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Search Results: 1 - 10 of 314865 matches for " John D. O'Brien "
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Validation of Automated White Matter Hyperintensity Segmentation
Sean D. Smart,Michael J. Firbank,John T. O'Brien
Journal of Aging Research , 2011, DOI: 10.4061/2011/391783
Abstract: Introduction. White matter hyperintensities (WMHs) are a common finding on MRI scans of older people and are associated with vascular disease. We compared 3 methods for automatically segmenting WMHs from MRI scans. Method. An operator manually segmented WMHs on MRI images from a 3T scanner. The scans were also segmented in a fully automated fashion by three different programmes. The voxel overlap between manual and automated segmentation was compared. Results. Between observer overlap ratio was 63%. Using our previously described in-house software, we had overlap of 62.2%. We investigated the use of a modified version of SPM segmentation; however, this was not successful, with only 14% overlap. Discussion. Using our previously reported software, we demonstrated good segmentation of WMHs in a fully automated fashion. 1. Introduction Magnetic resonance imaging (MRI) is now widely used in the diagnosis of diseases by doctors and is particularly useful for scanning images of the brain and detecting cerebrovascular disorders. White matter hyperintensities (WMHs) are a common finding in elderly people which are associated with vascular risk factors and an increased risk of decline in cognitive and motor function [1]. A number of methods have been used to quantify the hyperintensities to correlate to clinical data such as visual ratings, volumetric measuring, and WMHs pattern [2–6]. An investigation with the LADIS study cohort found that volumetric measurement was more sensitive than visual rating to detect differences in WMHs between groups with versus without memory symptoms although both volumetric measurement and visual rating detected differences in WMHs relating to age and gait disturbance [7]. Currently, there is no accepted gold standard for a fully automated WMHs segmentation program. The SPM package (http://www.fil.ion.ucl.ac.uk/spm/software/) has a widely used segmentation tool which classes brain tissue into grey, white matter, and CSF, using a combination of image intensity and a priori knowledge regarding distribution of tissue types. The default does not include information about WMHs, and these can be misclassified as grey matter [8]. Adding information regarding the a priori distribution of WMHs may help to improve the segmentation of WMHs in SPM. The study aims to investigate the ability of SPM to segment WMHs from (a) T1 weighted and (b) T1 + FLAIR images using a priori information about WMHs distribution. Results will be compared to manual segmentation of WMHs from FLAIR images, an in-house WMHs segmentation program [9], and a different
Topological Symmetry Groups of K_{4r+3}
Dwayne Chambers,Erica Flapan,John D. O'Brien
Mathematics , 2009, DOI: 10.3934/dcdss.2011.4.1401
Abstract: We present the concept of the topological symmetry group as a way to analyze the symmetries of non-rigid molecules. Then we characterize all of the groups which can occur as the topological symmetry group of an embedding of the complete graph K_{4r+3} in S^3.
An integrative statistical model for inferring strain admixture within clinical Plasmodium falciparum isolates
John D. O'Brien,Zamin Iqbal,Lucas Amenga-Etego
Quantitative Biology , 2015,
Abstract: Since the arrival of genetic typing methods in the late 1960's, researchers have puzzled at the clinical consequence of observed strain mixtures within clinical isolates of Plasmodium falciparum. We present a new statistical model that infers the number of strains present and the amount of admixture with the local population (panmixia) using whole-genome sequence data. The model provides a rigorous statistical approach to inferring these quantities as well as the proportions of the strains within each sample. Applied to 168 samples of whole-genome sequence data from northern Ghana, the model provides significantly improvement fit over models implementing simpler approaches to mixture for a large majority (129/168) of samples. We discuss the possible uses of this model as a window into within-host selection for clinical and epidemiological studies and outline possible means for experimental validation.
Mixture model of pottery distributions from Lake Chad Basin archaeological sites reveals ancient segregation patterns
John D. O'Brien,Kathryn Lin,Scott MacEachern
Statistics , 2015,
Abstract: We present a new statistical approach to analyzing an extremely common archaeological data type -- potsherds -- that infers the structure of cultural relationships across a set of excavations. This method, applied to data from a set of complex, culturally heterogeneous sites around the Mandara mountains in the Lake Chad Basin, articulates currently understood cultural succession into the Iron Age. We show how the approach can be integrated with radiocarbon dates to provide detailed portraits of cultural dynamics and deposition patterns within single excavations that, in this context, indicate historical ethnolinguistic segregation patterns. We conclude with a discussion of the many possible model extensions using other archaeological data types.
