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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

A comprehensive evaluation of outcomes from patient handling interventions

Fray, Mike January 2010 (has links)
Assisting less able people to move in a healthcare setting is a very common occurrence but carries risks to staff and patients. The scientific study of patient handling activities and interventions to help reduce musculoskeletal disorders in the workplace is a relatively new but growing area. Recent literature reviews have identified two key factors, the lack of high quality studies and the lack of strong links between patient handling interventions and reduced musculoskeletal injury. This study has systematically reviewed the available literature and investigated the potential outcome measures used to show benefits of improved patient handling. A wide range of outcomes has been identified concentrated on the benefits to staff, patients and organisations. No methods were identified to compare different benefits, outcomes or intervention strategies. This study used mixed methods to develop a tool to compare the results of all types of interventions: a. Focus group studies in four EU countries recorded a priority list of the 12 most important outcomes from patient handling interventions b. The most suitable method for examining the 12 outcomes was identified c. The Intervention Evaluation Tool (IET) was developed as a single measurement tool d. The IET was translated and used in four EU countries to evaluate its usability and its usefulness to patient handling practitioners The EU trials and subsequent expert review have given favourable feedback for the IET. The IET creates 12 outcome evaluations with detail and differentiation, and an overall performance score to assist an organisation to target its future interventions. The method can be used to compare interventions, and the performance between organisations and countries across the EU. Though the IET needs more field trials and validity testing it is hoped that a wider application may be to create a benchmarking method that can assist in the improvement of patient handling systems across Europe.
2

Investigation into the anti-inflammatory activity of PXR and the minor isoform PXR3

Alleyne, Jerusalem January 2013 (has links)
The Pregnane X receptor (PXR) , is a nuclear receptor (NR) which heterodimerizes with RXRa (Retinoid X Receptor alpha) to regulate xenobiotic metabolism. The NR1I2 gene produces three isoforms, PXR1, PXR2 and PXR3. However, only the function of the major isoform PXRl is known. Moreover, PXR has been shown to have an anti-inflammatory function. This is interesting, since the processes of xenobiotic metabolism and inflammation antagonize each other. The mechanism by which PXR performs this anti-inflammatory function remains unclear. However, other nuclear receptors such as PPARa and PPARy repress pro-inflammatory gene induction via transrepression. This is a mechanism that facilitates transcriptional repression by the atypical association of NRs with co-regulatory and co-repressor complexes at foreign response elements. It is thought that SUMOylation allows these NRs to attain transrepressive functions. PXR is conjugated with SUM03 chains so it is believed that it too utilizes transrepression to mediate its anti-inflammatory actions. To study this, the five PXRIIPXR3 lysines were mutated. Additionally, five other so-called 'functional sites' which are critical to the transactivation role of PXR were also mutated. This was important to determine if the transactivation and repressive roles utilized similar mechanism of action. Luciferase reporter assay experiments were performed in RAW264.7 cells to investigate both the transactivation and repressive activities of the aforementioned mutants. Firstly, it was observed that both the putative SUMO sites and functional sites decreased PXREM induction and that PXR3 was transcriptionally inactive. Secondly, PXRl and PXR3 reduced the induction of the IL-8, iNOS and AP-l reporters used. However, the putative PXRl SUMO sites were less able to repress induction of the IL-8 reporter, while the functional mutants repressed induction just as well as wild type PXRl. Interestingly also, both the putative SUMO and functional PXR3 mutants repressed the IL-8 reporter as potently as the wild type.
3

The assessment of sensory threshold levels using physiological pressure algometry for the evaluation of electro-physiological neuromodulation for chronic pain

