Results of a phase IIa clinical trial of an anti-inflammatory molecule, chaperonin 10, in multiple sclerosis

Background Chaperonin 10 (Cpn10) is a mitochondrial molecule involved in protein folding. The aim of this study was to determine the safety profile of Cpn10 in patients with multiple sclerosis (MS). Methods A total of 50 patients with relapse-remitting or secondary progressive MS were intravenously administered 5 mg or 10 mg of Cpn10 weekly for 12 weeks in a double-blind, randomized, placebo controlled, phase II trial. Clinical reviews, including Expanded Disability Status Scale and magnetic resonance imaging (MRI) with Gadolinium, were undertaken every 4 weeks. Stimulation of patient peripheral blood mononuclear cells with lipopolysaccharide ex vivo was used to measure the in vivo activity of Cpn10. Results No significant differences in the frequency of adverse events were seen between treatment and placebo arms. Leukocytes from both groups of Cpn10-treated patients produced significantly lower levels of critical proinflammatory cytokines. A trend toward improvement in new Gadolinium enhancing lesions on MRI was observed, but this difference was not statistically significant. No differences in clinical outcome measures were seen. Conclusions Cpn10 is safe and well tolerated when administered to patients with MS for 3 months, however, a further extended phase II study primarily focused on efficacy is warranted.

Tools of the trade: quick measures and validated tools for assessing health and wellness. How you can better help your clients/employees help themselves

Worksite wellness efforts can generate enormous health-care savings. Many of the methods available to obtain health and wellness measures can be confusing and lack clarity; for example it can be difficult to understand if measures are appropriate for individuals or population health. Come along and enjoy a hands-on learning experience about measures and better understanding health and wellness outcomes from baseline, midway and beyond.

Chromosomal aberrations in squamous cell carcinoma and solar keratoses revealed by comparative genomic hybridization

OBJECTIVE: To identify chromosomal copy numbers of frequent genetic aberrations within squamous cell carcinomas (SCCs) and solar keratoses (SKs), and provide further evidence to support or challenge current dogma concerning the relationship between these lesions. DESIGN: Retrospective analysis of genetic aberrations in DNA from SK and SCC biopsy specimens by comparative genomic hybridization. SETTING: University-based research laboratory in Queensland, Australia. PATIENTS: Twenty-two biopsy specimens from patients with diagnosed SKs (n = 7), cutaneous SCCs (n = 10), or adjoining lesions (n = 5). MAIN OUTCOME MEASURES: Identification of frequent genetic aberrations both specific to SK and SCC and shared by these lesions to investigate their clonal relationship. RESULTS: Shared genomic imbalances were identified in SK and SCC. Frequent gains were located at chromosome arms 3q, 17q, 4p, 14q, Xq, 5p, 9q, 8q, 17p, and 20q, whereas shared regional losses were observed at 9p, 3p, 13q, 17p, 11p, 8q, and 18p. Significant loss of 18q was observed only in SCC lesions. CONCLUSIONS: Our results demonstrate that numerous chromosomal aberrations are shared by the 2 lesions, suggesting a clonal relationship between SK and SCC. Additionally, the genomic loss of 18q may be a significant event in SK progression to SCC. Finally, the type and frequency of aberrations suggests a common mode of tumorigenesis in SCC-derived tumors.

Impact of a school-based food garden on attitudes and identification skills regarding vegetables and fruit : a 12-month intervention trial

Objective To determine changes in ability to identify specific vegetables and fruits, and attitudes towards vegetables and fruit, associated with the introduction of a school-based food garden. Design A 12-month intervention trial using a historical control (control n 132, intervention n 120), class-based, self-administered questionnaires requiring one-word answers and 3-point Likert scale responses. Setting A state primary school (grades 4 to 7) in a low socio-economic area of Brisbane, Australia. Intervention The introduction of a school-based food garden, including the funding of a teacher coordinator for 11 h/week to facilitate integration of garden activities into the curriculum. Main outcome measures Ability to identify a series of vegetables and fruits, attitudes towards vegetables and fruit. Analysis Frequency distributions for each item were generated and χ2 analyses were used to determine statistical significance. Exploratory factor analysis was employed to detect major trends in data. Results The intervention led to enhanced ability to identify individual vegetables and fruits, greater attention to origins of produce (garden-grown and fresh), changes to perceived consumption of vegetables and fruits, and enhanced confidence in preparing fruit and vegetable snacks, but decreased interest in trying new fruits. Conclusions The introduction of this school-based food garden was associated with skill and attitudinal changes conducive to enhancing vegetable and fruit consumption. The ways in which such changes might impact on dietary behaviours and intake require further analysis.

High frequency high power converters for industrial applications

The main contribution of this project was to investigate power electronics technology in designing and developing high frequency high power converters for industrial applications. Therefore, the research was conducted at two levels; first at system level which mainly encapsulated the circuit topology and control scheme and second at application level which involves with real-world applications. Pursuing these objectives, varied topologies have been developed and proposed within this research. The main aim was to resolving solid-state switches limited power rating and operating speed while increasing the system flexibility considering the application characteristics. The developed new power converter configurations were applied to pulsed power and high power ultrasound applications for experimental validation.

