Naive Physics, Event Perception, Lexical Semantics, and Language Acquisition

This thesis proposes a computational model of how children may come to learn the meanings of words in their native language. The proposed model is divided into two separate components. One component produces semantic descriptions of visually observed events while the other correlates those descriptions with co-occurring descriptions of those events in natural language. The first part of this thesis describes three implementations of the correlation process whereby representations of the meanings of whole utterances can be decomposed into fragments assigned as representations of the meanings of individual words. The second part of this thesis describes an implemented computer program that recognizes the occurrence of simple spatial motion events in simulated video input.

An Integrated Neural Network-Event-Related Potentials Model of Temporal and Probability Context Effects on Event Categorization

We present a neural network that adapts and integrates several preexisting or new modules to categorize events in short term memory (STM), encode temporal order in working memory, evaluate timing and probability context in medium and long term memory. The model shows how processed contextual information modulates event recognition and categorization, focal attention and incentive motivation. The model is based on a compendium of Event Related Potentials (ERPs) and behavioral results either collected by the authors or compiled from the classical ERP literature. Its hallmark is, at the functional level, the interplay of memory registers endowed with widely different dynamical ranges, and at the structural level, the attempt to relate the different modules to known anatomical structures.

Strategies to prevent potentially inappropriate prescribing and adverse drug reactions in older patients

INTRODUCTION: Potentially inappropriate prescribing (PIP) is a major contributor to adverse drug reactions and overall increased healthcare costs. The aim of this thesis was to identify, develop and implement strategies with the potential to prevent PIP and ADRs in older patients. METHODS: A systematic review of the qualitative literature (Meta-synthesis); A qualitative study in Irish hospitals; A randomised controlled trial (RCT) to assess the impact of an online educational module on doctors’ prescribing knowledge and confidence; Exploration of the potential for a frailty index score to enable doctors identify patients at increased risk of PIP and ADRs; Exploration of the potential for the SHiM tool to enable doctors to optimise prescribing for older patients. RESULTS: The meta-synthesis identified four key concepts: (i) Desire to please the patient; (ii) Feeling of being forced to prescribe; (iii) Tension between experience and guidelines; (iv) Prescriber fear. Similar themes also emerged from the qualitative study. In the RCT, the online educational module resulted in a highly significant 22% difference in test scores between intervention and control groups. The studies exploring the frailty index score showed a significant positive relationship between a patient’s frailty status and their likelihood of experiencing PIP/ADRs. Patients above a frailty threshold of 0.16 were at least twice as likely to experience PIP/ADRs. SHiM was found to be a useful tool in terms of reconciling patients’ medications. However, the evidence for it being capable of preventing clinically relevant adverse events was poor. CONCLUSION:Qualitative research in this thesis has proposed novel theories relating to the causative factors of PIP in older patients. In doing so, it has identified several areas for intervention and laid down a road map for future research.

Colony sex ratios vary with breeding structure but not relatedness asymmetry in the facultatively polygynous ant Pheidole pallidula

We investigated sex allocation in a Mediterranean population of the facultatively polygynous (multiple queen per colony) ant Pheidole pallidula. This species shows a strong split sex ratio, with most colonies producing almost exclusively a single-sex brood. Our genetic (microsatellite) analyses reveal that P. pallidula has an unusual breeding system, with colonies being headed by a single or a few unrelated queens. As expected in such a breeding system, our results show no variation in relatedness asymmetry between monogynous (single queen per colony) and polygynous colonies. Nevertheless, sex allocation was tightly associated with the breeding structure, with monogynous colonies producing a male-biased brood and polygynous colonies almost only females. In addition, sex allocation was closely correlated with colony total sexual productivity. Overall, our data show that when colonies become more productive (and presumably larger) they shift from monogyny to polygyny and from male production to female production, a pattern that has never been reported in social insects.

Acute eosinophilic pneumonia secondary to daptomycin: a report of three cases.

We describe 3 cases of daptomycin-induced pulmonary toxic effects that are consistent with drug-induced acute eosinophilic pneumonia. Patients presented similarly with dyspnea, cough, hypoxia, and diffuse ground-glass opacities at chest computed tomography. Clinical suspicion for this adverse drug event and cessation of daptomycin until definitive diagnosis can be made is crucial.

Triangular flow in event-by-event ideal hydrodynamics in Au+Au collisions at √SNN = 200A GeV

The first calculation of triangular flow ν3 in Au+Au collisions at √sNN = 200A GeV from an event-by-event (3 + 1) d transport+hydrodynamics hybrid approach is presented. As a response to the initial triangularity Ie{cyrillic, ukrainian}3 of the collision zone, ν3 is computed in a similar way to the standard event-plane analysis for elliptic flow ν2. It is found that the triangular flow exhibits weak centrality dependence and is roughly equal to elliptic flow in most central collisions. We also explore the transverse momentum and rapidity dependence of ν2 and ν3 for charged particles as well as identified particles. We conclude that an event-by-event treatment of the ideal hydrodynamic evolution startingwith realistic initial conditions generates the main features expected for triangular flow. © 2010 The American Physical Society.

Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania.

Fixed dose combination abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) among HIV-1 and tuberculosis (TB)-coinfected patients was evaluated and outcomes between early vs. delayed initiation were compared. In a randomized, pilot study conducted in the Kilimanjaro Region of Tanzania, HIV-infected inpatients with smear-positive TB and total lymphocyte count <1200/mm(3) were randomized to initiate ABC/3TC/ZDV either 2 (early) or 8 (delayed) weeks after commencing antituberculosis therapy and were followed for 104 weeks. Of 94 patients screened, 70 enrolled (41% female, median CD4 count 103 cells/mm(3)), and 33 in each group completed 104 weeks. Two deaths and 12 serious adverse events (SAEs) were observed in the early arm vs. one death, one clinical failure, and seven SAEs in the delayed arm (p = 0.6012 for time to first grade 3/4 event, SAE, or death). CD4 cell increases were +331 and +328 cells/mm(3), respectively. TB-immune reconstitution inflammatory syndromes (TB-IRIS) were not observed in any subject. Using intent-to-treat (ITT), missing = failure analyses, 74% (26/35) vs. 89% (31/35) randomized to early vs. delayed therapy had HIV RNA levels <400 copies/ml at 104 weeks (p = 0.2182) and 66% (23/35) vs. 74% (26/35), respectively, had HIV RNA levels <50 copies/ml (p = 0.6026). In an analysis in which switches from ABC/3TC/ZDV = failure, those receiving early therapy were less likely to be suppressed to <400 copies/ml [60% (21/35) vs. 86% (30/35), p = 0.030]. TB-IRIS was not observed among the 70 coinfected subjects beginning antiretroviral treatment. ABC/3TC/ZDV was well tolerated and resulted in steady immunologic improvement. Rates of virologic suppression were similar between early and delayed treatment strategies with triple nucleoside regimens when substitutions were allowed.

Event memory: A theory of memory for laboratory, autobiographical, and fictional events.

An event memory is a mental construction of a scene recalled as a single occurrence. It therefore requires the hippocampus and ventral visual stream needed for all scene construction. The construction need not come with a sense of reliving or be made by a participant in the event, and it can be a summary of occurrences from more than one encoding. The mental construction, or physical rendering, of any scene must be done from a specific location and time; this introduces a "self" located in space and time, which is a necessary, but need not be a sufficient, condition for a sense of reliving. We base our theory on scene construction rather than reliving because this allows the integration of many literatures and because there is more accumulated knowledge about scene construction's phenomenology, behavior, and neural basis. Event memory differs from episodic memory in that it does not conflate the independent dimensions of whether or not a memory is relived, is about the self, is recalled voluntarily, or is based on a single encoding with whether it is recalled as a single occurrence of a scene. Thus, we argue that event memory provides a clearer contrast to semantic memory, which also can be about the self, be recalled voluntarily, and be from a unique encoding; allows for a more comprehensive dimensional account of the structure of explicit memory; and better accounts for laboratory and real-world behavioral and neural results, including those from neuropsychology and neuroimaging, than does episodic memory.

Component Neural Systems for the Creation of Emotional Memories during Free Viewing of a Complex, Real-World Event.

To investigate the neural systems that contribute to the formation of complex, self-relevant emotional memories, dedicated fans of rival college basketball teams watched a competitive game while undergoing functional magnetic resonance imaging (fMRI). During a subsequent recognition memory task, participants were shown video clips depicting plays of the game, stemming either from previously-viewed game segments (targets) or from non-viewed portions of the same game (foils). After an old-new judgment, participants provided emotional valence and intensity ratings of the clips. A data driven approach was first used to decompose the fMRI signal acquired during free viewing of the game into spatially independent components. Correlations were then calculated between the identified components and post-scanning emotion ratings for successfully encoded targets. Two components were correlated with intensity ratings, including temporal lobe regions implicated in memory and emotional functions, such as the hippocampus and amygdala, as well as a midline fronto-cingulo-parietal network implicated in social cognition and self-relevant processing. These data were supported by a general linear model analysis, which revealed additional valence effects in fronto-striatal-insular regions when plays were divided into positive and negative events according to the fan's perspective. Overall, these findings contribute to our understanding of how emotional factors impact distributed neural systems to successfully encode dynamic, personally-relevant event sequences.

The centrality of event scale: a measure of integrating a trauma into one's identity and its relation to post-traumatic stress disorder symptoms.

