Understanding patient access patterns for primary health-care services for Aboriginal and Islander people in Queensland: a geospatial mapping approach.

This paperexplores the patterns ofpatients'accessingsix Aboriginal and Islander CommunityControlled Health Services (AICCHSs) in Queensland. Between August 2011 and February 2014, 26199 patients made at least one visit over a 2-year period prior to at least one of six Queensland AICCHS - one urban service (RA 1) in south-east Queensland, and five services in regional towns (RA 3) in Far North Queensland. Geospatial mapping of addresses for these registered patients was undertaken. The outcomes analysed included travel times to, the proportion of catchment populations using each AICCHS and an assessment of alternative mainstream general practice availability to these patients was made. In brief, the use of AICCHS was higher than Australian Bureau of Statistics census data would suggest. Approximately 20% of clients travel more than 30min to seek Aboriginal Health services, but only 8% of patients travelled longer than 60min. In the major city site, many other general practitioner (GP) services were bypassed. The data suggest Aboriginal and Islander patients in Queensland appear to value community-controlled primary care services. The number of Indigenous clients in regional locations in the Far North Queensland registered with services is often higher than the estimated resident population numbers.

Advanced rural skills training: are recently qualified GPs using their procedural skills?

INTRODUCTION: The number of GPs providing procedural services in rural areas is declining; however, few studies have investigated issues directly relevant to recently qualified doctors. Limited published data and anecdotal reports in Australia suggest that a large proportion of doctors leave rural procedural practice soon after training. This study aimed to: (1) describe where GPs practice in the 5 years after advanced rural skills training; (2) describe the proportion of doctors using their advanced skills; (3) measure doctors' ratings of the quality of support and how critical the year directly following training is in future career choices; and (4) measure the association between support and use of advanced skills. METHODS: A cross-sectional, postal survey was undertaken of doctors who had completed advanced rural skills training in Queensland between 1995 and June 2009. Data were collected on a three-page, structured questionnaire. General practice colleges, the three Queensland regional training providers and one national training provider were approached in order to identify and mail questionnaires to eligible doctors. Descriptive statistics were prepared for practice history information, and attitudinal ratings. A χ(2) test was used to analyse the association between support and use of skills. RESULTS: Sixty-one completed questionnaires were returned resulting in an unadjusted response rate of 51.7%. Respondents had completed a range of training posts: obstetrics and gynaecology (37.7%), anaesthetics (18%), anaesthetics and obstetrics and gynaecology (11.5%) and Aboriginal and Torres Strait Islander health (11.5%). Thirty-nine respondents (63.9%) were using skills related to their advanced training at the time of the study. In the first 5 years after training, the percentage of doctors using their advanced rural skills decreased from 75.4% to 61.1%. The year directly following advanced training was rated as 'critical' or 'very critical' in their future career choices by 68.9% of respondents. However, ratings of the quality of support received in that year were varied, with 21.4% reporting 'very poor' support. There was a statistically significant association between ratings of support in the year directly following training and the use of skills 3 years after training (χ(2) = 8.715, df = 2, p = 0.013). CONCLUSIONS: This study has shown that while the majority of doctors are using skills related to their advanced rural skills training, there is room for improvement through training and career planning support, extending formal support mechanisms into the first year after training, improving opportunities to use advanced skills and improving systems to re-engage doctors into procedural practice.

Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state.

A major challenge in neurobiology is to understand mechanisms underlying human neuronal diversification. Motor neurons (MNs) represent a diverse collection of neuronal subtypes, displaying differential vulnerability in different human neurodegenerative diseases. The ability to manipulate cell subtype diversification is critical to establish accurate, clinically relevant in vitro disease models. Retinoid signalling contributes to caudal precursor specification and subsequent MN subtype diversification. Here we investigate the necessity for retinoic acid in motor neurogenesis from human embryonic stem cells. We show that activin/nodal signalling inhibition, followed by sonic hedgehog agonist treatment, is sufficient for MN precursor specification, which occurs even in the presence of retinoid pathway antagonists. Importantly, precursors mature into HB9/ChAT-expressing functional MNs. Furthermore, retinoid-independent motor neurogenesis results in a ground state biased to caudal, medial motor columnar identities from which a greater retinoid-dependent diversity of MNs, including those of lateral motor columns, can be selectively derived in vitro.

Polypropylenimine dendrimer-induced gene expression changes: the effect of complexation with DNA, dendrimer generation and cell type.

