Quantifying mutual-understanding in dialogue

PhDThere are two components of communication that provide a natural index of mutual-understanding in dialogue. The first is Repair; the ways in which people detect and deal with problems with understanding. The second is Ellipsis/Anaphora; the use of expressions that depend directly on the accessibility of the local context for their interpretation. This thesis explores the use of these two phenomena in systematic comparative analyses of human-human dialogue under different task and media conditions. In order to do this it is necessary to a) develop reliable, valid protocols for coding the different Repair and Ellipsis/Anaphora phenomena b) establish their baseline patterns of distribution in conversation and c) model their basic statistical inter-relationships and their predictive value. Two new protocols for coding Repair and Ellipsis/Anaphora phenomena are presented and applied to two dialogue corpora, one of ordinary 'everyday' conversations and one of task-oriented dialogues. These data illustrate that there are significant differences in how understanding is created and negotiated across conditions. Repair is shown to be a ubiquitous feature in all dialogue. The goals of the speaker directly affect the type of Repair used. Giving instructions leads to a higher rate of self-editing; following instructions increases corrections and requests for clarification. Medium and familiarity also influence Repair; when eye contact is not possible there are a greater number of repeats and clarifications. Anaphora are used less frequently in task-oriented dialogue whereas types of Ellipsis increase. The use of Elliptical phrases that check, confirm or acknowledge is higher when there is no eye contact. Familiar pairs use more elliptical expressions, especially endophora and elliptical questions. Following instructions leads to greater use of elliptical (non-sentential) phrases. Medium, task and social norms all have a measureable effect on the components of dialogue that underpin mutual-understanding

Acute toxicity and health-related quality of life after accelerated whole breast irradiation in 5 fractions with simultaneous integrated boost

Introduction: Acceleration of radiotherapy in 5 fractions for breast cancer can reduce the burden of treatment. We report on acute toxicity after whole-breast irradiation with a simultaneous integrated boost in 5 fractions over 10-12 days. Material and methods: Acute toxicity and health-related quality of life (HRQoL) of 200 patients, randomized between a 15or 5-fractions schedule, were collected, using the CTCAE toxicity scoring system, the Multidimensional Fatigue Inventory, EORTC QLQ-C30 and BR23 and the BREAST-Q questionnaire. The prescribed dose to the breast was either 15*2.67 Gy (40.05 Gy) or 5*5.7 Gy (28.5 Gy). 90% of patients received a SIB to a cumulative dose of 46.8 Gy (15*3.12 Gy) or 31 Gy (5*6.2 Gy). Results: Physician-assessed toxicity was lower for the 5-fractions group. A significant difference was observed for breast pain (p = 0.002), fatigue (p < 0.0001), breast edema (p = 0.001) and dermatitis (p = 0.003). Patients treated in 5 fractions reported better mean HRQoL scores for breast symptoms (p = 0.001) and physical well-being (p = 0.001). A clinically important deterioration in HRQoL of 10 points or more was also less frequently observed in the latter group for physical functioning (p = 0.0005), social functioning (p = 0.0007), fatigue (p = 0.003), breast symptoms (p = 0.0002) and physical wellbeing (p = 0.002). Conclusion: In this single institute study, acute toxicity of accelerated breast radiotherapy in 5 fractions over 10-12 days seems to compare favourably to hypofractionated breast radiotherapy in 15 fractions. Less breast edema, dermatitis, desquamation, breast pain and fatigue are seen. Social and physical functioning are also less disturbed and patients have a better future perspective

A QM/MM study of the nature of the entatic state in plastocyanin

Plastocyanin is a copper containing protein that is involved in the electron transfer process in photosynthetic organisms. The active site of plastocyanin is described as an entatic state whereby its structure represents a compromise between the structures favored by the oxidized and reduced forms. In this study, the nature of the entatic state is investigated through density functional theory-based hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations. The strain energy is computed to be 12.8 kcal/mol and 14.5 kcal/mol for the oxidized and reduced forms of the protein, indicating that the active site has an intermediate structure. It is shown that the energy gap between the oxidized and reduced forms varies significantly with the fluctuations in the structure of the active site at room temperature. An accurate determination of the reorganization energy requires averaging over conformation and a large region of the protein around the active site to be treated at the quantum mechanical level

Adolescent Self-Organization and Adult Smoking and Drinking over Fifty Years of Follow-Up:The British 1946 Birth Cohort

