The Enantioselective Construction of Tetracyclic Diterpene Skeletons with Friedel-Crafts Alkylation and Palladium-catalyzed Cycloalkenylation Reactions

Due to the profound extent to which natural products inspire medicinal chemists in drug discovery, there is demand for innovative syntheses of these often complex materials. This article describes the synthesis of tricarbocyclic natural product architectures through an extension of the enantioselective Birch-Cope sequence with intramolecular Friedel-Crafts alkylation reactions. Additionally, palladium-catalyzed enol silane cycloalkenylation of the tricarbocyclic structures afforded the challenging bicyclo[3.2.1]octane C/D ring system found in the gibberellins and the ent-kauranes, two natural products with diverse medicinal value. In the case of the ent-kaurane derivative, an unprecedented alkene rearrangement converted four alkene isomers to one final product

36. A prospective, randomized study to compare the value of two fractionation schemes of palliative radiotherapy for inoperable non-small cell lung cancer

A prospective, randomized study was conducted in eight Polish institutions to compare the value of two fractionation schemes of palliative radiotherapy for inoperable non-small cell lung cancer. Assessed was the impact of either treatment on the degree and duration of relief of tumor-related symptoms and on patient's performance status. Secondary endpoints included treatment side-effects, objective response and overall survival. One hundred patients were randomly assigned to the dose of 20 Gy/5×/5 days (Arm A) or 16 Gy/2×/8 days (Arm B). There were 90 men and 10 women aged between 47 and 79 (mean 66). Eighty four patients had locally advanced tumor and 16 patients had metastatic disease. Squamous cell carcinoma was diagnosed in 65 patients, adenocarcinoma – in 9 patients, large cell carcinoma – in 1 patient and unspecified non-small cell carcinoma – in 25 patients. Fifty five patients were assigned to Arm A and 45 – to Arm B. Ninety eight patients received assigned treatment whereas two patients died before the end of treatment. The final results of the study will be presented at the conference

A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma

<p>Abstract</p> <p>Background</p> <p>Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab.</p> <p>Methods</p> <p>In this randomized, double-blind, phase II biomarker study (ClinicalTrials.gov NCT00261365), 82 pretreated or treatment-naïve patients with unresectable stage III/IV melanoma were induced with 3 or 10 mg/kg ipilimumab every 3 weeks for 4 doses; at Week 24, patients could receive maintenance doses every 12 weeks. Efficacy was evaluated per modified World Health Organization response criteria and safety was assessed continuously. Candidate biomarkers were evaluated in tumor biopsies collected pretreatment and 24 to 72 hours after the second ipilimumab dose. Polymorphisms in immune-related genes were also evaluated.</p> <p>Results</p> <p>Objective response rate, response patterns, and safety were consistent with previous trials of ipilimumab in melanoma. No associations between genetic polymorphisms and clinical activity were observed. Immunohistochemistry and histology on tumor biopsies revealed significant associations between clinical activity and high baseline expression of FoxP3 (p = 0.014) and indoleamine 2,3-dioxygenase (p = 0.012), and between clinical activity and increase in tumor-infiltrating lymphocytes (TILs) between baseline and 3 weeks after start of treatment (p = 0.005). Microarray analysis of mRNA from tumor samples taken pretreatment and post-treatment demonstrated significant increases in expression of several immune-related genes, and decreases in expression of genes implicated in cancer and melanoma.</p> <p>Conclusions</p> <p>Baseline expression of immune-related tumor biomarkers and a post-treatment increase in TILs may be positively associated with ipilimumab clinical activity. The observed pharmacodynamic changes in gene expression warrant further analysis to determine whether treatment-emergent changes in gene expression may be associated with clinical efficacy. Further studies are required to determine the predictive value of these and other potential biomarkers associated with clinical response to ipilimumab.</p

Multimaterial 4D Printing with Tailorable Shape Memory Polymers

We present a new 4D printing approach that can create high resolution (up to a few microns), multimaterial shape memory polymer (SMP) architectures. The approach is based on high resolution projection microstereolithography (PμSL) and uses a family of photo-curable methacrylate based copolymer networks. We designed the constituents and compositions to exhibit desired thermomechanical behavior (including rubbery modulus, glass transition temperature and failure strain which is more than 300% and larger than any existing printable materials) to enable controlled shape memory behavior. We used a high resolution, high contrast digital micro display to ensure high resolution of photo-curing methacrylate based SMPs that requires higher exposure energy than more common acrylate based polymers. An automated material exchange process enables the manufacture of 3D composite architectures from multiple photo-curable SMPs. In order to understand the behavior of the 3D composite microarchitectures, we carry out high fidelity computational simulations of their complex nonlinear, time-dependent behavior and study important design considerations including local deformation, shape fixity and free recovery rate. Simulations are in good agreement with experiments for a series of single and multimaterial components and can be used to facilitate the design of SMP 3D structures

