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Biomedical subjects

D Briggs

Publications and source records attributed to D Briggs.

At least 19 recordsLinked to original sources
PubMed2006

ToF-SIMS investigation of octadecylphosphonic acid monolayers on a mica substrate.

In this paper, time-of-flight secondary ion mass spectrometry (ToF-SIMS) under static conditions was used to investigate self-assembled monolayers (SAMs) of octadecylphosphonic acid (OPA) formed on freshly cleaved muscovite mica substrates. The coverage of OPA on mica ranged from 20 to 100%, with a film thickness of 1.7+/-0.2 nm, which was determined by atomic force microscopy (AFM) imaging. The relative intensity of the specific secondary ion species associated with the OPA and with the exposed mica substrate exhibited good correlation with surface coverage. An excellent correlation was also observed (R2=0.98) between the relative SIMS [OPA-H]- intensity and the surface carbon concentration (OPA C 1s, in atomic %) from XPS at the prescribed surface coverage. The observation of positive and negative OPA molecular attachment of secondary ions involving the substrate species is discussed in terms of the chemical affinity of the OPA phosphonate headgroup for the cleaved mica surface as well as the sampling depth. In addition, the OPA molecular attachment species formed with the potassium ions on the cleaved mica substrate dominated the positive secondary ion mass spectrum in the high-mass range. A temperature-dependent, ToF-SIMS study employing in situ heating of a 100% coverage OPA monolayer revealed that the molecules begin to diffuse above approximately 80 degrees C, resulting in a decrease in the relative secondary ion yield of the OPA-specific secondary ions. This observation is hypothesized to be due to a decrease in the effective coverage of the substrate by the OPA molecules, which in turn could be due to the formation of multilayers upon heating in an effort to minimize the energy of the system. The interesting behavior of the novel OPA dimer species as a function of temperature is also reported. It was observed that the relative intensity of OPA and the mica-specific secondary ion peak intensities to that of Si (mica substrate) provides an effective means to estimate the change in coverage at elevated temperatures.

Journal Article↗
PubMed2006

A polymorphism in the promoter region of the CD86 (B7.2) gene is associated with systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease of unknown aetiology characterized by fibrosis of the skin and internal organs, vascular abnormalities and humoral autoimmunity. Strong T-cell-dependent autoantibody and HLA associations are found in SSc subsets. The co-stimulatory molecule, CD86, expressed by antigen-presenting cells, plays a crucial role in priming naïve lymphocytes. We hypothesized that SSc, or one of the disease subsets, could be associated with single-nucleotide polymorphisms of the CD86 gene. Using sequence specific primer-polymerase chain reaction (SSP-PCR) methodology, we assessed four CD86 polymorphisms in 221 patients with SSc and 227 healthy control subjects from the UK. Haplotypes were constructed by inference and confirmed using PHASE algorithm. We found a strong association between SSc and a specific haplotype (haplotype 5), which was more prevalent in patients than in controls (29% vs 15%, OR = 2.3, chi(2) = 12, P = 0.0005). This association could be attributed to the novel -3479 promoter polymorphism; a significant difference was observed in the distribution of the CD86 -3479 G allele in patients with SSc compared to controls (43.7% vs. 32.4%, OR = 1.7, chi(2) = 12.1, P = 0.0005). TRANSFAC analyses suggest that the CD86-3479T allele contains putative GATA and TBP sites, whereas G allele does not. We assessed the relative DNA protein-binding activity of the -3479 polymorphism in vitro using electromobility gel shift assays (EMSA), which showed that the -3479G allele has less binding affinity compared to the T allele for nuclear proteins. These findings highlight the importance of co-stimulatory pathways in SSc pathogenesis.

Algorithms↗
PubMed2005

Allergic reactions in the community: a questionnaire survey of members of the anaphylaxis campaign.

