Center for Epidemiology and Biostatistics

West Melbourne, Australia

Center for Epidemiology and Biostatistics

West Melbourne, Australia
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Scurrah K.J.,Center for Epidemiology and Biostatistics | Scurrah K.J.,University of Melbourne | Lamantia A.,Center for Epidemiology and Biostatistics | Ellis J.A.,Murdoch Childrens Research Institute | And 2 more authors.
Circulation: Cardiovascular Genetics | Year: 2017

Background - Renin-angiotensin-aldosterone system genes have been inconsistently associated with blood pressure, possibly because of unrecognized influences of sex-dependent genetic effects or gene-gene interactions (epistasis). Methods and Results - We tested association of systolic blood pressure with single-nucleotide polymorphisms (SNPs) at renin (REN), angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AGTR1), and aldosterone synthase (CYP11B2), including sex-SNP or SNP-SNP interactions. Eighty-eight tagSNPs were tested in 2872 white individuals in 809 pedigrees from the Victorian Family Heart Study using variance components models. Three SNPs (rs8075924 and rs4277404 at ACE and rs12721297 at AGTR1) were individually associated with lower systolic blood pressure with significant (P<0.00076) effect sizes ≈1.7 to 2.5 mm Hg. Sex-specific associations were seen for 3 SNPs in men (rs2468523 and rs2478544 at AGT and rs11658531 at ACE) and 1 SNP in women (rs12451328 at ACE). SNP-SNP interaction was suggested (P<0.005) for 14 SNP pairs, none of which had shown individual association with systolic blood pressure. Four SNP pairs were at the same gene (2 for REN, 1 for AGT, and 1 for AGTR1). The SNP rs3097 at CYP11B2 was represented in 5 separate pairs. Conclusions - SNPs at key renin-angiotensin-aldosterone system genes associate with systolic blood pressure individually in both sexes, individually in one sex only and only when combined with another SNP. Analyses that incorporate sex-dependent and epistatic effects could reconcile past inconsistencies and account for some of the missing heritability of blood pressure and are generally relevant to SNP association studies for any phenotype. © 2017 American Heart Association, Inc.


Shelton A.L.,Monash University | Cornish K.M.,Monash University | Godler D.,Murdoch Childrens Research Institute | Bui Q.M.,Center for Epidemiology and Biostatistics | And 2 more authors.
Neurology | Year: 2017

Objective: To examine the interrelationships between fragile X mental retardation 1 (FMR1) mRNA and the FMR1 exon 1/intron 1 boundary methylation, white matter microstructure, and executive function, in women with a FMR1 premutation expansion (PM; 55-199 CGG repeats) and controls (CGG, 44). Methods: Twenty women with PM without fragile X-associated tremor/ataxia syndrome (FXTAS) and 20 control women between 22 and 54 years of age completed this study. FMR1 mRNA and methylation levels for 9 CpG sites within the FMR1 exon 1/intron 1 boundary from peripheral blood samples were analyzed. To measure white matter microstructure, diffusion-weighted imaging was used, from which fractional anisotropy (FA) and mean diffusivity (MD) values from anatomic regions within the corpus callosum and cerebellar peduncles were extracted. Executive function was assessed across a range of tasks. Results: No differences were revealed in white matter microstructure between women with PM and controls. However, we reveal that for women with PM (but not controls), higher FMR1 mRNA correlated with lower MD values within the middle cerebellar peduncle and Paced Auditory Serial Addition Test scores, higher methylation of the FMR1 exon 1/intron 1 boundary correlated with lower MD within the inferior and middle cerebellar peduncles and longer prosaccade latencies, and higher FA values within the corpus callosum and cerebellar peduncle regions corresponded to superior executive function. Conclusions: We provide evidence linking white matter microstructure to executive dysfunction and elevated FMR1 mRNA and FMR1 exon 1/intron 1 boundary methylation in women with PM without FXTAS. This suggests that the FXTAS phenotype may not be distinct but may form part of a spectrum of PM involvement. © 2017 American Academy of Neurology.


Abebe D.S.,University of Oslo | Abebe D.S.,Addis Ababa Institute of Technology | Bjune G.,University of Oslo | Ameni G.,Addis Ababa Institute of Technology | And 2 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2011

OBJECTIVES: To determine the prevalence of pulmonary tuberculosis (PTB) and associated risk factors among inmates in three major prison settings of Eastern Ethiopia. DESIGN: Between July and November, 2008, 371 prisoners with a history of cough of ≥2 weeks were screened for PTB using direct smear microscopy and culture. Data were analysed using descriptive statistics and multivariable logistic regression. RESULTS: Of 371 PTB suspects identified by active screening, 33 (8.9%) were confirmed as smear- or culture-positive PTB. Together with the 11 PTB patients already on treatment, the point prevalence of PTB was 1913 per 100 000 (95%CI 1410-2580), about seven times higher than that of the general population. Eleven newly diagnosed PTB patients were sharing a cell with known TB patients. Factors significantly associated with PTB were young age (15-44 years of age) (OR 3.73), urban residence (OR 3.59), having a cough > 4 weeks (OR 3.15), and sharing a cell with a TB patient (OR 3.39) or a prisoner with chronic cough (OR 4.5). CONCLUSIONS: The study documented a high prevalence of PTB among Ethiopian prisoners. Sociod emographic and TB management factors were identified to be underlying causes of the high transmission rate and the acquisition of new cases. Active surveillance of TB and implementing prevention and control guidelines are imperative. © 2011 The Union.


Sidebotham P.,University of Warwick | Fraser J.,University of Warwick | Fraser J.,Bristol Royal Hospital for Children | Covington T.,Review Centre | And 6 more authors.
The Lancet | Year: 2014

Many factors affect child and adolescent mortality in high-income countries. These factors can be conceptualised within four domains-intrinsic (biological and psychological) factors, the physical environment, the social environment, and service delivery. The most prominent factors are socioeconomic gradients, although the mechanisms through which they exert their eff ects are complex, affect all four domains, and are often poorly understood. Although some contributing factors are relatively fi xed-including a child's sex, age, ethnic origin, and genetics, some parental characteristics, and environmental conditions-others might be amenable to interventions that could lessen risks and help to prevent future child deaths. We give several examples of health service features that could affect child survival, along with interventions, such as changes to the physical or social environment, which could affect upstream (distal) factors.


Alwan N.,University of Leeds | Greenwood D.,Center for Epidemiology and Biostatistics | Simpson N.,University of Leeds | McArdle H.,University of Aberdeen | Cade J.,University of Leeds
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2010

Objective To examine the relationship between dietary supplement use during pregnancy and birth outcomes. Design A prospective birth cohort. Setting Leeds, UK. Sample One thousand two hundred and seventy-four pregnant women aged 18-45 years. Methods Dietary supplement intake was ascertained using three questionnaires for the first, second and third trimesters. Dietary intake was reported in a 24-hour dietary recall administered by a research midwife at 8-12 weeks of gestation. Information on delivery details and antenatal pregnancy complications was obtained from the hospital maternity records. Main outcome measures Birthweight, birth centile and preterm birth. Results Reported dietary supplement use declined from 82% of women in the first trimester of pregnancy to 22% in the second trimester and 33% in the third trimester. Folic acid was the most commonly reported supplement taken. Taking any type of daily supplement during any trimester was not significantly associated with size at birth taking into account known relevant confounders. Women taking multivitamin-mineral supplements in the third trimester were more likely to experience preterm birth (adjusted OR = 3.4, 95% CI 1.2, 9.6, P = 0.02). Conclusions Regular multivitamin-mineral supplement use during pregnancy, in a developed country setting, is not associated with size at birth. However, it appears to be associated with preterm birth if taken daily in the third trimester. The mechanism for this is unclear and our study's findings need confirming by other cohorts and/or trials in developed countries. © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.


Biffa D.,Center for Epidemiology and Biostatistics | Biffa D.,Hawassa University | Bogale A.,Tuskegee University | Skjerve E.,Center for Epidemiology and Biostatistics | Skjerve E.,Hawassa University
BMC Public Health | Year: 2010

Background. Bovine Tuberculosis (BTB) is a widespread and endemic disease of cattle in Ethiopia posing a significant threat to public health. Regular surveillance by skin test, bacteriology and molecular methods is not feasible due to lack of resource. Thus, routine abattoir (RA) inspection will continue to play a key role for national surveillance. We evaluated efficiency of RA inspection for diagnosis of Mycobacterium bovis infection and discussed its public health implications in light of a high risk of human exposure. Methods. The study was conducted in five abattoirs: Addis Ababa, Adama, Hawassa, Yabello and Melge-Wondo abattoirs. The efficiency of routine abattoir (RA) inspection was validated in comparison to detailed abattoir (DA) inspection, followed by culture and microscopy (CM) and region of difference (RD) deletion analysis. Diagnostic accuracies (with corresponding measures of statistical uncertainty) were determined by computing test property statistics (sensitivity and specificity) and likelihood estimations using web-based SISA diagnostic statistics software. Post-test probability of detecting TB infected carcasses was estimated using nomograms. Agreement between RA and DA inspections was measured using kappa statistics. The study was conducted and reported in accordance with standards for reporting of diagnostic accuracy (STARD) requirements. Both routine and detailed meat inspection protocols were performed on a subpopulation of 3322 cattle selected randomly from among 78,269 cattle slaughtered during the study period. Three hundred thirty seven carcasses identified through detailed meat inspection protocols were subjected to culture and microscopy; of the 337, a subset of 105 specimens for culture and microscopy were subjected to further molecular testing. Results. There was a substantial agreement between RA and DA inspections in Addis Ababa (Kappa = 0.7) and Melge-Wondo abattoirs (Kappa = 0.67). In Adama, Hawassa and Yabello abattoirs, the agreement was however poor (Kappa 0.2). RA inspection was able to detect only 117 of the total 3322 carcasses inspected (3.5%). The sensitivity (Sn) and specificity (Sp) of RA inspection were 28.2% (95/337) [95%CI: 23.4-33.0] and 99.3% (2963/2985) [95%CI: 99.0-99.6], respectively, when DA inspection was considered as reference test. When culture and microscopy (CM) was considered as reference test, the Sn and Sp of RA were 55.2% (58/105) [95%CI: 45.7-64.7] and 84.1% (195/232) [95%CI: 79.3-88.8]. RA inspection failed to detect 71.8% (242/337) and 44.8% (47/105) of TB infected carcasses as judged by DA inspection and CM, respectively. On the other hand, a much higher sensitivity of DA was obtained when CM and RD deletion analysis were considered as reference tests (96.3% (105/109) and 100.0% (24/24), respectively). Conclusions. The study results indicate that meat inspection protocols currently utilized in abattoirs are insufficient to detect the majority of TB lesions at the gross level. DA inspection protocols were demonstrated to improve the detection level by approximately 3-fold. The failure of current inspection techniques to detect approximately 70% of carcasses presented with grossly-visible lesions of TB at the slaughter-plants indicates the magnitude of meat-borne zoonotic TB as an on-going risk to public health. Standardization of abattoir inspection protocols (in line with international sanitary requirements), enhanced training and proficiency testing of meat inspections, and raising public awareness are recommended as essential and cost-effective interventions to improve meat inspection service in Ethiopia, with subsequent protection of consumers' health. © 2010 Biffa et al; licensee BioMed Central Ltd.


Stormoen M.,Center for Epidemiology and Biostatistics | Skjerve E.,Center for Epidemiology and Biostatistics | Aunsmo A.,Center for Epidemiology and Biostatistics | Aunsmo A.,SalMar Farming AS
Journal of Fish Diseases | Year: 2013

The aim of this study was to model sea lice levels and the effect on reproduction by a stochastic simulation model and to evaluate the uncertainty of lice estimates based upon counts. Two empirical data sets were examined to parameterize the models. An overall fit of the data to the Poisson distribution was found and thus was used as the base of the stochastic models. In the model, salmon lice reproduction is not linear with the number of adult females and at low lice loads a smaller proportion of the adult female lice will reproduce. Depending on the variance structure, it was estimated that between 40% and 60% of the adult female lice will reproduce at an abundance of 0.5 adult females per fish. Lice counts, especially when examining few fish at low lice loads, are uncertain and at a true abundance of 0.1 one may count between 0 and 5 lice when examining 10 fish. Understanding the dynamics of sea lice reproduction is a key factor in the development of sustainable control strategies. © 2012 Blackwell Publishing Ltd.


