Fragile and conflict affected states: report from the Consultation on Collaboration for Applied Health Research and Delivery

PubMed Central

2014-01-01

Fragile and Conflict Affected States present difficult contexts to achieve health system outcomes and are neglected in health systems research. This report presents key debates from the Consultation of the Collaboration for Applied Health Research and Delivery, Liverpool, June, 2014.

Role of DNA secondary structures in fragile site breakage along human chromosome 10

PubMed Central

Dillon, Laura W.; Pierce, Levi C. T.; Ng, Maggie C. Y.; Wang, Yuh-Hwa

2013-01-01

The formation of alternative DNA secondary structures can result in DNA breakage leading to cancer and other diseases. Chromosomal fragile sites, which are regions of the genome that exhibit chromosomal breakage under conditions of mild replication stress, are predicted to form stable DNA secondary structures. DNA breakage at fragile sites is associated with regions that are deleted, amplified or rearranged in cancer. Despite the correlation, unbiased examination of the ability to form secondary structures has not been evaluated in fragile sites. Here, using the Mfold program, we predict potential DNA secondary structure formation on the human chromosome 10 sequence, and utilize this analysis to compare fragile and non-fragile DNA. We found that aphidicolin (APH)-induced common fragile sites contain more sequence segments with potential high secondary structure-forming ability, and these segments clustered more densely than those in non-fragile DNA. Additionally, using a threshold of secondary structure-forming ability, we refined legitimate fragile sites within the cytogenetically defined boundaries, and identified potential fragile regions within non-fragile DNA. In vitro detection of alternative DNA structure formation and a DNA breakage cell assay were used to validate the computational predictions. Many of the regions identified by our analysis coincide with genes mutated in various diseases and regions of copy number alteration in cancer. This study supports the role of DNA secondary structures in common fragile site instability, provides a systematic method for their identification and suggests a mechanism by which DNA secondary structures can lead to human disease. PMID:23297364

Earthquake fragility assessment of curved and skewed bridges in Mountain West region : research brief.

DOT National Transportation Integrated Search

2016-09-01

the ISSUE : the RESEARCH : Earthquake Fragility : Assessment of Curved : and Skewed Bridges in : Mountain West Region : Reinforced concrete bridges with both skew and curvature are common in areas with complex terrains. : These bridges are irregular ...

Patterns of funding allocation for tuberculosis control in fragile states.

PubMed

Warsame, A; Patel, P; Checchi, F

2014-01-01

To assess recent (2006-2010) tuberculosis (TB) funding patterns in conflict and non-conflict-affected fragile states to inform global policy. The Creditor Reporting System was analysed for official development assistance funding disbursements towards TB control in 11 conflict-affected states, 17 non-conflict-affected fragile states and 38 comparable non-fragile states. The amounts of funding, funding relative to burden, funding relative to malaria and human immunodeficiency virus (HIV) control, disbursements relative to commitments, sources of funding as well as funding activities were extracted and analysed. Fragile states received on average more per capita for TB control relative to non-fragile states (US0.159 vs. US0.079). However conflict-affected fragile states received on average less per capita than non-conflict-affected states (US0.144 vs. US0.203), despite worse development indicators. Conflict-affected fragile states also received on average only 70% of TB funds already committed. Analysis by burden revealed the least disparity in funding in highest prevalence settings. Analysis of funding activities suggests increasing importance of TB-HIV integration, multidrug-resistant TB and research in both fragile and non-fragile states. Relative to non-conflict-affected fragile states, conflict-affected fragile states received approximately two thirds the per capita funding for TB. This study revealed disparities in TB control funding between fragile and non-fragile as well as between conflict and non-conflict-affected fragile states. Findings suggest possible avenues for improving the allocation of global TB funding.

Fragile X Syndrome in Males: Diagnostic, Behavioral, and Educational Implications.

ERIC Educational Resources Information Center

Bellinger, Diane; And Others

This paper reviews the research on fragile X syndrome, the second most common cause of mental retardation related to chromosomal anomaly. It notes that far more males than females are affected by the fragile X syndrome, which typically results in craniofacial changes, delays in growth and development, speech/language difficulties, and cognitive…

Consistency between Research and Clinical Diagnoses of Autism among Boys and Girls with Fragile X Syndrome

ERIC Educational Resources Information Center

Klusek, J.; Martin, G. E.; Losh, M.

2014-01-01

Background: Prior research suggests that 60-74% of males and 16-45% of females with fragile X syndrome (FXS) meet criteria for autism spectrum disorder (ASD) in research settings. However, relatively little is known about the rates of clinical diagnoses in FXS and whether such diagnoses are consistent with those performed in a research setting…

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

PubMed

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.

Heart Activity and Autistic Behavior in Infants and Toddlers with Fragile X Syndrome

PubMed Central

Roberts, Jane E.; Tonnsen, Bridgette; Robinson, Ashley; Shinkareva, Svetlana V.

2014-01-01

The present study contrasted physiological arousal in infants and toddlers with fragile X syndrome to typically developing control participants and examined physiological predictors early in development to autism severity later in development in fragile X syndrome. Thirty-one males with fragile X syndrome (ages 8–40 months) and 25 age-matched control participants were included. The group with fragile X syndrome showed shorter interbeat intervals (IBIs), lower vagal tone (VT), and less modulation of IBI. Data suggested a nonlinear effect with IBI and autistic behavior; however, a linear effect with VT and autistic behavior emerged. These findings suggest that atypical physiological arousal emerges within the first year and predicts severity of autistic behavior in fragile X syndrome. These relationships are complex and dynamic, likely reflecting endogenous factors assumed to reflect atypical brain function secondary to reduced fragile X mental retardation protein. This research has important implications for the early identification and treatment of autistic behaviors in young children with fragile X syndrome. PMID:22515825

The Fragile X Continuum: New Advances and Perspectives

ERIC Educational Resources Information Center

Cornish, K.; Turk, J.; Hagerman, R.

2008-01-01

Fragile X syndrome is the world's most common hereditary cause of intellectual disability in men and to a lesser extent in women. The disorder is caused by the silencing of a single gene on the X chromosome, the Fragile X Mental Retardation Gene-1. A substantial body of research across the disciplines of molecular genetics, child psychiatry and…

Fragile X Syndrome: An Aging Perspective

ERIC Educational Resources Information Center

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…

Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site.

PubMed

Letessier, Anne; Millot, Gaël A; Koundrioukoff, Stéphane; Lachagès, Anne-Marie; Vogt, Nicolas; Hansen, R Scott; Malfoy, Bernard; Brison, Olivier; Debatisse, Michelle

2011-02-03

Common fragile sites have long been identified by cytogeneticists as chromosomal regions prone to breakage upon replication stress. They are increasingly recognized to be preferential targets for oncogene-induced DNA damage in pre-neoplastic lesions and hotspots for chromosomal rearrangements in various cancers. Common fragile site instability was attributed to the fact that they contain sequences prone to form secondary structures that may impair replication fork movement, possibly leading to fork collapse resulting in DNA breaks. Here we show, in contrast to this view, that the fragility of FRA3B--the most active common fragile site in human lymphocytes--does not rely on fork slowing or stalling but on a paucity of initiation events. Indeed, in lymphoblastoid cells, but not in fibroblasts, initiation events are excluded from a FRA3B core extending approximately 700 kilobases, which forces forks coming from flanking regions to cover long distances in order to complete replication. We also show that origins of the flanking regions fire in mid-S phase, leaving the site incompletely replicated upon fork slowing. Notably, FRA3B instability is specific to cells showing this particular initiation pattern. The fact that both origin setting and replication timing are highly plastic in mammalian cells explains the tissue specificity of common fragile site instability we observed. Thus, we propose that common fragile sites correspond to the latest initiation-poor regions to complete replication in a given cell type. For historical reasons, common fragile sites have been essentially mapped in lymphocytes. Therefore, common fragile site contribution to chromosomal rearrangements in tumours should be reassessed after mapping fragile sites in the cell type from which each tumour originates.

Psychological Well-Being of Mothers of Youth with Fragile X Syndrome: Syndrome Specificity and within-Syndrome Variability

ERIC Educational Resources Information Center

Lewis, P.; Abbeduto, L.; Murphy, M.; Richmond, E.; Giles, N.; Bruno, L.; Schroeder, S.; Anderson, J.; Orsmond, G.

2006-01-01

Background: Research on parental well-being has focused largely on Down syndrome and autism; however, fragile X syndrome is likely to pose different challenges for parents compared with these other diagnostic conditions. Moreover, there is considerable variability among youth with fragile X syndrome; for example, 25% to 33% of affected youth meet…

Scaling up nutrition in fragile and conflict-affected states: the pivotal role of governance.

PubMed

Taylor, Sebastian A J; Perez-Ferrer, Carolina; Griffiths, Andrew; Brunner, Eric

2015-02-01

Acute and chronic undernutrition undermine conditions for health, stability and socioeconomic development across the developing world. Although fragile and conflict-affected states have some of the highest rates of undernutrition globally, their response to the multilateral 'Scaling Up Nutrition' (SUN) initiative in its first two-year period was ambivalent. The purpose of this research was to investigate factors affecting fragile and conflict-affected states' engagement with SUN, and to examine what differentiated those fragile states that joined SUN in its first phase from those that did not. Drawing on global databases (Unicef, World Bank, UNDP), and qualitative country case studies (Afghanistan, the Democratic Republic of Congo, Sierra Leone, Pakistan and Yemen) we used bivariate logistic regressions and principal component analysis to assess social, economic and political factors across 41 fragile states looking for systematic differences between those that had signed up to SUN before March 2013 (n = 16), and those that had not (n = 25). While prevalence of malnutrition, health system functioning and level of citizen empowerment had little or no impact on a fragile state's likelihood of joining SUN, the quality of governance (QOG) strongly predicted accession. SUN-signatory fragile states scored systematically better on the World Bank's Country Policy and Institutional Assessment (CPIA) and the Worldwide Governance Indicators 'effectiveness of government' indices. We conclude that strengthening governance in fragile states may enhance their engagement with initiatives such as SUN, but also (recognising the potential for endogeneity), that the way aid is structured and delivered in fragile states may be an underlying determinant of whether and how governance in such contexts improves. The research demonstrates that more nuanced analysis of conditions within and among countries classed as 'fragile and conflict-affected' is both possible and necessary if aid policies are to be shaped in ways that support rather than undermine growth in governance capacity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Learning about Fragile X Syndrome

MedlinePlus

... Physical problems that have been seen include eye, orthopedic, heart and skin problems. Girls who have the ... to their sons. Top of page NHGRI Clinical Research on Fragile X Syndrome Currently, NHGRI is not ...

Clinicians' experiences with the fragile X clinical and research consortium.

PubMed

Liu, Jessica A; Hagerman, Randi J; Miller, Robert M; Craft, Lisa T; Finucane, Brenda; Tartaglia, Nicole; Berry-Kravis, Elizabeth M; Sherman, Stephanie L; Kidd, Sharon A; Cohen, Jeffrey

2016-12-01

The objectives of the study were to assess the attitudes and experiences of clinicians involved in a consortium of clinics serving people with fragile X-associated disorders to gauge satisfaction with the consortium and its efforts to improve quality of life for patients and the community. An internet survey was sent to 26 fragile X (FX) clinic directors participating in the Fragile X Clinical and Research Consortium (FXCRC). Respondents were asked to complete 19 questions on consortium performance and outcomes relevant for their own clinic. The response rate was 84% (22/26), with two surveys providing incomplete data. Assistance with clinic establishment, opportunities for research collaborations, and access to colleagues and information were highly valued. Approximately 76% of clinicians reported improvements in patient care and 60% reported an increase in patient services. There was a 57% increase in participation in a FX-related clinical trial among clinics since joining the FXCRC (24% vs. 81%). Overall, respondents reported primarily positive experiences from participation in the FXCRC. Common suggestions for improvement included additional financial support and increased utilization of collected patient data for research purposes. Additionally, a Clinic Services Checklist was administered annually to examine changes in services offered over time. There were several important changes regarding the provision of services by clinics, often with multiple clinics changing with respect to a service. In conclusion, the FXCRC has led to the establishment and sustainment of fragile X clinics in the U.S., fostered cooperation among fragile X clinicians, and provided clinics with a platform to share recommendations and best practices to maximize quality of life for their patients and the overall fragile X community. The results from the survey and checklist also provide suggestions to strengthen the FXCRC and enhance future collaborations among FXCRC members. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

PubMed

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.

Adjusting for car occupant injury liability in relation to age, speed limit, and gender-specific driver crash involvement risk.

PubMed

Keall, Michael; Frith, William

2004-12-01

It is well established that older drivers' fragility is an important factor associated with higher levels of fatal crash involvement for older drivers. There has been less research on age-related fragility with respect to the sort of minor injuries that are more common in injury crashes. This study estimates a quantity that is related to injury fragility: the probability that a driver or a passenger of that driver will be injured in crashes involving two cars. The effects of other factors apart from drivers' fragility are included in this measure, including the fragility of the passengers, the crashworthiness of cars driven, seatbelt use by the occupants, and characteristics of crashes (including configuration and impact speed). The car occupant injury liability estimates appropriately includes these factors to adjust risk curves by age, gender, and speed limit accounting for overrepresentation in crashes associated with fragility and these other factors.

The mGluR theory of fragile X mental retardation.

PubMed

Bear, Mark F; Huber, Kimberly M; Warren, Stephen T

2004-07-01

Many of the diverse functional consequences of activating group 1 metabotropic glutamate receptors require translation of pre-existing mRNA near synapses. One of these consequences is long-term depression (LTD) of transmission at hippocampal synapses. Loss of fragile X mental retardation protein (FMRP), the defect responsible for fragile X syndrome in humans, increases LTD in mouse hippocampus. This finding is consistent with the growing evidence that FMRP normally functions as a repressor of translation of specific mRNAs. Here we present a theory that can account for diverse neurological and psychiatric aspects of fragile X syndrome, based on the assumption that many of the protein-synthesis-dependent functions of metabotropic receptors are exaggerated in fragile X syndrome. The theory suggests new directions for basic research as well as novel therapeutic approaches for the treatment of humans with fragile X, the most frequent inherited cause of mental retardation and an identified cause of autism.

Flooding Fragility Experiments and Prediction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Curtis L.; Tahhan, Antonio; Muchmore, Cody

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.

Parents' Decisions to Screen Their Newborn for Fragile X Syndrome. FPG Snapshot #63

ERIC Educational Resources Information Center

FPG Child Development Institute, 2011

2011-01-01

State newborn screening (NBS) programs have expanded in recent years, and more tests may be added in the future. The expansion of neonatal screening raises ethical, legal, and social questions. The questions surrounding NBS for fragile X syndrome (FXS) typify these concerns. FXS is an X-linked genetic condition that is the most common inherited…

Remote sensing research on fragile ecological environment in continental river basin

NASA Astrophysics Data System (ADS)

Wang, Ranghui; Peng, Ruyan; Zhang, Huizhi

2003-07-01

Based on some remote sensing data and software platform of image processing and analysis, the standard image for ecological thematic mapping is decided. Moreover, the vegetation type maps and land sandy desertification type maps are made. Relaying on differences of natural resources and ecological environment in Tarim River Basin, the assessment indicator system and ecological fragility index (EFI) of ecological environment are built up. The assessment results are very severely. That is, EFI is only 0.08 in Akesu River Basin, it belongs to slight fragility area. EFI of Yarkant River Basin and upper reaches of Tarim River Basin are 0.23 and 0.25 respectively, both of them belong to general fragility areas. Meanwhile, EFI of Hotan River Basin and middle reaches of Tarim River Basin are 0.32 and 0.49 respectively; they all belong to middle fragility areas. However, the fragility of the lower reaches of Tarim River Basin belongs to severe fragility area that the EFI is 0.87.The maladjustment among water with hot and land as well as salt are hindrance of energy transfer and material circulation and information transmission. It is also the main reason that caused ecological environment fragility.

Aid effectiveness and programmatic effectiveness: a proposed framework for comparative evaluation of different aid interventions in a particular health system.

PubMed

Haque, Hasibul; Hill, Philip C; Gauld, Robin

2017-01-01

Against a backdrop of changing concepts of aid effectiveness, development effectiveness, health systems strengthening, and increasing emphasis on impact evaluation, this article proposes a theory-driven impact evaluation framework to gauge the effect of aid effectiveness principles on programmatic outcomes of different aid funded programs in the health sector of a particular country. The foundation and step-by-step process of implementing the framework are described. With empirical evidence from the field, the steps involve analysis of context, program designs, implementation mechanisms, outcomes, synthesis, and interpretation of findings through the programs' underlying program theories and interactions with the state context and health system. The framework can be useful for comparatively evaluating different aid interventions both in fragile and non-fragile state contexts.

Design prototype detection tools of Porous Tree using microcontroller Arduino Uno R3 and piezoelectric sensor

NASA Astrophysics Data System (ADS)

Sujadi, H.; Bastian, A.; Tira

2018-05-01

In the city, many trees are found uprooted and cause accidents and many losses. No exception in the area of Majalengka Regency of West Java Province which can also anytime an accident or disaster caused by fallen trees, where in Majalengka district is logging trees on the street and public places are not done regularly. Based on the above problems, the need for tools that can detect a porous tree, to assist in the sorting of trees which should be felled and not felled by the party who has the authority of the general management of BMCK. Previously created tools to detect porous trees imported from Hungary and Germany, namely Arbosonic3D and Sonic Tomography. This design uses piezoelectric sensors to detect how much pressure is received by fragile and fragile trees, of course the fragile and fragile strength of trees will be different when exposed to the same pressure given the fragile density of fragile and fragile trees, then the data sent to Arduino Uno R3 to be processed into an information. This research produces a means of detecting the loss of a tree for early detection and no falling trees.

Seismic Fragility Analysis of a Condensate Storage Tank with Age-Related Degradations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nie, J.; Braverman, J.; Hofmayer, C

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 structuresmore » 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 and Appendices G through I.« less

What has been learned from mouse models of the Fragile X Premutation and Fragile X-associated tremor/ataxia syndrome?

PubMed

Foote, Molly M; Careaga, Milo; Berman, Robert F

2016-08-01

To describe in this review how research using mouse models developed to study the Fragile X premutation (PM) and Fragile X-associated tremor/ataxia syndrome (FXTAS) have contributed to understanding these disorders. PM carriers bear an expanded CGG trinucleotide repeat on the Fragile X Mental Retardation 1 (FMR1) gene, and are at risk for developing the late onset neurodegenerative disorder FXTAS. Much has been learned about these genetic disorders from the development and study of mouse models. This includes new insights into the early cellular and molecular events that occur in PM carriers and in FXTAS, the presence of multiorgan pathology beyond the CNS, immunological dysregulation, unexpected synthesis of a potentially toxic peptide in FXTAS (i.e., FMRpolyG), and evidence that the disease process may be halted or reversed by appropriate molecular therapies given early in the course of disease.

It is time for everyone to own the bone.

PubMed

Bunta, Andrew D

2011-08-01

The current status of the population's bone health has caused considerable concern in the USA and around the world. In keeping with that situation, the US Surgeon General issued a special report on Bone Health and Osteoporosis in 2004 calling attention to a rapidly increasing healthcare problem especially linked to a growing and aging population base. The report specifically cited the medical profession's failure to treat the underlying osteoporosis in elderly individuals with fragility fractures with a 20% treatment rate as the norm. It was noted that an individual fracture was a sentinel event that provided a "teachable moment" for the patient in order to prevent future fractures. Additional statistics revealed the annual total number of fragility fractures, more than two million, exceeded the combined annual total incidence of stroke, myocardial infarction, and breast cancer. Realizing that the American Heart Association and the cardiology community had a successful US national program encouraging the use of beta blockers in patients after myocardial infarction in order to prevent recurrences, the American Orthopaedic Association (AOA) embarked on a course leading to the development of a program to improve bone healthcare in elderly patients with fragility fractures. The cardiology project, "Get With The Guidelines" (GWTG), included a registry in order to document improvement in cardiac patient care. Therefore, the AOA, a leadership group of orthopaedic surgeons, decided it was time to engage the orthopaedic community in a quality improvement initiative patterned after GWTG. Thus, Own the Bone was created as a multidisciplinary program in order to engage patients and physicians from different specialties who might be involved with the bone health concerns of patients with fragility fractures. After the success of a pilot study from 2005 to 2006, Own the Bone was launched as a US national quality improvement program in 2009. It involves a turnkey protocol, utilizing a web-based registry, in order to complete ten basic measures of patient care in patients 50 years and older with fragility fractures. Those measures center on information and counseling on nutrition, physical activity, lifestyle changes, diagnosis and treatment of osteoporosis, and communication to the patient and primary care physician, mentioning the need for osteoporosis care. While this project was initially meant to be implemented in a hospital setting, it can also be applied in an outpatient clinic or emergency care facility. The program continues to expand to numerous hospitals in many states with the support of a growing number of orthopedists and allied medical specialists interested in bone health and osteoporosis. Thus, Own the Bone is a systems-based, quality improvement initiative which provides many benefits for patients with fragility fractures and their treating physicians.

Parental Relationships in Fragile Families

ERIC Educational Resources Information Center

McLanahan, Sara; Beck, Audrey N.

2010-01-01

As nonmarital childbearing escalated in the United States over the past half century, fragile families--defined as unmarried couples with children--drew increased interest from researchers and policy makers. Sara McLanahan and Audrey Beck discuss four aspects of parental relationships in these families: the quality of parents' intimate…

Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field

PubMed Central

Hunsaker, Michael R.

2013-01-01

It has become increasingly important that the field of behavioral genetics identifies not only the gross behavioral phenotypes associated with a given mutation, but also the behavioral endophenotypes that scale with the dosage of the particular mutation being studied. Over the past few years, studies evaluating the effects of the polymorphic CGG trinucleotide repeat on the FMR1 gene underlying Fragile X-Associated Disorders have reported preliminary evidence for a behavioral endophenotype in human Fragile X Premutation carrier populations as well as the CGG knock-in (KI) mouse model. More recently, the behavioral experiments used to test the CGG KI mouse model have been extended to the Fmr1 knock-out (KO) mouse model. When combined, these data provide compelling evidence for a clear neurocognitive endophenotype in the mouse models of Fragile X-Associated Disorders such that behavioral deficits scale predictably with genetic dosage. Similarly, it appears that the CGG KI mouse effectively models the histopathology in Fragile X-Associated Disorders across CGG repeats well into the full mutation range, resulting in a reliable histopathological endophenotype. These endophenotypes may influence future research directions into treatment strategies for not only Fragile X Syndrome, but also the Fragile X Premutation and Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). PMID:24627796

Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders

DTIC Science & Technology

2016-12-01

1 AWARD NUMBER: W81XWH-14-1-0433 TITLE: Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders PRINCIPAL INVESTIGATOR: Anis...SUBTITLE 5a. CONTRACT NUMBER Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders 5b. GRANT NUMBER W81XWH-14-1-0433 5c. PROGRAM...bumetanide to mice rescues synaptic and circuit dysfunction in Fragile X mice. 15. SUBJECT TERMS Autism Spectrum Disorders, Fragile X Syndrome Angelman

Capacity Development for Education Systems in Fragile Contexts. Working Paper

ERIC Educational Resources Information Center

Davies, Lynn

2009-01-01

This paper examines fragility, capacity development and education and the links between these by analysing relevant research and policy literature. It proposes ways forward for action and reflection at national, regional and international levels. An important element of capacity development in education systems is the establishment of education…

The Expressed Emotion of Mothers of Children with Fragile X Syndrome

ERIC Educational Resources Information Center

Coleman, Jeanine M.

2010-01-01

A review of the literature revealed that mothers with children with fragile X syndrome (FXS) face many challenges, including managing their child's behavior which is a defining characteristic of children with FXS (Epstein, Riley, & Sobesky, 2002). Parents and professionals have become increasingly aware through research and everyday experiences…

Strengthening Fragile Families through Research and Practice

ERIC Educational Resources Information Center

Bembry, James X.

2011-01-01

Almost one third of all children in the United States are born to unmarried parents. This figure is even higher among poor and minority populations. Because of their heightened risk for economic and social problems and family dissolution, disadvantaged, unmarried parents have been called "fragile families." In 2002 the Bush administration…

Imitation in Fragile X Syndrome: Implications for Autism

ERIC Educational Resources Information Center

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…

An Examination of Charitable Meal Programs in Five Canadian cities.

PubMed

Pettes, Tyler; Dachner, Naomi; Gaetz, Stephen; Tarasuk, Valerie

2016-01-01

While there has recently been considerable research and public investment in strategies to address homelessness in Canada, food charity remains the primary response to hunger, with little evaluation of current efforts and no initiatives to develop more effective approaches. Using data from a 2010-2011 survey of charitable food assistance in five Canadian cities, this study was undertaken to describe charitable meal provisioning in each city and to compare the relative roles of emergency programs and multi-service agencies and their capacity to meet food needs. Most meals were provided by multi-service agencies, but like emergency programs, these agencies were heavily dependent on donations and they were more likely than emergency programs to report constraints and service interruptions because demands exceeded available supplies. Our findings underscore the resource-limited and often fragile nature of charitable meal programs in Canada and highlight the need for more effective models of response to problems of hunger.

FORWARD: A Registry and Longitudinal Clinical Database to Study Fragile X Syndrome

PubMed Central

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

2017-01-01

BACKGROUND AND OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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-today lives of individuals living with FXS and their families, and short-term and long-term outcomes. PMID:28814539

FORWARD: A Registry and Longitudinal Clinical Database to Study Fragile X Syndrome.

PubMed

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.

A sample of Canadian orthopedic surgeons expressed willingness to participate in osteoporosis management for fragility fracture patients

PubMed Central

Bogoch, Earl R.; Snowden, Elizabeth

2008-01-01

Objective The orthopedic community is in a unique position to initiate and provide osteoporosis care in fragility fracture patients to prevent future hip fractures in a high-risk population. The attitudes and intentions of Canadian orthopedic surgeons in the domain of osteoporosis care are unknown. Our objective was to identify current attitudes and osteoporosis management practices and to determine their overall willingness to participate in osteoporosis care for fragility fracture patients. Methods A real-time interactive polling session was conducted at the 58th Annual Meeting of the Canadian Orthopaedic Association. Results Of the orthopedic surgeons who responded, 90.4% agreed that the current emphasis on osteoporosis in orthopedic practice is appropriate; 85.2% of surgeons indicated that they currently refer or personally investigate for osteoporosis, or both, in fragility fracture patients. Conclusion Most of the Canadian orthopedic surgeons sampled consider themselves to be currently engaged or ready to engage in osteoporosis care for fragility fracture patients. Focus should now shift from education and persuasion to program support through provision of resources and system modification that will enable Canadian orthopedic surgeons to effectively manage osteoporosis in their fracture patients. PMID:18248700

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

PubMed

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.

Identifying and Mitigating Risks in Security Sector Assistance for Africa’s Fragile States

DTIC Science & Technology

2015-01-01

The Logframe Handbook: A Logical Framework Approach to Project Cycle Management , Washington, D.C., 2005. 34 Identifying and Mitigating Risks in SSA...Fragile States 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER... Project Unique Identification Code (PUIC) for the project that produced this document is HQD126409. v Contents Preface

Navigating toward research success in times of uncertainty: funding opportunities for early career investigators in nephrology.

PubMed

Ikizler, T Alp; Lovett, David H; Chertow, Glenn M; Mitch, William E; Schiller, Brigitte

2015-03-01

There is considerable concern within the nephrology community about recent federal budget cuts and the decreasing availability of funds for research. This is especially difficult for junior investigators who are about to start a career as physician-scientists. Accordingly, it is imperative that resources other than federal funds be made available to these individuals during this most delicate yet crucial transition period. This commentary aims to provide an overview of nonfederal funding resources, focusing on the Norman S. Coplon Extramural Grant Program. This program emphasizes support of investigators at the most fragile period in their development of an academic career; it has provided >$11 million of research funds to more than 80 individuals since 2000. The outcome has been stellar, with more than 130 publications originating from these projects and >90% of awardees staying in academia. We hope these accomplishments will encourage similar activities by other entities and scientific programs in addition to ones that are ongoing. Ultimately, these collective efforts will inspire young researchers to use their knowledge, passion, and dedication to advance research into kidney diseases. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Molecular analyses of neurogenic defects in a human pluripotent stem cell model of fragile X syndrome.

PubMed

Boland, Michael J; Nazor, Kristopher L; Tran, Ha T; Szücs, Attila; Lynch, Candace L; Paredes, Ryder; Tassone, Flora; Sanna, Pietro Paolo; Hagerman, Randi J; Loring, Jeanne F

2017-03-01

New research suggests that common pathways are altered in many neurodevelopmental disorders including autism spectrum disorder; however, little is known about early molecular events that contribute to the pathology of these diseases. The study of monogenic, neurodevelopmental disorders with a high incidence of autistic behaviours, such as fragile X syndrome, has the potential to identify genes and pathways that are dysregulated in autism spectrum disorder as well as fragile X syndrome. In vitro generation of human disease-relevant cell types provides the ability to investigate aspects of disease that are impossible to study in patients or animal models. Differentiation of human pluripotent stem cells recapitulates development of the neocortex, an area affected in both fragile X syndrome and autism spectrum disorder. We have generated induced human pluripotent stem cells from several individuals clinically diagnosed with fragile X syndrome and autism spectrum disorder. When differentiated to dorsal forebrain cell fates, our fragile X syndrome human pluripotent stem cell lines exhibited reproducible aberrant neurogenic phenotypes. Using global gene expression and DNA methylation profiling, we have analysed the early stages of neurogenesis in fragile X syndrome human pluripotent stem cells. We discovered aberrant DNA methylation patterns at specific genomic regions in fragile X syndrome cells, and identified dysregulated gene- and network-level correlates of fragile X syndrome that are associated with developmental signalling, cell migration, and neuronal maturation. Integration of our gene expression and epigenetic analysis identified altered epigenetic-mediated transcriptional regulation of a distinct set of genes in fragile X syndrome. These fragile X syndrome-aberrant networks are significantly enriched for genes associated with autism spectrum disorder, giving support to the idea that underlying similarities exist among these neurodevelopmental diseases. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of Sustained Maternal Responsivity on Later Vocabulary Development in Children with Fragile X Syndrome

ERIC Educational Resources Information Center

Brady, Nancy; Warren, Steven F.; Fleming, Kandace; Keller, Juliana; Sterling, Audra

2014-01-01

Purpose: This research explored whether sustained maternal responsivity (a parent-child interaction style characterized by warmth, nurturance, and stability as well as specific behaviors, such as contingent positive responses to child initiations) was a significant variable predicting vocabulary development of children with fragile X syndrome…

Fragile Families and Child Wellbeing

ERIC Educational Resources Information Center

Waldfogel, Jane; Craigie, Terry-Ann; Brooks-Gunn, Jeanne

2010-01-01

Jane Waldfogel, Terry-Ann Craigie, and Jeanne Brooks-Gunn review recent studies that use data from the Fragile Families and Child Wellbeing Study (FFCWS) to examine why children who grow up in single-mother and cohabiting families fare worse than children born into married-couple households. They also present findings from their own new research.…

A Multidisciplinary Approach to the Management of Individuals with Fragile X Syndrome

ERIC Educational Resources Information Center

Alanay, Y.; Unal, F.; Turanli, G.; Alikasifoglu, M.; Alehan, D.; Akyol, U.; Belgin, E.; Sener, C.; Aktas, D.; Boduroglu, I.; Utine, E.; Volkan-Salanci, B.; Ozusta, S.; Genc, A.; Basar, F.; Sevinc, S.; Tuncbilek, E.

2007-01-01

Background: Fragile X syndrome (FXS) is the most common inherited form of intellectual disability. Since the identification of the responsible gene ("FMR1") and its protein (FMRP), there has been enormous progress in both clinical and pathogenetic research on the neurobehavioural aspects of the condition. However, studies regarding other medical…

Moving Toward Integrative, Multidimensional Research in Modern Psychiatry: Lessons Learned From Fragile X Syndrome.

PubMed

Fung, Lawrence K; Reiss, Allan L

2016-07-15

The field of psychiatry is approaching a major inflection point. The basic science behind cognition, emotion, behavior, and social processes has been advancing rapidly in the past 20 years. However, clinical research supporting the classification system in psychiatry has not kept up with these scientific advances. To begin organizing the basic science of psychiatry in a comprehensive manner, we begin by selecting fragile X syndrome, a neurogenetic disease with cognitive-behavioral manifestations, to illustrate key concepts in an integrative, multidimensional model. Specifically, we describe key genetic and molecular mechanisms (e.g., gamma-aminobutyric acidergic dysfunction and metabotropic glutamate receptor 5-associated long-term depression) relevant to the pathophysiology of fragile X syndrome as well as neural correlates of cognitive-behavioral symptoms. We then describe what we have learned from fragile X syndrome that may be applicable to other psychiatric disorders. We conclude this review by discussing current and future opportunities in diagnosing and treating psychiatric diseases. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

[The HIV/AIDS pandemic: African women at the heart of the control program or the difficulties with regard to gender].

PubMed

Moulin, B; Louis, J P

1999-01-01

The AIDS pandemia in developing countries forces forth the question of women's rights in Africa and underscores their extreme physical and sociocultural vulnerability. Experience gained during a program designed to reduce mother-to-child transmission of HIV in the Ivory Coast highlights the socially imposed and therefore intricate nature of differences between men and women and of the resulting relationships. Defending a woman's right to know her serologic status empowers her in the fight for emancipation but can also make her more fragile by undermining support from medical staff and family environment. To prevent the risk of outcasting, exclusion, and fragilization, gender must be given greater emphasis in planning future programs. Careful consideration must be devoted to the special sociocultural factors that affect women in Africa.

Seeking Clarity in New Jersey for Leadership Preparation Program Design: Confusion, Fragility, and Unintended Consequences

ERIC Educational Resources Information Center

Doolittle, Gini

2013-01-01

In 2004, the New Jersey Department of Education issued a mandate to the 17 leadership preparation program providers to revise their leadership preparation programs after completing a critical friends review. This case study explores the challenges, programmatic, and political experiences of one preparation program as state support dwindled.…

Agricultural Fragility Estimates Subjected to Volcanic Ash Fall Hazards

NASA Astrophysics Data System (ADS)

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 Korea. References Nimlos, T. J. and Hans, Z., The Distribution and Thickness of Volcanic Ash in Montana, Northwest Science, Vol. 56, No. 3, 1982. Wilson, T., Kaye, G., Stewart, C., and Cole, J., Impacts of the 2006 Eruption of Merapi Volcano, Indonesia, on Agriculture and Infrastructure, GNS Science Report, 2007.

Paternal Incarceration and Children's Physically Aggressive Behaviors: Evidence from the Fragile Families and Child Wellbeing Study

ERIC Educational Resources Information Center

Wildeman, Christopher

2010-01-01

This study extends research on the consequences of mass imprisonment and the causes of children's behavioral problems by considering the effects of paternal incarceration on children's physical aggression at age 5 using data from the Fragile Families and Child Wellbeing Study. Results suggest that paternal incarceration is associated with…

Growth of Expressive Syntax in Children with Fragile X Syndrome

ERIC Educational Resources Information Center

Komesidou, Rouzana; Brady, Nancy C.; Fleming, Kandace; Esplund, Amy; Warren, Steven F.

2017-01-01

Purpose: This research explored syntactic growth in children with fragile X syndrome (FXS) over a 5-year period, and variability in growth in relation to autism symptoms, nonverbal cognition, maternal responsivity, and gender. Method: Language samples at 4 time points from 39 children with FXS, 31 boys and 8 girls, were analyzed using the Index of…

Knowledge and Perceptions about Fragile X Syndrome: Implications for Diagnosis, Intervention, and Research

ERIC Educational Resources Information Center

Finucane, Brenda; Haas-Givler, Barbara; Simon, Elliott W.

2013-01-01

We surveyed 439 professionals in the field of autism to assess their knowledge and perceptions about fragile X syndrome (FXS) and related issues. Almost half had worked with at least one child diagnosed with FXS, yet most lacked basic knowledge about the condition, underestimated its significance in the etiology of autism spectrum disorders, and…

A Fragile Coalition: University and High School.

ERIC Educational Resources Information Center

Smith, Eugene

1981-01-01

Since 1978, the University of Washington has offered two of its freshman writing courses at Sequim High School, for advanced students wishing to earn college credit. The author discusses program's operations, advantages, and disadvantages, and compares it to the Advanced Placement Program. (SJL)

Fragile X syndrome: from molecular genetics to therapy.

PubMed

D'Hulst, C; Kooy, R F

2009-09-01

Fragile X syndrome, the main cause of inherited mental retardation, is caused by transcriptional silencing of the fragile X mental retardation gene, FMR1. Absence of the associated protein FMRP leads to the dysregulation of many genes creating a phenotype of ADHD, anxiety, epilepsy and autism. The core aim of this review is to summarise two decades of molecular research leading to the characterisation of cellular and molecular pathways involved in the pathology of this disease and as a consequence to the identification of two new promising targets for rational therapy of fragile X syndrome, namely the group 1 metabotrope glutamate receptors (Gp1 mGluRs) and the gamma-amino butyric acid A receptors (GABA(A)Rs). As no current clinical treatments are directed specifically at the underlying neuronal defect due to absence of FMRP, this might open new powerful therapeutic strategies.

Fragility Fracture Incidence in Chronic Obstructive Pulmonary Disease (COPD) Patients Associates With Nanoporosity, Mineral/Matrix Ratio, and Pyridinoline Content at Actively Bone-Forming Trabecular Surfaces.