Variations in markers of adolescent self-organization predict a range of economic and health-related outcomes in general population studies. Using a population-based birth cohort study we investigated associations between adolescent self-organization and two common factors over adulthood influencing health, smoking and alcohol consumption. The MRC National Survey of Health and Development (the British 1946 birth cohort) was used to test associations between a dimensional measure of adolescent self-organization derived from teacher ratings, and summary longitudinal measures of smoking and alcohol consumption over the ensuing five decades. Multinomial regression models were adjusted for sex, adolescent emotional and conduct problems, occupational social class of origin, childhood cognition, educational attainment and adult occupational social class. With all covariates adjusted, higher adolescent self-organization was associated with fewer smoking pack years, although not with quitting; there was no association with alcohol consumption across adulthood (none or heavy compared with light to moderate). Adolescent self-organization appears to be protective against smoking, but not against heavy alcohol consumption. Interpretation of this differential effect should be embedded in an understanding of the social and sociodemographic context in which these health behaviours occur over time

Platelets and thrombogenesis--Current concepts

Anticoagulants, although effective in the treatment of venous thrombotic disease, have not been generally helpful in preventing arterial thrombosis. The reason for this disparity may lie in the type of clot formed in each case. In veins a "red thrombus" is formed, consisting of erythrocytes, leukocytes, fibrin, and platelets randomly distributed, whereas in arteries a "white thrombus" consisting mainly of platelets and fibrin strands is the obstructing lesion1. The predominance of platelets in this "white" clot has focused attention on their importance in arterial occlusion and has suggested that therapeutic maneuvers directed at platelet function may be more useful than standard anticoagulant therapy. This review presents the recent advances in the study of platelet morphology and function, and concludes by discussing possible therapeutic avenues.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34128/1/0000412.pd

Effects of affective symptoms in adolescence and adulthood on trajectories of cognitive function from middle to late adulthood

Background: Little is known about the link between affective symptoms and cognitive function across the life course. This study aims to investigate whether affective symptoms in adolescence and adulthood predict trajectories of cognitive function from middle to late adulthood. Methods: Data from the MRC National Survey of Health and Development (NSHD), a cohort of 5362 individuals born in mainland UK in 1946, were utilised. Linear mixed models were used to model cognitive trajectories (memory and processing speed) over a three decade period (from 43 to 69) and to test effects of affective symptoms in adolescence (ages 13-15) and adulthood (ages 36 and 43) on baseline cognitive function (age 43) and decline in cognitive function (from 43 to 69). Models were adjusted for sex, childhood cognition, childhood socioeconomic position, and education. Results: A quadratic model best fitted memory and processing speed data. Models revealed that adolescent affective symptoms were associated with lower memory (b=-1.11, SE=0.53, p=.04) and processing speed (b=-18.17, SE=7.53, p=.02) at baseline, but not with rates of decline over time from 43 to 69. There were no significant associations between adult affective symptoms and cognitive trajectories. Limitations: Missing data is a potential limitation of this study. This was dealt with using maximum likelihood estimation and multiple imputation. Conclusions: Findings suggest that adolescent, but not adult, affective symptoms are important predictors of cognitive function in midlife, but not rate of cognitive decline. This highlights the importance of early intervention to manage mental health in adolescence to protect later cognitive function

Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1

Tissues with high metabolic rates often use lipids, as well as glucose, for energy, conferring a survival advantage during feast and famine1. Current dogma suggests that high-energy–consuming photoreceptors depend on glucose2, 3. Here we show that the retina also uses fatty acid β-oxidation for energy. Moreover, we identify a lipid sensor, free fatty acid receptor 1 (Ffar1), that curbs glucose uptake when fatty acids are available. Very-low-density lipoprotein receptor (Vldlr), which is present in photoreceptors4 and is expressed in other tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acid5, 6. In the retinas of Vldlr−/− mice with low fatty acid uptake6 but high circulating lipid levels, we found that Ffar1 suppresses expression of the glucose transporter Glut1. Impaired glucose entry into photoreceptors results in a dual (lipid and glucose) fuel shortage and a reduction in the levels of the Krebs cycle intermediate α-ketoglutarate (α-KG). Low α-KG levels promotes stabilization of hypoxia-induced factor 1a (Hif1a) and secretion of vascular endothelial growth factor A (Vegfa) by starved Vldlr−/− photoreceptors, leading to neovascularization. The aberrant vessels in the Vldlr−/− retinas, which invade normally avascular photoreceptors, are reminiscent of the vascular defects in retinal angiomatous proliferation, a subset of neovascular age-related macular degeneration (AMD)7, which is associated with high vitreous VEGFA levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in macular telangiectasia, neovascular AMD and other retinal diseases

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care