High functioning male with fragile X syndrome and fragile X-associated tremor/ataxia syndrome.

Science.gov (United States)

Basuta, Kirin; Schneider, Andrea; Gane, Louise; Polussa, Jonathan; Woodruff, Bryan; Pretto, Dalyir; Hagerman, Randi; Tassone, Flora

2015-09-01

Fragile X syndrome (FXS) affects individuals with more than 200 CGG repeats (full mutation) in the fragile X mental retardation 1 (FMR1) gene. Those born with FXS experience cognitive and social impairments, developmental delays, and some features of autism spectrum disorders. Carriers of a premutation (55-200 CGG repeats) are generally not severely affected early in life; however, are at high risk of developing the late onset neurodegenerative disorder, Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), or Fragile X-associated Primary Ovarian Insufficiency (FXPOI), and may have other medical conditions such as developmental delay, autism spectrum disorders, hypertension, anxiety, and immune-mediated disorders. Here we present a case of a 58-year-old man with a borderline IQ, average memory skills, and executive function deficits. He met criteria for multiple psychiatric diagnoses and presented with tremor and ataxia, meeting criteria for FXTAS. Molecular testing unveiled a completely unmethylated FMR1 full mutation in peripheral blood mononucleated cells with elevated FMR1 mRNA and premutation alleles of different sizes in two other tissues (primary fibroblasts and sperm), indicating the presence of allele instability based on both inter- and intra-tissue mosaicism. The observation of FXTAS in this case of a full mutation mosaic man suggests that the pathogenic mechanism underlying this disorder is not observed exclusively in premutation carriers as it was originally thought. The concomitant presence of features of FXS and late onset neurological deterioration with probable FXTAS likely result from a combined molecular pathology of elevated FMR1 mRNA levels, a molecular hallmark of FXTAS and low FMRP expression that leads to FXS. © 2015 Wiley Periodicals, Inc.

Fragility correlates thermodynamic and kinetic properties of glass forming liquids

Energy Technology Data Exchange (ETDEWEB)

Reddy, C.Narayana [Maharani’s Science College for Women, Bangalore 560001 (India); Viswanatha, R.; Chethana, B.K. [Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012 (India); Gowda, V.C.Veeranna [Government First Grade College, Jayanagara, Bangalore 560070 (India); Rao, K.J., E-mail: kalyajrao@yahoo.co.in [Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012 (India)

2015-03-15

Graphical abstract: The suggested new fragility parameter correlates viscosity and configurational entropy. - Highlights: • A new fragility function, F=ΔT/ΔC{sub p}×C{sub p}{sup l}/T{sub g} has been proposed. • A three parameter viscosity function using the new F reproduces Angell fragility plot. • A new ΔC{sub p} function is derived which directly relates Adam–Gibbs function with the fragility based viscosity function. - Abstract: In our earlier communication we proposed a simple fragility determining function, ([NBO]/V{sub m}{sup 3}T{sub g}), which we have now used to analyze several glass systems using available thermal data. A comparison with similar fragility determining function, ΔC{sub p}/C{sub p}{sup l}, introduced by Chryssikos et al. in their investigation of lithium borate glasses has also been performed and found to be more convenient quantity for discussing fragilities. We now propose a new function which uses both ΔC{sub p} and ΔT and which gives a numerical fragility parameter, F whose value lies between 0 and 1 for glass forming liquids. F can be calculated through the use of measured thermal parameters ΔC{sub p}, C{sub p}{sup l}, T{sub g} and T{sub m}. Use of the new fragility values in reduced viscosity equation reproduces the whole range of viscosity curves of the Angell plot. The reduced viscosity equation can be directly compared with the Adam–Gibbs viscosity equation and a heat capacity function can be formulated which reproduces satisfactorily the ΔC{sub p} versus ln(T{sub r}) curves and hence the configurational entropy.

[Relationship between previous severity of illness and outcome of in-hospital cardiac arrest].

Science.gov (United States)

Serrano, M; Rodríguez, J; Espejo, A; del Olmo, R; Llanos, S; Del Castillo, J; López-Herce, J

2014-07-01

To analyze the relationship between previous severity of illness, lactic acid, creatinine and inotropic index with mortality of in-hospital cardiac arrest (CA) in children, and the value of a prognostic index designed for adults. The study included total of 44 children aged from 1 month to 18 years old who suffered a cardiac arrest while in hospital. The relationship between previous severity of illness scores (PRIMS and PELOD), lactic acid, creatinine, treatment with vasoactive drugs, inotropic index with return of spontaneous circulation and survival at hospital discharge was analyzed. The large majority (90.3%) of patients had a return of spontaneous circulation, and 59% survived at hospital discharge. More than two-thirds (68.2%) were treated with inotropic drugs at the time of the CA. The patients who died had a higher lactic acid before the CA (3.4 mmol/L) than survivors (1.4 mmol/L), P=.04. There were no significant differences in PRIMS, PELOD, creatinine, inotropic drugs, and inotropic index before CA between patients who died and survivors. A high lactic acid previous to cardiac arrest could be a prognostic factor of in-hospital cardiac arrest in children. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Ectodermal Dysplasia Skin Fragility Syndrome

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Ayça Alan Atalay

2014-06-01

Full Text Available Ectodermal dysplasia-skin fragility syndrome (EDSFS is a rare autosomal recessive genodermatosis first described in 1997 by Mc Grath. EDSFS results from loss of function mutations in plakophilin-1 (PKP1. PKP1 is a structural component of desmosomes, cellcell adhesion complexes. It is also found as a nuclear protein in several cell types that are lack of desmosomes. In skin, however, PKP1 expression is confined mainly to suprabasal keratinocytes and the outer root sheath of hair follicules. Loss of function mutation in PKP1 leads to extensive skin fragility, bullae and erosions following minor trauma, focal keratoderma with painful fissures, alopecia, and nail dystrophy. In some patients hypohidrosis may also be seen. EDSFS is now considered as a specific suprabasal form of epidermolysis bullosa simplex. In this report we describe a 20 year old EDSFS case.

Fragile X-associated tremor/ataxia syndrome: another phenotype of the fragile X gene.

Science.gov (United States)

Hessl, David; Grigsby, Jim

2016-08-01

Neuropsychologists have an important role in evaluating patients with fragile X-associated disorders, but most practitioners are unaware of the recently identified neurodegenerative movement disorder known as fragile X-associated tremor ataxia syndrome (FXTAS). The objective of this editorial is to orient the reader to FXTAS and highlight the importance of clinical neuropsychology in describing the fragile X premutation phenotype and the role practitioners may have in assessing and monitoring patients with or at risk for neurodegeneration. We issued a call for papers for the special issue, highlighting the primary objective of familiarizing clinical neuropsychologists with FXTAS, and with the neuropsychological phenotype of both male and female asymptomatic carriers. Eight papers are included, including an overview of the fragile X-associated disorders (Grigsby), a review of the neuroradiological and neurological aspects of FXTAS and how the disorder compares to other movement disorders (O'Keefe et al.), a perspective on the prominence of white matter disease and dementia in FXTAS (Filley), and a review of mouse models of FXTAS (Foote). There are four research papers, including one on self-reported memory problems in FXTAS (Birch et al.), and three papers focused on the neuropsychiatric aspects of the fragile X premutation, a review (Bourgeois), an examination of autism-related traits (Schneider), and a research paper on executive functioning and psychopathology (Grigsby). The issue highlights the importance of awareness of fragile X-associated disorders for neuropsychologists, an awareness that must reach beyond neurodevelopmental aspects related to fragile X syndrome into the realm of neurodegenerative disease and aging.

Influence of carbide precipitation upon hydrogen fragilization of an AISI 304 steel

International Nuclear Information System (INIS)

Hazarabedian, A.E.; Ovejero Garcia, J.

1991-01-01

The present work deals with austenitic stainless steels for a family of steels that is renowned for its high resistance to hydrogen fragilization. Nevertheless, these steels may suffer hydrogen fragilization under severe working conditions. This fact is strongly dependent on many factors -composition, grain size, other phases present, corrosion sensitivity, etc.-. While there are studies that show how intergranular corrosion is influenced by corrosion sensitivity -mainly due to carbide precipitation in grain boundaries-, there are no reports about the effect of the carbide precipitation itself on hydrogen fragilization for these steels. (Author) [es

Fluorescent in-situ hybridization of cattle and sheep chromosomes with cloned human fragile-X DNA

DEFF Research Database (Denmark)

Ali, Ahmd; Thomsen, Preben Dybdahl; Babar, M.E.

2009-01-01

An extensive study on spontaneous and 5-Fluorodeoxyuridine induced fragile sites identified Xq31 in cattle (Bos taurus) and (Xq24, Xq26) in sheep (Ovis aries) in addition to several autosomal fragile sites (under publication). A ZOO-FISH study using three cloned human fragile-X probes with CCG....../CGG(n) trinucleotide repeat sequence was carried out to determine homology between human and bovine fragile-X. The hybridisation results showed only a weak signal on a human chromosome that was not an X with all three fragile site probes. No signals were detected in sheep chromosomes. The signal of all three human...... fragile-X probes on cattle chromosomes was however, medium-prominent sub-centromeric signal on two homologues. BrdU administration in 12 h before harvesting identified these homologues to be chromosome number 5. In addition retrospective slides of cattle and sheep chromosomes used for fragile site studies...

The highly fragile glass former Decalin

International Nuclear Information System (INIS)

Eibl, Stefan

2009-01-01

Systems exhibiting the glass transition can be classified by fragility. In this work we studied structural and dynamical aspects of highly fragile C 10 H 18 Decalin. Trans Decalin is locked into a pseudo-flat centrosymmetric conformation, while cis Decalin interchanges dynamically between chiral, pseudo-spherical ground states. On investigation of the phase behaviour trans Decalin was found to crystallise rapidly and cleanly; its crystal structure could be determined. From the crystal structure the dynamics of crystalline trans Decalin could be calculated using ab-initio lattice energy calculations and compared to measurements. Using neutron diffraction and molecular dynamics simulations the amorphous structure of Decalin was investigated. The difference in structure to the common molecular liquid Cumene is significant. The features of the amorphous structure of sphere-like cis Decalin show strong resemblance to the ones of Argon and metallic glasses. The dynamics of Decalin were investigated in the slightly supercooled liquid range. Using neutron scattering and optical spectroscopy, data was collected for a wide spectral range and several temperatures. The data suggests high fragility for the generic Decalin mixture, which is in agreement with the reported results. By contrast to previous estimations, an extrapolation of our data indicates cis Decalin to be only slightly less fragile than the generic mixture. Finally a lower limit to the four point susceptibility function χ 4 could be calculated and the number of correlated molecules determined. The evolution of this value as a function of T g /T and relaxation time are in agreement with literature. (author) [fr

Genetics Home Reference: fragile X syndrome

Science.gov (United States)

... Facebook Twitter Home Health Conditions Fragile X syndrome Fragile X syndrome Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Fragile X syndrome is a genetic condition that causes a ...

Study on the fragility of structure with several elements in its story. Part 2: structure with ductile elements

International Nuclear Information System (INIS)

Kai, Y.; Fukushima, S.

1995-01-01

The relationship among the fragility of element, that of story and that of system, is examined using the Monte Carlo simulation. In this study, 2-story models whose stories consist of 2 ductile elements are employed. A method is proposed which includes a nonlinear effect into the evaluation of elements capacities. This method does not require the nonlinear MCS, therefore saving computational efforts. Also, a method to estimate the stories and the system fragilities is proposed. (author). 2 refs., 7 figs., 3 tabs

X-ray diagnosis and treatment for severe respiratory complications during cardiac catheterizations on pediatric congenital heart disease

International Nuclear Information System (INIS)

Wang Cheng; Zhao Shihua; Jiang Shiliang; Huang Lianjun; Xu Zhongying; Ling Jian; Zheng Hong; Xie Ruolan; Lu Minjie

2005-01-01

Objective: To study the radiological features of severe respiratory complications during cardiac catheterizations on pediatric congenital heart disease so as to make early diagnosis and treatment. We also intend to find the mechanism of these complications. Methods: A total of 9 pediatric cases with severe respiratory complications during cardiac catheterizations were included in the study. The clinical manifestations, radiological features, and corresponding treatments were reviewed. Results: Most of the cases had severe hypoxia, with 6 cases presenting with bradycardia. Opacification of two lung fields was found in 7 cases, pulmonary edema in 1 case, and atelectasis of the upper right lung in 1 case. With intubation, oxygen inhalation and administration of certain drugs, all cases were saved except 1 case with pulmonary edema. Conclusion: Severe respiratory complications during cardiac catheterizations on pediatric congenital heart disease are emergent and critical, and they often presented with various manifestations. Early diagnosis and correct treatment are the key to successful salvage. (authors)

Systems fragility: The sociology of chaos.

Science.gov (United States)

Hodges, Lori R

2016-01-01

This article examines the concept of community fragility in emergency management from a systems perspective. Using literature that addresses fragility in four areas of complex systems, including ecosystems, social systems, sociotechnical systems, and complex adaptive systems, a theoretical framework focused on the emergency management field is created. These findings illustrate how community fragility factors can be used in the emergency management field to not only improve overall outcomes after disaster but also build less fragile systems and communities in preparation for future disasters.

Seismic fragility analyses of nuclear power plant structures based on the recorded earthquake data in Korea

International Nuclear Information System (INIS)

Joe, Yang Hee; Cho, Sung Gook

2003-01-01

This paper briefly introduces an improved method for evaluating seismic fragilities of components of nuclear power plants in Korea. Engineering characteristics of small magnitude earthquake spectra recorded in the Korean peninsula during the last several years are also discussed in this paper. For the purpose of evaluating the effects of the recorded earthquake on the seismic fragilities of Korean nuclear power plant structures, several cases of comparative studies have been performed. The study results show that seismic fragility analysis based on the Newmark's spectra in Korea might over-estimate the seismic capacities of Korean facilities. (author)

Fragile X syndrome and fragile X-associated disorders [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Akash Rajaratnam

2017-12-01

Full Text Available Fragile X syndrome (FXS is caused by a full mutation on the FMR1 gene and a subsequent lack of FMRP, the protein product of FMR1. FMRP plays a key role in regulating the translation of many proteins involved in maintaining neuronal synaptic connections; its deficiency may result in a range of intellectual disabilities, social deficits, psychiatric problems, and dysmorphic physical features. A range of clinical involvement is also associated with the FMR1 premutation, including fragile X-associated tremor ataxia syndrome, fragile X-associated primary ovarian insufficiency, psychiatric problems, hypertension, migraines, and autoimmune problems. Over the past few years, there have been a number of advances in our knowledge of FXS and fragile X-associated disorders, and each of these advances offers significant clinical implications. Among these developments are a better understanding of the clinical impact of the phenomenon known as mosaicism, the revelation that various types of mutations can cause FXS, and improvements in treatment for FXS.

Positron Emission Tomography (PET Quantification of GABAA Receptors in the Brain of Fragile X Patients.

Directory of Open Access Journals (Sweden)

Charlotte D'Hulst

Full Text Available Over the last several years, evidence has accumulated that the GABAA receptor is compromised in animal models for fragile X syndrome (FXS, a common hereditary form of intellectual disability. In mouse and fly models, agonists of the GABAA receptor were able to rescue specific consequences of the fragile X mutation. Here, we imaged and quantified GABAA receptors in vivo in brain of fragile X patients using Positron Emission Topography (PET and [11C]flumazenil, a known high-affinity and specific ligand for the benzodiazepine site of GABAA receptors. We measured regional GABAA receptor availability in 10 fragile X patients and 10 control subjects. We found a significant reduction of on average 10% in GABAA receptor binding potential throughout the brain in fragile X patients. In the thalamus, the brain region showing the largest difference, the GABAA receptor availability was even reduced with 17%. This is one of the first reports of a PET study of human fragile X brain and directly demonstrates that the GABAA receptor availability is reduced in fragile X patients. The study reinforces previous hypotheses that the GABAA receptor is a potential target for rational pharmacological treatment of fragile X syndrome.

Three Faces of Fragile X.

Science.gov (United States)

Lieb-Lundell, Cornelia C E

2016-11-01

Fragile X syndrome (FXS) is the first of 3 syndromes identified as a health condition related to fragile X mental retardation (FMR1) gene dysfunction. The other 2 syndromes are fragile X-associated primary ovarian insufficiency syndrome (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS), which together are referred to as fragile X-associated disorders (FXDs). Collectively, this group comprises the 3 faces of fragile X. Even though the 3 conditions share a common genetic defect, each one is a separate health condition that results in a variety of body function impairments such as motor delay, musculoskeletal issues related to low muscle tone, coordination limitations, ataxia, tremor, undefined muscle aches and pains, and, for FXTAS, a late-onset neurodegeneration. Although each FXD condition may benefit from physical therapy intervention, available evidence as to the efficacy of intervention appropriate to FXDs is lacking. This perspective article will discuss the genetic basis of FMR1 gene dysfunction and describe health conditions related to this mutation, which have a range of expressions within a family. Physical therapy concerns and possible assessment and intervention strategies will be introduced. Understanding the intergenerational effect of the FMR1 mutation with potential life-span expression is a key component to identifying and treating the health conditions related to this specific genetic condition. © 2016 American Physical Therapy Association.

Validity of Type D personality in Iceland: association with disease severity and risk markers in cardiac patients

OpenAIRE

Svansdottir, Erla; Karlsson, Hrobjartur D.; Gudnason, Thorarinn; Olason, Daniel T.; Thorgilsson, Hordur; Sigtryggsdottir, Unnur; Sijbrands, Eric J.; Pedersen, Susanne S.; Denollet, Johan

2011-01-01

textabstractType D personality has been associated with poor prognosis in cardiac patients. This study investigated the validity of the Type D construct in Iceland and its association with disease severity and health-related risk markers in cardiac patients. A sample of 1,452 cardiac patients completed the Type D scale (DS14), and a subgroup of 161 patients completed measurements for the five-factor model of personality, emotional control, anxiety, depression, stress and lifestyle factors. Th...

Fragility and hysteretic creep in frictional granular jamming.

Science.gov (United States)

Bandi, M M; Rivera, M K; Krzakala, F; Ecke, R E

2013-04-01

The granular jamming transition is experimentally investigated in a two-dimensional system of frictional, bidispersed disks subject to quasistatic, uniaxial compression without vibrational disturbances (zero granular temperature). Three primary results are presented in this experimental study. First, using disks with different static friction coefficients (μ), we experimentally verify numerical results that predict jamming onset at progressively lower packing fractions with increasing friction. Second, we show that the first compression cycle measurably differs from subsequent cycles. The first cycle is fragile-a metastable configuration with simultaneous jammed and unjammed clusters-over a small packing fraction interval (φ(1)disk displacements over the same packing fraction interval. This fragile behavior is explained through a percolation mechanism of stressed contacts where cluster growth exhibits spatial correlation with disk displacements and contributes to recent results emphasizing fragility in frictional jamming. Control experiments show that the fragile state results from the experimental incompatibility between the requirements for zero friction and zero granular temperature. Measurements with several disk materials of varying elastic moduli E and friction coefficients μ show that friction directly controls the start of the fragile state but indirectly controls the exponential pressure rise. Finally, under repetitive loading (compression) and unloading (decompression), we find the system exhibits pressure hysteresis, and the critical packing fraction φ(c) increases slowly with repetition number. This friction-induced hysteretic creep is interpreted as the granular pack's evolution from a metastable to an eventual structurally stable configuration. It is shown to depend on the quasistatic step size Δφ, which provides the only perturbative mechanism in the experimental protocol, and the friction coefficient μ, which acts to stabilize the pack.

Medical Image of the Week: Cardiac Magnetic Resonance Imaging Findings of Severe RV Failure

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Wickstrom K

2018-05-01

Full Text Available No abstract available. Article truncated at 150 words. A 56-year-old man with history a of alcohol abuse presents with progressive shortness of breath on exertion, bilateral lower extremity swelling and 12-pound weight gain over two weeks. His transthoracic echocardiography (Figure 1 demonstrated severely increased global right ventricle (RV size, severely dilated right atrium (RA, severe pulmonary artery (PA dilation, moderate tricuspid regurgitation (TR and right ventricular systolic pressure (RVSP estimated at 85 + central venous pressure (CVP in the context of severely reduced RV systolic function. Right heart catheterization (RHC showed PA pressure (systolic/diastolic, mean of 94/28, 51 mmHg with a PA occlusion pressure of 12 mmHg. After extensive evaluation, our patient’s presentation of right heart failure seemed to be a manifestation of idiopathic pulmonary arterial hypertension. Our patient subsequently had cardiac MRI (cMRI with findings shown above (Figure 2. CMRI is a valuable, three-dimensional imaging modality that provides detailed morphology of the cardiac chambers along with accurate …

Fragility Analysis of Concrete Gravity Dams

Science.gov (United States)

Tekie, Paulos B.; Ellingwood, Bruce R.

2002-09-01

Concrete gravity dams are an important part ofthe nation's infrastructure. Many dams have been in service for over 50 years, during which time important advances in the methodologies for evaluation of natural phenomena hazards have caused the design-basis events to be revised upwards, in some cases significantly. Many existing dams fail to meet these revised safety criteria and structural rehabilitation to meet newly revised criteria may be costly and difficult. A probabilistic safety analysis (PSA) provides a rational safety assessment and decision-making tool managing the various sources of uncertainty that may impact dam performance. Fragility analysis, which depicts fl%e uncertainty in the safety margin above specified hazard levels, is a fundamental tool in a PSA. This study presents a methodology for developing fragilities of concrete gravity dams to assess their performance against hydrologic and seismic hazards. Models of varying degree of complexity and sophistication were considered and compared. The methodology is illustrated using the Bluestone Dam on the New River in West Virginia, which was designed in the late 1930's. The hydrologic fragilities showed that the Eluestone Dam is unlikely to become unstable at the revised probable maximum flood (PMF), but it is likely that there will be significant cracking at the heel ofthe dam. On the other hand, the seismic fragility analysis indicated that sliding is likely, if the dam were to be subjected to a maximum credible earthquake (MCE). Moreover, there will likely be tensile cracking at the neck of the dam at this level of seismic excitation. Probabilities of relatively severe limit states appear to be only marginally affected by extremely rare events (e.g. the PMF and MCE). Moreover, the risks posed by the extreme floods and earthquakes were not balanced for the Bluestone Dam, with seismic hazard posing a relatively higher risk.

Surgical treatment of severe osteoporosis including new concept of advanced severe osteoporosis

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Jin Hwan Kim

2017-12-01

Full Text Available Severe osteoporosis is classified as those with a bone mineral density (BMD T-score of −2.5 or lower, and demonstrate one or more of osteoporotic, low-trauma, fragility fractures. According to the general principle of surgical approach, patients with severe osteoporosis require not only more thorough pre- and postoperative treatment plans, but improvements in surgical fixtures and techniques such as the concept of a locking plate to prevent bone deformity and maximizing the blood flow to the fracture site by using a minimally invasive plate osteosynthesis. Arthroplasty is often performed in cases of displaced femoral neck fracture. Otherwise internal fixation for the goal of bone union is the generally accepted option for intertrochanteric, subtrochanteric, and femoral shaft fractures. Most of osteoporotic spine fracture is stable compression fracture, but vertebroplasty or kyphoplasty may be performed some selective patients. If neurological paralysis, severe spinal instability, or kyphotic deformity occurs, open decompression or fusion surgery may be considered. In order to overcome shortcomings of the World Health Organization definition of osteoporosis, we proposed a concept of ‘advanced severe osteoporosis,’ which is defined by the presence of proximal femur fragility fracture or two or more fragility fractures in addition to BMD T-score of −2.5 or less. In conclusion, we need more meticulous approach for surgical treatment of severe osteoporosis who had fragility fracture. In cases of advanced severe osteoporosis, we recommend more aggressive managements using parathyroid hormone and receptor activator of nuclear factor kappa-B ligand monoclonal antibody.

Manipulations of attention dissociate fragile visual short-term memory from visual working memory.

Science.gov (United States)

Vandenbroucke, Annelinde R E; Sligte, Ilja G; Lamme, Victor A F

2011-05-01

People often rely on information that is no longer in view, but maintained in visual short-term memory (VSTM). Traditionally, VSTM is thought to operate on either a short time-scale with high capacity - iconic memory - or a long time scale with small capacity - visual working memory. Recent research suggests that in addition, an intermediate stage of memory in between iconic memory and visual working memory exists. This intermediate stage has a large capacity and a lifetime of several seconds, but is easily overwritten by new stimulation. We therefore termed it fragile VSTM. In previous studies, fragile VSTM has been dissociated from iconic memory by the characteristics of the memory trace. In the present study, we dissociated fragile VSTM from visual working memory by showing a differentiation in their dependency on attention. A decrease in attention during presentation of the stimulus array greatly reduced the capacity of visual working memory, while this had only a small effect on the capacity of fragile VSTM. We conclude that fragile VSTM is a separate memory store from visual working memory. Thus, a tripartite division of VSTM appears to be in place, comprising iconic memory, fragile VSTM and visual working memory. Copyright © 2011 Elsevier Ltd. All rights reserved.

Flooding Fragility Experiments and Prediction

Energy Technology Data Exchange (ETDEWEB)

Smith, Curtis L. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Tahhan, Antonio [Idaho National Lab. (INL), Idaho Falls, ID (United States); Muchmore, Cody [Idaho National Lab. (INL), Idaho Falls, ID (United States); Nichols, Larinda [Idaho National Lab. (INL), Idaho Falls, ID (United States); Bhandari, Bishwo [Idaho National Lab. (INL), Idaho Falls, ID (United States); Pope, Chad [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-09-01

This report describes the work that has been performed on flooding fragility, both the experimental tests being carried out and the probabilistic fragility predictive models being produced in order to use the text results. Flooding experiments involving full-scale doors have commenced in the Portal Evaluation Tank. The goal of these experiments is to develop a full-scale component flooding experiment protocol and to acquire data that can be used to create Bayesian regression models representing the fragility of these components. This work is in support of the Risk-Informed Safety Margin Characterization (RISMC) Pathway external hazards evaluation research and development.

Fragile X-associated disorders: Don't miss them.

Science.gov (United States)

Birch, Rachael C; Cohen, Jonathan; Trollor, Julian N

2017-01-01

Fragile X-associated disorders are a family of inherited disorders caused by expansions in the Fragile X Mental Retardation 1 (FMR1) gene. Premutation expansions of the FMR1 gene confer risk for fragile X-associated primary ovarian insufficiency and fragile X-associated tremor ataxia syndrome, as well as other medical and psychiatric comorbidities. Premutation expansions of the FMR1 gene are common in the general population. However, fragile X-associated disorders are frequently under-recognised and often misdiagnosed. The aim of this article is to describe fragile X-associated disorders and identify specific considerations for general practitioners (GPs) during identification and management of these disorders. GPs have a critical role in the identification of fragile X-associated disorders, as well as coordination of complex care needs. Prompt recognition and appropriate management of these disorders and potential medical and psychiatric comorbidities will have important implications not only for the affected patient, but also other family members who may be at risk.

Component fragilities - data collection, analysis and interpretation

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.

1986-01-01

As part of the component fragility research program sponsored by the US Nuclear Regulatory Commission, BNL is involved in establishing seismic fragility levels for various nuclear power plant equipment with emphasis on electrical equipment, by identifying, collecting and analyzing existing test data from various sources. BNL has reviewed approximately seventy test reports to collect fragility or high level test data for switchgears, motor control centers and similar electrical cabinets, valve actuators and numerous electrical and control devices of various manufacturers and models. Through a cooperative agreement, BNL has also obtained test data from EPRI/ANCO. An analysis of the collected data reveals that fragility levels can best be described by a group of curves corresponding to various failure modes. The lower bound curve indicates the initiation of malfunctioning or structural damage, whereas the upper bound curve corresponds to overall failure of the equipment based on known failure modes occurring separately or interactively. For some components, the upper and lower bound fragility levels are observed to vary appreciably depending upon the manufacturers and models. An extensive amount of additional fragility or high level test data exists. If completely collected and properly analyzed, the entire data bank is expected to greatly reduce the need for additional testing to establish fragility levels for most equipment

Component fragility research program

International Nuclear Information System (INIS)

Tsai, N.C.; Mochizuki, G.L.; Holman, G.S.

1989-11-01

To demonstrate how ''high-level'' qualification test data can be used to estimate the ultimate seismic capacity of nuclear power plant equipment, we assessed in detail various electrical components tested by the Pacific Gas ampersand Electric Company for its Diablo Canyon plant. As part of our Phase I Component Fragility Research Program, we evaluated seismic fragility for five Diablo Canyon components: medium-voltage (4kV) switchgear; safeguard relay board; emergency light battery pack; potential transformer; and station battery and racks. This report discusses our Phase II fragility evaluation of a single Westinghouse Type W motor control center column, a fan cooler motor controller, and three local starters at the Diablo Canyon nuclear power plant. These components were seismically qualified by means of biaxial random motion tests on a shaker table, and the test response spectra formed the basis for the estimate of the seismic capacity of the components. The seismic capacity of each component is referenced to the zero period acceleration (ZPA) and, in our Phase II study only, to the average spectral acceleration (ASA) of the motion at its base. For the motor control center, the seismic capacity was compared to the capacity of a Westinghouse Five-Star MCC subjected to actual fragility tests by LLNL during the Phase I Component Fragility Research Program, and to generic capacities developed by the Brookhaven National Laboratory for motor control center. Except for the medium-voltage switchgear, all of the components considered in both our Phase I and Phase II evaluations were qualified in their standard commercial configurations or with only relatively minor modifications such as top bracing of cabinets. 8 refs., 67 figs., 7 tabs

Seismic component fragility data base for IPEEE

International Nuclear Information System (INIS)

Bandyopadhyay, K.; Hofmayer, C.

1990-01-01

Seismic probabilistic risk assessment or a seismic margin study will require a reliable data base of seismic fragility of various equipment classes. Brookhaven National Laboratory (BNL) has selected a group of equipment and generically evaluated the seismic fragility of each equipment class by use of existing test data. This paper briefly discusses the evaluation methodology and the fragility results. The fragility analysis results when used in the Individual Plant Examination for External Events (IPEEE) Program for nuclear power plants are expected to provide insights into seismic vulnerabilities of equipment for earthquakes beyond the design basis. 3 refs., 1 fig., 1 tab

MUS81 promotes common fragile site expression

DEFF Research Database (Denmark)

Ying, Songmin; Minocherhomji, Sheroy; Chan, Kok Lung

2013-01-01

Fragile sites are chromosomal loci with a propensity to form gaps or breaks during early mitosis, and their instability is implicated as being causative in certain neurological disorders and cancers. Recent work has demonstrated that the so-called common fragile sites (CFSs) often impair the fait......Fragile sites are chromosomal loci with a propensity to form gaps or breaks during early mitosis, and their instability is implicated as being causative in certain neurological disorders and cancers. Recent work has demonstrated that the so-called common fragile sites (CFSs) often impair...... the faithful disjunction of sister chromatids in mitosis. However, the mechanisms by which CFSs express their fragility, and the cellular factors required to suppress CFS instability, remain largely undefined. Here, we report that the DNA structure-specific nuclease MUS81-EME1 localizes to CFS loci in early...

Determinants of Banking System Fragility : A Regional Perspective

NARCIS (Netherlands)

Degryse, H.A.; Elahi, M.A.; Penas, M.F.

2012-01-01

Abstract: Banking systems are fragile not only within one country but also within and across regions. We study the role of regional banking system characteristics for regional banking system fragility. We find that regional banking system fragility reduces when banks in the region jointly hold more

Employment Impact and Financial Burden for Families of Children with Fragile X Syndrome: Findings from the National Fragile X Survey

Science.gov (United States)

Ouyang, L.; Grosse, S.; Raspa, M.; Bailey, D.

2010-01-01

Background: The employment impact and financial burden experienced by families of children with fragile X syndrome (FXS) has not been quantified in the USA. Method: Using a national fragile X family survey, we analysed data on 1019 families with at least one child who had a full FXS mutation. Out-of-pocket expenditures related to fragile X were…

Financial fragility in the Great Moderation

NARCIS (Netherlands)

Bezemer, Dirk; Grydaki, Maria

2014-01-01

A nascent literature explores the measurement of financial fragility. This paper considers evidence for rising financial fragility during the 1984-2007 Great Moderation in the U.S. The literature suggests that macroeconomic stability combined with strong growth of credit to asset markets, in asset

Seismic fragility analyses of nuclear power plant structures based on the recorded earthquake data in Korea

International Nuclear Information System (INIS)

Cho, Sung Gook; Joe, Yang Hee

2005-01-01

By nature, the seismic fragility analysis results will be considerably affected by the statistical data of design information and site-dependent ground motions. The engineering characteristics of small magnitude earthquake spectra recorded in the Korean peninsula during the last several years are analyzed in this paper. An improved method of seismic fragility analysis is evaluated by comparative analyses to verify its efficiency for practical application to nuclear power plant structures. The effects of the recorded earthquake on the seismic fragilities of Korean nuclear power plant structures are also evaluated from the comparative studies. Observing the obtained results, the proposed method is more efficient for the multi-modes structures. The case study results show that seismic fragility analysis based on the Newmark's spectra in Korea might over-estimate the seismic capacities of Korean facilities

Seismic fragility analyses of nuclear power plant structures based on the recorded earthquake data in Korea

Energy Technology Data Exchange (ETDEWEB)

Cho, Sung Gook [Department of Civil and Environmental System Engineering, University of Incheon, 177 Dohwa-dong, Nam-gu, Incheon 402-749 (Korea, Republic of)]. E-mail: sgcho@incheon.ac.kr; Joe, Yang Hee [Department of Civil and Environmental System Engineering, University of Incheon, 177 Dohwa-dong, Nam-gu, Incheon 402-749 (Korea, Republic of)

2005-08-01

By nature, the seismic fragility analysis results will be considerably affected by the statistical data of design information and site-dependent ground motions. The engineering characteristics of small magnitude earthquake spectra recorded in the Korean peninsula during the last several years are analyzed in this paper. An improved method of seismic fragility analysis is evaluated by comparative analyses to verify its efficiency for practical application to nuclear power plant structures. The effects of the recorded earthquake on the seismic fragilities of Korean nuclear power plant structures are also evaluated from the comparative studies. Observing the obtained results, the proposed method is more efficient for the multi-modes structures. The case study results show that seismic fragility analysis based on the Newmark's spectra in Korea might over-estimate the seismic capacities of Korean facilities.

Frequency and severity of myocardial perfusion abnormalities using Tc-99m MIBI SPECT in cardiac syndrome X

International Nuclear Information System (INIS)

Saghari, Mohsen; Assadi, Majid; Eftekhari, Mohammad; Yaghoubi, Mohammad; Fard-Esfahani, Armaghan; Malekzadeh, Jan-Mohammad; Sichani, Babak Fallhi; Beiki, Davood; Takavar, Abbas

2006-01-01

Cardiac syndrome X is defined by a typical angina pectoris with normal or near normal (stenosis <40%) coronary angiogram with or without electrocardiogram (ECG) change or atypical angina pectoris with normal or near normal coronary angiogram plus a positive none-invasive test (exercise tolerance test or myocardial perfusion scan) with or without ECG change. Studies with myocardial perfusion imaging on this syndrome have indicated some abnormal perfusion scan. We evaluated the role of myocardial perfusion imaging (MPI) and also the severity and extent of perfusion abnormality using Tc-99m MIBI Single Photon Emission Computed Tomography (SPECT) in these patients. The study group consisted of 36 patients with cardiac syndrome X. The semiquantitative perfusion analysis was performed using exercise Tc-99m MIBI SPECT. The MPI results were analyzed by the number, location and severity of perfusion defects. Abnormal perfusion defects were detected in 13 (36.10%) cases, while the remaining 23 (63.90%) had normal cardiac imaging. Five of 13 (38.4%) abnormal studies showed multiple perfusion defects. The defects were localized in the apex in 3, apical segments in 4, midventricular segments in 12 and basal segments in 6 cases. Fourteen (56%) of all abnormal segments revealed mild, 7(28%) moderate and 4 (16%) severe reduction of tracer uptake. No fixed defects were identified. The vessel territories were approximately the same in all subjects. The Exercise treadmill test (ETT) was positive in 25(69%) and negative in 11(30%) patients. There was no consistent pattern as related to the extent of MPI defects or exercise test results. Our study suggests that multiple perfusion abnormalities with different levels of severity are common in cardiac syndrome X, with more than 30 % of these patients having at least one abnormal perfusion segment. Our findings suggest that in these patients microvascular angina is probably more common than is generally believed

Parenting Young Children with and without Fragile X Syndrome

Science.gov (United States)

Sterling, Audra; Barnum, Leah; Skinner, Debra; Warren, Steven F.; Fleming, Kandace

2012-01-01

The purpose of this study was to examine maternal parenting styles across age-matched siblings using a within-family design, in which one child has Fragile X syndrome. Thirteen families participated; children were aged 16 to 71 months. Mothers completed several videotaped activities with each child separately as well as an interview. Mothers used…

Seismic fragility curves of bridge piers accounting for ground motions in Korea

Science.gov (United States)

Nguyen, Duy-Duan; Lee, Tae-Hyung

2018-04-01

Korea is located in a slight-to-moderate seismic zone. Nevertheless, several studies pointed that the peak earthquake magnitude in the region can be reached to approximately 6.5. Accordingly, a seismic vulnerability evaluation of the existing structures accounting for ground motions in Korea is momentous. The purpose of this paper is to develop seismic fragility curves for bridge piers of a steel box girder bridge equipped with and without base isolators based on a set of ground motions recorded in Korea. A finite element simulation platform, OpenSees, is utilized to perform nonlinear time history analyses of the bridges. A series of damage states is defined based on a damage index which is expressed in terms of the column displacement ductility ratio. The fragility curves based on Korean motions were thereafter compared with the fragility curves generated using worldwide earthquakes to assess the effect of the two ground motion groups on the seismic fragility curves of the bridge piers. The results reveal that both non- and base-isolated bridge piers are less vulnerable during the Korean ground motions than that under worldwide earthquakes.

Chromosome fragility at FRAXA in human cleavage stage embryos at risk for fragile X syndrome.

Science.gov (United States)

Verdyck, Pieter; Berckmoes, Veerle; De Vos, Anick; Verpoest, Willem; Liebaers, Inge; Bonduelle, Maryse; De Rycke, Martine

2015-10-01

Fragile X syndrome (FXS), the most common inherited intellectual disability syndrome, is caused by expansion and hypermethylation of the CGG repeat in the 5' UTR of the FMR1 gene. This expanded repeat, also known as the rare fragile site FRAXA, causes X chromosome fragility in cultured cells from patients but only when induced by perturbing pyrimidine synthesis. We performed preimplantation genetic diagnosis (PGD) on 595 blastomeres biopsied from 442 cleavage stage embryos at risk for FXS using short tandem repeat (STR) markers. In six blastomeres, from five embryos an incomplete haplotype was observed with loss of all alleles telomeric to the CGG repeat. In all five embryos, the incomplete haplotype corresponded to the haplotype carrying the CGG repeat expansion. Subsequent analysis of additional blastomeres from three embryos by array comparative genomic hybridization (aCGH) confirmed the presence of a terminal deletion with a breakpoint close to the CGG repeat in two blastomeres from one embryo. A blastomere from another embryo showed the complementary duplication. We conclude that a CGG repeat expansion at FRAXA causes X chromosome fragility in early human IVF embryos at risk for FXS. © 2015 Wiley Periodicals, Inc.

The fragile X syndrome: Isolation of the FMR-1 gene and characterization of the fragile X mutation

NARCIS (Netherlands)

B.A. Oostra (Ben); A. Verkerk

1992-01-01

markdownabstractConclusion Rapid progress has been made in the analysis of the fragile X syndrome during 1991. Different groups have discovered that fragile X chromosomes are preferentially methylated. In these X chromosomes an insertion has been found in the methylated region. The FMR-1 gene,

Seismic fragility capacity of equipment

International Nuclear Information System (INIS)

Iijima, Toru; Abe, Hiroshi; Suzuki, Kenichi

2006-01-01

Seismic probabilistic safety assessment (PSA) is an available method to evaluate residual risks of nuclear plants that are designed on definitive seismic conditions. From our preliminary seismic PSA analysis, horizontal shaft pumps are important components that have significant influences on the core damage frequency (CDF). An actual horizontal shaft pump and some kinds of elements were tested to evaluate realistic fragility capacities. Our test results showed that the realistic fragility capacity of horizontal shaft pump would be at least four times as high as a current value, 1.6 x 9.8 m/s 2 , used for our seismic PSA. We are going to incorporate the fragility capacity data that were obtained from those tests into our seismic PSA analysis, and we expect that the reliability of seismic PSA should increase. (author)

Fragile X syndrome

Science.gov (United States)

... problems, or intellectual disability may not be present. Symptoms Behavior problems associated with fragile X syndrome include: Autism spectrum disorder Delay in crawling, walking, or twisting Hand flapping ...

The Detection and Analysis of Chromosome Fragile Sites

DEFF Research Database (Denmark)

Bjerregaard, Victoria A; Özer, Özgün; Hickson, Ian D

2018-01-01

A fragile site is a chromosomal locus that is prone to form a gap or constriction visible within a condensed metaphase chromosome, particularly following exposure of cells to DNA replication stress. Based on their frequency, fragile sites are classified as either common (CFSs; present in all...... for detection and analysis of chromosome fragile sites....

Association of cardiac troponin I with disease severity and outcomes in patients with pulmonary hypertension.

Science.gov (United States)

Vélez-Martínez, Mariella; Ayers, Colby; Mishkin, Joseph D; Bartolome, Sonja B; García, Christine K; Torres, Fernando; Drazner, Mark H; de Lemos, James A; Turer, Aslan T; Chin, Kelly M

2013-06-15

Previous studies have identified cardiac troponin I (cTnI) as an important marker in pulmonary hypertension (PH) prognosis. However, traditional assays are limited by poor sensitivity, even among patients at high risk. cTnI was measured in 255 PH patients using a new highly sensitive (hs) assay. Other measures included demographics, creatinine, 6-minute walk distance, hemodynamics, cardiac magnetic resonance imaging, and B-type natriuretic peptide level. The association between cTnI and survival was assessed using Kaplan-Meier analysis and Cox regression. cTnI was detectable with the hs assay in 95% of the patients with a median level of 6.9 pg/ml (IQR 2.7-12.6 pg/ml). Higher cTnI levels associated with higher levels of B-type natriuretic peptide, shorter 6-minute walk distance, and more severe hemodynamic and cardiac magnetic resonance imaging abnormalities. During a median follow-up of 3.5 years, 60 individuals died. Unadjusted event rates increased across higher cTnI quartiles (3, 5, 13, 17 events/100 person-years, respectively, p trend = 0.002). cTnI in the fourth (vs first) quartile remained associated with death in a final stepwise multivariable model that included clinical variables and hemodynamics (adjusted hazard ratio 5.3, 95% confidence interval 1.8-15.6). In conclusion, cTnI levels, detectable with a novel hs assay, identify patients with PH who have more severe hemodynamic and cardiac structural abnormalities and provide novel and independent prognostic information. This hs assay has the potential to detect more at-risk patients and improve current risk-stratification algorithms. Copyright © 2013 Elsevier Inc. All rights reserved.

THE IMPORTANCE OF THE ERYTHROCYTES OSMOTIC FRAGILITY TEST PERFORMED IN CHILDREN WITH INDIRECT HYPERBILIRUB1NEMIA

Directory of Open Access Journals (Sweden)

Ivana Stojanović

2005-07-01

Full Text Available The osmotic fragility test of erythrocytes is useful in the diagnosis of different types of hereditary hemolytic anemias followed with hyperbilirubinemia. Hemolytic anemias, characterized by accelerated destruction of red blood cells, are usually the consequence of many metabolic abnormalities like cellular membrane defect, erythrocyte enzymes defect or hemoglobin abnormalities – hemoglobinopathies. The object of our study was to assess the relationship between osmotic fragility test of erythrocytes and severity of indirect hyperbilirubinemia in some inherited erythrocytes’ disorders. We did the osmotic fragility test of erythrocytes by using Dacie, s method with normal values of erythrocytes hemolysis between 0,48 to 0,34% NaCl (minimal to maximal hemolysis. In hereditary spherocytosis, fragility of erythrocytes was increased (min. at 0,50 % NaCl to max. 0,44 % NaCl . In the child with β- thalassemia and cycle cell anemia erythrocytes fragility was decreased (min . at 0,42 to max. 0,32 % NaCl, that is 0,40% min. of hemolysis and 0,34% max. hemolysis in the second case. In newborn infants with high levels of indirect bilirubin in serum as a cause of physiological jaundice, the osmotic fragility test was within a normal range. Our findings point out the diagnostic value of osmotic fragility test in assessing patients with the indirect hyperbilirubinemia. This simple and important diagnostic test can be performed in small laboratories.

Behavioral Phenotype of Fragile X Syndrome in Adolescence and Adulthood

Science.gov (United States)

Smith, Leann E.; Barker, Erin T.; Seltzer, Marsha Mailick; Abbeduto, Leonard; Greenberg, Jan S.

2012-01-01

The present study explored the behavioral profile of individuals with fragile X syndrome during adolescence and adulthood. Individuals with both fragile X syndrome and autism (n = 30) were compared with (a) individuals diagnosed with fragile X syndrome (but not autism; n = 106) and (b) individuals diagnosed with autism (but not fragile X syndrome;…

Correlation of C-Reactive Protein and Cardiac Enzymes with Angiographic Severity of Coronary Artery Disease in Pakistani Patients with Acute Coronary Syndrome.

Science.gov (United States)

Saleem, Ayesha; Ali, Azmat

2017-02-01

To determine the correlation of C-reactive protein (CRP) levels with the severity of coronary stenosis on angiography and the association of cardiac enzymes with the degree of stenosis in acute coronary syndrome (ACS) patients. Secondly, to compare association of angiographic severity of vascular stenosis with CRP in patients with ST segment elevation myocardial infarction (STEMI) and non-STEMI / Unstable angina (UA). Prospective, descriptive study. Khan Research Laboratories (KRL) Hospital, from October 2014 to March 2015. CRP was measured on diagnosis of ACS in 70 patients. Cardiac enzymes were measured 6 hours after the onset of chest pain. Angiographic scoring for degree of stenosis and number of culprit vessels was done. Two groups consisting of patients with STEMI (group 1) and with NSTEMI/UA (group 2) were made. No correlation was found between CRP levels and angiographic stenosis in patients with ACS (r=0.162, p>0.05). No association was found between eosinophil count and severity of stenosis (p=0.88). Rise of cardiac enzymes and degree of coronary stenosis showed a positive correlation (p Rise in cardiac enzymes still grade high in predicting severity of vascular stenosis than eosinophil count or CRP levels.

Autism Spectrum Disorder and Fragile X Syndrome

Science.gov (United States)

... only after another family member has been diagnosed. Autism Spectrum Disorder and Fragile X Syndrome Fragile X syndrome is ... gene cause of ASD What Is Autism Spectrum Disorder? Autism spectrum disorder (ASD) is a behavioral diagnosis. The range ...

Molecular medicine of fragile X syndrome: based on known molecular mechanisms.

Science.gov (United States)

Luo, Shi-Yu; Wu, Ling-Qian; Duan, Ran-Hui

2016-02-01

Extensive research on fragile X mental retardation gene knockout mice and mutant Drosophila models has largely expanded our knowledge on mechanism-based treatment of fragile X syndrome (FXS). In light of these findings, several clinical trials are now underway for therapeutic translation to humans. Electronic literature searches were conducted using the PubMed database and ClinicalTrials.gov. The search terms included "fragile X syndrome", "FXS and medication", "FXS and therapeutics" and "FXS and treatment". Based on the publications identified in this search, we reviewed the neuroanatomical abnormalities in FXS patients and the potential pathogenic mechanisms to monitor the progress of FXS research, from basic studies to clinical trials. The pathological mechanisms of FXS were categorized on the basis of neuroanatomy, synaptic structure, synaptic transmission and fragile X mental retardation protein (FMRP) loss of function. The neuroanatomical abnormalities in FXS were described to motivate extensive research into the region-specific pathologies in the brain responsible for FXS behavioural manifestations. Mechanism-directed molecular medicines were classified according to their target pathological mechanisms, and the most recent progress in clinical trials was discussed. Current mechanism-based studies and clinical trials have greatly contributed to the development of FXS pharmacological therapeutics. Research examining the extent to which these treatments provided a rescue effect or FMRP compensation for the developmental impairments in FXS patients may help to improve the efficacy of treatments.

Relay testing parametric investigation of seismic fragility

International Nuclear Information System (INIS)

Bandyopadhyay, K.; Hofmayer, C.; Kassir, M.; Pepper, S.

1989-01-01

The seismic capacity of most electrical equipment is governed by malfunction of relays. An evaluation of the existing relay test data base at Brookhaven National Laboratory (BNL) has indicated that the seismic fragility of a relay may depend on various parameters related to the design or the input motion. In particular, the electrical mode, contact state, adjustment, chatter duration acceptance limit, and the frequency and the direction of the vibration input have been considered to influence the relay fragility level. For a particular relay type, the dynamics of its moving parts depends on the exact model number and vintage and hence, these parameters may also influence the fragility level. In order to investigate the effect of most of these parameters on the seismic fragility level, BNL has conducted a relay test program. The testing has been performed at Wyle Laboratories. Establishing the correlation between the single frequency fragility test input and the corresponding multifrequency response spectrum (TRS) is also an objective of this test program. This paper discusses the methodology used for testing and presents a brief summary of important test results. 1 ref., 10 figs

Seismic fragility of nuclear power plant components (Phase II)

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.; Kassir, M.K.; Pepper, S.E.

1990-02-01

As part of the Component Fragility Program which was initiated in FY 1985, three additional equipment classes have been evaluated. This report contains the fragility results and discussions on these equipment classes which are switchgear, I and C panels and relays. Both low and medium voltage switchgear assemblies have been considered and a separate fragility estimate for each type is provided. Test data on cabinets from the nuclear instrumentation/neutron monitoring system, plant/process protection system, solid state protective system and engineered safeguards test system comprise the BNL data base for I and C panels (NSSS). Fragility levels have been determined for various failure modes of switchgear and I ampersand C panels, and the deterministic results are presented in terms of test response spectra. In addition, the test data have been evaluated for estimating the respective probabilistic fragility levels which are expressed in terms of a median value, an uncertainty coefficient, a randomness coefficient and an HCLPF value. Due to a wide variation of relay design and the fragility level, a generic fragility level cannot be established for relays. 7 refs., 13 figs., 12 tabs

Resilience and the Fragile City

Directory of Open Access Journals (Sweden)

John de Boer

2015-04-01

Full Text Available Humanitarian, security, and development actors are witnessing two distinct but intertwined trends that will have a dramatic impact on their operations. The first relates to the fact that the locus of global poverty and vulnerability to disaster are increasingly concentrated in fragile and conflict affected states. The second trend is associated with the notion that the world has entered a period of unprecedented urbanization. For the first time in history, more people live inside urban centres than outside of them. As the world continues to urbanize, global emergencies will increasingly be concentrated in cities, particularly in lower income and fragile countries where the pace of urbanization is fastest. Yet, despite the growing risks facing urban populations living in fragile and conflict affected countries, there is very little understanding of what can be done to reduce the risks posed to these cities and their populations.

Seismic fragility evaluation of unreinforced masonry walls

International Nuclear Information System (INIS)

Park, Y.J.; Hofmayer, C.H.; Reich, M.; Lee, S.K.

1991-01-01

A practical analysis scheme to evaluate the seismic fragility of unreinforced masonry walls which are used at various places in older reactor facilities is presented. Among the several failure modes for such walls, the out-of-plane bending failure is considered to be a major risk contributor in seismic PRA studies. In order to evaluate this failure mode, the use of an equivalent linear approximation method is examined based on comparisons with available test data and nonlinear time history analyses. (author)

Seismic fragility levels of nuclear power plant equipment

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.

1987-01-01

Seismic fragility levels of safety-related electrical and mechanical equipment used in nuclear power plants are discussed. The fragility level is defined as the vibration level corresponding to initiation of equipment malfunctions. The test response spectrum is used as a measure of this vibration level. The fragility phenomenon of an equipment is represented by a number of response spectra corresponding to various failure modes. Analysis methods are described for determination of the fragility level by use of existing test data. Useful conversion factors are tabulated to transform test response spectra from one damping value to another. Results are presented for switch-gears and motor control centers. The capacity levels of these equipment assemblies are observed to be limited by malfunctioning of contactors, motor starters, relays and/or switches. The applicability of the fragility levels, determined in terms of test response spectra, to Seismic Margin Studies and Probabilistic Risk Assessments is discussed and specific recommendations are provided

Study on the Progress of Ecological Fragility Assessment in China

Science.gov (United States)

Chen, Pei; Hou, Kang; Chang, Yue; Li, Xuxiang; Zhang, Yunwei

2018-02-01

The basic elements of human survival are based on the ecological environment. The development of social economic and the security of the ecological environment are closely linked and interact with each other. The fragility of the environment directly affects the stability of the regional ecosystem and the sustainable development of the ecological environment. As part of the division of the national ecological security, the assessment of ecological fragility has become a hot and difficult issue in environmental research, and researchers at home and abroad have systematically studied the causes and states of ecological fragility. The assessment of regional ecological fragility is a qualitative and quantitative analysis of the unbalanced distribution of ecological environment factors caused by human socio-economic activities or changes in ecosystems. At present, researches on ecological fragility has not formed a complete and unified index assessment system, and the unity of the assessment model has a direct impact on the accuracy of the index weights. Therefore, the discussion on selection of ecological fragility indexes and the improvement of ecological fragility assessment model is necessary, which is good for the improvement of ecological fragility assessment system in China.

Successful resuscitation from two cardiac arrests in a female patient with critical aortic stenosis, severe mitral regurgitation and coronary artery disease

Directory of Open Access Journals (Sweden)

Mijušković Dragan

2012-01-01

Full Text Available Introduction. The incidence of sudden cardiac death in patients with severe symptomatic aortic stenosis is up to 34% and resuscitation is described as highly unsuccessful. Case report. A 72-year-old female patient with severe aortic stenosis combined with severe mitral regurgitation and three-vessel coronary artery disease was successfully resuscitated following two in-hospital cardiac arrests. The first cardiac arrest occurred immediately after intraarterial injection of low osmolar iodinated agent during coronary angiography. Angiography revealed 90% occlusion of the proximal left main coronary artery and circumflex branch. The second arrest followed induction of anesthesia. Following successful open-chest resuscitation, aortic valve replacement, mitral valvuloplasty and three-vessel aortocoronary bypass were performed. Postoperative pericardial tamponade required surgical revision. The patient recovered completely. Conclusion. Decision to start resuscitation may be justified in selected patients with critical aortic stenosis, even though cardiopulmonary resuscitation in such cases is generally considered futile.

Frequency of fragile-x in x‑linked mental retardation

African Journals Online (AJOL)

... with isolated mental retardation or autism of unknown etiology with considerable fragile X dysmorphic features or established family history of fragile X syndrome, chromosomal study that identifies the fragile site at Xq27.3 in addition to other cytogenetic abnormalities could be useful or early diagnosis and intervention by ...

Comprehensive clinical evaluation of a large Spanish family with Anderson-Fabry disease, novel GLA mutation and severe cardiac phenotype.

Science.gov (United States)

San Román-Monserrat, Irene; Moreno-Flores, Victoria; López-Cuenca, David; Rodríguez-González-Herrero, Elena; Guillén-Navarro, Encarna; Rodríguez-González-Herrero, Beatriz; Alegría-Fernández, Marisol; Poza-Cisneros, Gabriela; Piñero-Fernández, Juan A; Sornichero-Martínez, Javier; Gimeno-Blanes, Juan R

2014-06-06

Fabry disease is an X-linked multisystemic lysosomal-storage condition. We describe a large family with a novel GLA mutation: p.M187R/g7219 T>G. Anamnesis/physical-exam, blood/urine analysis, α-Gal-A activity and/or genetic study of at-risk individuals and multidisciplinary evaluation in confirmed cases. 4 males and 13 heterozygous-females displayed the mutation. Cardiac/renal/neurological disease was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy. Delta wave suggestive of accessory pathway was identified in 1 male and 2 females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2 females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz Severity-Score-Index was severe for males and females over 40 years. 4/15(26%) developed early renal disease. 2 males needed dialysis. 1 male died at 69 years in spite of kidney-heart transplant. We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation. The novel mutation p.M187R/g7219 T>G is associated with a particularly malignant cardiac phenotype in males and females over 40 years. Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with delta is being reported for the first time. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Wild-Type Male Offspring of fmr-1+/− Mothers Exhibit Characteristics of the Fragile X Phenotype

OpenAIRE

Zupan, Bojana; Toth, Miklos

2008-01-01

Fragile X syndrome is an X-linked disorder caused by the inactivation of the FMR-1 gene with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities, and hyperactivity. Males are more severely affected than heterozygote (H) females, who, as carriers, have a 50% chance of transmitting the mutated allele in each pregnancy. fmr-1 knockout (KO) mice reproduce fragile X symptoms, including hyperactivity, seizures, and abnormal sensory processing. In contrast ...

The Report on 2 Cases of Fragile X Syndrome Comorbid with Attention Deficit/Hyperactivity Disorder

Directory of Open Access Journals (Sweden)

Katayoun Khoushabi

2000-07-01

Full Text Available The term “fragile X syndrome” is named after a constriction recognizable on chromosome (at Xq 27.3 cultured at chromosome media without folic acid. The unstable part includes repetition of 3 nucleotides which is intensified at subsequent generation (DNA amplification and gives rise to a more severe phenotype in the individual. About 20% of males have normal fragile X syndrome. The daughters of these individuals have abnormal chromosomes (carrier and their grandchildren will be marked. In typical syndrome, the boys will suffer from mental retardation, macrocephalia, large or protruding ears, elongated face, and macroorchidism. In terms of behavioral comorbidity, symptoms are similar to pervasive developmental disorder such as autism and attention deficit/hyperactivity disorder. The impairments in cognitive abilities are manifested as learning difficulties to severe problems. Our patients were 2 boys (6 and 7 years old referred due to their hyperactivity. In physical examination, attention deficit/hyperactivity disorder as well as fragile X syndrome were confirmed. In chromosome culture test, the constriction at Xq 27.3 was specified.

Component fragilities. Data collection, analysis and interpretation

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.