PubMed

Paschalis, Eleftherios P; Gamsjaeger, Sonja; Dempster, David; Jorgetti, Vanda; Borba, Victoria; Boguszewski, Cesar L; Klaushofer, Klaus; Moreira, Carolina A

2017-01-01

Chronic obstructive pulmonary disease (COPD) is associated with low areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) and altered microstructure by bone histomorphometry and micro-computed tomography. Nevertheless, not all COPD patients sustain fragility fractures. In the present study, we used Raman microspectroscopic analysis to determine bone compositional properties at actively forming trabecular surfaces (based on double fluorescent labels) in iliac crest biopsies from 19 postmenopausal COPD patients (aged 62.1 ± 7.3 years). Additionally, we analyzed trabecular geometrical centers, representing tissue much older than the forming surfaces. Eight of the patients had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. None of the patients had taken oral glucocorticoids. The monitored parameters were mineral/matrix ratio (MM), nanoporosity, and relative glycosaminoglycan (GAG), lipid, and pyridinoline contents (PYD). There were no significant differences between the glucocorticoid-treated patients and those who did not receive any. On the other hand, COPD patients sustaining fragility fractures had significantly lower nanoporosity and higher MM and PYD values compared with COPD patients without fragility fractures. To the best of our knowledge, this is the first study to discriminate between fracture and non-fracture COPD patients based on differences in the material properties of bone matrix. Given that these bone material compositional differences are evident close to the cement line (a major bone interface), they may contribute to the inferior bone toughness and coupled with the lower lumbar spine bone mineral density values result in the fragility fractures prevalent in these patients. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Redesigning the care of fragility fracture patients to improve osteoporosis management: a health care improvement project.

PubMed

Harrington, J Timothy; Barash, Harvey L; Day, Sherry; Lease, Joellen

2005-04-15

To develop new processes that assure more reliable, population-based care of fragility fracture patients. A 4-year clinical improvement project was performed in a multispecialty, community practice health system using evidence-based guidelines and rapid cycle process improvement methods (plan-do-study-act cycles). Prior to this project, appropriate osteoporosis care was provided to only 5% of our 1999 hip fracture patients. In 2001, primary physicians were provided prompts about appropriate care (cycle 1), which resulted in improved care for only 20% of patients. A process improvement pilot in 2002 (cycle 2) and full program implementation in 2003 (cycle 3) have assured osteoporosis care for all willing and able patients with any fragility fracture. Altogether, 58% of 2003 fragility fracture patients, including 46% of those with hip fracture, have had a bone measurement, have been assigned to osteoporosis care with their primary physician or a consultant, and are being monitored regularly. Only 19% refused osteoporosis care. Key process improvements have included using orthopedic billings to identify patients, referring patients directly from orthopedics to an osteoporosis care program, organizing care with a nurse manager and process management computer software, assigning patients to primary or consultative physician care based on disease severity, and monitoring adherence to therapy by telephone. Reliable osteoporosis care is achievable by redesigning clinical processes. Performance data motivate physicians to reconsider traditional approaches. Improving the care of osteoporosis and other chronic diseases requires coordinated care across specialty boundaries and health system support.

A Retrospective Video Analysis of Canonical Babbling and Volubility in Infants with Fragile X Syndrome at 9-12 Months of Age

ERIC Educational Resources Information Center

Belardi, Katie; Watson, Linda R.; Faldowski, Richard A.; Hazlett, Heather; Crais, Elizabeth; Baranek, Grace T.; McComish, Cara; Patten, Elena; Oller, D. Kimbrough

2017-01-01

An infant's vocal capacity develops significantly during the first year of life. Research suggests early measures of pre-speech development, such as canonical babbling and volubility, can differentiate typical versus disordered development. This study offers a new contribution by comparing early vocal development in 10 infants with Fragile X…

Articulation and Noncomprehension Signaling in Adolescent and Adult Males with Down Syndrome and Fragile X Syndrome

ERIC Educational Resources Information Center

Fedak, Larissa Ann

2012-01-01

The purpose of this study was to determine whether or not decreased articulation of speech played a role in the ability of an individual with Down syndrome or Fragile X syndrome to signal noncomprehension and whether the two groups differed in their levels of articulation of speech and noncomprehension signaling ability. The research was conducted…

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

PubMed

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.

Spiritual impacts of the space program on the world

NASA Technical Reports Server (NTRS)

Esch, M.

1972-01-01

The lessons learned from the space program in showing how fragile the environment is on earth are discussed. Examples are cited of the reactions of the astronauts to the unique features of earth. The reactions of the populace in seeking better living conditions and their concern with improving the environment are given as two outgrowths of the program.

A Remedy to Crises: Danish Special Operations Forces in Whole-of-Government Stabilization Engagements

DTIC Science & Technology

2016-06-01

bolstering fragile states and preventing violence from erupting: “we will focus on building the capacity of others to prevent the causes and consequences of...assisting fragile states as well, emphasizing violence prevention in its 2013 adopted policy on stabilization efforts in conflict-affected...practices for violence prevention and countermeasures. Second, this research considers DANSOF capabilities and recent DANSOF involvement in

Turnaround Momentum Still Fragile

ERIC Educational Resources Information Center

Klein, Alyson

2012-01-01

The federal program providing billions of dollars to help states and districts close or remake some of their worst-performing schools remains a work in progress after two years, with more than 1,200 turnaround efforts under way but still no definitive verdict on its effectiveness. The School Improvement Grant (SIG) program, supercharged by a…

A Retrospective Video Analysis of Canonical Babbling and Volubility in Infants with Fragile X Syndrome at 9-12 Months of Age.

PubMed

Belardi, Katie; Watson, Linda R; Faldowski, Richard A; Hazlett, Heather; Crais, Elizabeth; Baranek, Grace T; McComish, Cara; Patten, Elena; Oller, D Kimbrough

2017-04-01

An infant's vocal capacity develops significantly during the first year of life. Research suggests early measures of pre-speech development, such as canonical babbling and volubility, can differentiate typical versus disordered development. This study offers a new contribution by comparing early vocal development in 10 infants with Fragile X syndrome and 14 with typical development. Results suggest infants with Fragile X syndrome produce fewer syllables and have significantly lower canonical babbling ratios compared to infants who are typically developing. Furthermore, the particular measures of babbling were strong predictors of group membership, adding evidence regarding the possible utility of these markers in early identification.

Fragility Analysis Methodology for Degraded Structures and Passive Components in Nuclear Power Plants - Illustrated using a Condensate Storage Tank

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nie, J.; Braverman, J.; Hofmayer, C.

2010-06-30

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 structuresmore » 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. In the Year 1 scope of work, BNL collected and reviewed degradation occurrences in US NPPs and identified important aging characteristics needed for the seismic capability evaluations. This information is presented in the Annual Report for the Year 1 Task, identified as BNL Report-81741-2008 and also designated as KAERI/RR-2931/2008. The report presents results of the statistical and trending analysis of this data and compares the results to prior aging studies. In addition, the report provides a description of U.S. current regulatory requirements, regulatory guidance documents, generic communications, industry standards and guidance, and past research related to aging degradation of SSCs. In the Year 2 scope of work, BNL carried out a research effort to identify and assess degradation models for the long-term behavior of dominant materials that are determined to be risk significant to NPPs. Multiple models have been identified for concrete, carbon and low-alloy steel, and stainless steel. These models are documented in the Annual Report for the Year 2 Task, identified as BNL Report-82249-2009 and also designated as KAERI/TR-3757/2009. This report describes the research effort performed by BNL for the Year 3 scope of work. The objective is for BNL to develop 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 combination of the three degradation scenarios. Insights from these fragility analyses are also presented.« less

Agreement between physicians' and nurses' clinical decisions for the management of the fracture liaison service (4iFLS): the Lucky Bone™ program.

PubMed

Senay, A; Delisle, J; Raynauld, J P; Morin, S N; Fernandes, J C

2016-04-01

We determined if nurses can manage osteoporotic fractures in a fracture liaison service by asking a rheumatologist and an internist to assess their clinical decisions. Experts agreed on more than 94 % of all nurses' actions for 525 fragility fracture patients, showing that their management is efficient and safe. A major care gap exists in the investigation of bone fragility and initiation of treatment for individuals who have sustained a fragility fracture. The implementation of a fracture liaison service (FLS) managed by nurses could be the key in resolving this problem. The aim of this project was to obtain agreement between physicians' and nurses' clinical decisions and evaluate if the algorithm of care is efficient and reliable for the management of a FLS. Clinical decisions of nurses for 525 subjects in a fracture liaison service between 2010 and 2013 were assessed by two independent physicians with expertise in osteoporosis treatment. Nurses succeeded in identifying all patients at risk and needed to refer 27 % of patients to an MD. Thereby, they managed autonomously 73 % of fragility fracture patients. No needless referrals were made according to assessing physicians. Agreement between each evaluator and nurses was of >97 %. Physicians' decisions were the same in >96 %, and Gwet AC11 coefficient was of >0.960 (almost perfect level of agreement). All major comorbidities were adequately managed. High agreement between nurses' and physicians' clinical decisions indicate that the independent management by nurses of a fracture liaison service is safe and should strongly be recommended in the care of patients with a fragility fracture. This kind of intervention could help resolve the existing care gap in bone fragility care as well as the societal economic burden associated with prevention and treatment of fragility fractures.

Measurement, "scriptural economies," and social justice: governing HIV/AIDS treatments by numbers in a fragile state, the Central African Republic (CAR).

PubMed

David, Pierre-Marie

2017-04-01

Fragile states have been raising increasing concern among donors since the mid-2000s. The policies of the Global Fund to fight HIV/AIDS, Malaria, and Tuberculosis (GF) have not excluded fragile states, and this source has provided financing for these countries according to standardized procedures. They represent interesting cases for exploring the meaning and role of measurement in a globalized context. Measurement in the field of HIV/AIDS and its treatment has given rise to a private outsourcing of expertise and auditing, thereby creating a new form of value based on the social process of registration and the creation of realities produced by the intervention itself. These "scriptural economies" must be questioned in terms of the production of knowledge, but also in terms of social justice. Governing HIV/AIDS treatments by numbers in a fragile state is explored in this article through the experience of the Central African Republic (CAR) in terms of epidemiology and access to antiretroviral drugs. The unexpected effects of performance-based programs in this context underline the need for global health governance to be re-embedded into a social justice framework. © 2016 John Wiley & Sons Ltd.

Minimizing disparities in osteoporosis care of minorities with an electronic medical record care plan.

PubMed

Navarro, Ronald A; Greene, Denise F; Burchette, Raoul; Funahashi, Tadashi; Dell, Richard

2011-07-01

Ethnic disparities in care have been documented with a number of musculoskeletal disorders including osteoporosis. We suggest a systems approach for ensuring osteoporosis care can minimize potential ethnic disparities in care. We evaluated variations in osteoporosis treatment by age, sex, and race/ethnicity by (1) measuring the rates of patients after a fragility fracture who had been evaluated by dual-energy xray absorptiometry and/or in whom antiosteoporosis treatment had been initiated and (2) determining the rates of osteoporosis treatment in patients who subsequently had a hip fracture. We implemented an integrated osteoporosis prevention program in a large health plan. Continuous screening of electronic medical records identified patients who met the criteria for screening for osteoporosis, were diagnosed with osteoporosis, or sustained a fragility fracture. At-risk patients were referred to care managers and providers to complete practice guidelines to close care gaps. Race/ethnicity was self-reported. Treatment rates after fragility fracture or osteoporosis treatment failures with later hip fracture were calculated. Data for the years 2008 to 2009 were stratified by age, sex, and race/ethnicity. Women (92.1%) were treated more often than men (75.2%) after index fragility fracture. The treatment rate after fragility fracture was similar among race/ethnic groups in either sex (women 87.4%-93.4% and men 69.3%-76.7%). Osteoporotic treatment before hip fracture was more likely in white men and women and Hispanic men than other race/ethnic and gender groups. Racial variation in osteoporosis care after fragility fracture in race/ethnic groups in this healthcare system was low when using the electronic medical record identifying care gaps, with continued reminders to osteoporosis disease management care managers and providers until those care gaps were closed.

Parental Relationships in Fragile Families

PubMed Central

McLanahan, Sara; Beck, Audrey N.

2011-01-01

Summary As nonmarital childbearing escalated in the United States over the past half century, fragile families—defined as unmarried couples with children—drew increased interest from researchers and policy makers. Sara McLanahan and Audrey Beck discuss four aspects of parental relationships in these families: the quality of parents’ intimate relationship, the stability of that relationship, the quality of the co-parenting relationship among parents who live apart, and nonresident fathers’ involvement with their child. At the time of their child’s birth, half of the parents in fragile families are living together and another third are living apart but romantically involved. Despite high hopes at birth, five years later only a third of parents are still together, and new partners and new children are common, leading to high levels of instability and complexity in these families. Drawing on findings from the Fragile Families and Child Wellbeing Study, McLanahan and Beck highlight a number of predictors of low relationship quality and stability in these families, including low economic resources, government policies that discourage marriage, gender distrust and acceptance of single motherhood, sex ratios that favor men, children from previous unions, and psychological factors that make it difficult for parents to maintain healthy relationships. No single factor appears to have a dominant effect. The authors next discuss two types of experiments that attempt to establish causal effects on parental relationships: those aimed at altering economic resources and those aimed at improving relationships. What can be done to strengthen parental relationships in fragile families? The authors note that although economic resources are a consistent predictor of stable relationships, researchers and policy makers lack good causal information on whether increasing fathers’ employment and earnings will increase relationship quality and union stability. They also note that analysts need to know more about whether relationship quality in fragile families can be improved directly and whether doing so will increase union stability, father involvement, and co-parenting quality. PMID:20964130

Parental relationships in fragile families.

PubMed

McLanahan, Sara; Beck, Audrey N

2010-01-01

As nonmarital childbearing escalated in the United States over the past half century, fragile families--defined as unmarried couples with children--drew increased interest from researchers and policy makers. Sara McLanahan and Audrey Beck discuss four aspects of parental relationships in these families: the quality of parents' intimate relationship, the stability of that relationship, the quality of the co-parenting relationship among parents who live apart, and nonresident fathers' involvement with their child. At the time of their child's birth, half of the parents in fragile families are living together and another third are living apart but romantically involved. Despite high hopes at birth, five years later only a third of parents are still together, and new partners and new children are common, leading to high levels of instability and complexity in these families. Drawing on findings from the Fragile Families and Child Wellbeing Study, McLanahan and Beck highlight a number of predictors of low relationship quality and stability in these families, including low economic resources, government policies that discourage marriage, gender distrust and acceptance of single motherhood, sex ratios that favor men, children from previous unions, and psychological factors that make it difficult for parents to maintain healthy relationships. No single factor appears to have a dominant effect. The authors next discuss two types of experiments that attempt to establish causal effects on parental relationships: those aimed at altering economic resources and those aimed at improving relationships. What can be done to strengthen parental relationships in fragile families? The authors note that although economic resources are a consistent predictor of stable relationships, researchers and policy makers lack good causal information on whether increasing fathers' employment and earnings will increase relationship quality and union stability. They also note that analysts need to know more about whether relationship quality in fragile families can be improved directly and whether doing so will increase union stability, father involvement, and co-parenting quality.

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

PubMed Central

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

Fragile X Syndrome and Targeted Treatment Trials

PubMed Central

Lauterborn, Julie; Au, Jacky; Berry-Kravis, Elizabeth

2014-01-01

Work in recent years has revealed an abundance of possible new treatment targets for fragile X syndrome (FXS). The use of animal models, including the fragile X knockout mouse which manifests a phenotype very similar to FXS in humans, has resulted in great strides in this direction of research. The lack of Fragile X Mental Retardation Protein (FMRP) in FXS causes dysregulation and usually overexpression of a number of its target genes, which can cause imbalances of neurotransmission and deficits in synaptic plasticity. The use of metabotropic glutamate receptor (mGluR) blockers and gamma amino-butyric acid (GABA) agonists have been shown to be efficacious in reversing cellular and behavioral phenotypes, and restoring proper brain connectivity in the mouse and fly models. Proposed new pharmacological treatments and educational interventions are discussed in this chapter. In combination, these various targeted treatments show promising preliminary results in mitigating or even reversing the neurobiological abnormalities caused by loss of FMRP, with possible translational applications to other neurodevelopmental disorders including autism. PMID:22009360

Fragile X syndrome and targeted treatment trials.

PubMed

Hagerman, Randi; Lauterborn, Julie; Au, Jacky; Berry-Kravis, Elizabeth

2012-01-01

Work in recent years has revealed an abundance of possible new treatment targets for fragile X syndrome (FXS). The use of animal models, including the fragile X knockout mouse which manifests a phenotype very similar to FXS in humans, has resulted in great strides in this direction of research. The lack of Fragile X Mental Retardation Protein (FMRP) in FXS causes dysregulation and usually overexpression of a number of its target genes, which can cause imbalances of neurotransmission and deficits in synaptic plasticity. The use of metabotropic glutamate receptor (mGluR) blockers and gamma amino-butyric acid (GABA) agonists have been shown to be efficacious in reversing cellular and behavioral phenotypes, and restoring proper brain connectivity in the mouse and fly models. Proposed new pharmacological treatments and educational interventions are discussed in this chapter. In combination, these various targeted treatments show promising preliminary results in mitigating or even reversing the neurobiological abnormalities caused by loss of FMRP, with possible translational applications to other neurodevelopmental disorders including autism.

Analysis of the ecological conservation behavior of farmers in payment for ecosystem service programs in eco-environmentally fragile areas using social psychology models.

PubMed

Deng, Jian; Sun, Pingsheng; Zhao, Fazhu; Han, Xinhui; Yang, Gaihe; Feng, Yongzhong

2016-04-15

Studies on the ecological conservation behavior of farmers usually focus on individual and socio-economic characteristics without consideration of the underlying psychological constructs, such as farmers' intention and perceptions. This study uses the theory of planned behavior (TPB), a typical social psychology construct, to analyze the factors affecting the intention and behavior of farmers for conserving the ecological achievements from payment for ecosystem service (PES) programs in eco-environmentally fragile areas. Questionnaires based on TPB were administered to 1004 farmers from the Grain to Green Program area in the Loess Plateau, China, with the resulting dataset used to identify the underlying factors determining farmers' intention and behavior based on the structural equation model. The results show that the farmers' intention and behavior toward conserving ecological achievements were explained well by TPB. The farmers'behavior was significantly positively affected by their intention toward conserving ecological achievements, and their intention was significantly influenced by their attitude (positive or negative value of performance), the subjective norm (social pressure in engaging behavior), and perceived behavioral control (perceptions of their ability). The farmers' degree of support for PES programs and their recognition of environmental effects were the factors that most influenced the farmers' attitude. Pressure from neighbors was the most potent driver of the subjective norm. Meanwhile, perceptions of their ability to perform the behavior were the most potent factors affecting intention and it was mostly driven by the farmers' feelings toward environmental improvement and perceived ability (time and labor) to participate in ecological conservation. The drivers of attitude, subjective norm, and perceived behavioral control can be used by policy makers to direct farmers' intention and behavior toward conserving ecological achievements in fragile eco-environmentally areas through PES programs. Thus, this strategy can improve the sustainability of ecological and environmental restoration programs. Copyright © 2016 Elsevier B.V. All rights reserved.

A Retrospective Video Analysis of Canonical Babbling and Volubility in Infants with Fragile X Syndrome at 9 – 12 Months of Age

PubMed Central

Belardi, Katie; Watson, Linda R.; Faldowski, Richard A.; Hazlett, Heather; Crais, Elizabeth; Baranek, Grace T.; McComish, Cara; Patten, Elena; Oller, D. Kimbrough

2017-01-01

An infant’s vocal capacity develops significantly during the first year of life. Research suggests early measures of pre-speech development, such as canonical babbling and volubility, can differentiate typical versus disordered development. This study offers a new contribution by comparing early vocal development in 10 infants with Fragile X syndrome and 14 with typical development. Results suggest infants with Fragile X syndrome produce fewer syllables and have significantly lower canonical babbling ratios (i.e., canonical syllables/total syllables) compared to infants who are typically developing. Furthermore, the particular measures of babbling were strong predictors of group membership, adding evidence regarding the possible utility of these markers in early identification. PMID:28247019

Role of maternal gesture use in speech use by children with fragile X syndrome.

PubMed

Hahn, Laura J; Zimmer, B Jean; Brady, Nancy C; Swinburne Romine, Rebecca E; Fleming, Kandace K

2014-05-01

The purpose of this study was to investigate how maternal gesture relates to speech production by children with fragile X syndrome (FXS). Participants were 27 young children with FXS (23 boys, 4 girls) and their mothers. Videotaped home observations were conducted between the ages of 25 and 37 months (toddler period) and again between the ages of 60 and 71 months (child period). The videos were later coded for types of maternal utterances and maternal gestures that preceded child speech productions. Children were also assessed with the Mullen Scales of Early Learning at both ages. Maternal gesture use in the toddler period was positively related to expressive language scores at both age periods and was related to receptive language scores in the child period. Maternal proximal pointing, in comparison to other gestures, evoked more speech responses from children during the mother-child interactions, particularly when combined with wh-questions. This study adds to the growing body of research on the importance of contextual variables, such as maternal gestures, in child language development. Parental gesture use may be an easily added ingredient to parent-focused early language intervention programs.

Measuring self-esteem in context: the importance of stability of self-esteem in psychological functioning.

PubMed

Kernis, Michael H

2005-12-01

In this article, I report on a research program that has focused on the joint roles of stability and level of self-esteem in various aspects of psychological functioning. Stability of self-esteem refers to the magnitude of short-term fluctuations that people experience in their current, contextually based feelings of self-worth. In contrast, level of self-esteem refers to representations of people's general, or typical, feelings of self-worth. A considerable amount of research reveals that self-esteem stability has predictive value beyond the predictive value of self-esteem level. Moreover, considering self-esteem stability provides one way to distinguish fragile from secure forms of high self-esteem. Results from a number of studies are presented and theoretical implications are discussed.

Autism and heritable bone fragility: A true association?

PubMed

Balasubramanian, Meena; Jones, Rebecca; Milne, Elizabeth; Marshall, Charlotte; Arundel, Paul; Smith, Kath; Bishop, Nicholas J

2018-06-01

Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; intelligence is reported to be normal. However, a minority of children seen also show symptomology consistent with an 'Autism Spectrum Disorder'. A joint genetics and psychology research study was undertaken to identify these patients using 'Gold Standard' research tools: Autism Diagnostic Inventory Revised (ADI-R); Autism Diagnostic Observation Schedule (ADOS) and undertake genetic analyses in them. A cohort of n  = 7 children with autistic traits and severe/complex OI were recruited to the study. The study was set-up to explore whether there was a genetic link between bone fragility and autism in a sub-set of patients with bone fragility identified with autism traits in our complex/severe OI clinic. This was not set-up as a prevalence study but rather an exploration of genetics in association with ADI/ADOS confirmed ASD and bone fragility. Standardised tools were used to confirm autism diagnosis. ADI and ADOS were completed by the Clinical Psychologist; ADI comprises a 93 item semi-structured clinical review with a diagnostic algorithm diagnosing Autism; ADOS is a semi-structured assessment of socialisation, communication and play/imagination which also provides a diagnostic algorithm. In patients recruited, those that fulfilled research criteria for diagnosis of autism using above tools were recruited to trio whole exome sequencing (WES). one patient had compound heterozygous variants in NBAS ; one patient had a variant in NRX1 ; one patient had a maternally inherited PLS3 variant; all the other patients in this cohort had pathogenic variants in COL1A1/COL1A2 . Although, not set out as an objective, we were able to establish that identifying autism had important clinical and social benefits for patients and their families in ensuring access to services, appropriate schooling, increased understanding of behaviour and support. It is important for clinicians looking after children with brittle bone disease, also referred to as Osteogenesis Imperfecta (OI) to be aware of early features of developmental delay/autistic traits especially with severe forms of OI as the emphasis is on their mobility and bone health. Ensuring appropriate assessment and access to services early-on will enable these patients to achieve their potential. Further investigations of genomics in bone fragility in relation to autism are required and dual diagnosis is essential for high quality clinical and educational provision.

Fragile X Syndrome Overview

MedlinePlus

... Browse AZTopics Browse A-Z Adrenal Gland Disorders Autism Spectrum Disorder (ASD) Down Syndrome Endometriosis Learning Disabilities ... NICHD Research Information Find a Study More Information Autism Spectrum Disorder (ASD) About NICHD Research Information Find ...

Fragile X Syndrome: Other FAQs

MedlinePlus

... Browse AZTopics Browse A-Z Adrenal Gland Disorders Autism Spectrum Disorder (ASD) Down Syndrome Endometriosis Learning Disabilities ... NICHD Research Information Find a Study More Information Autism Spectrum Disorder (ASD) About NICHD Research Information Find ...

Rebuilding research capacity in fragile states: the case of a Somali–Swedish global health initiative

PubMed Central

Dalmar, Abdirisak Ahmed; Hussein, Abdullahi Sheik; Walhad, Said Ahmed; Ibrahim, Abdirashid Omer; Abdi, Abshir Ali; Ali, Mohamed Khalid; Ereg, Derie Ismail; Egal, Khadra Ali; Shirwa, Abdulkadir Mohamed; Aden, Mohamed Hussain; Yusuf, Marian Warsame; Abdi, Yakoub Aden; Freij, Lennart; Johansson, Annika; Mohamud, Khalif Bile; Abdulkadir, Yusuf; Emmelin, Maria; Eriksen, Jaran; Erlandsson, Kerstin; Gustafsson, Lars L; Ivarsson, Anneli; Klingberg-Allvin, Marie; Kinsman, John; Källestål, Carina; Målqvist, Mats; Osman, Fatumo; Persson, Lars-Åke; Sahlén, Klas-Göran; Wall, Stig

2017-01-01

ABSTRACT This paper presents an initiative to revive the previous Somali–Swedish Research Cooperation, which started in 1981 and was cut short by the civil war in Somalia. A programme focusing on research capacity building in the health sector is currently underway through the work of an alliance of three partner groups: six new Somali universities, five Swedish universities, and Somali diaspora professionals. Somali ownership is key to the sustainability of the programme, as is close collaboration with Somali health ministries. The programme aims to develop a model for working collaboratively across regions and cultural barriers within fragile states, with the goal of creating hope and energy. It is based on the conviction that health research has a key role in rebuilding national health services and trusted institutions. PMID:28799463

Fragile X Mental Retardation Protein is Required for Programmed Cell Death and Clearance of Developmentally-Transient Peptidergic Neurons

PubMed Central

Gatto, Cheryl L.; Broadie, Kendal

2011-01-01

Fragile X syndrome (FXS), caused by loss of fragile X mental retardation 1 (FMR1) gene function, is the most common heritable cause of intellectual disability and autism spectrum disorders. The FMR1 product (FMRP) is an RNA-binding protein best established to function in activity-dependent modulation of synaptic connections. In the Drosophila FXS disease model, loss of functionally-conserved dFMRP causes synaptic overgrowth and overelaboration in pigment dispersing factor (PDF) peptidergic neurons in the adult brain. Here, we identify a very different component of PDF neuron misregulation in dfmr1 mutants: the aberrant retention of normally developmentally-transient PDF tritocerebral (PDF-TRI) neurons. In wild-type animals, PDF-TRI neurons in the central brain undergo programmed cell death and complete, processive clearance within days of eclosion. In the absence of dFMRP, a defective apoptotic program leads to constitutive maintenance of these peptidergic neurons. We tested whether this apoptotic defect is circuit-specific by examining crustacean cardioactive peptide (CCAP) and bursicon circuits, which are similarly developmentally-transient and normally eliminated immediately post-eclosion. In dfmr1 null mutants, CCAP/bursicon neurons also exhibit significantly delayed clearance dynamics, but are subsequently eliminated from the nervous system, in contrast to the fully persistent PDF-TRI neurons. Thus, the requirement of dFMRP for the retention of transitory peptidergic neurons shows evident circuit specificity. The novel defect of impaired apoptosis and aberrant neuron persistence in the Drosophila FXS model suggests an entirely new level of “pruning” dysfunction may contribute to the FXS disease state. PMID:21596027

Discours oraux--discours ecrits: quelles relations? Actes du 4eme colloque d'orthophoine/logopedie (Neuchatel, 3-4 octobre, 1996) (Oral Discourse--Written Discourse: What Is the Relationship? Proceedings of the Colloquium on Speech Therapy (4th, Neuchatel, Switzerland, October 3-4, 1996).

ERIC Educational Resources Information Center

Py, Bernard, Ed.

1996-01-01

Research papers on the relationship between oral and written language include: "Une distinction bien fragile: oral/ecrit" ("A Fragile Distinction: Oral/Written") (Francoise Gadet); "Oral et ecrit dans les representations des enseignants et dans les pratiques quotidiennes de la classe de francais" ("Oral and Written Language in Teachers'…

Integrating Sensor-Collected Intelligence

DTIC Science & Technology

2008-11-01

collecting, processing, data storage and fusion, and the dissemination of information collected by Intelligence, Surveillance, and Reconnaissance (ISR...Grid – Bandwidth Expansion (GIG-BE) program) to provide the capability to transfer data from sensors to accessible storage and satellite and airborne...based ISR is much more fragile. There was a purposeful drawdown of these systems following the Cold War and modernization programs were planned to

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

PubMed Central

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

Dynamic Changes of Landscape Pattern and Vulnerability Analysis in Qingyi River Basin

NASA Astrophysics Data System (ADS)

Li, Ziwei; Xie, Chaoying; He, Xiaohui; Guo, Hengliang; Wang, Li

2017-11-01

Environmental vulnerability research is one of the core areas of global environmental change research. Over the past 10 years, ecologically fragile zones or transition zones had been significantly affected by environmental degradation and climate change and human activities. In this paper, we analyzed the spatial and temporal changes of landscape pattern and landscape vulnerability degree in Qingyi River Basin by calculating the landscape sensitivity index and landscape restoration degree index based on Landsat images of 2005, 2010 and 2015. The results showed that: (1) The top conversion area was farmland, woodland and grassland area decreased, city land and rural residential land increased fastest. (2) The fragility of the landscape pattern along the Qingyi River gradually increased between 2005 and 2015, the downstream area was influenced by the influence of human activities. (3) Landscape pattern changes and fragility are mainly affected by urbanization. These findings are helpful for understanding the evolution of landscape pattern as well as urban ecology, which both have significant implications for urban planning and minimize the potential environmental impacts of urbanization in Qingyi River Basin.

What Are the Symptoms of Fragile X Syndrome?

MedlinePlus

... Browse AZTopics Browse A-Z Adrenal Gland Disorders Autism Spectrum Disorder (ASD) Down Syndrome Endometriosis Learning Disabilities ... NICHD Research Information Find a Study More Information Autism Spectrum Disorder (ASD) About NICHD Research Information Find ...

What Are the Treatments for Fragile X Syndrome?

MedlinePlus

... Browse AZTopics Browse A-Z Adrenal Gland Disorders Autism Spectrum Disorder (ASD) Down Syndrome Endometriosis Learning Disabilities ... NICHD Research Information Find a Study More Information Autism Spectrum Disorder (ASD) About NICHD Research Information Find ...

How Do Health Care Providers Diagnose Fragile X Syndrome?

MedlinePlus

... Browse AZTopics Browse A-Z Adrenal Gland Disorders Autism Spectrum Disorder (ASD) Down Syndrome Endometriosis Learning Disabilities ... NICHD Research Information Find a Study More Information Autism Spectrum Disorder (ASD) About NICHD Research Information Find ...

Next generation seismic fragility curves for California bridges incorporating the evolution in seismic design philosophy

NASA Astrophysics Data System (ADS)

Ramanathan, Karthik Narayan

Quantitative and qualitative assessment of the seismic risk to highway bridges is crucial in pre-earthquake planning, and post-earthquake response of transportation systems. Such assessments provide valuable knowledge about a number of principal effects of earthquakes such as traffic disruption of the overall highway system, impact on the regions’ economy and post-earthquake response and recovery, and more recently serve as measures to quantify resilience. Unlike previous work, this study captures unique bridge design attributes specific to California bridge classes along with their evolution over three significant design eras, separated by the historic 1971 San Fernando and 1989 Loma Prieta earthquakes (these events affected changes in bridge seismic design philosophy). This research developed next-generation fragility curves for four multispan concrete bridge classes by synthesizing new knowledge and emerging modeling capabilities, and by closely coordinating new and ongoing national research initiatives with expertise from bridge designers. A multi-phase framework was developed for generating fragility curves, which provides decision makers with essential tools for emergency response, design, planning, policy support, and maximizing investments in bridge retrofit. This framework encompasses generational changes in bridge design and construction details. Parameterized high-fidelity three-dimensional nonlinear analytical models are developed for the portfolios of bridge classes within different design eras. These models incorporate a wide range of geometric and material uncertainties, and their responses are characterized under seismic loadings. Fragility curves were then developed considering the vulnerability of multiple components and thereby help to quantify the performance of highway bridge networks and to study the impact of seismic design principles on the performance within a bridge class. This not only leads to the development of fragility relations that are unique and better suited for bridges in California, but also leads to the creation of better bridge classes and sub-bins that have more consistent performance characteristics than those currently provided by the National Bridge Inventory. Another important feature of this research is associated with the development of damage state definitions and grouping of bridge components in a way that they have similar consequences in terms of repair and traffic implications following a seismic event. These definitions are in alignment with the California Department of Transportation’s design and operational experience, thereby enabling better performance assessment, emergency response, and management in the aftermath of a seismic event. The fragility curves developed as a part of this research will be employed in ShakeCast, a web-based post-earthquake situational awareness application that automatically retrieves earthquake shaking data and generates potential damage assessment notifications for emergency managers and responders.

Modifications to risk-targeted seismic design maps for subduction and near-fault hazards

USGS Publications Warehouse

Liel, Abbie B.; Luco, Nicolas; Raghunandan, Meera; Champion, C.; Haukaas, Terje

2015-01-01

ASCE 7-10 introduced new seismic design maps that define risk-targeted ground motions such that buildings designed according to these maps will have 1% chance of collapse in 50 years. These maps were developed by iterative risk calculation, wherein a generic building collapse fragility curve is convolved with the U.S. Geological Survey hazard curve until target risk criteria are met. Recent research shows that this current approach may be unconservative at locations where the tectonic environment is much different than that used to develop the generic fragility curve. This study illustrates how risk-targeted ground motions at selected sites would change if generic building fragility curve and hazard assessment were modified to account for seismic risk from subduction earthquakes and near-fault pulses. The paper also explores the difficulties in implementing these changes.

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.

PubMed

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.

Vouchers in Fragile States: Reducing Barriers to Long-Acting Reversible Contraception in Yemen and Pakistan

PubMed Central

Boddam-Whetham, Luke; Gul, Xaher; Al-Kobati, Eman; Gorter, Anna C

2016-01-01

ABSTRACT In conflict-affected states, vouchers have reduced barriers to reproductive health services and have enabled health programs to use targeted subsidies to increase uptake of specific health services. Vouchers can also be used to channel funds to public- and private-service providers and improve service quality. The Yamaan Foundation for Health and Social Development in Yemen and the Marie Stopes Society (MSS) in Pakistan—both working with Options Consultancy Services—have developed voucher programs that subsidize voluntary access to long-acting reversible contraceptives (LARCs) and permanent methods (PMs) of family planning in their respective fragile countries. The programs focus on LARCs and PMs because these methods are particularly difficult for poor women to access due to their cost and to provider biases against offering them. Using estimates of expected voluntary uptake of LARCs and PMs for 2014 based on contraceptive prevalence rates, and comparing these with uptake of LARCs and PMs through the voucher programs, we show the substantial increase in service utilization that vouchers can enable by contributing to an expanded method choice. In the governorate of Lahj, Yemen, vouchers for family planning led to an estimated 38% increase in 2014 over the expected use of LARCs and PMs (720 vs. 521 expected). We applied the same approach in 13 districts of Punjab, Khyber Pakhtunkhwa (KPK), and Sindh provinces in Pakistan. Our calculations suggest that vouchers enabled 10 times more women than expected to choose LARCs and PMs in 2014 in those areas of Pakistan (73,639 vs. 6,455 expected). Voucher programs can promote and maintain access to family planning services where existing health systems are hampered. Vouchers are a flexible financing approach that enable expansion of contraceptive choice and the inclusion of the private sector in service delivery to the poor. They can keep financial resources flowing where the public sector is prevented from offering services, and ensure that alternative sources are available for reproductive health services such as family planning. Programs should consider using vouchers in fragile states to facilitate access to family planning services and support the countries’ health systems. PMID:27540129

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

PubMed

Hagerman, Randi; Hoem, Gry; Hagerman, Paul

2010-09-21

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 (mGluR)1/5 pathway and γ aminobutyric acid (GABA)A 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.

Osmotic fragility test

MedlinePlus

Spherocytosis - osmotic fragility; Thalassemia - osmotic fragility ... done to detect conditions called hereditary spherocytosis and thalassemia . Hereditary spherocytosis makes red blood cells more fragile ...

Geography Education Research and Why It Matters

ERIC Educational Resources Information Center

Lambert, David

2010-01-01

This paper provides a commentary on the "condition" of geography education research as a field of study. It does so partly through a comparative discussion with another subject field in education, mathematics. In the context of fragility and comparative weakness of research in geography education, the paper urges researchers to keep focused on…

The Fragile X Protein and Genome Function.

PubMed

Dockendorff, Thomas C; Labrador, Mariano

2018-05-23

The fragile X syndrome (FXS) arises from loss of expression or function of the FMR1 gene and is one of the most common monogenic forms of intellectual disability and autism. During the past two decades of FXS research, the fragile X mental retardation protein (FMRP) has been primarily characterized as a cytoplasmic RNA binding protein that facilitates transport of select RNA substrates through neural projections and regulation of translation within synaptic compartments, with the protein products of such mRNAs then modulating cognitive functions. However, the presence of a small fraction of FMRP in the nucleus has long been recognized. Accordingly, recent studies have uncovered several mechanisms or pathways by which FMRP influences nuclear gene expression and genome function. Some of these pathways appear to be independent of the classical role for FMRP as a regulator of translation and point to novel functions, including the possibility that FMRP directly participates in the DNA damage response and in the maintenance of genome stability. In this review, we highlight these advances and discuss how these new findings could contribute to our understanding of FMRP in brain development and function, the neural pathology of fragile X syndrome, and perhaps impact of future therapeutic considerations.

Multifarious Functions of the Fragile X Mental Retardation Protein.

PubMed

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.

Of Men and Mice: Modeling the Fragile X Syndrome

PubMed Central

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

Seismic Fragility Analysis of a Degraded Condensate Storage Tank

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nie, J.; Braverman, J.; Hofmayer, C.

