Naresuan University Journal
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New superior-inferior visual field asymmetry indices for detecting POAG and their agreement with the glaucoma hemifield test.
No full textPurposeTo describe and measure the discriminatory performance of three new superior-inferior asymmetry indices for detecting primary open angle glaucoma (POAG) and to compare these with the glaucoma hemifield test (GHT).MethodsIn all, 412 control and 247 POAG eyes were selected from a visual field database of patients attending the Manchester Royal Eye Hospital. Age-adjusted defect asymmetries were calculated for each of the 22 vertically mirrored test point pairs used in the GHT. The three new indices, hemifield mean difference (HMD) and hemifield standard deviation (HSD) of the asymmetry values along with the number of test pairs (NP) falling outside the 85% probability limits of the control population, were calculated. ROC curves of the indices and GHT were constructed. Agreement between the indices was explored with a proportional Venn diagram and 3 × 3 contingency tables. Cases of disagreement between the indices were reviewed.ResultsThe area under the ROC curves were HMD=0.745 (95% confidence interval (CI) 0.705-0.786), HSD=0.864 (95% CI 0.833-0.894), NP=0.863 (95% CI 0.832-0.893) and GHT=0.792 (95% CI 0.754-0.829). The Venn diagram and contingency tables highlighted the good agreement between HSD, NP and GHT. Agreement was 78% (HSD vs GHT) and 82% (NP vs GHT) in the control sample and 70% (HSD vs GHT) and 71% (NP vs GHT) in the POAG sample. Five cases are presented where disagreement existed between the indices.ConclusionsThe new HSD and NP asymmetry indices perform better than GHT in differentiating between normal and POAG eyes in this data set. GHT can fail to detect significant asymmetry, detected by HSD and NP, when an early defect crosses sector boundaries
Real time analysis of conformational control in electron transfer reactions of human cytochrome P450 reductase with cytochrome c
No full textProtein domain dynamics and electron transfer chemistry are often associated, but real-time analysis of domain motion in enzyme-catalysed reactions and the elucidation of mechanistic schemes that relate these motions to the reaction chemistry are major challenges for biological catalysis research. Previously we suggested that reduction of human cytochrome P450 reductase with the reducing coenzyme NADPH is accompanied by major structural re-orientation of the FMN- and FAD-binding domains through an inferred dynamic cycle of ‘open’ and ‘closed’ conformations of the enzyme (PLoS Biol, 2011, e1001222). However, these studies were restricted to stopped-flow/FRET analysis of the reductive half-reaction, and were compromised by fluorescence quenching of the acceptor by the flavin cofactors. Here we have improved the design of the FRET system, by using dye pairs with near-IR fluorescence, and extended studies on human cytochrome P450 reductase to the oxidative half-reaction using a double-mixing stopped-flow assay, thereby analysing in real-time conformational dynamics throughout the complete catalytic cycle. We correlate redox changes accompanying the reaction chemistry with protein dynamic changes observed by FRET, and show that redox chemistry drives a major re-orientation of the protein domains in both the reductive and oxidative half-reactions. Our studies using the tractable (soluble) surrogate electron acceptor cytochrome c provide a framework for analysing mechanisms of electron transfer in the endoplasmic reticulum between cytochrome P450 reductase and cognate P450 enzymes. More generally, our work emphasizes the importance of protein dynamics in intra- and inter-protein electron transfer, and establishes methodology for real-time analysis of structural changes throughout the catalytic cycle of complex redox proteins
Teaching Islamic Studies from the Perspective of Middle Eastern Studies at Manchester University
No full textEnvironmental sustainability issues in the food-energy-water nexus: breakfast cereals and snacks
No full textUnderstanding environmental impacts of complete food supply chains is important for the food industry to help devise strategies for reducing the impacts of current and future products. Breakfast cereals are one of the most important foods consumed in many countries, but their environmental impacts are currently unknown. Therefore, this study explores the environmental sustainability issues in the food–energy–water nexus by considering breakfast cereals manufactured by one of the world’s largest producers, Kellogg Europe. A life cycle assessment has been carried out for these purposes with the aim of helping the Company to integrate environmental sustainability considerations into the design of their products and packaging. The results indicate that the average global warming potential (GWP) of Kellogg’s breakfast cereals is 2.64 kg CO22 eq. per kg of product. The main GWP hotspots are the ingredients (48%) and energy used in the manufacturing process (23%); packaging and transport contribute 15% each. Rice is the single largest contributor to the GWP of the ingredients (38%). The manufacturing stage is the main contributor of primary energy demand (34%), while the ingredients are responsible for more than 90% of the water footprint. The ingredients are also the main contributors to most other environmental impacts, including land use (97%), depletion of elements (61%), eutrophication (71%), human toxicity (54%) and photochemical smog (50%). The impacts from packaging are high for freshwater and marine toxicity. The contribution of transport is significant for depletion of elements and fossil resources (23%), acidification (32%), ozone depletion (28%) and photochemical smog (24%). Improvement opportunities explored in the paper include better agricultural practices, recipe modifications, improved energy efficiency of manufacturing processes and use of alternative packaging. Impacts from consumption are also discussed
Identification of antithrombotic drugs related to total joint replacement using anonymised free-text notes: a search strategy in the Clinical Practice Research Datalink.
No full textOBJECTIVES: We aimed to design and test a method to extract information on antithrombotic therapy from anonymised free-text notes in the Clinical Practice Research Datalink (CPRD). SETTING: General practice database representative of the UK. PARTICIPANTS: All patients undergoing total hip replacement (THR, n=25 898) or total knee replacement (TKR, n=22 231) between January 2008 and October 2012 were included. Antithrombotic drug use related to THR or TKR was identified using anonymised free text and prescription data. PRIMARY AND SECONDARY OUTCOME MEASURES: Internal validity of our newly designed method was determined by calculating positive predictive values (PPVs) of hits for predefined keywords in a random sample of anonymised free-text notes. In order to determine potential detection bias, total joint replacement (TJR) patient characteristics were compared as per their status of exposure to antithrombotics. RESULTS: PPVs ranging between 97% and 99% for new oral anticoagulants (NOAC) or low-molecular weight heparins (LMWH) exposure related to TJR were obtained with our method. Our search strategy increased detection rates by 57%, yielding a total proportion of 18.5% of all THR and 18.6% of all TKR surgeries. Identified users of NOACs and LMWHs were largely similar with regards to age, sex, lifestyle, disease and drug history compared to patients without identified drug use. CONCLUSIONS: We have developed a useful method to identify additional exposure to NOACs or LMWHs with TJR surgery
Peptide Nanofiber Complexes with siRNA for Deep Brain Gene Silencing by Stereotactic Neurosurgery.
No full textPeptide nanofibers (PNFs) are one-dimensional assemblies of amphiphilic peptides in a cylindrical geometry. We postulated that peptide nanofibers (PNFs) can provide the tools for genetic intervention and be used for delivery of siRNA, as they can be engineered with positively charged amino acids that can electrostatically bind siRNA. The aim of this work was to investigate the use of PNFs as vectors for siRNA delivery and evaluate their potential in the therapy of neurodegenerative disorders. We designed a surfactant-like peptide (palmitoyl-GGGAAAKRK) able to self-assemble into PNFs, and demonstrated that complexes of PNF:siRNA are uptaken intracellularly and increase the residence time of siRNA in the brain. The biological activity of the complexes was investigated in vitro by analysing the down-regulation of the expression of a targeted protein (BCL2) and induction of apoptosis, and in vivo by analysing the relative gene expression upon stereotactic administration into a deep rat brain structure (the subthalamic nucleus). Gene expression levels of BCL2 mRNA showed that PNF:siBCL2 constructs were able to silence the target BCL2 in specific loci of the brain. Silencing of the BCL2 gene resulted in ablation of neuronal cell populations. Therefore, genetic interventions by PNF:siRNA complexes may lead to enhanced treatments of CNS pathologies
Cardiovascular comorbidity in rheumatic diseases.
