| 1. |
- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 2. |
- Topooco, Naira, et al.
(författare)
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Attitudes towards digital treatment for depression: A European stakeholder survey
- 2017
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Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background The integration of digital treatments into national mental health services is on the agenda in the European Union. The E-COMPARED consortium conducted a survey aimed at exploring stakeholders’ knowledge, acceptance and expectations of digital treatments for depression, and at identifying factors that might influence their opinions when considering the implementation of these approaches. Method An online survey was conducted in eight European countries: France, Germany, Netherlands, Poland, Spain, Sweden, Switzerland and The United Kingdom. Organisations representing government bodies, care providers, service-users, funding/insurance bodies, technical developers and researchers were invited to participate in the survey. The participating countries and organisations reflect the diversity in health care infrastructures and e-health implementation across Europe. Results A total of 764 organisations were invited to the survey during the period March–June 2014, with 175 of these organisations participating in our survey. The participating stakeholders reported moderate knowledge of digital treatments and considered cost-effectiveness to be the primary incentive for integration into care services. Low feasibility of delivery within existing care services was considered to be a primary barrier. Digital treatments were regarded more suitable for milder forms of depression. Stakeholders showed greater acceptability towards blended treatment (the integration of face-to-face and internet sessions within the same treatment protocol) compared to standalone internet treatments. Organisations in countries with developed e-health solutions reported greater knowledge and acceptability of digital treatments. Conclusion Mental health stakeholders in Europe are aware of the potential benefits of digital interventions. However, there are variations between countries and stakeholders in terms of level of knowledge about such interventions and their feasibility within routine care services. The high acceptance of blended treatments is an interesting finding that indicates a gradual integration of technology into clinical practice may fit the attitudes and needs of stakeholders. The potential of the blended treatment approach, in terms of enhancing acceptance of digital treatment while retaining the benefit of cost-effectiveness in delivery, should be further explored. Funding The E-COMPARED project has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 603098. © 2017 The Authors
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| 3. |
- Dees, M., et al.
(författare)
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Status and Future of Biomass Assessment for Energetic Use in Europe
- 2012
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Ingår i: 20th European Biomass Conference and Exhibition. - 9788889407547 ; , s. 23-24
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Konferensbidrag (refereegranskat)abstract
- Results from biomass potential assessments vary considerably, both on global and European level. On the other hand reliable figures on biomass potentials are an important basis for energy policy and for strategies that aim at an increase of use of biomass for energy both on EU-Level as well as e. g. on national level in the National Renewable Energy Action Plans (NREAPs) by the 27 member states. This paper is based on the findings of two projects, BEE and CEUBIOM. It presents an overview of the findings of these projects and includes an analysis of biomass potential aspects within the NREAPs. It presents how, based on an analysis of the status quo of potential studies, the projects developed proposals for a harmonisation of the methodologies and it presents the key areas they identified for future work in the field.
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| 4. |
- Engström, A E, et al.
(författare)
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Mechanical circulatory support with the Impella 5.0 device for postcardiotomy cardiogenic shock: a three-center experience
- 2013
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Ingår i: Minerva Cardioangiologica. - : Edizione Minerva Medica. - 0026-4725 .- 1827-1618. ; 61:5, s. 539-546
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Tidskriftsartikel (refereegranskat)abstract
- AIM:Postcardiotomy cardiogenic shock (PCCS) is associated with high mortality rates, despite full conventional treatment. Although the results of treatment with surgically implantable ventricular assist devices have been encouraging, the invasiveness of this treatment limits its applicability. Several less invasive devices have been developed, including the Impella system. The objective of this study was to describe our three-center experience with the Impella 5.0 device in the setting of PCCS.METHODS:From January 2004 through December 2010, a total of 46 patients were diagnosed with treatment-refractory PCCS and treated with the Impella 5.0 percutaneous left ventricular assist device at three european heart centers. Baseline and follow-up characteristics were collected retrospectively and entered into a dedicated database.RESULTS:Within the study cohort of 46 patients, mean logistic and additive EuroSCORES were 24 ± 19 and 10 ± 4. The majority of patients underwent coronary artery bypass grafting (48%) or combined surgery (33%). Half of all patients had been treated with an intra-aortic balloon pump before 5.0-implantation, 1 patient had been treated with an Impella 2.5 device. All patients were on mechanical ventilation and intravenous inotropes. The Kaplan-Meier estimate of overall 30-day survival was 39.5%.CONCLUSION:Thirty-day survival rates for patients with PCCS, refractory to aggressive conventional treatment and treated with the Impella 5.0 device, are comparable to those reported in studies evaluating surgically implantable VADs, whereas the Impella system is much less invasive. Therefore, mechanical circulatory support with the Impella 5.0 device is a suitable treatment modality for patients with severe PCCS.
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| 5. |
- Geris, J., et al.
(författare)
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Conceptual modelling to assess hydrological impacts and evaluate environmental flow scenarios in montane river systems regulated for hydropower
- 2014
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Ingår i: Rivers Research and Applications. - : Wiley. - 1535-1459 .- 1535-1467.
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Tidskriftsartikel (refereegranskat)abstract
- To improve understanding of natural and managed flow regimes in data-sparse regulated river systems in montane areas, the commonly used Hydrologiska Byråns Vattenbalansavdelning (HBV) conceptual run-off model was adapted to incorporate water regulation components. The extended model was then applied to the heavily regulated river Lyon (391 km2) in Scotland to reconstruct the natural flow regime and to assess the impacts of regulation at increasing spatial scales. Multi-criteria model evaluation demonstrated that the model performed well in capturing the dominant catchment processes and regulation effects, especially at the timescales at which operation rules apply. The main change as a result of regulation in the river Lyon is a decrease in inter-annual and intra-annual variability of all elements of the flow regime, in terms of magnitude, frequency, and duration. Although these impacts are most pronounced directly downstream of the impoundments, the regulation effects propagate throughout the river system. The modelling approach is flexible and widely applicable and only limited amounts of data are required. Moreover, results are easily communicated to stakeholders. It has the potential to contribute to the development of flow regimes that may be more beneficial to the ecological status of rivers. In the case of the river Lyon, it is likely that this involves a more variable release regime. The approach developed here provides a tool for assessing impacts on flow regimes and informing environmental flows in other data-sparse regions with heavily regulated montane river systems. Copyright © 2014 John Wiley & Sons, Ltd.
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| 6. |
- Kleiboer, A, et al.
(författare)
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European COMPARative Effectiveness research on blended Depression treatment versus treatment-as-usual (E-COMPARED): study protocol for a randomized controlled, non-inferiority trial in eight European countries
- 2016
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Ingår i: Trials. - London : BioMed Central. - 1745-6215. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Effective, accessible, and affordable depression treatment is of high importance considering the large personal and economic burden of depression. Internet-based treatment is considered a promising clinical and cost-effective alternative to current routine depression treatment strategies such as face-to-face psychotherapy. However, it is not clear whether research findings translate to routine clinical practice such as primary or specialized mental health care. The E-COMPARED project aims to gain knowledge on the clinical and cost-effectiveness of blended depression treatment compared to treatment-as-usual in routine care.Methods/design: E-COMPARED will employ a pragmatic, multinational, randomized controlled, non-inferiority trial in eight European countries. Adults diagnosed with major depressive disorder (MDD) will be recruited in primary care (Germany, Poland, Spain, Sweden, and the United Kingdom) or specialized mental health care (France, The Netherlands, and Switzerland). Regular care for depression is compared to "blended" service delivery combining mobile and Internet technologies with face-to-face treatment in one treatment protocol. Participants will be followed up at 3, 6, and 12 months after baseline to determine clinical improvements in symptoms of depression (primary outcome: Patient Health Questionnaire-9), remission of depression, and cost-effectiveness. Main analyses will be conducted on the pooled data from the eight countries (n = 1200 in total, 150 participants in each country).Discussion: The E-COMPARED project will provide mental health care stakeholders with evidence-based information and recommendations on the clinical and cost-effectiveness of blended depression treatment.Trial Registration: France: ClinicalTrials.gov NCT02542891 . Registered on 4 September 2015; Germany: German Clinical Trials Register DRKS00006866 . Registered on 2 December 2014; The Netherlands: Netherlands Trials Register NTR4962 . Registered on 5 January 2015; Poland: ClinicalTrials.Gov NCT02389660 . Registered on 18 February 2015; Spain: ClinicalTrials.gov NCT02361684 . Registered on 8 January 2015; Sweden: ClinicalTrials.gov NCT02449447 . Registered on 30 March 2015; Switzerland: ClinicalTrials.gov NCT02410616 . Registered on 2 April 2015; United Kingdom: ISRCTN registry, ISRCTN12388725 . Registered on 20 March 2015.
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| 7. |
- Wang, J. M., et al.
(författare)
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Melatonin receptor activation provides cerebral protection after traumatic brain injury by mitigating oxidative stress and inflammation via the Nrf2 signaling pathway
- 2019
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Ingår i: Free Radical Biology and Medicine. - : Elsevier BV. - 0891-5849. ; 131, s. 345-355
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is a principal cause of death and disability worldwide. Melatonin, a hormone made by the pineal gland, is known to have anti-inflammatory and antioxidant properties. In this study, using a weight-drop model of TBI, we investigated the protective effects of ramelteon, a melatonin MT1/MT2 receptor agonist, and its underlying mechanisms of action. Administration of ramelteon (10 mg/kg) daily at 10:00 a.m. alleviated TBI-induced early brain damage on day 3 and long-term neurobehavioral deficits on day 28 in C57BL/6 mice. Ramelteon also increased the protein levels of interleukin (IL)-10, IL-4, superoxide dismutase (SOD), glutathione, and glutathione peroxidase and reduced the protein levels of IL-1 beta, tumor necrosis factor, and malondialdehyde in brain tissue and serum on days 1, 3, and 7 post-TBI. Similarly, ramelteon attenuated microglial and astrocyte activation in the perilesional cortex on day 3. Furthermore, ramelteon decreased Keap 1 expression, promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation, and increased levels of downstream proteins, including SOD-1, heme oxygenase-1, and NQO1 on day 3 post-TBI. However, in Nrf2 knockout mice with TBI, ramelteon did not decrease the lesion volume, neuronal degeneration, or myelin loss on day 3; nor did it mitigate depression-like behavior or most motor behavior deficits on day 28. Thus, timed ramelteon treatment appears to prevent inflammation and oxidative stress via the Nrf2-antioxidant response element pathway and might represent a potential chronotherapeutic strategy for treating TBI.
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