screening tool prior to full sequencing analysis. The method has been validated in a sample of 266 individuals and shows high accuracy and robustness avoiding both the use of alternative time-consuming classical strategies (i.e. RFLP typing) and the need for high quantities of DNA template.
BACKGROUND: Discharge planning is a routine feature of health systems in many countries. The aim is to reduce hospital length of stay and unplanned readmission to hospital, and improve the co ordination of services following discharge from hospital thereby bridging the gap between hospital and place of discharge. Sometimes discharge planning is offered as part of an integrated package of care, which may cover both the hospital and community. The focus of this review is discharge planning that occurs while a patient is in hospital; we exclude studies that evaluate discharge planning with follow up care. OBJECTIVES: To determine the effectiveness of planning the discharge of patients moving from hospital. SEARCH STRATEGY: Relevant studies were identified using Medline, Embase, SIGLE database for grey literature, Bioethics database, Health Plan, Psych. Lit, Sociofile, CINAHL, Cochrane Library, Econ Lit, Social Science Citation Index, EPOC register. The review was updated using the EPOC trials register in August 2002. SELECTION CRITERIA STUDY DESIGN: randomised controlled trials (RCTs) that compare discharge planning (the development of an individualised discharge plan) with routine discharge care. PARTICIPANTS: all patients in hospital. INTERVENTION: the development of an individualised discharge plan. DATA COLLECTION AND ANALYSIS: Data analysis and quality assessment was undertaken independently by two reviewers using a data checklist. Studies are grouped according to patient group (elderly medical patients, surgical patients, and those with a mix of conditions), and by outcome. MAIN RESULTS: Three new studies were included in this update. In total we included eleven RCTS: 6 trials recruited patients with a medical condition (2,368 patients), and four recruited patients with a mix of medical and surgical conditions (2,983 patients), one of these four recruited medical and surgical patients as separate groups, and the final trial recruited 97 patients in a psychiatric hospital and from a general hospital. We failed to detect a difference between groups in mortality for elderly patients with a medical condition (OR 1.44 95% CI 0.82 to 2.51), hospital length of stay (weighted mean difference -0.86, 95% CI -1.9 to 0.18), readmission rates (OR 0.91 95% CI 0.67 to 1.23) and being discharged from hospital to home (OR 1.15 95% CI 0.72 to 1.82). This was also the case for trials recruiting patients recovering from surgery and those recruiting patients with a mix of medical and surgical conditions. One trial comparing a structured care pathway for patients recovering from a stroke with multidisciplinary care reported a significant rate of improvement in functional ability and quality of life for the control group (median change in Barthel score between 4 to 12 weeks of 2 points for the treatment group, versus 6 for the control group, p<0.01); (Euroqol scores at 6 months 63 for the treatment group, vs. 72 for the control group, p<0.005). Two trials reported that patients with medical conditions allocated to discharge planning reported increased satisfaction compared with those who received routine discharge. No statistically significant differences were reported for overall health care costs. REVIEWER'S CONCLUSIONS: The impact of discharge planning on readmission rates, hospital length of stay, health outcomes and cost is uncertain. This reflects a lack of power as the degree to which we could pool data was restricted by the different reported measures of outcome. It is possible that even a small reduction in length of stay, or readmission rate, could have an impact on the timeliness of subsequent admissions in a system where there is an shortage of acute hospital beds.
BACKGROUND: Microsomal triglyceride transfer protein (MTP) regulates the assembly of chylomicrons in the intestine and very-low-density lipoprotein (VLDL) in the liver. Common polymorphisms have been described that do not affect lipoproteins in non-diabetic subjects. Their effect in diabetes has not been described in a Caucasian population. AIM: To investigate the association of these three common polymorphisms with lipoproteins in type 2 diabetes. METHODS: Eighty-two patients consumed a high-fat test meal. Chylomicron and VLDL apoB48, apoB100, cholesterol, triglycerides and phospholipids were measured fasting, and at 4 and 6 h postprandially. MTP genotyping was performed by PCR-RFLP. RESULTS: Thirty-three subjects were heterozygous for the -493 G/T substitution. These patients had significantly lower LDL cholesterol (3.0 +/- 0.2 vs. 3.5 +/- 0.1 mmol/l, p < 0.02). In the postprandial period, they had higher levels of apoB48 in the VLDL fraction (4 h, 7.0 +/- 1.4 vs. 2.9 +/- 0.4 microg/ml plasma, p < 0.002; 6 h, 6.4 +/- 1.0 vs. 3.5 +/- 0.5 microg/ml plasma, p < 0.05). In the VLDL fraction there was significantly less cholesterol at 4 and 6 h (p < 0.05). The -400 A/T substitution gave very similar lipoprotein results, but there was significant linkage dysequilibrium between the two polymorphisms. No association was found between the -164 T/C polymorphism and either plasma lipids or the postprandial lipid profile. ApoE genotype was also examined, but did not influence the above results. DISCUSSION: The common -493 G/T MTP polymorphism is associated with changes in VLDL and LDL in Type 2 diabetic patients. The importance of the changes in apoB48-containing small particles requires further investigation. The significantly lower LDL cholesterol suggests that this polymorphism may confer protection against atherosclerosis in type 2 diabetes.
