725 research outputs found

    The relative success of alternative approaches to strategic information systems planning: an empirical analysis

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    Strategic information systems planning (SISP) is an exercise or ongoing activity that enables organisations to develop priorities for information systems development. It has been suggested that the ‘SISP approach’, a combination of method, process and implementation, is the most complete way of describing SISP activity. Based upon questionnaire responses from 267 IT Directors, four distinct approaches to SISP have been derived using cluster analysis. A comparison of these four approaches with five approaches of Earl, M.J., 1993. Experiences in SISP, MIS Quarterly, (March), 1–24, indicates that three bear strong similarities to the ‘organisational’, ‘business-led’, and ‘administrative’ approaches, whilst the fourth cluster is related to both Earl’s ‘method-driven’ and ‘technological’ approaches. An analysis of the relationship between SISP approach and SISP success demonstrates that the ‘organisational approach’ is significantly more successful than the other three approaches

    The ratio of initial/residual DNA damage predicts intrinsic radiosensitivity in seven cervix carcinoma cell lines.

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    The single-cell gel electrophoresis (comet) assay was used to measure radiation-produced DNA double-strand breaks (dsbs) in a series of seven cervical tumour cell lines (ME180, HT3, C33A, C41, SiHa, MS751 and CaSki). The proportion of DNA dsbs was measured immediately after radiation treatment (initial damage) and 16 h later after incubation at 37 degrees C (residual damage). Linear dose-response curves were seen for initial (slopes 0.23-0.66) and residual (slopes 0.16-0.87) DNA dsbs. Neither of the slopes of the linear regression analysis on the initial and on the residual DNA dsbs dose-response curves (range 0-80 Gy) correlated with SF2 (surviving fraction at 2 Gy) measured after high- (HDR) or low-dose-rate (LDR) irradiation. An association was evident between SF2 after HDR and LDR irradiation and the ratio of the absolute level of initial and residual damage after a single dose of 60 Gy. However, a significant correlation was found between HDR (r= -0.78, P = 0.04) and LDR (r = -0.86, P = 0.03) SF2 values and the ratio of the slopes of the initial and residual DNA dsbs dose-response curves (range 0.47-0.99), representing the fraction of DNA damage remaining. These results indicate that the neutral comet assay can be used to predict radiosensitivity of cervical tumour cell lines by assessing the ratio of initial and residual DNA dsbs

    Sebomic identification of sex- and ethnicity-specific variations in residual skin surface components (RSSC) for bio-monitoring or forensic applications

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    Background: “Residual skin surface components” (RSSC) is the collective term used for the superficial layer of sebum, residue of sweat, small quantities of intercellular lipids and components of natural moisturising factor present on the skin surface. Potential applications of RSSC include use as a sampling matrix for identifying biomarkers of disease, environmental exposure monitoring, and forensics (retrospective identification of exposure to toxic chemicals). However, it is essential to first define the composition of “normal” RSSC. Therefore, the aim of the current study was to characterise RSSC to determine commonalities and differences in RSSC composition in relation to sex and ethnicity. Methods: Samples of RSSC were acquired from volunteers using a previously validated method and analysed by high-pressure liquid chromatography–atmospheric pressure chemical ionisation–mass spectrometry (HPLC-APCI-MS). The resulting data underwent sebomic analysis. Results: The composition and abundance of RSSC components varied according to sex and ethnicity. The normalised abundance of free fatty acids, wax esters, diglycerides and triglycerides was significantly higher in males than females. Ethnicity-specific differences were observed in free fatty acids and a diglyceride. Conclusions: The HPLC-APCI-MS method developed in this study was successfully used to analyse the normal composition of RSSC. Compositional differences in the RSSC can be attributed to sex and ethnicity and may reflect underlying factors such as diet, hormonal levels and enzyme expression.Peer reviewedFinal Published versio

    Enforcement and compliance: critical practices for community rehabilitation companies and the new NPS?

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    Efforts to secure compliance have always been a core element of probation practice,although compliance has been constructed in diverse ways and promoted through different means throughout its history. This article takes a brief historical perspective and reviews recent research on enforcement practices and developing understandings of compliance. These guide a critical discussion of the practices that might develop as responsibilities for enforcement are divided between the new National Probation Service (NPS) and Community Rehabilitation Companies (CRCs) under the Transforming Rehabilitation agenda, highlighting inevitable tensions and challenges, and anticipating how inter-agency practices might shape the ongoing construction of compliance. Charging more than one agency with responsibilities in relation to enforcement is tricky and creates risks in terms of legitimacy, credibility and justice. On the whole, future prospects seem difficult, but not hopeless and, in particular, there are examples of positive practices in probation and youth justice for the NPS and CRCs to draw upon as they develop their inter-agency structures and processes. Elsewhere, initiatives in problem-solving courts, focused, for example, on drug users, may also give indicators of constructive ways forwar

    Effect of carboplatin when administered after dacarbazine failure: Clinical benefit of sequential therapy

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    Dacarbazine chemotherapy has been the mainstay of melanoma treatment for >30 years. In the early 2000s, carboplatin (with or without other agents, such as paclitaxel) was the most commonly used second‑line therapy in the UK. The aim of the present study was to report a significant response rate to second‑line carboplatin in patients from three UK institutions who had been previously treated and failed to respond to dacarbazine, and investigate whether sequential therapy may be more effective compared with combination therapy. A total of 104 patients were identified, the majority of whom were treated with carboplatin (area under the curve 5‑6) every 3 weeks for a maximum of 6 cycles. A total of 102 patients were evaluable for response, among whom 11 patients had an objective response (1 complete response and 10 partial responses) and 15 had stable disease, giving an overall response rate of 11% and disease control rate of 26%. The median progression‑free survival was 1.8 months (range, 0.2‑36+ months) and the median overall survival was 4.6 months (range, 0.2‑36+ months). Surprisingly, the majority of the patients who benefited from second‑line carboplatin therapy were those with visceral metastases, the survival of whom would not be expected to exceed 6 months after first‑line treatment

    The clinical and economic benefits of capecitabine and tegafur with uracil in metastatic colorectal cancer

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    Two oral fluoropyrimidine therapies have been introduced for metastatic colorectal cancer. One is a 5-fluorouracil pro-drug, capecitabine; the other is a combination of tegafur and uracil administered together with leucovorin. The purpose of this study was to compare the clinical effectiveness and cost-effectiveness of these oral therapies against standard intravenous 5-fluorouracil regimens. A systematic literature review was conducted to assess the clinical effectiveness of the therapies and costs were calculated from the UK National Health Service perspective for drug acquisition, drug administration, and the treatment of adverse events. A cost-minimisation analysis was used; this assumes that the treatments are of equal efficacy, although direct randomised controlled trial (RCT) comparisons of the oral therapies with infusional 5-fluorouracil schedules were not available. The cost-minimisation analysis showed that treatment costs for a 12-week course of capecitabine (£2132) and tegafur with uracil (£3385) were lower than costs for the intravenous Mayo regimen (£3593) and infusional regimens on the de Gramont (£6255) and Modified de Gramont (£3485) schedules over the same treatment period. Oral therapies result in lower costs to the health service than intravenous therapies. Further research is needed to determine the relative clinical effectiveness of oral therapies vs infusional regimens

    Cellular Radiosensitivity: How much better do we understand it?

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    Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation
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