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Biomedical subjects

Christopher Phillips

Publications and source records attributed to Christopher Phillips.

11 recordsLinked to original sources
PubMed2026

Quo vadis, BGA? A collaborative EDNAP exercise on the challenges and progress in forensic biogeographical ancestry inference.

There is a broad consensus that forensic tests for the prediction of externally visible characteristics (EVC) and analysis of biogeographic ancestry (BGA) of an individual are technically reliable. However, interpretation of the results and population-specific genotype distribution patterns remains challenging. EVC and BGA analyses provide valuable information for population genetics studies and as investigative leads for criminal cases, as well as for historical and contemporary identification tests. However, inaccurate or incorrect predictions, for example, from subjective bias in the interpretations made, have the potential to misdirect police investigations. The legal situation regarding EVC and BGA testing varies by country: ranging from countries where it is explicitly prohibited, to those without specific regulations on biogeographic ancestry prediction, and others that have already enacted laws governing its use. The reluctance to utilize these analyses is not only due to legal restrictions and data protection concerns, but also to initial limited sets of sufficiently comprehensive forensic DNA assays. Forensic BGA marker panels typically contain up to ∼300 SNPs. This relatively small number of genetic markers, along with limited reference population data, complicates the interpretation of results from donors of unknown origin. This paper presents the results of a collaborative EDNAP study, which, for the first time, evaluated the approach to reporting EVC and BGA data between international laboratories. For the study, DNA from nine individuals with self-reported ancestry was collected and analysed using various forensic panels differing in the number and composition of ancestry-informative markers genotyped, comprising: the Precision ID mtDNA Whole Genome Panel, the VISAGE Basic Tool and the VISAGE Enhanced Tool for Appearance and Ancestry Prediction, and the Ion AmpliSeq™ PhenoTrivium Panel. To ensure full data protection, all SNP genotypes and uniparental marker haplotypes obtained were not shared with third parties. Instead, the genetic data were analysed using a range of commonly used population analysis software packages. These analysis outcomes were then distributed to twelve European forensic laboratories (both academic and law enforcement institutions), who were asked to prepare reports based on their interpretation of the phenotypes and ancestry they inferred from the analysis data. A questionnaire sent alongside the genetic information, aimed to evaluate which difficulties were encountered by the participants in processing the BGA analysis data they were given.

Humans↗
PubMed2006

SUMO4 and MAP3K7IP2 single nucleotide polymorphisms and susceptibility to rheumatoid arthritis.

OBJECTIVE: To explore the role of single nuclear polymorphisms (SNP) in 2 candidate genes, SUMO4 and MAP3K7IP2, in susceptibility to rheumatoid arthritis (RA). METHODS: Two cohorts from different Spanish towns totalling 635 patients with RA and 826 controls were studied. Six SNP were genotyped by matrix assisted laser desorption-ionization time-of-flight (MALDI-TOF) with the MassARRAY SNP genotyping system. RESULTS: We found no association with susceptibility to RA for any of the SNP including a previously described functional variant in the SUMO4 gene (163A-->G). RA susceptibility was independent of the haplotypes defined by the 6 SNP and there was also no association with clinical features of RA. Conclusion. SUMO4 and MAP3K7IP2 SNP did not significantly influence predisposition to and features of RA, in contrast to previous genetic and functional evidence that suggested their involvement.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Human genome-wide screen of haplotype-like blocks of reduced diversity.

An important proportion of the human genome is organized in regions of high linkage disequilibrium (LD) and low haplotype diversity, referred to as haplotype blocks. Here, we perform a genome-wide screen of haplotype-like blocks presenting just two main haplotypes at a frequency higher than 1%, based on single-nucleotide polymorphism (SNP) frequencies from two populations: African-Americans and Caucasians, using data from the Celera SNP database. These haplotype-like blocks of reduced diversity are more abundant and of longer size in Caucasians, in agreement with population history. Several of the discovered blocks are good candidates for targets of natural selection, such as those blocks containing a cluster of bitter taste receptors or the apolipoprotein L1. In addition, several genes putatively involved in susceptibility to common diseases are included in these haplotype-like blocks of reduced diversity. This fact may present important implications in association studies, leading to a reduction of genotyping efforts.

Black People↗
PubMed2005

Flow dependence and repeatability of interrupter resistance in lower airways and nose.

