Studies into the characteristics and basic biology of dendritic cells and their use in the immunotherapy of malignancy

Dendritic cells (DCs) are the most potent of all antigen presenting cells, playing a central role in initiating and orchestrating immune responses. It has recently become possible to generate large numbers of DCs from either CD34+ haemopoietic progenitor cells or peripheral blood monocytes under the influence of various cytokines. With this advance there has been a great explosion of interest in using ex vivo generated DCs as part of immunotherapy programmes directed towards the treatment of malignancy, chronic infections and autoimmune diseases, as well as in the context of inducing tolerance following allogeneic transplantation. In all these settings the DCs need to be loaded with the appropriate antigens. This can be achieved by several methods, each of which has its advantages and disadvantages. In this thesis a comparison is made between the methods used to generate DCs from either CD34+ progenitor cells or CD14+ monocytes. The morphology, phenotype and functional characteristics of the resulting DCs are reported. Results are presented which demonstrate that the differentiation of monocytes into DCs under the influence of GM-CSF and IL-4 is a non-proliferative process and therefore does not lend itself to retroviral transduction, rendering this method of loading DCs with antigen inapplicable. The signal transduction pathways which are involved in the lipopolysaccharide (LPS)-induced maturation of monocyte derived DCs are also explored. The p38SAPK pathway and NF-KB pathways are shown to be important in regulating some but not all of the phenotypic changes which occur with LPS-induced maturation of DCs. The PI3 kinase pathway is shown to be important in maintaining the viability of LPS stimulated DCs. Finally, a clinically applicable method for generating DCs from CD34+ progenitor cells is described, and preliminary results are presented on two patients with non-Hodgkins Lymphoma treated with DCs generated in this manner and loaded with tumour antigens in the form of an autologous tumour cell lysate

TOPOLOGY ZOOM TO PHYSICAL PORTS FROM A DEVICE LEVEL

Common mapping tools typically provide for gradually zooming in and out for further in-depth location information without ever switching views. Techniques are described herein that allow zoom functionality to exist in the realm of Networking Topology mapping. Using natural user interactions, a user may simply zoom-in for more in-depth information and configuration abilities without losing a device mapping

Supporting Islanded Microgrid Operations in the Presence of Intermittent Wind Generation

Although microgrids have the potential to solve several sticky problems that beset the present-day grid, indiscriminate application can cause serious problems. Thorough studies are needed on many aspects to identify the potential problems and to develop effective mitigation techniques. Microgrids can operate in parallel with the main grid or as an isolated system to support customers isolated from the grid. during parallel operations, the microgrid supplies only a fraction of the power demand of the grid. However, in islanded operations, the microgrid must continue to supply 100% of power to the customers. Both types of operations are studied to identify the solutions needed for islanded operation. Even load variations and small disturbances can create challenging situations in an islanded mode particularly when the microgrid includes a large percentage of wind power. the use of Static Synchronous Compensator (STATCOM) is investigated for stabilizing the microgrid voltage during short circuit faults. ©2010 IEEE

Process design of a fully integrated continuous biopharmaceutical process using economic and ecological impact assessment

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DRUG UTILIZATION EVALUATION AND COST ANALYSIS OF ANTIEMETIC DRUGS PRESCRIBED IN ONCOLOGY WARD IN A QUATERNARY CARE HOSPITAL

Objective: Drug utilization is defined by the World Health Organization as the marketing, distribution, prescription, and use of drugs in society, withspecial emphasis on the resulting medical, social, and economic consequences. Our study is done to obtain the variation of drug use and costs of drug therapy, from which medical and social qualitative consequences can be found. Our study emphasizes on knowing the drug utilization and costincluded for antiemetics in patients undergoing chemotherapy in oncology ward.Methods: It was observational, prospective and non-interventional study.Results: Total of 141 patients were studied, out of which 77 (54.6%) patients were female and 64 (45.4%) patients were males. The majority of thepatients in this study belong to the age group of 40-49 (29%) and 60-69 (20%) years. The comparison with the standard protocol was made accordingto the use of antiemetics in the patients. Out of which, 137 (97%) patient profiles were found to be deviating from standard protocol, and 4 (3%)patient profiles were found following the standard protocol because of including prochlorperazine which is not mentioned in the standard protocol.Conclusion: As of future approach, education to physician for rational drug use and review of medication chart with patient consideration can givebetter health care and also cost effective treatment.Keywords: Drug use evaluation, Antiemetics, Chemotherapy

CT-based texture analysis potentially provides prognostic information complementary to interim fdg-pet for patients with hodgkin's and aggressive non-hodgkin's lymphomas

OBJECTIVES: The purpose of this study was to investigate the ability of computed tomography texture analysis (CTTA) to provide additional prognostic information in patients with Hodgkin's lymphoma (HL) and high-grade non-Hodgkin's lymphoma (NHL). METHODS: This retrospective, pilot-study approved by the IRB comprised 45 lymphoma patients undergoing routine 18F-FDG-PET-CT. Progression-free survival (PFS) was determined from clinical follow-up (mean-duration: 40 months; range: 10-62 months). Non-contrast-enhanced low-dose CT images were submitted to CTTA comprising image filtration to highlight features of different sizes followed by histogram-analysis using kurtosis. Prognostic value of CTTA was compared to PET FDG-uptake value, tumour-stage, tumour-bulk, lymphoma-type, treatment-regime, and interim FDG-PET (iPET) status using Kaplan-Meier analysis. Cox regression analysis determined the independence of significantly prognostic imaging and clinical features. RESULTS: A total of 27 patients had aggressive NHL and 18 had HL. Mean PFS was 48.5 months. There was no significant difference in pre-treatment CTTA between the lymphoma sub-types. Kaplan-Meier analysis found pre-treatment CTTA (medium feature scale, p=0.010) and iPET status (p<0.001) to be significant predictors of PFS. Cox analysis revealed that an interaction between pre-treatment CTTA and iPET status was the only independent predictor of PFS (HR: 25.5, 95% CI: 5.4-120, p<0.001). Specifically, pre-treatment CTTA risk stratified patients with negative iPET. CONCLUSION: CTTA can potentially provide prognostic information complementary to iPET for patients with HL and aggressive NHL