The Contribution of Geography to Disparities in Preventable Hospitalisations between Indigenous and Non-Indigenous Australians

Objectives

To quantify the independent roles of geography and Indigenous status in explaining disparities in Potentially Preventable Hospital (PPH) admissions between Indigenous and non-Indigenous Australians.

Design, setting and participants

Analysis of linked hospital admission data for New South Wales (NSW), Australia, for the period July 1 2003 to June 30 2008.

Main outcome measures

Age-standardised admission rates, and rate ratios adjusted for age, sex and Statistical Local Area (SLA) of residence using multilevel models.

Results

PPH diagnoses accounted for 987,604 admissions in NSW over the study period, of which 3.7% were for Indigenous people. The age-standardised PPH admission rate was 76.5 and 27.3 per 1,000 for Indigenous and non-Indigenous people respectively. PPH admission rates in Indigenous people were 2.16 times higher than in non-Indigenous people of the same age group and sex who lived in the same SLA. The largest disparities in PPH admission rates were seen for diabetes complications, chronic obstructive pulmonary disease and rheumatic heart disease. Both rates of PPH admission in Indigenous people, and the disparity in rates between Indigenous than non-Indigenous people, varied significantly by SLA, with greater disparities seen in regional and remote areas than in major cities.

Conclusions

Higher rates of PPH admission among Indigenous people are not simply a function of their greater likelihood of living in rural and remote areas. The very considerable geographic variation in the disparity in rates of PPH admission between Indigenous and non-Indigenous people indicates that there is potential to reduce unwarranted variation by characterising outlying areas which contribute the most to this disparity.     

Development of Peptide-Based Lineage-Specific Serology for Chronic Chagas Disease: Geographical and Clinical Distribution of Epitope Recognition

Background

Chagas disease, caused by infection with the protozoan Trypanosoma cruzi, remains a serious public health issue in Latin America. Genetically diverse, the species is sub-divided into six lineages, known as TcI–TcVI, which have disparate geographical and ecological distributions. TcII, TcV, and TcVI are associated with severe human disease in the Southern Cone countries, whereas TcI is associated with cardiomyopathy north of the Amazon. T. cruzi persists as a chronic infection, with cardiac and/or gastrointestinal symptoms developing years or decades after initial infection. Identifying an individual''s history of T. cruzi lineage infection directly by genotyping of the parasite is complicated by the low parasitaemia and sequestration in the host tissues.

Methodology/Principal Findings

We have applied here serology against lineage-specific epitopes of the T. cruzi surface antigen TSSA, as an indirect approach to allow identification of infecting lineage. Chagasic sera from chronic patients from a range of endemic countries were tested by ELISA against synthetic peptides representing lineage-specific TSSA epitopes bound to avidin-coated ELISA plates via a biotin labelled polyethylene glycol-glycine spacer to increase rotation and ensure each amino acid side chain could freely interact with their antibodies. 79/113 (70%) of samples from Brazil, Bolivia, and Argentina recognised the TSSA epitope common to lineages TcII/TcV/TcVI. Comparison with clinical information showed that a higher proportion of Brazilian TSSApep-II/V/VI responders had ECG abnormalities than non-responders (38% vs 17%; p<0.0001). Among northern chagasic sera 4/20 (20%) from Ecuador reacted with this peptide; 1/12 Venezuelan and 1/34 Colombian samples reacted with TSSApep-IV. In addition, a proposed TcI-specific epitope, described elsewhere, was demonstrated here to be highly conserved across lineages and therefore not applicable to lineage-specific serology.

Conclusions/Significance

These results demonstrate the considerable potential for synthetic peptide serology to investigate the infection history of individuals, geographical and clinical associations of T. cruzi lineages.     

Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial

BackgroundAntenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care.Methods and findingsThis was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24⁺¹ weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster–summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) −6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes.ConclusionsIn this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings.Trial registrationThis trial is registered with the ISRCTN registry, ISRCTN67698474.

Matias C Vieira and colleagues evaluate the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age in the DESiGN cluster randomised trial.     

Alpha repeat proteins (αRep) as expression and crystallization helpers

We have previously described a highly diverse library of artificial repeat proteins based on thermostable HEAT-like repeats, named αRep. αReps binding specifically to proteins difficult to crystallize have been selected and in several examples, they made possible the crystallization of these proteins. To further simplify the production and crystallization experiments we have explored the production of chimeric proteins corresponding to covalent association between the targets and their specific binders strengthened by a linker. Although chimeric proteins with expression partners are classically used to enhance expression, these fusions cannot usually be used for crystallization. With specific expression partners like a cognate αRep this is no longer true, and chimeric proteins can be expressed purified and crystallized. αRep selection by phage display suppose that at least a small amount of the target protein should be produced to be used as a bait for selection and this might, in some cases, be difficult. We have therefore transferred the αRep library in a new construction adapted to selection by protein complementation assay (PCA). This new procedure allows to select specific binders by direct interaction with the target in the cytoplasm of the bacteria and consequently does not require preliminary purification of target protein. αRep binders selected by PCA or by phage display can be used to enhance expression, stability, solubility and crystallogenesis of proteins that are otherwise difficult to express, purify and/or crystallize.     

