72 research outputs found
Genetic contributions to trail making test performance in UK Biobank
No full textThe Trail Making Test (TMT) is a widely used test of executive function and has been thought to be strongly associated with general cognitive function. We examined the genetic architecture of the TMT and its shared genetic aetiology with other tests of cognitive function in 23 821 participants from UK Biobank. The single-nucleotide polymorphism-based heritability estimates for trail-making measures were 7.9% (part A), 22.4% (part B) and 17.6% (part B − part A). Significant genetic correlations were identified between trail-making measures and verbal-numerical reasoning (rg40.6), general cognitive function (rg40.6), processing speed (rg40.7)and memory (rg40.3). Polygenic profile analysis indicated considerable shared genetic aetiology between trail making, general cognitive function, processing speed and memory (standardized β between 0.03 and 0.08). These results suggest that trail making is both phenotypically and genetically strongly associated with general cognitive function and processing speed
Genetic contributions to self-reported tiredness
No full textSelf-reported tiredness and low energy, often called fatigue, are associated with poorer physical and mental health. Twin studies have indicated that this has a heritability between 6 and 50%. In the UK Biobank sample (N=108 976), we carried out a genome-wide association study (GWAS) of responses to the question, 'Over the last two weeks, how often have you felt tired or had little energy?' Univariate GCTA-GREML found that the proportion of variance explained by all common single-nucleotide polymorphisms for this tiredness question was 8.4% (s.e.=0.6%). GWAS identified one genome-wide significant hit (Affymetrix id 1:64178756_C_T; P=1.36 × 10(-11)). Linkage disequilibrium score regression and polygenic profile score analyses were used to test for shared genetic aetiology between tiredness and up to 29 physical and mental health traits from GWAS consortia. Significant genetic correlations were identified between tiredness and body mass index (BMI), C-reactive protein, high-density lipoprotein (HDL) cholesterol, forced expiratory volume, grip strength, HbA1c, longevity, obesity, self-rated health, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, attention deficit hyperactivity disorder, bipolar disorder, major depressive disorder, neuroticism, schizophrenia and verbal-numerical reasoning (absolute rg effect sizes between 0.02 and 0.78). Significant associations were identified between tiredness phenotypic scores and polygenic profile scores for BMI, HDL cholesterol, low-density lipoprotein cholesterol, coronary artery disease, C-reactive protein, HbA1c, height, obesity, smoking status, triglycerides, type 2 diabetes, waist-hip ratio, childhood cognitive ability, neuroticism, bipolar disorder, major depressive disorder and schizophrenia (standardised β's had absolute values<0.03). These results suggest that tiredness is a partly heritable, heterogeneous and complex phenomenon that is phenotypically and genetically associated with affective, cognitive, personality and physiological processes.Molecular Psychiatry advance online publication, 14 February 2017; doi:10.1038/mp.2017.5.</p
Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N=112 151) and 24 GWAS consortia.
No full textCauses of the well-documented association between low levels of cognitive functioning and many adverse neuropsychiatric outcomes, poorer physical health and earlier death remain unknown. We used linkage disequilibrium regression and polygenic profile scoring to test for shared genetic aetiology between cognitive functions and neuropsychiatric disorders and physical health. Using information provided by many published genome-wide association study consortia, we created polygenic profile scores for 24 vascular-metabolic, neuropsychiatric, physiological-anthropometric and cognitive traits in the participants of UK Biobank, a very large population-based sample (N=112?151). Pleiotropy between cognitive and health traits was quantified by deriving genetic correlations using summary genome-wide association study statistics and to the method of linkage disequilibrium score regression. Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, autism, major depressive disorder, body mass index, intracranial volume, infant head circumference and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants, we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples.Molecular Psychiatry advance online publication, 26 January 2016; doi:10.1038/mp.2015.225
Vergunningenmanagement: Management van bestuursrechtelijke wet- en regelgeving bij ruimtelijke ontwikkelingsprojecten in stedelijke content
