Development and diagnostic validation of the Brisbane Evidence-Based Language Test

Purpose: To describe the development and determine the diagnostic accuracy of the Brisbane Evidence-Based Language Test in detecting aphasia. Methods: Consecutive acute stroke admissions (n = 100; mean = 66.49y) participated in a single (assessor) blinded cross-sectional study. Index assessment was the ∼45 min Brisbane Evidence-Based Language Test. The Brisbane Evidence-Based Language Test is further divided into four 15–25 min Short Tests: two Foundation Tests (severe impairment), Standard (moderate) and High Level Test (mild). Independent reference standard included the Language Screening Test, Aphasia Screening Test, Comprehensive Aphasia Test and/or Measure for Cognitive-Linguistic Abilities, treating team diagnosis and aphasia referral post-ward discharge. Results: Brisbane Evidence-Based Language Test cut-off score of ≤ 157 demonstrated 80.8% (LR+ =10.9) sensitivity and 92.6% (LR− =0.21) specificity. All Short Tests reported specificities of ≥ 92.6%. Foundation Tests I (cut-off ≤ 61) and II (cut-off ≤ 51) reported lower sensitivity (≥ 57.5%) given their focus on severe conditions. The Standard (cut-off ≤ 90) and High Level Test (cut-off ≤ 78) reported sensitivities of ≥ 72.6%. Conclusion: The Brisbane Evidence-Based Language Test is a sensitive assessment of aphasia. Diagnostically, the High Level Test recorded the highest psychometric capabilities of the Short Tests, equivalent to the full Brisbane Evidence-Based Language Test. The test is available for download from brisbanetest.org. Implications for rehabilitation: Aphasia is a debilitating condition and accurate identification of language disorders is important in healthcare. Language assessment is complex and the accuracy of assessment procedures is dependent upon a variety of factors. The Brisbane Evidence-Based Language Test is a new evidence-based language test specifically designed to adapt to varying patient need, clinical contexts and co-occurring conditions. In this cross-sectional validation study, the Brisbane Evidence-Based Language Test was found to be a sensitive measure for identifying aphasia in stroke

Medical students\u27 knowledge of HPV, HPV vaccine, and HPV-associated head and neck cancer

On the basis of their training, medical students are considered the best case scenario among university students in knowledge of the human papillomavirus (HPV). We evaluated differences in knowledge of HPV, HPV vaccine, and head and neck cancer (HNC) among medical students. A previously validated questionnaire was completed by 247 medical students at a Midwestern university. Outcomes of interest were knowledge score for HPV and HPV vaccine, and HNC, derived from combining questionnaire items to form HPV knowledge and HNC scores, and analyzed using multivariate linear regression. Mean scores for HPV knowledge were 19.4 out of 26, and 7.2 out of 12 for HNC knowledge. In the final multivariate linear regression model, sex, race, and year of study were independently associated with HPV and HPV vaccine knowledge. Males had significantly lower HPV vaccine knowledge than females (β = -1.53; 95% CI: -2.53, -0.52), as did nonwhite students (β = -1.05; 95% CI: -2.07, -0.03). There was a gradient in HPV vaccine knowledge based on the year of study, highest among fourth year students (β = 6.75; 95% CI: 5.17, 8.33). Results were similar for factors associated with HNC knowledge, except for sex. HNC knowledge similarly increased based on year of study, highest for fourth year students (β = 2.50; 95% CI: 1.72, 3.29). Among medical students, gaps remain in knowledge of HPV, HPV vaccine, and HPV-linked HNC. Male medical students have significantly lower knowledge of HPV. This highlights the need to increase medical student knowledge of HPV and HPV-linked HNC

Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum

As nonreplicating tubercle bacilli are tolerant to the cidal action of antibiotics and resistant to multiple stresses, identification of this persister-like population of tubercle bacilli in sputum presents exciting and tractable new opportunities to investigate both responses to chemotherapy and the transmission of tuberculosis

Middleborns disadvantaged? testing birth-order effects on fitness in pre-industrial finns

Parental investment is a limited resource for which offspring compete in order to increase their own survival and reproductive success. However, parents might be selected to influence the outcome of sibling competition through differential investment. While evidence for this is widespread in egg-laying species, whether or not this may also be the case in viviparous species is more difficult to determine. We use pre-industrial Finns as our model system and an equal investment model as our null hypothesis, which predicts that (all else being equal) middleborns should be disadvantaged through competition. We found no overall evidence to suggest that middleborns in a family are disadvantaged in terms of their survival, age at first reproduction or lifetime reproductive success. However, when considering birth-order only among same-sexed siblings, first-, middle-and lastborn sons significantly differed in the number of offspring they were able to rear to adulthood, although there was no similar effect among females. Middleborn sons appeared to produce significantly less offspring than first-or lastborn sons, but they did not significantly differ from lastborn sons in the number of offspring reared to adulthood. Our results thus show that taking sex differences into account is important when modelling birth-order effects. We found clear evidence of firstborn sons being advantaged over other sons in the family, and over firstborn daughters. Therefore, our results suggest that parents invest differentially in their offspring in order to both preferentially favour particular offspring or reduce offspring inequalities arising from sibling competition

Social inequalities in mental disorders and substance misuse in young adults:a birth cohort study in Southern Brazil

