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Ian White

Publications and source records attributed to Ian White.

At least 19 recordsLinked to original sources
PubMed2026

Short-Term Success, Long-Term Failure: Strain Turnover and Virulence Re-Emergence May Drive Relapse in Pouchitis.

BACKGROUND & AIMS: Pouchitis, de-novo small intestinal inflammation is the most common complication developing in patients with ulcerative colitis after total large bowel resection and ileal pouch-anal anastomosis (IPAA) reconstruction. While the first line treatment is antibiotics, the microbial properties underlying flare, remission, and relapse remain vague. We aimed to investigate how antibiotic treatment drives microbial shifts that underlie remission and contribute to relapse. METHODS: Patients after IPAA were prospectively recruited during clinical flare (active pouchitis defined by the pouchitis disease activity index) and received a two-week course of metronidazole with either ciprofloxacin or doxycycline. Longitudinal follow up was conducted during a year. Clinical data were recorded, and fecal samples were obtained during consequent flares, recovery, and relapses. Microbial gene repertoire, strains, and resistance to antibiotics were determined. Metagenomic sequencing was integrated with whole-genome sequencing of Escherichia coli isolates, providing strain-specific virulence and antibiotic resistance profiles. RESULTS: Patients (n=21) recruited provided 130 samples over one-year follow-up. Both antibiotic regimens induced rapid but transient clinical improvement, reflected by a decrease in fecal calprotectin (728 to 265 &#x3bc;g/g, p<.05), and a marked reduction in bacterial exotoxin genes (p<.05), yet both parameters rebounded by 6 weeks post-treatment. Antibiotic resistance gene abundance significantly increased during treatment (p<.05), without expansion of resistance gene diversity, indicating that pre-existing resistant strains increased. CONCLUSIONS: Antibiotic-induced remission in pouchitis likely results from a temporary suppression of exotoxin-producing bacteria, enabling resistant, low-virulence strains to transiently dominate; The fact that harmful strains quickly rebound after treatment cessation highlights the need for targeted approaches to achieve sustained microbial control.

Inflammatory bowel disease↗
PubMed2006

Regression dilution methods for meta-analysis: assessing long-term variability in plasma fibrinogen among 27,247 adults in 15 prospective studies.

BACKGROUND: Within-person variability in measured values of a risk factor can bias its association with disease. The extent of this regression dilution bias for plasma fibrinogen was investigated using repeat measurement data collected at varying time intervals on 27 247 adults in 15 prospective studies. METHODS: Regression dilution ratios (RDRs) were estimated from a linear regression of repeat measurements on baseline values in each study and for each time interval, and pooled allowing for within- and between-study heterogeneity. RDRs were estimated both without and with adjustment for confounders, and factors were investigated that might influence the RDRs. RESULTS: The unadjusted overall RDR was 0.51 (95% CI: 0.47, 0.55), which decreased to 0.46 (95% CI: 0.42, 0.49) after adjustment for age, sex and measured values of other established vascular risk factors. The RDR did not vary materially by assay method, age, sex or smoking status, but decreased at higher levels of baseline fibrinogen. CONCLUSION: It is appropriate to use an RDR of 0.5 to correct approximately for regression dilution bias in plasma fibrinogen values; however, this correction factor may produce somewhat conservative hazard ratios in adjusted analyses, at higher fibrinogen concentrations and in follow-up beyond a decade. More generally, the methods described in this report have widespread applicability to quantifying regression dilution bias in repeatability data from multiple prospective studies.

Adult↗
PubMed2006

The 2007 Census Test: a major step towards the 2011 Census.

The Office for National Statistics (ONS) is planning a major Census field test in 2007. It will form part of the planning and testing programme leading to up the next Census of Population for England and Wales in 2011, which will also include a Rehearsal in 2009. The 2007 Test will be a large-scale test in five local authority (LA) areas selected to reflect a range of field conditions, covering some 100,000 households in total. Within England the Test will cover parts of Bath and North East Somerset, Camden, Liverpool and Stoke-on-Trent. In Wales the Test will take place in Carmarthenshire. The selected LAs have been chosen to provide a varied cross-section of the population and types of housing that would be covered in a full census. This article sets out the main aims for the Test and describes the design and location of the sampled areas and the basis for their selection. It goes on to detail the ways (previously reported in Population Trend 1251) in which the ONS Census team and the LAs involved are working in partnership in planning the census enumeration with the long-term view of improving overall census coverage and user confidence in the results. The article notes that decisions on the topics to be covered in the 2007 Test have only recently been decided, and concludes with an overview of the qustions to be included in the 2007 Test questionnaire.

