Estimating summary measures of health: a structured workbook approach

BACKGROUND: Summary measures of health that combine mortality and morbidity into a single indicator are being estimated in the Canadian context for approximately 200 diseases and conditions. To manage the large amount of data and calculations for this many diseases, we have developed a structured workbook system with easy to use tools. We expect this system will be attractive to researchers from other countries or regions of Canada who are interested in estimating the health-adjusted life years (HALYs) lost to premature mortality and year-equivalents lost to reduced functioning, as well as population attributable fractions (PAFs) associated with risk factors. This paper describes the workbook system using cancers as an example, and includes the entire system as a free, downloadable package. METHODS: The workbook system was developed in Excel and runs on a personal computer. It is a database system that stores data on population structure, mortality, incidence, distributions of cases entering a multitude of health states, durations of time spent in health states, preference scores that weight for severity, life table estimates of life expectancies, and risk factor prevalence and relative risks. The tools are Excel files with embedded macro programs. The main tool generates workbooks that estimate HALY, one per disease, by copying data from the database into a pre-defined template. Other tools summarize the HALY results across diseases for easy analysis. RESULTS: The downloadable zip file contains the database files initialized with Canadian data for cancers, the tools, templates and workbooks that estimate PAF and a user guide. The workbooks that estimate HALY are generated from the system at a rate of approximately one minute per disease. The resulting workbooks are self-contained and can be used directly to explore the details of a particular disease. Results can be discounted at different rates through simple parameter modification. CONCLUSION: The structured workbook approach offers researchers an efficient, easy to use, and easy to understand set of tools for estimating HALY and PAF summary measures for their country or region of interest

Deriving utility scores for co-morbid conditions: a test of the multiplicative model for combining individual condition scores

BACKGROUND: The co-morbidity of health conditions is becoming a significant health issue, particularly as populations age, and presents important methodological challenges for population health research. For example, the calculation of summary measures of population health (SMPH) can be compromised if co-morbidity is not taken into account. One popular co-morbidity adjustment used in SMPH computations relies on a straightforward multiplicative combination of the severity weights for the individual conditions involved. While the convenience and simplicity of the multiplicative model are attractive, its appropriateness has yet to be formally tested. The primary objective of the current study was therefore to examine the empirical evidence in support of this approach. METHODS: The present study drew on information on the prevalence of chronic conditions and a utility-based measure of health-related quality of life (HRQoL), namely the Health Utilities Index Mark 3 (HUI3), available from Cycle 1.1 of the Canadian Community Health Survey (CCHS; 2000–01). Average HUI3 scores were computed for both single and co-morbid conditions, and were also purified by statistically removing the loss of functional health due to health problems other than the chronic conditions reported. The co-morbidity rule was specified as a multiplicative combination of the purified average observed HUI3 utility scores for the individual conditions involved, with the addition of a synergy coefficient s for capturing any interaction between the conditions not explained by the product of their utilities. The fit of the model to the purified average observed utilities for the co-morbid conditions was optimized using ordinary least squares regression to estimate s. Replicability of the results was assessed by applying the method to triple co-morbidities from the CCHS cycle 1.1 database, as well as to double and triple co-morbidities from cycle 2.1 of the CCHS (2003–04). RESULTS: Model fit was optimized at s = .99 (i.e., essentially a straightforward multiplicative model). These results were closely replicated with triple co-morbidities reported on CCHS 2000–01, as well as with double and triple co-morbidities reported on CCHS 2003–04. CONCLUSION: The findings support the simple multiplicative model for computing utilities for co-morbid conditions from the utilities for the individual conditions involved. Future work using a wider variety of conditions and data sources could serve to further evaluate and refine the approach

De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits:report of 25 new individuals and review of the literature

TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands

Nat Genet

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.Comment in : Genetic differential calculus. [Nat Genet. 2015] Comment in : Scaling up phenotyping studies. [Nat Biotechnol. 2015

Focal mechanisms, stress field and crustal rheology in the North Tanzanian Divergence (East African Rift) inferred from local seismicity analysis

PosterWe deployed a temporary local seismic network in the North Tanzanian Divergence (NTD) for 6 months in 2007 (35 stations, SEISMOTANZ'07 experiment). The region is characterized by major changes in the magmatic/tectonic nature of the rift, at the place where the eastern branch of the East African Rift enters the Tanzanian craton. More than 200 earthquakes were accurately located south of Lake Manyara

How Should Iron and Titanium be Combined in Oxides to Improve Photoelectrochemical Properties?

International audienceWe discuss here for the first time how to combine iron and titanium metal ions to achieve a high photoelectrochemical activity for TiO2-based photoanodes in water splitting devices. To do so, a wide range of photoelectrode materials with tailored Ti/Fe ratio and element vicinity were synthesized by using the versatility of aqueous sol–gel chemistry in combination with a microwave-assisted crystallization process. At low ferric concentrations, single phase TiO2 anatase doped with various Fe amounts were prepared. Strikingly, at higher ferric concentrations, we observed the concomitant crystallization of two polymorphs of Fe2TiO5. The as-synthesized compounds were tested as photoelectrodes and compared with pure nanoparticles of TiO2, Fe2TiO5, and α- or γ-Fe2O3 and with corresponding nanocomposites. When TiO2 is slightly doped by Fe, the performance of this photoelectrode improves particularly in the low-bias region (<1.0 V vs reversible hydrogen electrode.) The photoanode exhibits a higher photocurrent than nanocomposite with TiO2/Fe2O3 and FeTi2O5 and more cathodic onset potential. The former can be partly explained by a lower bandgap and a hole with a longer lifetime. For the latter, we propose that the nature of the heterojunction impacts charge carrier recombination. The results presented herein not only answer whether iron and titanium should be combined in the same structure or into heterostructured systems but also on the importance of the arrangement of ions in the structure to improve the performances of the photoanode

Descriptive Epidemiology of Osteoarthritis in British Columbia, Canada

Objectives Osteoarthritis (OA) is a highly prevalent and often disabling disease. Data on the incidence of OA in the general population are limited. Our objectives were (1) to estimate OA prevalence and incidence rates by age and sex in a geographically defined population of 4 million people (British Columbia, Canada) using an administrative database and (2) to determine the effects of different administrative definitions of OA and observation (run-in) time on such estimates. Methods We used data on all visits to health professionals and hospital admissions covered by the Medical Services Plan (MSP) of British Columbia (BC) for the fiscal years 1991/1992 through 2000/2001. OA was defined based on ICD-9 diagnostic codes required for administrative purposes. Results The overall prevalence of OA in 2001 was 10.8%; 8.9% in men and 12.6% in women. Prevalence was higher in women in all age groups. By age 70-74, about one-third of men and 40% of women had OA. I ncidence rates in 2000/2001 were 11.7 per 1000 person-years in the total population, 10.0 in men and 13.4 in women. Rates increased linearly with age between 50 and 80 years of age. Both prevalence and incidence depended strongly on the definition of OA and the run-in period. Conclusion Prevalence of physician-diagnosed OA in BC was slightly lower than self-reported prevalence of arthritis in population surveys. Routinely collected administrative data could be a valuable source of information for OA surveillance but more research is needed on the validity of OA diagnosis in administrative databases.Medicine, Faculty ofPharmaceutical Sciences, Faculty ofNon UBCMedicine, Department ofPopulation and Public Health (SPPH), School ofReviewedFacult