192 research outputs found
Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury
Introduction
Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods
We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results
Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P \u3c0.002), none of which achieved an AUC \u3e0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions
Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration
ClinicalTrials.gov number NCT01209169
Peripheral Nervous System Disease in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study
© 2019, American College of Rheumatology Objective: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. Methods: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. Results: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. Conclusion: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution
Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti–Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy
© 2018, American College of Rheumatology Objective: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti–tumor necrosis factor (anti-TNF) therapy and the occurrence of disease flare following withdrawal of anti-TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA). Methods: In this prospective, multicenter study, 137 patients with polyarticular-course JIA whose disease was clinically inactive while receiving anti-TNF therapy were enrolled. Patients were observed for an initial 6-month phase during which anti-TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti-TNF withdrawal. Spearman\u27s rank correlation test, Mann-Whitney U test, Kruskal-Wallis test, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti-TNF withdrawal. Results: Over the 6-month initial phase with anti-TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular-course JIA; following anti-TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti-TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti-TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti-TNF withdrawal were inversely correlated with the time to disease flare (r = −0.36). Conclusion: Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular-course JIA, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare
Elliptic flow of charged particles in Pb-Pb collisions at 2.76 TeV
We report the first measurement of charged particle elliptic flow in Pb-Pb
collisions at 2.76 TeV with the ALICE detector at the CERN Large Hadron
Collider. The measurement is performed in the central pseudorapidity region
(||<0.8) and transverse momentum range 0.2< < 5.0 GeV/. The
elliptic flow signal v, measured using the 4-particle correlation method,
averaged over transverse momentum and pseudorapidity is 0.087 0.002
(stat) 0.004 (syst) in the 40-50% centrality class. The differential
elliptic flow v reaches a maximum of 0.2 near = 3
GeV/. Compared to RHIC Au-Au collisions at 200 GeV, the elliptic flow
increases by about 30%. Some hydrodynamic model predictions which include
viscous corrections are in agreement with the observed increase.Comment: 10 pages, 4 captioned figures, published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/389
Equilibrium configurations of two charged masses in General Relativity
An asymptotically flat static solution of Einstein-Maxwell equations which
describes the field of two non-extreme Reissner - Nordstr\"om sources in
equilibrium is presented. It is expressed in terms of physical parameters of
the sources (their masses, charges and separating distance). Very simple
analytical forms were found for the solution as well as for the equilibrium
condition which guarantees the absence of any struts on the symmetry axis. This
condition shows that the equilibrium is not possible for two black holes or for
two naked singularities. However, in the case when one of the sources is a
black hole and another one is a naked singularity, the equilibrium is possible
at some distance separating the sources. It is interesting that for
appropriately chosen parameters even a Schwarzschild black hole together with a
naked singularity can be "suspended" freely in the superposition of their
fields.Comment: 4 pages; accepted for publication in Phys. Rev.
Two-pion Bose-Einstein correlations in central Pb-Pb collisions at = 2.76 TeV
The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb
collisions at TeV at the Large Hadron Collider is
presented. We observe a growing trend with energy now not only for the
longitudinal and the outward but also for the sideward pion source radius. The
pion homogeneity volume and the decoupling time are significantly larger than
those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/388
Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at TeV
Inclusive transverse momentum spectra of primary charged particles in Pb-Pb
collisions at = 2.76 TeV have been measured by the ALICE
Collaboration at the LHC. The data are presented for central and peripheral
collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross
section. The measured charged particle spectra in and GeV/ are compared to the expectation in pp collisions at the same
, scaled by the number of underlying nucleon-nucleon
collisions. The comparison is expressed in terms of the nuclear modification
factor . The result indicates only weak medium effects ( 0.7) in peripheral collisions. In central collisions,
reaches a minimum of about 0.14 at -7GeV/ and increases
significantly at larger . The measured suppression of high- particles is stronger than that observed at lower collision energies,
indicating that a very dense medium is formed in central Pb-Pb collisions at
the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10,
published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98
Measurement of D+- and D0 production in deep inelastic scattering using a lifetime tag at HERA
The production of D-+/-- and D-0-mesons has been measured with the ZEUS detector at HERA using an integrated luminosity of 133.6 pb(-1). The measurements cover the kinematic range 5 < Q(2) < 1000 GeV2, 0.02 < y < 0.7, 1.5 < p(T)(D) < 15 GeV and |eta(D)| < 1.6. Combinatorial background to the D-meson signals is reduced by using the ZEUS microvertex detector to reconstruct displaced secondary vertices. Production cross sections are compared with the predictions of next-to-leading-order QCD, which is found to describe the data well. Measurements are extrapolated to the full kinematic phase space in order to obtain the open-charm contribution, F-2(c (c) over bar), to the proton structure function, F-2
Planck intermediate results I : Further validation of new Planck clusters with XMM-Newton
Peer reviewe
The ALICE Transition Radiation Detector: Construction, operation, and performance
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection. (c) 2017 CERN for the benefit of the Authors. Published by Elsevier B.V
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