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Search Results: 1 - 10 of 11758 matches for " Laura Sauerbeck "
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The Familial Intracranial Aneurysm (FIA) study protocol
Joseph P Broderick, Laura R Sauerbeck, Tatiana Foroud, John Huston, Nathan Pankratz, Irene Meissner, Robert D Brown
BMC Medical Genetics , 2005, DOI: 10.1186/1471-2350-6-17
Abstract: The FIA Study includes 26 clinical centers which have extensive experience in the clinical management and imaging of intracerebral aneurysms. 475 families with affected sib pairs or with multiple affected relatives will be enrolled through retrospective and prospective screening of potential subjects with an IA. After giving informed consent, the proband or their spokesperson invites other family members to participate. Each participant is interviewed using a standardized questionnaire which covers medical history, social history and demographic information. In addition blood is drawn from each participant for DNA isolation and immortalization of lymphocytes. High- risk family members without a previously diagnosed IA undergo magnetic resonance angiography (MRA) to identify asymptomatic unruptured aneurysms. A 10 cM genome screen will be performed to identify FIA susceptibility loci. Due to the significant mortality of affected individuals, novel approaches are employed to reconstruct the genotype of critical deceased individuals. These include the intensive recruitment of the spouse and children of deceased, affected individuals.A successful, adequately-powered genetic linkage study of IA is challenging given the very high, early mortality of ruptured IA. Design features in the FIA Study that address this challenge include recruitment at a large number of highly active clinical centers, comprehensive screening and recruitment techniques, non-invasive vascular imaging of high-risk subjects, genome reconstruction of dead affected individuals using marker data from closely related family members, and inclusion of environmental covariates in the statistical analysis.Stroke is the third leading cause of death and the leading cause of disability among adults. Subarachnoid hemorrhage (SAH) due to rupture of IAs is one of the three main subtypes of stroke. The incidence of SAH as well as its 30-day mortality has remained stable for over 3 decades despite advances in diagno
Subarachnoid hemorrhage: tests of association with apolipoprotein E and elastin genes
Ritesh Kaushal, Daniel Woo, Prodipto Pal, Mary Haverbusch, Huifeng Xi, Charles Moomaw, Padmini Sekar, Brett Kissela, Dawn Kleindorfer, Matthew Flaherty, Laura Sauerbeck, Ranajit Chakraborty, Joseph Broderick, Ranjan Deka
BMC Medical Genetics , 2007, DOI: 10.1186/1471-2350-8-49
Abstract: At the APOE locus, no individual SNP was associated with SAH after correction for multiple comparisons. Haplotype analysis revealed significant association of the major haplotype (Hap1) in APOE with SAH (p = 0.001). The association stemmed from both the 5' promoter and the 3' region of the APOE gene. APOE ε2 and ε 4 were not significantly associated with SAH. No association was observed for ELN at genotype, allele, or haplotype level and our study failed to confirm previous reports of ELN association with aneurysmal SAH.This study suggests a role of the APOE gene in the etiology of aneurysmal SAH.Non-traumatic, spontaneous subarachnoid hemorrhage (SAH) affects 16,000 to 17,000 individuals each year in the United States [1-3]. SAH has a 30-day mortality rate exceeding 40%, and surviving patients often demonstrate significant morbidity [2,4]. Over 80% of SAH can be attributed to intracranial aneurysm (IA) rupture. Familial aggregation studies of SAH have consistently identified an increased risk of a first-degree relative with SAH or family history of SAH independent of smoking and hypertension [5].Variants of the apolipoprotein E (APOE) gene have been associated with Alzheimer's disease, lipid disorders and cardiovascular disease [6-8]. Previous studies have demonstrated that APOE ε4 and/or APOE ε2 are associated with lobar intracerebral hemorrhage (ICH) [9,10]. We recently reported that haplotypes which include polymorphisms in the 5' untranslated region of the APOE gene are risk factors for lobar ICH [11]. Specific to SAH, Kokubo et al. [12] found significant association of APOE ε4 with SAH in a Japanese population. Niskakangas et al. [13] reported association of APOE ε4 with adverse outcome after aneurysmal SAH. No study on other polymorphisms of APOE with regard to risk of SAH has yet been reported.In addition to APOE, the elastin (ELN) gene emerged as a putative gene for IA after linkage was found on 7q11, where ELN is located [14]. However, prior association st
Mitochondria, Amyloid β, and Alzheimer's Disease
Ryan D. Readnower,Andrew D. Sauerbeck,Patrick G. Sullivan
International Journal of Alzheimer's Disease , 2011, DOI: 10.4061/2011/104545
