| 1. |
|
|
| 2. |
- Cowie, M. R., et al.
(författare)
-
New medicinal products for chronic heart failure: advances in clinical trial design and efficacy assessment
- 2017
-
Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 19:6, s. 718-727
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the availability of a number of different classes of therapeutic agents with proven efficacy in heart failure, the clinical course of heart failure patients is characterized by a reduction in life expectancy, a progressive decline in health-related quality of life and functional status, as well as a high risk of hospitalization. New approaches are needed to address the unmet medical needs of this patient population. The European Medicines Agency (EMA) is undertaking a revision of its Guideline on Clinical Investigation of Medicinal Products for the Treatment of Chronic Heart Failure. The draft version of the Guideline was released for public consultation in January 2016. The Cardiovascular Round Table of the European Society of Cardiology (ESC), in partnership with the Heart Failure Association of the ESC, convened a dedicated two-day workshop to discuss three main topic areas of major interest in the field and addressed in this draft EMA guideline: (i) assessment of efficacy (i.e. endpoint selection and statistical analysis); (ii) clinical trial design (i.e. issues pertaining to patient population, optimal medical therapy, run-in period); and (iii) research approaches for testing novel therapeutic principles (i.e. cell therapy). This paper summarizes the key outputs from the workshop, reviews areas of expert consensus, and identifies gaps that require further research or discussion. Collaboration between regulators, industry, clinical trialists, cardiologists, health technology assessment bodies, payers, and patient organizations is critical to address the ongoing challenge of heart failure and to ensure the development and market access of new therapeutics in a scientifically robust, practical and safe way.
|
|
| 3. |
- Ballantyne, C., et al.
(författare)
-
Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA(2) and cardiovascular diseases
- 2007
-
Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8275. ; 14:1, s. 41344-41344
-
Forskningsöversikt (refereegranskat)abstract
- Background A large number of observational epidemiological studies have reported generally positive associations' between circulating mass and activity levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA(2) markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. Objectives By combination of data from individual participants from all relevant observational studies in a systematic,meta-analysis, with correction for regression dilution (using available data on serial measurements of Lp-PLA(2)), the Lp-PLA(2) Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA(2) with coronary heart disease (and, where data are sufficient with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA(2) and cardiovascular outcomes. Methods A central database is being established containing data on circulating Lp-PLA(2) values, sex and other potential confounding factors, age at baseline Lp-PLA(2) Measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA(2) will yield information on a total of about 15 000 cardiovascular disease endpoints.
|
|
| 4. |
- Ballantyne, C., et al.
(författare)
-
Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases
- 2007
-
Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - : Oxford University Press (OUP). - 1741-8267 .- 1741-8275 .- 2047-4873. ; 14:1, s. 3-11
-
Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: A large number of observational epidemiological studies have reported generally positive associations between circulating mass and activity levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA2 markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. OBJECTIVES: By combination of data from individual participants from all relevant observational studies in a systematic 'meta-analysis', with correction for regression dilution (using available data on serial measurements of Lp-PLA2), the Lp-PLA2 Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA2 with coronary heart disease (and, where data are sufficient, with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA2 and cardiovascular outcomes. METHODS: A central database is being established containing data on circulating Lp-PLA2 values, sex and other potential confounding factors, age at baseline Lp-PLA2 measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA2 will yield information on a total of about 15 000 cardiovascular disease endpoints.
|
|
| 5. |
- Sala, O E, et al.
(författare)
-
Biodiversity - Global biodiversity scenarios for the year 2100
- 2000
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 287:5459, s. 1770-1774
-
Tidskriftsartikel (refereegranskat)abstract
- Scenarios of changes in biodiversity for the year 2100 can now be developed based on scenarios of changes in atmospheric carbon dioxide, climate, vegetation, and Land use and the known sensitivity of biodiversity to these changes. This study identified a ranking of the importance of drivers of change, a ranking of the biomes with respect to expected changes, and the major sources of uncertainties. For terrestrial ecosystems, land-use change probably wilt have the largest effect, followed by climate change, nitrogen deposition, biotic exchange, and elevated carbon dioxide concentration. For freshwater ecosystems, biotic exchange is much more important. Mediterranean climate and grassland ecosystems likely will experience the greatest proportional change in biodiversity because of the substantial influence of all drivers of biodiversity change. Northern temperate ecosystems are estimated to experience the least biodiversity change because major land-use change has already occurred. Plausible changes in biodiversity in other biomes depend on interactions among the causes of biodiversity change. These interactions represent one of the largest uncertainties in projections of future biodiversity change.
|
|
| 6. |
- Ellsworth, D. S., et al.
(författare)
-
Convergence in phosphorus constraints to photosynthesis in forests around the world
- 2022
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Phosphorus (P) limitation is pervasive in tropical forests. Here the authors analyse the dependence of photosynthesis on leaf N and P in tropical forests, and show that incorporating leaf P constraints in a terrestrial biosphere model enhances its predictive power. Tropical forests take up more carbon (C) from the atmosphere per annum by photosynthesis than any other type of vegetation. Phosphorus (P) limitations to C uptake are paramount for tropical and subtropical forests around the globe. Yet the generality of photosynthesis-P relationships underlying these limitations are in question, and hence are not represented well in terrestrial biosphere models. Here we demonstrate the dependence of photosynthesis and underlying processes on both leaf N and P concentrations. The regulation of photosynthetic capacity by P was similar across four continents. Implementing P constraints in the ORCHIDEE-CNP model, gross photosynthesis was reduced by 36% across the tropics and subtropics relative to traditional N constraints and unlimiting leaf P. Our results provide a quantitative relationship for the P dependence for photosynthesis for the front-end of global terrestrial C models that is consistent with canopy leaf measurements.
|
|
| 7. |
- Sawle, G V, et al.
(författare)
-
Transplantation of fetal dopamine neurons in Parkinson's disease : PET [18F]6-L-fluorodopa studies in two patients with putaminal implants
- 1992
-
Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 31:2, s. 73-166
-
Tidskriftsartikel (refereegranskat)abstract
- Two patients with Parkinson's disease who underwent implantation of fetal mesencephalic tissue into the putamen were serially studied using positron emission tomography and [18F]6-L-fluorodopa ([18F]dopa). The uptake of [18F]dopa is related to the functional integrity of the presynaptic dopaminergic system. Preoperative studies revealed a marked decrease in putamen [18F]dopa uptake, with lesser involvement of the caudate. Two and 4 months, respectively, after operation, both patients demonstrated functional improvement, as described elsewhere. One patient was scanned 5, 8, and 13 months after the operation and the other was scanned 7 and 12 months after the operation. In both patients, [18F]dopa uptake increased within the operated putamen despite a progressive decrease in tracer uptake in the unoperated striatal structures. We believe that this increased uptake of [18F]dopa at the implantation site represents functional integrity within a surviving neural graft. While there has been little further clinical improvement beyond the fifth postoperative month, the uptake of [18F]dopa at the operation site in both patients has progressively increased. The kinetic data provide evidence of disease progression in the unoperated striatum, which, balanced against increasing graft function, may explain why clinical improvement reached a plateau within months after surgery.
|
|
| 8. |
- Tefferi, Ayalew, et al.
(författare)
-
Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis : recommendations from an ad hoc international expert panel
- 2007
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 110:4, s. 1092-1097
-
Tidskriftsartikel (refereegranskat)abstract
- The Janus kinase 2 mutation, JAK2V617F, is myeloid neoplasm-specific; its presence excludes secondary polycythemia, or thrombocytosis or bone marrow fibrosis from other causes. Furthermore, JAK2V617F or a JAK2 exon 12 mutation is present in virtually all patients with polycythemia vera (PV) whereas JAK2V617F also occurs in approximately half of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Therefore, JAK2 mutation screening holds the promise of a decisive diagnostic test in PV while being complementary to histology for the diagnosis of ET and PMF; the combination of molecular testing and histological review should also facilitate diagnosis of ET associated with borderline thrombocytosis. Accordingly, revision of the current World Health Organization (WHO) diagnostic criteria for PV, ET, and PMF is warranted; JAK2 mutation analysis should be listed as a major criterion for PV diagnosis and the platelet count threshold for ET diagnosis can be lowered from 600 to 450 x 109/L. The current document was prepared by an international expert panel of pathologists and clinical investigators in myeloproliferative disorders; it was subsequently presented to members of the Clinical Advisory Committee for the revision of the WHO Classification of Myeloid Neoplasms who endorsed the document and recommended its adoption by the WHO.
|
|
| 9. |
|
|
| 10. |
- Jurasz, J., et al.
(författare)
-
Complementarity of wind and solar power in North Africa : Potential for alleviating energy droughts and impacts of the North Atlantic Oscillation
- 2024
-
Ingår i: Renewable & sustainable energy reviews. - : Elsevier Ltd. - 1364-0321 .- 1879-0690. ; 191
-
Tidskriftsartikel (refereegranskat)abstract
- With growing gas and oil prices, electricity generation based on these fossil fuels is becoming increasingly expensive. Furthermore, the vision of natural gas as a transition fuel is subject to many constraints and uncertainties of economic, environmental, and geopolitical nature. Consequently, renewable energies such as solar and wind power are expected to reach new records of installed capacity over the upcoming years. Considering the above, North Africa is one of the regions with the largest renewable resource potential globally. While extensively studied in the literature, these resources remain underutilized. Thus, to contribute to their future successful deployment and integration with the power system, this study presents a spatial and temporal analysis of the nature of solar and wind resources over North Africa from the perspective of energy droughts. Both the frequency and maximal duration of energy droughts are addressed. Both aspects of renewables’ variable nature have been evaluated in the North Atlantic Oscillation (NAO) context. The analysis considers the period between 1960 and 2020 based on hourly reanalysis data (i.e., near-surface shortwave irradiation, wind speed, and air temperature) and the Hurrel NAO index. The findings show an in-phase relationship between solar power and winter NAO index, particularly over the coastal regions in western North Africa and opposite patterns in its eastern part. For wind energy, the connection with NAO has a more zonal pattern, with negative correlations in the north and positive correlations in the south. Solar energy droughts dominate northern Tunisia, Algeria, and Morocco, while wind energy droughts mainly occur in the Atlas Mountains range. On average, solar energy droughts tend not to exceed 2–3 consecutive days, with the longest extending for five days. Wind energy droughts can be as prolonged as 80 days (Atlas Mountains). Hybridizing solar and wind energy reduces the potential for energy droughts significantly. At the same time, the correlation between their occurrence and the NAO index remains low. These findings show the potential for substantial resilience to inter-annual climate variability, which could benefit the future stability of renewables-dominated power systems.
|
|