1985-01-01

As part of the component fragility research program sponsored by the US NRC, BNL is involved in establishing seismic fragility levels for various nuclear power plant equipment with emphasis on electrical equipment. To date, BNL has reviewed approximately seventy test reports to collect fragility or high level test data for switchgears, motor control centers and similar electrical cabinets, valve actuators and numerous electrical and control devices, e.g., switches, transmitters, potentiometers, indicators, relays, etc., of various manufacturers and models. BNL has also obtained test data from EPRI/ANCO. Analysis of the collected data reveals that fragility levels can best be described by a group of curves corresponding to various failure modes. The lower bound curve indicates the initiation of malfunctioning or structural damage, whereas the upper bound curve corresponds to overall failure of the equipment based on known failure modes occurring separately or interactively. For some components, the upper and lower bound fragility levels are observed to vary appreciably depending upon the manufacturers and models. For some devices, testing even at the shake table vibration limit does not exhibit any failure. Failure of a relay is observed to be a frequent cause of failure of an electrical panel or a system. An extensive amount of additional fregility or high level test data exists

Longitudinal Profiles of Adaptive Behavior in Fragile X Syndrome

Science.gov (United States)

Quintin, Eve-Marie; Jo, Booil; Lightbody, Amy A.; Hazlett, Heather Cody; Piven, Joseph; Hall, Scott S.; Reiss, Allan L.

2014-01-01

OBJECTIVE: To examine longitudinally the adaptive behavior patterns in fragile X syndrome. METHOD: Caregivers of 275 children and adolescents with fragile X syndrome and 225 typically developing children and adolescents (2–18 years) were interviewed with the Vineland Adaptive Behavior Scales every 2 to 4 years as part of a prospective longitudinal study. RESULTS: Standard scores of adaptive behavior in people with fragile X syndrome are marked by a significant decline over time in all domains for males and in communication for females. Socialization skills are a relative strength as compared with the other domains for males with fragile X syndrome. Females with fragile X syndrome did not show a discernible pattern of developmental strengths and weaknesses. CONCLUSIONS: This is the first large-scale longitudinal study to show that the acquisition of adaptive behavior slows as individuals with fragile X syndrome age. It is imperative to ensure that assessments of adaptive behavior skills are part of intervention programs focusing on childhood and adolescence in this condition. PMID:25070318

Fragile Butterfly

DEFF Research Database (Denmark)

2011-01-01

Valg af materiale/medie/form: Med indlevelse og en unik balance af sårbarhed i stemmen synger og fortolker Heidie sine egne sange, hvis lyriske tekster grundlæggende har to temaer: En dyb kærlighed til livet og det at turde kærligheden. Toneuniverset i Fragile Butterfly tager sit afsæt i jazzen...

Seismic fragility evaluation of unreinforced masonry walls

International Nuclear Information System (INIS)

Park, Y.J.; Hofmayer, C.H.; Reich, M.; Lee, S.K.

1991-01-01

A practical analysis scheme to evaluate the seismic fragility of unreinforced masonry walls which are used to various places in older reactor facilities is presented. Among the several failure modes for such walls, the out-of-plane bending failure is considered to be a major risk contributor in seismic PRA studies. In order to evaluate this failure mode, the use of an equivalent linear approximation method is examined based on comparisons with available test data and nonlinear time history analyses. 6 refs., 4 figs., 3 tabs

Tracking development assistance for health to fragile states: 2005-2011.

Science.gov (United States)

Graves, Casey M; Haakenstad, Annie; Dieleman, Joseph L

2015-03-19

Development assistance for health (DAH) has grown substantially, totaling more than $31.3 billion in 2013. However, the degree that countries with high concentrations of armed conflict, ethnic violence, inequality, debt, and corruption have received this health aid and how that assistance might be different from the funding provided to other countries has not been assessed. We combine DAH estimates and a multidimensional fragile states index for 2005 through 2011. We disaggregate and compare total DAH disbursed for fragile states versus stable states. Between 2005 and 2011, DAH per person in fragile countries increased at an annualized rate of 5.4%. In 2011 DAH to fragile countries totaled $6.2 billion, which is $5.05 per person. This is 43% of total DAH that is traced to a country. Comparing low-income countries, funding channeled to fragile countries was $7.22 per person while stable countries received $11.15 per person. Relative to stable countries, donors preferred to provide more funding to low-income fragile countries that have refugees or ongoing external intervention but tended to avoid providing funding to countries with political gridlock, flawed elections, or economic decline. In 2011, Ethiopia received the most health aid of all fragile countries, while the United States provided the most funds to fragile countries. In 2011, 1.2 billion people lived in fragile countries. DAH can bolster health systems and might be especially valuable in providing long-term stability in fragile environments. While external health funding to these countries has increased since 2005, it is, in per person terms, almost half as much as the DAH provided to stable countries of comparable income levels.

A note on families of fragility curves

International Nuclear Information System (INIS)

Kaplan, S.; Bier, V.M.; Bley, D.C.

1989-01-01

In the quantitative assessment of seismic risk, uncertainty in the fragility of a structural component is usually expressed by putting forth a family of fragility curves, with probability serving as the parameter of the family. Commonly, a lognormal shape is used both for the individual curves and for the expression of uncertainty over the family. A so-called composite single curve can also be drawn and used for purposes of approximation. This composite curve is often regarded as equivalent to the mean curve of the family. The equality seems intuitively reasonable, but according to the authors has never been proven. The paper presented proves this equivalence hypothesis mathematically. Moreover, the authors show that this equivalence hypothesis between fragility curves is itself equivalent to an identity property of the standard normal probability curve. Thus, in the course of proving the fragility curve hypothesis, the authors have also proved a rather obscure, but interesting and perhaps previously unrecognized, property of the standard normal curve

Development of fragility descriptions of equipment for seismic risk assessment of nuclear power plants

International Nuclear Information System (INIS)

Hardy, G.S.; Campbell, R.D.

1983-01-01

Probabilistic risk assessment (PRA) of a nuclear power plant for postulated hazard requires the development of fragility relationships for the plants' safety related equipment. The objective of this paper is to present some general results and conclusions concerning the development of these seismic fragility levels. Participation in fragility-related research and experience gained from the completion of several PRA studies of a variety of nuclear power plants have provided much insight as to the most vulnerable equipment and the most efficient use of resources for development of fragilities. Plants studied had seismic design bases ranging from very simple equivalent static analysis for some of the earlier plants to state-of-the-art complex multimode dyanamic analyses for plants currently under construction. Increased sophistication and rigor in seismic qualification of equipment has resulted for the most part in increased seismic resistance. The majority of equipment has been found, however, to possess more than adequate resistance to seismic loading regardless of the degree of sophistication utilized in design as long as seismic loading was included in the design process. This paper presents conclusions of the authors as to which items of equipment typically require an individual ''plant-specific'' fragility analysis and which can be treated in a generic fashion. In addition, general conclusions on the relative seismic capacity levels and most frequent failure modes are summarized for generic equipment groups

21 CFR 864.6600 - Osmotic fragility test.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Osmotic fragility test. 864.6600 Section 864.6600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6600 Osmotic fragility...

Association of Cardiac Hemodynamic Factors With Severity of White Matter Hyperintensities in Chronic Valvular Heart Disease.

Science.gov (United States)

Lee, Woo-Jin; Jung, Keun-Hwa; Ryu, Young Jin; Kim, Jeong-Min; Lee, Soon-Tae; Chu, Kon; Kim, Manho; Lee, Sang Kun; Roh, Jae-Kyu

2018-01-01

The cerebral white matter hyperintensity (WMH) is frequently noted in patients with chronic heart disease. Long-term alteration of cardiac hemodynamics might have an influence on the mechanism of cerebral WMH. To investigate the association between chronically altered cardiac hemodynamics and severity of cerebral WMH in patients with chronic valvular heart disease. This cross-sectional analysis identified 303 consecutive patients at a tertiary referral center between 2008 and 2016 who were 50 years or older, and diagnosed with severe chronic valvular heart disease and underwent cardiac catherization, echocardiography, and received brain magnetic resonance imaging. Among these patients, 71 with other demonstrated cardiac disease, central nervous system disease, and/or without sufficient catheterization data were excluded, and the remaining 232 patients were included in further analyses. The site and mechanism of valve diseases, as well as clinical and medication profiles, were reviewed. Cardiac catheterization parameters such as right atrial (RA) mean pressure, right ventricular pressure, and aortic mean pressure were obtained. Comprehensive echocardiographic hemodynamic markers such as left ventricular (LV) ejection fraction, LV mass index, LV end diastolic volume, cardiac index, and E/e' ratio were also obtained. White matter hyperintensity volume was quantitatively evaluated using volumetric analysis. This study included 232 patients (103 men [44.4%] and 129 women [55.6%]; mean [SD] (range) age, 65.6 [8.8] (51-88) years) in the final analysis. The mean (SD) WMH volume was 5.93 (7.14) mL (median [interquartile range], 4.33 [1.33-8.62] mL), and mean (SD) RA pressure was 10.0 (4.7) mm Hg. From the catheterization data, 147 patients (63.4%) were classified as having a disease involving the mitral valve; 93 (40.1%), aortic valve; 37 (15.9%), tricuspid valve; and 4 (1.7%), pulmonary valve. In multivariate linear regression analysis, adjusting the type and mechanism of

Molecular characterization of X chromosome fragility in idiopathic ...

African Journals Online (AJOL)

Heba Alla Hosny Omar

2015-11-23

Nov 23, 2015 ... Frequency of fragile X syndrome among male siblings and relatives of mentally retarded patients ... hence the wide clinical spectrum of disorders caused by this ... fragile X syndrome, autism and other less well-characterized.

Trio Fragile / Olga Kaljundi

Index Scriptorium Estoniae

Kaljundi, Olga, 1941-2001

1998-01-01

Tallinna Vene Draamateatri galeriis esinenud trupi "Trio Fragile" vernissaazhist. Trio loomingust ja osalejatest : kahe muusiku seltskonnas esineb ka 1984.a. Kunstiülikooli lõpetanud kunstnik Tõnu Talve.

Attentional Set-Shifting in Fragile X Syndrome

Science.gov (United States)

Van der Molen, M. J. W.; Van der Molen, M. W.; Ridderinkhof, K. R.; Hamel, B. C. J.; Curfs, L. M. G.; Ramakers, G. J. A.

2012-01-01

The ability to flexibly adapt to the changing demands of the environment is often reported as a core deficit in fragile X syndrome (FXS). However, the cognitive processes that determine this attentional set-shifting deficit remain elusive. The present study investigated attentional set-shifting ability in fragile X syndrome males with the…

Of Men and Mice: Modeling the Fragile X Syndrome

Science.gov (United States)

Dahlhaus, Regina

2018-01-01

The Fragile X Syndrome (FXS) is one of the most common forms of inherited intellectual disability in all human societies. Caused by the transcriptional silencing of a single gene, the fragile x mental retardation gene FMR1, FXS is characterized by a variety of symptoms, which range from mental disabilities to autism and epilepsy. More than 20 years ago, a first animal model was described, the Fmr1 knock-out mouse. Several other models have been developed since then, including conditional knock-out mice, knock-out rats, a zebrafish and a drosophila model. Using these model systems, various targets for potential pharmaceutical treatments have been identified and many treatments have been shown to be efficient in preclinical studies. However, all attempts to turn these findings into a therapy for patients have failed thus far. In this review, I will discuss underlying difficulties and address potential alternatives for our future research. PMID:29599705

Improved Iris Recognition through Fusion of Hamming Distance and Fragile Bit Distance.

Science.gov (United States)

Hollingsworth, Karen P; Bowyer, Kevin W; Flynn, Patrick J

2011-12-01

The most common iris biometric algorithm represents the texture of an iris using a binary iris code. Not all bits in an iris code are equally consistent. A bit is deemed fragile if its value changes across iris codes created from different images of the same iris. Previous research has shown that iris recognition performance can be improved by masking these fragile bits. Rather than ignoring fragile bits completely, we consider what beneficial information can be obtained from the fragile bits. We find that the locations of fragile bits tend to be consistent across different iris codes of the same eye. We present a metric, called the fragile bit distance, which quantitatively measures the coincidence of the fragile bit patterns in two iris codes. We find that score fusion of fragile bit distance and Hamming distance works better for recognition than Hamming distance alone. To our knowledge, this is the first and only work to use the coincidence of fragile bit locations to improve the accuracy of matches.

Effect of maternal age and cardiac disease severity on outcome of pregnancy in women with congenital heart disease.

Science.gov (United States)

Furenäs, Eva; Eriksson, Peter; Wennerholm, Ulla-Britt; Dellborg, Mikael

2017-09-15

There is an increasing prevalence of women with congenital heart defects reaching childbearing age. In western countries women tend to give birth at a higher age compared to some decades ago. We evaluated the CARdiac disease in PREGnancy (CARPREG) and modified World Health Organization (mWHO) risk classifications for cardiac complications during pregnancies in women with congenital heart defects and analyzed the impact of age on risk of obstetric and fetal outcome. A single-center observational study of cardiac, obstetric, and neonatal complications with data from cardiac and obstetric records of pregnancies in women with congenital heart disease. Outcomes of 496 pregnancies in 232 women, including induced abortion, miscarriage, stillbirth, and live birth were analyzed regarding complications, maternal age, mode of delivery, and two risk classifications: CARPREG and mWHO. There were 28 induced abortions, 59 fetal loss, 409 deliveries with 412 neonates. Cardiac (14%), obstetric (14%), and neonatal (15%) complications were noted, including one maternal death and five stillbirths. The rate of cesarean section was 19%. Age above 35years was of borderline importance for cardiac complications (p=0.054) and was not a significant additional risk factor for obstetric or neonatal complications. Both risk classifications had moderate clinical utility, with area under the curve (AUC) 0.71 for CARPREG and 0.65 for mWHO on cardiac complications. Pregnancy complications in women with congenital heart disease are common but severe complications are rare. Advanced maternal age does not seem to affect complication rate. Existing risk classification systems are insufficient in predicting complications. Copyright © 2017 Elsevier B.V. All rights reserved.

Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo.

Science.gov (United States)

Palpant, Nathan J; D'Alecy, Louis G; Metzger, Joseph M

2009-05-01

Intracellular acidosis is a profound negative regulator of myocardial performance. We hypothesized that titrating myofilament calcium sensitivity by a single histidine substituted cardiac troponin I (A164H) would protect the whole animal physiological response to acidosis in vivo. To experimentally induce severe hypercapnic acidosis, mice were exposed to a 40% CO(2) challenge. By echocardiography, it was found that systolic function and ventricular geometry were maintained in cTnI A164H transgenic (Tg) mice. By contrast, non-Tg (Ntg) littermates experienced rapid and marked cardiac decompensation during this same challenge. For detailed hemodymanic assessment, Millar pressure-conductance catheterization was performed while animals were treated with a beta-blocker, esmolol, during a severe hypercapnic acidosis challenge. Survival and load-independent measures of contractility were significantly greater in Tg vs. Ntg mice. This assay showed that Ntg mice had 100% mortality within 5 min of acidosis. By contrast, systolic and diastolic function were protected in Tg mice during acidosis, and they had 100% survival. This study shows that, independent of any beta-adrenergic compensation, myofilament-based molecular manipulation of inotropy by histidine-modified troponin I maintains cardiac inotropic and lusitropic performance and markedly improves survival during severe acidosis in vivo.

Developing empirical collapse fragility functions for global building types

Science.gov (United States)

Jaiswal, K.; Wald, D.; D'Ayala, D.

2011-01-01

Building collapse is the dominant cause of casualties during earthquakes. In order to better predict human fatalities, the U.S. Geological Survey’s Prompt Assessment of Global Earthquakes for Response (PAGER) program requires collapse fragility functions for global building types. The collapse fragility is expressed as the probability of collapse at discrete levels of the input hazard defined in terms of macroseismic intensity. This article provides a simple procedure for quantifying collapse fragility using vulnerability criteria based on the European Macroseismic Scale (1998) for selected European building types. In addition, the collapse fragility functions are developed for global building types by fitting the beta distribution to the multiple experts’ estimates for the same building type (obtained from EERI’s World Housing Encyclopedia (WHE)-PAGER survey). Finally, using the collapse probability distributions at each shaking intensity level as a prior and field-based collapse-rate observations as likelihood, it is possible to update the collapse fragility functions for global building types using the Bayesian procedure.

Treatment of Fragile X Syndrome with a Neuroactive Steroid

Science.gov (United States)

2013-08-01

Fulks JL, O’Bryhim BE et al (2010) Dopamine release and uptake impairments and behavioral alterations observed in mice that model fragile x mental...D2 dopamine receptor agonist. J Cogn Neurosci 4(1):58–68 Luo Y, Shan G et al (2010) Fragile x mental retardation protein regulates proliferation and...AD_________________ Award Number: W81XWH-11-1-0626 TITLE: Treatment of Fragile X Syndrome with a

Nuclear Power Plant Mechanical Component Flooding Fragility Experiments Status

Energy Technology Data Exchange (ETDEWEB)

Pope, C. L. [Idaho State Univ., Pocatello, ID (United States); Savage, B. [Idaho State Univ., Pocatello, ID (United States); Johnson, B. [Idaho State Univ., Pocatello, ID (United States); Muchmore, C. [Idaho State Univ., Pocatello, ID (United States); Nichols, L. [Idaho State Univ., Pocatello, ID (United States); Roberts, G. [Idaho State Univ., Pocatello, ID (United States); Ryan, E. [Idaho State Univ., Pocatello, ID (United States); Suresh, S. [Idaho State Univ., Pocatello, ID (United States); Tahhan, A. [Idaho State Univ., Pocatello, ID (United States); Tuladhar, R. [Idaho State Univ., Pocatello, ID (United States); Wells, A. [Idaho State Univ., Pocatello, ID (United States); Smith, C. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2017-07-24

This report describes progress on Nuclear Power Plant mechanical component flooding fragility experiments and supporting research. The progress includes execution of full scale fragility experiments using hollow-core doors, design of improvements to the Portal Evaluation Tank, equipment procurement and initial installation of PET improvements, designation of experiments exploiting the improved PET capabilities, fragility mathematical model development, Smoothed Particle Hydrodynamic simulations, wave impact simulation device research, and pipe rupture mechanics research.

Seismic fragility of nuclear power plant components. Phase I

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.

1986-06-01

As part of the Component Fragility Research Program, sponsored by the US Nuclear Regulatory Commission, BNL is involved in establishing seismic fragility levels for various nuclear power plant equipment by identifying, collecting and analyzing existing test data from various sources. In Phase I of this program, BNL has reviewed approximately seventy test reports to collect fragility or high level test data for switchgears, motor control centers and similar electrical cabinets, valve actuators and numerous electrical devices of various manufacturers and models. This report provides an assessment and evaluation of the data collected in Phase I. The fragility data for medium voltage and low voltage switchgears and motor control centers are analyzed using the test response spectra (TRS) as a measure of the fragility level. The analysis reveals that fragility levels can best be described by a group of TRS curves corresponding to various failure modes. The lower-bound curve indicates the initiation of malfunctioning or structural damage; whereas, the upper-bound curve corresponds to overall failure of the equipment based on known failure modes. High level test data for some components are included in the report. These data indicate that some components are inherently strong and do not exhibit any failure mode even when tested at the vibration limit of a shake table. The common failure modes are identified in the report. The fragility levels determined in this report have been compared with those used in the PRA and Seismic Margin Studies. It appears that the BNL data better correlate with the HCLPF (High Confidence of a Low Probability of Failure) level used in Seismic Margin Studies and can improve this level as high as 60% for certain applications. Specific recommendations are provided for proper application of BNL fragility data to other studies

Cardiac hyporesponsiveness in severe sepsis is associated with nitric oxide-dependent activation of G protein receptor kinase.

Science.gov (United States)

Dal-Secco, Daniela; DalBó, Silvia; Lautherbach, Natalia E S; Gava, Fábio N; Celes, Mara R N; Benedet, Patricia O; Souza, Adriana H; Akinaga, Juliana; Lima, Vanessa; Silva, Katiussia P; Kiguti, Luiz Ricardo A; Rossi, Marcos A; Kettelhut, Isis C; Pupo, André S; Cunha, Fernando Q; Assreuy, Jamil

2017-07-01

G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances. Sepsis causes an important cardiovascular dysfunction in which nitric oxide (NO) has a relevant role. The present study aimed to assess the putative effect of inducible NO synthase (NOS2)-derived NO on the activity of GRK2 in the context of septic cardiac dysfunction. C57BL/6 mice were submitted to severe septic injury by cecal ligation and puncture (CLP). Heart function was assessed by isolated and perfused heart, echocardiography, and β-adrenergic receptor binding. GRK2 was determined by immunofluorescence and Western blot analysis in the heart and isolated cardiac myocytes. Sepsis increased NOS2 expression in the heart, increased plasma nitrite + nitrate levels, and reduced isoproterenol-induced isolated ventricle contraction, whole heart tension development, and β-adrenergic receptor density. Treatment with 1400W or with GRK2 inhibitor prevented CLP-induced cardiac hyporesponsiveness 12 and 24 h after CLP. Increased labeling of total and phosphorylated GRK2 was detected in hearts after CLP. With treatment of 1400W or in hearts taken from septic NOS2 knockout mice, the activation of GRK2 was reduced. 1400W or GRK2 inhibitor reduced mortality, improved echocardiographic cardiac parameters, and prevented organ damage. Therefore, during sepsis, NOS2-derived NO increases GRK2, which leads to a reduction in β-adrenergic receptor density, contributing to the heart dysfunction. Isolated cardiac myocyte data indicate that NO acts through the soluble guanylyl cyclase/cGMP/PKG pathway. GRK2 inhibition may be a potential therapeutic target in sepsis-induced cardiac dysfunction. NEW & NOTEWORTHY The main novelty presented here is to show that septic shock induces cardiac hyporesponsiveness to isoproterenol by a mechanism dependent on nitric oxide and mediated by G protein-coupled receptor kinase isoform 2. Therefore

Flow cytometric osmotic fragility test and eosin-5'-maleimide dye-binding tests are better than conventional osmotic fragility tests for the diagnosis of hereditary spherocytosis.

Science.gov (United States)

Arora, R D; Dass, J; Maydeo, S; Arya, V; Radhakrishnan, N; Sachdeva, A; Kotwal, J; Bhargava, M

2018-03-24

Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia with heterogeneous clinico-laboratory manifestations. We evaluated the flow-cytometric tests: eosin-5'-maleimide (EMA) and flow-cytometric osmotic fragility test (FOFT) and the conventional osmotic fragility tests (OFT) for the diagnosis of hereditary spherocytosis (HS). One hundred two suspected HS patients underwent EMA, FOFT, incubated OFT (IOFT), and room temperature OFT (RT-OFT). In addition, 10 cases of immune hemolytic anemia (IHA) were included, and performance of the above 4 tests was evaluated. For EMA and FOFT, 5 normal controls were assessed together with the patients and cutoffs were calculated using receiver-operator-characteristics curve (ROC) analysis. The best cutoff for %EMA decrease was 12.5%, and for FOFT, %residual red cells (%RRC) was 25.6%. The sensitivity and specificity of RT-OFT was 62.06% and 86.3%, respectively, while that of IOFT was 79.31% and 87.67%, respectively. Both flow cytometric tests performed better. Sensitivity and specificity of EMA was 86.2% and 93.9% respectively, and that of FOFT was 96.6% and 98.63%, respectively. The combination of the FOFT with IOFT or EMA dye-binding test yields a sensitivity of 100%, but with EMA, it had a higher specificity. Hb/MCHC was a predictor of the severity of the disease while %EMA decrease and %RRC did not correlate with severity of the disease. Flow-cytometric osmotic fragility test is the best possible single test followed by EMA for diagnosis of HS. A combination of FOFT and EMA can correctly diagnose 100% patients. These tests are likely to replace conventional OFTs in future. © 2018 John Wiley & Sons Ltd.

Cardiac regeneration therapy: connections to cardiac physiology.

Science.gov (United States)

Takehara, Naofumi; Matsubara, Hiroaki

2011-12-01

Without heart transplantation, a large number of patients with failing hearts worldwide face poor outcomes. By means of cardiomyocyte regeneration, cardiac regeneration therapy is emerging with great promise as a means for restoring loss of cardiac function. However, the limited success of clinical trials using bone marrow-derived cells and myoblasts with heterogeneous constituents, transplanted at a wide range of cell doses, has led to disagreement on the efficacy of cell therapy. It is therefore essential to reevaluate the evidence for the efficacy of cell-based cardiac regeneration therapy, focusing on targets, materials, and methodologies. Meanwhile, the revolutionary innovation of cardiac regeneration therapy is sorely needed to help the millions of people who suffer heart failure from acquired loss of cardiomyocytes. Cardiac regeneration has been used only in limited species or as a developing process in the rodent heart; now, the possibility of cardiomyocyte turnover in the human heart is being revisited. In the pursuit of this concept, the use of cardiac stem/progenitor stem cells in the cardiac niche must be focused to usher in a second era of cardiac regeneration therapy for the severely injured heart. In addition, tissue engineering and cellular reprogramming will advance the next era of treatment that will enable current cell-based therapy to progress to "real" cardiac regeneration therapy. Although many barriers remain, the prevention of refractory heart failure through cardiac regeneration is now becoming a realistic possibility.

Tirilazad mesylate protects stored erythrocytes against osmotic fragility.

Science.gov (United States)

Epps, D E; Knechtel, T J; Bacznskyj, O; Decker, D; Guido, D M; Buxser, S E; Mathews, W R; Buffenbarger, S L; Lutzke, B S; McCall, J M

1994-12-01

The hypoosmotic lysis curve of freshly collected human erythrocytes is consistent with a single Gaussian error function with a mean of 46.5 +/- 0.25 mM NaCl and a standard deviation of 5.0 +/- 0.4 mM NaCl. After extended storage of RBCs under standard blood bank conditions the lysis curve conforms to the sum of two error functions instead of a possible shift in the mean and a broadening of a single error function. Thus, two distinct sub-populations with different fragilities are present instead of a single, broadly distributed population. One population is identical to the freshly collected erythrocytes, whereas the other population consists of osmotically fragile cells. The rate of generation of the new, osmotically fragile, population of cells was used to probe the hypothesis that lipid peroxidation is responsible for the induction of membrane fragility. If it is so, then the antioxidant, tirilazad mesylate (U-74,006f), should protect against this degradation of stored erythrocytes. We found that tirilazad mesylate, at 17 microM (1.5 mol% with respect to membrane lecithin), retards significantly the formation of the osmotically fragile RBCs. Concomitantly, the concentration of free hemoglobin which accumulates during storage is markedly reduced by the drug. Since the presence of the drug also decreases the amount of F2-isoprostanes formed during the storage period, an antioxidant mechanism must be operative. These results demonstrate that tirilazad mesylate significantly decreases the number of fragile erythrocytes formed during storage in the blood bank.

Improved Erythrocyte Osmotic Fragility and Packed Cell Volume ...

African Journals Online (AJOL)

Improved Erythrocyte Osmotic Fragility and Packed Cell Volume following administration of Aloe barbadensis Juice Extract in Rats. ... Abstract. Aloe barbadensis is a popular house plant that has a long history of a multipurpose folk remedy. ... Keywords: osmotic fragility, packed cell volume, haemoglobin, Aloe vera ...

The correlation between fragility, density, and atomic interaction in glass-forming liquids.

Science.gov (United States)

Wang, Lijin; Guan, Pengfei; Wang, W H

2016-07-21

The fragility that controls the temperature-dependent viscous properties of liquids as the glass transition is approached, in various glass-forming liquids with different softness of the repulsive part of atomic interactions at different densities, is investigated by molecular dynamic simulations. We show that the landscape of fragility in purely repulsive systems can be separated into three regions denoted as RI, RII, and RIII, respectively, with qualitatively disparate dynamic behaviors: RI which can be described by "softness makes strong glasses," RII where fragility is independent of softness and can only be tuned by density, and RIII with constant fragility, suggesting that density plays an unexpected role for understanding the repulsive softness dependence of fragility. What is more important is that we unify the long-standing inconsistence with respect to the repulsive softness dependence of fragility by observing that a glass former can be tuned more fragile if nonperturbative attraction is added into it. Moreover, we find that the vastly dissimilar influences of attractive interaction on fragility could be estimated from the structural properties of related zero-temperature glasses.

Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study.

Science.gov (United States)

van Ingen, Jakko; Kohl, Thomas A; Kranzer, Katharina; Hasse, Barbara; Keller, Peter M; Katarzyna Szafrańska, Anna; Hillemann, Doris; Chand, Meera; Schreiber, Peter Werner; Sommerstein, Rami; Berger, Christoph; Genoni, Michele; Rüegg, Christian; Troillet, Nicolas; Widmer, Andreas F; Becker, Sören L; Herrmann, Mathias; Eckmanns, Tim; Haller, Sebastian; Höller, Christiane; Debast, Sylvia B; Wolfhagen, Maurice J; Hopman, Joost; Kluytmans, Jan; Langelaar, Merel; Notermans, Daan W; Ten Oever, Jaap; van den Barselaar, Peter; Vonk, Alexander B A; Vos, Margreet C; Ahmed, Nada; Brown, Timothy; Crook, Derrick; Lamagni, Theresa; Phin, Nick; Smith, E Grace; Zambon, Maria; Serr, Annerose; Götting, Tim; Ebner, Winfried; Thürmer, Alexander; Utpatel, Christian; Spröer, Cathrin; Bunk, Boyke; Nübel, Ulrich; Bloemberg, Guido V; Böttger, Erik C; Niemann, Stefan; Wagner, Dirk; Sax, Hugo

2017-10-01

Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease. We included 24 M chimaera isolates from 21 cardiac surgery-related patients in Switzerland, Germany, the Netherlands, and the UK, 218 M chimaera isolates from various types of HCUs in hospitals, from LivaNova (formerly Sorin; London, UK) and Maquet (Rastatt, Germany) brand HCU production sites, and unrelated environmental sources and patients, as well as eight Mycobacterium intracellulare isolates. Isolates were analysed by next-generation whole-genome sequencing using Illumina and Pacific Biosciences technologies, and compared with published M chimaera genomes. Phylogenetic analysis based on whole-genome sequencing of 250 isolates revealed two major M chimaera groups. Cardiac surgery-related patient isolates were all classified into group 1, in which all, except one, formed a distinct subgroup. This subgroup also comprised isolates from 11 cardiac surgery-related patients reported from the USA, most isolates from LivaNova HCUs, and one from their production site. Isolates from other HCUs and unrelated patients were more widely distributed in the phylogenetic tree. HCU contamination with M chimaera at the LivaNova factory seems a likely source for cardiothoracic surgery-related severe M chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the UK, the USA, and Australia. Protective measures and heightened clinician awareness are essential to guarantee patient safety. Partly funded by the EU Horizon 2020 programme, its FP7 programme, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection

Fragile X and autism: Intertwined at the molecular level leading to targeted treatments

Directory of Open Access Journals (Sweden)

Hagerman Randi

2010-09-01

Full Text Available Abstract Fragile X syndrome (FXS is caused by an expanded CGG repeat (> 200 repeats in the 5' untranslated portion of the fragile mental retardation 1 gene (FMR1, leading to deficiency or absence of the FMR1 protein (FMRP. FMRP is an RNA carrier protein that controls the translation of several other genes that regulate synaptic development and plasticity. Autism occurs in approximately 30% of FXS cases, and pervasive developmental disorder, not otherwise specified (PDD-NOS occurs in an additional 30% of cases. Premutation repeat expansions (55 to 200 CGG repeats may also give rise to autism spectrum disorders (ASD, including both autism and PDD-NOS, through a different molecular mechanism that involves a direct toxic effect of the expanded CGG repeat FMR1 mRNA. RNA toxicity can also lead to aging effects including tremor, ataxia and cognitive decline, termed fragile X-associated tremor ataxia syndrome (FXTAS, in premutation carriers in late life. In studies of mice bearing premutation expansions, there is evidence of early postnatal neuronal cell toxicity, presenting as reduced cell longevity, decreased dendritic arborization and altered synaptic morphology. There is also evidence of mitochondrial dysfunction in premutation carriers. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in autism without fragile X mutations. Research regarding dysregulation of neurotransmitter systems in FXS, including the metabotropic glutamate receptor (mGluR1/5 pathway and γ aminobutyric acid (GABAA pathways, have led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism.

Molecular characterization of X chromosome fragility in idiopathic ...

African Journals Online (AJOL)

Background: Fragile X syndrome (FXS) is the most common form of inherited mental retardation. Frequency of fragile X syndrome among male siblings and relatives of mentally retarded patients is relatively high. Cytogenetic diagnosis of FXS is unreliable since it is ineffective for the diagnosis of premutated males or ...

The impact of autism spectrum disorder symptoms on gesture use in fragile X syndrome and Down syndrome

Directory of Open Access Journals (Sweden)

Emily Lorang

2017-12-01

Down syndrome demonstrating symptoms of autism spectrum disorder as distinctly different from children with Down syndrome and few to no symptoms of autism spectrum disorder when implementing interventions or therapy techniques. Severity of autism spectrum disorder symptoms in fragile X syndrome affects qualitative gesture use and motivation to communicate through social gestures, which may be an appropriate goal to target in children with fragile X syndrome and heightened autism spectrum disorder symptoms.

Fragile-to-fragile liquid transition at Tg and stable-glass phase nucleation rate maximum at the Kauzmann temperature TK

International Nuclear Information System (INIS)

Tournier, Robert F.

2014-01-01

An undercooled liquid is unstable. The driving force of the glass transition at T g is a change of the undercooled-liquid Gibbs free energy. The classical Gibbs free energy change for a crystal formation is completed including an enthalpy saving. The crystal growth critical nucleus is used as a probe to observe the Laplace pressure change Δp accompanying the enthalpy change −V m ×Δp at T g where V m is the molar volume. A stable glass–liquid transition model predicts the specific heat jump of fragile liquids at T≤T g , the Kauzmann temperature T K where the liquid entropy excess with regard to crystal goes to zero, the equilibrium enthalpy between T K and T g , the maximum nucleation rate at T K of superclusters containing magic atom numbers, and the equilibrium latent heats at T g and T K . Strong-to-fragile and strong-to-strong liquid transitions at T g are also described and all their thermodynamic parameters are determined from their specific heat jumps. The existence of fragile liquids quenched in the amorphous state, which do not undergo liquid–liquid transition during heating preceding their crystallization, is predicted. Long ageing times leading to the formation at T K of a stable glass composed of superclusters containing up to 147 atom, touching and interpenetrating, are evaluated from nucleation rates. A fragile-to-fragile liquid transition occurs at T g without stable-glass formation while a strong glass is stable after transition

Invertible chaotic fragile watermarking for robust image authentication

International Nuclear Information System (INIS)

Sidiropoulos, Panagiotis; Nikolaidis, Nikos; Pitas, Ioannis

2009-01-01

Fragile watermarking is a popular method for image authentication. In such schemes, a fragile signal that is sensitive to manipulations is embedded in the image, so that it becomes undetectable after any modification of the original work. Most algorithms focus either on the ability to retrieve the original work after watermark detection (invertibility) or on detecting which image parts have been altered (localization). Furthermore, the majority of fragile watermarking schemes suffer from robustness flaws. We propose a new technique that combines localization and invertibility. Moreover, watermark dependency on the original image and the non-linear watermark embedding procedure guarantees that no malicious attacks will manage to create information leaks.

Clinical neurogenetics: fragile x-associated tremor/ataxia syndrome.

Science.gov (United States)

Hall, Deborah A; O'Keefe, Joan A

2013-11-01

This article summarizes the clinical findings, genetics, pathophysiology, and treatment of fragile X-associated tremor ataxia syndrome. The disorder occurs from a CGG repeat (55-200) expansion in the fragile X mental retardation 1 gene. It manifests clinically in kinetic tremor, gait ataxia, and executive dysfunction, usually in older men who carry the genetic abnormality. The disorder has distinct radiographic and pathologic findings. Symptomatic treatment is beneficial in some patients. The inheritance is X-linked and family members may be at risk for other fragile X-associated disorders. This information is useful to neurologists, general practitioners, and geneticists. Copyright © 2013. Published by Elsevier Inc.

Cardiac arrest

Science.gov (United States)

... magnesium. These minerals help your heart's electrical system work. Abnormally high or low levels can cause cardiac arrest. Severe physical stress. Anything that causes a severe stress on your ...

Genetics Home Reference: fragile X-associated primary ovarian insufficiency

Science.gov (United States)

... Share: Email Facebook Twitter Home Health Conditions FXPOI Fragile X-associated primary ovarian insufficiency Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Fragile X-associated primary ovarian insufficiency ( FXPOI ) is a condition ...

Genetics Home Reference: fragile X-associated tremor/ataxia syndrome

Science.gov (United States)

... Share: Email Facebook Twitter Home Health Conditions FXTAS Fragile X-associated tremor/ataxia syndrome Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Fragile X-associated tremor/ataxia syndrome ( FXTAS ) is characterized by ...

Correlation of C-Reactive Protein and Cardiac Enzymes with Angiographic Severity of Coronary Artery Disease in Pakistani Patients with Acute Coronary Syndrome

International Nuclear Information System (INIS)

Saleem, A.; Ali, A.

2017-01-01

Objective: To determine the correlation of C-reactive protein (CRP) levels with the severity of coronary stenosis on angiography and the association of cardiac enzymes with the degree of stenosis in acute coronary syndrome (ACS) patients. Secondly, to compare association of angiographic severity of vascular stenosis with CRP in patients with ST segment elevation myocardial infarction (STEMI) and non-STEMI / Unstable angina (UA). Study Design: Prospective, descriptive study. Place and Duration of Study: Khan Research Laboratories (KRL) Hospital, from October 2014 to March 2015. Methodology: CRP was measured on diagnosis of ACS in 70 patients. Cardiac enzymes were measured 6 hours after the onset of chest pain. Angiographic scoring for degree of stenosis and number of culprit vessels was done. Two groups consisting of patients with STEMI (group 1) and with NSTEMI/UA (group 2) were made. Results: No correlation was found between CRP levels and angiographic stenosis in patients with ACS (r=0.162, p>0.05). No association was found between eosinophil count and severity of stenosis (p=0.88). Rise of cardiac enzymes and degree of coronary stenosis showed a positive correlation (p <0.001). There was significant difference in the means of coronary artery stenosis scores between the two groups (Gensini score of groups 1 and 2: 35.9 +- 4 and 14 +- 8, respectively) p<0.001, but there was no significant difference in CRP levels. Conclusion: CRP is a marker of inflammation in ACS rather than a risk factor for determining the severity of vascular stenosis. Rise in cardiac enzymes still grade high in predicting severity of vascular stenosis than eosinophil count or CRP levels. (author)

The correlation between fragility, density, and atomic interaction in glass-forming liquids

Energy Technology Data Exchange (ETDEWEB)

Wang, Lijin; Guan, Pengfei, E-mail: pguan@csrc.ac.cn [Beijing Computational Science Research Center, Beijing 100193 (China); Wang, W. H. [Institute of Physics, Chinese Academy of Sciences, Beijing 100190 (China)

2016-07-21

The fragility that controls the temperature-dependent viscous properties of liquids as the glass transition is approached, in various glass-forming liquids with different softness of the repulsive part of atomic interactions at different densities, is investigated by molecular dynamic simulations. We show that the landscape of fragility in purely repulsive systems can be separated into three regions denoted as R{sub I,} R{sub II}, and R{sub III}, respectively, with qualitatively disparate dynamic behaviors: R{sub I} which can be described by “softness makes strong glasses,” R{sub II} where fragility is independent of softness and can only be tuned by density, and R{sub III} with constant fragility, suggesting that density plays an unexpected role for understanding the repulsive softness dependence of fragility. What is more important is that we unify the long-standing inconsistence with respect to the repulsive softness dependence of fragility by observing that a glass former can be tuned more fragile if nonperturbative attraction is added into it. Moreover, we find that the vastly dissimilar influences of attractive interaction on fragility could be estimated from the structural properties of related zero-temperature glasses.

The correlation between fragility, density, and atomic interaction in glass-forming liquids

International Nuclear Information System (INIS)

Wang, Lijin; Guan, Pengfei; Wang, W. H.

2016-01-01

The fragility that controls the temperature-dependent viscous properties of liquids as the glass transition is approached, in various glass-forming liquids with different softness of the repulsive part of atomic interactions at different densities, is investigated by molecular dynamic simulations. We show that the landscape of fragility in purely repulsive systems can be separated into three regions denoted as R I, R II , and R III , respectively, with qualitatively disparate dynamic behaviors: R I which can be described by “softness makes strong glasses,” R II where fragility is independent of softness and can only be tuned by density, and R III with constant fragility, suggesting that density plays an unexpected role for understanding the repulsive softness dependence of fragility. What is more important is that we unify the long-standing inconsistence with respect to the repulsive softness dependence of fragility by observing that a glass former can be tuned more fragile if nonperturbative attraction is added into it. Moreover, we find that the vastly dissimilar influences of attractive interaction on fragility could be estimated from the structural properties of related zero-temperature glasses.

Cardiac gated ventilation

International Nuclear Information System (INIS)

Hanson, C.W. III; Hoffman, E.A.

1995-01-01

There are several theoretic advantages to synchronizing positive pressure breaths with the cardiac cycle, including the potential for improving distribution of pulmonary and myocardial blood flow and enhancing cardiac output. The authors evaluated the effects of synchronizing respiration to the cardiac cycle using a programmable ventilator and electron beam CT (EBCT) scanning. The hearts of anesthetized dogs were imaged during cardiac gated respiration with a 50 msec scan aperture. Multi slice, short axis, dynamic image data sets spanning the apex to base of the left ventricle were evaluated to determine the volume of the left ventricular chamber at end-diastole and end-systole during apnea, systolic and diastolic cardiac gating. The authors observed an increase in cardiac output of up to 30% with inspiration gated to the systolic phase of the cardiac cycle in a non-failing model of the heart

Screening and diagnosis for the fragile X syndrome among the mentally retarded: an epidemiological and psychological survey. Collaborative Fragile X Study Group

NARCIS (Netherlands)

B.B.A. de Vries (Bert); B.A. Oostra (Ben); M.F. Niermeijer (Martinus); A. Tibben (Arend); A.M.W. van den Ouweland (Ans); S. Mohkamsing; H.J. Duivenvoorden (Hugo); E. Mol; K. Gelsema; M. van Rijn; D.J.J. Halley (Dicky); L.A. Sandkuijl (Lodewijk)

1997-01-01

textabstractThe fragile X syndrome is an X-linked mental retardation disorder caused by an expanded CGG repeat in the first exon of the fragile X mental retardation (FMR1) gene. Its frequency, X-linked inheritance, and consequences for relatives all prompt for

Preserved entropy and fragile magnetism.

Science.gov (United States)

Canfield, Paul C; Bud'ko, Sergey L

2016-08-01

A large swath of quantum critical and strongly correlated electron systems can be associated with the phenomena of preserved entropy and fragile magnetism. In this overview we present our thoughts and plans for the discovery and development of lanthanide and transition metal based, strongly correlated systems that are revealed by suppressed, fragile magnetism, quantum criticality, or grow out of preserved entropy. We will present and discuss current examples such as YbBiPt, YbAgGe, YbFe2Zn20, PrAg2In, BaFe2As2, CaFe2As2, LaCrSb3 and LaCrGe3 as part of our motivation and to provide illustrative examples.

Fragility and cooperativity concepts in hydrogen-bonded organic glasses

International Nuclear Information System (INIS)

Delpouve, N.; Vuillequez, A.; Saiter, A.; Youssef, B.; Saiter, J.M.

2012-01-01

Molecular dynamics at the glass transition of three lactose/oil glassy systems have been investigated according to the cooperativity and fragility approaches. From Donth's approach, the cooperativity length is estimated by modulated temperature calorimetric measurements. Results reveal that modification of the disaccharide by oil leads to increase the disorder degree in the lactose, the size of the cooperative domains and the fragility index. These particular hydrogen-bonded organic glasses follow the general tendency observed on organic and inorganic polymers: the higher the cooperativity length, the higher the value of the fragility index at T g .

Finiteness Marking in Boys with Fragile X Syndrome

Science.gov (United States)

Sterling, Audra M.; Rice, Mabel L.; Warren, Steven F.

2012-01-01

Purpose: The current study investigated finiteness marking (e.g., he walk "s", he walk "ed") in boys with fragile X syndrome (FXS); the boys were grouped based on receptive vocabulary (i.e., borderline, impaired). Method: Twenty-one boys with the full mutation of fragile X, between the ages of 8 and 16 years participated. The…

Seismic fragilities for nuclear power plant risk studies

International Nuclear Information System (INIS)

Kennedy, R.P.; Ravindra, M.K.

1983-01-01

Seismic fragilities of critical structures and equipment are developed as families of conditional failure frequency curves plotted against peak ground acceleration. The procedure is based on available data combined with judicious extrapolation of design information on plant structures and equipment. Representative values of fragility parameters for typical modern nuclear power plants are provided. Based on the fragility evaluation for about a dozen nuclear power plants, it is proposed that unnecessary conservatism existing in current seismic design practice could be removed by properly accounting for inelastic energy absorption capabilities of structures. The paper discusses the key contributors to seismic risk and the significance of possible correlation between component failures and potential design and construction errors

Imaging in blunt cardiac injury: Computed tomographic findings in cardiac contusion and associated injuries.

Science.gov (United States)

Hammer, Mark M; Raptis, Demetrios A; Cummings, Kristopher W; Mellnick, Vincent M; Bhalla, Sanjeev; Schuerer, Douglas J; Raptis, Constantine A

2016-05-01

Blunt cardiac injury (BCI) may manifest as cardiac contusion or, more rarely, as pericardial or myocardial rupture. Computed tomography (CT) is performed in the vast majority of blunt trauma patients, but the imaging features of cardiac contusion are not well described. To evaluate CT findings and associated injuries in patients with clinically diagnosed BCI. We identified 42 patients with blunt cardiac injury from our institution's electronic medical record. Clinical parameters, echocardiography results, and laboratory tests were recorded. Two blinded reviewers analyzed chest CTs performed in these patients for myocardial hypoenhancement and associated injuries. CT findings of severe thoracic trauma are commonly present in patients with severe BCI; 82% of patients with ECG, cardiac enzyme, and echocardiographic evidence of BCI had abnormalities of the heart or pericardium on CT; 73% had anterior rib fractures, and 64% had pulmonary contusions. Sternal fractures were only seen in 36% of such patients. However, myocardial hypoenhancement on CT is poorly sensitive for those patients with cardiac contusion: 0% of right ventricular contusions and 22% of left ventricular contusions seen on echocardiography were identified on CT. CT signs of severe thoracic trauma are frequently present in patients with severe BCI and should be regarded as indirect evidence of potential BCI. Direct CT findings of myocardial contusion, i.e. myocardial hypoenhancement, are poorly sensitive and should not be used as a screening tool. However, some left ventricular contusions can be seen on CT, and these patients could undergo echocardiography or cardiac MRI to evaluate for wall motion abnormalities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effective updating process of seismic fragilities using Bayesian method and information entropy

International Nuclear Information System (INIS)

Kato, Masaaki; Takata, Takashi; Yamaguchi, Akira

2008-01-01

Seismic probabilistic safety assessment (SPSA) is an effective method for evaluating overall performance of seismic safety of a plant. Seismic fragilities are estimated to quantify the seismically induced accident sequences. It is a great concern that the SPSA results involve uncertainties, a part of which comes from the uncertainty in the seismic fragility of equipment and systems. A straightforward approach to reduce the uncertainty is to perform a seismic qualification test and to reflect the results on the seismic fragility estimate. In this paper, we propose a figure-of-merit to find the most cost-effective condition of the seismic qualification tests about the acceleration level and number of components tested. Then a mathematical method to reflect the test results on the fragility update is developed. A Bayesian method is used for the fragility update procedure. Since a lognormal distribution that is used for the fragility model does not have a Bayes conjugate function, a parameterization method is proposed so that the posterior distribution expresses the characteristics of the fragility. The information entropy is used as the figure-of-merit to express importance of obtained evidence. It is found that the information entropy is strongly associated with the uncertainty of the fragility. (author)

Forests, Fragility and Conflict : Overview and Case Studies

OpenAIRE

Harwell, Emily; Farah, Douglas; Blundell, Arthur G.

2011-01-01

This book provides a synthesis of key themes and current knowledge about the links among forests, armed conflict, poverty, and various aspects of state fragility. The main themes addressed are: how predatory, incapable, or absent states are fragile in different ways, and their diverse relationships to forests and conflict; the mechanisms by which forests facilitate or prolong conflict, inc...

Data-Driven Decision Making in Fragile Contexts : Evidence from Sudan

OpenAIRE

Hamilton, Alexander; Hammer, Craig

2017-01-01

Data deficiencies contribute to state fragility and exacerbate fragile states’ already limited capacity to provide basic services, public security and rule of law. The lack of robust, good quality data can also have a disabling effect on government efforts to manage political conflict, and indeed can worsen conflict, since violent settings pose substantial challenges to knowledge generation, capture and application. In short, in fragile contexts the need for reliable evidence at all levels ...

Bayesian methodology for generic seismic fragility evaluation of components in nuclear power plants

International Nuclear Information System (INIS)

Yamaguchi, Akira; Campbell, R.D.; Ravindra, M.K.

1991-01-01

Bayesian methodology for updating the seismic fragility of components in nuclear power plants is presented. The generic fragility data which have been evaluated based on the past SPSAs are combined with the seismic experience data. Although the seismic experience is limited to the acceleration range below the median capacity of the components, it has been found that the evidence is effective to update the fragility tail. In other words, the uncertainty of the fragility is reduced although the median capacity itself is not modified to a great extent. The annual frequency of failure is also reduced as a result of the updating of the fragility tail. The PDF of the seismic capacity is handled in discrete form, which enables the use of arbitrary type of prior distribution. Accordingly, the Log-N prior can be used which is consistent with the widely used fragility model. For evaluating posterior fragility parameters (A m and B U ), two methods have been proposed. Furthermore, it has been found that the importance of evidence used in the Bayesian methodology can be quantified by the entropy of the evidence. Only the events with high entropy need to be considered in the Bayesian updating of the fragility. The currently available seismic experience database for typical components can be utilized to develop the fragility tail which is contributive to the seismically-induced failure frequency. The combined use of generic fragility and seismic experience data, with the aid of Bayesian methodology, provides refined generic fragility curves which are useful for SPSA studies. (author)

Detection and Quantification of the Fragile X Mental Retardation Protein 1 (FMRP).

Science.gov (United States)

LaFauci, Giuseppe; Adayev, Tatyana; Kascsak, Richard; Brown, W Ted

2016-12-09

The final product of FMR1 gene transcription, Fragile X Mental Retardation Protein 1 (FMRP), is an RNA binding protein that acts as a repressor of translation. FMRP is expressed in several tissues and plays important roles in neurogenesis, synaptic plasticity, and ovarian functions and has been implicated in a number of neuropsychological disorders. The loss of FMRP causes Fragile X Syndrome (FXS). In most cases, FXS is due to large expansions of a CGG repeat in FMR1 -normally containing 6-54 repeats-to over 200 CGGs and identified as full mutation (FM). Hypermethylation of the repeat induces FMR1 silencing and lack of FMRP expression in FM male. Mosaic FM males express low levels of FMRP and present a less severe phenotype that inversely correlates with FMRP levels. Carriers of pre-mutations (55-200 CGG) show increased mRNA, and normal to reduced FMRP levels. Alternative splicing of FMR1 mRNA results in 24 FMRP predicted isoforms whose expression are tissues and developmentally regulated. Here, we summarize the approaches used by several laboratories including our own to (a) detect and estimate the amount of FMRP in different tissues, developmental stages and various pathologies; and (b) to accurately quantifying FMRP for a direct diagnosis of FXS in adults and newborns.

A Trial of Metformin in Individuals With Fragile X Syndrome

Science.gov (United States)

2018-04-10

Fragile X Syndrome; Fragile X Mental Retardation Syndrome; Mental Retardation, X Linked; Genetic Diseases, X-Linked; Trinucleotide Repeat Expansion; Fra(X) Syndrome; Intellectual Disability; FXS; Neurobehavioral Manifestations; Sex Chromosome Disorders

Fragility and cooperativity concepts in hydrogen-bonded organic glasses

Energy Technology Data Exchange (ETDEWEB)

Delpouve, N., E-mail: delpouve.nicolas@gmail.com [AMME-LECAP EA 4528 International Laboratory, University of Rouen, Avenue de l' Universite BP 12, 76801 Saint Etienne du Rouvray (France); Vuillequez, A.; Saiter, A.; Youssef, B.; Saiter, J.M. [AMME-LECAP EA 4528 International Laboratory, University of Rouen, Avenue de l' Universite BP 12, 76801 Saint Etienne du Rouvray (France)

2012-09-01

Molecular dynamics at the glass transition of three lactose/oil glassy systems have been investigated according to the cooperativity and fragility approaches. From Donth's approach, the cooperativity length is estimated by modulated temperature calorimetric measurements. Results reveal that modification of the disaccharide by oil leads to increase the disorder degree in the lactose, the size of the cooperative domains and the fragility index. These particular hydrogen-bonded organic glasses follow the general tendency observed on organic and inorganic polymers: the higher the cooperativity length, the higher the value of the fragility index at T{sub g}.

Seismic fragility analysis of structural components for HFBR facilities

International Nuclear Information System (INIS)

Park, Y.J.; Hofmayer, C.H.

1992-01-01

The paper presents a summary of recently completed seismic fragility analyses of the HFBR facilities. Based on a detailed review of past PRA studies, various refinements were made regarding the strength and ductility evaluation of structural components. Available laboratory test data were analysed to evaluate the formulations used to predict the ultimate strength and deformation capacities of steel, reinforced concrete and masonry structures. The biasness and uncertainties were evaluated within the framework of the fragility evaluation methods widely accepted in the nuclear industry. A few examples of fragility calculations are also included to illustrate the use of the presented formulations

Living cardiac patch: the elixir for cardiac regeneration.

Science.gov (United States)

Lakshmanan, Rajesh; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

2012-12-01

A thorough understanding of the cellular and muscle fiber orientation in left ventricular cardiac tissue is of paramount importance for the generation of artificial cardiac patches to treat the ischemic myocardium. The major challenge faced during cardiac patch engineering is to choose a perfect combination of three entities; cells, scaffolds and signaling molecules comprising the tissue engineering triad for repair and regeneration. This review provides an overview of various scaffold materials, their mechanical properties and fabrication methods utilized in cardiac patch engineering. Stem cell therapies in clinical trials and the commercially available cardiac patch materials were summarized in an attempt to provide a recent perspective in the treatment of heart failure. Various tissue engineering strategies employed thus far to construct viable thick cardiac patches is schematically illustrated. Though many strategies have been proposed for fabrication of various cardiac scaffold materials, the stage and severity of the disease condition demands the incorporation of additional cues in a suitable scaffold material. The scaffold may be nanofibrous patch, hydrogel or custom designed films. Integration of stem cells and biomolecular cues along with the scaffold may provide the right microenvironment for the repair of unhealthy left ventricular tissue as well as promote its regeneration.

Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system

NARCIS (Netherlands)

Bezzina, Connie R.; Rook, Martin B.; Groenewegen, W. Antoinette; Herfst, Lucas J.; van der Wal, Allard C.; Lam, Jan; Jongsma, Habo J.; Wilde, Arthur A. M.; Mannens, Marcel M. A. M.

2003-01-01

Cardiac conduction defects associate with mutations in SCN5A, the gene encoding the cardiac Na+ channel. In the present study, we characterized a family in which the proband was born in severe distress with irregular wide complex tachycardia. His older sister died at 1 year of age from severe

Agricultural Fragility Estimates Subjected to Volcanic Ash Fall Hazards

Science.gov (United States)

Ham, H. J.; Lee, S.; Choi, S. H.; Yun, W. S.

2015-12-01

Agricultural Fragility Estimates Subjected to Volcanic Ash Fall Hazards Hee Jung Ham1, Seung-Hun Choi1, Woo-Seok Yun1, Sungsu Lee2 1Department of Architectural Engineering, Kangwon National University, Korea 2Division of Civil Engineering, Chungbuk National University, Korea ABSTRACT In this study, fragility functions are developed to estimate expected volcanic ash damages of the agricultural sector in Korea. The fragility functions are derived from two approaches: 1) empirical approach based on field observations of impacts to agriculture from the 2006 eruption of Merapi volcano in Indonesia and 2) the FOSM (first-order second-moment) analytical approach based on distribution and thickness of volcanic ash observed from the 1980 eruption of Mt. Saint Helens and agricultural facility specifications in Korea. Fragility function to each agricultural commodity class is presented by a cumulative distribution function of the generalized extreme value distribution. Different functions are developed to estimate production losses from outdoor and greenhouse farming. Seasonal climate influences vulnerability of each agricultural crop and is found to be a crucial component in determining fragility of agricultural commodities to an ash fall. In the study, the seasonality coefficient is established as a multiplier of fragility function to consider the seasonal vulnerability. Yields of the different agricultural commodities are obtained from Korean Statistical Information Service to create a baseline for future agricultural volcanic loss estimation. Numerically simulated examples of scenario ash fall events at Mt. Baekdu volcano are utilized to illustrate the application of the developed fragility functions. Acknowledgements This research was supported by a grant 'Development of Advanced Volcanic Disaster Response System considering Potential Volcanic Risk around Korea' [MPSS-NH-2015-81] from the Natural Hazard Mitigation Research Group, Ministry of Public Safety and Security of

The Seismic Fragility Evaluation of an Offsite Transformer according to Aging Effects

International Nuclear Information System (INIS)

Kim, Min Kyu; Choi, In Kil

2008-01-01

A seismic fragility analysis was performed, especially for an aged electric power transmission system, in this study. A real electric transformer system for Korean Nuclear Power Plants was selected for the seismic fragility evaluation. In the case of a seismic fragility analysis we should use design material properties and conditions. However material properties and environmental conditions of most structures and equipment are changed according to a lapse of time. Aging conditions greatly affect the integrity of the structures and equipment at NPP sites, but it is very difficult to estimate them qualitatively. Integrity of an anchor bolt system was considered with the aging conditions for an electric transformer system. At first, a seismic fragility analysis was performed for a fine condition for an electric transformer system. After that, a seismic fragility analysis according to the fastener of an anchor bolt system was conducted. This study showed that a looser anchor bolt creates seismic responses and seismic fragility changes of more 10%

Diagnostic, carrier and prenatal genetic testing for fragile X ...

African Journals Online (AJOL)

Background. Fragile X syndrome (FXS), the most common inherited cause of intellectual disability (ID) worldwide, is caused by the expansion of a CGG repeat in the fragile X mental retardation gene (FMR-1) gene. Objectives. To review, retrospectively, the genetic services for FXS and other FMR-1-related disorders ...

Whole-of-Government Approaches to Fragile States in Africa

DEFF Research Database (Denmark)

Olsen, Gorm Rye

2013-01-01

For a number of years fragile states have been high on the foreign policy agendas of the USA and the EU. Both actors look upon fragile states with great concern and consider them as security threats. Officially they give priority to ‘whole-of-government approaches’ (wga) when addressing the threats...

