High fludarabine exposure and relationship with treatment-related mortality after nonmyeloablative hematopoietic cell transplantation.

Despite its common use in nonmyeloablative preparative regimens, the pharmacokinetics of fludarabine are poorly characterized in hematopoietic cell transplantation (HCT) recipients and exposure-response relationships remain undefined. The objective of this study was to evaluate the association between plasma F-ara-A exposure, the systemically circulating moiety of fludarabine, and engraftment, acute GVHD, TRM and OS after HCT. The preparative regimen consisted of CY 50 mg/kg/day i.v. day -6; plus fludarabine 30-40 mg/m²/day i.v. on days -6 to -2 and TBI 200 cGy on day -1. F-ara-A pharmacokinetics were carried out with the first dose of fludarabine in 87 adult patients. Median (range) F-ara-A area-under-the-curve (AUC((0-∞))) was 5.0 μg h/mL (2.0-11.0), clearance 15.3 L/h (6.2-36.6), C(min) 55 ng/mL (17-166) and concentration on day(zero) 16.0 ng/mL (0.1-144.1). Despite dose reductions, patients with renal insufficiency had higher F-ara-A exposures. There was strong association between high plasma concentrations of F-ara-A and increased risk of TRM and reduced OS. Patients with an AUC((0-∞)) greater than 6.5 μg h/mL had 4.56 greater risk of TRM and significantly lower OS. These data suggest that clinical strategies are needed to optimize dosing of fludarabine to prevent overexposure and toxicity in HCT

Epstein-Barr virus infections and DNA hybridization studies in posttransplantation lymphoma and lymphoproliferative lesions: The role of primary infection

Fourteen patients who developed B cell lymphomas or lymphoproliferative lesions after kidney, liver, heart, or heart-lung transplantation in Pittsburgh during 1981-1983 had active infection with Epstein-Barr virus (EBV)of the primary (six patients), reactivated (seven patients), or chronic (one patient) type. In transplant patients without tumors, the incidence of EBV infection was 30% (39 of 128). Only three of these patients had primary infections. Thus the frequency of active infection was significantly higher in patients with tumors, and patients with primary infections were at greater risk of developing tumors. Five of 13 tumors tested contained EBV nuclear antigen (EBNA) and nine of 11 contained EBV genomes detected by DNA-DNA hybridization with BamHI K, BamHI W, or EcoRI B cloned probes. All EBNA-positive tumors, except one, were also positive by hybridization. Only one tumor was negative for both EBNA and EBV DNA. These data suggest that EBV plays an etiologic role in the development of these lesions. © 1985 by The University of Chicago

On Resource-bounded versions of the van Lambalgen theorem

The van Lambalgen theorem is a surprising result in algorithmic information theory concerning the symmetry of relative randomness. It establishes that for any pair of infinite sequences $A$ and $B$, $B$ is Martin-L\"of random and $A$ is Martin-L\"of random relative to $B$ if and only if the interleaved sequence $A \uplus B$ is Martin-L\"of random. This implies that $A$ is relative random to $B$ if and only if $B$ is random relative to $A$ \cite{vanLambalgen}, \cite{Nies09}, \cite{HirschfeldtBook}. This paper studies the validity of this phenomenon for different notions of time-bounded relative randomness. We prove the classical van Lambalgen theorem using martingales and Kolmogorov compressibility. We establish the failure of relative randomness in these settings, for both time-bounded martingales and time-bounded Kolmogorov complexity. We adapt our classical proofs when applicable to the time-bounded setting, and construct counterexamples when they fail. The mode of failure of the theorem may depend on the notion of time-bounded randomness

Observation of contemporaneous optical radiation from a gamma-ray burst

The origin of gamma-ray bursts (GRBs) has been enigmatic since their discovery. The situation improved dramatically in 1997, when the rapid availability of precise coordinates for the bursts allowed the detection of faint optical and radio afterglows - optical spectra thus obtained have demonstrated conclusively that the bursts occur at cosmological distances. But, despite efforts by several groups, optical detection has not hitherto been achieved during the brief duration of a burst. Here we report the detection of bright optical emission from GRB990123 while the burst was still in progress. Our observations begin 22 seconds after the onset of the burst and show an increase in brightness by a factor of 14 during the first 25 seconds; the brightness then declines by a factor of 100, at which point (700 seconds after the burst onset) it falls below our detection threshold. The redshift of this burst, approximately 1.6, implies a peak optical luminosity of 5 times 10^{49} erg per second. Optical emission from gamma-ray bursts has been generally thought to take place at the shock fronts generated by interaction of the primary energy source with the surrounding medium, where the gamma-rays might also be produced. The lack of a significant change in the gamma-ray light curve when the optical emission develops suggests that the gamma-rays are not produced at the shock front, but closer to the site of the original explosion.Comment: 10 pages, 2 figures. Accepted for publication in Nature. For additional information see http://www.umich.edu/~rotse

Persistent Homology Analysis of Brain Artery Trees.