Load frequency control in a microgrid : challenges and improvements

A microgrid can span over a large area, especially in rural townships. In such cases, the distributed generators (DGs) must be controlled in a decentralized fashion, based on the locally available measurements. The main concerns are control of system voltage magnitude and frequency, which can either lead to system instability or voltage collapse. In this chapter, the operational challenges of load frequency control in a microgrid are discussed and few methods are proposed to meet these challenges. In particular, issues of power sharing, power quality and system stability are addressed, when the system operates under decentralized control. The main focus of this chapter is to provide solutions to improve the system performance in different situations. The scenarios considered are (a) when the system stability margin is low, (b) when the line impedance has a high R to X ratio, (c) when the system contains unbalanced and/or distorted loads. Also a scheme is proposed in which a microgrid can be frequency isolated from a utility grid while being capable of bidirectional power transfer. In all these cases, the use of angle droop in converter interfaced DGs is adopted. It has been shown that this results in a more responsive control action compared to the traditional frequency based droop control.

Frequency in hypertensives of alleles for a RFLP associated with the renin gene

The genetic basis of primary hypertension is not known. Renin is important in blood pressure and volume control and a HindIII restriction fragment length polymorphism (RFLP) is present within the human renin gene locus. To examine whether there is a relationship between this RFLP and primary hypertension, DNA and renin analyses were performed on leukocytes and plasma from hypertensive and normotensive individuals. In hypertensives the frequencies of alleles for the HindIII RFLP were found to be 0.55 and 0.45, compared with 0.60 and 0.40 in the total population of 231 subjects examined, a difference that was not statistically significant. There also appeared to be no significant difference in renin activity in plasma for hypertensive patients of each genotype, nor in their pre- or post-treatment blood pressures. We thus conclude that, within the limits of the present study, the suspected genetic abnormalities associated with primary hypertension in man do not appear to be related to a HindIII RFLP in the renin gene.

A parametric duration model of the reaction times of drivers distracted by mobile phone conversations

The use of mobile phones while driving is more prevalent among young drivers—a less experienced cohort with elevated crash risk. The objective of this study was to examine and better understand the reaction times of young drivers to a traffic event originating in their peripheral vision whilst engaged in a mobile phone conversation. The CARRS-Q Advanced Driving Simulator was used to test a sample of young drivers on various simulated driving tasks, including an event that originated within the driver’s peripheral vision, whereby a pedestrian enters a zebra crossing from a sidewalk. Thirty-two licensed drivers drove the simulator in three phone conditions: baseline (no phone conversation), hands-free and handheld. In addition to driving the simulator each participant completed questionnaires related to driver demographics, driving history, usage of mobile phones while driving, and general mobile phone usage history. The participants were 21 to 26 years old and split evenly by gender. Drivers’ reaction times to a pedestrian in the zebra crossing were modelled using a parametric accelerated failure time (AFT) duration model with a Weibull distribution. Also tested where two different model specifications to account for the structured heterogeneity arising from the repeated measures experimental design. The Weibull AFT model with gamma heterogeneity was found to be the best fitting model and identified four significant variables influencing the reaction times, including phone condition, driver’s age, license type (Provisional license holder or not), and self-reported frequency of usage of handheld phones while driving. The reaction times of drivers were more than 40% longer in the distracted condition compared to baseline (not distracted). Moreover, the impairment of reaction times due to mobile phone conversations was almost double for provisional compared to open license holders. A reduction in the ability to detect traffic events in the periphery whilst distracted presents a significant and measurable safety concern that will undoubtedly persist unless mitigated.

Effect of high-frequency resistance exercise on adaptive responses in skeletal muscle

PURPOSE: Regulation of skeletal muscle mass is highly dependent on contractile loading. The purpose of this study was to examine changes in growth factor and inflammatory pathways following high-frequency resistance training. METHODS: Using a novel design in which male Sprague-Dawley rats undertook a "stacked" resistance training protocol designed to generate a summation of transient exercise-induced signaling responses (four bouts of three sets × 10 repetitions of squat exercise, separated by 3 h of recovery), we determined the effects of high training frequency on signaling pathways and transcriptional activity regulating muscle mass. RESULTS: The stacked training regimen resulted in acute suppression of insulin-like growth factor 1 mRNA abundance (P < 0.05) and Akt phosphorylation (P < 0.05), an effect that persisted 48 h after the final training bout. Conversely, stacked training elicited a coordinated increase in the expression of tumor necrosis factor alpha, inhibitor kappa B kinase alpha/beta activity (P < 0.05), and p38 mitogen-activated protein kinase phosphorylation (P < 0.05) at 3 h after each training bout. In addition, the stacked series of resistance exercise bouts induced an increase in p70 S6 kinase phosphorylation 3 h after bouts ×3 and ×4, independent of the phosphorylation state of Akt. CONCLUSIONS: Our results indicate that high resistance training frequency extends the transient activation of inflammatory signaling cascades, concomitant with persistent suppression of key mediators of anabolic responses. We provide novel insights into the effects of the timing of exercise-induced overload and recovery on signal transduction pathways and transcriptional activity regulating skeletal muscle mass in vivo.

