Cost effectiveness of telecare management for pain and depression in patients with cancer: results from a randomized trial

OBJECTIVE: Pain and depression are prevalent and treatable symptoms among patients with cancer, yet they are often undetected and undertreated. The Indiana Cancer Pain and Depression (INCPAD) trial demonstrated that telecare management can improve pain and depression outcomes. This article investigates the incremental cost effectiveness of the INCPAD intervention. METHODS: The INCPAD trial was conducted in 16 community-based urban and rural oncology practices in Indiana. Of the 405 participants, 202 were randomized to the intervention group and 203 to the usual-care group. Intervention costs were determined, and effectiveness outcomes were depression-free days and quality-adjusted life years. RESULTS: The intervention group was associated with a yearly increase of 60.3 depression-free days (S.E. = 15.4; P < 0.01) and an increase of between 0.033 and 0.066 quality-adjusted life years compared to the usual care group. Total cost of the intervention per patient was US$1189, which included physician, nurse care manager and automated monitoring set-up and maintenance costs. Incremental cost per depression-free day was US$19.72, which yields a range of US$18,018 to US$36,035 per quality-adjusted life year when converted to that metric. When measured directly, the incremental cost per quality-adjusted life year ranged from US$10,826 based on the modified EQ-5D to US$73,286.92 based on the SF-12. CONCLUSION: Centralized telecare management, coupled with automated symptom monitoring, appears to be a cost effective intervention for managing pain and depression in cancer patients

CBP loss cooperates with PTEN haploinsufficiency to drive prostate cancer: implications for epigenetic therapy

Despite the high incidence and mortality of prostate cancer, the etiology of this disease is not fully understood. In this study, we develop functional evidence for CBP and PTEN interaction in prostate cancer based on findings of their correlate expression in the human disease. Cbppc−/−;Ptenpc+/− mice exhibited higher cell proliferation in the prostate and an early onset of high-grade prostatic intraepithelial neoplasia. Levels of EZH2 methyltransferase were increased along with its Thr350 phosphorylation in both mouse Cbp−/−;Pten+/− and human prostate cancer cells. CBP loss and PTEN deficiency cooperated to trigger a switch from K27-acetylated histone H3 to K27-trimethylated bulk histones, in a manner associated with decreased expression of the growth inhibitory EZH2 target genes DAB2IP, p27KIP1 and p21CIP1. Conversely, treatment with the histone deacetylase inhibitor panobinostat reversed this switch, in a manner associated with tumor suppression in Cbppc−/−;Ptenpc+/− mice. Our findings show how CBP and PTEN interact to mediate tumor suppression in the prostate, establishing a central role for histone modification in the etiology of prostate cancer and providing a rationale for clinical evaluation of epigenetic targeted therapy in prostate cancer patients

Philosophical and Educational Perspectives on Engineering and Technological Literacy, IV

In this fourth edition of Philosophical Perspectives on Engineering and Technological Literacy, the divisional publication of the Technological and Engineering Literacy and Philosophy of Engineering (TELPhE) Division of ASEE, is trying a new format. Over the years members of the division have noted that many of us keep coming back to the annual ASEE conference year after year not only for the technical papers, but the deep and wide-ranging conversations that crop up organically and spontaneously at the conference like flowers in the desert after a rain. This may be an appropriate metaphor since within our own academic institutions the opportunities to have wide ranging conversations with others who have similar interests in the larger questions that underlie engineering education are often difficult to start or hard to find. Such conversations matter; dialog is fundamental to the practice of both philosophy and literacy. It is a truism to say that we learn through interacting with others and refine our own ideas by sharpening them against those of others. However the practical reality of a conference is to at least not lose money and that of today’s academic life is to publish one’s work. In conjunction, however, these have the effect of steering academic writing towards papers and presentations rather than free ranging dialog. For TELPhE, a group focused on the ideas and narratives that underlie the learning of engineering, it is not clear that such outward facing, many-to-one, ways of communicating are by themselves meeting the Division’s needs. As Mark Twain is alleged to have said, “Let us make a special effort to stop communicating with each other, so we can have some conversation.” This edition begins with an anchoring paper, John Heywood’s Why Technological Literacy and for Whom? which was presented at the 2016 ASEE Annual Conference and Exhibition in New Orleans, Louisiana. In this paper Professor Heywood’s intent was “raise questions about the intent of technological literacy in society at the present time.” Following the ASEE conference a call was put out to all members of the TELPhE Division asking for short responses to Professor Heywood’s paper. These responses, in random order, follow the anchoring paper. Unlike more traditional journals each author was free to comment in the style and form they best saw fit; instruction for style and formatting were minimal to non-existent. The author’s papers have been left mostly “as is” with only consistency between fonts, layout, and similar issues addressed. In cases where a title was not provided by the author one was inserted; apologies to the authors in advance. It is hoped that this form of “dialog journal” will enable a wider ranging conversation within TELPhE that spans not only those who can attend the ASEE conference and whom stumble in to conversation, but also those whose time, circumstance, and resources don’t give them opportunities to attend. The larger goal of this format is to stimulate ongoing dialogs and capture them in ways that are both readable and archival.https://lib.dr.iastate.edu/ece_books/1003/thumbnail.jp

USP10 Regulates p53 Localization and Stability by Deubiquitinating p53

SummaryStability and localization of p53 is essential for its tumor suppressor function. Ubiquitination by the E3 ubiquitin ligase Mdm2 is the major regulatory mechanism of p53, which induces p53 nuclear export and degradation. However, it is unclear whether ubiquitinated cytoplasmic p53 can be recycled. Here, we report that USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53, reversing Mdm2-induced p53 nuclear export and degradation. After DNA damage, USP10 is stabilized, and a fraction of USP10 translocates to the nucleus to activate p53. The translocation and stabilization of USP10 is regulated by ATM -mediated phosphorylation of USP10 at Thr42 and Ser337. Finally, USP10 suppresses tumor cell growth in cells with wild-type p53, with USP10 expression downregulated in a high percentage of clear cell carcinomas, known to have few p53 mutations. These findings reveal USP10 to be a novel regulator of p53, providing an alternative mechanism of p53 inhibition in cancers with wild-type p53

Optimization of laser capture microdissection and RNA amplification for gene expression profiling of prostate cancer

BACKGROUND: To discover prostate cancer biomarkers, we profiled gene expression in benign and malignant cells laser capture microdissected (LCM) from prostate tissues and metastatic prostatic adenocarcinomas. Here we present methods developed, optimized, and validated to obtain high quality gene expression data. RESULTS: RNase inhibitor was included in solutions used to stain frozen tissue sections for LCM, which improved RNA quality significantly. Quantitative PCR assays, requiring minimal amounts of LCM RNA, were developed to determine RNA quality and concentration. SuperScript II™ reverse transcriptase was replaced with SuperScript III™, and SpeedVac concentration was eliminated to optimize linear amplification. The GeneChip(® )IVT labeling kit was used rather than the Enzo BioArray™ HighYield™ RNA transcript labeling kit since side-by-side comparisons indicated high-end signal saturation with the latter. We obtained 72 μg of labeled complementary RNA on average after linear amplification of about 2 ng of total RNA. CONCLUSION: Unsupervised clustering placed 5/5 normal and 2/2 benign prostatic hyperplasia cases in one group, 5/7 Gleason pattern 3 cases in another group, and the remaining 2/7 pattern 3 cases in a third group with 8/8 Gleason pattern 5 cases and 3/3 metastatic prostatic adenocarcinomas. Differential expression of alpha-methylacyl coenzyme A racemase (AMACR) and hepsin was confirmed using quantitative PCR

Emerging Roles of Urine-Derived Components for the Management of Bladder Cancer: One Man’s Trash is Another Man’s Treasure

Urinary bladder cancer (UBC) is the most common malignancy of the urinary tract in humans, with an estimated global prevalence of 1.1 million cases over 5 years. Due to high rates of recurrence and resistance to chemotherapy, UBC is one of the most expensive cancers to treat, resulting in significant health care costs. There is, therefore, a critical need to develop innovative molecular and cellular tools to refine patient stratification and help predict response to treatment. Urine is an underused resource of biological components shed from bladder tumors, such as exfoliated cells and extracellular vesicles, that could serve as molecular fingerprints and provide valuable biological insights into tumor phenotype and mechanisms of resistance to chemotherapy. Additionally, characterization of urine-derived extracellular vesicles and cells could be used as reliable biomarkers for prediction of response to neoadjuvant therapy

Abundance and Distribution of Enteric Bacteria and Viruses in Coastal and Estuarine Sediments—a Review

The long term survival of fecal indicator organisms (FIOs) and human pathogenic microorganisms in sediments is important from a water quality, human health and ecological perspective. Typically, both bacteria and viruses strongly associate with particulate matter present in freshwater, estuarine and marine environments. This association tends to be stronger in finer textured sediments and is strongly influenced by the type and quantity of clay minerals and organic matter present. Binding to particle surfaces promotes the persistence of bacteria in the environment by offering physical and chemical protection from biotic and abiotic stresses. How bacterial and viral viability and pathogenicity is influenced by surface attachment requires further study. Typically, long-term association with surfaces including sediments induces bacteria to enter a viable-but-non-culturable (VBNC) state. Inherent methodological challenges of quantifying VBNC bacteria may lead to the frequent under-reporting of their abundance in sediments. The implications of this in a quantitative risk assessment context remain unclear. Similarly, sediments can harbor significant amounts of enteric viruses, however, the factors regulating their persistence remains poorly understood. Quantification of viruses in sediment remains problematic due to our poor ability to recover intact viral particles from sediment surfaces (typically <10%), our inability to distinguish between infective and damaged (non-infective) viral particles, aggregation of viral particles, and inhibition during qPCR. This suggests that the true viral titre in sediments may be being vastly underestimated. In turn, this is limiting our ability to understand the fate and transport of viruses in sediments. Model systems (e.g., human cell culture) are also lacking for some key viruses, preventing our ability to evaluate the infectivity of viruses recovered from sediments (e.g., norovirus). The release of particle-bound bacteria and viruses into the water column during sediment resuspension also represents a risk to water quality. In conclusion, our poor process level understanding of viral/bacterial-sediment interactions combined with methodological challenges is limiting the accurate source apportionment and quantitative microbial risk assessment for pathogenic organisms associated with sediments in aquatic environments

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin