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Purpose: International data demonstrate association between clinical trial participation and reduced cancer mortality. Adolescents and young adults (AYA) have low clinical trial enrollment rates. We established a program to understand local barriers and develop targeted solutions that lead to greater AYA clinical trial participation. Method(s): A steering committee (SC) with expertise in adult and pediatric oncology, research ethics, and consumer representation was formed. The SC mapped barriers related to AYA trial access and established working groups (WGs) around three themes. Result(s): The Regulatory Awareness WG identified a lack of understanding of processes that support protocol approval for clinical trials across the AYA age range. A guideline to raise awareness was developed. The Access WG identified challenges for young adults (18-25 years) to access a pediatric hospital to enroll in a pediatric trial. A procedure was developed to streamline applications for access. The first six applications using this procedure have been successful. The Availability WG identified lack of pediatric-Adult oncology reciprocal relationships as a barrier to awareness of open trials, and future collaboration. An AYA Craft Group Framework was established to grow relationships within tumor streams across institutions; two craft groups are now operating locally. An additional achievement was a successful request to the Therapeutic Goods Administration for Australian adoption of the Food and Drug Administration Guidance on Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. Conclusion(s): This multipronged approach to improving AYA clinical trial access has relevance for other health environments. Our knowledge products are available as an online toolkit. Copyright © Justine A. Ellis et al., 2022; Published by Mary Ann Liebert, Inc. 2022.

Purpose: International data demonstrate association between clinical trial participation and reduced cancer mortality. Adolescents and young adults (AYA) have low clinical trial enrollment rates. We established a program to understand local barriers and develop targeted solutions that lead to greater AYA clinical trial participation. Method(s): A steering committee (SC) with expertise in adult and pediatric oncology, research ethics, and consumer representation was formed. The SC mapped barriers related to AYA trial access and established working groups (WGs) around three themes. Result(s): The Regulatory Awareness WG identified a lack of understanding of processes that support protocol approval for clinical trials across the AYA age range. A guideline to raise awareness was developed. The Access WG identified challenges for young adults (18-25 years) to access a pediatric hospital to enroll in a pediatric trial. A procedure was developed to streamline applications for access. The first six applications using this procedure have been successful. The Availability WG identified lack of pediatric-adult oncology reciprocal relationships as a barrier to awareness of open trials, and future collaboration. An AYA Craft Group Framework was established to grow relationships within tumor streams across institutions; two craft groups are now operating locally. An additional achievement was a successful request to the Therapeutic Goods Administration for Australian adoption of the Food and Drug Administration Guidance on Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. Conclusion(s): This multipronged approach to improving AYA clinical trial access has relevance for other health environments. Our knowledge products are available as an online toolkit.

Contains fulltext : 201620.pdf (Publisher’s version ) (Open Access)

Background: To characterize the existing national and multi-national registries and cohort studies in juvenile idiopathic arthritis (JIA) and identify differences as well as areas of potential future collaboration. Methods: We surveyed investigators from North America, Europe, and Australia about existing JIA cohort studies and registries. We excluded cross-sectional studies. We captured information about study design, duration, location, inclusion criteria, data elements and collection methods. Results: We received survey results from 18 studies, including 11 national and 7 multi-national studies representing 37 countries in total. Study designs included inception cohorts, prevalent disease cohorts, and new treatment cohorts (several of which contribute to pharmacosurveillance activities). Despite numerous differences, the data elements collected across the studies was quite similar, with most studies collecting at least 5 of the 6 American College of Rheumatology core set variables and the data needed to calculate the 3-variable clinical juvenile disease activity score. Most studies were collecting medication initiation and discontinuation dates and were attempting to capture serious adverse events. Conclusion: There is a wide-range of large, ongoing JIA registries and cohort studies around the world. Our survey results indicate significant potential for future collaborative work using data from different studies and both combined and comparative analyses.

Contains fulltext : 161600.PDF (publisher's version ) (Open Access), The present study is the first to investigate the benefits of episodic future thinking (EFT) at encoding on prospective memory (PM) in preschool (age: M = 66.34 months, SD = 3.28) and primary school children (age: M = 88.36 months, SD = 3.12). A second aim was to examine if self-projection influences the possible effects of EFT instructions. PM was assessed using a standard PM paradigm in children with a picture-naming task as the ongoing activity in which the PM task was embedded. Further, two first- and two second-order ToM tasks were administered as indicator of children’s self-projection abilities. Forty-one preschoolers and 39 school-aged children were recruited. Half of the participants in each age group were instructed to use EFT as a strategy to encode the PM task, while the others received standard PM instructions. Results revealed a significant age effect, with school-aged children significantly outperforming preschoolers and a significant effect of encoding condition with overall better performance when receiving EFT instructions compared to the standard encoding condition. Even though the interaction between age group and encoding condition was not significant, planned comparisons revealed first evidence that compared to the younger age group, older children's PM benefitted more from EFT instructions during intention encoding. Moreover, results showed that although self-projection had a significant impact on PM performance, it did not influence the effects of EFT instructions. Overall, results indicate that children can use EFT encoding strategies to improve their PM performance once EFT abilities are sufficiently developed. Further, they provide first evidence that in addition to executive functions, which have already been shown to influence the development of PM across childhood, self-projection seems to be another key mechanism underlying this development.

Background: A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this female bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. The JIA genetic risk variant, PTPN22 rs2476601, has been reported to show female-specific association in type 1 diabetes. Objective(s): We sought to determine whether PTPN22 rs2476601 exhibits a female-specific association with JIA. Method(s): The discovery sample was drawn from the Australian CLARITY JIA biobank. rs2476601 was genotyped in 413 cases (67% female, mean age 9.1 years) and 690 healthy controls (42% female, mean age 7.1 years). We used logistic regression to assess the association of rs2476601 with JIA in the total sample (males and females). We then explored the role of sex in this association: we adjusted the regression analysis for sex, stratified by sex, and performed a genotype x sex interaction analysis. Sensitivity analyses were performed by restricting to individuals of European descent, subtypes of oligoarticular and polyarticular RF negative disease course, and exclusion of systemic JIA. We sought to replicate the sex-specific associations in an independent JIA casecontrol sample collected from the USA and Norway and held at the Children's Hospital of Philadelphia. Analyses were performed using Stata or PLINK. Result(s): The outcomes of analyses are shown in the Table. rs2476601 was associated with all JIA in both the discovery and replication samples, and the association remained when adjusted for sex. When stratified by sex, a strong association was observed for females, but not for males. There was evidence for genotype-by-sex interaction (p=0.0087). Similar patterns were observed in all sensitivity analyses. In the replication sample, we also observed association of rs2476601 with JIA in females, but not in males. Conclusion(s):We have demonstrated, in both a discovery and replication sample, that the as

Item does not contain fulltext, OBJECTIVE: To determine relevant Fc-gamma receptor (FcgammaR) polymorphisms in relation to susceptibility to SLE and LN, and to determine the functional consequences of genetic associations found. METHODS: Using multiplex ligation-dependent probe amplification, copy number regions (CNRs) and relevant known functional single nucleotide polymorphisms of FcgammaRII and FcgammaRIII were determined in a LN-enriched cohort of 266 Dutch Caucasian SLE patients and 919 healthy Caucasian controls. Expression of FcgammaRs on leukocytes was assessed using flow cytometry. RESULTS: In multivariable analysis, low copy number of CNR1 (includingFCGR3B; odds ratio (OR) 2.04; 95% CI: 1.29, 3.23),FCGR2A-131RR (OR 2.00; 95% CI: 1.33, 2.99), and the 2B.4 haplotype ofFCGR2B(OR 1.59; 95% CI: 1.13, 2.24), but notFCGR2Copen reading frame, were significantly (all P < 0.01) and independently associated with susceptibility to SLE. The 2B.4 haplotype was negatively associated with LN and led to surface expression of FcgammaRIIb on neutrophils and monocytes. CONCLUSION: This study is the first to investigate the most relevant and functional single nucleotide polymorphisms and copy number variations of FcgammaRII and FcgammaRIII polymorphisms in one study population, enabling the determination of the individual contribution of each polymorphism in multivariable analysis. Three polymorphisms were shown to be independently associated with susceptibility to SLE. The novel findings of a negative association of the 2B.4 haplotype with LN, and increased expression of FcgammaRIIb on neutrophils and monocytes as a result of this 2B.4 haplotype warrant future research in the role of these cells and FcgammaRs in the pathogenesis of SLE and LN.