BACKGROUND: Allergic reactions to food are well recognized in both children and adults, but because of their relative infrequency their typical features may not be readily recognized by patients and their medical care givers who are not allergists. OBJECTIVE: We sought to investigate the circumstances and clinical characteristics of food allergies in adults and children in the community. METHODS: Self-completed questionnaire responses over a 6-month period from 109 members of the Anaphylaxis Campaign, the major British patient resource group for people who have suffered severe allergic reactions. RESULTS: One hundred and nine respondents reported 126 reactions during the study period. Seventy-five were children (under 16 years, median age 6 years at the time of reaction). Predictably more boys than girls were reported to have had reactions but more women reported reactions than men (P<0.05). Although the groups were equally aware of their food allergies the children had undergone diagnostic tests more often (P<0.001). Foods were implicated in 112 (89%) of reports. Restaurants were implicated less often (14%) than in other series, probably reflecting British eating habits. Children with asthma reported more severe reactions than those without asthma (P=0.008), although frequency or severity of recent asthma symptoms was not associated with severity of allergic reaction reported. When available, self-injectable adrenaline was used in 35% of severe reactions and 13% of non-severe reactions (P=0.01). A quarter of adults who received one dose of adrenaline also received a second dose. CONCLUSION: The allergens implicated in this report reflect previous data from similar patient groups in North America. Asthmatic children suffer more severe reactions than non-asthmatic children. It appears that British adults need better access to expert care of their allergies. Even when it is prescribed and available self-injectable adrenaline appears under-used in severe reactions. The incidence of severe but non-fatal allergic reactions in the UK may have been underestimated in the past.

Adolescent↗
PubMed2003

Utility of historical vehicle-control data in the interpretation of the local lymph node assay.

The accepted approach to the interpretation of local lymph node assay (LLNA) data requires comparison of responses in the test groups with background activity found in concurrent vehicle-treated controls. However, of established value in the interpretation of toxicity test data is the use of historical control values that provide one criterion against which to judge the integrity of individual experiments. Specifically, the availability of robust and relevant historical control data permits examination of whether, in any individual experiment, control values fall within the expected range. With the most commonly used vehicle employed in the LLNA, acetone/olive oil (4 : 1) (v/v), the mean values, standard deviations and normal ranges are increasingly well established for a given laboratory, although there is some variation between laboratories, particularly with regard to expected ranges. Against this background, it is possible to identify (and, if appropriate, eliminate) a concurrent vehicle-control value that falls well outside the expected range. To explore critically the potential merits of this approach, one specific example is examined in detail.

Animals↗
PubMed2002

Cancer risks in populations living near landfill sites in Great Britain.

Previous studies have raised concerns about possible excess risks of bladder, brain and hepatobiliary cancers and leukaemias near landfill sites. Several cancers have been implicated, but no consistent pattern has emerged. We present a large nationwide analysis of selected cancers near landfill sites in Great Britain. The base population comprised people living within 2 km of 9565 (from a total of 19 196) landfill sites that were operational at some time from 1982 to 1997, with populations living more than 2 km from a landfill as reference. Risks of cancers at the above sites were computed with adjustment for age, sex, year of diagnosis, region and deprivation. National post-coded registers provided a total of 341 856 640 person-years for the adult cancer analyses and 113 631 443 person-years for childhood leukaemia. There were 89 786 cases of bladder cancer, 36 802 cases of brain cancer, 21 773 cases of hepatobiliary cancer, 37 812 cases of adult leukaemia and 3973 cases of childhood leukaemia. In spite of the very large scale of this national study, we found no excess risks of cancers of the bladder and brain, hepatobiliary cancer or leukaemia, in populations living within 2 km of landfill sites. The results were similar if the analysis were restricted to landfill sites licensed to carry special (hazardous) waste. Our results do not support suggestions of excess risks of cancer associated with landfill sites reported in other studies.

Child↗
PubMed2002

Can we determine a threshold level for allergenic foods by statistical analysis of published data in the literature?

