To compare the performance of 3 published delayed graft function (DGF) calculators that compute the theoretical risk of DGF for each patient.
This single-center, retrospective study included 247 ...consecutive kidney transplants from a deceased donor. These kidney transplantations were performed at our institution between January 2003 and December 2012. We compared the occurrence of observed DGF in our cohort with the predicted DGF according to three different published calculators. The accuracy of the calculators was evaluated by means of the c-index (receiver operating characteristic curve).
DGF occurred in 15.3% of the transplants under study. The c index of the Irish calculator provided an area under the curve (AUC) of 0.69 indicating an acceptable level of prediction, in contrast to the poor performance of the Jeldres nomogram (AUC = 0.54) and the Chapal nomogram (AUC = 0.51). With the Irish algorithm the predicted DGF risk and the observed DGF probabilities were close. The mean calculated DGF risk was significantly different between DGF-positive and DGF-negative subjects (
< 0.0001). However, at the level of the individual patient the calculated risk of DGF overlapped very widely with ranges from 10% to 51% for recipients with DGF and from 4% to 56% for those without DGF. The sensitivity, specificity and positive predictive value of a calculated DGF risk ≥ 30% with the Irish nomogram were 32%, 91% and 38%.
Predictive models for DGF after kidney transplantation are performant in the population in which they were derived, but less so in external validations.
Results are presented of a search for new particles decaying to large numbers of jets in association with missing transverse momentum, using 4.7 fb^-1 of pp collision data at sqrt(s) = 7 TeV ...collected by the ATLAS experiment at the Large Hadron Collider in 2011. The event selection requires missing transverse momentum, no isolated electrons or muons, and from >=6 to >=9 jets. No evidence is found for physics beyond the Standard Model. The results are interpreted in the context of a MSUGRA/CMSSM supersymmetric model, where, for large universal scalar mass m_0, gluino masses smaller than 840 GeV are excluded at the 95% confidence level, extending previously published limits. Within a simplified model containing only a gluino octet and a neutralino, gluino masses smaller than 870 GeV are similarly excluded for neutralino masses below 100 GeV.
A 12-month multicenter, double-blind trial in which maintenance renal transplant patients were randomized to remain on mycophenolate mofetil (MMF) or convert to enteric-coated mycophenolate sodium ...(EC-MPS, myfortic) has demonstrated that conversion from MMF to EC-MPS is safe. Patients completing the study were invited to enter an open-label extension. Upon entry to the extension, patients who had received MMF during the randomized phase were converted to EC-MPS ("newly-exposed EC-MPS" group) and were monitored separately from those who had been randomized to EC-MPS ("long-term EC-MPS" group). The aim of the extension study was to collect long-term safety and efficacy data on EC-MPS, and to confirm the safety of conversion from MMF to EC-MPS in a larger patient population.
All patients received EC-MPS 720 mg b.i.d. with cyclosporine microemulsion and corticosteroids per local practice. Data derived from the analysis of the first 24 months of the extension phase are presented.
Of the 297 patients who completed the core study, 260 (88%) entered the extension; 195 (75%) completed the 24-month extension visit. For on-treatment patients > 95% of the planned daily dose of EC-MPS was administered, and < 13% of patients in both groups had discontinued EC-MPS due to adverse events by 24 months. The overall incidence of adverse events during the extension phase, including infections and hematological abnormalities, was comparable to that seen in the core study, with a similar safety profile in the newly-exposed and long-term EC-MPS groups. There were 3 deaths during the first 24 months of the extension, and 2 graft failures in both the "newly-exposed" and "long-term" EC-MPS groups.
These data demonstrate that long-term use of EC-MPS is effective and has an acceptable tolerability profile in renal transplant patients, and confirm that conversion of maintenance renal transplant patients from MMF to EC-MPS is a safe therapeutic option.
Two simultaneous frequencies of quasi-periodic millisecond modulation of the X-ray flux (twin kilohertz quasi-periodic oscillations) have recently been detected in an accreting 2.5 ms X-ray pulsar. ...Their difference, equal to about ½ of the neutron star spin rate, clearly indicates that resonant oscillations of the accretion disk have been observed. Similar nonlinear resonances may be spontaneously excited in the accretion disk in the absence of a pulsar, e.g., in black holes. We identify modes of disk oscillations whose frequencies are in agreement with the two observed ones when the rotating neutron star is modeled with realistic equations of state.
