Research around practice partnerships: An example of building partnerships to address overweight and obesity in children

Prevention and management of childhood overweight and obesity is a health priority for governments and communities throughout the developed world. A conceptual model, Research around Practice in Childhood Obesity (RAPICO), has been developed to guide capacity building in a coordinated 'bench to fieldwork' initiative to address this public health problem. Translation of research findings into sustainable responses with optimal fit requires consideration of context-specific relevance, cost-effectiveness, feasibility and levels of available support. The RAPICO model uses program theory to describe a framework for progressing practitionercommunityresearch partnerships to address low, medium and high levels of risk for childhood overweight and obesity within community settings. A case study describing the development of a logic model to inform risk-linked responses to childhood overweight and obesity is presented for the Ipswich community in south-east Queensland.

Burden attributable to child maltreatment in Australia

Child maltreatment is a complex phenomenon, with four main types (childhood sexual abuse, physical abuse, emotional abuse, and neglect) highly interrelated. All types of maltreatment have been linked to adverse health consequences and exposure to multiple forms of maltreatment increases risk. In Australia to date, only burden attributable to childhood sexual abuse has been estimated. This study synthesized the national evidence and quantified the burden attributable to the four main types of child maltreatment. Meta-analyses, based on quality-effects models, generated pooled prevalence estimates for each maltreatment type. Exposure to child maltreatment was examined as a risk factor for depressive disorders, anxiety disorders and intentional self-harm using counterfactual estimation and comparative risk assessment methods. Adjustments were made for co-occurrence of multiple forms of child maltreatment. Overall, an estimated 23.5% of self-harm, 20.9% of anxiety disorders and 15.7% of depressive disorders burden in males; and 33.0% of self-harm, 30.6% of anxiety disorders and 22.8% of depressive disorders burden in females was attributable to child maltreatment. Child maltreatment was estimated to cause 1.4% (95% uncertainty interval 0.4–2.3%) of all disability-adjusted life years (DALYs) in males, and 2.4% (0.7–4.1%) of all DALYs in females in Australia in 2010. Child maltreatment contributes to a substantial proportion of burden from depressive and anxiety disorders and intentional self-harm in Australia. This study demonstrates the importance of including all forms of child maltreatment as risk factors in future burden of disease studies.

The genetics of osteoporosis: Future diagnostic possibilities

The risk of developing osteoporosis is determined by the interaction of several mostly unknown genes and environmental factors. Genetic studies in osteoporosis have largely focussed on association studies of a small number of candidate genes, with few linkage studies performed, and large areas of the genome remaining unexplored. Identifying the genes involved in osteoporosis would be a major advance in our understanding of the causation of the disease, and lead to advances in diagnosis, risk prediction, and potentially preventive and therapeutic measures.

Simulating the dissipation of two herbicides using micro paddy lysimeters

A set of packed micro paddy lysimeters, placed in a greenhouse, was used to simulate the dissipation of two herbicides, simetryn and thiobencarb, in a controlled environment. Data from a field monitoring study in 2003, including the soil condition and water balances, were used in the simulation. The herbicides were applied and monitored over a period of 21 d. The water balances under two water management scenarios, intermittent irrigation management (AI) and continuous irrigation management (CI), were simulated. In the AI scenario, the pattern of herbicide dissipation in the surface water of the field were simulated, following the first-order kinetics. In the CI scenario, similarity was observed in most lysimeter and field concentrations, but there were differences in some data points. Dissipation curves of both herbicides in the surface water of the two simulated scenarios were not significantly different (P > 0.05) from the field data except for intercept of the thiobencarb curve in the CI scenario. The distribution of simetryn and thiobencarb in the soil profile after simulation were also similar to the field data. The highest concentrations of both herbicides were found on the topsoil layer at 0-2.5 cm depth. Only a small amount of herbicides moved down to the deeper soil layers. Micro paddy lysimeters are thus a good alternative for the dissipation study of pesticides in the paddy environment.

Prediction of the fate of oxytetracycline and oxolinic acid in a fish pond using simulation model: A preliminary study

The fate of two popular antibiotics, oxytetracycline and oxolinic acid, in a fish pond were simulated using a computational model. The VDC model, which is designed based on a model for predicting pesticide fate and transport in paddy fields, was modified to take into account the differences between the pond and the paddies as well as those between the fish and the rice plant behaviors. The pond conditions were set following the typical practice in South East Asia aquaculture. The two antibiotics were administered to the animal in the pond through medicated feed during a period of 5 days as in actual practice. Concentrations of oxytetracycline in pond water were higher than those of oxolinic acid at the beginning of the simulation. Dissipation rate of oxytetracycline is also higher as it is more readily available for degradation in the water. For the long term, oxolinic acid was present at higher concentration than oxytetracycline in pond water as well as pond sediment. The simulated results were expected to be conservative and can be useful for the lower tier assessment of exposure risk of veterinary medicine in aquaculture industry but more data are needed for the complete validation of the model.

