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Biomedical subjects

B Robson

Publications and source records attributed to B Robson.

At least 19 recordsLinked to original sources

Postnatal zidovudine in prevention of vertical HIV-1 transmission in a service setting.

We sought to determine the efficacy of a 4-6 week course of zidovudine (ZDV) in a group of infants exposed to HIV-1. A retrospective chart review was conducted on HIV-1-exposed neonates identified from February 1998 to August 1999. These infants received ZDV and their mothers were counselled regarding the risks and benefits of breastfeeding. After informed consent was obtained, the HIV-1-status of the infant was determined by RNA-PCR after 1 month of age. Thirty-three HIV-1-exposed neonates were identified; seven infants were excluded, five because of insufficient data and two because of maternal ZDV administration. In all but three, the diagnosis was suspected because of maternal illness, 19 of 26 mothers having either stage 3 or 4 disease. The transmission rate was 15.4 per cent (4 of 26). Errors in ZDV administration were detected in 20 neonates of whom four were infected (p = 1; Fischer's exact test). Antenatal diagnosis of HIV-1 status was associated with fewer medication errors in HIV-1-exposed neonates (p = 0.017, Fisher's exact test). It was concluded that a transmission rate of 15.4 per cent in symptomatic mothers suggests efficacy. Under similar circumstances, transmission rates varying between 37 and 67 per cent have been reported. Antenatal diagnosis is significantly associated with compliance to the regimen. Early identification of at-risk neonates and familiarity with the regimen may improve the outcome.

Anti-HIV Agents↗

Evaluating the impact of a locality based social policy intervention on mental health: conceptual and methodological issues.

Urban regeneration initiatives provide an opportunity for examining the impact of changes in socio-economic circumstances on the mental health of different groups and individuals within localities. This paper sets out the conceptual and methodological bases for evaluating the impact of a population based social policy intervention on mental health. We suggest the need to integrate a range of disciplinary and methodological developments in research on health inequalities in exploring the impact of urban regeneration on mental health. A combination of multi-level modelling, subjective indicators and narrative accounts of individuals about mental health in the context of locality and personal changes are central for developing theories and methods appropriate for exploring the action and interaction of effects operating between structural and individual/agency levels.

Evaluation Studies as Topic↗

Disparities in health: common myths and uncommon truths.

A reappraisal of disparities by deprivation provides new and important information. NZDep96 is an area-based index of socioeconomic deprivation that uses nine variables measured in the 1996 census. The distribution of the Māori ethnic group is sharply skewed towards the most deprived deciles with only three percent in decile 1 and twenty-six percent residing in decile 10 meshblocks. More than half (56%) of Māori live in areas represented by the three most deprived deciles. This pattern is consistent within both sectors of the Māori ethnic group: sole Māori--those who give Māori as their only ethnicity and mixed Māori--those who give Māori as only one of their ethnicities. This is a 'distribution gap'. Within disparities analysis, there is also evidence of an 'outcome gap'. That is, the health outcomes of Māori are different from non-Māori, even after controlling for deprivation. For example, overseas data on life expectancy at birth have demonstrated social class gradients with lower life expectancy among manual workers and increasing life expectancy for trades-people, through to managerial and professional workers. This gradient is also evident in Aotearoa with life expectancy at birth decreasing as deprivation increases. A third dimension is evident in a review of disparities by deprivation,--a 'gradient gap'. This describes the relationship between ethnicity and increasing deprivation. It is as if the effect of increasing deprivation compounds risk for Māori whereas Pākehā do not seem subject to this effect. Analyses that foreground disparities have been portrayed as oppositional or secondary to Māori health development. In such frameworks where a disparity focus intersects with a development focus, the impression is given that the two are interconnected but move past each other in different directions. Our analysis promotes the disparities focus and the development focus as parallel reinforcing variables, each informing the other in the design and provision of services that have as their starting point, Māori needs. These services offer hope and opportunity for Māori but risk the vulnerability of special provision services (e.g. cuts in government expenditure). Furthermore the may delay the imperative of addressing the societal drivers that perpetuate disparities. This tension to engage in remedial reform is an important dilemma in Māori health development.

