Recent patterns in chronic disease mortality in remote living Indigenous Australians

Background: Despite the well-recognised Indigenous-non-Indigenous health disparity, some reports suggest improvements in Indigenous mortality. Our aim was to quantify Indigenous mortality in Outer Regional (OR), Remote (R), and Very Remote (VR) areas in New South Wales, Queensland, South Australia, Western Australia, and the Northern Territory and changes in mortality from 1998 to 2005

Molecular Correlates of Social Dominance: A Novel Role for Ependymin in Aggression

Theoretical and empirical studies have sought to explain the formation and maintenance of social relationships within groups. The resulting dominance hierarchies have significant fitness and survival consequences dependent upon social status. We hypothesised that each position or rank within a group has a distinctive brain gene expression profile that correlates with behavioural phenotype. Furthermore, transitions in rank position should determine which genes shift in expression concurrent with the new dominance status. We used a custom cDNA microarray to profile brain transcript expression in a model species, the rainbow trout, which forms tractable linear hierarchies. Dominant, subdominant and submissive individuals had distinctive transcript profiles with 110 gene probes identified using conservative statistical analyses. By removing the dominant, we characterised the changes in transcript expression in sub-dominant individuals that became dominant demonstrating that the molecular transition occurred within 48 hours. A strong, novel candidate gene, ependymin, which was highly expressed in both the transcript and protein in subdominants relative to dominants, was tested further. Using antibody injection to inactivate ependymin in pairs of dominant and subdominant zebrafish, the subdominant fish exhibited a substantial increase in aggression in parallel with an enhanced competitive ability. This is the first study to characterise the molecular signatures of dominance status within groups and the first to implicate ependymin in control of aggressive behaviour. It also provides evidence for indirect genetic effect models in which genotype/phenotype of an individual is influenced by conspecific interactions within a group. The variation in the molecular profile of each individual within a group may offer a new explanation of intraspecific variation in gene expression within undefined groups of animals and provides new candidates for empirical study

A predictive model for the early identification of patients at risk for a prolonged intensive care unit length of stay

<p>Abstract</p> <p>Background</p> <p>Patients with a prolonged intensive care unit (ICU) length of stay account for a disproportionate amount of resource use. Early identification of patients at risk for a prolonged length of stay can lead to quality enhancements that reduce ICU stay. This study developed and validated a model that identifies patients at risk for a prolonged ICU stay.</p> <p>Methods</p> <p>We performed a retrospective cohort study of 343,555 admissions to 83 ICUs in 31 U.S. hospitals from 2002-2007. We examined the distribution of ICU length of stay to identify a threshold where clinicians might be concerned about a prolonged stay; this resulted in choosing a 5-day cut-point. From patients remaining in the ICU on day 5 we developed a multivariable regression model that predicted remaining ICU stay. Predictor variables included information gathered at admission, day 1, and ICU day 5. Data from 12,640 admissions during 2002-2005 were used to develop the model, and the remaining 12,904 admissions to internally validate the model. Finally, we used data on 11,903 admissions during 2006-2007 to externally validate the model.</p> <p>Results</p> <p>The variables that had the greatest impact on remaining ICU length of stay were those measured on day 5, not at admission or during day 1. Mechanical ventilation, PaO₂: FiO₂ratio, other physiologic components, and sedation on day 5 accounted for 81.6% of the variation in predicted remaining ICU stay. In the external validation set observed ICU stay was 11.99 days and predicted total ICU stay (5 days + day 5 predicted remaining stay) was 11.62 days, a difference of 8.7 hours. For the same patients, the difference between mean observed and mean predicted ICU stay using the APACHE day 1 model was 149.3 hours. The new model's r²was 20.2% across individuals and 44.3% across units.</p> <p>Conclusions</p> <p>A model that uses patient data from ICU days 1 and 5 accurately predicts a prolonged ICU stay. These predictions are more accurate than those based on ICU day 1 data alone. The model can be used to benchmark ICU performance and to alert physicians to explore care alternatives aimed at reducing ICU stay.</p

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP