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Biomedical subjects

P Gill

Publications and source records attributed to P Gill.

At least 19 recordsLinked to original sources

Comparison of glutathione S-transferase-Pi expression at mRNA levels in oesophageal mucosa using RT-PCR-ELISA in individuals with reflux diseases, adenocarcinoma and squamous cell carcinoma.

OBJECTIVES: To develop a RT-PCR technique coupled with Enzyme Linked Immunosobant Assay (ELISA) i.e. RT-PCR-ELISA for measurement of class-Pi glutathione S-transferase (GST-P)-specific mRNA in esophageal diseases. METHODS: In this study, 66 esophageal tissue biopsies diagnosed as non-erosive reflux disease (NERD), gastroesophageal reflux disease (GERD), adenocarcinoma (ADC), and squamous cell carcinoma (SCC) were used. Standardization of the RT-PCR-ELISA was carried out using specific GST-Pi and beta-actin primers, biotin labeled probe, DIG-labeling RT-PCR and anti-DIG-HRP conjugate. RESULTS: The results of RT-PCR-ELISA based on OD ratio of GST-Pi mRNA/beta-actin showed that there was no significant difference in GST-Pi expression in normal, NERD and GERD samples. Overexpression of GST-Pi in malignant tissues (ADC and SCC) was distinguishable. The OD ratio of GST-Pi mRNA expression to beta-actin mRNA was 1.17+/-0.13 and 1.3+/-0.13 in ADC and SCC samples, respectively, which is significantly higher (P<0.05) than matching control (0.78+/-0.06 and 0.85+/-0.07). CONCLUSIONS: RT-PCR-ELISA showed that GST-Pi expression was not altered in GERD and NERD esophagus, whereas, in ADC and SCC samples, it was significantly higher (P<0.05) as compared to inflamed and normal tissues.

Adenocarcinoma↗

Primary prevention of cardiovascular disease: a web-based risk score for seven British black and minority ethnic groups.

OBJECTIVE: To recalibrate an existing Framingham risk score to produce a web-based tool for estimating the 10-year risk of coronary heart disease (CHD) and cardiovascular disease (CVD) in seven British black and minority ethnic groups. DESIGN: Risk prediction models were recalibrated against survey data on ethnic group risk factors and disease prevalence compared with the general population. Ethnic- and sex-specific 10-year risks of CHD and CVD, at the means of the risk factors for each ethnic group, were calculated from the product of the incidence rate in the general population and the prevalence ratios for each ethnic group. SETTING: Two community-based surveys. PARTICIPANTS: 3778 men and 4544 women, aged 35-54, from the Health Surveys for England 1998 and 1999 and the Wandsworth Heart and Stroke Study. MAIN OUTCOME MEASURES: 10-year risk of CHD and CVD. RESULTS: 10-year risk of CHD and CVD for non-smoking people aged 50 years with a systolic blood pressure of 130 mm Hg and a total cholesterol to high density lipoprotein cholesterol ratio of 4.2 was highest in men for those of Pakistani and Bangladeshi origin (CVD risk 12.6% and 12.8%, respectively). CHD risk in men with the same risk factor values was lowest in Caribbeans (2.8%) and CVD risk was lowest in Chinese (5.4%). Women of Pakistani origin were at highest risk and Chinese women at lowest risk for both outcomes with CVD risks of 6.6% and 1.2%, respectively. A web-based risk calculator (ETHRISK) allows 10-year risks to be estimated in routine primary care settings for relevant risk factor and ethnic group combinations. CONCLUSIONS: In the absence of cohort studies in the UK that include significant numbers of black and minority ethnic groups, this risk score provides a pragmatic solution to including people from diverse ethnic backgrounds in the primary prevention of CVD.

Adult↗

DNA commission of the International Society of Forensic Genetics: Recommendations on the interpretation of mixtures.

The DNA commission of the International Society of Forensic Genetics (ISFG) was convened at the 21st congress of the International Society for Forensic Genetics held between 13 and 17 September in the Azores, Portugal. The purpose of the group was to agree on guidelines to encourage best practice that can be universally applied to assist with mixture interpretation. In addition the commission was tasked to provide guidance on low copy number (LCN) reporting. Our discussions have highlighted a significant need for continuing education and research into this area. We have attempted to present a consensus from experts but to be practical we do not claim to have conveyed a clear vision in every respect in this difficult subject. For this reason, we propose to allow a period of time for feedback and reflection by the scientific community. Then the DNA commission will meet again to consider further recommendations.

