22 resultados para Bart Giamatti


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It has been 25 years since the publication of a comprehensive review of the full spectrum of salesperformance drivers. This study takes stock of the contemporary field and synthesizes empirical evidence from the period 1982–2008. The authors revise the classification scheme for sales performance determinants devised by Walker et al. (1977) and estimate both the predictive validity of its sub-categories and the impact of a range of moderators on determinant-sales performance relationships. Based on multivariate causal model analysis, the results make two major observations: (1) Five sub-categories demonstrate significant relationships with sales performance: selling-related knowledge (ß=.28), degree of adaptiveness (ß=.27), role ambiguity (ß=-.25), cognitive aptitude (ß=.23) and work engagement (ß=.23). (2) These sub-categories are moderated by measurement method, research context, and salestype variables. The authors identify managerial implications of the results and offer suggestions for further research, including the conjecture that as the world is moving toward a knowledge-intensive economy, salespeople could be functioning as knowledge-brokers. The results seem to back this supposition and indicate how it might inspire future research in the field of personal selling.

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Background: In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival.
Methods: In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. The trial is registered, ISRCTN27286448.
Findings: 1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months [IQR 10·3—29·2] in the control group vs 17·0 months [9·4—30·1] in the cetuximab group; HR 1·04, 95% CI 0·87—1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months [IQR 5·0—12·5] in the control group vs 8·6 months [5·1—13·8] in the cetuximab group; HR 0·96, 0·82—1·12, p=0·60). Overall response rate increased from 57% (n=209) with chemotherapy alone to 64% (n=232) with addition of cetuximab (p=0·049). Grade 3 and higher skin and gastrointestinal toxic effects were increased with cetuximab (14 vs 114 and 67 vs 97 patients in the control group vs the cetuximab group with KRAS wild-type tumours, respectively). Overall survival differs by somatic mutation status irrespective of treatment received: BRAF mutant, 8·8 months (IQR 4·5—27·4); KRAS mutant, 14·4 months (8·5—24·0); all wild-type, 20·1 months (11·5—31·7).
Interpretation: This trial has not confirmed a benefit of addition of cetuximab to oxaliplatin-based chemotherapy in first-line treatment of patients with advanced colorectal cancer. Cetuximab increases response rate, with no evidence of benefit in progression-free or overall survival in KRAS wild-type patients or even in patients selected by additional mutational analysis of their tumours. The use of cetuximab in combination with oxaliplatin and capecitabine in first-line chemotherapy in patients with widespread metastases cannot be recommended.

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Background: Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease. Methods: We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimer's disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS.
Results: Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points (95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P<0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points higher (95% CI, 0.6 to 1.8; P<0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P = 0.02). The efficacy of donepezil and of memantine did not differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone.
Conclusions: In patients with moderate or severe Alzheimer's disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months. (Funded by the U.K. Medical Research Council and the U.K. Alzheimer's Society; Current Controlled Trials number, ISRCTN49545035).

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Although less likely to be reported in clinical trials than expressions of the statistical significance of differences in outcomes, whether or not a treatment has delivered a specified minimum clinically important difference (MCID) is also relevant to patients and their caregivers and doctors. Many dementia treatment randomised controlled trials (RCTs) have not reported MCIDs and, where they have been done, observed differences have not reached these.

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Alzheimer's disease (AD) is the commonest cause of dementia. Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not recommended by the England and Wales National Institute for Health and Clinical Excellence. However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in particular, what to do as the condition progresses from moderate to severe. Options include continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to establish the most effective drug option for people with AD who are progressing from moderate to severe dementia despite treatment with donepezil.

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This article analyses the dynamics of electoral competition in a multilevel setting. It is based on a content analysis of the party manifestos of the Spanish PP and PSOE in eight regional elections held between 2001 and 2003. It provides an innovative coding scheme for analysing regional party manifestos and on that basis seeks to account for inter-regional, intra-party and inter-party differences in regional campaigning. The authors have tried to explain the inter-regional variation of the issue profiles of state-wide parties in regional elections on the basis of a model with four independent variables: the asymmetric nature of the system, the electoral cycle, the regional party systems and the organisation of the state-wide parties. Three of their hypotheses are rejected, but the stronger variations in the regional issue profiles of the PSOE corroborate the assumption that parties with a more decentralised party organisation support regionally more diverse campaigning. The article concludes by offering an alternative explanation for this finding and by suggesting avenues for further research.

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This article investigates the link between regionalization of the structure of government, regional elections and regionalism on the one hand, and the organization of state-wide political parties in Spain and the UK on the other. It particularly looks at two aspects of the relations between the central and regional levels of party organization: integration of the regional branches in central decision making and autonomy of the regional branches. It argues that the party factors are the most crucial elements explaining party change and that party leaders mediate between environmental changes and party organization. The parties' history and beliefs and the strength of the central leadership condition their ability or willingness to facilitate the emergence of meso-level elites. The institutional and electoral factors are facilitating factors that constitute additional motives for or against internal party decentralization

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The study reveals the salience of particular issues in the manifestos of the main British parties for the 1997 and 2003 UK general elections, as well as the 2003 Scottish and Welsh elections, using the method introduced by the Comparative Manifesto Project (CMP) and a modified list of issue categories to reflect the division of government competences between the central and regional governments. Ideological and social base of a party, as well as the delimitation of government competences, are found to be important determinants of issue salience. A more consensual institutional design of the regional government in Scotland and Wales seems to have conditioned larger differences among the issue profiles of parties competing in regional elections, in comparison with general elections. With the institutionalisation of devolution, however, we observe an increase in the similarity of the issue profiles of the same parties in general and in Scottish and Welsh elections, as well as among different parties competing in the same regional elections. © 2005 Taylor & Francis.

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Are older adults risk seeking or risk averse? Answering this question might depend on both the task used and the analysis performed. By modeling responses to the Balloon Analogue Risk Task (BART), our results illustrate the value of modeling as compared to relying on common analysis techniques. While analysis of overall measures suggested initially that older and younger adults do not differ in their risky decisions, our modeling results indicated that younger adults were at first more willing to take greater risks. Furthermore, older adults may be more cautious when their decision making is based on initial perceptions of risk, rather than learning following some experience with a task.

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Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons.

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This work demonstrates that instead of paraelectric PbTiO(3), completely c-oriented ferroelectric PbTiO(3) thin films were directly grown on (001)-SrTiO(3) substrates by pulsed-laser deposition with thickness up to 340 nm at a temperature well above the Curie temperature of bulk PbTiO(3). The influence of laser-pulse frequency, substrate-surface termination on growth, and functional properties were studied using x-ray diffraction, transmission electron microscopy, and piezoresponse force microscopy. At low growth rates (frequency 8 Hz) a domains were formed for film thickness above 20-100 nm. Due to coherency strains the Curie temperature (T(c)) of the monodomain films was increased approximately by 350 degrees C with respect to the T(c) of bulk PbTiO(3) even for 280-nm-thick films. Nonetheless, up to now this type of growth mode has been considered unlikely to occur since the Matthews-Blakeslee (MB) model already predicts strain relaxation for films having a thickness of only similar to 10 nm. However, the present work disputes the applicability of the MB model. It clarifies the physical reasons for the large increase in T(c) for thick films, and it is shown that the experimental results are in good agreement with the predictions based on the monodomain model of Pertsev et al. [Phys. Rev. Lett. 80, 1988 (1998)].