1,075 research outputs found

    Classification of fresh edible oils using a coated piezoelectric sensor array-based electronic nose with soft computing approach for pattern recognition

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    An electronic nose based on an array of six bulk acoustic wave polymer-coated piezoelectric quartz (PZQ) sensors with soft computing-based pattern recognition was used for the classi-fication of edible oils. The electronic nose was presented with 346 samples of fresh edible oil headspace volatiles, generated at 45°C. Extra virgin olive (EVO), nonvirgin olive oil (NVO) and sunflower oil (SFO) were used over a period of 30 days. The sensor responses were visualized by plotting the results from principal component analysis (PCA). Classification of edible oils was carried out using fuzzy c-means as well as radial basis function (RBF) neural networks both from a raw data and data after having been preprocessed by fuzzy c-means. The fuzzy c-means results were poor (74%) due to the different cluster sizes. The result of RBF with fuzzy c-means preprocessing was 95% and 99% for raw data input. RBF networks with fuzzy c-means preprocessing provide the advantage of a simple architecture that is quicker to train.</p

    Antibiotic pharmacoeconomics: an attempt to find the real cost of hospital antibiotic prescribing.

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    Antibiotics account for a large part of all hospital pharmacy budgets, but the actual cost of their prescription is unknown. These costs include intravenous administration, labour, serum antibiotic assay, monitoring of haematological and biochemical indices, disposal of sharps and adverse effects. An in-house method of costing antibiotic therapy is presented, to quantify these hidden expenses. Since not only an awareness, but an accurate quantification, of hidden costs is required, a study of various hospital procedures relating directly to antibiotic therapy was undertaken in an acute medical ward; this involved the identification of particular staff members performing various procedures, consumables used and time taken. The cost of five-day courses of gentamicin, penicillin G, ampicillin, flucloxacillin, cefuroxime, ceftotaxime and erythromycin has been calculated; drug and hidden costs for each are presented graphically for comparison. The breakdown cost for gentamicin is presented to illustrate the method. The costing of adverse effects has not been attempted. We suggest that costings of this sort are used in cost-benefit analysis of antibiotic use. These calculations have been incorporated into a computer spreadsheet and this costing service will be offered to clinical areas of our hospital

    Management of imatinib-resistant CML patients

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    Imatinib has had marked impact on outcomes in chronic myelogenous leukemia (CML) patients for all stages of the disease and is endorsed by international treatment guidelines as the first line option. Although imatinib is highly effective and well tolerated, the development of resistance represents a clinical challenge. Since the most frequently identified mechanism of acquired imatinib resistance is bcr-abl kinase domain point mutations, periodic hematologic, cytogenetic, and molecular monitoring is critical throughout imatinib therapy. Once cytogenetic remission is achieved, residual disease can be monitored by bcr-abl transcript levels as assayed by reverse transcription polymerase chain reaction (RT-PCR). Detection of bcr-abl mutants prior to and during imatinib therapy can aid in risk stratification as well as in determining therapeutic strategies. Thus, mutation screening is indicated in patients lacking or losing hematologic response. Moreover, search for mutations should also be performed when a 3-log reduction of bcr-abl transcripts is not achieved or there is a reproducible increase of transcript levels. In patients harboring mutations which confer imatinib resistance, novel second line tyrosine kinase inhibitors have demonstrated encouraging efficacy with low toxicity. Only the T315I bcr-abl mutant has proved totally resistant to all clinically available bcr-abl inhibitors. Strategies to further increase the rates of complete molecular remissions represent the next frontier in the targeted therapy of CML patients

    Growth Arrest of BCR-ABL Positive Cells with a Sequence-Specific Polyamide-Chlorambucil Conjugate

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    Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, has significantly improved the clinical outcome of patients with CML. However, subsets of patients lose their response to treatment through the emergence of imatinib-resistant cells, and imatinib treatment is less durable for patients with late stage CML. Although alternative Bcr-Abl tyrosine kinase inhibitors have been developed to overcome drug resistance, a cocktail therapy of different kinase inhibitors and additional chemotherapeutics may be needed for complete remission of CML in some cases. Chlorambucil has been used for treatment of B cell chronic lymphocytic leukemia, non-Hodgkin's and Hodgkin's disease. Here we report that a DNA sequence-specific pyrrole-imidazole polyamide-chlorambucil conjugate, 1R-Chl, causes growth arrest of cells harboring both unmutated BCR-ABL and three imatinib resistant strains. 1R-Chl also displays selective toxicities against activated lymphocytes and a high dose tolerance in a murine model

