Basel, Switzerland
Basel, Switzerland

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Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-2 | Award Amount: 8.13M | Year: 2013

Mental disorders are leading causes of disability, absence from work and premature retirement in Europe. While magnetic resonance imaging (MRI) facilities are broadly available and a vast research literature exists, few neuroimaging applications have reached clinical practice in psychiatry. A major problem is that mental illnesses are currently diagnosed as discrete entities defined clinically. Instead, recent results show that mental disorders are best understood as quantitative alterations in neural systems relevant across traditional diagnostic boundaries that reflect individual, genetic and environmental risk factors. In the IMAGEMEND consortium, we aim to discover these systems to identify the patient characteristics most relevant for treatment, derive biomarkers and decision rules from this systems-level dimensional account, and systematically validate biomarker panels in patient, high-risk and epidemiological samples to produce automated imaging-based diagnostic and predictive tests tailored for wide distribution throughout Europe in standard clinical settings. Focusing on schizophrenia, bipolar disorder and attention deficit-hyperactivity disorder, we have assembled Europes largest dataset combining neuroimaging, genetic, environmental, cognitive and clinical information on approximately 13000 participants, and have recruited international replication datasets of more than 30000 people. This unique resource will be processed using a new generation of multivariate statistical analysis to optimize existing imaging technology for the benefit of patients. We will also develop new imaging technology to enable the direct imaging-based therapeutic modification of neural circuits through rapid real-time MRI. Our deliverables will promote personalized treatment through more accurate patient stratification, allow diagnoses at the pre-symptomatic stage for early intervention and prevention, and improve prediction of treatment response and disease progression.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.3.1-1 | Award Amount: 7.75M | Year: 2014

Transition to adulthood is the period of onset of most of the serious mental disorders that disable or kill in adult life. Current service configuration of distinct Child and Adolescent Mental Health (CAMHS) and Adult Mental Health (AMHS) Services is considered the weakest link where the care pathway should be most robust. Transition-related discontinuity of care is a major socioeconomic and societal challenge for the EU. The MILESTONE project is an EU-wide study determining care gaps in current services across diverse healthcare systems and robustly evaluating an innovative transitional care model. In ten high-quality work packages we will map current services and transitional policies across EU; develop and validate transition-specific outcomes measures; conduct a longitudinal cohort study of transition process and outcomes across eight EU countries; develop and test, in a cluster-randomised trial, the clinical and cost-effectiveness of an innovative transitional care model; create clinical, organisational, policy and ethics guidelines for improving care and outcomes for transition age youth; and develop and implement training packages for clinicians across EU. The project will provide robust evidence for the most cost-effective way to meet the as-yet-unmet need of young people who fall through the CAMHS-AMHS divide; facilitate the development of integrated models of care and function; improve health care outcomes and system efficiencies; and ensure take-up of best practice. The project has active and intensive participation of young people, carers, advocacy groups and key stakeholders and involves two SMEs, Concentris and HealthTracker. Findings from the project will transform mental health care in EU for young people. Our results will assist policy makers in making informed and evidence-based decisions for improving health systems, enhancing patient outcomes, quality of life, service satisfaction, and improving health status at individual and population levels.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 6.19M | Year: 2016

Understanding mechanisms underlying comorbid disorders poses a challenge for developing precision medicine tools. Psychiatric disorders are highly comorbid, and are among the last areas of medicine, where classification is driven by phenomenology rather than pathophysiology. We will study comorbidity between the most frequent psychiatric conditions, ADHD, mood/anxiety, and substance use disorders, and a highly prevalent somatic disease, obesity. ADHD, a childhood-onset disorder, forms the entry into a lifelong negative trajectory characterized by these comorbidities. Common mechanisms underlying this course are unknown, despite their relevance for early detection, prevention, and treatment. Our interdisciplinary team of experts will integrate epidemiologic/genetic approaches with experimental designs to address those issues. We will determine disease burden of comorbidity, calculate its socioeconomic impact, and reveal risk factors. We will study biological pathways of comorbidity and derive biomarkers, prioritizing two candidate mechanisms (circadian rhythm and dopaminergic neurotransmission), but also leveraging large existing data sets to identify new ones. A pilot clinical trial to study non-pharmacologic, dopamine-based and chronobiological treatments will be performed, employing innovative mHealth to monitor and support patients daily life. Integration of findings will lead to prediction algorithms enhancing early diagnosis and prevention of comorbidity. Finally, we will screen to repurpose existing pharmacological compounds. Integrating complementary approaches based on large-scale, existing data and innovative data collection, we maximize value for money in this project, leading to insight into the mechanisms underlying this comorbidity triad with its huge burden for healthcare, economy, and society. This will facilitate early detection and non-invasive, scalable, and low-cost treatment, creating opportunities for substantial and immediate societal impact.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-04-2016 | Award Amount: 10.41M | Year: 2017