Cities could hold the key to understanding fragility | IDRC ...

International Development Research Centre (IDRC) Digital Library (Canada)

Cities are engines of economic growth and the primary sites of basic service delivery. Yet weak governance, along with inequalities related to income, social class, religion, and gender, may lead to a breakdown of systems and structures, and eventually to "fragile cities." Although the fragile cities concept is relatively new, ...

Relationship between seasonal weather changes, risk of dehydration, and incidence of severe bradyarrhythmias requiring urgent temporary transvenous cardiac pacing in an elderly population

Science.gov (United States)

Palmisano, Pietro; Accogli, Michele; Zaccaria, Maria; Vergari, Alessandra; De Luca De Masi, Gabriele; Negro, Luca; De Blasi, Sergio

2014-09-01

There is little information on any seasonal variations or meteorological factors associated with symptomatic bradyarrhythmias requiring cardiac pacing. The aim of this single-center study was to investigate the seasonal distribution of the incidence of severe, life-threatening bradyarrhythmias requiring urgent temporary transvenous cardiac pacing in an elderly population. Consecutive patients who underwent urgent temporary transvenous cardiac pacing between 2007 and 2012 were enrolled. The baseline characteristics of the patients and some meteorological parameters, including the calculation the daily heat index (HI), were recorded. During the study period, 79 consecutive patients (mean age 82 ± 8 years, 41 % male) underwent urgent temporary transvenous cardiac pacing, mainly for third-degree atrioventricular block (79 %). The incidence of bradyarrhythmias was significantly higher in summer than in the other seasons ( P 90 °F for >3 h per day for at least 10 days ( P renal function impairment and hyperkalemia (all P < 0.05). This study showed an increased incidence of severe bradyarrhythmias in an elderly population during the hottest months of the year. In these months, in subjects characterized by increased susceptibility to dehydration, the risk of developing bradyarrhythmias was increased significantly.

EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders

Science.gov (United States)

Biancalana, Valérie; Glaeser, Dieter; McQuaid, Shirley; Steinbach, Peter

2015-01-01

Different mutations occurring in the unstable CGG repeat in 5' untranslated region of FMR1 gene are responsible for three fragile X-associated disorders. An expansion of over ∼200 CGG repeats when associated with abnormal methylation and inactivation of the promoter is the mutation termed ‘full mutation' and is responsible for fragile X syndrome (FXS), a neurodevelopmental disorder described as the most common cause of inherited intellectual impairment. The term ‘abnormal methylation' is used here to distinguish the DNA methylation induced by the expanded repeat from the ‘normal methylation' occurring on the inactive X chromosomes in females with normal, premutation, and full mutation alleles. All male and roughly half of the female full mutation carriers have FXS. Another anomaly termed ‘premutation' is characterized by the presence of 55 to ∼200 CGGs without abnormal methylation, and is the cause of two other diseases with incomplete penetrance. One is fragile X-associated primary ovarian insufficiency (FXPOI), which is characterized by a large spectrum of ovarian dysfunction phenotypes and possible early menopause as the end stage. The other is fragile X-associated tremor/ataxia syndrome (FXTAS), which is a late onset neurodegenerative disorder affecting males and females. Because of the particular pattern and transmission of the CGG repeat, appropriate molecular testing and reporting is very important for the optimal genetic counselling in the three fragile X-associated disorders. Here, we describe best practice guidelines for genetic analysis and reporting in FXS, FXPOI, and FXTAS, including carrier and prenatal testing. PMID:25227148

[Cardiac cachexia].

Science.gov (United States)

Miján, Alberto; Martín, Elvira; de Mateo, Beatriz

2006-05-01

Chronic heart failure (CHF), especially affecting the right heart, frequently leads to malnutrition. If the latter is severe and is combined to other factors, it may lead to cardiac cachexia. This one is associated to increased mortality and lower survival of patients suffering from it. The causes of cardiac cachexia are diverse, generally associated to maintenance of a negative energy balance, with increasing evidence of its multifactorial origin. Neurohumoral, inflammatory, immunological, and metabolic factors, among others, are superimposed in the patient with CHF, leading to involvement and deterioration of several organs and systems, since this condition affects both lean (or active cellular) mass and adipose and bone tissue osteoporosis. Among all, the most pronounced deterioration may be seen at skeletal muscle tissue, at both structural and functional levels, the heart not being spared. As for treatment, it should be based on available scientific evidence. Assessment of nutritional status of any patient with CHF is a must, with the requirement of nutritional intervention in case of malnutrition. In this situation, especially if accompanied by cardiac cachexia, it is required to modify energy intake and oral diet quality, and to consider the indication of specific complementary or alternative artificial nutrition. Besides, the causal relationship of the beneficial role of moderate physical exertion is increasing, as well as modulation of metabolic and inflammatory impairments observed in cardiac cachexia with several drugs, leading to a favorable functional and structural response in CHF patients.

Radiology of Osteogenesis Imperfecta, Rickets and Other Bony Fragility States.

Science.gov (United States)

Calder, Alistair D

2015-01-01

This section gives an overview of radiological findings in bony fragility states, with a special focus on osteogenesis imperfecta (OI) and rickets. Conventional radiological assessment of bone density is inaccurate and imprecise and only reliably detects severe osteopaenia. However, other aspects of bone structure and morphology can be assessed, and it is possible to distinguish between osteopaenic and osteomalacic states. OI is a heterogeneous group of disorders of type 1 collagen formation and processing that are characterised by varying degrees of bony fragility, with presentations varying from perinatal lethality to asymptomatic. Radiological diagnosis of severe forms is usually straightforward, but that of milder disease may be challenging because specific features are often absent. However, a multidisciplinary approach is usually successful. Features of OI, including Wormian bones, skull base deformities, vertebral involvement and long bone fractures and deformities, are reviewed in this section. Rickets is best defined as a disorder of the growth plate characterised by the impaired apoptosis of hypertrophied chondrocytes. Vitamin D deficiency is a common cause of rickets. The patho-anatomical basis of radiological findings in rickets is reviewed and illustrated. Rickets is frequently accompanied by hyperparathyroidism and osteomalacia. Rickets used to be classified as calciopaenic or phosphopaenic but is now referred to as parathyroid hormone or fibroblast growth factor 23 mediated, respectively [1]. The radiological features of the two forms are reviewed. © 2015 S. Karger AG, Basel.

The effect of sleep apnea severity on cardiac autonomic activity during night time in obstructive sleep apnea patients

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Gulay Ozkececi

Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: Impaired autonomic cardiac function is an important consequence of obstructive sleep apnea (OSA. This impairment is mainly due to intermittent hypoxia episodes following apneas. However, the impact of apnea severity on autonomic cardiac function remains unclear. The aim of this study was to evaluate the relationship between the severity of sleep apnea and heart rate turbulence (HRT and heart rate variability (HRV in OSA. DESIGN AND SETTING: Observational cross-sectional study conducted in the Departments of Cardiology and Pulmonary Diseases, Afyon Kocatepe University, Turkey. METHODS: 106 patients with OSA and 27 healthy volunteers were enrolled. Based on apnea hypopnea index (AHI values, obstructive sleep apnea severity was classified as follows: mild OSA (AHI ≥ 5 and 30. HRV and HRT parameters were assessed via 24-hour digital Holter electrocardiogram recordings for all subjects. RESULTS: HRV and HRT results were significantly lower among OSA patients than among control subjects (P < 0.05. However, there were no significant differences in HRT and HRV between the three patient subgroups. Correlations did emerge between AHI and the NN-interval parameter RMSSD and between oxygen desaturation and turbulence slope (respectively: r = -0.22, P = 0.037; and r = -0.28, P = 0.025. CONCLUSION: HRT and HRV results deteriorate in OSA. Correlations between apnea severity and these parameters seem to be present.

Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.

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Yuping Luo

2010-04-01

Full Text Available Fragile X syndrome (FXS, the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP. FMRP is an RNA-binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs. We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3beta. Dysregulation of GSK3beta led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis.

Glycogen synthase kinase-3: A promising therapeutic target for Fragile X Syndrome

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Marjelo M. Mines

2011-11-01

Full Text Available Recent advances in understanding the pathophysiological mechanisms contributing to Fragile X Syndrome (FXS have increased optimism that drug interventions can provide significant therapeutic benefits. FXS results from inadequate expression of functional fragile X mental retardation protein (FMRP. FMRP may have several functions, but it is most well-established as an RNA-binding protein that regulates translation, and it is by this mechanism that FMRP is capable of affecting numerous cellular processes by selectively regulating protein levels. The multiple cellular functions regulated by FMRP suggest that multiple interventions may be required for reversing the effects of deficient FMRP. Evidence that inhibitors of glycogen synthase kinase-3 (GSK3 may contribute to the therapeutic treatment of FXS is reviewed here. In the mouse model of FXS, which lacks FMRP expression (FX mice, GSK3 is hyperactive in several brain regions. Furthermore, significant improvements in several FX-related phenotypes have been obtained in FX mice following the administration of lithium, and in some case other GSK3 inhibitors. These responses include normalization of heightened audiogenic seizure susceptibility and of hyperactive locomotor behavior, enhancement of passive avoidance learning retention and of sociability behaviors, and corrections of macroorchidism, neuronal spine density, and neural plasticity measured electrophysiologically as long term depression. A pilot clinical trial of lithium in FXS patients also found improvements in several measures of behavior. Taken together, these findings indicate that lithium and other inhibitors of GSK3 are promising candidate therapeutic agents for treating FXS.

Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

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Peter Moritz Becher

2017-01-01

Full Text Available Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

Soil-Structure Interaction Effect on Fragility Curve of 3D Models of Concrete Moment-Resisting Buildings

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Ali Anvarsamarin

2018-01-01

Full Text Available This paper presents the probabilistic generation of collapse fragility curves for evaluating the performance of 3D, reinforced concrete (RC moment-resisting building models, considering soil-structure interaction (SSI by concentration on seismic uncertainties. It considers collapse as the loss of lateral load-resisting capacity of the building structures due to severe ground shaking and consequent large interstory drifts intensified by P-Δ effects as well as the strength and stiffness deterioration of their lateral load carrying systems. The estimation of the collapse performance of structures requires the relation between the intensity measure (IM and the probability of collapse that is determined using the generated collapse fragility curves. Considering a number of 6-, 12-, and 18-story, 3D, RC moment-resisting buildings, two scalar IMs are employed to estimate their collapse fragility curve. On the other hand, the effect of the site soil type on the collapse fragility curves was taken into account by considering the soil-structure interaction. According to the obtained results, adopting the average of spectral acceleration (Saavg intensity measure is more efficient in capturing the effect of the inherent uncertainties of the strong ground motions on the structural response parameters. In addition, considering the SSI for soil type D with shear-wave velocity of 180 m/s to 360 m/s reduces the median of intensity measure (IM = Sa(T1 of fragility curve in 6-, 12-, and 18-story buildings by 4.92%, 22.26%, and 23.03%, respectively.

Obesity, Food Selectivity, and Physical Activity in Individuals with Fragile X Syndrome

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Raspa, Melissa; Bailey, Donald B., Jr.; Bishop, Ellen; Holiday, David; Olmsted, Murrey

2010-01-01

National survey data from 884 families were used to examine the overall health of children and adults with fragile X syndrome. Results indicate the rate of obesity in adults with fragile X syndrome is similar to the general population (30%). Male children with fragile X syndrome, however, had higher rates of obesity (31%) when compared with…

Ectodermal dysplasia-skin fragility syndrome: A rare case report

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Subhash Kashyap

2015-01-01

Full Text Available Ectodermal dysplasia/skin fragility syndrome (ED-SFS is a newly described autosomal recessive disorder characterized by skin fragility and blistering, palmoplantar keratoderma, abnormal hair growth, nail dystrophy, and occasionally defective sweating. It results from mutations in the PKP1 gene encoding plakophilin 1 (PKP1, which is an important component of stratifying epithelial desmosomes and a nuclear component of many cell types. Only 12 cases of this rare genodermatosis have been reported so far. We present an unusual case of ED-SFS in a 12-year boy who was normal at birth but subsequently developed skin fragility, hair and nail deformities, abnormal dentition, palmoplantar keratoderma, and abnormal sweating but no systemic abnormality.

Detection and Quantification of the Fragile X Mental Retardation Protein 1 (FMRP

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Giuseppe LaFauci

2016-12-01

Full Text Available The final product of FMR1 gene transcription, Fragile X Mental Retardation Protein 1 (FMRP, is an RNA binding protein that acts as a repressor of translation. FMRP is expressed in several tissues and plays important roles in neurogenesis, synaptic plasticity, and ovarian functions and has been implicated in a number of neuropsychological disorders. The loss of FMRP causes Fragile X Syndrome (FXS. In most cases, FXS is due to large expansions of a CGG repeat in FMR1—normally containing 6–54 repeats—to over 200 CGGs and identified as full mutation (FM. Hypermethylation of the repeat induces FMR1 silencing and lack of FMRP expression in FM male. Mosaic FM males express low levels of FMRP and present a less severe phenotype that inversely correlates with FMRP levels. Carriers of pre-mutations (55–200 CGG show increased mRNA, and normal to reduced FMRP levels. Alternative splicing of FMR1 mRNA results in 24 FMRP predicted isoforms whose expression are tissues and developmentally regulated. Here, we summarize the approaches used by several laboratories including our own to (a detect and estimate the amount of FMRP in different tissues, developmental stages and various pathologies; and (b to accurately quantifying FMRP for a direct diagnosis of FXS in adults and newborns.

International Companies in Fragile States

DEFF Research Database (Denmark)

Patey, Luke; Kragelund, Peter

Denmark must not fail to promote corporate social responsibility in fragile states. International companies remain active in these environments, and often worsen rather than alleviate poor governance. Financial transparency and human rights initiatives offer the first step in ensuring...

Robust-yet-fragile nature of interdependent networks

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Tan, Fei; Xia, Yongxiang; Wei, Zhi

2015-05-01

Interdependent networks have been shown to be extremely vulnerable based on the percolation model. Parshani et al. [Europhys. Lett. 92, 68002 (2010), 10.1209/0295-5075/92/68002] further indicated that the more intersimilar networks are, the more robust they are to random failures. When traffic load is considered, how do the coupling patterns impact cascading failures in interdependent networks? This question has been largely unexplored until now. In this paper, we address this question by investigating the robustness of interdependent Erdös-Rényi random graphs and Barabási-Albert scale-free networks under either random failures or intentional attacks. It is found that interdependent Erdös-Rényi random graphs are robust yet fragile under either random failures or intentional attacks. Interdependent Barabási-Albert scale-free networks, however, are only robust yet fragile under random failures but fragile under intentional attacks. We further analyze the interdependent communication network and power grid and achieve similar results. These results advance our understanding of how interdependency shapes network robustness.

Epidemiology of "fragile skin": results from a survey of different skin types

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Haftek M

2013-12-01

Full Text Available Marek Haftek,1 Christine Coutanceau,2 Charles Taïeb3 1Université Lyon 1, Laboratoire de Recherche Dermatologique, Faculté de Médecine et de Pharmacie, Lyon, 2Département Médical, Laboratoires Dermatologiques A-Derma, Lavaur, 3Public Health, Pierre Fabre SA, Paris, France Background: Epidemiologic information regarding the prevalence of "fragile skin" in different adult populations is currently limited. The objective of the current survey was to assess the occurrence of perceived "fragile skin" across different skin types in the general adult population. Methods: Individuals aged 15–65 years from five representative geographic regions (France, Spain, Sweden, Japan, and the US were interviewed and grouped into the following skin types: Caucasian North skin (n=1,218, Caucasian South skin (n=1,695, Asian skin (n=1,500, and Black skin (n=500. The main survey question was "In your opinion, do you have fragile skin?" Concepts relating to the nature and appearance of an individual's skin were also evaluated. Results: A total of 4,913 individuals were interviewed. Subjects in the Caucasian North, Caucasian South, Asian, and Black skin type groups responded positively to the question "In your opinion, do you have fragile skin?" in the following proportions: 24.44%, 29.71%, 52.67%, and 42.20%, respectively. With the exception of individuals in the Black skin group, "fragile skin" was prevalent in significantly more women than men (P<0.0001. Compared with other age categories, the prevalence of "fragile skin" was significantly higher in individuals aged 15–34 years (P<0.0001, regardless of skin type. In general, individuals reporting "fragile skin" were 2–3-fold more likely to respond positively to a series of questions relating to the nature and appearance of their skin. The prevalence of "fragile skin" was also higher in individuals who experienced dermatosis (skin lesions of any type in the previous 12 months. Conclusion: Whilst these

Rescue of Synaptic Phenotypes and Spatial Memory in Young Fragile X Mice.

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Sun, Miao-Kun; Hongpaisan, Jarin; Alkon, Daniel L

2016-05-01

Fragile X syndrome (FXS) is characterized by synaptic immaturity, cognitive impairment, and behavioral changes. The disorder is caused by transcriptional shutdown in neurons of thefragile X mental retardation 1gene product, fragile X mental retardation protein. Fragile X mental retardation protein is a repressor of dendritic mRNA translation and its silencing leads to dysregulation of synaptically driven protein synthesis and impairments of intellect, cognition, and behavior, and FXS is a disorder that currently has no effective therapeutics. Here, young fragile X mice were treated with chronic bryostatin-1, a relatively selective protein kinase Cεactivator, which induces synaptogenesis and synaptic maturation/repair. Chronic treatment with bryostatin-1 rescues young fragile X mice from the disorder phenotypes, including normalization of most FXS abnormalities in 1) hippocampal brain-derived neurotrophic factor expression, 2) postsynaptic density-95 levels, 3) transformation of immature dendritic spines to mature synapses, 4) densities of the presynaptic and postsynaptic membranes, and 5) spatial learning and memory. The therapeutic effects were achieved without downregulation of metabotropic glutamate receptor (mGluR) 5 in the hippocampus and are more dramatic than those of a late-onset treatment in adult fragile X mice. mGluR5 expression was in fact lower in fragile X mice and its expression was restored with the bryostatin-1 treatment. Our results show that synaptic and cognitive function of young FXS mice can be normalized through pharmacological treatment without downregulation of mGluR5 and that bryostatin-1-like agents may represent a novel class of drugs to treat fragile X mental retardation at a young age and in adults. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Survey of seismic fragilities used in PRA studies of nuclear power plants

International Nuclear Information System (INIS)

Park, Y.J.; Hofmayer, C.H.; Chokshi, N.C.

1998-01-01

In recent years, seismic PRA studies have been performed on a large number of nuclear power plants in the USA. This paper presents a summary of a survey on fragility databases and the range of evaluated fragility values of various equipment categories based on past PRAs. The survey includes the use of experience data, the interpretations of available test data, and the quantification of uncertainties. The surveyed fragility databases are limited to data available in the public domain such as NUREG reports, conference proceedings and other publicly available reports. The extent of the availability of data as well as limitations are studied and tabulated for various equipment categories. The survey of the fragility values in past PRA studies includes not only the best estimate values, but also the dominant failure modes and the estimated uncertainty levels for each equipment category. The engineering judgments employed in estimating the uncertainty in the fragility values are also studied. This paper provides a perspective on the seismic fragility evaluation procedures for equipment in order to clearly identify the engineering analysis and judgment used in past seismic PRA studies

Prevalence and factors associated with fragility syndrome in older adults attending

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Milton Carlos Gonzáles-Mechán

2017-03-01

Full Text Available Objectives: To identify the prevalence and factors associated with fragility syndrome in older adults attending the EsSalud (Peruvian Social Security Health Insurance primary health care service, Chiclayo - Peru. Materials and methods: A descriptive, prospective and cross-sectional study was conducted on a sample consisting of 326 older adults from urban areas and surrounding districts of Chiclayo, who attend the outpatient service at the Hospital Naylamp and Policlínico Chiclayo Oeste. A data collection sheet including social-demographic variables, comorbidity and polypharmacy, and fragility syndrome clinical criteria was filled in. Results: The prevalence of fragility was 17.5% and that of pre-fragility, 40.9%. The most frequent fragility clinical criteria were as follows: self-reported fatigue (42.3% and decreased grip strength (32.8%. The bivariate analysis showed an association with age, level of education, occupation (class IV and V concerning manual work, comorbidity (class II, asymptomatic disease or asymptomatic disease that requires medication but is under control, polypharmacy, anemia, Parkinson’s disease and non-vascular neurological disease. The final prediction model covering the age (1.08, 95% CI: 1.03 to 1.12, higher education level as a preventive variable (0.21, 95% CI: 0.07 to 0.62, type II comorbidity (11 08, 95% CI: 1.45 to 84.38 and polypharmacy (2.49, 95% CI: 1.24 to 5.03 predicts the likelihood of fragility syndrome in 75.6%. Conclusions: There is a high prevalence of fragility in the elderly population attending the primary health care service, and a significant association with age, higher education level, type II comorbidity and polypharmacy

Fragility: The Next Wave in Critical Infrastructure Protection

OpenAIRE

Allan McDougall

2009-01-01

In North America today, we are about to embark on a significant effort to repair, or even upgrade, many aspects of our infrastructure. Many of these efforts are linked to economic recovery packages. Others are based on sheer need. The challenge for decision makers and planners involves ensuring that scarce economic resources are put to their best use. Understanding the concept of fragility plays a pivotal part in reaching that understanding.Fragility, like many other systems—particularly Info...

Mathematical Definition, Mapping, and Detection of (Anti)Fragility

OpenAIRE

Taleb, Nassim N.; Douady, Raphael

2012-01-01

URL des Documents de travail : http://centredeconomiesorbonne.univ-paris1.fr/documents-de-travail/; Documents de travail du Centre d'Economie de la Sorbonne 2014.93 - ISSN : 1955-611X; We provide a mathematical definition of fragility and antifragility as negative or positive sensitivity to a semi-measure of dispersion and volatility (a variant of negative or positive "vega") and examine the link to nonlinear effects. We integrate model error (and biases) into the fragile or antifragile conte...

Fabrication and transfer of fragile 3D PDMS microstructures

International Nuclear Information System (INIS)

Karlsson, J Mikael; Haraldsson, Tommy; Carlborg, Carl Fredrik; Van der Wijngaart, Wouter; Hansson, Jonas; Russom, Aman

2012-01-01

We present a method for PDMS microfabrication of fragile membranes and 3D fluidic networks, using a surface modified water-dissolvable release material, poly(vinyl alcohol), as a tool for handling, transfer and release of fragile polymer microstructures. The method is well suited for the fabrication of complex multilayer microfluidic devices, here shown for a PDMS device with a thin gas permeable membrane and closely spaced holes for vertical interlayer connections fabricated in a single layer. To the authors’ knowledge, this constitutes the most advanced PDMS fabrication method for the combination of thin, fragile structures and 3D fluidics networks, and hence a considerable step in the direction of making PDMS fabrication of complex microfluidic devices a routine endeavour. (paper)

Fragility Variation of Lithium Borate Glasses Studied by Temperature-Modulated DSC

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Matsuda, Yu; Fukawa, Yasuteru; Kawashima, Mitsuru; Kojima, Seiji

2008-02-01

The fragility of lithium borate glass system has been investigated by Temperature-Modulated Differential Scanning Calorimetry (TMDSC). The frequency and temperature dependences of dynamic specific heat have been observed in the vicinity of a glass transition temperature Tg. It is shown that the value of the fragility index m can be determined from the temperature dependence of the α-relaxation times observed by TMDSC, when the raw phase angle is properly corrected. The composition dependence of the fragility has been also discussed.

Fragility non-hip fracture patients are at risk.

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Gosch, M; Druml, T; Nicholas, J A; Hoffmann-Weltin, Y; Roth, T; Zegg, M; Blauth, M; Kammerlander, C

2015-01-01

Fragility fractures are a growing worldwide health care problem. Hip fractures have been clearly associated with poor outcomes. Fragility fractures of other bones are common reasons for hospital admission and short-term disability, but specific long-term outcome studies of non-hip fragility fractures are rare. The aim of our trial was to evaluate the 1-year outcomes of non-hip fragility fracture patients. This study is a retrospective cohort review of 307 consecutive older inpatient non-hip fracture patients. Patient data for analysis included fracture location, comorbidity prevalence, pre-fracture functional status, osteoporosis treatments and sociodemographic characteristics. The main outcomes evaluated were 1-year mortality and post-fracture functional status. As compared to the expected mortality, the observed 1-year mortality was increased in the study group (17.6 vs. 12.2 %, P = 0.005). After logistic regression, three variables remained as independent risk factors for 1-year mortality among non-hip fracture patients: malnutrition (OR 3.3, CI 1.5-7.1), Charlson comorbidity index (CCI) (OR 1.3, CI 1.1-1.5) and the Parker Mobility Score (PMS) (OR 0.85, CI 0.74-0.98). CCI and PMS were independent risk factors for a high grade of dependency after 1 year. Management of osteoporosis did not significantly improve after hospitalization due to a non-hip fragility fracture. The outcomes of older non-hip fracture patients are comparable to the poor outcomes of older hip fracture patients, and appear to be primarily related to comorbidities, pre-fracture function and nutritional status. The low rate of patients on osteoporosis medications likely reflects the insufficient recognition of the importance of osteoporosis assessment and treatment in non-hip fracture patients. Increased clinical and academic attention to non-hip fracture patients is needed.

METHODOLOGICAL CONTRIBUTION FOR THE ANALYSIS OF EMERGENT FRAGILITY: case study of the municipality of Colombo, Paraná.

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Luciano de Almeida

2009-06-01

Full Text Available This paper proposes an adaptation of the methodology of Environmental Fragility in order to detect Emergent Fragility.  We discuss the need for methods for measuring the impact of agriculture  which take different agricultural practices and ways of using natural resources into account. This methodological analysis is carried out through a case study of the municipality of Colombo, Paraná, in the Greater Curitiba Metropolitan Region.  This municipality is situated in an area of water springs and above an aquifer. It can be characterized by the presence of conventional and intensive vegetable production as well as the cultivation of several annual crops.   We elaborated several charts on Environmental Fragility (Potential and Emergent and evaluated the impact that agriculture has had on the quality and availability of water resources in the area we studied.  We went on to generate new parameters for distinguishing agricultural practices and their respective environmental impacts. Data have shown that, to the extent that different forms of agricultural use of soil are recognized and analyzed with greater precision, prospects for emergent fragility also vary. In the case of Colombo, data show that capacity for soil protection is greater when our proposed methodology is implemented, yet reaffirm the notion that agriculture that is practiced in areas where vegetables are grown implies high levels of soil vulnerability, also affecting water sources. Furthermore, we are led to conclude that the methodological procedures we propose are important in order to break with an erroneous view that generalizes the environmental impacts that agriculture causes, and in order to place greater value on the use of more  conservationist agricultural techniques.

Risk factors for fragility fracture in Seremban district, Malaysia: a comparison of patients with fragility fracture in the orthopedic ward versus those in the outpatient department.

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Keng Yin Loh; King Hock Shong; Soo Nie Lan; Lo, Wan-Yi; Shu Yuen Woon

2008-01-01

Osteoporosis is a silent disease and becomes clinically significant in the presence of fragility fracture. Identifying risk factors that are associated with osteoporosis in the community is important in reducing the incidence of fragility fracture. The aim of this study is to identify risk factors associated with fragility fracture in the Seremban District of Malaysia. This is a population comparison study between orthopedic ward patients and outpatients attending a community health clinic for 6 months. Epidemiological data and the possible risk factors for osteoporosis were collected by direct interview. This study demonstrates that advancing age, low body weight, smoking, lack of regular exercise, low consumption of calcium containing foods, and using bone depleting drugs (steroids, thyroid hormone, and frusemides) are major risk factors for fragility fracture. Most of these risk factors are modifiable through effective lifestyle intervention.

Clinical aspects of the fragile X syndrome.

Science.gov (United States)

Brown, W Ted

2012-01-01

Fragile X syndrome patients express a wide array of cognitive and other gender-specific phenotypic features. These manifestations result not only from molecular mechanisms that are altered as a result of the expansion of a CGG-repeat region in the FMR1 promoter, but also genetic factors such as founder effects and mosaicism. In this chapter, I will summarize the many and varied features of fragile X syndrome as they present themselves in a clinical setting and describe the procedures that are used to diagnose patients. Finally, I will briefly touch on recent developments that will affect patient screening in the future.

The World Bank and Fragile States: Dynamics of Cooperation and Aid Structure

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Solomatin A.

2018-03-01

Full Text Available The eradication of extreme poverty in fragile states is one of the central problems of global governance at the present time. Development of these states is hindered by instability, weak public and social institutions or ongoing conflicts and violence. The World Bank is a key partner of fragile states, which account for almost a third of the world’s population. This article is a continuation of research exploring the evolution of conceptual and practical approaches by the World Bank to cooperation with fragile states. Its methodology is based on a multilevel analysis of the securitization of foreign aid as proposed by J. Lind and J. Howell of the London School of Economics. The main focus of this examination is on the dynamics of the change of scale and structure of the World Bank’s aid to fragile states in comparison with global armed trends of providing aid to fragile states as well. This article concludes that statements about the priority of the Bank’s work in fragile states have not yet been realized in practice. The Bank remains committed to the standard approach to working with this group of recipients, which involves serious risks. The World Bank leans toward supporting projects in fragile states which increases volatility and reduces aid predictability. This trend undermines the development potentials of recipient states. Attention is drawn to political factors influencing aid flows to fragile states and particularly to the tendency of increasing the share of aid provided to fragile states through multi donor trust funds rather than through the mechanisms of the International Development Association (IDA. This trend indicates that the Bank is no longer a central point of aid distribution to the recipients, pointing to the lack of trust of donor states in the existing mechanisms and rules of aid distribution. It also reveals the expanding role of donors’ strategic interests in the process of choosing recipients of World Bank aid.

Raman and DSC studies of fragility in tellurium-zinc oxide glass formers

International Nuclear Information System (INIS)

Stavrou, Elissaios; Kripotou, Sotiria; Raptis, Constantine; Turrell, Sylvia; Syassen, Karl

2011-01-01

Raman scattering and differential scanning calorimetry (DSC) measurements have been carried out in four mixed (TeO 2 ) 1-x (ZnO) x (x = 0.1, 0.2, 0.3, 0.4) glasses at high temperatures (Raman and DSC through the glass transition) and high pressures (Raman) with the aim of determining the fragility of these glass forming oxides. Four different criteria, corresponding to four parameters, were applied to assess the fragility of the glasses. From the DSC studies, we have obtained the fragility parameter m which corresponds to the slopes of Arrhenius (lnQ vs. 1/T g , were Q is the heating rate) plots, and the glass transition width ΔT g . Also, from the low-frequency Raman scattering, and in particular the boson peak intensity of the glasses at T g , we have estimated the fragility ratio r R (T g ) = I min /I max whose value serves as another (empirical) fragility criterion. Finally, from high pressure Raman measurements on the glasses, we have estimated the Grueneisen parameter γ T for each glass, which constitutes the fourth fragility parameter adopted in this work. Considering the four parameters ΔT g , m, r (T g ) and γ T and the generally accepted (empirical) fragility criteria, we conclude that the mixed tellurium-zinc oxides constitute strong-to-intermediate glass formers (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

Seismic fragility of ventilation stack of nuclear power plant

International Nuclear Information System (INIS)

Nefedov, S.S.; Yugai, T.Z.; Kalinkin, I.V.; Vizir, P.L.

2003-01-01

Fragility study of safety related elements is necessary step in seismic PSA of nuclear power plant (NPP). In present work fragility was analyzed after the example of the ventilation stack of NPP. Ventilation stack, considered in present work, is a separately erected construction with height of 100 m made of cast-in-place reinforced concrete. In accordance with IAEA terminology fragility of element is defined as conditional probability of its failure at given level of seismic loading. Failure of a ventilation stack was considered as development of the plastic hinge in some section of a shaft. Seismic ground acceleration a, which corresponds to failure, could be defined as limit seismic acceleration of ventilation stack [a]. Limit seismic acceleration [a] was considered as random value. Sources of its variation are connected with stochastic nature of factors determining it (properties of construction materials, soils etc.), and also with uncertainties of existing analytical techniques. Random value [a] was assumed to be distributed lognormally. Median m[a] and logarithmically standard deviation β of this distribution were defined by 'scaling method' developed by R.P. Kennedy et al. Using this values fragility curves were plotted for different levels of confidence probability. (author)

Serum cardiac troponin I and cardiac troponin T concentrations in dogs with gastric dilatation-volvulus.

Science.gov (United States)

Schober, Karsten E; Cornand, Corinna; Kirbach, Babett; Aupperle, Heike; Oechtering, Gerhard

2002-08-01

To determine whether serum concentrations of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) are increased in dogs with gastric dilatationvolvulus (GDV) and whether concentrations correlate with severity of ECG abnormalities or outcome. Prospective case series. 85 dogs with GDV. Serum cTnl and cTnT concentrations were measured 12 to 24, 48, 72, and 96 hours after surgery. Dogs were grouped on the basis of severity of ECG abnormalities and outcome. cTnl and cTnT were detected in serum from 74 (87%) and 43 (51%) dogs, respectively. Concentrations were significantly different among groups when dogs were grouped on the basis of severity of ECG abnormalities (none or mild vs moderate vs severe). Dogs that died (n = 16) had significantly higher serum cTnI (24.9 ng/ml) and cTnT (0.18 ng/ml) concentrations than did dogs that survived (2.05 and dogs with high serum cardiac troponin concentrations. Results indicate that concentrations of cTnI and cTnT suggestive of myocardial cell injury can commonly be found in serum from dogs with GDV and that serum cardiac troponin concentrations are associated with severity of ECG abnormalities and outcome.

[Cardiac and metabolic risk factors in severe mental disorders. Task of a prevention manager].

Science.gov (United States)

Lederbogen, F; Schwarz, P; Häfner, S; Schweiger, U; Bohus, M; Deuschle, M

2015-07-01

People with severe mental disorders have a reduction in life expectancy of 13-30 % compared with the general population. This severe disadvantage is primarily due to an increased prevalence of cardiac and metabolic disorders, especially coronary heart disease (CHD) and type 2 diabetes mellitus and are the result of untoward health behavior characterized by smoking, low levels of physical activity and unhealthy dietary habits. Obesity, arterial hypertension and lipid disorders are also associated with this behavior and further increase the risk of CHD and type 2 diabetes. Thus, people with mental disorders constitute a population with a high risk of cardiovascular events. Appropriate measures for prevention and therapy are urgently indicated but rarely applied. This article presents new organizational structures to overcome this deficit with a prevention manager playing a central role in organizing and applying preventive and therapeutic care. Results from cardiology and diabetic medicine have shown the effectiveness of pooling this responsibility. The measure has the potential to reduce the increased mortality of people with severe mental disorders.

Handbook of nuclear power plant seismic fragilities, Seismic Safety Margins Research Program

International Nuclear Information System (INIS)

Cover, L.E.; Bohn, M.P.; Campbell, R.D.; Wesley, D.A.

1983-12-01

The Seismic Safety Margins Research Program (SSMRP) has a gola to develop a complete fully coupled analysis procedure (including methods and computer codes) for estimating the risk of an earthquake-induced radioactive release from a commercial nuclear power plant. As part of this program, calculations of the seismic risk from a typical commercial nuclear reactor were made. These calculations required a knowledge of the probability of failure (fragility) of safety-related components in the reactor system which actively participate in the hypothesized accident scenarios. This report describes the development of the required fragility relations and the data sources and data reduction techniques upon which they are based. Both building and component fragilities are covered. The building fragilities are for the Zion Unit 1 reactor which was the specific plant used for development of methodology in the program. Some of the component fragilities are site-specific also, but most would be usable for other sites as well

Cities could hold the key to understanding fragility | CRDI - Centre ...

International Development Research Centre (IDRC) Digital Library (Canada)

Cities are engines of economic growth and the primary sites of basic service delivery. Yet weak governance, along with inequalities related to income, social class, religion, and gender, may lead to a breakdown of systems and structures, and eventually to "fragile cities." Although the fragile cities concept is relatively new, ...

Hematology and erythrocyte osmotic fragility of the Franquet's fruit bat (Epomops franqueti).

Science.gov (United States)

Ekeolu, Oyetunde Kazeem; Adebiyi, Olamide Elizabeth

2018-03-15

Hematological parameters are vital diagnostic tools for understanding health dynamics of humans and animals. Franquet's fruit bat (Epomops franqueti) is host to several parasites such as protozoa, bacteria, viruses and mites. Yet, studies exploring the values of its blood components with interest for research or food purposes are scarce. Thus, this study was carried out to investigate the hematological values of the adult E. franqueti. Seventeen (nine female and eight male) apparently healthy adult E. franqueti were captured from their roosting colony. Blood samples were collected for determination of erythrocyte indices [red blood cell count (RBC), packed cell volume (PCV), hemoglobin (Hb) concentration, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC)] and leukocyte indices [total white blood cell counts (WBC), lymphocytes, eosinophil, monocytes, neutrophil count and erythrocytes osmotic fragility]. There were no significant (p≥0.05) sex-related differences in RBC, PCV, Hb concentration, MCV, MCH, MCHC and total and differential WBC of E. franqueti. Erythrocyte osmotic fragility was significantly higher in female than in male E. franqueti at 0.1% NaCl. These considerations are critical in establishing reference ranges of blood parameters for E. franqueti and may provide insight to why they serve as reservoir hosts for several microorganisms.

RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility

Directory of Open Access Journals (Sweden)

Aisling Frizzell

2014-03-01

Full Text Available Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG repeat expansions and fragility, likely by unwinding problematic hairpins.

Fragile X syndrome: A review of clinical management

Science.gov (United States)

Lozano, Reymundo; Azarang, Atoosa; Wilaisakditipakorn, Tanaporn; Hagerman, Randi J

2016-01-01

Summary The fragile X mental retardation 1 gene, which codes for the fragile X mental retardation 1 protein, usually has 5 to 40 CGG repeats in the 5′ untranslated promoter. The full mutation is the almost always the cause of fragile X syndrome (FXS). The prevalence of FXS is about 1 in 4,000 to 1 in 7,000 in the general population although the prevalence varies in different regions of the world. FXS is the most common inherited cause of intellectual disability and autism. The understanding of the neurobiology of FXS has led to many targeted treatments, but none have cured this disorder. The treatment of the medical problems and associated behaviors remain the most useful intervention for children with FXS. In this review, we focus on the non-pharmacological and pharmacological management of medical and behavioral problems associated with FXS as well as current recommendations for follow-up and surveillance. PMID:27672537

[Predictive value of early phrase echocardiography and cardiac biological markers in patients with severe sepsis: a five-year single-center retrospective study].

Science.gov (United States)

Zang, Xuefeng; Chen, Wei; Sheng, Bo; Zhao, Lei; Gu, Xuyun; Zhen, Jie; Liu, Ping

2018-04-01

To assess the predictive value of early phrase echocardiography and cardiac biomarkers in patients with severe sepsis. A retrospective analysis of severe septic patients (patients with acute coronary syndrome and end stage renal disease were excluded) in department of intensive care unit of Capital Medical University Affiliated Beijing Shijitan Hospital from January 2013 to December 2017 was conducted. The acute physiology and chronic health evaluation II (APACHE II) score, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), myoglobin (MYO), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB) within 6 hours after admission, and bedside echocardiography indexes [left ventricular ejection fraction (LVEF), the ratio of the peak blood flow velocity in the early stage of the mitral valve and the peak blood flow rate of the mitral valve (E/A ratio)] within 6 hours after diagnosis were recorded. The differences of indexes between patients with decreased contractile function (LVEF value in severe sepsis patients. (1) A total of 316 patients were enrolled in the survey period. Decreased cardiac systolic function (LVEF value for prognosis in severe sepsis patient, among which NT-proBNP and cTnI had higher predictive value [the area under ROC curve (AUC) were 0.920 and 0.901 respectively, both P values measured by echocardiography in early phrase were unrelated to 28-day prognosis. APACHE II score, E/A ratio, NT-proBNP, cTnI, MYO, CK and CK-MB were related to 28-day prognosis. APACHE II scores and NT-proBNP were independent prognostic factors in severe sepsis patient.

Modeling Fragile X Syndrome in Drosophila

Science.gov (United States)

Drozd, Małgorzata; Bardoni, Barbara; Capovilla, Maria

2018-01-01

Intellectual disability (ID) and autism are hallmarks of Fragile X Syndrome (FXS), a hereditary neurodevelopmental disorder. The gene responsible for FXS is Fragile X Mental Retardation gene 1 (FMR1) encoding the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in RNA metabolism and modulating the expression level of many targets. Most cases of FXS are caused by silencing of FMR1 due to CGG expansions in the 5′-UTR of the gene. Humans also carry the FXR1 and FXR2 paralogs of FMR1 while flies have only one FMR1 gene, here called dFMR1, sharing the same level of sequence homology with all three human genes, but functionally most similar to FMR1. This enables a much easier approach for FMR1 genetic studies. Drosophila has been widely used to investigate FMR1 functions at genetic, cellular, and molecular levels since dFMR1 mutants have many phenotypes in common with the wide spectrum of FMR1 functions that underlay the disease. In this review, we present very recent Drosophila studies investigating FMRP functions at genetic, cellular, molecular, and electrophysiological levels in addition to research on pharmacological treatments in the fly model. These studies have the potential to aid the discovery of pharmacological therapies for FXS. PMID:29713264

Association between change in BMD and fragility fracture in women and men.

Science.gov (United States)

Berger, Claudie; Langsetmo, Lisa; Joseph, Lawrence; Hanley, David A; Davison, K Shawn; Josse, Robert G; Prior, Jerilynn C; Kreiger, Nancy; Tenenhouse, Alan; Goltzman, David

2009-02-01

Our objective was to estimate the relationship between longitudinal change in BMD and fragility fractures. We studied 3635 women and 1417 men 50-85 yr of age in the Canadian Multicentre Osteoporosis Study who had at least two BMD measurements (lumbar spine, femoral neck, total hip, and trochanter) within the first 5 yr of the study and fragility fractures (any, main, forearm/wrist, ribs, hip) within the first 7 yr. Multiple logistic regression was used to model the relationship between baseline BMD, BMD change, and fragility fractures. We found that, among nonusers of antiresorptives, independent of baseline BMD, a decrease of 0.01 g/cm(2)/yr in total hip BMD was associated with an increased risk of fragility fracture with ORs of 1.15 (95% CI: 1.01; 1.32) in women and 1.34 (95% CI: 1.02; 1.78) in men. The risk of fragility fractures in subgroups such as fast losers and those with osteopenia was better estimated by models that included BMD change than by models that included baseline BMD but excluded BMD change. Although the association between baseline BMD and fragility fractures was similar in users and nonusers of antiresorptives, the association was stronger in nonusers compared with users. These results show that BMD change in both men and women is an independent risk factor for fragility fractures and also predicts fracture risk in those with osteopenia. The results suggest that BMD change should be included with other variables in a comprehensive fracture prediction model to capture its contribution to osteoporotic fracture risk.

Thermalization as an Invisibility Cloak for Fragile Quantum Superpositions

OpenAIRE

Hahn, Walter; Fine, Boris V.

2017-01-01

We propose a method for protecting fragile quantum superpositions in many-particle systems from dephasing by external classical noise. We call superpositions "fragile" if dephasing occurs particularly fast, because the noise couples very differently to the superposed states. The method consists of letting a quantum superposition evolve under the internal thermalization dynamics of the system, followed by a time reversal manipulation known as Loschmidt echo. The thermalization dynamics makes t...

Babies at Double Jeopardy: Medically Fragile Infants and Child Neglect

Science.gov (United States)

Fullar, Suzanne A.

2008-01-01

Medically fragile infants, those born prematurely or with other complex medical or genetic problems, are at risk of long-term health and developmental problems. When a medically fragile infant comes home to a family with significant social problems such as domestic violence, mental illness, or substance abuse, the infant is at double jeopardy--at…

Revision of the AESJ Standard for Seismic Probabilistic Risk Assessment (PRA). Updating requirements based on the lessons learned from the Fukushima Dai-ichi NPP Accidents (3). Fragility evaluation and outline of the updated points

International Nuclear Information System (INIS)

Yamaguchi, Akira; Nakamura, Susumu; Mihara, Yoshinori

2014-01-01

Lessons learned from Great East Japan earthquake and other new findings had been accumulated on the fragility evaluation of buildings and components. And also new analysis and evaluation method had been proposed with the advancement of recent analysis and evaluation technology. These were reflected in revision of the AESJ Standard for Seismic Probabilistic Risk Assessment (PRA). Scope of the fragility evaluation were extended to all equipment on the site, severe accident management equipment including portable equipment and earthquake concomitant incident (such as tsunami) countermeasure equipment. This article described outlines of updating points of the fragility evaluation of the AESJ Standard for Seismic PRA; (1) requirements for seismic induced other risk evaluations such as fire, inundation and tsunami, (2) simulation technology based on recent findings such as three dimensional responses of buildings / structures and its effect on equipment, (3) requirements of the fragility evaluation for various failure mode of several equipment such as severe accident management equipment, fine failure mode of buildings / structures, failures of equipment related with earthquake concomitant incidents (embankment and seawall) and spent fuel pool, and (4) requirements for the fragility evaluation of aftershocks and soil deformation due to fault displacement. (T. Tanaka)

Cardiac tamponade in a patient with severe dengue fever

Directory of Open Access Journals (Sweden)

Ana Isabel Vieira Fernandes

Full Text Available Abstract A 26-year-old postpartum female presented with symptoms characteristic of dengue fever on the 16th day of puerperium. On the third day of the illness, the patient presented a clinical picture consistent with shock. Tests determined primary infection with dengue virus serotype 2. Cardiac tamponade was confirmed by echocardiography. This rare manifestation is described in a patient without any associated comorbidity.

Fragility curves for bridges under differential support motions

DEFF Research Database (Denmark)

Konakli, Katerina

2012-01-01

This paper employs the notion of fragility to investigate the seismic vulnerability of bridges subjected to spatially varying support motions. Fragility curves are developed for four highway bridges in California with vastly different structural characteristics. The input in this analysis consists...... of simulated ground motion arrays with temporal and spectral nonstationarities, and consistent with prescribed spatial variation patterns. Structural damage is quantified through displacement ductility demands obtained from nonlinear time-history analysis. The potential use of the ‘equal displacement’ rule...... to approximately evaluate displacement demands from analysis of the equivalent linear systems is examined....

Fragility of chalcogenide glass in relation to characteristic temperature T0/Tg

Science.gov (United States)

Shaker, A. M.; Shanker Rao, T.; Lilly Shanker Rao, T.; Venkataraman, K.

2018-03-01

The present study reports the mutual relationship between the fragility index m and the characteristic temperature T0/Tg. The fragility of the chalcogenide amorphous glass of Ge10Se50Te40 is calculated by utilizing glass transition temperature (Tg) measured by DSC (Differential Scanning Calorimetry) at different heating rates (β) in the range 5 to 20 K/min. Vogel-Fulcher-Tammann (VFT) equation is fitted to the data of Tg. In addition to the VFT method, three other methods are also used to evaluate m. The fragility index m of the Ge10Se50Te40 system showed the trend of decrease with increasing heating rate but remained stable around 22 for the heating rate 10 K/min. The value of m for the glass is near the lower limit (m ≈ 16) this indicates the alloy is a strong glass forming material in accordance of Angell’s interpretation of fragility. The calculated values of characteristic temperature T0/Tg is very close to 1 which also indicates that clearly the system is most fragile.

Fragile X premutation carriers: A systematic review of neuroimaging findings.

Science.gov (United States)

Brown, Stephanie S G; Stanfield, Andrew C

2015-05-15

Expansion of the CGG repeat region of the FMR1 gene from less than 45 repeats to between 55 and 200 repeats is known as the fragile X premutation. Carriers of the fragile X premutation may develop a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). Recent evidence suggests that premutation carriers experience other psychiatric difficulties throughout their lifespan. Medline, EMBASE and PsychINFO were searched for all appropriate English language studies published between January 1990 and December 2013. 419 potentially relevant articles were identified and screened. 19 articles were included in the analysis. We discuss key structural magnetic resonance imaging (MRI) findings such as the MCP sign and white matter atrophy. Additionally, we discuss how functional MRI results have progressed our knowledge of how FXTAS may manifest, including reduced brain activation during social and memory tasks in multiple regions. This systematic review may have been limited by the search for articles on just 3 scientific databases. Differing techniques and methods of analyses between research groups and primary research articles may have caused differences in results between studies. Current MRI studies into the fragile X premutation have been important in the diagnosis of FXTAS and identifying potential pathophysiological mechanisms. Associations with blood based measures have also demonstrated that neurodevelopmental and neurodegenerative aspects of the fragile X premutation could be functionally and pathologically separate. Larger longitudinal studies will be required to investigate these conclusions. Copyright © 2015 Elsevier B.V. All rights reserved.

Fragile Cities: a Critical Perspective on the Repertoire for New Urban Humanitarian Interventions

Directory of Open Access Journals (Sweden)

Manoela Miklos

Full Text Available Abstract At the end of the 1990s, researchers involved in the debate on the new wars introduced discussion about the urban dimension of contemporary conflicts into the International Relations discipline. The innovative debate about urban fragility is one of the many lines of inquiry that emerge within the framework of the relationship between cities and contemporary conflicts. This paper seeks to demonstrate that the concept of ‘fragile city’ offers a new and relevant analytical framework for understanding contemporary urban violence and inequality. Moreover, this same concept could also be instrumental in making fragile cities the new locus of international humanitarianism. The notion of fragile city emerges to describe new emergency situations more closely linked to urban contexts than to national dynamics, as previously described in the literature on fragile states. The concept of fragile city is a groundbreaking tool for understanding the human consequences of inequality in urban settings, but might also be used as a rhetorical vehicle for the reproduction of old dynamics and the inauguration of new intervention practices in urban areas that were previously inaccessible to humanitarian action, especially cities in Latin America.

Component Fragility Research Program: Phase 1, Demonstration tests: Volume 1, Summary report

International Nuclear Information System (INIS)

Holman, G.S.; Chou, C.K.; Shipway, G.D.; Glozman, V.

1987-08-01

This report describes tests performed in Phase I of the NRC Component Fragility Research Program. The purpose of these tests was to demonstrate procedures for characterizing the seismic fragility of a selected component, investigating how various parameters affect fragility, and finally using test data to develop practical fragility descriptions suitable for application in probabilistic risk assessments. A three-column motor control center housing motor controllers of various types and sizes as well as relays of different types and manufacturers was subjected to seismic input motions up to 2.5g zero period acceleration. To investigate the effect of base flexibility on the structural behavior of the MCC and on the functional behavior of the electrical devices, multiple tests were performed on each of four mounting configurations: four bolts per column with top bracking, four bolts per column with no top brace, four bolts per column with internal diagonal bracking, and two bolts per column with no top or internal bracking. Device fragility was characterized by contact chatter correlated to local in-cabinet response at the device location. Seismic capacities were developed for each device on the basis of local input motion required to cause chatter; these results were then applied to develop probabilistic fragility curves for each type of device, including estimates of the ''high-confidence low probability of failure'' capacity of each

Fragile X mental retardation protein participates in non-coding RNA pathways.

Science.gov (United States)

Li, En-Hui; Zhao, Xin; Zhang, Ce; Liu, Wei

2018-02-20

Fragile X syndrome is one of the most common forms of inherited intellectual disability. It is caused by mutations of the Fragile X mental retardation 1(FMR1) gene, resulting in either the loss or abnormal expression of the Fragile X mental retardation protein (FMRP). Recent research showed that FMRP participates in non-coding RNA pathways and plays various important roles in physiology, thereby extending our knowledge of the pathogenesis of the Fragile X syndrome. Initial studies showed that the Drosophila FMRP participates in siRNA and miRNA pathways by interacting with Dicer, Ago1 and Ago2, involved in neural activity and the fate determination of the germline stem cells. Subsequent studies showed that the Drosophila FMRP participates in piRNA pathway by interacting with Aub, Ago1 and Piwi in the maintenance of normal chromatin structures and genomic stability. More recent studies showed that FMRP is associated with lncRNA pathway, suggesting a potential role for the involvement in the clinical manifestations. In this review, we summarize the novel findings and explore the relationship between FMRP and non-coding RNA pathways, particularly the piRNA pathway, thereby providing critical insights on the molecular pathogenesis of Fragile X syndrome, and potential translational applications in clinical management of the disease.

Fragile X Premutation Carrier Epidemiology and Symptomatology in Israel-Results from a Tertiary Child Developmental Center.

Science.gov (United States)

Gabis, Lidia V; Gruber, Noah; Berkenstadt, Michal; Shefer, Shahar; Attia, Odelia Leon; Mula, Dana; Cohen, Yoram; Elizur, Shai E

2016-10-01

Fragile X syndrome (FXS) is the most prevalent known genetically inherited cause for autism and intellectual disability. Premutation state can cause several clinical disorders as well. We aimed to perform a nesting approach to acquire data with regard to first degree relatives of index fragile X cases at the largest child development center in Israel in order to map characteristics of Israeli FXS permutation women carriers. Seventy-nine women were referred due to a related fragile X syndrome patient, mainly an offspring or sibling. General information regarding demographics, ethnicity, and associated medical conditions were collected using interviews and structured questionnaires. Thirteen (17 %) of the women who were referred as "carrier" were proven to be actually full mutation. The mean years of education were 14 (±1.51, range 12-17). Twenty-one women (27 %) originated from Tunisia (mainly from the island of Djerba). Ten women (13 %) reported delivery of their affected offspring beyond 41 gestational weeks. Twenty-two percent of women with premutation reported symptoms consistent with learning difficulties, mainly dyscalculia, and 14 % reported ADHD symptoms. Awareness about clinical disorders of the carriers was existent only in 25 % of the patients. Increased awareness and knowledge dissemination concerning premutation symptomatology and associated medical conditions are warranted. We suggest a national registry to be installed in different countries in order to identify fragile X premutation carriers at increased risk for various medical complications.

Incarceration in fragile families.

Science.gov (United States)

Wildeman, Christopher; Western, Bruce

2010-01-01

Since the mid-1970s the U.S. imprisonment rate has increased roughly fivefold. As Christopher Wildeman and Bruce Western explain, the effects of this sea change in the imprisonment rate--commonly called mass imprisonment or the prison boom--have been concentrated among those most likely to form fragile families: poor and minority men with little schooling. Imprisonment diminishes the earnings of adult men, compromises their health, reduces familial resources, and contributes to family breakup. It also adds to the deficits of poor children, thus ensuring that the effects of imprisonment on inequality are transferred intergenerationally. Perversely, incarceration has its most corrosive effects on families whose fathers were involved in neither domestic violence nor violent crime before being imprisoned. Because having a parent go to prison is now so common for poor, minority children and so negatively affects them, the authors argue that mass imprisonment may increase future racial and class inequality--and may even lead to more crime in the long-term, thereby undoing any benefits of the prison boom. U.S. crime policy has thus, in the name of public safety, produced more vulnerable families and reduced the life chances of their children. Wildeman and Western advocate several policy reforms, such as limiting prison time for drug offenders and for parolees who violate the technical conditions of their parole, reconsidering sentence enhancements for repeat offenders, and expanding supports for prisoners and ex-prisoners. But Wildeman and Western argue that criminal justice reform alone will not solve the problems of school failure, joblessness, untreated addiction, and mental illness that pave the way to prison. In fact, focusing solely on criminal justice reforms would repeat the mistakes the nation made during the prison boom: trying to solve deep social problems with criminal justice policies. Addressing those broad problems, they say, requires a greater social

Cardiac and metabolic changes in long-term high fructose-fat fed rats with severe obesity and extensive intramyocardial lipid accumulation.

Science.gov (United States)

Axelsen, Lene N; Lademann, Jacob B; Petersen, Jørgen S; Holstein-Rathlou, Niels-Henrik; Ploug, Thorkil; Prats, Clara; Pedersen, Henrik D; Kjølbye, Anne Louise

2010-06-01

Metabolic syndrome and obesity-related diseases are affecting more and more people in the Western world. The basis for an effective treatment of these patients is a better understanding of the underlying pathophysiology. Here, we characterize fructose- and fat-fed rats (FFFRs) as a new animal model of metabolic syndrome. Sprague-Dawley rats were fed a 60 kcal/100 kcal fat diet with 10% fructose in the drinking water. After 6, 12, 18, 24, 36, and 48 wk of feeding, blood pressure, glucose tolerance, plasma insulin, glucose, and lipid levels were measured. Cardiac function was examined by in vivo pressure volume measurements, and intramyocardial lipid accumulation was analyzed by confocal microscopy. Cardiac AMP-activated kinase (AMPK) and hepatic phosphoenolpyruvate carboxykinase (PEPCK) levels were measured by Western blotting. Finally, an ischemia-reperfusion study was performed after 56 wk of feeding. FFFRs developed severe obesity, decreased glucose tolerance, increased serum insulin and triglyceride levels, and an initial increased fasting glucose, which returned to control levels after 24 wk of feeding. The diet had no effect on blood pressure but decreased hepatic PEPCK levels. FFFRs showed significant intramyocardial lipid accumulation, and cardiac hypertrophy became pronounced between 24 and 36 wk of feeding. FFFRs showed no signs of cardiac dysfunction during unstressed conditions, but their hearts were much more vulnerable to ischemia-reperfusion and had a decreased level of phosphorylated AMPK at 6 wk of feeding. This study characterizes a new animal model of the metabolic syndrome that could be beneficial in future studies of metabolic syndrome and cardiac complications.

Direct Cardiac Reprogramming: Advances in Cardiac Regeneration

Directory of Open Access Journals (Sweden)

Olivia Chen

2015-01-01

Full Text Available Heart disease is one of the lead causes of death worldwide. Many forms of heart disease, including myocardial infarction and pressure-loading cardiomyopathies, result in irreversible cardiomyocyte death. Activated fibroblasts respond to cardiac injury by forming scar tissue, but ultimately this response fails to restore cardiac function. Unfortunately, the human heart has little regenerative ability and long-term outcomes following acute coronary events often include chronic and end-stage heart failure. Building upon years of research aimed at restoring functional cardiomyocytes, recent advances have been made in the direct reprogramming of fibroblasts toward a cardiomyocyte cell fate both in vitro and in vivo. Several experiments show functional improvements in mouse models of myocardial infarction following in situ generation of cardiomyocyte-like cells from endogenous fibroblasts. Though many of these studies are in an early stage, this nascent technology holds promise for future applications in regenerative medicine. In this review, we discuss the history, progress, methods, challenges, and future directions of direct cardiac reprogramming.

RTEL1 inhibits trinucleotide repeat expansions and fragility.