Alleles↗

Predictors of patients' preferences for treatments to prevent heart disease.

OBJECTIVES: To determine the relationship between expressed preferences for drug treatment to prevent coronary disease and several participant and general practitioner characteristics among patients attending coronary risk screening. DESIGN: Face-to-face interviews with patients. At the first interview, a researcher asked participants to imagine six scenarios representing different levels of pretreatment five-year coronary risk. In each case they were asked whether they would choose treatment that would reduce their coronary risk by 30% of pretreatment risk. At the second interview participants were told their coronary risk and asked whether they would choose treatment. Sociodemographic variables were collected to investigate their relationship to patients' treatment preferences. PARTICIPANTS: Patients identified as likely to be at high coronary risk were invited to attend for risk screening and to participate in the study. SETTING: 13 practices in the West Midlands. RESULTS: Participants' preferences varied widely: at the first interview 112 (55.2%) of 203 participants preferred treatment at 3% five-year coronary risk but 31 (15.3%) preferred no treatment even at 30% five-year coronary risk. Age, sex, education and drug treatment history did not affect preferences, but lower social class was associated with preferring treatment at lower risk. Preferences expressed at the second interview were generally consistent with preferences at the first interview (kappa = 0.510, 95% CI 0.380 to 0.639). CONCLUSIONS: Patients attending for coronary risk screening express stable preferences for drug treatment to prevent coronary heart disease. Their preferences vary widely and may be associated with social class.

Adult↗

DNA Commission of the International Society of Forensic Genetics (ISFG): an update of the recommendations on the use of Y-STRs in forensic analysis.

The DNA Commission of the International Society of Forensic Genetics (ISFG) regularly publishes guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. A previous recommendation published in 2001 has already addressed Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). Since then, the use of Y-STRs has become very popular, and a numerous new loci have been introduced. The current recommendations address important aspects to clarify problems regarding the nomenclature, the definition of loci and alleles, population genetics and reporting methods.

Alleles↗

DNA Commission of the International Society of Forensic Genetics (ISFG): an update of the recommendations on the use of Y-STRs in forensic analysis.

The DNA Commission of the International Society of Forensic Genetics (ISFG) regularly publishes guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. A previous recommendation published in 2001 has already addressed Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). Since then, the use of Y-STRs has become very popular, and numerous new loci have been introduced. The current recommendations address important aspects to clarify problems regarding the nomenclature, the definition of loci and alleles, population genetics and reporting methods

Alleles↗

Analysis of artificially degraded DNA using STRs and SNPs--results of a collaborative European (EDNAP) exercise.

Recently, there has been much debate about what kinds of genetic markers should be implemented as new core loci that constitute national DNA databases. The choices lie between conventional STRs, ranging in size from 100 to 450 bp; mini-STRs, with amplicon sizes less than 200 bp; and single nucleotide polymorphisms (SNPs). There is general agreement by the European DNA Profiling Group (EDNAP) and the European Network of Forensic Science Institutes (ENFSI) that the reason to implement new markers is to increase the chance of amplifying highly degraded DNA rather than to increase the discriminating power of the current techniques. A collaborative study between nine European and US laboratories was organised under the auspices of EDNAP. Each laboratory was supplied with a SNP multiplex kit (Foren-SNPs) provided by the Forensic Science Service, two mini-STR kits provided by the National Institute of Standards and Technology (NIST) and a set of degraded DNA stains (blood and saliva). Laboratories tested all three multiplex kits, along with their own existing DNA profiling technique, on the same sets of degraded samples. Results were collated and analysed and, in general, mini-STR systems were shown to be the most effective. Accordingly, the EDNAP and ENFSI working groups have recommended that existing STR loci are reengineered to provide smaller amplicons, and the adoption of three new European core loci has been agreed.

Analysis of Variance↗

Interpretation of repeat measurement DNA evidence allowing for multiple contributors and population substructure.

Due to the circumstances in some forensic cases, very small amounts of DNA (<100 pg) may be obtained. This, in turn, may affect the reliability of the PCR process, and so it may be advisable to repeat the amplification process for confirmatory purposes. Gill et al. [Forensic Sci. Int. 112 (2000) 17] proposed a method for the statistical evaluation of the PCR replicate information. In this paper we formalize the method proposed by Gill et al. [Forensic Sci. Int. 112 (2000) 17], and extend it to allow for cases involving mixed stains and for population substructure.

Alleles↗

Validation of a 21-locus autosomal SNP multiplex for forensic identification purposes.