Abstract: Hypometabolism is a hallmark of Alzheimer's disease (AD) and implicates a mitochondrial role in the neuropathology associated with AD. Mitochondrial amyloid-beta (Aβ) accumulation precedes extracellular Aβ deposition. In addition to increasing oxidative stress, Aβ has been shown to directly inhibit mitochondrial enzymes. Inhibition of mitochondrial enzymes as a result of oxidative damage or Aβ interaction perpetuates oxidative stress and leads to a hypometabolic state. Additionally, Aβ has also been shown to interact with cyclophilin D, a component of the mitochondrial permeability transition pore, which may promote cell death. Therefore, ample evidence exists indicating that the mitochondrion plays a vital role in the pathophysiology observed in AD. 1. Introduction The incidence of Alzheimer’s disease (AD) in the US is expected to increase to as many as 13.2 million by 2050 [1]. AD pathology is characterized by the progressive accumulation of senile plaques (consisting of amyloid β-peptide, Aβ) and neurofibrillary tangles (consisting of aggregates of the microtubule-associated protein tau). Oxidative damage has been implicated to play an early role in the pathogenesis of AD [2]. In AD patients a significant decrease in energy metabolism is observed in the frontal and temporal lobes as indicated by in vivo positron emission tomography (PET) [3]. Correlated with this increase in oxidative damage and decrease in energy metabolism is a decrease in mitochondrial enzyme (cytochrome c oxidase, pyruvate dehydrogenase, α-ketoglutarate dehydrogenase) activity in AD patients [4–6]. Mitochondrial dysfunction has been shown to play a key role in age-related neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease [7]. Mitochondria produce the majority of ATP in cells and function to maintain Ca2+ homeostasis. Mitochondria produce ATP by coupling electron transfer to the pumping of protons across the inner mitochondrial membrane. However, electrons can escape the electron transport chain and reduce oxygen to form reactive oxygen species (ROS). Oxidative damage results from a disturbance in the ROS-antioxidant balance that favors oxidation. Oxidative damage to mitochondria may be especially relevant in neurodegenerative disease since mitochondria are regulators of both cellular metabolism and apoptosis [8]. 2. Mitochondrial Enzyme Oxidative Damage and ROS Production A hallmark of AD is hypometabolism which, importantly, precedes the clinical presentation of the disease [9, 10]. Early studies utilizing PET indicated that brain metabolism
Genome screen in familial intracranial aneurysm
Tatiana Foroud, Laura Sauerbeck, Robert Brown, Craig Anderson, Daniel Woo, Dawn Kleindorfer, Matthew L Flaherty, Ranjan Deka, Richard Hornung, Irene Meissner, Joan E Bailey-Wilson, Carl Langefeld, Guy Rouleau, E Sander Connolly, Dongbing Lai, Daniel L Koller, John Huston, Joseph P Broderick, the FIA Study Investigators [Familial Intracranial Aneurysm Study Investigators]
BMC Medical Genetics , 2009, DOI: 10.1186/1471-2350-10-3
Abstract: Families with multiple members having ruptured or unruptured IA were recruited and all available medical records and imaging data were reviewed to classify possible IA subjects as definite, probable or possible IA or not a case. A 6 K SNP genome screen was performed in 333 families, representing the largest linkage study of IA reported to date. A 'narrow' (n = 705 definite IA cases) and 'broad' (n = 866 definite or probable IA) disease definition were used in multipoint model-free linkage analysis and parametric linkage analysis, maximizing disease parameters. Ordered subset analysis (OSA) was used to detect gene × smoking interaction.Model-free linkage analyses detected modest evidence of possible linkage (all LOD < 1.5). Parametric analyses yielded an unadjusted LOD score of 2.6 on chromosome 4q (162 cM) and 3.1 on chromosome 12p (50 cM). Significant evidence for a gene × smoking interaction was detected using both disease models on chromosome 7p (60 cM; p ≤ 0.01). Our study provides modest evidence of possible linkage to several chromosomes.These data suggest it is unlikely that there is a single common variant with a strong effect in the majority of the IA families. Rather, it is likely that multiple genetic and environmental risk factors contribute to the susceptibility for intracranial aneurysms.Subarachnoid hemorrhage due to the rupture of an intracranial aneurysm (IA) occurs in 16,000 to 17,000 persons in the U.S. annually and nearly half of affected persons are dead within the first 30 days. There are several important factors which modulate the risk of SAH. The incidence of SAH increases moderately with advancing age and it is the only stroke subtype in which women have a higher age-adjusted risk of SAH as compared to men [1]. Cigarette smoking has consistently been identified as the most important modifiable risk factor for SAH [2] with an average odds ratio of 3.1 [2,3]. In population-based and cohort studies, 70–75% of persons with SAH have a prior hist
Combining Public Key Encryption with Schnorr Digital Signature  [PDF]
Laura Savu
Journal of Software Engineering and Applications (JSEA) , 2012, DOI: 10.4236/jsea.2012.52016
Abstract: This article presents a new signcryption scheme which is based on the Schnorr digital signature algorithm. The new scheme represents my personal contribution to signcryption area. I have implemented the algorithm in a program and here are provided the steps of the algorithm, the results and some examples. The paper also contains the presentation of the original Signcryption scheme, based on ElGamal digital signature and discusses the practical applications of Signcryption in real life. The purpose of the study is to combine the public key encryption with Schnorr digital signature in order to obtain less computational and communicational costs. Signcryption primitive is a better approach then Encrypt-then-Sign or Sign-then-Encrypt methods regarding the costs. All these algorithms offer the possibility to transmit a message over an insecure channel providing both authenticity and confidentiality.
Practical Stabilization for Uncertain Pseudo-Linear and Pseudo-Quadratic MIMO Systems  [PDF]
Laura Celentano
International Journal of Modern Nonlinear Theory and Application (IJMNTA) , 2013, DOI: 10.4236/ijmnta.2013.21004

