The X-ray Properties of Optically Selected Clusters of Galaxies

We present the results of Chandra and Suzaku X-ray observations of nine moderate-redshift (0.16 < z < 0.42) clusters discovered via the Red-sequence Cluster Survey (RCS). Surface brightness profiles are fitted to beta models, gas masses are determined, integrated spectra are extracted within R2500, and X-ray temperatures and luminosities are inferred. The Lx-Tx relationship expected from self-similar evolution is tested by comparing this sample to our previous X-ray investigation of nine high-redshift (0.6 < z < 1.0) optically selected clusters. We find that optically selected clusters are systematically less luminous than X-ray selected clusters of similar X-ray temperature at both moderate and high-z. We are unable to constrain evolution in the Lx-Tx relation with these data, but find it consistent with no evolution, within relatively large uncertainties. To investigate selection effects, we compare the X-ray properties of our sample to those of clusters in the representative X-ray selected REXCESS sample, also determined within R2500. We find that while RCS cluster X-ray properties span the entire range of those of massive clusters selected by other methods, their average X-ray properties are most similar to those of dynamically disturbed X-ray selected clusters. This similarity suggests that the true cluster distribution might contain a higher fraction of disturbed objects than are typically detected in X-ray selected surveys.Comment: 13 pages, 5 figures; accepted for publication in MNRAS. Figure quality reduced to comply with arXiv file size requirement

Literature review of tri-colored bat natural history with implications to management

In the past decade, caverniculous bat populations have plummeted due to White-nose syndrome (WNS). Tri-colored bat (Perimyotis subflavus) populations have declined drastically in areas where WNS has been found, leading to the decision to protect tri-colored bats under the federal Endangered Species Act in the United States. At this time, there has not been a thorough review of the literature, nor a concise summary of the tri-colored bat’s life history, diet, threats, or habitat preferences. This absence creates more work for policy makers, federal “Take” permit applicants, and conservationists to find, access, and review critical details of tri-colored bats. A major point of confusion stems from the multiple common names and genera tri-colored bats have been classified under since it was first described a century and a half ago. To address the lack of concise summary, we scoured the scientific literature and compiled nearly a century of data to provide a robust review of the ecology, life history, winter and summer habitats, as well as created maps and figures showing counties where studies have occurred, white-nose syndrome is present, and where bats have been documented. Additionally, this paper highlights data gaps and suggests future research topics that may better inform conservation and management decisions for tri-colored bats

Multiplexable fluorescence lifetime imaging (FLIM) probes for Abl and Src-family kinases

Many commonly employed strategies to map kinase activities in live cells require expression of genetically encoded proteins (e.g. FRET sensors). In this work, we describe the development and preliminary application of a set of cell-penetrating, fluorophore labelled peptide substrates for fluorescence lifetime imaging (FLIM) of Abl and Src-family kinase activities. These probes do not rely on FRET pairs or genetically-encoded protein expression. We further demonstrate probe multiplexing and pixel-by-pixel quantification to estimate the relative proportion of modified probe, suggesting that this strategy will be useful for detailed mapping of single cell and subcellular dynamics of multiple kinases concurrently in live cells

Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naïve, Metastatic, Castration-Resistant Prostate Cancer

Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327). The primary biomarker endpoint was analysis of post-treatment CTCs to confirm the hypothesis that clinical response was associated with taxane drug-target engagement, evidenced by decreased percent androgen receptor nuclear localization (%ARNL) and increased microtubule bundling. Results Sixty-three patients were randomly assigned to docetaxel (n = 41) or cabazitaxel (n = 22); 44.4% received prior potent androgen receptor-targeted therapy. Overall, 35 patients (55.6%) had confirmed ≥ 50% PSA responses, exceeding the historical control rate of 45.4% (TAX327). Of 61 treated patients, 33 (54.1%) had ≥ 30% PSA declines by C4 and did not switch taxane, 15 patients (24.6%) who did not achieve ≥ 30% PSA declines by C4 switched taxane, and 13 patients (21.3%) discontinued therapy before or at C4. Of patients switching taxane, 46.7% subsequently achieved ≥ 50% PSA decrease. In 26 CTC-evaluable patients, taxane-induced decrease in %ARNL (cycle 1 day 1 v cycle 1 day 8) was associated with a higher rate of ≥ 50% PSA decrease at C4 ( P = .009). Median composite progression-free survival was 9.1 months (95% CI, 4.9 to 11.7 months); median overall survival was not reached at 14 months. Common grade 3 or 4 adverse events included fatigue (13.1%) and febrile neutropenia (11.5%). Conclusion The early taxane switch strategy was associated with improved PSA response rates versus TAX327. Taxane-induced shifts in %ARNL may serve as an early biomarker of clinical benefit in patients treated with taxanes

Art/Act: A WGS Online Magazine

22 pages“Art, Activism, and Popular Culture” (WGS 199) investigates how art and activism intersect to address pressing contemporary social issues concerning gender, race, and sexuality. In particular, the course focuses on how art is utilized as feminist activism, and vice versa, to address social issues such as the prison industrial complex, sexual assault, media production, institutional critique, and HIV/AIDS. The course takes on a special emphasis on how artists-activists-students have utilized art to organize and create change on the college campus. Along with rigorous reading and writing, in the Winter 2016 term, students also engaged in the topic of art and activism through constructionist learning— learning through creating—in a special lab component of the class. In collaboration with the Jordan Schnitzer Museum of Art, students participated in a special museum activity to explore art history and the politics of institutional critique on campus

Functional Characterization of Circulating Tumor Cells with a Prostate-Cancer-Specific Microfluidic Device

Cancer metastasis accounts for the majority of cancer-related deaths owing to poor response to anticancer therapies. Molecular understanding of metastasis-associated drug resistance remains elusive due to the scarcity of available tumor tissue. Isolation of circulating tumor cells (CTCs) from the peripheral blood of patients has emerged as a valid alternative source of tumor tissue that can be subjected to molecular characterization. However, issues with low purity and sensitivity have impeded adoption to clinical practice. Here we report a novel method to capture and molecularly characterize CTCs isolated from castrate-resistant prostate cancer patients (CRPC) receiving taxane chemotherapy. We have developed a geometrically enhanced differential immunocapture (GEDI) microfluidic device that combines an anti-prostate specific membrane antigen (PSMA) antibody with a 3D geometry that captures CTCs while minimizing nonspecific leukocyte adhesion. Enumeration of GEDI-captured CTCs (defined as intact, nucleated PSMA+/CD45− cells) revealed a median of 54 cells per ml identified in CRPC patients versus 3 in healthy donors. Direct comparison with the commercially available CellSearch® revealed a 2–400 fold higher sensitivity achieved with the GEDI device. Confocal microscopy of patient-derived GEDI-captured CTCs identified the TMPRSS2:ERG fusion protein, while sequencing identified specific androgen receptor point mutation (T868A) in blood samples spiked with only 50 PC C4-2 cells. On-chip treatment of patient-derived CTCs with docetaxel and paclitaxel allowed monitoring of drug-target engagement by means of microtubule bundling. CTCs isolated from docetaxel-resistant CRPC patients did not show any evidence of drug activity. These measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new anticancer agents

Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks