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- Martin, P., et al.
(författare)
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Overview of the RFX-mod fusion science programme
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:10, s. 104018-
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Forskningsöversikt (refereegranskat)abstract
- This paper reports the highlights of the RFX-mod fusion science programme since the last 2010 IAEA Fusion Energy Conference. The RFX-mod fusion science programme focused on two main goals: exploring the fusion potential of the reversed field pinch (RFP) magnetic configuration and contributing to the solution of key science and technology problems in the roadmap to ITER. Active control of several plasma parameters has been a key tool in this endeavour. New upgrades on the system for active control of magnetohydrodynamic (MHD) stability are underway and will be presented in this paper. Unique among the existing fusion devices, RFX-mod has been operated both as an RFP and as a tokamak. The latter operation has allowed the exploration of edge safety factor q edge < 2 with active control of MHD stability and studies concerning basic energy and flow transport mechanisms. Strong interaction has continued with the stellarator community in particular on the physics of helical states and on three-dimensional codes.
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- Sunn Pedersen, Thomas, et al.
(författare)
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Experimental confirmation of efficient island divertor operation and successful neoclassical transport optimization in Wendelstein 7-X
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4, s. 042022-042022
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Tidskriftsartikel (refereegranskat)abstract
- We present recent highlights from the most recent operation phases of Wendelstein 7-X, the most advanced stellarator in the world. Stable detachment with good particle exhaust, low impurity content, and energy confinement times exceeding 100 ms, have been maintained for tens of seconds. Pellet fueling allows for plasma phases with reduced ion-temperature-gradient turbulence, and during such phases, the overall confinement is so good (energy confinement times often exceeding 200 ms) that the attained density and temperature profiles would not have been possible in less optimized devices, since they would have had neoclassical transport losses exceeding the heating applied in W7-X. This provides proof that the reduction of neoclassical transport through magnetic field optimization is successful. W7-X plasmas generally show good impurity screening and high plasma purity, but there is evidence of longer impurity confinement times during turbulence-suppressed phases.
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- Zuin, M., et al.
(författare)
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Overview of the RFX-mod fusion science activity
- 2017
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Ingår i: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 57:10
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports the main recent results of the RFX-mod fusion science activity. The RFX-mod device is characterized by a unique flexibility in terms of accessible magnetic configurations. Axisymmetric and helically shaped reversed-field pinch equilibria have been studied, along with tokamak plasmas in a wide range of q(a) regimes (spanning from 4 down to 1.2 values). The full range of magnetic configurations in between the two, the so-called ultra-low q ones, has been explored, with the aim of studying specific physical issues common to all equilibria, such as, for example, the density limit phenomenon. The powerful RFX-mod feedback control system has been exploited for MHD control, which allowed us to extend the range of experimental parameters, as well as to induce specific magnetic perturbations for the study of 3D effects. In particular, transport, edge and isotope effects in 3D equilibria have been investigated, along with runaway mitigations through induced magnetic perturbations. The first transitions to an improved confinement scenario in circular and D-shaped tokamak plasmas have been obtained thanks to an active modification of the edge electric field through a polarized electrode. The experiments are supported by intense modeling with 3D MHD, gyrokinetic, guiding center and transport codes. Proposed modifications to the RFX-mod device, which will enable further contributions to the solution of key issues in the roadmap to ITER and DEMO, are also briefly presented.
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- Barosi, G., et al.
(författare)
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A unified definition of clinical resistance/intolerance to hydroxyurea in essential thrombocythemia : results of a consensus process by an international working group
- 2007
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 21:2, s. 277-280
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Tidskriftsartikel (refereegranskat)abstract
- A widely accepted definition of resistance or intolerance to hydroxyurea (HU) in patients with essential thrombocythemia (ET) is lacking. An international working group (WG) was convened to develop a consensus formulation of clinically significant criteria for defining resistance/intolerance to HU in ET. To this aim, an analytic hierarchy process (AHP), a multiple-attribute decision-making technique, was used. The steps consisted of selecting the candidate criteria for defining resistance/intolerance; identifying the motivations that could influence the preference of the WG for any individual criterion; comparing the candidate criteria in a pair-wise manner; and grading them according their ability to fulfill the motivations. Every step in the model was derived by questionnaires or group discussion. The WG proposed that the definition of resistance/intolerance should require the fulfillment of at least one of the following criteria: platelet count greater than 600,000/micro l after 3 months of at least 2 g/day of HU (2.5 g/day in patients with a body weight over 80 kg); platelet count greater than 400,000/micro l and WBC less than 2500/micro l or Hb less than 10 g/dl at any dose of HU; presence of leg ulcers or other unacceptable muco-cutaneous manifestations at any dose of HU; HU-related fever.
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- Barosi, G, et al.
(författare)
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Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms : consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
- 2015
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 29:1, s. 20-26
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.
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- Barbui, Tiziano, et al.
