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Träfflista för sökning "WFRF:(Jaffe A. S.) "

Sökning: WFRF:(Jaffe A. S.)

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  • Koulouridis, E., et al. (författare)
  • The XXL Survey: XII. Optical spectroscopy of X-ray-selected clusters and the frequency of AGN in superclusters
  • 2016
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592, s. Art. no. A11-
  • Forskningsöversikt (refereegranskat)abstract
    • Context. This article belongs to the first series of XXL publications. It presents multifibre spectroscopic observations of three 0.55 deg2 fields in the XXL Survey, which were selected on the basis of their high density of X-ray-detected clusters. The observations were obtained with the AutoFib2+WYFFOS (AF2) wide-field fibre spectrograph mounted on the 4.2 m William Herschel Telescope. Aims. The paper first describes the scientific rationale, the preparation, the data reduction, and the results of the observations, and then presents a study of active galactic nuclei (AGN) within three superclusters. Methods. To determine the redshift of galaxy clusters and AGN, we assign high priority to a) the brightest cluster galaxies (BCGs), b) the most probable cluster galaxy candidates, and c) the optical counterparts of X-ray point-like sources. We use the outcome of the observations to study the projected (2D) and the spatial (3D) overdensity of AGN in three superclusters. Results. We obtained redshifts for 455 galaxies in total, 56 of which are counterparts of X-ray point-like sources. We were able to determine the redshift of the merging supercluster XLSSC-e, which consists of six individual clusters at z ~ 0.43, and we confirmed the redshift of supercluster XLSSC-d at z ~ 0.3. More importantly, we discovered a new supercluster, XLSSC-f, that comprises three galaxy clusters also at z ~ 0.3. We find a significant 2D overdensity of X-ray point-like sources only around the supercluster XLSSC-f. This result is also supported by the spatial (3D) analysis of XLSSC-f, where we find four AGN with compatible spectroscopic redshifts and possibly one more with compatible photometric redshift. In addition, we find two AGN (3D analysis) at the redshift of XLSSC-e, but no AGN in XLSSC-d. Comparing these findings with the optical galaxy overdensity we conclude that the total number of AGN in the area of the three superclusters significantly exceeds the field expectations. All of the AGN found have luminosities below 7 × 1042 erg s-1. Conclusions. The difference in the AGN frequency between the three superclusters cannot be explained by the present study because of small number statistics. Further analysis of a larger number of superclusters within the 50 deg2 of the XXL is needed before any conclusions on the effect of the supercluster environment on AGN can be reached.
  • Mair, J., et al. (författare)
  • How is cardiac troponin released from injured myocardium?
  • 2018
  • Ingår i: European Heart Journal-Acute Cardiovascular Care. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 7:6, s. 553-560
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiac troponin I and cardiac troponin T are nowadays the criterion biomarkers for the laboratory diagnosis of acute myocardial infarction due to their very high sensitivities and specificities for myocardial injury. However, still many aspects of their degradation, tissue release and elimination from the human circulation are incompletely understood. Myocardial injury may be caused by a variety of different mechanisms, for example, myocardial ischaemia, inflammatory and immunological processes, trauma, drugs and toxins, and myocardial necrosis is preceded by a substantial reversible prelethal phase. Recent experimental data in a pig model of myocardial ischaemia demonstrated cardiac troponin release into the circulation from apoptotic cardiomyocytes as an alternative explanation for clinical situations with increased cardiac troponin without any other evidence for myocardial necrosis. However, the comparably lower sensitivities of all currently available imaging modalities, including cardiac magnetic resonance imaging for the detection of particularly non-focal myocardial necrosis in patients, has to be considered for cardiac troponin test result interpretation in clinical settings without any other evidence for myocardial necrosis apart from increased cardiac troponin concentrations as well.