A single nucleotide polymorphism (SNP) multiplex has been developed to analyse highly degraded and low copy number (LCN) DNA template, i.e. <100 pg, for scenarios including mass disaster identification. The multiplex consists of 20 autosomal non-coding loci plus Amelogenin for sex determination, amplified in a single tube PCR reaction and visualised on the Applied Biosystems 3100 capillary electrophoresis (CE) system. Allele-specific primers tailed with shared universal tag sequences were designed to speed multiplex design and balance the amplification efficiencies of all loci through the use of a single reverse and two differentially labelled allele denoting forward universal primers. As the multiplex is intended for use with samples too degraded for conventional profiling, a computer program was specifically developed to aid interpretation. Critical factors taken into account by the software include empirically determined extremes of heterozygous imbalance (Hb) and the drop-out threshold (Ht) defined as the maximum peak height of a surviving heterozygous allele, where its partner may have dropped out. The discrimination power of the system is estimated at 1 in 4.5 million, using a White Caucasian population database. Comparisons using artificially degraded samples profiled with both the SNP multiplex and AMPFISTR SGM plus (Applied Biosystems) demonstrated a greater likelihood of obtaining a profile using SNPs for certain sample types. Saliva stains degraded for 147 days generated an 81% complete SNP profile whilst short tandem repeats (STRs) were only 18% complete; similarly blood degraded for 243 days produced full SNP profiles but only 9% with STRs. Reproducibility studies showed concordance between SNP profiles for different sample types, such as blood, saliva, semen and hairs, for the same individual, both within and between different DNA extracts.

Amelogenin↗

Factors influencing clinicians' decisions to prescribe medication to prevent coronary heart disease.

BACKGROUND AND OBJECTIVE: There are variations between individual clinicians as to the thresholds at which preventive treatment for coronary heart disease (CHD) should commence. Patients' decisions may be influenced by clinicians' recommendations. Free text comments added by respondents to closed questionnaires may identify areas which are of real concern to them about the topic being studied. The study aimed to identify issues voluntarily raised by clinicians surrounding the decision to prescribe preventive treatment for CHD. METHODS: An analysis was undertaken of the free text comments made by cardiologists, general practitioners and practice nurses who responded to a closed question postal questionnaire in which they were asked to identify at which level of pretreatment risk they would offer treatment. RESULTS AND DISCUSSION: A similar percentage of respondents in each professional group provided free text comments. Clinicians' concerns centred on five main themes around prescribing decisions: the risks and benefits of treatment, the patient's role in treatment decisions, patient characteristics, costs to patients, and costs to the health services. Different issues may be of more concern to some professional groups than others. CONCLUSION: In addition to the use of risk assessment tools and guidelines, clinicians' actual prescribing behaviour may be influenced by more subjective factors. Patients at similar risk may receive different advice depending on the individual clinician they consult.

Attitude of Health Personnel↗

Mass screening for antimicrobial resistant Escherichia coli in dairy cows in northern New South Wales.

OBJECTIVE: To describe aspects of the epidemiology of antimicrobial resistance in Escherichia coli shed in the faeces of milking cows in a dairying region of New South Wales. DESIGN: A survey based on multi-stage sampling with repeated measures made within herds for estimating within-herd correlation of resistance status, and with repeated measures made on identical specimens for estimating test-retest reliability. PROCEDURE: From a population of 110 dairy herds, 30 were selected at random and from each herd between 5 and 10 faecal specimens were obtained from fresh manure pats. E coli from faecal specimens were grown on hydrophobic grid membrane filters (HGMF) and replicated onto chromogenic agar and agar containing antimicrobials (gentamicin, ampicillin, tetracycline and sulfamethoxazole). Image analysis was used to assess colony growth. Data were analysed descriptively, by generalised linear mixed models and by Taylor series linearisation to account for attributes of the survey design. RESULTS: Of the 10,279 E coli isolates assessed, 91% expressed no resistance, 7.3% were resistant to sulfamethoxazole, 3.6% to tetracycline, 2.2% to ampicillin and 0.09% to gentamicin. The most common multiple resistance phenotype was ampicillin-tetracycline-sulfamethoxazole (1.8% of isolates). Most multiple resistant isolates appeared clustered within particular herds but were too rare to obtain valid estimates of variance, confidence intervals or intra-herd correlation. The estimated proportion of isolates in the population that were susceptible to all four antimicrobials was 97% (95% CI: 91% to 100%) and 55% of cows had no resistance detected in faecal E coli (95% CI: 27% to 83%). Within-herd correlation of shedding status (any resistance pattern) was absent and test-retest reliability of the measurement system was estimated to be at the lower end of good (0.40) but increased to excellent (0.89) after excluding sulfamethoxazole resistance, which had a greater measurement error. CONCLUSION: Antimicrobial resistance was uncommon in E coli in the population of dairy cows studied. HGMF and image analysis is an effective tool for detecting rare forms of resistant E coli that are not uniformly distributed in livestock populations.

