Bayesian Hidden Markov Modeling of Array CGH Data

Genomic alterations have been linked to the development and progression of cancer. The technique of Comparative Genomic Hybridization (CGH) yields data consisting of fluorescence intensity ratios of test and reference DNA samples. The intensity ratios provide information about the number of copies in DNA. Practical issues such as the contamination of tumor cells in tissue specimens and normalization errors necessitate the use of statistics for learning about the genomic alterations from array-CGH data. As increasing amounts of array CGH data become available, there is a growing need for automated algorithms for characterizing genomic profiles. Specifically, there is a need for algorithms that can identify gains and losses in the number of copies based on statistical considerations, rather than merely detect trends in the data. We adopt a Bayesian approach, relying on the hidden Markov model to account for the inherent dependence in the intensity ratios. Posterior inferences are made about gains and losses in copy number. Localized amplifications (associated with oncogene mutations) and deletions (associated with mutations of tumor suppressors) are identified using posterior probabilities. Global trends such as extended regions of altered copy number are detected. Since the posterior distribution is analytically intractable, we implement a Metropolis-within-Gibbs algorithm for efficient simulation-based inference. Publicly available data on pancreatic adenocarcinoma, glioblastoma multiforme and breast cancer are analyzed, and comparisons are made with some widely-used algorithms to illustrate the reliability and success of the technique.

Visual and quantitative electroencephalographic analysis of healthy young and adult cats under medetomidine sedation

A study was designed to investigate the effect of medetomidine sedation on quantitative electroencephalography (q-EEG) in healthy young and adult cats to determine objective guidelines for diagnostic EEG recordings and interpretation. Preliminary visual examination of EEG recordings revealed high-voltage low-frequency background activity. Spindles, k-complexes and vertex sharp transients characteristic of sleep or sedation were superimposed on a low background activity. Neither paroxysmal activity nor EEG burst-suppression were observed. The spectral analysis of q-EEG included four parameters, namely, relative power (%), and mean, median and peak frequency (Hz) of all four frequency bands (delta, theta, alpha and beta). The findings showed a prevalence of slow delta and theta rhythms as opposed to fast alpha and beta rhythms in both young (group A) and adult (group B) cats. A posterior gradient was reported for the theta band and an anterior gradient for the alpha and beta bands in both groups, respectively. The relative power value in group B compared to group A was significantly higher for theta, alpha and beta bands, and lower for the delta band. The mean and median frequency values in group B was significantly higher for delta, theta and beta bands and lower for the alpha band. The study has shown that a medetomidine sedation protocol for feline EEG may offer a method for investigating bio-electrical cortical activity. The use of q-EEG analysis showed a decrease in high frequency bands and increased activity of the low frequency band in healthy cats under medetomidine sedation.

An analysis of the spatial and temporal patterns of highly pathogenic avian influenza occurrence in Vietnam using national surveillance data

The objectives of this study were to describe the spatio-temporal pattern of an epidemic of highly pathogenic avian influenza (HPAI) in Vietnam and to identify potential risk factors for the introduction and maintenance of infection within the poultry population. The results indicate that during the time period 2004–early 2006 a sequence of three epidemic waves occurred in Vietnam as distinct spatial and temporal clusters. The risk of outbreak occurrence increased with a greater percentage of rice paddy fields, increasing domestic water bird and chicken density. It increased with reducing distance to higher population density aggregations, and in the third epidemic wave with increasing percentage of aquaculture. The findings indicate that agri-livestock farming systems involving domestic water birds and rice production in river delta areas are important for the maintenance and spread of infection. While the government’s control measures appear to have been effective in the South and Central parts of Vietnam, it is likely that in the North of Vietnam the vaccination campaign led to transmission of infection which was subsequently brought under control.

