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Search Results: 1 - 10 of 464843 matches for " Owen A. Ross "
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Copy number variation in Parkinson's disease
Mathias Toft, Owen A Ross
Genome Medicine , 2010, DOI: 10.1186/gm183
Abstract: Traditional cytogenetic approaches first showed that variations in chromosome copy number could cause disease in humans. However, it is only with the recent advances in genome scanning technology that screening for human structural mutations and their role in disease susceptibility has really come into the limelight. Completion of the human genome project showed that copy number variation is a widespread and common phenomenon in humans [1]. A copy number variant (CNV) is a region of DNA in which allelic-number differences have been found by comparison of two or more independent genomes. These DNA segments may range from less than one kilobase (kb) to several megabases (Mb) in size and can be caused by genomic rearrangements such as deletions, multiplications, inversions and translocations [2]. The vast majority of CNVs are unbalanced, may be limited to a single gene or include a contiguous set of genes and can either be inherited or caused by de novo events. Altered expression levels of these CNV genes may be responsible for observed phenotypic variability, complex behavioral traits and disease susceptibility. So far, CNVs have been implicated in the pathogeneses of several neurological disorders, including Parkinson's disease (PD) [3,4].PD is a common neurodegenerative disorder affecting approximately 1% of the population aged over 60 years. The disease presents clinically as a movement disorder characterized by tremor at rest, bradykinesia, rigidity and postural instability. Neuropathological changes leading to a diagnosis of PD are dopaminergic cell loss in the substantia nigra accompanied by the formation of Lewy bodies, which are intracytoplasmic protein aggregates within the remaining neurons. The neuropathology associated with PD progresses over time, and in more advanced stages, patients develop a range of non-motor symptoms, including cognitive decline. Although drugs such a levodopa or surgical intervention (deep brain stimulation) can help alleviate the m
Landscape Scale Influences of Forest Area and Housing Density on House Loss in the 2009 Victorian Bushfires
Owen Price, Ross Bradstock
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073421
Abstract: Previous investigations into the factors associated with house loss in wildfires have focused on the house construction and its immediate environment (e.g. gardens). Here, we examine how nearby native forest and other houses can influence house loss. Specifically, we used a sample of 3500 houses affected by the Victorian bushfires of February 7th 2009 to explore how the amount of forest, proportion of forest burned by crown fire and the number of nearby houses affected house loss and how far from the house this influence was exerted. These fires were the most destructive in Australian history and so represent the extreme of fire risk. Using generalized linear modeling we found that the probability of house loss increased with forest extent and the proportion burnt by crown fire and this relationship was strongest for forest measured 1 km from the houses. Houses were more likely to be destroyed if there were other houses within 50 m and if they were on a slope. A model containing these variables predicted house loss with 72% accuracy. Our findings have three important implications: i) management to change the occurrence of crown fire will be effective in reducing house loss; ii) this management may be required up to 1 km away from houses in some situations (a much larger zone than is currently used); iii) high density of houses may increase risk of loss. Given the potentially large width of this management zone and the hazard from nearby houses, it may be more sensible to concentrate on modification of buildings to reduce their vulnerability.
Evaluation of the Role of SNCA Variants in Survival without Neurological Disease
Michael G. Heckman, Alexandra I. Soto-Ortolaza, Nancy N. Diehl, Minerva M. Carrasquillo, Ryan J. Uitti, Zbigniew K. Wszolek, Neill R. Graff-Radford, Owen A. Ross
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042877
Abstract: Background A variety of definitions of successful aging have been proposed, many of which relate to longevity, freedom from disease and disability, or preservation of high physical and cognitive function. Many behavioral, biomedical, and psychological factors have been linked with these various measures of successful aging, however genetic predictors are less understood. Parkinson's disease (PD) is an age-related neurodegenerative disorder, and variants in the α-synuclein gene (SNCA) affect susceptibility to PD. This exploratory study examined whether SNCA variants may also promote successful aging as defined by survival without neurological disease. Methods We utilized 769 controls without neurological disease (Mean age: 79 years, Range: 33–99 years) and examined the frequency of 20 different SNCA variants across age groups using logistic regression models. We also included 426 PD cases to assess the effect of these variants on PD risk. Results There was a significant decline in the proportion of carriers of the minor allele of rs10014396 as age increased (P = 0.021), from 30% in controls younger than 60 to 14% in controls 90 years of age or older. Findings were similar for rs3775439, where the proportion of carriers of the minor allele declined from 32% in controls less than 60 years old to 19% in those 90 or older (P = 0.025). A number of SNCA variants, not including rs10014396 or rs3775439, were significantly associated with susceptibility to PD. Conclusions In addition to its documented roles in PD and α-synucleinopathies, our results suggest that SNCA has a role in survival free of neurological disease. Acknowledging that our findings would not have withstood correction for multiple testing, validation in an independent series of aged neurologically normal controls is needed.