2011-05-16

The Korea Atomic Energy Research Institute (KAERI) and Brookhaven National Laboratory are conducting a collaborative research project to develop seismic capability evaluation technology for degraded structures and components in nuclear power plants (NPPs). One of the goals of this collaboration endeavor is to develop seismic fragility analysis methods that consider the potential effects of age-related degradation of structures, systems, and components (SSCs). The essential part of this collaboration is aimed at achieving a better understanding of the effects of aging on the performance of SSCs and ultimately on the safety of NPPs. A recent search of the degradation occurrences ofmore » structures and passive components (SPCs) showed that the rate of aging related degradation in NPPs was not significantly large but increasing, as the plants get older. The slow but increasing rate of degradation of SPCs can potentially affect the safety of the older plants and become an important factor in decision making in the current trend of extending the operating license period of the plants (e.g., in the U.S. from 40 years to 60 years, and even potentially to 80 years). The condition and performance of major aged NPP structures such as the containment contributes to the life span of a plant. A frequent misconception of such low degradation rate of SPCs is that such degradation may not pose significant risk to plant safety. However, under low probability high consequence initiating events, such as large earthquakes, SPCs that have slowly degraded over many years could potentially affect plant safety and these effects need to be better understood. As part of the KAERI-BNL collaboration, a condensate storage tank (CST) was analyzed to estimate its seismic fragility capacities under various postulated degradation scenarios. CSTs were shown to have a significant impact on the seismic core damage frequency of a nuclear power plant. The seismic fragility capacity of the CST was developed for five cases: (1) a baseline analysis where the design condition (undegraded) is assumed, (2) a scenario with degraded stainless steel tank shell, (3) a scenario with degraded anchor bolts, (4) a scenario with anchorage concrete cracking, and (5) a perfect correlation of the above three degradation scenarios. This paper will present the methodology for the time-dependent fragility calculation and discuss the insights drawn from this study. To achieve a better understanding of the effects of aging on the performance of structures and passive components (SPCs) in nuclear power plants (NPPs), the Korea Atomic Energy Research Institute (KAERI) and Brookhaven National Laboratory (BNL) are collaborating to develop seismic fragility analysis methods that consider age-related degradation of SPCs. The rate of age-related degradation of SPCs was not found to be significantly large, but increasing as the plants get older. The slow but increasing rate of degradation of SPCs can potentially affect the safety of the older plants and become an important factor in decision making in the current trend of extending the operating license period of the plants (e.g., in the U.S. from 40 years to 60 years, and even potentially to 80 years). In this paper, a condensate storage tank (CST) was analyzed to estimate its seismic fragility capacities under various postulated degradation scenarios. This paper will present the methodology for the time-dependent fragility calculation and discuss the insights drawn from this study.« less

Employment impact and financial burden for families of children with fragile X syndrome: findings from the National Fragile X Survey.

PubMed

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

2010-10-01

The employment impact and financial burden experienced by families of children with fragile X syndrome (FXS) has not been quantified in the USA. 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 reported. We used logistic regression to examine the role of insurance, number of affected children, and number of total co-occurring conditions in predicting the financial burden and employment impact of FXS, while adjusting for race, education, marital status and other sociodemographic predictors. Almost half of families affected by FXS reported that they had experienced an increased financial burden and nearly 60% stated that they had had to change work hours or stop work because of FXS. Families with health insurance that met family needs were significantly less likely to report an excess financial burden. The type of insurance (private or public) was not associated with the reported financial burden. Affected children's mutation status, especially male children with the full mutation, was associated with employment impact. The total number of co-occurring conditions was associated with both financial burden and employment impact. Families affected by FXS experienced a significant employment impact and financial burden. Policies designed to help families with FXS need to take into consideration the dimension of co-occurring conditions. © 2010 The Authors. Journal of Intellectual Disability Research © 2010 Blackwell Publishing Ltd.

Psychiatric and autistic comorbidity in fragile X syndrome across ages.

PubMed

Gabis, Lidia V; Baruch, Yael Kesner; Jokel, Ariela; Raz, Raanan

2011-08-01

Fragile X syndrome is caused by CGG trinucleotide repeat expansion within the fragile X mental retardation 1 gene, when repeat number exceeds 200. The typical psychiatric profile of fragile X syndrome patients includes cognitive and behavioral deficits, psychiatric comorbidity, and autistic characteristics. Specific psychiatric features have not yet been clarified, specifically in relationship to age and genetic characteristics. The objective of this study was to characterize psychiatric comorbidities in subjects with fragile X syndrome at different ages. Subjects with fragile X syndrome and their unaffected siblings were recruited and their parents filled out functional-behavioral and psychiatric comorbidities questionnaires. Adolescents with fragile X syndrome showed decreased prevalence of functional-behavioral deficits. Incidence and severity of most psychiatric comorbidities were lower in older subjects. Incidence of generalized anxiety disorder increased with age in the fragile X syndrome group. The typical profile of patients with fragile X syndrome changes with age. Unaffected siblings exhibit anxiety and motor tics.

Satellite Cells in Muscular Dystrophy - Lost in Polarity

PubMed Central

Chang, Natasha C.; Chevalier, Fabien P.; Rudnicki, Michael A.

2016-01-01

Recent findings employing the mdx mouse model for Duchenne muscular dystrophy (DMD) have revealed that muscle satellite stem cells play a direct role in contributing to disease etiology and progression of DMD, the most common and severe form of muscular dystrophy. Lack of dystrophin expression in DMD has critical consequences in satellite cells including an inability to establish cell polarity, abrogation of asymmetric satellite stem cell divisions and failure to enter the myogenic program. Thus, muscle wasting in dystrophic mice is not only caused by myofiber fragility, but is exacerbated by intrinsic satellite cell dysfunction leading to impaired regeneration. Despite intense research and clinical efforts, there is still no effective cure for DMD. In this review, we highlight recent research advances in DMD and discuss the current state of treatment and importantly, how we can incorporate satellite cell-targeted therapeutic strategies to correct satellite cell dysfunction in DMD. PMID:27161598

Treatments for fragile X syndrome: a closer look at the data.

PubMed

Hall, Scott S

2009-01-01

Research into the determinants and developmental course of fragile X syndrome (FXS) has made remarkable progress over the last 25 years. However, treatments to ameliorate the symptoms of FXS have been less forthcoming. While there is optimism in the field that the pace of intervention research is quickening, there has been a bias toward psychopharmacological approaches to treatment. A closer look at the data from those investigations reveals a paucity of evidence that medications can improve intellectual and adaptive functioning in FXS, or decrease associated behavioral and/or emotional issues. Work in other related disorders (e.g., autism) has shown that dramatic improvements in intellectual and adaptive functioning, as well as behavioral and emotional problems, can occur if intensive behavioral treatment is begun early in the child's life. It is hoped that future research efforts will evaluate these intensive early intervention strategies in children with FXS, perhaps in combination with pharmacological approaches.

Behavioral Phenotype of Fragile X Syndrome in Adolescence and Adulthood

PubMed Central

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; n = 135) on measures of autism symptoms, adaptive functioning, behavior problems, and psychological symptoms. Results indicated that individuals dually diagnosed with fragile X syndrome and autism displayed greater communication and social reciprocity impairments than individuals with fragile X syndrome only. Individuals in the dually diagnosed group also exhibited higher levels of repetitive and challenging behaviors than either comparison group, suggesting a unique profile of vulnerability for those diagnosed with both fragile X syndrome and autism. PMID:22264109

A tertiary care-primary care partnership model for medically complex and fragile children and youth with special health care needs.

PubMed

Gordon, John B; Colby, Holly H; Bartelt, Tera; Jablonski, Debra; Krauthoefer, Mary L; Havens, Peter

2007-10-01

To evaluate the impact of a tertiary care center special needs program that partners with families and primary care physicians to ensure seamless inpatient and outpatient care and assist in providing medical homes. Up to 3 years of preenrollment and postenrollment data were compared for patients in the special needs program from July 1, 2002, through June 30, 2005. A tertiary care center pediatric hospital and medical school serving urban and rural patients. A total of 227 of 230 medically complex and fragile children and youth with special needs who had a wide range of chronic disorders and were enrolled in the special needs program. Care coordination provided by a special needs program pediatric nurse case manager with or without a special needs program physician. Preenrollment and postenrollment tertiary care center resource utilization, charges, and payments. A statistically significant decrease was found in the number of hospitalizations, number of hospital days, and tertiary care center charges and payments, and an increase was found in the use of outpatient services. Aggregate data revealed a decrease in hospital days from 7926 to 3831, an increase in clinic visits from 3150 to 5420, and a decrease in tertiary care center payments of $10.7 million. The special needs program budget for fiscal year 2005 had a deficit of $400,000. This tertiary care-primary care partnership model improved health care and reduced costs with relatively modest institutional support.

Report on: "The 1st Workshop on National Immunization Programs and Vaccine Coverage in ASEAN Countries, April 30, 2015, Pattaya, Thailand".

PubMed

Hattasingh, Weerawan; Pengsaa, Krisana; Thisyakorn, Usa

2016-03-04

The 1st Workshop on National Immunization Programs and Vaccine Coverage in Association of Southeast Asian Nations (ASEAN) Countries Group (WNIPVC-ASEAN) held a meeting on April 30, 2015, Pattaya, Thailand under the auspices of the Pediatric Infectious Diseases Society and the World Health Organization (WHO). Reports on the current status and initiatives of the national immunization program (NIP) in each ASEAN countries that attended were presented. These reports along with survey data collected from ministries of health in ASEAN countries NIPs demonstrate that good progress has been made toward the goal of the Global Vaccine Action Plan (GVAP). However, some ASEAN countries have fragile health care systems that still have insufficient vaccine coverage of some basic EPI antigens. Most ASEAN countries still do not have national coverage of some new and underused vaccines, and raising funds for the expansion of NIPs is challenging. Also, there is insufficient research into disease burden of vaccine preventable diseases and surveillance. Health care workers must advocate NIPs to government policy makers and other stakeholders as well as improve research and surveillance to achieve the goals of the GVAP. Copyright © 2016. Published by Elsevier Ltd.. All rights reserved.

Comparison Groups in Autism Family Research: Down Syndrome, Fragile X Syndrome, and Schizophrenia

ERIC Educational Resources Information Center

Seltzer, Marsha Mailick; Abbeduto, Leonard; Krauss, Marty Wyngaarden; Greenberg, Jan; Swe, April

2004-01-01

This paper examines methodological challenges inherent in conducting research on families of children with autism and in comparing these families with others who are coping with different types of disabilities or who have nondisabled children. Although most comparative research has contrasted families whose child has autism with those whose child…

Established and Evolving Spoken Research Process Genres: Plenary Lecture and Poster Session Discussions at Academic Conferences.

ERIC Educational Resources Information Center

Shalom, Celia

1993-01-01

Two types of main hall discussions at an ecology conference were studied: plenary lecture discussion as an accepted, established spoken research process genre with its own conventions; and poster session discussion as a fragile, embryonic research process genre struggling for definition. (14 references) (Author/LB)

Behavioral Phenotype of Fragile X Syndrome in Adolescence and Adulthood

ERIC Educational Resources Information Center

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;…

Neurogenetic and Neurodevelopmental Pathways to Learning Disabilities.

ERIC Educational Resources Information Center

Mazzocco, Michele M. M.; And Others

1997-01-01

This paper reviews ongoing research designed to specify the cognitive, behavioral, and neuroanatomical phenotypes of specific genetic etiologies of learning disability. The genetic disorders at the focus of the research include reading disability, neurofibromatosis type 1, Tourette syndrome, and fragile X syndrome. Implications for identifying…

The Overreliance of Accreditors on Consensus Standards.

ERIC Educational Resources Information Center

Murray, Frank B.

2001-01-01

Argues that the legitimacy of accreditation in teacher education is rooted in political consensus, power, and scholarship. Because these roots are fragile, there is no accepted concept of educational malpractice. The legitimacy of accreditation should be rooted in scholarly evidence that the program has fulfilled the claim that its graduates are…

National Fragile X Foundation

MedlinePlus

Donate Contact PS3G Home About About Us Finances 2016 Annual Impact Report (PDF) Learn FXS FXPOI FXTAS Newly Diagnosed Premutation Carriers Treatment and Intervention Prevalence,Genetics and Inheritance Testing Webinars Research ...

Modeling Fragile X Syndrome in Drosophila

PubMed Central

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

Seismic assessment of a multi-span steel railway bridge in Turkey based on nonlinear time history

NASA Astrophysics Data System (ADS)

Yılmaz, Mehmet F.; Çağlayan, Barlas Ö.

2018-01-01

Many research studies have shown that bridges are vulnerable to earthquakes, graphically confirmed by incidents such as the San Fernando (1971 USA), Northridge (1994 USA), Great Hanshin (1995 Japan), and Chi-Chi (1999 Taiwan) earthquakes, amongst many others. The studies show that fragility curves are useful tools for bridge seismic risk assessments, which can be generated empirically or analytically. Empirical fragility curves can be generated where damage reports from past earthquakes are available, but otherwise, analytical fragility curves can be generated from structural seismic response analysis. Earthquake damage data in Turkey are very limited, hence this study employed an analytical method to generate fragility curves for the Alasehir bridge. The Alasehir bridge is part of the Manisa-Uşak-Dumlupınar-Afyon railway line, which is very important for human and freight transportation, and since most of the country is seismically active, it is essential to assess the bridge's vulnerability. The bridge consists of six 30 m truss spans with a total span 189 m supported by 2 abutments and 5 truss piers, 12.5, 19, 26, 33, and 40 m. Sap2000 software was used to model the Alasehir bridge, which was refined using field measurements, and the effect of 60 selected real earthquake data analyzed using the refined model, considering material and geometry nonlinearity. Thus, the seismic behavior of Alasehir railway bridge was determined and truss pier reaction and displacements were used to determine its seismic performance. Different intensity measures were compared for efficiency, practicality, and sufficiency and their component and system fragility curves derived.

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

PubMed

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.

Fragile X syndrome and fragile X-associated tremor ataxia syndrome.

PubMed

Hall, Deborah A; Berry-Kravis, Elizabeth

2018-01-01

Fragile X-associated disorders encompass several conditions, which are caused by expansion mutations in the fragile X mental retardation 1 (FMR1) gene. Fragile X syndrome is the most common inherited etiology of intellectual disability and results from a full mutation or >200 CGG repeats in FMR1. It is associated with developmental delay, autism spectrum disorder, and seizures. Fragile X-associated tremor/ataxia syndrome is a progressive neurodegenerative disease that occurs in premutation carriers of 55-200 CGG repeats in FMR1 and is characterized by kinetic tremor, gait ataxia, parkinsonism, executive dysfunction, and neuropathy. Fragile X-associated primary ovarian insufficiency also occurs in premutation carrier women and manifests with infertility and early menopause. The diseases constituting fragile X-associated disorders differ mechanistically, due to the distinct molecular properties of premutation versus full mutations. Fragile X syndrome occurs when there is a lack of fragile X mental retardation protein (FMRP) due to FMR1 methylation and silencing. In fragile X-associated tremor ataxia syndrome, a toxic gain of function is postulated with the production of excess CGG repeat-containing FMR1 mRNA, abnormal translation of the repeat sequence leading to production of polyglycine, polyalanine, and other polypeptides and to outright deficits in translation leading to reduced FMRP at larger premutation sizes. The changes in underlying brain chemistry due to FMR1 mutations have led to therapeutic studies in these disorders, with some progress being made in fragile X syndrome. This paper also summarizes indications for testing, genetic counseling issues, and what the future holds for these disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Cholinergic Dysfunction in Fragile X Syndrome and Potential Intervention

PubMed Central

Kesler, Shelli R; Lightbody, Amy A; Reiss, Allan L

2009-01-01

Males with fragile X syndrome are at risk for significant cognitive and behavioral deficits, particularly those involving executive prefrontal systems. Disruption of the cholinergic system secondary to fragile X mental retardation protein deficiency may contribute to the cognitive-behavioral impairments associated with fragile X. We measured choline in the dorsolateral prefrontal cortex of 9 males with fragile X syndrome and 9 age-matched typically developing controls using 1H magnetic resonance spectroscopy. Right choline/creatine was significantly reduced in the fragile X group compared to controls. In controls, both left and right choline was significantly positively correlated with intelligence and age was significantly negatively correlated with left choline. There were no correlations in the fragile X group. Subjects with fragile X syndrome participating in a pilot open-label trial of donepezil, an acetylcholinesterase inhibitor, demonstrated significantly improved cognitive-behavioral function. Studies utilizing biochemical neuroimaging techniques such as these have the potential to significantly impact the design of treatment strategies for fragile X syndrome and other genetic disorders by helping identify neurochemical targets for intervention as well as serving as metrics for treatment efficacy. PMID:19215057

Expanding the Supply of Pasteurized Donor Milk: Understanding Why Peer-to-Peer Milk Sharers in the United States Do Not Donate to Milk Banks.

PubMed

Perrin, Maryanne Tigchelaar; Goodell, L Suzanne; Fogleman, April; Pettus, Hannah; Bodenheimer, Amanda L; Palmquist, Aunchalee E L

2016-05-01

Lactating women in the United States have several options for what they do with excess breast milk, including donating to milk banks that serve medically fragile infants, sharing directly with families seeking milk, and selling to individuals or for-profit entities. The World Health Organization and the US Surgeon General have issued calls to increase access to pasteurized donor milk for medically fragile infants. To explore how lactating women with a surplus of breast milk come to the decision to share their milk with a peer rather than donate to a milk bank. A qualitative design using a grounded theory approach was employed. Semistructured telephone interviews were conducted with 27 women who had shared milk with a peer but not with a milk bank. Five dominant themes were identified: a strong belief in the value of breast milk, unexpected versus planned donation, sources of information regarding milk exchange, concerns and knowledge gaps about milk banks, and helping and connecting. This research offers insights into potential strategies for promoting milk bank donation among peer-to-peer milk sharers, including developing donor education campaigns focused on knowledge gaps regarding milk banks and developing health care professional referral programs that can reduce barriers associated with the convenience of milk bank donation. © The Author(s) 2016.

Fragile--Handle with Care: Regression Analyses That Include Categorical Data.

ERIC Educational Resources Information Center

Brown, Diane Peacock

In education and the social sciences, problems of interest to researchers and users of research often involve variables that do not meet the assumptions of regression in the area of an equal interval scale relative to a zero point. Various coding schemes exist that allow the use of regression while still answering the researcher's questions of…

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

ERIC Educational Resources Information Center

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…

Earthquake Loss Estimates in Near Real-Time

NASA Astrophysics Data System (ADS)

Wyss, Max; Wang, Rongjiang; Zschau, Jochen; Xia, Ye

2006-10-01

The usefulness to rescue teams of nearreal-time loss estimates after major earthquakes is advancing rapidly. The difference in the quality of data available in highly developed compared with developing countries dictates that different approaches be used to maximize mitigation efforts. In developed countries, extensive information from tax and insurance records, together with accurate census figures, furnish detailed data on the fragility of buildings and on the number of people at risk. For example, these data are exploited by the method to estimate losses used in the Hazards U.S. Multi-Hazard (HAZUSMH)software program (http://www.fema.gov/plan/prevent/hazus/). However, in developing countries, the population at risk is estimated from inferior data sources and the fragility of the building stock often is derived empirically, using past disastrous earthquakes for calibration [Wyss, 2004].

Are multiple visual short-term memory storages necessary to explain the retro-cue effect?

PubMed

Makovski, Tal

2012-06-01

Recent research has shown that change detection performance is enhanced when, during the retention interval, attention is cued to the location of the upcoming test item. This retro-cue advantage has led some researchers to suggest that visual short-term memory (VSTM) is divided into a durable, limited-capacity storage and a more fragile, high-capacity storage. Consequently, performance is poor on the no-cue trials because fragile VSTM is overwritten by the test display and only durable VSTM is accessible under these conditions. In contrast, performance is improved in the retro-cue condition because attention keeps fragile VSTM accessible. The aim of the present study was to test the assumptions underlying this two-storage account. Participants were asked to encode an array of colors for a change detection task involving no-cue and retro-cue trials. A retro-cue advantage was found even when the cue was presented after a visual (Experiment 1) or a central (Experiment 2) interference. Furthermore, the magnitude of the interference was comparable between the no-cue and retro-cue trials. These data undermine the main empirical support for the two-storage account and suggest that the presence of a retro-cue benefit cannot be used to differentiate between different VSTM storages.

Can a decision aid enable informed decisions in neonatal nursery recruitment for a fragile X newborn screening study?

PubMed

Bailey, Donald B; Bann, Carla; Bishop, Ellen; Guarda, Sonia; Barnum, Leah; Roche, Myra

2013-04-01

To determine whether a brochure based on principles of informed decision making improved attention to study materials or altered decisions made by parents invited to participate in a fragile X syndrome newborn screening study. A total of 1,323 families were invited to participate in a newborn screening study to identify infants with fragile X syndrome as well as premutation carrier infants. Of these families, 716 received the original project brochure and 607 were given a new decision aid brochure. Families were more likely to look at the new decision aid and mothers were more likely to read it completely, but the proportion of mothers who read the entire decision aid was only 14%. Families were more likely to rate the decision aid as very helpful. Consistent with informed decision making theory and research, participants receiving the decision aid brochure were less likely to agree to participate. The decision aid increased attention to and perceived helpfulness of educational information about the study, but most families did not read it completely. The study suggests that even well-designed study materials are not fully reviewed in the context of in-hospital postpartum study recruitment and may need to be accompanied by a research recruiter to obtain informed consent.

Finding FMR1 mosaicism in Fragile X syndrome

PubMed Central

Gonçalves, Thaís Fernandez; dos Santos, Jussara Mendonça; Gonçalves, Andressa Pereira; Tassone, Flora; Mendoza-Morales, Guadalupe; Ribeiro, Márcia Gonçalves; Kahn, Evelyn; Boy, Raquel; Pimentel, Márcia Mattos Gonçalves; Santos-Rebouças, Cíntia Barros

2016-01-01

OBJETIVE Almost all patients with Fragile X Syndrome (FXS) exhibit a CGG repeat expansion (full mutation) in the Fragile Mental Retardation 1 gene (FMR1). Here, we report five unrelated males with FXS harboring a somatic full mutation/deletion mosaicism. METHODS Mutational profiles were only elucidated by using a combination of molecular approaches (CGG-based PCR, Sanger sequencing, MS-MLPA, Southern blot and mPCR). RESULT Four patients exhibited small deletions encompassing the CGG repeats tract and flanking regions, whereas the remaining had a larger deletion comprising at least exon 1 and part of intron 1 of FMR1 gene. The presence of a 2–3 base pairs microhomology in proximal and distal non-recurrent breakpoints without scars supports the involvement of microhomology mediated induced repair (MMBIR) mechanism in three small deletions. CONCLUSION Our data highlights the importance of using different research methods to elucidate atypical FXS mutational profiles, which are clinically undistinguishable and may have been underestimated. PMID:26716517

Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome

PubMed Central

Hagerman, Randi; Hagerman, Paul

2014-01-01

Summary Fragile X syndrome, the leading heritable form of cognitive impairment, is caused by epigenetic silencing of the fragile X (FMR1) gene consequent to large expansions (>200 repeats) of a non-coding CGG-repeat element. Smaller, “premutation” expansions (55–200 repeats) can give rise to a family of neurodevelopmental (ADHD, autism spectrum disorder, seizure disorder) and neurodegenerative (FXTAS) clinical phenotypes through an entirely distinct molecular mechanism involving increased FMR1 mRNA production and toxicity. Basic cellular, animal, and human studies have helped to elucidate the underlying RNA toxicity mechanism, while clinical research is providing a more nuanced picture of the spectrum of clinical involvement. Whereas advances on both mechanistic and clinical fronts are driving new approaches to targeted treatment, two important issues/needs are emerging: to define the extent to which the mechanisms contributing to FXTAS also contribute to other neurodegenerative and medical disorders, and to redefine FXTAS in light of its differing presentations and associated features. PMID:23867198

Emerging role of the KCNT1 Slack channel in intellectual disability.

PubMed

Kim, Grace E; Kaczmarek, Leonard K

2014-01-01

The sodium-activated potassium KNa channels Slack and Slick are encoded by KCNT1 and KCNT2, respectively. These channels are found in neurons throughout the brain, and are responsible for a delayed outward current termed I KNa. These currents integrate into shaping neuronal excitability, as well as adaptation in response to maintained stimulation. Abnormal Slack channel activity may play a role in Fragile X syndrome, the most common cause for intellectual disability and inherited autism. Slack channels interact directly with the fragile X mental retardation protein (FMRP) and I KNa is reduced in animal models of Fragile X syndrome that lack FMRP. Human Slack mutations that alter channel activity can also lead to intellectual disability, as has been found for several childhood epileptic disorders. Ongoing research is elucidating the relationship between mutant Slack channel activity, development of early onset epilepsies and intellectual impairment. This review describes the emerging role of Slack channels in intellectual disability, coupled with an overview of the physiological role of neuronal I KNa currents.

Newly-Identified Fragile Sites Push Stressed Cells toward Cancer | Center for Cancer Research

Cancer.gov

The genomes of cancer cells are often riddled with chromosomal alterations such as amplifications, deletions, and even translocations, where a piece of one chromosome breaks off and attaches to another. Understanding how these changes arise can give researchers new insights into the process of cancer development.

Those They Leave behind: Paternal Incarceration and Maternal Instrumental Support

ERIC Educational Resources Information Center

Turney, Kristin; Schnittker, Jason; Wildeman, Christopher

2012-01-01

As the American imprisonment rate has risen, researchers have become increasingly concerned about the implications of mass imprisonment for family life. The authors extend this research by examining how paternal incarceration is linked to perceived instrumental support among the mothers of inmates' children. Results from the Fragile Families and…

The ABCs of the US Broad Spectrum Antimicrobials Program: Antibiotics, Biosecurity, and Congress

PubMed Central

2015-01-01

Antibiotic resistance has been increasing at an alarming rate in the United States and globally for decades, but the problem has only recently gained broad attention at the highest levels of the US government. More and more patients are dying of infections that do not respond to antibiotics that are currently available. Meanwhile, the antibacterial product pipeline remains fragile in part because of a lack of commercial interest from pharmaceutical companies. The Biomedical Advanced Research and Development Authority (BARDA) Broad Spectrum Antimicrobials (BSA) program leads the US government's effort to bridge this gap by advancing new antibacterials through late stages of clinical development. Other commentators have described in detail BARDA's structure, process, and role in antibacterial development. This commentary offers a public policy perspective on the emerging politics of antibiotic resistance in the context of US biosecurity politics and medical countermeasure (MCM) development. It identifies promising developments and difficult challenges that together will ultimately determine whether BARDA can become a global leader for antibiotic development. PMID:26569379

Fragile Families and Child Wellbeing

PubMed Central

Waldfogel, Jane; Craigie, Terry-Ann; Brooks-Gunn, Jeanne

2011-01-01

Summary Jane Waldfogel, Terry-Ann Craigie, and Jeanne Brooks-Gunn review recent studies that use data from the Fragile Families and Child Wellbeing Study (FFCWS) to examine why children who grow up in single-mother and cohabiting families fare worse than children born into married-couple households. They also present findings from their own new research. Analysts have investigated five key pathways through which family structure might influence child well-being: parental resources, parental mental health, parental relationship quality, parenting quality, and father involvement. It is also important to consider the role of the selection of different types of men and women into different family types, as well as family stability. But analysts remain uncertain how each of these elements shapes children's outcomes. In addition to providing an overview of findings from other studies using FFCWS, Waldfogel, Craigie, and Brooks-Gunn report their own estimates of the effect of a consistently defined set of family structure and stability categories on cognitive, behavioral, and health outcomes of children in the FFCWS study at age five. The authors find that the links between fragile families and child outcomes are not uniform. Family instability, for example, seems to matter more than family structure for cognitive and health outcomes, whereas growing up with a single mother (whether that family structure is stable or unstable over time) seems to matter more than instability for behavior problems. Overall, their results are consistent with other research findings that children raised by stable single or cohabiting parents are at less risk than those raised by unstable single or cohabiting parents. The authors conclude by pointing to three types of policy reforms that could improve outcomes for children. The first is to reduce the share of children growing up in fragile families (for example, through reducing the rate of unwed births or promoting family stability among unwed parents). The second is to address the pathways that place such children at risk (for example, through boosting resources in single-parent homes or fostering father involvement in fragile families). The third is to address directly the risks these children face (for example, through high-quality early childhood education or home-visiting policies). PMID:20964133

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

PubMed

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.

Osteo-cise: Strong Bones for Life: Protocol for a community-based randomised controlled trial of a multi-modal exercise and osteoporosis education program for older adults at risk of falls and fractures

PubMed Central

2012-01-01

Background Osteoporosis affects over 220 million people worldwide, and currently there is no ‘cure’ for the disease. Thus, there is a need to develop evidence-based, safe and acceptable prevention strategies at the population level that target multiple risk factors for fragility fractures to reduce the health and economic burden of the condition. Methods/design The Osteo-cise: Strong Bones for Life study will investigate the effectiveness and feasibility of a multi-component targeted exercise, osteoporosis education/awareness and behavioural change program for improving bone health and muscle function and reducing falls risk in community-dwelling older adults at an increased risk of fracture. Men and women aged ≥60 years will participate in an 18-month randomised controlled trial comprising a 12-month structured and supervised community-based program and a 6-month ‘research to practise’ translational phase. Participants will be randomly assigned to either the Osteo-cise intervention or a self-management control group. The intervention will comprise a multi-modal exercise program incorporating high velocity progressive resistance training, moderate impact weight-bearing exercise and high challenging balance exercises performed three times weekly at local community-based fitness centres. A behavioural change program will be used to enhance exercise adoption and adherence to the program. Community-based osteoporosis education seminars will be conducted to improve participant knowledge and understanding of the risk factors and preventative measures for osteoporosis, falls and fractures. The primary outcomes measures, to be collected at baseline, 6, 12, and 18 months, will include DXA-derived hip and spine bone mineral density measurements and functional muscle power (timed stair-climb test). Secondary outcomes measures include: MRI-assessed distal femur and proximal tibia trabecular bone micro-architecture, lower limb and back maximal muscle strength, balance and function (four square step test, functional reach test, timed up-and-go test and 30-second sit-to-stand), falls incidence and health-related quality of life. Cost-effectiveness will also be assessed. Discussion The findings from the Osteo-cise: Strong Bones for Life study will provide new information on the efficacy of a targeted multi-modal community-based exercise program incorporating high velocity resistance training, together with an osteoporosis education and behavioural change program for improving multiple risk factors for falls and fracture in older adults at risk of fragility fracture. Trial registration Australian New Zealand Clinical Trials Registry reference ACTRN12609000100291 PMID:22640372

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lijin; Guan, Pengfei, E-mail: pguan@csrc.ac.cn; 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 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}more » 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.« less

Systems fragility: The sociology of chaos.

PubMed

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.

Ethics, Education Policy and Research: The Phonics Question Reconsidered

ERIC Educational Resources Information Center

Ellis, Sue; Moss, Gemma

2014-01-01

This paper argues that direct control of the early years literacy curriculum recently exercised by politicians in England has made the boundaries between research, policy and practice increasingly fragile. It describes how policy came to focus most effort on the use of synthetic phonics programmes in the early years. It examines why the…

Organizational Learning and the Transnationalization of Further Education: Pedagogical Research on Cross-Border Organizations

ERIC Educational Resources Information Center

Göhlich, Michael; Engel, Nicolas; Höhne, Thomas

2014-01-01

With the processes of migration, globalization and (in our research context: especially) European unification, not only territorial borders but also cultural traditions become fragile (Eberhard et al., 2009). The daily challenges, as well as the opportunities afforded by crossing national, cultural, and linguistic borders, are growing (Beyer &…

Preschoolers' Understanding of Subtraction-Related Principles

ERIC Educational Resources Information Center

Baroody, Arthur J.; Lai, Meng-lung; Li, Xia; Baroody, Alison E.

2009-01-01

Little research has focused on an informal understanding of subtractive negation (e.g., 3 - 3 = 0) and subtractive identity (e.g., 3 - 0 = 3). Previous research indicates that preschoolers may have a fragile (i.e., unreliable or localized) understanding of the addition-subtraction inverse principle (e.g., 2 + 1 - 1 = 2). Recognition of a small…

Attendance at Fragile X Specialty Clinics: Facilitators and Barriers

ERIC Educational Resources Information Center

Kidd, Sharon A.; Raspa, Melissa; Clark, Renée; Usrey-Roos, Holly; Wheeler, Anne C.; Liu, Jessica A.; Wylie, Amanda; Sherman, Stephanie L.

2017-01-01

The objectives were to describe the demographic characteristics of children with Fragile X syndrome (FXS) and to determine predictors of attendance at Fragile X (FX) clinics. Findings from the Community Support Network (CSN) and Our Fragile X World (OFXW) samples showed that children who attended FX Clinics were mostly male, high-school aged or…

Medically Fragile Children: Report from State Committee on Medically Fragile Child Referent Group.

ERIC Educational Resources Information Center

Michigan State Dept. of Education, Lansing. Special Education Services.

This report is the product of a committee charged to define "medically fragile," explore the array of educational services available and/or needed for children in Michigan considered medically fragile, identify current information and gaps in the information, and identify areas of interagency collaboration. The report discusses critical…

Cognitive, Behavioral, and Adaptive Functioning in Fragile X and Non-Fragile X Retarded Men.

ERIC Educational Resources Information Center

Dykens, Elisabeth; And Others

1988-01-01

Evaluation of the cognitive, behavioral, and adaptive functioning of 12 retarded men with fragile X syndrome indicated that fragile X men were largely indistinguishable from comparison groups. They were, however, significantly more likely to have achieved levels of adaptive functioning commensurate with their intellectual abilities. (Author/DB)

An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

PubMed Central

Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes

2016-01-01

Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome. PMID:26788253

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

PubMed

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.

Summary Report: Visitor Safety and Security at Corps of Engineers Projects.

DTIC Science & Technology

1982-10-01

23 Incident Reporting System. ..... .............. 23 Contract Law Enforcement ...... .............. 25 Project Management...average length of stay being 3.3 days. Contract Law Enforcement Conclusions , The Corps’ contract law enforcement program is extremely fragile in terms...to prohibit the public display alcoholic beverages and consumption of alcoholic beverages. Use contract law initiate law enforcement contracts

Special Day Class Teachers' Perceptions of the Role of the School Nurse

ERIC Educational Resources Information Center

Leier, Janice L.; Cureton, Virginia Young; Canham, Daryl L.

2003-01-01

School nurses are on the front lines of health care in public schools. The integration of students' health care needs as components of educational programs has become increasingly important as medically fragile children rely on school nurses to deliver or coordinate their health care services. The purpose of this descriptive study was to determine…

The Role of Ocean Exploration and Research in the Creation and Management of Marine Protected Areas (MPAs)

NASA Astrophysics Data System (ADS)

Valette-Silver, N. J.; Pomponi, S.; Smith, J. R.; Potter, J.

2012-12-01

Over the past decades, the NOAA Office of Ocean Exploration and Research (OER), through its programs (Ocean Exploration Program and National Undersea Research Program), and in collaboration with its federal and academic partners, has contributed to the discovery of new ocean features, species, ecosystems, habitats and processes. These new discoveries have led to the development of new policies and management actions. Exploration, research and technology advancement have contributed to the characterization and the designation of marine sanctuaries, reserves, restricted fishing areas, and monuments in US waters. For example, the collaborative efforts of OER and partners from the Cooperative Institute for Ocean Exploration, Research and Technology (CIOERT) have resulted in the discovery of new species of deep sea corals on the outer continental shelf and upper slope of the South Atlantic Bight. The species of coral found in these deep sea reefs are growing very slowly and provide habitat for many commercially valuable species of fish and other living resources. It is not yet completely clear how these habitats connect with the shallower reefs and habitats and if they could be playing a role of refugia for shallower species. Unfortunately, signs of fishing destruction on these unique and fragile habitats are obvious (e.g., abandoned nets, completely decimated habitats by trawling). OER funded research on mesophotic and deep-sea Lophelia coral reefs off the southeastern US was instrumental in the designation of the deep-water Coral Habitat Area of Particular Concern (CHAPC) that is now protecting these fragile reefs. Other examples of OER's contribution to discoveries leading to the designation of protected areas include the characterization and boundary determination of new designated Marine National Monuments and Marine Sanctuaries in the Pacific Ocean. After designation of a protected area, it is imperative to monitor the resource, improve understanding of its functioning, and thus be in a position to better protect it. While most of the reef fish surveys are conducted in shallow areas (0-20 m), it is recognized that many commercially exploited fish stocks also utilize deeper habitats (50-400m). However, traditional methods (e.g., hook-and-line) for sampling these bottom fish species cannot be used in many areas of the Northwestern Hawaiian Islands Coral Reef Ecosystem Reserve [now a Monument] and other restricted fishing areas. Our ability to assess and monitor ocean living marine resources is important for ecosystem management as well as for determining the effectiveness of Marine Protected Areas (MPAs). The development and deployment of non-extractive sampling methods such as autonomous camera systems to collect information about the spatial distribution and relative abundance of bottom fish species is one of the preferred methods. In addition, OER and the Hawaii Undersea Research Lab (HURL) were two of the first groups to conduct scientific research in the Northwestern Hawaiian Islands Coral Reef Ecosystem Reserve after it was established in 2000. Submersible dives (down to 2000 m) or ROV dives into the depths surrounding the remote islands, banks, and atolls have led to dozens of discoveries of new and yet to be identified species.

Future orientation and competence to stand trial: the fragility of competence.

PubMed

Kivisto, Aaron J; Moore, Todd M; Fite, Paula A; Seidner, Bruce G

2011-01-01

The current study examined the direct, indirect, and interactive effects of age, intellectual ability, psychiatric symptomatology, and future orientation on juvenile adjudicative competence utilizing a secondary sample of 927 youth from the MacArthur Juvenile Adjudicative Competence Study. Consistent with previous research, age, intellectual ability, and future orientation were found to be positively associated with competence, and psychiatric symptomatology was weakly negatively related to competence. Tests of indirect effects revealed that the development of an orientation toward future consequences partially explains the relationship between age and the capacity to reason about legal decision-making. Further, tests of invariance revealed that the competence of immature adolescents is particularly "fragile," in that smaller deficits in cognitive abilities appear to pose greater problems in youths regarding their adjudicative competence than in their more mature peers. Findings are discussed in regard to forensic practice as well as for future research.