The interrupter technique, the simplest method for measuring airflow resistance (R(int)) is particularly valuable under field conditions. We investigate whether during tidal breathing, variations in the flow at which interruption occurs contribute to variability of results. Using a portable device with mouthpiece, sets of 10 measurements of R(int) (R(int,mo)) were made in inspiration and expiration at 0.05 l s(-1) intervals from 0.1 up to 0.9 l s(-1) flow in 22 normal adults, 11 children (5-9 years) and 12 COPD patients. R(int) was also measured via nasal-mask in normal adults (R(int,na)). Intra-subject coefficient of variation was obtained at each flow and flow-dependence of R(int) was assessed. In normal subjects, R(int)-flow relationships were consistent, with a narrow range of absolute values. R(int,na), but not R(int,mo), rose with increasing flow, especially >0.4 l s(-1). Repeatability was poor at flows <0.3 l s(-1) but improved with increasing flow and was better in inspiration than expiration. In children, repeatability was better than in adults and R(int,mo) was not flow dependent at < or =0.4 l s(-1). By contrast, in COPD patients repeatability was less good and R(int,mo) increased with increasing flows. R(int,mo) and R(int,na) should be measured at fixed inspiratory flows. The best signal-to-noise ratios were obtained at 0.4 l s(-1) for R(int) in normal adults and COPD patients and at 0.3 l s(-1) in children.

Adult↗
PubMed2005

Relative efficiency of the linkage disequilibrium mapping approach in detecting candidate genes for schizophrenia in different European populations.

Detection of susceptibility genes in indirect association studies depends not only on the degree of linkage disequilibrium between the disease variant and the SNP marker but also on the difference in their allele frequencies. Little is known about how variations in these parameters may affect the power of indirect association studies among related populations. Toward this goal, we genotyped 40 SNPs at four loci in samples from three European populations, Galician, Greek, and Norwegian. We compared the relative efficiency of all pairs of SNPs in detecting each other in each one of the populations. Our results show that a low percentage of marker SNPs may detect association in some populations but be totally ineffective in others. Therefore, these differences have to be an additional factor to consider when a replication study fails to confirm initial associations, especially if the replication is focused on very few markers.

Chromosome Mapping↗
PubMed2005

Effect of treating depression on quality-of-life and exercise tolerance in severe COPD.

The aim of this study was to determine whether treating concomitant depression improves quality of life and exercise tolerance in COPD patients. Out-patients with moderate to severe, stable COPD completed Hospital Anxiety-Depression (HAD) and General Health questionnaires. A psychiatrist interviewed those with high scores. In a randomised, double-blind fashion, 28 depressed COPD patients took a selective serotonin re-uptake inhibitor, Paroxetine 20 mg daily, or matched placebo for 6 weeks. Subsequently, all patients took un-blinded Paroxetine for 3 months. From these questionnaires, 35% of 135 patients had significant depression, but this was confirmed by psychiatric interview in only 21%. Throughout the study, there were no changes in laboratory lung function nor in home peak flow. Six weeks' treatment produced no significant differences between placebo and treatment group in either depression, quality of life scores or 6-minute walking distances, although overall improvements in depression, correlated with increases in walking distance. Three months of un-blinded treatment, significantly improved depression scores (self-complete HAD, Beck's Depression and psychiatrist-completed Montgomery-Asberg scores), walking distances (369 to 427 m, p = 0.0003) and St. George's Respiratory Questionnaire Total Scores (65 to 58, p = 0.033). Although self-complete questionnaires over-diagnose depression, the condition is nevertheless common in patients with moderately severe COPD. Six weeks of antidepressants is insufficient to improve either depression, quality of life or exercise tolerance. However, our study suggests that a longer course of treatment may be effective and that improvements in depression are associated with improvements in exercise tolerance. A larger, double blind study with a longer treatment period is indicated.

Aged↗
PubMed2004

Comparison of oral and depot intra-muscular steroids in assessing steroid-responsiveness in COPD.

Non-compliance or euphoria may limit the usefulness of prednisolone tablets in assessing steroid-responsiveness in chronic obstructive pulmonary disease (COPD). Depot intra-muscular methyl-prednisolone (imMP), producing a plateau steroid effect over two weeks, may be more reliable. Following two weeks of placebo, twenty-seven COPD patients (mean FEV 1 43% predicted) participated in a two-week randomised, double-blind, placebo-controlled, parallel-design trial taking either 120 mg imMP with placebo tablets or placebo injection with prednisolone 30 mg daily. After each period, post-bronchodilator FEV 1, forced vital capacity (FVC), inspiratory capacity (IC) and six-minute walking distance (6MWD) were assessed and patients completed both quality-of-life scores (St. George's 30 and Short Form 36) and mood scores (Hospital Anxiety and Depression scores and Altman's Self-rating Mania Scale). There were no significant changes in 6MWD, quality of life or mood scores after either type of steroids and no change in lung function after imMP. By contrast, there were small mean improvements in lung function on oral prednisolone (mean FEV 1, FVC and IC increased by 100, 320 and 150 ml, respectively). Only the improvement in FVC was significantly greater after prednisolone compared with imMP. Single depot intra-muscular injections of steroids have no advantage over oral daily prednisolone in testing steroid-responsiveness in COPD patients.

Administration, Oral↗
PubMed2004

Heart to Heart: a computerized decision aid for assessment of coronary heart disease risk and the impact of risk-reduction interventions for primary prevention.