BACKGROUND: The aim of this paper was to investigate whether a statistical model could be developed to estimate a "threshold" dose for foods eliciting allergic reactions in susceptible patients. The threshold dose is defined to be one that elicits allergic reactions in a given (small) proportion of susceptible patients, using data from published studies. METHODS: Based on data available from the literature, we developed a statistical model using the actual allergen content in the four foods, where data for allergen content are available (peanut, soy, egg, milk). RESULTS: The model demonstrated that the threshold doses giving a reaction of one in a million in susceptible patients were within the same order of magnitude for egg, milk and soy, but were an order of magnitude lower for peanut flour: 0.005 mg of cow's milk, 0.002 mg of fresh hen's egg, 0.0007 mg of peanut, or 0.0013 mg of soy flour. CONCLUSIONS: Although several assumptions were made in creating this statistical model, we demonstrated that the previously published differences in threshold doses for various foods can be largely eliminated by comparing actual allergen content; this may therefore serve as a model for further studies.

Allergens↗
PubMed2002

Immune responses to native beta(2)-glycoprotein I in patients with systemic lupus erythematosus and the antiphospholipid syndrome.

OBJECTIVE: To identify HLA class II associations with anti beta(2)-glycoprotein I (beta2GPI) antibodies in a cohort of Caucasian patients with systemic lupus erythematosus (SLE) and to determine whether these HLA genotypes act as restriction elements for lymphocyte proliferation to native human beta2GPI in vitro. METHODS: Anti-beta2GPI antibodies were detected in patient sera using enzyme-linked immunosorbent assays (ELISAs). HLA class II alleles (DRB1, DQB1) were determined by polymerase chain reaction-based DNA genotyping. In vitro peripheral blood mononuclear cell (PBMC) responses to native human beta2GPI were measured in a 7-day proliferation assay. RESULTS: We identified three groups of Caucasian SLE patients using these ELISAs. In group 1, 16 out of 18 SLE patients (89%) with anti-beta2GPI antibodies were positive for HLA-DRB1*0401/4/8, DR11 or DRB1*1302 (P=0.001 vs controls) compared with 23 out of 53 patients (43%) in group 2 with anti-cardiolipin antibodies only, 57 out of 151 patients (38%) in group 3 (SLE patients without anticardiolipin antibodies) and 109 out of 225 controls (48%). Fourteen patients with anti-beta2GPI antibodies had greater median stimulation indices to beta2GPI in vitro compared with the 15 controls studied (P=0.04). CONCLUSION: The HLA class II and PBMC proliferation data suggest that beta2GPI may be both a T- and B-cell autoantigen in SLE.

Adolescent↗
PubMed2001

Risk of adverse birth outcomes in populations living near landfill sites.

OBJECTIVE: To investigate the risk of adverse birth outcomes associated with residence near landfill sites in Great Britain. DESIGN: Geographical study of risks of adverse birth outcomes in populations living within 2 km of 9565 landfill sites operational at some time between 1982 and 1997 (from a total of 19 196 sites) compared with those living further away. SETTING: Great Britain. SUBJECTS: Over 8.2 million live births, 43 471 stillbirths, and 124 597 congenital anomalies (including terminations). MAIN OUTCOME MEASURES: All congenital anomalies combined, some specific anomalies, and prevalence of low and very low birth weight (<2500 g and <1500 g). RESULTS: For all anomalies combined, relative risk of residence near landfill sites (all waste types) was 0.92 (99% confidence interval 0.907 to 0.923) unadjusted, and 1.01 (1.005 to 1.023) adjusted for confounders. Adjusted risks were 1.05 (1.01 to 1.10) for neural tube defects, 0.96 (0.93 to 0.99) for cardiovascular defects, 1.07 (1.04 to 1.10) for hypospadias and epispadias (with no excess of surgical correction), 1.08 (1.01 to 1.15) for abdominal wall defects, 1.19 (1.05 to 1.34) for surgical correction of gastroschisis and exomphalos, and 1.05 (1.047 to 1.055) and 1.04 (1.03 to 1.05) for low and very low birth weight respectively. There was no excess risk of stillbirth. Findings for special (hazardous) waste sites did not differ systematically from those for non-special sites. For some specific anomalies, higher risks were found in the period before opening compared with after opening of a landfill site, especially hospital admissions for abdominal wall defects. CONCLUSIONS: We found small excess risks of congenital anomalies and low and very low birth weight in populations living near landfill sites. No causal mechanisms are available to explain these findings, and alternative explanations include data artefacts and residual confounding. Further studies are needed to help differentiate between the various possibilities.

