Graz, Austria

The Medical University of Graz is a university in Graz, Austria. Wikipedia.


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Grant
Agency: European Commission | Branch: H2020 | Program: CSA | Phase: INFRADEV-2-2015 | Award Amount: 1.44M | Year: 2016

ERINHA2 aims to complete the work carried out during the first preparatory phase (PP1) - ERINHA - in order to reach the financial, administrative and technical maturity necessary to complete the establishment of the Research Infrastructre and ensure that the operation phase can begin in 2018. ERINHA2 will therefore finalise the decision to use the status of an association and prepare the necessary legal document to register the RI depending on the country voted on to host the Central Coordinating Unit. ERINHA2 will prepare all procedures and protocols (human resources, IPR, ethics) needed to effectively operate the RI. The financial and business plans prepared in ERINHA (PP1) will updated and presented to national and international stakeholders to obtain their agreement to fund the infrastructure. An overarching group of activities - WP5, Stakeholders and commitment - will aim to accompany all partner countries in their efforts to obtain agreements and funding. This WP5 will ensure all relevant stakeholders and potential users are informed of the progress, services and benefits of ERINHA. The utlimate outcome of ERINHA2 will be the signtature of the ERINHA statutes among the founding countries to officially establish the RI and enter into the construction phase.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-24-2015 | Award Amount: 18.47M | Year: 2016

The management of febrile patients is one of the most common and important problems facing healthcare providers. Distinction between bacterial infections and trivial viral infection on clinical grounds is unreliable, and as a result innumerable patients worldwide undergo hospitalization, invasive investigation and are treated with antibiotics for presumed bacterial infection when, in fact, they are suffering from self-resolving viral infection. We aim to improve diagnosis and management of febrile patients, by application of sophisticated phenotypic, transcriptomic (genomic, proteomic) and bioinformatic approaches to well characterised large-scale, multi-national patient cohorts already recruited with EU funding. We will identify, and validate promising new discriminators of bacterial and viral infection including transcriptomic and clinical phenotypic markers. The most accurate markers distinguishing bacterial and viral infection will be evaluated in prospective cohorts of patients reflecting the different health care settings across European countries. By linking sophisticated new genomic and proteomic approaches to careful clinical phenotyping, and building on pilot data from our previous studies we will develop a comprehensive management plan for febrile patients which can be rolled out in healthcare systems across Europe.


Grant
Agency: European Commission | Branch: H2020 | Program: CSA | Phase: SC1-HCO-02-2016 | Award Amount: 2.08M | Year: 2017

Molecular in vitro diagnostics and biomedical research have allowed great progress in personalised medicine but further progress is limited by insufficient guidelines for pre-analytical workflow steps (sample collection, preservation, storage, transport, processing etc.) as well as by insufficient quality assurance of diagnostic practice. This allows using compromised patients samples with post collection changes in cellular and extra-cellular biomolecules profiles thus often making diagnostic test results unreliable or even impossible. To tackle this, SPIDA4P aims to generate and implement a comprehensive portfolio of 22 pan-European pre-analytical CEN/Technical Specifications and ISO/International Standards, addressing the important pre-analytical workflows applied to personalized medicine. These will also applicable to biomarker discovery, development and validation as well as to biobanks. Corresponding External Quality Assurance (EQA) Schemes will be developed and implemented as well, aiming to survey the resulting quality of samples and diagnostic practice. SPIDIA4P will ensure stakeholder organisations involvements as well as training, education, and counselling as additional major foci of the project. The consortium will closely coordinate with large European public research consortia to obtain access to research and validation studies data serving as evidence for the new standards developments and achieved improvements of diagnosis, patient stratification and prognosis of disease outcome. At this crucial moment in the development of personalised medicine, SPIDIA4P proposes a coordination and support action that reunites 19 highly experienced partners in international standardisation for in vitro diagnostics, coming from private industry including SMEs, public institutions and from one official European Standards Organisation. This strong consortium is balanced and empowered to maximise the impacts of in vitro diagnostics on personalised medicine.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: INFRAIA-1-2014-2015 | Award Amount: 10.23M | Year: 2015

The Europlanet 2020 Research Infrastructure (EPN2020-RI) will address key scientific and technological challenges facing modern planetary science by providing open access to state-of-the-art research data, models and facilities across the European Research Area. Its Transnational Access activities will provide access to world-leading laboratory facilities that simulate conditions found on planetary bodies as well as specific analogue field sites for Mars, Europa and Titan. Its Virtual Access activities will make available the diverse datasets and visualisation tools needed for comparing and understanding planetary environments in the Solar System and beyond. By providing the underpinning facilities that European planetary scientists need to conduct their research, EPN2020-RI will create cooperation and effective synergies between its different components: space exploration, ground-based observations, laboratory and field experiments, numerical modelling, and technology. EPN2020-RI builds on the foundations of successful FP6 and FP7 Europlanet programmes that established the Europlanet brand and built structures that will be used in the Networking Activities of EPN2020-RI to coordinate the European planetary science communitys research. It will disseminate its results to a wide range of stakeholders including industry, policy makers and, crucially, both the wider public and the next generation of researchers and opinion formers, now in education. As an Advanced Infrastructure we place particular emphasis on widening the participation of previously under-represented research communities and stakeholders. We will include new countries and Inclusiveness Member States, via workshops, team meetings, and personnel exchanges, to broaden/widen/expand and improve the scientific and innovation impact of the infrastructure. EPN2020-RI will therefore build a truly pan-European community that shares common goals, facilities, personnel, data and IP across national boundaries


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-EJD | Phase: MSCA-ITN-2014-EJD | Award Amount: 3.88M | Year: 2015

Many natural and artificial systems are often composed of oscillatory elements which, besides evolving according to their own non-trivial internal dynamics, mutually interact. As a result, many temporal and spatial scales are typically present, often accompanied by the spontaneous emergence of collective properties. Altogether, such features make the task of understanding the resulting evolution a challenging interdisciplinary problem. Zero-knowledge methods do generally require too large amount of data to allow drawing meaningful conclusions. In order to overcome this limitation, it is necessary to add skilful hypotheses about the structure of the underlying model and, thereby, on the relevant variables. This task is often tackled in an ad hoc way and the approach is based rather on personal preferences than on objective elements. The goal of this project is to fill the gap, by developing a general and coherent set of tools for the system identification and control, as well as to improve our ability to make predictions. The task will be pursued by combining top-down with bottom-up approaches which will be used to identify the most appropriate variables. Such analysis will be integrated by performing suitable case studies and mutually validating the various techniques to test the correctness of the underlying assumptions (both in the context of theoretical models as well as in experimental time series, such as physiological and neural data). A user-friendly software package will be ultimately developed to make the methods accessible to a broad set of potential users, including those with minimal theoretical competences. Furthermore, we will train a new generation of scientists able to implement a broad range of interdisciplinary approaches to the multivariate time signals that may be generated by the evolution of complex systems.


Holzer P.,Medical University of Graz
Pharmacology and Therapeutics | Year: 2011

Approximately 20 of the 30 mammalian transient receptor potential (TRP) channel subunits are expressed by specific neurons and cells within the alimentary canal. They subserve important roles in taste, chemesthesis, mechanosensation, pain and hyperalgesia and contribute to the regulation of gastrointestinal motility, absorptive and secretory processes, blood flow, and mucosal homeostasis. In a cellular perspective, TRP channels operate either as primary detectors of chemical and physical stimuli, as secondary transducers of ionotropic or metabotropic receptors, or as ion transport channels. The polymodal sensory function of TRPA1, TRPM5, TRPM8, TRPP2, TRPV1, TRPV3 and TRPV4 enables the digestive system to survey its physical and chemical environment, which is relevant to all processes of digestion. TRPV5 and TRPV6 as well as TRPM6 and TRPM7 contribute to the absorption of Ca2+ and Mg 2+, respectively. TRPM7 participates in intestinal pacemaker activity, and TRPC4 transduces muscarinic acetylcholine receptor activation to smooth muscle contraction. Changes in TRP channel expression or function are associated with a variety of diseases/disorders of the digestive system, notably gastro-esophageal reflux disease, inflammatory bowel disease, pain and hyperalgesia in heartburn, functional dyspepsia and irritable bowel syndrome, cholera, hypomagnesemia with secondary hypocalcemia, infantile hypertrophic pyloric stenosis, esophageal, gastrointestinal and pancreatic cancer, and polycystic liver disease. These implications identify TRP channels as promising drug targets for the management of a number of gastrointestinal pathologies. As a result, major efforts are put into the development of selective TRP channel agonists and antagonists and the assessment of their therapeutic potential. © 2011 Elsevier Inc.


Ulz P.,Medical University of Graz
Nature Genetics | Year: 2016

The analysis of cell-free DNA (cfDNA) in plasma represents a rapidly advancing field in medicine. cfDNA consists predominantly of nucleosome-protected DNA shed into the bloodstream by cells undergoing apoptosis. We performed whole-genome sequencing of plasma DNA and identified two discrete regions at transcription start sites (TSSs) where nucleosome occupancy results in different read depth coverage patterns for expressed and silent genes. By employing machine learning for gene classification, we found that the plasma DNA read depth patterns from healthy donors reflected the expression signature of hematopoietic cells. In patients with cancer having metastatic disease, we were able to classify expressed cancer driver genes in regions with somatic copy number gains with high accuracy. We were able to determine the expressed isoform of genes with several TSSs, as confirmed by RNA-seq analysis of the matching primary tumor. Our analyses provide functional information about cells releasing their DNA into the circulation. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Autoimmunity and immune dysregulation may lead to cytopenia and represent key features of many primary immunodeficiencies (PIDs). Especially when cytopenia is the initial symptom of a PID, the order and depth of diagnostic steps have to be performed in accordance with both an immunologic and a hematologic approach and will help exclude disorders such as systemic lupus erythematosus, common variable immunodeficiency, and autoimmune lymphoproliferative syndromes, hemophagocytic disorders, lymphoproliferative diseases, and novel differential diagnoses such as MonoMac syndrome (GATA2 deficiency), CD27 deficiency, lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency, activated PI3KD syndrome (APDS), X-linked immunodeficiency with magnesium defect (MAGT1 deficiency), and others. Immunosuppressive treatment often needs to be initiated urgently, which impedes further relevant immunologic laboratory analyses aimed at defining the underlying PID. Awareness of potentially involved disease spectra ranging from hematologic to rheumatologic and immunologic disorders is crucial for identifying a certain proportion of PID phenotypes and genotypes among descriptive diagnoses such as autoimmune hemolytic anemia, chronic immune thrombocytopenia, Evans syndrome, severe aplastic anemia/refractory cytopenia, and others. A synopsis of pathomechanisms, novel differential diagnoses, and advances in treatment options for cytopenias in PID is provided to facilitate multidisciplinary management and to bridge different approaches. © 2014 by The American Society of Hematology.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-09-2016 | Award Amount: 4.95M | Year: 2017

