Doctor of Philosophy

dissertationDomain adaptation of natural language processing systems is challenging because it requires human expertise. While manual e ort is e ective in creating a high quality knowledge base, it is expensive and time consuming. Clinical text adds another layer of complexity to the task due to privacy and con dentiality restrictions that hinder the ability to share training corpora among di erent research groups. Semantic ambiguity is a major barrier for e ective and accurate concept recognition by natural language processing systems. In my research I propose an automated domain adaptation method that utilizes sublanguage semantic schema for all-word word sense disambiguation of clinical narrative. According to the sublanguage theory developed by Zellig Harris, domain-speci c language is characterized by a relatively small set of semantic classes that combine into a small number of sentence types. Previous research relied on manual analysis to create language models that could be used for more e ective natural language processing. Building on previous semantic type disambiguation research, I propose a method of resolving semantic ambiguity utilizing automatically acquired semantic type disambiguation rules applied on clinical text ambiguously mapped to a standard set of concepts. This research aims to provide an automatic method to acquire Sublanguage Semantic Schema (S3) and apply this model to disambiguate terms that map to more than one concept with di erent semantic types. The research is conducted using unmodi ed MetaMap version 2009, a concept recognition system provided by the National Library of Medicine, applied on a large set of clinical text. The project includes creating and comparing models, which are based on unambiguous concept mappings found in seventeen clinical note types. The e ectiveness of the nal application was validated through a manual review of a subset of processed clinical notes using recall, precision and F-score metrics

The Effectiveness of Exercise Interventions for the Management of Frailty: A Systematic Review

This systematic review examines the effectiveness of current exercise interventions for the management of frailty. Eight electronic databases were searched for randomized controlled trials that identified their participants as “frail” either in the title, abstract, and/or text and included exercise as an independent component of the intervention. Three of the 47 included studies utilized a validated definition of frailty to categorize participants. Emerging evidence suggests that exercise has a positive impact on some physical determinants and on all functional ability outcomes reported in this systematic review. Exercise programs that optimize the health of frail older adults seem to be different from those recommended for healthy older adults. There was a paucity of evidence to characterize the most beneficial exercise program for this population. However, multicomponent training interventions, of long duration (≥5 months), performed three times per week, for 30–45 minutes per session, generally had superior outcomes than other exercise programs. In conclusion, structured exercise training seems to have a positive impact on frail older adults and may be used for the management of frailty

Comparative effectiveness of beta-interferons and glatiramer acetate for relapsing-remitting multiple sclerosis : systematic review and network meta-analysis of trials including recommended dosages

This work is part of a larger report commissioned by the NIHR HTA Programme as project number ID809. Aileen Clarke and G.J. Melendez-Torres are partly supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care West Midlands at the University Hospitals Birmingham NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, NIHR, NICE or the Department of Health and Social Care.Peer reviewedPublisher PD

The Structure of Ca2+ Sensor Case16 Reveals the Mechanism of Reaction to Low Ca2+ Concentrations

Here we report the first crystal structure of a high-contrast genetically encoded circularly permuted green fluorescent protein (cpGFP)-based Ca2+ sensor, Case16, in the presence of a low Ca2+ concentration. The structure reveals the positioning of the chromophore within Case16 at the first stage of the Ca2+-dependent response when only two out of four Ca2+-binding pockets of calmodulin (CaM) are occupied with Ca2+ ions. In such a “half Ca2+-bound state”, Case16 is characterized by an incomplete interaction between its CaM-/M13-domains. We also report the crystal structure of the related Ca2+ sensor Case12 at saturating Ca2+ concentration. Based on this structure, we postulate that cpGFP-based Ca2+ sensors can form non-functional homodimers where the CaM-domain of one sensor molecule binds symmetrically to the M13-peptide of the partner sensor molecule. Case12 and Case16 behavior upon addition of high concentrations of free CaM or M13-peptide reveals that the latter effectively blocks the fluorescent response of the sensor. We speculate that the demonstrated intermolecular interaction with endogenous substrates and homodimerization can impede proper functioning of this type of Ca2+ sensors in living cells

The UK medical education database (UKMED) what is it?:Why and how might you use it?

The development of UKMED has not been directly funded by but has received support from the General Medical Council and Medical Schools Council as well as staff time from all participating organisations.Peer reviewedPublisher PD

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy