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.)

Design of an Event Based Messaging System

B2B document handling is moving from paper to electronic networks and electronic domain very rapidly. Moving, handling and transforming large electronic business documents requires a lot from the systems handling them. This paper explores new technologies such as SOA, event-driven systems and ESB and a scalable, event-driven enterprise service bus is created to demonstrate these new approaches to message handling. As an end result, we have a small but fully functional messaging system with several different components. This is the first larger Java-project done in-house, so on the side we developed our own set of best practices of Java development, setting up configurations, tools, code repositories and class naming and much more.

Building a creative city brand through an international mega-event : Case: Helsinki World Design Capital 2012

In order to grow, cities are increasingly competing for attention, jobs, investments, visitors, residents and significant events. Cities need to come up with creative solutions to keep up with the competition; they ought to become creative cities. Attracting talented and diverse inhabitants is a key factor in developing a creative city, which on is characterized by openness, tolerance, vibrancy and diversity. Along the need for renewed city images city brand building has become popular. Helsinki is the World Design Capital 2012 (WDC 2012) and this mega-event presents a meaningful opportunity for the city to broadcast itself globally. The purpose of this study is to evaluate how Helsinki brands itself as a creative city through an international mega-event. The sub-aims are to: 1) Map the factors behind the creative city and their relation to the city of Helsinki, 2) Describe the city branding process, 3) Evaluate the role of the Helsinki World Design Capital 2012 mega-event in Helsinki’s creative city brand building. First, the theory discusses the concept of the creative city that has gained growing attention during the past decade. Then, the city branding process is described and the benefits of hosting a mega-event are presented. Finally, co-branding a city and a mega-event in order to generate maximum benefit from the mega-event, is reviewed. This is a qualitative research for which data was collected through three face-to-face interviews, the World Design Capital 2012 bid, Helsinki’s economic development strategy, a consulting firm’s research report on the case city and web-pages. The research reveals that Helsinki has shown interest in the creative city discussion. The terminology around the concept is however approached carefully. Helsinki fits many of the creative city characteristics and recognizes its flaws for which improvement strategies have been planned. Bottlenecks keeping the city from promoting a more open mind were mainly revealed in its organizational structures. Helsinki has no official brand strategy; nonetheless pressure to develop one is present. The World Design Capital 2012 mega-event is seen as a meaningful stepping board to strengthen Helsinki’s identity and image, and start thinking about a city brand. The brand strategies of the mega-event support the values and virtues of the city itself, which enables benefits of co-branding introduces in the theory part. Helsinki has no official brand and doesn’t call itself a creative city, however this study shows signs of the city taking steps towards building a creative city brand with the help of the Helsinki World Design Capital 2012 mega-event.

Discrete Event Systems based Design Patterns for Diagnosability Analysis of Automated Manufacturing Systems

The main goal of this thesis is to facilitate the process of industrial automated systems development applying formal methods to ensure the reliability of systems. A new formulation of distributed diagnosability problem in terms of Discrete Event Systems theory and automata framework is presented, which is then used to enforce the desired property of the system, rather then just verifying it. This approach tackles the state explosion problem with modeling patterns and new algorithms, aimed for verification of diagnosability property in the context of the distributed diagnosability problem. The concepts are validated with a newly developed software tool.

Reliability and validity of the Impact of Event Scale (IES): version for Brazilian burn victims

