| 1. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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Tidskriftsartikel (refereegranskat)abstract
- Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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| 2. |
- Düring, J., et al.
(författare)
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Lactate, lactate clearance and outcome after cardiac arrest : A post-hoc analysis of the TTM-Trial
- 2018
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 62:10, s. 1436-1442
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Tidskriftsartikel (refereegranskat)abstract
- Background: Admission lactate and lactate clearance are implemented for risk stratification in sepsis and trauma. In out-of-hospital cardiac arrest, results regarding outcome and lactate are conflicting. Methods: This is a post-hoc analysis of the Target Temperature Management trial in which 950 unconscious patents after out-of-hospital cardiac arrest were randomized to a temperature intervention of 33°C or 36°C. Serial lactate samples during the first 36 hours were collected. Admission lactate, 12-hour lactate, and the clearance of lactate within 12 hours after admission were analyzed and the association with 30-day mortality assessed. Results: Samples from 877 patients were analyzed. In univariate logistic regression analysis, the odds ratio for death by day 30 for each mmol/L was 1.12 (1.08-1.16) for admission lactate, P <.01, 1.21 (1.12-1.31) for 12-hour lactate, P <.01, and 1.003 (1.00-1.01) for each percentage point increase in 12-hour lactate clearance, P =.03. Only admission lactate and 12-hour lactate levels remained significant after adjusting for known predictors of outcome. The area under the receiver operating characteristic curve was 0.65 (0.61-0.69), P <.001, 0.61 (0.57-0.65), P <.001, and 0.53 (0.49-0.57), P =.15 for admission lactate, 12-hour lactate, and 12-hour lactate clearance, respectively. Conclusions: Admission lactate and 12-hour lactate values were independently associated with 30-day mortality after out-of-hospital cardiac arrest while 12-hour lactate clearance was not. The clinical value of lactate as the sole predictor of outcome after out-of-hospital cardiac arrest is, however, limited.
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| 3. |
- Lett, Signe, et al.
(författare)
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Can bryophyte groups increase functional resolution in tundra ecosystems?
- 2022
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Ingår i: Arctic Science. - Ottawa : Canadian Science Publishing. - 2368-7460. ; 8:3, s. 609-637
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Tidskriftsartikel (refereegranskat)abstract
- The relative contribution of bryophytes to plant diversity, primary productivity, and ecosystem functioning increases towards colder climates. Bryophytes respond to environmental changes at the species level, but because bryophyte species are relatively difficult to identify, they are often lumped into one functional group. Consequently, bryophyte function remains poorly resolved. Here, we explore how higher resolution of bryophyte functional diversity can be encouraged and implemented in tundra ecological studies. We briefly review previous bryophyte functional classifications and the roles of bryophytes in tundra ecosystems and their susceptibility to environmental change. Based on shoot morphology and colony organization, we then propose twelve easily distinguishable bryophyte functional groups. To illustrate how bryophyte functional groups can help elucidate variation in bryophyte effects and responses, we compiled existing data on water holding capacity, a key bryophyte trait. Although plant functional groups can mask potentially high interspecific and intraspecific variability, we found better separation of bryophyte functional group means compared with previous grouping systems regarding water holding capacity. This suggests that our bryophyte functional groups truly represent variation in the functional roles of bryophytes in tundra ecosystems. Lastly, we provide recommendations to improve the monitoring of bryophyte community changes in tundra study sites.
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| 4. |
- Baldock, Paul A., et al.
(författare)
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Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis
- 2007
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Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 282:26, s. 19092-19102
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Tidskriftsartikel (refereegranskat)abstract
- The importance of neuropeptide Y (NPY) and Y2 receptors in the regulation of bone and energy homeostasis has recently been demonstrated. However, the contributions of the other Y receptors are less clear. Here we show that Y1 receptors are expressed on osteoblastic cells. Moreover, bone and adipose tissue mass are elevated in Y1(-/-) mice with a generalized increase in bone formation on cortical and cancellous surfaces. Importantly, the inhibitory effects of NPY on bone marrow stromal cells in vitro are absent in cells derived from Y1(-/-) mice, indicating a direct action of NPY on bone cells via this Y receptor. Interestingly, in contrast to Y2 receptor or germ line Y1 receptor deletion, conditional deletion of hypothalamic Y1 receptors in adult mice did not alter bone homeostasis, food intake, or adiposity. Furthermore, deletion of both Y1 and Y2 receptors did not produce additive effects in bone or adiposity. Thus Y1 receptor pathways act powerfully to inhibit bone production and adiposity by nonhypothalamic pathways, with potentially direct effects on bone tissue through a single pathway with Y2 receptors.