Polymorphic genes of detoxification and mitochondrial enzymes and risk for progressive supranuclear palsy: a case control study
Lisa F Potts, Alex C Cambon, Owen A Ross, Rosa Rademakers, Dennis W Dickson, Ryan J Uitti, Zbigniew K Wszolek, Shesh N Rai, Matthew J Farrer, David W Hein, Irene Litvan
BMC Medical Genetics , 2012, DOI: 10.1186/1471-2350-13-16
Abstract: DNA from 553 autopsy-confirmed Caucasian PSP cases (266 females, 279 males; age at onset 68 ± 8 years; age at death 75 ± 8) from the Society for PSP Brain Bank and 425 clinical control samples (197 females, 226 males; age at draw 72 ± 11 years) from healthy volunteers were genotyped using Taqman PCR and the SequenomiPLEX Gold assay.The proportion of NAT2 rapid acetylators compared to intermediate and slow acetylators was larger in cases than in controls (OR = 1.82, p < 0.05). There were no allelic or genotypic associations with PSP for any other SNPs tested with the exception of MAPT (p < 0.001).Our results show that NAT2 rapid acetylator phenotype is associated with PSP, suggesting that NAT2 may be responsible for activation of a xenobiotic whose metabolite is neurotoxic. Although our results need to be further confirmed in an independent sample, NAT2 acetylation status should be considered in future genetic and epidemiological studies of PSP.Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian disorder. Classically, patients present with progressive postural instability and falls followed by slow and hypometric vertical saccades and eventually vertical supranuclear gaze palsy.Neuropathologically, PSP is characterized by deposits of four-repeat microtubule associated protein tau (encoded by the MAPT gene) aggregates in neurons and glia of the basal ganglia and brain-stem [1]. Additionally, there is mitochondrial dysfunction, decreased ATP levels and inflammation in the brains of PSP patients [2-4]. The MAPT H1 haplotype has been consistently reported to be associated with PSP; however, it is also common in the general population, suggesting that gene-gene or gene-environment interactions are likely required for the development of this disease [5,6]. Recently, MAPT H1 was also associated with risk of Parkinson's disease (PD) suggesting shared pathways of disease [7]. Early-onset PD and PSP can present with a similar phenotype and be misdiagn
Radical Resection of Adult Low Grade Oligodendroglioma without Adjuvant Therapy: Results of a Prospective Treatment Protocol—Surgical Treatment of Low-Grade Oligodendroglioma  [PDF]
Donald A. Ross, Lynda Yang, Oren Sagher, Amy M. Ross
Journal of Cancer Therapy (JCT) , 2011, DOI: 10.4236/jct.2011.22030
Abstract: The goal of this work was to demonstrate prospectively that maximal surgical resection of low grade oligodendrogliomas without adjuvant therapy does not reduce life expectancy over that of historical controls. All patients with surgically accessible grade II oligodendrogliomas underwent maximal resection using stereotactic guidance and/or cortical mapping and were followed with serial MRI scans without adjuvant therapy until either progression or spread into brain regions deemed not surgically resectable. Nineteen patients were treated between 1993 and 2006. Ten patients required reoperation an average of 55 months after their first surgery. Nine patients progressed to anaplastic tumors an average of 42 months after their first surgery: six patients died from their tumors an average of 73 months after diagnosis, two are still alive 76 and 18 months after progression, and one was lost to follow up. Ten patients are alive and progression-free an average of 116 months after diagnosis, one of whom was lost to follow up at 106 months from diagnosis. Four patients are alive and event-free an average of 125 months after diagnosis. All are male and three had tumors in the superior frontal gyrus. The event-free survival, progression-free survival, and overall survival of our patients are not worse than those of patients treated with postoperative adjuvant therapy. Withholding adjuvant therapy at diagnosis appears to be safe. It will be important to establish the molecular differences between the patients who did very well and those who progressed so that adjuvant therapy could be offered to the latter.
