Scalable iterative methods for sampling from massive Gaussian random vectors

Sampling from Gaussian Markov random fields (GMRFs), that is multivariate Gaussian ran- dom vectors that are parameterised by the inverse of their covariance matrix, is a fundamental problem in computational statistics. In this paper, we show how we can exploit arbitrarily accu- rate approximations to a GMRF to speed up Krylov subspace sampling methods. We also show that these methods can be used when computing the normalising constant of a large multivariate Gaussian distribution, which is needed for both any likelihood-based inference method. The method we derive is also applicable to other structured Gaussian random vectors and, in particu- lar, we show that when the precision matrix is a perturbation of a (block) circulant matrix, it is still possible to derive O(n log n) sampling schemes.Comment: 17 Pages, 4 Figure

Recent Advances in Image-Guided Radiotherapy for Head and Neck Carcinoma

Radiotherapy has a well-established role in the management of head and neck cancers. Over the past decade, a variety of new imaging modalities have been incorporated into the radiotherapy planning and delivery process. These technologies are collectively referred to as image-guided radiotherapy and may lead to significant gains in tumor control and radiation side effect profiles. In the following review, these techniques as they are applied to head and neck cancer patients are described, and clinical studies analyzing their use in target delineation, patient positioning, and adaptive radiotherapy are highlighted. Finally, we conclude with a brief discussion of potential areas of further radiotherapy advancement

Cardiovascular and neuropsychiatric risks of varenicline and bupropion in smokers with chronic obstructive pulmonary disease

BACKGROUND: Varenicline and bupropion are effective smoking cessation treatments, but there are concerns about their safety in smokers with COPD. OBJECTIVE: To investigate whether varenicline and bupropion are associated with serious adverse cardiovascular and neuropsychiatric events in smokers with COPD. METHODS: In a retrospective cohort study, we used data from 14 350 patients with COPD included in the QResearch database, which holds data from 753 National Health Service general practices across England. We identified patients with COPD who received a prescription of nicotine replacement therapy (NRT; N=10 426; reference group), bupropion (N=350) or varenicline (N=3574) in the period between January 2007 and June 2012. Patients were followed up for 6 months to compare incident cardiovascular (ie, ischaemic heart disease, stroke, heart failure, peripheral vascular disease and cardiac arrhythmias) and neuropsychiatric (ie, depression and self-harm) events using Cox proportional hazards models, adjusted for potential confounders. Propensity score analysis was used as an additional approach to account for potential confounding by indication. We also modelled the effects of possible unmeasured confounders. RESULTS: Neither bupropion nor varenicline showed an increased risk of adverse events compared with NRT. Varenicline was associated with a significantly reduced risk of heart failure (HR=0.56, 95% CI 0.34 to 0.92) and depression (HR=0.73, 95% CI 0.61 to 0.86). Similar results were obtained from the propensity score analysis. Modelling of unmeasured confounding provided additional evidence that an increased risk of these adverse events was very unlikely. CONCLUSION: In smokers with COPD, varenicline and bupropion do not appear to be associated with an increased risk of cardiovascular events, depression or self-harm in comparison with NRT

Evaluating Antioxidant Activity of Selected Plant Species Native to Cedarville, Ohio

Over the past several decades, there has been an increase in the number of synthetic drug molecules developed and utilized to treat various conditions. Although these synthetic drugs have proven useful, there has been growing public concern regarding the potentially negative long-term effects of synthetic agents on the body. As a result, there has been an increased interest in identifying and utilizing plant extracts and purified compounds since they are perceived to be a more natural alternative to synthetic drugs. The goal of this study was to evaluate the specific antioxidant properties of alsike clover Trifolum hybridum when produced under differing growing conditions. The alsike clover was collected from the campus of Cedarville University, Cedarville, Ohio for testing. Alsike clover was removed from the field in January 2013, and transplanted indoors under grow lights for 14 days. These plants were then subjected to three separate 60-day treatments: control treatment - watering to field capacity with no fertilizer; positive treatment - watering to field capacity with fertilizer; and negative treatment - half of the water given to the field capacity treatment with no fertilizer. The rationale for choosing these different treatments was to evaluate the effects of specific growing conditions on bioactive secondary metabolite production in alsike clover. The biological evaluation was accomplished by conducting diphenylpicrylhyrazyl (DPPH) free-radical scavenging and Folin Ciocalteu assays to assess the concentration of polyphenolic compounds. Results from these experiments indicate that the biological and chemical profiles of alsike clover can be influenced by the environmental conditions under which the plants are grown

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I

The role of discharge variability in determining alluvial stratigraphy

We illustrate the potential for using physics-based modeling to link alluvial stratigraphy to large river morphology and dynamics. Model simulations, validated using ground penetrating radar data from the Río Paraná, Argentina, demonstrate a strong relationship between bar-scale set thickness and channel depth, which applies across a wide range of river patterns and bar types. We show that hydrologic regime, indexed by discharge variability and flood duration, exerts a first-order influence on morphodynamics and hence bar set thickness, and that planform morphology alone may be a misleading variable for interpreting deposits. Indeed, our results illustrate that rivers evolving under contrasting hydrologic regimes may have very similar morphology, yet be characterized by marked differences in stratigraphy. This realization represents an important limitation on the application of established theory that links river topography to alluvial deposits, and highlights the need to obtain field evidence of discharge variability when developing paleoenvironmental reconstructions. Model simulations demonstrate the potential for deriving such evidence using metrics of paleocurrent variance