1,652 research outputs found
Proceedings of the European Workshop on the Evaluation of Farm Investment Support, Investment Support for Improvement of Processing and Marketing of Agricultural Products
No full textContents: i - Angela Bergschmidt, Walter Dirksmeyer and Bernhard Forstner - Proceedings of the European Evaluation Workshop – Foreword -- PAPERS PRESENTED IN THE PLENARY SESSIONS -- 3 - Stefan Meyer - Methods for the Evaluation of Investment Support -- 15 - Andrea Pufahl - Programme Evaluation of Rural Development Plans – Purpose, Approaches and Exemplary Results -- 27 - Carel Gosselink - Agri Finance: Lost without Support? -- 33 - Anne Margarian - How to Evaluate a Measure without Goals – Considerations on the Basis of the Paradigmatic Example of Farm Investment Support in Germany -- 45 - Rudy Ooijen - Ex Ante Evaluations of Rural Development Programmes – Not just an Appraisal -- PAPERS PRESENTED IN THE SESSION ON FARM INVESTMENT SUPPORT -- 61 - Angela Bergschmidt and Walter Dirksmeyer - A Comparison of Farm Investment Support in Selected EU Member States -- 69 - Monika Beck and Thomas Dogot - The Use of Impact Indicators for the Evaluation of Farm Investment Support – A Case Study Based on the Rural Development Programme for Wallonia (2000 – 2006) -- 79 - Barbara Costantini and Maria Cristina Sibilla - Implementation of Farm Investment Support in Italy – Mid-Term Analysis -- 93 - Pawel Chmielinski - Regional Absorption Capacity of Farm Investment Support in Poland -- 105 - Luis A. Collado Cueto - Effectiveness and Impacts of Farm Investment Support in Spain – The Experience of the Updated Mid-Term Evaluation (2000 – 2006) -- 121 - Dimitros Lianos and Triantafyllia Giotopoulou - The Experience of the Evaluation of Farm Investment Support in Greece -- 133 - Bernhard Forstner - Evaluation of Farm Investment Support in Germany – Lessons Learned from the Application of Different Approaches -- 147 - Stephan Pfefferli - Impact Analysis of Investment Support for Agricultural Buildings in Switzerland -- 159 - Justyna Ziólkowska, Joanna Nargiello and Cezary Klimkowski - The Analysis of Changes in Farm Investment Support Policy in Poland after Joining the European Union -- PAPERS PRESENTED IN THE SESSION ON INVESTMENT SUPPORT FOR IMPROVEMENT OF PROCESSING AND MARKETING OF AGRICULTURAL PRODUCTS -- 177 - Inge Uetrecht, Heinz Wendt, Volker Krah and Annette Trefflich - The Implementation of Investment Support for Improving Processing and Marketing of Agricultural Products in the EU Member States – An Overview -- 187 -Andreas Pölking - Synthesis of the RDP Mid-Term Evaluation in Germany (16 Länder) and EC 15 in 2005 – Methodologies, Possibilities, Pitfalls and some Selected Results -- 195 - Julia Neuwirth and Karlheinz Pistrich - Improving Processing and Marketing of Agricultural Products – Organisation, Problems and Results of Evaluation in Austria -- 201 - Alois Grabner - Improving of Processing and Marketing of Agricultural Products – Assessment of Projects -- 205 - Pedro Serrano - Support to Processing and Marketing of Agricultural Products in Portugal -- 215 - Mark Temple - Two Approaches to Evaluation – The Case of the Processing and Marketing Grant in England -- 227 - Jochen Nölle and Josef Efken - Does Complete Field Research Build a Good Basis to Evaluating the Measure? -- CLOSURE OF THE EUROPEAN EVALUATION WORKSHOP -- 241 - Bernhard Forstner and Heinz Wendt - Summary and Final Discussion --
Short laws for finite groups and residual finiteness growth
No full text We prove that for every n ∈ N n \in \mathbb {N} and δ > 0 \delta >0 there exists a word w n ∈ F 2 w_n \in F_2 of length O ( n 2 / 3 log ( n ) 3 + δ ) O(n^{2/3} \log (n)^{3+\delta }) which is a law for every finite group of order at most n n . This improves upon the main result of Andreas Thom [Israel J. Math. 219 (2017), pp. 469–478] by the second named author. As an application we prove a new lower bound on the residual finiteness growth of non-abelian free groups. </p
Across Diagnostic Boundaries: Genetic Variants for Neuropsychiatric Disorders and their Association with Human Brain Structure
No full textWith the advances in genome-wide association studies (GWAS), hundreds of genetic variants have been identified for neuropsychiatric disorders. Strikingly, many of these genetic variants showed complex associations across diagnostic groups. For example, the second cross-disorder GWAS meta-analysis by the Psychiatric Genomics Consortium (Lee et al., 2019) identified 11 antagonistic single-nucleotide polymorphisms (SNPs) that were associated with an increased risk for one neuropsychiatric disorder, while being protective against another disorder. Furthermore, the cross-disorder GWAS meta-analysis uncovered 23 highly pleiotropic SNPs that were associated with at least four neuropsychiatric disorders and 22 SNPs that were predominantly associated with schizophrenia (SCZ) but not with the other disorders. The underlying molecular mechanisms by which these genetic variants alter the risk of distinct neuropsychiatric disorders are largely unclear. The present thesis conducted two imaging genetic studies to uncover the associations between antagonistic, highly pleiotropic, and predominantly SCZ-associated SNPs with brain structure and brain-related traits.
Study 1 performed a systematic characterization of the 11 antagonistic SNPs. Here, eight of the 11 antagonistic SNPs were significantly associated with at least one brain structural phenotype using the GWAS summary statistics from the ENIGMA and CHARGE consortia. Several of the implicated phenotypes were found to be altered in patients with bipolar disorder, major depression, or SCZ compared to controls. Six of the eight antagonistic SNPs were significantly associated with gene expression in brain tissue, and all eight antagonistic SNPs were significantly associated with cognitive-behavioral traits. Furthermore, rs301805 and rs1933802 were significantly associated with voxel-wise gray matter volume in data from the FOR2107 study.
Study 2 used data from the UK Biobank (n=28,952) to examine the association of a genetic risk score of highly pleiotropic SNPs (PleioPsych-GRS) and a genetic risk score of predominantly SCZ-associated SNPs (SCZ-GRS) with brain structure and outcomes related to mental health. To prioritize individual SNPs, the association of each SNP with brain structure was investigated. Study 2 found that the PleioPsych-GRS was not significantly associated with brain structural phenotypes after multiple testing corrections, whereas the SCZ-GRS was significantly associated with left and right putamen volume and left and right lateral orbitofrontal surface area, among others. The PleioPsych-GRS and the SCZ-GRS were significantly associated with eight and four outcomes related to mental health, respectively. Furthermore, two highly pleiotropic and ten predominantly SCZ-associated SNPs were significantly associated with at least one brain structural phenotype.
