| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 3. |
- Geser, F, et al.
(författare)
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The European Multiple System Atrophy-Study Group (EMSA-SG)
- 2005
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Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 112:12, s. 1677-1686
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. The European Multiple System Atrophy-Study Group (EMSA-SG) is an academic network comprising 23 centers across Europe and Israel that has constituted itself already in January 1999. This international forum of established experts under the guidance of the University Hospital of Innsbruck as coordinating center is supported by the 5th framework program of the European Union since March 2001 (QLK6-CT-2000-00661). Objectives. Primary goals of the network include (1) a central Registry for European multiple system atrophy (MSA) patients, (2) a decentralized DNA Bank, (3) the development and validation of the novel Unified MSA Rating Scale (UMSARS), (4) the conduction of a Natural History Study (NHS), and (5) the planning or implementation of interventional therapeutic trials. Methods. The EMSA-SG Registry is a computerized data bank localized at the coordinating centre in Innsbruck collecting diagnostic and therapeutic data of MSA patients. Blood samples of patients and controls are recruited into the DNA Bank. The UMSARS is a novel specific rating instrument that has been developed and validated by the EMSA-SG. The NHS comprises assessments of basic anthropometric data as well as a range of scales including the UMSARS, Unified Parkinson's Disease Rating Scale (UPDRS), measures of global disability, Red Flag list, MMSE (Mini Mental State Examination), quality of live measures, i.e. EuroQoL 5D (EQ-5D) and Medical Outcome Study Short Form (SF-36) as well as the Beck Depression Inventory (BDI). In a subgroup of patients dysautonomic features are recorded in detail using the Queen Square Cardiovascular Autonomic Function Test Battery, the Composite Autonomic Symptom Scale (COMPASS) and measurements of residual urinary volume. Most of these measures are repeated at 6-monthly follow up visits for a total study period of 24 months. Surrogate markers of the disease progression are identified by the EMSA-SG using magnetic resonance and diffusion weighted imaging (MRI and DWI, respectively). Results. 412 patients have been recruited into the Registry so far. Probable MSA-P was the most common diagnosis (49% of cases). 507 patients donated DNA for research. 131 patients have been recruited into the NHS. There was a rapid deterioration of the motor disorder (in particular akinesia) by 26.1% of the UMSARS II, and - to a lesser degree - of activities of daily living by 16.8% of the UMSARS I in relation to the respective baseline scores. Motor progression was associated with low motor or global disability as well as low akinesia or cerebellar subscores at baseline. Mental function did not deteriorate during this short follow up period. Conclusion. For the first time, prospective data concerning disease progression are available. Such data about the natural history and prognosis of MSA as well as surrogate markers of disease process allow planning and implementation of multi-centre phase II/III neuroprotective intervention trials within the next years more effectively. Indeed, a trial on growth hormone in MSA has just been completed, and another on minocycline will be completed by the end of this year.
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| 4. |
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| 5. |
- Schrag, A, et al.