Heart Activity and Autistic Behavior in Infants and Toddlers with Fragile X Syndrome

ERIC Educational Resources Information Center

Roberts, Jane E.; Tonnsen, Bridgette; Robinson, Ashley; Shinkareva, Svetlana V.

2012-01-01

The present study contrasted physiological arousal in infants and toddlers with fragile X syndrome to typically developing control participants and examined physiological predictors early in development to autism severity later in development in fragile X syndrome. Thirty-one males with fragile X syndrome (ages 8-40 months) and 25 age-matched…

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

ERIC Educational Resources Information Center

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…

Osmotic fragility changes in preserved blood: measurements by coil planet centrifuge and parpart methods.

PubMed

Sasakawa, S; Tokunaga, E; Hasegawa, G; Nakagawa, S

1977-09-01

The coil planet centrifuge (CPC) can be used to measure the osmotic fragility of erythrocytes. Fragility measured by this method alters when different salts are used. The CPC and Parpart methods were used to measure the changes during storage in red cell osmotic fragility in ACD or CPD blood with or without adenine. More marked changes were detected by the CPC method, especially in old cells. The changes of fragility of erythrocytes during storage seem to occur mainly in old cells. Adenine is effective in preventing such changes.

Haïti and the health marketplace: the role of the private, informal market in filling the gaps left by the state.

PubMed

Durham, J; Michael, Marcos; Hill, P S; Paviignani, E

2015-09-28

In most societies the health marketplace is pluralistic in character, with a mix of formal and informal providers. In high-income countries, state regulation of the market helps ensure quality and access and mitigate market failures. In the present study, using Haiti as a case study, we explore what happens to the functioning of the pluralistic health marketplace in severely disrupted environments where the informal sector is able to flourish. The overall research design was qualitative. Research methods included an extensive documentary and policy analysis, based on peer-reviewed articles, books and "grey" literature--government policy and program reports, unpublished research and evaluations, reviews and reviews from key multilateral and bilateral donors, and non-government organisations, combined with field site visits and in-depth key informant interviews (N = 45). The findings show that state fragility has resulted in a privatised, commoditised and largely unregulated and informal health market. While different market segments can be identified, in reality the boundaries between international/domestic, public/private, for profit/not-for-profit, legal/illegal are hazy and shifting. The lack of state capacity to provide an enabling environment, establish, and enforce its regulatory framework has resulted in a highly segmented, heterogeneous and informal health market. The result is deplorable health indices which are far below regional averages and many other low-income countries. Working in fragile states with limited capacity to undertake the core function of securing the health of its population requires new and innovative ways of working. This needs longer time-frames, combining incremental top-down and bottom-up strategies which recognize and work with state and civil society, public and private actors, formal and informal institutions, and progressively facilitate changes in the different market functions of supply, demand, regulation and supporting functions.

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

ERIC Educational Resources Information Center

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…

Differential Impact of the "FMR1" Gene on Visual Processing in Fragile X Syndrome

ERIC Educational Resources Information Center

Kogan, Cary S.; Boutet, Isabelle; Cornish, Kim; Zangenehpour, Shahin; Mullen, Kathy T.; Holden, Jeanette J. A.; Kaloustian, Vazken M. Der; Andermann, Eva; Chaudhuri, Avi

2004-01-01

Fragile X syndrome (FXS) is the most common form of heritable mental retardation, affecting (~ around) 1 in 4000 males. The syndrome arises from expansion of a trinucleotide repeat in the 5'-untranslated region of the fragile X mental retardation 1 ("FMR1") gene, leading to methylation of the promoter sequence and lack of the fragile X mental…

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

ERIC Educational Resources Information Center

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…

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

ERIC Educational Resources Information Center

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…

[Soil seed bank research of China mining areas: necessity and challenges].

PubMed

Chang, Qing; Zhang, Da-Wei; Li, Xue; Peng, Jian; Guan, Ai-Nong; Liu, Xiao-Si

2011-05-01

Soil seed bank consists of all living seeds existed in soil and its surface litter, especially in topsoil, and can reflect the characteristics of regional biodiversity. As the base of vegetation restoration and potential greening material, topsoil and its seed bank are the limited and non-renewable resources in mining areas. The study of soil seed bank has become one of the hotspots in the research field of vegetation restoration and land reclamation in China mining areas. Owing to the special characteristics of mining industry, the soil seed bank study of mining areas should not only concern with the seed species, quantities, and their relations with ground surface vegetation, but also make use of the research results on the soil seed bank of other fragile habitats. Besides, a breakthrough should be sought in the thinking ways and research approach. This paper analyzed the particularity of mining area's soil seek bank research, summarized the research progress in the soil seed bank of mining areas and other fragile habitats, and put forward the challenges we are facing with. It was expected that this paper could help to reinforce the soil seed bank research of China mining areas, and provide scientific guidelines for taking great advantage of the significant roles of soil seed bank in land reclamation and vegetation restoration in the future.

Human Lymphoid Translocation Fragile Zones Are Hypomethylated and Have Accessible Chromatin

PubMed Central

Lu, Zhengfei; Tsai, Albert G.; Pardo, Carolina E.; Müschen, Markus; Kladde, Michael P.

2015-01-01

Chromosomal translocations are a hallmark of hematopoietic malignancies. CG motifs within translocation fragile zones (typically 20 to 600 bp in size) are prone to chromosomal translocation in lymphomas. Here we demonstrate that the CG motifs in human translocation fragile zones are hypomethylated relative to the adjacent DNA. Using a methyltransferase footprinting assay on isolated nuclei (in vitro), we find that the chromatin at these fragile zones is accessible. We also examined in vivo accessibility using cellular expression of a prokaryotic methylase. Based on this assay, which measures accessibility over a much longer time interval than is possible with in vitro methods, these fragile zones were found to be more accessible than the adjacent DNA. Because DNA within the fragile zones can be methylated by both cellular and exogenous methyltransferases, the fragile zones are predominantly in a duplex DNA conformation. These observations permit more-refined models for why these zones are 100- to 1,000-fold more prone to undergo chromosomal translocation than the adjacent regions. PMID:25624348

Modelling fragile X syndrome in the laboratory setting: A behavioral perspective.

PubMed

Melancia, Francesca; Trezza, Viviana

2018-04-25

Fragile X syndrome is the most common form of inherited mental retardation and the most frequent monogenic cause of syndromic autism spectrum disorders. The syndrome is caused by the loss of the Fragile X Mental Retardation Protein (FMRP), a key RNA-binding protein involved in synaptic plasticity and neuronal morphology. Patients show intellectual disability, social deficits, repetitive behaviors and impairments in social communication. The aim of this review is to outline the importance of behavioral phenotyping of animal models of FXS from a developmental perspective, by showing how the behavioral characteristics of FXS at the clinical level can be translated into effective, developmentally-specific and clinically meaningful behavioral readouts in the laboratory setting. After introducing the behavioral features, diagnostic criteria and off-label pharmacotherapy of FXS, we outline how FXS-relevant behavioral features can be modelled in laboratory animals in the course of development: we review the progress to date, discuss how behavioral phenotyping in animal models of FXS is essential to identify potential treatments, and discuss caveats and future directions in this research field. Copyright © 2018. Published by Elsevier B.V.

Father Doesn't Know Best? Parents' Control of Money and Children's Food Insecurity

ERIC Educational Resources Information Center

Kenney, Catherine T.

2008-01-01

Although developing-country research has found that spending on children varies depending on which parent controls income, developed-country research tends to ignore intrahousehold allocation. This study uses Fragile Families and Child Wellbeing Study data (N = 1,073 couples) to analyze how mothers versus fathers controlling money affects U.S.…

International Arid Lands Consortium: Better land stewardship in water and watershed management

Treesearch

Peter F. Ffolliott; James T. Fisher; Menachem Sachs; Darrell W. DeBoer; Jeffrey O. Dawson; Timothy E. Fulbright; John Tracy

2000-01-01

The International Arid Lands Consortium (IALC) was established in 1990 to promote research, education, and training for the development, management, and restoration of arid and semi-arid lands throughout the world. One activity of IALC members and cooperators is to support research and development and demonstration projects that enhance management of these fragile...

Microbial ecology of deep-water mid-Atlantic canyons

USGS Publications Warehouse

Kellogg, Christina A.

2011-01-01

The research described in this fact sheet will be conducted from 2012 to 2014 as part of the U.S. Geological Survey's DISCOVRE (DIversity, Systematics, and COnnectivity of Vulnerable Reef Ecosystems) Program. This integrated, multidisciplinary effort will be investigating a variety of topics related to unique and fragile deep-sea ecosystems from the microscopic level to the ecosystem level. One goal is to improve understanding, at the microbiological scale, of the benthic communities (including corals) that reside in and around mid-Atlantic canyon habitats and their associated environments. Specific objectives include identifying and characterizing the microbial associates of deep-sea corals, characterizing the microbial biofilms on hard substrates to better determine their role in engineering the ecosystem, and adding a microbial dimension to benthic community structure and function assessments by characterizing micro-eukaryotes, bacteria, and archaea in deep-sea sediments.

Natural Selection, Childrearing, and the Ethics of Marriage (and Divorce): Building a Case for the Neuroenhancement of Human Relationships.

PubMed

Earp, Brian D; Sandberg, Anders; Savulescu, Julian

2012-12-01

We argue that the fragility of contemporary marriages-and the corresponding high rates of divorce-can be explained (in large part) by a three-part mismatch: between our relationship values, our evolved psychobiological natures, and our modern social, physical, and technological environment. "Love drugs" could help address this mismatch by boosting our psychobiologies while keeping our values and our environment intact. While individual couples should be free to use pharmacological interventions to sustain and improve their romantic connection, we suggest that they may have an obligation to do so as well, in certain cases. Specifically, we argue that couples with offspring may have a special responsibility to enhance their relationships for the sake of their children. We outline an evolutionarily informed research program for identifying promising biomedical enhancements of love and commitment.

Risk of fragility fracture among patients with sarcoidosis: a population-based study 1976-2013.

PubMed

Ungprasert, P; Crowson, C S; Matteson, E L

2017-06-01

Incidence of fragility fracture of a population-based cohort of 345 patients with sarcoidosis was compared with age and sex-matched comparators. The incidence of fragility fracture was higher among patients with sarcoidosis with hazard ratio (HR) of 2.18. Several chronic inflammatory disorders increase the risk of fragility fracture. However, little is known about the risk of fragility fracture in patients with sarcoidosis. This study was conducted using a previously identified population-based cohort of 345 patients with incident sarcoidosis from Olmsted County, Minnesota. Diagnosis of sarcoidosis required physician diagnosis supported by biopsy showing non-caseating granuloma, radiographic evidence of intrathoracic sarcoidosis, and compatible clinical presentations without evidence of other granulomatous diseases. Sex and age-matched subjects randomly selected from the same underlying population were used as comparators. Medical records of cases and comparators were reviewed for baseline characteristics and incident fragility fracture. Fragility fractures were observed in 34 patients with sarcoidosis, corresponding to a cumulative incidence of 5.6% at 10 years, while 18 fragility fractures were observed among comparators for a cumulative incidence of 2.4% at 10 years. The HR of fragility fractures among cases compared with comparators was 2.18 (95% confidence interval [CI], 1.23-3.88). The risk of fragility fracture by site was significantly higher among patients with sarcoidosis, and was due to a higher rate of distal forearm fracture (HR 3.58; 95% CI 1.53-8.40). Statistically non-significant increased risk was also observed in proximal femur (HR 1.66; 95% CI 0.45-6.06) and proximal humerus (HR 3.27; 95% CI 0.66-16.21). Risk of vertebral fracture was not increased (HR 1.00; 95% CI 0.32-3.11). Patients with sarcoidosis have an increased risk of fragility fracture which is primarily driven by the higher incidence of distal forearm fracture.

Fragile X Syndrome

MedlinePlus

Fragile X syndrome is the most common form of inherited developmental disability. A problem with a specific gene causes ... the protein. This causes the symptoms of Fragile X. People with only a small change in the ...

Fragility correlates thermodynamic and kinetic properties of glass forming liquids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reddy, C.Narayana; Viswanatha, R.; Chethana, B.K.

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{submore » 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.« less

Just for Us: An Academic Medical Center-Community Partnership to Maintain the Health of a Frail Low-Income Senior Population

ERIC Educational Resources Information Center

Yaggy, Susan D.; Michener, J. Lloyd; Yaggy, Duncan; Champagne, Mary T.; Silberberg, Mina; Lyn, Michelle; Johnson, Fred; Yarnall, Kimberly S. H.

2006-01-01

Purpose: To promote health and maintain independence, Just for Us provides financially sustainable, in-home, integrated care to medically fragile, low-income seniors and disabled adults living in subsidized housing. Design and Methods: The program provides primary care, care management, and mental health services delivered in patient's homes by a…

A Trial of Metformin in Individuals With Fragile X Syndrome

ClinicalTrials.gov

2018-06-05

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

Fragile X Mental Retardation Syndrome: Structure of the KH1-KH2 Domains of Fragile X Mental Retardation Protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valverde,R.; Poznyakova, I.; Kajander, T.

Fragile X syndrome is the most common form of inherited mental retardation in humans, with an estimated prevalence of about 1 in 4000 males. Although several observations indicate that the absence of functional Fragile X Mental Retardation Protein (FMRP) is the underlying basis of Fragile X syndrome, the structure and function of FMRP are currently unknown. Here, we present an X-ray crystal structure of the tandem KH domains of human FMRP, which reveals the relative orientation of the KH1 and KH2 domains and the location of residue Ile304, whose mutation to Asn is associated with a particularly severe incidence ofmore » Fragile X syndrome. We show that the Ile304Asn mutation both perturbs the structure and destabilizes the protein.« less

Perseveration in the Connected Speech of Boys with Fragile X Syndrome with and Without Autism Spectrum Disorder

PubMed Central

Martin, Gary E.; Roberts, Joanne E.; Helm-Estabrooks, Nancy; Sideris, John; Vanderbilt, Jacqueline; Moskowitz, Lauren

2012-01-01

Verbal perseveration is a frequently reported language characteristic of males with Fragile X syndrome and may be a defining feature or hallmark of the syndrome. We compared the verbal perseveration of boys with Fragile X syndrome with (n = 29) and without (n = 30) autism spectrum disorder, boys with Down syndrome (n = 27), and typically developing boys (n = 25) at similar nonverbal mental ages. During a social interaction, boys with both Fragile X syndrome and autism spectrum disorder produced significantly more topic perseveration than all other groups. In social interaction as compared to narration, boys with Fragile X syndrome (regardless of autism status) produced significantly more topic perseveration. These findings suggest that autism status, as well as language sampling context, affect perseveration in boys with Fragile X syndrome. PMID:22998486

Pharmacological reversal of synaptic plasticity deficits in the mouse model of fragile X syndrome by group II mGluR antagonist or lithium treatment.

PubMed

Choi, Catherine H; Schoenfeld, Brian P; Bell, Aaron J; Hinchey, Paul; Kollaros, Maria; Gertner, Michael J; Woo, Newton H; Tranfaglia, Michael R; Bear, Mark F; Zukin, R Suzanne; McDonald, Thomas V; Jongens, Thomas A; McBride, Sean M J

2011-03-22

Fragile X syndrome is the leading single gene cause of intellectual disabilities. Treatment of a Drosophila model of Fragile X syndrome with metabotropic glutamate receptor (mGluR) antagonists or lithium rescues social and cognitive impairments. A hallmark feature of the Fragile X mouse model is enhanced mGluR-dependent long-term depression (LTD) at Schaffer collateral to CA1 pyramidal synapses of the hippocampus. Here we examine the effects of chronic treatment of Fragile X mice in vivo with lithium or a group II mGluR antagonist on mGluR-LTD at CA1 synapses. We find that long-term lithium treatment initiated during development (5-6 weeks of age) and continued throughout the lifetime of the Fragile X mice until 9-11 months of age restores normal mGluR-LTD. Additionally, chronic short-term treatment beginning in adult Fragile X mice (8 weeks of age) with either lithium or an mGluR antagonist is also able to restore normal mGluR-LTD. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of Fragile X syndrome is an important advance, in that this identifies and validates these targets as potential therapeutic interventions for the treatment of individuals afflicted with Fragile X syndrome. Copyright © 2010 Elsevier B.V. All rights reserved.

Beyond the Factor of Safety: Developing Fragility Curves to Characterize System Reliability

DTIC Science & Technology

2010-07-01

increasingly common compo- nents of flood risk assessments. This report introduces the concept of the fragility curve and shows how fragility curves are...curves are identified in the literature on structures and risk assessment to identify what methods have been used to develop fragility curves in...and disadvantages of the various approaches are considered. DISCLAIMER: The contents of this report are not to be used for advertising

Fragile x syndrome.

PubMed

McLennan, Yingratana; Polussa, Jonathan; Tassone, Flora; Hagerman, Randi

2011-05-01

Recent data from a national survey highlighted a significant difference in obesity rates in young fragile X males (31%) compared to age matched controls (18%). Fragile X syndrome (FXS) is the most common cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat (>200) on the promotor region of the fragile X mental retardation 1 gene (FMR1). As a result, the promotor region often becomes methylated which leads to a deficiency or absence of the FMR1 protein (FMRP). Common characteristics of FXS include mild to severe cognitive impairments in males but less severe cognitive impairment in females. Physical features of FXS include an elongated face, prominent ears, and post-pubertal macroorchidism. Severe obesity in full mutation males is often associated with the Prader-Willi phenotype (PWP) which includes hyperphagia, lack of satiation after meals, and hypogonadism or delayed puberty; however, there is no deletion at 15q11-q13 nor uniparental maternal disomy. Herein, we discuss the molecular mechanisms leading to FXS and the Prader-Willi phenotype with an emphasis on mouse FMR1 knockout studies that have shown the reversal of weight increase through mGluR antagonists. Finally, we review the current medications used in treatment of FXS including the atypical antipsychotics that can lead to weight gain and the research regarding the use of targeted treatments in FXS that will hopefully have a significantly beneficial effect on cognition and behavior without weight gain.

Genetics Home Reference: fragile X syndrome

MedlinePlus

... Citation on PubMed Koukoui SD, Chaudhuri A. Neuroanatomical, molecular genetic, and behavioral correlates of fragile X syndrome. Brain ... GJ, Dictenberg J. The fragile X syndrome: from molecular genetics to neurobiology. Ment Retard Dev Disabil Res Rev. ...

Growth in stature in fragile X families: A mixed longitudinal study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loesch, D.Z.; Huggins, R.M.; Hoang, N.H.

1995-09-11

The effect of fragile X on growth in stature was estimated in individuals aged 5-20 years from 50 fragile X families. The multivariate normal model for pedigree analysis was applied to the mixed longitudinal data, which varied with regard to intervals between the measurements and their number in individual subjects, totalling 349 measurement data points from fragile X families, and 292 data points from unrelated normal subjects. The results of genetic and regression analysis showed that, in fragile X boys and girls, total pubertal height gain is impaired, whereas the rate of growth during the preadolescent period is increased, comparedmore » with the growth rate of nonfragile X subjects. Moreover, the growth parameters in fragile X males were found to be correlated with the size of CGG trinucleotide expansion. The hypothesis of premature activation of the hypothalamo-pituitary gonadal axis is postulated as the cause of growth impairment in fragile X boys and girls, which should be verified by data on the timing of pubertal stages, hormone levels, and bone maturation. 33 refs., 2 figs., 3 tabs.« less

Construct exploit constraint in crash analysis by bypassing canary

NASA Astrophysics Data System (ADS)

Huang, Ning; Huang, Shuguang; Huang, Hui; Chang, Chao

2017-08-01

Selective symbolic execution is a common program testing technology. Developed on the basis of it, some crash analysis systems are often used to test the fragility of the program by constructing exploit constraints, such as CRAX. From the study of crash analysis based on symbolic execution, this paper find that this technology cannot bypass the canary stack protection mechanisms. This paper makes the improvement uses the API hook in Linux. Experimental results show that the use of API hook can effectively solve the problem that crash analysis cannot bypass the canary protection.

Fragile X Syndrome: Keys to the Molecular Genetics of Synaptic Plasticity

ERIC Educational Resources Information Center

Lombroso, Paul J.; Ogren, Marilee P.

2008-01-01

Fragile X syndrome, the most common form of inherited mental retardation is discussed. The relationship between specific impairments in synaptic plasticity and Fragile X syndrome is investigated as it strengthens synaptic contacts between neurons.

Do Individuals with Fragile X Syndrome Show Developmental Stuttering or Not? Comment on "Speech Fluency in Fragile X Syndrome" by Van Borsel, Dor and Rondal

ERIC Educational Resources Information Center

Howell, Peter

2008-01-01

Van Borsel, Dor, and Rondal (2007) examined the speech of seven boys and two young male adults with fragile X syndrome and considered whether their speech was comparable to that reported in the developmental stuttering literature. They listed five criteria which led them to conclude that the speech patterns of speakers with fragile X syndrome…

Strength of the repulsive part of the interatomic potential determines fragility in metallic liquids

NASA Astrophysics Data System (ADS)

Pueblo, Christopher E.; Sun, Minhua; Kelton, K. F.

2017-08-01

The dynamical behaviour of liquids is frequently characterized by the fragility, which can be defined from the temperature dependence of the shear viscosity, η (ref. ). For a strong liquid, the activation energy for η changes little with cooling towards the glass transition temperature, Tg. The change is much greater in fragile liquids, with the activation energy becoming very large near Tg. While fragility is widely recognized as an important concept--believed, for example, to play an important role in glass formation--the microscopic origin of fragility is poorly understood. Here, we present new experimental evidence showing that fragility reflects the strength of the repulsive part of the interatomic potential, which can be determined from the steepness of the pair distribution function near the hard-sphere cutoff. On the basis of an analysis of scattering data from ten different metallic alloy liquids, we show that stronger liquids have steeper repulsive potentials.

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.

PubMed

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.

The quest for fragile X biomarkers.

PubMed

Westmark, Cara J

2014-12-01

Fragile X is the most common form of inherited intellectual disability and the leading known genetic cause of autism. There is currently no cure or approved medication for fragile X although various drugs target specific disease symptoms and a large number of therapeutics are in various stages of clinical development. Multiple recent clinical trials have failed on their primary endpoints indicating that there is a compelling need for validated biomarkers and outcome measures in fragile X. There are currently no validated blood-based biomarkers to assess disease severity or to monitor drug efficacy in fragile X syndrome. Herein, we review candidate blood protein biomarkers including extracellular-regulated kinase, phosphoinositide 3-kinase, matrix metalloproteinase 9, amyloid-beta and amyloid-beta protein precursor. Bench-to-bedside plans for fragile X syndrome are severely limited by the lack of validated outcome measures. The reviewed candidate biomarkers are at early stages of validation and deserve further investigation.

The Role of Fragile Sites in Sporadic Papillary Thyroid Carcinoma

PubMed Central

Dillon, Laura W.; Lehman, Christine E.; Wang, Yuh-Hwa

2012-01-01

The incidence of thyroid cancer is increasing, especially papillary thyroid carcinoma (PTC), making it currently the fastest-growing cancer among women. Reasons for this increase remain unclear, but several risk factors including radiation exposure and improved detection techniques have been suggested. Recently, the induction of chromosomal fragile site breakage was found to result in the formation of RET/PTC1 rearrangements, a common cause of PTC. Chromosomal fragile sites are regions of the genome with a high susceptibility to forming DNA breaks and are often associated with cancer. Exposure to a variety of external agents can induce fragile site breakage, which may account for some of the observed increase in PTC. This paper discusses the role of fragile site breakage in PTC development, external fragile site-inducing agents that may be potential risk factors for PTC, and how these factors are especially targeting women. PMID:22762011

Sustained Engagement to Create Resilient Communities: How a Collaborative Design Approach Can Broker and Mobilise Practitioner-Participant Interaction

ERIC Educational Resources Information Center

McAra, Marianne

2016-01-01

When conducting research with young people, studies consistently cite the need to establish trust and rapport with participants. However, what frequently goes unreported is how to evolve these often highly fragile research relationships, and the subtle tensions and negotiations that can occur. In this article I reflect on my experience of…

Brief Review of Current Research in FXS: Implications for Treatment with Psychotropic Medication

ERIC Educational Resources Information Center

Valdovinos, Maria G.

2007-01-01

The purpose of this paper is to provide a brief review of current research in fragile X syndrome (FXS) with regards to the morphology and behavioral phenotype associated with FXS and the use of psychotropic medication for the treatment of behavior problems (e.g., aggression) often seen in FXS (full mutation). The lack of production of the fragile…

Struggles of the Novice Counselor and Therapists.

ERIC Educational Resources Information Center

Skovholt, Thomas M.; Ronnestad, Michael H.

2003-01-01

Review of theory and research on counselor/therapist development identified seven stressors of novice practitioners, catalyzed by the ambiguity of professional work. Sources of stress include acute performance anxiety, scrutiny of professional gatekeepers, porous or rigid emotional boundaries, fragile and incomplete practitioner identity,…

Reading in Children With Fragile X Syndrome: Phonological Awareness and Feasibility of Intervention.

PubMed

Adlof, Suzanne M; Klusek, Jessica; Hoffmann, Anne; Chitwood, Kerrie L; Brazendale, Allison; Riley, Karen; Abbeduto, Leonard J; Roberts, Jane E

2018-05-01

Individuals with fragile X syndrome (FXS) present with significant deficits in reading skills, but scant research exists to understand the characteristics of the reading delays or best practices for reading instruction with this population. Study 1 examined the relationship between phonological awareness and reading skills in individuals with FXS. Study 2 evaluated the feasibility of a web-based reading intervention, which incorporated phonological awareness and phonics instruction but was originally developed for mainstream students, for children with FXS. Results suggest that phonological awareness and reading skills are correlated in this population, and that instruction targeting phonological awareness and phonics should not be ruled out for individuals with FXS. Further studies are needed to examine their potential effects.

Improvements in osteoporosis testing and care are found following the wide scale implementation of the Ontario Fracture Clinic Screening Program: An interrupted time series analysis.

PubMed

Beaton, Dorcas E; Mamdani, Muhammad; Zheng, Hong; Jaglal, Susan; Cadarette, Suzanne M; Bogoch, Earl R; Sale, Joanna E M; Sujic, Rebeka; Jain, Ravi

2017-12-01

We evaluated a system-wide impact of a health intervention to improve treatment of osteoporosis after a fragility fracture. The intervention consisted of assigning a screening coordinator to selected fracture clinics to identify, educate, and follow up with fragility fracture patients and inform their physicians of the need to evaluate bone health. Thirty-seven hospitals in the province of Ontario (Canada) were assigned a screening coordinator. Twenty-three similar hospitals were control sites. All hospitals had orthopedic services and handled moderate-to-higher volumes of fracture patients. Administrative health data were used to evaluate the impact of the intervention.Fragility fracture patients (≥50 years; hip, humerus, forearm, spine, or pelvis fracture) were identified from administrative health records. Cases were fractures treated at 1 of the 37 hospitals assigned a coordinator. Controls were the same types of fractures at the control sites. Data were assembled for 20 quarters before and 10 quarters after the implementation (from January 2002 to March 2010). To test for a shift in trends, we employed an interrupted time series analysis-a study design used to evaluate the longitudinal effects of interventions, through regression modelling. The primary outcome measure was bone mineral density (BMD) testing. Osteoporosis medication initiation and persistence rates were secondary outcomes in a subset of patients ≥66 years of age.A total of 147,071 patients were used in the analysis. BMD testing rates increased from 17.0% pre-intervention to 20.9% post-intervention at intervention sites (P < .01) compared with no change at control sites (14.9% and 14.9%, P = .33). Medication initiation improved significantly at intervention sites (21.6-23.97%; P = .02) but not at control sites (17.5-18.5%; P = .27). Persistence with bisphosphonates decreased at all sites, from 59.9% to 56.4% at intervention sites (P = .02) and more so from 62.3% to 54.2% at control sites (P < .01) using 50% proportion of days covered (PDC 50).Significant improvements in BMD testing and treatment initiation were observed after the initiation of a coordinator-based screening program to improve osteoporosis management following fragility fracture.

Improvements in osteoporosis testing and care are found following the wide scale implementation of the Ontario Fracture Clinic Screening Program

PubMed Central

Beaton, Dorcas E.; Mamdani, Muhammad; Zheng, Hong; Jaglal, Susan; Cadarette, Suzanne M.; Bogoch, Earl R.; Sale, Joanna E. M.; Sujic, Rebeka; Jain, Ravi

2017-01-01

Abstract We evaluated a system-wide impact of a health intervention to improve treatment of osteoporosis after a fragility fracture. The intervention consisted of assigning a screening coordinator to selected fracture clinics to identify, educate, and follow up with fragility fracture patients and inform their physicians of the need to evaluate bone health. Thirty-seven hospitals in the province of Ontario (Canada) were assigned a screening coordinator. Twenty-three similar hospitals were control sites. All hospitals had orthopedic services and handled moderate-to-higher volumes of fracture patients. Administrative health data were used to evaluate the impact of the intervention. Fragility fracture patients (≥50 years; hip, humerus, forearm, spine, or pelvis fracture) were identified from administrative health records. Cases were fractures treated at 1 of the 37 hospitals assigned a coordinator. Controls were the same types of fractures at the control sites. Data were assembled for 20 quarters before and 10 quarters after the implementation (from January 2002 to March 2010). To test for a shift in trends, we employed an interrupted time series analysis—a study design used to evaluate the longitudinal effects of interventions, through regression modelling. The primary outcome measure was bone mineral density (BMD) testing. Osteoporosis medication initiation and persistence rates were secondary outcomes in a subset of patients ≥66 years of age. A total of 147,071 patients were used in the analysis. BMD testing rates increased from 17.0% pre-intervention to 20.9% post-intervention at intervention sites (P < .01) compared with no change at control sites (14.9% and 14.9%, P = .33). Medication initiation improved significantly at intervention sites (21.6–23.97%; P = .02) but not at control sites (17.5–18.5%; P = .27). Persistence with bisphosphonates decreased at all sites, from 59.9% to 56.4% at intervention sites (P = .02) and more so from 62.3% to 54.2% at control sites (P < .01) using 50% proportion of days covered (PDC 50). Significant improvements in BMD testing and treatment initiation were observed after the initiation of a coordinator-based screening program to improve osteoporosis management following fragility fracture. PMID:29310418

An investigation into the crystallization tendency/kinetics of amorphous active pharmaceutical ingredients: A case study with dipyridamole and cinnarizine.

PubMed

Baghel, Shrawan; Cathcart, Helen; Redington, Wynette; O'Reilly, Niall J

2016-07-01

Amorphous drug formulations have great potential to enhance solubility and thus bioavailability of BCS class II drugs. However, the higher free energy and molecular mobility of the amorphous form drive them towards the crystalline state which makes them unstable. Accurate determination of the crystallization tendency/kinetics is the key to the successful design and development of such systems. In this study, dipyridamole (DPM) and cinnarizine (CNZ) have been selected as model compounds. Thermodynamic fragility (mT) was measured from the heat capacity change at the glass transition temperature (Tg) whereas dynamic fragility (mD) was evaluated using methods based on extrapolation of configurational entropy to zero [Formula: see text] , and heating rate dependence of Tg [Formula: see text] . The mean relaxation time of amorphous drugs was calculated from the Vogel-Tammann-Fulcher (VTF) equation. Furthermore, the correlation between fragility and glass forming ability (GFA) of the model drugs has been established and the relevance of these parameters to crystallization of amorphous drugs is also assessed. Moreover, the crystallization kinetics of model drugs under isothermal conditions has been studied using Johnson-Mehl-Avrami (JMA) approach to determine the Avrami constant 'n' which provides an insight into the mechanism of crystallization. To further probe into the crystallization mechanism, the non-isothermal crystallization kinetics of model systems were also analysed by statistically fitting the crystallization data to 15 different kinetic models and the relevance of model-free kinetic approach has been established. The crystallization mechanism for DPM and CNZ at each extent of transformation has been predicted. The calculated fragility, glass forming ability (GFA) and crystallization kinetics are found to be in good correlation with the stability prediction of amorphous solid dispersions. Thus, this research work involves a multidisciplinary approach to establish fragility, GFA and crystallization kinetics as stability predictors for amorphous drug formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

CMP‑N‑acetylneuraminic acid synthetase interacts with fragile X related protein 1.

PubMed

Ma, Yun; Tian, Shuai; Wang, Zongbao; Wang, Changbo; Chen, Xiaowei; Li, Wei; Yang, Yang; He, Shuya

2016-08-01

Fragile X mental retardation protein (FMRP), fragile X related 1 protein (FXR1P) and FXR2P are the members of the FMR protein family. These proteins contain two KH domains and a RGG box, which are characteristic of RNA binding proteins. The absence of FMRP, causes fragile X syndrome (FXS), the leading cause of hereditary mental retardation. FXR1P is expressed throughout the body and important for normal muscle development, and its absence causes cardiac abnormality. To investigate the functions of FXR1P, a screen was performed to identify FXR1P‑interacting proteins and determine the biological effect of the interaction. The current study identified CMP‑N‑acetylneuraminic acid synthetase (CMAS) as an interacting protein using the yeast two‑hybrid system, and the interaction between FXR1P and CMAS was validated in yeast using a β‑galactosidase assay and growth studies with selective media. Furthermore, co‑immunoprecipitation was used to analyze the FXR1P/CMAS association and immunofluorescence microscopy was performed to detect expression and intracellular localization of the proteins. The results of the current study indicated that FXR1P and CMAS interact, and colocalize in the cytoplasm and the nucleus of HEK293T and HeLa cells. Accordingly, a fragile X related 1 (FXR1) gene overexpression vector was constructed to investigate the effect of FXR1 overexpression on the level of monosialotetrahexosylganglioside 1 (GM1). The results of the current study suggested that FXR1P is a tissue‑specific regulator of GM1 levels in SH‑SY5Y cells, but not in HEK293T cells. Taken together, the results initially indicate that FXR1P interacts with CMAS, and that FXR1P may enhance the activation of sialic acid via interaction with CMAS, and increase GM1 levels to affect the development of the nervous system, thus providing evidence for further research into the pathogenesis of FXS.

Developmental expression of the neuroligins and neurexins in fragile X mice.

PubMed

Lai, Jonathan K Y; Doering, Laurie C; Foster, Jane A

2016-03-01

Neuroligins and neurexins are transsynaptic proteins involved in the maturation of glutamatergic and GABAergic synapses. Research has identified synaptic proteins and function as primary contributors to the development of fragile X syndrome. Fragile X mental retardation protein (FMRP), the protein that is lacking in fragile X syndrome, binds neuroligin-1 and -3 mRNA. Using in situ hybridization, we examined temporal and spatial expression patterns of neuroligin (NLGN) and neurexin (NRXN) mRNAs in the somatosensory (S1) cortex and hippocampus in wild-type (WT) and fragile X knockout (FMR1-KO) mice during the first 5 weeks of postnatal life. Genotype-based differences in expression included increased NLGN1 mRNA in CA1 and S1 cortex, decreased NLGN2 mRNA in CA1 and dentate gyrus (DG) regions of the hippocampus, and increased NRXN3 mRNA in CA1, DG, and S1 cortex between female WT and FMR1-KO mice. In male mice, decreased expression of NRXN3 mRNA was observed in CA1 and DG regions of FMR1-KO mice. Sex differences in hippocampal expression of NLGN2, NRXN1, NRXN2, and NRXN3 mRNAs and in S1 cortex expression of NRXN3 mRNAs were observed WT mice, whereas sex differences in NLGN3, NRXN1, NRXN2, and NRXN3 mRNA expression in the hippocampus and in NLGN1, NRXN2 and NRXN3 mRNA expression in S1 cortex were detected in FMR1-KO mice. These results provide a neuroanatomical map of NLGN and NRXN expression patterns over postnatal development in WT and FMR1-KO mice. The differences in developmental trajectory of these synaptic proteins could contribute to long-term differences in CNS wiring and synaptic function. © 2015 Wiley Periodicals, Inc.

Cross border waters: Fragile treasures for the 21st Century; Ninth U.S./Mexico Border States Conference on Recreation, Parks, and Wildlife; 1998, June 3-6

Treesearch

G. J. Gottfried; C. B. Edminster; Madelyn C. Dillon

1998-01-01

This conference brought together scientists and resource managers from government, universities, and private organizations in the United States and Mexico. In a continuing international forum, participants exchanged information on existing or potential cooperative projects, agency functions and programs, and issues were concerning natural and cultural resource...

[The effect of heavy metal ions and peptide bioregulators on the expression of chromosome fragile sites in the individuals of different age groups and breast cancer patients].

PubMed

Dzhokhadze, T A; Ganozishvili, M N; Lezhava, T A

2008-09-01

Expression rates of chromosome fragile sites in peripheral blood lymphocytes have been studied in clinically healthy individuals of different age groups (20-38 yrs and 75-86 yrs) and breast cancer patients (8 cases). In individuals with a normal check-up of different age groups the heavy metal (nickel, zinc and cobalt) ions were also examined on their influence on the expression of the fragile sites and the peptide bioregulators (Livagen and Epithalon) were tested on their ability to correct the pattern of expression. Short-term lymphocyte cultures were used as tested material. The analysis showed that the chromosomes of people from young and old age groups differ from each other by the expression pattern of fragile sites - the chromosomes of young individuals were found to be more active by spontaneous formation of fragile sites. They were also sensitive to their induction by heavy metals. Both tested bioregulators lessen heavy metals effect that was statistically reliable only for the young people group. As for the patients with breast cancer general elevated fragility of chromosomes and specific distribution of the fragile sites along the chromosomes were revealed.

Targeted Upregulation of FMRP Expression as an Approach to the Treatment of Fragile X Syndrome

DTIC Science & Technology

2015-08-01

form of autism, and a relatively common cause of epilepsy . The syndrome is caused by partial or complete silencing of the fragile X (FMR1) gene when...potential to correct ALL of the clinical domains of fragile X syndrome, including epilepsy -like activity observed for both those with FXS and carriers of...the FMR1 gene. 15. SUBJECT TERMS Fragile X, autism, FMR1, FXTAS, CGG repeat, epilepsy , seizures, FMRP, PTSD, premutation, iPSC, progenitor, calcium

Neurosteroids Reverse Tonic Inhibition Deficits in Fragile X Syndrome

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-15-1-0190 TITLE: Neurosteroids Reverse Tonic Inhibition Deficits in Fragile X Syndrome PRINCIPAL INVESTIGATOR: Dr...14 July 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Neurosteroids Reverse Tonic Inhibition Deficits in Fragile X Syndrome 5b. GRANT NUMBER...18 9. Appendices……………………………………………………………18 2 1. Introduction Fragile X syndrome (FXS) is the most common form of inherited

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

PubMed Central

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

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

PubMed

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.

