A nonantisense sequence-selective effect of a phosphorothioate oligodeoxynucleotide directed against the epidermal growth factor receptor in A431 cells

The overexpression of epidermal growth factor receptor (EGFr) has been implicated as a causative factor and a poor prognostic marker in a number of carcinomas. Therefore, strategies that down-regulate EGFr expression may be therapeutically useful. We designed antisense ODNs complementary to the initiation codon region of the EGFr mRNA and evaluated their efficacy in several tumor-derived cells, including the A431 cell line that express amplified levels of EGFr. A 15-mer phosphorothioate (PS) antisense ODN (erbB1AS15) induced a concentration-dependent reduction in proliferation that was accompanied by a change in the morphology of A431 cells into more tightly clustered and discrete colonies. A 15-mer sense (PS) control oligodeoxynucleotide (ODN) and a phosphodiester (PO) version of erbB1AS15 had little or no effect on cell number of morphology, and erbB1AS15 (PS) did not induce these effects in control cell lines expressing lower levels of EGFr. The effects of erbB1AS15 (PS) on A431 cells were not mediated by a true antisense mechanism in that there was no reduction in the level of EGFr mRNA or protein over a 24-hr period, as determined by Northern and Western blotting, respectively. However, autophosphorylation of the receptor was significantly reduced by erbB1AS15 (PS) and not by control ODNs. The results of further studies suggested that this effect was mediated by a direct, dose-dependent inhibition of the EGFr tyrosine kinase enzyme and was not due to impairment of either ligand-binding or receptor dimerization. These data suggest that erbB1AS15 (PS) can inhibit proliferation and alter the morphology of A431 cells by a sequence-selective, but nonantisense mechanism affecting receptor tyrosine kinase activity.

The link between the management of employees and patient mortality in acute hospitals

The relationship between human resource management practices and organizational performance (including quality of care in health-care organizations) is an important topic in the organizational sciences but little research has been conducted examining this relationship in hospital settings. Human resource (HR) directors from sixty-one acute hospitals in England (Hospital Trusts) completed questionnaires or interviews exploring HR practices and procedures. The interviews probed for information about the extensiveness and sophistication of appraisal for employees, the extent and sophistication of training for employees and the percentage of staff working in teams. Data on patient mortality were also gathered. The findings revealed strong associations between HR practices and patient mortality generally. The extent and sophistication of appraisal in the hospitals was particularly strongly related, but there were links too with the sophistication of training for staff, and also with the percentages of staff working in teams.

"High commitment" strategies:it ain't what you do; it's the way that you do it

Purpose: This paper sets out to contribute to the advancement of knowledge, particularly with regard to the processes of implementation and the role of managers engaged in such high commitment strategies and work practices. Design/methodology/approach: This study is part of a research project investigating the extent to which employee involvement predicts job performance (as well as job satisfaction, wellbeing and organisational commitment) in the NHS, using both quantitative and qualitative methods. The main focus of this paper is to present evidence from four of the 20 case studies to show the barriers to implementing employee involvement as well as highlighting the techniques and practices that have proven to be most successful. Findings: Employee involvement is used successfully by management and has enabled frontline staff to contribute their knowledge to their work. Research limitations/implications: The ethical issues of confidentiality and anonymity permeated the research process throughout. Practical implications: The link between "high commitment" strategies and organisational performance is of great interest to academics and practitioners alike. One of these "high commitment" strategies, namely employee involvement, has been an important HR strategy for the NHS in the UK. Originality/value: Other organisations can learn from the findings by implementing the successful parts. © Emerald Group Publishing Limited.

Intergroup conflict and intergroup effectiveness in organizations:theory and scale development

Many see the absence of conflict between groups as indicative of effective intergroup relations. Others consider its management a suitable effectiveness criterion. In this article we demarcate a different approach and propose that these views are deficient in describing effective intergroup relations. The article theorizes alternative criteria of intergroup effectiveness rooted in team representatives' subjective value judgements and assesses the psychometric characteristics of a short measure based on these criteria. Results on empirical validity suggest the measure to be a potential alternative outcome of organizational conflict. Implications for both the study of intergroup relations and conflict theory are discussed. © 2005 Psychology Press Ltd.