Censuses↗

Beyond proteins.

Increased understanding of the biological principles of protein structure and folding, combined with advances in protein-synthetic chemistry, should not only allow us to borrow from biology but also to depart from it and so produce protein-like, but non-protein, molecules and molecular devices. However, radical departures from protein-like forms into more-robust and truly novel 'smart' polymers and materials first require a solution to the protein-folding problem using only fundamental physicochemical principles. Any such practical solution may not come from raw computing power alone but rather from a deeper understanding of topological principles.

Biotechnology↗

The incidence of hepatocellular carcinoma in New Zealand.

AIM: To measure the incidence rate of hepatocellular carcinoma (HCC) in New Zealand, by ethnicity, sex, region and age. METHODS: Cancer Registry data for 1983-94 were used to calculate rates of primary liver cancer (ICD code 155.0) and HCC (both ICD code 155.0 and ICD-O morphology code 8170) directly standardised to Segi's world population and standardised for region. RESULTS: Rates of HCC per 100,000 person years 6.6 and 1.3 for Maori males and females, 14.7 and 4.6 for Pacific people, and 0.8 and 0.3 for Other (inclusive of Chinese). The rates for Chinese for 1989-94 were 19.9 and 5.8. These rates are likely to be underestimates due to imperfect sensitivity of ICD-O code 8170 registrations for HCC. The rates of HCC for Maori and Pacific people (sexes combined) were 7.3 and 18.0 times that for other for 1983-94; the HCC rate for Chinese was 25.8 times greater than Europeans for 1989-94. Rates of HCC tended to be higher in the north of New Zealand, compared to the south, for Maori and Other/Europeans, but there was no apparent regional gradient for Pacific people and Chinese. CONCLUSIONS: Non-Europeans have higher rates of HCC than Europeans due to variations in hepatitis B carriage. Males have higher rates than females, and Maori and Europeans living in the north of New Zealand have higher rates of HCC than those living in the south. It is estimated that any hepatitis B screening and follow-up programme will detect one incident case of HCC per year per 2000 hepatitis B carriers in the target population, or one incident case per 1000 carriers actually participating in regular follow-up.

Carcinoma, Hepatocellular↗

Comparison of reported prevalences of recent asthma in longitudinal and cross-sectional studies.

A potential source of bias in prevalence rates reported for symptoms and diagnoses of asthma in longitudinal studies could arise if repeated questioning of subjects or previous experience of lung function and airway responsiveness tests increased awareness of respiratory symptoms. We wished to determine the extent of any such bias by comparing reported prevalence rates from a longitudinal and cross-sectional study within similar populations. The prevalences of wheezing in the last year, waking with chest tightness, waking with shortness of breath, waking with coughing, having an attack of asthma in the last year, and current use of medications for asthma were determined using identical questions in two populations. Self-completed questionnaire responses of 946 subjects, 21 yrs of age, participating in the seventh respiratory assessment in the longitudinal Dunedin Multidisciplinary Health and Development Research Study were compared with responses provided by 991 subjects, aged 20-22 yrs, completing a postal questionnaire on one occasion only for the New Zealand section of the European Community Respiratory Health Study. The prevalence rates were not significantly different between the two populations, for all of the reported symptoms and for medication use. Differences in responses between genders were similar in each study, with all responses being more common in females. We conclude that repeated questioning regarding respiratory symptoms and repeated lung function and bronchial challenge testing in a longitudinal study of asthma did not bias prevalence rates compared with those obtained in a similar population of the same age studied on only one occasion.

Adult↗

Conferences point to growing concern about possible links between breast cancer, environment.

Evidence is growing that there may be a connection between certain chemicals in the environment and the rising incidence of breast cancer in North America. Two recent Canadian conferences have been held to disseminate information and another is planned for 1996. "We have a situation that is similar to global warming, " Devra Lee Davis, founder of the US Breast Cancer Prevention Collaborative Research Group, warned people attending a conference in Niagara Falls, Ont. "Breast cancer continues to increase. The increase is greatest among older women who have fewer of the known risk factors. It makes sense to try to limit exposure to things that could be promoting the disease."