Lobar Distribution of Low Grade Oligodendroglioma: Distribution, Molecular Characteristics, and Survival Based upon Location  [PDF]
Donald A. Ross, Shao Tao, Sakir Gultekin, Amy M. Ross
Journal of Cancer Therapy (JCT) , 2014, DOI: 10.4236/jct.2014.513126
Abstract:

Grade II oligodendrogliomas are rare and slow growing tumors, making long-term follow up difficult, but necessary for better understanding. In this retrospective study a review of all grade II oligodendrogliomas encountered in the last 20 years at one institution, was undertaken to determine if specific tumor location and immunohistochemical analysis had any impact on recurrence rate, progression free survival, or life expectancy. Eighty-nine grade II oligodendroglioms cases were reviewed (38 females and 51 males; mean age was 40.3 ± 13.8 years). Tumor location was: frontal lobe (44, 49.4%) and superior frontal gyrus (30, 33.7%). 1p19q data were available in 49 patients. Twenty-nine cases were co-deleted (59.2%). There was no significant difference in the incidence of 1p19q co-deletion between superior frontal gyrus tumors vs. other frontal tumors or extra-frontal tumors (p= 0.45). Follow up of at least 3 months after diagnosis was available in 79 patients (mean follow up: 93.2 months). In recurrence analysis, recurrence by 1p19q status and recurrence by location revealed no significant differences. In analysis of progression, progression by 1p19q status and progression by location revealed no significant differences. An analysis of deaths for the sample, deaths by 1p19q status and deaths by location revealed no significant differences. There was a higher death rate among patients >50 years of age, however this, too, was not significant.There did not appear to be any advantage in recurrence rate, progression free survival, or life expectancy for tumors located in the frontal lobe or superior frontal gyrus. 1p19q co-deletion did not appear to confer an advantage as measured by time to recurrence, time to progression, or overall survival. Other than age, eloquent location, Karnofsky status, and overall tumor size as reported by others, tumor location and 1p19q status in low grade oligodendrogliomas are not currently predictive of survival.

Resolving the Trophic Relations of Cryptic Species: An Example Using Stable Isotope Analysis of Dolphin Teeth
Kylie Owen,Kate Charlton-Robb,Ross Thompson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016457
Abstract: Understanding the foraging ecology and diet of animals can play a crucial role in conservation of a species. This is particularly true where species are cryptic and coexist in environments where observing feeding behaviour directly is difficult. Here we present the first information on the foraging ecology of a recently identified species of dolphin (Southern Australian bottlenose dolphin (SABD)) and comparisons to the common bottlenose dolphin (CBD) in Victoria, Australia, using stable isotope analysis of teeth. Stable isotope signatures differed significantly between SABD and CBD for both δ13C (?14.4‰ vs. ?15.5‰ respectively) and δ15N (15.9‰ vs. 15.0‰ respectively), suggesting that the two species forage in different areas and consume different prey. This finding supports genetic and morphological data indicating that SABD are distinct from CBD. In Victoria, the SABD is divided into two distinct populations, one in the large drowned river system of Port Phillip Bay and the other in a series of coastal lakes and lagoons called the Gippsland Lakes. Within the SABD species, population differences were apparent. The Port Phillip Bay population displayed a significantly higher δ15N than the Gippsland Lakes population (17.0‰ vs. 15.5‰), suggesting that the Port Phillip Bay population may feed at a higher trophic level - a result which is supported by analysis of local food chains. Important future work is required to further understand the foraging ecology and diet of this newly described, endemic, and potentially endangered species of dolphin.
Population Recovery following Decline in an Endangered Stream-Breeding Frog (Mixophyes fleayi) from Subtropical Australia
David Alan Newell, Ross Lindsay Goldingay, Lyndon Owen Brooks
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058559
Abstract: Amphibians have undergone dramatic declines and extinctions worldwide. Prominent among these have been the stream-breeding frogs in the rainforests of eastern Australia. The amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) has been postulated as the primary cause of these declines. We conducted a capture-mark-recapture study over a 7-year period on the endangered Fleay’s barred frog (Mixophyes fleayi) at two independent streams (30 km apart) in order to assess the stability of these populations. This species had undergone a severe decline across its narrow geographic range. Mark-recapture modelling showed that the number of individuals increased 3–10 fold along stream transects over this period. Frog detection probabilities were frequently above 50% but declined as the populations increased. Adult survival was important to overall population persistence in light of low recruitment events, suggesting that longevity may be a key factor in this recovery. One male and female were present in the capture record for >6 years. This study provides an unambiguous example of population recovery in the presence of Bd.
Non-supersymmetric smooth geometries and D1-D5-P bound states
Vishnu Jejjala,Owen Madden,Simon F. Ross,Georgina Titchener
Physics , 2005, DOI: 10.1103/PhysRevD.71.124030
Abstract: We construct smooth non-supersymmetric soliton solutions with D1-brane, D5-brane and momentum charges in type IIB supergravity compactified on T^4 x S^1, with the charges along the compact directions. This generalises previous studies of smooth supersymmetric solutions. The solutions are obtained by considering a known family of U(1) x U(1) invariant metrics, and studying the conditions imposed by requiring smoothness. We discuss the relation of our solutions to states in the CFT describing the D1-D5 system, and describe various interesting features of the geometry.
Mathematical table turning revisited
Bill Baritompa,Rainer L"owen,Burkard Polster,Marty Ross
Mathematics , 2005,
Abstract: We investigate under which conditions a rectangular table can be placed with all four feet touching a continuous ground by turning it on the spot.
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