Aminoglutethimide-induced leucopenia in a mouse model:effects of metabolic and structural determinates

A model of human leucopenia has been developed further in the female mouse. Following daily administration to female mice of 50 mg/kg of the aromatase inhibitor aminoglutethimide, significant falls in platelet and white cell counts occurred after 2 and 3 weeks. At week 4, drug dosage was stopped and the cell counts recovered at the end of that week, although on rechallenge at the beginning of week 5, both platelet and white cell counts fell rapidly. Administration to the mice of structural analogues of aminoglutethimide, such as WSP-3, glutethimide and 4-nitroglutethimide, showed no reductions in platelet and white cell counts. The haemotoxicity of aminoglutethimide over 21 days was unaffected by the presence of either the P-450 inhibitor SKF-525A or the hepatic P-450 inducer phenobarbitone. However, the co-administration of cimetidine abolished the haemotoxicity of aminoglutethimide in terms of platelet and white cell levels. In in vitro studies, both aminoglutethimide and WSP-3 were oxidised to cytotoxic species, although aminoglutethimide was significantly more cytotoxic than WSP-3. The NADPH-dependent covalent binding of 14C aminoglutethimide to mouse microsomes in vitro was significantly reduced by the presence of cimetidine. The activation of the compound to reactive species in vitro, the inhibitory effects of cimetidine in vivo and in vitro, as well as the rapid fall in the in vivo white cell count on rechallenge with aminoglutethimide suggest that this model illustrates a form of leucopenia which may be related to hapten formation and subsequent immune-mediated platelet and white cell lysis. © 2003 Elsevier B.V. All rights reserved.

Early design verification of complex assembly variability using a hybrid - model based and physical testing - methodology

Design verification in the digital domain, using model-based principles, is a key research objective to address the industrial requirement for reduced physical testing and prototyping. For complex assemblies, the verification of design and the associated production methods is currently fragmented, prolonged and sub-optimal, as it uses digital and physical verification stages that are deployed in a sequential manner using multiple systems. This paper describes a novel, hybrid design verification methodology that integrates model-based variability analysis with measurement data of assemblies, in order to reduce simulation uncertainty and allow early design verification from the perspective of satisfying key assembly criteria.

Fluctuation-driven traffic congestion in a scale-free model of the Internet

In studies of complex heterogeneous networks, particularly of the Internet, significant attention was paid to analysing network failures caused by hardware faults or overload. There network reaction was modelled as rerouting of traffic away from failed or congested elements. Here we model network reaction to congestion on much shorter time scales when the input traffic rate through congested routes is reduced. As an example we consider the Internet where local mismatch between demand and capacity results in traffic losses. We describe the onset of congestion as a phase transition characterised by strong, albeit relatively short-lived, fluctuations of losses caused by noise in input traffic and exacerbated by the heterogeneous nature of the network manifested in a power-law load distribution. The fluctuations may result in the network strongly overreacting to the first signs of congestion by significantly reducing input traffic along the communication paths where congestion is utterly negligible. © 2013 IEEE.

Towards a multilevel model of the high performance work systems–workplace safety relationship