Congenital Abnormalities↗
PubMed2001

Outdoor sulphur dioxide and respiratory symptoms in Czech and Polish school children: a small-area study (SAVIAH). Small-Area Variation in Air Pollution and Health.

OBJECTIVES: Air pollution has been linked to respiratory outcomes but controversy persists about its long-term effects. We used a novel technique to estimate the outdoor concentrations of sulphur dioxide (SO2) at small-area level to study the long-term effects on respiratory symptoms and disease in children. METHODS: As part of the international SAVIAH study, parents of 8,013 children aged 7-10 studied in Prague (Czech Republic) and Poznan (Poland) completed a questionnaire covering respiratory health, demographic and socio-economic factors and health behaviours (response rate 91%). This report is based on 6,959 children with complete data. Outdoor SO2 was measured by passive samplers at 80 sites in Poznan and 50 sites in Prague during 2-week campaigns. Concentrations of SO2 at each point (location) in the study areas were estimated from these data by modelling in a geographical information system. The mean of the estimated SO2 concentrations at children's homes and schools was used as an indicator of exposure to outdoor SO2. RESULTS: The prevalence of respiratory outcomes was similar in both cities. In the pooled data, 12% of children had experienced wheezing/whistling in the past 12 months; 28% had a lifetime prevalence of wheezing/whistling; 14% had a dry cough at night; and 3% had had asthma diagnosed by a doctor. The estimated mean exposure to outdoor SO2 was 80 (range 44-140) microg/m3 in Poznan and 84 (66-97) microg/m3 in Prague. After socio-economic characteristics and other covariates were controlled for, SO2 was associated with wheezing/whistling in the past 12 months (adjusted OR per 50 microg/m3 1.32, 95% CI 1.10-1.57), lifetime prevalence of wheezing/whistling (OR 1.13, 95% CI 0.99-1.30), and lifetime prevalence of asthma diagnosed by a doctor (OR 1.39, 95% CI 1.01-1.92). The association with dry cough at night did not reach statistical significance. CONCLUSIONS: In these two Central European cities with relatively high levels of air pollution, small-area based indicators of long-term outdoor winter concentrations of SO2 were associated with wheezing/whistling and with asthma diagnosed by a doctor.

Air Pollutants↗
PubMed2001

A prevalidation study on in vitro tests for acute skin irritation. results and evaluation by the Management Team.

