1. |
- Potts, Simon G., et al.
(author)
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Developing European conservation and mitigation tools for pollination services: approaches of the STEP (Status and Trends of European Pollinators) project
- 2011
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In: Journal of Apicultural Research. - 0021-8839 .- 2078-6913. ; 50:2, s. 152-164
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Research review (peer-reviewed)abstract
- Pollinating insects form a key component of European biodiversity, and provide a vital ecosystem service to crops and wild plants. There is growing evidence of declines in both wild and domesticated pollinators, and parallel declines in plants relying upon them. The STEP project (Status and Trends of European Pollinators, 2010-2015, www.step-project.net) is documenting critical elements in the nature and extent of these declines, examining key functional traits associated with pollination deficits, and developing a Red List for some European pollinator groups. Together these activities are laying the groundwork for future pollinator monitoring programmes. STEP is also assessing the relative importance of potential drivers of pollinator declines, including climate change, habitat loss and fragmentation, agrochemicals, pathogens, alien species, light pollution, and their interactions. We are measuring the ecological and economic impacts of declining pollinator services and floral resources, including effects on wild plant populations, crop production and human nutrition. STEP is reviewing existing and potential mitigation options, and providing novel tests of their effectiveness across Europe. Our work is building upon existing and newly developed datasets and models, complemented by spatially-replicated campaigns of field research to fill gaps in current knowledge. Findings are being integrated into a policy-relevant framework to create evidence-based decision support tools. STEP is establishing communication links to a wide range of stakeholders across Europe and beyond, including policy makers, beekeepers, farmers, academics and the general public. Taken together, the STEP research programme aims to improve our understanding of the nature, causes, consequences and potential mitigation of declines in pollination services at local, national, continental and global scales.
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3. |
- Van Deerlin, Vivian M, et al.
(author)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
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Journal article (peer-reviewed)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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4. |
- von Sarnowski, Bettina, et al.
(author)
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Lifestyle Risk Factors for Ischemic Stroke and Transient Ischemic Attack in Young Adults in the Stroke in Young Fabry Patients Study
- 2013
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In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 44:1, s. 119-125
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Journal article (peer-reviewed)abstract
- Background and Purpose-Although many stroke patients are young or middle-aged, risk factor profiles in these age groups are poorly understood. Methods-The Stroke in Young Fabry Patients (sifap1) study prospectively recruited a large multinational European cohort of patients with cerebrovascular events aged 18 to 55 years to establish their prevalence of Fabry disease. In a secondary analysis of patients with ischemic stroke or transient ischemic attack, we studied age-and sex-specific prevalences of various risk factors. Results-Among 4467 patients (median age, 47 years; interquartile range, 40-51), the most frequent well-documented and modifiable risk factors were smoking (55.5%), physical inactivity (48.2%), arterial hypertension (46.6%), dyslipidemia (34.9%), and obesity (22.3%). Modifiable less well-documented or potentially modifiable risk factors like high-risk alcohol consumption (33.0%) and short sleep duration (20.6%) were more frequent in men, and migraine (26.5%) was more frequent in women. Women were more often physically inactive, most pronouncedly at ages <35 years (18-24: 38.2%; 25-34: 51.7%), and had high proportions of abdominal obesity at age 25 years or older (74%). Physical inactivity, arterial hypertension, dyslipidemia, obesity, and diabetes mellitus increased with age. Conclusions-In this large European cohort of young patients with acute ischemic cerebrovascular events, modifiable risk factors were highly prevalent, particularly in men and older patients. These data emphasize the need for vigorous primary and secondary prevention measures already in young populations targeting modifiable lifestyle vascular risk factors. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00414583. (Stroke. 2013; 44: 119-125.)
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5. |
- Cocron, Peter, et al.
(author)
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Driver and vehicle behaviour to power train failures in electric vehicles : experimental results of field and simulator studies
- 2014
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Reports (other academic/artistic)abstract
- New electric power trains can be subject to different failures when compared to those arising in conventional vehicles. The objectives for active safety investigations within the EVERSAFE project were to address vehicle stability under these failure conditions and the driver response to relevant types of failures. Failure conditions that affect the vehicle stability are believed to be significantly different from today’s conventional internal combustion engine cars, and may potentially be a substantial safety problem if not treated in a correct manner. To study these effects, two examples of system failures and their consequences on the driver response and vehicle stability were investigated with the help of three studies.The first two studies investigated a failure of wheel hub motors (WHMs), an emerging technology among the future generation of electric vehicles (EV). The main benefits of a WHM are its controllability, high efficiency, high power density and low weight. However, the direct connection to the wheel comes along with the potential disadvantage in case a failure occurs in the system.The third study conducted within the active safety focus of the EVERSAFE project examined a failure of the regenerative braking (RB) system. The latter is a system designed to convert kinetic energy to chemical energy stored in the energy storage system (i.e. battery) while the vehicle decelerates.
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- Flores, Xavier, et al.
