Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia

Optimal conditioning therapy for hematopoietic cell transplantation (HCT) in acute myelogenous leukemia (AML) remains undefined. We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1 mg/kg every 6 hours for 4 days) and cyclophosphamide (60 mg/kg IV × 2 days) - (Bu/Cy) with 100 consecutive AML patients treated with pharmacokinetic targeted IV busulfan (AUC < 6000 μM/L*min per day × 4 days) and fludarabine (40 mg/m2 × 4 days) - (t-IV Bu/Flu). The Bu/Cy and t-IV Bu/Flu groups significantly differed according to donor relation, stem cell source, aGVHD prophylaxis, remission status, primary vs. secondary disease, median age, and % blasts prior to HCT (p < 0.01 for each). Conditioning with t-IV Bu/Flu reduced early toxicity including idiopathic pneumonia syndrome (IPS) and hepatic veno-occlusive disease (VOD). Additionally, the trajectory of early NRM (100 day: 16% vs. 3%, and1 year: 25% vs. 15% for Bu/Cy and t-IV Bu/Flu, respectively) favored t-IV Bu/Flu. Grade II-IV aGVHD (48% vs. 82%, p < 0.0001), as well as moderate/severe cGVHD (7% vs. 40%, p < 0.0001) differed between the Bu/Cy and t-IV Bu/Flu groups, due to the predominance of peripheral blood stem cells in the t-IV Bu/Flu group. Pharmacokinetic targeting of intravenous busulfan in combination with fludarabine is associated with reduced conditioning regimen related toxicity compared to oral busulfan and cyclophosphamide. However, multivariable analysis did not demonstrate significant differences in overall survival (p = 0.78) or non-relapse mortality (p = 0.6) according to conditioning regimen delivered

Evolutionary Trajectory of White Spot Syndrome Virus (WSSV) Genome Shrinkage during Spread in Asia

Background - White spot syndrome virus (WSSV) is the sole member of the novel Nimaviridae family, and the source of major economic problems in shrimp aquaculture. WSSV appears to have rapidly spread worldwide after the first reported outbreak in the early 1990s. Genomic deletions of various sizes occur at two loci in the WSSV genome, the ORF14/15 and ORF23/24 variable regions, and these have been used as molecular markers to study patterns of viral spread over space and time. We describe the dynamics underlying the process of WSSV genome shrinkage using empirical data and a simple mathematical model. Methodology/Principal Findings - We genotyped new WSSV isolates from five Asian countries, and analyzed this information together with published data. Genome size appears to stabilize over time, and deletion size in the ORF23/24 variable region was significantly related to the time of the first WSSV outbreak in a particular country. Parameter estimates derived from fitting a simple mathematical model of genome shrinkage to the data support a geometric progression (

A search for pair-produced resonances in four-jet final states at root s=13 TeV with the ATLAS detector

A search for massive coloured resonances which are pair-produced and decay into two jets is presented. The analysis uses 36.7 fb−1 − 1 of √ s = 13 TeV pp collision data recorded by the ATLAS experiment at the LHC in 2015 and 2016. No significant deviation from the background prediction is observed. Results are interpreted in a SUSY simplified model where the lightest supersymmetric particle is the top squark, ̃ t ~ , which decays promptly into two quarks through R-parity-violating couplings. Top squarks with masses in the range 100 GeV<̃<410 100 GeV < m t ~ < 410 GeV GeV are excluded at 95% confidence level. If the decay is into a b-quark and a light quark, a dedicated selection requiring two b-tags is used to exclude masses in the ranges 100 GeV<̃<470 100 GeV < m t ~ < 470 GeV GeV and 480 GeV<̃<610 480 GeV < m t ~ < 610 GeV GeV . Additional limits are set on the pair-production of massive colour-octet resonances

Measurements of electroweak Wjj production and constraints on anomalous gauge couplings with the ATLAS detector

Measurements of the electroweak production of a W boson in association with two jets at high dijet invariant mass are performed using root s = 7 and 8 TeV proton-proton collision data produced by the Large Hadron Collider, corresponding respectively to 4.7 and 20.2 fb(-1) of integrated luminosity collected by the ATLAS detector. The measurements are sensitive to the production of a W boson via a triple-gauge-boson vertex and include both the fiducial and differential cross sections of the electroweak process

Corticofugal modulation of acoustically induced Fos expression in the rat auditory pathway

To investigate the corticofugal modulation of acoustic information ascending through the auditory pathway of the rat, immunohistochemical techniques were used to study the functional expression of Fos protein in neurons. With auditory stimulation at different frequencies, Fos expression in the medial geniculate body (MGB), inferior colliculus (IC), superior olivary complex, and cochlear nucleus was examined, and the extent of Fos expression on the two sides was compared. Strikingly, we found densely Fos-labeled neurons in all divisions of the MGB after both presentation of an auditory stimulus and administration of a γ-aminobutyric acid type A (GABAA) antagonist (bicuculline methobromide; BIM) to the auditory cortex. The location of Fos-labeled neurons in the ventral division (MGv) after acoustic stimulation at different frequencies was in agreement with the known tonotopic organization. That no Fos-labeled neurons were found in the MGv with acoustic stimuli alone suggests that the transmission of ascending thalamocortical information is critically governed by corticofugal modulation. The dorsal (DCIC) and external cortices (ECIC) of the IC ipsilateral to the BIM-injected cortex showed a significantly higher number of Fos-labeled neurons than the contralateral IC. However, no difference in the number of Fos-labeled neurons was found between the central nucleus of the IC on either side, indicating that direct corticofugal modulation occurs only in the ECIC and DCIC. Further investigations are needed to assess the functional implications of the morphological differences observed between the descending corticofugal projections to the thalamus and the IC. © 2007 Wiley-Liss, Inc.link_to_subscribed_fulltex

A rough multi-objective genetic algorithm for uncertain constrained multi-objective solid travelling salesman problem

This paper addresses a rough multi-objective genetic algorithm (R-MOGA) to solve constrained multi-objective solid travelling salesman problems (CMOSTSPs) in rough, fuzzy rough and random rough environments. In the proposed R-MOGA, “3- and 5-level linguistic-based rough age oriented selection” and “adaptive crossover” are used along with a new generation-dependent mutation. In the present study, the age of each chromosome is termed as 3-level by young, middle and old and 5-level by very young, young, middle, old and very old. Here, we model the CMOSTSP with travelling costs and times as two objectives and a constraint for route risk/discomfort factors. The costs, times and risk/discomfort are rough, fuzzy rough and random rough in nature. To test the efficiency, combining same size single objective problems from standard TSPLIB, the results of such multi-objective problems are obtained by the proposed algorithm, simple MOGA and NSGA-II are compared. Moreover, a statistical analysis (analysis of variance) is carried out to show the supremacy of the proposed algorithm.</p