No full textPatients with rheumatoid arthritis (RA) and other inflammatory joint diseases (IJDs) have an increased risk of premature death compared with the general population, mainly because of the risk of cardiovascular disease, which is similar in patients with RA and in those with diabetes mellitus. Pathogenic mechanisms and clinical expression of cardiovascular comorbidities vary greatly between different rheumatic diseases, but atherosclerosis seems to be associated with all IJDs. Traditional risk factors such as age, gender, dyslipidaemia, hypertension, smoking, obesity and diabetes mellitus, together with inflammation, are the main contributors to the increased cardiovascular risk in patients with IJDs. Although cardiovascular risk assessment should be part of routine care in such patients, no disease-specific models are currently available for this purpose. The main pillars of cardiovascular risk reduction are pharmacological and nonpharmacological management of cardiovascular risk factors, as well as tight control of disease activity
Bilingual term alignment from comparable corpora in English discharge summary and Chinese discharge summary
No full textBackground: Electronic medical record (EMR) systems have become widely used throughout the world to improve the quality of healthcare and the efficiency of hospital services. A bilingual medical lexicon of Chinese and English is needed to meet the demand for the multi-lingual and multi-national treatment. We make efforts to extract a bilingual lexicon from English and Chinese discharge summaries with a small seed lexicon. The lexical terms can be classified into two categories: single-word terms (SWTs) and multi-word terms (MWTs). For SWTs, we use a label propagation (LP; context-based) method to extract candidates of translation pairs. For MWTs, which are pervasive in the medical domain, we propose a term alignment method, which firstly obtains translation candidates for each component word of a Chinese MWT, and then generates their combinations, from which the system selects a set of plausible translation candidates. Results: We compare our LP method with a baseline method based on simple context-similarity. The LP based method outperforms the baseline with the accuracies: 4.44% Acc1, 24.44% Acc10, and 62.22% Acc100, where AccN means the top N accuracy. The accuracy of the LP method drops to 5.41% Acc10 and 8.11% Acc20 for MWTs. Our experiments show that the method based on term alignment improves the performance for MWTs to 16.22% Acc10 and 27.03% Acc20. Conclusions: We constructed a framework for building an English-Chinese term dictionary from discharge summaries in the two languages. Our experiments have shown that the LP-based method augmented with the term alignment method will contribute to reduction of manual work required to compile a bilingual sydictionary of clinical terms
Pilot study of a randomised trial of a guided e-learning health promotion intervention for managers based on management standards for the improvement of employee well-being and reduction of sickness absence: the GEM (Guided E-learning for Managers) study
No full textGood work is good for health and well-being. Key to maintaining and improving employee well-being is the knowledge and practice of their managers. There have been very few systematic studies of manager training in relation to employee well-being and sickness absence. This pilot study tested the acceptability and feasibility of using an already developed e-learning program for managers to help managers understand and learn how to support and value their employees. This program was completed online by managers in separate modules over 10 weeks. We recruited 424 employees and 41 managers from a mental health trust. Three groups of employees and their managers were randomised to receive the intervention and one group was the control group in which managers did not receive the intervention. Employees completed work and health questionnaires before and after the intervention. There was only a very small effect of the intervention on employees’ well-being and levels of psychological distress. Accompanying qualitative research demonstrated that the intervention was acceptable and interesting to managers who took part. Some managers said that they had too little time to complete the intervention and fewer managers completed the intervention than we hoped. The trial and the intervention were feasible to those who took part. The economic assessment of the trial was also feasible. A future trial may need to gain more buy-in from senior managers for the trial, encourage managers to complete the intervention, leave a longer time for the intervention to work and strengthen the intervention to encourage behaviour change in managers