Raheem, Tarek M. A. January 2013 (has links)
Background: Chronic pain is a major health problem due to both its prevalence and the difficulties associated with its adequate diagnosis and treatment. The field of medical physiology has offered possible answers to those difficulties, namely; physiological pressure algometry and electro-physiological neuromodulation. Aims: To explore the diagnostic potential of a physiological pressure algometry device in patient populations suffering from hyperalgesia due to chronic pain; and to use this device to, both, assess and quantify the therapeutic response of patients undergoing various electrophysiological neuromodulation therapies for chronic pain. Methods: Five clinical phases, I–V, conducted on a total of two hundred and seven patients suffering from chronic pain. Results: Phase I; there was a highly significant negative correlation between the pressure pain threshold (PPT) values and each of the visual analogue scale (VAS) and numerical rating scale (NRS) scores; for PPT and VAS; ρ= -0.453 and for PPT and NRS; ρ= -0.413 (p<0.0005 in both cases). Phase II; there were clinically and statistically significant improvements in each of the VAS and NRS scores, and PPT following the activation of the spinal cord stimulation equipment (p<0.0005 in all three cases). Phase III; for the active percutaneous electrical nerve stimulation (PENS) treatments, there were clinically and statistically significant improvements in the NRS scores and PPT after therapy (p<0.0005 in both cases). For the sham treatments, there were neither clinically nor statistically significant changes (p=0.317 and p=0.055 respectively). Phase IV; there were clinically and statistically significant reductions in the median NRS scores; from 7.25 before PENS therapy to 3 after therapy (p<0.05). Phase V; there were clinically significant improvements in the PPT and NRS/VAS scores following the activation of the peripheral nerve stimulation equipment. Key Words: chronic pain, medical physiology, physiological pressure algometry, electrophysiological neuromodulation.
4

Development of a sample bank and clinical database for the retrospective analysis of unrelated bone marrow transplants : a pilot study of 138 transplants using RSCA for high resolution HLA matching

Pay, Andrea Louise Poppy January 2005 (has links)
The Anthony Nolan Register provides donors for allogeneic stem cell transplantation for haematological disorders. A clinical database and sample bank were established for the ongoing analysis of transplants from Register donors. Clinical data and blood samples were collected from donors and patients transplanted in the UK from 1996 onwards. DNA was extracted from all samples received, and used for the detection of HLA mismatches at six loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) by RSCA, and HA-1 by SSP. 138 donor/patient pairs were selected for a pilot study. HLA matching between patient and donor, along with the diagnosis of the patient, donor and patient age, CMV status and gender, and the T cell depletion status of the transplant were analysed for their effect on transplant outcome. The outcome variables studied included overall survival, disease free survival, transplant related mortality, relapse incidence, and the occurrence of acute and chronic GvHD. Patients with AML had decreased overall and disease free survival, and patients with CML had increased risk of relapse. Transplant from a same sex donor increased the risk of death or relapse, and male patients receiving stem cells from female donors showed reduced overall survival. Developing acute GvHD increased the risk of transplant related mortality. A mismatch at HLA class I and at class II was associated with unfavourable outcome for all survival variables. The inclusion of HLA-DPB1 matching did not alter the effects seen when other mismatches were present. Matching at the allele level for all loci gave an increased risk of relapse compared with patients mismatched with their donor for HLA-DPB1 only, indicating that a mismatch for HLA-DPB1 alone may protect from relapse. The data from this study was used to calculate the numbers required for a definitive study, for the optimisation of donor selection from the Register.
5

Disease kinds and functional explanations

Dragulinescu, Stefan January 2010 (has links)
The present thesis is concerned with the character of kinds in human somatic pathology and the relation that these kinds and their members have with function-based explanations. More precisely, in the first part of the thesis I investigate whether diseased organisms, grouped together on grounds of their shared pathological features, could form natural kinds, taking into account that the paradigmatic natural kinds are the kinds of the exact sciences. The second part of the thesis has as a backdrop the Humean/anti-Humean debate over causation (and the specific construal of explanations according to which to explain is to pinpoint causes). In this backdrop, I enquire into what sort of function-based explanations we could provide for the symptoms and pathological behaviours exhibited by diseased organisms, if we construe such organisms as members of natural kinds. I argue in the first part of the thesis that from a metaphysical point of view, the organisms dealt with in somatic medicine form natural kinds in the same sense in which we take the kinds dealt with in the exact sciences as natural. By comparing a 'classical', exact science kind with a kind of disease, I show that whatever features are associated with natural kind membership (e.g, involvement in laws or inductions, explanatory relevance, possession of 'essential' properties, instantiation of substantive universals, etc.) there is no 'ontological gap' between disease kinds and the kinds in the exact sciences. The conclusion that diseases are natural kinds has a certain proviso regarding the question of whether the identity of the individual members of natural kinds is dependent upon their kind membership. Should diseases not be natural kinds, the proviso says, it would be because the properties characteristic of natural kinds must have an identity-influence over the kind members. I present in addition serious problems posed by outlining such identity bearing properties. In the second part of the thesis, I argue that function based explanations concerned with diseased organisms - if we construe such organisms as being members of natural kinds - should illuminate positive causes for the symptoms and pathological behaviours they exhibit. We could obtain such function-based explanations, I suggest, if we interpret the functioning of biological items as the manifesting of causal powers. Against the background of the Humean vs. anti-Humean debate on causation, I show that Nancy Cartwright's capacities are a plausible variant for the powers at work in 'pathological' functioning. I argue that one could track down these capacities if one viewed healthy organisms as nomological machines, in the sense in which Cartwright understands this notion. I also suggest that capacities are necessary in order to vindicate general and, more importantly, singular causal claims involved in medical diagnosis and hence to found satisfactory functional explanations.
6

