The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial: study design and rationale

Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA.CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA.CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least I year. The TRA.CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA.CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies. (Am Heart J 2009; 158:327-34.)

Pressure-Frequency Sensing Subxiphoid Access System for Use in Percutaneous Cardiac Electrophysiology: Prototype Design and Pilot Study Results

We have designed, built, and tested an early prototype of a novel subxiphoid access system intended to facilitate epicardial electrophysiology, but with possible applications elsewhere in the body. The present version of the system consists of a commercially available insertion needle, a miniature pressure sensor and interconnect tubing, read-out electronics to monitor the pressures measured during the access procedure, and a host computer with user-interface software. The nominal resolution of the system is <0.1 mmHg, and it has deviations from linearity of <1%. During a pilot series of human clinical studies with this system, as well as in an auxiliary study done with an independent method, we observed that the pericardial space contained pressure-frequency components related to both the heart rate and respiratory rate, while the thorax contained components related only to the respiratory rate, a previously unobserved finding that could facilitate access to the pericardial space. We present and discuss the design principles, details of construction, and performance characteristics of this system.

Design analysis for refolding monomeric protein

Renaturation of protein expressed as inclusion bodies within Escherichia coli is a key step in many bioprocesses. Operating conditions for the refolding step dramatically affect the amount of protein product recovered, and hence profoundly influence the process economics. The first systematic comparison of refolding conducted in batch, fed-batch and continuous stirred-tank reactors is provided Refolding is modeled as kinetic competition between first-order refolding (equilibrium reaction) and irreversible aggregation (second-order). Simulations presented allow direct comparison between different flowsheets and refolding schemes using a dimensionless economic objective. As expected from examination of the reaction kinetics, batch operation is the most inefficient merle. For the base process considered, the overall cost of fed-batch and continuous refolding is virtually identical (less than half that of the batch process). Reactor selection and optimization of refolding using overall economics are demonstrated to be vitally important.

Investigating the influence of achievement on self-concept using an intra-class design and a comparison of the PASS and SDQ-1 self-concept tests

Background. The formation and measurement of self-concept were the foci of this research. Aims. The study aimed to investigate the influence of achievement on academic self-concept and to compare the Perception of Ability Scale for Students (PASS, Boersma & Chapman, 1992) with the Self-Description Questionnaire-1 (SDQ-1, Marsh, 1988). Sample. The participants were 479 grade 5 (mean age 126.6 months) coeducational Australian students, located in 18 schools. Method. An intra-class research design was used to investigate the influence of frame-of-reference on self-concept development. Results. As students' academic scores rose above their class mean their self-concepts increased and as students' academic scores fell below their class mean their self-concepts decreased. Students' difference from class mean predicted their self-concept scores. This finding was consistently shown across the reading, spelling, and mathematics domains using test and teaching rating data. A comparison between the PASS and the SDQ-1 demonstrated concurrent validity across self-concept domains. Conclusion. The findings support the notions that the social environment is a significant agent that influences self-concept, and that teacher ratings and standardised tests of achievement and the PASS and the SDQ-1 are valid measures for self-concept research.