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Biomedical subjects

Tom Smith

Publications and source records attributed to Tom Smith.

14 recordsLinked to original sources
PubMed2003

Estimation of infection and recovery rates for highly polymorphic parasites when detectability is imperfect, using hidden Markov models.

A Bayesian hierarchical model is proposed for estimating parasitic infection dynamics for highly polymorphic parasites when detectability of the parasite using standard tests is imperfect. The parasite dynamics are modelled as a non-homogeneous hidden two-state Markov process, where the observed process is the detection or failure to detect a parasitic genotype. This is assumed to be conditionally independent given the hidden process, that is, the underlying true presence of the parasite, which evolves according to a first-order Markov chain. The model allows the transition probabilities of the hidden states as well as the detectability parameter of the test to depend on a number of covariates. Full Bayesian inference is implemented using Markov chain Monte Carlo simulation. The model is applied to a panel data set of malaria genotype data from a randomized controlled trial of bed nets in Tanzanian children aged 6-30 months, with the age of the host and bed net use as covariates. This analysis confirmed that the duration of infections with parasites belonging to the MSP-2 FC27 allelic family increased with age.

Algorithms↗
PubMed2003

Local evolvability of statistically neutral GasNet robot controllers.

In this paper we introduce and apply the concept of local evolvability to investigate the behaviour of populations during evolutionary search. We focus on the evolution of GasNet neural network controllers for a robotic visual discrimination problem, showing that the evolutionary process undergoes long neutral fitness epochs. We show that the local evolvability properties of the search space surrounding a group of statistically neutral solutions do vary across the course of an evolutionary run, especially during periods of population takeover. However, once takeover is complete there is no evidence for further increase in local evolvability across fitness epochs. We also see no evidence for the neutral evolution of increased solution robustness, but show that this may be due to the ability of evolutionary algorithms to focus search on volumes of the fitness landscape with above average robustness.

Adaptation, Physiological↗
PubMed2003

Molecular monitoring in malaria vaccine trials.

Molecular techniques offer new approaches for malaria field trials, particularly PCR techniques, which facilitate accurate diagnosis of Plasmodium infections and increase the power of estimates of vaccine effects on malaria prevalence or incidence. Molecular methods also help to assess selective effects of vaccines. Longitudinal genotyping data can be used to initiate novel analyses of parasite dynamics, including estimates of incidence of infection with individual parasite clones and duration of infections. In addition, high-throughput methods can be used to apply these techniques routinely in randomized controlled trials, as well as programme-based evaluations of malaria control.

Animals↗
PubMed2003

The epidemiology of malaria in Papua New Guinea.

Papua New Guinea (PNG) is a patchwork of different ecological zones, inhabited by human populations of exceptional cultural and linguistic diversity. This results in complex variations in vector ecology and malaria epidemiology. Malaria is the main cause of morbidity in many health facilities in lowland areas, but it is absent in much of the highlands. All four human malaria species occur, but endemicity varies widely, with Plasmodium falciparum locally reaching holo-endemic levels that are rarely found outside sub-Saharan Africa. The high frequency of Plasmodium vivax is an important difference to most African situations. PNG is therefore a prime location for studies of interactions between different parasite species, and of the biology of local human genetic adaptation and its implications for malaria morbidity and mortality.

Animals↗
PubMed2003

Cardiopulmonary resuscitation: attitudes and perceptions of junior doctors.

Many junior doctors feel cardiac arrests are unsatisfactorily managed and experience high levels of stress during the procedure, often feeling they are inadequately trained for the task. Juniors also regard 'do not resuscitate' orders as decisions for teams, not individuals.

Attitude of Health Personnel↗
PubMed2002

Assessment of positivity in immuno-assays with variability in background measurements: a new approach applied to the antibody response to Plasmodium falciparum MSP2.

