Institution
Medical University of Graz
Education•Graz, Steiermark, Austria•
About: Medical University of Graz is a education organization based out in Graz, Steiermark, Austria. It is known for research contribution in the topics: Population & Medicine. The organization has 5684 authors who have published 12349 publications receiving 417282 citations.
Topics: Population, Medicine, Cancer, Transplantation, Vitamin D and neurology
Papers published on a yearly basis
Papers
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Hieab H.H. Adams1, Derrek P. Hibar2, Vincent Chouraki3, Vincent Chouraki4 +432 more•Institutions (110)
TL;DR: Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling.
Abstract: Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
185 citations
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University of Lorraine1, European Medicines Agency2, Humboldt University of Berlin3, University of Alberta4, University of Hull5, University of Minnesota6, Stavanger University Hospital7, Icahn School of Medicine at Mount Sinai8, University of Gothenburg9, Athens State University10, Northwestern University11, Duke University12, Linköping University13, Merck & Co.14, Tufts University15, Takeda Pharmaceutical Company16, University of Paris17, University of Brescia18, Bayer HealthCare Pharmaceuticals19, Medical University of Graz20, Albert Einstein College of Medicine21, University of London22, University of Zurich23, Novartis24, Harvard University25, Food and Drug Administration26, Campbell University27, Sahlgrenska University Hospital28, Amgen29, University of Glasgow30
TL;DR: The HFA‐ESC convened a group of expert heart failure clinical investigators, biostatisticians, regulators, and pharmaceutical industry scientists to evaluate the challenges of defining heart failure endpoints in clinical trials and to develop a consensus framework, and this report summarizes the group's recommendations for achieving common views on heart failureEndpoint selection.
Abstract: Endpoint selection is a critically important step in clinical trial design. It poses major challenges for investigators, regulators, and study sponsors, and it also has important clinical and practical implications for physicians and patients. Clinical outcomes of interest in heart failure trials include all-cause mortality, cause-specific mortality, relevant non-fatal morbidity (e.g. all-cause and cause-specific hospitalization), composites capturing both morbidity and mortality, safety, symptoms, functional capacity, and patient-reported outcomes. Each of these endpoints has strengths and weaknesses that create controversies regarding which is most appropriate in terms of clinical importance, sensitivity, reliability, and consistency. Not surprisingly, a lack of consensus exists within the scientific community regarding the optimal endpoint(s) for both acute and chronic heart failure trials. In an effort to address these issues, the Heart Failure Association of the European Society of Cardiology (HFA-ESC) convened a group of expert heart failure clinical investigators, biostatisticians, regulators, and pharmaceutical industry scientists (Nice, France, 1213 February 2012) to evaluate the challenges of defining heart failure endpoints in clinical trials and to develop a consensus framework. This report summarizes the groups recommendations for achieving common views on heart failure endpoints in clinical trials.
184 citations
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TL;DR: Resting TPR and PVR were higher than in the supine position and decreased more prominently during exercise, suggesting the release of resting pulmonary vasoconstriction, and may form a basis to define normal PVR at rest and exercise.
Abstract: The physiological range of pulmonary vascular resistance (PVR) and total pulmonary resistance (TPR), and the impact of exercise, age and posture have been a matter of debate for many years. We performed a systematic literature review including all right heart catheterisation data where individual PVR and TPR of healthy subjects both at rest and exercise were available. Data were stratified according to age, exercise level and posture. Supine resting PVR in subjects aged <24 yrs, 24-50 yrs, 51-69 yrs and ≥70 yrs was 61±23, 69±28, 86±15 and 90±39 dyn·s·cm(-5), respectively. Corresponding TPR was 165±50, 164±46, 226±64 and 223±45 dyn·s·cm(-5), respectively. During moderate exercise in subjects aged ≤50 yrs, an 85% increase in cardiac output was associated with a 25% decrease in TPR (p<0.0001) and a 12% decrease in PVR (p<0.01). At 51-69 yrs of age there was no significant decrease in TPR and PVR. In individuals aged ≥70 yrs TPR even increased by 17% (p=0.01), while PVR did not change significantly. At higher exercise levels, TPR decreased in all age groups. In the upright position, based on a limited number of data, resting TPR and PVR were higher than in the supine position and decreased more prominently during exercise, suggesting the release of resting pulmonary vasoconstriction. These data may form a basis to define normal PVR at rest and exercise.
184 citations
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TL;DR: A polarized distribution of gene-dense vs gene-poor chromatin within CTs with respect to the nuclear border is demonstrated and regional gene density is revealed as the decisive parameter determining the radial positioning of chromatin in the nucleus in contrast to band assignment, replication timing, and transcriptional activity.
Abstract: G- and R-bands of metaphase chromosomes are characterized by profound differences in gene density, CG content, replication timing, and chromatin compaction. The preferential localization of gene-dense, transcriptionally active, and early replicating chromatin in the nuclear interior and of gene-poor, later replicating chromatin at the nuclear envelope has been demonstrated to be evolutionary-conserved in various cell types. Yet, the impact of different local chromatin features on the radial nuclear arrangement of chromatin is still not well understood. In particular, it is not known whether radial chromatin positioning is preferentially shaped by local gene density per se or by other related parameters such as replication timing or transcriptional activity. The interdependence of these distinct chromatin features on the linear deoxyribonucleic acid (DNA) sequence precludes a simple dissection of these parameters with respect to their importance for the reorganization of the linear DNA organization into the distinct radial chromatin arrangements observed in the nuclear space. To analyze this problem, we generated probe sets of pooled bacterial artificial chromosome (BAC) clones from HSA 11, 12, 18, and 19 representing R/G-band-assigned chromatin, segments with different gene density and gene loci with different expression levels. Using multicolor 3D flourescent in situ hybridization (FISH) and 3D image analysis, we determined their localization in the nucleus and their positions within or outside the corresponding chromosome territory (CT). For each BAC data on local gene density within 2- and 10-Mb windows, as well as GC (guanine and cytosine) content, replication timing and expression levels were determined. A correlation analysis of these parameters with nuclear positioning revealed regional gene density as the decisive parameter determining the radial positioning of chromatin in the nucleus in contrast to band assignment, replication timing, and transcriptional activity. We demonstrate a polarized distribution of gene-dense vs gene-poor chromatin within CTs with respect to the nuclear border. Whereas we confirm previous reports that a particular gene-dense and transcriptionally highly active region of about 2 Mb on 11p15.5 often loops out from the territory surface, gene-dense and highly expressed sequences were not generally found preferentially at the CT surface as previously suggested.
183 citations
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Erasmus University Rotterdam1, University of Florence2, University of Barcelona3, Aarhus University4, VU University Medical Center5, Medical University of Graz6, University of Cambridge7, Carlos III Health Institute8, Autonomous University of Barcelona9, University of Graz10, University of Ioannina11
TL;DR: It is demonstrated that the COLIA1 Sp1 polymorphism is associated with reduced BMD and could predispose to incident vertebral fractures in women, independent of BMD, which is the largest ever performed in the field of osteoporosis genetics for a single gene.
Abstract: Background Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been no very-large-scale studies of COLIA1 alleles in relation to these phenotypes.
182 citations
Authors
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Name | H-index | Papers | Citations |
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Ian J. Deary | 166 | 1795 | 114161 |
James F. Wilson | 146 | 677 | 101883 |
Nancy L. Pedersen | 145 | 890 | 94696 |
William Wijns | 127 | 752 | 95517 |
Andrew Simmons | 102 | 460 | 36608 |
Franz Fazekas | 101 | 629 | 49775 |
Hans-Peter Hartung | 100 | 810 | 49792 |
Michael Trauner | 98 | 667 | 35543 |
Dietmar Fuchs | 97 | 1119 | 39758 |
Funda Meric-Bernstam | 96 | 753 | 36803 |
Ulf Landmesser | 94 | 564 | 46096 |
Aysegul A. Sahin | 93 | 322 | 30038 |
Frank Madeo | 92 | 269 | 45942 |
Takayoshi Ohkubo | 91 | 631 | 69634 |
Jürgen C. Becker | 90 | 637 | 28741 |