Early life is an important window of opportunity to improve health across the full lifecycle. European pregnancy and child cohort studies together offer an unique opportunity to identify a wide range of early life stressors linked with individual biological, developmental and health trajectory variations, and to the onset and evolution of non-communicable diseases. LIFECYCLE will establish the EuroCHILD Cohort Network, which brings together existing, successful pregnancy and child cohorts and biobanks, by developing a governance structure taking account of national and European ethical, legal and societal implications, a shared data-management platform and data-harmonization strategies. LIFECYCLE will enrich this EuroCHILD Cohort Network by generating new integrated data on early life stressors related to socio-economic, migration, urban environment and life-style determinants, and will capitalize on these data by performing hypothesis-driven research on early life stressors influencing cardio-metabolic, respiratory and mental health trajectories during the full lifecycle, and the underlying epigenetic mechanisms. LIFECYCLE will translate these results into recommendations for targeted strategies and personalized prediction models to improve health trajectories for current and future Europeans generations by optimizing their earliest phase of life. To strengthen this long-term collaboration, LIFECYCLE will organize yearly international meetings open to pregnancy and child cohort researchers, introduce a Fellowship Training Programme for exchange of junior researchers between European pregnancy or child cohorts, and develop e-learning modules for researchers performing life-course health studies. Ultimately, LIFECYCLE will lead to a unique sustainable EuroCHILD Cohort Network, and provide recommendations for targeted prevention strategies by identification of novel markers of early life stressors related to health trajectories throughout the lifecycle.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-3 | Award Amount: 8.15M | Year: 2013

Aggression is a basic physiological trait with important roles throughout evolution, both in defence and predation. When expressed in humans in the wrong context, aggression leads to maladjustment, social impairment and crime. Despite this, knowledge about aggression aetiology is limited and current treatment strategies are insufficient. Contingent to a subdivision into impulsive and instrumental subtypes, we investigate the aetiology of maladaptive aggression in paediatric conduct disorders most strongly predisposing to pathological aggression, ADHD and conduct disorder, and in the general population. We employ highly innovative approaches in humans and animal models and maximize the output from the project by optimally balancing the use of large, existing data sets with new data acquisition. Through this, we build a knowledge chain from molecule to behaviour, investigating known and novel genes, gene-networks and their epigenetic interactions, and mapping their mode of action from the molecular via the cellular to the brain-circuit level. This is accompanied by highly powered analyses of the neural substrates of the aggression subtypes. Based on innovative bioinformatic multimodal data integration, our interdisciplinary research will lead to novel, accurate algorithms for reliable aggression prediction, which will be validated in existing longitudinal studies in children and tested for their predictive value in adult outcome. In addition to this approach towards prevention, we test promising non-pharmacological biofeedback for personalised treatment and prevention of overt aggression. For the identification of novel pharmacological compounds in aggression treatment, we introduce a new animal model, the zebrafish. The Aggressotype consortium is based on successful existing collaborations. It includes experts in childhood and adult psychiatry and research-intensive SMEs ensuring maximal dissemination, clinical implementation and business development opportunities.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.1.1-1 | Award Amount: 14.69M | Year: 2013

Cancers are genetic disease arising from the accumulation of multiple molecular alterations in affected cells. Large-scale genomic, transcriptomic and proteomic analyses have established comprehensive catalogues of molecules which are altered in their structure and/or abundance in malignant tumors as compared to healthy tissues. Far less developed are concepts and methods to integrate data from different sources and to directly interrogate gene functions on a large scale in order to differentiate driver alterations, which directly contribute to tumor progression, from indolent passenger alterations. As a consequence, examples of successful translation of knowledge generated from omics approaches into novel clinical concepts and applications are scarce. Pancreatic cancer is a prime example of this dilemma. Representing the 4th to 5th most common cause of cancer related deaths, it is a disease with a major socioeconomic impact. Despite enormous advances in the identification of molecular changes associated with the disease, new treatment options have not emerged. Thus, 5-year survival rates remain unchanged at a dismal 6%, the lowest for all solid tumors. Using pancreatic cancer as a model disease, the goal of this integrative project is to develop novel cellular and animal models, as well as novel strategies to generate, analyze and integrate large scale metabolic and transcriptomic data from these models, in order to systematically characterize and validate novel targets for therapeutic intervention. In addition to the general tumor cell population, special consideration will be given to sub-populations of tumor-initiating cells, a.k.a. tumor stem cells. To this end, the consortium comprises i) SMEs with strong focus on technology development, ii) clinical and academic partners with extensive experience in pancreatic cancer molecular biology and management of pancreatic cancer patients, and iii) technology and data analysis experts from academic groups.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-04-2016 | Award Amount: 9.71M | Year: 2017

The projects overall aim is to improve the health, development and quality of life of children and adults born very preterm (VPT, < 32 weeks of gestation) or very low birth weight (VLBW, < 1500g) approximately 50 000 births each year in Europe by establishing an ICT platform to integrate, harmonise and exploit the wealth of data from 20 European cohorts of VPT/VLBW children and adults and their families constituted from the early 1980s to the present, together with data from national registries. VPT/VLBW births have higher risks of cerebral palsy, visual and auditory deficits, impaired cognitive ability, psychiatric disorders and social problems than infants born at term and account for more than a third of the health and educational budgets for children. They may also face higher risks of non-communicable disease as they age. There is emerging evidence of reduced mental health, quality of life, partnering, family life and employment chances and wealth in adulthood. The platform will enable stratified sub-group analyses of sociodemographic and clinical characteristics, neonatal complications, and otherwise rare medical conditions that cannot be studied in national population cohorts. The broad temporal, geographic, cultural and health system diversity makes it possible to study the impact of socioeconomic and organisational contexts and determine the generalisability of outcomes for VPT/VLBW populations. The RECAP platform creates a value chain to promote research and innovation using population cohorts, beginning with the integration of VPT/VLBW cohorts to the translation and dissemination of new knowledge. It will be based on a sustainable governance framework, state-of-the art data management and sharing technologies, tools to strengthen research capacity, a hypothesis-driven research agenda and broad stakeholder participation, including researchers, clinicians, educators, policy makers and very preterm children and adults and their families.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.2-1 | Award Amount: 7.83M | Year: 2014

Background: Hyperinsulinaemic hypoglycaemia (HH) is a potentially lethal disease caused by over functioning beta cells derived from the pancreatic islets of Langerhans. Lethal HH and brain damage is a problem especially in infants with congenital HH. Current therapeutic approaches are associated with severe side effects/morbidity (diabetes, exocrine pancreas insufficiency etc.) considered acceptable in relation to the lethal outcome of HH although massively reducing quality of life and also life expectancy. Aims and objectives: In order to significantly improve therapy of this awful disorder, we propose to develop a simultaneous imaging/therapy platform allowing diagnostic imaging as well as image guided surgical, photodynamic or radiopeptide therapy to selectively resect/destroy diseased beta cells. This platform will enable delivery of patient-individual tailored therapy, increasing cure rate while significantly reducing or even avoiding side effects. The platform will integrate information from pre-clinical imaging for optimal therapy planning with intra-operative imaging for image guided surgery. By implementation of extended field optical coherence tomography, information on a histopathological level will allow increased precision of therapy. Highly innovative photodynamic therapy will enable selective (endoscopic) destruction of diseased beta cells without resection of pancreatic tissue. Outcome: Our highly-innovative integrated imaging/therapy (theranostic) platform will allow diagnosis and monitoring of disease, support and guide therapeutic intervention, predict outcome of intervention and individual prognosis. This technology will massively improve therapy, especially in infants, by improving cure rates while significantly reducing morbidity for improved quality of life and increased life expectancy. We will contribute to the goals of the International Rare Diseases Research Consortium (IRDiRC): 200 new therapies.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-3 | Award Amount: 5.84M | Year: 2014

Conduct Disorder (CD) is the key paediatric disorder characterized by severe aggression. It is heterogeneous, and our understanding of the neurobiology to subtype aggression is limited. MATRICS is a multidisciplinary consortium of academic partners and SMEs that focuses on the subtyping of aggression both within CD and of the broader cross-disorder trait of aggression. MATRICS will test the hypothesis that reactive and instrumental aggression result from aberrant autonomic reactivity coupled to the differential impairment of three basic neural functions: 1) regulation of control mechanisms of aggression, 2) emotional value rating of others, and 3) empathy and moral decision making. MATRICS will employ the same psychological tasks assessing 1), 2) and 3) in animal aggression models and human CD samples concurrent with the assessment of neural, neurochemical, (epi)-genetic and autonomic nervous system markers. These data will be integrated with matching expression profiling from neurons derived from CD IPSCs. MATRICS also examines how environmental risks, whether or not they interact with genetic factors, are translated in epigenetic and neural changes. MATRICS will data-mine existing large integrated imaging-genetics cohorts (NeuroIMAGE; IMAGEN) and prospective cohorts (TRAILS; ALSPAC) with follow-up into adulthood and the (epi)genetic profiling of the PERS CD cohort, and collect a large new CD cohort and controls for collection of MRI, (epi)-genetic, biochemical and environmental measures. Bayesian machine learning tools will integrate multi-source and multi-level data, and generate predictive algorithms of persistent aggression into adulthood. MATRICS will identify new potentially druggable targets, develop novel animal models and conduct pilot medication and neuro/biofeedback studies in high-risk and CD patients. MATRICS builds on existing fruitful EU collaborations which maximises feasibility and successful output.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: FETOPEN-01-2016-2017 | Award Amount: 5.73M | Year: 2017

We envision a radical redesign of Earth observation platforms for sustained operation at significantly lower altitudes than the current state of the art, using a combination of new aerodynamic materials, aerodynamic control and air-breathing electric propulsion for drag-compensation, for a variety of observation methods with the aim of creating a new platform paradigm. This vision requires foundational research in spacecraft aerodynamic characterization, in material aerodynamics and atomic oxygen resistance, in electric propulsion, and control methods. These activities are by their nature multidisciplinary covering atmospheric science, surface chemistry and material characterization, control engineering, spacecraft design, payload engineering, etc.

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