Censuses↗
PubMed2005

Quantitative trait locus analysis of longitudinal quantitative trait data in complex pedigrees.

There is currently considerable interest in genetic analysis of quantitative traits such as blood pressure and body mass index. Despite the fact that these traits change throughout life they are commonly analyzed only at a single time point. The genetic basis of such traits can be better understood by collecting and effectively analyzing longitudinal data. Analyses of these data are complicated by the need to incorporate information from complex pedigree structures and genetic markers. We propose conducting longitudinal quantitative trait locus (QTL) analyses on such data sets by using a flexible random regression estimation technique. The relationship between genetic effects at different ages is efficiently modeled using covariance functions (CFs). Using simulated data we show that the change in genetic effects over time can be well characterized using CFs and that including parameters to model the change in effect with age can provide substantial increases in power to detect QTL compared with repeated measure or univariate techniques. The asymptotic distributions of the methods used are investigated and methods for overcoming the practical difficulties in fitting CFs are discussed. The CF-based techniques should allow efficient multivariate analyses of many data sets in human and natural population genetics.

Chromosome Mapping↗
PubMed2005

Confidence in polymerase chain reaction diagnosis can be improved by Bayesian estimation of post-test disease probability.

OBJECTIVE: Polymerase chain reaction (PCR) techniques allow highly sensitive detection of specific DNA for diagnosis of infectious and genetic disease, but uncertainty relating to sensitivity and contamination has frequently resulted in controversy over results. We propose a new design in which the PCR contamination rate is estimated experimentally. The sensitivity of duplicate test results, and hence the post-test disease probabilities, can be derived algebraically, but wide confidence limits around these point estimates reduce their usefulness. STUDY DESIGN AND SETTING: We have developed a Bayesian method which gives better estimates of post-test disease probability and can substantially reduce uncertainty by using the prior belief that sensitivity is not lower than 90%. RESULTS: With 100 duplicate test samples and 100 control samples, we find that the post-test disease probability for concordant results (both positive or both negative) is generally unequivocal. The post-test disease probability for discordant results (one test positive and one negative) is often sufficiently clear to allow useful interpretation of individual test results, depending on the context. CONCLUSION: Using this approach, the performance of a PCR can be evaluated experimentally allowing post-test disease probability to be estimated, giving improved confidence in test results.

Bayes Theorem↗
PubMed2005

Deodorants: an experimental provocation study with isoeugenol.

Axillary dermatitis is common and overrepresented in people with contact allergy to fragrances. Many people suspect their deodorants to be the incriminating products. In order to investigate the significance of isoeugenol in deodorants for the development of axillary dermatitis when used by people with and without contact allergy to isoeugenol, patch tests with deodorants and ethanol solutions with isoeugenol, as well as repeated open application tests (ROAT) with roll-on deodorants with and without isoeugenol at various concentrations, were performed in 35 dermatitis patients, 10 without and 25 with contact allergy to isoeugenol. A positive ROAT was observed only in patients hypersensitive to isoeugenol (P<0.001) and only in the axilla to which the deodorants containing isoeugenol had been applied (P<0.001). Deodorants containing isoeugenol in the concentration range of 0.0063-0.2% used 2 times daily on healthy skin can thus elicit axillary dermatitis within a few weeks in people with contact allergy to isoeugenol.

Adult↗
PubMed2004

Impacts of runoff from sulfuric soils on sediment chemistry in an estuarine lake.

The impact of runoff from sulfuric soils in the heavily drained Cudgen Lake floodplain, eastern Australia on water quality and downstream coastal lake sediments has been examined. The oxidation of sulfidic soils and the transformation into sulfuric soils leads to changes not only in the upper soil profile but also affects drainage water quality and the chemistry of bottom sediments in receiving waters. Oxidation transforms the soil from a sink for sulfur and metals to a significant source for downstream environments. Sulfuric soils within the Cudgen Lake catchment contain 9.18 x 10(5) mol H+ per hectare as well as elevated concentration of metals (e.g. Al, Fe, Mn) and sulfate. These products of sulfidic soil oxidation are transported efficiently from the soil profile by the constructed drainage network and into the downstream lake system. The acid volatile sulfur (AVS), chromium reducible sulfur (CRS), total sulfur, organic carbon, and reactive iron contents present in the solid phase of the lake sediments are reported. The AVS/CRS, DOP and DOS values observed in the lake sediments show that natural monosulfide formation in the near surface sediments has been enhanced due to increased inputs of organic matter, sulfate, ferrous iron and other metals following development of the catchment. There are elevated concentrations of metals (e.g. As, Al, Cd, Cr, Hg, Zn and Pb) in the upper layer of monosulfidic lake sediments compared with the underlying pyritic sediments some of which exceed sediment quality guidelines. These metals could be released by dredging or through re-suspension during high flow conditions or enter the food chain.

