Common Benign Melanocytic and Non-Melanocytic Skin Tumors among the Elderly: Results of the Graz Study on Health and Aging.

BACKGROUND AND OBJECTIVES: Benign skin tumors are the most common skin findings and contribute to the major reasons for consulting a dermatologist. However, the frequency of benign skin tumors concerning different body areas and their relationship with sun-related behavior have not been sufficiently characterized. We aimed to improve knowledge about the anatomic distribution of the most frequently occurring benign skin tumors among a healthy predominant elderly population. Furthermore, we investigated associations with sun-related habits. METHODS: In total, 100 participants, 37 men, and 63 women (mean age: 67.2 years; range: 46-86 years) were enrolled in the Graz Study on Health and Aging (GSHA) cohort. Full body images were investigated for melanocytic nevi, seborrheic keratoses, hemangiomas, dermatofibromas, and lentigines. Information on the phenotypic trait, sun exposure, use of sun-protective measures, and history of sunburns was collected in a questionnaire. RESULTS: Common melanocytic nevi were the most frequently encountered skin lesions. Male sex was associated with multiple common nevi on the abdomen and the presence of atypical nevi. High sun exposure in central European latitudes during adolescence was positively associated with multiple common nevi on the total body. Multiple common nevi and atypical nevi on the back correlated with frequent use of sunscreens with SPF during young adulthood and adolescence, respectively. CONCLUSION: Our study adds new knowledge about the most frequently occurring benign skin tumors, considering all visible body areas. This research may serve as a reference basis for following epidemiological studies.

Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage.

OBJECTIVE: Observational studies point to an inverse correlation between low-density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH. METHODS: We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high-density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses. RESULTS: We identified 410, 339, 393, and 317 lipid-related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10-100 ). While one SD increase in the PRSs for total cholesterol (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.85-0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81-0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65-0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42-0.82; p = 0.002), respectively. INTERPRETATION: Genetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56-66.

Corticosteroids and Regional Variations in Thickness of the Human Cerebral Cortex across the Lifespan.

Exposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n = 21 251; 4-97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas. In all participants, cortical thickness correlated negatively with the expression of both NR3C1 and NR3C2 across 34 cortical regions. The magnitude of this correlation varied across the lifespan. From childhood through early adulthood, the profile similarity (between NR3C1/NR3C2 expression and thickness) increased with age. Conversely, both profile similarities decreased with age in late life. These variations do not reflect age-related changes in NR3C1 and NR3C2 expression, as observed in 5 databases of gene expression in the human cerebral cortex (502 donors). Based on the co-expression of NR3C1 (and NR3C2) with genes specific to neural cell types, we determine the potential involvement of microglia, astrocytes, and CA1 pyramidal cells in mediating the relationship between corticosteroid exposure and cortical thickness. Therefore, corticosteroids may influence brain structure to a variable degree throughout life.

Global and Regional Development of the Human Cerebral Cortex: Molecular Architecture and Occupational Aptitudes.

We have carried out meta-analyses of genome-wide association studies (GWAS) (n = 23 784) of the first two principal components (PCs) that group together cortical regions with shared variance in their surface area. PC1 (global) captured variations of most regions, whereas PC2 (visual) was specific to the primary and secondary visual cortices. We identified a total of 18 (PC1) and 17 (PC2) independent loci, which were replicated in another 25 746 individuals. The loci of the global PC1 included those associated previously with intracranial volume and/or general cognitive function, such as MAPT and IGF2BP1. The loci of the visual PC2 included DAAM1, a key player in the planar-cell-polarity pathway. We then tested associations with occupational aptitudes and, as predicted, found that the global PC1 was associated with General Learning Ability, and the visual PC2 was associated with the Form Perception aptitude. These results suggest that interindividual variations in global and regional development of the human cerebral cortex (and its molecular architecture) cascade-albeit in a very limited manner-to behaviors as complex as the choice of one's occupation.

RNA Expression of DNA Damage Response Genes in Muscle-Invasive Bladder Cancer: Influence on Outcome and Response to Adjuvant Cisplatin-Based Chemotherapy.