Item does not contain fulltext, OBJECTIVES: Juvenile idiopathic arthritis (JIA) is considered a complex genetic autoimmune disease. We investigated the association of genetic variants previously implicated in JIA, autoimmunity and/or immunoregulation, with susceptibility to JIA. METHODS: A genetic association study was performed in 639 JIA patients and 1613 healthy controls of northwest European descent. Ninety-three single nucleotide polymorphisms (SNP) were genotyped in a candidate gene approach. Results of the entire JIA patient group (all subtypes) were compared with results obtained, alternatively, with a clinically homogeneous patient group including only oligoarticular and rheumatoid factor (RF) negative polyarticular JIA patients (n=493). Meta-analyses were performed for all SNPs that have been typed in other Caucasian JIA cohorts before. RESULTS: SNPs in or near PTPN22, VTCN1, the IL2-IL21 region, ANKRD55 and TNFA were confirmed to be associated with JIA (p<0.05), strengthening the evidence for involvement of these genes in JIA. In the majority of these replicated SNPs, effect sizes were larger when analysing a homogeneous patient cohort than when analysing all subtypes. We identified two novel associations with oligoarticular and RF-negative polyarticular JIA: CD226 rs763361 (OR 1.30, 95% CI 1.12 to 1.51, p=0.0006) and CD28 rs1980422 (OR 1.29, 95% CI 1.07 to 1.55, p=0.008). Meta-analyses including reported studies confirmed the association of both SNPs with susceptibility to JIA (OR 1.16, p=0.001 and OR 1.18, p=0.001, for rs763361 and rs1980422, respectively). CONCLUSIONS: The CD226 gene has been identified as novel association with JIA, and a SNP near CD28 as a suggestive association. Both genes are probable candidate risk factors, since they are involved in costimulation of T cells.

Background: Our understanding of the genetic factors underlying juvenile idiopathic arthritis (JIA) is growing, but remains incomplete. Recently, a number of novel genetic loci were reported to be associated with JIA at (or near) genome-wide significance in a large case-control discovery sample using the Immunochip genotyping array. However, independent replication of findings has yet to be performed. We therefore attempted to replicate these newly identified loci in the Australian CLARITY JIA case-control sample. Finding(s): Genotyping was successfully performed on a total of 404 JIA cases (mean age 6.4 years, 68% female) and 676 healthy child controls (mean age 7.1 years, 42% female) across 19 SNPs previously associated with JIA. We replicated a significant association (p < 0.05, odds ratio (OR) in a direction consistent with the previous report) for seven loci, six replicated for the first time - C5orf56-IRF1 (rs4705862), ERAP2-LNPEP (rs27290), PRR5L (rs4755450), RUNX1 (rs9979383), RUNX3 (rs4648881), and UBE2L3 (rs2266959). Conclusion(s): We have carried out the first independent replication of association for six genes implicated in JIA susceptibility. Our data significantly strengthens the evidence that these loci harbor true disease associated variants. Thus, this study makes an important contribution to the growing body of international data that is revealing the genetic risk landscape of JIA.Copyright © 2014 Chiaroni-Clarke et al.

Objective Susceptibility to juvenile idiopathic arthritis (JIA) is presumed to be determined by both genes and environment. However, the environmental factors remain largely unknown. The hygiene hypothesis suggests that exposure to siblings, as a marker of exposure to microbes in early life, may protect against the development of later immune disorders. Some prior evidence suggests this may also be true for JIA. The present study was undertaken to test this hypothesis in detail. Methods We conducted a comprehensive analysis of the role of sibling exposure in JIA risk within the Childhood Arthritis Risk Factor Identification Study JIA case-hospital control sample (302 cases and 676 controls) from Victoria, Australia. Results We found that, compared to being an only child, having any siblings was protective against JIA, with an adjusted odds ratio (OR) of 0.46 (95% confidence interval [95% CI] 0.28-0.74) (P=0.001). The protective association appeared to increase with increasing number of siblings (e.g., for >=3 siblings, adjusted OR 0.25 [95% CI 0.13-0.48], P<0.001). A protective association of siblings was also observed when we considered cumulative sibling years by age 6 (e.g., for >=3 years of exposure versus no exposure, adjusted OR 0.49 [95% CI 0.30-0.79], P=0.003). We also compared cases to a second control sample (n=341) collected from the community and weighted to represent the child population of Victoria. Data remained supportive of an association between sibling exposure and protection against JIA, particularly for exposure to younger siblings. Conclusion Increased exposure to siblings is associated with a reduced risk of disease in our sample. This suggests that increased microbial exposure in childhood may confer protection against the development of JIA.Copyright © 2015, American College of Rheumatology.