A prevalidation study on in vitro tests for acute skin irritation was conducted during 1999 and 2000. The overall objective of validation in this area, of which this prevalidation study is an initial stage, is to identify tests capable of discriminating irritants (I) from non-irritants (NI), as defined according to European Union (EU) risk phrases ("R38"; no classification) and the harmonised OECD criteria ("Irritant"; no label). This prevalidation study specifically addressed aspects of: protocol refinement (phase I), protocol transfer (phase II), and protocol performance (phase III), in accordance with the prevalidation scheme defined by the European Centre for the Validation of Alternative Methods (ECVAM). The tests evaluated were: EpiDerm (phases I, II and III), EPISKIN (phases I, II and III), PREDISKIN (phases I and II, and additional protocol refinement), the non-perfused pig ear method (phases I and II, and additional protocol refinement), and the mouse skin integrity function test (SIFT; phases I and II). Modified, standardised test protocols and well-defined prediction models were available for each of the tests at the end of phase I. The results of phase I (intralaboratory reproducibility) were sufficiently promising for all of the tests to progress to phase II. Protocol transfer between the Lead Laboratory and Laboratory 2 was undertaken for all five tests during phase II, and additional refinements were made to the test protocols. For EpiDerm, EPISKIN and the SIFT, the intralaboratory and interlaboratory reproducibilities were acceptable; however, better standardisation of certain aspects of the test protocols was needed prior to commencing phase III. Neither PREDISKIN nor the pig ear test performed sufficiently well in phase II to progress to phase III. The PREDISKIN protocol was overly sensitive, resulting in the prediction of all the NI chemicals as I. The variability in the pig ear test results was too great, indicating that the test would show limited predictive ability. In additional studies (a repeat of phase I), further modification of the PREDISKIN protocol and a change in the prediction model considerably improved the ability of the test to distinguish I from NI chemicals. However, attempts to improve the intralaboratory reproducibility of the pig ear test were unsuccessful. In phase III an initial assessment of the reproducibility and predictive ability, in three independent laboratories per test, was undertaken for the EpiDerm and EPISKIN tests (the SIFT was a late inclusion in the prevalidation study, and is being evaluated in a separate phase III study). A set of 20 coded chemicals (10 I, 10 NI) were tested with the final, refined, test protocols. The intralaboratory reproducibility was acceptable for both EpiDerm and EPISKIN. The interlaboratory reproducibility was considered to be acceptable for EPISKIN; however, for EpiDerm, analysis of variance (ANOVA) indicated that there was a statistically significant laboratory effect on the overall variability, suggesting that the interlaboratory transferability of the test needs to be improved. The EpiDerm test had an overall accuracy of 58%, with an over-prediction rate of 37% and an under-prediction rate of 47%. The EPISKIN test had an overall accuracy of 58%, showing an under-prediction rate of 23% and an over-prediction rate of 60%. It is concluded that, as yet, none of the tests evaluated in this prevalidation study are ready for inclusion in a formal validation study on in vitro tests for acute skin irritation. Overall protocol performance of the SIFT is currently being evaluated in a phase III study. Further studies are also in progress to improve the test protocols and prediction models for EpiDerm and EPISKIN.

Animal Testing Alternatives↗
PubMed2001

Statistical model for assessing the proportion of subjects with subjective sensitisations in adverse reactions to foods.

The outcome from a Double-Blind Placebo-Controlled Food Challenge is often of a subjective nature and cannot be measured directly. Reactions to placebo challenges are frequently observed, implying that some of the responses in the study are in fact 'false responses'. In order to adjust for these false responses, previous studies have used various methods, including removing subjects from the analysis who reacted to the placebo. Simply ignoring the false responses can lead to misleading estimates for the true proportion of sensitised individuals. This paper outlines two models which can account for these false responses. In the single challenge study, a simple model is developed which enables the estimation of the rate of false responses in the study, as well as the true proportion of sensitised subjects. This model is very easy to apply in practice. For a repeated challenge study, a more complicated model is developed which again enables the estimation of the rate of false responses and the true proportion of sensitised subjects.

Controlled Clinical Trials as Topic↗
PubMed2001

Serological responses of coyotes to two commercial rabies vaccines.

Between August 1993 and September 1994 we documented serological responses of coyotes (Canis latrans) vaccinated with two commercial rabies vaccines licensed for use in domestic dogs. Serologic responses were documented by testing for rabies virus neutralizing antibodies with the rapid fluorescent focus inhibition test (RFFIT) at 30, 90, 180, 270, and 365 days post-vaccination. All coyotes vaccinated with Imrab 3 (Rhone-Merieux, Inc.), and 75% of those vaccinated with Dura-Rab 3 (Immunovet, Inc.) seroconverted, as evidenced by the presence of antirabies antibody titers > or = 1:5 in one or more of the five post-vaccination samples. The percent of coyotes showing a titer > or = 1:5 was generally greater and titer levels appeared higher and more persistent among animals vaccinated with Imrab 3 than Dura-Rab 3. Presence of titers via RFFIT tests demonstrates the antibodies produced in coyotes by these rabies vaccines functionally bind and neutralize rabies virus in vitro, but these results do not constitute a demonstration of protection required for licensure for use in coyotes.

Animals↗
PubMed2000

Altered folate metabolism and disposition in mothers affected by a spina bifida pregnancy: influence of 677c --> t methylenetetrahydrofolate reductase and 2756a --> g methionine synthase genotypes.