Aims. The aims of this study were to assess the internal reliability (internal consistency), construct validity, sensitivity and ceiling and floor effects of the Brazilian-Portuguese version of the Impact of Event Scale (IES). Design. Methodological research design. Method. The Brazilian-Portuguese version of the IES was applied to a group of 91 burned patients at three times: the first week after the burn injury (time one), between the fourth and the sixth months (time two) and between the ninth and the 12th months (time three). The internal consistency, construct validity (convergent and dimensionality), sensitivity and ceiling and floor effects were tested. Results. Cronbach`s alpha coefficients showed high internal consistency for the total scale (0 center dot 87) and for the domains intrusive thoughts (0 center dot 87) and avoidance responses (0 center dot 76). During the hospitalisation (time one), the scale showed low and positive correlations with pain measures immediately before (r = 0 center dot 22; p < 0 center dot 05) and immediately after baths and dressings (r = 0 center dot 21; p < 0 center dot 05). After the discharge, we found strong and negative correlations with self-esteem (r = -0 center dot 52; p < 0 center dot 01), strong and positive with depression (r = 0 center dot 63; p < 0 center dot 01) and low and negative with the Bodily pain (r = -0 center dot 24; p < 0 center dot 05), Social functioning (r = -0 center dot 34; p < 0 center dot 01) and Mental health (r = -0 center dot 27; p < 0 center dot 05) domains of the SF-36 at time two. Regarding the sensitivity, no statistically significant differences were observed between mean scale scores according to burned body surface (p = 0 center dot 21). The floor effect was observed in most of the IES items. Conclusion. The adapted version of the scale showed to be reliable and valid to assess postburn reactions on the impact of the event in the group of patients under analysis. Relevance to clinical practice. The Impact of Event Scale can be used in research and clinical practice to assess nursing interventions aimed at decreasing stress during rehabilitation.

Multi-Objective Optimization Design of Tanker Ships via a Genetic Algorithm

The cost of a new ship design heavily depends on the principal dimensions of the ship; however, dimensions minimization often conflicts with the minimum oil outflow (in the event of an accidental spill). This study demonstrates one rational methodology for selecting the optimal dimensions and coefficients of form of tankers via the use of a genetic algorithm. Therein, a multi-objective optimization problem was formulated by using two objective attributes in the evaluation of each design, specifically, total cost and mean oil outflow. In addition, a procedure that can be used to balance the designs in terms of weight and useful space is proposed. A genetic algorithm was implemented to search for optimal design parameters and to identify the nondominated Pareto frontier. At the end of this study, three real ships are used as case studies. [DOI:10.1115/1.4002740]

The beliefs of nurses who were involved in a whistleblowing event

Background. Nursing codes of ethics bind nurses to the role of patient advocate and compel them to take action when the rights or safety of a patient are jeopardized. Reporting misconduct is known as whistleblowing and studies indicate that there are personal and professional risks involved in blowing the whistle. Aim. The aim of this study was to explore the beliefs of nurses who wrestled with this ethical dilemma. Design. A descriptive survey design was used to examine the beliefs of nurses in Western Australia who reported misconduct (whistleblowers) and of those who did not report misconduct (nonwhistleblowers). Methods. The instrument listed statements from current ethical codes, statements from traditional views on nursing and statements of beliefs related to the participant's whistleblowing experience. Respondents were asked to rate each item on a five-point Likert format which ranged from strongly agree to strongly disagree. Data were analysed using a Pearson's correlation matrix and one-way ANOVA. To further explore the data, a factor analysis was run with varimax rotation. Results. Results indicated that whistleblowers supported the beliefs inherent in patient advocacy, while nonwhistleblowers retained a belief in the traditional role of nursing. Participants who reported misconduct (whistleblowers) supported the belief that nurses were primarily responsible to the patient and should protect a patient from incompetent or unethical people. Participants who did not report misconduct (nonwhistleblowers) supported the belief that nurses are obligated to follow a physician's order at all times and that nurses are equally responsible to the patient, the physician and the employer. Conclusion. These findings indicate that nurses may respond to ethical dilemmas based on different belief systems.

REMPLI discreet event simulation system

This document presents the design choices on the simulation mechanism used to test the Tansport Layer implementation in the REMPLI project [www.rempli.org].

SOFHIA: a CAD environment to design digital control systems

"Series Title: IFIP - The International Federation for Information Processing, ISSN 1868-4238"

The ethnography of study abroad: what is study abroad as a cultural event?

