1,268 research outputs found

    Toward Maximizing Immunotherapy in Metastatic Castration-Resistant Prostate Cancer – Rationale for Combinatorial Approaches Using Chemotherapy

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    Prostate cancer is particularly suited for active immunotherapy because of the expression of a distinctive number of antigens which are overexpressed on prostate cancer cells and cell lines. There is evidence in this disease that tumors promote immune tolerance starting early in the disease course. As such, chemotherapy, by suppressing tumors and activating immune system homeostatic mechanisms, may help overcome this tumor-induced immune tolerance. Sipuleucel-T which has recently been approved in the US, is an autologous cellular product immunotherapy that induces immune activity likely through activation of dendritic cells. This was associated with a survival benefit in the absence of significant toxicity. However, a post hoc analysis of phase III trial participants found a substantial survival benefit to receiving docetaxel some months after sipuleucel-T. However, another phase III immunotherapy trial combining a prostate cancer therapeutic vaccine GVAX plus docetaxel versus standard docetaxel therapy in advanced prostate cancer, observed a lower overall survival with the vaccine regimen. These trials highlight major unresolved questions concerning the optimum choice, dosing, and timing of chemotherapy relative to active immunotherapy and the overall merits of considering this approach. The ideal treatment approach remains unclear; advances in biomarker validation and trial design may likely improve our ability to assess biologic benefit irrespective of the development of true antitumor immunity

    Equity and cash in intercorporate asset sales : theory and evidence

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    the authors develop a two-sided asymmetric information model of asset sales that incorporates the key differences from mergers and allows the information held by each party to be impounded in the transaction. Buyer information is conveyed through a first-stage competitive auction. A seller with unfavorable information about the asset accepts the cash offer of the highest bidder. A seller with favorable information proposes a take-it-or-leave-it counteroffer that entails buyer equity. Thus, the cash-equity decision reflects seller, but not buyer, information in contrast to theoretical and empirical findings for mergers. The central prediction of our model is that there are relatively large gains in wealth for both buyers and sellers in equity-based asset sales, whereas cash asset sales generate significantly smaller gains that typically accrue only to sellers. Our empirical results are consistent with the predictions of our theoretical model.Asset sales; means of payment; auctions; two-sided asymmetric information

    A BOLD Assumption

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    Identifying Adverse Childhood Experiences (ACEs) in a Federally Qualified Health Center using the Pediatric ACEs and Related Life Events Screener

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    Background: Evidence links adverse childhood experiences (ACEs) to health issues later in life. Most research has been conducted in adults but there is a lack of recent research on the impact of ACEs in the pediatric population particularly in relation to mental health conditions. Utilizing the Pediatric ACEs Screener (PEARLS) health care providers can screen for ACEs at earlier ages. Purpose: The aim of this evidence-based project is to determine if there is an increase of newly diagnosed mental health related disorders when using PEARLS compared to not using PEARLS in the previous months before implementation. Methods: ACEs were identified using PEARLS at well-child visits. Regardless of scores, participants received verbal or written education on reducing stressors related to ACEs. Behavioral health outcomes were obtained via chart audits. Results: A total of 2,037 PEARLS were administered. Of that, 1949 screened negative for ACEs and 88 (4.3%) screened positive. Screening for ACEs identified that patients who screened positive who had a higher frequency of having a behavioral health diagnosis. Implications for Practice: Screening for ACEs exposure in pediatrics can provide early detection and timely interventions to reduce the adverse impacts of ACEs. Conclusion: Implementing of ACEs screening in a pediatric population was simple but did not result in an increase in identification of behavioral health diagnoses

    An inbred line of the diploid strawberry Fragaria vesca f. semperflorens for genomic and molecular genetic studies in the Rosaceae