  • Matosin, N, et al. (författare)
  • Associations of psychiatric disease and ageing with FKBP5 expression converge on superficial layer neurons of the neocortex
  • 2023
  • Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 145:4, s. 439-459
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification and characterisation of novel targets for treatment is a priority in the field of psychiatry. FKBP5 is a gene with decades of evidence suggesting its pathogenic role in a subset of psychiatric patients, with potential to be leveraged as a therapeutic target for these individuals. While it is widely reported that FKBP5/FKBP51 mRNA/protein (FKBP5/1) expression is impacted by psychiatric disease state, risk genotype and age, it is not known in which cell types and sub-anatomical areas of the human brain this occurs. This knowledge is critical to propel FKBP5/1-targeted treatment development. Here, we performed an extensive, large-scale postmortem study (n = 1024) of FKBP5/1, examining neocortical areas (BA9, BA11 and ventral BA24/BA24a) derived from subjects that lived with schizophrenia, major depression or bipolar disorder. With an extensive battery of RNA (bulk RNA sequencing, single-nucleus RNA sequencing, microarray, qPCR, RNAscope) and protein (immunoblot, immunohistochemistry) analysis approaches, we thoroughly investigated the effects of disease state, ageing and genotype on cortical FKBP5/1 expression including in a cell type-specific manner. We identified consistently heightened FKBP5/1 levels in psychopathology and with age, but not genotype, with these effects strongest in schizophrenia. Using single-nucleus RNA sequencing (snRNAseq; BA9 and BA11) and targeted histology (BA9, BA24a), we established that these disease and ageing effects on FKBP5/1 expression were most pronounced in excitatory superficial layer neurons of the neocortex, and this effect appeared to be consistent in both the granular and agranular areas examined. We then found that this increase in FKBP5 levels may impact on synaptic plasticity, as FKBP5 gex levels strongly and inversely correlated with dendritic mushroom spine density and brain-derived neurotrophic factor (BDNF) levels in superficial layer neurons in BA11. These findings pinpoint a novel cellular and molecular mechanism that has potential to open a new avenue of FKBP51 drug development to treat cognitive symptoms in psychiatric disorders.
  • Mueller, C., et al. (författare)
  • Cardiovascular biomarkers in patients with COVID-19
  • 2021
  • Ingår i: European Heart Journal-Acute Cardiovascular Care. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 10:3, s. 310-319
  • Tidskriftsartikel (refereegranskat)abstract
    • The coronavirus disease 2019 (COVID-19) pandemic has increased awareness that severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) may have profound effects on the cardiovascular system. COVID-19 often affects patients with pre-existing cardiac disease, and may trigger acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE), acute myocardial infarction (AMI), and acute heart failure (AHF). However, as COVID-19 is primarily a respiratory infectious disease, there remain substantial uncertainty and controversy whether and how cardiovascular biomarkers should be used in patients with suspected COVID-19. To help clinicians understand the possible value as well as the most appropriate interpretation of cardiovascular biomarkers in COVID-19, it is important to highlight that recent findings regarding the prognostic role of cardiovascular biomarkers in patients hospitalized with COVID-19 are similar to those obtained in studies for pneumonia and ARDS in general. Cardiovascular biomarkers reflecting pathophysiological processes involved in COVID-19/pneumonia and its complications have a role evaluating disease severity, cardiac involvement, and risk of death in COVID-19 as well as in pneumonias caused by other pathogens. First, cardiomyocyte injury, as quantified by cardiac troponin concentrations, and haemodynamic cardiac stress, as quantified by natriuretic peptide concentrations, may occur in COVID-19 as in other pneumonias. The level of those biomarkers correlates with disease severity and mortality. Interpretation of cardiac troponin and natriuretic peptide concentrations as quantitative variables may aid in risk stratification in COVID-19/pneumonia and also will ensure that these biomarkers maintain high diagnostic accuracy for AMI and AHF. Second, activated coagulation as quantified by D-dimers seems more prominent in COVID-19 as in other pneumonias. Due to the central role of endothelitis and VTE in COVID-19, serial measurements of D-dimers may help physicians in the selection of patients for VTE imaging and the intensification of the level of anticoagulation from prophylactic to slightly higher or even therapeutic doses.
  • Pickering, John W., et al. (författare)
  • Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection A Collaborative Meta-analysis
  • 2017
  • Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 166:10, s. 715-724
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: High-sensitivity assays for cardiac troponin T (hs-cTnT) are sometimes used to rapidly rule out acute myocardial infarction (AMI). Purpose: To estimate the ability of a single hs-cTnT concentration below the limit of detection (<0.005 mu g/L) and a nonischemic electrocardiogram (ECG) to rule out AMI in adults presenting to the emergency department (ED) with chest pain. Data Sources: EMBASE and MEDLINE without language restrictions (1 January 2008 to 14 December 2016). Study Selection: Cohort studies involving adults presenting to the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT measurements were obtained and AMI outcomes adjudicated during initial hospitalization. Data Extraction: Investigators of studies provided data on the number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements <0.005 mu g/L) and the number who had AMI during hospitalization (primary outcome) or a major adverse cardiac event (MACE) or death within 30 days (secondary outcomes), by risk classification (low or not low risk). Two independent epidemiologists rated risk of bias of studies. Data Synthesis: Of 9241 patients in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%) low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7% (95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%; pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died. Limitation: Few studies, variation in timing and methods of reference standard troponin tests, and heterogeneity of risk and prevalence of AMI across studies. Conclusion: A single hs-cTnT concentration below the limit of detection in combination with a nonischemic ECG may successfully rule out AMI in patients presenting to EDs with possible emergency acute coronary syndrome.
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