Biological Availability↗
PubMed2004

Characteristics of teams, staff and patients: associations with outcomes of patients in assertive outreach.

BACKGROUND: Little is known about what characteristics of teams, staff and patients are associated with a favourable outcome of severe mental illness managed by assertive outreach. AIMS: To identify predictors of voluntary and compulsory admissions in routine assertive outreach services in the UK. METHOD: Nine features of team organisation and policy, five variables assessing staff satisfaction and burn-out and eleven patient characteristics taken from the baseline data of the Pan-London Assertive Outreach Study were tested as predictors of voluntary and compulsory admissions within a 9-month follow-up period. RESULTS: Weekend working, staff burn-out and lack of contact of the patient with out and lack of contact of the patient with other services were associated independently with a higher probability of both voluntary and compulsory admission. In addition, admissions in the past predicted further voluntary and compulsory admissions, and teams not working extended hours predicted compulsory admissions in the follow-up period. CONCLUSIONS: Characteristics of team working practice, staff burn-out and patients' history are associated independently with outcome. Patient contact with other services is a positive prognostic factor.

Adolescent↗
PubMed2004

The use of linear mixed models to estimate variance components from data on twin pairs by maximum likelihood.

It is shown that maximum likelihood estimation of variance components from twin data can be parameterized in the framework of linear mixed models. Standard statistical packages can be used to analyze univariate or multivariate data for simple models such as the ACE and CE models. Furthermore, specialized variance component estimation software that can handle pedigree data and user-defined covariance structures can be used to analyze multivariate data for simple and complex models, including those where dominance and/or QTL effects are fitted. The linear mixed model framework is particularly useful for analyzing multiple traits in extended (twin) families with a large number of random effects.

Algorithms↗
PubMed2004

The 2011 Census: a proposed design for England and Wales.

This article sets out the proposed design for a 2011 Census in England and Wales, as part of the ONS's proposed future population statistics system. The design draws on experiences from the 2001 Census and changes in available technology, and takes account of the many comments received from respondents to a Discussion Paper published in October 2003 and of views expressed at a joint ONS/RSS Conference on 11-12 November 2003. The article highlights the statistical and operational strategic aims for the 2011 Census, the major changes proposed from the 2001 approach, and gives an indication of the benefits and risks. It is important to note that this design remains a proposal at present, the elements of which will be subject to further research building on comments received during consultation and a detailed testing programme over the coming years.

Censuses↗
PubMed2003

Longitudinal variance-components analysis of the Framingham Heart Study data.

The Framingham Heart Study offspring cohort, a complex data set with irregularly spaced longitudinal phenotype data, was made available as part of Genetic Analysis Workshop 13. To allow an analysis of all of the data simultaneously, a mixed-model- based random-regression (RR) approach was used. The RR accounted for the variation in genetic effects (including marker-specific quantitative trait locus (QTL) effects) across time by fitting polynomials of age. The use of a mixed model allowed both fixed (such as sex) and random (such as familial environment) effects to be accounted for appropriately. Using this method we performed a QTL analysis of all of the available adult phenotype data (26,106 phenotypic records). In addition to RR, conventional univariate variance component techniques were applied. The traits of interest were BMI, HDLC, total cholesterol, and height. The longitudinal method allowed the characterization of the change in QTL effects with aging. A QTL affecting BMI was shown to act mainly at early ages.

Adult↗
PubMed2003

Lack of association between polymorphisms in angiotensin-converting-enzyme and methylenetetrahydrofolate reductase genes and normal cognitive ageing in humans.

The hypothesis that polymorphisms at two candidate genes that code for angiotensin-converting-enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR) are associated with normal cognitive ageing was tested using a sample (n=536) of healthy 80-year-old people who were born in 1921 and whose cognitive ability at age 11 was measured in the Scottish Mental Survey 1932. Cognitive ability at age 11 and age 80 was assessed using the Moray House Test. Cognitive ageing was defined as the change in IQ from age 11 to 80. There was no significant association between the tested ACE and MTHFR polymorphisms and IQ score at age 11, IQ at age 80, and IQ change (all P>0.05). The ACE genotypes deviated significantly from Hardy-Weinberg equilibrium proportions (P=0.02), which could indicate that this gene is under selection. Polymorphisms at the two studied genes are unlikely to be risk factors for normal cognitive ageing.

