Jezelf kunnen zijn komt je levenskwaliteit ten goede: ULB peilt naar situatie van holebien transgenderwerknemers

info:eu-repo/semantics/published

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

ALBUM AMICORUM de Jan Isaac Vanden Brugge, dit Pontanus (1592-1627). In-8, mar. br. jans. (Hans Asper.)

Vanden Brugge (Jan Isaac), dit Pontanus. Album amicorum (1591-1627)

Comment vivre en vue du sens ? L’acte libre selon Jan Patočka

Dans cet exposé, l’auteur tente de montrer que le sens que le phénoménologue tchèque Jan Patočka (1907-1977) donne primordialement à « l’action » n’est pas un sens politique, mais plutôt un sens phénoménologique et existentiel. Pris sur ce plan d’analyse, le problème de l ’ agir libre doit être posé au départ de la question la plus fondamentale : Comment vivre en vue du sens ? – question qui concerne en premier lieu l’être individuel et non l’agir-ensemble. En analysant le sens que Patočka donne au monde naturel de la vie, au problème du vital, aux termes « possibilité » et « liberté », l’auteur montre que l’action au sens le plus fondamental, que Patočka nomme « action tragique », est ce qui fait de l’existence humaine un mouvement vivant ouvert sur la totalité du monde.

De rol van het Internationaal Strafhof in het voorkomen van internationale misdrijven door middel van tijdige interventie

De la Doctrina de Intervención Humanitaria y ex post facto Instituciones Judiciales a la noción de responsabilidad de proteger y el papel preventivo de la Corte Penal Internacional. Lección inaugural como Presidente en Derecho Penal Internacional y Procedimiento Penal Internacional en la Universidad de Utrecht, emitido el 18 de octubre 2010

Nitrogen flows from European watersheds to coastal marine waters

Nitrogen flows from European watersheds to coastal marine waters Executive summary Nature of the problem • Most regional watersheds in Europe constitute managed human territories importing large amounts of new reactive nitrogen. • As a consequence, groundwater, surface freshwater and coastal seawater are undergoing severe nitrogen contamination and/or eutrophication problems. Approaches • A comprehensive evaluation of net anthropogenic inputs of reactive nitrogen (NANI) through atmospheric deposition, crop N fixation,fertiliser use and import of food and feed has been carried out for all European watersheds. A database on N, P and Si fluxes delivered at the basin outlets has been assembled. • A number of modelling approaches based on either statistical regression analysis or mechanistic description of the processes involved in nitrogen transfer and transformations have been developed for relating N inputs to watersheds to outputs into coastal marine ecosystems. Key findings/state of knowledge • Throughout Europe, NANI represents 3700 kgN/km2/yr (range, 0–8400 depending on the watershed), i.e. five times the background rate of natural N2 fixation. • A mean of approximately 78% of NANI does not reach the basin outlet, but instead is stored (in soils, sediments or ground water) or eliminated to the atmosphere as reactive N forms or as N2. • N delivery to the European marine coastal zone totals 810 kgN/km2/yr (range, 200–4000 depending on the watershed), about four times the natural background. In areas of limited availability of silica, these inputs cause harmful algal blooms. Major uncertainties/challenges • The exact dimension of anthropogenic N inputs to watersheds is still imperfectly known and requires pursuing monitoring programmes and data integration at the international level. • The exact nature of ‘retention’ processes, which potentially represent a major management lever for reducing N contamination of water resources, is still poorly understood. • Coastal marine eutrophication depends to a large degree on local morphological and hydrographic conditions as well as on estuarine processes, which are also imperfectly known. Recommendations • Better control and management of the nitrogen cascade at the watershed scale is required to reduce N contamination of ground- and surface water, as well as coastal eutrophication. • In spite of the potential of these management measures, there is no choice at the European scale but to reduce the primary inputs of reactive nitrogen to watersheds, through changes in agriculture, human diet and other N flows related to human activity.

Integrating nitrogen fluxes at the European scale

Executive summary Nature of the problem • Environmental problems related to nitrogen concern all economic sectors and impact all media: atmosphere, pedosphere, hydrosphere and anthroposphere. • Therefore, the integration of fluxes allows an overall coverage of problems related to reactive nitrogen (Nr) in the environment, which is not accessible from sectoral approaches or by focusing on specific media. Approaches • This chapter presents a set of high resolution maps showing key elements of the N flux budget across Europe, including N2 and Nr fluxes. • Comparative nitrogen budgets are also presented for a range of European countries, highlighting the most efficient strategies for mitigating Nr problems at a national scale. A new European Nitrogen Budget (EU-27) is presented on the basis of state-of-the-art Europe-wide models and databases focusing on different segments of Europe’s society. Key findings • From c. 18 Tg Nr yr −1 input to agriculture in the EU-27, only about 7 Tg Nr yr− 1 find their way to the consumer or are further processed by industry. • Some 3.7 Tg Nr yr−1 is released by the burning of fossil fuels in the EU-27, whereby the contribution of the industry and energy sectors is equal to that of the transport sector. More than 8 Tg Nr yr−1 are disposed of to the hydrosphere, while the EU-27 is a net exporter of reactive nitrogen through atmospheric transport of c. 2.3 Tg Nr yr−1. • The largest single sink for Nr appears to be denitrifi cation to N2 in European coastal shelf regions (potentially as large as the input of mineral fertilizer, about 11 Tg N yr–1 for the EU-27); however, this sink is also the most uncertain, because of the uncertainty of Nr import from the open ocean. Major uncertainties • National nitrogen budgets are diffi cult to compile using a large range of data sources and are currently available only for a limited number of countries. • Modelling approaches have been used to fill in the data gaps in some of these budgets, but it became obvious during this study that further research is needed in order to collect necessary data and make national nitrogen budgets inter-comparable across Europe. • In some countries, due to inconsistent or contradictory information coming from different data sources, closure of the nitrogen budget was not possible. Recommendations • The large variety of problems associated with the excess of Nr in the European environment,including adverse impacts, requires an integrated nitrogen management approach that would allow for creation and closure of N budgets within European environments. • Development of nitrogen budgets nationwide, their assessment and management could become an effective tool to prioritize measures and prevent unwanted side effects.

Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue

Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances.

Effect of Acute Psychological Stress on Prefrontal GABA Concentration Determined by Proton Magnetic Resonance Spectroscopy

Objective Impaired function of the central gamma-aminobutyric acid (GABA) system, which provides the brain’s major inhibitory pathways, is thought to play an important role in the pathophysiology of anxiety disorders. The effect of acute psychological stress on the human GABA-ergic system is still unknown, however. The purpose of this study was to determine the effect of acute stress on prefrontal GABA levels. Method A recently developed noninvasive magnetic resonance spectroscopy method was used to measure changes in the GABA concentration of the prefrontal cortex in 10 healthy human subjects during a threat-of-shock condition and during a safe condition (two sessions on different days). The main outcome measure was the mean GABA concentration within a 3×3×2-cm3 voxel selected from the medial prefrontal cortex. Results Prefrontal GABA decreased by approximately 18% in the threat-of-shock condition relative to the safe condition. This reduction was specific to GABA, since the concentrations of N-acetyl-aspartate, choline-containing compounds, and glutamate/glutamine levels obtained in the same spectra did not change significantly. Conclusions This result appeared compatible with evidence from preclinical studies in rodents, which showed rapid presynaptic down-regulation of GABA-ergic neurotransmission in response to acute psychological stress. The molecular mechanism and functional significance of this reduced inhibitory effect of acute psychological stress in relation to impaired GABA-ergic function in anxiety disorders merit further investigation.

Long-term tissue coverage of a biodegradable polylactide polymer-coated biolimus-eluting stent: comparative sequential assessment with optical coherence tomography until complete resorption of the polymer

Biolimus-eluting stents (BESs) with a biodegradable polymer in abluminal coating achieve more complete coverage at 9 months compared with sirolimus-eluting stents (SESs) with a durable polymer, as assessed by optical coherence tomography (OCT). Whether this advantage persists or augments after complete resorption of the polymer (>12 months) is unknown.

Tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent vs. a fluoropolymer-coated everolimus-eluting stent at 13-month follow-up: an optical coherence tomography substudy from the RESOLUTE All Comers trial

Aims To compare the tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent (ZES) vs. a fluoropolymer-coated everolimus-eluting stent (EES) at 13 months, using optical coherence tomography (OCT) in an ‘all-comers' population of patients, in order to clarify the mechanism of eventual differences in the biocompatibility and thrombogenicity of the devices. Methods and results Patients randomized to angiographic follow-up in the RESOLUTE All Comers trial (NCT00617084) at pre-specified OCT sites underwent OCT follow-up at 13 months. Tissue coverage and apposition were assessed strut by strut, and the results in both treatment groups were compared using multilevel logistic or linear regression, as appropriate, with clustering at three different levels: patient, lesion, and stent. Fifty-eight patients (30 ZES and 28 EES), 72 lesions, 107 stents, and 23 197 struts were analysed. Eight hundred and eighty-seven and 654 uncovered struts (7.4 and 5.8%, P= 0.378), and 216 and 161 malapposed struts (1.8 and 1.4%, P= 0.569) were found in the ZES and EES groups, respectively. The mean thickness of coverage was 116 ± 99 µm in ZES and 142 ± 113 µm in EES (P= 0.466). No differences in per cent neointimal volume obstruction (12.5 ± 7.9 vs. 15.0 ± 10.7%) or other areas–volumetric parameters were found between ZES and EES, respectively. Conclusion No significant differences in tissue coverage, malapposition, or lumen/stent areas and volumes were detected by OCT between the hydrophilic polymer-coated ZES and the fluoropolymer-coated EES at 13-month follow-up.

Age-modulated association between prefrontal NAA and the BDNF gene

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of psychiatric and neurological disorders and in the mechanisms of antidepressant pharmacotherapy. Psychiatric and neurological conditions have also been associated with reduced brain levels of N-acetyl-aspartate (NAA), which has been used as a putative marker of neural integrity. However, few studies have explored the relationship between BDNF polymorphisms and NAA levels directly. Here, we present data from a single-voxel proton magnetic resonance spectroscopy study of 64 individuals and explore the relationship between BDNF polymorphisms and prefrontal NAA level. Our results indicate an association between a single nucleotide polymorphism (SNP) within BDNF, known as rs1519480, and reduced NAA level (p = 0.023). NAA levels were further predicted by age and Asian ancestry. There was a significant rs1519480 × age interaction on NAA level (p = 0.031). Specifically, the effect of rs1519480 on NAA level became significant at age ⩾34.17 yr. NAA level decreased with advancing age for genotype TT (p = 0.001) but not for genotype CT (p = 0.82) or CC (p = 0.34). Additional in silico analysis of 142 post-mortem brain samples revealed an association between the same SNP and reduced BDNF mRNA expression in the prefrontal cortex. The rs1519480 SNP influences BDNF mRNA expression and has an impact on prefrontal NAA level over time. This genetic mechanism may contribute to inter-individual variation in cognitive performance seen during normal ageing, as well as contributing to the risk for developing psychiatric and neurological conditions.