Evaluational adjectives

This paper demarcates a theoretically interesting class of "evaluational adjectives." This class includes predicates expressing various kinds of normative and epistemic evaluation, such as predicates of personal taste, aesthetic adjectives, moral adjectives, and epistemic adjectives, among others. Evaluational adjectives are distinguished, empirically, in exhibiting phenomena such as discourse-oriented use, felicitous embedding under the attitude verb `find', and sorites-susceptibility in the comparative form. A unified degree-based semantics is developed: What distinguishes evaluational adjectives, semantically, is that they denote context-dependent measure functions ("evaluational perspectives")—context-dependent mappings to degrees of taste, beauty, probability, etc., depending on the adjective. This perspective-sensitivity characterizing the class of evaluational adjectives cannot be assimilated to vagueness, sensitivity to an experiencer argument, or multidimensionality; and it cannot be demarcated in terms of pretheoretic notions of subjectivity, common in the literature. I propose that certain diagnostics for "subjective" expressions be analyzed instead in terms of a precisely specified kind of discourse-oriented use of context-sensitive language. I close by applying the account to `find x PRED' ascriptions

Measurement of tamsulosin in human serum by liquid chromatography-tandem mass spectrometry

AbstractA simple, sensitive and robust method to extract tamsulosin from human serum, and quantify by liquid chromatography–tandem mass spectrometry (LC–MS/MS) was developed and validated and is applicable as a measure of compliance in clinical research. Tamsulosin was extracted from human serum (100μL) via liquid–liquid extraction with methyl tert-butyl ether (2mL) following dilution with 0.1M ammonium hydroxide (100μL), achieving 99.9% analyte recovery. Internal standard, d9-finasteride, was synthesised in-house. Analyte and internal standard were separated on an Ascentis® Express C18 (100mm×3mm, 2.7μm) column using a gradient elution with mobile phases methanol and 2mM aqueous ammonium acetate (5:95, v/v). Total run-time was 6min. Tamsulosin was quantified using a triple quadrupole mass spectrometer operated in multi-reaction-monitoring (MRM) mode using positive electrospray ionisation. Mass transitions monitored for quantitation were: tamsulosin m/z 409→228 and d9-finasteride m/z 382→318, with the structural formulae of ions confirmed by Fourier transform ion cyclotron resonance mass spectrometry (within 10ppm). The limit of quantitation was 0.2ng/mL, and the method was validated in the linear range 0.2–50ng/mL with acceptable inter- and intra-assay precision and accuracy and stability suitable for routine laboratory practice. The method was successfully applied to samples taken from research volunteers in a clinical study of benign prostatic hyperplasia

Brief Report: A Phase II Study of Sunitinib in Malignant Pleural Mesothelioma. The NCIC Clinical Trials Group

IntroductionMalignant pleural mesothelioma (MPM) is an aggressive malignancy that most often presents at an advanced, incurable stage. After the failure of standard first-line cisplatin/antifolate chemotherapy, there is no accepted treatment. The vascular endothelial growth factor pathway may be a relevant therapeutic target in MPM.MethodsThis open-labeled phase II trial evaluated single-agent sunitinib, an inhibitor of multiple receptor tyrosine kinases including the vascular endothelial growth factor receptors, given at 50 mg daily orally for 4 weeks followed by a 2-week rest, in patients with advanced MPM. Two cohorts were studied: cohort 1, in which patients had previously received cisplatin-based chemotherapy, and cohort 2, consisting of previously untreated patients. A two-stage design was used for both cohorts; the primary outcome was objective response rate as determined by the RECIST criteria modified for MPM. Secondary outcomes included rates and duration of disease control, progression-free survival and overall survival, and safety and tolerability.ResultsA total of 35 eligible patients were enrolled (17 to cohort 1 and 18 to cohort 2). Neither cohort met the criteria for continuing to the second stage of accrual; only one objective response, confirmed by independent review, was observed in a previously untreated patient. Median progression-free and overall survivals were 2.8 and 8.3 months in cohort 1, and 2.7 and 6.7 months in cohort 2, respectively. Observed toxicity was within that expected for sunitinib.ConclusionsSunitinib, similar to other angiogenesis inhibitors, has limited activity in MPM. Future trials of angiogenesis inhibitors given as single agents in unselected patients with MPM are not warranted

Microfluidic Endothelium for Studying the Intravascular Adhesion of Metastatic Breast Cancer Cells

BACKGROUND:The ability to properly model intravascular steps in metastasis is essential in identifying key physical, cellular, and molecular determinants that can be targeted therapeutically to prevent metastatic disease. Research on the vascular microenvironment has been hindered by challenges in studying this compartment in metastasis under conditions that reproduce in vivo physiology while allowing facile experimental manipulation. METHODOLOGY/PRINCIPAL FINDINGS:We present a microfluidic vasculature system to model interactions between circulating breast cancer cells with microvascular endothelium at potential sites of metastasis. The microfluidic vasculature produces spatially-restricted stimulation from the basal side of the endothelium that models both organ-specific localization and polarization of chemokines and many other signaling molecules under variable flow conditions. We used this microfluidic system to produce site-specific stimulation of microvascular endothelium with CXCL12, a chemokine strongly implicated in metastasis. CONCLUSIONS/SIGNIFICANCE:When added from the basal side, CXCL12 acts through receptor CXCR4 on endothelium to promote adhesion of circulating breast cancer cells, independent of CXCL12 receptors CXCR4 or CXCR7 on tumor cells. These studies suggest that targeting CXCL12-CXCR4 signaling in endothelium may limit metastases in breast and other cancers and highlight the unique capabilities of our microfluidic device to advance studies of the intravascular microenvironment in metastasis

Patient Safety in Radiology

AbstractMedical imaging (in short radiology) includes diagnostic and interventional procedures and has an essential role in the diagnosis and treatment of diseases. The objective in this field of medicine is focused on providing diagnostic and therapeutic benefit to the patients along with protecting them from the possible hazards associated with the procedures. By continuously upgrading imaging technologies and improving imaging modalities, such as ultrasound imaging, X-ray-based imaging (radiography, fluoroscopy, and computed tomography), magnetic resonance imaging (MRI), and interventional radiology, safety has become more and more crucial. The potential hazards in radiology for the patients and the staff are multidimensional and will be discussed in the chapter

Repair of a juxtarenal abdominal aortic aneurysm in a patient with situs inversus totalis using a retroperitoneal approach

Situs inversus totalis (SIT) is a rare condition characterized by the mirror image location of all of the thoracic and abdominal organs. There are only a handful of reports documenting the presence and repair of an abdominal aortic aneurysm in the setting of SIT. Here, we present a rare case of a juxtarenal abdominal aortic aneurysm repaired through a retroperitoneal approach in a patient with SIT. We demonstrate that the retroperitoneal approach is a safe and effective method to manage complex aortic aneurysm disease in a patient with SIT