Breast Neoplasms↗

PRO-LIGAND: an approach to de novo molecular design. 1. Application to the design of organic molecules.

An approach to de novo molecular design, PRO-LIGAND, has been developed that, in the environment of a large, integrated molecular design and simulation system, provides a unified framework for the generation of novel molecules which are either similar or complementary to a specified target. The approach is based on a methodology that has proved to be effective in other studies--placing molecular fragments upon target interaction sites-but incorporates many novel features such as the use of a rapid graph-theoretical algorithm for fragment placing, a generalised driver for structure generation which offers a large variety of fragment assembly strategies to the user and the pre-screening of library fragments. After a detailed description of the relevant modules of the package, PRO-LIGAND's efficacy in aiding rational drug design is demonstrated by its ability to design mimics of methotrexate and potential inhibitors for dihydrofolate reductase and HIV-1 protease.

Computer Simulation↗

PRO-LIGAND: an approach to de novo molecular design. 3. A genetic algorithm for structure refinement.

Recently, the development of computer programs which permit the de novo design of molecular structures satisfying a set of steric and chemical constraints has become a burgeoning area of research and many operational systems have been reported in the literature. Experience with PRO-LIGAND-the de novo design methodology embodied in our in-house molecular design and simulation system PRO-METHEUS-has suggested that the addition of a genetic algorithm (GA) structure refinement procedure can 'add value' to an already useful tool. Starting with the set of designed molecules as an initial population, the GA can combine features from both high- and low-scoring structures and, over a number of generations, produce individuals of better score than any of the starting structures. This paper describes how we have implemented such a procedure and demonstrates its efficacy in improving two sets of molecules generated by different de novo design projects.

Algorithms↗

PRO_LIGAND: an approach to de novo molecular design. 2. Design of novel molecules from molecular field analysis (MFA) models and pharmacophores.

A computational approach for molecular design, PRO_LIGAND, has been developed within the PROMETHEUS molecular design and simulation system in order to provide a unified framework for the de novo generation of diverse molecules which are either similar or complementary to a specified target. In this instance, the target is a pharmacophore derived from a series of active structures either by a novel interpretation of molecular field analysis data or by a pharmacophore-mapping procedure based on clique detection. After a brief introduction to PRO_LIGAND, a detailed description is given of the two pharmacophore generation procedures and their abilities are demonstrated by the elucidation of pharmacophores for steroid binding and ACE inhibition, respectively. As a further indication of its efficacy in aiding the rational drug design process, PRO_LIGAND is then employed to build novel organic molecules to satisfy the physicochemical constraints implied by the pharmacophores.

Angiotensin-Converting Enzyme Inhibitors↗

The self reported prevalence of asthma symptoms amongst adult New Zealanders.

AIMS: To examine the prevalence of asthma symptoms in a random population sample of New Zealand adults aged 20-44 years drawn from the general and Maori electoral rolls as phase I of an international study of asthma prevalence. METHODS: Subjects aged 20-44 years in Auckland, Hawkes Bay, Wellington and Christchurch, were selected randomly from the electoral rolls and sent a one page screening questionnaire, asking about respiratory symptoms, asthma attacks and asthma treatment. They were also asked to record their ethnic affiliation. Nonresponders were subsequently sent two written reminders followed by a telephone questionnaire where possible. RESULTS: A response rate of 84% was achieved. The study found a high prevalence of asthma symptoms, with 26% reporting wheezing in the last year, 8% experiencing an attack of asthma in the last year and 9% currently using asthma medication. Females were more likely to have had wheezing in the last year (26.6%) and be on treatment for asthma (9.8%) compared with males (24.7% and 7.5% respectively). Small regional differences were found with more reported symptoms and asthma treatment in Wellington and Christchurch, compared with Auckland and Hawkes Bay. Maori were more frequently symptomatic (35.2%) than nonPolynesian (24.8%) but were no more likely to report an attack of asthma (Maori 9.0%, nonPolynesian 7.7%) or be currently receiving asthma treatment (Maori 10.0%, nonPolynesian 8.6%). Asthma symptoms tended to decline with age in non Maori but increased with age in Maori. Adjustment of prevalence rates by two independent methods suggests that nonresponse bias has not significantly inflated these rates. CONCLUSIONS: The symptoms of asthma and their treatment are common in young New Zealanders, affecting one in three Maori and one in four nonMaori. One in ten of this adult population currently receive asthma treatment.