War crimes, conditionality and EU integration in the Western Balkans

The baleful legacy of the wars of the 1990s continues to dog the states and societies of the former Yugoslavia and has overshadowed the disappointingly slow and hesitant trajectory of the region towards the EU. At the start of the new millennium, with the removal of key wartime leaders from the political scene in both Croatia and Serbia, it was widely hoped that the region would prove able to ‘leave the past behind’ and rapidly move on to the hopeful new agenda of EU integration. The EU’s Copenhagen criteria, which in 1993 first explicitly set out the basic political conditions expected of aspirant EU Member States, proved effective in the case of the new democracies of Central and Eastern Europe in supporting the entrenchment of democratic norms and practices, and stimulating reconciliation and good neighbourly relations among countries with turbulent histories. Building on this experience, the Stabilisation and Association Process, launched for the countries of the Western Balkans in 1999, included both full cooperation with the International Criminal Tribunal for the former Yugoslavia (ICTY) and regional reconciliation among the political conditions set for advancing these countries on the path to EU integration. EU political conditionality was intended to support the efforts of new political leaders to redefine national goals away from the nationalist enmities of the past and focus firmly on forging a path to a better future. This Chaillot Paper examines the extent to which this strategy has worked, especially in the light of the difficulties it has encountered in the face of strong resistance to cooperation among sections of the former Yugoslav population, many of whom have not yet fully acknowledged the crimes committed during the 1990s. Key chapters in the volume raise the vital questions of leadership and political will. EU political conditionality does not work unless the EU has a partner ready and willing to ‘play the game’, which presupposes that EU integration has become the overriding priority on the national political agenda.

Getting along with others:an examination of the ethnomethodological roots of perference organization and its relationship to complimenting

The well-established sociolinguistic literature on complimenting claims that compliments are formulaic (Manes and Wolfson 1981). The purpose of this thesis is to demonstrate that the claim is invalid, to describe an alternative approach to the study of compliments, and to draw on an extensive collection of compliments in order to show that complimenting is a diverse, interactive process. A prerequisite for such work is a means of deciding whether a given utterance is a compliment, but this issue is neglected in the literature. The conversation analytic notion of preference appeared capable of providing this criterion, but research revealed that it was too ill-defined to serve such a purpose. The thesis was, therefore, obliged to clarify the notion of preference before applying it to a study of compliments. The necessary clarification was found in the enthnomethodological roots of conversation analysis, and the thesis provides a clear and consistent means of determining whether utterances are preferred to dispreferred. The criteria used in the determination of preference are applied, in the final chapter, to the study of compliments. The results of the study contrast markedly with those of the sociolinguistic researchers, and they provide significant grounds for rejecting the claim that compliments are formulaic.

Rewarding customer service? Using reward and recognition to deliver your customer service strategy

This report examines the role of reward and recognition in helping organisations deliver excellent customer service. It identifies the impact that reward and recognition practice has upon customer service and highlights which practices are more effective; shows the extent to which employees are satisfied with the rewards and recognition they receive; indicates those approaches to reward and recognition most associated with staff commitment; and looks at how other factors affect employee satisfaction with reward and recognition.

Servitization capabilities for advanced services:a multi-actor perspective

Servitization is the process by which manufacturers add services to their product offerings and even replace products with services. The capabilities necessary to develop and deliver advanced services as part of servitization are often discussed in the literature from the manufacturer’s perspective, e.g., having a service-focused culture or the ability to sell solutions. Recent research has acknowledged the important role of customers and, to a lesser extent, other actors (e.g., intermediaries) in bringing about successful servitization, particularly for use-oriented and results-oriented advanced services. The objective of this study is to identify the capabilities required to successful develop advanced services as part of servitization by considering the perspective of manufacturers, intermediaries and customers. This study involved interviews with 33 managers in 28 large UK-based companies from these three groups, about servitization capabilities. The findings suggest that there are eight broad capabilities that are important for advanced services; 1) personnel with expertise and deep technical product knowledge, 2) methodologies for improving operational processes, helping to manage risk and reduce costs, 3) the evolution from being a product- focused manufacturer to embracing a services culture, 4) developing trusting relationships with other actors in the network to support the delivery of advanced services, 5) new innovation activities focused on financing contracts (e.g., ‘gain share’) and technology implementation (e.g., Web-based applications), 6) customer intimacy through understanding their business challenges in order to develop suitable solutions, 7) extensive infrastructure (e.g., personnel, service centres) to deliver a local service, and 8) the ability to tailor service offerings to each customer’s requirements and deliver these responsively to changing needs. The capabilities required to develop and deliver advanced services align to a need to enhance the operational performance of supplied products throughout their lifecycles and as such require greater investment than the capabilities for base and intermediate services.

Cerebellar morphology in developmental dyslexia

Recent evidence has suggested cerebellar anomalies in developmental dyslexia. Therefore, we investigated cerebellar morphology in subjects with documented reading disabilities. We obtained T1-weighted magnetic resonance images in the coronal and sagittal planes from 11 males with prior histories of developmental dyslexia, and nine similarly-aged male controls. Proton magnetic resonance spectra (TE=136 ms, TR=2.4 s) were obtained bilaterally in the cerebellum. Phonological decoding skill was measured using non-word reading. Handedness was assessed using both the Annett questionnaire of hand preference and Annett’s peg moving task. Cerebellar symmetry was observed in the dyslexics but there was significant asymmetry (right grey matter>left grey matter) in controls. The interpretation of these results depended whether a motor- or questionnaire-based method was used to determine handedness. The degree of cerebellar symmetry was correlated with the severity of dyslexics’ phonological decoding deficit. Those with more symmetric cerebella made more errors on a nonsense word reading measure of phonological decoding ability. Left cerebellar metabolite ratios were shown to correlate significantly with the degree of cerebellar asymmetry (P<0.05) in controls. This relationship was absent in developmental dyslexics. Cerebellar morphology reflects the higher degree of symmetry found previously in the temporal and parietal cortex of dyslexics. The relationship of cerebellar asymmetry to phonological decoding ability and handedness, together with our previous finding of altered metabolite ratios in the cerebellum of dyslexics, lead us to suggest that there are alterations in the neurological organisation of the cerebellum which relate to phonological decoding skills, in addition to motor skills and handedness.