(författare)
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Philadelphia-Negative Classical Myeloproliferative Neoplasms : Critical Concepts and Management Recommendations From European LeukemiaNet
- 2011
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:6, s. 761-770
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Tidskriftsartikel (refereegranskat)abstract
- We present a review of critical concepts and produce recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, first-and second-line therapy, and therapy for special issues. Key questions were selected according the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet (ELN) were convened. Patients with polycythemia vera (PV) and essential thrombocythemia (ET) should be defined as high risk if age is greater than 60 years or there is a history of previous thrombosis. Risk stratification in primary myelofibrosis (PMF) should start with the International Prognostic Scoring System (IPSS) for newly diagnosed patients and dynamic IPSS for patients being seen during their disease course, with the addition of cytogenetics evaluation and transfusion status. High-risk patients with PV should be managed with phlebotomy, low-dose aspirin, and cytoreduction, with either hydroxyurea or interferon at any age. High-risk patients with ET should be managed with cytoreduction, using hydroxyurea at any age. Monitoring response in PV and ET should use the ELN clinicohematologic criteria. Corticosteroids, androgens, erythropoiesis-stimulating agents, and immunomodulators are recommended to treat anemia of PMF, whereas hydroxyurea is the first-line treatment of PMF-associated splenomegaly. Indications for splenectomy include symptomatic portal hypertension, drug-refractory painful splenomegaly, and frequent RBC transfusions. The risk of allogeneic stem-cell transplantation-related complications is justified in transplantation-eligible patients whose median survival time is expected to be less than 5 years.
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- Barosi, Giovanni, et al.
(författare)
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Response criteria for essential thrombocythemia and polycythemia vera : result of a European LeukemiaNet consensus conference
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 113:20, s. 4829-4833
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Tidskriftsartikel (refereegranskat)abstract
- European experts were convened to develop a definition of response to treatment in polycythemia vera (PV) and essential thrombocythemia (ET). Clinicohematologic (CH), molecular, and histologic response categories were selected. In ET, CH complete response (CR) was: platelet count less than or equal to 400 x 10(9)/L, no disease-related symptoms, normal spleen size, and white blood cell count less than or equal to 10 x 10(9)/L. Platelet count less than or equal to 600 x 10(9)/L or a decrease greater than 50% was partial response (PR). In PV, CH-CR was: hematocrit less than 45% without phlebotomy, platelet count less than or equal to 400 x 10(9)/L, white blood cell count less than or equal to 10 x 10(9)/L, and no disease-related symptoms. A hematocrit less than 45% without phlebotomy or response in 3 or more of the other criteria was defined as PR. In both ET and in PV, molecular CR was a reduction of any molecular abnormality to undetectable levels. Molecular PR was defined as a reduction more than or equal to 50% in patients with less than 50% mutant allele burden, or a reduction more than or equal to 25% in patients with more than 50% mutant allele burden. Bone marrow histologic response in ET was judged on megakaryocyte hyperplasia while on cellularity and reticulin fibrosis in PV. The combined use of these response definitions should help standardize the design and reporting of clinical studies.
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| 24. |
- Chowdhary, N, et al.
(författare)
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Reducing the Risk of Cognitive Decline and Dementia: WHO Recommendations
- 2022
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 12, s. 765584-
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Tidskriftsartikel (refereegranskat)abstract
- With population ageing worldwide, dementia poses one of the greatest global challenges for health and social care in the 21st century. In 2019, around 55 million people were affected by dementia, with the majority living in low- and middle-income countries. Dementia leads to increased costs for governments, communities, families and individuals. Dementia is overwhelming for the family and caregivers of the person with dementia, who are the cornerstone of care and support systems throughout the world. To assist countries in addressing the global burden of dementia, the World Health Organisation (WHO) developed the Global Action Plan on the Public Health Response to Dementia 2017–2025. It proposes actions to be taken by governments, civil society, and other global and regional partners across seven action areas, one of which is dementia risk reduction. This paper is based on WHO Guidelines on risk reduction of cognitive decline and dementia and presents recommendations on evidence-based, multisectoral interventions for reducing dementia risks, considerations for their implementation and policy actions. These global evidence-informed recommendations were developed by WHO, following a rigorous guideline development methodology and involved a panel of academicians and clinicians with multidisciplinary expertise and representing geographical diversity. The recommendations are considered under three broad headings: lifestyle and behaviour interventions, interventions for physical health conditions and specific interventions. By supporting health and social care professionals, particularly by improving their capacity to provide gender and culturally appropriate interventions to the general population, the risk of developing dementia can be potentially reduced, or its progression delayed.
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| 25. |
- De Stefano, V., et al.
(författare)
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High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with Vitamin K antagonists
- 2016
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 30:10, s. 2032-2038
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Tidskriftsartikel (refereegranskat)abstract
- The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recurrences, venous in 36 cases, with an incidence rate (IR) of 6.5 per 100 pt-years (95% confidence interval (CI): 4.9-8.6). One hundred fifty-five patients received VKA; the IR of recurrent thrombosis per 100 pt-years was 4.7 (95% CI: 2.8-7.3) on VKA and 8.9 (95% CI: 5.7-13.2) off VKA (P=0.03). In patients receiving VKA, the IR of recurrent thrombosis per 100 pt-years was 5.3 (95% CI: 3.2-8.4) among 108 patients on long-term VKA and 12.8 (95% CI: 7.3-20.7) after discontinuation among the 47 who ceased treatment (P=0.008), with a doubled risk of recurrence after stopping VKA (hazard ratio: 2.21, 95% CI: 1.19-5.30). The IR of major bleeding per 100 pt-years was 2.4 (95%: CI: 1.1-4.5) on VKA and 0.7 (95% CI: 0.08-2.5) off VKA (P=0.08). In conclusion, in MPN patients with VTE recurrent thrombosis is significantly reduced by VKA and caution should be adopted in discontinuation; however, the incidence of recurrence on treatment remains high, calling for clinical trials aimed to improve prophylaxis in this setting.
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