We introduce a new scale that measures how central an event is to a person's identity and life story. For the most stressful or traumatic event in a person's life, the full 20-item Centrality of Event Scale (CES) and the short 7-item scale are reliable (alpha's of .94 and .88, respectively) in a sample of 707 undergraduates. The scale correlates .38 with PTSD symptom severity and .23 with depression. The present findings are discussed in relation to previous work on individual differences related to PTSD symptoms. Possible connections between the CES and measures of maladaptive attributions and rumination are considered along with suggestions for future research.

Reliving, emotions, and fragmentation in the autobiographical memories of veterans diagnosed with PTSD

Fifty veterans diagnosed with posttraumatic stress disorder (PTSD) each recalled four autobiographical memories: one from the 2 years before service, one non-combat memory from the time in service, one from combat, and one from service that had often come as an intrusive memory. For each memory, they provided 21 ratings about reliving, belief, sensory properties, reexperiencing emotions, visceral emotional responses, fragmentation, and narrative coherence. We used these ratings to examine three claims about traumatic memories: a separation of cognitive and visceral aspects of emotion, an increased sense of reliving, and increased fragmentation. There was evidence for a partial separation of cognitive judgments of reexperiencing an emotion and reports of visceral symptoms of the emotion, with visceral symptoms correlating more consistently with scores on PTSD tests. Reliving, but not fragmentation of the memories, increased with increases in the trauma relatedness of the event and with increases in scores on standardized tests of PTSD severity. Copyright © 2004 John Wiley & Sons, Ltd.

A dose-finding study of lanreotide (a somatostatin analog) in patients with colorectal carcinoma

BACKGROUND. Laboratory data suggest that insulin-like growth factor-1 (IGE-1) may stimulate the growth of different human tumors. At least in acromegalic patients, somatostatin (SMS) analogs, such as lanreotide, suppress the serum levels of growth hormone (GH) and IGE-1. METHODS. To evaluate the tolerability and biologic activity of different doses of lanreotide in patients with advanced colorectal carcinoma, consecutive groups of 3 patients each were subcutaneous treated with lanreotide at doses of 1, 2, 3, 4, 5, or 6 mg three times a day for 2 months. In the event of Grade 3 side effects, 3 additional patients were treated with the same dose before the next dose escalation. Serum samples were obtained on Days 0, 15, 30, and 60 for serum GH, IGF-1, and lanreotide assessment. RESULTS. Twenty-four patients were enrolled and all were evaluable. Except for the 3 and 6 mg doses, for which the observation of a Grade 3 side effect required that an additional three patients be treated, it was sufficient to treat 3 patients at each dose. The overall incidence of side effects was as follows: changes in bowel habits, 83%; abdominal cramps, 79%; diarrhea, 17%; vomiting, 17%; nausea, 21%; steatorrhea, 78%; hyperglycemia, 35%; laboratory hypothyroidism, 39%; gallstones, 13%; and weight loss, 17%. No evidence of an increase in the incidence, intensity, or duration of side effects was observed with dose escalation. Serum IGF-1 levels were as follows: Day 13: 63%, 60%, and 67% of the baseline values for the low (12 mg), intermediate (3-4 mg), and high (5- 6 mg) dose groups, respectively; Day 30: 63%, 59%, and 51%, respectively; and Day 60: 73%, 69%, and 47%, respectively. Serum lanreotide levels declined during treatment in all of the dose groups (90 ng/mL on Day 15, and 35 ng/mL on Day 60 for the 5-6 mg group; 10 ng/mL on Day 15, and 1.5 ng/mL on Day 60 for the 1-2 mg group). No antitumor activity or tumor marker reduction was observed. CONCLUSIONS. No increase in toxicity was observed when subcutaneous lanreotide doses were escalated to 6 mg three times a day for 2 months. The highest doses seemed to maintain reduced serum IGF-1 levels; with the lowest doses, a 'rebound' in serum IGF-1 levels was observed during treatment. Nevertheless, intermittent subcutaneous injections do not ensure constant serum drug concentrations over time.

Event models for tumor classification with SAGE gene expression data

Serial Analysis of Gene Expression (SAGE) is a relatively new method for monitoring gene expression levels and is expected to contribute significantly to the progress in cancer treatment by enabling a precise and early diagnosis. A promising application of SAGE gene expression data is classification of tumors. In this paper, we build three event models (the multivariate Bernoulli model, the multinomial model and the normalized multinomial model) for SAGE data classification. Both binary classification and multicategory classification are investigated. Experiments on two SAGE datasets show that the multivariate Bernoulli model performs well with small feature sizes, but the multinomial performs better at large feature sizes, while the normalized multinomial performs well with medium feature sizes. The multinomial achieves the highest overall accuracy.