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    <p>Abstract</p> <p>Background</p> <p>The diploid woodland strawberry (<it>Fragaria vesca</it>) is an attractive system for functional genomics studies. Its small stature, fast regeneration time, efficient transformability and small genome size, together with substantial EST and genomic sequence resources make it an ideal reference plant for <it>Fragaria </it>and other herbaceous perennials. Most importantly, this species shares gene sequence similarity and genomic microcolinearity with other members of the Rosaceae family, including large-statured tree crops (such as apple, peach and cherry), and brambles and roses as well as with the cultivated octoploid strawberry, <it>F</it>. ×<it>ananassa</it>. <it>F. vesca </it>may be used to quickly address questions of gene function relevant to these valuable crop species. Although some <it>F. vesca </it>lines have been shown to be substantially homozygous, in our hands plants in purportedly homozygous populations exhibited a range of morphological and physiological variation, confounding phenotypic analyses. We also found the genotype of a named variety, thought to be well-characterized and even sold commercially, to be in question. An easy to grow, standardized, inbred diploid <it>Fragaria </it>line with documented genotype that is available to all members of the research community will facilitate comparison of results among laboratories and provide the research community with a necessary tool for functionally testing the large amount of sequence data that will soon be available for peach, apple, and strawberry.</p> <p>Results</p> <p>A highly inbred line, YW5AF7, of a diploid strawberry <it>Fragaria vesca </it>f. <it>semperflorens </it>line called "Yellow Wonder" (Y2) was developed and examined. Botanical descriptors were assessed for morphological characterization of this genotype. The plant line was found to be rapidly transformable using established techniques and media formulations.</p> <p>Conclusion</p> <p>The development of the documented YW5AF7 line provides an important tool for Rosaceae functional genomic analyses. These day-neutral plants have a small genome, a seed to seed cycle of 3.0 - 3.5 months, and produce fruit in 7.5 cm pots in a growth chamber. YW5AF7 is runnerless and therefore easy to maintain in the greenhouse, forms abundant branch crowns for vegetative propagation, and produces highly aromatic yellow fruit throughout the year in the greenhouse. <it>F. vesca </it>can be transformed with <it>Agrobacterium tumefaciens</it>, making these plants suitable for insertional mutagenesis, RNAi and overexpression studies that can be compared against a stable baseline of phenotypic descriptors and can be readily genetically substantiated.</p

    Divisional Buyouts by Private Equity and the Market for Divested Assets

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    We study the role and performance of private equity (PE) in corporate asset sales. Corporate sellers obtain significantly positive excess returns in PE deals, gains in wealth significantly greater than for intercorporate asset sales. Based on exit valuations for 98% of PE deals, we find gains in enterprise value in buyouts are significantly greater than for benchmark firms. Corporate seller excess returns are positively correlated with subsequent gains in asset enterprise value. A parsimonious auction model suggests that only restructuring capabilities of PE (not acquisition of undervalued assets) can explain the pattern of the gains generated in these PE deals

    Re-annotation of the woodland strawberry (Fragaria vesca) genome

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    Fragaria vesca is a low-growing, small-fruited diploid strawberry species commonly called woodland strawberry. It is native to temperate regions of Eurasia and North America and while it produces edible fruits, it is most highly useful as an experimental perennial plant system that can serve as a model for the agriculturally important Rosaceae family. A draft of the F. vesca genome sequence was published in 2011 [Nat Genet 43:223,2011]. The first generation annotation (version 1.1) were developed using GeneMark-ES+[Nuc Acids Res 33:6494,2005]which is a self-training gene prediction tool that relies primarily on the combination of ab initio predictions with mapping high confidence ESTs in addition to mapping gene deserts from transposable elements. Based on over 25 different tissue transcriptomes, we have revised the F. vesca genome annotation, thereby providing several improvements over version 1.1. The new annotation, which was achieved using Maker, describes many more predicted protein coding genes compared to the GeneMark generated annotation that is currently hosted at the Genome Database for Rosaceae (http://www.rosaceae.org/). Our new annotation also results in an increase in the overall total coding length, and the number of coding regions found. The total number of gene predictions that do not overlap with the previous annotations is 2286, most of which were found to be homologous to other plant genes. We have experimentally verified one of the new gene model predictions to validate our results. Using the RNA-Seq transcriptome sequences from 25 diverse tissue types, the re-annotation pipeline improved existing annotations by increasing the annotation accuracy based on extensive transcriptome data. It uncovered new genes, added exons to current genes, and extended or merged exons. This complete genome re-annotation will significantly benefit functional genomic studies of the strawberry and other members of the Rosaceae.https://doi.org/10.1186/s12864-015-1221-
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