Elevated ERK/p90 ribosomal S6 kinase activity underlies audiogenic seizure susceptibility in fragile X mice.

PubMed

Sawicka, Kirsty; Pyronneau, Alexander; Chao, Miranda; Bennett, Michael V L; Zukin, R Suzanne

2016-10-11

Fragile X syndrome (FXS) is the most common heritable cause of intellectual disability and a leading genetic form of autism. The Fmr1 KO mouse, a model of FXS, exhibits elevated translation in the hippocampus and the cortex. ERK (extracellular signal-regulated kinase) and mTOR (mechanistic target of rapamycin) signaling regulate protein synthesis by activating downstream targets critical to translation initiation and elongation and are known to contribute to hippocampal defects in fragile X. Here we show that the effect of loss of fragile X mental retardation protein (FMRP) on these pathways is brain region specific. In contrast to the hippocampus, ERK (but not mTOR) signaling is elevated in the neocortex of fragile X mice. Phosphorylation of ribosomal protein S6, typically a downstream target of mTOR, is elevated in the neocortex, despite normal mTOR activity. This is significant in that S6 phosphorylation facilitates translation, correlates with neuronal activation, and is altered in neurodevelopmental disorders. We show that in fragile X mice, S6 is regulated by ERK via the "alternative" S6 kinase p90-ribosomal S6 kinase (RSK), as evidenced by the site of elevated phosphorylation and the finding that ERK inhibition corrects elevated RSK and S6 activity. These findings indicate that signaling networks are altered in the neocortex of fragile X mice such that S6 phosphorylation receives aberrant input from ERK/RSK. Importantly, an RSK inhibitor reduces susceptibility to audiogenic seizures in fragile X mice. Our findings identify RSK as a therapeutic target for fragile X and suggest the therapeutic potential of drugs for the treatment of FXS may vary in a brain-region-specific manner.

Advances in the Treatment of Fragile X Syndrome

PubMed Central

Hagerman, Randi J.; Berry-Kravis, Elizabeth; Kaufmann, Walter E.; Ono, Michele Y.; Tartaglia, Nicole; Lachiewicz, Ave; Kronk, Rebecca; Delahunty, Carol; Hessl, David; Visootsak, Jeannie; Picker, Jonathan; Gane, Louise; Tranfaglia, Michael

2010-01-01

The FMR1 mutations can cause a variety of disabilities, including cognitive deficits, attention-deficit/hyperactivity disorder, autism, and other socioemotional problems, in individuals with the full mutation form (fragile X syndrome) and distinct difficulties, including primary ovarian insufficiency, neuropathy and the fragile X-associated tremor/ataxia syndrome, in some older premutation carriers. Therefore, multigenerational family involvement is commonly encountered when a proband is identified with a FMR1 mutation. Studies of metabotropic glutamate receptor 5 pathway antagonists in animal models of fragile X syndrome have demonstrated benefits in reducing seizures, improving behavior, and enhancing cognition. Trials of metabotropic glutamate receptor 5 antagonists are beginning with individuals with fragile X syndrome. Targeted treatments, medical and behavioral interventions, genetic counseling, and family supports are reviewed here. PMID:19117905

The developmental trajectory of disruptive behavior in Down syndrome, fragile X syndrome, Prader-Willi syndrome and Williams syndrome.

PubMed

Rice, Lauren J; Gray, Kylie M; Howlin, Patricia; Taffe, John; Tonge, Bruce J; Einfeld, Stewart L

2015-06-01

The aim of this study was to investigate the developmental trajectories of verbal aggression, physical aggression, and temper tantrums in four genetic syndrome groups. Participants were part of the Australian Child to Adult Development Study (ACAD), which collected information from a cohort of individuals with an intellectual disability at five time points over 18 years. Data were examined from a total of 248 people with one of the four following syndromes: Down syndrome, Fragile X syndrome, Prader-Willi syndrome, or Williams syndrome. Changes in behaviors were measured using validated items from the Developmental Behavior Checklist (DBC). The results indicate that, while verbal aggression shows no evidence of diminishing with age, physical aggression, and temper tantrums decline with age before 19 years for people with Down syndrome, Fragile X syndrome, and William syndrome; and after 19 years for people with Prader-Willi syndrome. These findings offer a somewhat more optimistic outlook for people with an intellectual disability than has previously been suggested. Research is needed to investigate the mechanisms predisposing people with PWS to persistence of temper tantrums and physical aggression into adulthood. © 2015 Wiley Periodicals, Inc.

Global Identification of Disease Associated Genes in Fragile X Cells

DTIC Science & Technology

2016-08-01

for this study listed as follows: 1) Validate the co-localized R-loop formation and chromosome fragility in Fragile X cells, particularly at the brain ...retardation protein February 2016, NGS Data Analysis & Informatics Conference, San Diego, California (Poster presentation) Title: Global detection

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

PubMed

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

2011-11-01

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 deficits related to fragile X syndrome. Eye tracking was used to psychophysically measure the limits of spatial and temporal attention in infants with fragile X syndrome and age-matched neurotypically developing infants. Results from these experiments revealed that infants with fragile X syndrome experience drastically reduced resolution of temporal attention in a genetic dose-sensitive manner, but have a spatial resolution of attention that is not impaired. Coarse temporal attention could have significant knock-on effects for the development of perceptual, cognitive and motor abilities in individuals with the disorder.

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

PubMed Central

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 deficits related to fragile X syndrome. Eye tracking was used to psychophysically measure the limits of spatial and temporal attention in infants with fragile X syndrome and age-matched neurotypically developing infants. Results from these experiments revealed that infants with fragile X syndrome experience drastically reduced resolution of temporal attention in a genetic dose-sensitive manner, but have a spatial resolution of attention that is not impaired. Coarse temporal attention could have significant knock-on effects for the development of perceptual, cognitive and motor abilities in individuals with the disorder. PMID:22075522

Leadership mentoring in nursing research, career development and scholarly productivity: A systematic review.

PubMed

Hafsteinsdóttir, Thóra B; van der Zwaag, Angeli M; Schuurmans, Marieke J

2017-10-01

Although nursing has been an academic discipline for decades, the infrastructure for nursing research in many countries is still fragile and struggling. Postdoctoral nurses have difficulties developing sustaining careers in nursing research due to lack of career opportunities. Considerable research has been conducted on leadership and mentoring in various areas of nursing. We aimed to systematically review the literature investigating leadership programs and mentoring for postdoctoral nurse researchers, as well as the influence of leadership and mentoring on research productivity, research career development, leadership knowledge and skills, the nurses' health and well-being, staff relationships, work culture and collaboration, salaries and postdoctoral nurses' experiences. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was conducted. The electronic databases PubMed, CINAHL and EMBASE were searched without time limits for eligible studies up to January 2016. Reference lists of included articles were also searched manually and authors were contacted to inquire about other relevant papers. Two authors independently assessed eligibility of studies for inclusion. Titles and abstracts were matched with the inclusion criteria: studies investigating leadership and mentoring programs for postdoctoral nurses and leadership and mentoring influencing research productivity, and career development; and leadership knowledge and skills and other outcomes. The quality of the studies was appraised using the Centre for Evidence-Based Medicine for surveys, the Critical Appraisal Skill Program Qualitative Appraisal Checklist for qualitative studies, and a critical appraisal list for mixed methods studies. Any disagreements were resolved by consensus. Data were extracted by two reviewers. We screened 1775 titles and abstracts, resulting in 15 studies, which included quantitative, descriptive, qualitative and mixed methods designs and involved 3855 postdoctoral nurses. Two studies presenting mentoring programs for postdoctoral nurses were identified. Other studies investigated the influence of mentoring on various outcomes. The findings showed a positive influence of mentoring on research productivity, including increase in publications and grant writing and research career development, improved leadership skills and knowledge. Furthermore, mentoring positively influenced nurses' health and well-being, staff relationships, work culture and collaboration. Postdoctoral nurses' experience of mentoring, mentorship, leadership and peer-support is essential in supporting ongoing research activity. Although there is a lack of studies with robust designs investigating leadership and mentoring programs, our results document some evidence of mentoring's influence on research productivity, career development and other outcomes of postdoctoral nurses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures.

PubMed

Patsch, Janina M; Li, Xiaojuan; Baum, Thomas; Yap, Samuel P; Karampinos, Dimitrios C; Schwartz, Ann V; Link, Thomas M

2013-08-01

The goal of this magnetic resonance (MR) imaging study was to quantify vertebral bone marrow fat content and composition in diabetic and nondiabetic postmenopausal women with fragility fractures and to compare them with nonfracture controls with and without type 2 diabetes mellitus. Sixty-nine postmenopausal women (mean age 63 ± 5 years) were recruited. Thirty-six patients (47.8%) had spinal and/or peripheral fragility fractures. Seventeen fracture patients were diabetic. Thirty-three women (52.2%) were nonfracture controls. Sixteen women were diabetic nonfracture controls. To quantify vertebral bone marrow fat content and composition, patients underwent MR spectroscopy (MRS) of the lumbar spine at 3 Tesla. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry (DXA) of the hip and lumbar spine (LS) and quantitative computed tomography (QCT) of the LS. To evaluate associations of vertebral marrow fat content and composition with spinal and/or peripheral fragility fractures and diabetes, we used linear regression models adjusted for age, race, and spine volumetric bone mineral density (vBMD) by QCT. At the LS, nondiabetic and diabetic fracture patients had lower vBMD than controls and diabetics without fractures (p = 0.018; p = 0.005). However, areal bone mineral density (aBMD) by DXA did not differ between fracture and nonfracture patients. After adjustment for age, race, and spinal vBMD, the prevalence of fragility fractures was associated with -1.7% lower unsaturation levels (confidence interval [CI] -2.8% to -0.5%, p = 0.005) and +2.9% higher saturation levels (CI 0.5% to 5.3%, p = 0.017). Diabetes was associated with -1.3% (CI -2.3% to -0.2%, p = 0.018) lower unsaturation and +3.3% (CI 1.1% to 5.4%, p = 0.004) higher saturation levels. Diabetics with fractures had the lowest marrow unsaturation and highest saturation. There were no associations of marrow fat content with diabetes or fracture. Our results suggest that altered bone marrow fat composition is linked with fragility fractures and diabetes. MRS of spinal bone marrow fat may therefore serve as a novel tool for BMD-independent fracture risk assessment. Copyright © 2013 American Society for Bone and Mineral Research.

Degraded speech sound processing in a rat model of fragile X syndrome

PubMed Central

Engineer, Crystal T.; Centanni, Tracy M.; Im, Kwok W.; Rahebi, Kimiya C.; Buell, Elizabeth P.; Kilgard, Michael P.

2014-01-01

Fragile X syndrome is the most common inherited form of intellectual disability and the leading genetic cause of autism. Impaired phonological processing in fragile X syndrome interferes with the development of language skills. Although auditory cortex responses are known to be abnormal in fragile X syndrome, it is not clear how these differences impact speech sound processing. This study provides the first evidence that the cortical representation of speech sounds is impaired in Fmr1 knockout rats, despite normal speech discrimination behavior. Evoked potentials and spiking activity in response to speech sounds, noise burst trains, and tones were significantly degraded in primary auditory cortex, anterior auditory field and the ventral auditory field. Neurometric analysis of speech evoked activity using a pattern classifier confirmed that activity in these fields contains significantly less information about speech sound identity in Fmr1 knockout rats compared to control rats. Responses were normal in the posterior auditory field, which is associated with sound localization. The greatest impairment was observed in the ventral auditory field, which is related to emotional regulation. Dysfunction in the ventral auditory field may contribute to poor emotional regulation in fragile X syndrome and may help explain the observation that later auditory evoked responses are more disturbed in fragile X syndrome compared to earlier responses. Rodent models of fragile X syndrome are likely to prove useful for understanding the biological basis of fragile X syndrome and for testing candidate therapies. PMID:24713347

A clinical research integration special program (CRISP) for young women with primary ovarian insufficiency

PubMed Central

FALORNI, A.; MINARELLI, V.; EADS, C. M.; JOACHIM, C. M.; PERSANI, L.; ROSSETTI, R.; BEIM, P. YURTTAS; PELLEGRINI, V. A.; SCHNATZ, P. F.; RAFIQUE, S.; KISSELL, K.; CALIS, K. A.; POPAT, V.; NELSON, L. M.

2015-01-01

Large-scale medical sequencing provides a focal point around which to reorganize health care and health care research. Mobile health (mHealth) is also currently undergoing explosive growth and could be another innovation that will change the face of future health care. We are employing primary ovarian insufficiency (POI) as a model rare condition to explore the intersection of these potentials. As both sequencing capabilities and our ability to intepret this information improve, sequencing for medical purposes will play an increasing role in health care beyond basic research: it will help guide the delivery of care to patients. POI is a serious chronic disorder and syndrome characterized by hypergonadotrophic hypogonadism before the age of 40 years and most commonly presents with amenorrhea. It may have adverse health effects that become fully evident years after the initial diagnosis. The condition is most commonly viewed as one of infertility, however, it may also be associated with adverse long-term outcomes related to inadequate bone mineral density, increased risk of cardiovascular disease, adrenal insufficiency, hypothyroidism and, if pregnancy ensues, having a child with Fragile X Syndrome. There may also be adverse outcomes related to increased rates of anxiety and depression. POI is also a rare disease, and accordingly, presents special challenges. Too often advances in research are not effectively integrated into community care at the point of service for those with rare diseases. There is a need to connect community health providers in real time with investigators who have the requisite knowledge and expertise to help manage the rare disease and to conduct ongoing research. Here we review the pathophysiology and management of POI and propose the development of an international Clinical Research Integration Special Program (CRISP) for the condition. PMID:25288327

Fragile X syndrome: a preclinical review on metabotropic glutamate receptor 5 (mGluR5) antagonists and drug development.

PubMed

Pop, Andreea S; Gomez-Mancilla, Baltazar; Neri, Giovanni; Willemsen, Rob; Gasparini, Fabrizio

2014-03-01

Fragile X syndrome (FXS) is considered the leading inherited cause of intellectual disability and autism. In FXS, the fragile X mental retardation 1 (FMR1) gene is silenced and the fragile X mental retardation protein (FMRP) is not expressed, resulting in the characteristic features of the syndrome. Despite recent advances in understanding the pathophysiology of FXS, there is still no cure for this condition; current treatment is symptomatic. Preclinical research is essential in the development of potential therapeutic agents. This review provides an overview of the preclinical evidence supporting metabotropic glutamate receptor 5 (mGluR5) antagonists as therapeutic agents for FXS. According to the mGluR theory of FXS, the absence of FMRP leads to enhanced glutamatergic signaling via mGluR5, which leads to increased protein synthesis and defects in synaptic plasticity including enhanced long-term depression. As such, efforts to develop agents that target the underlying pathophysiology of FXS have focused on mGluR5 modulation. Animal models, particularly the Fmr1 knockout mouse model, have become invaluable in exploring therapeutic approaches on an electrophysiological, behavioral, biochemical, and neuroanatomical level. Two direct approaches are currently being investigated for FXS treatment: reactivating the FMR1 gene and compensating for the lack of FMRP. The latter approach has yielded promising results, with mGluR5 antagonists showing efficacy in clinical trials. Targeting mGluR5 is a valid approach for the development of therapeutic agents that target the underlying pathophysiology of FXS. Several compounds are currently in development, with encouraging results.

Planetary science

NASA Technical Reports Server (NTRS)

Marshall, John R.; Bridges, Frank; Gault, Donald; Greeley, Ronald; Houpis, Harry; Lin, Douglas; Weidenschilling, Stuart

1987-01-01

The following types of experiments for a proposed Space Station Microgravity Particle Research Facility are described: (1) low velocity collisions between fragile particles; (2) low velocity collisions of ice particles; (3) plasma-dust interaction; and (4) aggregation of finely-comminuted geological materials. The required capabilities and desired hardware for the facility are detailed.

Stabilizer, a new low growing Siberian wheatgrass cultivar for use on semiarid lands

USDA-ARS?s Scientific Manuscript database

The United States Department of Agriculture - Agricultural Research Service announces the public release of the cultivar 'Stabilizer' Siberian wheatgrass [Agropyron fragile (Roth) Candargy] as a low growing, rapid establishing revegetation grass for use on rangelands and roadsides, and as a grass co...

Infantile Amnesia: Forgotten but Not Gone

ERIC Educational Resources Information Center

Li, Stella; Callaghan, Bridget L.; Richardson, Rick

2014-01-01

Unlike adult memories that can be remembered for many years, memories that are formed early in life are more fragile and susceptible to being forgotten (a phenomenon known as "infantile" or "childhood" amnesia). Nonetheless, decades of research in both humans and nonhuman animals demonstrate the importance of early life…

Education, Conflict and Development

ERIC Educational Resources Information Center

Paulson, Julia, Ed.

2011-01-01

Under various names--education and conflict, education and fragility, education and insecurity, etc.--the understanding of linkages between education and violent conflict has emerged as an important and pressing area of inquiry. Work and research by practitioners and scholars has clearly pointed to the negative potential of education to contribute…

Risk of fragility fracture among patients with sarcoidosis: a population-based study 1976-2013-supplementary presentation.

PubMed

Ungprasert, P; Crowson, C S; Matteson, E L

2018-05-01

Incidence of fragility fracture of a population-based cohort of 345 patients with sarcoidosis was compared with age- and sex-matched comparators. The incidence of fragility fracture was higher among patients with sarcoidosis with a hazard ratio (HR) of 2.18.

Newborn Screening for Fragile X Syndrome

ERIC Educational Resources Information Center

Bailey, Donald B., Jr.

2004-01-01

Newborn screening for fragile X syndrome (FXS) is technically possible, and in the relatively near future accurate and inexpensive screening technologies are likely to be available. When that happens, will America's public health system adopt newborn screening for fragile X syndrome? This article addresses this issue by first placing screening for…

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

PubMed

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.

A Broader Definition of Fragility: The Communities and Schools of Brazil's "Favelas"

ERIC Educational Resources Information Center

Straubhaar, Rolf

2012-01-01

Though the existing literature on the "favelas" (or shantytowns) of Brazil thoroughly documents the chaotic and violent nature of life within them, few connections have been made between the literature on "favelas", fragility and small states, particularly with regard to the fragile state of educational institutions in…

The Medically Fragile Child in the School Setting. Second Edition.

ERIC Educational Resources Information Center

American Federation of Teachers, Washington, DC.

This guide for teachers whose classes include a medically fragile child considers roles and responsibilities of teachers with these students, teachers' rights as school employees, and possible solutions and protections for local unions to pursue. Chapter 1 provides an overview. It defines "medically fragile," summarizes legal…

Attentional Set-Shifting in Fragile X Syndrome

ERIC Educational Resources Information Center

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…

Academic Skills of Boys With Fragile X Syndrome: Profiles and Predictors

ERIC Educational Resources Information Center

Roberts, Jane E.; Schaaf, Jennifer M.; Skinner, Martie; Wheeler, Anne; Hooper, Stephen; Hatton, Deborah D.; Bailey, Donald B., Jr.

2005-01-01

The academic achievement of boys with fragile X syndrome and the relation between several predictive factors and academic performance are reported. Boys with fragile X syndrome displayed significant deficits in all academic skill areas. Relative strengths were observed in general knowledge, reflecting the ability to integrate experiential…

Speech Fluency in Fragile X Syndrome

ERIC Educational Resources Information Center

Van Borsel, John; Dor, Orianne; Rondal, Jean

2008-01-01

The present study investigated the dysfluencies in the speech of nine French speaking individuals with fragile X syndrome. Type, number, and loci of dysfluencies were analysed. The study confirms that dysfluencies are a common feature of the speech of individuals with fragile X syndrome but also indicates that the dysfluency pattern displayed is…

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)

ERIC Educational Resources Information Center

Hagerman, Paul J.; Hagerman, Randi J.

2004-01-01

Carriers of fragile X mental retardation 1 ("FMR1") premutation alleles (55 to 200 CGG repeats) are generally spared the more serious neurodevelopmental problems associated with the full-mutation carriers (greater than 200 repeats) of fragile X syndrome. However, some adult male premutation carriers (55-200 repeats) develop a neurological syndrome…

Reanalysis of the fragility of glycerol at very high pressures using new Tg data

NASA Astrophysics Data System (ADS)

Lyon, Kevin; Oliver, William

Direct measurements of the glass transition temperature of glycerol between 1 atm and 6.7 GPa from our lab allow reanalysis of high-pressure viscosity data, which were limited to approximately 107 poise. Previous attempts to determine Tg (P) and fragility by extrapolation of the viscosity data by many orders of magnitude led to inconclusive results. Tg (P) data constrain the value of viscosity at the glass transition providing for more accurate determinations of isobaric fragilities. Over most of the pressure range, a constant fragility is found in agreement with analysis of high-pressure dielectric data by Paluch et al.. Discrepancies in the pressure dependence of the fragility of glycerol at very low pressures exist in the literature and will also be discussed.

Three Faces of Fragile X.

PubMed

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.

A Bone Health Intervention for Chinese Immigrants in Santa Clara County.

PubMed

Zou, Joanne; Hampton, Michelle DeCoux; Shade, Kate; Kaku, Leonard

Among Chinese immigrants, osteoporosis is undertreated, misdiagnosed, and a leading cause of fragility fractures. In orthopaedic surgery departments, prevention education and health behavior change programs are necessary to improve their bone health. The purpose of this study was to examine the effectiveness of an osteoporosis prevention education program on participants' self-efficacy with regard to exercise and nutrition when provided by an orthopaedic surgery team during an annual Chinese Health Fair in Santa Clara County, CA. This pilot study used a single-group pretest and posttest design. Chinese immigrants at risk of osteoporosis were recruited during a 1-day health fair. The Bone Health Intervention (BHI) included orthopaedic surgeon consultation, visual aids including osteoporosis images and bone models, a video that included a discussion on calcium and vitamin D in the Chinese diet and culturally-acceptable exercise, and osteoporosis educational handouts. The Osteoporosis Self-Efficacy Scale (OSES) was utilized to measure participants' confidence in the ability to participate in self-care behaviors related to physical activity and calcium intake before and after the intervention. Paired t tests were used to compare participants' OSES scores pre- and postintervention. There was a significant increase in mean OSES scores postintervention, indicating that the intervention could be an effective method of increasing participants' self-efficacy regarding calcium intake and time spent in exercising. These results indicate that a culturally meaningful education program can potentially reduce fragility fracture risk. Orthopaedic health providers are ideal candidates to deliver preventive care education to improve outcomes for Chinese immigrants.

Masters of defence: biomechanics of stinging nettles

NASA Astrophysics Data System (ADS)

Jensen, Kaare H.; Knoblauch, Jan

2017-11-01

The techniques employed by plants and animals to defend themselves are very varied. Some involve extremely refined armaments. Stinging nettles employ hollow needle-like stinging hairs constructed from silica, the mineral from which we make glass, and they are filled with poison. The hairs are remarkably rigid and rarely break. Yet the tip is so sharp that the slightest touch cuts human skin, and so fragile that it breaks at that touch and releases poison into the wound. How the seemingly antagonist mechanical functions of rigidity and fragility are achieved, however, is unknown. We combine experiments on real and synthetic stingers to elucidate the poison injection mechanism. The design of plant stingers is compared to other natural systems and optimal stinging strategies are discussed. This work was supported by a research Grant (13166) from VILLUM FONDEN.

Voicing the strengths of Pacific Island parent caregivers of children who are medically fragile.

PubMed

Haley, Janice; Harrigan, Rosanne C

2004-07-01

Research is deficient regarding the strengths of Pacific Island parents of children who are medically fragile. The purpose of this qualitative ethnographic study was to explore the strengths of Pacific Island parents of these children. Audiotaped interviews were analyzed using Text Smart and peer review. The core theme reflecting strength was positive energy. Participants believed that parents needed to have the ability to handle emotional feelings, solve problems, connect with their spirituality, find meaning, take care of themselves, use family support, use community support, use a positive attitude, be resourceful, meet a challenge, interact with nature, and focus on the present. Themes were affirmed by the literature with the exception of interacting with nature, which may be indigenous to the population's cultural orientation.

Basic Energy Sciences Program Update

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

2016-01-04

The U.S. Department of Energy’s (DOE) Office of Basic Energy Sciences (BES) supports fundamental research to understand, predict, and ultimately control matter and energy at the electronic, atomic, and molecular levels to provide the foundations for new energy technologies and to support DOE missions in energy, environment, and national security. The research disciplines covered by BES—condensed matter and materials physics, chemistry, geosciences, and aspects of physical biosciences— are those that discover new materials and design new chemical processes. These disciplines touch virtually every aspect of energy resources, production, conversion, transmission, storage, efficiency, and waste mitigation. BES also plans, constructs, andmore » operates world-class scientific user facilities that provide outstanding capabilities for imaging and spectroscopy, characterizing materials of all kinds ranging from hard metals to fragile biological samples, and studying the chemical transformation of matter. These facilities are used to correlate the microscopic structure of materials with their macroscopic properties and to study chemical processes. Such experiments provide critical insights to electronic, atomic, and molecular configurations, often at ultrasmall length and ultrafast time scales.« less

Fragile X syndrome and an isodicentric X chromosome in a woman with multiple anomalies, developmental delay, and normal pubertal development.

PubMed

Freedenberg, D L; Gane, L W; Richards, C S; Lampe, M; Hills, J; O'Connor, R; Manchester, D; Taylor, A; Tassone, F; Hulseberg, D; Hagerman, R J; Patil, S R

1999-07-30

We report on an individual with developmental delays, short stature, skeletal abnormalities, normal pubertal development, expansion of the fragile X triplet repeat, as well as an isodicentric X chromosome. S is a 19-year-old woman who presented for evaluation of developmental delay. Pregnancy was complicated by a threatened miscarriage. She was a healthy child with intellectual impairment noted in infancy. Although she had global delays, speech was noted to be disproportionately delayed with few words until age 3.5 years. Facial appearance was consistent with fragile X syndrome. Age of onset of menses was 11 years with normal breast development. A maternal male second cousin had been identified with fragile X syndrome based on DNA studies. The mother of this child (S's maternal first cousin) and the grandfather (S's maternal uncle) were both intellectually normal but were identified as carrying triplet expansions in the premutation range. S's mother had some school difficulties but was not identified as having global delays. Molecular analysis of S's fragile X alleles noted an expansion of more than 400 CGG repeats in one allele. Routine cytogenetic studies of peripheral blood noted the presence of an isodicentric X in 81of 86 cells scored. Five of 86 cells were noted to be 45,X. Cytogenetic fra(X) studies from peripheral blood showed that the structurally normal chromosome had the fragile site in approximately 16% of the cells. Analysis of maternal fragile X alleles identified an allele with an expansion to approximately 110 repeats. FMRP studies detected the expression of the protein in 24% of cells studied. To our knowledge, this is the first patient reported with an isodicentric X and fragile X syndrome. Whereas her clinical phenotype is suggestive of fragile X syndrome, her skeletal abnormalities may represent the presence of the isodicentric X. Treatment of S with 20 mg/day of Prozac improved her behavior. In the climate of cost con trol, this individual reinforces the recommendation of obtaining chromosomes on individuals with developmental delay even with a family history of fragile X syndrome. Copyright 1999 Wiley-Liss, Inc.

Adding faculty in transportation areas - year 2 and 3 : research progress on seismic fragility assessment of bridge structures

DOT National Transportation Integrated Search

2011-02-01

The NUTC provides funds to help departments build up their faculty in the transportation field over the next five years. Broadareas will be considered as listed in the UTC mission or other areas that relate to State Departments of Transportation and ...

Fragility of Pedagogical Content Knowledge in Geography

ERIC Educational Resources Information Center

Arenas-Martija, Andoni; Salinas-Silva, Victor; Margalef-García, Leonor; Otero-Auristondo, Maria

2017-01-01

This research aims to evaluate the geographical knowledge of nine teachers in the region of Valparaiso, Chile. An interpretive case study was conducted with data collected through classroom observations, interviews, and questionnaires, and these data were then analyzed through triangulation. The findings showed that these teachers, who are the…

Why many polymers are so fragile: A new perspective

DOE PAGES

Dalle-Ferrier, C.; Kisliuk, A.; Hong, L.; ...

2016-10-21

Many polymers exhibit much steeper temperature dependence of their structural relaxation time (higher fragility) than liquids of small molecules, and the mechanism of this unusually high fragility in polymers remains a puzzle. To reveal additional hints for understanding the underlying mechanism, we analyzed correlation of many properties of polymers to their fragility on example of model polymer polystyrene with various molecular weights (MWs). Here, we demonstrate that these correlations work for short chains (oligomers), but fail progressively with increase in MW. Our surprising discovery is that the steepness of the temperature dependence (fragility) of the viscosity that is determined bymore » chain relaxation follows the correlations at all molecular weights. These results suggest that the molecular level relaxation still follows the behavior usual for small molecules even in polymers, and its fragility (chain fragility) falls in the range usual for molecular liquids. It is the segmental relaxation that has this unusually high fragility. We also speculate that many polymers cannot reach an ergodic state on the time scale of segmental dynamics due to chain connectivity and rigidity. This leads to sharper decrease in accessible configurational entropy upon cooling and results in steeper temperature dependence of segmental relaxation. Our proposed scenario provides a new important insight into the specifics of polymer dynamics: the role of ergodicity time and length scale. At the end, we suggest that a similar scenario can be applicable also to other molecular systems with slow intra-molecular degrees of freedom and to chemically complex systems where the time scale of chemical fluctuations can be longer than the time scale of structural relaxation.« less

Why many polymers are so fragile: A new perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dalle-Ferrier, C.; Kisliuk, A.; Hong, L.

Many polymers exhibit much steeper temperature dependence of their structural relaxation time (higher fragility) than liquids of small molecules, and the mechanism of this unusually high fragility in polymers remains a puzzle. To reveal additional hints for understanding the underlying mechanism, we analyzed correlation of many properties of polymers to their fragility on example of model polymer polystyrene with various molecular weights (MWs). Here, we demonstrate that these correlations work for short chains (oligomers), but fail progressively with increase in MW. Our surprising discovery is that the steepness of the temperature dependence (fragility) of the viscosity that is determined bymore » chain relaxation follows the correlations at all molecular weights. These results suggest that the molecular level relaxation still follows the behavior usual for small molecules even in polymers, and its fragility (chain fragility) falls in the range usual for molecular liquids. It is the segmental relaxation that has this unusually high fragility. We also speculate that many polymers cannot reach an ergodic state on the time scale of segmental dynamics due to chain connectivity and rigidity. This leads to sharper decrease in accessible configurational entropy upon cooling and results in steeper temperature dependence of segmental relaxation. Our proposed scenario provides a new important insight into the specifics of polymer dynamics: the role of ergodicity time and length scale. At the end, we suggest that a similar scenario can be applicable also to other molecular systems with slow intra-molecular degrees of freedom and to chemically complex systems where the time scale of chemical fluctuations can be longer than the time scale of structural relaxation.« less

Aberrant face and gaze habituation in fragile x syndrome.

PubMed

Bruno, Jennifer Lynn; Garrett, Amy S; Quintin, Eve-Marie; Mazaika, Paul K; Reiss, Allan L

2014-10-01

The authors sought to investigate neural system habituation to face and eye gaze in fragile X syndrome, a disorder characterized by eye-gaze aversion, among other social and cognitive deficits. Participants (ages 15-25 years) were 30 individuals with fragile X syndrome (females, N=14) and a comparison group of 25 individuals without fragile X syndrome (females, N=12) matched for general cognitive ability and autism symptoms. Functional MRI (fMRI) was used to assess brain activation during a gaze habituation task. Participants viewed repeated presentations of four unique faces with either direct or averted eye gaze and judged the direction of eye gaze. Four participants (males, N=4/4; fragile X syndrome, N=3) were excluded because of excessive head motion during fMRI scanning. Behavioral performance did not differ between the groups. Less neural habituation (and significant sensitization) in the fragile X syndrome group was found in the cingulate gyrus, fusiform gyrus, and frontal cortex in response to all faces (direct and averted gaze). Left fusiform habituation in female participants was directly correlated with higher, more typical levels of the fragile X mental retardation protein and inversely correlated with autism symptoms. There was no evidence for differential habituation to direct gaze compared with averted gaze within or between groups. Impaired habituation and accentuated sensitization in response to face/eye gaze was distributed across multiple levels of neural processing. These results could help inform interventions, such as desensitization therapy, which may help patients with fragile X syndrome modulate anxiety and arousal associated with eye gaze, thereby improving social functioning.

Fragile X-related element 2 methylation analysis may provide a suitable option for inclusion of fragile X syndrome and/or sex chromosome aneuploidy into newborn screening: a technical validation study.

PubMed

Inaba, Yoshimi; Herlihy, Amy S; Schwartz, Charles E; Skinner, Cindy; Bui, Quang M; Cobb, Joanna; Shi, Elva Z; Francis, David; Arvaj, Alison; Amor, David J; Pope, Kate; Wotton, Tiffany; Cohen, Jonathan; Hewitt, Jacqueline K; Hagerman, Randi J; Metcalfe, Sylvia A; Hopper, John L; Loesch, Danuta Z; Slater, Howard R; Godler, David E

2013-04-01

We show that a novel fragile X-related epigenetic element 2 FMR1 methylation test can be used along with a test for sex-determining region Y (SRY) to provide the option of combined fragile X syndrome and sex chromosome aneuploidy newborn screening. Fragile X-related epigenetic element 2, SRY, and FMR1 CGG repeat analyses were performed on blood and saliva DNA, and in adult and newborn blood spots. The cohort consisted of 159 controls (CGG <40), 187 premutation (CGG 56-170), and 242 full-mutation (CGG ~200-2,000) males and females, 106 sex chromosome aneuploidy individuals, and 151 cytogenetically normal controls. At the 0.435 threshold, fragile X-related epigenetic element 2 analysis in males was robust on both blood DNA and newborn blood spots, with specificity and sensitivity of ~100% for full-mutation genotype. In females, the specificity was 99%, whereas half of full-mutation females were above the 0.435 threshold in both blood DNA and newborn blood spots. Furthermore, at this threshold, the test could not differentiate individuals with Klinefelter syndrome from female controls without using the SRY marker. When combined with SRY analysis, the test was consistent with most results for sex chromosome aneuploidies from karyotyping. Setting specific thresholds for fragile X-related epigenetic element 2 analysis and including the SRY marker provides the option to either include or exclude detection of sex chromosome aneuploidies as part of fragile X syndrome newborn screening.

"Better safe than sorry": a qualitative content analysis of participant's perspectives of fall-related concerns and balance in older women with osteoporosis after balance training.

PubMed

Halvarsson, Alexandra; Ståhle, Agneta; Halén, Carolina; Roaldsen, Kirsti Skavberg

2015-07-03

To explore how older women with osteoporosis perceive fall-related concerns and balance in daily life after having participated in balance training. Explorative study. Semi-structured interviews were conducted with 19 women (66-84 years), with osteoporosis recruited from an ongoing RCT; participants were asked about their perceived fall-related concerns and balance. Interviews were taped and transcribed verbatim. Data were analyzed using inductive qualitative content analysis. One underlying theme emerged: "Internalized risk perception related to experience of bodily fragility", and three manifest categories: empowerment, safety and menace. A dynamic process between the categories was found, in which contextual and personal factors influenced perceptions of fall-related concerns and balance, i.e. winter season may lead a person who is highly empowered and/or uses active strategies into a situation of perception of menace and avoidance of activity. To cope with the fragility caused by osteoporosis informants had an internalized risk perception that protected them against possible threats and harm. Informants perceived improved empowerment and self-efficacy after participation in balance training. They resumed activities and became more active and independent in daily life using safety precautions and fall-prevention strategies. Depending on contextual factors, some situations still invoked fear and led to avoidance. Implication for Rehabilitation Risk awareness protecting against possible threats and harms seems to be internalized in older women living with osteoporosis. When designing fall prevention programs, it is important to recognize that contextual and personal factors have a major influence on how older women with osteoporosis perceive fall-related concerns and balance. Perception of fragility and risk seems to be a significant problem for older women with osteoporosis and health-care providers should encourage their patients to participate in tailored balance training programs to overcome these concerns.