Adult↗

Novel algorithms for searching conformational space.

The modelling of biological molecules by molecular dynamics is beset by a range of problems. The most important of these is the multiple-minima problem. The deep metastable minima can cause difficulties in proper equilibration of a molecular system and result in the simulated system being trapped in a long-lived metastable state. One way to overcome these problems is to re-engineer the 'Newtonian Rules' in order to more efficiently search conformational space. Re-engineering of the 'Newtonian Rules' implies a redesign of the physical laws arising from them. This is done in various ways by the RUSH, Hybrid Monte Carlo and PEACS algorithms. This paper explores applications of these algorithms, and compares them to a traditional molecular dynamics method.

Alanine↗

A method for rapidly assessing and refining simple solvent treatments in molecular modelling. Example studies on the antigen-combining loop H2 from FAB fragment McPC603.

Different simple solvent models have been implemented in an extended simulated annealing process (ESAP), developed by Higo et al. [(1992) Biopolymers, 32, 33-43] and proven to be able to predict ab initio the conformation of the antigen-combining loop H2 from FAB McPC603. The rationale used here provides a useful new method for testing solvent models in general. The different solvent models comprise a high dielectric constant, a screened coulomb potential, a dummy water model and a statistical continuum treatment of the solvent effect in which the reaction field and the solvent accessible area is accounted for. To assess the effect of the solvent, we tested the ability of simulations to retain the experimental conformation of loop H2. We compared the different structures obtained at the end of the annealing process in terms of root mean square deviation (r.m.s.d.), for both the backbone and for all atoms, root mean square (r.m.s.) fluctuation, solvent accessible surface area (ASA), hydrogen bonding network and phi-psi plot distribution. The relationship between the r.m.s.d. and the internal energy of a structure is also evaluated in terms of precision and another possible method for obtaining the best conformation is discussed. The accuracy of modelling the coarse effect of the solvent and the similarities of the resulting structures with respect to the X-ray reference structure are examined. The possible choice of one of these solvent models in the structure determination of an unknown loop structure is discussed.

Algorithms↗

Community-based asthma care: trial of a "credit card" asthma self-management plan.

Although asthma self-management plans are widely recommended as essential in the long-term treatment of adult asthma, there have been few studies examining their use. Our objective was to assess the effect of a "credit card" adult asthma self-management plan in a community experiencing major health problems from asthma, by means of a before and after intervention trial of the efficacy of the "credit card" plan, when introduced through community-based asthma clinics. The participants were 69 Maori people with asthma. The "credit card" plan consisted of written guidelines for the self-management of asthma, based on self-assessment of asthma severity, printed on a plastic card. On one side, management guidelines were based on the interpretation of peak expiratory flow rate (PEFR) recordings, whilst the reverse side was based on symptoms. The outcome measures used were before and after comparison of markers of asthma morbidity and requirement for acute medical treatment; and a structured questionnaire assessing the acceptability and use of the credit card plan. Following the introduction of the plan, the mean PEFR increased from 347 to 389 l.min-1, the percentage of nights woken fell from 30.4 to 16.9%, and the number of days "out of action" fell from 3.8 to 1.7%. The requirements for acute medical treatment also fell during the intervention period. Most participants commented favourably on the content and usefulness of the plan. In the situation of worsening asthma, 28% of subjects found the peak flow side of the card most helpful, 7% the symptoms side, and 48% found both sides equally helpful.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