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Sökning: WFRF:(Kurland S)

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1.
  • Boström, Hans, et al. (författare)
  • PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis.
  • 1996
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 85:6, s. 863-73
  • Tidskriftsartikel (refereegranskat)abstract
    • A mouse platelet-derived growth factor A chain (PDGF-A) null allele is shown to be homozygous lethal, with two distinct restriction points, one prenatally before E10 and one postnatally. Postnatally surviving PDGF-A-deficient mice develop lung emphysema secondary to the failure of alveolar septation. This is apparently caused by the loss of alveolar myofibroblasts and associated elastin fiber deposits. PDGF alpha receptor-positive cells in the lung having the location of putative alveolar myofibroblast progenitors were specifically absent in PDGF-A null mutants. We conclude that PDGF-A is crucial for alveolar myofibroblast ontogeny. We have previously shown that PDGF-B is required in the ontogeny of kidney mesangial cells. The PDGFs therefore appear to regulate the generation of specific populations of myofibroblasts during mammalian development. The two PDGF null phenotypes also reveal analogous morphogenetic functions for myofibroblast-type cells in lung and kidney organogenesis.
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  • Bowden, John A., et al. (författare)
  • Harmonizing lipidomics : NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
  • 2017
  • Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 58:12, s. 2275-2288
  • Tidskriftsartikel (refereegranskat)abstract
    • As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra-and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium.jlr While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.
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  • Cone, David C, et al. (författare)
  • Pilot Test of the SALT Mass Casualty Triage System
  • 2019
  • Ingår i: Prehospital Emergency Care. - : Taylor & Francis. - 1090-3127 .- 1545-0066. ; 13:4, s. 536-40
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: No existing mass casualty triage system has been scientifically scrutinized or validated. A recent work group sponsored by the Centers for Disease Control and Prevention, using a combination of expert opinion and the extremely limited research data available, created the SALT (sort-assess-lifesaving interventions-treat/transport) triage system to serve as a national model. An airport crash drill was used to pilot test the SALT system.OBJECTIVE: To assess the accuracy and speed with which trained paramedics can triage victims using this new system.METHODS: Investigators created 50 patient scenarios with a wide range of injuries and severities, and two additional uninjured victims were added at the time of the drill. Students wearing moulage and coached on how to portray their injuries served as "victims." Assuming proper application of the SALT system, the patient scenarios were designed such that 16 patients would be triaged as T1/red/immediate, 12 as T2/yellow/delayed, 14 as T3/green/minimal, and 10 as T4/black/dead. Paramedics were trained to proficiency in the SALT system one week prior to the drill using a 90-minute didactic/practical session, and were given "flash cards" showing the triage algorithm to be used if needed during the drill. Observers blinded to the study purpose timed and recorded the triage process for each patient during the drill. Simple descriptive statistics were used to analyze the data.RESULTS: The two paramedics assigned to the role of triage officers applied the SALT algorithm correctly to 41 of the 52 patients (78.8% accuracy). Seven patients intended to be T2 were triaged as T1, and two patients intended to be T3 were triaged as T2, for an overtriage rate of 13.5%. Two patients intended to be T2 were triaged as T3, for an undertriage rate of 3.8%. Triage times were recorded by the observers for 42 of the 52 patients, with a mean of 15 seconds per patient (range 5-57 seconds).CONCLUSIONS: The SALT mass casualty triage system can be applied quickly in the field and appears to be safe, as measured by a low undertriage rate. There was, however, significant overtriage. Further refinement is needed, and effect on patient outcomes needs to be evaluated.
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9.
  • Holroyd, Brian R., et al. (författare)
  • Clinical Informatics Competencies in the Emergency Medicine Specialist Training Standards of Five International Jurisdictions
  • 2018
  • Ingår i: AEM education and training. - : Wiley-VCH Verlagsgesellschaft. - 2472-5390. ; 2:4, s. 293-300
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The field of clinical informatics (CI), and specifically the electronic health record, has been identified as a key facilitator to achieve a sustainable evidence-based health care system for the future. International graduate medical education (GME) programs have been challenged to ensure that their trainees are provided with appropriate skills to deliver effective and efficient health care in an evolving environment.Objectives: This study explored how international emergency medicine (EM) specialist training standards address competencies and training in relevant areas of CI.Methods: A list of categories of CI competencies relative to EM was developed following a thematic review of published references documenting CI curriculum and competencies. Publicly available documents outlining core content, curriculum, and competencies from international organizations responsible for specialty GME and/or credentialing in EM for Australasia, Canada, Europe, the United Kingdom, and the United States were identified. These EM training standards were reviewed to identify inclusion of topics related to the relevant categories of CI competencies.Results: A total of 23 EM curriculum documents were included in the review. Curricula content related to critical appraisal/evidence-based medicine, leadership, quality improvement, and privacy/security were included in all EM curricula. The CI topics related to fundamental computer skills, computerized provider order entry, and patient-centered informatics were only included in the EM curricula documents for the United States and were absent for the other jurisdictions.Conclusion: There is variation in the CI-related content of the international EM specialty training standards reviewed. Given the increasing importance of CI in the future delivery of health care, organizations responsible for training and credentialing specialist emergency physicians must ensure that their training standards incorporate relevant CI content, thus ensuring that their trainees gain competence in essential aspects of CI.
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10.