Heart to Heart is a computer-based decision aid for patients and providers that provides personalized, evidence-based information about coronary heart disease (CHD) risk and potential risk-reducing interventions. To develop Heart to Heart, the authors used Framing-ham risk equations and systematic reviews of risk-reducing interventions. The Web version was programmed using PHP: Hypertext Processor, a Web-based programming language, and has separate interfaces for providers and patients. The authors subsequently developed a modified version for personal digital assistants. Heart to Heart uses information about a patient's CHD risk factors (age, gender, total and high-density lipoprotein cholesterol levels, diabetes, smoking, systolic blood pressure, and left ventricular hypertrophy) to calculate risk of total CHD events over 5 or 10 years. Patients and providers can then examine the effect of introducing one or more risk-reducing interventions (aspirin, lipid-lowering drug therapy, antihypertensive medication, or smoking cessation) on the patient's CHD risk. Future research will be directed to determining whether Heart to Heart can improve utilization of effective CHD risk-reducing interventions.

Adult↗
PubMed2002

The role of alpha-methylacyl-CoA racemase in bile acid synthesis.

According to current views, the second peroxisomal beta-oxidation pathway is responsible for the degradation of the side chain of bile acid intermediates. Peroxisomal multifunctional enzyme type 2 [peroxisomal multifunctional 2-enoyl-CoA hydratase/(R)-3-hydroxyacyl-CoA dehydrogenase; MFE-2] catalyses the second (hydration) and third (dehydrogenation) reactions of the pathway. Deficiency of MFE-2 leads to accumulation of very-long-chain fatty acids, 2-methyl-branched fatty acids and C(27) bile acid intermediates in plasma, but bile acid synthesis is not blocked completely. In this study we describe an alternative pathway, which allows MFE-2 deficiency to be overcome. The alternative pathway consists of alpha-methylacyl-CoA racemase and peroxisomal multifunctional enzyme type 1 [peroxisomal multifunctional 2-enoyl-CoA hydratase/(S)-3-hydroxyacyl-CoA dehydrogenase; MFE-1]. (24E)-3alpha,7alpha,12alpha-Trihydroxy-5beta-cholest-24-enoyl-CoA, the presumed physiological isomer, is hydrated by MFE-1 with the formation of (24S,25S)-3alpha,7alpha,12alpha,24-tetrahydroxy-5beta-cholestanoyl-CoA [(24S,25S)-24-OH-THCA-CoA], which after conversion by a alpha-methylacyl-CoA racemase into the (24S,25R) isomer can again be dehydrogenated by MFE-1 to 24-keto-3alpha,7alpha,12alpha-trihydroxycholestanoyl-CoA, a physiological intermediate in cholic acid synthesis. The discovery of the alternative pathway of cholesterol side-chain oxidation will improve diagnosis of peroxisomal deficiencies by identification of serum 24-OH-THCA-CoA diastereomer profiles.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2002

Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force.

BACKGROUND: The use of aspirin to prevent cardiovascular disease events in patients without a history of cardiovascular disease is controversial. PURPOSE: To examine the benefits and harms of aspirin chemoprevention. DATA SOURCES: MEDLINE (1966 to May 2001). STUDY SELECTION: 1) Randomized trials at least 1 year in duration that examined aspirin chemoprevention in patients without previously known cardiovascular disease and 2) systematic reviews, recent trials, and observational studies that examined rates of hemorrhagic strokes and gastrointestinal bleeding secondary to aspirin use. DATA EXTRACTION: One reviewer read and extracted data from each included article and constructed evidence tables. A second reviewer checked the accuracy of the data extraction. Discrepancies were resolved by consensus. DATA SYNTHESIS: Meta-analysis was performed, and the quantitative results of the review were then used to model the consequences of treating patients with different levels of baseline risk for coronary heart disease. Five trials examined the effect of aspirin on cardiovascular events in patients with no previous cardiovascular disease. For patients similar to those enrolled in the trials, aspirin reduces the risk for the combined end point of nonfatal myocardial infarction and fatal coronary heart disease (summary odds ratio, 0.72 [95% CI, 0.60 to 0.87]). Aspirin increased the risk for hemorrhagic strokes (summary odds ratio, 1.4 [CI, 0.9 to 2.0]) and major gastrointestinal bleeding (summary odds ratio, 1.7 [CI, 1.4 to 2.1]). All-cause mortality (summary odds ratio, 0.93 [CI, 0.84 to 1.02]) was not significantly affected. For 1000 patients with a 5% risk for coronary heart disease events over 5 years, aspirin would prevent 6 to 20 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. For patients with a risk of 1% over 5 years, aspirin would prevent 1 to 4 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. CONCLUSIONS: The net benefit of aspirin increases with increasing cardiovascular risk. In the decision to use aspirin chemoprevention, the patient's cardiovascular risk and relative utility for the different clinical outcomes prevented or caused by aspirin use must be considered.

Adult↗