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- Forouzanfar, Mohammad H, et al.
(author)
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Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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| 3. |
- Litaudon, X., et al.
(author)
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Development of steady-state scenarios compatible with ITER-like wall conditions
- 2007
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In: Plasma Physics and Controlled Fusion. - 0741-3335 .- 1361-6587. ; 49:12B, s. B529-B550
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Journal article (peer-reviewed)abstract
- A key issue for steady-state tokamak operation is to determine the edge conditions that are compatible both with good core confinement and with the power handling and plasma exhaust capabilities of the plasma facing components (PFCs) and divertor systems. A quantitative response to this open question will provide a robust scientific basis for reliable extrapolation of present regimes to an ITER compatible steady-state scenario. In this context, the JET programme addressing steady-state operation is focused on the development of non-inductive, high confinement plasmas with the constraints imposed by the PFCs. A new beryllium main chamber wall and tungsten divertor together with an upgrade of the heating/fuelling capability are currently in preparation at JET. Operation at higher power with this ITER-like wall will impose new constraints on non-inductive scenarios. Recent experiments have focused on the preparation for this new phase of JET operation. In this paper, progress in the development of advanced tokamak (AT) scenarios at JET is reviewed keeping this long-term objective in mind. The approach has consisted of addressing various critical issues separately during the 2006-2007 campaigns with a view to full scenario integration when the JET upgrades are complete. Regimes with internal transport barriers (ITBs) have been developed at q(95) similar to 5 and high triangularity, 3 (relevant to the ITER steady-state demonstration) by applying more than 30 MW of additional heating power reaching beta(N) similar to 2 at B(o) similar to 3.1 T. Operating at higher 6 has allowed the edge pedestal and core densities to be increased pushing the ion temperature closer to that of the electrons. Although not yet fully integrated into a performance enhancing ITB scenario, Neon seeding has been successfully explored to increase the radiated power fraction (up to 60%), providing significant reduction of target tile power fluxes (and hence temperatures) and mitigation of edge localized mode (ELM) activity. At reduced toroidal magnetic field strength, high beta(N) regimes have been achieved and q-profile optimization investigated for use in steady-state scenarios. Values of beta(N) above the 'no-wall magnetohydrodynamic limit' (beta(N) similar to 3.0) have been sustained for a resistive current diffusion time in high-delta configurations (at 1.2 MA/1.8 T). In this scenario, ELM activity has been mitigated by applying magnetic perturbations using error field correction coils to provide ergodization of the magnetic field at the plasma edge. In a highly shaped, quasi-double null X-point configuration, ITBs have been generated on the ion heat transport channel and combined with 'grassy' ELMs with similar to 30 MW of applied heating power (at 1.2 MA/2.7 T, q(95) similar to 7). Advanced algorithms and system identification procedures have been developed with a view to developing simultaneously temperature and q-profile control in real-time. These techniques have so far been applied to the control of the q-profile evolution in JET AT scenarios.
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| 4. |
- Sediva, A, et al.
(author)
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Europe Immunoglobulin Map
- 2014
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In: JOURNAL OF CLINICAL IMMUNOLOGY. - : Oxford University Press (OUP). - 0271-9142. ; 178178 Suppl 1, s. 141-143
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Conference paper (other academic/artistic)
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| 5. |
- Evans, M., et al.