Human Resource (HR) systems and practices generally referred to as High Performance Work Practices (HPWPs), (Huselid, 1995) (sometimes termed High Commitment Work Practices or High Involvement Work Practices) have attracted much research attention in past decades. Although many conceptualizations of the construct have been proposed, there is general agreement that HPWPs encompass a bundle or set of HR practices including sophisticated staffing, intensive training and development, incentive-based compensation, performance management, initiatives aimed at increasing employee participation and involvement, job safety and security, and work design (e.g. Pfeffer, 1998). It is argued that these practices either directly and indirectly influence the extent to which employees’ knowledge, skills, abilities, and other characteristics are utilized in the organization. Research spanning nearly 20 years has provided considerable empirical evidence for relationships between HPWPs and various measures of performance including increased productivity, improved customer service, and reduced turnover (e.g. Guthrie, 2001; Belt & Giles, 2009). With the exception of a few papers (e.g., Laursen &Foss, 2003), this literature appears to lack focus on how HPWPs influence or foster more innovative-related attitudes and behaviours, extra role behaviors, and performance. This situation exists despite the vast evidence demonstrating the importance of innovation, proactivity, and creativity in its various forms to individual, group, and organizational performance outcomes. Several pertinent issues arise when considering HPWPs and their relationship to innovation and performance outcomes. At a broad level is the issue of which HPWPs are related to which innovation-related variables. Another issue not well identified in research relates to employees’ perceptions of HPWPs: does an employee actually perceive the HPWP –outcomes relationship? No matter how well HPWPs are designed, if they are not perceived and experienced by employees to be effective or worthwhile then their likely success in achieving positive outcomes is limited. At another level, research needs to consider the mechanisms through which HPWPs influence –innovation and performance. The research question here relates to what possible mediating variables are important to the success or failure of HPWPs in impacting innovative behaviours and attitudes and what are the potential process considerations? These questions call for theory refinement and the development of more comprehensive models of the HPWP-innovation/performance relationship that include intermediate linkages and boundary conditions (Ferris, Hochwarter, Buckley, Harrell-Cook, & Frink, 1999). While there are many calls for this type of research to be made a high priority, to date, researchers have made few inroads into answering these questions. This symposium brings together researchers from Australia, Europe, Asia and Africa to examine these various questions relating to the HPWP-innovation-performance relationship. Each paper discusses a HPWP and potential variables that can facilitate or hinder the effects of these practices on innovation- and performance- related outcomes. The first paper by Johnston and Becker explores the HPWPs in relation to work design in a disaster response organization that shifts quickly from business as usual to rapid response. The researchers examine how the enactment of the organizational response is devolved to groups and individuals. Moreover, they assess motivational characteristics that exist in dual work designs (normal operations and periods of disaster activation) and the implications for innovation. The second paper by Jørgensen reports the results of an investigation into training and development practices and innovative work behaviors (IWBs) in Danish organizations. Research on how to design and implement training and development initiatives to support IWBs and innovation in general is surprisingly scant and often vague. This research investigates the mechanisms by which training and development initiatives influence employee behaviors associated with innovation, and provides insights into how training and development can be used effectively by firms to attract and retain valuable human capital in knowledge-intensive firms. The next two papers in this symposium consider the role of employee perceptions of HPWPs and their relationships to innovation-related variables and performance. First, Bish and Newton examine perceptions of the characteristics and awareness of occupational health and safety (OHS) practices and their relationship to individual level adaptability and proactivity in an Australian public service organization. The authors explore the role of perceived supportive and visionary leadership and its impact on the OHS policy-adaptability/proactivity relationship. The study highlights the positive main effects of awareness and characteristics of OHS polices, and supportive and visionary leadership on individual adaptability and proactivity. It also highlights the important moderating effects of leadership in the OHS policy-adaptability/proactivity relationship. Okhawere and Davis present a conceptual model developed for a Nigerian study in the safety-critical oil and gas industry that takes a multi-level approach to the HPWP-safety relationship. Adopting a social exchange perspective, they propose that at the organizational level, organizational climate for safety mediates the relationship between enacted HPWS’s and organizational safety performance (prescribed and extra role performance). At the individual level, the experience of HPWP impacts on individual behaviors and attitudes in organizations, here operationalized as safety knowledge, skills and motivation, and these influence individual safety performance. However these latter relationships are moderated by organizational climate for safety. A positive organizational climate for safety strengthens the relationship between individual safety behaviors and attitudes and individual-level safety performance, therefore suggesting a cross-level boundary condition. The model includes both safety performance (behaviors) and organizational level safety outcomes, operationalized as accidents, injuries, and fatalities. The final paper of this symposium by Zhang and Liu explores leader development and relationship between transformational leadership and employee creativity and innovation in China. The authors further develop a model that incorporates the effects of extrinsic motivation (pay for performance: PFP) and employee collectivism in the leader-employee creativity relationship. The papers’ contributions include the incorporation of a PFP effect on creativity as moderator, rather than predictor in most studies; the exploration of the PFP effect from both fairness and strength perspectives; the advancement of knowledge on the impact of collectivism on the leader- employee creativity link. Last, this is the first study to examine three-way interactional effects among leader-member exchange (LMX), PFP and collectivism, thus, enriches our understanding of promoting employee creativity. In conclusion, this symposium draws upon the findings of four empirical studies and one conceptual study to provide an insight into understanding how different variables facilitate or potentially hinder the influence various HPWPs on innovation and performance. We will propose a number of questions for further consideration and discussion. The symposium will address the Conference Theme of ‘Capitalism in Question' by highlighting how HPWPs can promote financial health and performance of organizations while maintaining a high level of regard and respect for employees and organizational stakeholders. Furthermore, the focus on different countries and cultures explores the overall research question in relation to different modes or stages of development of capitalism.

Changes in autofluorescence based organoid model of muscle invasive urinary bladder cancer

Muscle invasive urinary bladder cancer is one of the most lethal cancers and its detection at the time of transurethral resection remains limited and diagnostic methods are urgently needed. We have developed a muscle invasive transitional cell carcinoma (TCC) model of the bladder using porcine bladder scaffold and the human bladder cancer cell line 5637. The progression of implanted cancer cells to muscle invasion can be monitored by measuring changes in the spectrum of endogenous fluorophores such as reduced nicotinamide dinucleotide (NADH) and flavins. We believe this could act as a useful tool for the study of fluorescence dynamics of developing muscle invasive bladder cancer in patients.

Development and validation of a computationally efficient pseudo 3D model for planar SOFC integrated with a heating furnace

Efficient numerical models facilitate the study and design of solid oxide fuel cells (SOFCs), stacks, and systems. Whilst the accuracy and reliability of the computed results are usually sought by researchers, the corresponding modelling complexities could result in practical difficulties regarding the implementation flexibility and computational costs. The main objective of this article is to adapt a simple but viable numerical tool for evaluation of our experimental rig. Accordingly, a model for a multi-layer SOFC surrounded by a constant temperature furnace is presented, trained and validated against experimental data. The model consists of a four-layer structure including stand, two interconnects, and PEN (Positive electrode-Electrolyte-Negative electrode); each being approximated by a lumped parameter model. The heating process through the surrounding chamber is also considered. We used a set of V-I characteristics data for parameter adjustment followed by model verification against two independent sets of data. The model results show a good agreement with practical data, offering a significant improvement compared to reduced models in which the impact of external heat loss is neglected. Furthermore, thermal analysis for adiabatic and non-adiabatic process is carried out to capture the thermal behaviour of a single cell followed by a polarisation loss assessment. Finally, model-based design of experiment is demonstrated for a case study.