Value of a national burden-of-disease study: a comparison of estimates between the Australian Burden of Disease Study 2015 and the Global Burden of Disease Study 2017.

BACKGROUND: Estimates of burden of disease are important for monitoring population health, informing policy and service planning. Burden estimates for the same population can be reported differently by national studies [e.g. the Australian Burden of Disease Study (ABDS) and the Global Burden of Disease Study (GBDS)]. METHODS: Australian ABDS 2015 and GBDS 2017 burden estimates and methods for 2015 were compared. Years of life lost (YLL), years lived with disability (YLD) and disability-adjusted life years (DALY) measures were compared for overall burden and 'top 50' causes. Disease-category definitions (based on ICD-10), redistribution algorithms, data sources, disability weights, modelling methods and assumptions were reviewed. RESULTS: GBDS 2017 estimated higher totals than ABDS 2015 for YLL, YLD and DALY for Australia. YLL differences were mainly driven by differences in the allocation of deaths to disease categories and the redistribution of implausible causes of death. For YLD, the main drivers were data sources, severity distributions and modelling strategies. Most top-50 diseases for DALY had a similar YLL:YLD composition reported. CONCLUSIONS: Differences in the ABDS and GBDS estimates reflect the different purposes of local and international studies and differences in data and modelling strategies. The GBDS uses all available evidence and is useful for international comparisons. National studies such as the ABDS have the flexibility to meet local needs and often the advantage of access to unpublished data. It is important that all data sources, inputs and models be assessed for quality and appropriateness. As studies evolve, differences should be accounted for through increased transparency of data and methods.

Technical Study of Automated High-Throughput High-Sensitive Ceruloplasmin Assay on Dried Blood Spots-Reinstate the Potential Use for Newborn Screening of Wilson Disease.

In this study, we modified a fully automatic immunoassay on ceruloplasmin concentration on dried blood spots (DBS) to increase its analytical sensitivity in order to accurately differentiate newborns from true Wilson disease (WD) patients. Modifications to the assay parameters of the Roche/Hitachi Cobas c systems immunoturbidimetric assay are adjusted to lower the limit of quantitation to 0.60 mg/L from 30 mg/L. This enables sensitive measurement of ceruloplasmin in eluent after DBS extraction. In addition, reference intervals and receiver operating characteristic curve analysis for diagnostic cut-off were established using DBS of neonates and WD adult patients. After DBS whole blood calibration, the 95th percentile of the reference interval for newborns was 86-229 mg/L. The cut-off value of 54 mg/L was found to be the most optimal point for differentiating true adult WD from newborn controls. This test shows a high area under curve of 1.000 with 100% sensitivity and specificity in differentiating normal newborns from WD adult samples. However, the results should be further validated with true newborn WD patient samples together with the consideration of other factors that can also lead to low ceruloplasmin levels. This test shows application potential in newborn screening for WD, which can save lives through early identification and timely treatment.

A signaling network for patterning of neuronal connectivity in the Drosophila brain.

The precise number and pattern of axonal connections generated during brain development regulates animal behavior. Therefore, understanding how developmental signals interact to regulate axonal extension and retraction to achieve precise neuronal connectivity is a fundamental goal of neurobiology. We investigated this question in the developing adult brain of Drosophila and find that it is regulated by crosstalk between Wnt, fibroblast growth factor (FGF) receptor, and Jun N-terminal kinase (JNK) signaling, but independent of neuronal activity. The Rac1 GTPase integrates a Wnt-Frizzled-Disheveled axon-stabilizing signal and a Branchless (FGF)-Breathless (FGF receptor) axon-retracting signal to modulate JNK activity. JNK activity is necessary and sufficient for axon extension, whereas the antagonistic Wnt and FGF signals act to balance the extension and retraction required for the generation of the precise wiring pattern.

Medical disorders of suicides in Australia: analysis using a multiple-cause-of-death approach.

The impaired health of a person who has committed suicide is often suggested among the proximate causes of suicidal behaviour. The introduction in 1997 of multiple-cause-of-death coding by the Australian Bureau of Statistics provided an opportunity to examine health impairments recorded on the death certificates of suicides. Data for the quinquennium 1997-2001 revealed a high prevalence of mental and behavioural disorders, in particular among women and among young and adolescent suicides. Comparison of multiple causes of death attributed to those who died in accidents with those recorded as suicides revealed that of the chronic and terminal illnesses, HIV and cancer were probably the conditions likely to trigger suicidal action.

The ICF as a framework for national data: the introduction of ICF into Australian data dictionaries.

PURPOSE: A country's data may influence and inform its policy and services, if suitably designed. This paper describes how two related and interacting activities--work on disability concepts and classification as well as the preparation of national data dictionaries--have been carried out in Australia, with this purpose. METHOD: Three key ingredients were combined. A broadly based advisory group was established to ensure the use of disability concepts that are meaningful not only to policy makers but also to the Australian community. This group advised on two 'twin' activities: participation in the revision of the key international classification for disability, and specification of data elements for a national data dictionary according to international standards. RESULTS: National data elements were developed, based on the Beta-2 draft ICIDH-2, and accepted for use in Australian national data dictionaries on a trial basis. CONCLUSION: The purpose and process have been accepted as valuable, and there is interested anticipation of new Australian standard data elements based on the ICF.

Proper connectivity of Drosophila motion detector neurons requires Atonal function in progenitor cells.

BACKGROUND: Vertebrates and invertebrates obtain visual motion information by channeling moving visual cues perceived by the retina through specific motion sensitive synaptic relays in the brain. In Drosophila, the series of synaptic relays forming the optic lobe are known as the lamina, medulla, lobula and lobula plate neuropiles. The fly's motion detection output neurons, called the T4 and T5 cells, reside in the lobula plate. Adult optic lobe neurons are derived from larval neural progenitors in two proliferating compartments known as the outer and inner proliferation centers (OPC and IPC). Important insight has been gained into molecular mechanisms involved in the development of the lamina and medulla from the OPC, though less is known about the development of the lobula and lobula plate. RESULTS: Here we show that the proneural gene Atonal is expressed in a subset of IPC progenitors that give rise to the higher order motion detection neurons, T4 and T5, of the lobula plate. We also show that Atonal does not act as a proneural gene in this context. Rather, it is required specifically in IPC neural progenitors to regulate neurite outgrowth in the neuronal progeny. CONCLUSIONS: Our findings reveal that a proneural gene is expressed in progenitors but is required for neurite development of their progeny neurons. This suggests that transcriptional programs initiated specifically in progenitors are necessary for subsequent neuronal morphogenesis.

Conditional mutagenesis in Drosophila.

Most genes function at multiple stages of metazoan development, in dividing and nondividing cells. Generating mouse conditional knock-outs (cKO), where a gene can be eliminated in a temporally and spatially controlled manner, is a valuable technique because it allows study of gene function at any stage of life. In contrast and despite the development of many other powerful genetic tools, cKO has thus far been lacking in Drosophila. We combined several recent molecular and genetic technical advances in an approach termed integrase-mediated approach for gene knock-out (IMAGO). IMAGO allows the replacement of any genomic sequence, such as a gene, with another desired sequence, including cKO alleles that can be used to create positively marked mutant cells. IMAGO should also be applicable to other genetic model organisms.