BACKGROUND: Erectile dysfunction (ED) is one complication of diabetes for which the treatment is rationed. Despite considerable public debate there has been no formal assessment of the views of patients and sufferers of the priority of treating ED. AIMS: To determine the perceptions of diabetic patients of the relative priority of treating ED in comparison with treatments for other diabetic complications and common medical conditions. METHODS: Psychological measures were used to assess subjects' perceptions of the relative importance of ED in comparison with eight other common problems (blindness, foot ulcers, high blood pressure, impotence, kidney disease, high cholesterol, migraine, mild indigestion and sleeping difficulties). The concept of willingness to pay was used to assess the amount per month participants would be prepared to pay for treatment for ED and other conditions. Four groups (controls, healthy diabetic men, impotent diabetic men and impotent diabetic men not in a sexual relationship) were studied. RESULTS: Significant differences were found between the four groups with regard to the ranking of the importance of ED compared with other health problems. Impotent diabetic male patients were prepared to pay more for treatment for their condition than all other conditions except blindness and renal failure. CONCLUSIONS: Men with diabetes, in particular ED sufferers, believe ED has a major impact on quality of life and is as important to treat as many other conditions associated with diabetes.
This paper reviews hierarchical observation models, used in functional neuroimaging, in a Bayesian light. It emphasizes the common ground shared by classical and Bayesian methods to show that conventional analyses of neuroimaging data can be usefully extended within an empirical Bayesian framework. In particular we formulate the procedures used in conventional data analysis in terms of hierarchical linear models and establish a connection between classical inference and parametric empirical Bayes (PEB) through covariance component estimation. This estimation is based on an expectation maximization or EM algorithm. The key point is that hierarchical models not only provide for appropriate inference at the highest level but that one can revisit lower levels suitably equipped to make Bayesian inferences. Bayesian inferences eschew many of the difficulties encountered with classical inference and characterize brain responses in a way that is more directly predicated on what one is interested in. The motivation for Bayesian approaches is reviewed and the theoretical background is presented in a way that relates to conventional methods, in particular restricted maximum likelihood (ReML). This paper is a technical and theoretical prelude to subsequent papers that deal with applications of the theory to a range of important issues in neuroimaging. These issues include; (i) Estimating nonsphericity or variance components in fMRI time-series that can arise from serial correlations within subject, or are induced by multisubject (i.e., hierarchical) studies. (ii) Spatiotemporal Bayesian models for imaging data, in which voxels-specific effects are constrained by responses in other voxels. (iii) Bayesian estimation of nonlinear models of hemodynamic responses and (iv) principled ways of mixing structural and functional priors in EEG source reconstruction. Although diverse, all these estimation problems are accommodated by the PEB framework described in this paper.
In Friston et al. ((2002) Neuroimage 16: 465-483) we introduced empirical Bayes as a potentially useful way to estimate and make inferences about effects in hierarchical models. In this paper we present a series of models that exemplify the diversity of problems that can be addressed within this framework. In hierarchical linear observation models, both classical and empirical Bayesian approaches can be framed in terms of covariance component estimation (e.g., variance partitioning). To illustrate the use of the expectation-maximization (EM) algorithm in covariance component estimation we focus first on two important problems in fMRI: nonsphericity induced by (i) serial or temporal correlations among errors and (ii) variance components caused by the hierarchical nature of multisubject studies. In hierarchical observation models, variance components at higher levels can be used as constraints on the parameter estimates of lower levels. This enables the use of parametric empirical Bayesian (PEB) estimators, as distinct from classical maximum likelihood (ML) estimates. We develop this distinction to address: (i) The difference between response estimates based on ML and the conditional means from a Bayesian approach and the implications for estimates of intersubject variability. (ii) The relationship between fixed- and random-effect analyses. (iii) The specificity and sensitivity of Bayesian inference and, finally, (iv) the relative importance of the number of scans and subjects. The forgoing is concerned with within- and between-subject variability in multisubject hierarchical fMRI studies. In the second half of this paper we turn to Bayesian inference at the first (within-voxel) level, using PET data to show how priors can be derived from the (between-voxel) distribution of activations over the brain. This application uses exactly the same ideas and formalism but, in this instance, the second level is provided by observations over voxels as opposed to subjects. The ensuing posterior probability maps (PPMs) have enhanced anatomical precision and greater face validity, in relation to underlying anatomy. Furthermore, in comparison to conventional SPMs they are not confounded by the multiple comparison problem that, in a classical context, dictates high thresholds and low sensitivity. We conclude with some general comments on Bayesian approaches to image analysis and on some unresolved issues.