No full textRuimtelijke ontwikkelingsprojecten in stedelijke context zijn complexe opgaven. Dit hangt samen met de steeds schaarser wordende ruimte in Nederland, juridische regelverdichting en steeds mondiger wordende omwonenden. Projectmanagers hebben de taak dit soort ontwikkelingsprojecten succesvol te laten verlopen. Een onderdeel van deze taak is de aansturing van het vergunningtraject, vergunningenmanagement genoemd. Het blijkt in de praktijk nog al eens mis te gaan bij omgang met de bestuursrechtelijke wet- en regelgeving tijdens het vergunningtraject. Dit met grote gevolgen voor het ontwikkelingsproces. Dit afstudeeronderzoek is een verkennende studie naar de knelpunten die zich voordoen tijdens het vergunningtraject van ruimtelijke ontwikkelingsprojecten. De doelstelling van het onderzoek is inzicht verkrijgen in deze knelpunten, om vervolgens een bijdrage te leveren aan het terugdringen van de storingen. Deze doelstelling wordt bereikt door het geven van vorm en inhoud aan het begrip vergunningenmanagement, het aandragen van oplossingen voor de knelpunten in het vergunningtraject en het doen van aanbevelingen richting de bouwpraktijk. Methodiek Tijdens het onderzoek verschillende onderzoeksmethoden toegepast. Er is literatuuronderzoek gedaan naar de kenmerken van ruimtelijke ontwikkelingsprojecten en naar verschillende managementmethoden die toepasbaar zijn bij de aansturing van ontwikkelingsprojecten en het vergunningtraject in het bijzonder. Vervolgens is er een ordening gemaakt van de meest relevante wetgeving en procedures waarmee men te maken kan krijgen tijdens het vergunningtraject, waarbij het accent is gelegd op woningbouwprojecten. Er is een casusonderzoek uitgevoerd aan de hand van een aantal woningbouwprojecten en er zijn interviews gehouden onder zowel private als publieke partijen. Met het casusonderzoek en de interviews is inzicht verkregen in de knelpunten en storingen die zich voordoen tijdens het vergunningtraject en mogelijke oplossingen daarvoor. Conclusies Uit het onderzoek is gebleken dat de complexiteit van de wet- en regelgeving en de rol van de gemeente in het vergunningtraject als knelpunt worden gezien. Hiernaast zijn een aantal specifieke momenten in het vergunningtraject aangeduid als knelpunt. Deze zijn de onduidelijkheid betreffende indieningsvereisten bij vergunningaanvragen, de lengte en onvoorspelbaarheid van behandeltermijnen en bezwaarprocedures. De vrijstellingprocedure volgens artikel 19 van de Wet op de Ruimtelijke Ordening wordt gezien als specifieke regelgeving waarbij de bovenstaande knelpunten regelmatig voorkomen. Het gevolg van de bovengenoemde knelpunten is dat er storingen optreden in het ontwikkelingsproces. Deze storingen doen zich voor in de vorm van vertragingen en overschrijdingen van de financiele begroting. In het ergste geval zorgen de knelpunten voor het volledig beeindigen van het ontwikkelingsproces. Door het toepassen van vergunningenmanagement kan de projectmanager deze storingen terugdringen. Vergunningenmanagement moet hierbij worden gezien als een weldoordachte manier van handelen bij het organiseren en coordineren van alle activiteiten in het vergunningtraject. In het begin van het vergunningtraject moet er rekening gehouden worden met een groot aantal verschillende factoren, zoals toepasselijke wet- en regelgeving, politiek draagvlak en maatschappelijke belangen. Deze fase van het vergunningtraject vraagt om een procesmatige managementbenadering. Naarmate het vergunningtraject vordert worden de randvoorwaarden duidelijk er wordt er inzicht verkregen in welke juridische procedures er gevolgd moeten worden. In de loop van het vergunningtraject zal de procesmatige aanpak plaats maken voor een meer project matige aanpak: projectmanagement. Uit het onderzoek zijn een aantal oplossingen naar voren gekomen die door de projectmanager geimplementeerd kunnen worden bij de aansturing van het vergunningtraject. Deze oplossingen zijn in het concluderend deel van dit rapport opgenomen. In het Adviesrapport Vergunningenmanagement is dit onderzoeksrapport 'vertaald' naar een document voor de bouwpraktijk. Hierin komen de resultaten uit het onderzoek terug en worden deze geillustreerd door pragmatische tips en verwijzingen.Architectur
Ureum: Hot Gas Recycle Process
No full textDocument(en) uit de collectie Chemische ProcestechnologieDelftChemTechApplied Science
De debutanizer
No full textDocument uit de collectie Chemische ProcestechnologieDelftChemTechApplied Science
Pleiotropy between neuroticism and physical and mental health: findings from 108 038 men and women in UK Biobank
No full textPeople with higher levels of neuroticism have an increased risk of several types of mental disorder. Higher neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between neuroticism and 17 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between neuroticism scores in 108 038 people in UK Biobank and health-related measures from 14 large genome-wide association studies (GWAS). Summary information for the 17 GWAS was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre, and population stratification. Genetic correlations were identified between neuroticism and anorexia nervosa (rg = 0.17), major depressive disorder (rg = 0.66) and schizophrenia (rg = 0.21). Polygenic risk for several health-related measures were associated with neuroticism, in a positive direction in the case of bipolar disorder, borderline personality, major depressive disorder , negative affect , neuroticism (Genetics of Personality Consortium), schizophrenia , and coronary artery disease , and smoking (β between 0.009 – 0.043) and in a negative direction in the case of BMI (β = -0.0095). A high level of pleiotropy exists between neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia
Elevated pCO2 exposure during fertilization of the bay scallop Argopecten irradians reduces larval survival but not subsequent shell size
No full textAuthor Posting. © Inter-Research, 2014. This article is posted here by permission of Inter-Research for personal use, not for redistribution. The definitive version was published in Marine Ecology Progress Series 498 (2014): 173-186, doi:10.3354/meps10621.Ocean acidification, characterized by elevated partial pressure of CO2 (pCO2), generally has negative effects on early life stages of invertebrates. We tested the idea that fertilization is a critical CO2 exposure stage for the bay scallop Argopecten irradians by determining the effects on bay scallops of exposure to high CO2 (pCO2 ~2600 ppm, pH ~7.30) from fertilization to 7 d old. To assess the possibility of persistent effects of exposure during fertilization, further treatments included switches from high CO2 to ambient CO2 (pCO2 ~480 ppm, pH ~7.96) and from ambient CO2 to high CO2 at 2 h post-fertilization. Survival of larvae decreased significantly when they were fertilized in high CO2. A switch in CO2 conditions 2 h post-fertilization did not change this effect, suggesting that the critical exposure window for this survival effect is within the first 2 h. In contrast, CO2 conditions during fertilization did not affect larval shell size, but the switch treatments showed that exposure to high CO2 after 2 h post-fertilization decreased shell size, indicating that the exposure window for a size effect was later in development, possibly during shell calcification. Finally, a shell deformity was seen in scallops with continuous exposure to high CO2 and those switched from ambient CO2 to high CO2 at 2 h post-fertilization. Decreased survival during fertilization and smaller larval shell size due to ocean acidification could ultimately reduce the population size of this commercially important bivalve, which has already seen dramatic population decline due to loss of juvenile habitat.This work was funded by a Mellon
Joint Initiatives Award to L.S.M. and D.C.M., and awards to
L.S.M. and M.M.W. to D.C.M., and to A.L.C. & D.C.M.
through NOAA Sea Grant #NA10OAR4170083. M.M.W.
was funded through a Na tional Defense Science and Engineering
Graduate Fellowship through the American Society
for Engineering Education
Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions
No full textDifferences in general cognitive function have been shown to be partly heritable and to show genetic correlations with several psychiatric and physical disease states. However, to date, few single-nucleotide polymorphisms (SNPs) have demonstrated genome-wide significance, hampering efforts aimed at determining which genetic variants are most important for cognitive function and which regions drive the genetic associations between cognitive function and disease states. Here, we combine multiple large genome-wide association study (GWAS) data sets, from the CHARGE cognitive consortium (n=53 949) and UK Biobank (n=36 035), to partition the genome into 52 functional annotations and an additional 10 annotations describing tissue-specific histone marks. Using stratified linkage disequilibrium score regression we show that, in two measures of cognitive function, SNPs associated with cognitive function cluster in regions of the genome that are under evolutionary negative selective pressure. These conserved regions contained ~2.6% of the SNPs from each GWAS but accounted for ~40% of the SNP-based heritability. The results suggest that the search for causal variants associated with cognitive function, and those variants that exert a pleiotropic effect between cognitive function and health, will be facilitated by examining these enriched regions.</p
The Gerber-Shiu expected discounted penalty-reward function under an affine jump-diffusion model.
No full textWe provide a unified analytical treatment of first passage problems under an affine state-dependent jump-diffusion model (with drift and volatility depending linearly on the state). Our proposed model, that generalizes several previously studied cases, may be used for example for obtaining probabilities of ruin in the presence of interest rates under the rational investement strategies proposed by Berk & Green (2004)First passage problems; Risk process; Stochastic rates of interest; Ruin with interest; Affine jump-diffusion models; Penalty/reward functions at ruin;
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