Periconceptional folate prevents spina bifida although the mechanisms involved are unclear. We present the genotype frequency for the 677 ct methylenetetrahydrofolate reductase (MTHFR) and 2756ag methionine synthase (MetSyn) polymorphisms. Calculated odds ratios (OR) show that neither the homozygous recessive genotype, carriage of the mutant allele, nor frequency of the mutant allele represent significantly increased risk for neural tube defect (NTD). This is true for both polymorphisms. Simultaneous carriage of t and g alleles is also not a significantly increased risk for NTD. OR and 95% CI for carriage of (i) t allele, (ii) g allele, and (iii) simultaneous carriage of t and g alleles in NTD are 0.89 (0.28-2.82), 0.97 (0.28-3.30), and 0.61 (0.11-3.52), respectively. OR and 95% CI for frequency of t and g alleles are 0.94 (0.42-2.13) and 0.88 (0. 29-2.67), respectively. Unlike some previous studies, we could not detect a significantly increased risk for NTD conferred by the 677ct MTHFR tt genotype; OR 0.98 (0.19-6.49). Differences were found to exist in the circulating whole blood folate profile: total formyl-H(4)PteGlu was significantly higher than total 5-methyl-H(4)PteGlu in control (P = 0.036) but not NTD blood. When broken down into the various 677 ct MTHFR and 2756ag MetSyn genotypes, carriage of the 677ct MTHFR allele appears to affect formyl-H(4)PteGlu metabolism in non-NTD mothers. In addition, NTD mothers exhibited noticeably lower formyl-H(4)PteGlu levels compared to controls; these effects, however, were not significant. 2756ag MetSyn is similarly associated with an altered formyl-H(4)PteGlu disposition. The ag genotype had significantly more formyl-H(4)PteGlu relative to 5-methyl-H(4)PteGlu than wildtype 2756ag MetSyn (P = 0.024). This heterozygous increase in the relative formyl-H(4)PteGlu level holds true for controls only; no such relationship occurred in NTD samples. Folyl hexaglutamates are the active cellular coenzyme forms. We showed that where 5-methyl-H(4)PteGlu(6) predominates, Hcy levels are highest. As the relative abundance of formyl-H(4)PteGlu(6) increased, so Hcy decreased, presumably due to increased Hcy remethylation, a process in which 5-methyl-H(4)PteGlu(6) is demethylated and downstream folates like formyl-H(4)PteGlu(6) are produced. The negative linear association between the hexaglutamate ratio (formyl-H(4)PteGlu(6)/5-methyl-H(4)PteGlu(6)) and Hcy is significant for control (r = -0.64, P = 0.003) but not NTD samples. This effect, centering on Hcy remethylation, is supported by a statistically elevated formyl-H(4)PteGlu(6) to 5-methyl-H(4)PteGlu(6) level in controls relative to NTDs (P = 0.047). The overall (polymorphism independent) effect of exogenous 5,10-methenyl-H(4)PteGlu(1) substrate on the cellular folate profile was to preferentially increase formyl-H(4)PteGlu, while exogenous 5-methyl-H(4)PteGlu(1) substrate dramatically increased metabolic production of 5, 10-methylene-H(4)PteGlu. The following differences were observed between NTD and control samples: (i) a reduced expansion of the formyl-H(4)PteGlu(6) pool in NTD with exogenous 5, 10-methenyl-H(4)PteGlu(1) (P = 0.0005 for control expansion, NS for NTD increase); (ii) a reduced initial expansion of the 5, 10-methylene-H(4)PteGlu pool in NTD following treatment with exogenous 5-methyl-H(4)PteGlu(1) substrate (difference between subject groups; P = 0.031). In addition, taking polymorphisms into account, lysate from NTD-MTHFR wildtypes utilized less exogenous 5-methyl-H(4)PteGlu(1) substrate than control-MTHFR wildtypes in the short (P = 0.011) and long term (P = 0.036). Commensurate with this latter effect, the initial production of 5,10-methylene-H(4)PteGlu due to exogenous 5-methyl-H(4)PteGlu(1) substrate was significantly reduced in the NTD-MTHFR wildtype (P = 0.037). These two MTHFR wildtype effects imply that the 677 ct polymorphism is not the only mutation affecting folate metabolism in NTD mothers. (ABSTRACT TRUNCATED)

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2000

Distribution of primary renal diseases leading to end-stage renal failure in the United States, Europe, and Australia/New Zealand: results from an international comparative study.