Recent research in the field of study abroad shows that study abroad participation among all U.S. students increased 20% since 2001 and nearly 200,000 U.S. students currently go abroad each year. Additionally, about 8% of all undergraduate degree recipients receive part of their education abroad. Although quantitative studies have dominated research on study abroad, my research project calls for a qualitative approach since the goal is to understand what study abroad is as a cultural event, what authentic cultural immersion is, how program stakeholders understand and perceive cultural immersion, and how cultural immersion in programs can be improved. Following the tradition of ethnographic and case study approaches in study abroad research, my study also pivots on ethnography. As an ethnographer I collected data mainly through participant observation, semi-structured interviews, and document analysis. The study abroad participants were a group of undergraduate native speakers of English studying Spanish for seven weeks in Cádiz, a small costal city in southern Spain, as well as program coordinators, host community members, and professors. I also examined the specific program design features, particularly the in-class and out-of-class activities that students participated in. The goal was to understand if these features were conducive to authentic immersion in the language and culture. Eventually, I elaborated an ethnographic evaluation of the study abroad program and its design features suggesting improvements in order to enhance the significance and value of study abroad as a cultural event. Among other things, I discussed the difficulties that students had at the beginning of their sojourn to understand local people, get used to their host families’ small apartments, get adjusted to new schedules and eating habits, and venture out from the main group to individually explore the new social and cultural fabric and interact with the host community. The program evaluation revealed the need for carefully-designed pre-departure preparation sessions, pre-departure credit-bearing courses in intercultural communication, and additional language practice abroad and opportunities to come in contact with the local community through internships, volunteer or field work. My study gives an important contribution in study abroad research and education. It benefits students, teachers, and study abroad directors and coordinators in suggesting ideas on how to improve the program and optimize the students’ cultural experiences abroad. This study is also important because it investigated how US undergraduate learners studying the Spanish language and culture approach and perceive the study abroad experience in Spain.

Visuo-motor pathways in humans revealed by event-related fMRI.

Whether different brain networks are involved in generating unimanual responses to a simple visual stimulus presented in the ipsilateral versus contralateral hemifield remains a controversial issue. Visuo-motor routing was investigated with event-related functional magnetic resonance imaging (fMRI) using the Poffenberger reaction time task. A 2 hemifield x 2 response hand design generated the "crossed" and "uncrossed" conditions, describing the spatial relation between these factors. Both conditions, with responses executed by the left or right hand, showed a similar spatial pattern of activated areas, including striate and extrastriate areas bilaterally, SMA, and M1 contralateral to the responding hand. These results demonstrated that visual information is processed bilaterally in striate and extrastriate visual areas, even in the "uncrossed" condition. Additional analyses based on sorting data according to subjects' reaction times revealed differential crossed versus uncrossed activity only for the slowest trials, with response strength in infero-temporal cortices significantly correlating with crossed-uncrossed differences (CUD) in reaction times. Collectively, the data favor a parallel, distributed model of brain activation. The presence of interhemispheric interactions and its consequent bilateral activity is not determined by the crossed anatomic projections of the primary visual and motor pathways. Distinct visuo-motor networks need not be engaged to mediate behavioral responses for the crossed visual field/response hand condition. While anatomical connectivity heavily influences the spatial pattern of activated visuo-motor pathways, behavioral and functional parameters appear to also affect the strength and dynamics of responses within these pathways.

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

BACKGROUND AND OBJECTIVES: The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. PROTOCOL DESIGN: The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, <145-135; 2, <135-125; 3, <125 mmHg); two different LDL-C targets (target A, 2.8-1.8; target B, <1.8 mmol/l). The trial is to be conducted on 7500 patients aged at least 65 years (2500 in Europe, 5000 in China) with hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. OUTCOMES: Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be adjudicated by committees blind to randomized allocation. A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety. SAMPLE SIZE CALCULATION: It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up, and this should provide at least 80% power to detect a 25% stroke difference between SBP targets and a 20% difference between LDL-C targets.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study.

BACKGROUND: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. METHODS AND RESULTS: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. CONCLUSIONS: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.