In conclusion, this thesis showed that antagonistic, predominantly SCZ-associated and, to a lesser extent, highly pleiotropic SNPs for neuropsychiatric disorders were associated with brain structure. In addition, the SNPs were associated with traits related to mental health, cognition, and behavior. These findings provided a notion of how these SNPs might influence disease development and led to the prioritization of selected SNPs and brain regions relevant for further investigations. Future work should extend these findings by exploring the association of these SNPs with additional brain modalities, including white matter microstructure and structural and functional connectivity of the human brain
Contribution of common genetic variants to disease status and symptom dimensions in affective and psychotic disorders
No full textAffective and psychotic disorders, such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia spectrum disorders (SSD), represent complex psychiatric conditions with a moderate to high heritability. Throughout the last decade, genome-wide association studies (GWAS) have demonstrated the association of many common genetic variants with disease risk. However, the pathophysiological mechanisms of affective and psychotic disorders are still incompletely understood and it is expected that many more disease-associated genetic loci await identification. Moreover, while the different affective and psychotic disorders are considered distinct entities by current diagnostic systems, they exhibit notable phenotypic overlaps and substantial genetic correlations. This suggests that etiological processes may be partially shared between diagnostic groups. Against this backdrop, the three studies included in this thesis were conducted to improve our understanding of the role of common genetic variation in affective and psychotic disorders. In particular, in the first and second study, the contribution of common genetic variants to symptom dimensions of acute and lifetime psychopathology observed across MDD, BD, and SSD was examined. In the third study, the largest GWAS meta-analysis of BD to date was conducted, which revealed novel disease-associated loci and provided insights into the underlying pathobiology via a plethora of GWAS downstream analyses. Altogether, the results of this research expand our knowledge on the complex relationships of common genetic variants with disease status and symptom dimensions within and across affective and psychotic disorders
Sofic groups and diophantine approximation
No full textWe prove the algebraic eigenvalue conjecture of J. Dodziuk, P. Linnell, V. Mathai, T. Schick, and S. Yates (see [2]) for sofic groups. Moreover, we give restrictions on the spectral measure of elements in the integral group ring. Finally, we define integer operators and prove a quantization of the operator norm below 2. To the knowledge of the author, there is no group known that is not sofic. (c) 2007 Wiley Periodicals, Inc
De Diæta Ad Longævitatem
No full text... Præside ... Francisco Josepho De Oberkamp ... Publicæ Eruditorum disquisitioni submittit Author Andreas Josephus Reyss ...Heidelberg, Univ., Diss., 175
Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study
No full textOBJECTIVES: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients. METHODS: A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models. RESULTS: BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment. CONCLUSIONS: The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype
Molecular Genetic Screening in Patients With ACE Inhibitor/Angiotensin Receptor Blocker-Induced Angioedema to Explore the Role of Hereditary Angioedema Genes
No full textAngioedema is a relatively rare but potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As with hereditary forms of angioedema (HAE), this adverse reaction is mediated by bradykinin. Research suggests that ACEi/ARB-induced angioedema has a multifactorial etiology. In addition, recent case reports suggest that some ACEi/ARB-induced angioedema patients may carry pathogenic HAE variants. The aim of the present study was to investigate the possible association between ACEi/ARB-induced angioedema and HAE genes
via
systematic molecular genetic screening in a large cohort of ACEi/ARB-induced angioedema cases. Targeted re-sequencing of five HAE-associated genes (
SERPING1
,
F12
,
PLG
,
ANGPT1
, and
KNG1
) was performed in 212 ACEi/ARB-induced angioedema patients recruited in Germany/Austria, Sweden, and Denmark, and in 352 controls from a German cohort. Among patients, none of the identified variants represented a known pathogenic variant for HAE. Moreover, no significant association with ACEi/ARB-induced angioedema was found for any of the identified common [minor allele frequency (MAF) >5%] or rare (MAF < 5%) variants. However, several non-significant trends suggestive of possible protective effects were observed. The lowest
p
-value for an individual variant was found in
PLG
(rs4252129, p.R523W,
p
= 0.057,
p
.adjust > 0.999, Fisher’s exact test). Variant p.R523W was found exclusively in controls and has previously been associated with decreased levels of plasminogen, a precursor of plasmin which is part of a pathway directly involved in bradykinin production. In addition, rare, potentially functional variants (MAF < 5%, Phred-scaled combined annotation dependent depletion score >10) showed a nominally significant enrichment in controls both: 1) across all five genes; and 2) in the
F12
gene alone. However, these results did not withstand correction for multiple testing. In conclusion, our results suggest that HAE-associated mutations are, at best, a rare cause of ACEi/ARB-induced angioedema. Furthermore, we were unable to identify a significant association between ACEi/ARB-induced angioedema and other variants in the investigated genes. Further studies with larger sample sizes are warranted to draw more definite conclusions concerning variants with limited effect sizes, including protective variants
Genetic and functional analyses implicate microRNA 499A in bipolar disorder development
No full textAbstract
Bipolar disorder (BD) is a complex mood disorder with a strong genetic component. Recent studies suggest that microRNAs contribute to psychiatric disorder development. In BD, specific candidate microRNAs have been implicated, in particular
miR-137
,
miR-499a
,
miR-708
,
miR-1908
and
miR-2113
. The aim of the present study was to determine the contribution of these five microRNAs to BD development. For this purpose, we performed: (i) gene-based tests of the five microRNA coding genes, using data from a large genome-wide association study of BD; (ii) gene-set analyses of predicted, brain-expressed target genes of the five microRNAs; (iii) resequencing of the five microRNA coding genes in 960 BD patients and 960 controls and (iv) in silico and functional studies for selected variants. Gene-based tests revealed a significant association with BD for
MIR499A
,
MIR708
,
MIR1908
and
MIR2113
. Gene-set analyses revealed a significant enrichment of BD associations in the brain-expressed target genes of
miR-137
and
miR-499a-5p
. Resequencing identified 32 distinct rare variants (minor allele frequency < 1%), all of which showed a non-significant numerical overrepresentation in BD patients compared to controls (
p
= 0.214). Seven rare variants were identified in the predicted stem-loop sequences of
MIR499A
and
MIR2113
. These included rs142927919 in
MIR2113
(
p
nom
= 0.331) and rs140486571 in
MIR499A
(
p
nom
= 0.297). In silico analyses predicted that rs140486571 might alter the
miR-499a
secondary structure. Functional analyses showed that rs140486571 significantly affects
miR-499a
processing and expression. Our results suggest that
MIR499A
dysregulation might contribute to BD development. Further research is warranted to elucidate the contribution of the
MIR499A
regulated network to BD susceptibility.Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659Bundesministerium für Bildung und Forschung https://doi.org/10.13039/501100002347Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung https://doi.org/10.13039/50110000171
High-voltage capacitively coupled contactless conductivity detection for conventional and microchip capillary electrophoresis
No full textThis thesis focuses on the optimisation of capacitively coupled contactless conductivity detection for capillary and microchip electrophoresis and its applications in analytical chemistry. First, the effect of high excitation voltages and operation frequencies on the capacitively coupled contactless conductivity detector cell for conventional capillary electrophoresis is evaluated. The detector electrodes comprised two steel tubes cut from hypodermic needles, through which the capillaries were inserted. It is demonstrated that increasing excitation voltages from 25 V pp, to 250 Vpp improves the detection limits by a factor of 10. The high actuator voltage approach was also investigated for contactless conductivity detection on a glass-microchip device with ancm long channel. The detector electrodes formed part of the microchip and were placed on the microchip directly above the microchannel. In a separate project the simplification of on-microchip contactless conductivity detection was accomplished. This was achieved by integrating the detector electrodes on to a chip-holder specifically designed for this purpose. Thus the electrodes were a part of the holder, an improvement of the previous arrangement whereby the detector electrodes were situated on the microdevice. Finally the applications and advantages of the optimised high-voltage capacitively coupled contactless conductivity detection for inorganic and organic analysis were demonstrated. The separation and detection of 14 metal ions was accomplished in less than six minutes. The compatibility of this detector with non-UV transparent, polymer capillaries has been demonstrated. The detection of native amino acids has been evaluated. Part of the work was dedicated to the on-chip analysis of various classes of organic ions. The two immunoproteins human immunoglobulin M (IgM) and immunoglobulin G (IgG), were analysed in their unlabelled state on both capillary and lab-on-chip platforms. All species involved in an immunological interaction between IgM and IgG could be detected. A method for the analysis of selected basic pharmaceutical drug substances was developed. Detection limits comparable to those supplied by direct UV detection were obtained. Main component assays of selected pharmaceutical preparations have been demonstrated
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