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- Block, Linda, et al.
(författare)
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Age, SAPS 3 and female sex are associated with decisions to withdraw or withhold intensive care
- 2019
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 63:9, s. 1210-1215
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intensive care treat critically ill patients. When intensive care is not considered beneficial for the patient, decisions to withdraw or withhold treatments are made. We aimed to identify independent patient variables that increase the odds for receiving a decision to withdraw or withhold intensive care. Methods: Registry study using data from the Swedish Intensive Care Registry (SIR) 2014-2016. Age, condition at admission, including co-morbidities (Simplified Acute Physiology Score version 3, SAPS 3), diagnosis, sex, and decisions on treatment limitations were extracted. Patient data were divided into a full care (FC) group, and a withhold or withdraw (WW) treatment group. Results: Of all 97095 cases, 47.1% were 61-80 years old, 41.9% were women and 58.1% men. 14996 (15.4%) were allocated to the WW group and 82149 (84.6%) to the FC group. The WW group, compared with the FC group, was older (P < 0.001), had higher SAPS 3 (P < 0.001) and were predominantly female (P < 0.001). Compared to patients 16-20 years old, patients >81 years old had 11 times higher odds of being allocated to the WW group. Higher SAPS 3 (continuous) increased the odds of being allocated to the WW group by odds ratio [OR] 1.085, (CI 1.084-1.087). Female sex increased the odds of being allocated to the WW group by 18% (1.18; CI 1.13- 1.23). Conclusion: Older age, higher SAPS 3 at admission and female sex were found to be independent variables that increased the odds to receive a decision to withdraw or withhold intensive care. © 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
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- Feigin, Valery L., et al.
(författare)
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Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2019
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
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- Golkaram, Mahdi, et al.
(författare)
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The role of chromatin density in cell population heterogeneity during stem cell differentiation
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7, s. 13307:1-11
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Tidskriftsartikel (refereegranskat)abstract
- We incorporate three-dimensional (3D) conformation of chromosome (Hi-C) and single-cell RNA sequencing data together with discrete stochastic simulation, to explore the role of chromatin reorganization in determining gene expression heterogeneity during development. While previous research has emphasized the importance of chromatin architecture on activation and suppression of certain regulatory genes and gene networks, our study demonstrates how chromatin remodeling can dictate gene expression distribution by folding into distinct topological domains. We hypothesize that the local DNA density during differentiation accentuate transcriptional bursting due to the crowding effect of chromatin. This phenomenon yields a heterogeneous cell population, thereby increasing the potential of differentiation of the stem cells.
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- Hellander, Stefan, et al.
(författare)
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Mesoscopic-microscopic spatial stochastic simulation with automatic system partitioning
- 2017
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 147:23
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Tidskriftsartikel (refereegranskat)abstract
- The reaction-diffusion master equation (RDME) is a model that allows for efficient on-lattice simulation of spatially resolved stochastic chemical kinetics. Compared to off-lattice hard-sphere simulations with Brownian dynamics or Green's function reaction dynamics, the RDME can be orders of magnitude faster if the lattice spacing can be chosen coarse enough. However, strongly diffusion-controlled reactions mandate a very fine mesh resolution for acceptable accuracy. It is common that reactions in the same model differ in their degree of diffusion control and therefore require different degrees of mesh resolution. This renders mesoscopic simulation inefficient for systems with multiscale properties. Mesoscopic-microscopic hybrid methods address this problem by resolving the most challenging reactions with a microscale, off-lattice simulation. However, all methods to date require manual partitioning of a system, effectively limiting their usefulness as "black-box" simulation codes. In this paper, we propose a hybrid simulation algorithm with automatic system partitioning based on indirect a priori error estimates. We demonstrate the accuracy and efficiency of the method on models of diffusion-controlled networks in 3D.
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