Governmentality in higher education : a critical analysis of the National Survey of Student Engagement (NSSE)

In this dissertation, the National Survey of Student Engagement (NSSE) serves as a nodal point through which to examine the power relations shaping the direction and practices of higher education in the twenty-first century. Theoretically, my analysis is informed by Foucault’s concept of governmentality, briefly defined as a technology of power that influences or shapes behavior from a distance. This form of governance operates through apparatuses of security, which include higher education. Foucault identified three essential characteristics of an apparatus—the market, the milieu, and the processes of normalization—through which administrative mechanisms and practices operate and govern populations. In this project, my primary focus is on the governance of faculty and administrators, as a population, at residential colleges and universities. I argue that the existing milieu of accountability is one dominated by the neoliberal assumption that all activity—including higher education—works best when governed by market forces alone, reducing higher education to a market-mediated private good. Under these conditions, what many in the academy believe is an essential purpose of higher education—to educate students broadly, to contribute knowledge for the public good, and to serve as society’s critic and social conscience (Washburn 227)—is being eroded. Although NSSE emerged as a form of resistance to commercial college rankings, it did not challenge the forces that empowered the rankings in the first place. Indeed, NSSE data are now being used to make institutions even more responsive to market forces. Furthermore, NSSE’s use has a normalizing effect that tends to homogenize classroom practices and erode the autonomy of faculty in the educational process. It also positions students as part of the system of surveillance. In the end, if aspects of higher education that are essential to maintaining a civil society are left to be defined solely in market terms, the result may be a less vibrant and, ultimately, a less just society.

Colonization history of the Swiss Rhine basin by the bullhead (Cottus gobio): inference under a Bayesian spatially explicit framework

The present distribution of freshwater fish in the Alpine region has been strongly affected by colonization events occurring after the last glacial maximum (LGM), some 20,000 years ago. We use here a spatially explicit simulation framework to model and better understand their colonization dynamics in the Swiss Rhine basin. This approach is applied to the European bullhead (Cottus gobio), which is an ideal model organism to study fish past demographic processes since it has not been managed by humans. The molecular diversity of eight sampled populations is simulated and compared to observed data at six microsatellite loci under an approximate Bayesian computation framework to estimate the parameters of the colonization process. Our demographic estimates fit well with current knowledge about the biology of this species, but they suggest that the Swiss Rhine basin was colonized very recently, after the Younger Dryas some 6600 years ago. We discuss the implication of this result, as well as the strengths and limits of the spatially explicit approach coupled to the approximate Bayesian computation framework.

Linking physiology with behaviour: Functional specialisation of the visual field is reflected in gaze patterns during visual search

Based on neurophysiological findings and a grid to score binocular visual field function, two hypotheses concerning the spatial distribution of fixations during visual search were tested and confirmed in healthy participants and patients with homonymous visual field defects. Both groups showed significant biases of fixations and viewing time towards the centre of the screen and the upper screen half. Patients displayed a third bias towards the side of their field defect, which represents oculomotor compensation. Moreover, significant correlations between the extent of these three biases and search performance were found. Our findings suggest a new, more dynamic view of how functional specialisation of the visual field influences behaviour.

Neglect-like visual exploration behaviour after theta burst transcranial magnetic stimulation of the right posterior parietal cortex

The right posterior parietal cortex (PPC) is critically involved in visual exploration behaviour, and damage to this area may lead to neglect of the left hemispace. We investigated whether neglect-like visual exploration behaviour could be induced in healthy subjects using theta burst repetitive transcranial magnetic stimulation (rTMS). To this end, one continuous train of theta burst rTMS was applied over the right PPC in 12 healthy subjects prior to a visual exploration task where colour photographs of real-life scenes were presented on a computer screen. In a control experiment, stimulation was also applied over the vertex. Eye movements were measured, and the distribution of visual fixations in the left and right halves of the screen was analysed. In comparison to the performance of 28 control subjects without stimulation, theta burst rTMS over the right PPC, but not the vertex, significantly decreased cumulative fixation duration in the left screen-half and significantly increased cumulative fixation duration in the right screen-half for a time period of 30 min. These results suggest that theta burst rTMS is a reliable method of inducing transient neglect-like visual exploration behaviour.