TYPE 1 DIABETES is one of the most COMMON CHRONIC diseases in children with a RAPID increase in number of cases particularly in young children. Type 1 diabetes is associated with LIFE-LONG dependency on insulin administration. POOR glucose control leads to diabetes COMPLICATIONS, e.g. eye, heart, kidney disease, including BRAIN changes in young children. Episodes of VERY LOW glucose levels may be life threatening and are a major complication. The ARTIFICIAL PANCREAS addresses the problem of LOW and HIGH glucose levels by delivering insulin BELOW and ABOVE pre-set amounts according to real-time sensor GLUCOSE levels, combining glucose SENSOR, insulin PUMP, and CONTROL ALGORITHM. The Artificial pancreas promises to TRANSFORM management of type 1 diabetes but EVIDENCE supporting its use during FREE LIVING in YOUNG CHILDREN is MISSING. The project evaluates the biomedical, psychosocial, and cost effectiveness of NOVEL INDIVIDUALISED artificial pancreas in young children aged 1 to 7 years with type 1 diabetes. Following a PILOT (n=24), in the MAIN study (n=94) half of the participants (n=47) will be treated over 12 MONTHS by the ARTIFICIAL PANCREAS and the other half (n=47) by STATE-OF-THE-ART PREDICTIVE LOW GLUCOSE MANAGEMENT insulin pump therapy. Each treatment will last ONE YEAR. QUALITY OF LIFE will be assessed and semi-structured INTERVIEWS conducted to understand the impact on daily life. HEALTH TECHNOLOGY ASSESSMENT will support reimbursement. The project will OPTIMISE artificial pancreas and SPEARHEAD SYSTEM-WIDE improvements in health care quality and health outcomes in YOUNG CHILDERN with TYPE 1 DIABETES who live with the disease LONGEST. By IMPROVING THERAPEUTIC OUTCOMES, the project will CHANGE clinical practice and INFLUENCE national and international treatment guidelines making the artificial pancreas WIDELY ACCEPTABLE as the state-of-art treatment modality in young children.


Borderline pulmonary arterial hypertension (PAH), characterized by a marked exercise-induced increase in pulmonary artery pressure (PAP) with normal resting values, may precede overt PAH in systemic sclerosis (SSc). We undertook the present study to investigate whether PAH treatment is safe in these patients and might attenuate hemodynamic progression. SSc patients with borderline PAH underwent right heart catheterization at baseline, after a 12-month observation period, and subsequently after 6 months of bosentan therapy. Changes in mean PAP at 50W during the observation period versus during therapy were compared. Ten patients completed the study. Mean PAP at rest, at 50W, and during maximal exercise increased significantly during the observation period (mean ± SD increases of 2.5 ± 3.0 mm Hg [P = 0.03], 4.0 ± 2.9 mm Hg [P = 0.002], and 6.8 ± 4.1 mm Hg [P = 0.0005], respectively) and tended to decrease during the treatment period (decreases of 2.5 ± 3.9 mm Hg [P = 0.07], 1.5 ± 4.5 mm Hg [P = 0.32], and 1.8 ± 7.0 mm Hg [P = 0.43], respectively). The changes during the observation period versus the therapy period were significantly different (P = 0.03 at rest, P = 0.01 at 50W [primary end point], and P = 0.02 during maximal exercise). The changes in resting pulmonary vascular resistance were also significantly different during the observation period (increase of 8 ± 25 dynes · seconds · cm(-5) ) versus during the therapy period (decrease of 45 ± 22 dynes · seconds · cm(-5) ) (P < 0.0005). Changes in resting pulmonary arterial wedge pressure were not significantly different between the observation period and the treatment period, despite the significant increase during the observation period (2.6 ± 2.5 mm Hg [P = 0.01]). No relevant adverse effects were reported. In SSc patients with borderline abnormal pulmonary hemodynamics, resting and exercise PAP may increase significantly within 1 year of observation. Bosentan might be safe and effective to attenuate these changes. Randomized controlled trials are warranted to confirm the exploratory findings of this hypothesis-generating pilot study. Copyright © 2012 by the American College of Rheumatology.

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