Imputation Estimators Partially Correct for Model Misspecification
Vladimir N. Minin,John D. O'Brien,Arseni Seregin
Statistics , 2009, DOI: 10.2202/1544-6115.1650
Abstract: Inference problems with incomplete observations often aim at estimating population properties of unobserved quantities. One simple way to accomplish this estimation is to impute the unobserved quantities of interest at the individual level and then take an empirical average of the imputed values. We show that this simple imputation estimator can provide partial protection against model misspecification. We illustrate imputation estimators' robustness to model specification on three examples: mixture model-based clustering, estimation of genotype frequencies in population genetics, and estimation of Markovian evolutionary distances. In the final example, using a representative model misspecification, we demonstrate that in non-degenerate cases, the imputation estimator dominates the plug-in estimate asymptotically. We conclude by outlining a Bayesian implementation of the imputation-based estimation.
Dating the time of viral subtype divergence
John D O'Brien, Zhen-Su She, Marc A Suchard
BMC Evolutionary Biology , 2008, DOI: 10.1186/1471-2148-8-172
Abstract: Precise estimates are sorely lacking for dating the emergence and divergence of viral subtypes. Improved estimates equip epidemiologists and virologists to begin to correlate these important establishing events with historical demographic changes, geographical invasions and zoonoses, the transferring of a virus from one host species to another [7,1,25]. For example, archeological sequence data can furnish accurate dates and show that substantial genomic changes associate with geographical invasion and zoonosis [14,17]. Further, the recent availability of viral gene sequences sampled at a pace commensurate with their rate of nucleotide substitution vastly augments the ability to rigorously infer the time scale of phylogenies and hence determine the time of the most recent common ancestor (TMRCA) for different viral types [18,26,6].Systematic studies characterize the substitution process and substitution rate process of several classes of viral subtypes in, for example, Dengue, influenza subtype A, human immunodeficiency virus (HIV) and the virus responsible for sudden acute respiratory syndrome (SARS). For the last three viruses, a unique zoonotic transfer appears to co-occur with substantial changes in both the composition of nucleotides and amino acids as well as alterations in the rate of nucleotide substitution [15,14,1]. In Dengue, where a single subtype simultaneously inhabits two hosts (humans and Aedes aegypti) in a persistent zoonotic process, the introduction of the virus to new geographical environments associates with a dramatic increase in sequence diversity [25]. Unfortunately, no studies thus far analyze the rate of nucleotide substitution during either geographical invasion or zoonosis. Consequently, studies of the date of origins of viral subtypes must use strong a priori assumptions on the rate structure of nucleotide substitution.Two primary methods find use to date the time of viral subtype divergence. The most commonly employed approach determine
The Influence of Variable Rainfall Frequency on Germination and Early Growth of Shade-Tolerant Dipterocarp Seedlings in Borneo
Michael J. OBrien, Christopher D. Philipson, John Tay, Andy Hector
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070287
Abstract: Climate change induced alterations to rainfall patterns have the potential to affect the regeneration dynamics of plant species, especially in historically everwet tropical rainforest. Differential species response to infrequent rainfall may influence seed germination and seedling establishment in turn affecting species distributions. We tested the role of watering frequency intervals (from daily to six-day watering) on the germination and the early growth of Dipterocarpaceae seedlings in Borneo. We used seeds that ranged in size from 500 to 20,000 mg in order to test the role of seed mass in mediating the effects of infrequent watering. With frequent rainfall, germination and seedling development traits bore no relationship to seed mass, but all metrics of seedling growth increased with increasing seed mass. Cumulative germination declined by 39.4% on average for all species when plants were watered at six-day intervals, and days to germination increased by 76.5% on average for all species from daily to six-day intervals. Final height and biomass declined on average in the six-day interval by 16% and 30%, respectively, but the percentage decrease in final size was greater for large-seeded species. Rooting depth per leaf area also significantly declined with seed mass indicating large-seeded species allocate relatively more biomass for leaf production. This difference in allocation provided an establishment advantage to large-seeded species when water was non-limiting but inhibited their growth under infrequent rainfall. The observed reduction in the growth of large-seeded species under infrequent rainfall would likely restrict their establishment in drier microsites associated with coarse sandy soils and ridge tops. In total, these species differences in germination and initial seedling growth indicates a possible niche axis that may help explain both current species distributions and future responses to climate change.
Influence of Nanoparticle Size and Shape on Oligomer Formation of an Amyloidogenic Peptide
Edward P. O'Brien,John E. Straub,Bernard R. Brooks,D. Thirumalai
Quantitative Biology , 2011, DOI: 10.1021/jz200330k
Abstract: Understanding the influence of macromolecular crowding and nanoparticles on the formation of in-register $\beta$-sheets, the primary structural component of amyloid fibrils, is a first step towards describing \emph{in vivo} protein aggregation and interactions between synthetic materials and proteins. Using all atom molecular simulations in implicit solvent we illustrate the effects of nanoparticle size, shape, and volume fraction on oligomer formation of an amyloidogenic peptide from the transthyretin protein. Surprisingly, we find that inert spherical crowding particles destabilize in-register $\beta$-sheets formed by dimers while stabilizing $\beta$-sheets comprised of trimers and tetramers. As the radius of the nanoparticle increases crowding effects decrease, implying smaller crowding particles have the largest influence on the earliest amyloid species. We explain these results using a theory based on the depletion effect. Finally, we show that spherocylindrical crowders destabilize the ordered $\beta$-sheet dimer to a greater extent than spherical crowders, which underscores the influence of nanoparticle shape on protein aggregation.
The Emerging Role of Statins in Glaucoma Pathological Mechanisms and Therapeutics  [PDF]
O. Pokrovskaya, D. Wallace, C. OBrien
Open Journal of Ophthalmology (OJOph) , 2014, DOI: 10.4236/ojoph.2014.44021
Abstract: Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and hence have a profound effect in lowering serum cholesterol. Their predominant clinical use to date is in primary and secondary prevention of cardiovascular disease. However recently interest has developed regarding the so-called “pleiotropic” effects of statins—these drugs have significant anti-fibrotic, anti-inflammatory, and immunomodulatory properties. Such effects of statins have already been shown to be beneficial in modulating the pathological mechanisms involved in pul-monary fibrosis, renal disease, non-ischaemic cardiac failure, and tissue scarring. Many of these actions are mediated by inhibition of the Rho kinase pathway. Epidemiological studies suggest that patients who take statins have a lower risk of developing glaucoma, and lower rates of glaucoma progression. Here, we review what is known about the pleiotropic effect of statins to date, and examine how these effects may modulate the molecular mechanisms involved in glaucoma pathogenesis.
Case Study of High Blood Glucose Concentration Effects of 850 MHz Electromagnetic Fields Using Gtem Cell
Nattaphong Boriraksantikul;Kiran D. Bhattacharyya;Paul J. D. Whiteside;Christine O'Brien;Phumin Kirawanich;John A. Viator;Naz E. Islam
PIER B , 2012, DOI: 10.2528/PIERB12022015
Abstract: The effect of 850 MHz electromagnetic radiation on diabetic blood at 2 W and 60 W power levels was investigated and compared with normal blood cells. The power levels respectively represent radiations from a cell phone and the cell phone tower, both operating 850 MHz. A GTEM cell was designed for the tests to generate the desired uniform electromagnetic field and power in a shielded environment. Blood samples, having normal and high glucose concentrations, were placed in the usable area inside the GTEM cell for 10, 30, 60 minutes and the glucose levels and red and white blood cell viabilities were monitored and compared with the controls. Results show that the 850 MHz exposure significantly influences the blood cell counts and the glucose level in both normal and high glucose blood samples. In cell survivability analysis in normal blood samples it was found that the white blood cells are significantly higher than the control at 60 min exposure from cell phone radiation, while both the white and red blood cell are significantly higher following a 30 min exposure from tower radiation. For high glucose blood tests at 30 and 60 min exposure times, the tower radiation for 60 min and the cell phone radiation at both the exposure times show significantly changes in white blood cell counts, whereas there was no effect in red blood cells. Also, for 30 and 60 min exposure times, the glucose level in normal blood samples increased from cell phone radiation and decreased due to tower radiation. Finally, in high glucose blood samples, the glucose level decreased significantly for a 30 minute tower exposure, while the glucose level increased significantly for the cell phones exposure duration of 60 min and for tower exposure duration of 10 min. Electromagnetic radiation effects on cells can be better analyzed through a combination of the frequency, power and test duration as a single factor as opposed to the effects of frequency alone.
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