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Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR) = 1.62, P = 3.9 × 10−8) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR = 1.15, P = 3.9 × 10−4; discovery and replication combined OR = 1.21, P = 4.7 × 10−8). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke.

Evidence that activating mutations of the KRAS oncogene abolish the response to anti-epidermal growth factor receptor therapy has revolutionized the treatment of advanced colorectal cancer. This has resulted in the urgent demand for KRAS mutation testing in the clinical setting to aid choice of therapy. The aim of this study was to evaluate six different KRAS mutation detection methodologies on two series of primary colorectal cancer samples. Two series of 80 frozen and 74 formalin-fixed paraffin-embedded tissue samples were sourced and DNA was extracted at a central site before distribution to seven different testing sites. KRAS mutations in codons 12 and 13 were assessed by using single strand conformation polymorphism analysis, pyrosequencing, high resolution melting analysis, dideoxy sequencing, or the commercially available TIB Molbiol (Berlin, Germany) or DxS Diagnostic Innovations (Manchester, UK) kits. In frozen tissue samples, concordance in KRAS status (defined as consensus in at least five assays) was observed in 66/80 (83%) cases. In paraffin tissue, concordance was 46/74 (63%) if all assays were considered or 71/74 (96%) using the five best performing assays. These results demonstrate that a variety of detection methodologies are suitable and provide comparable results for KRAS mutation analysis of clinical

Every year, acute lymphoblastic leukaemia (ALL) affects about 400 children aged o15 years in France,

In general, the observed modest effect sizes of the significant variants suggest many genes of small influence play a role in exceptional longevity, which is consistent with results for other polygenic traits. Our results also suggest that genes related to cardiovascular health may be implicated in exceptional longevity. Future studies should examine the roles of gender and ethnicity and carefully consider study design, including the selection of appropriate controls.

BackgroundElectronic health (eHealth) literacy is needed to effectively engage with Web-based health resources. The 8-item eHealth literacy scale (eHEALS) is a commonly used self-report measure of eHealth literacy. Accumulated evidence has suggested that the eHEALS is unidimensional. However, a recent study by Sudbury-Riley and colleagues suggested that a theoretically-informed three-factor model fit better than a one-factor model. The 3 factors identified were awareness (2 items), skills (3 items), and evaluate (3 items). It is important to determine whether these findings can be replicated in other populations.ObjectiveThe aim of this cross-sectional study was to verify the three-factor eHEALS structure among magnetic resonance imaging (MRI) and computed tomography (CT) medical imaging outpatients.MethodsMRI and CT outpatients were recruited consecutively in the waiting room of one major public hospital. Participants self-completed a touchscreen computer survey, assessing their sociodemographic, scan, and internet use characteristics. The eHEALS was administered to internet users, and the three-factor structure was tested using structural equation modeling.ResultsOf 405 invited patients, 87.4% (354/405) were interested in participating in the study, and of these, 75.7% (268/354) were eligible. Of the eligible participants, 95.5% (256/268) completed all eHEALS items. Factor loadings were 0.80 to 0.94 and statistically significant (P<.001). All reliability measures were acceptable (indicator reliability: awareness=.71-.89, skills=.78-.80, evaluate=.64-.79; composite reliability: awareness=.89, skills=.92, evaluate=.89; variance extracted estimates: awareness=.80, skills=.79, evaluate=.72). Two out of three goodness-of-fit indices were adequate (standardized root mean square residual (SRMR)=.038; comparative fit index (CFI)=.944; root mean square error of approximation (RMSEA)=.156). Item 3 was removed because of its significant correlation with item 2 (Lagrange multiplier [LM] estimate 104.02; P<.001) and high loading on 2 factors (LM estimate 91.11; P<.001). All 3 indices of the resulting 7-item model indicated goodness of fit (χ211=11.3; SRMR=.013; CFI=.999; RMSEA=.011).ConclusionsThe three-factor eHEALS structure was supported in this sample of MRI and CT medical imaging outpatients. Although further factorial validation studies are needed, these 3 scale factors may be used to identify individuals who could benefit from interventions to improve eHealth literacy awareness, skill, and evaluation competencies.

Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (Pcombined=3.32 × 10−15, OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a cis-eQTL for CDKN2B, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating CDKN2B expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining CDKN2A exon 3 usage (P=0.01). These findings provide new insights into the critical role of the CDKN2 locus in BCP-ALL aetiology.

BackgroundRecently the dementia field has shifted focus away from the early diagnosis debate in favour of ‘timely’ diagnosis. ‘Timely’ diagnosis disclosure takes into consideration the preferences and unique circumstances of the individual. Determining when diagnosis disclosure is ‘timely’ may be particularly complex if there are differing views between the individual, their family, and their health care providers regarding disclosure. This study explores the preferences of consumers regarding when a diagnosis of dementia should be communicated.MethodsA cross-sectional survey was conducted with English-speaking adults attending outpatient clinics at an Australian hospital. Participants were recruited by a research assistant in the clinic waiting room and invited to complete the survey on a web-connected iPad. The survey included questions examining socio-demographics and experience with dementia. Two scenarios were used to explore preferences for timing of diagnosis disclosure.ResultsOf 446 participants, 92% preferred a diagnosis of dementia to be disclosed as soon as possible. Preferences were not associated with socio-demographics or previous dementia experience. Most participants also preferred disclosure to occur as soon as possible if their spouse or partner was diagnosed with dementia (88%). There was strong correlation between preferences for self and preferences for spouse (0.91).ConclusionsThese findings provide guidance to health care providers about preferences for disclosure of a dementia diagnosis, and may help to overcome potential barriers to timely diagnosis. As the prevalence of dementia increases, consumers’ preference for diagnosis to occur as soon as possible has important implications for the health system.Electronic supplementary materialThe online version of this article (10.1186/s12913-018-3409-y) contains supplementary material, which is available to authorized users.