    Delivering precision antimicrobial therapy through closed-loop control systems

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    Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients

    Securing recruitment and obtaining informed consent in minority ethnic groups in the UK

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    Background: Previous health research has often explicitly excluded individuals from minority ethnic backgrounds due to perceived cultural and communication difficulties, including studies where there might be language/literacy problems in obtaining informed consent. This study addressed these difficulties by developing audio-recorded methods of obtaining informed consent and recording data. This report outlines 1) our experiences with securing recruitment to a qualitative study investigating alternative methods of data collection, and 2) the development of a standardised process for obtaining informed consent from individuals from minority ethnic backgrounds whose main language does not have an agreed written form. Methods: Two researchers from South Asian backgrounds recruited adults with Type 2 diabetes whose main language was spoken and not written, to attend a series of focus groups. A screening tool was used at recruitment in order to assess literacy skills in potential participants. Informed consent was obtained using audio-recordings of the patient information and recording patients' verbal consent. Participants' perceptions of this method of obtaining consent were recorded. Results: Recruitment rates were improved by using telephone compared to face-to-face methods. The screening tool was found to be acceptable by all potential participants. Audio-recorded methods of obtaining informed consent were easy to implement and accepted by all participants. Attrition rates differed according to ethnic group. Snowballing techniques only partly improved participation rates. Conclusion: Audio-recorded methods of obtaining informed consent are an acceptable alternative to written consent in study populations where literacy skills are variable. Further exploration of issues relating to attrition is required, and a range of methods may be necessary in order to maximise response and participation

    The occurrence and management of fluid retention associated with TKI therapy in CML, with a focus on dasatinib

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    Tyrosine kinase inhibitors (TKIs) like dasatinib and nilotinib are indicated as second-line treatment for chronic myeloid leukemia resistant or intolerant to the current first-line TKI imatinib. These are agents are well tolerated, but potent and as such should be monitored for potentially serious side-effects like fluid retention and pleural effusions. Here we present key clinical trial data and safety considerations for all FDA approved TKIs in context for effective management of fluid retention and pleural effusions. Altering the dasatinib regimen from 70 mg twice daily to 100 mg daily reduces the risk of pleural effusion for patients taking dasatinib. Should pleural effusion develop, dasatinib should be interrupted until the condition resolves. Patients with a history of pleural effusion risk factors should be monitored closely while taking dasatinib. Patients receiving imatinib and nilotinib are not without risk of fluid retention. All patients should also be educated to recognize and report key symptoms of fluid retention or pleural effusion. Pleural effusions are generally managed by dose interruption/reduction and other supportive measures in patients with chronic myeloid leukemia receiving dasatinib therapy

    P-loop mutations and novel therapeutic approaches for imatinib failures in chronic myeloid leukemia

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    Imatinib was the first BCR-ABL-targeted agent approved for the treatment of patients with chronic myeloid leukemia (CML) and confers significant benefit for most patients; however, a substantial number of patients are either initially refractory or develop resistance. Point mutations within the ABL kinase domain of the BCR-ABL fusion protein are a major underlying cause of resistance. Of the known imatinib-resistant mutations, the most frequently occurring involve the ATP-binding loop (P-loop). In vitro evidence has suggested that these mutations are more oncogenic with respect to other mutations and wild type BCR-ABL. Dasatinib and nilotinib have been approved for second-line treatment of patients with CML who demonstrate resistance (or intolerance) to imatinib. Both agents have marked activity in patients resistant to imatinib; however, they have differential activity against certain mutations, including those of the P-loop. Data from clinical trials suggest that dasatinib may be more effective vs. nilotinib for treating patients harboring P-loop mutations. Other mutations that are differentially sensitive to the second-line tyrosine kinase inhibitors (TKIs) include F317L and F359I/V, which are more sensitive to nilotinib and dasatinib, respectively. P-loop status in patients with CML and the potency of TKIs against P-loop mutations are key determinants for prognosis and response to treatment. This communication reviews the clinical importance of P-loop mutations and the efficacy of the currently available TKIs against them
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