Measurements of immune responses often exhibit considerable heterogeneity, making it impossible to clearly distinguish responders and nonresponders to particular antigens. Typically, in, for example, enzyme-linked immunosorbent assay (ELISA) procedures, a nonexposed control group is used to assign a cutoff value of positivity, calculated as the mean plus either 2 or 3 standard deviations (S.D.). This can cause extremely biased estimates of response rates when the background is variable, and especially when there is overlap between the distribution of the control levels and that of responders. This problem is compounded when results of assays with different background levels are compared. We illustrate this with hypothetical data sets reflecting frequent patterns seen in laboratory and epidemiological studies. We propose that such data should be analysed by statistical modelling of the ratio of numbers of test samples/control samples as a function of the readout from the assay. Rather than classifying samples dichotomously as negative or positive, this provides estimates of the prevalence of positivity lambda, and the probability, for each sample, that the measured activity is above background. Several statistical methods can provide such estimates. Analyses of simulated data sets using our preferred estimation method [a latent class model (LCM)] demonstrate that this gives more reliable results than the traditional assignment using cutoff values. We have applied this approach to the analysis of ELISA assessments of antibodies against distinct regions of the Plasmodium falciparum merozoite surface protein 2 (MSP2) in human sera from Tanzania.

Animals↗
PubMed2002

Lead exposure in Mexican radiator repair workers.

BACKGROUND: Lead exposure was investigated among 73 Mexican radiator repair workers (RRWs), 12 members of their family (4 children and 8 wives), and 36 working controls. RRWs were employed at 4 radiator repair shops in Mexico City and 27 shops in Cuernavaca and surrounding areas. METHODS: Exposure was assessed directly through the use of personal air sampling and hand wipe samples. In addition, industrial hygiene inspections were performed and detailed questionnaires were administered. Blood lead levels were measured by graphite furnace atomic absorption spectroscopy (AAS). RESULTS: The mean (SD) values for blood lead of the RRWs, 35.5 (13.5) microg/dl, was significantly greater than the same values for the working controls, 13.6 (8.7) microg/dl; P < 001. After excluding a single outlier (247 microg/m(3)), air lead levels ranged from 0 to 99 microg/m(3) with a mean (SD) value of 19 (23) microg/m(3) (median = 7.9 microg/m(3)). In a final multivariate regression model of elevated blood lead levels, the strongest predictors were smoking (vs. non-smoking), the number of radiators repaired per day on average, and the use (vs. non-use) of a uniform while at work, which were associated with blood lead elevations of 11.4 microg/dl, 1.95 microg/dl/radiator/day, and 16.4 microg/dl, respectively (all P <.05). Uniform use was probably a risk factor because they were not laundered regularly and consequently served as reservoir of contamination on which RRWs frequently wiped their hands. CONCLUSIONS: Lead exposure is a significant problem of radiator repair work, a small industry that is abundant in Mexico and other developing countries.

Adult↗
PubMed2002

A point mutation in codon 76 of pfcrt of P. falciparum is positively selected for by Chloroquine treatment in Tanzania.

This study was undertaken to validate the relevance of Chloroquine (CQ) resistance markers pfcrt(76) and pfmdr1(86) in an endemic area in Tanzania. After treatment with CQ, recrudescence was distinguished from new infection by msp2 genotyping, and the number of concurrent infections was also determined. The rate of children with recrudescent parasites at day 7 and/or day 14 amounted to a parasitological failure rate of 22.4% using PCR. The mean multiplicity of infection at day 0 was 3.2 (n=71). The allelic frequencies of the mutated pfcrt(76) and pfmdr1(86) were estimated to be 92 and 77%, respectively. Both values exceeded by far the observed frequency of 14% of recrudescent parasites as calculated on the whole analysed parasite population taking multiple infections into account. Although neither mutant allele is of predictive value for parasitological resistance, there is evidence for a role of pfcrt(76) in CQ resistance in the natural parasite population. All wild-type pfcrt(76) alleles were eliminated before day 3, after the onset of CQ treatment and no recrudescent parasite with the wild-type allele was observed at later time points. The discrepancy between the rate of resistant parasites (14%) and the frequency of the mutant pfcrt(76) allele (92%), however, indicates that other polymorphisms and other factors must be involved in CQ resistance. No selective elimination of the pfmdr1(86) wild-type allele was observed.