Neurophysiological evaluation of convergent afferents innervating the human esophagus and area of referred pain on the anterior chest wall

Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. Esophageal evoked potentials (EEP) were recorded from the vertex following 200 electrical stimuli, and anterior chest wall evoked potentials (ACWEP) were recorded following 40 heat pulses. The fear of pain questionnaire (FPQ) was administered on V1. Statistical data are shown as point estimates of difference +/- 95% confidence interval. Pain thresholds increased between V1 and V3 [Eso-PT: V1-V3 = -17.9 mA (-27.9, -7.9) P < 0.001; ACW-PT: V1-V3 = -3.38 degrees C (-5.33, -1.42) P = 0.001]. The morphology of cortical responses from both sites was consistent and equivalent [P1, N1, P2, N2 complex, where P1 and P2 are is the first and second positive (downward) components of the CEP waveform, respectively, and N1 and N2 are the first and second negative (upward) components, respectively], indicating activation of similar cortical networks. For EEP, N1 and P2 latencies decreased between V1 and V3 [N1: V1-V3 = 13.7 (1.8, 25.4) P = 0.02; P2: V1-V3 = 32.5 (11.7, 53.2) P = 0.003], whereas amplitudes did not differ. For ACWEP, P2 latency increased between V1 and V3 [-35.9 (-60, -11.8) P = 0.005] and amplitudes decreased [P1-N1: V1-V3 = 5.4 (2.4, 8.4) P = 0.01; P2-N2: 6.8 (3.4, 10.3) P < 0.001]. The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Adelta fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 (r = -0.57, P = 0.05). These data provide the first neurophysiological evidence of convergent esophageal and somatic pain pathways in humans.

The effect of Gaussian noise on the threshold, dynamic range, and loudness of analogue cochlear implant stimuli

The deliberate addition of Gaussian noise to cochlear implant signals has previously been proposed to enhance the time coding of signals by the cochlear nerve. Potentially, the addition of an inaudible level of noise could also have secondary benefits: it could lower the threshold to the information-bearing signal, and by desynchronization of nerve discharges, it could increase the level at which the information-bearing signal becomes uncomfortable. Both these effects would lead to an increased dynamic range, which might be expected to enhance speech comprehension and make the choice of cochlear implant compression parameters less critical (as with a wider dynamic range, small changes in the parameters would have less effect on loudness). The hypothesized secondary effects were investigated with eight users of the Clarion cochlear implant; the stimulation was analogue and monopolar. For presentations in noise, noise at 95% of the threshold level was applied simultaneously and independently to all the electrodes. The noise was found in two-alternative forced-choice (2AFC) experiments to decrease the threshold to sinusoidal stimuli (100 Hz, 1 kHz, 5 kHz) by about 2.0 dB and increase the dynamic range by 0.7 dB. Furthermore, in 2AFC loudness balance experiments, noise was found to decrease the loudness of moderate to intense stimuli. This suggests that loudness is partially coded by the degree of phase-locking of cochlear nerve fibers. The overall gain in dynamic range was modest, and more complex noise strategies, for example, using inhibition between the noise sources, may be required to get a clinically useful benefit. © 2006 Association for Research in Otolaryngology.

Identifying (territorial) tensions in the servitization value chain

Purpose: To understand the tensions that servitization activities create between actors within networks. Design/methodology/approach: Interviews were conducted with manufacturers, intermediaries and customers across a range of industrial sectors. Findings: Tensions relating to two key sets of capabilities are identified: in developing or acquiring (i) operant technical expertise and (ii) operand service infrastructure. The former tension concerns whom knowledge is co-created with and where expertise resides. The latter involves a territorial investment component; firms developing strategies to acquire greater access to, or ownership of, infrastructures closer to customers. Developing and acquiring these capabilities is a strategic decision on the part of managers of servitizing firms, in order to gain recognized power and control in a particular territory. Originality/value: This paper explores how firms’ servitization activities involve value appropriation (from the rest of the network), contrasting with the narrative norm for servitization: that it creates additional value. There is a need to understand the tensions that servitization activities create within networks. Some firms may be able to improve servitization performance through co-operation rather than competition, generating co-opetitive relationships. Others may need to become much more aggressive, if they are to take a greater share of the ‘value’ from the value chain.