Science.gov (United States)

Frizzell, Aisling; Nguyen, Jennifer H G; Petalcorin, Mark I R; Turner, Katherine D; Boulton, Simon J; Freudenreich, Catherine H; Lahue, Robert S

2014-03-13

Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG) repeat expansions and fragility, likely by unwinding problematic hairpins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Selective Spatial Processing Deficits in an At-Risk Subgroup of the Fragile X Premutation

Science.gov (United States)

Hocking, Darren R.; Kogan, Cary S.; Cornish, Kim M.

2012-01-01

Until a decade ago, it was assumed that males with the fragile X premutation were unaffected by any cognitive phenotype. Here we examined the extent to which CGG repeat toxicity extends to visuospatial functioning in male fragile X premutation carriers who are asymptomatic for a late-onset neurodegenerative disorder, fragile X-associated…

Assessment of the Internal Pressure Fragility of the Hanul NPP Units 3 and 4 Containment Building Using a Nonlinear Finite Element Analysis

Energy Technology Data Exchange (ETDEWEB)

Park, Hyung Kui; Hahm, Dea Gi; Choi, In Kil [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-10-15

The sensitivity of the concrete strength is relatively higher compared to that of the steel strength. According to changes in the structure of the material, about 6-10% ultimate internal pressure differences occurred. Thirty sets of an FE model considering the material uncertainty of concrete and steel were composed for the internal pressure fragility assessment. From the internal pressure fragility assessment of the target containment building, the median capacity of liner leakage is estimated to be 116 psi. As can be seen from the Fukushima nuclear power plant accident, the containment building is the final protecting shield to prevent radiation leakage. Thus, a structural soundness evaluation for the containment pressure loads owing to a severe accident is very important. Recently, a probabilistic safety assessment has been commonly used to take into account the possible factors of uncertainty in a structural system. An assessment of the internal pressure fragility of the CANDU type containment buildings considering the correlation of structural material variables, and an assessment of the internal pressure fragility of the CANDU type containment buildings using a nonlinear finite element analysis, were also performed. However, for PWR type containment buildings, a fragility assessment has not been performed yet using a nonlinear finite element model (FEM) analysis. In this study, for the Hanul NPP units 3 and 4 containment building, the internal pressure fragility assessment was established using an FEM analysis. To do this, a three-dimensional finite element model, material property values, and a sensitive analysis were developed. A nonlinear finite element analysis of the Hanul NPP units 3 and 4 containment building was performed for a material sensitivity analysis and internal pressure fragility assessment.

Assessment of the Internal Pressure Fragility of the Hanul NPP Units 3 and 4 Containment Building Using a Nonlinear Finite Element Analysis

International Nuclear Information System (INIS)

Park, Hyung Kui; Hahm, Dea Gi; Choi, In Kil

2013-01-01

The sensitivity of the concrete strength is relatively higher compared to that of the steel strength. According to changes in the structure of the material, about 6-10% ultimate internal pressure differences occurred. Thirty sets of an FE model considering the material uncertainty of concrete and steel were composed for the internal pressure fragility assessment. From the internal pressure fragility assessment of the target containment building, the median capacity of liner leakage is estimated to be 116 psi. As can be seen from the Fukushima nuclear power plant accident, the containment building is the final protecting shield to prevent radiation leakage. Thus, a structural soundness evaluation for the containment pressure loads owing to a severe accident is very important. Recently, a probabilistic safety assessment has been commonly used to take into account the possible factors of uncertainty in a structural system. An assessment of the internal pressure fragility of the CANDU type containment buildings considering the correlation of structural material variables, and an assessment of the internal pressure fragility of the CANDU type containment buildings using a nonlinear finite element analysis, were also performed. However, for PWR type containment buildings, a fragility assessment has not been performed yet using a nonlinear finite element model (FEM) analysis. In this study, for the Hanul NPP units 3 and 4 containment building, the internal pressure fragility assessment was established using an FEM analysis. To do this, a three-dimensional finite element model, material property values, and a sensitive analysis were developed. A nonlinear finite element analysis of the Hanul NPP units 3 and 4 containment building was performed for a material sensitivity analysis and internal pressure fragility assessment

Takagi-Sugeno Fuzzy Systems Non-fragile H-infinity Filtering

CERN Document Server

Chang, Xiao-Heng

2012-01-01

"Takagi-Sugeno Fuzzy Systems Non-fragile H-infinity Filtering" investigates the problem of non-fragile H-infinity filter design for T-S fuzzy systems. The nonlinear plant is represented by a T-S fuzzy model. Given a T-S fuzzy system, the objective of this book is to design an H-infinity filter with the gain variations such that the filtering error system guarantees a prescribed H-infinity performance level. Furthermore, it demonstrates that the solution of non-fragile H-infinity filter design problem can be obtained by solving a set of linear matrix inequalities (LMIs). The intended audiences are graduate students and researchers both from the fields of engineering and mathematics. Dr. Xiao-Heng Chang is an Associate Professor at the College of Engineering, Bohai University, Jinzhou, Liaoning, China. He is also a Postdoctoral Researcher at the College of Information Science and Engineering, Northeastern University, Shenyang, China.

Severe antiphospholipid syndrome and cardiac surgery: Perioperative management.

Science.gov (United States)

Mishra, Pankaj Kumar; Khazi, Fayaz Mohammed; Yiu, Patrick; Billing, John Stephen

2016-06-01

Antiphospholipid syndrome is an antiphospholipid antibody-mediated prothrombotic state leading to arterial and venous thrombosis. This condition alters routine in-vitro coagulation tests, making results unreliable. Antiphospholipid syndrome patients requiring cardiac surgery with cardiopulmonary bypass present a unique challenge in perioperative anticoagulation management. We describe 3 patients with antiphospholipid syndrome who had successful heart valve surgery at our institution. We have devised an institutional protocol for antiphospholipid syndrome patients, and all 3 patients were managed according to this protocol. An algorithm-based approach is recommended because it improves team work, optimizes treatment, and improves patient outcome. © The Author(s) 2015.

Family Environment and Behavior Problems in Children, Adolescents, and Adults with Fragile X Syndrome

Science.gov (United States)

Greenberg, Jan S.; Seltzer, Marsha Mailick; Baker, Jason K.; Smith, Leann E.; Warren, Steven F.; Brady, Nancy; Hong, Jinkuk

2012-01-01

We examine how the family environment is associated with aspects of the Fragile X syndrome phenotype during childhood, adolescence, and adulthood. Mothers of children (n = 48), adolescents (n = 85), and adults (n = 34) with Fragile X syndrome participated in a multisite study. For children and adults with Fragile X syndrome, the presence of warmth…

Flap Endonuclease 1 Limits Telomere Fragility on the Leading Strand*

Science.gov (United States)

Teasley, Daniel C.; Parajuli, Shankar; Nguyen, Mai; Moore, Hayley R.; Alspach, Elise; Lock, Ying Jie; Honaker, Yuchi; Saharia, Abhishek; Piwnica-Worms, Helen; Stewart, Sheila A.

2015-01-01

The existence of redundant replication and repair systems that ensure genome stability underscores the importance of faithful DNA replication. Nowhere is this complexity more evident than in challenging DNA templates, including highly repetitive or transcribed sequences. Here, we demonstrate that flap endonuclease 1 (FEN1), a canonical lagging strand DNA replication protein, is required for normal, complete leading strand replication at telomeres. We find that the loss of FEN1 nuclease activity, but not DNA repair activities, results in leading strand-specific telomere fragility. Furthermore, we show that FEN1 depletion-induced telomere fragility is increased by RNA polymerase II inhibition and is rescued by ectopic RNase H1 expression. These data suggest that FEN1 limits leading strand-specific telomere fragility by processing RNA:DNA hybrid/flap intermediates that arise from co-directional collisions occurring between the replisome and RNA polymerase. Our data reveal the first molecular mechanism for leading strand-specific telomere fragility and the first known role for FEN1 in leading strand DNA replication. Because FEN1 mutations have been identified in human cancers, our findings raise the possibility that unresolved RNA:DNA hybrid structures contribute to the genomic instability associated with cancer. PMID:25922071

Fragile Elite

DEFF Research Database (Denmark)

Bregnbæk, Susanne

China's One Child Policy and its rigorous national focus on educational testing are well known. But what happens to those "lucky" few at the very top of the pyramid? Fragile Elite explores the contradictions of being an elite student through ethnographic research conducted at two top universities...... in China. It uncovers the intimate psychological strains students suffer under the pressure imposed on them by parents and state, where the state acts as a parent, and the parents sometimes reinforce the state. The book offers insights into the intergenerational tensions as work in relation to the ongoing...... shifts in educational policy and definition of what a "quality" student, child, and citizen is in contemporary China....

Cardiac I123-MIBG Correlates Better than Ejection Fraction with Symptoms Severity in Systolic Heart Failure

Energy Technology Data Exchange (ETDEWEB)

Miranda, Sandra M.; Moscavitch, Samuel D.; Carestiato, Larissa R. [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Felix, Renata M. [Departamento de Medicina Nuclear, Hospital Pró-Cardíaco, Rio de Janeiro, RJ (Brazil); Rodrigues, Ronaldo C.; Messias, Leandro R. [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Azevedo, Jader C. [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Departamento de Medicina Nuclear, Hospital Pró-Cardíaco, Rio de Janeiro, RJ (Brazil); Nóbrega, Antonio Cláudio L.; Mesquita, Evandro Tinoco [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Mesquita, Claudio Tinoco, E-mail: ctinocom@cardiol.br [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Departamento de Medicina Nuclear, Hospital Pró-Cardíaco, Rio de Janeiro, RJ (Brazil)

2013-07-15

The association of autonomic activation, left ventricular ejection fraction (LVEF) and heart failure functional class is poorly understood. Our aim was to correlate symptom severity with cardiac sympathetic activity, through iodine-123-metaiodobenzylguanidine ({sup 123}I-MIBG) scintigraphy and with LVEF in systolic heart failure (HF) patients without previous beta-blocker treatment. Thirty-one patients with systolic HF, class I to IV of the New York Heart Association (NYHA), without previous beta-blocker treatment, were enrolled and submitted to {sup 123}I-MIBG scintigraphy and to radionuclide ventriculography for LVEF determination. The early and delayed heart/mediastinum (H/M) ratio and the washout rate (WR) were performed. According with symptom severity, patients were divided into group A, 13 patients in NYHA class I/II, and group B, 18 patients in NYHA class III/IV. Compared with group B patients, group A had a significantly higher LVEF (25% ± 12% in group B vs. 32% ± 7% in group A, p = 0.04). Group B early and delayed H/M ratios were lower than group A ratios (early H/M 1.49 ± 0.15 vs. 1.64 ± 0.14, p = 0.02; delayed H/M 1.39 ± 0.13 vs. 1.58 ± 0.16, p = 0.001, respectively). WR was significantly higher in group B (36% ± 17% vs. 30% ± 12%, p= 0.04). The variable that showed the best correlation with NYHA class was the delayed H/M ratio (r= -0.585; p=0.001), adjusted for age and sex. This study showed that cardiac {sup 123}I-MIBG correlates better than ejection fraction with symptom severity in systolic heart failure patients without previous beta-blocker treatment.

The Evaluation of Corneal Fragility After UVA/Riboflavin Crosslinking.

Science.gov (United States)

Li, Zhiwei; Wang, Yumeng; Xu, Yanyun; Jhanji, Vishal; Zhang, Chunxiao; Mu, Guoying

2017-03-01

To evaluate the fragility of cornea after UVA/riboflavin crosslinking (CXL). Sixty New Zealand rabbits received UVA/riboflavin crosslinking treatment (wavelength 365 nm, irradiance 3.0 mW/cm, and total dose 5.4 J/cm) on right eyes. Animals were sacrificed before and immediately after treatment (day 0), day 1, 3, 7, and 28 after treatment. A 4×10 mm corneal strip for biomechanical evaluation was harvested after sacrifice. The corneal fragility was evaluated by measurement of elongation rate, whereby the elongation rate equals elongation length/baseline length. The Youngs modulus and maximal stress were 1.41±0.51 MPa and 5.56±1.84 MPa before CXL, and increased to 2.31±0.68 MPa (P=0.008) and 9.25±2.74 MPa (P=0.04), respectively, on day 0, then maintained a stable level within a 28 days follow-up. The elongation rate was 62.04±9.34% before CXL and decreased to 48.95%±8.24% (P=0.02) on day 0, then maintained a stable level within a 28 days follow-up. This study showed an increase in the corneal fragility after UVA/riboflavin crosslinking along with an increase in the corneal stiffness. A long-term follow-up should be taken to evaluate the potential deleterious effect of the increasing corneal fragility after UVA/riboflavin crosslinking.

[Severity of disease scoring systems and mortality after non-cardiac surgery].

Science.gov (United States)

Reis, Pedro Videira; Sousa, Gabriela; Lopes, Ana Martins; Costa, Ana Vera; Santos, Alice; Abelha, Fernando José

2018-04-05

Mortality after surgery is frequent and severity of disease scoring systems are used for prediction. Our aim was to evaluate predictors for mortality after non-cardiac surgery. Adult patients admitted at our surgical intensive care unit between January 2006 and July 2013 was included. Univariate analysis was carried using Mann-Whitney, Chi-square or Fisher's exact test. Logistic regression was performed to assess independent factors with calculation of odds ratio and 95% confidence interval (95% CI). 4398 patients were included. Mortality was 1.4% in surgical intensive care unit and 7.4% during hospital stay. Independent predictors of mortality in surgical intensive care unit were APACHE II (OR=1.24); emergent surgery (OR=4.10), serum sodium (OR=1.06) and FiO 2 at admission (OR=14.31). Serum bicarbonate at admission (OR=0.89) was considered a protective factor. Independent predictors of hospital mortality were age (OR=1.02), APACHE II (OR=1.09), emergency surgery (OR=1.82), high-risk surgery (OR=1.61), FiO 2 at admission (OR=1.02), postoperative acute renal failure (OR=1.96), heart rate (OR=1.01) and serum sodium (OR=1.04). Dying patients had higher scores in severity of disease scoring systems and longer surgical intensive care unit stay. Some factors influenced both surgical intensive care unit and hospital mortality. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

The Role of Chain Length in Nonergodicity Factor and Fragility of Polymers

DEFF Research Database (Denmark)

Dalle-Ferrie, Cecile; Niss, Kristine; Sokolov, Alexei

2010-01-01

The mechanism that leads to different fragility values upon approaching the glass transition remains a topic of active discussion. Many researchers are trying to find an answer in the properties of the frozen glassy state. Following this approach, we focus here on a previously proposed relationship...... between the fragility of glass-formers and their nonergodicity factor, determined by inelastic X-ray scattering (IXS) in the glass. We extend this molecular liquid study to two model polymers— polystyrene (PS) and polyisobutylene (PIB)—for which we change the molecular weight. Polymers offer...... the opportunity to change the fragility without altering the chemical structure, just by changing the chain length. Thus, we specifically chose PS and PIB because they exhibit opposite dependences of fragility with molecular weight. Our analysis for these two polymers reveals no unique correlation between...

C.A.U.S.E.: Cardiac arrest ultra-sound exam--a better approach to managing patients in primary non-arrhythmogenic cardiac arrest.

Science.gov (United States)

Hernandez, Caleb; Shuler, Klaus; Hannan, Hashibul; Sonyika, Chionesu; Likourezos, Antonios; Marshall, John

2008-02-01

Cardiac arrest is a condition frequently encountered by physicians in the hospital setting including the Emergency Department, Intensive Care Unit and medical/surgical wards. This paper reviews the current literature involving the use of ultrasound in resuscitation and proposes an algorithmic approach for the use of ultrasound during cardiac arrest. At present there is the need for a means of differentiating between various causes of cardiac arrest, which are not a direct result of a primary ventricular arrhythmia. Identifying the cause of pulseless electrical activity or asystole is important as the underlying cause is what guides management in such cases. This approach, incorporating ultrasound to manage cardiac arrest aids in the diagnosis of the most common and easily reversible causes of cardiac arrest not caused by primary ventricular arrhythmia, namely; severe hypovolemia, tension pneumothorax, cardiac tamponade, and massive pulmonary embolus. These four conditions are addressed in this paper using four accepted emergency ultrasound applications to be performed during resuscitation of a cardiac arrest patient with the aim of determining the underlying cause of a cardiac arrest. Identifying the underlying cause of cardiac arrest represents the one of the greatest challenges of managing patients with asystole or PEA and accurate determination has the potential to improve management by guiding therapeutic decisions. We include several clinical images demonstrating examples of cardiac tamponade, massive pulmonary embolus, and severe hypovolemia secondary to abdominal aortic aneurysm. In conclusion, this protocol has the potential to reduce the time required to determine the etiology of a cardiac arrest and thus decrease the time between arrest and appropriate therapy.

On the pressure dependence of the fragility of glycerol

Energy Technology Data Exchange (ETDEWEB)

Pawlus, S; Paluch, M; Ziolo, J [Institute of Physics, University of Silesia, Uniwersytecka 4, 40-007 Katowice (Poland); Roland, C M [Naval Research Laboratory, Chemistry Division, Code 6120, Washington, DC 20375-5342 (United States)

2009-08-19

This work was motivated by ostensibly contradictory results from different groups regarding the effect of pressure on the fragility of glycerol. We present new experimental data for an intermediate pressure regime showing that the fragility increases with pressure up to about 1.8 GPa, becoming invariant at higher pressures. There is no discrepancy among the various literature data taken in toto. The behavior of glycerol is quite distinct from that of normal liquids, a result of its substantial hydrogen bonding. (fast track communication)

Behavioral Intervention for Problem Behavior in Children with Fragile X Syndrome

Science.gov (United States)

Moskowitz, Lauren J.; Carr, Edward G.; Durand, V. Mark

2011-01-01

Parents and professionals typically report problem behavior as a significant concern for children with fragile X syndrome. In the present study, the authors explored whether behaviorally based interventions would result in a reduction in problem behavior and an improvement in quality of life for 3 children with fragile X syndrome and their…

Fragile X syndrome in two siblings with major congenital malformations

Energy Technology Data Exchange (ETDEWEB)

Giampietro, P.F.; Haas, B.R.; Lipper, E. [Cornell Univ. Medical Center, New York, NY (United States)] [and others

1996-05-17

We report on 2 brothers with both fragile X and VACTERL-H syndrome. The first sibling, age 5, had bilateral cleft lip and palate, ventricular septal defect, and a hypoplastic thumb. The second sibling, age 2{1/2}, had a trachesophageal fistula, esophageal atresia, and vertebral abnormality. High-resolution chromosome analysis showed a 46,XY chromosome constitution in both siblings. By PCR and Southern blot analysis, the siblings were found to have large triplet repeat expansions in the fragile X gene (FMR 1) and both had methylation mosaicism. Enzyme kinetic studies of iduronate sulfatase demonstrated a two-fold increase in activity in the first sib as compared to the second. Possible mechanisms through which the fragile X mutation can cause down-regulation of adjacent loci are discussed. 24 refs., 4 figs.

Seismic Fragility Assessment of an Isolated Multipylon Cable-Stayed Bridge Using Shaking Table Tests

Directory of Open Access Journals (Sweden)

Yutao Pang

2017-01-01

Full Text Available In recent decades, cable-stayed bridges have been widely built around the world due to the appealing aesthetics and efficient and fast mode of construction. Numerous studies have concluded that the cable-stayed bridges are sensitive to earthquakes because they possess low damping characteristics and high flexibility. Moreover, cable-stayed bridges need to warrant operability especially in the moderate-to-severe earthquakes. The provisions implemented in the seismic codes allow obtaining adequate seismic performance for the cable-stayed bridge components; nevertheless, they do not provide definite yet reliable rules to protect the bridge. To date, very few experimental tests have been carried out on the seismic fragility analysis of cable-stayed bridges which is the basis of performance-based analyses. The present paper is aimed at proposing a method to derive the seismic fragility curves of multipylon cable-stayed bridge through shake table tests. Toward this aim, a 1/20 scale three-dimensional model of a 22.5 m cable-stayed bridge in China is constructed and tested dynamically by using the shaking table facility of Tongji University. The cable-stayed bridge contains three pylons and one side pier. The outcomes of the comprehensive shaking table tests carried out on cable-stayed bridge have been utilized to derive fragility curves based on a systemic approach.

Essays on financial fragility and regulation

NARCIS (Netherlands)

Ma, K.

2013-01-01

This thesis investigates various issues in regulation, with three chapters on financial fragility and banking regulation, and one chapter on competition policy. Chapter 2 studies banks’ herding driven by their need for market liquidity, highlighting a trade-off between systemic risk and liquidity

Managing Public Finance and Procurement in Fragile and Conflicted Settings

OpenAIRE

Porter, Doug; Andrews, Matt; Turkewitz, Joel; Wescotttz, Clay

2011-01-01

Discusses ways to enhance the incentives for elites to invest political capital in achieving (1) functional results through the formal public finance management (PFM) system; (2) the effectiveness of agencies responsible for services and regulating activities; and (3) better performance of civil service officials. Using the Public Expenditure and Financial Accountability (PEFA) Performance Measurement Framework, countries affected by conflict and fragility can be compared with non-fragile poo...

Transesophageal echocardiography for cardiac thromboembolic risk assessment in patients with severe, symptomatic aortic valve stenosis referred for potential transcatheter aortic valve implantation.

Science.gov (United States)

Lenders, Guy D; Paelinck, Bernard P; Wouters, Kristien; Claeys, Marc J; Rodrigus, Inez E; Van Herck, Paul L; Vrints, Christiaan J; Bosmans, Johan M

2013-05-15

Stroke is a devastating complication after transcatheter aortic valve implantation (TAVI) and might partially be related to cardiac embolization. The aim of this single-center prospective study was to determine the incidence of intracardiac thrombi and left atrial spontaneous echo contrast (SEC), both known predictors of cardiac embolic stroke, in patients referred for potential TAVI. One hundred four consecutive patients with severe symptomatic aortic valve stenosis and at high or very high risk for surgery were included and underwent transesophageal echocardiography. In 11 patients (10.6%), intracardiac thrombi were detected, and 25 patients (24%) showed dense grade 2 SEC. Atrial fibrillation (p risk patients with severe aortic valve stenosis referred for potential TAVI is high and can accurately be detected using transesophageal echocardiography. Systematic thromboembolic evaluation using transesophageal echocardiography is thus recommended in patients referred for TAVI. Copyright © 2013 Elsevier Inc. All rights reserved.

Fragility Modeling of Aging Containment Metallic Pressure Boundaries

International Nuclear Information System (INIS)

Cherry, J.L.; Ellingwood, B.R.

1999-01-01

The containment in a nuclear power plant (NPP) provides a barrier against the release of radioactivity in the event of an accident. Corrosion that has been observed in some steel containments and liners of reinforced concrete containments has raised questions about their ability to perform this function. The performance of corroded containments during events at or beyond the design basis is impacted by numerous sources of uncertainty. A fragility model of the containment provides a relatively simple depiction of the impact of uncertainties on structural performance and a basis for decision-making in the presence of uncertainty. Moreover, it is a necessary ingredient of any time-dependent structural reliability analysis. A nonlinear finite element analysis of containment response furnishes the necessary platform to perform numerical experiments to determine containment fragility. A statistically-based sampling plan minimizes the finite element computations required to develop the fragility curve. The -percentile (or other fractile) then gives a statistically based indication of the lower bound on containment capacity, and can be used as a screening tool to determine whether more refined further analysis or tests to support service life evaluations are warranted

Management of functional Sprint Fidelis leads at cardiac resynchronization therapy-defibrillator generator replacement: a novel option for preventing inappropriate shocks from lead failure in fragile patients with high risk of sudden death.

Science.gov (United States)

Zhu, Dennis W X; Chu, Matthew M; House, Chad M

2017-12-01

In patients with a functional Sprint Fidelis lead at generator replacement, the manufacturer recommended to either continue to use the existing lead or replace it with a new lead. For those patients who continue to use a functional Fidelis lead, the risk of inappropriate shocks remains present if the lead fails in the future. We evaluated the feasibility of an alternative approach at the time of cardiac resynchronization therapy-defibrillator (CRT-D) generator replacement in patients with a functional bipolar left ventricular (LV) lead for prevention of inappropriate shocks from future Fidelis lead failure. During the procedure, the pace/sense IS-1 connection pin of the functional Fidelis lead was intentionally inserted into the LV port of the new CRT-D generator, while the existing bipolar LV lead IS-1 connection pin was inserted into the right ventricular (RV) pace/sense port. After such switching, the existing bipolar LV lead was used for functional LV pacing/sensing, while the Fidelis lead was used for functional RV pacing and high voltage shock only and could no longer be used for the purpose of sensing and detecting. This approach precluded oversensing and inappropriate shocks should the functional Fidelis lead fail in the future. Six fragile patients, who were not considered suitable candidates for lead replacement, underwent the alternative approach. During a follow-up of 35 ± 23 months, the CRT-D system functioned normally in five patients. The Fidelis lead fractured in one patient 7 months after generator replacement. The malfunction was detected promptly and the defected lead was replaced. No inappropriate detections or shock was triggered. In CRT-D patients with a functional Fidelis lead and a bipolar LV lead, switching of the Fidelis lead pace/sense IS-1 pin with the bipolar LV lead IS-1 pin at generator replacement did not affect normal system function. This novel approach may be valuable in fragile patients with high risk of sudden death for

Cardiac valve disease: an unreported feature in Ehlers Danlos syndrome arthrocalasia type?

Directory of Open Access Journals (Sweden)

Melis Daniela

2012-11-01

Full Text Available Abstract Ehlers Danlos syndrome (EDS athrocalasia type (type VII, is characterized by joint hypermobility, skin hyperextensibility and tissue fragility. No heart involvement has been reported. Two forms have been described: type VII A and VII B. The abnormally processed collagen α2(I and the skipping of the exon 6 in COL1A2 gene are typically detected in EDS type VII B. We describe a seven-year old female, with a phenotype consistent with EDS type VII B and a diagnosis further confirmed by biochemical and molecular analyses. Cardiac ultrasound showed normal data in the first year of life. When she was 5 years old, the patient developed mitral valve regurgitation, and aortic and tricuspidal insufficiency at 7 years of age. To our knowledge, this is the first report of cardiac valvular involvement in EDS VII B. This feature probably has been underreported for the limited follow-up of the patients. Echocardiography might be warranted in the clinical assessment of EDS VII patients.

Hemolysis, myopathy, and cardiac disease associated with hereditary phosphofructokinase deficiency in two Whippets

Science.gov (United States)

Gerber, Karen; Harvey, John W.; D'Agorne, Sara; Wood, Jonathan; Giger, Urs

2009-01-01

Two male castrated Whippet littermates were presented at 1 year of age for pallor, tachycardia, systolic heart murmur, dark yellow to orange feces, intermittent lethargy, pigmenturia, and muscle shivering or cramping after exercise. Persistent macrocytic hypochromic anemia with marked reticulocytosis and metarubricytosis was found when CBC results were compared with reference values for Whippets. Increased serum creatine kinase activity and hyperkalemia also were sometimes present over the 4-year period of evaluation. Progressively increasing serum concentrations of N-terminal prohormone brain natriuretic peptide suggested cardiac disease. Erythrocytes from the whippets were less osmotically fragile but more alkaline fragile than those from control dogs. Erythrocyte phosphofructokinase (PFK) activities and 2,3-diphosphoglycerate concentrations were decreased. Restriction enzyme-based DNA test screening and DNA sequencing revealed the same mutation in the muscle-PFK gene of the Whippets as seen in English Springer Spaniel dogs with PFK deficiency. This is the first report of PFK deficiency in Whippet dogs. In addition to causing hemolysis and exertional myopathy, heart disease may be a prominent clinical component of PFK deficiency in this breed and has not been previously recognized in PFK-deficient English Springer Spaniels. PMID:19228357

Flap Endonuclease 1 Limits Telomere Fragility on the Leading Strand.

Science.gov (United States)

Teasley, Daniel C; Parajuli, Shankar; Nguyen, Mai; Moore, Hayley R; Alspach, Elise; Lock, Ying Jie; Honaker, Yuchi; Saharia, Abhishek; Piwnica-Worms, Helen; Stewart, Sheila A

2015-06-12

The existence of redundant replication and repair systems that ensure genome stability underscores the importance of faithful DNA replication. Nowhere is this complexity more evident than in challenging DNA templates, including highly repetitive or transcribed sequences. Here, we demonstrate that flap endonuclease 1 (FEN1), a canonical lagging strand DNA replication protein, is required for normal, complete leading strand replication at telomeres. We find that the loss of FEN1 nuclease activity, but not DNA repair activities, results in leading strand-specific telomere fragility. Furthermore, we show that FEN1 depletion-induced telomere fragility is increased by RNA polymerase II inhibition and is rescued by ectopic RNase H1 expression. These data suggest that FEN1 limits leading strand-specific telomere fragility by processing RNA:DNA hybrid/flap intermediates that arise from co-directional collisions occurring between the replisome and RNA polymerase. Our data reveal the first molecular mechanism for leading strand-specific telomere fragility and the first known role for FEN1 in leading strand DNA replication. Because FEN1 mutations have been identified in human cancers, our findings raise the possibility that unresolved RNA:DNA hybrid structures contribute to the genomic instability associated with cancer. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Seismic fragility analysis of the block masonry wall in nuclear power plants

International Nuclear Information System (INIS)

Wang, Z-L.; Pandey, M.D.; Xie, X-C.

2014-01-01

The evaluation of seismic fragility of a structure is an integral part in the Seismic Probabilistic Risk Analysis (SPRA). The block masonry wall, a commonly used barrier in nuclear power plants, is fairly vulnerable to failure under an earthquake. In practice, the seismic fragility of block walls is commonly evaluated using a simple deterministic approach called Conservative Deterministic Failure Margin (CDFM) method. This paper presents a more formal fragility analysis of a block wall based on rigorous probabilistic methods and the accuracy of the CDFM method is evaluated by comparison to the more rigorous FA method. (author)

Fragility and structure of Al-Cu alloy melts

International Nuclear Information System (INIS)

Lv Xiaoqian; Bian Xiufang; Mao Tan; Li Zhenkuan; Guo Jing; Zhao Yan

2007-01-01

The dynamic viscosity measurements are performed for Al-Cu alloy melts with different compositions using an oscillating-cup viscometer. The results show that the viscosities of Al-Cu alloy melts increase with the copper content increasing, and also have a correlation with the correlation radius of clusters, which is measured by the high-temperature X-ray diffractometer. It has also been found that the fragilities of superheated melts (M) of hypereutectic Al-Cu alloys increase with the copper content increasing. There exists a relationship between the fragility and the structure in Al-Cu alloy melts. The value of the M reflects the variation of activation energy for viscous flow

Seismic fragility capacity of equipment--horizontal shaft pump test

International Nuclear Information System (INIS)

Iijima, T.; Abe, H.; Suzuki, K.

2005-01-01

The current seismic fragility capacity of horizontal shaft pump is 1.6 x 9.8 m/s 2 (1.6 g), which was decided from previous vibration tests and we believe that it must have sufficient margin. The purpose of fragility capacity test is to obtain realistic seismic fragility capacity of horizontal shaft pump by vibration tests. Reactor Building Closed Cooling Water (RCW) Pump was tested as a typical horizontal shaft pump, and then bearings and liner rings were tested as important parts to evaluate critical acceleration and dispersion. Regarding RCW pump test, no damage was found, though maximum input acceleration level was 6 x 9.8 m/s 2 (6 g). Some kinds of bearings and liner rings were tested on the element test. Input load was based on seismic motion which was same with the RCW pump test, and maximum load was equivalent to over 20 times of design seismic acceleration. There was not significant damage that caused emergency stop of pump but degradation of surface roughness was found on some kinds of bearings. It would cause reduction of pump life, but such damage on bearings occurred under large seismic load condition that was equivalent to over 10 to 20 g force. Test results show that realistic fragility capacity of horizontal shaft pump would be at least four times as higher as current value which has been used for our seismic PSA. (authors)

Comparison of intraerythrocyte and intraleucocyte Sodium content and erythrocyte fragility in normotensive subjects

International Nuclear Information System (INIS)

Paci, A.; Cocci, F.; Cristofani, R.; Piras, F.; Balzan, S.; Mezzasalma, L.; Ghione; Giachetti, M.

1988-01-01

The Sodium content of mononuclear leucocytes and erythrocytes and the osmotic fragility of erythrocytes were measured in 22 young male volunteers before and after three days of increased Sodium intake. Analysis of variance for repeated measurements showed no significant correlations between intraleucocyte and intraerythrocyte Sodium and between intraerythrocyte Sodium and osmotic fragility. On the other hand, a highly significant relation was present between osmotic fragility and intraleucocyte Sodium before high salt intake, which disappeared after 3 days of increased salt intake

State of the Art in Input Ground Motions for Seismic Fragility and Risk Assessment

Energy Technology Data Exchange (ETDEWEB)

Kim, Jung Han; Choi, In Kil; Kim, Min Kyu [KAERI, Daejeon (Korea, Republic of)

2016-05-15

The purpose of a Seismic Probabilistic Safety Analysis (SPSA) is to determine the probability distribution of core damage due to the potential effects of earthquakes. The SPSA is performed based on four steps, a seismic hazard analysis, a component fragility evaluation, a plant system and accident sequence analysis, and a consequence analysis. There are very different spectrum shapes in every ground motions. The structural response and the seismic load applied to equipment are greatly influenced by a spectral shape of the input ground motion. Therefore the input ground motion need to be determined under the same assumption in risk calculation. Several technic for the determination of input ground motions has developed and reviewed in this study. In this research, the methodologies of the determination of input ground motion for the seismic risk assessment are reviewed and discussed. It has developed to reduce the uncertainty in fragility curves and to remove the conservatism in risk values.

Structure and management of tuberculosis control programs in fragile states--Afghanistan, DR Congo, Haiti, Somalia.

Science.gov (United States)

Mauch, Verena; Weil, Diana; Munim, Aayid; Boillot, Francois; Coninx, Rudi; Huseynova, Sevil; Powell, Clydette; Seita, Akihiro; Wembanyama, Henriette; van den Hof, Susan

2010-07-01

Health care delivery is particularly problematic in fragile states often connected with increased incidence of communicable diseases, among them tuberculosis. This article draws upon experiences in tuberculosis control in four fragile states from which four lessons learned were derived. A structured inventory to extract common themes specific for TB control in fragile states was conducted among twelve providers of technical assistance who have worked in fragile states. The themes were applied to the TB control programs of Afghanistan, DR Congo, Haiti and Somalia during the years 2000-2006. Case notifications and treatment outcomes have increased in all four countries since 2003 (treatment success rates 81-90%). Access to care and case detection however have remained insufficient (case detection rates 39-62%); There are four lessons learned: 1. TB control programs can function in fragile states. 2. National program leadership and stewardship are essential for quality and sustained TB control. 3. Partnerships with non-governmental providers are vital for continuous service delivery; 4. TB control programs in fragile states require consistent donor support. Despite challenges in management, coordination, security, logistics and funding, TB control programs can function in fragile states, but face considerable problems in access to diagnosis and treatment and therefore case detection. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

I’m incredible—or am I? : On the socialization of fragile self-views in children

NARCIS (Netherlands)

Brummelman, E.

2015-01-01

I’m incredible—or am I? This is a recurring and daunting question for children with fragile self-views, whose feelings of self-worth crumble in the face of setbacks. What are the origins of children’s fragile self-views, and how can interventions reduce the fragility of children’s self-views? The

Axonal neuropathy in female carriers of the fragile X premutation with fragile x-associated tremor ataxia syndrome.

Science.gov (United States)

Ram, Suresh; Devapriya, Inoka A; Fenton, Grace; Mcvay, Lindsey; Nguyen, Danh V; Tassone, Flora; Maselli, Ricardo A; Hagerman, Randi J

2015-08-01

In this study we examined whether females with the fragile X-associated tremor ataxia syndrome (FXTAS) and non-FXTAS premutation carriers have electrophysiological signs of underlying peripheral neuropathy. Nerve conduction studies (NCS) were performed on 19 women with FXTAS, 20 non-FXTAS carriers, and 26 age-matched controls. The results were compared with existing data on corresponding male carriers. Women with FXTAS and non-FXTAS carriers had reduced sensory nerve action potential amplitudes. Also, there was a strong trend for reduced compound muscle action potential amplitudes in women with FXTAS, but not in non-FXTAS carriers. No significant slowing of nerve conduction velocities, prolongation of F-wave latencies, or associations with molecular measures was observed. This study suggests an underlying axonal neuropathy in women with FXTAS. However, in comparison to men with FXTAS, the NCS abnormalities in women were less severe, possibly due to the effect of a normal X chromosome. © 2014 Wiley Periodicals, Inc.

Cardiac function in acute hypothyroidism

International Nuclear Information System (INIS)

Donaghue, K.; Hales, I.; Allwright, S.; Cooper, R.; Edwards, A.; Grant, S.; Morrow, A.; Wilmshurst, E.; Royal North Shore Hospital, Sydney

1985-01-01

It has been established that chronic hypothyroidism may affect cardiac function by several mechanisms. It is not known how long the patient has to be hypothyroid for cardiac involvement to develop. This study was undertaken to assess the effect of a short period of hypothyroidism (10 days) on cardiac function. Nine patients who had had total tyroidectomy, had received ablative radioiodine for thyroid cancer and were euthyroid on replacement therapy were studied while both euthyroid and hypothyroid. Cardiac assessment was performed by X-ray, ECG, echocardiography and gated blood-pool scans. After 10 days of hypothyroidisms, the left-ventricular ejection fraction failed to rise after exercise in 4 of the 9 patients studied, which was significant (P<0.002). No significant changes in cardiac size or function at rest were detected. This functional abnormality in the absence of any demonstrable change in cardiac size and the absence of pericardial effussion with normal basal function suggest that short periods of hypothyroidism may reduce cardiac reserve, mostly because of alterations in metabolic function. (orig.)

Thermalization as an invisibility cloak for fragile quantum superpositions

Science.gov (United States)

Hahn, Walter; Fine, Boris V.

2017-07-01

We propose a method for protecting fragile quantum superpositions in many-particle systems from dephasing by external classical noise. We call superpositions "fragile" if dephasing occurs particularly fast, because the noise couples very differently to the superposed states. The method consists of letting a quantum superposition evolve under the internal thermalization dynamics of the system, followed by a time-reversal manipulation known as Loschmidt echo. The thermalization dynamics makes the superposed states almost indistinguishable during most of the above procedure. We validate the method by applying it to a cluster of spins ½.

Skeletal stem cells and their contribution to skeletal fragility

DEFF Research Database (Denmark)

Aldahmash, A.

2016-01-01

Age-related osteoporotic fractures are major health care problem worldwide and are the result of impaired bone formation, decreased bone mass and bone fragility. Bone formation is accomplished by skeletal stem cells (SSC) that are recruited to bone surfaces from bone marrow microenvironment....... This review discusses targeting SSC to enhance bone formation and to abolish age-related bone fragility in the context of using stem cells for treatment of age-related disorders. Recent studies are presented that have demonstrated that SSC exhibit impaired functions during aging due to intrinsic senescence...

Dopamine transporter imaging study in parkinsonism occurring in fragile X premutation carriers.

Science.gov (United States)

Ceravolo, R; Antonini, A; Volterrani, D; Rossi, C; Goldwurm, S; Di Maria, E; Kiferle, L; Bonuccelli, U; Murri, L

2005-12-27

The authors studied four patients with parkinsonism carrying the fragile X premutation using SPECT with ([23)I]FP-CIT. They found evidence of preserved presynaptic nigrostriatal function, suggesting that parkinsonism in the X fragile premutation might be related to postsynaptic dopaminergic changes or different neurotransmitter alterations.

Epilepsy in fragile-X-syndrome mimicking panayiotopoulos syndrome: Description of three patients.

Science.gov (United States)

Bonanni, Paolo; Casellato, Susanna; Fabbro, Franco; Negrin, Susanna

2017-10-01

Fragile-X-syndrome is the most common cause of inherited intellectual disability. Epilepsy is reported to occur in 10-20% of individuals with Fragile-X-syndrome. A frequent seizure/electroencephalogram (EEG) pattern resembles that of benign rolandic epilepsy. We describe the clinical features, EEG findings and evolution in three patients affected by Fragile-X-syndrome and epilepsy mimicking Panayiotopoulos syndrome. Age at seizure onset was between 4 and about 7 years. Seizures pattern comprised a constellation of autonomic symptoms with unilateral deviation of the eyes and ictal syncope. Duration of the seizures could be brief or lengthy. Interictal EEGs revealed functional multifocal abnormalities. The evolution was benign in all patients with seizures remission before the age of 14. This observation expands the spectrum of benign epileptic phenotypes present in Fragile-X-syndrome and may be quite helpful in guiding anticonvulsant management and counseling families as to expectations regarding seizure remission. © 2017 Wiley Periodicals, Inc.

Cardiac fluid dynamics meets deformation imaging.

Science.gov (United States)

Dal Ferro, Matteo; Stolfo, Davide; De Paris, Valerio; Lesizza, Pierluigi; Korcova, Renata; Collia, Dario; Tonti, Giovanni; Sinagra, Gianfranco; Pedrizzetti, Gianni

2018-02-20

Cardiac function is about creating and sustaining blood in motion. This is achieved through a proper sequence of myocardial deformation whose final goal is that of creating flow. Deformation imaging provided valuable contributions to understanding cardiac mechanics; more recently, several studies evidenced the existence of an intimate relationship between cardiac function and intra-ventricular fluid dynamics. This paper summarizes the recent advances in cardiac flow evaluations, highlighting its relationship with heart wall mechanics assessed through the newest techniques of deformation imaging and finally providing an opinion of the most promising clinical perspectives of this emerging field. It will be shown how fluid dynamics can integrate volumetric and deformation assessments to provide a further level of knowledge of cardiac mechanics.

Cardiac biomarkers in Neonatology

OpenAIRE

Vijlbrief, D.C.

2015-01-01

In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

Animal models of cardiac cachexia.

Science.gov (United States)

Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

2016-09-15

Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effect of atom mismatch on the fragility of supercooled Lennard-Jones binary mixtures

International Nuclear Information System (INIS)

Sun Minhua; Sun Yongli; Wang Aiping; Ma Congxiao; Li Jiayun; Cheng Weidong; Liu Fang

2006-01-01

The shear viscosity of the well-known binary Lennard-Jones mixture is simulated under constant temperature and constant volume conditions (NVT) by a molecular-dynamics (MD) method. The effect of atomic size mismatch on the fragility parameter and glass-forming ability is studied. The fragility parameters calculated from shear viscosity data decrease with the increment of the atomic size mismatch. The value of the fragility changes from 168.963 to 22.976 when the mismatch changes from 0.023 to 0.25. It is shown that the fragility parameter is sensitive to the atomic size mismatch. The calculated pair distribution functions and mean square displacements indicate that the glass-forming ability increases with the atomic size mismatch

Empirical Fragility Analysis of Buildings and Boats Damaged By the 2011 Great East Japan Tsunami and Their Practical Application

Science.gov (United States)

Suppasri, A.; Charvet, I.; Leelawat, N.; Fukutani, Y.; Muhari, A.; Futami, T.; Imamura, F.

2014-12-01

This study focused in turn on detailed data of buildings and boats damage caused by the 2011 tsunami in order to understand its main causes and provide damage probability estimates. Tsunami-induced building damage data was collected from field surveys, and includes inundation depth, building material, number of stories and occupancy type for more than 80,000 buildings. Numerical simulations with high resolution bathymetry and topography data were conducted to obtain characteristic tsunami measures such as flow velocity. These data were analyzed using advanced statistical methods, ordinal regression analysis to create not only empirical 2D tsunami fragility curves, but also 3D tsunami fragility surfaces for the first time. The effect of floating debris was also considered, by using a binary indicator of debris impact based on the proximity of a structure from a debris source (i.e. washed away building). Both the 2D and 3D fragility analyses provided results for each different building damage level, and different topography. While 2D fragility curves provide easily interpretable results relating tsunami flow depth to damage probability for different damage levels, 3D fragility surfaces allow for several influential tsunami parameters to be taken into account thus reduce uncertainty in the probability estimations. More than 20,000 damaged boats were used in the analysis similar to the one carried out on the buildings. Detailed data for each boat comprises information on the damage ratio (paid value over insured value), tonnage, engine type, material type and damage classification. The 2D and 3D fragility analyses were developed using representative tsunami heights for each port obtained from field surveys and flow velocities obtained from the aforementioned simulations. The results are currently being adapted for practical disaster mitigation. They are being integrated with the probabilistic tsunami hazard analysis, in order to create offshore and onshore

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

Science.gov (United States)

Gross, Christina; Berry-Kravis, Elizabeth M; Bassell, Gary J

2012-01-01

Fragile X syndrome (FXS) is an inherited neurodevelopmental disease caused by loss of function of the fragile X mental retardation protein (FMRP). In the absence of FMRP, signaling through group 1 metabotropic glutamate receptors is elevated and insensitive to stimulation, which may underlie many of the neurological and neuropsychiatric features of FXS. Treatment of FXS animal models with negative allosteric modulators of these receptors and preliminary clinical trials in human patients support the hypothesis that metabotropic glutamate receptor signaling is a valuable therapeutic target in FXS. However, recent research has also shown that FMRP may regulate diverse aspects of neuronal signaling downstream of several cell surface receptors, suggesting a possible new route to more direct disease-targeted therapies. Here, we summarize promising recent advances in basic research identifying and testing novel therapeutic strategies in FXS models, and evaluate their potential therapeutic benefits. We provide an overview of recent and ongoing clinical trials motivated by some of these findings, and discuss the challenges for both basic science and clinical applications in the continued development of effective disease mechanism-targeted therapies for FXS. PMID:21796106

FMR1 Knockout mice: A model to study fragile X mental retardation

Energy Technology Data Exchange (ETDEWEB)

Oostra, B.A.; Bakker, C.E.; Reyniers, E. [Erasmus Univ., Rotterdam (Netherlands)] [and others

1994-09-01

The fragile X syndrome is the most frequent form of inherited mental retardation in humans with an incidence of 1 in 1250 males and 1 in 2500 females. The clinical syndrome includes moderate to severe mental retardation, autistic behavior, macroorchidism, and facial features, such as long face with mandibular prognathism and large, everted ears. The molecular basis for this disease is a large expansion of a triplet repeat (CGG){sub n} in the 5{prime} untranslated region of the FMR1 gene. Due to this large expansion of the CGG repeat, the promoter region becomes methylated and the FMR1 gene is subsequently silenced. Hardly anything is known about the physiologic function of FMR1 and the pathologic mechanisms leading to these symptoms. Since the FMR1 gene is highly conserved in the mouse, we used the mouse to design a knockout model for the fragile X syndrome. These knockout mice lacking Fmrp have normal litter size suggesting that FMR1 is not essential in human gametogenesis and embryonic development. The knockout mice show the abnormalities also seen in the affected organs of human patients. Mutant mice show a gradual development through time of macroorchidism. In the knockout mice we observed cognitive defects in the form of deficits in learning (as shown by the hidden platform Morris water maze task) and behavioral abnormalities such as increased exploratory behavior and hyperactivity. Therefore this knockout mouse may serve as a valuable tool in studying the role of FMR1 in the fragile X syndrome and may serve as a model to elucidate the mechanisms involved in macroorchidism, abnormal behavior, and mental retardation.

A nonsense mutation in FMR1 causing fragile X syndrome

DEFF Research Database (Denmark)

Grønskov, Karen; Brøndum-Nielsen, Karen; Dedic, Alma

2011-01-01

Fragile X syndrome is a common cause of inherited intellectual disability. It is caused by lack of the FMR1 gene product FMRP. The most frequent cause is the expansion of a CGG repeat located in the 5'UTR of FMR1. Alleles with 200 or more repeats become hypermethylated and transcriptionally silent....... Only few patients with intragenic point mutations in FMR1 have been reported and, currently, routine analysis of patients referred for fragile X syndrome includes solely analysis for repeat expansion and methylation status. We identified a substitution in exon 2 of FMR1, c.80C>A, causing a nonsense...... mutation p.Ser27X, in a patient with classical clinical symptoms of fragile X syndrome. The mother who carried the mutation in heterozygous form presented with mild intellectual impairment. We conclude that further studies including western blot and DNA sequence analysis of the FMR1 gene should...

Seismic margins review of nuclear power plants: Fragility aspects

International Nuclear Information System (INIS)

Ravindra, M.K.; Hardy, G.S.; Hashimoto, P.S.

1987-01-01

The fragility analysis is utilised in the seismic margin review in initial screening of certain components in the plant based on their generically high seismic capacities. A detailed walkdown of the plant is conducted to confirm that the initial screening is valid i.e., the generically high seismic capacity components do not possess any potential weaknesses (e.g., inadequate bracing, inadequate anchorage and potential systems interaction). For the components that are screened in, their seismic capacities are evaluated using either a probabilistic analysis of a deterministic evaluation. Based on a system analysis, the Boolean expressions for critical accident sequences are derived. These Boolean expressions are quantified using the component fragilities and nonseismic unavailabilities of components. The final product is the High Confidence Low Probability of Failure (HCLPF) capacity of the plant and the identification of potential seismic vulnerabilities in the plant. The objective of the paper is to describe the application of fragility analysis procedures in the seismic margin review of Maine Yankee and to document the insights obtained in this trial plant review. (orig./HP)

Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death

DEFF Research Database (Denmark)

Nyegaard, Mette; Overgaard, Michael Toft; Sondergaard, M.T.

2012-01-01

a substantial part of sudden cardiac deaths in young individuals. Mutations in RYR2, encoding the cardiac sarcoplasmic calcium channel, have been identified as causative in approximately half of all dominantly inherited CPVT cases. Applying a genome-wide linkage analysis in a large Swedish family with a severe......Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion in individuals without structural cardiac abnormalities. Although rare, CPVT is suspected to cause...... calmodulin-binding-domain peptide at low calcium concentrations. We conclude that calmodulin mutations can cause severe cardiac arrhythmia and that the calmodulin genes are candidates for genetic screening of individual cases and families with idiopathic ventricular tachycardia and unexplained sudden cardiac...

Clinical assessment tools identify functional deficits in fragility fracture patients

Directory of Open Access Journals (Sweden)

Ames TD

2016-05-01

Full Text Available Tyler D Ames,1 Corinne E Wee,1 Khoi M Le,1 Tiffany L Wang,1 Julie Y Bishop,2 Laura S Phieffer,2 Carmen E Quatman2 1The Ohio State University College of Medicine, 2Department of Orthopaedics, The Ohio State University Wexner Medical Center, Columbus, OH, USA Purpose: To identify inexpensive, noninvasive, portable, clinical assessment tools that can be used to assess functional performance measures that may put older patients at risk for falls such as balance, handgrip strength, and lumbopelvic control.Patients and methods: Twenty fragility fracture patients and 21 healthy control subjects were evaluated using clinical assessment tools (Nintendo Wii Balance Board [WBB], a handheld dynamometer, and an application for the Apple iPod Touch, the Level Belt that measure functional performance during activity of daily living tasks. The main outcome measurements were balance (WBB, handgrip strength (handheld dynamometer, and lumbopelvic control (iPod Touch Level Belt, which were compared between fragility fracture patients and healthy controls.Results: Fragility fracture patients had lower scores on the vertical component of the WBB Torso Twist task (P=0.042 and greater medial–lateral lumbopelvic sway during a 40 m walk (P=0.026 when compared to healthy controls. Unexpectedly, the fracture patients had significantly higher scores on the left leg (P=0.020 and total components (P=0.010 of the WBB Single Leg Stand task as well as less faults during the left Single Leg Stand task (P=0.003.Conclusion: The clinical assessment tools utilized in this study are relatively inexpensive and portable tools of performance measures capable of detecting differences in postural sway between fragility fracture patients and controls. Keywords: fall risk, geriatric fracture, Nintendo Wii Balance Board, Level Belt, fragility fracture

Fragility analysis methodology for degraded structures and passive components in nuclear power plantsIllustrated using a condensate storage tank

International Nuclear Information System (INIS)

Nie, Jinsuo; Braverman, Joseph; Hofmayer, Charles; Choun, Young Sun; Kim, Min Kyu; Choi, In Kil

2010-06-01

This report describes the seismic fragility capacity for a condensate storage tank with various degradation scenarios. The conservative deterministic failure margin method has been utilized for the undegraded case and has been modified to accommodate the degraded cases. A total of five seismic fragility analysis cases have been described: (1) undegraded case, (2) degraded stainless tank shell, (3) degraded anchor bolts, (4) anchorage concrete cracking, and (5) a perfect correlation of the three degradation scenarios. Insights from these fragility analyses are also presented. An overview of the methods for seismic fragility analysis and generic approaches to incorporate time-dependent degradation models into a fragility analysis is presented. Fundamental concepts of seismic fragility analysis are summarized to facilitate discussions in later sections. The seismic fragility analysis of the undegraded CST, which is assumed to have all of its components in design condition, is described. The subject CST was located in an operating Korean NPP. The baseline fragility capacity of the CST is calculated and the basic procedure of seismic fragility analysis is established. This report presents the results and insights of the seismic fragility analysis of the CST under various postulated degradation scenarios

Ocular Motor Indicators of Executive Dysfunction in Fragile X and Turner Syndromes

Science.gov (United States)

Lasker, Adrian G.; Mazzocco, Michele M. M.; Zee, David S.

2007-01-01

Fragile X and Turner syndromes are two X-chromosome-related disorders associated with executive function and visual spatial deficits. In the present study, we used ocular motor paradigms to examine evidence that disruption to different neurological pathways underlies these deficits. We tested 17 females with fragile X, 19 females with Turner…

Visual Pathway Deficit in Female Fragile X Premutation Carriers: A Potential Endophenotype

Science.gov (United States)

Keri, Szabolcs; Benedek, Gyorgy

2009-01-01

Previous studies indicated impaired magnocellular (M) and relatively spared parvocellular (P) visual pathway functioning in patients with fragile X syndrome. In this study, we assessed M and P pathways in 22 female fragile X premutation carriers with normal intelligence and in 20 healthy non-carrier controls. Testing procedure included visual…

Wild-type male offspring of fmr-1+/- mothers exhibit characteristics of the fragile X phenotype.

Science.gov (United States)

Zupan, Bojana; Toth, Miklos

2008-10-01

Fragile X syndrome is an X-linked disorder caused by the inactivation of the FMR-1 gene with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities, and hyperactivity. Males are more severely affected than heterozygote (H) females, who, as carriers, have a 50% chance of transmitting the mutated allele in each pregnancy. fmr-1 knockout (KO) mice reproduce fragile X symptoms, including hyperactivity, seizures, and abnormal sensory processing. In contrast to the expectation that wild-type (WT) males born to H (fmr-1(+/-)) mothers (H>WT) are behaviorally normal and indistinguishable from WT males born to WT mothers (WT>WT); here, we show that H>WT offspring are more active than WT>WT offspring and that their hyperactivity is similar to male KO mice born to H or KO (fmr-1(-/-)) mothers (H>KO/KO>KO). H>WT mice, however, do not exhibit seizures or abnormal sensory processing. Consistent with their hyperactivity, the effect of the D2 agonist quinpirole is reduced in H>WT as well as in H>KO and KO>KO mice compared to WT>WT offspring, suggesting a diminished feedback inhibition of dopamine release. Our data indicate that some aspects of hyperactivity and associated dopaminergic changes in 'fragile X' mice are a maternal fmr-1 genotype rather than an offspring fmr-1 genotype effect.

Food insecurity and child behavior problems in fragile families.

Science.gov (United States)

King, Christian

2018-02-01

Food insecurity remains a persistent problem in the United States. Several studies have shown that food insecurity is associated with child externalizing and internalizing behavior problems. However, some potential methodological limitations remain. For example, most studies use a household measure of food insecurity while there is evidence that children, especially younger ones, tend to be shielded by their parents from experiencing food insecurity. In addition, the mechanisms through which food insecurity affects children are not well understood. This study uses longitudinal data from the Fragile Families and Child Wellbeing Study to address these limitations. Fixed-effects models show that the association is even larger using a measure of child food insecurity instead of a household one. Correlated-random effects models show a large difference in child behavior problems between food secure and food insecure children due to unobserved heterogeneity. In addition, the association between child food insecurity and child externalizing behaviors remains largely unexplained while food insecurity among adults explains almost all the variation in the association with child internalizing behaviors. Food insecure children and parents are at risk of micronutrient deficiencies, which may lead to behavior problems in young children. These findings underscore the need for greater focus on reducing the risk of food insecurity, especially for children in fragile families, in order to reduce behavior problems and improve their educational attainment. Copyright © 2017 Elsevier B.V. All rights reserved.

Divergent effects of obesity on fragility fractures

Directory of Open Access Journals (Sweden)

Caffarelli C

2014-09-01

Full Text Available Carla Caffarelli, Chiara Alessi, Ranuccio Nuti, Stefano Gonnelli Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy Abstract: Obesity was commonly thought to be advantageous for maintaining healthy bones due to the higher bone mineral density observed in overweight individuals. However, several recent studies have challenged the widespread belief that obesity is protective against fracture and have suggested that obesity is a risk factor for certain fractures. The effect of obesity on fracture risk is site-dependent, the risk being increased for some fractures (humerus, ankle, upper arm and decreased for others (hip, pelvis, wrist. Moreover, the relationship between obesity and fracture may also vary by sex, age, and ethnicity. Risk factors for fracture in obese individuals appear to be similar to those in nonobese populations, although patterns of falling are particularly important in the obese. Research is needed to determine if and how visceral fat and metabolic complications of obesity (type 2 diabetes mellitus, insulin resistance, chronic inflammation, etc are causally associated with bone status and fragility fracture risk. Vitamin D deficiency and hypogonadism may also influence fracture risk in obese individuals. Fracture algorithms such as FRAX® might be expected to underestimate fracture probability. Studies specifically designed to evaluate the antifracture efficacy of different drugs in obese patients are not available; however, literature data may suggest that in obese patients higher doses of the bisphosphonates might be required in order to maintain efficacy against nonvertebral fractures. Therefore, the search for better methods for the identification of fragility fracture risk in the growing population of adult and elderly subjects with obesity might be considered a clinical priority which could improve the prevention of fracture in obese individuals. Keywords: bone mineral density, BMI

Mechanisms of diabetes mellitus-induced bone fragility

DEFF Research Database (Denmark)

Napoli, Nicola; Chandran, Manju; Pierroz, Dominique D

2017-01-01

The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM...... and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia......-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus....

Cardiac changes in anorexia nervosa.