Communication for Development Interventions in Fragile States: A Systematic Review

PubMed Central

Skuse, Andrew; Rodger, Dianne; Power, Gerry; Mbus, Domenic Friguglietti; Brimacombe, Tait

2013-01-01

Executive summary Background A wide range of contextual and programmatic factors frame, affect and constrain communication for development (C4D) interventions undertaken in fragile or conflict affected states. For the purposes of this review, contextual factors include culture, poverty, different stages of conflict (such as latent, open or post-conflict scenarios), policy, legislation and so on, while programmatic factors include the type of intervention, formative and summative evaluation, project design and management, human and financial resources and so on. Understanding the various factors that influence C4D interventions in fragile states is important to improving practice, implementation and evaluation, as well as to the future development of methodologies and frameworks that can be utilised in conflict or crisis situations. Objective The objective of this review is to assess the contextual and programmatic factors that influence communication for development interventions in fragile states. Types of participants Persons regardless of age, gender and ethnicity – living in fragile states. Phenomena of interest The contextual and programmatic factors that influence communication for development (C4D) interventions in fragile states. Types of studies Qualitative peer reviewed studies, expert opinion, discussion papers, project reports, policy papers, position papers and other text. Search strategy Searches were conducted for published and unpublished material (between January 2001 – September 2011), including grey literature, in the English language. Databases searched were: Academic Search Premier; African Women's Bibliographic Database; Anthropology Plus; Bibliography of Asian Studies; Educational Resources Information Centre; Ingenta Connect; JSTOR; Scopus; and Sociological Abstracts; Communication for Social Change Consortium; DevComm (World Bank); Eldis; Search for Common Ground; The Communication Initiative; United Nations Development Programme; United Nations Educational, Scientific and Cultural Organization; and United Nations High Commissioner for Refugees. Methodological quality Each identified source was critically appraised by two independent reviewers for methodological quality and thematic relevance prior to inclusion in the review. The appraisal process employed the System for the Unified Management, Assessment and Review of Information (SUMARI) software developed by the Joanna Briggs Institute. Data collection Data was extracted using the standardised extraction tools. Data synthesis Data were categorised and synthesised using standardised SUMARI extraction tools. This involved the identification of a set of analytical findings, followed by the allocation of specific categories representative of each, i.e. digital divide. A process of aggregation followed via which these initial categories were (where possible) collated into broader synthesised findings. The results of this process are set out in the form of a series of statements that represent a wider trend informed by the data. Results A total of 239 sources were retrieved for detailed examination. 156 of these sources were excluded after review of the full paper/publication leaving 83 sources that were assessed for methodological quality using the SUMARI system. A total of 26 papers (19 qualitative papers and 7 textual/opinion pieces) were included in the review for appraisal and data extraction. A further 57 papers were assessed and excluded. Following extraction, a discussion was developed that examined the relevance of the findings from a realist perspective. Conclusions This review identifies that while different initiatives can be pursued in different conflict situations, their direction and content needs to be driven by a close understanding of context, which in turn is driven by a range of influencing factors (contextual and programmatic), which in turn reflect and build upon existing C4D practice principles. While identifying influencing factors that affect C4D implementation is critical to effective practice, this systematic review also highlights a need for early, more thorough and longer-term C4D interventions within fragile states (especially those that can be characterised by latent conflict and chronic instability). Early communication intervention can help reduce tension and promote reconciliation, but also enable development and humanitarian agencies to be better placed to address situations that may escalate into open conflict. Implications for policy and practice A wide range of contextual and programmatic factors combine to both constrain and provide opportunities for C4D initiatives in fragile states. Such factors need to be recognised, negotiated and addressed by practitioners in design, implementation and evaluation in order to enhance the overall effectiveness of C4D initiatives. Implications for research The quality of the evidence base relating to C4D interventions in fragile states is relatively weak. The difficultly of conducting rigorous evaluation and research in conflict-affected contexts should not be underestimated. This highlights a need to improve our understanding of communications environments within fragile states and the related need to develop appropriate methodological frameworks and tools that enable effective mapping and the identification of appropriate communication interventions to occur.

Finiteness Marking in Boys with Fragile X Syndrome

ERIC Educational Resources Information Center

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…

International Fragile X Conference Proceedings (3rd, Snowmass/Aspen, Colorado, 1992).

ERIC Educational Resources Information Center

Hagerman, Randi Jenssen, Ed.; McKenzie, Pamela, Ed.

This proceedings document presents the texts or summaries of 52 papers given at a 1992 conference on Fragile X syndrome. Preliminary information includes names and institutional affiliations of conference faculty, information about the National Fragile X Foundation, awards presented at the conference, and a list of resource centers (by state).…

Behavioral Intervention for Problem Behavior in Children with Fragile X Syndrome

ERIC Educational Resources Information Center

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…

Examining the Function of Problem Behavior in Fragile X Syndrome: Preliminary Experimental Analysis

ERIC Educational Resources Information Center

Langthorne, Paul; McGill, Peter; O'Reilly, Mark F.; Lang, Russell; Machalicek, Wendy; Chan, Jeffrey Michael; Rispoli, Mandy

2011-01-01

Fragile X syndrome is the most common inherited cause of intellectual and developmental disability. The influence of environmental variables on behaviors associated with the syndrome has received only scant attention. The current study explored the function served by problem behavior in fragile X syndrome by using experimental functional analysis…

Memory Skills of Boys with Fragile X Syndrome

ERIC Educational Resources Information Center

Ornstein, Peter A.; Schaaf, Jennifer M.; Hooper, Stephen R.; Hatton, Deborah D.; Mirrett, Penny; Bailey, Donald B., Jr.

2008-01-01

Multiple aspects of memory were examined in 42 boys with fragile X syndrome and a comparison group of 42 typically developing boys matched on MA. Working memory, incidental memory, and deliberate memory were assessed with a battery that included both free-recall and recognition tasks. Findings indicated that boys with fragile X syndrome performed…

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

ERIC Educational Resources Information Center

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 Syndrome. Early Developments. Volume 8, Number 2, Summer 2004

ERIC Educational Resources Information Center

Manuel, John

2004-01-01

Eleven years ago, FPG Child Development Institute (FPG) launched a longitudinal study of a little known form of mental retardation known as fragile X syndrome (FXS). The Carolina Fragile X Project has since grown into a multidisciplinary team studying diverse aspects of the condition, ranging from early identification to school performance. The…

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

ERIC Educational Resources Information Center

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…

Management of Medically Fragile Infants.

ERIC Educational Resources Information Center

Ueda, Dawn; Caulfield, Rick

2001-01-01

Discusses the role of the Child Life Specialist in helping to meet the special needs of medically fragile children. Argues that since many child care professionals may come into contact with medically fragile children at some point in their careers, it is important to examine child life as a specialization in the health care profession. (SD)

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

ERIC Educational Resources Information Center

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…

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

ERIC Educational Resources Information Center

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…

Social Behavior and Cortisol Reactivity in Children with Fragile X Syndrome

ERIC Educational Resources Information Center

Hessl, David; Glaser, Bronwyn; Dyer-Friedman, Jennifer; Reiss, Allan L.

2006-01-01

Objective: To examine the association between limbic-hypothalamic-pituitary-adrenal (L-HPA) axis reactivity and social behavior in children with fragile X syndrome (FXS). Method: Salivary cortisol changes and concurrent anxiety-related behaviors consistent with the behavioral phenotype of FXS were measured in 90 children with the fragile X full…

Interplay of intermolecular interactions and flexibility to mediate glass forming ability and fragility: A study of chemical analogs

NASA Astrophysics Data System (ADS)

Saini, Manoj K.; Jin, Xiao; Wu, Tao; Liu, Yingdan; Wang, Li-Min

2018-03-01

We have investigated the enthalpic and dielectric relaxations of four groups of quinoline analogs having similar structural properties (i.e., rigidity, stiffness, and bulkiness) but a different steric character and the nature of intermolecular interactions and flexibility. The dielectric fragility index (md) and the enthalpic one (mH), determined by the Tool-Narayanaswamy-Moynihan-Hodge formalism, are comparable. Generally, for the four sets of molecules of similar structures, both the interactions and flexibility are found to be critical in making the large span of fragility (i.e., from 59 to 131) and glass forming ability. By contrast, individual impacts of the interaction and flexibility can only explain fragility partly among each group of isomers. We found that the molecules with high fragility are of relatively low liquid density, reflecting the joint impact of the interactions and flexibility. An interesting result is observed among the isomers that the molecules which are fragile have enhanced glass forming ability. The results are unveiling the joint impacts of molecular structure (flexibility) and intermolecular interaction on the molecular dynamics.

Do individuals with fragile X syndrome show developmental stuttering or not? Comment on "Speech fluency in fragile X syndrome" by van Borsel, Dor and Rondal.

PubMed

Howell, Peter

2008-02-01

Van Borsel, Dor, and Rondal (2007) examined the speech of seven boys and two young male adults with fragile X syndrome and considered whether their speech was comparable to that reported in the developmental stuttering literature. They listed five criteria which led them to conclude that the speech patterns of speakers with fragile X syndrome differed from those observed in developmental stuttering. The differences noted were: 1) distribution of type of dysfluency; 2) the class of word on which dysfluency occurred; 3) whether word length affected dysfluency; 4) number of times words and phrases were repeated; and 5) whether there were influences of material type on fluency (spontaneous speech, repeated material etc.). They concluded that the speech of speakers with fragile X syndrome differed from developmental stuttering. The comparisons that van Borsel et al. (2007) made between participant groups were not for speakers of comparable ages. Comparisons with groups of corresponding ages support the opposite conclusion, namely the young speakers with fragile X syndrome show patterns similar to developmental stuttering.

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

NASA Astrophysics Data System (ADS)

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.

Assessing the Fragile X Syndrome Newborn Screening Landscape.

PubMed

Riley, Catharine; Wheeler, Anne

2017-06-01

Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability. Early identification is an important step in linking FXS individuals with appropriate and timely medical and social services. Newborn screening (NBS) is 1 approach that has been used for other conditions to facilitate early identification. A literature review was conducted to identify issues, barriers, challenges, and approaches to addressing challenges related to NBS for FXS. Search terms included: fragile X syndrome, FMR1, newborn screening, screening, and genetic testing. To supplement the literature review, 9 key informant interviews were conducted. Information gathered through these interviews supplemented what was identified in the literature. Information from both the literature review and supplemental interviews was reviewed by 3 researchers who discussed and came to consensus on thematic areas and categorization of issues. The barriers and challenges related to NBS for FXS identified in the literature and by experts and stakeholders are categorized into 5 thematic areas: public health burden, treatment, timing, screening/testing methodologies, and translating results. Summaries of these issues and barriers are provided, along with potential approaches to addressing them. The issues and barriers described in this article highlight limited areas of knowledge that need be addressed to improve our understanding of FXS and the potential benefit of NBS. The landscape of NBS for FXS could be influenced by a series of research findings over time or a larger breakthrough that demonstrates an effective targeted treatment that has to be implemented early in life. Copyright © 2017 by the American Academy of Pediatrics.

Participation in the Supplemental Nutrition Assistance Program and maternal depressive symptoms: Moderation by program perception.

PubMed

Bergmans, Rachel S; Berger, Lawrence M; Palta, Mari; Robert, Stephanie A; Ehrenthal, Deborah B; Malecki, Kristen

2018-01-01

Previous studies have observed an association between participation in the Supplemental Nutrition Assistance Program (SNAP) and depression, which is contrary to SNAP's potential to alleviate food insecurity and financial strain. This study investigated the impact of change in SNAP participation status on maternal depression, and whether perceptions of government assistance moderate this association. Data were from the Fragile Families and Child Wellbeing Study (FFCWS). Logistic regression models with individual-specific fixed-effects, were fit to SNAP-eligible mothers who changed SNAP participation and depression status (N = 256) during waves 2 to 4. Perceptions of government assistance were defined as feelings of humiliation or loss of freedom and tested for interactions with SNAP participation. Perceptions of government assistance moderated the association between SNAP participation and depression (p-interaction = 0.0208). Those with positive perceptions of welfare had 0.27 (95% CI = 0.08 to 0.89) times lower odds of depression when enrolled vs. not enrolled in SNAP. Among those with negative perceptions of welfare, SNAP enrollment was not associated with depression (OR = 1.13; 95% CI = 0.85 to 1.51). Evidence suggests that SNAP mental health benefits may be context specific. SNAP's capacity to improve mental health may depend on individual perceptions of government assistance. More research is needed to determine whether interventions aimed at mitigating negative perceptions of programs like SNAP could ameliorate poor mental health among program participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of the Technical Review Panel of the Global Fund to Fight HIV/AIDS, Tuberculosis and Malaria: an analysis of grant recommendations.

PubMed

Schmidt-Traub, Guido

2018-04-01

The independent Technical Review Panel (TRP) of the Global Fund to Fight HIV/AIDS, Tuberculosis and Malaria is a unique mechanism to review funding proposals and to provide recommendations on their funding. Its functioning and performance have received little attention in the scientific literature. We aimed to identify predictors for TRP recommendations, whether these were in line with the Global Fund's ambition to give priority to countries most in need, and whether they correlated with grant performance. We combined data on proposals and applications under the Rolling Continuation Channel, TRP recommendations and grant implementation during the rounds-based mechanism (2002-2010) with country characteristics. Ordered logistic and OLS regressions were used to identify predictors for per-capita funding requests, TRP recommendations, Global Fund funding and grant performance ratings. We tested for financial suppression of large funding proposals and whether fragile or English-speaking countries performed differently from other countries. We found that funding requests and TRP recommendations were consistent with disease burden, but independent of other country characteristics. Countries with larger populations requested less funding per capita, but there is no evidence of financial suppression by the TRP. Proposals from fragile countries were as likely to be recommended as proposals from other countries, and resulting grants performed equally well except for lower performance of HIV/AIDS grants. English-speaking countries obtained more funding for TB and malaria than other countries. In conclusion, the independent TRP acted in line with the guiding principles of the Global Fund to direct funding to countries most in need without ex ante country allocation. The Global Fund appears to have promoted learning on how to design and implement large-scale programs in fragile and non-fragile countries. Other pooled financing mechanisms may consider TRP operating principles to generate high-quality demand, to promote learning and to direct resources to countries most in need.

Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome.

PubMed

Dölen, Gül; Bear, Mark F

2008-03-15

Metabotropic glutamate receptors (mGluRs) have been implicated in a diverse variety of neuronal functions. Studies reviewed here indicate that exaggerated signalling through mGluR5 can account for multiple cognitive and syndromic features of fragile X syndrome, the most common inherited form of mental retardation and autism. Since a reduction of mGluR5 signalling can reverse fragile X phenotypes, these studies provide a compelling rationale for the use of mGluR5 antagonists for the treatment of fragile X and related disorders.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rafi, S.K.; Surana, R.B.; Christopher, K.L.

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 ofmore » 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.« less

Babies at Double Jeopardy: Medically Fragile Infants and Child Neglect

ERIC Educational Resources Information Center

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…

Self-Injurious Behavior and Fragile X Syndrome: Findings from the National Fragile X Survey

ERIC Educational Resources Information Center

Symons, Frank J.; Byiers, Breanne J.; Raspa, Melissa; Bishop, Ellen; Bailey, Donald B., Jr.

2010-01-01

We used National Fragile X Survey data in order to examine reported self-injurious behavior (SIB) to (a) generate lifetime and point prevalence estimates, (b) document detailed features of SIB (frequency, types, location, severity) in relation to gender, and (c) compare comorbid conditions between matched pairs (SIB vs. no SIB). Results indicate…

Language and Learning in Boys with Fragile X Syndrome: Syntactic Processing and the Role of Phonological Memory

ERIC Educational Resources Information Center

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…

Expressive Language during Conversational Speech in Boys with Fragile X Syndrome

ERIC Educational Resources Information Center

Roberts, Joanne E.; Hennon, Elizabeth A.; Price, Johanna R.; Dear, Elizabeth; Anderson, Kathleen; Vandergrift, Nathan A.

2007-01-01

We compared the expressive syntax and vocabulary skills of 35 boys with fragile X syndrome and 27 younger typically developing boys who were at similar nonverbal mental levels. During a conversational speech sample, the boys with fragile X syndrome used shorter, less complex utterances and produced fewer different words than did the typically…

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

ERIC Educational Resources Information Center

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…

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

ERIC Educational Resources Information Center

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…

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

ERIC Educational Resources Information Center

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…

Sensory Impairment and Head Circumference in Fragile X Syndrome, Down Syndrome and Idiopathic Intellectual Disability.

ERIC Educational Resources Information Center

Turk, Jeremy; Patton, Michael

2000-01-01

Eighteen boys with fragile X syndrome were compared with 42 with idiopathic intellectual disability, and 45 with Down syndrome. Boys with Down syndrome had more sensory problems and smaller head circumferences than normal. Head circumferences of boys with fragile X syndrome and with idiopathic intellectual disability were larger than normal.…

The Perception of Biological and Mechanical Motion in Female Fragile X Premutation Carriers

ERIC Educational Resources Information Center

Keri, Szabolcs; Benedek, Gyorgy

2010-01-01

Previous studies reported impaired visual information processing in patients with fragile x syndrome and in premutation carriers. In this study, we assessed the perception of biological motion (a walking point-light character) and mechanical motion (a rotating shape) in 25 female fragile x premutation carriers and in 20 healthy non-carrier…

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

ERIC Educational Resources Information Center

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…

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

ERIC Educational Resources Information Center

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;…

Male-Female Characteristics of Fragile X Syndrome.

ERIC Educational Resources Information Center

Caron, Jackie

Fragile X syndrome is the most common cause of mental retardation next to Down syndrome. The syndrome is more prevalent in males because they only have one X chromosome, where the gene for fragile X is carried, while women have two X chromosomes and the normal gene can compensate for the affected chromosome. Certain physical features are…

Fragile X Mental Retardation Protein Regulates Heterosynaptic Plasticity in the Hippocampus

ERIC Educational Resources Information Center

Connor, Steven A.; Hoeffer, Charles A.; Klann, Eric; Nguyen, Peter V.

2011-01-01

Silencing of a single gene, FMR1, is linked to a highly prevalent form of mental retardation, characterized by social and cognitive impairments, known as fragile X syndrome (FXS). The FMR1 gene encodes fragile X mental retardation protein (FMRP), which negatively regulates translation. Knockout of Fmr1 in mice results in enhanced long-term…

Predictors of Stress in Mothers and Fathers of Children with Fragile X Syndrome

ERIC Educational Resources Information Center

McCarthy, Annette; Cuskelly, Monica; van Kraayenoord, Christina E.; Cohen, Jonathan

2006-01-01

This study examined parental and family stress and functioning where there is a child with fragile X syndrome. Mothers and fathers in 40 families were asked about their child with fragile X syndrome, family supports, their psychological stress, the marital relationship, and their family stress. Results indicate parents were well adjusted in terms…

Linguistic and Cognitive Functioning and Autism Symptoms in Young Children with Fragile X Syndrome

ERIC Educational Resources Information Center

Philofsky, Amy; Hepburn, Susan L.; Hayes, Athena; Hagerman, Randi; Rogers, Sally J.

2004-01-01

Linguistic and cognitive profiles were examined in 18 children with autism and 18 children with fragile X syndrome (mean ages = 34 months). State-of-the-art diagnostic procedures for autism symptom identification were administered. Eight children with fragile X met criteria for autism. Comparison of linguistic and cognitive profiles (autism,…

Iron accumulation and dysregulation in the putamen in fragile X-associated tremor/ataxia syndrome.

PubMed

Ariza, Jeanelle; Rogers, Hailee; Hartvigsen, Anna; Snell, Melissa; Dill, Michael; Judd, Derek; Hagerman, Paul; Martínez-Cerdeño, Verónica

2017-04-01

Fragile X-associated tremor/ataxia syndrome is an adult-onset disorder associated with premutation alleles of the FMR1 gene. This disorder is characterized by progressive action tremor, gait ataxia, and cognitive decline. Fragile X-associated tremor/ataxia syndrome pathology includes dystrophic white matter and intranuclear inclusions in neurons and astrocytes. We previously demonstrated that the transport of iron into the brain is altered in fragile X-associated tremor/ataxia syndrome; therefore, we also expect an alteration of iron metabolism in brain areas related to motor control. Iron is essential for cell metabolism, but uncomplexed iron leads to oxidative stress and contributes to the development of neurodegenerative diseases. We investigated a potential iron modification in the putamen - a structure that participates in motor learning and performance - in fragile X-associated tremor/ataxia syndrome. We used samples of putamen obtained from 9 fragile X-associated tremor/ataxia syndrome and 9 control cases to study iron localization using Perl's method, and iron-binding proteins using immunostaining. We found increased iron deposition in neuronal and glial cells in the putamen in fragile X-associated tremor/ataxia syndrome. We also found a generalized decrease in the amount of the iron-binding proteins transferrin and ceruloplasmin, and decreased number of neurons and glial cells that contained ceruloplasmin. However, we found increased levels of iron, transferrin, and ceruloplasmin in microglial cells, indicating an attempt by the immune system to remove the excess iron. Overall, found a deficit in proteins that eliminate extra iron from the cells with a concomitant increase in the deposit of cellular iron in the putamen in Fragile X-associated tremor/ataxia syndrome. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Isolation of the human chromosomal band Xq28 within somatic cell hybrids by fragile X site breakage.

PubMed Central

Warren, S T; Knight, S J; Peters, J F; Stayton, C L; Consalez, G G; Zhang, F P

1990-01-01

The chromosomal fragile-site mapping to Xq27.3 is associated with a frequent form of mental retardation and is prone to breakage after induced deoxyribonucleotide pool perturbation. The human hypoxanthine phosphoribosyltransferase (HPRT) and glucose-6-phosphate dehydrogenase (G6PD) genes flank the fragile X chromosome site and can be used to monitor integrity of the site in human-hamster somatic cell hybrids deficient in the rodent forms of these activities. After induction of the fragile X site, negative selection for HPRT and positive enrichment for G6PD resulted in 31 independent colonies of HPRT-,G6PD+ phenotype. Southern blot analysis demonstrated the loss of all tested markers proximal to the fragile X site with retention of all tested human Xq28 loci in a majority of the hybrids. In situ hybridization with a human-specific probe demonstrated the translocation of a small amount of human DNA to rodent chromosomes in these hybrids, suggesting chromosome breakage at the fragile X site and the subsequent translocation of Xq28. Southern blot hybridization of hybrid-cell DNA, resolved by pulsed-field gel electrophoresis, for human-specific repetitive sequences revealed abundant CpG-islands within Xq28, consistent with its known gene density. The electrophoretic banding patterns of human DNA among the hybrids were remarkably consistent, suggesting that fragile X site breakage is limited to a relatively small region in Xq27-28. These somatic cell hybrids, containing Xq27.3-qter as the sole human DNA, will aid the search for DNA associated with the fragile X site and will augment the high resolution genomic analysis of Xq28, including the identification of candidate genes for genetic-disease loci mapping to this region. Images PMID:2339126

Age-dependent cognitive impairment in a Drosophila fragile X model and its pharmacological rescue.

PubMed

Choi, Catherine H; McBride, Sean M J; Schoenfeld, Brian P; Liebelt, David A; Ferreiro, David; Ferrick, Neal J; Hinchey, Paul; Kollaros, Maria; Rudominer, Rebecca L; Terlizzi, Allison M; Koenigsberg, Eric; Wang, Yan; Sumida, Ai; Nguyen, Hanh T; Bell, Aaron J; McDonald, Thomas V; Jongens, Thomas A

2010-06-01

Fragile X syndrome afflicts 1 in 2,500 individuals and is the leading heritable cause of mental retardation worldwide. The overriding clinical manifestation of this disease is mild to severe cognitive impairment. Age-dependent cognitive decline has been identified in Fragile X patients, although it has not been fully characterized nor examined in animal models. A Drosophila model of this disease has been shown to display phenotypes bearing similarity to Fragile X symptoms. Most notably, we previously identified naive courtship and memory deficits in young adults with this model that appear to be due to enhanced metabotropic glutamate receptor (mGluR) signaling. Herein we have examined age-related cognitive decline in the Drosophila Fragile X model and found an age-dependent loss of learning during training. We demonstrate that treatment with mGluR antagonists or lithium can prevent this age-dependent cognitive impairment. We also show that treatment with mGluR antagonists or lithium during development alone displays differential efficacy in its ability to rescue naive courtship, learning during training and memory in aged flies. Furthermore, we show that continuous treatment during aging effectively rescues all of these phenotypes. These results indicate that the Drosophila model recapitulates the age-dependent cognitive decline observed in humans. This places Fragile X in a category with several other diseases that result in age-dependent cognitive decline. This demonstrates a role for the Drosophila Fragile X Mental Retardation Protein (dFMR1) in neuronal physiology with regard to cognition during the aging process. Our results indicate that misregulation of mGluR activity may be causative of this age onset decline and strengthens the possibility that mGluR antagonists and lithium may be potential pharmacologic compounds for counteracting several Fragile X symptoms.

Molecular fragil X screening in normal populations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spence, W.C.; Black, S.H.; Fallon, L.

In December, 1993, we initiated a pilot project in which DNA fragile X (fraX) testing was offered during routine prenatal or genetic counseling to all pregnant women seen at the Genetics & IVF Institute, most of whom were referred for the indication of advanced maternal age. A brochure on fragile X syndrome was sent to each patient prior to her appointment and was reviewed by a counselor or physician during the counseling session. As of June 1995, 3,345 patients were offered testing; 474 women with no identified family history of mental retardation or learning disability and 214 women with amore » positive family history accepted the test on a self-pay basis. The second population screened was 271 potential donors in our anonymous egg donor program. DNA from blood was tested by Southern blot using EcoRI/EagI and StB12.3. If an expansion was detected, CGG repeat number was determined by PCR-based analysis. Among the 474 patients with unremarkable family histories, three fraX carriers were identified (repeat sizes = 60+), whereas none were found in the 214 patients with a positive family history. Among the potential egg donors, two high borderline patients were identified (repeat sizes = between 50 and 59). Our ongoing study indicates that screening of pregnant or preconceptual populations for fraX carrier status using DNA testing is accepted by many patients and is an important addition to current medical practice. 12 refs., 1 tab.« less

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

PubMed

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.

Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans.

PubMed

Won, Jinyoung; Jin, Yunho; Choi, Jeonghyun; Park, Sookyoung; Lee, Tae Ho; Lee, Sang-Rae; Chang, Kyu-Tae; Hong, Yonggeun

2017-06-20

Fragile X syndrome (FXS) is the most common monogenic form of autism spectrum disorder (ASD). FXS with ASD results from the loss of fragile X mental retardation ( fmr ) gene products, including fragile X mental retardation protein (FMRP), which triggers a variety of physiological and behavioral abnormalities. This disorder is also correlated with clock components underlying behavioral circadian rhythms and, thus, a mutation of the fmr gene can result in disturbed sleep patterns and altered circadian rhythms. As a result, FXS with ASD individuals may experience dysregulation of melatonin synthesis and alterations in melatonin-dependent signaling pathways that can impair vigilance, learning, and memory abilities, and may be linked to autistic behaviors such as abnormal anxiety responses. Although a wide variety of possible causes, symptoms, and clinical features of ASD have been studied, the correlation between altered circadian rhythms and FXS with ASD has yet to be extensively investigated. Recent studies have highlighted the impact of melatonin on the nervous, immune, and metabolic systems and, even though the utilization of melatonin for sleep dysfunctions in ASD has been considered in clinical research, future studies should investigate its neuroprotective role during the developmental period in individuals with ASD. Thus, the present review focuses on the regulatory circuits involved in the dysregulation of melatonin and disruptions in the circadian system in individuals with FXS with ASD. Additionally, the neuroprotective effects of melatonin intervention therapies, including improvements in neuroplasticity and physical capabilities, are discussed and the molecular mechanisms underlying this disorder are reviewed. The authors suggest that melatonin may be a useful treatment for FXS with ASD in terms of alleviating the adverse effects of variations in the circadian rhythm.

Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans

PubMed Central

Won, Jinyoung; Jin, Yunho; Choi, Jeonghyun; Park, Sookyoung; Lee, Tae Ho; Lee, Sang-Rae; Chang, Kyu-Tae; Hong, Yonggeun

2017-01-01

Fragile X syndrome (FXS) is the most common monogenic form of autism spectrum disorder (ASD). FXS with ASD results from the loss of fragile X mental retardation (fmr) gene products, including fragile X mental retardation protein (FMRP), which triggers a variety of physiological and behavioral abnormalities. This disorder is also correlated with clock components underlying behavioral circadian rhythms and, thus, a mutation of the fmr gene can result in disturbed sleep patterns and altered circadian rhythms. As a result, FXS with ASD individuals may experience dysregulation of melatonin synthesis and alterations in melatonin-dependent signaling pathways that can impair vigilance, learning, and memory abilities, and may be linked to autistic behaviors such as abnormal anxiety responses. Although a wide variety of possible causes, symptoms, and clinical features of ASD have been studied, the correlation between altered circadian rhythms and FXS with ASD has yet to be extensively investigated. Recent studies have highlighted the impact of melatonin on the nervous, immune, and metabolic systems and, even though the utilization of melatonin for sleep dysfunctions in ASD has been considered in clinical research, future studies should investigate its neuroprotective role during the developmental period in individuals with ASD. Thus, the present review focuses on the regulatory circuits involved in the dysregulation of melatonin and disruptions in the circadian system in individuals with FXS with ASD. Additionally, the neuroprotective effects of melatonin intervention therapies, including improvements in neuroplasticity and physical capabilities, are discussed and the molecular mechanisms underlying this disorder are reviewed. The authors suggest that melatonin may be a useful treatment for FXS with ASD in terms of alleviating the adverse effects of variations in the circadian rhythm. PMID:28632163

Discrete cosine transform and hash functions toward implementing a (robust-fragile) watermarking scheme

NASA Astrophysics Data System (ADS)

Al-Mansoori, Saeed; Kunhu, Alavi

2013-10-01

This paper proposes a blind multi-watermarking scheme based on designing two back-to-back encoders. The first encoder is implemented to embed a robust watermark into remote sensing imagery by applying a Discrete Cosine Transform (DCT) approach. Such watermark is used in many applications to protect the copyright of the image. However, the second encoder embeds a fragile watermark using `SHA-1' hash function. The purpose behind embedding a fragile watermark is to prove the authenticity of the image (i.e. tamper-proof). Thus, the proposed technique was developed as a result of new challenges with piracy of remote sensing imagery ownership. This led researchers to look for different means to secure the ownership of satellite imagery and prevent the illegal use of these resources. Therefore, Emirates Institution for Advanced Science and Technology (EIAST) proposed utilizing existing data security concept by embedding a digital signature, "watermark", into DubaiSat-1 satellite imagery. In this study, DubaiSat-1 images with 2.5 meter resolution are used as a cover and a colored EIAST logo is used as a watermark. In order to evaluate the robustness of the proposed technique, a couple of attacks are applied such as JPEG compression, rotation and synchronization attacks. Furthermore, tampering attacks are applied to prove image authenticity.

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

PubMed

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.

Neurological and endocrine phenotypes of fragile X carrier women.

PubMed

Hall, D; Todorova-Koteva, K; Pandya, S; Bernard, B; Ouyang, B; Walsh, M; Pounardjian, T; Deburghraeve, C; Zhou, L; Losh, M; Leehey, M; Berry-Kravis, E

2016-01-01

Women who carry fragile X mental retardation 1 (FMR1)gene premutation expansions frequently report neurological or endocrine symptoms and prior studies have predominantly focused on questionnaire report of medical issues. Premutation carrier (PMC) women (n = 33) and non-carrier controls (n = 13) were recruited and evaluated by a neurologist, neuropsychologist, and endocrinologist. Blood and skin biopsies were collected for molecular measures. Scales for movement disorders, neuropathy, cognitive function, psychiatric symptoms, sleep, and quality of life were completed. The average age of the women was 51 years (n = 46) and average CGG repeat size was 91 ± 24.9 in the FMR1 PMC women. Seventy percent of the PMC women had an abnormal neurological examination. PMC women had significantly higher scores on the Fragile X-Associated Tremor Ataxia Syndrome (FXTAS) rating scale, more neuropathy, and difficulty with tandem gait compared to controls. Central sensitivity syndromes, a neuroticism profile on the NEO Personality Profile, and sleep disorders were also prevalent. Discrepancies between subject report and examination findings were also seen. This pilot study suggests that women with the FMR1 premutation may have a phenotype that overlaps with that seen in FXTAS. Additional research with larger sample sizes is warranted to better delineate the clinical features. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Progress toward therapeutic potential for AFQ056 in Fragile X syndrome.

PubMed

Sourial, Mary; Cheng, Connie; Doering, Laurie C

2013-01-01

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading single-gene cause of autism. It is caused by the lack of production of the Fragile X mental retardation protein (FMRP), resulting in cognitive deficits, hyperactivity, and autistic behaviors. Breakthrough advances in potential therapy for FXS followed the discovery that aberrant group 1 metabotropic glutamate receptor (mGluR) signaling is an important constituent of the pathophysiology of the syndrome. Research has indicated that upon neuronal stimulation, FMRP acts downstream of group 1 mGluRs (mGluRs1/5) to inhibit protein synthesis, long-term depression, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor internalization. To offset the deficits caused by the lack of FMRP, many pharmaceutical companies have designed medicinal drugs to target the unrestrained stimulation of mGluR5 signaling in FXS. Indeed, promising results from animal and clinical studies suggest that mGluR5 antagonists such as AFQ056 can successfully correct many of the deficits in FXS. In this review, we cover the animal studies performed to date that test the role of AFQ056 as a selective mGluR5 antagonist to alleviate the phenotypes of FXS.

Low bone mineral density and fragility fractures in permanent vegetative state patients.

PubMed

Oppl, Bastian; Michitsch, Gabriele; Misof, Barbara; Kudlacek, Stefan; Donis, Johann; Klaushofer, Klaus; Zwerina, Jochen; Zwettler, Elisabeth

2014-01-01

Disuse of the musculoskeletal system causes bone loss. Whether patients in vegetative state, a dramatic example of immobilization after severe brain injury, suffer from bone loss and fractures is currently unknown. Serum markers of bone turnover, bone mineral density (BMD) measurements, and clinical data were cross-sectionally analyzed in 30 consecutive vegetative state patients of a dedicated apallic care unit between 2003 and 2007 and compared with age- and sex-matched healthy individuals. Vegetative state patients showed low calcium levels and vitamin D deficiency compared with healthy controls. Serum bone turnover markers revealed high turnover as evidenced by markedly elevated carboxy-terminal telopeptide of type I collagen (β-crosslaps) and increased levels of alkaline phosphatase. BMD measured by dual-energy X-ray absorptiometry (DXA) scanning showed strongly decreased T- and Z-scores for hip and spine. Over a period of 5 years, 8 fragility fractures occurred at peripheral sites in 6 of 30 patients (n = 3 femur, n = 2 tibia, n = 2 fibula, n = 1 humerus). In conclusion, high bone turnover and low BMD is highly prevalent in vegetative state patients, translating into a clinically relevant problem as shown by fragility fractures in 20% of patients over a time period of 5 years. . © 2014 American Society for Bone and Mineral Research.

Breastfeeding protects against hip fracture in postmenopausal women: the Tromsø study.

PubMed

Bjørnerem, Ashild; Ahmed, Luai A; Jørgensen, Lone; Størmer, Jan; Joakimsen, Ragnar M

2011-12-01

Despite reported bone loss during pregnancy and lactation, no study has shown deleterious long-term effects of parity or breastfeeding. Studies have shown higher bone mineral density and reduced risk for fracture in parous than in nulliparous women or no effect of parity and breastfeeding, so long-term effects are uncertain. We studied the effect of parity and breastfeeding on risk for hip, wrist and non-vertebral fragility fractures (hip, wrist, or proximal humerus) in 4681 postmenopausal women aged 50 to 94 years in the Tromsø Study from 1994-95 to 2010, using Cox's proportional hazard models. During 51 906 person-years, and a median of 14.5 years follow-up, 442, 621, and 1105 of 4681 women suffered incident hip, wrist, and fragility fractures, and the fracture rates were 7.8, 11.4, and 21.3 per 1000 person-years, respectively. The risk for hip, wrist, and fragility fracture did not differ between parous (n = 4230, 90.4%) and nulliparous women (n = 451, 9.6%). Compared with women who did not breast-feed after birth (n = 184, 4.9%), those who breastfed (n = 3564, 95.1%) had 50% lower risk for hip fracture (HR 0.50; 95% CI 0.32 to 0.78), and 27% lower risk for fragility fracture (HR 0.73; 95% CI 0.54 to 0.99), but similar risk for wrist fracture, after adjustment for age, BMI, height, physical activity, smoking, a history of diabetes, previous fracture of hip or wrist, use of hormone replacement therapy, and length of education. Each 10 months longer total duration of breastfeeding reduced the age-adjusted risk for hip fracture by 12% (HR 0.88; 95% CI 0.78 to 0.99, p for trend = 0.03) before, and marginally after, adjustment for BMI and other covariates (HR 0.91; 95% CI 0.80 to 1.04). In conclusion, this data indicates that pregnancy and breastfeeding has no long-term deleterious effect on bone fragility and fractures, and that breastfeeding may contribute to a reduced risk for hip fracture after menopause. Copyright © 2011 American Society for Bone and Mineral Research.

Language Phenotypes and Intervention Planning: Bridging Research and Practice

ERIC Educational Resources Information Center

Fidler, Deborah J.; Philofsky, Amy; Hepburn, Susan L.

2007-01-01

This paper focuses on the communication and language phenotypes associated with three genetic disorders: Down syndrome, Williams syndrome, and fragile X syndrome. It is argued that there is empirical evidence that these disorders predispose children to specific profiles of strength and weakness in some areas of speech, language, and communication,…

Life Is Not a Bed of Roses....

ERIC Educational Resources Information Center

Govako, Boris Ivanovich

1990-01-01

Expresses concern over increasing number of divorces in Soviet Union. Offers reasons gleaned from survey research. Concludes that one of reasons for fragility of marriage today is misunderstanding of true meaning of family and inability to protect values. Warns that young people are being prepared only for work to the detriment of their health and…

Cockpit Display of Traffic Information and the Measurement of Pilot Workload: An Annotated Bibliography

DTIC Science & Technology

1982-02-01

fragile data bases. With correction of this deficiency and further research on time sharing behavior or function interlacing, these methods should prove to...parameLers used were (1) amplitude - as a measure of amplitude variations, the difference between two successive heart rate values- tk2 ) frequency - as a

E-Learning "Bites" for Adult Learners: Mixed Messages from Research

ERIC Educational Resources Information Center

Morrison, Marlene

2005-01-01

Accompanying awareness of the potential for lifelong learning to secure social inclusion and economic survival, e-learning has grown in significance and a fragile consensus about its purposes has emerged among stakeholders. The University for Industry (Ufi) and its e-learning arm, learndirect, have focused efforts especially (but not entirely)…

Sexual Orientation and School Discipline: New Evidence from a Population-Based Sample

ERIC Educational Resources Information Center

Mittleman, Joel

2018-01-01

Sexual minorities' risk for exclusionary discipline is a commonly cited indicator of the challenges that these students face. The current study addresses this issue by introducing a new data source for research on sexual minority students: the Fragile Families and Childhood Wellbeing Study. In this geographically diverse, population-based sample,…

Education for Democracy in Israel: Structural Impediments and Basic Dilemmas

ERIC Educational Resources Information Center

Neuberger, Benyamin

2007-01-01

Research in Israel has shown a high level of non-democratic, and even anti-democratic, attitudes among Israeli high-school students. Similar findings in the adult population indicate that this is not a "childhood disorder" that evaporates with age, but something which could pose a threat to Israel's young and fragile democracy. The…

Re-Mediating Current Activity for the Future

ERIC Educational Resources Information Center

Gutierrez, Kris D.