Genetic determinants of heel bone properties: Genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n 5 14 260), velocity of sound (VOS; n 5 15 514) and BMD (n 5 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n 5 11 452) and new genotyping in 15 cohorts (de novo n 5 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 3 108) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 3 1014). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 3 106 also had the expected direction of association with any fracture (P < 0.05), including threeSNPswithP < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, thisGWAstudy reveals the effect of several genescommon to central DXA-derivedBMDand heel ultrasound/DXAmeasures and points to anewgenetic locus with potential implications for better understanding of osteoporosis pathophysiology.

Meta-analysis of genome-wide studies identifies MEF2C SNPs associated with bone mineral density at forearm

Background Forearm fractures affect 1.7 million individuals worldwide each year and most occur earlier in life than hip fractures. While the heritability of forearm bone mineral density (BMD) and fracture is high, their genetic determinants are largely unknown. Aim To identify genetic variants associated with forearm BMD and forearm fractures. Methods BMD at distal radius, measured by dualenergy x-ray absorptiometry, was tested for association with common genetic variants. We conducted a metaanalysis of genome-wide association studies for BMD in 5866 subjects of European descent and then selected the variants for replication in 715 Mexican American samples. Gene-based association was carried out to supplement the single-nucleotide polymorphism (SNP) association test. We then tested the BMD-associated SNPs for association with forearm fracture in 2023 cases and 3740 controls. Results We found that five SNPs in the introns of MEF2C were associated with forearm BMD at a genome-wide significance level (p<5×10-8) in meta-analysis (lead SNP, rs11951031[T] -0.20 SDs per allele, p=9.01×10-9). The gene-based association test suggested an association between MEF2C and forearm BMD ( p=0.003). The association between MEF2C variants and risk of fracture did not achieve statistical significance (SNP rs12521522[A]: OR=1.14 (95% CI 0.92 to 1.35), p=0.14). Meta-analysis also revealed two genome-wide suggestive loci at CTNNA2 and 6q23.2. Conclusions These findings demonstrate that variants at MEF2C were associated with forearm BMD, implicating this gene in the determination of BMD at forearm.

A genome-wide asociation study identifies new psoriasis susceptibility loci and an interaction betwEn HLA-C and ERAP1

To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P < 5-10 -8 and two loci with a combined P < 5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis.

Effects of PTPN22 C1858T polymorphism on susceptibility and clinical characteristics of British Caucasian rheumatoid arthritis patients

Objectives. To confirm the association of a functional single-nucleotide polymorphism (SNP), C1858T (rs2476601), in the PTPN22 gene of British Caucasian rheumatoid arthritis (RA) patients and to evaluate its influence on the RA phenotype. Methods. A total of 686 RA patients and 566 healthy volunteers, all of British Caucasian origin, were genotyped for C1858T polymorphism by PCR-restriction fragment length polymorphism assay. Data were analysed using SPSS software and the χ 2 test as applicable. Results. The PTPN22 1858T risk allele was more prevalent in the RA patients (13.9%) compared with the healthy controls (10.3%) (P = 0.008, odds ratio 1.4, 95% confidence interval 1.09-1.79). The association of the T allele was restricted to those with rheumatoid factor (RF)-positive disease (n = 524, 76.4%) (P = 0.004, odds ratio 1.5, 95% confidence interval 1.1-1.9). We found no association between PTPN22 and the presence of the HLA-DRB1 shared epitope or clinical characteristics. Conclusions. We confirmed the previously reported association of PTPN22 with RF-positive RA, which was independent from the HLA-DRB1 genotype.