Purpose To investigate the association between mental disorders and substance misuse at 30 years of age with gender, socioeconomic position at birth, and family income trajectories. Methods The 1982 Pelotas Birth Cohort was used; all 5914 children born alive at hospital were originally enrolled (99.2% of all city births). In 2012, 3701 subjects were located and interviewed (68% retention rate). Mental disorders and substance misuse were assessed, and their prevalence analysed according to gender, socioeconomic status at birth, and four different income trajectories: always poor, never poor, poor at birth/non-poor at age 30, and non-poor at birth/poor at age 30. Results While women presented higher prevalence of mental disorders, substance misuse was much more frequent among men. Individuals in the lowest income quintile at birth presented 2–5 times more mental disorders and substance misuse than those in the highest quintile. Young adults who were always poor or were not poor at birth but were poor at 30 years of age had a higher prevalence of mental disorders than the other groups. Conclusions The high rates of mental disorders and lifetime suicide attempts in young adults, especially those who were always poor or became poor after childhood, suggest that recent socioeconomic-related stressful situations may have a higher impact on the current mental health than events earlier in life. However, we could not identify at what specific ages socioeconomic changes were more important

Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent

Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter‐individual variability in associations between body weight and dairy consumption. Methods and results: A genome‐wide interaction study to discover genetic variants that account for variation in BMI in the context of low‐fat, high‐fat and total dairy intake in cross‐sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta‐analyzed. Twenty‐six genetic variants reached the selected significance threshold (p‐interaction \u3c10−7), and six independent variants (LINC01512‐rs7751666, PALM2/AKAP2‐rs914359, ACTA2‐rs1388, PPP1R12A‐rs7961195, LINC00333‐rs9635058, AC098847.1‐rs1791355) were evaluated meta‐analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3’ of LINC00333) was replicated (p‐interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p‐interaction = 7.36 × 10−8) such that each serving of low‐fat dairy was associated with 0.225 kg m−2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2‐rs1388) approached interaction replication significance for low‐fat dairy exposure. Conclusion: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight

Transethnic insight into the genetics of glycaemic traits: fine-mapping results from the Population Architecture using Genomics and Epidemiology (PAGE) consortium

AIMS/HYPOTHESIS: Elevated levels of fasting glucose and fasting insulin in non-diabetic individuals are markers of dysregulation of glucose metabolism and are strong risk factors for type 2 diabetes. Genome-wide association studies have discovered over 50 SNPs associated with these traits. Most of these loci were discovered in European populations and have not been tested in a well-powered multi-ethnic study. We hypothesised that a large, ancestrally diverse, fine-mapping genetic study of glycaemic traits would identify novel and population-specific associations that were previously undetectable by European-centric studies. METHODS: A multiethnic study of up to 26,760 unrelated individuals without diabetes, of predominantly Hispanic/Latino and African ancestries, were genotyped using the Metabochip. Transethnic meta-analysis of racial/ethnic-specific linear regression analyses were performed for fasting glucose and fasting insulin. We attempted to replicate 39 fasting glucose and 17 fasting insulin loci. Genetic fine-mapping was performed through sequential conditional analyses in 15 regions that included both the initially reported SNP association(s) and denser coverage of SNP markers. In addition, Metabochip-wide analyses were performed to discover novel fasting glucose and fasting insulin loci. The most significant SNP associations were further examined using bioinformatic functional annotation. RESULTS: Previously reported SNP associations were significantly replicated (p ≤ 0.05) in 31/39 fasting glucose loci and 14/17 fasting insulin loci. Eleven glycaemic trait loci were refined to a smaller list of potentially causal variants through transethnic meta-analysis. Stepwise conditional analysis identified two loci with independent secondary signals (G6PC2-rs477224 and GCK-rs2908290), which had not previously been reported. Population-specific conditional analyses identified an independent signal in G6PC2 tagged by the rare variant rs77719485 in African ancestry. Further Metabochip-wide analysis uncovered one novel fasting insulin locus at SLC17A2-rs75862513. CONCLUSIONS/INTERPRETATION: These findings suggest that while glycaemic trait loci often have generalisable effects across the studied populations, transethnic genetic studies help to prioritise likely functional SNPs, identify novel associations that may be population-specific and in turn have the potential to influence screening efforts or therapeutic discoveries. DATA AVAILABILITY: The summary statistics from each of the ancestry-specific and transethnic (combined ancestry) results can be found under the PAGE study on dbGaP here: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000356.v1.p1

Meta-analysis across Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium provides evidence for an association of serum vitamin D with pulmonary function

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (SD 29) nmol/l for EA and 49 (SD 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1.1 ml in EA (95 % CI 0.9, 1.3; P< 0.0001) and 1.8 ml (95 % CI 1.1, 2.5; P< 0.0001) in AA (P-race (difference) = 0.06), and forced vital capacity (FVC) was higher by 1.3 ml in EA (95 % CI 1.0, 1.6; P <0.0001) and 1.5 ml (95 % CI 0.8, 2.3; P= 0.0001) in AA (P-race difference = 0.56). Among EA, the 25(OH)D-FVC association was stronger in smokers: per 1 nmol/l higher 25(OH) D, FVC was higher by 1.7 ml (95 % CI 1.1, 2.3) for current smokers and 1.7 ml (95 % CI 1.2, 2.1) for former smokers, compared with 0.8 ml (95 % CI 0.4, 1.2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations

Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10-pulmonary function association

Rationale: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health. Objective: To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility. Methods: Associations of n-3 PUFA biomarkers (a-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV1, FVC, and FEV1/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N=16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N=11,962) and replicated in one cohort (N=1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNPassociations and their interactions with n-3PUFAs. Results: DPA and DHA were positively associated with FEV1 and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P-2df = 9.4 x 10(-9) across discovery and replication cohorts). The rs11693320-A allele (frequency, similar to 80%) was associated with lower FVC (P-SNP = 2.1 x 10(-9); beta(SNP) = 2161.0 ml), and the association was attenuated by higher DHA levels (P-SNPxDHA interaction = 2.1x10(-7); beta(SNPxDHA interaction) = 36.2 ml). Conclusions: We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction