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- Boström, Hans, et al.
(författare)
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PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis.
- 1996
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 85:6, s. 863-73
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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)
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Harmonizing lipidomics : NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
- 2017
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 58:12, s. 2275-2288
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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)
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Pilot Test of the SALT Mass Casualty Triage System
- 2019
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Ingår i: Prehospital Emergency Care. - : Taylor & Francis. - 1090-3127 .- 1545-0066. ; 13:4, s. 536-40
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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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- Holroyd, Brian R., et al.
(författare)
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Clinical Informatics Competencies in the Emergency Medicine Specialist Training Standards of Five International Jurisdictions
- 2018
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Ingår i: AEM education and training. - : Wiley-VCH Verlagsgesellschaft. - 2472-5390. ; 2:4, s. 293-300
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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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- Kurland, Charles, et al.
(författare)
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Origin and evolution of the mitochondrial proteome
- 2000
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Ingår i: Microbiology and Molecular Biology Reviews. - 1092-2172. ; 64:4, s. 786-786
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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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