Measuring, analysing and visualising brain deformation using non-rigid registration

Hartkens, Thomas January 2003 (has links)
No description available.
7

Human psychophysiological responses to visceral and somatic pain : the development of integrated, reproducible human pain phenotypes

Farmer, Adam Donald January 2011 (has links)
Abstract Background Pain is the ubiquitous human experience, yet displays considerable inter- and intraindividual variability in health and disease. Many factors have been proposed to account for these differences. Pain activates a complex stress response, multiply determined through genetic, psychological, physiological and neuroanatomical factors. Chronic pain is a central defining characteristic of functional gastrointestinal disorders. They represent a major challenge for modern health care. An integrated understanding of the pathophysiology of these disorders remains to be elucidated. Aims To investigate human psychophysiological responses to visceral and somatic pain in health and disease, in order to develop multidimensional and reproducible pain phenotypes. Methods Study I, in healthy volunteers, investigated personality traits, hypothalamic pituitary adrenal axes and selective novel non-invasive measures of autonomic tone in response to visceral and somatic pain. Study 2 examined the salience of genetic polymorphisms of the serotonin transporter. Study 3 evaluated the reproducibility of these responses after a period of one year. Study 4 utilised the methods of studies I and 2 in a case control study of patients with functional chest pain. Key Results Studies I, 2 and 3 - Two pain phenotypes, or clusters, were found - cluster I (39%) had higher neuroticism scores, with higher sympathetic and hypothalamic pituitary adrenal axis tone at rest, and a predominant parasympathetic response to pain in the presence of the short allele of the serotonin transporter. Cluster 2 (61 %) displayed the converse profile in the absence of the short allele. These responses were stable at an interval of one year. Study 4 - similar phenotypes were observed in patients with functional chest pain, although the Cluster I phenotype was overrepresented in patients in comparison to the controls (71 % vs. 29%). Conclusions and Inferences This series of studies provides evidence for the existence of two reproducible human pain phenotypes in health, which have clinical salience in patients with functional chest pain. By phenotyping pain responses, subject homogeneity in future studies may be improved. Furthermore, such phenotyping techniques may open new therapeutic avenues by facilitating the selective targeting of nociceptive aberrancies, particularly in functional gastrointestinal disorders.
8

Investigation of galectin-3 interaction with N. meningitidis and its dimerization with laminin receptor