(author)
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Assessing the use of activated sludge process design guidelines in wastewater treatment plant projects: A methodology based on global sensitivity analysis
- 2012
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In: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152. ; 38, s. 50-58
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Journal article (peer-reviewed)abstract
- Design inputs (wastewater characteristics, operational settings, effluent requirements or safety factors, ...) need to be supplied when using activated sludge process design guidelines (ASPDG) to determine the design outputs (biological reactor volume, the dissolved oxygen demand or the different internal/external recycle flow-rates). The values of the design inputs might have strong effects on the future characteristics of the plant under study. For this reason, there is a need to determine how both design inputs and outputs are linked and how they affect wastewater treatment plant (WWTP) designs. In this paper we assess ASPDG with a methodology based on Monte Carlo (MC) simulations and Global Sensitivity Analysis (GSA). The novelty of this approach relies on working with design input and output ranges instead of single values, identifying the most influential design inputs on the different design outputs and improving the interpretation of the generated results with a set of visualization tools. The variation in these design inputs is attributed to epistemic uncertainty, natural variability as well as operator, owner and regulator decision ranges. Design outputs are calculated by sampling the previously defined input ranges and propagating this variation through the design guideline. Standard regression coefficients (SRC), cluster analysis (CA) and response surfaces (RS) are used to identify/interpret the design inputs that influence the variation on the design outputs the most. The illustrative case study uses the widely recognized Metcalf & Eddy guidelines and presents a didactic design example for an organic carbon (C) and nitrogen (N) removal pre-denitrifying activated sludge plant. Results show that the proposed GSA can satisfactorily decompose the variance of the design outputs (R-2 > 0.7): aerobic (V-AER) and anoxic (V-ANOX) volume, air demand (Q(AIR)) and internal recycle flow rate (Q(INTR)). Response surfaces are proposed to facilitate the visualization of how, when and why the design outputs may change when the most influential design inputs are modified. Finally, it is demonstrated that the proposed method is useful for process engineers providing a regional instead of a local picture of a design problem. (C) 2012 Elsevier Ltd. All rights reserved.
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8. |
- Fritschi, Sarah K., et al.
(author)
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A beta seeds resist inactivation by formaldehyde
- 2014
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In: Acta Neuropathologica. - : Springer Verlag (Germany). - 0001-6322 .- 1432-0533. ; 128:4, s. 477-484
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Journal article (peer-reviewed)abstract
- Cerebral beta-amyloidosis can be exogenously induced by the intracerebral injection of brain extracts containing aggregated beta-amyloid (A beta) into young, pre-depositing A beta precursor protein- (APP) transgenic mice. Previous work has shown that the induction involves a prion-like seeding mechanism in which the seeding agent is aggregated A beta itself. Here we report that the beta-amyloid-inducing activity of Alzheimers disease (AD) brain tissue or aged APP-transgenic mouse brain tissue is preserved, albeit with reduced efficacy, after formaldehyde fixation. Moreover, spectral analysis with amyloid conformation-sensitive luminescent conjugated oligothiophene dyes reveals that the strain-like properties of aggregated A beta are maintained in fixed tissues. The resistance of A beta seeds to inactivation and structural modification by formaldehyde underscores their remarkable durability, which in turn may contribute to their persistence and spread within the body. The present findings can be exploited to establish the relationship between the molecular structure of A beta aggregates and the variable clinical features and disease progression of AD even in archived, formalin-fixed autopsy material.
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9. |
- Gallagher, Michael D., et al.
(author)
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TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions
- 2014
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 127:3, s. 407-418
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Journal article (peer-reviewed)abstract
- Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease.
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10. |
- Jander, Nikolaus, et al.
(author)
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Indexing aortic valve area by body surface area increases the prevalence of severe aortic stenosis
- 2014
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In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 100:1, s. 28-33
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Journal article (peer-reviewed)abstract
- Background To account for differences in body size in patients with aortic stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to calculate indexed AVA (AVA(index)). Cut-off values for severe stenosis are <1.0cm(2) for AVA and <0.6cm(2)/m(2) for AVA(index). Objective To investigate the influence of indexation on the prevalence of severe aortic stenosis and on the predictive accuracy regarding clinical outcome. Methods Echocardiographic and anthropometric data from a retrospective cohort of 2843 patients with aortic stenosis (jet velocity >2.5m/s) and from 1525 patients prospectively followed in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial were analysed. Results The prevalence of severe stenosis increased with the AVA(index) criterion compared to AVA from 71% to 80% in the retrospective cohort, and from 29% to 44% in SEAS (both p<0.001). Overall, the predictive accuracy for aortic valve events was virtually identical for AVA and AVA(index) in the SEAS population (mean follow-up of 46months; area under the receiver operating characteristic curve: 0.67 (95% CI 0.64 to 0.70) vs 0.68 (CI 0.65 to 0.71) (NS). However, 213 patients additionally categorised as severe by AVA(index) experienced significantly less valve related events than those fulfilling only the AVA criterion (p<0.001). Conclusions Indexing AVA by BSA (AVA(index)) significantly increases the prevalence of patients with criteria for severe stenosis by including patients with a milder degree of the disease without improving the predictive accuracy for aortic valve related events.
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