| 1. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 2. |
- 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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| 3. |
- Brooker, R.W., et al.
(författare)
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Facilitation in plant communities: the past, the present, and the future
- 2008
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Ingår i: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 96:1, s. 18-34
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Tidskriftsartikel (refereegranskat)abstract
- 1. Once neglected, the role of facilitative interactions in plant communities has received considerable attention in the last two decades, and is now widely recognized. It is timely to consider the progress made by research in this field.2. We review the development of plant facilitation research, focusing on the history of the field, the relationship between plant–plant interactions and environmental severity gradients, and attempts to integrate facilitation into mainstream ecological theory. We then consider future directions for facilitation research.3. With respect to our fundamental understanding of plant facilitation, clarification of the relationship between interactions and environmental gradients is central for further progress, and necessitates the design and implementation of experiments that move beyond the clear limitations of previous studies.4. There is substantial scope for exploring indirect facilitative effects in plant communities, including their impacts on diversity and evolution, and future studies should connect the degree of non-transitivity in plant competitive networks to community diversity and facilitative promotion of species coexistence, and explore how the role of indirect facilitation varies with environmental severity.5. Certain ecological modelling approaches (e.g. individual-based modelling), although thus far largely neglected, provide highly useful tools for exploring these fundamental processes.6. Evolutionary responses might result from facilitative interactions, and consideration of facilitation might lead to re-assessment of the evolution of plant growth forms.7. Improved understanding of facilitation processes has direct relevance for the development of tools for ecosystem restoration, and for improving our understanding of the response of plant species and communities to environmental change drivers.8. Attempts to apply our developing ecological knowledge would benefit from explicit recognition of the potential role of facilitative plant–plant interactions in the design and interpretation of studies from the fields of restoration and global change ecology.9. Synthesis: Plant facilitation research provides new insights into classic ecological theory and pressing environmental issues. Awareness and understanding of facilitation should be part of the basic ecological knowledge of all plant ecologists.
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| 4. |
- Butterfield, B. J., et al.
(författare)
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Alpine cushion plants inhibit the loss of phylogenetic diversity in severe environments
- 2013
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Ingår i: Ecology Letters. - : Wiley. - 1461-0248 .- 1461-023X. ; 16:4, s. 478-486
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Tidskriftsartikel (refereegranskat)abstract
- Biotic interactions can shape phylogenetic community structure (PCS). However, we do not know how the asymmetric effects of foundation species on communities extend to effects on PCS. We assessed PCS of alpine plant communities around the world, both within cushion plant foundation species and adjacent open ground, and compared the effects of foundation species and climate on alpha (within-microsite), beta (between open and cushion) and gamma (open and cushion combined) PCS. In the open, alpha PCS shifted from highly related to distantly related with increasing potential productivity. However, we found no relationship between gamma PCS and climate, due to divergence in phylogenetic composition between cushion and open sub-communities in severe environments, as demonstrated by increasing phylo-beta diversity. Thus, foundation species functioned as micro-refugia by facilitating less stress-tolerant lineages in severe environments, erasing a global productivity – phylogenetic diversity relationship that would go undetected without accounting for this important biotic interaction.
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| 5. |
- Dankiewicz, Josef, et al.
(författare)
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Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): A randomized clinical trial - Rationale and design
- 2019
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 217, s. 23-31
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Tidskriftsartikel (refereegranskat)abstract
- Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted. Methods: The TTM2-trial is an international, multicenter, parallel group, investigator-initiated, randomized, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and early treatment of fever (≥37.8°C). Participants will be randomized within 3 hours of return of spontaneous circulation with the intervention period lasting 40 hours in both groups. Sedation will be mandatory for all patients throughout the intervention period. The clinical team involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention. Prognosticators, outcome-assessors, the steering group, the trial coordinating team, and trial statistician will be blinded. The primary outcome will be all-cause mortality at 180 days after randomization. We estimate a 55% mortality in the control group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The main secondary neurological outcome will be poor functional outcome (modified Rankin Scale 4–6) at 180 days after arrest. Discussion: The TTM2-trial will compare hypothermia to 33°C with normothermia and early treatment of fever (≥37.8°C) after out-of-hospital cardiac arrest. © 2019
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| 9. |
- Nishiyama, C, et al.
(författare)
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Apples to apples or apples to oranges? International variation in reporting of process and outcome of care for out-of-hospital cardiac arrest
- 2014
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Ingår i: Resuscitation. - : Elsevier Ireland Ltd.. - 0300-9572 .- 1873-1570. ; 85:11, s. 1599-1609
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Survival after out-of-hospital cardiac arrest (OHCA) varies between communities, due in part to variation in the methods of measurement. The Utstein template was disseminated to standardize comparisons of risk factors, quality of care, and outcomes in patients with OHCA. We sought to assess whether OHCA registries are able to collate common data using the Utstein template. A subsequent study will assess whether the Utstein factors explain differences in survival between emergency medical services (EMS) systems. STUDY DESIGN: Retrospective study. SETTING: This retrospective analysis of prospective cohorts included adults treated for OHCA, regardless of the etiology of arrest. Data describing the baseline characteristics of patients, and the process and outcome of their care were grouped by EMS system, de-identified, and then collated. Included were core Utstein variables and timed event data from each participating registry. This study was classified as exempt from human subjects' research by a research ethics committee. MEASUREMENTS AND MAIN RESULTS: Thirteen registries with 265 first-responding EMS agencies in 13 countries contributed data describing 125,840 cases of OHCA. Variation in inclusion criteria, definition, coding, and process of care variables were observed. Contributing registries collected 61.9% of recommended core variables and 42.9% of timed event variables. Among core variables, the proportion of missingness was mean 1.9±2.2%. The proportion of unknown was mean 4.8±6.4%. Among time variables, missingness was mean 9.0±6.3%. CONCLUSIONS: International differences in measurement of care after OHCA persist. Greater consistency would facilitate improved resuscitation care and comparison within and between communities.
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