The future workplace:views from the floor

Speculation on the future of work and the nature of the future workplace has come to dominate much academic discourse in recent years. Rarely however has the voice of what might be termed the average skilled employee been heard; those who are still shaping a career and may be most at the mercy of whatever changes occur. This study seeks to fill this gap. Stemming from a 1-year research project at Cranfield School of Management, this paper focuses on data collected from a survey exploring the understanding of current and future organisations, and the nature of current and future leadership. The survey was carried out in 2003 and sampled 469 MBA graduates and a further 340 respondents to a web-based questionnaire. The paper provides an overview of the academic discourse on the future workplace, explores the perceptions and expectations of the sample and draws conclusions regarding significant anticipated trends for the future workplace as seen by those on the shop floor. These centre around increased flexibility and autonomy, but with limited awareness of the nature of leadership skills required to lead such a workforce. © 2006 Elsevier Ltd. All rights reserved.

Biochemical aspects of Tourette's Syndrome

Kynurenine (KYN) is the first stable metabolite of the kynurenine pathway, the major route of tryptophan. (TRP) metabolIsm. In the liver, cortisol-inducible tIyptophan-2,3-dioxygenase (TDO) is the first enzyme and rate limiting step. In extrahepatic tissues, it is superceded by indoleamine-2,3-dioxygenase (IDO), an enzyme with a wider substrate specificity. Earlier work in this research group has found substantial elevations in plasma KYN in fasting Tourette's Syndrome (TS) patients with normal TRP and neopterin. The aim of our initial pilot study was to confirm this increase in KYN in fasting human TS patients compared with normal controls, and to see how changes in diet :ay influence certain kynurenine pathway variables. However, we failed to detect a change in plasma KYN, TRP, kynurenic acid (KYNA), neopterin or cortisol between the fasting TS and control groups. Moreover, none of the variables was affected by dietary status, and thus candidates selected for the larger cross-sectional study were permitted to eat and drink freely on the day that blood samples were submitted, but were requested to avoid products containing caffeine, aspirin or nicotine. In the cross-sectional study, TS patients exhibited significantly higher plasma KYN concentrations than controls, although the magnitude of the change was much smaller than originally found. This may be due to differences in detection procedure and the seasonal fluctuation of some biochemical variables, notably cortisol. The generalised increase in neopterin in the TS subject group, suggests a difference in the activity of cytokine-inducible IDO as a likely source for this elevated KYN. Other kynurenine pathway metabolites, specifIcally TRP, 3-hydroxykynurenine (HKY), 3-hydroxyanthranilic acid (HAA) and KYNA were unchanged. In view of recent speculation of the potential therapeutic effects of nicotine in TS, the lower KYN concentrations observed in TS smokers, compared with non-smoking TS patients, was another interesting finding. Tic-like movements, such as head-shakes (HS), which occur in rodents both spontaneously and following diverse drug treatments, closely resemble tic behaviours in humans. The animal tic model was used to examine what effects nicotine may have on shaking behaviours and on selected TRP metabolites. Acute systemic administration of nicotine to mice, produced a dose-dependent reduction in HS frequency (induced by the 5-HT2A/2C agonist DOl), which appeared to be mediated via central nicotinic cholinergic receptors, since mecamylamine pretreatment abolished this effect. Conversely, twice daily subcutaneous injections of nicotine for 7 days, led to an increase in spontaneous and DOI-induced HS. Chronic nicotine also caused a significant elevation m plasma and whole brain KYN concentrations, but plasma TRP, HKY, HAA and KYNA were unaltered. In addition, no change in brain 5-HT or 5-HIAA concentrations or 5-HT turnover, was found. Despite contrasting results from human and animal studIes, a role for nicotine in the mediation of tic-like movements is indicated. The relevance of the kynurenine pathway to TS and the potential role played by nicotine in modifying tic-like behaviours is discussed.