Science.gov (United States)

Spaulding-Barclay, Michael A; Stern, Jessica; Mehler, Philip S

2016-04-01

Introduction Anorexia nervosa is an eating disorder, which is associated with many different medical complications as a result of the weight loss and malnutrition that characterise this illness. It has the highest mortality rate of any psychiatric disorder. A large portion of deaths are attributable to the cardiac abnormalities that ensue as a result of the malnutrition associated with anorexia nervosa. In this review, the cardiac complications of anorexia nervosa will be discussed. A comprehensive literature review on cardiac changes in anorexia nervosa was carried out. There are structural, functional, and rhythm-type changes that occur in patients with anorexia nervosa. These become progressively significant as ongoing weight loss occurs. Cardiac changes are inherent to anorexia nervosa and they become more life-threatening and serious as the anorexia nervosa becomes increasingly severe. Weight restoration and attention to these cardiac changes are crucial for a successful treatment outcome.

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice.

Science.gov (United States)

Foote, Molly; Arque, Gloria; Berman, Robert F; Santos, Mónica

2016-10-01

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55-200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments.

Evaluation of structural fragilities for an IPEEE seismic probabilistic risk assessment study

International Nuclear Information System (INIS)

Ghiocel, D.M.; Wilson, P.R.; Stevenson, J.D.

1995-01-01

The paper presents the main issues and results of a structural fragility analysis for a Seismic Probabilistic Risk Assessment (SPRA) study of a nuclear power plant (NPP) in the Eastern US. The fragility evaluations were performed for the Reactor Building, Auxiliary Building, Intake Structure and Diesel Generator Building. The random seismic input is defined in terms of the Uniform Hazard Spectrum (UHS) earthquake on the NPP site anchored to a reference level of 0.40 g Zero Period Ground Acceleration (ZPGA). Because of the soft soil conditions new Soil-Structure Interaction (SSI) analyses were performed using the original finite element (stick) structural models and the complex frequency approach. The soil deposit randomness was described by the variations in both the low strain soil shear modules and in its dependence with the shear strain. The probabilistic SSI analyses were performed using digital simulation techniques. The critical failure modes for each structure are investigated and the fragility evaluations are discussed. Concluding remarks and recommendations for improving the quality of the structural fragility analyses are included

Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice

Science.gov (United States)

Foote, Molly; Arque, Gloria; Berman, Robert F.; Santos, Mónica

2016-01-01

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder that affects some carriers of the Fragile X premutation (PM). In PM carriers there is a moderate expansion of a CGG trinucleotide sequence (55-200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the Fragile X Mental Retardation Protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that cause PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically we will discuss the construct, face and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms and potential treatments. PMID:27255703

Seismic Margin Assessment for Research Reactor using Fragility based Fault Tree Analysis

Energy Technology Data Exchange (ETDEWEB)

Kwag, Shinyoung; Oh, Jinho; Lee, Jong-Min; Ryu, Jeong-Soo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

The research reactor has been often subjected to external hazards during the design lifetime. Especially, a seismic event can be one of significant threats to the failure of structure system of the research reactor. This failure is possibly extended to the direct core damage of the reactor. For this purpose, the fault tree for structural system failure leading to the core damage under an earthquake accident is developed. The failure probabilities of basic events are evaluated as fragility curves of log-normal distributions. Finally, the plant-level seismic margin is investigated by the fault tree analysis combining with fragility data and the critical path is identified. The plant-level probabilistic seismic margin assessment using the fragility based fault tree analysis was performed for quantifying the safety of research reactor to a seismic hazard. For this, the fault tree for structural system failure leading to the core damage of the reactor under a seismic accident was developed. The failure probabilities of basic events were evaluated as fragility curves of log-normal distributions.

Fragile X Syndrome: An Aging Perspective

Science.gov (United States)

Schneider, Andrea; Ligsay, Andrew; Hagerman, Randi J.

2013-01-01

Cognitive and behavioral correlates of molecular variations related to the FMR1 gene have been studied rather extensively, but research about the long-term outcome in individuals with fragile X spectrum disorders remains sparse. In this review, we present an overview of aging research and recent findings in regard to cellular and clinical…

Ventilation and gas exchange management after cardiac arrest.

Science.gov (United States)

Sutherasan, Yuda; Raimondo, Pasquale; Pelosi, Paolo

2015-12-01

For several decades, physicians had integrated several interventions aiming to improve the outcomes in post-cardiac arrest patients. However, the mortality rate after cardiac arrest is still as high as 50%. Post-cardiac arrest syndrome is associated with high morbidity and mortality due to not only poor neurological outcome and cardiovascular failure but also respiratory dysfunction. To minimize ventilator-associated lung injury, protective mechanical ventilation by using low tidal volume ventilation and driving pressure may decrease pulmonary complications and improve survival. Low level of positive end-expiratory pressure (PEEP) can be initiated and titrated with careful cardiac output and respiratory mechanics monitoring. Furthermore, optimizing gas exchange by avoiding hypoxia and hyperoxia as well as maintaining normocarbia may improve neurological and survival outcome. Early multidisciplinary cardiac rehabilitation intervention is recommended. Minimally invasive monitoring techniques, that is, echocardiography, transpulmonary thermodilution method measuring extravascular lung water, as well as transcranial Doppler ultrasound, might be useful to improve appropriate management of post-cardiac arrest patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fragility of superheated melts and glass-forming ability in Pr-based alloys

International Nuclear Information System (INIS)

Meng, Q.G.; Zhou, J.K.; Zheng, H.X.; Li, J.G.

2006-01-01

The kinetic viscosity (η) of superheated melts, thermal properties (T x , T m , T L ) and X-ray diffraction analysis on the Pr-based bulk metallic glasses (BMG) are reported and discussed. A new refined concept, the superheated fragility defined as M' = E S δ x /k B , has been developed based on common solidification theory and the Arrhenius equation. The interrelationship between this kind of fragility and the glass-forming ability (GFA) is elaborated on and evaluated in Pr-based BMG and Al-based amorphous ribbon alloys. Using viscosity data of superheated melts, it is shown, theoretically and experimentally, that the fragility parameter M' may be used as a GFA indicator for metallic alloys

Banking Fragility in Colombia: An Empirical Analysis Based on Balance Sheets

OpenAIRE

Ignacio Lozano; Alexander Guarín

2014-01-01

In this paper, we study the empirical relationship between credit funding sources and the financial vulnerability of the Colombian banking system. We propose a statistical model to measure and predict banking-fragility episodes associated with credit funding sources classified into retail deposits and wholesale funds. We compute the probability of financial fragility for both the aggregated banking system and the individual banks. Our approach performs a Bayesian averaging of estimated logit ...

The prospects for ecosystem services provision in fragile states’ urban areas

OpenAIRE

Bogadi, Antonija

2018-01-01

In fragile states context of climate change vulnerability, poverty and lack of infrastructure, the ability of ecosystem services to provide for numerous human needs is indispensable. The focus of this paper is describing the prospects for ecosystem services provision in fragile states’ urban areas. This paper presents a distinct approach by analyzing actors with capacity to provide ecosystem services in urban areas: government, international partners and citizens. Using infrastructure investm...

Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload

Directory of Open Access Journals (Sweden)

Sujith Dassanayaka

2018-07-01

Full Text Available Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2. An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. Keywords: Heart failure, Hypertrophy, Oxidative stress, Aldehydes, Cardiac remodeling, Hormesis

Fragile X premutation in women: recognizing the health challenges beyond primary ovarian insufficiency.

Science.gov (United States)

Hoyos, Luis R; Thakur, Mili

2017-03-01

Fragile X premutation carriers have 55-200 CGG repeats in the 5' untranslated region of the FMR1 gene. Women with this premutation face many physical and emotional challenges in their life. Approximately 20% of these women will develop fragile X-associated primary ovarian insufficiency (FXPOI). In addition, they suffer from increased rates of menstrual dysfunction, diminished ovarian reserve, reduction in age of menopause, infertility, dizygotic twinning, and risk of having an offspring with a premutation or full mutation. Consequent chronic hypoestrogenism may result in impaired bone health and increased cardiovascular risk. Neuropsychiatric issues include risk of developing fragile X-associated tremor/ataxia syndrome, neuropathy, musculoskeletal problems, increased prevalence of anxiety, depression, and sleep disturbances independent of the stress of raising an offspring with fragile X syndrome and higher risk of postpartum depression. Some studies have reported a higher prevalence of thyroid abnormalities and hypertension in these women. Reproductive health providers play an important role in the health supervision of women with fragile X premutation. Awareness of these risks and correlation of the various manifestations could help in early diagnosis and coordination of care and services for these women and their families. This paper reviews current evidence regarding the possible conditions that may present in women with premutation-sized repeats beyond FXPOI.

Emerging pharmacologic treatment options for fragile X syndrome

Science.gov (United States)

Schaefer, Tori L; Davenport, Matthew H; Erickson, Craig A

2015-01-01

Fragile X syndrome (FXS) is the most common single gene cause of intellectual disability and autism spectrum disorder. Caused by a silenced fragile X mental retardation 1 gene and the subsequent deficiency in fragile X mental retardation protein, patients with FXS experience a range of physical, behavioral, and intellectual debilitations. The FXS field, as a whole, has recently met with some challenges, as several targeted clinical trials with high expectations of success have failed to elucidate significant improvements in a variety of symptom domains. As new clinical trials in FXS are planned, there has been much discussion about the use of the commonly used clinical outcome measures, as well as study design considerations, patient stratification, and optimal age range for treatment. The evidence that modification of these drug targets and use of these failed compounds would prove to be efficacious in human clinical study were rooted in years of basic and translational research. There are questions arising as to the use of the mouse models for studying FXS treatment development. This issue is twofold: many of the symptom domains and molecular and biochemical changes assessed and indicative of efficacy in mouse model study are not easily amenable to clinical trials in people with FXS because of the intolerability of the testing paradigm or a lack of noninvasive techniques (prepulse inhibition, sensory hypersensitivity, startle reactivity, or electrophysiologic, biochemical, or structural changes in the brain); and capturing subtle yet meaningful changes in symptom domains such as sociability, anxiety, and hyperactivity in human FXS clinical trials is challenging with the currently used measures (typically parent/caregiver rating scales). Clinicians, researchers, and the pharmaceutical industry have all had to take a step back and critically evaluate the way we think about how to best optimize future investigations into pharmacologic FXS treatments. As new clinical

Side Effects of Minocycline Treatment in Patients with Fragile X Syndrome and Exploration of Outcome Measures

Science.gov (United States)

Utari, Agustini; Chonchaiya, Weerasak; Rivera, Susan M.; Schneider, Andrea; Hagerman, Randi J.; Faradz, Sultana M. H.; Ethell, Iryna M.; Nguyen, Danh V.

2010-01-01

Minocycline can rescue the dendritic spine and synaptic structural abnormalities in the fragile X knock-out mouse. This is a review and preliminary survey to document side effects and potential outcome measures for minocycline use in the treatment of individuals with fragile X syndrome. We surveyed 50 patients with fragile X syndrome who received…

The effects of malnutrition on cardiac function in African children.

Science.gov (United States)

Silverman, Jonathan A; Chimalizeni, Yamikani; Hawes, Stephen E; Wolf, Elizabeth R; Batra, Maneesh; Khofi, Harriet; Molyneux, Elizabeth M

2016-02-01

Cardiac dysfunction may contribute to high mortality in severely malnourished children. Our objective was to assess the effect of malnutrition on cardiac function in hospitalised African children. Prospective cross-sectional study. Public referral hospital in Blantyre, Malawi. We enrolled 272 stable, hospitalised children ages 6-59 months, with and without WHO-defined severe acute malnutrition. Cardiac index, heart rate, mean arterial pressure, stroke volume index and systemic vascular resistance index were measured by the ultrasound cardiac output monitor (USCOM, New South Wales, Australia). We used linear regression with generalised estimating equations controlling for age, sex and anaemia. Our primary outcome, cardiac index, was similar between those with and without severe malnutrition: difference=0.22 L/min/m(2) (95% CI -0.08 to 0.51). No difference was found in heart rate or stroke volume index. However, mean arterial pressure and systemic vascular resistance index were lower in children with severe malnutrition: difference=-8.6 mm Hg (95% CI -12.7 to -4.6) and difference=-200 dyne s/cm(5)/m(2) (95% CI -320 to -80), respectively. In this largest study to date, we found no significant difference in cardiac function between hospitalised children with and without severe acute malnutrition. Further study is needed to determine if cardiac function is diminished in unstable malnourished children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Cardiac cone-beam CT

International Nuclear Information System (INIS)

Manzke, Robert

2005-01-01

This doctoral thesis addresses imaging of the heart with retrospectively gated helical cone-beam computed tomography (CT). A thorough review of the CT reconstruction literature is presented in combination with a historic overview of cardiac CT imaging and a brief introduction to other cardiac imaging modalities. The thesis includes a comprehensive chapter about the theory of CT reconstruction, familiarizing the reader with the problem of cone-beam reconstruction. The anatomic and dynamic properties of the heart are outlined and techniques to derive the gating information are reviewed. With the extended cardiac reconstruction (ECR) framework, a new approach is presented for the heart-rate-adaptive gated helical cardiac cone-beam CT reconstruction. Reconstruction assessment criteria such as the temporal resolution, the homogeneity in terms of the cardiac phase, and the smoothness at cycle-to-cycle transitions are developed. Several reconstruction optimization approaches are described: An approach for the heart-rate-adaptive optimization of the temporal resolution is presented. Streak artifacts at cycle-to-cycle transitions can be minimized by using an improved cardiac weighting scheme. The optimal quiescent cardiac phase for the reconstruction can be determined automatically with the motion map technique. Results for all optimization procedures applied to ECR are presented and discussed based on patient and phantom data. The ECR algorithm is analyzed for larger detector arrays of future cone-beam systems throughout an extensive simulation study based on a four-dimensional cardiac CT phantom. The results of the scientific work are summarized and an outlook proposing future directions is given. The presented thesis is available for public download at www.cardiac-ct.net

Fragility fractures and bone remodeling in type 2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Tatiana O. Yalochkina

2017-11-01

Full Text Available Fracture risk is significantly increased in both type 1 and type 2 diabetes and individuals with diabetes experience worse fracture outcomes compared to normoglycemic individuals. Patients with T1DM have decreased bone mineral density (BMD, whereas patients with T2DM demonstrate increased BMD compared to healthy control. The latest studies show increased incidence of low-traumatic fractures in patients with T2DM instead of high bone mineral density (BMD. The risk of osteoporotic fractures in patients with T2DM can be explained by disease complications and increased risk of falls and consequent trauma. However, the most important cause of bone fragility in T2DM is the deterioration in bone microarchitecture, the mechanism of which is not completely understood. High BMD in patients with T2DM does not allow us to use dual-energy X-ray-absorptiometry as a “gold standard” test for diagnosticsof osteoporosis. Consequently,new risk factors and diagnostic algorithm as well as treatment strategy should be developed for patients with T2DM. In addition to this, some researchers considered that the group of T2DM is geterogenous and physicians might face patients with osteoporosis and mild diabetes that add very little to bone fragility; patients with osteoporosis and moderate or severe diabetes which also affects bone tissue –diabetoosteoporosis; and patients without osteoporosis but severe diabetes which cause bone tissue deterioration with the development of diabetic bone disease. New diagnostic tools and algorithm and new experimental research are needed for better understanding bone deterioration in patients with T2DM. This review summarizes our current knowledge on fracture rate, risk factors for fractures and causes of bone deterioration in subjects with T2DM.

An Investigation of Narrative Ability in Boys with Autism and Fragile X Syndrome

Science.gov (United States)

Hogan-Brown, Abigail L.; Losh, Molly; Martin, Gary E.; Mueffelmann, Deborah J.

2013-01-01

Whereas pragmatic language difficulties are characteristic of both autism and Fragile X syndrome, it is unclear whether such deficits are qualitatively similar or whether certain skills are differentially affected. This study compared narrative competence in boys with autism, Fragile X syndrome, Down syndrome, and typical development. Results…

The Search for an Effective Therapy to Treat Fragile X Syndrome: Dream or Reality?

OpenAIRE

Castagnola, Sara; Bardoni, Barbara; Maurin, Thomas

2017-01-01

Fragile X Syndrome (FXS) is the most common form of intellectual disability and a primary cause of autism. It originates from the lack of the Fragile X Mental Retardation Protein (FMRP), which is an RNA-binding protein encoded by the Fragile X Mental Retardation Gene 1 (FMR1) gene. Multiple roles have been attributed to this protein, ranging from RNA transport (from the nucleus to the cytoplasm, but also along neurites) to translational control of mRNAs. Over the last 20 years many studies ha...

Fragility analysis of a seismically-isolated emergency diesel generator

International Nuclear Information System (INIS)

Choun, Young Sun; Choi, In Kil; Ohtori, Yasuki

2005-01-01

The seismic capacity of an Emergency Diesel Generator (EDG) in nuclear power plants influences the seismic safety of the plants significantly. A recent study showed that the increase of the seismic capacity of the EDG could reduce the core damage frequency (CDF) remarkably. It is known that the major failure mode of the EDG is a concrete coning failure due to the pulling out of the anchor bolts. The use of base isolators instead of anchor bolts can increase the seismic capacity of the EDG without any major problems. The fragility curves for a base-isolated EDG should be different from those for a conventional type because the major failure mode of the base-isolated EDG will not be a concrete coning one any more. The governing failure mode of the base-isolated EDG must be the damage of the isolators. This study introduces a fragility evaluation method for an isolated EDG, and evaluates the fragilities for the isolated EDG and compares them with those for the conventional one. Evaluation of the ground motion index is also carried out to determine the governing parameter suitable for representing the seismic responses of the base isolator

Breastfeeding of a medically fragile foster child.

Science.gov (United States)

Gribble, Karleen D

2005-02-01

A case is presented in which a medically fragile baby was breastfed by her foster mother. As a result, the child's physical and emotional health were improved. The mechanisms whereby human milk improves health are well known. The act of breastfeeding may also have an analgesic and relaxant effect as a result of hormonal influences and skin-to-skin contact. Many foster babies may benefit from human milk or breastfeeding. However, the risk of disease transmission must be minimized. Provision of human milk to all medically fragile foster babies is desirable. Breastfeeding by the foster mother may be applicable in cases in which the child is likely to be in long-term care, the child has been previously breastfed, or the child's mother expresses a desire that the infant be breastfed. However, social barriers must be overcome before breastfeeding of foster babies can become more common.

UCP3 Ablation Exacerbates High-Salt Induced Cardiac Hypertrophy and Cardiac Dysfunction

Directory of Open Access Journals (Sweden)

Hongmei Lang

2018-04-01

Full Text Available Background/Aims: Excessive salt intake and left ventricular hypertrophy (LVH are both critical for the development of hypertension and heart failure. The uncoupling protein 3 (UCP3 plays a cardio-protective role in early heart failure development. However, the potential role for UCP3 in salt intake and LVH is unclear. Methods: UCP3-/- and C57BL/6 mice were placed on either a normal-salt (NS, 0.5% or a high-salt (HS, 8% diet for 24 weeks. The cardiac function, endurance capacity, energy expenditure, and mitochondrial functional capacity were measured in each group. Results: Elevated blood pressure was only observed in HS-fed UCP3-/- mice. High salt induced cardiac hypertrophy and dysfunction were observed in both C57BL/6 and UCP3-/- mice. However, the cardiac lesions were more profound in HS-fed UCP3-/- mice. Furthermore, HS-fed UCP3-/-mice experienced more severe mitochondrial respiratory dysfunction compared with HS-fed C57BL/6 mice, represented by the decreased volume of oxygen consumption and heat production at the whole-body level. Conclusion: UCP3 protein was involved in the incidence of high-salt induced hypertension and the progression of cardiac dysfunction in the early stages of heart failure. UCP3 ablation exacerbated high-salt-induced cardiac hypertrophy and cardiac dysfunction.

Effects of hyperoxia and caffeine on the expression of fragile site at Xq27.3

Energy Technology Data Exchange (ETDEWEB)

Rafi, S.K.; Surana, R.B.; Christopher, K.L. [Armed Forces Institute of Pathology, Washington, DC (United States)] [and others

1996-02-02

To enhance the cytogenetic expression of the fragile X chromosome, we studied the effects of hyperoxia and caffeine on the induction of fragile Xq27.3. A lymphoblastoid cell line (GM 06912) derived from a fragile X male proband was cultured in RPMI 1640 containing 16% dialyzed fetal calf serum. The cells were synchronously subjected to one of 3 different atmospheric oxygen tensions (21%, 21.3 kPa, hyperoxic) during the last 24 hours of the 72 hour culture, immediately after the addition of 2{prime}-deoxy-5-fluorouridine (FUdR) at 25 ng/ml. To study the enhancing effect of caffeine, with or without hyperoxia, a second set of cultures was additionally subjected to caffeine (2.5 mM) during the last 6 hours of the culture. When the fragility of hyperoxic cells (38.1 kPa dissolved oxygen) was compared to that of normoxic control cells (13.3 kPa dissolved oxygen), the difference was significant (P < 0.05). These data suggest that there is a mean increase in the fragile Xq27.3 expressivity as the dissolved oxygen tension increases. Additionally, we observed that caffeine, with or without hyperoxia, significantly (P <0.05) suppressed the expression of the fragile X site in this lymphoblastoid cell line. 34 refs., 2 tabs.

Fragile X-associated tremor/ataxia syndrome: phenotypic comparisons with other movement disorders.

Science.gov (United States)

Robertson, Erin E; Hall, Deborah A; McAsey, Andrew R; O'Keefe, Joan A

2016-08-01

The purpose of this paper is to review the typical cognitive and motor impairments seen in fragile X-associated tremor/ataxia syndrome (FXTAS), essential tremor (ET), Parkinson disease (PD), spinocerebellar ataxias (SCAs), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) in order to enhance diagnosis of FXTAS patients. We compared the cognitive and motor phenotypes of FXTAS with each of these other movement disorders. Relevant neuropathological and neuroimaging findings are also reviewed. Finally, we describe the differences in age of onset, disease severity, progression rates, and average lifespan in FXTAS compared to ET, PD, SCAs, MSA, and PSP. We conclude with a flow chart algorithm to guide the clinician in the differential diagnosis of FXTAS. By comparing the cognitive and motor phenotypes of FXTAS with the phenotypes of ET, PD, SCAs, MSA, and PSP we have clarified potential symptom overlap while elucidating factors that make these disorders unique from one another. In summary, the clinician should consider a FXTAS diagnosis and testing for the Fragile X mental retardation 1 (FMR1) gene premutation if a patient over the age of 50 (1) presents with cerebellar ataxia and/or intention tremor with mild parkinsonism, (2) has the middle cerebellar peduncle (MCP) sign, global cerebellar and cerebral atrophy, and/or subcortical white matter lesions on MRI, or (3) has a family history of fragile X related disorders, intellectual disability, autism, premature ovarian failure and has neurological signs consistent with FXTAS. Peripheral neuropathy, executive function deficits, anxiety, or depression are supportive of the diagnosis. Distinct profiles in the cognitive and motor domains between these movement disorders may guide practitioners in the differential diagnosis process and ultimately lead to better medical management of FXTAS patients.

Non-fragile multivariable PID controller design via system augmentation

Science.gov (United States)

Liu, Jinrong; Lam, James; Shen, Mouquan; Shu, Zhan

2017-07-01

In this paper, the issue of designing non-fragile H∞ multivariable proportional-integral-derivative (PID) controllers with derivative filters is investigated. In order to obtain the controller gains, the original system is associated with an extended system such that the PID controller design can be formulated as a static output-feedback control problem. By taking the system augmentation approach, the conditions with slack matrices for solving the non-fragile H∞ multivariable PID controller gains are established. Based on the results, linear matrix inequality -based iterative algorithms are provided to compute the controller gains. Simulations are conducted to verify the effectiveness of the proposed approaches.

Resolution of Spatial and Temporal Visual Attention in Infants with Fragile X Syndrome

Science.gov (United States)

Farzin, Faraz; Rivera, Susan M.; Whitney, David

2011-01-01

Fragile X syndrome is the most common cause of inherited intellectual impairment and the most common single-gene cause of autism. Individuals with fragile X syndrome present with a neurobehavioural phenotype that includes selective deficits in spatiotemporal visual perception associated with neural processing in frontal-parietal networks of the…

Fragile X checklists: A meta-analysis and development of a simplified universal clinical checklist.

Science.gov (United States)

Lubala, Toni Kasole; Lumaka, Aimé; Kanteng, Gray; Mutesa, Léon; Mukuku, Olivier; Wembonyama, Stanislas; Hagerman, Randi; Luboya, Oscar Numbi; Lukusa Tshilobo, Prosper

2018-04-06

Clinical checklists available have been developed to assess the risk of a positive Fragile X syndrome but they include relatively small sample sizes. Therefore, we carried out a meta-analysis that included statistical pooling of study results to obtain accurate figures on the prevalence of clinical predictors of Fragile X syndrome among patients with intellectual disability, thereby helping health professionals to improve their referrals for Fragile X testing. All published studies consisting of cytogenetic and/or molecular screening for fragile X syndrome among patients with intellectual disability, were eligible for the meta-analysis. All patients enrolled in clinical checklists trials of Fragile X syndrome were eligible for this review, with no exclusion based on ethnicity or age. Odds ratio values, with 95% confidence intervals as well as Cronbach coefficient alpha, was reported to assess the frequency of clinical characteristics in subjects with intellectual disability with and without the fragile X mutation to determine the most discriminating. The following features were strongly associated with Fragile X syndrome: skin soft and velvety on the palms with redundancy of skin on the dorsum of hand [OR: 16.85 (95% CI 10.4-27.3; α:0.97)], large testes [OR: 7.14 (95% CI 5.53-9.22; α: 0.80)], large and prominent ears [OR: 18.62 (95% CI 14.38-24.1; α: 0.98)], pale blue eyes [OR: 8.97 (95% CI 4.75-16.97; α: 0.83)], family history of intellectual disability [OR: 3.43 (95% CI 2.76-4.27; α: 0.81)] as well as autistic-like behavior [OR: 3.08 (95% CI 2.48-3.83; α: 0.77)], Flat feet [OR: 11.53 (95% CI 6.79-19.56; α:0.91)], plantar crease [OR: 3.74 (95% CI 2.67-5.24; α: 0.70)]. We noted a weaker positive association between transverse palmar crease [OR: 2.68 (95% CI 1.70-4.18; α: 0.51)], elongated face [OR: 3.69 (95% CI 2.84-4.81; α: 0.63)]; hyperextensible metacarpo-phalangeal joints [OR: 2.68 (95% CI 2.15-3.34; α: 0.57)] and the Fragile X syndrome. This study

State fragility and its regional implications for peace and stability

DEFF Research Database (Denmark)

Mandrup, Thomas

of the Cold war left a security void, and the fragility, and in some instances collapse, of the state structures resulted in new state formations and new conflicts, both intra- and inter-state in nature. However, conflicts and security challenges in East Africa are due to amongst other things porous borders......, fragile states and bad governance regional in nature, and cannot be solved by the individual states alone. Regional institutions have been in a weak position dealing with these challenges, and attempts have been to strengthen the capacity of these regional institutions. This paper investigates...

Post cardiac injury syndrome

DEFF Research Database (Denmark)

Nielsen, S L; Nielsen, F E

1991-01-01

The post-pericardiotomy syndrome is a symptom complex which is similar in many respects to the post-myocardial infarction syndrome and these are summarized under the diagnosis of the Post Cardiac Injury Syndrome (PCIS). This condition, which is observed most frequently after open heart surgery, i...... on the coronary vessels, with cardiac tamponade and chronic pericardial exudate. In the lighter cases, PCIS may be treated with NSAID and, in the more severe cases, with systemic glucocorticoid which has a prompt effect....

Assessment of cardiac sympathetic nerve integrity with positron emission tomography

International Nuclear Information System (INIS)

Raffel, David M.; Wieland, Donald M.

2001-01-01

The autonomic nervous system plays a critical role in the regulation of cardiac function. Abnormalities of cardiac innervation have been implicated in the pathophysiology of many heart diseases, including sudden cardiac death and congestive heart failure. In an effort to provide clinicians with the ability to regionally map cardiac innervation, several radiotracers for imaging cardiac sympathetic neurons have been developed. This paper reviews the development of neuronal imaging agents and discusses their emerging role in the noninvasive assessment of cardiac sympathetic innervation

Fragility fractures at Auckland City Hospital: we can do better.

Science.gov (United States)

Braatvedt, Geoffrey; Wilkinson, Susan; Scott, Marilyn; Mitchell, Paul; Harris, Roger

2017-12-01

This study describes in detail the burden of caring for patients aged ≥ 50 years seen in one year with a fragility fracture in a large urban environment and shows that these fractures result in a long length of stay and significant mortality. Intervention to prevent further fracture was poorly done. To examine the epidemiology of fragility fracture in patients over age 50 years and record the number who received appropriate secondary prevention treatment. All patients aged ≥ 50 years presenting with a fracture during the 12 months following July 1 st 2011, to Auckland City Hospital or residing in central Auckland at the time of their fracture, were identified from hospital and Accident Compensation Corporation records. A random sample of 55% of these patient's records were reviewed to establish the type of fracture, prior fracture and falls history, and use of bisphosphonates in the 12 months before presentation. Their length of stay (LOS) by type of fracture was recorded. The use of bisphosphonate drugs in the following 12 months was obtained from centralised national records of prescriptions. 2729 patients aged ≥ 50 years presented with a fragility fracture in the central Auckland region in one year. Fifty-six percent of these patients were seen at Auckland Hospital and of these, 82% patients required admission with a mean LOS of 20 days (SD ± 24 days).The remaining 44% of patients were looked after in the private outpatient sector. Approximately 30% of the admissions were for hip fracture. Sixty-four percent of patients with a fragility fracture did not receive a potent bisphosphonate, 12% were considered not appropriate for treatment, and 24% received a potent bisphosphonate during their admission or in the next 12 months. Approximately 1 in 18 people aged ≥ 50 years presented in one year with a fragility fracture.Secondary prevention strategies were poorly implemented. Additional resources for identifying and initiating secondary fracture prevention

Compound risk: History of traumatic stress predicts posttraumatic stress disorder symptoms and severity in sudden cardiac arrest survivors.

Science.gov (United States)

Rosman, Lindsey; Ford, Jessica; Whited, Amanda; Cahill, John; Lampert, Rachel; Mosesso, Vincent N; Lawless, Christine; Sears, Samuel F

2016-08-01

Sudden cardiac arrest (SCA) survivors can develop posttraumatic stress disorder (PTSD) which is associated with worse clinical outcomes. The purpose of this study was to evaluate the prevalence and predictors of PTSD in a large sample of SCA survivors. Prior history of psychological trauma and the effects of repeated trauma exposure on subsequent PTSD and symptom severity after SCA were also explored. A retrospective, cross-sectional study of 188 SCA survivors from the Sudden Cardiac Arrest Association patient registry completed an online questionnaire that included measures of PTSD, trauma history, sociodemographics, general health, and cardiac history. Sixty-three (36.2%) SCA survivors in this sample scored above the clinical cutoff for PTSD. Female gender, worse general health, and younger age predicted PTSD symptoms after SCA. Additionally, 50.2% of SCA survivors (n = 95) reported a history of trauma exposure and 25.4% (n = 48) of the total sample endorsed a traumatic stress response to a historic trauma. Results indicated that a traumatic stress response to a historic trauma was a stronger predictor of PTSD after SCA (odds ratio = 4.77) than all other variables in the model. PTSD symptoms are present in over one-third of SCA survivors. While demographic or health history variables predicted PTSD after SCA, a history of traumatic stress response to a previous trauma emerged as the strongest predictor of these symptoms. Routine assessment and interdisciplinary management are discussed as potential ways to expedite survivors' recovery and return to daily living. © The European Society of Cardiology 2015.

Cerebral protein synthesis in a knockin mouse model of the fragile X premutation

NARCIS (Netherlands)

M. Qin (Mei); T. Huang (Tianjian); Z. Liu (Zhonghua); M. Kader (Michael); T. Burlin (Thomas); Z. Xia (Zengyan); Z. Zeidler (Zachary); R.K. Hukema (Renate); C.B. Smith (Carolyn B.)

2014-01-01

textabstractThe (CGG)n-repeat in the 5’-untransiated region of the fragile X mental retardation gene (FMRi) gene is polymorphic and may become unstable on transmission to the next generation. In fragile X syndrome, CGG repeat lengths exceed 200, resulting in silencing of FMRi and absence of its

Fragile X syndrome: Are signaling lipids the missing culprits?

Science.gov (United States)

Tabet, Ricardos; Vitale, Nicolas; Moine, Hervé

2016-11-01

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and autism. FXS results from the absence of FMRP, an RNA binding protein associated to ribosomes that influences the translation of specific mRNAs in post-synaptic compartments of neurons. The main molecular consequence of the absence of FMRP is an excessive translation of neuronal protein in several areas of the brain. This local protein synthesis deregulation is proposed to underlie the defect in synaptic plasticity responsible for FXS. Recent findings in neurons of the fragile X mouse model (Fmr1-KO) uncovered another consequence of the lack of FMRP: a deregulation of the diacylglycerol (DAG)/phosphatidic acid (PA) homeostasis. DAG and PA are two interconvertible lipids that influence membrane architecture and that act as essential signaling molecules that activate various downstream effectors, including master regulators of local protein synthesis and actin polymerization. As a consequence, DAG and PA govern a variety of cellular processes, including cell proliferation, vesicle/membrane trafficking and cytoskeletal organization. At the synapse, the level of these lipids is proposed to influence the synaptic activation status. FMRP appears as a master regulator of this neuronal process by controlling the translation of a diacylglycerol kinase enzyme that converts DAG into PA. The deregulated levels of DAG and PA caused by the absence of FMRP could represent a novel therapeutic target for the treatment of FXS. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Fragile sites, dysfunctional telomere and chromosome fusions: What is 5S rDNA role?

Science.gov (United States)

Barros, Alain Victor; Wolski, Michele Andressa Vier; Nogaroto, Viviane; Almeida, Mara Cristina; Moreira-Filho, Orlando; Vicari, Marcelo Ricardo

2017-04-15

Repetitive DNA regions are known as fragile chromosomal sites which present a high flexibility and low stability. Our focus was characterize fragile sites in 5S rDNA regions. The Ancistrus sp. species shows a diploid number of 50 and an indicative Robertsonian fusion at chromosomal pair 1. Two sequences of 5S rDNA were identified: 5S.1 rDNA and 5S.2 rDNA. The first sequence gathers the necessary structures to gene expression and shows a functional secondary structure prediction. Otherwise, the 5S.2 rDNA sequence does not contain the upstream sequences that are required to expression, furthermore its structure prediction reveals a nonfunctional ribosomal RNA. The chromosomal mapping revealed several 5S.1 and 5S.2 rDNA clusters. In addition, the 5S.2 rDNA clusters were found in acrocentric and metacentric chromosomes proximal regions. The pair 1 5S.2 rDNA cluster is co-located with interstitial telomeric sites (ITS). Our results indicate that its clusters are hotspots to chromosomal breaks. During the meiotic prophase bouquet arrangement, double strand breaks (DSBs) at proximal 5S.2 rDNA of acrocentric chromosomes could lead to homologous and non-homologous repair mechanisms as Robertsonian fusions. Still, ITS sites provides chromosomal instability, resulting in telomeric recombination via TRF2 shelterin protein and a series of breakage-fusion-bridge cycles. Our proposal is that 5S rDNA derived sequences, act as chromosomal fragile sites in association with some chromosomal rearrangements of Loricariidae. Copyright © 2017 Elsevier B.V. All rights reserved.

Acquired valvar disease and cardiac tumours

International Nuclear Information System (INIS)

Ruttley, M.

1985-01-01

Investigation must determine the severity of the valve fault or faults, the effect on cardiac function and the significance of any associated cardiac disease in order that surgical referral can be made when appropriate with knowledge of operative risk and prognosis; radiology plays an important part in this. Radiological features will depend on the valve or valves affected, the type and severity of the haemodynamic disturbance and its time scale of development and duration. They may be modified by embolism or infection and there may be specific radiological manifestations of the underlying disease

Fragile areas in the Alpine region: a reading between innovation and marginality

Directory of Open Access Journals (Sweden)

Federica Corrado

2010-05-01

Full Text Available The paper proposes a reading and description of fragile Alpine areas that overturns the conventional standpoint, according to which marginality is often synonymous with handicap. The paper starts form a different point of view, able to recognize specific local potentialities that can still be activated with a specific creative effort. The reading regards fragile Alpine areas in the Provinces of Turin and Cuneo and is based on an empirical analysis of the actions underlying current micro-territorial innovative development trends.Cet article propose une lecture et une description des territoires alpins fragiles, en jetant un autre regard, où le concept de fragilité est associé à celui de handicap, c’est-à-dire un autre regard sur l’identification des potentiels locaux spécifiques qui peuvent être encore activés à travers une force créatrice propre aux Alpes. La lecture est effectuée en fonction des territoires alpins fragiles qui font partie des provinces de Turin et Coni et se base sur une analyse empirique des initiatives qui enclenchent en quelque façon des dynamiques micro-territoriales de développement innovant.

Sleep Apnea and Nocturnal Cardiac Arrhythmia: A Populational Study

Directory of Open Access Journals (Sweden)

Fatima Dumas Cintra

2014-11-01

Full Text Available Background: The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. The authors hypothesized that nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea. Objective: To analyze the relationship between obstructive sleep apnea and abnormal heart rhythm during sleep in a population sample. Methods: Cross-sectional study with 1,101 volunteers, who form a representative sample of the city of São Paulo. The overnight polysomnography was performed using an EMBLA® S7000 digital system during the regular sleep schedule of the individual. The electrocardiogram channel was extracted, duplicated, and then analyzed using a Holter (Cardio Smart® system. Results: A total of 767 participants (461 men with a mean age of 42.00 ± 0.53 years, were included in the analysis. At least one type of nocturnal cardiac rhythm disturbance (atrial/ventricular arrhythmia or beat was observed in 62.7% of the sample. The occurrence of nocturnal cardiac arrhythmias was more frequent with increased disease severity. Rhythm disturbance was observed in 53.3% of the sample without breathing sleep disorders, whereas 92.3% of patients with severe obstructive sleep apnea showed cardiac arrhythmia. Isolated atrial and ventricular ectopy was more frequent in patients with moderate/severe obstructive sleep apnea when compared to controls (p < 0.001. After controlling for potential confounding factors, age, sex and apnea-hypopnea index were associated with nocturnal cardiac arrhythmia. Conclusion: Nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea and the prevalence increases with disease severity. Age, sex, and the Apnea-hypopnea index were predictors of arrhythmia in this sample.

Organizational changes help Benin NGO better protect fragile ...

International Development Research Centre (IDRC) Digital Library (Canada)

2016-04-28

Apr 28, 2016 ... ... climate change adaptation, and sustainable management of fragile ecosystems. ... build community-level capacity for sustainable development through ... solution is to build new houses in more secure areas and to relocate ...

Metoclopramide-induced cardiac arrest

Directory of Open Access Journals (Sweden)

Martha M. Rumore

2011-11-01

Full Text Available The authors report a case of cardiac arrest in a patient receiving intravenous (IV metoclopramide and review the pertinent literature. A 62-year-old morbidly obese female admitted for a gastric sleeve procedure, developed cardiac arrest within one minute of receiving metoclopramide 10 mg via slow intravenous (IV injection. Bradycardia at 4 beats/min immediately appeared, progressing rapidly to asystole. Chest compressions restored vital function. Electrocardiogram (ECG revealed ST depression indicative of myocardial injury. Following intubation, the patient was transferred to the intensive care unit. Various cardiac dysrrhythmias including supraventricular tachycardia (SVT associated with hypertension and atrial fibrillation occurred. Following IV esmolol and metoprolol, the patient reverted to normal sinus rhythm. Repeat ECGs revealed ST depression resolution without pre-admission changes. Metoclopramide is a non-specific dopamine receptor antagonist. Seven cases of cardiac arrest and one of sinus arrest with metoclopramide were found in the literature. The metoclopramide prescribing information does not list precautions or adverse drug reactions (ADRs related to cardiac arrest. The reaction is not dose related but may relate to the IV administration route. Coronary artery disease was the sole risk factor identified. According to Naranjo, the association was possible. Other reports of cardiac arrest, severe bradycardia, and SVT were reviewed. In one case, five separate IV doses of 10 mg metoclopramide were immediately followed by asystole repeatedly. The mechanism(s underlying metoclopramide’s cardiac arrest-inducing effects is unknown. Structural similarities to procainamide may play a role. In view of eight previous cases of cardiac arrest from metoclopramide having been reported, further elucidation of this ADR and patient monitoring is needed. Our report should alert clinicians to monitor patients and remain diligent in surveillance and

Fragile X mental retardation protein controls ion channel expression and activity.

Science.gov (United States)

Ferron, Laurent

2016-10-15

Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome, the most common cause of inherited intellectual disability and autism. FMRP is an RNA-binding protein involved in the control of local translation, which has pleiotropic effects, in particular on synaptic function. Analysis of the brain FMRP transcriptome has revealed hundreds of potential mRNA targets encoding postsynaptic and presynaptic proteins, including a number of ion channels. FMRP has been confirmed to bind voltage-gated potassium channels (K v 3.1 and K v 4.2) mRNAs and regulates their expression in somatodendritic compartments of neurons. Recent studies have uncovered a number of additional roles for FMRP besides RNA regulation. FMRP was shown to directly interact with, and modulate, a number of ion channel complexes. The sodium-activated potassium (Slack) channel was the first ion channel shown to directly interact with FMRP; this interaction alters the single-channel properties of the Slack channel. FMRP was also shown to interact with the auxiliary β4 subunit of the calcium-activated potassium (BK) channel; this interaction increases calcium-dependent activation of the BK channel. More recently, FMRP was shown to directly interact with the voltage-gated calcium channel, Ca v 2.2, and reduce its trafficking to the plasma membrane. Studies performed on animal models of fragile X syndrome have revealed links between modifications of ion channel activity and changes in neuronal excitability, suggesting that these modifications could contribute to the phenotypes observed in patients with fragile X-associated disorders. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Early White-Matter Abnormalities of the Ventral Frontostriatal Pathway in Fragile X Syndrome

Science.gov (United States)

Haas, Brian W.; Barnea-Goraly, Naama; Lightbody, Amy A.; Patnaik, Swetapadma S.; Hoeft, Fumiko; Hazlett, Heather; Piven, Joseph; Reiss, Allan L.

2009-01-01

Aim: Fragile X syndrome is associated with cognitive deficits in inhibitory control and with abnormal neuronal morphology and development. Method: In this study, we used a diffusion tensor imaging (DTI) tractography approach to reconstruct white-matter fibers in the ventral frontostriatal pathway in young males with fragile X syndrome (n = 17;…

Autism Is Associated with the Fragile-X Syndrome.

Science.gov (United States)

Brown, W. Ted.; And Others

1982-01-01

The authors describe their methods for establishing the presence or absence of the fragile-X chromosome and discuss some of the clinical implications of their findings in relation to the clinical diagnosis of autism. (SW)

Program outline of seismic fragility capacity tests on nuclear power plant equipment

International Nuclear Information System (INIS)

Lijima, T.; Abe, H.; Fujita, T.

2004-01-01

A seismic probabilistic safety assessment (PSA) is an available method to evaluate residual risk of nuclear plant that is designed with definitive seismic design condition. Seismic fragility capacity data are necessary for seismic PSA, but we don't have sufficient data of active components of nuclear plants in Japan. This paper describes a plan of seismic fragility capacity tests on nuclear power plant equipment. The purpose of those tests is to obtain seismic fragility capacity of important equipment from a safety design point of view. And the equipment for the fragility capacity tests were selected considering effect on core damage frequency (CDF) that was evaluated by our preliminary seismic PSA. Consequently horizontal shaft pump, electric cabinets, Control Rod Drive system (CRD system) of BWR and PWR plant and vertical shaft pump were selected. The seismic fragility capacity tests are conducted from phase-1 to phase-3, and horizontal shaft pump and electric cabinets are tested on phase-1. The fragility capacity test consists of two types of tests. One is actual equipment test and another is element test. On actual equipment test, a real size model is tested with high-level seismic motion, and critical acceleration and failure mode are investigated. Regarding fragility test phase-1, we selected typical type horizontal shaft pump and electric cabinets for the actual equipment test. Those were Reactor Building Closed Cooling Water (RCW) Pump and eight kinds of electric cabinets such as relay cabinet, motor control center. On the test phase-1, maximum input acceleration for the actual equipment test is intended to be 6-G-force. Since the shaking table of TADOTSU facility did not have capability for high acceleration, we made vibration amplifying system. In this system, amplifying device is mounted on original shaking table and it moves in synchronization with original table. The element test is conducted with many samples and critical acceleration, median and

Extracorporeal life support in pediatric cardiac patients

Directory of Open Access Journals (Sweden)

Matteo Di NARDO

2016-10-01

Full Text Available Extracorporeal Life Support (ECLS is a valuable tool in the management of neonates and older children with severe cardiac or respiratory failure. In this review, we focus on ECLS when used for neonatal and pediatric cardiac disease. Strict selection of patients and timely deployment are necessary to optimize outcomes. Although every attempt should be made to deploy ECLS urgently rather than emergently, extracorporeal cardiopulmonary resuscitation (ECPR is being increasingly used and reasonable survival rates have been achieved after initiation of ECLS during active compressions of the chest following in-hospital cardiac arrest. Contraindications to ECLS are falling over time, although lethal chromosomal abnormalities, severe irreversible brain injury, and extremely low gestational age and weight (<32 weeks gestation or <1.5 kg remain firm contraindications.

Fragile X-associated tremor/ataxia syndrome.

Science.gov (United States)

Hoem, Gry; Koht, Jeanette

2017-10-31

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a hereditary neurodegenerative disorder caused by a mutation on the X chromosome. The major signs and symptoms are tremor, ataxia and parkinsonism. Up to one in 2 000 persons over 50 years of age will develop the syndrome. There is reason to believe that too few individuals in Norway undergo testing for this condition.

Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

Directory of Open Access Journals (Sweden)

Hansen eWang

2015-02-01

Full Text Available Autism spectrum disorders (ASDs are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases.

The Pathophysiology of Fragile X (and What It Teaches Us about Synapses)

Science.gov (United States)

Bhakar, Asha L.; Dölen, Gül; Bear, Mark F.

2014-01-01

Fragile X is the most common known inherited cause of intellectual disability and autism, and it typically results from transcriptional silencing of FMR1 and loss of the encoded protein, FMRP (fragile X mental retardation protein). FMRP is an mRNA-binding protein that functions at many synapses to inhibit local translation stimulated by metabotropic glutamate receptors (mGluRs) 1 and 5. Recent studies on the biology of FMRP and the signaling pathways downstream of mGluR1/5 have yielded deeper insight into how synaptic protein synthesis and plasticity are regulated by experience. This new knowledge has also suggested ways that altered signaling and synaptic function can be corrected in fragile X, and human clinical trials based on this information are under way. PMID:22483044

Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

Science.gov (United States)

Wang, Hansen; Pati, Sandipan; Pozzo-Miller, Lucas; Doering, Laurie C.

2015-01-01

Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases. PMID:25767435

Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition

DEFF Research Database (Denmark)

Fabiansen, Christian; Lykke, Mikkel; Hother, Anne-Louise

2015-01-01

BACKGROUND: Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition. OBJECTIVE: To determine malnutrition-induced echocardiographic disturbances...... and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model. METHODS AND RESULTS: Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet...... groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (pMalnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide...

Recent advances in assays for the fragile X-related disorders.

Science.gov (United States)

Hayward, Bruce E; Kumari, Daman; Usdin, Karen

2017-10-01

The fragile X-related disorders are a group of three clinical conditions resulting from the instability of a CGG-repeat tract at the 5' end of the FMR1 transcript. Fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI) are disorders seen in carriers of FMR1 alleles with 55-200 repeats. Female carriers of these premutation (PM) alleles are also at risk of having a child who has an FMR1 allele with >200 repeats. Most of these full mutation (FM) alleles are epigenetically silenced resulting in a deficit of the FMR1 gene product, FMRP. This results in fragile X Syndrome (FXS), the most common heritable cause of intellectual disability and autism. The diagnosis and study of these disorders is challenging, in part because the detection of alleles with large repeat numbers has, until recently, been either time-consuming or unreliable. This problem is compounded by the mosaicism for repeat length and/or DNA methylation that is frequently seen in PM and FM carriers. Furthermore, since AGG interruptions in the repeat tract affect the risk that a FM allele will be maternally transmitted, the ability to accurately detect these interruptions in female PM carriers is an additional challenge that must be met. This review will discuss some of the pros and cons of some recently described assays for these disorders, including those that detect FMRP levels directly, as well as emerging technologies that promise to improve the diagnosis of these conditions and to be useful in both basic and translational research settings.

Behavioral Assessment of Social Anxiety in Females with Turner or Fragile X Syndrome.

Science.gov (United States)

Lesniak-Karpiak, Katarzyna; Mazzocco, Michele M. M.; Ross, Judith L.

2003-01-01

This study compared 29 females with Turner syndrome and 21 females with fragile X syndrome (ages 6-22) on a videotaped role-play interaction with 34 females in a comparison group. Three of eight behavioral measures of social skills differentiated the participant groups. Fragile-X subjects required more time to initiate interactions and Turner…

Financial Liberalization and Financial Fragility

OpenAIRE

Enrica Detragiache; Asli Demirgüç-Kunt

1998-01-01

The authors study the empirical relationship between banking crises and financial liberalization using a panel of data for 53 countries for 1980-95. They find that banking crises are more likely to occur in liberalized financial systems. But financial liberalization's impact on a fragile banking sector is weaker where the institutional environment is strong--especially where there is respect for the rule of law, a low level of corruption, and good contract enforcement. They examine evidence o...

Seismic fragility of RC shear walls in nuclear power plant Part 1: Characterization of uncertainty in concrete constitutive model

International Nuclear Information System (INIS)

Syed, Sammiuddin; Gupta, Abhinav

2015-01-01

Highlights: • A framework is proposed for seismic fragility assessment of Reinforced Concrete structures. • Experimentally validated finite element models are used to conduct nonlinear simulations. • Critical parameters in concrete constitutive model are identified to conduct nonlinear simulations. • Uncertainties in model parameters of concrete damage plasticity model is characterized. • Closed form expressions are used to compute the damage variables and plasticity. - Abstract: This two part manuscript proposes a framework for seismic fragility assessment of reinforced concrete structures in nuclear energy facilities. The novelty of the proposed approach lies in the characterization of uncertainties in the parameters of the material constitutive model. Concrete constitutive models that comprehensively address different damage states such as tensile cracking, compression failure, stiffness degradation, and recovery of degraded stiffness due to closing of previously formed cracks under dynamic loading are generally defined in terms of a large number of variables to characterize the plasticity and damage at material level. Over the past several years, many different studies have been presented on evaluation of fragility for reinforced concrete structures using nonlinear time history simulations. However, almost all of these studies do not consider uncertainties in the parameters of a comprehensive constitutive model. Part-I of this two-part manuscript presents a study that is used to identify uncertainties associated with the critical parameters in nonlinear concrete damage plasticity model proposed by Lubliner et al. (1989. Int. J. Solids Struct., 25(3), 299) and later modified by Lee and Fenves (1998a. J. Eng. Mech., ASCE, 124(8), 892) and Lee and Fenves (1998b. Earthquake Eng. Struct. Dyn., 27(9), 937) for the purpose of seismic fragility assessment. The limitations in implementation of the damage plasticity model within a finite element framework and

Seismic fragility of RC shear walls in nuclear power plant Part 1: Characterization of uncertainty in concrete constitutive model

Energy Technology Data Exchange (ETDEWEB)

Syed, Sammiuddin [Department of Civil, Construction, and Environmental Engineering, North Carolina State University, 426 Mann Hall, Campus Box 7908, Raleigh, NC 27695-7908 (United States); Gupta, Abhinav, E-mail: agupta1@ncsu.edu [Department of Civil, Construction, and Environmental Engineering, North Carolina State University, 413 Mann Hall, Campus Box 7908, Raleigh, NC 27695-7908 (United States)

2015-12-15

Highlights: • A framework is proposed for seismic fragility assessment of Reinforced Concrete structures. • Experimentally validated finite element models are used to conduct nonlinear simulations. • Critical parameters in concrete constitutive model are identified to conduct nonlinear simulations. • Uncertainties in model parameters of concrete damage plasticity model is characterized. • Closed form expressions are used to compute the damage variables and plasticity. - Abstract: This two part manuscript proposes a framework for seismic fragility assessment of reinforced concrete structures in nuclear energy facilities. The novelty of the proposed approach lies in the characterization of uncertainties in the parameters of the material constitutive model. Concrete constitutive models that comprehensively address different damage states such as tensile cracking, compression failure, stiffness degradation, and recovery of degraded stiffness due to closing of previously formed cracks under dynamic loading are generally defined in terms of a large number of variables to characterize the plasticity and damage at material level. Over the past several years, many different studies have been presented on evaluation of fragility for reinforced concrete structures using nonlinear time history simulations. However, almost all of these studies do not consider uncertainties in the parameters of a comprehensive constitutive model. Part-I of this two-part manuscript presents a study that is used to identify uncertainties associated with the critical parameters in nonlinear concrete damage plasticity model proposed by Lubliner et al. (1989. Int. J. Solids Struct., 25(3), 299) and later modified by Lee and Fenves (1998a. J. Eng. Mech., ASCE, 124(8), 892) and Lee and Fenves (1998b. Earthquake Eng. Struct. Dyn., 27(9), 937) for the purpose of seismic fragility assessment. The limitations in implementation of the damage plasticity model within a finite element framework and

Paradoxical effect of baclofen on social behavior in the fragile X syndrome mouse model

NARCIS (Netherlands)

S. Zeidler (Shimriet); A.S. Pop (Andreea); I.A. Jaafar; H. De Boer (Helen); R.A.M. Buijsen (Ronald); C. de Esch (Celine); I.M. Nieuwenhuizen-Bakker; R.K. Hukema (Renate); R. Willemsen (Rob)

2018-01-01

textabstractIntroduction: Fragile X syndrome (FXS) is a common monogenetic cause of intellectual disability, autism spectrum features, and a broad range of other psychiatric and medical problems. FXS is caused by the lack of the fragile X mental retardation protein (FMRP), a translational regulator

Emotion Potentiated Startle in Fragile X Syndrome

Science.gov (United States)

Ballinger, Elizabeth C.; Cordeiro, Lisa; Chavez, Alyssa D.; Hagerman, Randi J.; Hessl, David

2014-01-01

Social avoidance and anxiety are prevalent in fragile X syndrome (FXS) and are potentially mediated by the amygdala, a brain region critical for social behavior. Unfortunately, functional brain resonance imaging investigation of the amygdala in FXS is limited by the difficulties experienced by intellectually impaired and anxious participants. We…

Cardiac sympathetic neuronal imaging using PET

International Nuclear Information System (INIS)

Lautamaeki, Riikka; Tipre, Dnyanesh; Bengel, Frank M.

2007-01-01

Balance of the autonomic nervous system is essential for adequate cardiac performance, and alterations seem to play a key role in the development and progression of various cardiac diseases. PET imaging of the cardiac autonomic nervous system has advanced extensively in recent years, and multiple pre- and postsynaptic tracers have been introduced. The high spatial and temporal resolution of PET enables noninvasive quantification of neurophysiologic processes at the tissue level. Ligands for catecholamine receptors, along with radiolabeled catecholamines and catecholamine analogs, have been applied to determine involvement of sympathetic dysinnervation at different stages of heart diseases such as ischemia, heart failure, and arrhythmia. This review summarizes the recent findings in neurocardiological PET imaging. Experimental studies with several radioligands and clinical findings in cardiac dysautonomias are discussed. (orig.)

Local variation of fragility and glass transition temperature of ultra-thin supported polymer films.

Science.gov (United States)

Hanakata, Paul Z; Douglas, Jack F; Starr, Francis W

2012-12-28

Despite extensive efforts, a definitive picture of the glass transition of ultra-thin polymer films has yet to emerge. The effect of film thickness h on the glass transition temperature T(g) has been widely examined, but this characterization does not account for the fragility of glass-formation, which quantifies how rapidly relaxation times vary with temperature T. Accordingly, we simulate supported polymer films of a bead-spring model and determine both T(g) and fragility, both as a function of h and film depth. We contrast changes in the relaxation dynamics with density ρ and demonstrate the limitations of the commonly invoked free-volume layer model. As opposed to bulk polymer materials, we find that the fragility and T(g) do not generally vary proportionately. Consequently, the determination of the fragility profile--both locally and for the film as a whole--is essential for the characterization of changes in film dynamics with confinement.

On the fragility of fractional-order PID controllers for FOPDT processes.

Science.gov (United States)

Padula, Fabrizio; Visioli, Antonio

2016-01-01

This paper analyzes the fragility issue of fractional-order proportional-integral-derivative controllers applied to integer first-order plus-dead-time processes. In particular, the effects of the variations of the controller parameters on the achieved control system robustness and performance are investigated. Results show that this kind of controllers is more fragile with respect to the standard proportional-integral-derivative controllers and therefore a significant attention should be paid by the user in their tuning. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Angiotensin converting enzyme DD genotype is associated with acute coronary syndrome severity and sudden cardiac death in Taiwan: a case-control emergency room study.

Science.gov (United States)

Chen, Ying-Hsin; Liu, Jui-Ming; Hsu, Ren-Jun; Hu, Sheng-Chuan; Harn, Horng-Jyh; Chen, Shee-Ping; Jeng, Jing-Ren; Wu, Chieh-Lin; Ho, Jar-Yi; Yu, Cheng-Ping

2012-02-15

Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms have been associated with acute coronary syndrome (ACS); however, several controversial results have also been found in different studied populations. This hospital-based, emergency room, case-control study in Taiwan retrospectively investigated 111 ACS patients, and 195 non-coronary subjects as a control group, to study the effects of ACE I/D polymorphism in the most urgent ACS patients. ACE I/D polymorphisms were determined by polymerase chain reaction-based assays and their associations with ACS risk, severity, and sudden cardiac death were determined. The ACE DD genotype was associated with ACS incidence. The DD genotype was associated with a significant 4-fold higher risk of ACS in multivariate analysis (odds ratio (OR) = 4.295; 95% confidence interval (CI): 1.436-12.851, p = 0.009), and a 3.35-fold higher risk of acute myocardial infarction. DD genotype carriers also had more than 3-fold higher risks of stenosis in all the three coronary arteries, left anterior descending artery infarction, and anterior wall infarction. In addition, the DD genotype was also associated with a higher risk of sudden cardiac death (OR = 6.484, 95% CI: 1.036-40.598, p = 0.046). This study demonstrated that the ACE DD genotype is an independent risk factor for ACS, and in particular, for acute myocardial infarction. In addition, the ACE DD genotype is also associated with greater ACS severity and a higher risk of sudden cardiac death. ACE genotyping is recommended for patients with a history of ACS, and more intensive preventive care is suggested for patients with the DD genotype.

A clinical study of mentally retarded children with fragile X syndrome inSaudi Arabia

International Nuclear Information System (INIS)

Al-Husain, M.; Salih, Mustafa A.M.; Zaki, Osama K.; Al-Othman, L.; Al-Nasser, Mohammed N.

2000-01-01

Studies on fragile X syndrome are scarce in Saudi Arabia and othercountries of the Arabian Peninsula. The few studies previously done haveeither been in the form of case reports or those performed oninstitutionalized mentally retarded patients. The aim of this study was todetermine the prevalence of fragile X syndrome among cases with mentalretardation who have been referred to the pediatric neurology clinics of KingKhalid University Hospital (KKUH) in Riyadh. Cytogenetic studies wereperformed in 94 cases that were referred to the pediatric neurology clinicsof KKUH because of mental retardation and/or delayed milestones ofdevelopment, from July 1995 to December 1997. Six male probands (6.4%) showedthe classic fragile X chromosome and another six (including a four year oldgirl) were detected, following extension of the cytogenetic studies to all 32first-degree relatives. Affection of more than one sibling was ascertained infour families. One family had four brothers with fragile X syndrome, whereasanother formed part of a large kindred with twelve males and five females whowere mentally retarded. A clinical, physical and psychological screeningchecklist was applied to the eleven affected males. Large testicular size,long face and short attention span were the most frequent features and eachwas detected in nine patients (82%). Pes planus and history of delayed speechwere found in eight patients (73%). The study showed that the fragile Xsyndrome clinical screening checklist has been applied in other populationsmight equally valuable and applicable among the population of Saudi Arabia.However, the presence of pale blue eyes can be excluded and more weight givento positive family history of mental to the most common clinical diagnosticfeatures of fragile X syndrome. (author)

Growth, history, or institutions? What explains state fragility in sub-Saharan Africa

OpenAIRE

Bertocchi, Graziella; Guerzoni, Andrea

2010-01-01

We explore the determinants of state fragility in sub-Saharan Africa. Controlling for a wide range of economic, demographic, geographic and institutional regressors, we find that institutions, and in particular the civil liberties index and the number of revolutions, are the main determinants of fragility, even taking into account their potential endogeneity. Economic factors such as income growth and investment display a non robust impact after controlling for omitted variables and reverse c...

ASCI 2010 contrast media guideline for cardiac imaging: a report of the Asian Society of Cardiovascular Imaging cardiac computed tomography and cardiac magnetic resonance imaging guideline working group

Science.gov (United States)

Kitagawa, Kakuya; Tsai, I-Chen; Chan, Carmen; Yu, Wei; Yong, Hwan Seok; Choi, Byoung Wook

2010-01-01

The use of contrast media for cardiac imaging becomes increasing as the widespread of cardiac CT and cardiac MR. A radiologist needs to carefully consider the indication and the injection protocol of contrast media to be used as well as the possibility of adverse effect. There are several guidelines for contrast media in western countries. However, these are focusing the adverse effect of contrast media. The Asian Society of Cardiovascular Imaging, the only society dedicated to cardiovascular imaging in Asia, formed a Working Group and created a guideline, which summarizes the integrated knowledge of contrast media for cardiac imaging. In cardiac imaging, coronary artery evaluation is feasible by non-contrast MR angiography, which can be an alternative examination in high risk patients for the use of iodine contrast media. Furthermore, the body habitus of Asian patients is usually smaller than that of their western counterparts. This necessitates modifications in the injection protocol and in the formula for calculation of estimated glomerular filtration rate. This guideline provided fundamental information for the use of contrast media for Asian patients in cardiac imaging. PMID:20931289

Cytogenetic abnormalities and fragile-x syndrome in Autism Spectrum Disorder

Directory of Open Access Journals (Sweden)

Reddy Kavita S

2005-01-01

Full Text Available Abstract Background Autism is a behavioral disorder with impaired social interaction, communication, and repetitive and stereotypic behaviors. About 5–10 % of individuals with autism have 'secondary' autism in which an environmental agent, chromosome abnormality, or single gene disorder can be identified. Ninety percent have idiopathic autism and a major gene has not yet been identified. We have assessed the incidence of chromosome abnormalities and Fragile X syndrome in a population of autistic patients referred to our laboratory. Methods Data was analyzed from 433 patients with autistic traits tested using chromosome analysis and/or fluorescence in situ hybridization (FISH and/or molecular testing for fragile X syndrome by Southern and PCR methods. Results The median age was 4 years. Sex ratio was 4.5 males to 1 female [354:79]. A chromosome (cs abnormality was found in 14/421 [3.33 %] cases. The aberrations were: 4/14 [28%] supernumerary markers; 4/14 [28%] deletions; 1/14 [7%] duplication; 3/14 [21%] inversions; 2/14 [14%] translocations. FISH was performed on 23 cases for reasons other than to characterize a previously identified cytogenetic abnormality. All 23 cases were negative. Fragile-X testing by Southern blots and PCR analysis found 7/316 [2.2 %] with an abnormal result. The mutations detected were: a full mutation (fM and abnormal methylation in 3 [43 %], mosaic mutations with partial methylation of variable clinical significance in 3 [43%] and a permutation carrier [14%]. The frequency of chromosome and fragile-X abnormalities appears to be within the range in reported surveys (cs 4.8-1.7%, FRAX 2–4%. Limitations of our retrospective study include paucity of behavioral diagnostic information, and a specific clinical criterion for testing. Conclusions Twenty-eight percent of chromosome abnormalities detected in our study were subtle; therefore a high resolution cytogenetic study with a scrutiny of 15q11.2q13, 2q37 and Xp23

Multipartnered Fertility and Depression among Fragile Families

Science.gov (United States)

Turney, Kristin; Carlson, Marcia J.

2011-01-01

We used data from the Fragile Families and Child Wellbeing Study to examine the association between multipartnered fertility (MPF)--when parents have children with more than one partner--and depression. Random-effects models suggested that MPF is associated with a greater likelihood of depression, net of family structure and other covariates.…

Comparative Erythrocytes Osmotic Fragility Test and some ...

African Journals Online (AJOL)

Erythrocytes osmotic fragility and haematological parameters of subjects with HbAS (sickle cell trait) and HbSS (sickle cell anaemia) were determined and compared with subjects with HbAA (normal adult haemoglobin), which acted as control. They were divided into three groups of 40 subjects for HbAA, 35 subjects for ...

Cardiac rhabdomyoma associated with tuberosclerosis complex in a newborn

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Birgin Torer

2016-03-01

Full Text Available Cardiac rhabdomyomas are the most comman cardiac tumors in children. They are hamartomatous benign tumors composed of myocytes. They often presents as multiple lesions involving the ventricular cavities. Rhabdomyomas are usually detected in utero by fetal echocardiography. Although patients with cardiac rhabdomyomas are generally asymptomatic these tumors may cause heart failure, severe arrhyhmias and sudden death. Cardiac rhabdomyomas are often associated with tuberosclerosis and they may be the earliest manifestation of tuberosclerosis. Here, we report a newborn infant with antenatally detected cardiac rhabdomyomas associated with tuberosclerosis and we want to emphasize that other diagnostic features of tuberosclerosis should be evaluated in patients with cardiac rhabdomyomas. [Cukurova Med J 2016; 41(0.100: 56-59

Young Adult Female Fragile X Premutation Carriers Show Age- and Genetically-Modulated Cognitive Impairments

Science.gov (United States)

Goodrich-Hunsaker, Naomi J.; Wong, Ling M.; McLennan, Yingratana; Srivastava, Siddharth; Tassone, Flora; Harvey, Danielle; Rivera, Susan M.; Simon, Tony J.

2011-01-01

The high frequency of the fragile X premutation in the general population and its emerging neurocognitive implications highlight the need to investigate the effects of the premutation on lifespan cognitive development. Until recently, cognitive function in fragile X premutation carriers (fXPCs) was presumed to be unaffected by the mutation. Here…

Determination of a modal interaction correction for narrowband fragility data

International Nuclear Information System (INIS)

Kana, D.D.; Pomerening, D.J.

1987-01-01

Laboratory tests for safety equipment operation under seismic environments in nuclear power plants have typically included various motion simulations based on either successively-applied multiple narrowband waveforms or simultaneous multifrequency broadband random waveforms. However, only broadband excitations are directly applicable when equipment performance is affected by interaction between simultaneously responding modes. Therefore, a modal interaction correction factor is developed so that a narrowed response spectrum can be transformed to an approximately equivalent broadband spectrum which accounts for modal interaction effects. The approach includes study of the fragility response of a simple two-degree-of-freedom oscillator for representative narrowband and broadband excitations, and relating the two resulting fragility response spectra. It is found that multiplication of the narrowband response spectrum by an 0.7 factor produces a conservative equivalent broadband response spectrum. The results are interpreted in terms of a secondary device responding on a primary support structure, or a primary structure having two resonances. The approach is useful for updating existing test results based on narrowband spectra, developing composite spectra for similar equipment, or providing more flexibility in designing new tests, and is applicable to qualification proof test data as well as fragility data. 10 refs., 8 figs

Seismic Fragility Curves of Industrial Buildings by Using Nonlinear Analysis

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Mohamed Nazri Fadzli

2017-01-01

Full Text Available This study presents the steel fragility curves and performance curves of industrial buildings of different geometries. The fragility curves were obtained for different building geometries, and the performance curves were developed based on lateral load, which is affected by the geometry of the building. Three records of far-field ground motion were used for incremental dynamic analysis (IDA, and the design lateral loads for pushover analysis (POA. All designs were based on British Standard (BS 5950; however, Eurocode 8 was preferred for seismic consideration in the analysis because BS 5950 does not specify any seismic provision. The five levels of performance stated by FEMA-273, namely, operational phase, immediate occupancy, damage control, life safety, and collapse prevention (CP were used as main guidelines for evaluating structural performance. For POA, Model 2 had highest base shear, followed by Model 1 and Model 3, even though Model 2 has a smaller structure compared with Model 3. Meanwhile, the fragility curves showed that the probability of reaching or exceeding the CP level of Model 2 is the highest, followed by that of Models 1 and 3.

Structure and management of tuberculosis control programs in fragile states--Afghanistan, DR Congo, Haiti, Somalia

NARCIS (Netherlands)

Mauch, Verena; Weil, Diana; Munim, Aayid; Boillot, Francois; Coninx, Rudi; Huseynova, Sevil; Powell, Clydette; Seita, Akihiro; Wembanyama, Henriette; van den Hof, Susan

2010-01-01

Health care delivery is particularly problematic in fragile states often connected with increased incidence of communicable diseases, among them tuberculosis. This article draws upon experiences in tuberculosis control in four fragile states from which four lessons learned were derived. A structured

A novel RNA transcript with antiapoptotic function is silenced in fragile X syndrome.

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Ahmad M Khalil

2008-01-01

Full Text Available Several genome-wide transcriptomics efforts have shown that a large percentage of the mammalian genome is transcribed into RNAs, however, only a small percentage (1-2% of these RNAs is translated into proteins. Currently there is an intense interest in characterizing the function of the different classes of noncoding RNAs and their relevance to human disease. Using genomic approaches we discovered FMR4, a primate-specific noncoding RNA transcript (2.4 kb that resides upstream and likely shares a bidirectional promoter with FMR1. FMR4 is a product of RNA polymerase II and has a similar half-life to FMR1. The CGG expansion in the 5' UTR of FMR1 appears to affect transcription in both directions as we found FMR4, similar to FMR1, to be silenced in fragile X patients and up-regulated in premutation carriers. Knockdown of FMR4 by several siRNAs did not affect FMR1 expression, nor vice versa, suggesting that FMR4 is not a direct regulatory transcript for FMR1. However, FMR4 markedly affected human cell proliferation in vitro; siRNAs knockdown of FMR4 resulted in alterations in the cell cycle and increased apoptosis, while the overexpression of FMR4 caused an increase in cell proliferation. Collectively, our results demonstrate an antiapoptotic function of FMR4 and provide evidence that a well-studied genomic locus can show unexpected functional complexity. It cannot be excluded that altered FMR4 expression might contribute to aspects of the clinical presentation of fragile X syndrome and/or related disorders.

The osmotic fragility of human erythrocytes is inhibited by laser irradiation

International Nuclear Information System (INIS)

Habodaszova, D.; Sikurova, L.; Waczulikova, I.

2004-01-01

In this study we investigated the influence of green laser irradiation (532 nm, 30 mW, 31,7 J/cm 2 ) on the membrane integrity of human erythrocytes and compared the results with the effect of infrared laser irradiation (810 nm, 50 mW, 31,3 J/cm 2 ). To evaluate the membrane integrity of erythrocytes, one clinical parameter, the osmotic fragility, was investigated. We observed a decrease in osmotic fragility of the erythrocytes after irradiation by the green laser light as well as by the infrared laser compared to non-irradiated controls (Authors)

Measurements of the Poisson ratio and fragility of glass-forming liquids

DEFF Research Database (Denmark)

Christensen, Tage Emil; Olsen, Niels Boye

Recently much attention has been given to models and phenomenology of glass-forming liquids that correlates fast and slow degrees of freedom . In particular the Poisson ratio has been correlated with fragility. We present data on shear - and bulk modulus obtained by the techniques...... of the piezoelectric transducers PBG and PSG on a number of glass-forming liquids. Hereby the Poisson ratio can be found. Furthermore the PSG also gives the temperature dependence of shear viscosity and thereby the fragility. The validity of the conjectured relation is discussed...

The definition of exertion-related cardiac events.

Science.gov (United States)

Rai, M; Thompson, P D

2011-02-01

Vigorous physical activity increases the risk of sudden cardiac death (SCD) and acute myocardial infarction (AMI) but there is no standard definition as to what constitutes an exertion-related cardiac event, specifically the time interval between physical exertion and cardiac event. A systematic review of studies related to exertion-related cardiac events was performed and the time interval between exertion and the event or the symptoms leading to the event was looked for in all the articles selected for inclusion. A total of 12 of 26 articles "suggested" or "defined" exertion-related events as those events whose symptoms started during or within 1 h of exertion. Others used definitions of 0.5 h, 2 h, "during exertion", "during or immediately post exertion" and "during or within several hours after exertion". It is suggested, therefore, that the definition of an exertion-related cardiac event be established as a cardiac event in which symptoms started during or within 1 h of physical exertion.

Fragile X founder effect and distribution of CGG repeats among the mentally retarded population of Andalusia, South Spain

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Yolanda de Diego

2002-01-01

Full Text Available Fragile X syndrome is the most common inherited form of mental retardation. We investigated the prevalence of the Fragile X syndrome in the population with mental retardation of unknown etiology in Andalusia, South Spain. We analyzed 322 unrelated patients (280 males and 42 females, and found a fragile X syndrome frequency of 6.5%. Among the non-fragile X chromosomes, the 29 CGG repeat was the most common allele. At the linked microsatellite DXS548 locus, we found a new allele which we called "allele 10" (17 CA. Similar to other south European populations, allele 2 (25 CA at the DXS548 locus and the fragile X allele were in linkage disequilibrium supporting the idea of a common founder chromosome predisposing to the CGG expansion.

Modeling Family Adaptation to Fragile X Syndrome

Science.gov (United States)

Raspa, Melissa; Bailey, Donald, Jr.; Bann, Carla; Bishop, Ellen

2014-01-01

Using data from a survey of 1,099 families who have a child with Fragile X syndrome, we examined adaptation across 7 dimensions of family life: parenting knowledge, social support, social life, financial impact, well-being, quality of life, and overall impact. Results illustrate that although families report a high quality of life, they struggle…

Fragility: The Next Wave in Critical Infrastructure Protection

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Allan McDougall

2009-01-01

Full Text Available In North America today, we are about to embark on a significant effort to repair, or even upgrade, many aspects of our infrastructure. Many of these efforts are linked to economic recovery packages. Others are based on sheer need. The challenge for decision makers and planners involves ensuring that scarce economic resources are put to their best use. Understanding the concept of fragility plays a pivotal part in reaching that understanding.Fragility, like many other systems—particularly Information Technology (IT systems—works on the concept of subjects and objects. Subjects are those entities that seek to exploit the services (or capacity offered by the object. Objects, on the other hand, are those entities that deliver some good or service to the overall system. Of course, something may act as the object in one pairing and the subject in another pairing—they are not exclusive in nature.

Fragile-to-strong transition in liquid silica

Science.gov (United States)

Geske, Julian; Drossel, Barbara; Vogel, Michael

2016-03-01

We investigate anomalies in liquid silica with molecular dynamics simulations and present evidence for a fragile-to-strong transition at around 3100 K-3300 K. To this purpose, we studied the structure and dynamical properties of silica over a wide temperature range, finding four indicators of a fragile-to-strong transition. First, there is a density minimum at around 3000 K and a density maximum at 4700 K. The turning point is at 3400 K. Second, the local structure characterized by the tetrahedral order parameter changes dramatically around 3000 K from a higher-ordered, lower-density phase to a less ordered, higher-density phase. Third, the correlation time τ changes from an Arrhenius behavior below 3300 K to a Vogel-Fulcher-Tammann behavior at higher temperatures. Fourth, the Stokes-Einstein relation holds for temperatures below 3000 K, but is replaced by a fractional relation above this temperature. Furthermore, our data indicate that dynamics become again simple above 5000 K, with Arrhenius behavior and a classical Stokes-Einstein relation.

Fragile-to-strong transition in liquid silica

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Julian Geske

2016-03-01

Full Text Available We investigate anomalies in liquid silica with molecular dynamics simulations and present evidence for a fragile-to-strong transition at around 3100 K-3300 K. To this purpose, we studied the structure and dynamical properties of silica over a wide temperature range, finding four indicators of a fragile-to-strong transition. First, there is a density minimum at around 3000 K and a density maximum at 4700 K. The turning point is at 3400 K. Second, the local structure characterized by the tetrahedral order parameter changes dramatically around 3000 K from a higher-ordered, lower-density phase to a less ordered, higher-density phase. Third, the correlation time τ changes from an Arrhenius behavior below 3300 K to a Vogel-Fulcher-Tammann behavior at higher temperatures. Fourth, the Stokes-Einstein relation holds for temperatures below 3000 K, but is replaced by a fractional relation above this temperature. Furthermore, our data indicate that dynamics become again simple above 5000 K, with Arrhenius behavior and a classical Stokes-Einstein relation.

Mechanisms of diabetes mellitus-induced bone fragility.

Science.gov (United States)

Napoli, Nicola; Chandran, Manju; Pierroz, Dominique D; Abrahamsen, Bo; Schwartz, Ann V; Ferrari, Serge L

2017-04-01

The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus.

Premature ovarian failure (POF in Brazilian fragile X carriers

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Angela M. Vianna-Morgante

1999-12-01

Full Text Available The gynecological and reproductive histories of 193 women from fragile X families were surveyed. Among the 101 carriers of the premutation, 14 experienced premature menopause, contrarily to their 37 fully mutated and 55 noncarrier female relatives. Although premature menopause showed a tendency to cluster in certain fragile X families, as a group, the premutated women experienced menopause earlier than noncarriers. This suggests that premature menopause may be the extreme effect of a spectrum of ovarian anomalies associated with the fragile X premutation.Entrevistamos 193 mulheres de famílias com afetados pela síndrome do cromossomo X frágil, quanto a sua história ginecológica e reprodutiva. Entre as 101 portadoras da pré-mutação, 14 tiveram menopausa precoce, mas nenhuma das 37 portadoras da mutação completa ou das 55 não portadoras apresentaram esta anomalia. Observamos uma tendência para a concentração da menopausa precoce em certas famílias, o que poderia significar uma peculiariedade de certas pré-mutações. Entretanto, o fato de as mulheres pré-mutadas tenderem a entrar em menopausa mais cedo do que as não portadoras sugere que a menopausa precoce seja o extremo do espectro de efeitos ovarianos da pré-mutação.

Mathematical Models of Cardiac Pacemaking Function

Science.gov (United States)

Li, Pan; Lines, Glenn T.; Maleckar, Mary M.; Tveito, Aslak

2013-10-01

Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

Epidemiology of diabetes mellitus in the fragility fracture population of a region of Southern Italy.

Science.gov (United States)

Notarnicola, A; Maccagnano, G; Tafuri, S; Moretti, L; Laviola, L; Moretti, B

2016-01-01

Increased risk of osteoporosis and its clinical significance in patients with diabetes is controversial. This study aims to increase the data which are available regarding the prevalence of diabetes mellitus in patients affected by fragility fracture in Italy. We retrospectively studied Hospital Discharge Data (HDD) in the Apulian database for the period 2006–2010 to identify a fragility fracture diagnosis in males over 65 years of age and in females over 50. The database was then checked for drug prescriptions to identify those persons who had taken at least one osteoporosis drug. Within this latter group, thanks to hospital admission and prescription records, the subjects affected with diabetes mellitus were identified. Between 2006 and 2010 in Apulia 177,639 patients were hospitalized and diagnosed as having fragility fracture. The greatest number of those fragility fractures were found to be in the 70 to 79 age range (64,917 total; females 56,994, males 7,923). The prevalence of diabetes subjects in Apulia in this period was estimated at 6.5%. In the same region and period 21.1% of subjects affected by diabetes experienced a fragility fracture; in particular, this number was 27% for males and for 20.5% females. This is the first study providing data on the prevalence of fragility fractures and diabetes in the Apulian population. The data confirm that diabetes is a risk factor which influences bone density and risk of fractures and therefore the need of osteoporosis screening and treatment in diabetic patients.

Development of fragility functions to estimate homelessness after an earthquake

Science.gov (United States)

Brink, Susan A.; Daniell, James; Khazai, Bijan; Wenzel, Friedemann

2014-05-01

Immediately after an earthquake, many stakeholders need to make decisions about their response. These decisions often need to be made in a data poor environment as accurate information on the impact can take months or even years to be collected and publicized. Social fragility functions have been developed and applied to provide an estimate of the impact in terms of building damage, deaths and injuries in near real time. These rough estimates can help governments and response agencies determine what aid may be required which can improve their emergency response and facilitate planning for longer term response. Due to building damage, lifeline outages, fear of aftershocks, or other causes, people may become displaced or homeless after an earthquake. Especially in cold and dangerous locations, the rapid provision of safe emergency shelter can be a lifesaving necessity. However, immediately after an event there is little information available about the number of homeless, their locations and whether they require public shelter to aid the response agencies in decision making. In this research, we analyze homelessness after historic earthquakes using the CATDAT Damaging Earthquakes Database. CATDAT includes information on the hazard as well as the physical and social impact of over 7200 damaging earthquakes from 1900-2013 (Daniell et al. 2011). We explore the relationship of both earthquake characteristics and area characteristics with homelessness after the earthquake. We consider modelled variables such as population density, HDI, year, measures of ground motion intensity developed in Daniell (2014) over the time period from 1900-2013 as well as temperature. Using a base methodology based on that used for PAGER fatality fragility curves developed by Jaiswal and Wald (2010), but using regression through time using the socioeconomic parameters developed in Daniell et al. (2012) for "socioeconomic fragility functions", we develop a set of fragility curves that can be

Primary Retrograde Tibiotalocalcaneal Nailing For Fragility Ankle Fractures.

Science.gov (United States)

Taylor, Benjamin C; Hansen, Dane C; Harrison, Ryan; Lucas, Douglas E; Degenova, Daniel

2016-01-01

Ankle fragility fractures are difficult to treat due to poor bone quality and soft tissues as well as the near ubiquitous presence of comorbidities including diabetes mellitus and peripheral neuropathy. Conventional open reduction and internal fixation in this population has been shown to lead to a significant rate of complications. Given the high rate of complications with contemporary fixation methods, the present study aims to critically evaluate the use of acute hindfoot nailing as a percutaneous fixation technique for high-risk ankle fragility fractures. In this study, we retrospectively evaluated 31 patients treated with primary retrograde tibiotalocalcaneal nail without joint preparation for a mean of 13.6 months postoperatively from an urban Level I trauma center during the years 2006-2012. Overall, there were two superficial infections (6.5%) and three deep infections (9.7%) in the series. There were 28 (90.3%) patients that went on to radiographic union at a mean of 22.2 weeks with maintenance of foot and ankle alignment. There were three cases of asymptomatic screw breakage observed at a mean of 18.3 months postoperatively, which were all treated conservatively.. This study shows that retrograde hindfoot nailing is an acceptable treatment option for treatment of ankle fragility fractures. Hindfoot nailing allows early weightbearing, limited soft tissue injury, and a relatively low rate of complications, all of which are advantages to conventional open reduction internal fixation techniques. Given these findings, larger prospective randomized trials comparing this treatment with conventional open reduction internal fixation techniques are warranted.

Repeat-mediated genetic and epigenetic changes at the FMR1 locus in the Fragile X-related disorders

Science.gov (United States)

Usdin, Karen; Hayward, Bruce E.; Kumari, Daman; Lokanga, Rachel A.; Sciascia, Nicholas; Zhao, Xiao-Nan

2014-01-01

The Fragile X-related disorders are a group of genetic conditions that include the neurodegenerative disorder, Fragile X-associated tremor/ataxia syndrome (FXTAS), the fertility disorder, Fragile X-associated primary ovarian insufficiency (FXPOI) and the intellectual disability, Fragile X syndrome (FXS). The pathology in all these diseases is related to the number of CGG/CCG-repeats in the 5′ UTR of the Fragile X mental retardation 1 (FMR1) gene. The repeats are prone to continuous expansion and the increase in repeat number has paradoxical effects on gene expression increasing transcription on mid-sized alleles and decreasing it on longer ones. In some cases the repeats can simultaneously both increase FMR1 mRNA production and decrease the levels of the FMR1 gene product, Fragile X mental retardation 1 protein (FMRP). Since FXTAS and FXPOI result from the deleterious consequences of the expression of elevated levels of FMR1 mRNA and FXS is caused by an FMRP deficiency, the clinical picture is turning out to be more complex than once appreciated. Added complications result from the fact that increasing repeat numbers make the alleles somatically unstable. Thus many individuals have a complex mixture of different sized alleles in different cells. Furthermore, it has become apparent that the eponymous fragile site, once thought to be no more than a useful diagnostic criterion, may have clinical consequences for females who inherit chromosomes that express this site. This review will cover what is currently known about the mechanisms responsible for repeat instability, for the repeat-mediated epigenetic changes that affect expression of the FMR1 gene, and for chromosome fragility. It will also touch on what current and future options are for ameliorating some of these effects. PMID:25101111

High-Throughput Screening to Identify Compounds That Increase Fragile X Mental Retardation Protein Expression in Neural Stem Cells Differentiated From Fragile X Syndrome Patient-Derived Induced Pluripotent Stem Cells.

Science.gov (United States)

Kumari, Daman; Swaroop, Manju; Southall, Noel; Huang, Wenwei; Zheng, Wei; Usdin, Karen

2015-07-01

: Fragile X syndrome (FXS), the most common form of inherited cognitive disability, is caused by a deficiency of the fragile X mental retardation protein (FMRP). In most patients, the absence of FMRP is due to an aberrant transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. FXS has no cure, and the available treatments only provide symptomatic relief. Given that FMR1 gene silencing in FXS patient cells can be partially reversed by treatment with compounds that target repressive epigenetic marks, restoring FMRP expression could be one approach for the treatment of FXS. We describe a homogeneous and highly sensitive time-resolved fluorescence resonance energy transfer assay for FMRP detection in a 1,536-well plate format. Using neural stem cells differentiated from an FXS patient-derived induced pluripotent stem cell (iPSC) line that does not express any FMRP, we screened a collection of approximately 5,000 known tool compounds and approved drugs using this FMRP assay and identified 6 compounds that modestly increase FMR1 gene expression in FXS patient cells. Although none of these compounds resulted in clinically relevant levels of FMR1 mRNA, our data provide proof of principle that this assay combined with FXS patient-derived neural stem cells can be used in a high-throughput format to identify better lead compounds for FXS drug development. In this study, a specific and sensitive fluorescence resonance energy transfer-based assay for fragile X mental retardation protein detection was developed and optimized for high-throughput screening (HTS) of compound libraries using fragile X syndrome (FXS) patient-derived neural stem cells. The data suggest that this HTS format will be useful for the identification of better lead compounds for developing new therapeutics for FXS. This assay can also be adapted for FMRP detection in clinical and research settings. ©AlphaMed Press.

SEISMIC FRAGILITY ANALYSIS OF IMPROVED RC FRAMES USING DIFFERENT TYPES OF BRACING

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HAMED HAMIDI JAMNANI

2017-04-01

Full Text Available Application of bracings to increase the lateral stiffness of building structures is a technique of seismic improvement that engineers frequently have recourse to. Accordingly, investigating the role of bracings in concrete structures along with the development of seismic fragility curves are of overriding concern to civil engineers. In this research, an ordinary RC building, designed according to the 1st edition of Iranian seismic code, was selected for examination. According to FEMA 356 code, this building is considered to be vulnerable. To improve the seismic performance of this building, 3 different types of bracings, which are Concentrically Braced Frames, Eccentrically Braced Frames and Buckling Restrained Frames were employed, and each bracing element was distributed in 3 different locations in the building. The researchers developed fragility curves and utilized 30 earthquake records on the Peak Ground Acceleration seismic intensity scale to carry out a time history analysis. Tow damage scale, including Inter-Story Drifts and Plastic Axial Deformation were also used. The numerical results obtained from this investigation confirm that Plastic Axial Deformation is more reliable than conventional approaches in developing fragility curves for retrofitted frames. In lieu of what is proposed, the researchers selected the suitable damage scale and developed and compared log-normal distribution of fragility curves first for the original and then for the retrofitted building.

Currency crisis and external fragility: a Minskyan interpretation applied to the Brazilian economy between 1999 and 2013

Directory of Open Access Journals (Sweden)

Victor Hugo Rocha Sarto

2016-12-01

Full Text Available This work has two goals. The first one is to develop an interpretation for open economies founded on Minsky’s financial fragility hypothesis about the process of a currency crisis and its determinants. The deterioration of an economy’s external financial structure is identified as the reason for the increase of its crisis susceptibility. With this approach, we create external fragility indexes intending to measure an economy’s crisis susceptibility. Our second objective is to evaluate the Brazilian external fragility between 1999 and 2013 using the index and the interpretation previously developed. The results suggest that Brazilian’s external fragility suffered a gradual and significant decrease and tends to follow stable trend in the coming years.

QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

NARCIS (Netherlands)

De Bruin, ML; Hoes, AW; Leufkens, HGM

2003-01-01

Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice, and

Brief Report: Acamprosate in Fragile X Syndrome

Science.gov (United States)

Erickson, Craig A.; Mullett, Jennifer E.; McDougle, Christopher J.

2010-01-01

Glutamatergic dysfunction is implicated in the pathophysiology of fragile X syndrome (FXS). We report on the first trial of acamprosate, a drug with putative mGluR5 antagonism, in three adults with FXS and autism. Medical records describing open-label treatment with acamprosate in 3 patients with FXS and a comorbid diagnosis of autistic disorder…

Soil erosion fragility assessment using an impact model and geographic information system

OpenAIRE

Jorge,Luiz Alberto Blanco

2009-01-01

A study was taken in a 1566 ha watershed situated in the Capivara River basin, municipality of Botucatu, São Paulo State, Brazil. This environment is fragile and can be subjected to different forms of negative impacts, among them soil erosion by water. The main objective of the research was to develop a methodology for the assessment of soil erosion fragility at the various different watershed positions, using the geographic information system ILWIS version 3.3 for Windows. An impact model wa...

On the importance of uncertain factors in seismic fragility assessment

International Nuclear Information System (INIS)

Borgonovo, E.; Zentner, I.; Pellegri, A.; Tarantola, S.; Rocquigny, E. de

2013-01-01

This paper addresses the definition of importance measures for helping the modeller to detect the factors on which to focus modelling activity and data collection in seismic fragility analysis. We study sensitivity measures consistent with the decision-support criteria of interest, namely, the (mean) fragility curve and the “High Confidence of Low Probability of Failure” (HCLPF) value. The importance measures are obtained analytically for the EPRI safety factor method, which is nowadays used worldwide for seismic risk assessment of nuclear plants. We illustrate and discuss the use of both variance-based and CDF-based importance measures in the application to two case studies, the first analytical and based on the EPRI method, the second numerical.

Scaling in soft spheres: fragility invariance on the repulsive potential softness

International Nuclear Information System (INIS)

Michele, Cristiano De; Sciortino, Francesco; Coniglio, Antonio

2004-01-01

We address the question of the dependence of the fragility of glass forming supercooled liquids on the 'softness' of an interacting potential by performing numerical simulation of a binary mixture of soft spheres with different power n of the interparticle repulsive potential. We show that the temperature dependence of the diffusion coefficients for various n collapses onto a universal curve, supporting the unexpected view that fragility is not related to the hard core repulsion. We also find that the configurational entropy correlates with the slowing down of the dynamics for all studied n. (letter to the editor)

Fragile X founder chromosomes in Italy: A few initial events and possible explanation for their heterogeneity

Energy Technology Data Exchange (ETDEWEB)

Chiurazzi, P.; Genuardi, M.; Kozak, L.; Neri, G. [Universita Cattolica and Centro Ricerche per la Disabilita Mentale e Motoria, Roma (Italy)] [and others

1996-07-12

A total of 137 fragile X and 235 control chromosomes from various regions of Italy were haplotyped by analyzing two neighbouring marker microsatellites, FRAXAC1 and DXS548. The number of CGG repeats at the 5{prime} end of the FMR1 gene was also assessed in 141 control chromosomes and correlated with their haplotypes. Significant linkage disequilibrium between some {open_quotes}major{close_quotes} haplotypes and fragile X was observed, while other {open_quotes}minor{close_quotes} haplotypes may have originated by subsequent mutation at the marker microsatellite loci and/or recombination between them. Recent evidence suggests that the initial mechanism leading to CGG instability might consist of rare (10{sup -6/-7}) CGG repeat slippage events and/or loss of a stabilizing AGG via A-to-C transversion. Also, the apparently high variety of fragile X chromosomes may be partly due to the relatively high mutation rate (10{sup -4/-5}) of the microsatellite markers used in haplotyping. Our fragile X sample also showed a higher than expected heterozygosity when compared to the control sample and we suggest that this might be explained by the chance occurrence of the few founding events on different chromosomes, irrespective of their actual frequency in the population. Alternatively, a local mechanism could enhance the microsatellite mutation rate only on fragile X chromosomes, or fragile X mutations might occur more frequently on certain background haplotypes. 59 refs., 4 figs.

[Cardiac sarcoidosis: diagnostics, treatment and follow-up].

Science.gov (United States)

Dudziak, Maria; Jankowska, Hanna; Dorniak, Karolina

2018-03-27

Sarcoidosis is a generalised granulomatous disorder of unknown aetiology. Cardiac involvement may affect conduction system, myocardium, valvular apparatus and pericardium. Clinical spectrum ranges from asymptomatic involvement to sudden cardiac death. Patients with biopsy-proven extracardiac sarcoidosis should be screened for cardiac involvement (standard ECG, 24-hour Holter ECG, echocardiography) and in case of any abnormalities found on these tests, more advanced diagnostic methods should be used. Steroid treatment is still the mainstay of therapy in cardiac sarcoidosis. Several immunosuppresive agents are also effective and used in different combinations with steroids, as well as heart failure treatment (including ACE inhibitors, angiotensin receptor blockers, beta-blockers and diuretics). Advanced heart block requires pacemaker implantation, and implantable cardioverterdefibrillator is an effective treatment in primary and secondary prophylaxis of sudden cardiac death. Heart transplantation is considered in advanced, drug-resistant heart failure or incessant ventricular arrhythmias unresponsive to other forms of therapy. © 2018 MEDPRESS.

Fragile X syndrome in females - a familial case report and review of the literature.

Science.gov (United States)

Stembalska, Agnieszka; Łaczmańska, Izabela; Gil, Justyna; Pesz, Karolina A

2016-01-01

Fragile X syndrome (FXS), one of the manifestations of FMR1-related disorders, is one of the most frequent genetic causes of intellectual disability. In over 99% of all cases it results from the expansion of CGG repeats in the 5'-untranslated region of the FMR1 gene and presents in males and in about 50% of the females with an FMR1 full mutation, usually with a milder phenotype. Although the morphologic and behavioral phenotype in males is a well-recognized entity, the presentation in females is variable and not as specific. The objective of this paper is to present a family with quite a severe expression of the disorder in two sisters with a full mutation. We report on a two-generation family where both males and females were found to be affected by FXS. We also present the diagnostic pathway and methods that led to the diagnosis of fragile X syndrome in the two sisters, as well as the method that explained the normal phenotype in their mother. The CGG repeats analysis in the FMR1 gene showed one normal allele and one allele with a full mutation in both sisters (probands) and their mother. A full mutation was also found in three male cousins of the probands. The analysis of the X-chromosome methylation status has shown a random X inactivation in proband 1 and 2 and a non-random one in the proband's mother, with the normal allele predominantly active. The reasons for different clinical presentations are discussed; moreover a review of the literature on females with FXS is presented. We hope that this paper will facilitate the future diagnosis of fragile X syndromes in females.

Non-fragile guaranteed cost control for uncertain neutral dynamic systems with time-varying delays in state and control input

International Nuclear Information System (INIS)

Lien, C.-H.

2007-01-01

This article considers non-fragile guaranteed cost control problem for a class of uncertain neutral system with time-varying delays in both state and control input. Delay-dependent criteria are proposed to guarantee the robust stabilization of systems. Linear matrix inequality (LMI) optimization approach is used to solve the non-fragile guaranteed cost control problem. Non-fragile guaranteed cost control for unperturbed neutral system is considered in the first step. Robust non-fragile guaranteed cost control for uncertain neutral system is designed directly from the unperturbed condition. An efficient approach is proposed to design the non-fragile guaranteed cost control for uncertain neutral systems. LMI toolbox of Matlab is used to implement the proposed results. Finally, a numerical example is illustrated to show the usefulness of the proposed results

Long-lasting Effects of Minocycline on Behavior in Young but not Adult Fragile X Mice

Science.gov (United States)

Dansie, Lorraine E.; Phommahaxay, Kelly; Okusanya, Ayodeji G.; Uwadia, Jessica; Huang, Mike; Rotschafer, Sarah E.; Razak, Khaleel A.; Ethell, Douglas W.; Ethell, Iryna M.

2013-01-01

Fragile X Syndrome (FXS) is the most common single-gene inherited form of intellectual disability with behaviors characteristic of autism. People with FXS display childhood seizures, hyperactivity, anxiety, developmental delay, attention deficits, and visual-spatial memory impairment, as well as a propensity for obsessive-compulsive disorder (OCD). Several of these aberrant behaviors and FXS-associated synaptic irregularities also occur in “fragile X mental retardation gene” knock-out (Fmr1 KO) mice. We previously reported that minocycline promotes the maturation of dendritic spines - postsynaptic sites for excitatory synapses - in the developing hippocampus of Fmr1 KO mice, which may underlie the beneficial effects of minocycline on anxiolytic behavior in young Fmr1 KO mice. In this study, we compared the effectiveness of minocycline treatment in young and adult Fmr1 KO mice, and determined the dependence of behavioral improvements on short-term versus long-term minocycline administration. We found that 4 and 8 week long treatments significantly reduced locomotor activity in both young and adult Fmr1 KO mice. Some behavioral improvements persisted in young mice post-treatment, but in adults the beneficial effects were lost soon after minocycline treatment was stopped. We also show, for the first time, that minocycline treatment partially attenuates the number and severity of audiogenic seizures in Fmr1 KO mice. This report provides further evidence that minocycline treatment has immediate and long-lasting benefits on FXS-associated behaviors in the Fmr1 KO mouse model. PMID:23660195

SUCCESSFUL APPLICATION OF PERIPHERAL VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION FOR CARDIAC ALLOGRAFT ANTIBODY-MEDIATED REJECTION WITH SEVERE HEMODYNAMIC COMPROMISE

Directory of Open Access Journals (Sweden)

V. N. Poptsov

2015-01-01

Full Text Available Introduction. Acute antibody-mediated rejection (AMR is one of the severe complications of early and late period after heart transplantation (HT. Only few case reports and studies presented of mechanical circulatory support (MCS application for refractory acute rejection causing hemodynamic compromise. Aim. We report the case of a woman with cardiogenic shock caused by severe AMR that was successfully treatment by peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO. Material and methods. In december 2014, a 60-year-old woman with dilated cardiomyopathy was operated for HT. The patient had a good initial cardiac allograft function and no and was discharged from ICU on the 4th day after HT. 1st endomyocardial biopsy (EMB (the 7th day after HT showed absence of acute cellular and antibody-mediated rejection. On the 11th day after HT patient aggravated and presented clinical signs of life-threatening acute cardiac allograft dysfunction: arterial blood pressure 78/49/38 mm Hg, HR 111 in min, CVP 20 mm Hg, PAP 47/34/25 mm Hg, PCWP 25 mm Hg, CI 1.5 l/min/m2, adrenalin 110 ng/kg/min, dopamine 15 mcg/kg/min. ECG showed impairment of systolic left (LVEF 25% and right (RVEF 15% ventricle function, left and right ventricle diffuse hypokinesis, thickness of IVS, LV and RV wall 1.7, 1.4 and 0.8 cm, tricuspid and mitral valve regurgitation 2–3 degrees. EMB presented AMR. In conscience peripheral VA ECMO was installed. We used peripheral transcutaneous cannulation technique via femoral vessels – arterial cannula 15 F, venous cannula – 23 F, vascular catheter 14 G for anterograde leg’s perfusion. ACT 130–150 sec. AMR therapy included: methylprednisolon pulse-therapy (10 mg/kg for 5 day, IgG, plasmapheresis (No 7, rituximab. Results. Under MCS by VA ECMO we noted quick improvement of hemodynamic, metabolic homeostasis and organ functions. On the 6th day of VA ECMO (blood flow 1.8 l/min: arterial blood pressure 133/81/54 mm Hg, CVP 5 mm

Resolution of spatial and temporal visual attention in infants with fragile X syndrome

OpenAIRE

Farzin, Faraz; Rivera, Susan M.; Whitney, David

2011-01-01

Fragile X syndrome is the most common cause of inherited intellectual impairment and the most common single-gene cause of autism. Individuals with fragile X syndrome present with a neurobehavioural phenotype that includes selective deficits in spatiotemporal visual perception associated with neural processing in frontal–parietal networks of the brain. The goal of the current study was to examine whether reduced resolution of spatial and/or temporal visual attention may underlie perceptual def...

The Social Consequences of Raising Medically Fragile and ...

African Journals Online (AJOL)

2011-10-02

Oct 2, 2011 ... who are medically fragile and/or developmentally challenged. It is an ... The overarching theme was the families' search for safety ... children. It is important for policy makers to understand the situation of such parents so ... their family members, children and families without disabilities and, service providers.

Intergenerational Relationships and Union Stability in Fragile Families

Science.gov (United States)

Hognas, Robin S.; Carlson, Marcia J.

2010-01-01

Using data from the Fragile Families and Child Wellbeing Study (N = 2,656), we examined the association between intergenerational relationships and parents' union stability 5 years after a baby's birth. Results showed that more amiable relationships between parents and each partner's parents, and children's spending more time with paternal…

STEM promotion through museum exhibits on cardiac monitoring & cardiac rhythm management.

Science.gov (United States)

Countryman, Jordan D; Dow, Douglas E

2014-01-01

Formal education in science, technology, engineering and math (STEM) does not successfully engage all of the students who have potential to become skilled in STEM activities and careers. Museum exhibits may be able to reach and engage a broader range of the public. STEM Exhibits that are both understandable and capture the imagination of viewers may contribute toward increased interest in STEM activities. One such topic for such an exhibit could be cardiac pacemakers and cardioverter defibrillators that sustain life. Although museums have existed for centuries, the available types of exhibit designs has dramatically increased in recent decades due to innovations in technology. Science and technology museums have especially taken advantage of the progression of exhibit design to developed new ways to communicate to their viewers. These novel presentation tools allow museums to more effectively convey to and engage viewers. This paper examines the techniques employed by museums in exhibits and considers the practices of several museums with exhibits related to cardiac monitoring (CM) and cardiac rhythm management (CRM).

Adaptive Skills, Behavior Problems, and Parenting Stress in Mothers of Boys with Fragile X Syndrome

Science.gov (United States)

Sarimski, Klaus

2010-01-01

The relationship of temperament, atypical behaviors, and adaptive behavior of young boys with Fragile X syndrome on mothers' parenting stress was analyzed. Twenty-six boys with Fragile X syndrome (30-88 months of age) participated. The overall development of the participants was significantly delayed with a specific profile of adaptive behaviors…

Mathematical Models of Cardiac Pacemaking Function

Directory of Open Access Journals (Sweden)

Pan eLi

2013-10-01

Full Text Available Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

Improvements in or relating to storage or shipping containers for fragile objects

International Nuclear Information System (INIS)

1979-01-01

A storage or shipping container for fragile objects such as pellets for use in a laser fusion chamber is described. It comprises a base, a stem having a reduced tip in which a pellet can be mounted and a frangible bulb (glass or plastic) adapted to fit over the stem and be sealed on the base. Protective material (fluid or gas) can be introduced into the bulb. The space within the sealed capsule between the stem and the bulb can be filled with an appropriate gas, solid or liquid to reduce chemical reaction or vibration. A modified container allows several small pellets to be stored or shipped. Several of the containers described can be placed inside a second container which has recesses to take their bases and the surrounding space filled with viscous liquid or solid such as paraffin to reduce shock. (U.K.)

Prefrontal Cortex Dysfunction in Fragile X Mice Depends on the Continued Absence of Fragile X Mental Retardation Protein in the Adult Brain.

Science.gov (United States)

Siegel, Jennifer J; Chitwood, Raymond A; Ding, James M; Payne, Clayton; Taylor, William; Gray, Richard; Zemelman, Boris V; Johnston, Daniel

2017-08-02

Fragile X Syndrome (FX) is generally considered a developmental disorder, arising from a mutation that disrupts the transcription of Fragile X Mental Retardation Protein (FMRP). However, FMRP regulates the transcription of other proteins and participates in an unknown number of protein-protein interactions throughout life. In addition to known developmental issues, it is thus likely that some dysfunction is also due to the ongoing absence of FMRP. Dissociating dysfunction due to developmental dysregulation from dysfunction due to the continued absence of FMRP is necessary to understand the different roles of FMRP and to treat patients effectively throughout life. We show here that FX model mice display substantial deficits in a PFC-dependent task. We then use conditional knock-out mice to eliminate FMRP only in the PFC alone of adult mice. We observe an increase in the proportion of nonlearners and a delay in the onset of learning in both FX and conditional knock-out mice. The results suggest that these deficits (1) are due to the absence of FMRP in the PFC alone and (2) are not the result of developmental dysregulation. Furthermore, PFC-associated deficits are rescued by initiating production of FMRP in adult conditional restoration mice, suggesting that PFC dysfunction may persist as long as FMRP is absent and therefore can be rescued after development. The data suggest that it is possible to dissociate the roles of FMRP in neural function from developmental dysregulation, and that PFC function can be restored in the adult FX brain. SIGNIFICANCE STATEMENT The absence of Fragile X Mental Retardation Protein (FMRP) from birth results in developmental disabilities and lifelong impairments. We show here that in mouse models PFC dysfunction in Fragile X Syndrome (FX) can be attributed to the continued absence of FMRP from the PFC, independent of FMRP status during development. Furthermore, initiation of FMRP production in the PFC of adult FX animals rescues PFC

Repeat-mediated epigenetic dysregulation of the FMR1 gene in the fragile X-related disorders.

Science.gov (United States)

Usdin, Karen; Kumari, Daman

2015-01-01

The fragile X-related disorders are members of the Repeat Expansion Diseases, a group of genetic conditions resulting from an expansion in the size of a tandem repeat tract at a specific genetic locus. The repeat responsible for disease pathology in the fragile X-related disorders is CGG/CCG and the repeat tract is located in the 5' UTR of the FMR1 gene, whose protein product FMRP, is important for the proper translation of dendritic mRNAs in response to synaptic activation. There are two different pathological FMR1 allele classes that are distinguished only by the number of repeats. Premutation alleles have 55-200 repeats and confer risk of fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency. Full mutation alleles on the other hand have >200 repeats and result in fragile X syndrome, a disorder that affects learning and behavior. Different symptoms are seen in carriers of premutation and full mutation alleles because the repeat number has paradoxical effects on gene expression: Epigenetic changes increase transcription from premutation alleles and decrease transcription from full mutation alleles. This review will cover what is currently known about the mechanisms responsible for these changes in FMR1 expression and how they may relate to other Repeat Expansion Diseases that also show repeat-mediated changes in gene expression.

Hemodilution, kidney dysfunction and cardiac surgery

Directory of Open Access Journals (Sweden)

Fabio Papa Taniguchi

2009-03-01

Full Text Available Hemodilution has been used in cardiac surgery to reduce blood viscosity and peripheral vascular resistance, decrease the need for blood transfusions, attenuate the risk of transfusions and diminish systemic inflammatory response syndrome and hospital costs. The lowest hematocrit level during cardiopulmonary bypass has been stated as 20%. However, severe hemodilution in cardiopulmonary bypass for patients undergoing cardiac surgery has been recognized as a risk factor for hospital deaths and reduced long-term survival. The introduction of normothermia restarted the debate about the lowest acceptable hematocrit during cardiopulmonary bypass. The objective of this review is to evaluate hemodilution during cardiac surgery as a risk factor for the development of post-operative acute renal failure.

Multifarious Functions of the Fragile X Mental Retardation Protein.

Science.gov (United States)

Davis, Jenna K; Broadie, Kendal

2017-10-01

Fragile X syndrome (FXS), a heritable intellectual and autism spectrum disorder (ASD), results from the loss of Fragile X mental retardation protein (FMRP). This neurodevelopmental disease state exhibits neural circuit hyperconnectivity and hyperexcitability. Canonically, FMRP functions as an mRNA-binding translation suppressor, but recent findings have enormously expanded its proposed roles. Although connections between burgeoning FMRP functions remain unknown, recent advances have extended understanding of its involvement in RNA, channel, and protein binding that modulate calcium signaling, activity-dependent critical period development, and the excitation-inhibition (E/I) neural circuitry balance. In this review, we contextualize 3 years of FXS model research. Future directions extrapolated from recent advances focus on discovering links between FMRP roles to determine whether FMRP has a multitude of unrelated functions or whether combinatorial mechanisms can explain its multifaceted existence. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systems Fragility: The Sociology of Chaos

Science.gov (United States)

2015-03-01

shuttle explosion was found to be “a failure in the joint between the two lower segments of the right Solid Rocket Motor.” The report goes on to state...2013, http://www.bloomberg.com/news/2013-09-24/flooded-estes-park-greets- tourists -as- locals-can-t-flush html 137 Koehler, Kress, and Miller, What... market research questions about animals.166 For the purposes of this research, purposive event sampling is used to study community fragility in

Inactivation of the maternal fragile X gene results in sensitization of GABAB receptor function in the offspring

OpenAIRE

Zupan, Bojana; Toth, Miklos

2008-01-01

Fragile X syndrome is an X linked disorder caused by the inactivation of the FMR-1 gene with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities and hyperactivity. Although Fragile X syndrome is considered a typical Mendelian disorder, we have recently reported that the environment, specifically the fmr-1+/− or fmr-1−/− (H or KO) maternal environment, elicits on its own a partial fragile X-like phenotype and can contribute to the overall phenotype of...

The Trajectory of Mathematics Skills and Working Memory Thresholds in Girls with Fragile X Syndrome

Science.gov (United States)

Murphy, Melissa M.; Mazzocco, Michele M. M.

2009-01-01

Fragile X syndrome is a common genetic disorder associated with executive function deficits and poor mathematics achievement. In the present study, we examined changes in math performance during the elementary and middle school years in girls with fragile X syndrome, changes in the working memory loads under which children could complete a…

Efficacy of pasireotide in controlling severe hypercortisolism until cardiac transplantation

Directory of Open Access Journals (Sweden)

Roberto Attanasio

2017-03-01

Full Text Available Cushing’s syndrome is associated with increased morbidity and mortality. Although surgery is the first-line treatment, drugs can still play a role as an ancillary treatment to be employed while waiting for surgery, after unsuccessful operation or in patients unsuitable for surgery. We were asked to evaluate a 32-year-old male waiting for cardiac transplantation. Idiopathic hypokinetic cardiomyopathy had been diagnosed since 6 years. He was on treatment with multiple drugs, had a pacemaker, an implantable cardioverter and an external device for the support of systolic function. Physical examination showed severely impaired general status, signs of hypercortisolism and multiple vertebral compression fractures. We administered teriparatide, and the few evaluable parameters supported the diagnosis of ACTH-dependent hypercortisolism: serum cortisol was 24.2 μg/dL in the morning and 20.3 μg/dL after overnight 1 mg dexamethasone, urinary free cortisol (UFC was 258 μg/24 h and ACTH 125 pg/mL. Pituitary CT was negative. Pasireotide 300 μg bid was administered and uptitrated to 600 μg bid. Treatment was well tolerated, achieving dramatic improvement of clinical picture with progressive normalization of serum cortisol and ACTH levels as well as UFC. After 4 months, the patient underwent successful heart transplantation. Many complications ensued and were overcome. Pituitary MRI was negative. On pasireotide 300 μg bid and prednisone 2.5 mg/day (as part of immunosuppressive therapy, morning serum cortisol and ACTH were 15.6 μg/dL and 54 pg/mL respectively, UFC was 37 μg/24 h, fasting glucose: 107 mg/dL and HbA1c: 6.5%. In conclusion, primary treatment with pasireotide achieved remission of hypercortisolism, thus allowing the patient to undergo heart transplantation.

Imitation in Fragile X Syndrome: Implications for Autism

Science.gov (United States)

Macedoni-Luksic, Marta; Greiss-Hess, Laura; Rogers, Sally J.; Gosar, David; Lemons-Chitwood, Kerrie; Hagerman, Randi

2009-01-01

To address the specific impairment of imitation in autism, the imitation abilities of 22 children with fragile X syndrome (FXS) with and without autism were compared. Based on previous research, we predicted that children with FXS and autism would have significantly more difficulty with non-meaningful imitation tasks. After controlling for…

The Neuroanatomy and Neuroendocrinology of Fragile X Syndrome

Science.gov (United States)

Hessl, David; Rivera, Susan M.; Reiss, Allan L.

2004-01-01

Fragile X syndrome (FXS), caused by a single gene mutation on the X chromosome, offers a unique opportunity for investigation of gene-brain-behavior relationships. Recent advances in molecular genetics, human brain imaging, and behavioral studies have started to unravel the complex pathways leading to the cognitive, psychiatric, and physical…

Normal RNAi response in human fragile x fibroblasts

DEFF Research Database (Denmark)

Madsen, Charlotte; Grønskov, Karen; Brøndum-Nielsen, Karen

2009-01-01

BACKGROUND: Fragile x syndrome is caused by loss of expression of the FMRP protein involved in the control of a large number of mRNA targets. The Drosophila ortholog dFXR interacts with a protein complex that includes Argonaute2, an essential component of the RNA-induced silencing complex (RISC...

Ricci curvature: An economic indicator for market fragility and systemic risk.

Science.gov (United States)

Sandhu, Romeil S; Georgiou, Tryphon T; Tannenbaum, Allen R

2016-05-01

Quantifying the systemic risk and fragility of financial systems is of vital importance in analyzing market efficiency, deciding on portfolio allocation, and containing financial contagions. At a high level, financial systems may be represented as weighted graphs that characterize the complex web of interacting agents and information flow (for example, debt, stock returns, and shareholder ownership). Such a representation often turns out to provide keen insights. We show that fragility is a system-level characteristic of "business-as-usual" market behavior and that financial crashes are invariably preceded by system-level changes in robustness. This was done by leveraging previous work, which suggests that Ricci curvature, a key geometric feature of a given network, is negatively correlated to increases in network fragility. To illustrate this insight, we examine daily returns from a set of stocks comprising the Standard and Poor's 500 (S&P 500) over a 15-year span to highlight the fact that corresponding changes in Ricci curvature constitute a financial "crash hallmark." This work lays the foundation of understanding how to design (banking) systems and policy regulations in a manner that can combat financial instabilities exposed during the 2007-2008 crisis.

Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X.

Science.gov (United States)

Hagerman, R J; Leehey, M; Heinrichs, W; Tassone, F; Wilson, R; Hills, J; Grigsby, J; Gage, B; Hagerman, P J

2001-07-10

The authors report five elderly men with the fragile X premutation who had a progressive action tremor associated with executive function deficits and generalized brain atrophy. These individuals had elevated fragile X mental retardation 1 gene (FMR1) messenger RNA and normal or borderline levels of FMR1 protein. The authors propose that elevations of FMR1 messenger RNA may be causative for a neurodegenerative syndrome in a subgroup of elderly men with the FMR1 premutation.

Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

Science.gov (United States)

Sourial, Mary; Doering, Laurie C

2017-07-01

The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Comparison of main-shock and aftershock fragility curves developed for New Zealand and US buildings

Science.gov (United States)

Uma, S.R.; Ryu, H.; Luco, N.; Liel, A.B.; Raghunandan, M.

2011-01-01

Seismic risk assessment involves the development of fragility functions to express the relationship between ground motion intensity and damage potential. In evaluating the risk associated with the building inventory in a region, it is essential to capture 'actual' characteristics of the buildings and group them so that 'generic building types' can be generated for further analysis of their damage potential. Variations in building characteristics across regions/countries largely influence the resulting fragility functions, such that building models are unsuitable to be adopted for risk assessment in any other region where a different set of building is present. In this paper, for a given building type (represented in terms of height and structural system), typical New Zealand and US building models are considered to illustrate the differences in structural model parameters and their effects on resulting fragility functions for a set of main-shocks and aftershocks. From this study, the general conclusion is that the methodology and assumptions used to derive basic capacity curve parameters have a considerable influence on fragility curves.

[The fragility of the self].

Science.gov (United States)

Rubia Vila, Francisco José

2002-01-01

This presentation raises the hypothesis that the "self" is a construction of the brain and extremely fragile. In order to support this statement, Prof. Rubia provides three different reasonings: firstly, we are not borne with the "self", but rather it is the result of development during childhood; secondly, the self is subject to cultural influences, so that the perception of this "self" or of the own personality varies according to different cultures. And thirdly, the self is not indivisible, as shown by epileptic patients with a "split-brain" operation, or the psychiatric cases of double personality or the multiple personality disorder.

Effect of laser light on the fragility and permeability of the red blood cell membrane

International Nuclear Information System (INIS)

El-Yassin, H. D.