Alqahtani, Fulwah Yahya Saleh January 2012 (has links)
Meningococcal meningitis from the causative organism Neisseria meningitidis is the leading cause of meningitis globally. This bacterium is among a limited number of pathogens that have the propensity to cross the blood brain barrier (BBB) vasculature causing meningitis. It has been recently demonstrated that Neisseria meningitidis targets the laminin receptor (37 LRP/67 LR) on the surface of human brain microvascular endothelial cells, and two meningococcal outer membrane proteins, PorA and PilQ, have been identified as bacterial ligands. Interestingly, this interaction is hypothesized to underlie meningococcal tropism for the central nervous system (CNS). There are two isoforms of laminin receptor; monomeric 37 kDa laminin receptor precursor (37 LRP) and mature 67 kDa laminin receptor (67 LR). The relationship between the 67 LR and its precursor 37 LRP is not completely understood, but previous observations have suggested that 37 LRP can undergo homo- and/or hetero- dimerization with Galectin-3 (Gal-3) to form mature 67 LR. Gal-3 is the only member of the chimera-type group of galectins, and has one C-terminal carbohydrate recognition domain (CRD) that is responsible for binding the ß-galactoside moieties of mono- or oligosaccharides on several host and bacterial molecules, including neisserial lipooligosaccharide (LOS). To identify the LOS-independent meningococcal ligands that bind Gal-3, binding of lactose liganded Gal-3 and CRD with meningococci was investigated using ELISA assay. Neisseria meningitidis bound lactose liganded Gal-3 significantly more than H. pylori, which is known to bind Gal-3 via LPS. This binding was not inhibited by increasing concentrations of lactose. Also the lactose liganded CRDof Gal-3 bound meningococci but to a lesser extent than full molecule. Importantly, binding of Gal-3 was conserved among 25 meningococcal clinical isolates tested in the current study. A meningococcal mutant lacking the glycosyltransferase required for chain elongation from the core lipid A-(KDO)2-Hep2 showed reduced binding to lactose-liganded Gal-3, but binding was not abolished indicating that the meningococcal-Gal-3 binding was not entirely LOS-dependant. Using a re-tagging approach, meningococcal PilQ and PilE proteins were identified as Gal-3 binding ligands. Mutation of the genes encoding either of these two molecules in strain MC58 led to a significant reduction in Gal-3 binding. PilQ is not known to be glycosylated, therefore its interaction with Gal-3 is likely to be protein-mediated. PilE is post-translationally glycosylated and deletion of the pilin glycosylation genes pglC and/or pglL dramatically reduced bacterial-Gal-3 binding. Given the binding of meningococcal PilQ to 37 LRP/67 LR and Gal-3, this study sought to investigate possible dimerization between 37 LRP and Gal-3 to form 67 LR. Double immunofluorescence staining of endogenous receptors revealed colocalization of 67 LR with its precursor and both of them with Gal-3 in HBMECs, astrocyte and COS7 cells. Moreover, co-expression of 37 LRP and Gal-3 fused to different fluorescent proteins indicated colocalization of these receptors in COS7 cells. Using bimolecular fluorescence complementation (BiFC) assays, the presence of 67 LR in homo- and hetero-dimer forms with Gal-3 has been confirmed in different cell lines. In addition, the recombinant laminin receptor bound Gal-3 and its CRD to comparable level. Further investigation for Gal-3 and 37 LRP dimerization mechanism revealed that the conserved cysteine (C173A) within the CRD of human Gal-3, which is known to abolish disulphide-mediated dimerization of murine Gal-3, is critical for Gal-3 homo- and hetero-dimerization with 37 LRP, whereas neither of the two cysteines on 37LR (cys148 and cys163) are required for dimerization. To examine the role of Gal-3 in meningococcal interaction with host cells, the adhesive and invasive capacities of meningococci were compared between Gal-3 transfected and non-transfected neuroblastoma cell line (N2a) cells. Transient expression of Gal-3 in mouse N2a cells significantly enhanced meningococcal invasion when compared with non-transfected cells. Moreover, infection of CD46-expressing transgenic mice with meningococcal strain MC58 significantly increased the expression of Gal-3 and 37 LRP in the brain. This work also attempts to study whether the 37 LRP/67 LR meningococcal ligands (rPorA, loop 4 of PorA and rPilQ) have any influence on the surface level of 67 LR and Gal-3. As indicated by flow cytometry analysis, recruitments of 67 LR and Gal-3 to the surface of HBMECs were increased in cells incubated with rPilQ, Loop 4 of PorA and more prominently rPorA. To examine these results in more detail, effect of each of these ligands on 37 LRP expression was investigated using qPCR. Loop4 of PorA and rPilQ induced 37 LRP expression significantly more than PBS. Although there was a trend for an increase in 37 LRP expression with treatment with rPorA, the difference was not statistically significant (p = 0.1507). Further investigation in future study for the effect of these bacterial adhesins on Gal-3 gene expression will be of great value. Collectively, these data revealed the capacity of Gal-3 to target meningococcal PilQ and PilE, as well as the previously known LOS and showed the importance of Gal-3 in the meningococcal-host cell interaction. This interaction may be part of host-cell defence against the organism, and/or, conversely, it may be part of a strategy adopted by the organism to modulate the host response and facilitate its invasion. Remarkably, the current findings also demonstrated the existence of 67 LR as homo- and hetero- dimer with Gal-3. This dimerization of two meningococcal host receptors may help to extend spectrum of their bacterial adhesins which may act cooperatively or synergistically at different stages of infection. Besides, the expression pattern of these receptors may suggest specific receptor repertoire in the BBB which might contribute in meningococcal tropism for the CNS.
9