This report notes the differences in the classification of the primary renal disease (PRD) used in different renal dialysis and transplant registries worldwide. The heterogeneity of coding systems complicates the comparative analysis of end-stage renal disease from different regions. Using data collected over two decades in the United States, Europe, and Australia/New Zealand, we present a method for reorganization of the classes of PRD that allows a straightforward comparison of retrospective data from these registries.

Adult↗
PubMed2000

Outdoor air concentrations of nitrogen dioxide and sulfur dioxide and prevalence of wheezing in school children.

We report analysis of data on outdoor air pollution and respiratory symptoms in children collected in the Czech part of the international Small Area Variations in Air pollution and Health (SAVIAH) Project, a methodological study designed to test the use of geographical information systems (GIS) in studies of environmental exposures and health at small area level. We collected the following data in two districts of Prague: (1) individual data on 3,680 children (response rate 88%) by questionnaires; (2) census-based socio-demographic data for small geographical units; (3) concentrations of nitrogen dioxide (NO2) and sulfur dioxide (SO2) measured by passive samplers in three 2-week surveys at 80 and 50 locations, respectively. We integrated all data into a geographical information system. Modeling of NO2 and SO2 allowed estimation of exposure to outdoor NO2 and SO2 at school and at home for each child. We examined the associations between air pollution and prevalence of wheezing or whistling in the chest in the last 12 months by logistic regression at individual level, weighted least squares regression at small area (ecological) level and multilevel modeling. The results varied by the level of analysis and method of exposure estimation. In multilevel analyses using individual data, odds ratios per 10 microg/m3 increase in concentrations were 1.16 (95% CI = 0.95-1.42) for NO2, and 1.08 (95% CI = 0.97-1.21) for SO2. While mapping of spatial distribution of NO2 and SO2 in the study area appeared valid, the interpolation from outdoor to personal exposures requires consideration.

Air Pollutants↗
PubMed2000

Australian Aboriginal trainee health service management program: a new initiative.

This paper explores the development, implementation and evaluation of the Australian Aboriginal trainee health service management program in New South Wales. In 1997, the two-year pilot program commenced with ten trainees. The program consisted of a combination of work-based placements, formal university education and Australian College of Health Service Executives (ACHSE) professional development sessions. The program has allowed trainees to gain professional skills and knowledge and broader work experience, in order to increase their employment opportunities throughout the Australian health care system.

Clinical Competence↗
PubMed1999

A complex population of RNAs exists in human ejaculate spermatozoa: implications for understanding molecular aspects of spermiogenesis.

The presence of mRNAs in human ejaculate spermatozoa is well established, yet little is known of the representation or function of these transcripts. To address these issues, the complexity of spermatozoal RNA was examined. As expected, testis-expressed mRNAs were detected by RT-PCR in mature human spermatozoa. Interestingly, when a testis cDNA library was probed with total spermatozoal RNA, less than 2% of plaques gave a strong hybridization signal, suggesting a rather unique sperm-derived population. To further define the sequence distribution, 18 strongly hybridizing clones were selected at random for end-sequence analysis. Twelve matched unique sequences in the EST, STS and NR databases, whereas five showed no similarity to any of the sequences in the databases. In addition, one clone belonged to the SINE repetitive element family. As demonstrated by sequencing randomly primed cloned inserts, short (SINE/MER) or long (LINE/ORF2) interspersed repeat-like sequences are also contained as part of the spermatozoal RNA fraction. It is now evident that human spermatozoa contain a rich repertoire of both known and unknown protein-encoding and non-coding RNAs. This provides a unique opportunity to identify and investigate the many genes responsible for the structure and function/dysfunction of the male gamete using spermatozoal RNA as the template.

Amino Acid Sequence↗