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| 5. |
- During, Melanie A. D., et al.
(författare)
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The Mesozoic terminated in boreal spring
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 603:7899, s. 91-94
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Tidskriftsartikel (refereegranskat)abstract
- The Cretaceous–Palaeogene mass extinction around 66 million years ago was triggered by the Chicxulub asteroid impact on the present-day Yucatán Peninsula. This event caused the highly selective extinction that eliminated about 76% of species, including all non-avian dinosaurs, pterosaurs, ammonites, rudists and most marine reptiles. The timing of the impact and its aftermath have been studied mainly on millennial timescales, leaving the season of the impact unconstrained. Here, by studying fishes that died on the day the Mesozoic era ended, we demonstrate that the impact that caused the Cretaceous–Palaeogene mass extinction took place during boreal spring. Osteohistology together with stable isotope records of exceptionally preserved perichondral and dermal bones in acipenseriform fishes from the Tanis impact-induced seiche deposits reveal annual cyclicity across the final years of the Cretaceous period. Annual life cycles, including seasonal timing and duration of reproduction, feeding, hibernation and aestivation, vary strongly across latest Cretaceous biotic clades. We postulate that the timing of the Chicxulub impact in boreal spring and austral autumn was a major influence on selective biotic survival across the Cretaceous–Palaeogene boundary.
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| 6. |
- Jendle, Johan, et al.
(författare)
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Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue
- 2009
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Ingår i: Diabetes, obesity and metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 11:12, s. 1163-1172
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Tidskriftsartikel (refereegranskat)abstract
- Aim The effect on body composition of liraglutide, a once-daily human glucagon-like peptide-1 analogue, as monotherapy or added to metformin was examined in patients with type 2 diabetes (T2D). Methods These were randomized, double-blind, parallel-group trials of 26 [Liraglutide Effect and Action in Diabetes-2 (LEAD-2)] and 52 weeks (LEAD-3). Patients with T2D, aged 18-80 years, body mass index (BMI) < 40 kg/m2 (LEAD-2), < 45 kg/m2 (LEAD-3) and HbA1c 7.0-11.0% were included. Patients were randomized to liraglutide 1.8, 1.2 or 0.6 mg/day, placebo or glimepiride 4 mg/day, all combined with metformin 1.5-2 g/day in LEAD-2 and to liraglutide 1.8, 1.2 or glimepiride 8 mg/day in LEAD-3. LEAD-2/3: total lean body tissue, fat tissue and fat percentage were measured. LEAD-2: adipose tissue area and hepatic steatosis were assessed. Results LEAD-2: fat percentage with liraglutide 1.2 and 1.8 mg/metformin was significantly reduced vs. glimepiride/metformin (p < 0.05) but not vs. placebo. Visceral and subcutaneous adipose tissue areas were reduced from baseline in all liraglutide/metformin arms. Except with liraglutide 0.6 mg/metformin, reductions were significantly different vs. changes seen with glimepiride (p < 0.05) but not with placebo. Liver-to-spleen attenuation ratio increased with liraglutide 1.8 mg/metformin possibly indicating reduced hepatic steatosis. LEAD-3: reductions in fat mass and fat percentage with liraglutide monotherapy were significantly different vs. increases with glimepiride (p < 0.01). Conclusion Liraglutide (monotherapy or added to metformin) significantly reduced fat mass and fat percentage vs. glimepiride in patients with T2D.
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| 7. |
- Qamar, Ahsan, et al.
(författare)
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Dependency Modeling and Model Management in Mechatronic Design
- 2012
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Ingår i: Journal of Computing and Information Science in Engineering. - ASME : ASME International. - 1530-9827 .- 1944-7078. ; 12:4, s. 041009-
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Tidskriftsartikel (refereegranskat)abstract
- Mechatronic design is traditionally supported through domain-specific design activities throughout the product development process. The partitioning into domain-specific problems leads to a situation where product properties influence each other, hence giving rise to dependencies. These dependencies play a key role in the prediction of properties and, as a result, in the decision-making process. The important question is how to manage the dependencies for efficient and effective decision making? The aim of this paper is threefold. First, we investigate the nature of dependencies and study how to model them. The paper proposes appropriate terminology taking into account the synthesis and analysis nature of both the properties and the dependencies. This terminology will be the core of the new dependency modeling language. The concepts related to dependency modeling are then illustrated through a simple robot design example, where the creation and importance of a dependency model are explained. Second, we study practical approaches for consistency management and model management in the presence of dependencies. Six levels-of-detail in modeling dependencies are presented; emphasizing that modeling at a higher level-of-detail ensures that more inconsistencies are avoided. Available languages such as OMG SysML™ are evaluated for a possible creation of the dependency models leading toward executable dependency networks. However, at present, SysML does not provide sufficiently rich language constructs to model dependencies. Third, we compare our dependency modeling approach to other state-of-the-art approaches such as dependency modeling with a design structure matrix (DSM), and highlight the benefits of the terminology proposed in this paper. We aim to convince the reader that there is substantial value in modeling dependencies explicitly, especially to avoid inconsistencies, which is not the current state of practice. However, an overall value from dependency modeling can only be obtained if the cost of creating the dependency model is reasonable. Issues such as human interaction/effort and model management through product lifecycle management (PLM) are discussed.
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| 8. |
- Ambati, Aditya, et al.
(författare)
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Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 118:12
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Tidskriftsartikel (refereegranskat)abstract
- Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 x 10(-9)) within the 3'region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R-2 = 0.15; P < 2.0 x 10(-22) at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.
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| 9. |
- Chew, Michelle, et al.
(författare)
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Extravascular lung water index: Diagnostic accuracy and relation to lung injury and mortality in patients with shock
- 2011
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 37:1 Suppl, s. 98-98
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Konferensbidrag (refereegranskat)abstract
- INTRODUCTION. The diagnosis of acute lung injury may be more robust if more accurate physiological markers can be identified. Extravascular lung water index (EVLWI) may be useful and has been shown to correlate with respiratory function and mortality in patients with sepsis and ARDS. Whether this applies to a wider population, and which index performs best, are unclear. OBJECTIVES. We hypothesized that EVLWI correlates with respiratory function and mortality in patients with documented systemic inflammation and shock. We investigated EVLW indexed to actual and predicted body weight, and pulmonary blood volume. We investigated the diagnostic accuracy of EVLWI for lung injury. METHODS. In 51 patients with shock and SIRS, EVLWI was measured within 6 h of ICU admission and indexed to actual weight (EVLWI/ABW), predicted body weight (EVLWI/ PBW) and pulmonary blood volume (EVLWI/PBV). Relationships to lung injury and ICUmortality were investigated. Positive and negative likelihood ratios, pre- and post-test odds and ROC curves were calculated. RESULTS. EVLWI was higher among patients with lung injury and was significantly correlated with respiratory parameters. EVLWI/ABW was higher among non-survivors and gave the best positive likelihood ratios for diagnosing ALI/ARDS. In contrast, EVLWI/PBV gave better diagnostic value for severe lung injury according to Murray's LIS criteria. The post-test odds for ALI and ARDS increased threefold when using EVLWI/ABW as a bedside test. The post-test odds of severe lung injury increased eightfold using EVLWI/PBV. EVLWI/ABW and EVLWI/PBV generated the best ROC curves for mortality prediction with a sensitivity of 68% and specificity of 63-72%. CONCLUSIONS. EVLWI was associated with degree of lung injury, regardless of the index used, supporting its usefulness as a bedside indicator for disease severity. EVLWI/PBV and EVLW/ABW gave the best diagnostic accuracies for the diagnosis of lung injury, and generated the bestROCcurves for mortality prediction.EVLWI/ABWwas significantly increased in non-survivors. Further studies are needed to confirm the additional value of EVLWI for the early identification of lung injury.
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| 10. |
- Dichgans, Martin, et al.
(författare)
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METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration : An initiative of the Joint Programme for Neurodegenerative Disease Research
- 2016
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 12:12, s. 1235-1249
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Tidskriftsartikel (refereegranskat)abstract
- Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.
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