Choque cultural organizacional: Estrategias de trabajo de campo etnográfico para el investigador novato en ciencias de la salud

Die vermehrte Nutzung ethnografischer Methoden in der Gesundheitsforschung erlaubt eine intensive Analyse empirisch erhobener Daten. Indem ich das Konzept des Kulturschocks von OBERG (1960) verwende, reflektiere ich die Erfahrungen, die ich als Novizin in meiner Feldforschung gewonnen habe, die eine institutionelle Ethnografie von Arbeitsplätzen im Feld der psychischen Gesundheitsversorgung zum Ziel hatte. Ich behandele dabei auch Themen, die üblicherweise in Ethnografien ausgespart bleiben, so bspw. den Umgang mit Rollenwidersprüchen, aber auch ethische, emotionale und praktische Belange. Ich schließe mit einigen Ratschlägen für Noviz/innen, um möglichst effektiv mit einigen der typischen Dilemmata in dieser Art von Forschung umgehen zu können.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs150298The increased use of ethnography in health science research warrants an in-depth examination of the experiential account of ethnographic data collection. Using OBERG's classic definition of "culture shock" as a framework, I share my experience as a novice researcher conducting fieldwork as part of an institutional ethnography on workplace mental health. I draw attention to the typically unspoken aspects of ethnography throughout this account by providing insights on role contradictions, in addition to ethical, emotional, and practical issues that are not readily addressed in traditional methodological descriptions of ethnography. I conclude with a variety of strategies for the novice health science researcher to effectively negotiate some of the typical dilemmas experienced in this type of research.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs150298El incremento en el uso de la etnografía en la investigación en ciencias de la salud garantiza un examen en profundidad del relato experiencial de la recolección de datos etnográficos. Con el marco de trabajo de la definición clásica de OBERG de "choque cultural", comparto mi experiencia como investigador novato realizando trabajo de campo como parte de una etnografía institucional sobre el lugar de trabajo de la salud mental. Llamo la atención sobre los aspectos típicamente tácitos de la etnografía a lo largo del relato al brindar perspectivas sobre las contradicciones en el rol, además de las cuestiones éticas, emocionales y prácticas que no son fácilmente abordadas en las descripciones metodológicas tradicionales de la etnografía. Concluyo con una variedad de estrategias para el investigador novato en ciencias de la salud para negociar eficazmente algunos de los dilemas típicos experimentados en este tipo de investigación.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs15029

Organizational culture shock: ethnographic fieldwork strategies for the novice health science researcher

The increased use of ethnography in health science research warrants an in-depth examination of the experiential account of ethnographic data collection. Using Oberg's classic definition of "culture shock" as a framework, I share my experience as a novice researcher conducting fieldwork as part of an institutional ethnography on workplace mental health. I draw attention to the typically unspoken aspects of ethnography throughout this account by providing insights on role contradictions, in addition to ethical, emotional, and practical issues that are not readily addressed in traditional methodological descriptions of ethnography. I conclude with a variety of strategies for the novice health science researcher to effectively negotiate some of the typical dilemmas experienced in this type of research. (author's abstract)Die vermehrte Nutzung ethnografischer Methoden in der Gesundheitsforschung erlaubt eine intensive Analyse empirisch erhobener Daten. Indem ich das Konzept des Kulturschocks von Oberg (1960) verwende, reflektiere ich die Erfahrungen, die ich als Novizin in meiner Feldforschung gewonnen habe, die eine institutionelle Ethnografie von Arbeitsplätzen im Feld der psychischen Gesundheitsversorgung zum Ziel hatte. Ich behandele dabei auch Themen, die üblicherweise in Ethnografien ausgespart bleiben, so bspw. den Umgang mit Rollenwidersprüchen, aber auch ethische, emotionale und praktische Belange. Ich schließe mit einigen Ratschlägen für Noviz/innen, um möglichst effektiv mit einigen der typischen Dilemmata in dieser Art von Forschung umgehen zu können. (Autorenreferat