(författare)
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Health-related quality of life in multiple system atrophy
- 2006
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 21:6, s. 809-815
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Tidskriftsartikel (refereegranskat)abstract
- Although multiple system atrophy (MSA) is a neurodegenerative disorder leading to progressive disability and decreased life expectancy, little is known about patients' own evaluation of their illness and factors associated with poor health-related quality of life (Hr-QoL). We, therefore, assessed Hr-QoL and its determinants in MSA. The following scales were applied to 115 patients in the European MSA-Study Group (EMSA-SG) Natural History Study: Medical Outcome Study Short Form (SF-36), EQ-513, Beck Depression Inventory (BDI), Mini-Mental state examination (MMSE), Unified MSA Rating Scale (UMSARS), Hoehn & Yahr (H&Y) Parkinson's disease staging scale, Composite Autonomic Symptom Scale (COMPASS), and Parkinson's Disease Sleep Scale (PDSS). Forty-six percent of patients had moderate to severe depression (BDI >= 17); Hr-QoL scores on the SF-36 and EQ-5D were significantly impaired. Pain, the only domain with similar scores in MSA and published PD patients, was reported more frequently in patients with MSA-P (predominantly parkinsonian motor subtype) than MSA-C (predominantly cerebellar motor subtype; 76% vs. 50%; P = 0.005). Hr-QoL scores correlated most strongly with UMSARS motor, COMPASS, and BDI scores but not with MMSE scores, age at onset, or disease duration. The COMPASS and UMSARS activities of daily living scores were moderate-to-strong predictors for the SF-36 physical summary score and the BDI and UMSARS motor scores for the SF-36 mental summary score. This report is the first study to show that Hr-QoL is significantly impaired in MSA. Although not all possible factors related to impaired Hr-QoL in MSA could be assessed, autonomic dysfunction, motor impairment, and depression were most closely associated with poor Hr-QoL, and therapeutic management, therefore, should concentrate upon these aspects of the disease. (c) 2006 Movement Disorder Society.
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| 6. |
- Anderson, J. L., et al.
(författare)
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The Fishery Performance Indicators: A Management Tool for Triple Bottom Line Outcomes
- 2015
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Pursuit of the triple bottom line of economic, community and ecological sustainability has increased the complexity of fishery management; fisheries assessments require new types of data and analysis to guide science-based policy in addition to traditional biological information and modeling. We introduce the Fishery Performance Indicators (FPIs), a broadly applicable and flexible tool for assessing performance in individual fisheries, and for establishing cross-sectional links between enabling conditions, management strategies and triple bottom line outcomes. Conceptually separating measures of performance, the FPIs use 68 individual outcome metrics-coded on a 1 to 5 scale based on expert assessment to facilitate application to data poor fisheries and sectors-that can be partitioned into sectorbased or triple-bottom-line sustainability-based interpretative indicators. Variation among outcomes is explained with 54 similarly structured metrics of inputs, management approaches and enabling conditions. Using 61 initial fishery case studies drawn from industrial and developing countries around the world, we demonstrate the inferential importance of tracking economic and community outcomes, in addition to resource status.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Gamble, LD, et al.
(författare)
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A G316A Polymorphism in the Ornithine Decarboxylase Gene Promoter Modulates MYCN-Driven Childhood Neuroblastoma
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of ODC1, results in genotypes wildtype GG, and variants AG/AA. CRISPR-cas9 technology was used to investigate the effects of AG clones from wildtype MYCN-amplified SK-N-BE(2)-C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. AG clones exhibited decreased ODC1 expression, growth rates, and histone acetylation and increased sensitivity to ODC1 inhibition. MYCN was a stronger transcriptional regulator of the ODC1 promoter containing the G allele, and preferentially bound the G allele over the A. Two neuroblastoma cohorts were used to investigate the clinical impact of the SNP. In the study cohort, the minor AA genotype was associated with improved survival, while poor prognosis was associated with the GG genotype and AG/GG genotypes in MYCN-amplified and non-amplified patients, respectively. These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele-specific regulation by the MYCN oncoprotein.
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| 11. |
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| 12. |
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| 13. |
- Nguyen-Cong, Kien, et al.
(författare)
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Extreme Metastability of Diamond and its Transformation to the BC8 Post-Diamond Phase of Carbon
- 2024
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Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 15:4, s. 1152-1160
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Tidskriftsartikel (refereegranskat)abstract
- Diamond possesses exceptional physical properties due to its remarkably strong carbon-carbon bonding, leading to significant resilience to structural transformations at very high pressures and temperatures. Despite several experimental attempts, synthesis and recovery of the theoretically predicted post-diamond BC8 phase remains elusive. Through quantum-accurate multimillion atom molecular dynamics (MD) simulations, we have uncovered the extreme metastability of diamond at very high pressures, significantly exceeding its range of thermodynamic stability. We predict the post-diamond BC8 phase to be experimentally accessible only within a narrow high pressure-temperature region of the carbon phase diagram. The diamond to BC8 transformation proceeds through premelting followed by BC8 nucleation and growth in the metastable carbon liquid. We propose a double-shock compression pathway for BC8 synthesis, which is currently being explored in experiments at the National Ignition Facility.
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| 14. |
- Santo, E. E., et al.
(författare)
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Oncogenic activation of FOXR1 by 11q23 intrachromosomal deletion-fusions in neuroblastoma
- 2012
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 31:12, s. 1571-1581
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma tumors frequently show loss of heterozygosity of chromosome 11q with a shortest region of overlap in the 11q23 region. These deletions are thought to cause inactivation of tumor suppressor genes leading to haploinsufficiency. Alternatively, micro-deletions could lead to gene fusion products that are tumor driving. To identify such events we analyzed a series of neuroblastomas by comparative genomic hybridization and single-nucleotide polymorphism arrays and integrated these data with Affymetrix mRNA profiling data with the bioinformatic tool R2 (http://r2.amc.nl). We identified three neuroblastoma samples with small interstitial deletions at 11q23, upstream of the forkhead-box R1 transcription factor (FOXR1). Genes at the proximal side of the deletion were fused to FOXR1, resulting in fusion transcripts of MLL-FOXR1 and PAFAH1B2-FOXR1. FOXR1 expression has only been detected in early embryogenesis. Affymetrix microarray analysis showed high FOXR1 mRNA expression exclusively in the neuroblastomas with micro-deletions and rare cases of other tumor types, including osteosarcoma cell line HOS. RNAi silencing of FOXR1 strongly inhibited proliferation of HOS cells and triggered apoptosis. Expression profiling of these cells and reporter assays suggested that FOXR1 is a negative regulator of fork-head box factor-mediated transcription. The neural crest stem cell line JoMa1 proliferates in culture conditional to activity of a MYC-ER transgene. Over-expression of the wild-type FOXR1 could functionally replace MYC and drive proliferation of JoMa1. We conclude that FOXR1 is recurrently activated in neuroblastoma by intrachromosomal deletion/fusion events, resulting in overexpression of fusion transcripts. Forkhead-box transcription factors have not been previously implicated in neuroblastoma pathogenesis. Furthermore, this is the first identification of intrachromosomal fusion genes in neuroblastoma. Oncogene (2012) 31, 1571-1581; doi:10.1038/onc.2011.344; published online 22 August 2011
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| 15. |
- Schilling, S., et al.
(författare)
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Differential effects of familial Alzheimer's disease-causing mutations on amyloid precursor protein (APP) trafficking, proteolytic conversion, and synaptogenic activity
- 2023
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Ingår i: Acta Neuropathologica Communications. - 2051-5960. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The amyloid precursor protein (APP) is a key player in Alzheimer`s disease (AD) and the precursor of the A beta peptide, which is generated by consecutive cleavages of beta- and gamma-secretases. Familial Alzheimer's disease (FAD) describes a hereditary subgroup of AD that represents a low percentage of AD cases with an early onset of the disease. Different APP FAD mutations are thought to have qualitatively different effects on its proteolytic conversion. However, few studies have explored the pathogenic and putative physiological differences in more detail. Here, we compared different FAD mutations, located at the beta- (Swedish), alpha- (Flemish, Arctic, Iowa) or gamma-secretase (Iberian) cleavage sites. We examined heterologous expression of APP WT and FAD mutants in non-neuronal cells and their impact on presynaptic differentiation in contacting axons of co-cultured neurons. To decipher the underlying molecular mechanism, we tested the subcellular localization, the endocytosis rate and the proteolytic processing in detail by immunoprecipitation-mass spectrometry. Interestingly, we found that only the Iberian mutation showed altered synaptogenic function. Furthermore, the APP Iowa mutant shows significantly decreased alpha-secretase processing which is in line with our results that APP carrying the Iowa mutation was significantly increased in early endosomes. However, most interestingly, immunoprecipitation-mass spectrometry analysis revealed that the amino acid substitutions of APP FAD mutants have a decisive impact on their processing reflected in altered A beta profiles. Importantly, N-terminally truncated A beta peptides starting at position 5 were detected preferentially for APP Flemish, Arctic, and Iowa mutants containing amino acid substitutions around the alpha-secretase cleavage site. The strongest change in the ratio of A beta 40/A beta 42 was observed for the Iberian mutation while APP Swedish showed a substantial increase in A beta 1-17 peptides. Together, our data indicate that familial AD mutations located at the alpha-, beta-, and gamma-secretase cleavage sites show considerable differences in the underlying pathogenic mechanisms.
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| 16. |
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| 17. |
- Volkmann, J, et al.
(författare)
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Selecting deep brain stimulation or infusion therapies in advanced Parkinson's disease : an evidence-based review
- 2013
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 260:11, s. 2701-2714
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Tidskriftsartikel (refereegranskat)abstract
- Motor complications in Parkinson’s disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.
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| 18. |
- Abou-Zeid, Nancy, et al.
(författare)
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Towards a cancer mission in Horizon Europe: recommendations
- 2020
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Ingår i: Molecular Oncology. - : Wiley Open Access. - 1878-0261 .- 1574-7891. ; 14:8, s. 1589-1615
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive translational cancer research approach focused on personalized and precision medicine, and covering the entire cancer research–care–prevention continuum has the potential to achieve in 2030 a 10-year cancer-specific survival for 75% of patients diagnosed in European Union (EU) member states with a well-developed healthcare system. Concerted actions across this continuum that spans from basic and preclinical research through clinical and prevention research to outcomes research, along with the establishment of interconnected high-quality infrastructures for translational research, clinical and prevention trials and outcomes research, will ensure that science-driven and social innovations benefit patients and individuals at risk across the EU. European infrastructures involving comprehensive cancer centres (CCCs) and CCC-like entities will provide researchers with access to the required critical mass of patients, biological materials and technological resources and can bridge research with healthcare systems. Here, we prioritize research areas to ensure a balanced research portfolio and provide recommendations for achieving key targets. Meeting these targets will require harmonization of EU and national priorities and policies, improved research coordination at the national, regional and EU level and increasingly efficient and flexible funding mechanisms. Long-term support by the EU and commitment of Member States to specialized schemes are also needed for the establishment and sustainability of trans-border infrastructures and networks. In addition to effectively engaging policymakers, all relevant stakeholders within the entire continuum should consensually inform policy through evidence-based advice.
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| 19. |
- Asche, Frank, et al.
(författare)
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Aquaculture: Externalities and Policy Options
- 2022
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Ingår i: Review of Environmental Economics and Policy. - : University of Chicago Press. - 1750-6816 .- 1750-6824. ; 16:2, s. 282-305
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Forskningsöversikt (refereegranskat)abstract
- The future of aquaculture will depend critically on the extent of key externalities, how governance evolves to address these externalities, and the extent to which markets and other institutions provide incentives for technological innovation. Governance in this context refers to natural resource management and environmental regulation by governments as well as private sector initiatives and efforts by nongovernmental organizations that seek to influence consumer behavior, supply chain management, and production practices. Potential market failures in aquaculture include natural resource scarcities that stem from the problem of the commons and a number of environmental externalities. To consider appropriate policies and governance structures, we distinguish between externalities that are endogenous (determined within the sector) and externalities that are exogenous (determined outside the sector).
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| 20. |
- Asche, F., et al.
(författare)
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Fisheries performance in Africa: An analysis based on data from 14 countries
- 2021
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Ingår i: Marine Policy. - : Elsevier BV. - 0308-597X. ; 125
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Tidskriftsartikel (refereegranskat)abstract
- The Fishery Performance Indicators is a data collection tool that allows collection of comparable fisheries data in the environmental, economic and community pillars even under data poor circumstances. In this paper, data collected for 35 fisheries in 14 African countries are analyzed and compared to global averages. Similar to a previous global analysis, the different pillars of sustainability were positively correlated. The results are even more pronounced for Africa than globally. The only exception is the relationship between environment and community pillars in Africa, which is statistically insignificant, and this is also the case for open access fisheries globally. The average scores in Africa are lower than global average scores in all dimensions, which is not unexpected given the high number of open access fisheries. However, factors that are not fisheries specific may be more important for this result, suggesting that a country's governance, economic conditions, and development status are important for fisheries performance. © 2020 Elsevier Ltd
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| 21. |
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| 22. |
- Brooks, D J, et al.
(författare)
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Treatment of end-of-dose wearing-off in Parkinson's disease: Stalevo (R) (levodopa/carbidopa/entacapone) and levodopa/DDCI given in combination with Comtess (R)/Comtan (R) (Entacapone) provide equivalent improvements in symptom control superior to that of traditional levodopa/DDCI treatment
- 2005
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Ingår i: European Neurology. - : S. Karger AG. - 1421-9913 .- 0014-3022. ; 53:4, s. 197-202
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the efficacy of the new optimised levoclopa, Stalevo(R) (levoclopa, carbidopa and entacapone) in patients with Parkinson's disease experiencing end-of-close wearing-off. Treatment with Stalevo was compared to treatment with traditional immediate-release levodopa and dopa-decarboxylase inhibitor (DDCl) formulations along with adjunct entacapone (Comtess(R)/Comtan(R)). A European, open, parallel-group, active treatment-controlled phase IIIb study evaluating 176 patients randomised to switch from their current regimen of levodopa/DDCl to either an equivalent dose of Stalevo or levodopa/DDCl plus entacapone. After 6 weeks, treatments were assessed using the Clinical Global Impression of Change, the Unified Parkinson's Disease Rating Scale and a Motor Fluctuations Questionnaire. Over 70% of patients in both the Stalevo, and adjunct entacapone arms felt that they were clinically improved and over 80% experienced a reduction in fluctuations. Although there was no significant difference between Stalevo and levodopa/DDCl plus entacapone with regard to motor improvement and side effects, 81% of patients stated that they preferred treatment with Stalevo compared with taking two separate tablets (i.e. levodopa/DDCl and entacapone). Stalevo was well tolerated and safe when substituted for levodopa DDCl preparations.
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| 23. |
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| 24. |
- Eggert, Håkan, 1961, et al.
(författare)
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Trade and resources: Welfare effects of the Lake Victoria fisheries boom
- 2015
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Ingår i: Fisheries Research. - : Elsevier BV. - 0165-7836. ; 167, s. 156-163
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Tidskriftsartikel (refereegranskat)abstract
- We examine the welfare implications of the Tanzanian fisheries boom resulting from Lake Victoria Nile perch exports during 1993-2008. In the literature, there are two opposing views on the effect of fish trade: some argue that fish trade can act as an engine of growth, while others contend that trade in fish negatively affects food security, local economies and incomes of the poor. We apply a micro level perspective using data from two years, the first from a 1993 World Bank household survey and the second, our own study from 2008, both covering about 520 households in the two regions, Mwanza and Mara, by Lake Victoria. Our results indicate increasing average income and a reduction in the share of household expenditure on food, both of which are positive indicators of welfare. For the poorest part of the population, urban areas had a substantial reduction in the fraction below the basic needs level, while the change in the rural areas was insignificant. However, growth in both areas was modest and inequality seems to have increased during the period. We conclude that there is more support in our data for a positive than a negative effect of the fish boom on the well-being of those residing in Mwanza and Mara. © 2015 Elsevier B.V.
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| 25. |
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| 26. |
- Jafari, Rouhollah, et al.
(författare)
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Dynamical quantum phase transitions following a noisy quench
- 2024
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Ingår i: PHYSICAL REVIEW B. - 2469-9950 .- 2469-9969. ; 109:18
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Tidskriftsartikel (refereegranskat)abstract
- We study how time -dependent energy fluctuations impact the dynamical quantum phase transitions (DQPTs) following a noisy ramped quench of the transverse magnetic field in a quantum Ising chain. By numerically solving the stochastic Schr & ouml;dinger equation of the mode-decoupled fermionic Hamiltonian of the problem, we identify two generic scenarios: Depending on the amplitude of the noise and the rate of the ramp, the expected periodic sequence of noiseless DQPTs may either be uniformly shifted in time or else replaced by a disarray of closely spaced DQPTs. Guided by an exact noise master equation, we trace the phenomenon to the interplay between noise -induced excitations which accumulate during the quench and the near -adiabatic dynamics of the massive modes of the system. Our analysis generalizes to any one-dimensional fermionic two -band model subject to a noisy quench.
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| 27. |
- Kovar, Heinrich, et al.
(författare)
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The first European interdisciplinary ewing sarcoma research summit.
- 2012
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- The European Network for Cancer Research in Children and Adolescents (ENCCA) provides an interaction platform for stakeholders in research and care of children with cancer. Among ENCCA objectives is the establishment of biology-based prioritization mechanisms for the selection of innovative targets, drugs, and prognostic markers for validation in clinical trials. Specifically for sarcomas, there is a burning need for novel treatment options, since current chemotherapeutic treatment protocols have met their limits. This is most obvious for metastatic Ewing sarcoma (ES), where long term survival rates are still below 20%. Despite significant progress in our understanding of ES biology, clinical translation of promising laboratory results has not yet taken place due to fragmentation of research and lack of an institutionalized discussion forum. To fill this gap, ENCCA assembled 30 European expert scientists and five North American opinion leaders in December 2011 to exchange thoughts and discuss the state of the art in ES research and latest results from the bench, and to propose biological studies and novel promising therapeutics for the upcoming European EWING2008 and EWING2012 clinical trials.
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| 28. |
- Lincoff, A. Michael, et al.
(författare)
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Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI Randomized Controlled Trial
- 2014
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 35:37, s. 2516-2523
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Tidskriftsartikel (refereegranskat)abstract
- Aims Delcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). Methods and results A multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50,150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for similar to 2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed. Conclusions Selective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury.
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| 29. |
- Tilton, John E., et al.
(författare)
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Public policy and future mineral supplies
- 2018
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Ingår i: Resources policy. - : Elsevier. - 0301-4207 .- 1873-7641. ; 57, s. 55-60
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Tidskriftsartikel (refereegranskat)abstract
- A widespread and pessimistic view of the availability of mineral commodities calls for strong government initiatives to ensure adequate future supplies. This article provides a more market oriented and optimistic perspective, one that focuses on production costs and prices rather than physical availability. It sees short-run shortages continuing to plague commodity markets in the future as in the past. Though painful while they last, these shortages are temporary and do not pose a serious long-run threat to human welfare. Moreover, even without government intervention, they self-correct. The sharply higher prices that they evoke create strong incentives that foster supply and curb demand.Potentially more serious are long-run shortages due to mineral depletion. Such shortages are often thought to be inevitable, a conclusion that flows directly from the physical view of depletion. For various reasons, we reject this view of depletion in favor of an economic view. The latter recognizes that depletion may create long-run shortages, but stresses that this need not be the case if new technology can continue to offset the cost-increasing effects of depletion in the future as it has in the past. The economic view also suggests that a list of mineral commodities most threatened by depletion can best be compiled using cumulative availability curves rather than the more common practice of calculating commodity life expectancies based on estimates of available stocks.
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