BACKGROUND: Perioperative cisplatin-based chemotherapy (CBC) can improve the outcome of patients with muscle-invasive bladder cancer (MIBC), but it is still to be defined which patients benefit. Mutations in DNA damage response genes (DDRG) can predict the response to CBC. The value of DDRG expression as a marker of CBC treatment effect remains unclear. MATERIAL AND METHODS: RNA expression of the nine key DDRG (BCL2, BRCA1, BRCA2, ERCC2, ERCC6, FOXM1, RAD50, RAD51, and RAD52) was assessed by qRT-PCR in a cohort of 61 MICB patients (median age 66 y, 48 males, 13 females) who underwent radical cystectomy in a tertiary care center. The results were validated in the The Cancer Genome Atlas (TCGA) cohort of MIBC (n = 383). Gene expression was correlated with disease-free survival (DFS) and overall survival (OS). Subgroup analyses were performed in patients who received adjuvant cisplatin-based chemotherapy (ACBC) (Mannheim n = 20 and TCGA n = 75). RESULTS: Low expression of RAD52 was associated with low DFS in both the Mannheim and the TCGA cohorts (Mannheim: p = 0.039; TCGA: p = 0.017). This was especially apparent in subgroups treated with ACBC (Mannheim: p = 0.0059; TCGA: p = 0.012). Several other genes showed an influence on DFS in the Mannheim cohort (BRCA2, ERCC2, FOXM1) where low expression was associated with poor DFS (p < 0.05 for all). This finding was not fully supported by the data in the TCGA cohort, where high expression of FOXM1 and BRCA2 correlated with poor DFS. CONCLUSION: Low expression of RAD52 correlated with decreased DFS in the Mannheim and the TCGA cohort. This effect was especially pronounced in the subset of patients who received ACBC, making it a promising indicator for response to ACBC on the level of gene expression.

Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis.

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.

Association of variants in HTRA1 and NOTCH3 with MRI-defined extremes of cerebral small vessel disease in older subjects.

We report a composite extreme phenotype design using distribution of white matter hyperintensities and brain infarcts in a population-based cohort of older persons for gene-mapping of cerebral small vessel disease. We demonstrate its application in the 3C-Dijon whole exome sequencing (WES) study (n = 1924, nWESextremes = 512), with both single variant and gene-based association tests. We used other population-based cohort studies participating in the CHARGE consortium for replication, using whole exome sequencing (nWES = 2,868, nWESextremes = 956) and genome-wide genotypes (nGW = 9924, nGWextremes = 3308). We restricted our study to candidate genes known to harbour mutations for Mendelian small vessel disease: NOTCH3, HTRA1, COL4A1, COL4A2 and TREX1. We identified significant associations of a common intronic variant in HTRA1, rs2293871 using single variant association testing (Pdiscovery = 8.21 × 10-5, Preplication = 5.25 × 10-3, Pcombined = 4.72 × 10-5) and of NOTCH3 using gene-based tests (Pdiscovery = 1.61 × 10-2, Preplication = 3.99 × 10-2, Pcombined = 5.31 × 10-3). Follow-up analysis identified significant association of rs2293871 with small vessel ischaemic stroke, and two blood expression quantitative trait loci of HTRA1 in linkage disequilibrium. Additionally, we identified two participants in the 3C-Dijon cohort (0.4%) carrying heterozygote genotypes at known pathogenic variants for familial small vessel disease within NOTCH3 and HTRA1. In conclusion, our proof-of-concept study provides strong evidence that using a novel composite MRI-derived phenotype for extremes of small vessel disease can facilitate the identification of genetic variants underlying small vessel disease, both common variants and those with rare and low frequency. The findings demonstrate shared mechanisms and a continuum between genes underlying Mendelian small vessel disease and those contributing to the common, multifactorial form of the disease.

BICD2 mutational analysis in hereditary spastic paraplegia and hereditary motor and sensory neuropathy.