Polypropylenimine (PPI) dendrimers appear attractive non-viral vectors for the delivery of genes, antisense oligonucleotides, and small interfering RNA (siRNA). However, the effects of these synthetic gene delivery vectors on global gene expression are poorly understood. Here we have examined the toxicogenomics of generation 2 (DAB-8) and generation 3 (DAB-16) PPI dendrimers in two human cell lines. At concentrations and treatment protocols routinely used for gene and oligonucleotide transfection, PPI dendrimers alone elicited marked changes in endogenous gene expression in A431 epithelial cells. The extent of PPI-induced gene changes appeared to be dependent on the dendrimer generation as the number of genes affected was greater with G3 compared to G2 PPI dendrimers in A431 cells. The signature of DAB16-induced gene changes in A549 cells was different to those elicited in A431 cells implying a strong dependence on cell type. The DAB-16 polymer complexed with DNA (dendriplexes) also elicited marked gene expression changes in A549 cells but with a signature that was different from the polymer alone implying that dendriplexes are "recognised" by cells as chemical entities that are distinct from the polymer alone. Alterations in expression of a variety of gene ontologies were observed including those involved in defence responses, cell proliferation and apoptosis. Although there was a tendency for increased DNA damage in cells treated with DAB16 alone or its DNA dendriplexes as detected by the COMET assay, these differences were not statistically significant. These data show for the first time that PPI-dendrimers, separate from their capability as transfection reagents, can intrinsically alter the expression of many endogenous genes that could potentially lead to them exerting multiple biological effects in cells. The impact and consequences of polymer-induced gene changes should guide their rational use as delivery systems for gene-based therapeutics.

Antistreptokinase antibodies: implications for thrombolysis in a region with endemic streptococcal infection.

AIMS: To determine antistreptokinase antibody (anti-SK) titres in patients with the acute coronary syndrome from communities with endemic group A streptococcal infection because of the implications for streptokinase (SK) thrombolysis. METHODS: Anti-SK titres were determined using a standard method in 47 consecutive SK naive patients, presenting to the Mt Isa Hospital emergency department, Australia, with an acute coronary syndrome. Both indigenous and non-indigenous subjects were enrolled. Antistreptolysin O (ASOT) and anti-DNAse B (ADB) titres were also determined. RESULTS: Indigenous patients were more likely to have anti-SK antibodies (p < 0.001) than the non-indigenous cohort. Anti-SK antibody titres also correlated well with ASOT/ADB titres. CONCLUSIONS: Anti-SK antibodies are highly prevalent in SK naive indigenous patients presenting with the acute coronary syndrome. Streptokinase should not be used for thrombolysis in populations with endemic group A streptococcal infection.

Maternal ante-natal parameters as predictors of persistent postnatal glucose intolerance: a comparative study between Afro-Caribbeans, Asians and Caucasians.

AIMS: To measure the prevalence of persistent glucose intolerance at 6-12 weeks postpartum in various ethnic groups to assess the value of targeted postpartum screening. METHODS: A retrospective study was performed using computerized databases from two large maternity units within one UK region. Both units used the same screening strategy for gestational diabetes mellitus (GDM) and the same postpartum follow-up at 6-12 weeks using a 75-g oral glucose tolerance test (OGTT). A total of 221 women with a diagnosis of GDM/impaired glucose tolerance (IGT) in the index pregnancy in addition to a completed postpartum 75-g OGTT were studied. Of these, 91 were Caucasian, 89 were of Indo-Asian (Asian) origin and 41 were of Afro-Caribbean origin. RESULTS: The study showed that 35% Indo-Asians had persistent postpartum glucose intolerance compared with 7% Caucasians and 5% Afro-Caribbeans (P < 0.003). Insulin requirement during pregnancy and a diagnosis of gestational diabetes prior to 20 weeks of pregnancy were predictive for persistent postpartum glucose intolerance amongst Indo-Asians. CONCLUSIONS: The frequency of postpartum glucose intolerance among Indo-Asian women is significantly greater than among age-matched Caucasian and Afro-Caribbean women. We suggest that all Indo-Asian women with gestational diabetes should undergo postpartum screening for persistent glucose intolerance. However, in non-Asian women selective screening may be more cost effective.

Caveolin-1 expression and caveolae biogenesis during cell transdifferentiation in lung alveolar epithelial primary cultures.

Caveolae are omega-shaped invaginations of the plasmalemma possessing a cytoplasmic membrane protein coat of caveolin. Caveolae are present in the in vivo alveolar epithelial type I (ATI) lung cell, but absent in its progenitor, the alveolar epithelial type II (ATII) cell. In primary culture ATII cells grown on a plastic substratum acquire with time an ATI-"like" phenotype. We demonstrate that freshly isolated rat ATII cells lack caveolae and expression of caveolin-1 (a critical caveolae structural protein). As the ATII cells acquire an ATI-like phenotype in primary culture caveolin-1 expression increases, with caveolin-1 signal at 192 h postseeding up to 50-fold greater than at 60 h; caveolae were morphologically evident only after 132 h. When maintaining the differentiated ATII phenotype with time, i.e., culture upon collagen with an apical interface of air, a temporal increase in caveolin-1 expression was not observed, with only very faint signals evident even at 192 h postseeding; at no time did these cultures display caveolae. In late primary ATII cultures caveolin-1 expression and caveolae biogenesis occur as a function of in vitro transformation from the ATII to the ATI-like phenotype. The results have broad implications for the in vitro study of the role of caveolae and caveolin in alveolar epithelial cell biology.