(author)
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Use of fast-acting insulin aspart in insulin pump therapy in clinical practice
- 2019
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In: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 21:9, s. 2039-2047
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Journal article (peer-reviewed)abstract
- Fast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart (IAsp) containing the additional excipients niacinamide and L-arginine. The improved pharmacological profile and greater early glucose-lowering action of faster aspart compared with IAsp suggests that faster aspart may be advantageous for people with diabetes using continuous subcutaneous insulin infusion (CSII). The recent onset 5 trial was the first to evaluate the efficacy and safety of an ultra-fast-acting insulin in CSII therapy in a large number of participants with type 1 diabetes (T1D). Non-inferiority of faster aspart to IAsp in terms of change from baseline in HbA1c was confirmed, with an estimated treatment difference (ETD) of 0.09% (95% CI, 0.01; 0.17; P < 0.001 for non-inferiority [0.4% margin]). Faster aspart was superior to IAsp in terms of change from baseline in 1-hour post-prandial glucose (PPG) increment after a meal test (ETD [95% CI], −0.91 mmol/L [−1.43; −0.39]; P = 0.001), with statistically significant improvements also at 30 minutes and 2 hours. The overall rate of severe or blood glucose-confirmed hypoglycaemia was not statistically significantly different between treatments, with an estimated rate ratio of 1.00 (95% CI, 0.85; 1.16). A numerical imbalance in severe hypoglycaemic episodes between faster aspart and IAsp was seen in the treatment (21 vs 7) and the 4-week run-in periods (4 vs 0). Experience from clinical practice indicates that all pump settings should be reviewed when initiating faster aspart with CSII, and that the use of continuous glucose monitoring or flash glucose monitoring, along with a good understanding of meal content and bolus type, may also facilitate optimal use. This review summarizes the available clinical evidence for faster aspart administered via CSII and highlights practical considerations based on clinical experience that may help healthcare providers and individuals with T1D successfully initiate and adjust faster aspart with CSII. © 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
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| 6. |
- Mantica, P., et al.
(author)
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A Key to Improved Ion Core Confinement in the JET Tokamak : Ion Stiffness Mitigation due to Combined Plasma Rotation and Low Magnetic Shear
- 2011
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 107:13, s. 135004-
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Journal article (peer-reviewed)abstract
- New transport experiments on JET indicate that ion stiffness mitigation in the core of a rotating plasma, as described by Mantica et al. [Phys. Rev. Lett. 102, 175002 (2009)] results from the combined effect of high rotational shear and low magnetic shear. The observations have important implications for the understanding of improved ion core confinement in advanced tokamak scenarios. Simulations using quasilinear fluid and gyrofluid models show features of stiffness mitigation, while nonlinear gyrokinetic simulations do not. The JET experiments indicate that advanced tokamak scenarios in future devices will require sufficient rotational shear and the capability of q profile manipulation.
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| 9. |
- Birkeland, Kare I., et al.
(author)
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Insulin degludec in type 1 diabetes : a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine
- 2011
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 34:3, s. 661-665
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes.RESEARCH DESIGN AND METHODS: In this 16-week, randomized, open-label trial, participants (mean: 45.8 years old, A1C 8.4%, fasting plasma glucose [FPG] 9.9 mmol/L, BMI 26.9 kg/m(2)) received subcutaneous injections of IDeg(A) (600 mu mol/L; n = 59), IDeg(B) (900 mu mol/L; n = 60), or insulin glargine (IGlar; n = 59), all given once daily in the evening. Insulin aspart was administered at mealtimes.RESULTS: At 16 weeks, mean A1C was comparable for IDeg(A) (7.8 +/- 0.8%), IDeg(B) (8.0 +/- 1.0%), and IGlar (7.6 +/- 0.8%), as was FPG (8.3 +/- 4.0, 8.3 +/- 2.8, and 8.9 +/- 3.5 mmol/L, respectively). Estimated mean rates of confirmed hypoglycemia were 28% lower for IDeg(A) compared with IGlar (rate ratio [RR]: 0.72 [95% CI 0.52-1.00]) and 10% lower for IDeg(B) compared with IGlar (RR: 0.90 [0.65-1.24]); rates of nocturnal hypoglycemia were 58% lower for IDeg(A) (RR: 0.42 [0.25-0.69]) and 29% lower for IDeg(B) (RR: 0.71 [0.44-1.16]). Mean total daily insulin dose was similar to baseline. The frequency and pattern of adverse events was similar between insulin treatments.CONCLUSIONS: In this clinical exploratory phase 2 trial in people with type 1 diabetes, IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses, with reduced rates of hypoglycemia.
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