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

Get screened: a pragmatic randomized controlled trial to increase mammography and colorectal cancer screening in a large, safety net practice

Abstract Background Most randomized controlled trials of interventions designed to promote cancer screening, particularly those targeting poor and minority patients, enroll selected patients. Relatively little is known about the benefits of these interventions among unselected patients. Methods/Design "Get Screened" is an American Cancer Society-sponsored randomized controlled trial designed to promote mammography and colorectal cancer screening in a primary care practice serving low-income patients. Eligible patients who are past due for mammography or colorectal cancer screening are entered into a tracking registry and randomly assigned to early or delayed intervention. This 6-month intervention is multimodal, involving patient prompts, clinician prompts, and outreach. At the time of the patient visit, eligible patients receive a low-literacy patient education tool. At the same time, clinicians receive a prompt to remind them to order the test and, when appropriate, a tool designed to simplify colorectal cancer screening decision-making. Patient outreach consists of personalized letters, automated telephone reminders, assistance with scheduling, and linkage of uninsured patients to the local National Breast and Cervical Cancer Early Detection program. Interventions are repeated for patients who fail to respond to early interventions. We will compare rates of screening between randomized groups, as well as planned secondary analyses of minority patients and uninsured patients. Data from the pilot phase show that this multimodal intervention triples rates of cancer screening (adjusted odds ratio 3.63; 95% CI 2.35 - 5.61). Discussion This study protocol is designed to assess a multimodal approach to promotion of breast and colorectal cancer screening among underserved patients. We hypothesize that a multimodal approach will significantly improve cancer screening rates. The trial was registered at Clinical Trials.gov NCT00818857http://deepblue.lib.umich.edu/bitstream/2027.42/78264/1/1472-6963-10-280.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78264/2/1472-6963-10-280.pdfPeer Reviewe

Logarithmic Corrections to Schwarzschild and Other Non-extremal Black Hole Entropy in Different Dimensions

Euclidean gravity method has been successful in computing logarithmic corrections to extremal black hole entropy in terms of low energy data, and gives results in perfect agreement with the microscopic results in string theory. Motivated by this success we apply Euclidean gravity to compute logarithmic corrections to the entropy of various non-extremal black holes in different dimensions, taking special care of integration over the zero modes and keeping track of the ensemble in which the computation is done. These results provide strong constraint on any ultraviolet completion of the theory if the latter is able to give an independent computation of the entropy of non-extremal black holes from microscopic description. For Schwarzschild black holes in four space-time dimensions the macroscopic result seems to disagree with the existing result in loop quantum gravity.Comment: LaTeX, 40 pages; corrected small typos and added reference

Quantum Gravity in Everyday Life: General Relativity as an Effective Field Theory

This article is meant as a summary and introduction to the ideas of effective field theory as applied to gravitational systems. Contents: 1. Introduction 2. Effective Field Theories 3. Low-Energy Quantum Gravity 4. Explicit Quantum Calculations 5. ConclusionsComment: 56 pages, 2 figures, JHEP style, Invited review to appear in Living Reviews of Relativit

Logarithmic Corrections to Extremal Black Hole Entropy from Quantum Entropy Function

We evaluate the one loop determinant of matter multiplet fields of N=4 supergravity in the near horizon geometry of quarter BPS black holes, and use it to calculate logarithmic corrections to the entropy of these black holes using the quantum entropy function formalism. We show that even though individual fields give non-vanishing logarithmic contribution to the entropy, the net contribution from all the fields in the matter multiplet vanishes. Thus logarithmic corrections to the entropy of quarter BPS black holes, if present, must be independent of the number of matter multiplet fields in the theory. This is consistent with the microscopic results. During our analysis we also determine the complete spectrum of small fluctuations of matter multiplet fields in the near horizon geometry.Comment: LaTeX file, 52 pages; v2: minor corrections, references adde

Visualizing the Effects of rTMS in a Patient Sample: Small N vs. Group Level Analysis

The use of transcranial magnetic stimulation (TMS) to assess changes in cortical excitability is a tool used with increased prevalence in healthy and impaired populations. One factor of concern with this technique is how to achieve adequate statistical power given constraints of a small number of subjects and variability in responses. This paper compares a single pulse excitability measure using traditional group-level statistics vs single subject analyses in a patient population of subjects with focal hand dystonia, pre and post repetitive TMS (rTMS). Results show significant differences in cortical excitability for 4/5 subjects using a split middle line analysis on plots of individual subject data. Group level statistics (ANOVA), however, did not detect any significant findings. The consideration of single subject statistics for TMS excitability measures may assist researchers in describing the variably of rTMS outcome measures

Personality trait development in midlife: exploring the impact of psychological turning points

This study examined long-term personality trait development in midlife and explored the impact of psychological turning points on personality change. Selfdefined psychological turning points reflect major changes in the ways people think or feel about an important part of their life, such as work, family, and beliefs about themselves and about the world. This study used longitudinal data from the Midlife in the US survey to examine personality trait development in adults aged 40–60 years. The Big Five traits were assessed in 1995 and 2005 by means of self-descriptive adjectives. Seven types of self-identified psychological turning points were obtained in 1995. Results indicated relatively high stability with respect to rankorders and mean-levels of personality traits, and at the same time reliable individual differences in change. This implies that despite the relative stability of personality traits in the overall sample, some individuals show systematic deviations from the sample mean-levels. Psychological turning points in general showed very little influence on personality trait change, although some effects were found for specific types of turning points that warrant further research, such as discovering that a close friend or relative was a much better person than one thought they were