  • Kurland, Charles, et al. (författare)
  • Origin and evolution of the mitochondrial proteome
  • 2000
  • Ingår i: Microbiology and Molecular Biology Reviews. - 1092-2172. ; 64:4, s. 786-786
  • Tidskriftsartikel (refereegranskat)abstract
    • The endosymbiotic theory for the origin of mitochondria requires substantial modification. The three identifiable ancestral sources to the proteome of mitochondria are proteins descended from the ancestral alpha -proteobacteria symbiont, proteins with no homology to bacterial orthologs, and diverse proteins with bacterial affinities not derived from alpha -proteobacteria. Random mutations in the form of deletions large and small seem to have eliminated nonessential genes from the endosymbiont-mitochondrial genome lineages. This process, together with the transfer of genes from the endosymbiont-mitochondrial genome to nuclei, has led to a marked reduction in the size of mitochondrial genomes. All proteins of bacterial descent that are encoded by nuclear genes were probably transferred by the same mechanism, involving the disintegration of mitochondria ol bacteria by the intracellular membranous vacuoles of cells to release nucleic acid fragments that transform the nuclear genome. This ongoing process has intermittently introduced bacterial genes to nuclear. genomes. The genomes of the last common ancestor of all organisms, in particular of mitochondria, encoded cytochrome oxidase homologues. There are no phylogenetic indications either in the mitochondrial proteome ol in the nuclear genomes that the initial or subsequent function of the ancestor to the mitochondria was anaerobic. In contrast there are indications that relatively advanced eukaryotes adapted to anaerobiosis by dismantling their mitochondria and refitting them as hydrogenosomes. Accordingly, a continuous history of aerobic respiration seems to have been the fate of most mitochondrial lineages. The initial phases of this history may have involved aerobic respiration by the symbiont functioning as a scavenger of toxic oxygen. The transition to mitochondria capable of active ATP export to the host cell seems to have required recruitment of eukaryotic ATP transport proteins from the nucleus. The identity of the ancestral host of the alpha -proteobacterial endosymbiont is unclear; but there is no indication that it was an autotroph. There are no indications of a specific alpha -proteobacterial origin to genes for glycolysis. In the absence of data to the contrary it is assumed that the ancestral host cell was a heterotroph.
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  • Lo, Ronson S L, et al. (författare)
  • Sepsis - where are the emergency physicians?
  • 2016
  • Ingår i: European journal of emergency medicine. - : Lippincott Williams & Wilkins. - 0969-9546 .- 1473-5695. ; 23:3, s. 159-159
  • Tidskriftsartikel (refereegranskat)
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13.
  • Obregón, C., et al. (författare)
  • Valuing and understanding fish populations in the Anthropocene : Key questions to address
  • 2018
  • Ingår i: Journal of Fish Biology. - : Blackwell Publishing Ltd. - 0022-1112 .- 1095-8649. ; 92:3, s. 828-845
  • Tidskriftsartikel (refereegranskat)abstract
    • Research on the values of fish populations and fisheries has primarily focused on bio-economic aspects; a more nuanced and multidimensional perspective is mostly neglected. Although a range of social aspects is increasingly being considered in fisheries research, there is still no clear understanding as to how to include these additional values within management policies nor is there a cogent appreciation of the major knowledge gaps that should be tackled by future research. This paper results from a workshop held during the 50th anniversary symposium of the Fisheries Society of the British Isles at the University of Exeter, UK, in July 2017. Here, we aim to highlight the current knowledge gaps on the values of fish populations and fisheries thus directing future research. To this end, we present eight questions that are deeply relevant to understanding the values of fish populations and fisheries. These can be applied to all habitats and fisheries, including freshwater, estuarine and marine.
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  • Reusch, T. B. H., et al. (författare)
  • The Baltic Sea as a time machine for the future coastal ocean
  • 2018
  • Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Coastal global oceans are expected to undergo drastic changes driven by climate change and increasing anthropogenic pressures in coming decades. Predicting specific future conditions and assessing the best management strategies to maintain ecosystem integrity and sustainable resource use are difficult, because of multiple interacting pressures, uncertain projections, and a lack of test cases for management. We argue that the Baltic Sea can serve as a time machine to study consequences and mitigation of future coastal perturbations, due to its unique combination of an early history of multistressor disturbance and ecosystem deterioration and early implementation of cross-border environmental management to address these problems. The Baltic Sea also stands out in providing a strong scientific foundation and accessibility to long-term data series that provide a unique opportunity to assess the efficacy of management actions to address the breakdown of ecosystem functions. Trend reversals such as the return of top predators, recovering fish stocks, and reduced input of nutrient and harmful substances could be achieved only by implementing an international, cooperative governance structure transcending its complex multistate policy setting, with integrated management of watershed and sea. The Baltic Sea also demonstrates how rapidly progressing global pressures, particularly warming of Baltic waters and the surrounding catchment area, can offset the efficacy of current management approaches. This situation calls for management that is (i) conservative to provide a buffer against regionally unmanageable global perturbations, (ii) adaptive to react to new management challenges, and, ultimately, (iii) multisectorial and integrative to address conflicts associated with economic trade-offs.
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  • Zhong, Lei, et al. (författare)
  • The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1 alpha
  • 2010
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 140:2, s. 280-293
  • Tidskriftsartikel (refereegranskat)abstract
    • SIRT6 is a member of a highly conserved family of NAD(+)-dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6-deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the expression of multiple glycolytic genes. Specifically, SIRT6 appears to function as a corepressor of the transcription factor Hif1 alpha, a critical regulator of nutrient stress responses. Consistent with this notion, SIRT6-deficient cells exhibit increased Hif1 alpha activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration. Our studies uncover a role for the chromatin factor SIRT6 as a master regulator of glucose homeostasis and may provide the basis for novel therapeutic approaches against metabolic diseases, such as diabetes and obesity.
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