We have previously demonstrated that diabetes is associated with an increase in intestinal microsomal triglyceride transfer protein (MTP) mRNA in both the rat and rabbit models. The present study was designed to investigate the relationship between MTP expression and chylomicron assembly in an insulin resistant non-diabetic animal model. Ten insulin resistant Zucker obese fa/fa rats and ten lean fa/minus sign rats were examined at 8-10 weeks of age. The lymph duct was cannulated and lymph collected for 4 h. Lymph chylomicrons were isolated by ultracentrifugation and their composition determined. RNA was extracted from intestinal mucosa and from the liver. MTP mRNA was measured using the RNase protection assay. Blood sugar in the fatty rats was significantly higher (6.3 +/-1.2 vs. 5.4 +/-0.4 P<0.05) and plasma insulin was almost six times that of the lean rats (P<0.001). Plasma cholesterol and phospholipid but not triglyceride were significantly increased in the obese animals (P<0.01). Obese animals secreted significantly more lymph chylomicron apo B48 (0.05 +/-0.02 vs. 0.02 +/-0.01 mg/h P<0.005), triglyceride (9.7 +/-5.3 vs. 3.8+/-1.9 mg/h P<0.005) and phospholipid (1.5 +/-0.7 vs. 0.4 +/-0.3 mg/h P<0.001). The only difference in the chylomicron particle composition between the two groups was a significant increase in phospholipid (P<0.01). Intestinal MTP mRNA expression was significantly higher in the fatty compared to the lean rats (22.1 +/-9.5 vs. 7.8+/-5.6 amol MTP mRNA/microg total RNA P<0.001) as was hepatic MTP mRNA expression (6.9 +/-3.5 vs. 3.4 +/-1.5 amol MTP mRNA/microg total RNA, P<0.01). Thus in this animal model of insulin resistance, increased MTP, which was associated with increased chylomicron particle number, may play a crucial role in the development of atherosclerosis.
OBJECTIVES: To establish a methodology by which all women attending for termination of pregnancy (TOP) at British Pregnancy Advisory Service (BPAS) branches may be approached to participate in Chlamydia trachomatis screening. To examine the feasibility of monitoring C trachomatis prevalence and the impact of charging for screening on the uptake rate in this population. METHODS: Patients attending for TOP at participating BPAS branches were offered a test for chlamydia infection and asked to complete a questionnaire. Urine samples from participants were tested using a nucleic acid amplification test (NAAT). RESULTS: 1001 women provided a urine sample, a 77% response rate among those participating in the study. Factors significantly associated with taking up chlamydia screening included symptoms, previous TOP, parity, and no previous chlamydial test. Overall prevalence of genital chlamydial infection was 7.5%, with highest age specific prevalences occurring among attendees aged 20-24 years (11.5%) and under 20 years (10.8%). In univariate analysis, chlamydia positivity was significantly associated with respondent age and previous diagnosis with chlamydia. Only 35% of women who had the screening test would have done so had they been asked to pay the pound 20 clinical, administrative, and laboratory costs of the examination. CONCLUSIONS: We have demonstrated the feasibility of routine chlamydia screening and the potential for prospective prevalence monitoring across the nationwide BPAS service. In most cases the chlamydia result was available within the clinical contact period for the TOP. Charging patients directly for the test could reduce uptake of chlamydia screening to levels unsatisfactory for both the public health and prevalence monitoring purposes.
B-cell differentiation is accompanied by a dramatic increase in cytoplasmic accumulation and stability of the IgM heavy chain (mu) secretory mRNA. Despite considerable effort, the mechanism is unknown. We have identified three short motifs upstream of the secretory poly(A) site, which, when mutated in the mu heavy chain gene, significantly increase the accumulation of the secretory form of poly(A)(+) mRNA relative to the membrane form and regulate the expression of the secretory poly(A) site in a developmental manner. We show that these motifs bind U1A and inhibit polyadenylation in vitro and in vivo. Overexpression of U1A in vivo results in the selective inhibition of the secretory form. Thus, this novel mechanism selectively controls post-cleavage expression of the mu secretory mRNA. We present evidence that this mechanism is used to regulate alternative expression of other genes.
A collaborative exercise was carried out by the European DNA Profiling Group (EDNAP) in the frame work of the STADNAP program, i.e. standardization of DNA profiling in Europe, in order to evaluate the performance of a Y-chromosome STR pentaplex, which includes the loci DYS19, DYS389 I and II, DYS390 and DYS393 and to determine whether uniformity of results could be achieved among different European laboratories. Laboratories were asked to analyze the five Y-STRs using singleplex and multiplex conditions in three bloodstains and one mixed stain (95% female and 5% male). All the laboratories reported the same results even for the mixed stain included in the exercise. This demonstrates the reproducibility and robustness of Y-chromosome STR typing even with multiplex formats and proves the usefulness of Y-STR systems for analyzing mixed stains with a male component.A total of 930 male samples from 10 different populations from Europe were also analysed for all the loci included in the pentaplex. Eight of these ten populations also included haplotype data. As for single gene analysis, haplotype diversity was higher in Germany and Italy and lower in Western European countries and Finland. Pairwise haplotype analysis shows the Finnish departure from the rest of the populations and a relatively homogeneity in the other European populations with F(ST) estimates lower than 0.05.UPGMA analysis shows an association of Western European population (Ireland, UK, Portugal and Galicia) on the one hand and central European populations on the other.
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