Eliminating Ditransitives

Abstract. We discuss how higher arity verbs such as give or promise can be treated in an algebraic framework that admits only unary and binary relations and does not rely on event variables

Ontologies, Mental Disorders and Prototypes

As it emerged from philosophical analyses and cognitive research, most concepts exhibit typicality effects, and resist to the efforts of defining them in terms of necessary and sufficient conditions. This holds also in the case of many medical concepts. This is a problem for the design of computer science ontologies, since knowledge representation formalisms commonly adopted in this field do not allow for the representation of concepts in terms of typical traits. However, the need of representing concepts in terms of typical traits concerns almost every domain of real world knowledge, including medical domains. In particular, in this article we take into account the domain of mental disorders, starting from the DSM-5 descriptions of some specific mental disorders. On this respect, we favor a hybrid approach to the representation of psychiatric concepts, in which ontology oriented formalisms are combined to a geometric representation of knowledge based on conceptual spaces

Insulin Glargine in the Intensive Care Unit: A Model-Based Clinical Trial Design

Online 4 Oct 2012Introduction: Current succesful AGC (Accurate Glycemic Control) protocols require extra clinical effort and are impractical in less acute wards where patients are still susceptible to stress-induced hyperglycemia. Long-acting insulin Glargine has the potential to be used in a low effort controller. However, potential variability in efficacy and length of action, prevent direct in-hospital use in an AGC framework for less acute wards. Method: Clinically validated virtual trials based on data from stable ICU patients from the SPRINT cohort who would be transferred to such an approach are used to develop a 24-hour AGC protocol robust to different Glargine potencies (1.0x, 1.5x and 2.0x regular insulin) and initial dose sizes (dose = total insulin over prior 12, 18 and 24 hours). Glycemic control in this period is provided only by varying nutritional inputs. Performance is assessed as %BG in the 4.0-8.0mmol/L band and safety by %BG<4.0mmol/L. Results: The final protocol consisted of Glargine bolus size equal to insulin over the previous 18 hours. Compared to SPRINT there was a 6.9% - 9.5% absolute decrease in mild hypoglycemia (%BG<4.0mmol/L) and up to a 6.2% increase in %BG between 4.0 and 8.0mmol/L. When the efficacy is known (1.5x assumed) there were reductions of: 27% BG measurements, 59% insulin boluses, 67% nutrition changes, and 6.3% absolute in mild hypoglycemia. Conclusion: A robust 24-48 clinical trial has been designed to safely investigate the efficacy and kinetics of Glargine as a first step towards developing a Glargine-based protocol for less acute wards. Ensuring robustness to variability in Glargine efficacy significantly affects the performance and safety that can be obtained

A randomized trial of bevacizumab for newly diagnosed glioblastoma.

BACKGROUND: Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known. METHODS: In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. At disease progression, the assigned treatment was revealed, and bevacizumab therapy could be initiated or continued. The trial was designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary end points, with the addition of bevacizumab. RESULTS: A total of 978 patients were registered, and 637 underwent randomization. There was no significant difference in the duration of overall survival between the bevacizumab group and the placebo group (median, 15.7 and 16.1 months, respectively; hazard ratio for death in the bevacizumab group, 1.13). Progression-free survival was longer in the bevacizumab group (10.7 months vs. 7.3 months; hazard ratio for progression or death, 0.79). There were modest increases in rates of hypertension, thromboembolic events, intestinal perforation, and neutropenia in the bevacizumab group. Over time, an increased symptom burden, a worse quality of life, and a decline in neurocognitive function were more frequent in the bevacizumab group. CONCLUSIONS: First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. Progression-free survival was prolonged but did not reach the prespecified improvement target. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00884741.)