Rodent Models of Conditioned Fear: Behavioral Measures of Fear and Memory

Pavlovian fear conditioning is a robust technique for examining behavioral and cellular components of fear learning and memory. In fear conditioning, the subject learns to associate a previously neutral stimulus with an inherently noxious co-stimulus. The learned association is reflected in the subjects' behavior upon subsequent re-exposure to the previously neutral stimulus or the training environment. Using fear conditioning, investigators can obtain a large amount of data that describe multiple aspects of learning and memory. In a single test, researchers can evaluate functional integrity in fear circuitry, which is both well characterized and highly conserved across species. Additionally, the availability of sensitive and reliable automated scoring software makes fear conditioning amenable to high-throughput experimentation in the rodent model; thus, this model of learning and memory is particularly useful for pharmacological and toxicological screening. Due to the conserved nature of fear circuitry across species, data from Pavlovian fear conditioning are highly translatable to human models. We describe equipment and techniques needed to perform and analyze conditioned fear data. We provide two examples of fear conditioning experiments, one in rats and one in mice, and the types of data that can be collected in a single experiment. © 2012 Springer Science+Business Media, LLC.

Measurement as legitimacy versus legitimacy of measures : Performance evaluation of social enterprise

Purpose The purpose of this paper is to review the growing emphasis on quantifiable performance measures such as social return on investment (SROI) in third sector organisations – specifically, social enterprise – through a legitimacy theory lens. It then examines what social enterprises value (i.e. consider important) in terms of performance evaluation, using a case study approach. Design/methodology/approach Case studies involving interviews, documentary analysis, and observation, of three social enterprises at different life-cycle stages with different funding structures, were constructed to consider “what measures matter” from a practitioner's perspective. Findings Findings highlight a priority on quality outcomes and impacts in primarily qualitative terms to evaluate performance. Further, there is a noticeable lack of emphasis on financial measures other than basic access to financial resources to continue pursuing social goals. Social implications The practical challenges faced by social enterprises – many of which are small to medium sized – in evaluating performance and by implication organisational legitimacy are contrasted with measures such as SROI which are resource intensive and have inherent methodological limitations. Hence, findings suggest the limited and valuable resources of social enterprises would be better allocated towards documenting the actual outcomes and impacts as a first step, in order to evaluate social and financial performance in terms appropriate to each objective, in order to demonstrate organisational legitimacy. Originality/value Findings distinguish between processes which may hold symbolic legitimacy for select stakeholder groups, and processes which hold substantive, cognitive legitimacy for stakeholders more broadly, in the under-researched context of social enterprise.

The ISR and ESR scales : measures of the project manager-stakeholder relationship

In this paper, we develop two stakeholder relationships scales. These scales assess project managers’ perceived competence in establishing and maintaining high quality, effective relationships with people internal to the project as well as those stakeholders who are external to the project. We developed the scales using an online survey study of three hundred and seventy three complex project managers from a sub-set of the Australian Defence Industry. Both the internal stakeholder relationships’ scale and the external stakeholder relationships’ scale demonstrated validity and reliability. This research has implications for the interpersonal work relationships’ literature and the stakeholder management literature. We recommend future research tests these scales with multiple samples, across different project types and project industries. The stakeholder relationships’ scales should be versatile enough to be applied to project management generally but are best suited to large-scale complex project environments.

Bone matters in lung cancer

Background: Bone metastases are a significant and undertreated clinical problem in patients with advanced lung cancer. Design: We reviewed the incidence of bone metastases and skeletal-related events (SREs) in patients with lung cancer and examined the burden on patients' lives and on health care systems. Available therapies to improve survival and lessen the impact of SREs on quality of life (QoL) were also investigated. Results: Bone metastases are common in lung cancer; however, owing to short survival times, data on the incidences of SREs are limited. As with other cancers, the costs associated with treating SREs in lung cancer are substantial. Bisphosphonates reduce the frequency of SREs and improve measures of pain and QoL in patients with lung cancer; however, nephrotoxicity is a common complication of therapy. Denosumab, a recently approved bone-targeted therapy, is superior to zoledronic acid in increasing the time to first on-study SRE in patients with solid tumours, including lung cancer. Additional roles of bone-targeted therapies beyond the prevention of SREs are under investigation. Conclusions: With increasing awareness of the consequences of SREs, bone-targeted therapies may play a greater role in the management of patients with lung cancer, with the aim of delaying disease progression and preserving QoL. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.