New representations of tree-structured data objects, using ideas from topological data analysis, enable improved statistical analyses of a population of brain artery trees. A number of representations of each data tree arise from persistence diagrams that quantify branching and looping of vessels at multiple scales. Novel approaches to the statistical analysis, through various summaries of the persistence diagrams, lead to heightened correlations with covariates such as age and sex, relative to earlier analyses of this data set. The correlation with age continues to be significant even after controlling for correlations from earlier significant summaries

Superfluid behaviour of a two-dimensional Bose gas

Two-dimensional (2D) systems play a special role in many-body physics. Because of thermal fluctuations, they cannot undergo a conventional phase transition associated to the breaking of a continuous symmetry. Nevertheless they may exhibit a phase transition to a state with quasi-long range order via the Berezinskii-Kosterlitz-Thouless (BKT) mechanism. A paradigm example is the 2D Bose fluid, such as a liquid helium film, which cannot Bose-condense at non-zero temperature although it becomes superfluid above a critical phase space density. Ultracold atomic gases constitute versatile systems in which the 2D quasi-long range coherence and the microscopic nature of the BKT transition were recently explored. However, a direct observation of superfluidity in terms of frictionless flow is still missing for these systems. Here we probe the superfluidity of a 2D trapped Bose gas with a moving obstacle formed by a micron-sized laser beam. We find a dramatic variation of the response of the fluid, depending on its degree of degeneracy at the obstacle location. In particular we do not observe any significant heating in the central, highly degenerate region if the velocity of the obstacle is below a critical value.Comment: 5 pages, 3 figure

The 'Parekh Report' - national identities with nations and nationalism

‘Multiculturalists’ often advocate national identities. Yet few study the ways in which ‘multiculturalists’ do so and in this article I will help to fill this gap. I will show that the Commission for Multi-Ethnic Britain’s report reflects a previously unnoticed way of thinking about the nature and worth of national identities that the Commission’s chair, and prominent political theorist, Bhikhu Parekh, had been developing since the 1970s. This way of thinking will be shown to avoid the questionable ways in which conservative and liberal nationalists discuss the nature and worth of national identities while offering an alternative way to do so. I will thus show that a report that was once criticised for the way it discussed national identities reflects how ‘multiculturalists’ think about national identities in a distinct and valuable way that has gone unrecognised

Are lay people good at recognising the symptoms of schizophrenia?

©2013 Erritty, Wydell. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Aim: The aim of this study was to explore the general public’s perception of schizophrenia symptoms and the need to seekhelp for symptoms. The recognition (or ‘labelling’) of schizophrenia symptoms, help-seeking behaviours and public awareness of schizophrenia have been suggested as potentially important factors relating to untreated psychosis. Method: Participants were asked to rate to what extent they believe vignettes describing classic symptoms (positive and negative) of schizophrenia indicate mental illness. They were also asked if the individuals depicted in the vignettes required help or treatment and asked to suggest what kind of help or treatment. Results: Only three positive symptoms (i.e., Hallucinatory behaviour, Unusual thought content and Suspiciousness) of schizophrenia were reasonably well perceived (above 70%) as indicating mental illness more than the other positive or negative symptoms. Even when the participants recognised that the symptoms indicated mental illness, not everyone recommended professional help. Conclusion: There may be a need to improve public awareness of schizophrenia and psychosis symptoms, particularly regarding an awareness of the importance of early intervention for psychosis

Desperately constructing ethnic audiences: Anti-immigration discourses and minority audience research in the Netherlands

This article examines how minority ethnic audiences are measured, and thus constructed, in the Netherlands today. The analysis shows that this process is tightly woven into the dominant assimilationist and neoliberal discourse. This discourse portrays specific minority groups as deviant in relation to an essentialized notion of Dutchness. Furthermore, it presents social inclusion as an opportunity that is limited to well-adjusted, profitable consumers. Different attempts to represent minority audiences – including efforts to promote a more just minority representation in Dutch media – are compelled to accommodate to this dominant discourse. The article underscores the limited scope for contesting current hegemonic representations of minority groups and national belonging in the Netherlands