A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. PTPN22 rs2476601 is associated with JIA and numerous other autoimmune diseases, and has been reported to show female-specific association with type 1 diabetes. We performed main effect and sex-stratified association analyses to determine whether a sex-specific association exists in JIA. As expected, rs2476601 was associated with JIA in our discovery (413 cases and 690 controls) and replication (1008 cases and 9284 controls) samples. Discovery sample sex-stratified analyses demonstrated an association specifically in females (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.52-3.63, P=0.00011) but not males (OR=0.91, 95% CI=0.52-1.60, P=0.75). This was similarly observed in the replication sample. There was evidence for genotype-by-sex interaction (P interaction =0.009). The association between rs2476601 and JIA appears restricted to females, partly accounting for the predominance of females with this disease.Copyright © 2015 Macmillan Publishers Limited All rights reserved.

Personalised nutrition (PN) has the potential to reduce disease risk and optimise health and performance. Although previous research has shown good acceptance of the concept of PN in the UK, preferences regarding the delivery of a PN service (e.g. online v. face-to-face) are not fully understood. It is anticipated that the presence of a free at point of delivery healthcare system, the National Health Service (NHS), in the UK may have an impact on end-user preferences for deliverances. To determine this, supplementary analysis of qualitative data obtained from focus group discussions on PN service delivery, collected as part of the Food4Me project in the UK and Ireland, was undertaken. Irish data provided comparative analysis of a healthcare system that is not provided free of charge at the point of delivery to the entire population. Analyses were conducted using the ‘framework approach’ described by Rabiee (Focus-group interview and data analysis. Proc Nutr Soc 63, 655-660). There was a preference for services to be led by the government and delivered face-to-face, which was perceived to increase trust and transparency, and add value. Both countries associated paying for nutritional advice with increased commitment and motivation to follow guidelines. Contrary to Ireland, however, and despite the perceived benefit of paying, UK discussants still expected PN services to be delivered free of charge by the NHS. Consideration of this unique challenge of free healthcare that is embedded in the NHS culture will be crucial when introducing PN to the UK.

Item does not contain fulltext, Introduction: Neurotic psychopathology has been extensively examined as a risk factor for nicotine dependence (ND). Genetic stratification may partially explain variability in risk estimates. Genetic variants that compromise dopaminergic neurotransmission may motivate exposure to dopamine-stimulating agents, including nicotine. The 7-repeat allele of a Variable Number Tandem Repeat (VNTR) polymorphism in DRD4 (and evolutionary derivatives 5, 6, and 8 repeats; 7R+) is associated with reduced dopamine receptor function. The purpose of this study was to examine association between both smoking initiation (SI) and progression to ND by young adulthood and (a) history of neuroticism during adolescence, (b) DRD4 7R+, and (c) interaction between neuroticism and DRD4 7R+. Methods: Participants were drawn from the Victorian Adolescent Health Cohort Study, a longitudinal study of the health and well-being of young Australians across 8 waves (14–24 years). Neuroticism was measured at Waves 3 and 6 (mean 15.9 and 17.4 years). SI was defined as any smoking at any wave. ND was measured at Wave 8 (mean 24.1 years). Genotype data for the DRD4 VNTR were available for 839 participants. Results: While adolescent neuroticism was associated with SI, evidence for association with progression to ND was weak. However, there was evidence of interaction between neuroticism and DRD4 7R+: The odds of progression to ND among those with a history of neuroticism were more than 3.5-fold higher among 7R+ carriers. Conclusions: Without considering stratification by 7R+, the association between progression to ND and neuroticism would have been assumed barely significant. However, among those carrying DRD4 7R+, risk of progression was considerably intensified.