INTRODUCTION: Mutations in the BICD2 gene are causative for an autosomal dominant form of spinal muscular atrophy (SMALED2). Further, BICD2 mutations have been implicated in hereditary spastic paraplegia (HSP), but only very few such patients have been described. In this report we aimed to investigate the frequency of BICD2 mutations in patients with HSP and hereditary motor and sensory neuropathy (HMSN) who were negative for the most common known genetic causes. METHODS: The cohorts comprised 171 HSP and 189 HMSN patients. Mutational analysis was performed with high-resolution melting analysis followed by Sanger sequencing. RESULTS: In both cohorts, we found no known or likely pathogenic mutations in the BICD2 gene. DISCUSSION: BICD2 mutations appear rather unlikely to cause a phenotype of HMSN and are a very rare cause of the HSP phenotype. Muscle Nerve 59:484-486, 2019.

Vitamin and bioactive compound diversity of seven fruit species from south Brazil.

BACKGROUND: The consumption of native tropical fruits represents an important source of bioactive food and vitamins for consumers. The aim of this study was to determine the composition of vitamins, bioactive compounds and the antioxidant activity of seven native fruits of the Myrtaceae family from south Brazil. RESULTS: Sample 1 of Eugenia pyriformis presented the highest value of ß-carotene (0.1021 g kg-1 ), lutein (0.0511 g kg-1 ), zeaxanthin (0.0370 g kg-1 ), and α-carotene (0.0112 g kg-1 ), of all analyzed samples. The three samples of Eugenia uniflora L presented the highest lycopene (0.1876, 0.1240 and 0.1615 g kg-1 ) and vitamin A content (0.106, 0.035 and 0.178 g kg-1 RAE) of all seven species analyzed. The cyanidin 3-glucoside was the most common anthocyanin found in fruits in the present study. Two samples of Plinia peruviana presented higher antioxidant capacity by the ABTS radical method (0.80 and 0.67 mol TEs kg-1 ) among the fruits analyzed. The samples of Campomanesia xanthocarpa analyzed stood out owing to the high content of vitamin C present (23.89, 36.83 and 35.05 g kg-1 ). The values of pantothenic acid in Plinia peruviana account for 20% of daily requirements. CONCLUSION: In conclusion, the native fruits studied can provide an appreciable amount of vitamins and bioactive compounds. © 2018 Society of Chemical Industry.

Meta-analysis of genome-wide association studies identifies 1q22 as a susceptibility locus for intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.

Gray matter heritability in family-based and population-based studies using voxel-based morphometry.

BACKGROUND: The combination of genetics and imaging has improved their understanding of the brain through studies of aggregate measures obtained from high-resolution structural imaging. Voxel-wise analyses have the potential to provide more detailed information of genetic influences on the brain. Here they report a large-scale study of the heritability of gray matter at voxel resolution (1 × 1 × 1 mm). METHODS: Validated voxel-based morphometry (VBM) protocols were applied to process magnetic resonance imaging data of 3,239 unrelated subjects from a population-based study and 491 subjects from two family-based studies. Genome-wide genetic data was used to estimate voxel-wise gray matter heritability of the unrelated subjects and pedigree-structure was used to estimate heritability in families. They subsequently associated two genetic variants, known to be linked with subcortical brain volume, with most heritable voxels to determine if this would enhance their association signals. RESULTS: Voxels significantly heritable in both estimates mapped to subcortical structures, but also voxels in the language areas of the left hemisphere were found significantly heritable. When comparing regional patterns of heritability, family-based estimates were higher than population-based estimates. However, regional consistency of the heritability measures across study designs was high (Pearson's correlation coefficient = 0.73, P = 2.6 × 10-13 ). They further show enhancement of the association signal of two previously discovered genetic loci with subcortical volume by using only the most heritable voxels. CONCLUSION: Gray matter voxel-wise heritability can be reliably estimated with different methods. Combining heritability estimates from multiple studies is feasible to construct reliable heritability maps of gray matter voxels. Hum Brain Mapp 38:2408-2423, 2017. © 2017 Wiley Periodicals, Inc.

Genetics of vascular dementia - review from the ICVD working group.

