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- Davies, J. I., et al.
(författare)
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Global surgery, obstetric, and anaesthesia indicator definitions and reporting: An Utstein consensus report
- 2021
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 18:8
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Tidskriftsartikel (refereegranskat)abstract
- Background Indicators to evaluate progress towards timely access to safe surgical, anaesthesia, and obstetric (SAO) care were proposed in 2015 by the Lancet Commission on Global Surgery. These aimed to capture access to surgery, surgical workforce, surgical volume, perioperative mortality rate, and catastrophic and impoverishing financial consequences of surgery. Despite being rapidly taken up by practitioners, data points from which to derive the indicators were not defined, limiting comparability across time or settings. We convened global experts to evaluate and explicitly define-for the first time-the indicators to improve comparability and support achievement of 2030 goals to improve access to safe affordable surgical and anaesthesia care globally. Methods and findings The Utstein process for developing and reporting guidelines through a consensus building process was followed. In-person discussions at a 2-day meeting were followed by an iterative process conducted by email and virtual group meetings until consensus was reached. The meeting was held between June 16 to 18, 2019; discussions continued until August 2020. Participants consisted of experts in surgery, anaesthesia, and obstetric care, data science, and health indicators from high-, middle-, and low-income countries. Considering each of the 6 indicators in turn, we refined overarching descriptions and agreed upon data points needed for construction of each indicator at current time (basic data points), and as each evolves over 2 to 5 (intermediate) and >5 year (full) time frames. We removed one of the original 6 indicators (one of 2 financial risk protection indicators was eliminated) and refined descriptions and defined data points required to construct the 5 remaining indicators: geospatial access, workforce, surgical volume, perioperative mortality, and catastrophic expenditure. A strength of the process was the number of people from global institutes and multilateral agencies involved in the collection and reporting of global health metrics; a limitation was the limited number of participants from low- or middle-income countries-who only made up 21% of the total attendees. Conclusions To track global progress towards timely access to quality SAO care, these indicators-at the basic level-should be implemented universally as soon as possible. Intermediate and full indicator sets should be achieved by all countries over time. Meanwhile, these evolutions can assist in the short term in developing national surgical plans and collecting more detailed data for research studies.
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- Jolkkonen, Mikael, et al.
(författare)
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Kinetic evidence for different mechanisms of interaction of black mamba toxins MT alpha and MT beta with muscarinic receptors
- 2001
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Ingår i: Toxicon. - 0041-0101 .- 1879-3150. ; 39:2-3, s. 377-382
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Tidskriftsartikel (refereegranskat)abstract
- By studying the influence of two toxins from the black mamba Dendroaspis polylepis on the kinetics of [H-3]-N-methylscopolamine binding to muscarinic acetylcholine receptors from rat cerebral cortex, it was revealed that these toxins, MT alpha and MT beta, interact with the receptors via kinetically distinct mechanisms. MT beta bound to receptors in a one-step, readily reversible process with the dissociation constant K-d = 5.3 mu M. The binding mechanism of MT alpha was more complex, involving at least two consecutive steps. A fast receptor-toxin complex formation (K-T = 3.8 mu M) was followed by a slow process of isomerisation of this complex (k(i) = 1.8 x 10(-2) s(-1), half-time 39 s). A similar two-step interaction mechanism has been established for a related toxin, MT2 from the green mamba D. angusticeps (K-T = 1.4 mu M, k(i) = 8.3 x 10(-4) s(-1), half-time 840 s). The slow isomerisation process delays the effect of MT alpha and MT2, but increases their apparent potency compared to toxins unable to induce the isomerisation process.
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- Lund, P E, et al.
(författare)
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The orexin OX1 receptor activates a novel Ca2+ influx pathway necessary for coupling to phospholipase C.
- 2000
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 275:40, s. 30806-12
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Tidskriftsartikel (refereegranskat)abstract
- Ca(2+) elevations in Chinese hamster ovary cells stably expressing OX(1) receptors were measured using fluorescent Ca(2+) indicators fura-2 and fluo-3. Stimulation with orexin-A led to pronounced Ca(2+) elevations with an EC(50) around 1 nm. When the extracellular [Ca(2+)] was reduced to a submicromolar concentration, the EC(50) was increased 100-fold. Similarly, the inositol 1,4,5-trisphosphate production in the presence of 1 mm external Ca(2+) was about 2 orders of magnitude more sensitive to orexin-A stimulation than in low extracellular Ca(2+). The shift in the potency was not caused by depletion of intracellular Ca(2+) but by a requirement of extracellular Ca(2+) for production of inositol 1,4,5-trisphosphate. Fura-2 experiments with the "Mn(2+)-quench technique" indicated a direct activation of a cation influx pathway by OX(1) receptor independent of Ca(2+) release or pool depletion. Furthermore, depolarization of the cells to +60 mV, which almost nullifies the driving force for Ca(2+) entry, abolished the Ca(2+) response to low concentrations of orexin-A. The results thus suggest that OX(1) receptor activation leads to two responses, (i) a Ca(2+) influx and (ii) a direct stimulation of phospholipase C, and that these two responses converge at the level of phospholipase C where the former markedly enhances the potency of the latter.
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- Nasman, J., et al.
(författare)
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Recombinant expression of a selective blocker of M-1 muscarinic receptors
- 2000
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 271:2, s. 435-439
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Tidskriftsartikel (refereegranskat)abstract
- Mamba venoms contain peptides with high selectivity for muscarinic receptors, Due to the limited availability of the M-1 muscarinic receptor-selective MT7 or ml-toxin 1, the peptide was expressed in Sf9 cells using a synthetic cDNA and purified, The isolated peptide had over four orders of magnitude higher affinity for the M-1 compared to M-2-M-5 muscarinic receptors, The peptide strongly inhibited Ca2+ mobilisation ;through recombinant and endogenously expressed M-1 receptors, having no effect on the function of the other subtypes. The MT7 peptide provides a unique tool for identification and functional characterisation of M-1 receptors in cells and tissues,
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- Papakokkinou, Eleni, et al.
(författare)
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Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis
- 2021
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. Data sources Systematic literature search in four databases. Study Selection Observational studies reporting the prevalence of NS after BA in adult patients with CD. Data extraction Data extraction and risk of bias assessment were performed by three independent investigators. Data synthesis Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I-2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. Conclusions Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.
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- Akerman, J. J., et al.
(författare)
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Two-stage crossover from thermal to quantum flux creep of dilute vortex ensembles in various high-T-c superconducting thin films
- 2001
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 64:9
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Tidskriftsartikel (refereegranskat)abstract
- The thermal-to-quantum flux creep crossover at low vortex densities has been studied in YBa2Cu3O7, TlBa2CaCu2O7-delta, and HgBa2CaCu2O6+delta thin films using ac susceptibility. The crossover temperatures T-cr are 10-11, 17, and 30 K, respectively. Both thermal and quantum flux creep is suppressed as the vortex density is decreased. We observe a two-stage nature in the crossover behavior which appears to be a general property of all the three materials studied.
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