Visual and spectral analysis of sleep EEG in acute hemispheric stroke

BACKGROUND: Reports on the effects of focal hemispheric damage on sleep EEG are rare and contradictory. PATIENTS AND METHODS: Twenty patients (mean age +/- SD 53 +/- 14 years) with a first acute hemispheric stroke and no sleep apnea were studied. Stroke severity [National Institute of Health Stroke Scale (NIHSS)], volume (diffusion-weighted brain MRI), and short-term outcome (Rankin score) were assessed. Within the first 8 days after stroke onset, 1-3 sleep EEG recordings per patient were performed. Sleep scoring and spectral analysis were based on the central derivation of the healthy hemisphere. Data were compared with those of 10 age-matched and gender-matched hospitalized controls with no brain damage and no sleep apnea. RESULTS: Stroke patients had higher amounts of wakefulness after sleep onset (112 +/- 53 min vs. 60 +/- 38 min, p < 0.05) and a lower sleep efficiency (76 +/- 10% vs. 86 +/- 8%, p < 0.05) than controls. Time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep and total sleep time were lower in stroke patients, but differences were not significant. A positive correlation was found between the amount of SWS and stroke volume (r = 0.79). The slow-wave activity (SWA) ratio NREM sleep/wakefulness was lower in patients than in controls (p < 0.05), and correlated with NIHSS (r = -0.47). CONCLUSION: Acute hemispheric stroke is accompanied by alterations of sleep EEG over the healthy hemisphere that correlate with stroke volume and outcome. The increased SWA during wakefulness and SWS over the healthy hemisphere contralaterally to large strokes may reflect neuronal hypometabolism induced transhemispherically (diaschisis).

Simbrain: A visual framework for neural network analysis and education

Simbrain is a visually-oriented framework for building and analyzing neural networks. It emphasizes the analysis of networks which control agents embedded in virtual environments, and visualization of the structures which occur in the high dimensional state spaces of these networks. The program was originally intended to facilitate analysis of representational processes in embodied agents, however it is also well suited to teaching neural networks concepts to a broader audience than is traditional for neural networks courses. Simbrain was used to teach a course at a new university, UC Merced, in its inaugural year. Experiences from the course and sample lessons are provided.

Antiplatelets versus Anticoagulants for the Treatment of Cervical Artery Dissection: Bayesian Meta-Analysis

OBJECTIVE To compare the effects of antiplatelets and anticoagulants on stroke and death in patients with acute cervical artery dissection. DESIGN Systematic review with Bayesian meta-analysis. DATA SOURCES The reviewers searched MEDLINE and EMBASE from inception to November 2012, checked reference lists, and contacted authors. STUDY SELECTION Studies were eligible if they were randomised, quasi-randomised or observational comparisons of antiplatelets and anticoagulants in patients with cervical artery dissection. DATA EXTRACTION Data were extracted by one reviewer and checked by another. Bayesian techniques were used to appropriately account for studies with scarce event data and imbalances in the size of comparison groups. DATA SYNTHESIS Thirty-seven studies (1991 patients) were included. We found no randomised trial. The primary analysis revealed a large treatment effect in favour of antiplatelets for preventing the primary composite outcome of ischaemic stroke, intracranial haemorrhage or death within the first 3 months after treatment initiation (relative risk 0.32, 95% credibility interval 0.12 to 0.63), while the degree of between-study heterogeneity was moderate (τ(2) = 0.18). In an analysis restricted to studies of higher methodological quality, the possible advantage of antiplatelets over anticoagulants was less obvious than in the main analysis (relative risk 0.73, 95% credibility interval 0.17 to 2.30). CONCLUSION In view of these results and the safety advantages, easier usage and lower cost of antiplatelets, we conclude that antiplatelets should be given precedence over anticoagulants as a first line treatment in patients with cervical artery dissection unless results of an adequately powered randomised trial suggest the opposite.

Analysis of eye and head coordination in a visual peripheral recognition task

Coordinated eye and head movements simultaneously occur to scan the visual world for relevant targets. However, measuring both eye and head movements in experiments allowing natural head movements may be challenging. This paper provides an approach to study eye-head coordination: First, we demonstra- te the capabilities and limits of the eye-head tracking system used, and compare it to other technologies. Second, a beha- vioral task is introduced to invoke eye-head coordination. Third, a method is introduced to reconstruct signal loss in video- based oculography caused by cornea reflection artifacts in order to extend the tracking range. Finally, parameters of eye- head coordination are identified using EHCA (eye-head co- ordination analyzer), a MATLAB software which was developed to analyze eye-head shifts. To demonstrate the capabilities of the approach, a study with 11 healthy subjects was performed to investigate motion behavior. The approach presented here is discussed as an instrument to explore eye-head coordination, which may lead to further insights into attentional and motor symptoms of certain neurological or psychiatric diseases, e.g., schizophrenia.