Context. The Event Horizon Telescope (EHT) collaboration recently obtained first images of the surroundings of the supermassive compact object M87* at the center of the galaxy M87. Aims. We want to ...develop a simple analytic disk model for the accretion flow of M87*. Compared to general-relativistic magnetohydrodynamic (GRMHD) models, it has the advantage of being independent of the turbulent character of the flow, and controlled by only few easy-to-interpret, physically meaningful parameters. We want to use this model to predict the image of M87* assuming that it is either a Kerr black hole, or an alternative compact object. Methods. We compute the synchrotron emission from the disk model and propagate the resulting light rays to the far-away observer by means of relativistic ray tracing. Such computations are performed assuming different spacetimes (Kerr, Minkowski, non-rotating ultracompact star, rotating boson star or Lamy spinning wormhole). We perform numerical fits of these models to the EHT data. Results. We discuss the highly-lensed features of Kerr images and show that they are intrinsically linked to the accretion-flow properties, and not only to gravitation. This fact is illustrated by the notion of secondary ring that we introduce. Our model of spinning Kerr black hole predicts mass and orientation consistent with the EHT interpretation. The non-Kerr images result in similar quality of the numerical fits and may appear very similar to Kerr images, once blurred to the EHT resolution. This implies that a strong test of the Kerr spacetime may be out of reach with the current data. We notice that future developments of the EHT could alter this situation. Conclusions. Our results show the importance of studying alternatives to the Kerr spacetime in order to be able to test the Kerr paradigm unambiguously.
Isodisomy (ID) is a genetic anomaly defined as the inheritance of two copies of the same genetic material from one parent. ID in an offspring is a rare cause of recessive genetic diseases via ...inheritance of two copies of a mutated gene from one carrier parent. We studied a newborn female with a mut(o) of methylmalonic acidemia and complete absence of insulin-producing beta cells in otherwise normal-appearing pancreatic islets, causing insulin-dependent diabetes mellitus. The patient died 2 wk after birth. Serotyping of the HLA antigens, DNA typing of HLA-B and HLA class II loci, study of polymorphic DNA markers of chromosome 6, and cytogenetic analysis demonstrated paternal ID, involving at least a 25-centiMorgan portion of the chromosome pair that encompasses the MHC. ID probably caused methylmalonic acidemia by duplication of a mutated allele of the corresponding gene on the chromosome 6 inherited from the father. It is also very likely that ID was etiologically related to the agenesis of beta cells and consequent insulin-dependent diabetes mellitus in our patient. We thus speculate on the existence of a gene on chromosome 6 involved in beta cell differentiation.
The cosmic blackbody background radiation pervades the entire Universe, and so falls into every astrophysical black hole. The blueshift of the infalling photons, measured by a static observer, is ...infinite at the event horizon. This raises a question as to whether a "firewall" of high energy density may form just outside the horizon, or whether the effect can be attributed exclusively to a singular behavior of the static observer's frame at the horizon. In principle, the presence of such a firewall may alter the motion of the infalling matter, influence the black hole evolution, or even invalidate the vacuum Einstein field equation solution as a realistic approximation for black holes. In this paper we show by means of analytic calculations that all these effects indeed exist, but their magnitude is typically negligibly small, even though the matter stress tensor is divergent in the static frame at r = 2M. That is not surprising because of the divergent relation of that frame to a freely falling frame as r arrow right 2M; however, it represents a kind of classical analogue for the black hole complementarity principle that has been proposed for quantum effects near a black hole. What is perhaps more surprising is the divergence of the radiation stress tensor for massive particles moving on circular geodesic orbits for values of r approaching r = 3M. However such orbits will not occur for infalling matter in realistic accretion discs.
Kidney transplantation is the best treatment for patients with end-stage renal failure, but uncertainty remains about the best immunosuppression strategy. Long-term graft survival has not improved ...substantially, and one possible explanation is calcineurin inhibitor (CNI) nephrotoxicity. CNI exposure could be minimized by using more potent induction therapy or alternative maintenance therapy to remove CNIs completely. However, the safety and efficacy of such strategies are unknown.
The Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy (3C) Study is a multicentre, open-label, randomized controlled trial with 852 participants which is addressing two important questions in kidney transplantation. The first question is whether a Campath (alemtuzumab)-based induction therapy strategy is superior to basiliximab-based therapy, and the second is whether, from 6 months after transplantation, a sirolimus-based maintenance therapy strategy is superior to tacrolimus-based therapy. Recruitment is complete, and follow-up will continue for around 5 years post-transplant. The primary endpoint for the induction therapy comparison is biopsy-proven acute rejection by 6 months, and the primary endpoint for the maintenance therapy comparison is change in estimated glomerular filtration rate from baseline to 2 years after transplantation. The study is sponsored by the University of Oxford and endorsed by the British Transplantation Society, and 18 centers for adult kidney transplant are participating.
Late graft failure is a major issue for kidney-transplant recipients. If our hypothesis that minimizing CNI exposure with Campath-based induction therapy and/or an elective conversion to sirolimus-based maintenance therapy can improve long-term graft function and survival is correct, then patients should experience better graft function for longer. A positive outcome could change clinical practice in kidney transplantation.
ClinicalTrials.gov, NCT01120028 and ISRCTN88894088.
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