The threat of rebellion: claiming entitled personhood in Central Africa

A recent anthropological literature on arms‐carrying and violence has sought to understand these undertakings as modes of labour and work. In contrast, I focus on threats, specifically threats made in conjunction with rebellion in the Central African Republic (CAR). Doing so show what the violence/labour approach has missed. Far from seeking to adapt to the exigencies of flexible, uncertain labour circumstances, these men seek to leverage the interests of international interveners in Central African conflicts and revive a statist, entitlement‐centred system in which getting paid indicates status, not work produced. As such, their threats are a critique of their expendability, and a critique of violence, at the same time as they perpetuate the importance of a capacity for violence as a political and personal asset.     

Morphometric Differences of Vocal Tract Articulators in Different Loudness Conditions in Singing

IntroductionDynamic MRI analysis of phonation has gathered interest in voice and speech physiology. However, there are limited data addressing the extent to which articulation is dependent on loudness.ResultsThe data show articulatory differences with respect to changes of both pitch and loudness. Here, lip opening and pharynx width were increased. While the vertical larynx position was rising with pitch it was lower for greater loudness. Especially, the lip opening and pharynx width were more strongly correlated with the sound pressure level than with pitch.ConclusionFor the vowel /a/ loudness has an effect on articulation during singing which should be considered when articulatory vocal tract data are interpreted.     

The Silk Road Health Project: How Mobility and Migration Status Influence HIV Risks among Male Migrant Workers in Central Asia

Objectives

We examined whether mobility, migrant status, and risk environments are associated with sexually transmitted infections (STIs) and HIV risk behaviors (e.g. sex trading, multiple partners, and unprotected sex).

Methods

We used Respondent Driven Sampling (RDS) to recruit external male migrant market vendors from Kyrgyzstan, Uzbekistan, and Tajikistan as well internal migrant and non-migrant market vendors from Kazakhstan. We conducted multivariate logistic regressions to examine the effects of mobility combined with the interaction between mobility and migration status on STIs and sexual risk behaviors, when controlling for risk environment characteristics.

Results

Mobility was associated with increased risk for biologically-confirmed STIs, sex trading, and unprotected sex among non-migrants, but not among internal or external migrants. Condom use rates were low among all three groups, particularly external migrants. Risk environment factors of low-income status, debt, homelessness, and limited access to medical care were associated with unprotected sex among external migrants.

Conclusion

Study findings underscore the role mobility and risk environments play in shaping HIV/STI risks. They highlight the need to consider mobility in the context of migration status and other risk environment factors in developing effective prevention strategies for this population.     

Structural and Psycho-Social Limits to Climate Change Adaptation in the Great Barrier Reef Region

Adaptation, as a strategy to respond to climate change, has limits: there are conditions under which adaptation strategies fail to alleviate impacts from climate change. Research has primarily focused on identifying absolute bio-physical limits. This paper contributes empirical insight to an emerging literature on the social limits to adaptation. Such limits arise from the ways in which societies perceive, experience and respond to climate change. Using qualitative data from multi-stakeholder workshops and key-informant interviews with representatives of the fisheries and tourism sectors of the Great Barrier Reef region, we identify psycho-social and structural limits associated with key adaptation strategies, and examine how these are perceived as more or less absolute across levels of organisation. We find that actors experience social limits to adaptation when: i) the effort of pursuing a strategy exceeds the benefits of desired adaptation outcomes; ii) the particular strategy does not address the actual source of vulnerability, and; iii) the benefits derived from adaptation are undermined by external factors. We also find that social limits are not necessarily more absolute at higher levels of organisation: respondents perceived considerable opportunities to address some psycho-social limits at the national-international interface, while they considered some social limits at the local and regional levels to be effectively absolute.     

Truncated human LMP-1 triggers differentiation of C2C12 cells to an osteoblastic phenotype in vitro

LIM mineralization protein-1 （LMP-1） is a novel intracellular osteoinductive protein that has been shown to induce bone formation both in vitro and in viva. LMP-1 contains an N-terminal PDZ domain and three C-terminal LIM domains. In this study, we investigated whether a truncated form of human LMP-1 （hLMP-1 [t]）, lacking the three C-terminal LIM domains, triggers the differentiation of pluripotent myoblastic C2C12 cells to the osteoblast lineage. C2C12 cells were transiently transduced with AdS-hLMP-1 （t）-green fluorescent protein or viral vector control. The expression of hLMP-1 （t） RNA and the truncated protein were examined. The results showed that hLMP-1 （t） blocked myotube formation in C2C12 cultures and significantly enhanced the alkaline phosphatase （ALP） activity. In addition, the expressions of ALP, osteocalcin, and bone morphogenetic protein （BMP）-2 and BMP-7 genes were also increased. The induction of these key osteogenic markers suggests that hLMP- 1 （t） can trigger the pluripotent myoblastic C2C12 cells to differentiate into osteoblastic lineage, thus extending our previous observation that LMP-1 and LMP-1 （t） enhances the osteoblastic phenotype in cultures of cells already committed to the osteoblastic lineage. Therefore, C2C12 cells are an appropriate model system for the examination of LMP-1 induction of the osteoblastic phenotype and the study of mechanisms of LMP-1 action.