Toxicogenomics of synthetic and natural nanoparticles in the nematode C. elegans

Polak, Natasa January 2014 (has links)
Natural and synthetic nanoparticles (NP) are microscopic particles, which are characterized by their small size (< 0.1 μm). It is now well established that exposure to NPs can represent a serious risk to human health and the environment. To establish the modes of action of NP toxicity, this project utilizes the nematode Caenorhabditis elegans to conduct baseline studies to screen the toxicological effects (on life-history traits, fitness, and metabolism) of metal oxide based synthetic (30 nm ZnONPs), and naturally occurring (Carbon Black M120 and NIST 1648a) NPs. The results indicate that: 1) The Nanosight NTA technique is a suitable tool to evaluate particle aggregation in biological test media. 2) All tested particles exert a shared toxic response that is manifested by a decrease in reproductive potential. The toxic effects were dose responsive to ZnONPs exposure, but not to NIST and CB. 3) The DCFH-DA assay provided in vitro evidence of the oxidative potential of particles, as the intracellular total ROS levels were altered. 4) The whole genome, qPCR analyses, and microscopy provided evidence that the majority of transcripts involved in stress response pathways (e.g. sod family; cat-2,-3; hsp-16.1) did not alter or were only marginally affected by the particles. Nevertheless, the most profound effects were the down regulation of the ribosomal RNA transcript (rrn-3.1) with increasing NIST concentrations, and the induction of cep-1 gene (p53 human orthologous) with ZnONPs. 5) Finally, spectroscopic strategies identified the importance of metallochelators in the protection from ZnONP induced toxicity. Overall, the results of this study suggest that the use of sensitive nematode mutants combined with genomic tools represents a powerful approach to assess the physicochemical toxicity of different types of particles.
10

Difficult decisions : autonomy, prenatal choice and prognostic ambiguity

Leonard, Samantha Jane January 2014 (has links)
New methods of fetal anomaly detection will offer increasingly detailed information to prospective parents but are likely to lead to more frequent discovery of anomalies with an ambiguous prognosis for the future child. It is important to consider the ethical implications of such ambiguity prior to introducing new tests. An examination of the bioethics literature reveals 'promoting autonomy' as the predominant justification for fetal anomaly detection. Two questions arise: does the fetal anomaly detection programme as it stands promote autonomy, and is 'promoting autonomy' an appropriate ethical principle in this context? To answer these questions, an empirical bioethics approach using a reflexive balancing methodology is employed. This examines qualitative data from interviews of prospective parents who had had to decide, on the basis of such an ambiguous prognosis, whether or not to continue their pregnancy. On the basis of different accounts of autonomy, it is argued that the fetal anomaly detection programme does not promote autonomy when decisions are based on an uncertain prognosis. Moreover, 'promoting autonomy' is not, on its own, an appropriate aim in this setting, as the participants did not use their choice as a means of self-expression, the decisions were made by two people and were heavily swayed by considerations for the future child, and under conditions of uncertainty it is not possible to attain the level of rational decision-making required by most accounts of autonomy. Furthermore, the impacts of the decision reduce the benefit of any potential opportunity for self-expression through these choices. The data indicated that a welfare approach might be more appropriate, and it was concluded that, whilst a welfare approach did not entirely encompass all of the nuances of the participants' experiences, it was the better fit, giving some useful indications for an ethical framework for an expanded offer of testing.

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