Phase II trial of temsirolimus for relapsed/refractory primary CNS lymphoma

Purpose: In this phase II study (NCT00942747), temsirolimus was tested in patients with relapsed or refractory primary CNS lymphoma (PCNSL). Patients and Methods: Immunocompetent adults with histologically confirmed PCNSL after experiencing high-dose methotrexate-based chemotherapy failure who were not eligible for or had experienced high-dose chemotherapy with autologous stem-cell transplant failure were included. The first cohort (n = 6) received 25 mg temsirolimus intravenously once per week. All consecutive patients received 75 mg intravenously once per week. Results: Thirty-seven eligible patients (median age, 70 years) were included whose median time since their last treatment was 3.9 months (range, 0.1 to 14.6 months). Complete response was seen in five patients (13.5%), complete response unconfirmed in three (8%), and partial response in 12 (32.4%) for an overall response rate of 54%. Median progression-free survival was 2.1 months (95% CI, 1.1 to 3.0 months). The most frequent Common Toxicity Criteria ≥ 3° adverse event was hyperglycemia in 11 (29.7%) patients, thrombocytopenia in eight (21.6%), infection in seven (19%), anemia in four (10.8%), and rash in three (8.1%). Fourteen blood/CSF pairs were collected in nine patients (10 pairs in five patients in the 25-mg cohort and four pairs in four patients in the 75-mg cohort). The mean maximum blood concentration was 292 ng/mL for temsirolimus and 37.2 ng/mL for its metabolite sirolimus in the 25-mg cohort and 484 ng/mL and 91.1 ng/mL, respectively, in the 75-mg cohort. Temsirolimus CSF concentration was 2 ng/mL in one patient in the 75-mg cohort; in all others, no drug was found in their CSF. Conclusion: Single-agent temsirolimus at a weekly dose of 75 mg was found to be active in relapsed/refractory patients with PCNSL; however, responses were usually short lived

A Central Excess of Stripped-Envelope Supernovae within Disturbed Galaxies

This paper presents an analysis of core-collapse supernova distributions in isolated and interacting host galaxies, paying close attention to the selection effects involved in conducting host galaxy supernova studies. When taking into account all of the selection effects within our host galaxy sample, we draw the following conclusions: i) Within interacting, or 'disturbed', systems there is a real, and statistically significant, increase in the fraction of stripped-envelope supernovae in the central regions. A discussion into what may cause this increased fraction, compared to the more common type IIP supernovae, and type II supernovae without sub-classifications, is presented. Selection effects are shown not to drive this result, and so we propose that this study provides direct evidence for a high-mass weighted initial mass function within the central regions of disturbed galaxies. ii) Within 'undisturbed' spiral galaxies the radial distribution of type Ib and type Ic supernovae is statistically very different, with the latter showing a more centrally concentrated distribution. This could be driven by metallicity gradients in these undisturbed galaxies, or radial variations in other properties (binarity or stellar rotation) driving envelope loss in progenitor stars. This result is not found in 'disturbed' systems, where the distributions of type Ib and Ic supernovae are consistent.Comment: Accepted for publication in MNRA

Use of bioanalyzer electropherograms for quality control and target evaluation in microarray expression profiling studies of ocular tissues

Expression profiling with DNA microarrays has been used to examine the transcriptome of a wide spectrum of vertebrate cells and tissues. The sensitivity and accuracy of the data generated is dependent on the quality and composition of the input RNA. In this report, we examine the quality and array performance of over 200 total RNA samples extracted from ocular tissues and cells that have been processed in a microarray core laboratory over a 7-year period. Total RNA integrity and cRNA target size distribution were assessed using the 2100 Bioanalyzer. We present Affymetrix GeneChip array performance metrics for different ocular samples processed according to a standard microarray assay workflow including several quality control checkpoints. Our review of ocular sample performance in the microarray assay demonstrates the value of considering tissue-specific characteristics in evaluating array data. Specifically, we show that Bioanalyzer electropherograms reveal highly abundant mRNAs in lacrimal gland targets that are correlated with variation in array assay performance. Our results provide useful benchmarks for other gene expression studies of ocular systems

Cytolytic T-cell response against Epstein-Barr virus in lung cancer patients and healthy subjects

<p>Abstract</p> <p>Background</p> <p>This study aimed to examine whether EBV seropositive patients with lung cancer have an altered virus-specific CTL response, as compared to age-matched healthy controls and whether any variation in this response could be attributed to senescence.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells from lung cancer patients, age-matched and younger healthy individuals were used to measure EBV-specific CTLs after in vitro amplification with the GLCTLVAML and RYSIFFDYM peptides followed by HLA-multimer staining.</p> <p>Results</p> <p>Lung cancer patients and aged-matched controls had significantly lesser EBV-specific CTL than younger healthy individuals. Multimer positive populations from either group did not differ with respect to the percentage of multimer positive CTLs and the intensity of multimer binding.</p> <p>Conclusions</p> <p>This study provides evidence that patients with lung cancer exhibit an EBV-specific CTL response equivalent to that of age-matched healthy counterparts. These data warrant the examination of whether young individuals have a more robust anti-tumor response, as is the case with the anti-EBV response.</p