2012-01-01

The growing poverty and inequity in America should create a sense of urgency in researchers to leverage what they know for the public good--to intervene more productively and vigorously in an ever more fragile public educational system and to address the increasing vulnerability of far too many youth in the United States. The current worldwide…

15 CFR 921.40 - Ongoing oversight and evaluations of designated National Estuarine Research Reserves.

Code of Federal Regulations, 2013 CFR

2013-01-01

... need to keep some areas off limits to the public in order to protect fragile resources. (5) Inadequate... the ability to protect the Reserve site and resources from offsite impacts. (7) Inadequate... on use of the Reserve are adhered to, or evidence that Reserve resources are being damaged or...

15 CFR 921.40 - Ongoing oversight and evaluations of designated National Estuarine Research Reserves.

Code of Federal Regulations, 2014 CFR

2014-01-01

... need to keep some areas off limits to the public in order to protect fragile resources. (5) Inadequate... the ability to protect the Reserve site and resources from offsite impacts. (7) Inadequate... on use of the Reserve are adhered to, or evidence that Reserve resources are being damaged or...

15 CFR 921.40 - Ongoing oversight and evaluations of designated National Estuarine Research Reserves.

Code of Federal Regulations, 2011 CFR

2011-01-01

... need to keep some areas off limits to the public in order to protect fragile resources. (5) Inadequate... the ability to protect the Reserve site and resources from offsite impacts. (7) Inadequate... on use of the Reserve are adhered to, or evidence that Reserve resources are being damaged or...

15 CFR 921.40 - Ongoing oversight and evaluations of designated National Estuarine Research Reserves.

Code of Federal Regulations, 2012 CFR

2012-01-01

... need to keep some areas off limits to the public in order to protect fragile resources. (5) Inadequate... the ability to protect the Reserve site and resources from offsite impacts. (7) Inadequate... on use of the Reserve are adhered to, or evidence that Reserve resources are being damaged or...

Maternal Employment Stability in Early Childhood: Links with Child Behavior and Cognitive Skills

ERIC Educational Resources Information Center

Pilkauskas, Natasha V.; Brooks-Gunn, Jeanne; Waldfogel, Jane

2018-01-01

Although many studies have investigated links between maternal employment and children's wellbeing, less research has considered whether the stability of maternal employment is linked with child outcomes. Using unique employment calendar data from the Fragile Families and Child Wellbeing Study (N = 2,011), an urban birth cohort study of largely…

Knowledge Ecologies in Fragile Online Learning Environments. Research: Information and Communication Technologies

ERIC Educational Resources Information Center

Henning, Elizabeth; Van der Westhuizen, Duan; Diseko, Rabaitse

2005-01-01

This article gives an account of an inquiry into two different postgraduate student groups' ways of engaging with a virtual learning environment. Using a variety of data sources, including learning artefacts, interview data, open-ended qualitative questionnaires and online discussion postings, the inquiry captured processes of engagement of the…

Cellular Basis for Learning Impairment in Fragile X Syndrome

DTIC Science & Technology

2015-08-01

the leading cause of inherited intellectual disability and results in cognitive impairment, hyperactivity , attention deficits , seizure disorders ...impairment, hyperactivity , attention deficits and seizure disorders . Previous studies using a mouse model for FXS (Fmr1- KO) have described impairments in...neurogenesis in adult fragile X mice, test fragile X mice for learning deficits in hippocampal-independent tasks, and determine how synaptic

Brief Report: Autism of the Asperger Type Associated with an Autosomal Fragile Site.

ERIC Educational Resources Information Center

Saliba, Joseph R.; Griffiths, Mike

1990-01-01

This case study describes a 12-year-old boy with autism in association with the folate-sensitive fragile site fra(2)(q13). Cytogenetic results of blood analysis are described, and two possibilities are discussed: the fragile site may be a coincidental finding unrelated to the autism, or may represent an area of potential gene damage. (JDD)

Does Attention Constrain Developmental Trajectories in Fragile X Syndrome? A 3-Year Prospective Longitudinal Study

ERIC Educational Resources Information Center

Cornish, Kim; Cole, Victoria; Longhi, Elena; Karmiloff-Smith, Annette; Scerif, Gaia

2012-01-01

Basic attentional processes and their impact on developmental trajectories in fragile X syndrome were assessed in a 3-year prospective study. Although fragile X syndrome is a monogenic X-linked disorder, there is striking variability in outcomes even in young boys with the condition. Attention is a key factor constraining interactions with the…

Discourse Skills of Boys with Fragile X Syndrome in Comparison to Boys with Down Syndrome

ERIC Educational Resources Information Center

Roberts, Joanne; Martin, Gary E.; Moskowitz, Lauren; Harris, Adrianne A.; Foreman, Jamila; Nelson, Lauren

2007-01-01

Purpose: This study compared the conversational discourse skills of boys who have fragile X syndrome with and without autism spectrum disorder (ASD) with those of boys with Down syndrome and boys who are typically developing. Method: Participants were boys who have fragile X syndrome with (n = 26) and without (n = 28) ASD, boys with Down syndrome…

It's Not about "You," It's about "Us": A Black Woman Administrator's Efforts to Disrupt White Fragility in an Urban School

ERIC Educational Resources Information Center

Patton, Lori D.; Jordan, Jodi L.

2017-01-01

This case centers on a Black woman school administrator and efforts to disrupt Whiteness among an urban elementary school teaching staff. The case details the resistance she encounters while encouraging teachers to confront "White fragility" and consider how their fragile perspectives on race and racism shape how they educate Black…

Effects of Sampling Context on Spontaneous Expressive Language in Males with Fragile X Syndrome or Down Syndrome

ERIC Educational Resources Information Center

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…

Perseveration in the Connected Speech of Boys with Fragile X Syndrome with and without Autism Spectrum Disorder

ERIC Educational Resources Information Center

Martin, Gary E.; Roberts, Joanne E.; Helm-Estabrooks, Nancy; Sideris, John; Vanderbilt, Jacqueline; Moskowitz, Lauren

2012-01-01

Verbal perseveration is a frequently reported language characteristic of males with Fragile X syndrome and may be a defining feature or hallmark of the syndrome. We compared the verbal perseveration of boys with Fragile X syndrome with (n = 29) and without (n = 30) autism spectrum disorder, boys with Down syndrome (n = 27), and typically…

Role of microRNA Pathway in Mental Retardation

PubMed Central

Qurashi, Abrar; Chang, Shuang; Jin, Peng

2007-01-01

Deficits in cognitive functions lead to mental retardation (MR). Understanding the genetic basis of inherited MR has provided insights into the pathogenesis of MR. Fragile X syndrome is one of the most common forms of inherited MR, caused by the loss of functional Fragile X Mental Retardation Protein (FMRP). MicroRNAs (miRNAs) are endogenous, single-stranded RNAs between 18 and 25 nucleotides in length, which have been implicated in diversified biological pathways. Recent studies have linked the miRNA pathway to fragile X syndrome. Here we review the role of the miRNA pathway in fragile X syndrome and discuss its implication in MR in general. PMID:17982588

Interferon-γ Drives Treg Fragility to Promote Anti-tumor Immunity.

PubMed

Overacre-Delgoffe, Abigail E; Chikina, Maria; Dadey, Rebekah E; Yano, Hiroshi; Brunazzi, Erin A; Shayan, Gulidanna; Horne, William; Moskovitz, Jessica M; Kolls, Jay K; Sander, Cindy; Shuai, Yongli; Normolle, Daniel P; Kirkwood, John M; Ferris, Robert L; Delgoffe, Greg M; Bruno, Tullia C; Workman, Creg J; Vignali, Dario A A

2017-06-01

Regulatory T cells (T regs ) are a barrier to anti-tumor immunity. Neuropilin-1 (Nrp1) is required to maintain intratumoral T reg stability and function but is dispensable for peripheral immune tolerance. T reg -restricted Nrp1 deletion results in profound tumor resistance due to T reg functional fragility. Thus, identifying the basis for Nrp1 dependency and the key drivers of T reg fragility could help to improve immunotherapy for human cancer. We show that a high percentage of intratumoral NRP1 + T regs correlates with poor prognosis in melanoma and head and neck squamous cell carcinoma. Using a mouse model of melanoma where Nrp1-deficient (Nrp1 -/- ) and wild-type (Nrp1 +/+ ) T regs can be assessed in a competitive environment, we find that a high proportion of intratumoral Nrp1 -/- T regs produce interferon-γ (IFNγ), which drives the fragility of surrounding wild-type T regs , boosts anti-tumor immunity, and facilitates tumor clearance. We also show that IFNγ-induced T reg fragility is required for response to anti-PD1, suggesting that cancer therapies promoting T reg fragility may be efficacious. Copyright © 2017 Elsevier Inc. All rights reserved.

Hippocampal neuronal subtypes develop abnormal dendritic arbors in the presence of Fragile X astrocytes.

PubMed

Jacobs, S; Cheng, C; Doering, L C

2016-06-02

Astrocytes are now recognized as key players in the neurobiology of neurodevelopmental disorders such as Fragile X syndrome. However, the nature of Fragile X astrocyte-mediated control of dendrite development in subtypes of hippocampal neurons is not yet known. We used a co-culture procedure in which wildtype primary hippocampal neurons were cultured with astrocytes from either a wildtype or Fragile X mouse, for either 7, 14 or 21 days. The neurons were processed for immunocytochemistry with the dendritic marker MAP2, classified by morphological criteria into one of five neuronal subtypes, and subjected to Sholl analyses. Both linear and semi-log methods of Sholl analyses were applied to the neurons in order to provide an in depth analysis of the dendritic arborizations. We found that Fragile X astrocytes affect the development of dendritic arborization of all subtypes of wildtype hippocampal neurons. Furthermore, we show that hippocampal neurons with spiny stellate neuron morphology exhibit the most pervasive developmental delays, with significant dendritic arbor alterations persisting at 21 days in culture. The results further dictate the critical role astrocytes play in governing neuronal morphology including altered dendrite development in Fragile X. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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 developmental switch in GABA polarity is delayed in fragile X mice.

PubMed

He, Qionger; Nomura, Toshihiro; Xu, Jian; Contractor, Anis

2014-01-08

Delays in synaptic and neuronal development in the cortex are key hallmarks of fragile X syndrome, a prevalent neurodevelopmental disorder that causes intellectual disability and sensory deficits and is the most common known cause of autism. Previous studies have demonstrated that the normal progression of plasticity and synaptic refinement during the critical period is altered in the cortex of fragile X mice. Although the disruptions in excitatory synapses are well documented in fragile X, there is less known about inhibitory neurotransmission during the critical period. GABAergic transmission plays a crucial trophic role in cortical development through its early depolarizing action. At the end of cortical critical period, response properties of GABA transform into their mature hyperpolarizing type due to developmental changes in intracellular chloride homeostasis. We found that the timing of the switch from depolarizing to hyperpolarizing GABA is delayed in the cortex of fragile X mice and there is a concurrent alteration in the expression of the neuronal chloride cotransporter NKCC1 that promotes the accumulation of intracellular chloride. Disruption of the trophic effects of GABA during cortical development could contribute to the altered trajectory of synaptic maturation in fragile X syndrome.

Rush Fracture Liaison Service for capturing "missed opportunities" to treat osteoporosis in patients with fragility fractures.

PubMed

Gupta, M J; Shah, S; Peterson, S; Baim, S

2018-06-04

In spite of being a public health problem of pandemic proportions, osteoporosis continues to be underdiagnosed and undertreated especially in older adults with fragility fractures. Confirmation of this hypothesis resulted in the development of a novel Fracture Liaison Service (Rush FLS). Results of the first 12 months of operation revealed that patients with confirmed fragility fracture do not have a timely diagnosis at fracture occurrence or treatment of their disease. The Rush FLS is an effective fracture liaison model. Determining the prevalence of undiagnosed and untreated osteoporosis in fragility fracture patients, either admitted to an academic tertiary care center or treated and discharged from the center's emergency department to be followed in the endocrinology bone clinic, using an innovative, educational, low-cost, physician-run Fracture Liaison Service (FLS). An automated alert was integrated into the electronic medical record at Rush University Medical Center (RUMC), triggered by historical and/or acute fracture(s) in patients 50 years or older, in patients that were either admitted to the hospital or in patients evaluated in the emergency department and discharged to be followed in the endocrinology bone clinic. We report the results of the first 12 months of operation in patients admitted to the hospital. First acute fragility fracture(s) were identified in 36% (80/223), only historical fragility fracture(s) in 28% (63/223) and both acute and historical fragility fracture(s) in 36% (80/223). The cumulative subgroup with historical fragility fractures with/without new fractures included 67% (96/143) without a previous diagnosis of osteoporosis. First acute fragility fracture group included 83.8% (67/80) without a previous diagnosis of osteoporosis. Rush FLS "captured missed opportunities" in 73.1% (163/223) of previously undiagnosed and 77.1% (172/223) of previously untreated osteoporosis patients. Dual-energy x-ray absorptiometry (DXA) prior to FLS consult was confirmed in 30% (67/223). Vitamin D deficiency (25-hydroxy vitamin D < 20 ng/ml) in 41.9% (78/186) including undetectable levels in 16.6% (31/186) and secondary hyperparathyroidism in 43.3% (78/180) were the most common laboratory confirmed secondary etiologies for bone loss. This study reported undiagnosed, uninvestigated, and untreated osteoporosis in the majority of fragility fracture patients seen by the Rush FLS in the first 12 months of operation.

Measurement, methods, and divergent patterns: Reassessing the effects of same-sex parents.

PubMed

Cheng, Simon; Powell, Brian

2015-07-01

Scholars have noted that survey analysis of small subsamples-for example, same-sex parent families-is sensitive to researchers' analytical decisions, and even small differences in coding can profoundly shape empirical patterns. As an illustration, we reassess the findings of a recent article by Regnerus regarding the implications of being raised by gay and lesbian parents. Taking a close look at the New Family Structures Study (NFSS), we demonstrate the potential for misclassifying a non-negligible number of respondents as having been raised by parents who had a same-sex romantic relationship. We assess the implications of these possible misclassifications, along with other methodological considerations, by reanalyzing the NFSS in seven steps. The reanalysis offers evidence that the empirical patterns showcased in the original Regnerus article are fragile-so fragile that they appear largely a function of these possible misclassifications and other methodological choices. Our replication and reanalysis of Regnerus's study offer a cautionary illustration of the importance of double checking and critically assessing the implications of measurement and other methodological decisions in our and others' research. Copyright © 2015 Elsevier Inc. All rights reserved.

Sudden cardiac arrest in schools: the role of the school nurse in AED program implementation.

PubMed

Boudreaux, Sharon; Broussard, Lisa

2012-01-01

A school nurse has many obstacles to overcome when providing emergency care for an age group ranging from four to adulthood. The 21st century school nurse faces the challenges of providing care to medically fragile children at multiple sites, with high student-nurse ratios. The implementation of an Automated External Defibrillation (AED) program can assist the school nurse and staff in providing necessary life-saving services for Sudden Cardiac Arrest (SCA) victims of all ages. The purpose of this article is to describe AED program implementation in a school setting, including the need, essential elements, benefits, and potential concerns related to this vital component of the American Heart Association five-link chain of survival.

Success, Failure, and Unfinished Business of Education, Prevention, Policy, and Intervention Programs on Substance Misuse in Brazilian Sport.

PubMed

Santos, Azenildo M

2015-01-01

The current Brazilian situation is such that it is difficult to obtain a worldwide evaluation of failure in education, intervention, or prevention programs. How fragile Brazil's anti-doping system is, its appropriateness as well as its relevance, with needed policy infrastructures for achieving the selected goals, and how wide the gap is between education and prevention program effectiveness between high-performance athletes and recreational practitioners who just want to look good. An additional concern, and ever present flaw regarding Brazil's "common sportsman" in day-to-day society is their not receiving known and necessary "sports education," enabling the development of an "at-risk" population for self-harm. Reflections on public health policy are noted.

Monitoring trail conditions: New methodological considerations

USGS Publications Warehouse

Marion, Jeffrey L.; Leung, Yu-Fai; Nepal, Sanjay K.

2006-01-01

The U.S. National Park Service (NPS) accommodates nearly 300 million visitors per year, visitation that has the potential to produce negative effects on fragile natural and cultural resources. The policy guidance from the NPS Management Policies recognizes the legitimacy of providing opportunities for public enjoyment of parks while acknowledging the need for managers to “seek ways to avoid, or to minimize to the greatest degree practicable, adverse impacts on park resources and values” (NPS 2001). Thus, relative to visitor use, park managers must evaluate the types and extents of resource impacts associated with recreational activities, and determine to what extent they are unacceptable and constitute impairment. Visitor impact monitoring programs can assist managers in making objective evaluations of impact acceptability and impairment and in selecting effective impact management practices by providing quantitative documentation of the types and extent of recreationrelated impacts on natural resources. Monitoring programs are explicitly authorized in Section 4.1 of the Management Policies: Natural systems in the national park system, and the human influences upon them, will be monitored to detect change. The Service will use the results of monitoring and research to understand the detected change and to develop appropriate management actions.

Tirilazad mesylate protects stored erythrocytes against osmotic fragility.

PubMed

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.

Fragile X spectrum disorders.

PubMed

Lozano, Reymundo; Rosero, Carolina Alba; Hagerman, Randi J

2014-11-01

The fragile X mental retardation 1 gene (FMR1), which codes for the fragile X mental retardation 1 protein (FMRP), is located at Xp27.3. The normal allele of the FMR1 gene typically has 5 to 40 CGG repeats in the 5' untranslated region; abnormal alleles of dynamic mutations include the full mutation (> 200 CGG repeats), premutation (55-200 CGG repeats) and the gray zone mutation (45-54 CGG repeats). Premutation carriers are common in the general population with approximately 1 in 130-250 females and 1 in 250-810 males, whereas the full mutation and Fragile X syndrome (FXS) occur in approximately 1 in 4000 to 1 in 7000. FMR1 mutations account for a variety of phenotypes including the most common monogenetic cause of inherited intellectual disability (ID) and autism (FXS), the most common genetic form of ovarian failure, the fragile X-associated primary ovarian insufficiency (FXPOI, premutation); and fragile X-associated tremor/ataxia syndrome (FXTAS, premutation). The premutation can also cause developmental problems including ASD and ADHD especially in boys and psychopathology including anxiety and depression in children and adults. Some premutation carriers can have a deficit of FMRP and some unmethylated full mutation individuals can have elevated FMR1 mRNA that is considered a premutation problem. Therefore the term "Fragile X Spectrum Disorder" (FXSD) should be used to include the wide range of overlapping phenotypes observed in affected individuals with FMR1 mutations. In this review we focus on the phenotypes and genotypes of children with FXSD.

Neuropsychiatry of fragile X-premutation carriers with and without fragile X-associated tremor-ataxia syndrome: implications for neuropsychology.

PubMed

Bourgeois, James A

2016-08-01

Clinical neuropsychologists benefit from clinical currency in recently ascertained neuropsychiatric illness, such as fragile X premutation (FXPM) disorders. The author reviewed the clinical literature through 2016 for neuropsychiatric phenotypes in FXPM disorders, including patients with fragile X-associated tremor/ataxia syndrome (FXTAS). A PubMed search using the search terms 'Fragile X,' 'Premutation,' 'Carriers,' 'Psychiatric,' 'Dementia,' 'Mood,' and 'Anxiety' for citations in the clinical literature through 2016 was reviewed for studies specifically examining the neuropsychiatric phenotype in FXPM patients. The relevant articles were classified according to specific neuropsychiatric syndromes, including child onset, adult onset with and without FXTAS, as well as common systemic comorbidities in FXPM patients. Eighty-six articles were reviewed for the neuropsychiatric and other phenotypes in FXPM patients. The neuropsychiatric phenotype in FXPM patients is distinct from that of full mutation (Fragile X Syndrome) patients. FXTAS is associated with a specific cortical-subcortical major or mild neurocognitive disorder (NCD). FXPM patients are at risk for neuropsychiatric illness. In addition, FXPM patients are at risk for other systemic conditions that should raise suspicion for FXPM-associated illnesses. Clinicians should consider a diagnosis of FXPM-associated neuropsychiatric illness when patients with specific clinical scenarios are encountered; especially in patient pedigrees consistent with a typical (often multigenerational) presentation of fragile X-associated conditions, confirmatory genetic testing should be considered. Clinical management should take into account the psychological challenges of a multigenerational genetic neuropsychiatric illness with a variable CNS and systemic clinical phenotype.

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

NASA Astrophysics Data System (ADS)

Tournier, Robert F.

2014-12-01

An undercooled liquid is unstable. The driving force of the glass transition at Tg 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 -Vm×Δp at Tg where Vm is the molar volume. A stable glass-liquid transition model predicts the specific heat jump of fragile liquids at T≤Tg, the Kauzmann temperature TK where the liquid entropy excess with regard to crystal goes to zero, the equilibrium enthalpy between TK and Tg, the maximum nucleation rate at TK of superclusters containing magic atom numbers, and the equilibrium latent heats at Tg and TK. Strong-to-fragile and strong-to-strong liquid transitions at Tg 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 TK 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 Tg without stable-glass formation while a strong glass is stable after transition.

Screening for fragile X syndrome.

PubMed

Murray, J; Cuckle, H; Taylor, G; Hewison, J

1997-01-01

BACKGROUND AND AIM OF REVIEW. In 1991, the gene responsible for fragile X syndrome, a common cause of learning disability, was discovered. As a result, diagnosis of the disorder has improved and its molecular genetics are now understood. This report seems to provide the information needed to decide whether to use DNA testing to screen for the disorder. HOW THE RESEARCH WAS CONDUCTED. A literature search of electronic reference databases of published and 'grey' literature was undertaken together with hand searching of the most recent publications. RESEARCH FINDINGS. NATURAL HISTORY. Physical characteristics of fragile X syndrome include facial atypia, joint laxity and, in boys, macro-orchidism. Most affected males have moderate-to-severe learning disabilities with IQs under 50 whereas most females have borderline IQs of 70-85. Behavioural problems are similar to those seen with autism and attention-deficit disorders. Although fragile X syndrome is not curable there are a number of medical, educational, psychological and social interventions that can improve the symptoms. About 6% of those with learning disabilities tested in institutions have fragile X syndrome. Population prevalence figures are 1 in 4000 in males and 1 in 8000 in females. GENETICS. The disorder is caused by a mutation in a gene on the X chromosome which includes a trinucleotide repeat sequence. The mutation is characterized by hyper-expansion of the repeat sequence leading to down-regulation of the gene. In males an allele with repeat size in excess of 200, termed a full mutation (FM), is always associated with the affected phenotype, whereas in females only half are affected. Individuals with alleles having repeat size in the range 55-199 are unaffected but in females the sequence is heritably unstable so that it is at high risk of expansion to an FM in her offspring. This allele is known as a pre-mutation (PM) to contrast it with the FM found in the affected individual. No spontaneous expansions directly from a normal allele to an FM have been observed. SCREENING STRATEGIES. The principal aims of screenng for fragile X syndrome is to reduce the birth prevalence of the disorder, by prenatal diagnosis and selective termination of pregnancy, or by reducing the number of pregnancies in women who have the FM or PM alleles. Possible screening strategies are: routine antenatal testing of apparently low risk pregnancies, preconceptual testing of young women, and systematic testing in affected families ('cascade' screening). A secondary aim is to bring forward the diagnosis of affected individuals so that they might benefit from early treatment. Active paediatric screening and neonatal screening could achieve this but there is no direct evidence of any great benefit from early diagnosis. SCREENING TESTS. Cytogenetic methods are unsuitable for screening purposes. Southern blotting of genomic DNA can be used but is inaccurate in measuring the size of small PMs, there is a long laboratory turnaround time, and it is relatively expensive. The best protocol is to amplify the DNA using polymerase chain reaction on all samples, and when there is a possible failure to amplify, a Southern blot.(ABSTRACT TRUNCATED)

The Glen Canyon Dam Adaptive Management Program: An experiment in science-based resource management

NASA Astrophysics Data System (ADS)

kaplinski, m

2001-12-01

In 1996, Glen Canyon Dam Adaptive Management (GCDAMP) program was established to provide input on Glen Canyon Dam operations and their affect on the Colorado Ecosystem in Grand Canyon. The GCDAMP is a bold experiment in federal resource management that features a governing partnership with all relevant stakeholders sitting at the same table. It is a complicated, difficult process where stakeholder-derived management actions must balance resource protection with water and power delivery compacts, the Endangered Species Act, the National Historical Preservation Act, the Grand Canyon Protection Act, National Park Service Policy, and other stakeholder concerns. The program consists of four entities: the Adaptive Management Workgroup (AMWG), the Technical Workgroup (TWG), the Grand Canyon Monitoring and Research Center (GCMRC), and independent review panels. The AMWG and TWG are federal advisory committees that consists of federal and state resource managers, Native American tribes, power, environmental and recreation interests. The AMWG is develops, evaluates and recommends alternative dam operations to the Secretary. The TWG translates AMWG policy and goals into management objectives and information needs, provides questions that serve as the basis for long-term monitoring and research activities, interprets research results from the GCMRC, and prepares reports as required for the AMWG. The GCMRC is an independent science center that is responsible for all GCDAMP monitoring and research activities. The GCMRC utilizes proposal requests with external peer review and an in-house staff that directs and synthesizes monitoring and research results. The GCMRC meets regularly with the TWG and AMWG and provides scientific information on the consequences of GCDAMP actions. Independent review panels consist of external peer review panels that provide reviews of scientific activities and the program in general, technical advice to the GCMRC, TWG and AMWG, and play a critical balancing role to ensure overall scientific credibility to the program. Many lessons have been learned and many challenges remain. Incorporation of social issues such as recreation experience and non-use economic valuation has been especially difficult and not entirely satisfactory to many stakeholders. Adaptive management can be frustrating and a fragile spirit of cooperation exists between stakeholders with opposing interests. Communication and flexibility is the key to program success. Scientific results need to be clearly stated to keep results relevant to managers, and managers must embrace the uncertainty of scientific endeavors. Managers must remain flexible in creating and revising program goals and objectives to incorporate new scientific results into meaningful management strategies.

Global Identification of Disease-Associated Genes in Fragile X Cells

DTIC Science & Technology

2017-03-01

identify those specific gene substrates of FMRP, particularly those expressed in the brain , that are implicated in FXS progression. Moreover, we use...the co-localized R-loop formation and chromosome fragility in Fragile X cells, particularly at the brain -expressed genes, by ChIP-seq (detecting...X mental retardation protein February 2016, NGS Data Analysis & Informatics Conference, San Diego, California (Poster presentation) Title: Global

Math Learning Disability and Math LD Subtypes: Evidence from Studies of Turner Syndrome, Fragile X Syndrome, and Neurofibromatosis Type 1.

ERIC Educational Resources Information Center

Mazzocco, Michele M. M.

2001-01-01

This study examined whether indicators of math learning disability were observed in 35 5- and 6-year-olds with either neurofibromatosis, Turner Syndrome, or fragile X syndrome and compared to controls. Findings indicate that girls with fragile X or Turner syndrome but not neurofibromatosis are significantly more likely to have specific math…

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

ERIC Educational Resources Information Center

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…

Delineating the Profile of Autism Spectrum Disorder Characteristics in Cornelia de Lange and Fragile X Syndromes

ERIC Educational Resources Information Center

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…

Teaching Reading to Youth with Fragile X Syndrome: Should Phonemic Awareness and Phonics Instruction Be Used? EBP Briefs. Volume 9, Issue 6

ERIC Educational Resources Information Center

Brazendale, Allison; Adlof, Suzanne; Klusek, Jessica; Roberts, Jane

2015-01-01

Clinical Question: Would a child with fragile X syndrome benefit more from phonemic awareness and phonics instruction or whole-word training to increase reading skills? Method: Systematic review. Study Sources: PsycINFO. Search Terms: fragile X OR Down syndrome OR cognitive impairment OR cognitive deficit OR cognitive disability OR intellectual…

Correlation of the fragility of metallic liquids with the high temperature structure, volume, and cohesive energy

NASA Astrophysics Data System (ADS)

Gangopadhyay, A. K.; Pueblo, C. E.; Dai, R.; Johnson, M. L.; Ashcraft, R.; Van Hoesen, D.; Sellers, M.; Kelton, K. F.

2017-04-01

The thermal expansion coefficients, structure factors, and viscosities of twenty-five equilibrium and supercooled metallic liquids have been measured using an electrostatic levitation (ESL) facility. The structure factor was measured at the Advanced Photon Source, Argonne, using the ESL. A clear connection between liquid fragility and structural and volumetric changes at high temperatures is established; the observed changes are larger for the more fragile liquids. It is also demonstrated that the fragility of metallic liquids is determined to a large extent by the cohesive energy and is, therefore, predictable. These results are expected to provide useful guidance in the future design of metallic glasses.

Fragility and glass transition for binary mixtures of 1,2-propanediol and LiBF4

NASA Astrophysics Data System (ADS)

Terashima, Y.; Mori, M.; Sugimoto, N.; Takeda, K.

2014-04-01

The fragility and glass transition for binary mixtures of 1,2-propanediol and LiBF4 were investigated by measuring the heating rate dependence of glass transition temperature (Tg) using differential scanning calorimetry. With increasing LiBF4 mole fraction, x, up to 0.25, fragility, m, increased rapidly from 53 to 85, and then remained approximately unchanged for x > 0.25. The concentration dependences of Tg and heat capacity jump at Tg also showed anomalies around x = 0.25. We suggest this mixture transformed from a moderate to quite fragile liquid at x = 0.25 because of a structural change from a hydrogen-bonding- to ionic-interaction-dominant system.

DNA Secondary Structure at Chromosomal Fragile Sites in Human Disease

PubMed Central

Thys, Ryan G; Lehman, Christine E; Pierce, Levi C. T; Wang, Yuh-Hwa

2015-01-01

DNA has the ability to form a variety of secondary structures that can interfere with normal cellular processes, and many of these structures have been associated with neurological diseases and cancer. Secondary structure-forming sequences are often found at chromosomal fragile sites, which are hotspots for sister chromatid exchange, chromosomal translocations, and deletions. Structures formed at fragile sites can lead to instability by disrupting normal cellular processes such as DNA replication and transcription. The instability caused by disruption of replication and transcription can lead to DNA breakage, resulting in gene rearrangements and deletions that cause disease. In this review, we discuss the role of DNA secondary structure at fragile sites in human disease. PMID:25937814

[The determination of chromosome fragile sites in the peripheral blood lymphocytes of patients with colorectal cancer taking into account the cancer pathology predisposition in the familial anamnesis].

PubMed

Nesina, I P; Polishchuk, L Z; Oliĭnichenko, P I

2000-01-01

Results of comparative study of spontaneous and 5-bromdeoxyuridine-induced fragility of peripheral blood lymphocytes chromosomes in 9 patients with colorectal adenocarcinoma were presented. It was shown the increase of average spontaneous level of chromosomal fragility in patients with tumor aggregation in family as well as without it to 4.5 +/- 1.0 and 5.3 +/- 1.1 per 100 tested cells, accordingly. The increase of average level of damaged chromosomes in spectrum of rare sites to 12.5 +/- 2.6 in the patients with tumor aggregation in pedigree comparing to the patients without oncopathology in family 8.0 +/- 1.7 was observed. The most number of rare fragile sites was observed in 1q21 site of the chromosome 1. Possible connection between fragile sites of chromosomes in normal cells and malignant processes in the patients with colorectal cancer is discussed.

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

PubMed

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.

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

PubMed

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.

Developing ShakeCast statistical fragility analysis framework for rapid post-earthquake assessment

USGS Publications Warehouse

Lin, K.-W.; Wald, D.J.

2012-01-01

When an earthquake occurs, the U. S. Geological Survey (USGS) ShakeMap estimates the extent of potentially damaging shaking and provides overall information regarding the affected areas. The USGS ShakeCast system is a freely-available, post-earthquake situational awareness application that automatically retrieves earthquake shaking data from ShakeMap, compares intensity measures against users’ facilities, sends notifications of potential damage to responsible parties, and generates facility damage assessment maps and other web-based products for emergency managers and responders. We describe notable improvements of the ShakeMap and the ShakeCast applications. We present a design for comprehensive fragility implementation, integrating spatially-varying ground-motion uncertainties into fragility curves for ShakeCast operations. For each facility, an overall inspection priority (or damage assessment) is assigned on the basis of combined component-based fragility curves using pre-defined logic. While regular ShakeCast users receive overall inspection priority designations for each facility, engineers can access the full fragility analyses for further evaluation.

Mapping Self-Reports of Working Memory Deficits to Executive Dysfunction in Fragile X Mental Retardation 1 ("FMR1") Gene Premutation Carriers Asymptomatic for FXTAS

ERIC Educational Resources Information Center

Kogan, Cary S.; Cornish, Kim M.

2010-01-01

Fragile X Syndrome is a neurodevelopmental disorder that is caused by the silencing of a single gene on the X chromosome, the Fragile X Mental Retardation 1 ("FMR1") gene. In recent years, the premutation ("carrier") status has received considerable attention and there is now an emerging consensus that despite intellectual functioning being within…

Application of Hybrid Geo-Spatially Granular Fragility Curves to Improve Power Outage Predictions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernandez, Steven J; Allen, Melissa R; Omitaomu, Olufemi A

2014-01-01

Fragility curves depict the relationship between a weather variable (wind speed, gust speed, ice accumulation, precipitation rate) and the observed outages for a targeted infrastructure network. This paper describes an empirical study of the county by county distribution of power outages and one minute weather variables during Hurricane Irene with the objective of comparing 1) as built fragility curves (statistical approach) to engineering as designed (bottom up) fragility curves for skill in forecasting outages during future hurricanes; 2) county specific fragility curves to find examples of significant deviation from average behavior; and 3) the engineering practices of outlier counties tomore » suggest future engineering studies of robustness. Outages in more than 90% of the impacted counties could be anticipated through an average or generic fragility curve. The remaining counties could be identified and handled as exceptions through geographic data sets. The counties with increased or decreased robustness were characterized by terrain more or less susceptible to persistent flooding in areas where above ground poles located their foundations. Land use characteristics of the area served by the power distribution system can suggest trends in the as built power grid vulnerabilities to extreme weather events that would be subjects for site specific studies.« less

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

PubMed

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.

Effect of sterol esters on lipid composition and antioxidant status of erythrocyte membrane of hypercholesterolemic rats.

PubMed

Sengupta, Avery; Ghosh, Mahua

2014-01-01

Hypercholesterolemia is a major cause of coronary heart disease. Erythrocyte membrane is affected during hypercholesterolemia. The effect of EPA-DHA rich sterol ester and ALA rich sterol ester on erythrocyte membrane composition, osmotic fragility in normal and hypercholesterolemic rats and changes in antioxidant status of erythrocyte membrane were studied. Erythrocyte membrane composition, osmotic fragility of the membrane and antioxidant enzyme activities was analyzed. Osmotic fragility data suggested that the erythrocyte membrane of hypercholesterolemia was relatively more fragile than that of the normal rats' membrane which could be reversed with the addition of sterol esters in the diet. The increased plasma cholesterol in hypercholesterolemic rats could also be lowered by the sterol ester administration. There was also marked changes in the antioxidant enzyme activities of the erythrocyte membrane. Antioxidant enzyme levels decreased in the membrane of the hypercholesterolemic subjects were increased with the treatment of the sterol esters. The antioxidative activity of ALA rich sterol ester was better in comparison to EPA-DHA rich sterol ester. In conclusion, rat erythrocytes appear to be deformed and became more fragile in cholesterol rich blood. This deformity and fragility was partially reversed by sterol esters by virtue of their ability to lower the extent of hypercholesterolemia.

Development of "fragility" in relaxor ferroelectrics

NASA Astrophysics Data System (ADS)

Wang, Yi-zhen; Chen, Lan; Wang, Hai-yan; Frank Zhang, X.; Fu, Jun; Xiong, Xiao-min; Zhang, Jin-xiu

2014-02-01

Relaxor ferroelectrics (RFs), a special class of the disordered crystals or ceramics, exhibit a pronounced slowdown of their dynamics upon cooling as glass-forming liquids, called the "Super-Arrhenius (SA)" relaxation. Despite great progress in glass-forming liquids, the "fragility" property of the SA relaxation in RFs remains unclear so far. By measuring the temperature-dependent dielectric relaxation in the typical relaxor Pb(Mg1/3Nb2/3)O3-x%PbTiO3 (PMN - x%PT) with 0 ≤ x ≤ 20.0, we in-depth study the "fragility" properties of the SA relaxation in PMN - x%PT. Such fascinating issues as the mechanism of the "fragility" at an atomic scale, the roles of the systematic configurational entropy change and interaction among relaxing units (RUs, including polar nanoregions and free dipoles) and the relation between "fragility" and ferroelectric order are investigated. Our results show that both the "fragility" of the temperature-dependent SA relaxation and ferroelectric order in the PMN - x%PT systems investigated arise thermodynamically from the configurational-entropy loss due to the attractive interaction among RUs, and develops as a power law, possibly diverging at the finite critical temperature Tc. A reasonable physical scenario, based on our "configurational-entropy-loss" theory and Nowick's "stress-induced-ordering" theory, was proposed.

Effects of Sampling Context on Spontaneous Expressive Language in Males with Fragile X Syndrome or Down Syndrome

PubMed Central

Kover, Sara T.; McDuffie, Andrea; Abbeduto, Leonard; Brown, W. Ted

2012-01-01

Purpose This study examined the impact of sampling context on multiple aspects of expressive language in males with fragile X syndrome in comparison to males with Down syndrome or typical development. Method Participants with fragile X syndrome (n = 27), ages 10 to 17 years, were matched groupwise on nonverbal mental age to adolescents with Down syndrome (n = 15) and typically developing 3- to 6-year-olds (n = 15). Language sampling contexts were an interview-style conversation and narration of a wordless book, with scripted examiner behavior. Language was assessed in terms of amount of talk, MLU of communication unit (MLCU), lexical diversity, fluency, and intelligibility. Results Participants with fragile X syndrome had lower MLCU and lexical diversity than participants with typical development. Participants with Down syndrome produced yet lower MLCU. A differential effect of context among those with fragile X syndrome, Down syndrome, and typical development emerged for the number of attempts per minute, MLCU, and fluency. For participants with fragile X syndrome, autism symptom severity related to the number of utterances produced in conversation. Aspects of examiner behavior related to participant performance. Conclusions Sampling context characteristics should be considered when assessing expressive language in individuals with neurodevelopmental disabilities. PMID:22232386

Mathematics learning disabilities in girls with fragile X or Turner syndrome during late elementary school.

