310 resultados para antibody directed enzyme prodrug therapy


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BACKGROUND Globally there are emerging trends for non-medical health professionals to expand their scope of practice into prescribing. The NPS Prescribing Competencies Framework and the Health Professionals Prescribing Pathway Program are recent initiatives to assist with implementation of prescribing for allied health professionals (AHPs). For AHPs to become prescribers, training programmes must be designed to extend their knowledge of medicines information and medicine management principles with the aim of optimising medicines related outcomes for patients. AIM To explore the understanding and confidence in clinical therapeutic choices for patient management of those AHPs enrolled in the Allied Health Prescribing Training Program Module One: Introduction to clinical therapeutics for prescribers, delivered by Queensland University of Technology, Brisbane. METHOD A pre-post survey was developed to explore key themes around understanding and confidence in selecting therapeutic choices for patients with varying complexities of conditions. Data were collected from participants in week one and 13 of the module via an online survey using a five-point Likert scale (1 = Strongly Agree (SA) to 5 = Strongly Disagree (SD)). RESULTS In the pre-Module survey the AHPs had a limited degree (D/SD) of understanding and confidence regarding the safe and effective use of medicines and appropriate therapeutic choices for managing patients, particularly with complex patients. This improved significantly in the post Module survey (A/SA).

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Androgens regulate biological pathways to promote proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen receptor (AR) targeted therapies exploit this dependence and are used in advanced prostate cancer to control disease progression. Contemporary treatment regimens involve sequential use of inhibitors of androgen synthesis or AR function. Although targeting the androgen axis has clear therapeutic benefit, its effectiveness is temporary, as prostate tumor cells adapt to survive and grow. The removal of androgens (androgen deprivation) has been shown to activate both epithelial-to-mesenchymal transition (EMT) and neuroendocrine transdifferentiation (NEtD) programs. EMT has established roles in promoting biological phenotypes associated with tumor progression (migration/invasion, tumor cell survival, cancer stem cell-like properties, resistance to radiation and chemotherapy) in multiple human cancer types. NEtD in prostate cancer is associated with resistance to therapy, visceral metastasis, and aggressive disease. Thus, activation of these programs via inhibition of the androgen axis provides a mechanism by which tumor cells can adapt to promote disease recurrence and progression. Brachyury, Axl, MEK, and Aurora kinase A are molecular drivers of these programs, and inhibitors are currently in clinical trials to determine therapeutic applications. Understanding tumor cell plasticity will be important in further defining the rational use of androgen-targeted therapies clinically and provides an opportunity for intervention to prolong survival of men with metastatic prostate cancer.

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This study investigated occupational therapy and physiotherapy students' level of confidence and knowledge of strategies for communicating with people with aphasia (PWA) before and after a communication partner-training (CPT) program. Twenty-eight physiotherapy and occupational therapy students participated in a pre–post CPT program. Students completed a customized mixed-methods questionnaire before and after the intervention. The CPT program involved a lecture about effective communication strategies followed by a conversation with PWA to practice strategies learnt. Before CPT, students were not confident with the possibility of communicating with PWA. Students demonstrated rudimentary knowledge of supported conversation, identifying a maximum of five strategies for communicating effectively with PWA. Following intervention, students demonstrated increased confidence. Students' knowledge of effective communication strategies improved, with students identifying a maximum of 16 suitable strategies post-training. The results suggest that occupational therapy and physiotherapy students have potential to benefit from practical training in supported communication with PWA, which may assist them during placements in clinical settings with neurological patients or subsequent employment.

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Breast cancer is the second most common cancer worldwide and the most common cancer reported in women. This malignant tumour is characterised by a number of specific features including uncontrolled cell proliferation. It ranks fifth in the world as a cause of cancer death in women. Early diagnosis increases 5 year survival rates up to 95%. Heparan sulfate proteoglycans (HSPGs) are complex proteins composed of a core protein to which a number of highly sulfated side chains are synthesised by a highly co-ordinated process resulting in distinct sulfation patterns, which determine specific interations with cell-signaling partners including growth factors, their receptors, ligands and morphogens. The enzymes responsible for chain initiation, elongation and sulfation are critical for creating HS chain variability conferring biological functionality. This study investigated single nucleotide polymorphism in SULF1, the enzyme responsible for the 6-0 desulfation of heparan sulfate side chains. We investigated this SNP in an Australian Caucasian case-control breast cancer population and found a significant association between SULF1 and breast cancer at both the allelic and genotypic level (allele, p=0.016; genotype, p=0.032). Our results suggest the res2623047 SNP in SULF1 may impact breast cancer susceptibility. Specifically, the T allele of rs2623047 in SULF1 is associated with a increased risk of developing breast cancer in our cohort. The identification of markers including SULF1 may improve detection of this disease at its earliest stages improving patient treatment and prognosis.

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The creation of a commercially viable and a large-scale purification process for plasmid DNA (pDNA) production requires a whole-systems continuous or semi-continuous purification strategy employing optimised stationary adsorption phase(s) without the use of expensive and toxic chemicals, avian/bovine-derived enzymes and several built-in unit processes, thus affecting overall plasmid recovery, processing time and economics. Continuous stationary phases are known to offer fast separation due to their large pore diameter making large molecule pDNA easily accessible with limited mass transfer resistance even at high flow rates. A monolithic stationary sorbent was synthesised via free radical liquid porogenic polymerisation of ethylene glycol dimethacrylate (EDMA) and glycidyl methacrylate (GMA) with surface and pore characteristics tailored specifically for plasmid binding, retention and elution. The polymer was functionalised with an amine active group for anion-exchange purification of pDNA from cleared lysate obtained from E. coli DH5α-pUC19 pellets in RNase/protease-free process. Characterization of the resin showed a unique porous material with 70% of the pores sizes above 300 nm. The final product isolated from anion-exchange purification in only 5 min was pure and homogenous supercoiled pDNA with no gDNA, RNA and protein contamination as confirmed with DNA electrophoresis, restriction analysis and SDS page. The resin showed a maximum binding capacity of 15.2 mg/mL and this capacity persisted after several applications of the resin. This technique is cGMP compatible and commercially viable for rapid isolation of pDNA.

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Transfusion-related acute lung injury (TRALI) has been the leading cause of transfusion-related morbidity and mortality in the UK and the USA in recent years. A threshold mechanism of TRALI has been proposed in which both patient factors (type and/or severity of clinical insult) and blood product factors (strength and/or concentration of antibodies or biological response modifiers) interact to surpass a threshold for TRALI development (Bux et al. Br J Haematol; 2007; 136: 788-99). The risk of developing antibody-mediated TRALI has been minimised by the introduction of risk-reduction strategies such as limiting the use of plasma from female donors. In contrast, there are no strategies currently in place to mitigate the development of non-antibody mediated TRALI as the mechanisms remain largely undefined. Previous studies have implicated non-polar lipids such as arachidonic acid and various species of hydroxyeicosatetranoic acid (HETE) in the development of non-antibody mediated TRALI (Silliman et al. Transfusion; 2011; 51: 2549-54), however the contribution of these lipids to the development of an inflammatory response in TRALI is poorly understood.

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This thesis examines and compares imaging methods used during the radiotherapy treatment of prostate cancer. The studies found that radiation therapists were able to localise and target the prostate consistently with planar imaging techniques and that the use of small gold markers in the prostate reduced the variation in prostate localisation when using volumetric imaging. It was concluded that larger safety margins are required when using volumetric imaging without gold markers.

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In this paper we present for the first time a complete symbolic navigation system that performs goal-directed exploration to unfamiliar environments on a physical robot. We introduce a novel construct called the abstract map to link provided symbolic spatial information with observed symbolic information and actual places in the real world. Symbolic information is observed using a text recognition system that has been developed specifically for the application of reading door labels. In the study described in this paper, the robot was provided with a floor plan and a destination. The destination was specified by a room number, used both in the floor plan and on the door to the room. The robot autonomously navigated to the destination using its text recognition, abstract map, mapping, and path planning systems. The robot used the symbolic navigation system to determine an efficient path to the destination, and reached the goal in two different real-world environments. Simulation results show that the system reduces the time required to navigate to a goal when compared to random exploration.

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Host and donor dendritic cells (DC) stimulate alloreactive donor T lymphocytes, and initiate GVHD. We have shown that polyclonal antibody to the DC surface activation marker human CD83 (anti hCD83), which depletes activated DC, can prevent human DC and T cell induced lethal xenogeneic GVHD in SCID mice without impairing T cell mediated anti-leukaemic and anti-viral (CMV and influenza) immunity (J Exp Med 2009; 206: 387). Therefore, we made and tested a polyclonal anti mouse CD83 (RAM83) antibody in murine HSCT models and developed a human mAb against hCD83 as a potential new therapeutic immunosuppressive agent.

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This paper critically evaluates the empirical evidence of 36 studies regarding the comparative cost-effectiveness of group and individual cognitive behaviour therapy (CBT) as a whole, and also for specific mental disorders (e.g. depression, anxiety, substance abuse) or populations (e.g. children). Methods of calculating costs, as well as methods of comparing treatment outcomes were appraised and criticized. Overall, the evidence that group CBT is more cost-effective than individual CBT is mixed, with group CBT appearing to be more cost effective in treating depression and children, but less cost effective in treating drugs and alcohol dependence, anxiety and social phobias. In addition, methodological weaknesses in the studies assessed are noted. There is a need to improve cost calculation methodology, as well as more solid and a greater number of empirical cost-effectiveness studies before a firm conclusion can be reached that group CBT is more cost effective then individual CBT.

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In 40 febrile neutropenic episodes during the induction and consolidation chemotherapy of acute leukaemia in Riyadh, 51% of organisms causing septicaemia were gram-negative, 26% gram-positive, 8% anaerobes and 15% fungi. In 21 (52%) febrile episodes there were pulmonary infiltrates; of the 12 where aetiology was known, six were due to fungi. Pulmonary infiltrates progressed to adult respiratory distress syndrome and death in nine instances. There was no significant occurrence of parasitic and tropical infections. The results show that the pattern of infections, during therapy of acute leukaemia in developing countries, may have important differences when compared with western centres. Empiric amphotericin B may need to be introduced at an earlier stage in patients with persistent fever or progressive pulmonary infiltrates.

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