Observed Consequences of Presupernova Instability in Very Massive Stars

This chapter concentrates on the deaths of very massive stars, the events leading up to their deaths, and how mass loss affects the resulting death. The previous three chapters emphasized the theory of wind mass loss, eruptions, and core collapse physics, but here we emphasize mainly the observational properties of the resulting death throes. Mass loss through winds, eruptions, and interacting binaries largely determines the wide variety of different types of supernovae that are observed, as well as the circumstellar environments into which the supernova blast waves expand. Connecting these observed properties of the explosions to the initial masses of their progenitor stars is, however, an enduring challenge and is especially difficult for very massive stars. Superluminous supernovae, pair instability supernovae, gamma ray bursts, and "failed" supernovae are all end fates that have been proposed for very massive stars, but the range of initial masses or other conditions leading to each of these (if they actually occur) are still very certain. Extrapolating to infer the role of very massive stars in the early universe is essentially unencumbered by observational constraints and still quite dicey.Comment: 39 pages, 5 figures, to appear as chapter in the book "Very Massive Stars in the Local Universe", ed. J. Vin

Doing politics in the recent Arab uprisings: Towards a political discourse analysis of the Arab Spring slogans

The present paper aims to analyse a number of those slogans collected from the sit-in quarters in Egypt, Libya and Yemen. Using political discourse analysis, it unravels various typical discourse structures and strategies that are used in slogans in the construction of a sub-genre of political discourse in the Arab world. Drawing data from several mediums, including banners, wall graffiti, audio-visual instruments, chanting, speeches and songs, this paper tries to show the extent to which the slogans serve as a medium by which political complaints and comments are dispensed and consumed. This paper draws on a rhetorical analysis to find out their persuasive effect on shaping the Arab intellect and on the change of the political atmosphere in the region. Lastly, this paper attempts to show to what extent the slogans meet the standards of political discourse and whether they can be considered as a sub-genre of political discourse or not.IS

Observational and Physical Classification of Supernovae

This chapter describes the current classification scheme of supernovae (SNe). This scheme has evolved over many decades and now includes numerous SN Types and sub-types. Many of these are universally recognized, while there are controversies regarding the definitions, membership and even the names of some sub-classes; we will try to review here the commonly-used nomenclature, noting the main variants when possible. SN Types are defined according to observational properties; mostly visible-light spectra near maximum light, as well as according to their photometric properties. However, a long-term goal of SN classification is to associate observationally-defined classes with specific physical explosive phenomena. We show here that this aspiration is now finally coming to fruition, and we establish the SN classification scheme upon direct observational evidence connecting SN groups with specific progenitor stars. Observationally, the broad class of Type II SNe contains objects showing strong spectroscopic signatures of hydrogen, while objects lacking such signatures are of Type I, which is further divided to numerous subclasses. Recently a class of super-luminous SNe (SLSNe, typically 10 times more luminous than standard events) has been identified, and it is discussed. We end this chapter by briefly describing a proposed alternative classification scheme that is inspired by the stellar classification system. This system presents our emerging physical understanding of SN explosions, while clearly separating robust observational properties from physical inferences that can be debated. This new system is quantitative, and naturally deals with events distributed along a continuum, rather than being strictly divided into discrete classes. Thus, it may be more suitable to the coming era where SN numbers will quickly expand from a few thousands to millions of events.Comment: Extended final draft of a chapter in the "SN Handbook". Comments most welcom

Flash Spectroscopy: Emission Lines from the Ionized Circumstellar Material Around &lt;10-Day-Old Type II Supernovae

The American Astronomical Society. All rights reserved.Supernovae (SNe) embedded in dense circumstellar material (CSM) may show prominent emission lines in their early-time spectra (≤10 days after the explosion), owing to recombination of the CSM ionized by the shock-breakout flash. From such spectra ("flash spectroscopy"), we can measure various physical properties of the CSM, as well as the mass-loss rate of the progenitor during the year prior to its explosion. Searching through the Palomar Transient Factory (PTF and iPTF) SN spectroscopy databases from 2009 through 2014, we found 12 SNe II showing flash-ionized (FI) signatures in their first spectra. All are younger than 10 days. These events constitute 14% of all 84 SNe in our sample having a spectrum within 10 days from explosion, and 18% of SNe II observed at ages <5 days, thereby setting lower limits on the fraction of FI events. We classified as "blue/featureless" (BF) those events having a first spectrum that is similar to that of a blackbody, without any emission or absorption signatures. It is possible that some BF events had FI signatures at an earlier phase than observed, or that they lack dense CSM around the progenitor. Within 2 days after explosion, 8 out of 11 SNe in our sample are either BF events or show FI signatures. Interestingly, we found that 19 out of 21 SNe brighter than an absolute magnitude MR = -18.2 belong to the FI or BF groups, and that all FI events peaked above MR = -17.6 mag, significantly brighter than average SNe II