Animals↗
PubMed2002

Does radical cure of asymptomatic Plasmodium falciparum place adults in endemic areas at increased risk of recurrent symptomatic malaria?

A cohort of 197 adults in Kassena-Nankana District (northern Ghana) was radically cured of malaria parasites to study subsequent incidence of malaria infection. During the following 20 weeks of the malaria transmission season, 49% experienced clinical attacks associated with Plasmodium falciparum parasitaemia. In a group of 202 adults identically followed-up 1 year later without being treated, only 38% experienced such episodes (log-rank test for equality of survivor functions, P=0.035). Clinical attacks in radically cured individuals presented with lower parasite densities but more symptoms. Randomized studies are needed to test the hypothesis that radical cure of P. falciparum enhances the risk and severity of subsequent clinical malaria attacks.

Adolescent↗
PubMed2002

The problem with rational approaches to reforming the NHS.

Several papers with a common theme published between May and August 2002 are drawn together to present a research-informed critique of economic logic present within recent NHS reform. They attempt to persuade the reader that excessive faith in predictive systems of thought that are underpinned by theories of rational behaviour is misplaced within the NHS. They suggest rational economic theory makes some problematic assumptions about human and individual behaviour. The problem is that there are many modes of thought at work within the NHS, and not all of these cogs are turned by economic rationality. Increasingly, over the last 10 years or so, economic concepts have become more and more prominent in the NHS. Their influence has gone beyond finance becoming a dominant issue. In addition to budgets, contracts and cost itemisation, theoretical relationships of supply and demand are now called upon to change professional behaviour. A new framework for the NHS has been built which is developing market forces. The papers provide some insight into whether the systems set in place to produce a patient-centred service do so in a meaningful way. The first paper examines an emerging primary care group (PCG). Now part of primary care trusts, PCGs were a lynchpin of new economic relationships in the new NHS. Community based, in theory PCGs take decisions made about healthcare resources closer to the patient for whom they are a proxy demander and shaper of services. To what extent do PCGs fulfil this role? The first paper is based on data collected during an in-depth 2 year observation study to test the applicability of health economics to healthcare organisations. It examines the early experience of commissioning services for coronary heart disease (CHD).

Aged↗
PubMed2002

Fitness landscapes and evolvability.

In this paper, we develop techniques based on evolvability statistics of the fitness landscape surrounding sampled solutions. Averaging the measures over a sample of equal fitness solutions allows us to build up fitness evolvability portraits of the fitness landscape, which we show can be used to compare both the ruggedness and neutrality in a set of tunably rugged and tunably neutral landscapes. We further show that the techniques can be used with solution samples collected through both random sampling of the landscapes and online sampling during optimization. Finally, we apply the techniques to two real evolutionary electronics search spaces and highlight differences between the two search spaces, comparing with the time taken to find good solutions through search.

Biological Evolution↗
PubMed2002

Clonal groupings in serogroup X Neisseria meningitidis.

The genetic diversity of 134 serogroup X Neisseria meningitis isolates from Africa, Europe, and North America was analyzed by multilocus sequence typing and pulsed-field gel electrophoresis. Although most European and American isolates were highly diverse, one clonal grouping was identified in sporadic disease and carrier strains isolated over the last 2 decades in the United Kingdom, the Netherlands, Germany, and the United States. In contrast to the diversity in the European and American isolates, most carrier and disease isolates recovered during the last 30 years in countries in the African meningitis belt belonged to a second clonal grouping. During the last decade, these bacteria have caused meningitis outbreaks in Niger and Ghana. These results support the development of a comprehensive conjugate vaccine that would include serogroup X polysaccharide.

Africa↗