2005-01-01

The resistance of red blood cells to hypotonic hemolysis is often characterized in terms of their osmotic fragility. The percentage of cells that hemolize when plotted as a function of different concentrations of NaCl forms fragility curve, which has a sigmoidal shape. In this study we show that the exposure of red blood cells to laser light converts the sigmoidal shape of the fragility curve to a hyperbolic one, which means that the old population of the red blood cells are the ones more affected by the light which cause their destruction. At the same time it seems that transport across the cell membrane is affected also. The biochemical and physiological implications of this finding are discussed. (author)

General rules prospected for the liquid fragility in various material groups and different thermodynamic conditions

Energy Technology Data Exchange (ETDEWEB)

Paluch, M.; Masiewicz, E.; Grzybowski, A.; Pawlus, S.; Wojnarowska, Z. [Institute of Physics, University of Silesia, Uniwersytecka 4, 40-007 Katowice (Poland); Silesian Center for Education and Interdisciplinary Research, 75 Pulku Piechoty 1A, 41-500 Chorzow (Poland); Pionteck, J. [Leibniz Institute of Polymer Research Dresden, Hohe Str. 6, D-01069 Dresden (Germany)

2014-10-07

The fragility parameter has been acknowledged as one of the most important characteristics of glass-forming liquids. We show that the mystery of the dramatic change in molecular dynamics of systems approaching the glass transition can be better understood by the high pressure study of fragility parameters defined in different thermodynamic conditions. We formulate and experimentally confirm a few rules obeyed by the fragility parameters, which are also rationalized by the density scaling law and its modification suggested for associated liquids. In this way, we successfully explore and gain a new insight into the pressure effect on molecular dynamics of van der Waals liquids, polymer melts, ionic liquids, and hydrogen-bonded systems near the glass transition.

[Role of cardiac magnetic resonance in cardiac involvement of Fabry disease].

Science.gov (United States)

Serra, Viviana M; Barba, Miguel Angel; Torrá, Roser; Pérez De Isla, Leopoldo; López, Mónica; Calli, Andrea; Feltes, Gisela; Torras, Joan; Valverde, Victor; Zamorano, José L

2010-09-04

Fabry disease is a hereditary disorder. Clinical manifestations are multisystemic. The majority of the patients remain undiagnosed until late in life, when alterations could be irreversible. Early detection of cardiac symptoms is of major interest in Fabry's disease (FD) in order to gain access to enzyme replacement therapy. Echo-Doppler tissular imaging (TDI) has been used as a cardiologic early marker in FD. This study is intended to determine whether the cardiac magnetic resonance is as useful tool as TDI for the early detection of cardiac affectation in FD. Echocardiography, tissue Doppler and Cardio magnetic resonance was performed in 20 patients with confirmed Fabry Disease. Left ventricular hypertrophy was defined as septum and left ventricular posterior wall thickness ≥12 mm. An abnormal TDI velocity was defined as (Sa), (Ea) and/or (Aa) velocities gadolinium-enhanced images sequences were obtained using magnetic resonance. Twenty patients included in the study were divided into three groups: 1. Those without left ventricular hypertrophy nor tissue Doppler impairment 2. Those without left ventricular hypertrophy and tissue Doppler impairment 3. Those with left ventricular hypertrophy and Tissue Doppler impairment. Late gadolinium enhancement was found in only one patient, who has already altered DTI and LVH. Tissue Doppler imaging (TDI) is the only diagnostic tool able to provide early detection of cardiac affectation in patients with FD. Magnetic resonance provides information of the disease severity in patients with LVH, but can not be used as an early marker of cardiac disease in patients with FD. However MRI could be of great value for diagnostic stratification. Copyright © 2009 Elsevier España, S.L. All rights reserved.

Seismic fragility test of a 6-inch diameter pipe system

International Nuclear Information System (INIS)

Chen, W.P.; Onesto, A.T.; DeVita, V.

1987-02-01

This report contains the test results and assessments of seismic fragility tests performed on a 6-inch diameter piping system. The test was funded by the US Nuclear Regulatory Commission (NRC) and conducted by ETEC. The objective of the test was to investigate the ability of a representative nuclear piping system to withstand high level dynamic seismic and other loadings. Levels of loadings achieved during seismic testing were 20 to 30 times larger than normal elastic design evaluations to ASME Level D limits would permit. Based on failure data obtained during seismic and other dynamic testing, it was concluded that nuclear piping systems are inherently able to withstand much larger dynamic seismic loadings than permitted by current design practice criteria or predicted by the probabilistic risk assessment (PRA) methods and several proposed nonlinear methods of failure analysis

Fragile Thermodynamic Order

International Nuclear Information System (INIS)

Bernhoeft, N.; Lander, G.H.; Colineau, E.

2003-01-01

An asymmetric shift in the position of the magnetic Bragg peak with respect to the fiducial lattice has been observed by resonant X-ray scattering in a diverse series of antiferromagnetic compounds. This apparent violation of Bragg's law is interpreted in terms of a dynamically phased order parameter. We demonstrate the use of this effect as a novel probe of fragile or dynamic thermodynamic order in strongly correlated electronic systems. In particular, fresh light is shed on the paradoxical situation encountered in URu 2 Si 2 where the measured entropy gain on passing through T Neel is incompatible with the ground state moment estimated by neutron diffraction. The intrinsic space-time averaging of the probe used to characterise the thermodynamic macroscopic state may play a crucial and previously neglected role. In turn, this suggests the further use of resonant X-ray scattering in investigations of systems dominated by quantum fluctuations. (author)

Mathematics Learning Disabilities in Girls with Fragile X or Turner Syndrome during Late Elementary School

Science.gov (United States)

Murphy, Melissa M.; Mazzocco, Michele M. M.

2008-01-01

The present study focuses on math and related skills among 32 girls with fragile X (n = 14) or Turner (n = 18) syndrome during late elementary school. Performance in each syndrome group was assessed relative to Full Scale IQ-matched comparison groups of girls from the general population (n = 32 and n = 89 for fragile X syndrome and Turner…

QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

DEFF Research Database (Denmark)

De Bruin, Marie L; Hoes, Arno W; Leufkens, Hubert G M

2003-01-01

Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice......, and subsequently focused on several specific groups of patients who could be extremely vulnerable for drug-induced arrhythmias. We performed a case-control study in which patients (cases), hospitalized for nonatrial cardiac arrhythmias from 1987 to 1998, were compared with their matched controls regarding current...... use of QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate conditional logistic regression, adjusting for potential confounding factors. Data were obtained from the PHARMO record linkage system. We identified 501 cases, 39 of whom used QTc...

Halogenated anaesthetics and cardiac protection in cardiac and non-cardiac anaesthesia

Directory of Open Access Journals (Sweden)

Landoni Giovanni

2009-01-01

Full Text Available Volatile anaesthetic agents have direct protective properties against ischemic myocardial damage. The implementation of these properties during clinical anaesthesia can provide an additional tool in the treatment or prevention, or both, of ischemic cardiac dysfunction in the perioperative period. A recent meta-analysis showed that desflurane and sevoflurane reduce postoperative mortality and incidence of myocardial infarction following cardiac surgery, with significant advantages in terms of postoperative cardiac troponin release, need for inotrope support, time on mechanical ventilation, intensive care unit and overall hospital stay. Multicentre, randomised clinical trials had previously demonstrated that the use of desflurane can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalisation following coronary artery bypass graft surgery either with and without cardiopulmonary bypass. The American College of Cardiology/American Heart Association Guidelines recommend volatile anaesthetic agents during non-cardiac surgery for the maintenance of general anaesthesia in patients at risk for myocardial infarction. Nonetheless, e vidence in non-coronary surgical settings is contradictory and will be reviewed in this paper together with the mechanisms of cardiac protection by volatile agents.

Social Approach and Emotion Recognition in Fragile X Syndrome

Science.gov (United States)

Williams, Tracey A.; Porter, Melanie A.; Langdon, Robyn

2014-01-01

Evidence is emerging that individuals with Fragile X syndrome (FXS) display emotion recognition deficits, which may contribute to their significant social difficulties. The current study investigated the emotion recognition abilities, and social approachability judgments, of FXS individuals when processing emotional stimuli. Relative to…

Therapeutic Targets and Translational Endpoints in Fragile X Syndrome

NARCIS (Netherlands)

C.E.F. de Esch (Celine)

2014-01-01

markdownabstract__Abstract__ Fragile X syndrome is the most common inherited cause of intellectual disability. It is more common in boys (1 in 4000) than girls (1 in 6000). In addition to the intellectual disability patients often exhibit behavioral abnormalities including hyperactivity and

External cardiac compression may be harmful in some scenarios of pulseless electrical activity.

Science.gov (United States)

Hogan, T S

2012-10-01

Pulseless electrical activity occurs when organised or semi-organised electrical activity of the heart persists but the product of systemic vascular resistance and the increase in systemic arterial flow generated by the ejection of the left venticular stroke volume is not sufficient to produce a clinically detectable pulse. Pulseless electrical activity encompasses a very heterogeneous variety of severe circulatory shock states ranging in severity from pseudo-cardiac arrest to effective cardiac arrest. Outcomes of cardiopulmonary resuscitation for pulseless electrical activity are generally poor. Impairment of cardiac filling is the limiting factor to cardiac output in many scenarios of pulseless electrical activity, including extreme vasodilatory shock states. There is no evidence that external cardiac compression can increase cardiac output when impaired cardiac filling is the limiting factor to cardiac output. If impaired cardiac filling is the limiting factor to cardiac output and the heart is effectively ejecting all the blood returning to it, then external cardiac compression can only increase cardiac output if it increases venous return and cardiac filling. Repeated cardiac compression asynchronous with the patient's cardiac cycle and raised mean intrathoracic pressure due to chest compression can be expected to reduce rather than to increase cardiac filling and therefore to reduce rather than to increase cardiac output in such circumstances. The hypothesis is proposed that the performance of external cardiac compression will have zero or negative effect on cardiac output in pulseless electrical activity when impaired cardiac filling is the limiting factor to cardiac output. External cardiac compression may be both directly and indirectly harmful to significant sub-groups of patients with pulseless electrical activity. We have neither evidence nor theory to provide comfort that external cardiac compression is not harmful in many scenarios of pulseless

External cardiac compression may be harmful in some scenarios of pulseless electrical activity.

LENUS (Irish Health Repository)

Hogan, T S

2012-10-01

Pulseless electrical activity occurs when organised or semi-organised electrical activity of the heart persists but the product of systemic vascular resistance and the increase in systemic arterial flow generated by the ejection of the left venticular stroke volume is not sufficient to produce a clinically detectable pulse. Pulseless electrical activity encompasses a very heterogeneous variety of severe circulatory shock states ranging in severity from pseudo-cardiac arrest to effective cardiac arrest. Outcomes of cardiopulmonary resuscitation for pulseless electrical activity are generally poor. Impairment of cardiac filling is the limiting factor to cardiac output in many scenarios of pulseless electrical activity, including extreme vasodilatory shock states. There is no evidence that external cardiac compression can increase cardiac output when impaired cardiac filling is the limiting factor to cardiac output. If impaired cardiac filling is the limiting factor to cardiac output and the heart is effectively ejecting all the blood returning to it, then external cardiac compression can only increase cardiac output if it increases venous return and cardiac filling. Repeated cardiac compression asynchronous with the patient\\'s cardiac cycle and raised mean intrathoracic pressure due to chest compression can be expected to reduce rather than to increase cardiac filling and therefore to reduce rather than to increase cardiac output in such circumstances. The hypothesis is proposed that the performance of external cardiac compression will have zero or negative effect on cardiac output in pulseless electrical activity when impaired cardiac filling is the limiting factor to cardiac output. External cardiac compression may be both directly and indirectly harmful to significant sub-groups of patients with pulseless electrical activity. We have neither evidence nor theory to provide comfort that external cardiac compression is not harmful in many scenarios of pulseless

Diabetes, cardiac disorders and asthma as risk factors for severe organ involvement among adult dengue patients: A matched case-control study.

Science.gov (United States)

Pang, Junxiong; Hsu, Jung Pu; Yeo, Tsin Wen; Leo, Yee Sin; Lye, David C

2017-01-03

Progression to severe organ involvement due to dengue infection has been associated with severe dengue disease, intensive care treatment, and mortality. However, there is a lack of understanding of the impact of pre-existing comorbidities and other risk factors of severe organ involvement among dengue adults. The aim of this retrospective case-control study is to characterize and identify risk factors that predispose dengue adults at risk of progression with severe organ involvement. This study involved 174 dengue patients who had progressed with severe organ involvement and 865 dengue patients without severe organ involvement, matched by the year of presentation of the cases, who were admitted to Tan Tock Seng Hospital between year 2005 and 2008. Age group of 60 years or older, diabetes, cardiac disorders, asthma, and having two or more pre-existing comorbidities were independent risk factors of severe organ involvement. Abdominal pain, clinical fluid accumulation, and hematocrit rise and rapid platelet count drop at presentation were significantly associated with severe organ involvement. These risk factors, when validated in a larger study, will be useful for triage by clinicians for prompt monitoring and clinical management at first presentation, to minimize the risk of severe organ involvement and hence, disease severity.

Fragile States, Infectious Disease and Health Security: The Case for Timor-Leste

Directory of Open Access Journals (Sweden)

John M. Quinn

2014-01-01

Full Text Available Timor-Leste is a very young and developing nation state. Endemic infectious disease and weakened health security coupled with its growing and inclusive public institutions keep Timor-Leste fragile and in transition on the spectrum of state stability. The objective here is to systematically review Timor-Leste's state and public health successes, showing how a fragile state can consistently improve its status on the continuum of stability and improve health security for the population. The case study follows a state case study approach, together with a disease burden review and a basic description of the health portrait in relation to Timor-Leste's fragile state status. Disease burden and health security are directly proportional to state stability and indirectly proportional to state failure. Timor-Leste is a clear example of how public health can feed into increased state stability. Our discussion attempts to describe how the weak and fragile island nation of Timor-Leste can continue on its current path of transition to state stability by increasing health security for its citizens. We surmise that this can be realized when public policy focuses on primary healthcare access, inclusive state institutions, basic hygiene and preventative vaccination programs. Based on our review, the core findings indicate that by increasing health security, a positive feedback loop of state stability follows. The use of Timor-Leste as a case study better describes the connection between public health and health security; and state stability, development and inclusive state institutions that promote health security.

Fetal cardiac assessment

International Nuclear Information System (INIS)

Greene, K.R.

1983-01-01

The better understanding of fetal cardiovascular physiology coupled with improved technology for non-invasive study of the fetus now enable much more detailed assessment of fetal cardiac status than by heart rate alone. Even the latter, relatively simple, measurement contains much more information than was previously realized. It is also increasingly clear that no single measurement will provide the answer to all clinical dilemmas either on cardiac function or the welfare of the fetus as a whole. There are obvious clinical advantages in measuring several variables from one signal and the measurement of heart rate, heart rate variation and waveform from the ECG in labour is a potentially useful combination. Systolic time intervals or flow measurements could easily be added or used separately by combining real-time and Doppler ultrasound probes

Cardiac nuclear medicine

Energy Technology Data Exchange (ETDEWEB)

Gerson, M.C.

1987-01-01

The book begins with a review of the radionuclide methods available for evaluating cardiac perfusion and function. The authors discuss planar and tomographic thallium myocardial imaging, first-pass and equilibrium radionuclide angiography, and imaging with infarct-avid tracers. Several common but more specialized procedures are then reviewed: nonogemetric measurement of left ventricular volume, phase (Fourier) analysis, stroke volume ratio, right ventricular function, and diastolic function. A separate chapter is devoted to drug interventions and in particular the use of radionuclide ventriculography to monitor doxorubicin toxicity and therapy of congestive heart failure. The subsequent chapters provide a comprehensive guide to test selection, accuracy, and results in acute myocardial infarction, in postmyocardial infarction, in chronic coronary artery disease, before and after medical or surgical revascularization, in valvular heart disease, in cardiomyopathies, and in cardiac trauma.

Cardiac nuclear medicine

International Nuclear Information System (INIS)

Gerson, M.C.

1987-01-01

The book begins with a review of the radionuclide methods available for evaluating cardiac perfusion and function. The authors discuss planar and tomographic thallium myocardial imaging, first-pass and equilibrium radionuclide angiography, and imaging with infarct-avid tracers. Several common but more specialized procedures are then reviewed: nonogemetric measurement of left ventricular volume, phase (Fourier) analysis, stroke volume ratio, right ventricular function, and diastolic function. A separate chapter is devoted to drug interventions and in particular the use of radionuclide ventriculography to monitor doxorubicin toxicity and therapy of congestive heart failure. The subsequent chapters provide a comprehensive guide to test selection, accuracy, and results in acute myocardial infarction, in postmyocardial infarction, in chronic coronary artery disease, before and after medical or surgical revascularization, in valvular heart disease, in cardiomyopathies, and in cardiac trauma

Seismic fragility of a reinforced concrete structure

Energy Technology Data Exchange (ETDEWEB)

Kurmann, Davide [Axpo Power AG, Baden (Switzerland); Proske, Dirk [Axpo Power AG, Doettingen (Switzerland); Cervenka, Jan [Cervenka Consulting, Prague (Czech Republic)

2013-05-15

Structures can be exposed to seismic loading. For structures of major importance, extreme seismic loadings have to be considered. The proof of safety for such loadings requires sophisticated analysis. This paper introduces an analysis method which of course still includes simplifications, but yields to a far more realistic estimation of the seismic load bearing capacity of reinforced concrete structures compared to common methods. It is based on the development of pushover curves and the application of time-histories for the dynamic model to a representative harmonic oscillator. Dynamic parameters of the oscillator, such as modal mass and damping are computed using a soil-structure-interaction analysis. Based on the pushover-curve nonlinear force-deformation-capacities are applied to the oscillator including hysteresis behaviour characteristics. The oscillator is then exposed to time-histories of several earthquakes. Based on this computation the ductility is computed. The ductility can be scaled based upon the scaling of the time-histories. Since both, the uncertainty of the earthquake by using different timehistories and the uncertainty of the structure by using characteristic and mean material values, are considered, the uncertainty of the structure under seismic loading can be explicitly represented by a fragility. (orig.)

Cardiac hybrid imaging

Energy Technology Data Exchange (ETDEWEB)

Gaemperli, Oliver [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); University Hospital Zurich, Nuclear Cardiology, Cardiovascular Center, Zurich (Switzerland); Kaufmann, Philipp A. [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

2014-05-15

Hybrid cardiac single photon emission computed tomography (SPECT)/CT imaging allows combined assessment of anatomical and functional aspects of cardiac disease. In coronary artery disease (CAD), hybrid SPECT/CT imaging allows detection of coronary artery stenosis and myocardial perfusion abnormalities. The clinical value of hybrid imaging has been documented in several subsets of patients. In selected groups of patients, hybrid imaging improves the diagnostic accuracy to detect CAD compared to the single imaging techniques. Additionally, this approach facilitates functional interrogation of coronary stenoses and guidance with regard to revascularization procedures. Moreover, the anatomical information obtained from CT coronary angiography or coronary artery calcium scores (CACS) adds prognostic information over perfusion data from SPECT. The use of cardiac hybrid imaging has been favoured by the dissemination of dedicated hybrid systems and the release of dedicated image fusion software, which allow simple patient throughput for hybrid SPECT/CT studies. Further technological improvements such as more efficient detector technology to allow for low-radiation protocols, ultra-fast image acquisition and improved low-noise image reconstruction algorithms will be instrumental to further promote hybrid SPECT/CT in research and clinical practice. (orig.)

Dementia in Fragile X-associated Tremor/Ataxia Syndrome

Directory of Open Access Journals (Sweden)

Ricardo Nitrini

Full Text Available Abstract Fragile X-associated tremor/ataxia syndrome (FXTAS is a cause of movement disorders and cognitive decline which has probably been underdiagnosed, especially if its prevalence proves similar to those of progressive supranuclear palsy and amyotrophic lateral sclerosis. We report a case of a 74-year-old man who presented with action tremor, gait ataxia and forgetfulness. There was a family history of tremor and dementia, and one of the patient's grandsons was mentally deficient. Neuropsychological evaluation disclosed a frontal network syndrome. MRI showed hyperintensity of both middle cerebellar peduncles, a major diagnostic hallmark of FXTAS. Genetic testing revealed premutation of the FMR1 gene with an expanded (CGG90 repeat. The diagnosis of FXTAS is important for genetic counseling because the daughters of the affected individuals are at high risk of having offspring with fragile X syndrome. Tremors and cognitive decline should raise the diagnostic hypothesis of FXTAS, which MRI may subsequently reinforce, while the detection of the FMR1 premutation can confirm the condition.

A Guide to Improving the Care of Patients with Fragility Fractures, Edition 2

Science.gov (United States)

Mears, Simon C.

2015-01-01

Over the past 4 decades, much has been learned about the pathophysiology and treatment of osteoporosis, the prevention of fragility fractures, and the perioperative management of patients who have these debilitating injuries. However, the volume of published literature on this topic is staggering and far too voluminous for any clinician to review and synthesize by him or herself. This manuscript thoroughly summarizes the latest research on fragility fractures and provides the reader with valuable strategies to optimize the prevention and management of these devastating injuries. The information contained in this article will prove invaluable to any health care provider or health system administrator who is involved in the prevention and management of fragility hip fractures. As providers begin to gain a better understanding of the principles espoused in this article, it is our hope that they will be able to use this information to optimize the care they provide for elderly patients who are at risk of or who have osteoporotic fractures. PMID:26246957

Validation of fragility fractures in primary care electronic medical records: A population-based study.

Science.gov (United States)

Martinez-Laguna, Daniel; Soria-Castro, Alberto; Carbonell-Abella, Cristina; Orozco-López, Pilar; Estrada-Laza, Pilar; Nogues, Xavier; Díez-Perez, Adolfo; Prieto-Alhambra, Daniel

2017-11-28

Electronic medical records databases use pre-specified lists of diagnostic codes to identify fractures. These codes, however, are not specific enough to disentangle traumatic from fragility-related fractures. We report on the proportion of fragility fractures identified in a random sample of coded fractures in SIDIAP. Patients≥50 years old with any fracture recorded in 2012 (as per pre-specified ICD-10 codes) and alive at the time of recruitment were eligible for this retrospective observational study in 6 primary care centres contributing to the SIDIAP database (www.sidiap.org). Those with previous fracture/s, non-responders, and those with dementia or a serious psychiatric disease were excluded. Data on fracture type (traumatic vs fragility), skeletal site, and basic patient characteristics were collected. Of 491/616 (79.7%) patients with a registered fracture in 2012 who were contacted, 331 (349 fractures) were included. The most common fractures were forearm (82), ribs (38), and humerus (32), and 225/349 (64.5%) were fragility fractures, with higher proportions for classic osteoporotic sites: hip, 91.7%; spine, 87.7%; and major fractures, 80.5%. This proportion was higher in women, the elderly, and patients with a previously coded diagnosis of osteoporosis. More than 4 in 5 major fractures recorded in SIDIAP are due to fragility (non-traumatic), with higher proportions for hip (92%) and vertebral (88%) fracture, and a lower proportion for fractures other than major ones. Our data support the validity of SIDIAP for the study of the epidemiology of osteoporotic fractures. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Surgical treatment for medically refractory focal epilepsy in a patient with fragile X syndrome.

Science.gov (United States)

Kenmuir, Cynthia; Richardson, Mark; Ghearing, Gena

2015-10-01

Medication resistant temporal lobe epilepsy occurs in a small population of patients with fragile X syndrome. We present the case of a 24-year-old man with medically refractory temporal lobe epilepsy and fragile X syndrome who underwent left anterior temporal lobectomy resulting in cessation of seizures. Our patient was diagnosed with fragile X syndrome with a fully mutated, fully methylated FMR1 gene resulting in 572 CGG repeats. He developed seizures initially controlled with Depakote monotherapy, but progressed to become medically refractive to combination treatment with Depakote, lamotrigine and zonisamide. Prolonged video EEG monitoring revealed interictal left temporal sharp waves and slowing as well as subclinical and clinical seizures, each with left temporal onset. 3T MRI was consistent with left mesial temporal sclerosis. After discussing the case in our multidisciplinary surgical epilepsy conference, he was referred for presurgical evaluation including neuropsychological testing and Wada testing. He underwent an asleep left anterior temporal lobectomy, sparing the superior temporal gyrus. Pathology showed neuronal loss and gliosis in the hippocampus and amygdala. Twelve months after surgery, the patient has not experienced a seizure. He is described by his parents as less perseverative and less restless. We have presented the case of a 24 year-old-man with fragile X syndrome who underwent successful left anterior temporal lobectomy for the treatment of medically refractory epilepsy who is now seizure free without further functional impairment. This case report demonstrates the feasibility of surgical treatment for a patient with comorbid fragile X syndrome and mesial temporal sclerosis. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Complete cardiac regeneration in a mouse model of myocardial infarction.

Science.gov (United States)

Haubner, Bernhard Johannes; Adamowicz-Brice, Martyna; Khadayate, Sanjay; Tiefenthaler, Viktoria; Metzler, Bernhard; Aitman, Tim; Penninger, Josef M

2012-12-01

Cardiac remodeling and subsequent heart failure remain critical issues after myocardial infarction despite improved treatment and reperfusion strategies. Recently, complete cardiac regeneration has been demonstrated in fish and newborn mice following resection of the cardiac apex. However, it remained entirely unclear whether the mammalian heart can also completely regenerate following a complex cardiac ischemic injury. We established a protocol to induce a severe heart attack in one-day-old mice using left anterior descending artery (LAD) ligation. LAD ligation triggered substantial cardiac injury in the left ventricle defined by Caspase 3 activation and massive cell death. Ischemia-induced cardiomyocyte death was also visible on day 4 after LAD ligation. Remarkably, 7 days after the initial ischemic insult, we observed complete cardiac regeneration without any signs of tissue damage or scarring. This tissue regeneration translated into long-term normal heart functions as assessed by echocardiography. In contrast, LAD ligations in 7-day-old mice resulted in extensive scarring comparable to adult mice, indicating that the regenerative capacity for complete cardiac healing after heart attacks can be traced to the first week after birth. RNAseq analyses of hearts on day 1, day 3, and day 10 and comparing LAD-ligated and sham-operated mice surprisingly revealed a transcriptional programme of major changes in genes mediating mitosis and cell division between days 1, 3 and 10 postnatally and a very limited set of genes, including genes regulating cell cycle and extracellular matrix synthesis, being differentially regulated in the regenerating hearts. We present for the first time a mammalian model of complete cardiac regeneration following a severe ischemic cardiac injury. This novel model system provides the unique opportunity to uncover molecular and cellular pathways that can induce cardiac regeneration after ischemic injury, findings that one day could be translated

Emerging Powers and Effective Governance in Fragile States | IDRC ...

International Development Research Centre (IDRC) Digital Library (Canada)

New and emerging development organizations are providing assistance to countries experiencing tensions and challenges after periods of conflict. This research will test whether their development assistance approaches are more effective at addressing the political and social realities of fragile states than those used by ...

Linking structure to fragility in bulk metallic glass-forming liquids

International Nuclear Information System (INIS)

Wei, Shuai; Stolpe, Moritz; Gross, Oliver; Gallino, Isabella; Hembree, William; Busch, Ralf; Evenson, Zach; Bednarcik, Jozef; Kruzic, Jamie J.

2015-01-01

Using in-situ synchrotron X-ray scattering, we show that the structural evolution of various bulk metallic glass-forming liquids can be quantitatively connected to their viscosity behavior in the supercooled liquid near T g . The structural signature of fragility is identified as the temperature dependence of local dilatation on distinct key atomic length scales. A more fragile behavior results from a more pronounced thermally induced dilatation of the structure on a length scale of about 3 to 4 atomic diameters, coupled with shallower temperature dependence of structural changes in the nearest neighbor environment. These findings shed light on the structural origin of viscous slowdown during undercooling of bulk metallic glass-forming liquids and demonstrate the promise of predicting the properties of bulk metallic glasses from the atomic scale structure

Linking structure to fragility in bulk metallic glass-forming liquids

Energy Technology Data Exchange (ETDEWEB)

Wei, Shuai, E-mail: shuai.wei@asu.edu, E-mail: m.stolpe@mx.uni-saarland.de [Department of Materials Science and Engineering, Saarland University, Campus C63, 66123 Saarbrücken (Germany); Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287 (United States); Stolpe, Moritz, E-mail: shuai.wei@asu.edu, E-mail: m.stolpe@mx.uni-saarland.de; Gross, Oliver; Gallino, Isabella; Hembree, William; Busch, Ralf [Department of Materials Science and Engineering, Saarland University, Campus C63, 66123 Saarbrücken (Germany); Evenson, Zach [Department of Materials Science and Engineering, Saarland University, Campus C63, 66123 Saarbrücken (Germany); Institut für Materialphysik im Weltraum, Deutsches Zentrum für Luft- und Raumfahrt (DLR), 51170 Köln (Germany); Bednarcik, Jozef [Deutsches Elektronen-Synchrotron DESY, Notkestrasse 85, D-22603 Hamburg (Germany); Kruzic, Jamie J. [Material Science, School of Mechanical, Industrial, and Manufacturing Engineering, Oregon State University, Corvallis, Oregon 97331 (United States)

2015-05-04

Using in-situ synchrotron X-ray scattering, we show that the structural evolution of various bulk metallic glass-forming liquids can be quantitatively connected to their viscosity behavior in the supercooled liquid near T{sub g}. The structural signature of fragility is identified as the temperature dependence of local dilatation on distinct key atomic length scales. A more fragile behavior results from a more pronounced thermally induced dilatation of the structure on a length scale of about 3 to 4 atomic diameters, coupled with shallower temperature dependence of structural changes in the nearest neighbor environment. These findings shed light on the structural origin of viscous slowdown during undercooling of bulk metallic glass-forming liquids and demonstrate the promise of predicting the properties of bulk metallic glasses from the atomic scale structure.

Post-surgical rehabilitative approach to fragility fractures.

Science.gov (United States)

Gimigliano, F; Iolascon, G; Riccio, I; Frizzi, L; Gimigliano, R

2013-10-01

Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. The most frequent sites of fragility fractures are the hip, the distal radius, the spine, the proximal humerus, and the ankle. In most cases, a surgical approach with subsequent rehabilitative treatment is required. The general aims of rehabilitation are to increase functioning and improve patients' activities, participation level, and quality of life.

Mean-coordination number dependence of the fragility in Ge-Se-In glass-forming liquids

International Nuclear Information System (INIS)

Saffarini, G.; Saiter, A.; Garda, M.R.; Saiter, J.M.

2007-01-01

Differential scanning calorimetry measurements have been performed on elemental Se as well as on Ge x Se 94- x In 6 (x=4, 8, and 11 at%) and on Ge y Se 88- y In 12 (y=5, 7, and 9 at%) chalcogenide glasses. From the cooling rate dependence of the fictive temperature, the apparent activation energies, Δh*, and the fragility indices, m, as defined in the strong-fragile glass-forming liquid concept, are determined. It is found that, in Ge-Se-In system, there is an evolution from strong (m=67) to fragile (m=116) glass-forming liquids. The dependence of 'm' on the mean-coordination number, Z, is also obtained. This dependence is rationalized by assuming that, in this glassy alloy system, there is a tendency for the formation of In 2 Se 3 clusters

The tsunami probabilistic risk assessment of nuclear power plant (3). Outline of tsunami fragility analysis

International Nuclear Information System (INIS)

Mihara, Yoshinori

2012-01-01

Tsunami Probabilistic Risk Assessment (PRA) standard was issued in February 2012 by Standard Committee of Atomic Energy Society of Japan (AESJ). This article detailed tsunami fragility analysis, which calculated building and structure damage probability contributing core damage and consisted of five evaluation steps: (1) selection of evaluated element and damage mode, (2) selection of evaluation procedure, (3) evaluation of actual stiffness, (4) evaluation of actual response and (5) evaluation of fragility (damage probability and others). As an application example of the standard, calculation results of tsunami fragility analysis investigation by tsunami PRA subcommittee of AESJ were shown reflecting latest knowledge of damage state caused by wave force and others acted by tsunami from the 'off the Pacific Coast of Tohoku Earthquake'. (T. Tanaka)

Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage.

Science.gov (United States)

Mutoh, Tomoko; Mutoh, Tatsushi; Nakamura, Kazuhiro; Yamamoto, Yukiko; Tsuru, Yoshiharu; Tsubone, Hirokazu; Ishikawa, Tatsuya; Taki, Yasuyuki

2017-04-01

Early brain injury/ischaemia (EBI) is a serious complication early after subarachnoid haemorrhage (SAH) that contributes to development of delayed cerebral ischaemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75 μg/kg/min) between 1.5 and 2.5 hours after SAH induction was monitored with Doppler echocardiography. Magnetic resonance imaging (MRI)-continuous arterial spin labelling was used for quantitative cerebral blood flow (CBF) measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3 days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P<.001), which was accompanied by improved hypoperfusion, incidence of DCI and functional recovery than Control (P<.05). The neuroprotective effects afforded by MIL or Control were attenuated by hypoxia-inducible factor (HIF) inhibition (P<.05). These results suggest that MIL improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral improvement in mice after severe SAH, in which HIF may be acting as a critical mediator. © 2017 John Wiley & Sons Australia, Ltd.

Consideration of time-evolving capacity distributions and improved degradation models for seismic fragility assessment of aging highway bridges

International Nuclear Information System (INIS)

Ghosh, Jayadipta; Sood, Piyush

2016-01-01

This paper presents a methodology to develop seismic fragility curves for deteriorating highway bridges by uniquely accounting for realistic pitting corrosion deterioration and time-dependent capacity distributions for reinforced concrete columns under chloride attacks. The proposed framework offers distinct improvements over state-of-the-art procedures for fragility assessment of degrading bridges which typically assume simplified uniform corrosion deterioration model and pristine limit state capacities. Depending on the time in service life and deterioration mechanism, this study finds that capacity limit states for deteriorating bridge columns follow either lognormal distribution or generalized extreme value distributions (particularly for pitting corrosion). Impact of column degradation mechanism on seismic response and fragility of bridge components and system is assessed using nonlinear time history analysis of three-dimensional finite element bridge models reflecting the uncertainties across structural modeling parameters, deterioration parameters and ground motion. Comparisons are drawn between the proposed methodology and traditional approaches to develop aging bridge fragility curves. Results indicate considerable underestimations of system level fragility across different damage states using the traditional approach compared to the proposed realistic pitting model for chloride induced corrosion. Time-dependent predictive functions are provided to interpolate logistic regression coefficients for continuous seismic reliability evaluation along the service life with reasonable accuracy. - Highlights: • Realistic modeling of chloride induced corrosion deterioration in the form of pitting. • Time-evolving capacity distribution for aging bridge columns under chloride attacks. • Time-dependent seismic fragility estimation of highway bridges at component and system level. • Mathematical functions for continuous tracking of seismic fragility along service

Cardiac telomere length in heart development, function, and disease.

Science.gov (United States)

Booth, S A; Charchar, F J

2017-07-01

Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. Copyright © 2017 the American Physiological Society.

Myostatin as a Marker for Doxorubicin Induced Cardiac Damage.

Science.gov (United States)

Kesik, Vural; Honca, Tevfik; Gulgun, Mustafa; Uysal, Bulent; Kurt, Yasemin Gulcan; Cayci, Tuncer; Babacan, Oguzhan; Gocgeldi, Ercan; Korkmazer, Nadir

2016-01-01

Doxorubicin (DXR) is an effective chemotherapeutic agent but causes severe cardiac failure over known doses. Thus, early detection and prevention of cardiac damage is important. Various markers have been tested for early detection of cardiac damage. Myostatin is a protein produced in skeletal muscle cells inhibits muscle differentiation and growth during myogenesis. We evaluated the role of myostatin as a marker for showing DXR induced cardiac damage and compared with well known cardiac markers like NT-proBNP, hs-TnT and CK in a rat model of chronic DXR cardiotoxicity. Myostatin, NT-proBNP, and hs-TnT but not CK rose significantly during DXR treatment. Myostatin can be used as an early marker of DXR induced cardiotoxicity. © 2016 by the Association of Clinical Scientists, Inc.

Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites

Directory of Open Access Journals (Sweden)

Pierce Levi CT

2009-01-01

Full Text Available Abstract Background Gene rearrangements such as chromosomal translocations have been shown to contribute to cancer development. Human chromosomal fragile sites are regions of the genome especially prone to breakage, and have been implicated in various chromosome abnormalities found in cancer. However, there has been no comprehensive and quantitative examination of the location of fragile sites in relation to all chromosomal aberrations. Results Using up-to-date databases containing all cancer-specific recurrent translocations, we have examined 444 unique pairs of genes involved in these translocations to determine the correlation of translocation breakpoints and fragile sites in the gene pairs. We found that over half (52% of translocation breakpoints in at least one gene of these gene pairs are mapped to fragile sites. Among these, we examined the DNA sequences within and flanking three randomly selected pairs of translocation-prone genes, and found that they exhibit characteristic features of fragile DNA, with frequent AT-rich flexibility islands and the potential of forming highly stable secondary structures. Conclusion Our study is the first to examine gene pairs involved in all recurrent chromosomal translocations observed in tumor cells, and to correlate the location of more than half of breakpoints to positions of known fragile sites. These results provide strong evidence to support a causative role for fragile sites in the generation of cancer-specific chromosomal rearrangements.

Ricci curvature: An economic indicator for market fragility and systemic risk

Science.gov (United States)

Sandhu, Romeil S.; Georgiou, Tryphon T.; Tannenbaum, Allen R.

2016-01-01

Quantifying the systemic risk and fragility of financial systems is of vital importance in analyzing market efficiency, deciding on portfolio allocation, and containing financial contagions. At a high level, financial systems may be represented as weighted graphs that characterize the complex web of interacting agents and information flow (for example, debt, stock returns, and shareholder ownership). Such a representation often turns out to provide keen insights. We show that fragility is a system-level characteristic of “business-as-usual” market behavior and that financial crashes are invariably preceded by system-level changes in robustness. This was done by leveraging previous work, which suggests that Ricci curvature, a key geometric feature of a given network, is negatively correlated to increases in network fragility. To illustrate this insight, we examine daily returns from a set of stocks comprising the Standard and Poor’s 500 (S&P 500) over a 15-year span to highlight the fact that corresponding changes in Ricci curvature constitute a financial “crash hallmark.” This work lays the foundation of understanding how to design (banking) systems and policy regulations in a manner that can combat financial instabilities exposed during the 2007–2008 crisis. PMID:27386522

Estimating structural collapse fragility of generic building typologies using expert judgment

Science.gov (United States)

Jaiswal, Kishor S.; Wald, D.J.; Perkins, D.; Aspinall, W.P.; Kiremidjian, Anne S.; Deodatis, George; Ellingwood, Bruce R.; Frangopol, Dan M.

2014-01-01

The structured expert elicitation process proposed by Cooke (1991), hereafter referred to as Cooke’s approach, is applied for the first time in the realm of structural collapse-fragility assessment for selected generic construction types. Cooke’s approach works on the principle of objective calibration scoring of judgments coupled with hypothesis testing used in classical statistics. The performance-based scoring system reflects the combined measure of an expert’s informativeness about variables in the problem area under consideration, and their ability to enumerate, in a statistically accurate way through expressing their true beliefs, the quantitative uncertainties associated with their assessments. We summarize the findings of an expert elicitation workshop in which a dozen earthquake-engineering professionals from around the world were engaged to estimate seismic collapse fragility for generic construction types. Development of seismic collapse fragility functions was accomplished by combining their judgments using weights derived from Cooke’s method. Although substantial effort was needed to elicit the inputs of these experts successfully, we anticipate that the elicitation strategy described here will gain momentum in a wide variety of earthquake seismology and engineering hazard and risk analyses where physical model and data limitations are inherent and objective professional judgment can fill gaps.

Heterogeneous stock rat: a unique animal model for mapping genes influencing bone fragility.

Science.gov (United States)

Alam, Imranul; Koller, Daniel L; Sun, Qiwei; Roeder, Ryan K; Cañete, Toni; Blázquez, Gloria; López-Aumatell, Regina; Martínez-Membrives, Esther; Vicens-Costa, Elia; Mont, Carme; Díaz, Sira; Tobeña, Adolf; Fernández-Teruel, Alberto; Whitley, Adam; Strid, Pernilla; Diez, Margarita; Johannesson, Martina; Flint, Jonathan; Econs, Michael J; Turner, Charles H; Foroud, Tatiana

2011-05-01

Previously, we demonstrated that skeletal mass, structure and biomechanical properties vary considerably among 11 different inbred rat strains. Subsequently, we performed quantitative trait loci (QTL) analysis in four inbred rat strains (F344, LEW, COP and DA) for different bone phenotypes and identified several candidate genes influencing various bone traits. The standard approach to narrowing QTL intervals down to a few candidate genes typically employs the generation of congenic lines, which is time consuming and often not successful. A potential alternative approach is to use a highly genetically informative animal model resource capable of delivering very high resolution gene mapping such as Heterogeneous stock (HS) rat. HS rat was derived from eight inbred progenitors: ACI/N, BN/SsN, BUF/N, F344/N, M520/N, MR/N, WKY/N and WN/N. The genetic recombination pattern generated across 50 generations in these rats has been shown to deliver ultra-high even gene-level resolution for complex genetic studies. The purpose of this study is to investigate the usefulness of the HS rat model for fine mapping and identification of genes underlying bone fragility phenotypes. We compared bone geometry, density and strength phenotypes at multiple skeletal sites in HS rats with those obtained from five of the eight progenitor inbred strains. In addition, we estimated the heritability for different bone phenotypes in these rats and employed principal component analysis to explore relationships among bone phenotypes in the HS rats. Our study demonstrates that significant variability exists for different skeletal phenotypes in HS rats compared with their inbred progenitors. In addition, we estimated high heritability for several bone phenotypes and biologically interpretable factors explaining significant overall variability, suggesting that the HS rat model could be a unique genetic resource for rapid and efficient discovery of the genetic determinants of bone fragility. Copyright �

Pharmacological targeting of CDK9 in cardiac hypertrophy.

Science.gov (United States)

Krystof, Vladimír; Chamrád, Ivo; Jorda, Radek; Kohoutek, Jirí

2010-07-01

Cardiac hypertrophy allows the heart to adapt to workload, but persistent or unphysiological stimulus can result in pump failure. Cardiac hypertrophy is characterized by an increase in the size of differentiated cardiac myocytes. At the molecular level, growth of cells is linked to intensive transcription and translation. Several cyclin-dependent kinases (CDKs) have been identified as principal regulators of transcription, and among these CDK9 is directly associated with cardiac hypertrophy. CDK9 phosphorylates the C-terminal domain of RNA polymerase II and thus stimulates the elongation phase of transcription. Chronic activation of CDK9 causes not only cardiac myocyte enlargement but also confers predisposition to heart failure. Due to the long interest of molecular oncologists and medicinal chemists in CDKs as potential targets of anticancer drugs, a portfolio of small-molecule inhibitors of CDK9 is available. Recent determination of CDK9's crystal structure now allows the development of selective inhibitors and their further optimization in terms of biochemical potency and selectivity. CDK9 may therefore constitute a novel target for drugs against cardiac hypertrophy.

A Benign Cardiac Growth but Not So Indolent

Science.gov (United States)

Reddy, Sahadev T.; Biederman, Robert W. W.

2016-01-01

Cardiac lipomatous hypertrophy is a rare benign condition that usually involves the interatrial septum. Due to its benign nature it rarely requires intervention. Its presence outside the interatrial septum is reported infrequently. We present a case of lipomatous hypertrophy in the intraventricular septum that was complicated by a severe, symptomatic, and disabling dynamic left ventricular outflow tract obstruction. The symptoms significantly improved following the excision of the mass. In our case transthoracic echocardiogram was used to visualize the mass and measure the severity of the obstruction; Cardiac Magnetic Resonance Imaging was used to characterize the mass and histopathology confirmed the diagnosis. PMID:27293911

Blood conservation in cardiac surgery: guidelines and controversies.

Science.gov (United States)

Mazer, C David

2014-02-01

Bleeding related to cardiac surgery is an important clinical problem. Perioperative anemia and transfusion of allogeneic blood products have both been associated with adverse outcome including mortality and major morbidity. Guidelines exist to help determine when the risks of anemia outweigh the risks of transfusion. Perioperative bleeding may be related to several factors including the use of new antithrombotic drugs. A variety of hemostatic drugs have been studied to reduce bleeding and transfusion, although several questions and concerns about them exist. Patient blood management programs can be valuable for management of patients undergoing cardiac surgery. Copyright © 2014. Published by Elsevier Ltd.

Cardiac fusion and complex congenital cardiac defects in thoracopagus twins: diagnostic value of cardiac CT

Energy Technology Data Exchange (ETDEWEB)

Goo, Hyun Woo [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Park, Jeong-Jun [University of Ulsan College of Medicine, Asan Medical Center, Department of Pediatric Cardiac Surgery, Seoul (Korea, Republic of); Kim, Ellen Ai-Rhan [University of Ulsan College of Medicine, Asan Medical Center, Division of Neonatology, Department of Pediatrics, Seoul (Korea, Republic of); Won, Hye-Sung [University of Ulsan College of Medicine, Asan Medical Center, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of)

2014-09-15

Most thoracopagus twins present with cardiac fusion and associated congenital cardiac defects, and assessment of this anatomy is of critical importance in determining patient care and outcome. Cardiac CT with electrocardiographic triggering provides an accurate and quick morphological assessment of both intracardiac and extracardiac structures in newborns, making it the best imaging modality to assess thoracopagus twins during the neonatal period. In this case report, we highlight the diagnostic value of cardiac CT in thoracopagus twins with an interatrial channel and complex congenital cardiac defects. (orig.)

Seismic fragility of nuclear power plant components: Phase 2, Motor control center, switchboard, panelboard and power supply

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.; Kassir, M.K.; Pepper, S.E.

1987-12-01

In Phase I of the Component Fragility Program, Brookhaven National Laboratory (BNL) has developed a procedure to establish the seismic fragility of nuclear power plant equipment by use of existing test data and demonstrated its application by considering two equipment pieces. In Phase II of the program, BNL has collected additional test data, and has further advanced and is applying the methodology to determine the fragility levels of selected essential equipment categories. The data evaluation of four equipment families, namely, motor control center, switchboard, panelboard and power supply has been completed. Fragility levels have been determined for various failure modes of each equipment class and the deterministic results are presented in terms of test response spectra. In addition, the test data have been analyzed for determination of the respective probabilistic fragility levels. To this end, a single g-value has been selected to approximately represent the test vibration level and a statistical analysis has been performed with the g-values corresponding to a particular failure mode. The zero period acceleration and the average spectral acceleration over a frequency range of interest are separately used as the single g-value. The resulting parameters are presented in terms of a median value, an uncertainty coefficient and a randomness coefficient. Ultimately, each fragility level is expressed in terms of a single descriptor called an HCLPF value corresponding to a high (95%) confidence of a low (5%) probability of failure. The important observations made in the process of data analysis are included in this report

Social Cognition in Adolescent Girls with Fragile X Syndrome

Science.gov (United States)

Turkstra, Lyn S.; Abbeduto, Leonard; Meulenbroek, Peter

2014-01-01

This study aimed to characterize social cognition, executive functions (EFs), and everyday social functioning in adolescent girls with fragile X syndrome, and identify relationships among these variables. Participants were 20 girls with FXS and 20 age-matched typically developing peers. Results showed significant between-groups differences in…

Biomarkers for cardiac cachexia: reality or utopia.

Science.gov (United States)

Martins, Telma; Vitorino, Rui; Amado, Francisco; Duarte, José Alberto; Ferreira, Rita

2014-09-25

Cardiac cachexia is a serious complication of chronic heart failure, characterized by significant weight loss and body wasting. Chronic heart failure-related muscle wasting results from a chronic imbalance in the activation of anabolic or catabolic pathways, caused by a series of immunological, metabolic, and neurohormonal processes. In spite of the high morbidity and mortality associated to this condition, there is no universally accepted definition or specific biomarkers for cardiac cachexia, which makes its diagnosis and treatment difficult. Several hormonal, inflammatory and oxidative stress molecules have been proposed as serological markers of prognosis in cardiac cachexia but with doubtful success. As individual biomarkers may have limited sensitivity and specificity, multimarker strategies involving mediators of the biological processes modulated by cardiac cachexia will strongly contribute for the diagnosis and management of the disease, as well as for the establishment of new therapeutic targets. An integrated analysis of the biomarkers proposed so far for cardiac cachexia is made in the present review, highlighting the biological processes to which they are related. Copyright © 2014 Elsevier B.V. All rights reserved.

The kinetic fragility of natural silicate melts

International Nuclear Information System (INIS)

Giordano, Daniele; Dingwell, Donald B

2003-01-01

Newtonian viscosities of 19 multicomponent natural and synthetic silicate liquids, with variable contents of SiO 2 (41-79 wt%), Al 2 O 3 (10-19 wt%), TiO 2 (0-3 wt%), FeO tot (0-11 wt%); alkali oxides (5-17 wt%), alkaline-earth oxides (0-35 wt%), and minor oxides, obtained at ambient pressure using the high-temperature concentric cylinder, the low-temperature micropenetration, and the parallel plates techniques, have been analysed. For each silicate liquid, regression of the experimentally determined viscosities using the well known Vogel-Fulcher-Tammann (VFT) equation allowed the viscosity of all these silicates to be accurately described. The results of these fits, which provide the basis for the subsequent analysis here, permit qualitative and quantitative correlations to be made between the VFT adjustable parameters (A VFT , B VFT , and T 0 ). The values of B VFT and T 0 , calibrated via the VFT equation, are highly correlated. Kinetic fragility appears to be correlated with the number of non-bridging oxygens per tetrahedrally coordinated cation (NBO/T). This is taken to infer that melt polymerization controls melt fragility in liquid silicates. Thus NBO/T might form an useful ingredient of a structure-based model of non-Arrhenian viscosity in multicomponent silicate melts

Primary Cardiac Leiomyoma Causing Right Ventricular Obstruction and Tricuspid Regurgitation.

Science.gov (United States)

Careddu, Lucio; Foà, Alberto; Leone, Ornella; Agostini, Valentina; Gargiulo, Gaetano Domenico; Rapezzi, Claudio; Di Bartolomeo, Roberto; Pacini, Davide

2017-09-01

We report the unique case of a primary cardiac leiomyoma originating from the right ventricle and involving the tricuspid valve in a 43-year-old woman. Echocardiography showed a giant mass causing severe pulmonary stenosis and tricuspid valve regurgitation. The patient underwent surgical excision and histologic examination revealed a primary cardiac leiomyoma. To the best of our knowledge only three cases of primary cardiac leiomyoma have so far been reported, and this is the first case of primary cardiac leiomyoma involving the tricuspid valve apparatus. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Blunt traumatic cardiac rupture: therapeutic options and outcomes.

Science.gov (United States)

Nan, Yu-Yun; Lu, Ming-Shian; Liu, Kuo-Sheng; Huang, Yao-Kuang; Tsai, Feng-Chun; Chu, Jaw-Ji; Lin, Pyng Jing

2009-09-01

Cardiac rupture following blunt thoracic trauma is rarely encountered by clinicians, since it commonly causes death at the scene. With advances in traumatology, blunt cardiac rupture had been increasingly disclosed in various ways. This study reviews our experience of patients with suspected blunt traumatic cardiac rupture and proposes treatment protocols for the same. This is a 5-year retrospective study of trauma patients confirmed with blunt traumatic cardiac rupture admitted to a university-affiliated tertiary trauma referral centre. The following information was collected from the patients: age, sex, mechanism of injury, initial effective diagnostic tool used for diagnosing blunt cardiac rupture, location and size of the cardiac injury, associated injury and injury severity score (ISS), reversed trauma score (RTS), survival probability of trauma and injury severity scoring (TRISS), vital signs and biochemical lab data on arrival at the trauma centre, time elapsed from injury to diagnosis and surgery, surgical details, hospital course and final outcome. The study comprised 8 men and 3 women with a median age of 39 years (range: 24-73 years) and the median follow-up was 5.5 months (range: 1-35 months). The ISS, RTS, and TRISS scores of the patients were 32.18+/-5.7 (range: 25-43), 6.267+/-1.684 (range: 2.628-7.841), and 72.4+/-25.6% (range: 28.6-95.5%), respectively. Cardiac injuries were first detected using focused assessment with sonography for trauma (FAST) in 4 (36.3%) patients, using transthoracic echocardiography in 3 (27.3%) patients, chest CT in 1 (9%) patient, and intra-operatively in 3 (27.3%) patients. The sites of cardiac injury comprised the superior vena cava/right atrium junction (n=4), right atrial auricle (n=1), right ventricle (n=4), left ventricular contusion (n=1), and diffuse endomyocardial dissection over the right and left ventricles (n=1). Notably, 2 had pericardial lacerations presenting as a massive haemothorax, which initially masked

Seismic fragility of reinforced concrete structures and components for application to nuclear facilities

International Nuclear Information System (INIS)

Gergely, P.

1984-09-01

The failure and fragility analyses of reinforced concrete structures and elements in nuclear reactor facilities within the Seismic Safety Margins Research Program (SSMRP) at the Lawrence Livermore National Laboratory are evaluated. Uncertainties in material modeling, behavior of low shear walls, and seismic risk assessment for nonlinear response receive special attention. Problems with ductility-based spectral deamplification and prediction of the stiffness of reinforced concrete walls at low stress levels are examined. It is recommended to use relatively low damping values in connection with ductility-based response reductions. The study of static nonlinear force-deflection curves is advocated for better nonlinear dynamic response predictions. Several details of the seismic risk analysis of the Zion plant are also evaluated. 73 references

Cardiac abnormalities after subarachnoid hemorrhage

NARCIS (Netherlands)

Bilt, I.A.C. van der

2016-01-01

Aneurysmal subarachnoid hemorrhage(aSAH) is a devastating neurological disease. During the course of the aSAH several neurological and medical complications may occur. Cardiac abnormalities after aSAH are observed often and resemble stress cardiomyopathy or Tako-tsubo cardiomyopathy(Broken Heart

[Acute cardiac failure in pheochromocytoma.

DEFF Research Database (Denmark)

Jønler, Morten; Munk, Kim

2008-01-01

Pheochromocytoma (P) is an endocrine catecholamine-secreting tumor. Classical symptoms like hypertension, attacks of sweating, palpitations, headache and palor are related to catecholamine discharge. We provide a case of P in a 71 year-old man presenting with acute cardiac failure, severe reduction...

Population-based studies of antithyroid drugs and sudden cardiac death

NARCIS (Netherlands)

C. van Noord (Charlotte); M.C.J.M. Sturkenboom (Miriam); S.M.J.M. Straus (Sabine); A. Hofman (Albert); J.C.M. Witteman (Jacqueline); B.H.Ch. Stricker (Bruno)

2009-01-01

textabstractWHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Thyroid hormone free T4 is associated with QTc-interval prolongation, which is a risk factor for sudden cardiac death. • The association between hyperthyroidism and ventricular arrhythmias or sudden cardiac death has been reported in several

Clinical skills: cardiac rhythm recognition and monitoring.

Science.gov (United States)

Sharman, Joanna

With technological advances, changes in provision of healthcare services and increasing pressure on critical care services, ward patients' severity of illness is ever increasing. As such, nurses need to develop their skills and knowledge to care for their client group. Competency in cardiac rhythm monitoring is beneficial to identify changes in cardiac status, assess response to treatment, diagnosis and post-surgical monitoring. This paper describes the basic anatomy and physiology of the heart and its conduction system, and explains a simple and easy to remember process of analysing cardiac rhythms (Resuscitation Council UK, 2000) that can be used in first-line assessment to assist healthcare practitioners in providing care to their patients.

Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study.

NARCIS (Netherlands)

van Ingen, Jakko; Kohl, Thomas A; Kranzer, Katharina; Hasse, Barbara; Keller, Peter M; Katarzyna Szafrańska, Anna; Hillemann, Doris; Chand, Meera; Schreiber, Peter Werner; Sommerstein, Rami; Berger, Christoph; Genoni, Michele; Rüegg, Christian; Troillet, Nicolas; Widmer, Andreas F; Becker, Sören L; Herrmann, Mathias; Eckmanns, Tim; Haller, Sebastian; Höller, Christiane; Debast, Sylvia B; Wolfhagen, Maurice J; Hopman, Joost; Kluytmans, Jan; Langelaar, Merel; Notermans, Daan W; Ten Oever, Jaap; van den Barselaar, Peter; Vonk, Alexander B A; Vos, Margreet C; Ahmed, Nada; Brown, Timothy; Crook, Derrick; Lamagni, Theresa; Phin, Nick; Smith, E Grace; Zambon, Maria; Serr, Annerose; Götting, Tim; Ebner, Winfried; Thürmer, Alexander; Utpatel, Christian; Spröer, Cathrin; Bunk, Boyke; Nübel, Ulrich; Bloemberg, Guido V; Böttger, Erik C; Niemann, Stefan; Wagner, Dirk; Sax, Hugo

2017-01-01

Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of

Toll-like receptor 9 mediated responses in cardiac fibroblasts.

Directory of Open Access Journals (Sweden)

Ingrid Kristine Ohm

Full Text Available Altered cardiac Toll-like receptor 9 (TLR9 signaling is important in several experimental cardiovascular disorders. These studies have predominantly focused on cardiac myocytes or the heart as a whole. Cardiac fibroblasts have recently been attributed increasing significance in mediating inflammatory signaling. However, putative TLR9-signaling through cardiac fibroblasts remains non-investigated. Thus, our aim was to explore TLR9-signaling in cardiac fibroblasts and investigate the consequence of such receptor activity on classical cardiac fibroblast cellular functions. Cultivated murine cardiac fibroblasts were stimulated with different TLR9 agonists (CpG A, B and C and assayed for the secretion of inflammatory cytokines (tumor necrosis factor α [TNFα], CXCL2 and interferon α/β. Expression of functional cardiac fibroblast TLR9 was proven as stimulation with CpG B and -C caused significant CXCL2 and TNFα-release. These responses were TLR9-specific as complete inhibition of receptor-stimulated responses was achieved by co-treatment with a TLR9-antagonist (ODN 2088 or chloroquine diphosphate. TLR9-stimulated responses were also found more potent in cardiac fibroblasts when compared with classical innate immune cells. Stimulation of cardiac fibroblasts TLR9 was also found to attenuate migration and proliferation, but did not influence myofibroblast differentiation in vitro. Finally, results from in vivo TLR9-stimulation with subsequent fractionation of specific cardiac cell-types (cardiac myocytes, CD45+ cells, CD31+ cells and cardiac fibroblast-enriched cell-fractions corroborated our in vitro data and provided evidence of differentiated cell-specific cardiac responses. Thus, we conclude that cardiac fibroblast may constitute a significant TLR9 responder cell within the myocardium and, further, that such receptor activity may impact important cardiac fibroblast cellular functions.

