Telaprevir or boceprevir based therapy for chronic hepatitis C infection: Development of resistance-associated variants in treatment failure

The use of triple-therapy, pegylated-interferon, ribavirin and either of the first generation hepatitis C virus (HCV) protease inhibitors telaprevir or boceprevir, is the new standard of care for treating genotype 1 chronic HCV. Clinical trials have shown response rates of around 70–80%, but there is limited data from the use of this combination outside this setting. Through an expanded access programme, we treated 59 patients, treatment naïve and experienced, with triple therapy. Baseline factors predicting treatment response or failure during triple therapy phase were identified in 58 patients. Thirty seven (63.8%) of 58 patients had undetectable HCV RNA 12 weeks after the end of treatment. Genotype 1a (p = 0.053), null-response to previous treatment (p = 0.034), the rate of viral load decline after 12 weeks of previous interferon-based treatment (p = 0.033) were all associated with triple-therapy failure. The most common cause of on-treatment failure for telaprevir-based regimens was the development of resistance-associated variants (RAVs) at amino acids 36 and/or 155 of HCV protease (p = 0.027) whereas in boceprevir-based regimens mutations at amino acid 54 were significant (p = 0.015). SVR12 rates approaching 64% were achieved using triple therapy outside the clinical trial setting, in a patient cohort that included cirrhotics.

The Finometer can function as a standalone instrument in blood pressure variability studies and does not require support equipment to determine breathing frequency

Objective: The Finometer (FMS, Finapres Measurement Systems, Amsterdam) records the beat-to-beat finger pulse contour and has been recommended for research studies assessing shortterm changes of blood pressure and its variability. Variability measured in the frequency domain using spectral analysis requires that the impact of breathing be restricted to high frequency spectra (> 0.15 Hz) so data from participants needs to be excluded when the breathing impact occurs in the low frequency spectra (0.04 - 0.15 Hz). This study tested whether breathing frequency can be estimated from standard Finometer recordings using either stroke volume oscillation frequency or spectral stroke volume variability maximum scores. Methods: 22 healthy volunteers were tested for 270s in the supine and upright positions. Finometer recorded the finger pulse contour and a respiratory transducer recorded breathing. Stoke volume oscillation frequency was calculated manually while the stroke volume spectral maximums were obtained using the software Cardiovascular Parameter Analysis (Nevrokard Kiauta, Izola, Slovenia). These estimates were compared to the breathing frequency using the Bland-Altman procedures. Results: Stroke volume oscillation frequency estimated breathing frequency to <±10% 95% levels of agreement in both supine (-7.7 to 7.0%) and upright (-6.7 to 5.4%) postures. Stroke volume variability maximum scores did not accurately estimate breathing frequency. Conclusions: Breathing frequency can be accurately derived from standard Finometer recordings using stroke volume oscillations for healthy individuals in both supine and upright postures. The Finometer can function as a standalone instrument in blood pressure variability studies and does not require support equipment to determine breathing frequency.

Success or failure in knowledge management systems: a universal issue

This paper takes a sociotechnical viewpoint of knowledge management system (KMS) implementation in organizations considering issues such as stakeholder disenfranchisement, lack of communication, and the low involvement of key personnel in system design asking whether KMS designers could learn from applying sociotechnical principles to their systems. The paper discusses design elements drawn from the sociotechnical principles essential for the success of IS and makes recommendations to increase the success of KMS in organizations. It also provides guidelines derived from Clegg’s Principles (2000) for KMS designers to enhance their designs. Our data comes from the application of a plurality of analysis methods on a large comprehensive global survey conducted from 2007 to 2011 of 1034 participants from 76 countries. The survey covers a variety of organizations of all types and sizes from a comprehensive selection of economic sectors and industries. Our results showed that users were not satisfied with the information and knowledge systems that they were being offered. In addition to multiple technology and usability issues, there were human and organisational barriers that prevented the systems from being used to their full potential. We recommend that users of KMS are integrated into the design team so that these usability and other barriers can be addressed during the feasibility stage as well as the actual design and implementation phases.

The troubling concept of class: reflecting on our ‘failure’ to encourage sociology students to re-cognise their classed locations using autobiographical methods

The troubling concept of class: reflecting on our ‘failure’ to encourage sociology students to re-cognise their classed locations using autobiographical methods Abstract This paper provides a narrative of the four authors‟ commitment to auto/biographical methods as teachers and researchers in „new‟ universities. As they went about their work, they observed that, whereas students engage with the gendered, sexualised and racialised processes when negotiating their identities, they are reluctant or unable to conceptualise „class-ifying‟ processes as key determinants of their life chances. This general inability puzzled the authors, given the students‟ predominantly working-class backgrounds. Through application of their own stories, the authors explore the sociological significance of this pedagogical „failure‟ to account for the troubling concept of class not only in the classroom but also in contemporary society.

Dynamic power- and failure-aware cloud resources allocation for Sets of independent tasks

Cloud computing is increasingly being adopted in different scenarios, like social networking, business applications, scientific experiments, etc. Relying in virtualization technology, the construction of these computing environments targets improvements in the infrastructure, such as power-efficiency and fulfillment of users’ SLA specifications. The methodology usually applied is packing all the virtual machines on the proper physical servers. However, failure occurrences in these networked computing systems can induce substantial negative impact on system performance, deviating the system from ours initial objectives. In this work, we propose adapted algorithms to dynamically map virtual machines to physical hosts, in order to improve cloud infrastructure power-efficiency, with low impact on users’ required performance. Our decision making algorithms leverage proactive fault-tolerance techniques to deal with systems failures, allied with virtual machine technology to share nodes resources in an accurately and controlled manner. The results indicate that our algorithms perform better targeting power-efficiency and SLA fulfillment, in face of cloud infrastructure failures.

Manutenção preditiva e pró-activa: filosofias alternativas ou complementares: estudo de caso

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica Ramo Manutenção e Produção

Estratégias e internacionalização na manutenção e produção

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

Modelling and aerodynamic simulation of a vehicle and failure analysis of a laminated front fender

Master Thesis in Mechanical Engineering field of Maintenance and Production

Análise dos modos de falha e seus efeitos (FMEA) aplicada a um secador industrial

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

Estágio na empresa SPECMAN para a prática de técnicas de controlo da condição

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

Avaliação de fiabilidade de sistemas elétricos e de automação em instalações de frio industrial

Dissertação para a obtenção do grau de Mestre em Engenharia Electrotécnica Ramo de Energia/Automação e Eletrónica Industrial

Aplicação de redes neuronais artificiais à deteção e isolamento de falhas em processos industriais

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

A importância do planeamento e orçamentação nas empreitadas de obras de instalações mecânicas

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

Metodologia para otimização da manutenção

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia da Manutenção