Murad M.K.,Trauma Care Foundation Iraq | Murad M.K.,University of Tromsø | Larsen S.,Center for Epidemiology and Biostatistics | Husum H.,University of Tromsø
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine | Year: 2012

Background: Blunt implementation of Western trauma system models is not feasible in low-resource communities with long prehospital transit times. The aims of the study were to evaluate to which extent a low-cost prehospital trauma system reduces trauma deaths where prehospital transit times are long, and to identify specific life support interventions that contributed to survival.Methods: In the study period from 1997 to 2006, 2,788 patients injured by land mines, war, and traffic accidents were managed by a chain-of-survival trauma system where non-graduate paramedics were the key care providers. The study was conducted with a time-period cohort design.Results: 37% of the study patients had serious injuries with Injury Severity Score ≥ 9. The mean prehospital transport time was 2.5 hours (95% CI 1.9 - 3.2). During the ten-year study period trauma mortality was reduced from 17% (95% CI 15 -19) to 4% (95% CI 3.5 - 5), survival especially improving in major trauma victims. In most patients with airway problems, in chest injured, and in patients with external hemorrhage, simple life support measures were sufficient to improve physiological severity indicators.Conclusion: In case of long prehospital transit times simple life support measures by paramedics and lay first responders reduce trauma mortality in major injuries. Delegating life-saving skills to paramedics and lay people is a key factor for efficient prehospital trauma systems in low-resource communities. © 2012 Murad et al; licensee BioMed Central Ltd.


Aasland K.E.,Laboratory Animal Unit | Skjerve E.,Center for Epidemiology and Biostatistics | Smith A.J.,Laboratory Animal Unit
Laboratory Animals | Year: 2010

A large number of methods for obtaining blood from mice have been published. In our facility, saphenous venepuncture is considered the method of choice for bleeding mice and is believed to have a number of welfare advantages when performed correctly. The aim of this study was to compare levels of haemolysis and plasma glucose in blood samples obtained by saphenous venepuncture and tail vein incision. The results indicate that saphenous venepuncture is the preferred method.


Biffa D.,Center for Epidemiology and Biostatistics | Bogale A.,Tuskegee University | Godfroid J.,Section for Arctic Veterinary Medicine | Skjerve E.,Center for Epidemiology and Biostatistics
Tropical Animal Health and Production | Year: 2012

Bovine TB is a disease of high economic and public health importance particularly in resource poor countries. Many aspects of pathogenesis of bovine TB in cattle have not been well understood. We carried out an investigation on 337 Ethiopian cattle with characteristic TB-like lesions to describe severity of pathology and factors associated with it. Severity of pathology was determined based upon gross lesion characteristics, distribution and presence/absence of viable mycobacteria. Molecular speciation of mycobacteria was performed using Gene-Probe's Accu-Probe method. Mycobacterium bovis was identified by genomic deletion analysis and spoligotyping. Data were analysed using descriptive statistics and regression model. The results showed that TB-like lesions and M. bovis were more frequently observed in lungs and respiratory lymph nodes. Mammary lesions yielded significant proportion of M. bovis upon culturing. Intestinal lesions were the second most frequently encountered pathology; upon culturing, however, the tissue specimens yielded the lowest proportion of M. bovis isolates. Sex, breed and management system were found to significantly affect TB manifestation. Female (β ± SE = 4.1 ± 1.0; P = 0.00) and exotic breed (β ± SE = 1.7 ± 0.9; P = 0.045) were at a relatively higher risk of developing severe tuberculosis. TB pathology was more severe in cattle raised under large-scale farming (β ± SE = 2.3 ± 0.5; P = 0.00). The fact that severe tuberculosis is linked to high degree of disease transmission potential warrants implementation of proper disease surveillance programs in large-scale farms. Isolation of M. bovis from mammary and muscle tissues implies a potential threat of zoonotic transmission, where raw milk and raw beef constitute a customary dietary regimen in Ethiopia. © 2011 Springer Science+Business Media B.V.

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