Dissociation of social and nonsocial anxiety in a mouse model of fragile X syndrome

OpenAIRE

Liu, Zhong-Hua; Smith, Carolyn Beebe

2009-01-01

Anxiety is a common symptom in fragile X patients. However, an anxiety-prone phenotype in mouse models of fragile X syndrome is not clear. In most studies of fmr1 knockout mice, decreased anxiety-like responses in exploratory-based models are found, but mice also exhibit abnormal social interactions. We hypothesize the coexistence of elevated social anxiety and reduced nonsocial anxiety in fmr1 knockout mice. In the present study, we applied an automated three-chambered social approach method...

FORWARD: A Registry and Longitudinal Clinical Database to Study Fragile X Syndrome.

Science.gov (United States)

Sherman, Stephanie L; Kidd, Sharon A; Riley, Catharine; Berry-Kravis, Elizabeth; Andrews, Howard F; Miller, Robert M; Lincoln, Sharyn; Swanson, Mark; Kaufmann, Walter E; Brown, W Ted

2017-06-01

Advances in the care of patients with fragile X syndrome (FXS) have been hampered by lack of data. This deficiency has produced fragmentary knowledge regarding the natural history of this condition, healthcare needs, and the effects of the disease on caregivers. To remedy this deficiency, the Fragile X Clinic and Research Consortium was established to facilitate research. Through a collective effort, the Fragile X Clinic and Research Consortium developed the Fragile X Online Registry With Accessible Research Database (FORWARD) to facilitate multisite data collection. This report describes FORWARD and the way it can be used to improve health and quality of life of FXS patients and their relatives and caregivers. FORWARD collects demographic information on individuals with FXS and their family members (affected and unaffected) through a 1-time registry form. The longitudinal database collects clinician- and parent-reported data on individuals diagnosed with FXS, focused on those who are 0 to 24 years of age, although individuals of any age can participate. The registry includes >2300 registrants (data collected September 7, 2009 to August 31, 2014). The longitudinal database includes data on 713 individuals diagnosed with FXS (data collected September 7, 2012 to August 31, 2014). Longitudinal data continue to be collected on enrolled patients along with baseline data on new patients. FORWARD represents the largest resource of clinical and demographic data for the FXS population in the United States. These data can be used to advance our understanding of FXS: the impact of cooccurring conditions, the impact on the day-to-day lives of individuals living with FXS and their families, and short-term and long-term outcomes. Copyright © 2017 by the American Academy of Pediatrics.

[Fragile X syndrome and white matter abnormalities: Case study of two brothers].

Science.gov (United States)

Wallach, E; Bieth, E; Sevely, A; Cances, C

2017-03-01

Fragile X syndrome is the most usual cause of hereditary intellectual deficiency. Typical symptoms combine intellectual deficiency, social anxiety, intense emotional vigilance, and a characteristic facial dysmorphy. This is subsequent to a complete mutation of the FMR1 gene, considering a semidominant transmission linked to the unstable X. The expansion of the CGG triplet greater than 200 units combined with a high methylation pattern lead to a transcriptional silence of the FMR1 gene, and the protein product, the FMRP, is not synthesized. This protein is involved in synaptic plasticity. Brain MRI can show an increased volume of the caudate nucleus and hippocampus, combined with hypoplasia of the cerebellar vermis. Fragile X Associated Tremor Ataxia Syndrome (FXTAS) syndrome is a neurodegenerative disorder occurring in carriers of the premutation in FMR1. Brain MRI shows an increased T2 signal in the middle cerebellar peduncles. This syndrome is linked to a premutation in the FMR1 gene. We report here the case of two brothers presenting a typical fragile X symptomatology. Brain MRI showed hyperintensities of the middle cerebellar peduncles. Such MRI findings support the assumption of a genetic mosaicism. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Delineating the Profile of Autism Spectrum Disorder Characteristics in Cornelia de Lange and Fragile X Syndromes

Science.gov (United States)

Moss, Joanna; Oliver, Chris; Nelson, Lisa; Richards, Caroline; Hall, Scott

2013-01-01

An atypical presentation of autism spectrum disorder is noted in Cornelia de Lange and Fragile X syndromes, but there are few detailed empirical descriptions. Participants in this study were individuals with Cornelia de Lange syndrome (n = 130, M age = 17.19), Fragile X syndrome (n = 182, M age = 16.94), and autism spectrum disorder (n = 142, M…

Roles of PDE1 in Pathological Cardiac Remodeling and Dysfunction.

Science.gov (United States)

Chen, Si; Knight, Walter E; Yan, Chen

2018-04-23

Pathological cardiac hypertrophy and dysfunction is a response to various stress stimuli and can result in reduced cardiac output and heart failure. Cyclic nucleotide signaling regulates several cardiac functions including contractility, remodeling, and fibrosis. Cyclic nucleotide phosphodiesterases (PDEs), by catalyzing the hydrolysis of cyclic nucleotides, are critical in the homeostasis of intracellular cyclic nucleotide signaling and hold great therapeutic potential as drug targets. Recent studies have revealed that the inhibition of the PDE family member PDE1 plays a protective role in pathological cardiac remodeling and dysfunction by the modulation of distinct cyclic nucleotide signaling pathways. This review summarizes recent key findings regarding the roles of PDE1 in the cardiac system that can lead to a better understanding of its therapeutic potential.

Fragile X Proteins FMRP and FXR2P Control Synaptic GluA1 Expression and Neuronal Maturation via Distinct Mechanisms

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Weixiang Guo

2015-06-01

Full Text Available Fragile X mental retardation protein (FMRP and its autosomal paralog FXR2P are selective neuronal RNA-binding proteins, and mice that lack either protein exhibit cognitive deficits. Although double-mutant mice display more severe learning deficits than single mutants, the molecular mechanism behind this remains unknown. In the present study, we discovered that FXR2P (also known as FXR2 is important for neuronal dendritic development. FMRP and FXR2P additively promote the maturation of new neurons by regulating a common target, the AMPA receptor GluA1, but they do so via distinct mechanisms: FXR2P binds and stabilizes GluA1 mRNA and enhances subsequent protein expression, whereas FMRP promotes GluA1 membrane delivery. Our findings unveil important roles for FXR2P and GluA1 in neuronal development, uncover a regulatory mechanism of GluA1, and reveal a functional convergence between fragile X proteins in neuronal development.

Prediction of significant conduction disease through noninvasive assessment of cardiac calcification.

Science.gov (United States)

Mainigi, Sumeet K; Chebrolu, Lakshmi Hima Bindu; Romero-Corral, Abel; Mehta, Vinay; Machado, Rodolfo Rozindo; Konecny, Tomas; Pressman, Gregg S

2012-10-01

Cardiac calcification is associated with coronary artery disease, arrhythmias, conduction disease, and adverse cardiac events. Recently, we have described an echocardiographic-based global cardiac calcification scoring system. The objective of this study was to evaluate the severity of cardiac calcification in patients with permanent pacemakers as based on this scoring system. Patients with a pacemaker implanted within the 2-year study period with a previous echocardiogram were identified and underwent blinded global cardiac calcium scoring. These patients were compared to matched control patients without a pacemaker who also underwent calcium scoring. The study group consisted of 49 patients with pacemaker implantation who were compared to 100 matched control patients. The mean calcium score in the pacemaker group was 3.3 ± 2.9 versus 1.8 ± 2.0 (P = 0.006) in the control group. Univariate and multivariate analysis revealed glomerular filtration rate and calcium scoring to be significant predictors of the presence of a pacemaker. Echocardiographic-based calcium scoring correlates with the presence of severe conduction disease requiring a pacemaker. © 2012, Wiley Periodicals, Inc.

Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model.

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Monyak, R E; Emerson, D; Schoenfeld, B P; Zheng, X; Chambers, D B; Rosenfelt, C; Langer, S; Hinchey, P; Choi, C H; McDonald, T V; Bolduc, F V; Sehgal, A; McBride, S M J; Jongens, T A

2017-08-01

Fragile X syndrome (FXS) is an undertreated neurodevelopmental disorder characterized by low intelligence quotent and a wide range of other symptoms including disordered sleep and autism. Although FXS is the most prevalent inherited cause of intellectual disability, its mechanistic underpinnings are not well understood. Using Drosophila as a model of FXS, we showed that select expression of dfmr1 in the insulin-producing cells (IPCs) of the brain was sufficient to restore normal circadian behavior and to rescue the memory deficits in the fragile X mutant fly. Examination of the insulin signaling (IS) pathway revealed elevated levels of Drosophila insulin-like peptide 2 (Dilp2) in the IPCs and elevated IS in the dfmr1 mutant brain. Consistent with a causal role for elevated IS in dfmr1 mutant phenotypes, the expression of dfmr1 specifically in the IPCs reduced IS, and genetic reduction of the insulin pathway also led to amelioration of circadian and memory defects. Furthermore, we showed that treatment with the FDA-approved drug metformin also rescued memory. Finally, we showed that reduction of IS is required at different time points to rescue circadian behavior and memory. Our results indicate that insulin misregulation underlies the circadian and cognitive phenotypes displayed by the Drosophila fragile X model, and thus reveal a metabolic pathway that can be targeted by new and already approved drugs to treat fragile X patients.

Cardiac and pericardial tumors: A potential application of positron emission tomography-magnetic resonance imaging.

Science.gov (United States)

Fathala, Ahmed; Abouzied, Mohei; AlSugair, Abdul-Aziz

2017-07-26

Cardiac and pericardial masses may be neoplastic, benign and malignant, non-neoplastic such as thrombus or simple pericardial cysts, or normal variants cardiac structure can also be a diagnostic challenge. Currently, there are several imaging modalities for diagnosis of cardiac masses; each technique has its inherent advantages and disadvantages. Echocardiography, is typically the initial test utilizes in such cases, Echocardiography is considered the test of choice for evaluation and detection of cardiac mass, it is widely available, portable, with no ionizing radiation and provides comprehensive evaluation of cardiac function and valves, however, echocardiography is not very helpful in many cases such as evaluation of extracardiac extension of mass, poor tissue characterization, and it is non diagnostic in some cases. Cross sectional imaging with cardiac computed tomography provides a three dimensional data set with excellent spatial resolution but utilizes ionizing radiation, intravenous iodinated contrast and relatively limited functional evaluation of the heart. Cardiac magnetic resonance imaging (CMR) has excellent contrast resolution that allows superior soft tissue characterization. CMR offers comprehensive evaluation of morphology, function, tissue characterization. The great benefits of CMR make CMR a highly useful tool in the assessment of cardiac masses. (Fluorine 18) fluorodeoxygluocse (FDG) positron emission tomography (PET) has become a corner stone in several oncological application such as tumor staging, restaging, treatment efficiency, FDG is a very useful imaging modality in evaluation of cardiac masses. A recent advance in the imaging technology has been the development of integrated PET-MRI system that utilizes the advantages of PET and MRI in a single examination. FDG PET-MRI provides complementary information on evaluation of cardiac masses. The purpose of this review is to provide several clinical scenarios on the incremental value of PET

Are We Ready for Fragile X Newborn Screening Testing?—Lessons Learnt from a Feasibility Study

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Tiffany Wotton

2018-02-01

Full Text Available Fragile X syndrome (FXS is the most prevalent heritable cause of cognitive impairment but is not yet included in a newborn screening (NBS program within Australia. This paper aims to assess the feasibility and reliability of population screening for FXS using a pilot study in one hospital. A total of 1971 mothers consented for 2000 newborns to be tested using routine NBS dried blood spot samples. DNA was extracted and a modified PCR assay with a chimeric CGG primer was used to detect fragile X alleles in both males and females in the normal, premutation, and full mutation ranges. A routine PCR-based fragile X assay was run in parallel to validate the chimeric primer assay. Babies with CGG repeat number ≥59 were referred for family studies. One thousand nine hundred and ninety NBS samples had a CGG repeat number less than 55 (1986 < 50; 10 had premutation alleles >54 CGG repeats (1/123 females and 1/507 males. There was complete concordance between the two PCR-based assays. A recent review revealed no clinically identified cases in the cohort up to 5 years later. The cost per test was $AUD19. Fragile X status can be determined on routine NBS samples using the chimeric primer assay. However, whilst this assay may not be considered cost-effective for population screening, it could be considered as a second-tier assay to a developed immunoassay for fragile X mental retardation protein (FMRP.

The Search for an Effective Therapy to Treat Fragile X Syndrome: Dream or Reality?

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Sara Castagnola

2017-11-01

Full Text Available Fragile X Syndrome (FXS is the most common form of intellectual disability and a primary cause of autism. It originates from the lack of the Fragile X Mental Retardation Protein (FMRP, which is an RNA-binding protein encoded by the Fragile X Mental Retardation Gene 1 (FMR1 gene. Multiple roles have been attributed to this protein, ranging from RNA transport (from the nucleus to the cytoplasm, but also along neurites to translational control of mRNAs. Over the last 20 years many studies have found a large number of FMRP mRNA targets, but it is still not clear which are those playing a critical role in the etiology of FXS. So far, no therapy for FXS has been found, making the quest for novel targets of considerable importance. Several pharmacological approaches have been attempted, but, despite some promising preclinical results, no strategy gave successful outcomes, due either to the induction of major side effects or to the lack of improvement of the phenotypes. However, these studies suggested that, in order to measure the effectiveness of a specific treatment, trials should be redesigned and new endpoints defined in FXS patients. Nevertheless, the search for new therapeutic targets for FXS is very active. In this context, the advances in animal modeling, coupled with better understanding of neurobiology and physiopathology of FXS, are of crucial importance in developing new selected treatments. Here, we discuss the pathways that were recently linked to the physiopathology of FXS (mGluR, GABAR, insulin, Insulin-like Growth Factor 1 (IGF-1, MPP-9, serotonin, oxytocin and endocannabinoid signaling and that suggest new approaches to find an effective therapy for this disorder. Our goal with this review article is to summarize some recent relevant findings on FXS treatment strategies in order to have a clearer view of the different pathways analyzed to date emphasizing those shared with other synaptic disorders.

The Search for an Effective Therapy to Treat Fragile X Syndrome: Dream or Reality?

Science.gov (United States)

Castagnola, Sara; Bardoni, Barbara; Maurin, Thomas

2017-01-01

Fragile X Syndrome (FXS) is the most common form of intellectual disability and a primary cause of autism. It originates from the lack of the Fragile X Mental Retardation Protein (FMRP), which is an RNA-binding protein encoded by the Fragile X Mental Retardation Gene 1 ( FMR1 ) gene. Multiple roles have been attributed to this protein, ranging from RNA transport (from the nucleus to the cytoplasm, but also along neurites) to translational control of mRNAs. Over the last 20 years many studies have found a large number of FMRP mRNA targets, but it is still not clear which are those playing a critical role in the etiology of FXS. So far, no therapy for FXS has been found, making the quest for novel targets of considerable importance. Several pharmacological approaches have been attempted, but, despite some promising preclinical results, no strategy gave successful outcomes, due either to the induction of major side effects or to the lack of improvement of the phenotypes. However, these studies suggested that, in order to measure the effectiveness of a specific treatment, trials should be redesigned and new endpoints defined in FXS patients. Nevertheless, the search for new therapeutic targets for FXS is very active. In this context, the advances in animal modeling, coupled with better understanding of neurobiology and physiopathology of FXS, are of crucial importance in developing new selected treatments. Here, we discuss the pathways that were recently linked to the physiopathology of FXS (mGluR, GABAR, insulin, Insulin-like Growth Factor 1 (IGF-1), MPP-9, serotonin, oxytocin and endocannabinoid signaling) and that suggest new approaches to find an effective therapy for this disorder. Our goal with this review article is to summarize some recent relevant findings on FXS treatment strategies in order to have a clearer view of the different pathways analyzed to date emphasizing those shared with other synaptic disorders.

Erythrocyte Osmotic Fragility and Excitability Score in Rabbit fed ...

African Journals Online (AJOL)

olayemitoyin

protect cells against oxidative stress in rats (Wang et al., 2000) and ... method, total red blood cell (RBC) count, total leukocyte (WBC) count .... maturative stages of the erythroblast (pluripotent stem cells) involved in cell formation (Kaur and. Kapoor, 2005). ... effect of zinc on chlorpyrifos- induced erythrocyte fragility in wistar ...

Modeling Family Dynamics in Children with Fragile X Syndrome

Science.gov (United States)

Hall, Scott S.; Burns, David D.; Reiss, Allan L.

2007-01-01

Few studies have examined the impact of children with genetic disorders and their unaffected siblings on family functioning. In this study, the reciprocal causal links between problem behaviors and maternal distress were investigated in 150 families containing a child with fragile X syndrome (FXS) and an unaffected sibling. Both children's…

Implicit Procedural Learning in Fragile X and Down Syndrome

Science.gov (United States)

Bussy, G.; Charrin, E.; Brun, A.; Curie, A.; des Portes, V.

2011-01-01

Background: Procedural learning refers to rule-based motor skill learning and storage. It involves the cerebellum, striatum and motor areas of the frontal lobe network. Fragile X syndrome, which has been linked with anatomical abnormalities within the striatum, may result in implicit procedural learning deficit. Methods: To address this issue, a…

Long term government debt, financial fragility, and sovereign default risk

NARCIS (Netherlands)

van der Kwaak, C.; van Wijnbergen, S.

2013-01-01

We analyze the interaction between bank rescues, financial fragility and sovereign debt discounts. To that end we set up a model that contains balance sheet constrained financial intermediaries financing both capital expenditure of intermediate goods producers and government deficits. The financial

Evidence of cardiac involvement in the fetal inflammatory response syndrome: disruption of gene networks programming cardiac development in nonhuman primates.

Science.gov (United States)

Mitchell, Timothy; MacDonald, James W; Srinouanpranchanh, Sengkeo; Bammler, Theodor K; Merillat, Sean; Boldenow, Erica; Coleman, Michelle; Agnew, Kathy; Baldessari, Audrey; Stencel-Baerenwald, Jennifer E; Tisoncik-Go, Jennifer; Green, Richard R; Gale, Michael J; Rajagopal, Lakshmi; Adams Waldorf, Kristina M

2018-04-01

Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understanding of the effects of inflammation on fetal cardiac development may lead to insight into the fetal origins of adult cardiovascular disease. The purpose of this study was to determine whether the fetal inflammatory response syndrome is associated with disruptions in gene networks that program fetal cardiac development. We obtained fetal cardiac tissue after necropsy from a well-described pregnant nonhuman primate model (pigtail macaque, Macaca nemestrina) of intrauterine infection (n=5) and controls (n=5). Cases with the fetal inflammatory response syndrome (fetal plasma interleukin-6 >11 pg/mL) were induced by either choriodecidual inoculation of a hypervirulent group B streptococcus strain (n=4) or intraamniotic inoculation of Escherichia coli (n=1). RNA and protein were extracted from fetal hearts and profiled by microarray and Luminex (Millipore, Billerica, MA) for cytokine analysis, respectively. Results were validated by quantitative reverse transcriptase polymerase chain reaction. Statistical and bioinformatics analyses included single gene analysis, gene set analysis, Ingenuity Pathway Analysis (Qiagen, Valencia, CA), and Wilcoxon rank sum. Severe fetal inflammation developed in the context of intraamniotic infection and a disseminated bacterial infection in the fetus. Interleukin-6 and -8 in fetal cardiac tissues were elevated significantly in fetal inflammatory response syndrome cases vs controls (P1.5-fold change, P<.05) in the fetal heart (analysis of variance). Altered expression of select genes was validated by quantitative reverse transcriptase polymerase chain reaction that included several with known functions in cardiac injury, morphogenesis

Language and Learning in Boys with Fragile X Syndrome: Syntactic Processing and the Role of Phonological Memory

Science.gov (United States)

Kover, Sara T.

2012-01-01

Fragile X syndrome is the leading inherited cause of intellectual disability. Most boys with fragile X syndrome have impaired cognition and language deficits, with significant within-syndrome variability. Syntax may be especially delayed relative to nonverbal cognition; however, little is known about the specificity of delay, the sources of that…

A Benign Cardiac Growth but Not So Indolent

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Adil S. Wani

2016-01-01

Full Text Available Cardiac lipomatous hypertrophy is a rare benign condition that usually involves the interatrial septum. Due to its benign nature it rarely requires intervention. Its presence outside the interatrial septum is reported infrequently. We present a case of lipomatous hypertrophy in the intraventricular septum that was complicated by a severe, symptomatic, and disabling dynamic left ventricular outflow tract obstruction. The symptoms significantly improved following the excision of the mass. In our case transthoracic echocardiogram was used to visualize the mass and measure the severity of the obstruction; Cardiac Magnetic Resonance Imaging was used to characterize the mass and histopathology confirmed the diagnosis.

Systematic review of pharmacological treatments in fragile X syndrome

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Tejada Maria-Isabel

2009-10-01

Full Text Available Abstract Background Fragile X syndrome (FXS is considered the most common cause of inherited mental retardation. Affected people have mental impairment that can include Attention Deficit and/or Hyperactivity Disorder (ADHD, autism disorder, and speech and behavioural disorders. Several pharmacological interventions have been proposed to treat those impairments. Methods Systematic review of the literature and summary of the evidence from clinical controlled trials that compared at least one pharmacological treatment with placebo or other treatment in individuals with diagnosis of FXS syndrome and assessed the efficacy and/or safety of the treatments. Studies were identified by a search of PubMed, EMBASE and the Cochrane Databases using the terms fragile X and treatment. Risk of bias of the studies was assessed by using the Cochrane Collaboration criteria. Results The search identified 276 potential articles and 14 studies satisfied inclusion criteria. Of these, 10 studies on folic acid (9 with crossover design, only 1 of them with good methodological quality and low risk of bias did not find in general significant improvements. A small sample size trial assessed dextroamphetamine and methylphenidate in patients with an additional diagnosis of ADHD and found some improvements in those taking methylphenidate, but the length of follow-up was too short. Two studies on L-acetylcarnitine, showed positive effects and no side effects in patients with an additional diagnosis of ADHD. Finally, one study on patients with an additional diagnosis of autism assessed ampakine compound CX516 and found no significant differences between treatment and placebo. Regarding safety, none of the studies that assessed that area found relevant side effects, but the number of patients included was too small to detect side effects with low incidence. Conclusion Currently there is no robust evidence to support recommendations on pharmacological treatments in patients with

Bile salt-induced increases in duodenal brush-border membrane proton permeability, fluidity, and fragility

International Nuclear Information System (INIS)

Zhao, D.L.; Hirst, B.H.

1990-01-01

Rabbit duodenal brush-border membrane vesicles were treated in vitro with deoxycholate, glycodeoxycholate, or taurodeoxycholate. Intravesicular [14C]glucose space at equilibrium, 0.54 microliters/mg protein, was reduced by exposure to the three bile salts in a concentration (0.1-5.0 mM)-dependent manner, equatable with increased membrane fragility. Net proton permeability (Pnet), determined by acridine orange fluorescence quenching, was increased from 6.3 x 10(-4) cm/sec in untreated vesicles, by approximately 120, 150, and 170%, by treatment with bile salts at 0.1, 0.5 and 1.0 mM, respectively. The three bile salts were equipotent. The increases in membrane fragility and Pnet were not accompanied by significant increases in membrane fluidity, as assessed from steady-state and time-resolved diphenylhexatriene fluorescence anisotropy. The data demonstrate direct effects of bile salts on duodenal apical membrane fragility and proton permeability that are likely to be early events in bile salt-induced mucosal damage

Mosaicism for the FMR1 gene influences adaptive skills development in fragile X-affected males

Energy Technology Data Exchange (ETDEWEB)

Cohen, I.L.; Sudhalter, V.; Nolin, S.L. [New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY (United States)

1996-08-09

Fragile X syndrome is one of the most common forms of inherited mental retardation, and the first of a new class of genetic disorders associated with expanded trinucleotide repeats. Previously, we found that about 41% of affected males are mosaic for this mutation in that some of their blood cells have an active fragile X gene and others do not. It has been hypothesized that these mosaic cases should show higher levels of functioning than those who have only the inactive full mutation gene, but previous studies have provided negative or equivocal results. In the present study, the cross-sectional development of communication, self-care, socialization, and motor skills was studied in 46 males with fragile X syndrome under age 20 years as a function of two variables: age and the presence or absence of mosaicism. The rate of adaptive skills development was 2-4 times as great in mosaic cases as in full mutation cases. There was also a trend for cases with autism to be more prevalent in the full-mutation group. These results have implications for prognosis, for the utility of gene or protein replacement therapies for this disorder, and for understanding the association between mental retardation, developmental disorders, and fragile X syndrome. 21 refs., 3 figs.

The numerical computation of seismic fragility of base-isolated Nuclear Power Plants buildings

International Nuclear Information System (INIS)

Perotti, Federico; Domaneschi, Marco; De Grandis, Silvia

2013-01-01

Highlights: • Seismic fragility of structural components in base isolated NPP is computed. • Dynamic integration, Response Surface, FORM and Monte Carlo Simulation are adopted. • Refined approach for modeling the non-linearities behavior of isolators is proposed. • Beyond-design conditions are addressed. • The preliminary design of the isolated IRIS is the application of the procedure. -- Abstract: The research work here described is devoted to the development of a numerical procedure for the computation of seismic fragilities for equipment and structural components in Nuclear Power Plants; in particular, reference is made, in the present paper, to the case of isolated buildings. The proposed procedure for fragility computation makes use of the Response Surface Methodology to model the influence of the random variables on the dynamic response. To account for stochastic loading, the latter is computed by means of a simulation procedure. Given the Response Surface, the Monte Carlo method is used to compute the failure probability. The procedure is here applied to the preliminary design of the Nuclear Power Plant reactor building within the International Reactor Innovative and Secure international project; the building is equipped with a base isolation system based on the introduction of High Damping Rubber Bearing elements showing a markedly non linear mechanical behavior. The fragility analysis is performed assuming that the isolation devices become the critical elements in terms of seismic risk and that, once base-isolation is introduced, the dynamic behavior of the building can be captured by low-dimensional numerical models

[Cardiac involvement in Churg-Strauss syndrome].

Science.gov (United States)

Brucato, Antonio; Maestroni, Silvia; Masciocco, Gabriella; Ammirati, Enrico; Bonacina, Edgardo; Pedrotti, Patrizia

2015-09-01

agents, particularly cyclophosphamide in case of myocardial inflammation. Thus, early diagnosis of cardiac involvement and subsequent therapy may prevent progression of cardiac disease. At present, the role of troponin and brain natriuretic peptide in monitoring and therapy remains unclear. Orthotopic heart transplantation is feasible in case of severe disease, even if the experience is limited in -EGPA, and optimal post-transplantation immunosuppressive strategy has yet to be defined.

Developmental Trajectories of Young Girls with Fragile X Syndrome

Science.gov (United States)

Hatton, Deborah D.; Wheeler, Anne; Sideris, John; Sullivan, Kelly; Reichardt, Alison; Roberts, Jane; Clark, Renee; Bailey, Donald B., Jr.

2009-01-01

To describe the early phenotype of girls with full mutation fragile X, we used 54 observations of 15 girls between the ages of 6 months and 9 years to examine developmental trajectories as measured by the Battelle Development Inventory. In this sample, autistic behavior was associated with poorer developmental outcomes, primarily due to…

Fiscal deficits, financial fragility, and the effectiveness of government policies

NARCIS (Netherlands)

Kirchner, M.; van Wijnbergen, S.

2012-01-01

Recent macro developments in the euro area have highlighted the interactions between fiscal policy, sovereign debt, and financial fragility. We take a structural macroeconomic model with frictions in the financial intermediation process, in line with recent research, but introduce asset choice and

Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins.

Directory of Open Access Journals (Sweden)

Eric K Johnson

Full Text Available Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.

Effects of Sampling Context on Spontaneous Expressive Language in Males with Fragile X Syndrome or Down Syndrome

Science.gov (United States)

Kover, Sara T.; McDuffie, Andrea; Abbeduto, Leonard; Brown, W. Ted

2012-01-01

Purpose: In this study, the authors examined the impact of sampling context on multiple aspects of expressive language in male participants with fragile X syndrome in comparison to male participants with Down syndrome or typical development. Method: Participants with fragile X syndrome (n = 27), ages 10-17 years, were matched groupwise on…

Seismic Fragility Analysis of a Condensate Storage Tank with Age-Related Degradations

Energy Technology Data Exchange (ETDEWEB)

Nie, J. [Brookhaven National Lab. (BNL), Upton, NY (United States); Braverman, J. [Brookhaven National Lab. (BNL), Upton, NY (United States); Hofmayer, C [Brookhaven National Lab. (BNL), Upton, NY (United States); Choun, Y-S [Brookhaven National Lab. (BNL), Upton, NY (United States); Kim, MK [Brookhaven National Lab. (BNL), Upton, NY (United States); Choi, I-K [Brookhaven National Lab. (BNL), Upton, NY (United States)

2011-04-01

The Korea Atomic Energy Research Institute (KAERI) is conducting a five-year research project to develop a realistic seismic risk evaluation system which includes the consideration of aging of structures and components in nuclear power plants (NPPs). The KAERI research project includes three specific areas that are essential to seismic probabilistic risk assessment (PRA): (1) probabilistic seismic hazard analysis, (2) seismic fragility analysis including the effects of aging, and (3) a plant seismic risk analysis. Since 2007, Brookhaven National Laboratory (BNL) has entered into a collaboration agreement with KAERI to support its development of seismic capability evaluation technology for degraded structures and components. The collaborative research effort is intended to continue over a five year period. The goal of this collaboration endeavor is to assist KAERI to develop seismic fragility analysis methods that consider the potential effects of age-related degradation of structures, systems, and components (SSCs). The research results of this multi-year collaboration will be utilized as input to seismic PRAs. This report describes the research effort performed by BNL for the Year 4 scope of work. This report was developed as an update to the Year 3 report by incorporating a major supplement to the Year 3 fragility analysis. In the Year 4 research scope, an additional study was carried out to consider an additional degradation scenario, in which the three basic degradation scenarios, i.e., degraded tank shell, degraded anchor bolts, and cracked anchorage concrete, are combined in a non-perfect correlation manner. A representative operational water level is used for this effort. Building on the same CDFM procedure implemented for the Year 3 Tasks, a simulation method was applied using optimum Latin Hypercube samples to characterize the deterioration behavior of the fragility capacity as a function of age-related degradations. The results are summarized in Section 5

Cardiac involvement in canine babesiosis : review article

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R.G. Lobetti

2005-06-01

Full Text Available Cardiac dysfunction in canine babesiosis has traditionally been regarded as a rare complication, with the majority of lesions reported as incidental findings at post-mortem examination. Recent studies have, however, demonstrated cardiac lesions in canine babesiosis. Cardiac troponins, especially troponin I, are sensitive markers of myocardial injury in canine babesiosis, and the magnitude of elevation of plasma troponin I concentrations appears to be proportional to the severity of the disease. ECG changes in babesiosis are similar to the pattern described for myocarditis and myocardial ischaemia and together with histopathological findings indicate that the heart suffers from the same pathological processes described in other organs in canine babesiosis, namely inflammation and hypoxia. The clinical application of the ECG appears to be limited and thus cardiovascular assessment should be based on functional monitoring rather than an ECG tracing. On cardiac histopathology from dogs that succumbed to babesiosis, haemorrhage, necrosis, inflammation and fibrin microthrombi in the myocardium were documented, all of which would have resulted in ECG changes and elevations in cardiac troponin. Myocardial damage causes left ventricular failure, which will result in hypotension and an expansion of the plasma volume due to homeostatic mechanisms.

Aggravating andmitigating factors associated with cyclist injury severity in Denmark

DEFF Research Database (Denmark)

Kaplan, Sigal; Vavatsoulas,, Konstantinos; Prato, Carlo Giacomo

2014-01-01

severity on Danish roads by examining a comprehensive set of accidents involving a cyclist and a collision partner between 2007 and 2011. Method: This study estimates a generalized ordered logit model of the severity of cyclist injuries because of its ability to accommodate the ordered-response nature...... of severity while relaxing the proportional odds assumption. Results: Model estimates show that cyclist fragility (children under 10 years old and elderly cyclists over 60 years of age) and cyclist intoxication are aggravating individual factors,while helmet use is a mitigating factor. Speed limits above 70...

Anxiety and depression among amyloid light-chain cardiac amyloidosis patients: The role of life satisfaction.

Science.gov (United States)

Smorti, Martina; Guarnieri, Silvia; Bergesio, Franco; Perfetto, Federico; Cappelli, Francesco

2016-06-01

The present study aimed to provide a contribution to the study of a rare disease, amyloid light-chain (AL) cardiac amyloidosis, which is the most common type of systemic amyloidosis. In AL amyloidosis prognosis is determined by cardiac involvement. Although the association between psychological distress (e.g. anxiety and depression) and AL cardiac amyloidosis is documented, very little is known about the psychosocial variables that may mediate the association. The aim of the study is therefore to examine the potential mediating role of life satisfaction in the relationship between cardiac symptom severity (independent variable) and anxious and depressive symptoms (dependent variables) in AL patients. Forty-three AL amyloidosis patients (57.1% males) with cardiac amyloidosis were administered the Satisfaction with Life Scale, the State-Trait Anxiety Inventory and the Centre for Epidemiological Study-Depression Scale. Clinical variables such as months since cardiac symptom onset and cardiac symptom severity were collected. Findings showed significant relationships between symptom severity and psychological disorders (e.g. anxiety and depression) and these were mediated by life satisfaction. Overall, findings highlight the importance of subjective well-being (e.g. life satisfaction) to reduce anxious and depressive symptoms and to improve general health in AL patients. © The European Society of Cardiology 2015.

Synaptic vesicle dynamic changes in a model of fragile X.

Science.gov (United States)

Broek, Jantine A C; Lin, Zhanmin; de Gruiter, H Martijn; van 't Spijker, Heleen; Haasdijk, Elize D; Cox, David; Ozcan, Sureyya; van Cappellen, Gert W A; Houtsmuller, Adriaan B; Willemsen, Rob; de Zeeuw, Chris I; Bahn, Sabine

2016-01-01

Fragile X syndrome (FXS) is a single-gene disorder that is the most common heritable cause of intellectual disability and the most frequent monogenic cause of autism spectrum disorders (ASD). FXS is caused by an expansion of trinucleotide repeats in the promoter region of the fragile X mental retardation gene (Fmr1). This leads to a lack of fragile X mental retardation protein (FMRP), which regulates translation of a wide range of messenger RNAs (mRNAs). The extent of expression level alterations of synaptic proteins affected by FMRP loss and their consequences on synaptic dynamics in FXS has not been fully investigated. Here, we used an Fmr1 knockout (KO) mouse model to investigate the molecular mechanisms underlying FXS by monitoring protein expression changes using shotgun label-free liquid-chromatography mass spectrometry (LC-MS(E)) in brain tissue and synaptosome fractions. FXS-associated candidate proteins were validated using selected reaction monitoring (SRM) in synaptosome fractions for targeted protein quantification. Furthermore, functional alterations in synaptic release and dynamics were evaluated using live-cell imaging, and interpretation of synaptic dynamics differences was investigated using electron microscopy. Key findings relate to altered levels of proteins involved in GABA-signalling, especially in the cerebellum. Further exploration using microscopy studies found reduced synaptic vesicle unloading of hippocampal neurons and increased vesicle unloading in cerebellar neurons, which suggests a general decrease of synaptic transmission. Our findings suggest that FMRP is a regulator of synaptic vesicle dynamics, which supports the role of FMRP in presynaptic functions. Taken together, these studies provide novel insights into the molecular changes associated with FXS.

Clinical and genetic predictors of major cardiac events in patients with Anderson-Fabry Disease.

Science.gov (United States)

Patel, Vimal; O'Mahony, Constantinos; Hughes, Derralynn; Rahman, Mohammad Shafiqur; Coats, Caroline; Murphy, Elaine; Lachmann, Robin; Mehta, Atul; Elliott, Perry M

2015-06-01

Anderson-Fabry Disease (AFD) is an X linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene. Some mutations are associated with prominent and, in many cases, exclusive cardiac involvement. The primary aims of this study were to determine the incidence of major cardiac events in AFD and to identify clinical and genetic predictors of adverse outcomes. We studied 207 patients with AFD (47% male, mean age 44 years, mean follow-up 7.1 years). Fifty-eight (28%) individuals carried mutations that have been previously associated with a cardiac predominant phenotype. Twenty-one (10%) developed severe heart failure (New York Heart Association functional class (NYHA) ≥3), 13 (6%) developed atrial fibrillation (AF), 13 (6%) received devices for the treatment of bradycardia; there were a total of 7 (3%) cardiac deaths. The incidence of the primary endpoint (a composite of new onset AF, NYHA ≥ 3 symptoms, device insertion for bradycardia and cardiac death) was 2.64 per 100 person-years (CI 1.78 to 3.77). Age (HR 1.04, CI 1.01 to 1.08, p=0.004), Mainz Severity Score Index score (HR 1.05, CI 1.01 to 1.09, p=0.012) and QRS duration (HR 1.03, CI 1.00 to 1.05, p=0.020) were significant independent predictors of the primary endpoint. The presence of a cardiac genetic variant did not predict the primary end point. AFD is associated with a high burden of cardiac morbidity and mortality. Adverse cardiac outcomes are associated with age, global disease severity and advanced cardiac disease but not the presence of cardiac genetic variants. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Acute nursing care of the older adult with fragility hip fracture

DEFF Research Database (Denmark)

Maher, A.B.; Meehan, A.J.; Hertz, K.

2013-01-01

. Pressure Ulcers. Fluid Balance/Nutrition. Constipation/Catheter Associated Urinary Tract Infection. Vigilant nursing assessment and prompt intervention may prevent the development of the complications we discuss. If they do occur and are identified early on, they may resolve with appropriate and timely......The second part of this paper provides those who care for orthopaedic patients with evidence-supported international perspectives about acute nursing care of the older adult with fragility hip fracture. Developed by an international group of nurse experts and guided by a range of information from...... research and clinical practice, it focuses on nurse sensitive quality indicators during the acute hospitalisation for fragility hip fracture. Optimal care for the patient who has experienced such a fracture is the focus. This includes (in the first, earlier, part):. Pain. Delirium. and in this part...

An Efficient Semi-fragile Watermarking Scheme for Tamper Localization and Recovery

Science.gov (United States)

Hou, Xiang; Yang, Hui; Min, Lianquan

2018-03-01

To solve the problem that remote sensing images are vulnerable to be tampered, a semi-fragile watermarking scheme was proposed. Binary random matrix was used as the authentication watermark, which was embedded by quantizing the maximum absolute value of directional sub-bands coefficients. The average gray level of every non-overlapping 4×4 block was adopted as the recovery watermark, which was embedded in the least significant bit. Watermarking detection could be done directly without resorting to the original images. Experimental results showed our method was robust against rational distortions to a certain extent. At the same time, it was fragile to malicious manipulation, and realized accurate localization and approximate recovery of the tampered regions. Therefore, this scheme can protect the security of remote sensing image effectively.

Preliminary Seismic Response and Fragility Analysis for DACS Cabinet

Energy Technology Data Exchange (ETDEWEB)

Oh, Jinho; Kwag, Shinyoung; Lee, Jongmin; Kim, Youngki [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-05-15

A DACS cabinet is installed in the main control room. The objective of this paper is to perform seismic analyses and evaluate the preliminary structural integrity and seismic capacity of the DACS cabinet. For this purpose, a 3-D finite element model of the DACS cabinet was developed and its modal analyses are carried out to analyze the dynamic characteristics. The response spectrum analyses and the related safety evaluation are then performed for the DACS cabinet subject to seismic loads. Finally, the seismic margin and seismic fragility of the DACS cabinet are investigated. A seismic analysis and preliminary structural integrity of the DACS cabinet under self weight and SSE load have been evaluated. For this purpose, 3-D finite element models of the DACS cabinet were developed. A modal analysis, response spectrum analysis, and seismic fragility analysis were then performed. From the structural analysis results, the DACS cabinet is below the structural design limit of under SSE 0.3g, and can structurally withstand until less than SSE 3g based on an evaluation of the maximum effective stresses. The HCLPF capacity for the DGRS of the SSE 0.3g is 0.55g. A modal analysis, response spectrum analysis, and seismic fragility analysis were then performed. From the structural analysis results, the DACS cabinet is below the structural design limit of under SSE 0.3g, and can structurally withstand until less than SSE 3g based on an evaluation of the maximum effective stresses. The HCLPF capacity for the DGRS of the SSE 0.3g is 0.55g. Therefore, it is concluded that the DACS cabinet was safely designed in that no damage to the preliminary structural integrity and sufficient seismic margin is expected.

Preliminary Seismic Response and Fragility Analysis for DACS Cabinet

International Nuclear Information System (INIS)

Oh, Jinho; Kwag, Shinyoung; Lee, Jongmin; Kim, Youngki

2013-01-01

A DACS cabinet is installed in the main control room. The objective of this paper is to perform seismic analyses and evaluate the preliminary structural integrity and seismic capacity of the DACS cabinet. For this purpose, a 3-D finite element model of the DACS cabinet was developed and its modal analyses are carried out to analyze the dynamic characteristics. The response spectrum analyses and the related safety evaluation are then performed for the DACS cabinet subject to seismic loads. Finally, the seismic margin and seismic fragility of the DACS cabinet are investigated. A seismic analysis and preliminary structural integrity of the DACS cabinet under self weight and SSE load have been evaluated. For this purpose, 3-D finite element models of the DACS cabinet were developed. A modal analysis, response spectrum analysis, and seismic fragility analysis were then performed. From the structural analysis results, the DACS cabinet is below the structural design limit of under SSE 0.3g, and can structurally withstand until less than SSE 3g based on an evaluation of the maximum effective stresses. The HCLPF capacity for the DGRS of the SSE 0.3g is 0.55g. A modal analysis, response spectrum analysis, and seismic fragility analysis were then performed. From the structural analysis results, the DACS cabinet is below the structural design limit of under SSE 0.3g, and can structurally withstand until less than SSE 3g based on an evaluation of the maximum effective stresses. The HCLPF capacity for the DGRS of the SSE 0.3g is 0.55g. Therefore, it is concluded that the DACS cabinet was safely designed in that no damage to the preliminary structural integrity and sufficient seismic margin is expected

Infant Development in Fragile X Syndrome: Cross-Syndrome Comparisons

Science.gov (United States)

Roberts, Jane E.; McCary, Lindsay M.; Shinkareva, Svetlana V.; Bailey, Donald B., Jr.

2016-01-01

This study examined the developmental profile of male infants with fragile X syndrome (FXS) and its divergence from typical development and development of infants at high risk for autism associated with familial recurrence (ASIBs). Participants included 174 boys ranging in age from 5 to 28 months. Cross-sectional profiles on the Mullen Scales of…

Cardiac tamponade: contrast reflux as an indicator of cardiac chamber equalization

Directory of Open Access Journals (Sweden)

Nauta Foeke Jacob

2012-05-01

Full Text Available Abstract Background Traumatic hemopericardium remains a rare entity; it does however commonly cause cardiac tamponade which remains a major cause of death in traumatic blunt cardiac injury. Objectives We present a case of blunt chest trauma complicated by cardiac tamponade causing cardiac chamber equalization revealed by reflux of contrast. Case report A 29-year-old unidentified male suffered blunt chest trauma in a motor vehicle collision. Computed tomography (CT demonstrated a periaortic hematoma and hemopericardium. Significant contrast reflux was seen in the inferior vena cava and hepatic veins suggesting a change in cardiac chamber pressures. After intensive treatment including cardiac massage this patient expired of cardiac arrest. Conclusion Reflux of contrast on CT imaging can be an indicator of traumatic cardiac tamponade.

Atomic and electronic structures of an extremely fragile liquid.

Science.gov (United States)

Kohara, Shinji; Akola, Jaakko; Patrikeev, Leonid; Ropo, Matti; Ohara, Koji; Itou, Masayoshi; Fujiwara, Akihiko; Yahiro, Jumpei; Okada, Junpei T; Ishikawa, Takehiko; Mizuno, Akitoshi; Masuno, Atsunobu; Watanabe, Yasuhiro; Usuki, Takeshi

2014-12-18

The structure of high-temperature liquids is an important topic for understanding the fragility of liquids. Here we report the structure of a high-temperature non-glass-forming oxide liquid, ZrO2, at an atomistic and electronic level. The Bhatia-Thornton number-number structure factor of ZrO2 does not show a first sharp diffraction peak. The atomic structure comprises ZrO5, ZrO6 and ZrO7 polyhedra with a significant contribution of edge sharing of oxygen in addition to corner sharing. The variety of large oxygen coordination and polyhedral connections with short Zr-O bond lifetimes, induced by the relatively large ionic radius of zirconium, disturbs the evolution of intermediate-range ordering, which leads to a reduced electronic band gap and increased delocalization in the ionic Zr-O bonding. The details of the chemical bonding explain the extremely low viscosity of the liquid and the absence of a first sharp diffraction peak, and indicate that liquid ZrO2 is an extremely fragile liquid.

Clinical application of cardiac SPECT

International Nuclear Information System (INIS)

Nishimura, Shigeyuki

1999-01-01

Single-photon emission computed tomography (SPECT) has replaced planar imaging techniques for myocardial scintigraphy. Thallium-201 was the dominant agent employed for myocardial perfusion imaging. Today new technetium-99m labelled radionuclides have been used as excellent alternatives to 201 Tl for detection of coronary artery disease, prognostification, and even assessment of myocardial viability. Pharmacologic stress imaging using either dipyridamole, adenosine or dobutamine is a substitute for exercise stress. Accurate determination of myocardial viability is vitally important for clinical decision making for patients with LV dysfunction who will most benefit from revascularization. Stunned and hibernated myocardium may result in profound regional LTV dysfunction in absence of necrosis. The various approach such as stress-redistribution-reinjection imaging, rest-redistribution imaging and stress-redistribution-24 hours delayed imaging has been utilized to assess myocardial viability with 201 Tl. Quantitative assessment of 99m Tc MIBI uptake reflect the degree of viability. 123 I-Metaiodobenzylguanidine (MIBG), an analog of norepinephrine, has been used for scintigraphic assessment of regional cardiac adrenergic innervation. Cardiac sympathetic denervation, assessed by 123 I-MIBG, due to ischemia in non-Q myocardial infarction and unstable angina has been shown. Quantitative cardiac MIBG scintigram was shown to have prognostic value in patients with severe congestive heart failure. 23 I-BMIPP (ρ-methyl-iodophenyl pentadecanoic acid) has been used to assess myocardial fatty acid utilization. BMIPP has the memory function of ischemia in unstable angina, since decreased BMIPP uptake persists several days after ischemic episode. Nuclear cardiology in Japan has experienced an expansion in the techniques including use of new radionuclides, 99m Tc perfusion agents, 123 I-MIBG and 23 I-BMIPP and in associated clinical application to the various cardiac diseases

GENERAL OVERGROWTH IN THE FRAGILE-X SYNDROME - VARIABILITY IN THE PHENOTYPIC-EXPRESSION OF THE FMR1 GENE MUTATION

NARCIS (Netherlands)

DEVRIES, BBA; ROBINSON, H; STOLTEDIJKSTRA, [No Value; GI, CVTP; DIJKSTRA, PF; VANDOOM, J; HALLEY, DJJ; OOSTRA, BA; TURNER, G; NIERMEIJER, MF

1995-01-01

The fragile X syndrome, which often presents in childhood with overgrowth, may in some cases show some diagnostic overlap with classical Sotos syndrome. We describe four fragile X patients with general overgrowth, all of whom are from families with other affected relatives who show the classic

A Case Report of Primary Cardiac Tumor in A Neonate

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Sh. Rejaei

2008-04-01

Full Text Available Introduction: Primary cardiac tumors are extremely rare in infants and children . Most primary cardiac tumors in pediatric age group are benign, and less than 10% of such tumors are malignant. Many of these tumors are asymptomatic and incidentally diagnosed. The clinical manifestations are very different and includes direct cardiac effect, systemic effect , and embolic phenomena. Every infant or child with an unusual cardiac murmur, unexplained congestive heart failure, or arrhythmia should be evaluated for cardiac tumors. Echocardiography has contributed significantly to the evaluation of these patients. Surgery is the only treatment for primary cardiac tumors that require intervention with a relatively good prognosis. Case Report: The patient was a 20 days old neonate presented with severe congestive heart failure. Evaluation of the patient showed primary cardiac tumor in the left atrium and ventricle. We recommended surgical removal of the tumor but her parents denied surgical intervention at all. Conclusion: After about one year follow up, congestive heart failure symptoms were controlled and the tumor size was decreased.

Immune mediated disorders in women with a fragile X expansion and FXTAS.

Science.gov (United States)

Jalnapurkar, Isha; Rafika, Nuva; Tassone, Flora; Hagerman, Randi

2015-01-01

Premutation alleles in fragile X mental retardation 1 (FMR1) can cause the late-onset neurodegenerative disorder, fragile X-associated tremor ataxia syndrome (FXTAS) and/or the fragile X-associated primary ovarian insufficiency in approximately 20% of heterozygotes. Heterozygotes of the FMR1 premutation have a higher incidence of immune mediated disorders such as autoimmune thyroid disorder, especially when accompanied by FXTAS motor signs. We describe the time course of symptoms of immune mediated disorders and the subsequent development of FXTAS in four women with an FMR1 CGG expansion, including three with the premutation and one with a gray zone expansion. These patients developed an immune mediated disorder followed by neurological symptoms that become consistent with FXTAS. In all patients we observed a pattern involving an initial appearance of disease symptoms-often after a period of heightened stress (depression, anxiety, divorce, general surgery) followed by the onset of tremor and/or ataxia. Immune mediated diseases are associated with the manifestations of FXTAS temporally, although further studies are needed to clarify this association. If a cause and effect relationship can be established, treatment of pre-existing immune mediated disorders may benefit patients with pathogenic FMR1 mutations. © 2014 Wiley Periodicals, Inc.

Transient cardiac arrest in patient with left ventricular noncompaction (spongiform cardiomyopathy).

Science.gov (United States)

Yamazaki, Shinya; Ito, Hiroshi; Kawaai, Hiroyoshi

2011-01-01

Left ventricular noncompaction (LVNC), also known as spongiform cardiomyopathy, is a severe disease that has not previously been discussed with respect to general anesthesia. We treated a child with LVNC who experienced cardiac arrest. Dental treatment under general anesthesia was scheduled because the patient had a risk of endocarditis due to dental caries along with a history of being uncooperative for dental care. During sevoflurane induction, severe hypotension and laryngospasm resulted in cardiac arrest. Basic life support (cardiopulmonary resuscitation) was initiated to resuscitate the child, and his cardiorespiratory condition improved. Thereafter, an opioid-based anesthetic was performed, and recovery was smooth. In LVNC, opioid-based anesthesia is suggested to avoid the significant cardiac suppression seen with a volatile anesthetic, once intravenous access is established. Additionally, all operating room staff should master Advanced Cardiac Life Support/Pediatric Advanced Life Support (including intraosseous access), and more than 1 anesthesiologist should be present to induce general anesthesia, if possible, for this high-risk patient.

Regulation of cardiac remodeling by cardiac Na/K-ATPase isoforms

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Lijun Catherine Liu

2016-09-01

Full Text Available Cardiac remodeling occurs after cardiac pressure/volume overload or myocardial injury during the development of heart failure and is a determinant of heart failure. Preventing or reversing remodeling is a goal of heart failure therapy. Human cardiomyocyte Na+/K+-ATPase has multiple α isoforms (1-3. The expression of the α subunit of the Na+/K+-ATPase is often altered in hypertrophic and failing hearts. The mechanisms are unclear. There are limited data from human cardiomyocytes. Abundant evidences from rodents show that Na+/K+-ATPase regulates cardiac contractility, cell signaling, hypertrophy and fibrosis. The α1 isoform of the Na+/K+-ATPase is the ubiquitous isoform and possesses both pumping and signaling functions. The α2 isoform of the Na+/K+-ATPase regulates intracellular Ca2+ signaling, contractility and pathological hypertrophy. The α3 isoform of the Na+/K+-ATPase may also be a target for cardiac hypertrophy. Restoration of cardiac Na+/K+-ATPase expression may be an effective approach for prevention of cardiac remodeling. In this article, we will overview: (1 the distribution and function of isoform specific Na+/K+-ATPase in the cardiomyocytes. (2 the role of cardiac Na+/K+-ATPase in the regulation of cell signaling, contractility, cardiac hypertrophy and fibrosis in vitro and in vivo. Selective targeting of cardiac Na+/K+-ATPase isoform may offer a new target for the prevention of cardiac remodeling.

Induced Pluripotent Stem Cells 10 Years Later: For Cardiac Applications.

Science.gov (United States)

Yoshida, Yoshinori; Yamanaka, Shinya

2017-06-09

Induced pluripotent stem cells (iPSCs) are reprogrammed cells that have features similar to embryonic stem cells, such as the capacity of self-renewal and differentiation into many types of cells, including cardiac myocytes. Although initially the reprogramming efficiency was low, several improvements in reprogramming methods have achieved robust and efficient generation of iPSCs without genomic insertion of transgenes. iPSCs display clonal variations in epigenetic and genomic profiles and cellular behavior in differentiation. iPSC-derived cardiac myocytes (iPSC cardiac myocytes) recapitulate phenotypic differences caused by genetic variations, making them attractive human disease models, and are useful for drug discovery and toxicology testing. In addition, iPSC cardiac myocytes can help with patient stratification in regard to drug responsiveness. Furthermore, they can be used as source cells for cardiac regeneration in animal models. Here, we review recent progress in iPSC technology and its applications to cardiac diseases. © 2017 American Heart Association, Inc.

Maternal role attainment with medically fragile infants: Part 2. relationship to the quality of parenting.

Science.gov (United States)

Holditch-Davis, Diane; Miles, Margaret Shandor; Burchinal, Margaret R; Goldman, Barbara Davis

2011-02-01

We examined which components of maternal role attainment (identity, presence, competence) influenced quality of parenting for 72 medically fragile infants, controlling for maternal education and infant illness severity. Maternal competence was related to responsiveness. Maternal presence and technology dependence were inversely related to participation. Greater competence and maternal education were associated with better normal caregiving. Presence was negatively related although competence was positively related to illness-related caregiving. Mothers with lower competence and more technology dependent children perceived their children as more vulnerable and child cues as more difficult to read. Maternal role attainment influenced parenting quality for these infants more than did child illness severity; thus interventions are needed to help mothers develop their maternal role during hospitalization and after discharge. © 2010 Wiley Periodicals, Inc. Res Nurs Health 34:35-48, 2011. Copyright © 2010 Wiley Periodicals, Inc.

Study of the Boson Peak and Fragility of Bioprotectant Glass-Forming Mixtures by Neutron Scattering

Directory of Open Access Journals (Sweden)

F. Migliardo

2013-01-01

Full Text Available The biological relevance of trehalose, glycerol, and their mixtures in several anhydrobiotic and cryobiotic organisms has recently promoted both experimental and simulation studies. In addition, these systems are employed in different industrial fields, such as pharmaceutical and cosmetic industries, as additives in mixtures for cryopreservation and in several formulations. This review article shows an overview of Inelastic Neutron Scattering (INS data, collected at different temperature values by the OSIRIS time-of-flight spectrometer at the ISIS Facility (Rutherford Appleton Laboratory, Oxford, UK and by the IN4 and IN6 spectrometers at the Institut Laue Langevin (ILL, Grenoble, France, on trehalose/glycerol mixtures as a function of the glycerol content. The data analysis allows determining the Boson peak behavior and discussing the findings in terms of fragility in relation to the bioprotective action of trehalose and glycerol.

A tool for the calculation of rockfall fragility curves for masonry buildings

Science.gov (United States)

Mavrouli, Olga

2017-04-01

Masonries are common structures in mountainous and coastal areas and they exhibit substantial vulnerability to rockfalls. For big rockfall events or precarious structures the damage is very high and the repair is not cost-effective. Nonetheless, for small or moderate rockfalls, the damage may vary in function of the characteristics of the impacting rock blocks and of the buildings. The evaluation of the expected damage for masonry buildings, and for different small and moderate rockfall scenarios, is useful for assessing the expected direct loss at constructed areas, and its implications for life safety. A tool for the calculation of fragility curves for masonry buildings which are impacted by rock blocks is presented. The fragility curves provide the probability of exceeding a given damage state (low, moderate and high) for increasing impact energies of the rock blocks on the walls. The damage states are defined according to a damage index equal to the percentage of the damaged area of a wall, as being proportional to the repair cost. Aleatoric and epistemic uncertainties are incorporated with respect to the (i) rock block velocity, (ii) rock block size, (iii) masonry width, and (iv) masonry resistance. The calculation of the fragility curves is applied using a Monte Carlo simulation. Given user-defined data for the average value of these four parameters and their variability, random scenarios are developed, the respective damage index is assessed for each scenario, and the probability of exceedance of each damage state is calculated. For the assessment of the damage index, a database developed by the results of 576 analytical simulations is used. The variables range is: wall width 0.4 - 1.0 m, wall tensile strength 0.1 - 0.6 MPa, rock velocity 1-20 m/s, rock size 1-20 m3. Nonetheless this tool permits the use of alternative databases, on the condition that they contain data that correlate the damage with the four aforementioned variables. The fragility curves can

Aortic valve bypass surgery in severe aortic valve stenosis: Insights from cardiac and brain magnetic resonance imaging.

Science.gov (United States)

Mantini, Cesare; Caulo, Massimo; Marinelli, Daniele; Chiacchiaretta, Piero; Tartaro, Armando; Cotroneo, Antonio Raffaele; Di Giammarco, Gabriele

2018-04-13

To investigate and describe the distribution of aortic and cerebral blood flow (CBF) in patients with severe valvular aortic stenosis (AS) before and after aortic valve bypass (AVB) surgery. We enrolled 10 consecutive patients who underwent AVB surgery for severe AS. Cardiovascular magnetic resonance imaging (CMR) and brain magnetic resonance imaging were performed as baseline before surgery and twice after surgery. Quantitative flow measurements were obtained using 1.5-T magnetic resonance imaging (MRI) scanner phase-contrast images of the ascending aorta, descending thoracic aorta (3 cm proximally and distally from the conduit-to-aorta anastomosis), and ventricular outflow portion of the conduit. The evaluation of CBF was performed using 3.0-T MRI scanner arterial spin labeling (ASL) through sequences acquired at the gray matter, dorsal default-mode network, and sensorimotor levels. Conduit flow, expressed as the percentage of total antegrade flow through the conduit, was 63.5 ± 8% and 67.8 ± 7% on early and mid-term postoperative CMR, respectively (P surgery in patients with severe AS, cardiac output is split between the native left ventricular outflow tract and the apico-aortic bypass, with two-thirds of the total antegrade flow passing through the latter and one-third passing through the former. In our experience, CBF assessment confirms that the flow redistribution does not jeopardize cerebral blood supply. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.