Animals↗

Hertz-level measurement of the optical clock frequency in a single 88Sr+ ion.

The frequency of the 5s 2S(1/2)-4d 2D(5/2) electric quadrupole clock transition in a single, trapped, laser-cooled 88Sr+ ion has been measured by using an optical frequency comb referenced to a cesium fountain primary frequency standard. The frequency of the transition is measured as 444,779,044,095,484.6 (1.5) hertz, with a fractional uncertainty within a factor of 3 of that of the cesium standard. Improvements required to obtain a cesium-limited frequency measurement are described and are expected to lead to a 88Sr+ optical clock with stability and reproducibility exceeding that of the primary cesium standard.

Journal Article↗

Measurement of the electric quadrupole moment of the 4d2D5/2 level in 88Sr+.

The quadrupole moment of the 4d (2)D(5/2) level in 88Sr+ has been measured to be 2.6(3)ea(2)(0), where a(0) is the Bohr radius and e the elementary charge. A single laser-cooled strontium ion was confined in an end cap trap with a variable dc quadrupole potential, and measurements were made on the 5s (2)S(1/2)-4d (2)D(5/2) transition at 674 nm using a femtosecond optical frequency comb. This work shows that measurements of the unperturbed 88Sr+ transition frequency with sub-Hz uncertainty are possible and is important in understanding the reproducibility of ion trap optical frequency standards.

Journal Article↗

Ethnicity and tracking blood pressure in children.

There is growing evidence that hypertension, one of the major modifiable risk factors for cardiovascular disease (CVD), is established early in life. Given this, it is important to discover when hypertension first becomes apparent. Further, it is of particular importance to examine the ethnic differences in blood pressure (BP) in children, given the variation in rates of CVD morbidity and mortality among adults from different ethnic groups.

Adolescent↗

Prescribing patterns in high-need Health Authority populations: how does an ethnically mixed composition affect volume and cost?

BACKGROUND: Prescribing is the most common therapeutic intervention in primary care, and there is substantial variation in prescribing practice across England. We investigate broad patterns of prescribing across Health Authorities in England, concentrating on ethnically diverse populations. METHODS: Initially we examined the association between a number of prescribing indicators from the Prescribing Support Unit Prescribing Toolkit and 'Needs Profiles'. We then considered whether the observed patterns of prescribing were appropriate, that is, could be largely explained by variations in the prevalence of a medical condition for which the corresponding group of drugs would be prescribed. RESULTS: The volume and cost of prescribing was generally lower in more ethnically diverse Health Authority populations when compared with more elderly or deprived populations. There was a significant negative association between ethnic composition and net-ingredient-cost per patient of cardiovascular drugs, but this disappeared upon adjusting for mortality from coronary heart disease. CONCLUSIONS: The volume and cost of prescribing was generally lower in more ethnically diverse Health Authority populations relative to other high-need population profiles. Further work on this subject matter is merited, particularly if individual level data is available.

Age Factors↗

Use of laser microdissection greatly improves the recovery of DNA from sperm on microscope slides.

Traditionally, sperms are isolated from vaginal cell mixtures by preferential extraction methods. Although these methods work well when there is a reasonable amount of DNA present, they are problematic when there are limited amounts (ca. 250 pg). In particular, the analysis of sperm from microscope slides has proven difficult. Here, we describe the use of laser capture microdissection (LM) for the isolation of spermatozoa from microscope slides containing sperms and vaginal cells. Such slides are frequently an important source of evidential material during the forensic investigation of rape and other sexual assaults. Low copy number (LCN) PCR was used to compare profiles of sperm DNA prepared using LM and preferential lysis. LM was found to outperform preferential lysis in 15 out of 16 samples. The application of LM to the processing of actual casework slides, and in particular the potential use of LM for the analysis of old cases, is discussed. Finally, 77 post-coital slides were processed in order to accurately assess the robustness of the technique. There was a significant association between the quality of the male profile recovered and time since intercourse that was independent of the number of sperms analysed, suggesting that the DNA was degraded even though the spermhead was intact.

Alleles↗