Bayesian clinical trial designs : Another option for trauma trials?

The UK-REBOA Trial is funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project number 14/199/09). PP was supported by the MRC Network of Hubs for Trials Methodology Research (MR/L004933/1-R/N/P/B1).Peer reviewedPublisher PD

Population Studies of the Heritable Influences on the Mind and Brain

Decades of prior genetic research using twin modelling designs has shown that differences in human behavior are strongly influenced by differences in our DNA. Through advances in DNA genotyping it has become feasible to study the genetic factors that contribute to human variation by large-scale genome-wide association studies (GWAS). In this thesis, our aim was to study the genetic variants, genes and genetic pathways that explain variation in a broad diversity of behavioral outcomes making use of big data analyses in large population cohorts. By integrating GWAS results and GWAS-derived polygenic risk scores with gene-expression data, functional gene-sets and MRI imaging of the brain, this thesis provides a step forward in understanding the association between genetic variation and health-related phenotypes, including intelligence, neuroticism and depression, and insomnia, and the pathways and cell-types in the brain through which these genetic factors act

Genetic associations with childhood brain growth, defined in two longitudinal cohorts

Genome-wide association studies (GWASs) are unraveling the genetics of adult brain neuroanatomy as measured by cross-sectional anatomic magnetic resonance imaging (aMRI). However, the genetic mechanisms that shape childhood brain development are, as yet, largely unexplored. In this study we identify common genetic variants associated with childhood brain development as defined by longitudinal aMRI. Genome-wide single nucleotide polymorphism (SNP) data were determined in two cohorts: one enriched for attention-deficit/hyperactivity disorder (ADHD) (LONG cohort: 458 participants; 119 with ADHD) and the other from a population-based cohort (Generation R: 257 participants). The growth of the brain's major regions (cerebral cortex, white matter, basal ganglia, and cerebellum) and one region of interest (the right lateral prefrontal cortex) were defined on all individuals from two aMRIs, and a GWAS and a pathway analysis were performed. In addition, association between polygenic risk for ADHD and brain growth was determined for the LONG cohort. For white matter growth, GWAS meta-analysis identified a genome-wide significant intergenic SNP (rs12386571, P = 9.09 × 10-9 ), near AKR1B10. This gene is part of the aldo-keto reductase superfamily and shows neural expression. No enrichment of neural pathways was detected and polygenic risk for ADHD was not associated with the brain growth phenotypes in the LONG cohort that was enriched for the diagnosis of ADHD. The study illustrates the use of a novel brain growth phenotype defined in vivo for further study

A Novel Root-Knot Nematode Resistance QTL on Chromosome Vu01 in Cowpea.

The root-knot nematode (RKN) species Meloidogyne incognita and M. javanica cause substantial root system damage and suppress yield of susceptible cowpea cultivars. The narrow-based genetic resistance conferred by the Rk gene, present in some commercial cultivars, is not effective against Rk-virulent populations found in several cowpea production areas. The dynamics of virulence within RKN populations require a broadening of the genetic base of resistance in elite cowpea cultivars. As part of this goal, F1 and F2 populations from the cross CB46-Null (susceptible) x FN-2-9-04 (resistant) were phenotyped for M. javanica induced root-galling (RG) and egg-mass production (EM) in controlled growth chamber and greenhouse infection assays. In addition, F[Formula: see text] families of the same cross were phenotyped for RG on field sites infested with Rk-avirulent M. incognita and M. javanica The response of F1 to RG and EM indicated that resistance to RKN in FN-2-9-04 is partially dominant, as supported by the degree of dominance in the F2 and F[Formula: see text] populations. Two QTL associated with both RG and EM resistance were detected on chromosomes Vu01 and Vu04. The QTL on Vu01 was most effective against aggressive M. javanica, whereas both QTL were effective against avirulent M. incognita Allelism tests with CB46 x FN-2-9-04 progeny indicated that these parents share the same RKN resistance locus on Vu04, but the strong, broad-based resistance in FN-2-9-04 is conferred by the additive effect of the novel resistance QTL on Vu01. This novel resistance in FN-2-9-04 is an important resource for broadening RKN resistance in elite cowpea cultivars

Coronary evaginations and peri-scaffold aneurysms following implantation of bioresorbable scaffolds: incidence, outcome, and optical coherence tomography analysis of possible mechanisms

Background Peri-stent coronary evaginations may disturb flow and have been proposed as possible risk factor for late stent thrombosis. We describe incidence, predictors, and possible mechanisms of coronary evaginations 12 months after implantation of bioresorbable vascular scaffolds (BVS).Methods and results One hundred and two BVS implanted in 90 patients (age 63 ± 13 years, 71 males, 14 diabetics) were analysed with angiography and optical coherence tomography (OCT) 12 months after implantation. Evaginations were identified as any hollow in the luminal vessel contour between well-apposed struts and were classified as major when extending ≥3 mm with a depth ≥10% of the BVS diameter. Fifty-five (54%) of the BVS (50(56%) of the patients) had at least one evagination (6.1 ± 6.2 evaginations per BVS), with a mean volume of 1.9 ± 1.9 mm³. Major evaginations were only found in one patient, and in-BVS aneurysms in three patients (4BVS). The presence of evaginations was strongly associated with that of malapposition (P = 0.003) and strut fractures (P = 0.01). No association could be shown between the presence and volume of the evaginations and any clinical variable or the presence of uncovered struts (P > 0.5). Peri-strut low- intensity areas (PSLIA) were present in 29 (53%) of the BVS with evaginations and 12 (26%) of those without (P = 0.0049); their presence was independently associated with the presence, the number (P P = 0.004) and with that of strut fracture. Conclusions Optical coherence tomography-detected evaginations are relatively common after BVS implantation, but, as for modern drug-eluting metallic stents, major evaginations are very rare. Optical coherence tomography evidence of immature neointima and strut fractures were associated with more severe development of evaginations

The Ionization Fraction in Dense Molecular Gas II: Massive Cores

We present an observational and theoretical study of the ionization fraction in several massive cores located in regions that are currently forming stellar clusters. Maps of the emission from the J = 1-> O transitions of C18O, DCO+, N2H+, and H13CO+, as well as the J = 2 -> 1 and J = 3 -> 2 transitions of CS, were obtained for each core. Core densities are determined via a large velocity gradient analysis with values typically 10^5 cm^-3. With the use of observations to constrain variables in the chemical calculations we derive electron fractions for our overall sample of 5 cores directly associated with star formation and 2 apparently starless cores. The electron abundances are found to lie within a small range, -6.9 < log10(x_e) < -7.3, and are consistent with previous work. We find no difference in the amount of ionization fraction between cores with and without associated star formation activity, nor is any difference found in electron abundances between the edge and center of the emission region. Thus our models are in agreement with the standard picture of cosmic rays as the primary source of ionization for molecular ions. With the addition of previously determined electron abundances for low mass cores, and even more massive cores associated with O and B clusters, we systematically examine the ionization fraction as a function of star formation activity. This analysis demonstrates that the most massive sources stand out as having the lowest electron abundances (x_e < 10^-8).Comment: 35 pages (8 figures), using aaspp4.sty, to be published in Astrophysical Journa

Integration of Heat Flow through Borders between Adjacent Zones in AixLib's Reduced-Order Model

For dynamically simulating the thermal behavior of a building, the reduced-order model (ROM) implemented in the Modelica IBPSA and AixLib libraries provides a time-efficient calculation method based on the standard VDI 6007-1. Additionally, the Python package TEASER features a possilibity to fill the model parameters with automatically generated typical and/or enriched building data. So far, both have not been capable of modelling heat flow through borders between thermal zones. In this contribution, we present the integration of this feature into the open-source software combination. Additional new features include non-constant soil temperatures and a new approach to estimate interior building elements in cases without proper knowledge. Calculation results are presented for an exemplary application and show satisfactory agreement with measured values. The respective code (including the example presented here) is in the process of being published as part of the AixLib and TEASER open-source repositiories

‘Een kakafonie van woeste woede’: reflecties op de opkomst van de ‘boze burger’

Brexit en het Oekraïne-referendum; de vaak luidruchtige en soms gewelddadige opstand tegen de komst van asielzoekerscentra; de verkiezing van Donald Trump in de VS en de electorale opmars van populistische partijen als PVV, FvD en Denk in eigen land; de (vooral op sociale media hevig gevoerde) Zwarte Pieten-discussie en woedende Groningers die Mark Rutte op tv de les lezen: de afgelopen paar jaren leken het tijdperk van ‘de boze burger’. Veel politici en bestuurders vinden het moei‐ lijk om om te gaan met diens opgekropte woede. Anderen werpen zich op als de bondgenoten van de ‘gewone burger’ of ‘kleine man’ tegen ‘dé elite’ en ‘hét systeem’. Beleid ‘emotioneert’ en de verh

Multivariate analysis reveals shared genetic architecture of brain morphology and human behavior.

Human variation in brain morphology and behavior are related and highly heritable. Yet, it is largely unknown to what extent specific features of brain morphology and behavior are genetically related. Here, we introduce a computationally efficient approach for multivariate genomic-relatedness-based restricted maximum likelihood (MGREML) to estimate the genetic correlation between a large number of phenotypes simultaneously. Using individual-level data (N = 20,190) from the UK Biobank, we provide estimates of the heritability of gray-matter volume in 74 regions of interest (ROIs) in the brain and we map genetic correlations between these ROIs and health-relevant behavioral outcomes, including intelligence. We find four genetically distinct clusters in the brain that are aligned with standard anatomical subdivision in neuroscience. Behavioral traits have distinct genetic correlations with brain morphology which suggests trait-specific relevance of ROIs. These empirical results illustrate how MGREML can be used to estimate internally consistent and high-dimensional genetic correlation matrices in large datasets