Aged↗
PubMed2003

Assertive outreach teams in London: models of operation. Pan-London Assertive Outreach Study, part 1.

BACKGROUND: Assertive outreach teams have been introduced in the UK, based on the assertive community treatment (ACT) model. It is unclear how models of community care translate from one culture to another or the degree of adaptation that may result. AIMS: To characterise London assertive outreach teams and determine whether there are distinct groups within them. METHOD: Semi-structured interviews with team managers plus one month's prospective process of care data collection were used to test for 'model fidelity' to ACT and, by cluster analysis, to identify groupings. RESULTS: Fidelity varied widely, with four teams (out of 24 studied) rated 'high fidelity' and three teams rated 'low fidelity' by US standards and 17 rated 'ACT-like'. Three clusters were identified, with voluntary sector teams being the most distinct group. CONCLUSIONS: There is wide variation in the practice of assertive outreach in London. The role of the voluntary sector requires increased attention. Heterogeneity in practice is a clinical challenge but a research opportunity in distinguishing effective from redundant components of the approach.

Adult↗
PubMed2003

Assertive outreach teams in London: staff experiences and perceptions. Pan-London Assertive Outreach Study, part 2.

BACKGROUND: The job satisfaction, burn-out and work experiences of assertive outreach team staff are likely to be important to the model's sustainability. AIMS: To describe self-reported views and work experiences of staff in London's 24 assertive outreach teams and to compare these with staff in community mental health teams (CMHTs) and between different types of assertive outreach team. METHOD: Confidential staff questionnaires in London's assertive outreach teams (n=187, response rate=89%) and nine randomly selected CMHTs (n=114, response rate=75%). RESULTS: Staff in assertive outreach teams and CMHTs were moderately satisfied with their jobs, with similar sources of satisfaction and stress. Mean scores were low or average for all sub-scales of the Maslach Burnout Inventory for the assertive outreach team and the CMHT staff, with some differences suggesting less burn-out in the assertive outreach teams. Nine of the 24 assertive outreach teams had team means in the high range for emotional exhaustion and there were significant differences between types of assertive outreach team in some components of burn-out and satisfaction. CONCLUSIONS: These findings are encouraging, but repeated investigation is needed when assertive outreach teams have been established for longer.

Adolescent↗
PubMed2003

Assertive outreach teams in London: patient characteristics and outcomes. Pan-London Assertive Outreach Study, part 3.

BACKGROUND: Although the model of assertive outreach has been widely adopted, it is unclear who receives assertive outreach in practice and what outcomes can be expected under routine conditions. AIMS: To assess patient characteristics and outcome in routine assertive outreach services in the UK. METHOD: Patients (n=580) were sampled from 24 assertive outreach teams in London. Outcomes--days spent in hospital and compulsory hospitalisation--were assessed over a 9-month follow-up. RESULTS: The 6-month prevalence rate of substance misuse was 29%, and 35% of patients had been physically violent in the past 2 years. During follow-up, 39% were hospitalised and 25% compulsorily admitted. Outcome varied significantly between team types. These differences did not hold true when baseline differences in patient characteristics were controlled for. CONCLUSIONS: Routine assertive outreach serves a wide range of patients with significant rates of substance misuse and violent behaviour. Over a 9-month period an average of 25% of assertive outreach patients can be expected to be hospitalised compulsorily. Differences in outcome between team types can be explained by differences in patient characteristics.

Adult↗
PubMed2003

Looking beyond the 2001 Census.

This article outlines the Office for National Statistics' strategic review process for the best way of meeting users' future requirements for information that has traditionally been collected by taking a census. It reports on a possible design for such a census in 2011 but also considers alternative approaches to collecting comparable information. The work described in this article is being undertaken within ONS and relates essentially to research on the census in England and Wales only. The General Register Office for Scotland and the Northern Ireland Statistics and Research Agency are, however, carrying out similar reviews.

Censuses↗
PubMed2002

The development of a simulation model of primary prevention strategies for coronary heart disease.

This paper describes the present state of development of a discrete-event micro-simulation model for coronary heart disease prevention. The model is intended to support health policy makers in assessing the impacts on health care resources of different primary prevention strategies. For each person, a set of times to disease events, conditional on the individual's risk factor profile, is sampled from a set of probability distributions that are derived from a new analysis of the Framingham cohort study on coronary heart disease. Methods used to model changes in behavioural and physiological risk factors are discussed and a description of the simulation logic is given. The model incorporates POST (Patient Oriented Simulation Technique) simulation routines.

Computer Simulation↗