In this paper the problem of practical stabilization for a significant class of MIMO uncertain pseudo-linear and pseudo-quadratic systems, with additional bounded nonlinearities and/or bounded disturbances, is considered. By using the concept of majorant system, via Lyapunov approach, new fundamental theorems, from which derive explicit formulas to design state feedback control laws, with a possible imperfect compensation of nonlinearities and disturbances, are stated. These results guarantee a specified convergence velocity of the linearized system of the majorant system and a desired steady-state output for generic uncertainties and/or generic bounded nonlinearities and/or bounded disturbances.

Book Announcement of L. Celentano, Robust Tracking Controllers Design with Generic References for Continuous and Discrete Uncertain Linear SISO Systems, LAP LAMBERT Academic Publishing, 2012  [PDF]
Laura Celentano
International Journal of Modern Nonlinear Theory and Application (IJMNTA) , 2014,

In this book new results on controller design techniques for the tracking of generic reference inputs are presented. They allow the design of a controller for an uncertain process, either continuous or discrete-time, without zeros, and with measurable state. The controller guarantees that the control system is Type 1 and has the desired constant gain and poles or that the control system tracks, with a specified maximum error and with a specified maximum time constant, a generic reference with bounded derivative (variation in the discrete-time case), also in the presence of a generic disturbance with bounded derivative (variation). In addition, it is considered the case in which the reference is known a priori.

The utility and the efficiency of the proposed methods are illustrated with attractive and significant examples of motion control and temperature control.

This book is useful for the design of control systems, especially for manufacturing systems, that are versatile, fast, precise and robust.

Gender in the American Anthology Apparatus: A Linguistic Analysis  [PDF]
Laura Aull
Advances in Literary Study (ALS) , 2014, DOI: 10.4236/als.2014.21008

Most American anthology and canon revision has focused on author and text selections but little on the anthology editorial apparatus. The following study responds to this gap by analyzing gender representation across prefaces and overviews of the Norton and Heath American anthologies (1979-2010). Through a combined rhetorical and corpus linguistic analysis, the study reveals disparate gender representation in these materials: women are increasingly mentioned over time, but men continue to emerge as individuals of importance while women are discussed primarily as a group. This examination suggests that the revisionist, feminist scrutiny of Norton and Heath inventory has not been brought to bear on the anthologies’ apparatus—and that discursive patterns therein remain largely invisible despite that they contradict efforts to revise gender bias in anthologies. In so doing, the study offers an exploratory analysis of new methods (combined linguistic and rhetorical analysis) and new sites (apparatus texts) for examining gender in canonical and pedagogical materials.

Does the Month of Birth Influence the Timing of Life Course Decisions? Evidence from a Natural Experiment in Italy  [PDF]
Laura Cavalli
Open Journal of Social Sciences (JSS) , 2014, DOI: 10.4236/jss.2014.21011
Abstract: Social scientists have observed for a long time a negative relationship between the time spent on education and the timing of family formation. Using data from the I.D.E.A. survey (2003), a birth-month experiment on a sample of 3000 young Italian adults is employed in order to explore whether a different month of birth leads to regular differences in life course decisions of young Italians. The results suggest that the “social” age, as determined by the school cohort, rather than the biological age, is an important determinant of the timing of demographic events during the transition to adulthood.
Controversial Theories on the Death Penalty  [PDF]
Laura Zavatta
Beijing Law Review (BLR) , 2017, DOI: 10.4236/blr.2017.82012
Abstract: The question of the right to carry firearms, but especially abolishing the death penalty, had a tremendous impact on the intellectual and political community of the whole world with the ideas of Beccaria that stimulated the urgency also of the founding fathers of the various American colonies to give life to the new Constitutions reforming the existing criminal law and proceeding to the elimination of the capital punishment in many cases. However, after about two hundred and fifty years, the death penalty, which seemed destined to be abolished by the end of the eighteenth century, is still in use in the American legal system and a great subject of debate, despite several Supreme Court rulings. Even in Italy, the period that preceded its unification, was marked by a return to the past with regard to the penal system and the conception of the death penalty. Similarly, although the European continent is “death penalty free”, and the modern criminal law is generally constituted from its rejection of torture, in recent years, with the escalation of acts of terrorism and global tension, it seems to reoccur the relationship between torture and right, as if it was a reconciliation between two old friends and a strategy to re-legalize torture.
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