Acute liver failure in children : a regional experience

Objective: To review the outcome of acute liver failure (ALF) and the effect of liver transplantation in children in Australia. Methodology: A retrospective review was conducted of all paediatric patients referred with acute liver failure between 1985 and 2000 to the Queensland Liver Transplant Service, a paediatric liver transplant centre based at the Royal Children's Hospital, Brisbane, that is one of three paediatric transplant centres in Australia. Results: Twenty-six patients were referred with ALF. Four patients did not require transplantation and recovered with medical therapy while two were excluded because of irreversible neurological changes and died. Of the 20 patients considered for transplant, three refused for social and/or religious reasons, with 17 patients listed for transplantation. One patient recovered spontaneously and one died before receiving a transplant. There were 15 transplants of which 40% (6/15) were < 2 years old. Sixty-seven per cent (10/15) survived > 1 month after transplantation. Forty per cent (6/15) survived more than 6 months after transplant. There were only four long term survivors after transplant for ALF (27%). Overall, 27% (6/22) of patients referred with ALF survived. Of the 16 patients that died, 44% (7/16) were from neurological causes. Most of these were from cerebral oedema but two patients transplanted for valproate hepatotoxicity died from neurological disease despite good graft function. Conclusions: Irreversible neurological disease remains a major cause of death in children with ALF. We recommend better patient selection and early referral and transfer to a transplant centre before onset of irreversible neurological disease to optimize outcome of children transplanted for ALF.

Susceptibility to ankylosing spondylitis

Sir The association between HLA‐B27 (B27) and ankylosing spondylitis (AS) has been known for 25 yr. Familial aggregation in AS is well established, and first‐degree relatives of AS patients have been shown to be at increased risk of developing the disease. The recurrence risk in siblings of AS patients is quite uncertain, previous studies have variously reported recurrence risks between 6.9 and 27% [1, 2]. Accurate knowledge of the sibling recurrence risk is important both to advise families of the likelihood of disease recurrence, and in genetic statistical analyses utilizing Risch's recurrence risk ratio [3]. This study was designed to determine the risk of developing AS in siblings and to determine the role of the major histocompatibility complex in familial recurrence of AS....

Flow pattern analysis in a highly stenotic patient-specific carotid bifurcation model using a turbulence model

The aim of this study is to investigate the blood flow pattern in carotid bifurcation with a high degree of luminal stenosis, combining in vivo magnetic resonance imaging (MRI) and computational fluid dynamics (CFD). A newly developed two-equation transitional model was employed to evaluate wall shear stress (WSS) distribution and pressure drop across the stenosis, which are closely related to plaque vulnerability. A patient with an 80% left carotid stenosis was imaged using high resolution MRI, from which a patient-specific geometry was reconstructed and flow boundary conditions were acquired for CFD simulation. A transitional model was implemented to investigate the flow velocity and WSS distribution in the patient-specific model. The peak time-averaged WSS value of approximately 73Pa was predicted by the transitional flow model, and the regions of high WSS occurred at the throat of the stenosis. High oscillatory shear index values up to 0.50 were present in a helical flow pattern from the outer wall of the internal carotid artery immediately after the throat. This study shows the potential suitability of a transitional turbulent flow model in capturing the flow phenomena in severely stenosed carotid arteries using patient-specific MRI data and provides the basis for further investigation of the links between haemodynamic variables and plaque vulnerability. It may be useful in the future for risk assessment of patients with carotid disease.

Effect of inflow and outflow angles on the computational hemodynamics in abdominal aortic aneurysm

To help with the clinical screening and diagnosis of abdominal aortic aneurysm (AAA), we evaluated the effect of inflow angle (IA) and outflow bifurcation angle (BA) on the distribution of blood flow and wall shear stress (WSS) in an idealized AAA model. A 2D incompressible Newtonian flow is assumed and the computational simulation is performed using finite volume method. The results showed that the largest WSS often located at the proximal and the distal end of the AAA. An increase in IA resulted in an increase in maximum WSS. We also found that WSS was maximal when BA was 90°. IA and BA are two important geometrical factors, they may help with AAA risk assessment along with the commonly used AAA diameter.

Fatigue crack propagation analysis of plaque rupture

Rupture of atheromatous plaque is the major cause of stroke or heart attack. Considering that the cardiovascular system is a classic fatigue environment, plaque rupture was treated as a chronic fatigue crack growth process in this study. Fracture mechanics theory was introduced to describe the stress status at the crack tip and Paris' law was used to calculate the crack growth rate. The effect of anatomical variation of an idealized plaque cross-section model was investigated. The crack initiation was considered to be either at the maximum circumferential stress location or at any other possible locations around the lumen. Although the crack automatically initialized at the maximum circumferential stress location usually propagated faster than others, it was not necessarily the most critical location where the fatigue life reached its minimum. We found that the fatigue life was minimum for cracks initialized in the following three regions: the midcap zone, the shoulder zone, and the backside zone. The anatomical variation has a significant influence on the fatigue life. Either a decrease in cap thickness or an increase in lipid pool size resulted in a significant decrease in fatigue life. Comparing to the previously used stress analysis, this fatigue model provides some possible explanations of plaque rupture at a low stress level in a pulsatile cardiovascular environment, and the method proposed here may be useful for further investigation of the mechanism of plaque rupture based on in vivo patient data.