Evaluation of DNA enzymes targeted against the RNA component of human telomerase

Glioblastoma Multiforme (GBM) is a highly malignant form of brain cancer for which there is currently no effective cure. Consequently, developing new therapies and elucidating effective targets is crucial for this fatal disease. In recent years, DNA enzymes, deoxyribonucleic acid molecules with enzymatic activity, have emerged. In the same manner as ribozymes, DNA enzymes are able to effect cleavage of RNA in a sequence-specific manner, and operate with catalytic efficiency. In this study, two DNA enzymes were designed to target the template region of human telomerase RNA (hTR), utilising the 10-23 and 8-17 catalytic motifs elucidated by Santoro and Joyce (1997). Telomerase is an RNA-dependent DNA polymerase, which stabilises telomere lengths by adding hexameric repeats (TTAGGG in humans) to chromosome termini, thus preventing the telomere shortening that usually occurs during mitotic cell division. Telomerase activity, whilst absent in normal somatic tissues, is present in almost 90% of all tumours. Thus, there is speculation that telomerase may be the much sought universal target for therapeutic intervention in cancer. In vitro cleavage assays showed both DNA enzymes to be catalytically competent. Unmodified phosphodiester (PO) backbone DNA enzymes were rapidly degraded in the presence of serum, with a half-life of 10 minutes. The common approach of introducing phosphorothioate (PS) linkages was used in an effort to overcome this instability. As a result of concurrent activity and stability studies on the DNA enzymes with various numbers of PS linkages, the DNA enzymes with a PO core and PS arms were chosen for use in further cell work. The cleavage activity of both was shown to be specific and affected by temperature, pH, MgCI2 concentration and enzyme concentration. Both DNA enzyme motifs reduced telomerase activity in cell lysates, as assessed by the telomerase repeat amplification protocol (TRAP) with an IC50 of 100nM. DNA enzymes being polyanionic molecules do not readily cross biological barriers. Cellular association of naked DNA enzyme was inefficient at less than 2%. Cellular delivery of the DNA enzymes was effectively improved using commercial cationic lipid formulations. However, the lipid-mediated delivery of DNA enzymes to U87-MG cells over a 4-hour period did not significantly inhibit cell proliferation compared to controls. This is possibly due to an expected lag period between the inhibition of telomere maintenance and cell death. Therefore, biodegradable polymer microspheres were investigated as a potential delivery option for prolonged and sustained delivery. In vitro release profiles showed that after an initial burst, sustained release of DNA enzymes was observed over 35 days. Finally, the efficacy and specificity of the DNA enzymes were demonstrated in a luciferase based reporter assay. Specific inhibition of luciferase expression was displayed at 10nM. Thus DNA enzymes have potential against endogenous cellular targets.

Accommodation in young adults wearing multifocal soft contact lenses under long- and short- wavelength lighting

Purpose: Several studies have suggested accommodative lags may serve as a stimulus for myopic growth, and while a blurred foveal image is believed to the main stimulus for accommodation, spectral composition of the retinal image is also believed to influence accommodative accuracy. Of particular interest is how altering spectral lighting conditions influences accommodation in the presence of soft multifocal contact lenses, which are currently being used off-label for myopia control. Methods: Accommodative responses were assessed using a Grand Seiko WAM-5500 autorefractor for four target distances: 25, 33, 50, and 100cm for 30 young adult subjects (14 myopic, 16 emmetropic; mean refractive errors (±SD, D) -4.22±2.04 and -0.15±0.67 respectively). Measurements were obtained with four different soft contact lenses, Single vision distance (SVD), Single vision near (SVN), Centre-Near (CN) and Centre-Distance (CD) (+1.50 add), and three different lighting conditions: red (peak λ 632nm), blue (peak λ 460nm), and white (peak λ 560nm). Corrections for chromatic differences in refraction were made prior to calculating accommodative errors. Results: The size of accommodative errors was significantly affected by lens design (p<0.001), lighting (p=0.027), and target distance (p=0.009). Mean accommodative errors were significantly larger with the SV lenses compared to the CD and CN designs (p<0.001). Errors were also significantly larger under blue light compared to white (p=0.004) and a significant interaction noted between lens design and lighting (p<0.001). Blue light generally decreased accommodative lags and increased accommodative leads relative to white and red light, the opposite was true of red light (p≤0.001). Lens design also significantly influenced direction of accommodative error (i.e. lag or lead) (p<0.001). Interactions with or between refractive groups were not found to be statistically significant for either the magnitude or direction of accommodative error (p>0.05 for all). Conclusions: Accuracy of accommodation is affected by both lens design and by wavelength of lighting. These accommodative lag data lend some support to recent speculation about the potential therapeutic value of lighting with a spectral bias towards blue during near work for myopia, although such treatment effects are likely to be more subtle under broad compared to the narrow spectrum lighting conditions used here.