BACKGROUND: Vascular dementia is a common disorder resulting in considerable morbidity and mortality. Determining the extent to which genes play a role in disease susceptibility and their pathophysiological mechanisms could improve our understanding of vascular dementia, leading to a potential translation of this knowledge to clinical practice. DISCUSSION: In this review, we discuss what is currently known about the genetics of vascular dementia. The identification of causal genes remains limited to monogenic forms of the disease, with findings for sporadic vascular dementia being less robust. However, progress in genetic research on associated phenotypes, such as cerebral small vessel disease, Alzheimer's disease, and stroke, have the potential to inform on the genetics of vascular dementia. We conclude by providing an overview of future developments in the field and how such work could impact patients and clinicians. CONCLUSION: The genetic background of vascular dementia is well established for monogenic disorders, but remains relatively obscure for the sporadic form. More work is needed for providing robust findings that might eventually lead to clinical translation.

Genetic variants in CETP increase risk of intracerebral hemorrhage.

OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH. METHODS: We performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk. RESULTS: Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10-4 ) with no heterogeneity across studies (I2 = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL-C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10-6 ). INTERPRETATION: Genetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740.

Quantifying synchrony patterns in the EEG of Alzheimer's patients with linear and non-linear connectivity markers.

We analyzed the relation of several synchrony markers in the electroencephalogram (EEG) and Alzheimer's disease (AD) severity as measured by Mini-Mental State Examination (MMSE) scores. The study sample consisted of 79 subjects diagnosed with probable AD. All subjects were participants in the PRODEM-Austria study. Following a homogeneous protocol, the EEG was recorded both in resting state and during a cognitive task. We employed quadratic least squares regression to describe the relation between MMSE and the EEG markers. Factor analysis was used for estimating a potentially lower number of unobserved synchrony factors. These common factors were then related to MMSE scores as well. Most markers displayed an initial increase of EEG synchrony with MMSE scores from 26 to 21 or 20, and a decrease below. This effect was most prominent during the cognitive task and may be owed to cerebral compensatory mechanisms. Factor analysis provided interesting insights in the synchrony structures and the first common factors were related to MMSE scores with coefficients of determination up to 0.433. We conclude that several of the proposed EEG markers are related to AD severity for the overall sample with a wide dispersion for individual subjects. Part of these fluctuations may be owed to fluctuations and day-to-day variability associated with MMSE measurements. Our study provides a systematic analysis of EEG synchrony based on a large and homogeneous sample. The results indicate that the individual markers capture different aspects of EEG synchrony and may reflect cerebral compensatory mechanisms in the early stages of AD.

Personality Polygenes, Positive Affect, and Life Satisfaction.

Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.

Genome-wide association study of kidney function decline in individuals of European descent.

Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.

Predicting stroke through genetic risk functions: the CHARGE Risk Score Project.

BACKGROUND AND PURPOSE: Beyond the Framingham Stroke Risk Score, prediction of future stroke may improve with a genetic risk score (GRS) based on single-nucleotide polymorphisms associated with stroke and its risk factors. METHODS: The study includes 4 population-based cohorts with 2047 first incident strokes from 22,720 initially stroke-free European origin participants aged ≥55 years, who were followed for up to 20 years. GRSs were constructed with 324 single-nucleotide polymorphisms implicated in stroke and 9 risk factors. The association of the GRS to first incident stroke was tested using Cox regression; the GRS predictive properties were assessed with area under the curve statistics comparing the GRS with age and sex, Framingham Stroke Risk Score models, and reclassification statistics. These analyses were performed per cohort and in a meta-analysis of pooled data. Replication was sought in a case-control study of ischemic stroke. RESULTS: In the meta-analysis, adding the GRS to the Framingham Stroke Risk Score, age and sex model resulted in a significant improvement in discrimination (all stroke: Δjoint area under the curve=0.016, P=2.3×10(-6); ischemic stroke: Δjoint area under the curve=0.021, P=3.7×10(-7)), although the overall area under the curve remained low. In all the studies, there was a highly significantly improved net reclassification index (P<10(-4)). CONCLUSIONS: The single-nucleotide polymorphisms associated with stroke and its risk factors result only in a small improvement in prediction of future stroke compared with the classical epidemiological risk factors for stroke.

Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Previous studies suggest that genetic variation plays a substantial role in occurrence and evolution of intracerebral hemorrhage (ICH). Genetic contribution to disease can be determined by calculating heritability using family-based data, but such an approach is impractical for ICH because of lack of large pedigree-based studies. However, a novel analytic tool based on genome-wide data allows heritability estimation from unrelated subjects. We sought to apply this method to provide heritability estimates for ICH risk, severity, and outcome. METHODS: We analyzed genome-wide genotype data for 791 ICH cases and 876 controls, and determined heritability as the proportion of variation in phenotype attributable to captured genetic variants. Contribution to heritability was separately estimated for the APOE (encoding apolipoprotein E) gene, an established genetic risk factor, and for the rest of the genome. Analyzed phenotypes included ICH risk, admission hematoma volume, and 90-day mortality. RESULTS: ICH risk heritability was estimated at 29% (SE, 11%) for non-APOE loci and at 15% (SE, 10%) for APOE. Heritability for 90-day ICH mortality was 41% for non-APOE loci and 10% (SE, 9%) for APOE. Genetic influence on hematoma volume was also substantial: admission volume heritability was estimated at 60% (SE, 70%) for non-APOEloci and at 12% (SE, 4%) for APOE. CONCLUSIONS: Genetic variation plays a substantial role in ICH risk, outcome, and hematoma volume. Previously reported risk variants account for only a portion of inherited genetic influence on ICH pathophysiology, pointing to additional loci yet to be identified.

Effects of meditation on pain intensity, physical function, quality of life and depression in adults with low back pain - A systematic review with meta-analysis.

BACKGROUND: Low back pain (LBP) is a common biopsychosocial health problem. Meditation may provide a complementary treatment option for LBP patients. OBJECTIVES: The aim of this systematic review with meta-analysis was to examine the effects of meditation on pain intensity, functional disability, quality of life, and depression in LBP populations. METHODS: This systematic review was conducted according to the PRISMA Guidelines. PubMed, Web of Science, CENTRAL, CamQuest and PubPsych were searched up to a publication date of June 2020. Inclusion criteria were RCTs or non-RCTs with LBP patients, aged at least 18 years, the application of a specific meditation technique, and pain intensity and/or functional disability as outcomes. Pooled SMDs were calculated at post-treatment and follow up. The Cochrane risk-of-bias tool was used to estimate risk of bias. The overall quality of evidence was assessed using the GRADE approach. RESULTS: 12 studies with a total of 1005 participants were included in this review. Compared to controls, meditation solely showed a significant positive effect on pain intensity (SMD = -0.27 [CI -0.43; -0.11]; p = 0.001; based on 10 studies with 934 participants) and physical quality of life (SMD = 0.21 [CI 0.07; 0.36]; p = 0.005; based on 5 studies with 756 participants) at post-treatment. At follow up (mean 20 weeks, range 4-52) there were no significant effects anymore. The quality of the evidence was moderate due to study limitations and imprecision. CONCLUSIONS: Meditation seems to be promising with regard to reducing short-term pain intensity in patients with LBP. However, additional well-designed and large trials are required in order to draw more reliable conclusions.

The potential of robot eyes as predictive cues in HRI-an eye-tracking study.

Robots currently provide only a limited amount of information about their future movements to human collaborators. In human interaction, communication through gaze can be helpful by intuitively directing attention to specific targets. Whether and how this mechanism could benefit the interaction with robots and how a design of predictive robot eyes in general should look like is not well understood. In a between-subjects design, four different types of eyes were therefore compared with regard to their attention directing potential: a pair of arrows, human eyes, and two anthropomorphic robot eye designs. For this purpose, 39 subjects performed a novel, screen-based gaze cueing task in the laboratory. Participants' attention was measured using manual responses and eye-tracking. Information on the perception of the tested cues was provided through additional subjective measures. All eye models were overall easy to read and were able to direct participants' attention. The anthropomorphic robot eyes were most efficient at shifting participants' attention which was revealed by faster manual and saccadic reaction times. In addition, a robot equipped with anthropomorphic eyes was perceived as being more competent. Abstract anthropomorphic robot eyes therefore seem to trigger a reflexive reallocation of attention. This points to a social and automatic processing of such artificial stimuli.