Prospective phase II clinical trial of autologous haematopoietic stem cell transplant for treatment refractory multiple sclerosis

Background Autologous haematopoietic stem cell transplantation (AHSCT) has been explored as a therapeutic intervention in multiple sclerosis (MS) over the last two decades; however, prospective clinical trials of the most common myeloablative conditioning regimen, BEAM, are limited. Furthermore, patient selection, optimal chemotherapeutic regimen and immunological changes associated with disease response require ongoing exploration. We present the outcomes, safety and immune reconstitution (IR) of patients with active, treatment refractory MS. Methods This study was a single-centre, phase II clinical trial of AHSCT for patients with active relapsing remitting (RRMS) and secondary progressive MS (SPMS). Patients underwent AHSCT using BEAM (carmustine, etoposide, cytarabine, melphalan)+antithymocyte globulin chemotherapeutic regimen. Outcomes The primary outcome was event-free survival (EFS); defined as no clinical or radiological relapses and no disability progression. Multiparameter flow cytometry was performed for evaluation of post-transplant IR in both MS and lymphoma patients receiving the same chemotherapy regimen. Results Thirty-five patients (20 RRMS, 15 SPMS) completed AHSCT, with a median follow-up of 36 months (range 12-66). The median Expanded Disability Status Scores (EDSS) was 6 (2-7) and patients had failed a median of 4 (2-7) disease modifying therapies. 66% failed treatment with natalizumab. EFS at 3 years was 60%, (70% RRMS). Sustained improvement in EDSS was seen in 15 (44%) of patients. There was no treatment-related mortality. A sustained rise in CD39 + T regulatory cells, immunosuppressive CD56 hi natural killer cells and ablation of proinflammatory mucosal-associated invariant T cells was seen for 12 months following AHSCT in patients with MS. These changes did not occur in patients with lymphoma receiving the same chemotherapy for AHSCT. Conclusions The EFS in our MS cohort is significantly greater than other high-efficacy immunosuppressive therapies and similar to other AHSCT studies despite a more heavily pretreated cohort. Trial registration number ACTRN12613000339752

Mobile device driven taxi management system

This dissertation is about the project ‘Mobile Device Driven Taxi Management System’. The project consist tree main software implementations as Server Sub System (SSS), Operator Desktop - Client application (ODC) and Vehicle Driver’s Mobile application (VDM). SSS is the core and service provider for both ODC and VDM applications. The main objective ofthe above Sub systems architecture is to use the currently available web and mobile technologies in development of the solution and high availability ofthe system in operation at the business point ofview. In the first phase of the Software Development Life Cycle the knowledge oftaxi management domain has been acquired. They have been analyzed and best architectural design was decided based on the requirement. Code level implementation and suitable tests wereconducted prior release of the software to the Business Client. Mainly the Iterative Model of Development has been used for Software development in the project to minimize the time and requirement gathering ambiguities. Then in each phase there have been modules were developed in the development of code. The software solution has been delivered to the business client and the solution has been deployed on their computer systems

Sensory interaction on static balance: A comparison concerning the history of falls of community-dwelling elderly

To determine whether elderly subjects with distinct histories of falls presented differences concerning the influence of sensory interaction on balance. Cross-sectional research. Ninety-six community-dwelling elderly subjects were divided into three groups, according to the history of falls within the past year (group 1, no falls; group 2, one fall; and group 3, recurrent falls). The Clinical Test of Sensory Interaction and Balance was used to evaluate the influence of sensory inputs on standing balance. The test required the subject to maintain stability during 30 s, under six conditions: (i) firm surface with eyes open; (ii) firm surface with eyes closed; (iii) firm surface with visual conflict; (iv) unstable surface with eyes open; (v) unstable surface with eyes closed; and (vi) unstable surface with visual conflict. The time expended on conditions and the number of abnormal cases were compared between groups. Each group was evaluated in relation to its performance in the progression of conditions. More abnormal cases occurred in group 3 compared to group 1 for conditions (iv) and (v); and compared to group 2 for condition (iv). Group 3 remained less time than group 1 under conditions (iv), (v) and (vi). Groups 1, 2 and 3 presented relevant decrements in trial duration from conditions (iv) to (v). For group 3, a significant decay was also noted from condition (i) to (ii). Sensorial interaction in the elderly varies according to their history of falls. Thus, it is possible to correctly guide the rehabilitation process and to prevent sensorial decays according to an individual's history of falls.9216517

Infusion of foam sclerosants results in a distance-dependent procoagulant activity, haemoconcentration and elevation of D-dimer levels

Objective To investigate the biological effects of foam sclerotherapy in vivo. Materials and methods Ultrasound-guided sclerotherapy was performed using a 3% sodium tetradecyl sulphate or polidocanol. A total of 15 mL of foam was injected. Samples were collected from antecubital veins, target saphenous veins and the adjoining deep veins before, immediately after and 1 hour after the procedure. Saphenous vein samples were also taken sequentially at set 15 cm intervals. Clotting times, D-dimer, cell counts and biochemical parameters were measured. D-dimer levels were repeated one week later. Results Forty procedures were performed. Systemic clotting times were not affected by the procedure. Injection of 0.5 mL of foam 5 cm away from the relevant junctions resulted in procoagulant activity in the adjoining deep veins (sodium tetradecyl sulphate) and the target saphenous veins (sodium tetradecyl sulphate and polidocanol). The procoagulant effect in the target veins reached a peak at 15 cm but normalised at 45 cm. D-dimer levels were significantly increased 1 hour after treatment with either agent and remained elevated one week later. Sodium tetradecyl sulphate and to a lesser degree polidocanol induced biochemical changes consistent with haemoconcentration. Conclusion Infusion of foam sclerosants results in a distance-dependent procoagulant activity in the exposed vessels. Foam sclerotherapy results in haemoconcentration and elevation of D-dimer. </jats:sec