Monitoring a simple hydrolysis process in an organic solid by observing methyl group rotation

We report a variety of experiments and calculations and their interpretations regarding methyl group (CH3) rotation in samples of pure 3-methylglutaric anhydride (1), pure 3-methylglutaric acid (2), and samples where the anhydride is slowly absorbing water from the air and converting to the acid [C6H8O3(1) + H2O → C6H10O4(2)]. The techniques are solid state 1H nuclear magnetic resonance (NMR) spin-lattice relaxation, single-crystal X-ray diffraction, electronic structure calculations in both isolated molecules and in clusters of molecules that mimic the crystal structure, field emission scanning electron microscopy, differential scanning calorimetry, and high resolution 1H NMR spectroscopy. The solid state 1H spin-lattice relaxation experiments allow us to observe the temperature dependence of the parameters that characterize methyl group rotation in both compounds and in mixtures of the two compounds. In the mixtures, both types of methyl groups (that is, molecules of 1 and 2) can be observed independently and simultaneously at low temperatures because the solid state 1H spin-lattice relaxation is appropriately described by a double exponential. We have followed the conversion 1 → 2 over periods of two years. The solid state 1H spin-lattice relaxation experiments in pure samples of 1 and 2 indicate that there is a distribution of NMR activation energies for methyl group rotation in 1 but not in 2 and we are able to explain this in terms of the particle sizes seen in the field emission scanning electron microscopy images

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

Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN

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Lettere En WysbegeerteFilosofiePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

The New Pragmatism.

Please help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected] En WysbegeerteFilosofi

Making a difference in cultural politics: Rorty's interventions

This article examines some general features of what Richard Rorty called "cultural politics." It attempts to explain why Rorty thought it both possible and desirable to give politics priority over ontology. He set aside traditional philosophical questions concerning what there is, while making those worth retaining subservient to cultural negotiation. Rorty's conception of cultural politics can perhaps avoid the complaint that by failing to deliver a substantial version of objectivity, he falls hostage to dangerous relativism. Editions Rodopi © 2011