PubMed

Murphy, Melissa M; Mazzocco, Michèle 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 syndrome, respectively). Differences between girls with fragile X and their comparison group emerged on untimed arithmetic calculations, mastery of counting skills, and arithmetic problem verification accuracy. Relative to girls in the comparison group, girls with Turner syndrome did not differ on untimed arithmetic calculations or problem verification accuracy, but they had limited mastery of counting skills and longer response times to complete the problem verification task. Girls with fragile X or Turner syndrome also differed from their respective comparison groups on math-related abilities, including visual-spatial, working memory, and reading skills, and the associations between math and those related skills. Together, these findings support the notion that difficulty with math and related skills among girls with fragile X or Turner syndrome continues into late elementary school and that the profile of math and related skill difficulty distinguishes the two syndrome groups from each other.

The fragility of omics risk and benefit perceptions.

PubMed

Börner, Franziska U; Schütz, Holger; Wiedemann, Peter

2011-03-25

How do individuals judge the risks and benefits of toxicogenomics, an emerging field of research which is completely unfamiliar to them? The hypothesis is that individuals' perceptions of the risks and benefits of toxicogenomics are fragile and can by influenced by different issues and context framings as a technology. The researchers expected that the effects on risk and benefit judgements would differ between lay individuals and experts in toxicogenomics. A 2×2×2 experiment that encompassed three factors was conducted. The first factor, issue framing incorporated the field of application for the technology (therapy vs. diagnosis setting). The second factor, context framing included organisations and institutions that would profit from the technology (companies vs. regulatory agencies) and the third factor encompasses the quality of individuals' level of knowledge, for example lay vs. expert knowledge. Research results suggest the differential power of framing effects. It seems that the clues provided by context frames - but not by issue frames - are able to influence the ways in which lay people and experts process information. The findings are interpreted in the line of the fuzzy trace theory that predicts reliance on fuzzy gist representations formed by stereotypes on a wide range of judgement problem including risk and benefit perceptions. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Early identification of autism in fragile X syndrome: a review

PubMed Central

McCary, L. M.; Roberts, J. E.

2014-01-01

Fragile X syndrome (FXS) is the leading genetic cause of autism, accounting for approximately 5% of autism cases with as many as 50% of individuals with FXS meeting DSM-IV-TR criteria for autistic disorder. Both FXS and idiopathic autism (IA) are attributed to genetic causes; however, FXS is an identified single gene disorder whereas autism is a complex disorder with multiple potential causes, some of which have been identified. Studies in IA have focused on the prospective longitudinal examination of infant siblings of children with autism as a target group due to their high risk of developing the disorder. We propose that this same model be applied to the study of infants with FXS. There is a lack of research focusing on the early development of autism within FXS and debate in the literature regarding how to best conceptualise this co-morbidity or whether it should be considered a co-morbid condition at all. Studying the emergence and stability of autism in infants with FXS has multiple benefits such as clarifying the underlying mechanisms of the development of autism in FXS and solidifying similarities and differences between co-morbid FXS with autism and IA. Infant research in both IA and FXS are discussed as well as conclusions and implications for practice and future research. PMID:22974167

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

PubMed Central

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

Fragile X spectrum disorders

PubMed Central

Lozano, Reymundo; Rosero, Carolina Alba; Hagerman, Randi J

2014-01-01

Summary The fragile X mental retardation 1 gene (FMR1), which codes for the fragile X mental retardation 1 protein (FMRP), is located at Xp27.3. The normal allele of the FMR1 gene typically has 5 to 40 CGG repeats in the 5′ untranslated region; abnormal alleles of dynamic mutations include the full mutation (> 200 CGG repeats), premutation (55–200 CGG repeats) and the gray zone mutation (45–54 CGG repeats). Premutation carriers are common in the general population with approximately 1 in 130–250 females and 1 in 250–810 males, whereas the full mutation and Fragile X syndrome (FXS) occur in approximately 1 in 4000 to 1 in 7000. FMR1 mutations account for a variety of phenotypes including the most common monogenetic cause of inherited intellectual disability (ID) and autism (FXS), the most common genetic form of ovarian failure, the fragile X-associated primary ovarian insufficiency (FXPOI, premutation); and fragile X-associated tremor/ataxia syndrome (FXTAS, premutation). The premutation can also cause developmental problems including ASD and ADHD especially in boys and psychopathology including anxiety and depression in children and adults. Some premutation carriers can have a deficit of FMRP and some unmethylated full mutation individuals can have elevated FMR1 mRNA that is considered a premutation problem. Therefore the term “Fragile X Spectrum Disorder” (FXSD) should be used to include the wide range of overlapping phenotypes observed in affected individuals with FMR1 mutations. In this review we focus on the phenotypes and genotypes of children with FXSD. PMID:25606363

Prevalent fragility fractures as risk factor for skeletal muscle function deficit and dysmobility syndrome in post-menopausal women.

PubMed

Iolascon, Giovanni; Moretti, Antimo; Giamattei, Maria Teresa; Migliaccio, Silvia; Gimigliano, Francesca

2015-10-01

Fragility fractures are a major burden for health and social care in elderly people. In order to identify earlier the "frail elders", new concepts of "dysmobility syndrome" and skeletal muscle function deficit (SMFD), including sarcopenia, osteoporosis, obesity, and mobility limitation, leading to a higher risk of fractures, have been recently introduced. There are very few studies investigating the association between fragility fractures and both the dysmobility syndrome and the SMFD. The objective of our study is to investigate the role of previous fragility fractures as a risk factor in determining the dysmobility syndrome and/or the SMFD in post-menopausal women. In this case-control study, we retrospectively examined data from the medical records of post-menopausal women aged 50 or older. We divided the study population in two groups. The first group includes women with a previous fragility fracture (cases) and the other group includes women without any previous osteoporotic fracture (controls). We identified the subjects with "dysmobility syndrome", "dynapenic SMFD", "sarcopenic SMFD", and "mixed SMFD" in both groups. Data collected refer to a 6-month period. We retrieved data of 121 post-menopausal women, 77 (63.64%) had already sustained a fragility fracture at any site (cases). The risk for dysmobility syndrome was significantly higher (adjusted OR for age and serum 25-OH vitamin D3 of 2.46) in the cases compared with the controls. An early diagnosis of conditions limiting mobility, including dysmobility syndrome, might be useful to identify, among patients with osteoporotic fractures, those who might have a higher risk of a new fragility fracture.

Impaired activity-dependent FMRP translation and enhanced mGluR-dependent LTD in Fragile X premutation mice

PubMed Central

Iliff, Adam J.; Renoux, Abigail J.; Krans, Amy; Usdin, Karen; Sutton, Michael A.; Todd, Peter K.

2013-01-01

Fragile X premutation-associated disorders, including Fragile X-associated Tremor Ataxia Syndrome, result from unmethylated CGG repeat expansions in the 5′ untranslated region (UTR) of the FMR1 gene. Premutation-sized repeats increase FMR1 transcription but impair rapid translation of the Fragile X mental retardation protein (FMRP), which is absent in Fragile X Syndrome (FXS). Normally, FMRP binds to RNA and regulates metabotropic glutamate receptor (mGluR)-mediated synaptic translation, allowing for dendritic synthesis of several proteins. FMRP itself is also synthesized at synapses in response to mGluR activation. However, the role of activity-dependent translation of FMRP in synaptic plasticity and Fragile X-premutation-associated disorders is unknown. To investigate this question, we utilized a CGG knock-in mouse model of the Fragile X premutation with 120–150 CGG repeats in the mouse Fmr1 5′ UTR. These mice exhibit increased Fmr1 mRNA production but impaired FMRP translational efficiency, leading to a modest reduction in basal FMRP expression. Cultured hippocampal neurons and synaptoneurosomes derived from CGG KI mice demonstrate impaired FMRP translation in response to the group I mGluR agonist 3,5-dihydroxyphenylglycine. Electrophysiological analysis reveals enhanced mGluR-mediated long-term depression (mGluR-LTD) at CA3–CA1 synapses in acute hippocampal slices prepared from CGG KI mice relative to wild-type littermates, similar to Fmr1 knockout mice. However, unlike mGluR-LTD in mice completely lacking FMRP, mGluR-LTD in CGG knock-in mice remains dependent on new protein synthesis. These studies demonstrate partially overlapping synaptic plasticity phenotypes in mouse models of FXS and Fragile X premutation disorders and support a role for activity-dependent synthesis of FMRP in enduring forms of synaptic plasticity. PMID:23250915

Grain Size of Recall Practice for Lengthy Text Material: Fragile and Mysterious Effects on Memory

ERIC Educational Resources Information Center

Wissman, Kathryn T.; Rawson, Katherine A.

2015-01-01

The current research evaluated the extent to which the grain size of recall practice for lengthy text material affects recall during practice and subsequent memory. The "grain size hypothesis" states that a smaller vs. larger grain size will increase retrieval success during practice that in turn will enhance subsequent memory for…

A Comparative Study of Educational Provision for Children with Neurogenetic Syndromes: Parent and Teacher Survey

ERIC Educational Resources Information Center

Reilly, C.; Senior, J.; Murtagh, L.

2015-01-01

Background: A number of neurogenetic syndromes have a high association with special educational needs including fragile X syndrome (FXS), Prader-Willi syndrome (PWS), Williams syndrome (WS) and Velo-Cardio-Facial syndrome (VCFS). There is a paucity of research on educational provision for children affected by these syndromes. Method: Parents…

A Population-Based Twin Study of Parentally Reported Tactile and Auditory Defensiveness in Young Children

ERIC Educational Resources Information Center

Goldsmith, H. H.; Van Hulle, C. A.; Arneson, C. L.; Schreiber, J. E.; Gernsbacher, M. A.

2006-01-01

Some adults and children exhibit defensive behaviors to tactile or auditory stimulation. These symptoms occur not only in subsets of children with ADHD, autism, and Fragile X syndrome, but also in the apparent absence of accompanying disorders. Relatively little research explores the correlates and antecedents of sensory defensiveness. Using a…

Creating Research/STEM Opportunities for Students - A Case for Collaboration

NASA Astrophysics Data System (ADS)

Baker, R. W.; Sprenger, A.

2016-02-01

A unique collaboration between a Regional Coastal Ocean Observing System, the Northwest Association of Networked Ocean Observing Systems, (NANOOS), a boat-based ocean science education non-profit organization, the Ocean Inquiry Project (OIP), an informal environmental education center, the Whidbey Watershed Stewards (WWS), and the South Whidbey School District, has resulted in an incredible STEM learning opportunity for middle school students. The year-long program challenges 200 6th and 7th graders at Langley Middle School on Whidbey Island WA, to investigate the fragile connection between the biotic and abiotic ocean, with a focus on ocean acidification, a growing environmental, economic concern in the school's local waters of Puget Sound. Students use a variety of field research techniques to collect original ocean data at a local marina, building an oceanographic time-series, over a 6 month time period (Nov - Apr) as the earth and ocean transition from winter into spring. Students have named their study "SWOOS" - the South Whidbey Ocean Observing Station. Every month, students measure parameters in seawater including temperature, salinity, pH, oxygen, and nitrates from their research site. Plankton samples are also collected and brought back to their science classroom to be analyzed. Students design and build their own "student buoys", which are deployed near the Langley Marina to collect temperature and light data throughout the 6-month research project. Students work with NANOOS staff to compare their data with data from other shore stations and buoys throughout Puget Sound and along the WA coast. The program culminates with a one-day oceanography cruise aboard a research vessel with state of the art equipment collecting data and working alongside University of Washington graduate students and scientists. Our program uses students' local environment, a variety of ocean research techniques and a compelling environmental issue to give students comprehensive knowledge of the scientific process, conceptual knowledge about current environmental threats and critical thinking skills so they will be armed with the fundamental 21stcentury skills needed to be able to make informed decisions into the future.

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

PubMed

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 has identified the highest risk features for patients with Fragile X syndrome that have been used to design a universal clinical checklist. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Early development in males with Fragile X syndrome: a review of the literature.

PubMed

Kau, Alice S M; Meyer, Walter A; Kaufmann, Walter E

2002-05-01

This article reviews the current bibliographic knowledge on early neurobehavioral development and milestones in Fragile X syndrome (FraX), with emphasis on males affected by the condition. Three broad areas of early development were examined: (1) gross and fine motor, (2) speech and language, and (3) social. The result of the current review indicates very limited information on the developmental milestones in all three areas. The scarce literature on motor development shows that in FraX there is an early developmental delay. Research on speech and language demonstrates pervasive deficits in conversational skills and severe developmental delay, with increasing discrepancy between language level and chronological age in young males with FraX. Finally, deficits in social development in FraX include abnormal gaze, approach and avoidance conflict, and high incidence of autistic spectrum disorders. Copyright 2002 Wiley-Liss, Inc.

Targeted Upregulation of FMRP Expression as an Approach to the Treatment of Fragile X Syndrome

DTIC Science & Technology

2016-10-01

Fragile X syndrome (FXS), the most common heritable form of intellectual disability and most common single-gene form of autism , is caused by partial...15. SUBJECT TERMS Fragile X, autism , FMR1, FXTAS, CGG repeat, epilepsy, seizures, FMRP, PTSD, premutation, iPSC, progenitor, calcium regulation...the most common heritable form of intellectual disability, the most common single-gene form of autism , and a relatively common cause of epilepsy

Role of Altered mGluR Activity in Cognitive Impairments in TSC: Implications for a Novel Method of Treatment

DTIC Science & Technology

2013-04-01

epilepsy, autism , anxiety and mood disorders. Fragile X syndrome (FXS), another form of inherited mental retardation and autism , shares many of the...therapeutic intervention for several of the deficits observed in TSC. 15. SUBJECT TERMS autism , Tuberous Sclerosis Complex, Fragile X Syndrome...clinical features being mental retardation, epilepsy, autism , anxiety and mood disorders (Prather & de Vries, 2004). Fragile X syndrome (FXS

Germline mosaicism at the fragile X locus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prior, T.W.; Papp, A.C.; Snyder, P.J.

We have identified a fragile X syndrome pedigree where the disorder is associated with a molecular deletion. The deletion was present in the DNA of 2 sons but was absent in the mother`s somatic cell (lymphocyte) DNA. The results are consistent with the deletion arising as a postzygotic event in the mother, who therefore is germinally mosaic. This finding has important implications for counseling fragile X families with deletion mutations. 13 refs., 2 figs.

Learning and Behavioral Deficits Associated with the Absence of the Fragile X Mental Retardation Protein: What a Fly and Mouse Model Can Teach Us

ERIC Educational Resources Information Center

Santos, Ana Rita; Kanellopoulos, Alexandros K.; Bagni, Claudia

2014-01-01

The Fragile X syndrome (FXS) is the most frequent form of inherited mental disability and is considered a monogenic cause of autism spectrum disorder. FXS is caused by a triplet expansion that inhibits the expression of the "FMR1" gene. The gene product, the Fragile X Mental Retardation Protein (FMRP), regulates mRNA metabolism in brain…

The Relationship of Repetitive Behavior and Sensory Behavior to Parenting Stress in Mothers of Boys with Autism and Mothers of Boys with Fragile X Syndrome

ERIC Educational Resources Information Center

Richardson, Lolita Lisa

2010-01-01

This study investigated the relationship between repetitive behaviors and sensory behavior to the parenting stress of mothers of boys with fragile X syndrome and mothers of boys with autism. Participants consisted of two groups: 51 mothers with boys diagnosed with fragile X syndrome (M = 71.3, SD = 56.5) and 30 mothers with boys diagnosed with…

Urban sustainability in an age of enduring inequalities: Advancing theory and ecometrics for the 21st-century city

PubMed Central

Sampson, Robert J.

2017-01-01

The environmental fragility of cities under advanced urbanization has motivated extensive efforts to promote the sustainability of urban ecosystems and physical infrastructures. Less attention has been devoted to neighborhood inequalities and fissures in the civic infrastructure that potentially challenge social sustainability and the capacity of cities to collectively address environmental challenges. This article draws on a program of research in three American cities—Boston, Chicago, and Los Angeles—to develop hypotheses and methodological strategies for assessing how the multidimensional and multilevel inequalities that characterize contemporary cities bear on sustainability. In addition to standard concerns with relative inequality in income, the article reviews evidence on compounded deprivation, racial cleavages, civic engagement, institutional cynicism, and segregated patterns of urban mobility and organizational ties that differentially connect neighborhood resources. Harnessing “ecometric” measurement tools and emerging sources of urban data with a theoretically guided framework on neighborhood inequality can enhance the pursuit of sustainable cities, both in the United States and globally. PMID:28062692

Urban sustainability in an age of enduring inequalities: Advancing theory and ecometrics for the 21st-century city.

PubMed

Sampson, Robert J

2017-08-22

The environmental fragility of cities under advanced urbanization has motivated extensive efforts to promote the sustainability of urban ecosystems and physical infrastructures. Less attention has been devoted to neighborhood inequalities and fissures in the civic infrastructure that potentially challenge social sustainability and the capacity of cities to collectively address environmental challenges. This article draws on a program of research in three American cities-Boston, Chicago, and Los Angeles-to develop hypotheses and methodological strategies for assessing how the multidimensional and multilevel inequalities that characterize contemporary cities bear on sustainability. In addition to standard concerns with relative inequality in income, the article reviews evidence on compounded deprivation, racial cleavages, civic engagement, institutional cynicism, and segregated patterns of urban mobility and organizational ties that differentially connect neighborhood resources. Harnessing "ecometric" measurement tools and emerging sources of urban data with a theoretically guided framework on neighborhood inequality can enhance the pursuit of sustainable cities, both in the United States and globally.

Pregnancy-associated osteoporosis presenting severe vertebral fractures.

PubMed

Ozturk, Cihat; Atamaz, Funda Calis; Akkurt, Halil; Akkoc, Yesim

2014-01-01

The syndrome of pregnancy-associated osteoporosis (PAO) is a rare disorder which occurs either in late pregnancy or early post-partum period leading to fragility fracture(s), most commonly in the vertebral bodies. We presented two cases with PAO who had compression fractures at multiple levels involving five vertebrae in one case and 10 vertebrae in the other. Their spinal bone mineral density values were below -2.5 standard deviations. Anti-osteoporotic treatments with nasal calcitonin 400 IU/day, vitamin D 300.000 IU single dose, calcium 1000 mg/day, vitamin D 880 IU/day were initiated. In one case, kyphoplasty was performed by a spinal surgeon. In addition to a thoracolumbosacral orthosis, a rehabilitation program including muscle strengthening, range of motion, relaxation and weight-bearing exercises was started for both cases. These cases emphasize that all pregnant women with complaints of back/lumbar pain should be carefully evaluated. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Deep brain stimulation in uncommon tremor disorders: indications, targets, and programming.

PubMed

Artusi, Carlo Alberto; Farooqi, Ashar; Romagnolo, Alberto; Marsili, Luca; Balestrino, Roberta; Sokol, Leonard L; Wang, Lily L; Zibetti, Maurizio; Duker, Andrew P; Mandybur, George T; Lopiano, Leonardo; Merola, Aristide

2018-03-06

In uncommon tremor disorders, clinical efficacy and optimal anatomical targets for deep brain stimulation (DBS) remain inadequately studied and insufficiently quantified. We performed a systematic review of PubMed.gov and ClinicalTrials.gov. Relevant articles were identified using the following keywords: "tremor", "Holmes tremor", "orthostatic tremor", "multiple sclerosis", "multiple sclerosis tremor", "neuropathy", "neuropathic tremor", "fragile X-associated tremor/ataxia syndrome", and "fragile X." We identified a total of 263 cases treated with DBS for uncommon tremor disorders. Of these, 44 had Holmes tremor (HT), 18 orthostatic tremor (OT), 177 multiple sclerosis (MS)-associated tremor, 14 neuropathy-associated tremor, and 10 fragile X-associated tremor/ataxia syndrome (FXTAS). DBS resulted in favorable, albeit partial, clinical improvements in HT cases receiving Vim-DBS alone or in combination with additional targets. A sustained improvement was reported in OT cases treated with bilateral Vim-DBS, while the two cases treated with unilateral Vim-DBS demonstrated only a transient effect. MS-associated tremor responded to dual-target Vim-/VO-DBS, but the inability to account for the progression of MS-associated disability impeded the assessment of its long-term clinical efficacy. Neuropathy-associated tremor substantially improved with Vim-DBS. In FXTAS patients, while Vim-DBS was effective in improving tremor, equivocal results were observed in those with ataxia. DBS of select targets may represent an effective therapeutic strategy for uncommon tremor disorders, although the level of evidence is currently in its incipient form and based on single cases or limited case series. An international registry is, therefore, warranted to clarify selection criteria, long-term results, and optimal surgical targets.

Emergency response vaccines--a challenge for the public sector and the vaccine industry.

PubMed

Milstien, Julie; Lambert, Scott

2002-11-22

In partnership with industry, WHO has developed a number of strategies to facilitate access to vaccines recommended for use in national immunization programs. These strategies have been necessitated by the increasing fragility of vaccine supply for developing markets. The potential global spread of epidemic disease has made it imperative to expand these efforts. A new concept is proposed, that of essential vaccines, defined as "vaccines of public health importance that should be accessible to all people at risk". Essential vaccines will include emergency response vaccines that have become important due to resurgent outbreaks, threatening global pandemics, and situations where a global emergency immunization response may be needed. While some of the approaches already developed will be applicable to emergency response vaccines, other novel approaches requiring public sector intervention will be necessary. Procurement, financing and allocation of these emergency response vaccines, if left to governments or private individuals based on ability to pay, will threaten equitable access. The challenge will be to ensure development of and equitable access to these vaccines while not threatening the already fragile supply of other essential vaccines.

Secondary prevention of osteoporosis in non-neck of femur fragility fractures: is it value for money? A retrospective, prospective and cross-sectional cohort study.

PubMed

Mettyas, Tamer; Carpenter, Clare

2013-12-01

Osteoporosis is one of the commonest bone diseases in which bone fragility is increased. Over 300,000 patients present to hospitals in the UK with fragility fractures each year, with medical and social care costs - most of which relate to hip fracture care - at around £2 billion. The number of these fractures rises by 2% a year. The 30 days mortality is 10% and 30% at 1 year. The purpose of this study is to review the current practice according to NICE and BOA guidelines of secondary prevention of osteoporosis and to suggest changes to these guidelines. Patients over 50 years old admitted as inpatients to our facility with non-neck-of-femur (NOF) fragility fractures in March and September 2008 were studied. Retrospectively (March), looking for risk factors and if treated or not, then prospectively (September), after introducing the new trauma admission sheet. Also cross-sectional study was performed by comparing the services provided for NOF and non-NOF fragility fractures in September. Two-sample t test is used to compare between percentages. Twenty-nine percent of fragility fractures are non-NOF fractures with a mean age of 70 years, while the remaining 71% are NOF fractures with a mean age of 80 years. There is a great difference in the care provided to these patients: non-NOF fragility fractures got less attention for assessment of osteoporosis (25%) and obtained less interest in investigations by medical staff (11%) and, finally, less intentions to treat osteoporosis (35%), compared to NOF fractures in which 35% of cases were assessed, 47% were investigated and 71% were treated for osteoporosis. Twenty-five percent of NOF fracture patients were found to have previous fragility fractures in the preceding years, while only 6% were on osteoporosis treatment before the fracture. Osteoporosis (a new epidemic) is the most common disease of the bone and its incidence is rising rapidly as the population ages. Though treatable, it is often left untreated. We believe that treating patients with non-NOF fragility fractures from osteoporosis before proceeding to NOF fractures would improve their quality of life and reduce the burden on hospital services and funding.

Fragility Analysis of a Concrete Gravity Dam Embedded in Rock and Its System Response Curve Computed by the Analytical Program GDLAD_Foundation

DTIC Science & Technology

2012-06-01

According to the Bernoulli equation for ideal flows, i.e. steady, frictionless, incompressible flows, the total head, H, at any point can be determined...centerline and using the Bernoulli equation for ideal flow with an assumption that the velocity is small, the total head equals the pressure head...the Bernoulli equation for ideal flows, i.e. steady, frictionless, incompressible flows, the total head, H, at any point can be determined by

Results and insights from the NCSU Insect Museum GigaPan project

PubMed Central

Bertone, Matthew A.; Blinn, Robert L.; Dew1, Tanner M. StanfieldKelly J.; Seltmann, Katja C.; Deans, Andrew R.

2012-01-01

Abstract Pinned insect specimens stored in museum collections are a fragile and valuable resource for entomological research. As such, they are usually kept away from viewing by the public and hard to access by experts. Here we present a method for mass imaging insect specimens, using GigaPan technology to achieve highly explorable, many-megapixel panoramas of insect museum drawers. We discuss the advantages and limitations of the system, and describe future avenues of collections research using this technology. PMID:22859883

NASA technology applications team. Applications of aerospace technology

NASA Technical Reports Server (NTRS)

1991-01-01

Discussed here are the activities of the Research Triangle Institute (RTI) Technology Applications Team for the period 1 October 1990 through 30 September 1991. Topics researched include automated data acquisition and analysis of highway pavement cracking, thermal insulation for refrigerators, the containment of paint removed from steel structures, improved technologies for Kuwait oil well control, sprayed zinc coatings for corrosion control of reinforcing steel in bridges, and the monitoring and life support of medically fragile children in the educational setting.

Porotic paradox: distribution of cortical bone pore sizes at nano- and micro-levels in healthy vs. fragile human bone.

PubMed

Milovanovic, Petar; Vukovic, Zorica; Antonijevic, Djordje; Djonic, Danijela; Zivkovic, Vladimir; Nikolic, Slobodan; Djuric, Marija

2017-05-01

Bone is a remarkable biological nanocomposite material showing peculiar hierarchical organization from smaller (nano, micro) to larger (macro) length scales. Increased material porosity is considered as the main feature of fragile bone at larger length-scales. However, there is a shortage of quantitative information on bone porosity at smaller length-scales, as well as on the distribution of pore sizes in healthy vs. fragile bone. Therefore, here we investigated how healthy and fragile bones differ in pore volume and pore size distribution patterns, considering a wide range of mostly neglected pore sizes from nano to micron-length scales (7.5 to 15000 nm). Cortical bone specimens from four young healthy women (age: 35 ± 6 years) and five women with bone fracture (age: 82 ± 5 years) were analyzed by mercury porosimetry. Our findings showed that, surprisingly, fragile bone demonstrated lower pore volume at the measured scales. Furtnermore, pore size distribution showed differential patterns between healthy and fragile bones, where healthy bone showed especially high proportion of pores between 200 and 15000 nm. Therefore, although fragile bones are known for increased porosity at macroscopic level and level of tens or hundreds of microns as firmly established in the literature, our study with a unique assessment range of nano-to micron-sized pores reveal that osteoporosis does not imply increased porosity at all length scales. Our thorough assessment of bone porosity reveals a specific distribution of porosities at smaller length-scales and contributes to proper understanding of bone structure which is important for designing new biomimetic bone substitute materials.

Hyponatremia Is Associated With Increased Osteoporosis and Bone Fractures in a Large US Health System Population.

PubMed

Usala, Rachel L; Fernandez, Stephen J; Mete, Mihriye; Cowen, Laura; Shara, Nawar M; Barsony, Julianna; Verbalis, Joseph G

2015-08-01

The significance of studies suggesting an increased risk of bone fragility fractures with hyponatremia through mechanisms of induced bone loss and increased falls has not been demonstrated in large patient populations with different types of hyponatremia. This matched case-control study evaluated the effect of hyponatremia on osteoporosis and fragility fractures in a patient population of more than 2.9 million. Osteoporosis (n = 30 517) and fragility fracture (n = 46 256) cases from the MedStar Health database were matched on age, sex, race, and patient record length with controls without osteoporosis (n = 30 517) and without fragility fractures (n = 46 256), respectively. Cases without matched controls or serum sodium (Na(+)) data or with Na(+) with a same-day blood glucose greater than 200 mg/dL were excluded. Incidence of diagnosis of osteoporosis and fragility fractures of the upper or lower extremity, pelvis, and vertebrae were the outcome measures. Multivariate conditional logistic regression models demonstrated that hyponatremia was associated with osteoporosis and/or fragility fractures, including chronic [osteoporosis: odds ratio (OR) 3.97, 95% confidence interval (CI) 3.59-4.39; fracture: OR 4.61, 95% CI 4.15-5.11], recent (osteoporosis: OR 3.06, 95% CI 2.81-3.33; fracture: OR 3.05, 95% CI 2.83-3.29), and combined chronic and recent hyponatremia (osteoporosis: OR 12.09, 95% CI 9.34-15.66; fracture: OR 11.21, 95% CI 8.81-14.26). Odds of osteoporosis or fragility fracture increased incrementally with categorical decrease in median serum Na(+). These analyses support the hypothesis that hyponatremia is a risk factor for osteoporosis and fracture. Additional studies are required to evaluate whether correction of hyponatremia will improve patient outcomes.

Emerging pharmacologic treatment options for fragile X syndrome

PubMed Central

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 trials are coming down the drug discovery pipeline, it is clear that the field is moving in a direction that values the development of molecular biomarkers, less subjective quantitative measures of symptom improvement, and rating scales developed specifically for use in FXS in conjunction with drug safety. While summarizing preclinical evidence, where applicable, and discussing challenges in FXS treatment development, this review details both completed clinical trials for the targeted and symptomatic treatment of FXS and introduces novel projects on the cusp of clinical trial investigation. PMID:25897255

Translation of Novel Serotonin 5-HT7 Agonist Drug Candidates in Rodent Models of Fragile X Syndrome

DTIC Science & Technology

2016-09-01

President of DELSIA (Delivering Science Innovation for Autism ) and Vice President, Innovative Technologies at Autism Speaks, Daniel Smith, who...in autism and Fragile X syndrome. Notably, there are no 9  pharmacotherapies approved for core symptoms of autism or Fragile X syndrome, thus, our...HT1A partial agonist for autism . 6th Cisbio HTRF symposium (Brewster, MA), September 14-17, 2015. Acknowledged DOD funding. Teaching Lectures. 10

Distinct Thermophysical and Interfacial Properties Associated with Low Molecular Weight Cyclic Polystyrene in Bulk and Confined States: Tg and Fragility

NASA Astrophysics Data System (ADS)

Zhang, Lanhe; Elupula, Ravinder; Grayson, Scott; Torkelson, John

Cyclic or ring polymers represent an exciting class of topologically distinctive polymers. The influence of ``end-to-end'' tethering and the unusual conformational properties associated with cyclic topologies have led to polymer dynamics significantly different from the linear counterpart. Bulk cyclic polystyrene (c-PS) exhibits very weak Tg- and fragility-molecular weight (MW) dependences compared to linear PS. In stark contrast to the substantial Tg-confinement effects in linear PS, a nearly completely suppressed confinement effect is discovered in low MW c-PS. The cyclic topology strongly restricts polymer-substrate interactions. Therefore, the near elimination of the Tg-confinement effect in c-PS originates mainly from a very weak perturbation to Tg near the free surface. Upon nanoscale confinement, linear PS films have been shown to have significantly reduced fragility compared to bulk. Despite having similar bulk fragility as high MW linear PS, low MW c-PS films show major suppression in fragility reduction with decreasing thickness. Due to a lack of chain ends, properties associated with the ring structure are not prone to be perturbed by either MW reduction or confinement. This result indicates a strong correlation between the susceptibility of fragility perturbation and the susceptibility of Tg perturbation, caused by chain topology and/or by confinement. This work was supported by The Dow Chemical Company, a McCormick School of Engineering Fellowship, and the NSF.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adichtchev, S. V.; Malinovsky, V. K.; Surovtsev, N. V., E-mail: lab21@iae.nsk.su

Low-frequency (down to 30 GHz) inelastic light scattering is studied in a multicomponent glass ZBLAN (ZrF{sub 4}-BaF{sub 2}-LaF{sub 3}-AlF{sub 3}-NaF) in a wide temperature range. The contributions of the THz vibrational spectrum (boson peak) and of the fast relaxation are extracted and analyzed. It is shown that the fast relaxation spectrum is described by a distribution of relaxation times leading to a power-law ν{sup α} dependence in the frequency range 30–300 GHz. Temperature dependence of α(T) is well described by the Gilroy-Phillips model, while the integrated intensity of the fast relaxation increases significantly with the temperature. This feature distinguishes themore » fast relaxation in ZBLAN from the case of most single-component glasses. Thermodynamic and kinetic fragility indexes are significantly different for the ZBLAN glass. The correlations between the boson peak intensity, elastic moduli, and fragility index, found earlier for single-component glasses, are fulfilled for the thermodynamic fragility index of ZBLAN. In contrast, the correlation between the fast relaxation intensity at T{sub g} and the fragility holds better for the kinetic fragility index of ZBLAN. We propose that thermodynamic and kinetic fragilities reflect different aspects of glassy dynamics in the case of glass formers with the complex chemical composition and structure topology: the former correlates with the elastic properties and the boson peak, the latter with the relaxation.« less

Why glass elasticity affects the thermodynamics and fragility of supercooled liquids

PubMed Central

Yan, Le; Düring, Gustavo; Wyart, Matthieu

2013-01-01

Supercooled liquids are characterized by their fragility: The slowing down of the dynamics under cooling is more sudden and the jump of specific heat at the glass transition is generally larger in fragile liquids than in strong ones. Despite the importance of this quantity in classifying liquids, explaining what aspects of the microscopic structure controls fragility remains a challenge. Surprisingly, experiments indicate that the linear elasticity of the glass—a purely local property of the free energy landscape—is a good predictor of fragility. In particular, materials presenting a large excess of soft elastic modes, the so-called boson peak, are strong. This is also the case for network liquids near the rigidity percolation, known to affect elasticity. Here we introduce a model of the glass transition based on the assumption that particles can organize locally into distinct configurations that are coupled spatially via elasticity. The model captures the mentioned observations connecting elasticity and fragility. We find that materials presenting an abundance of soft elastic modes have little elastic frustration: Energy is insensitive to most directions in phase space, leading to a small jump of specific heat. In this framework strong liquids turn out to lie the closest to a critical point associated with a rigidity or jamming transition, and their thermodynamic properties are related to the problem of number partitioning and to Hopfield nets in the limit of small memory. PMID:23576746

Why glass elasticity affects the thermodynamics and fragility of supercooled liquids.

PubMed

Yan, Le; Düring, Gustavo; Wyart, Matthieu

2013-04-16

Supercooled liquids are characterized by their fragility: The slowing down of the dynamics under cooling is more sudden and the jump of specific heat at the glass transition is generally larger in fragile liquids than in strong ones. Despite the importance of this quantity in classifying liquids, explaining what aspects of the microscopic structure controls fragility remains a challenge. Surprisingly, experiments indicate that the linear elasticity of the glass--a purely local property of the free energy landscape--is a good predictor of fragility. In particular, materials presenting a large excess of soft elastic modes, the so-called boson peak, are strong. This is also the case for network liquids near the rigidity percolation, known to affect elasticity. Here we introduce a model of the glass transition based on the assumption that particles can organize locally into distinct configurations that are coupled spatially via elasticity. The model captures the mentioned observations connecting elasticity and fragility. We find that materials presenting an abundance of soft elastic modes have little elastic frustration: Energy is insensitive to most directions in phase space, leading to a small jump of specific heat. In this framework strong liquids turn out to lie the closest to a critical point associated with a rigidity or jamming transition, and their thermodynamic properties are related to the problem of number partitioning and to Hopfield nets in the limit of small memory.

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

PubMed

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.

FMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome.

PubMed

Rajan-Babu, Indhu-Shree; Lian, Mulias; Cheah, Felicia S H; Chen, Min; Tan, Arnold S C; Prasath, Ethiraj B; Loh, Seong Feei; Chong, Samuel S

2017-07-19

Fragile X mental retardation 1 (FMR1) full-mutation expansion causes fragile X syndrome. Trans-generational fragile X syndrome transmission can be avoided by preimplantation genetic diagnosis (PGD). We describe a robust PGD strategy that can be applied to virtually any couple at risk of transmitting fragile X syndrome. This novel strategy utilises whole-genome amplification, followed by triplet-primed polymerase chain reaction (TP-PCR) for robust detection of expanded FMR1 alleles, in parallel with linked multi-marker haplotype analysis of 13 highly polymorphic microsatellite markers located within 1 Mb of the FMR1 CGG repeat, and the AMELX/Y dimorphism for gender identification. The assay was optimised and validated on single lymphoblasts isolated from fragile X reference cell lines, and applied to a simulated PGD case and a clinical in vitro fertilisation (IVF)-PGD case. In the simulated PGD case, definitive diagnosis of the expected results was achieved for all 'embryos'. In the clinical IVF-PGD case, delivery of a healthy baby girl was achieved after transfer of an expansion-negative blastocyst. FMR1 TP-PCR reliably detects presence of expansion mutations and obviates reliance on informative normal alleles for determining expansion status in female embryos. Together with multi-marker haplotyping and gender determination, misdiagnosis and diagnostic ambiguity due to allele dropout is minimised, and couple-specific assay customisation can be avoided.

Establishing special needs car seat loan program.

PubMed

Bull, M J; Stroup, K B; Stout, J; Doll, J P; Jones, J; Feller, N

1990-04-01

Car seat loan and rental programs have provided many families with low-cost access to child restraints. When an infant or child is unable to be accommodated in a standard car seat or seat belt owing to physical or medical problems, parents of these children have few, if any available resources. The establishment and operation of a loan program at the Indiana University School of Medicine for children who are medically fragile is reviewed in this article. This program was developed by the Automotive Safety for Children Program at the James Whitcomb Riley Hospital for Children, Indiana University Medical Center, to meet the special transportation needs of children with respiratory, orthopaedic, and other medical and physical difficulties. A summary table is included to highlight restraints that have performed satisfactorily during dynamic crash tests and are used to meet patient transportation needs at Riley Hospital. Guidelines for establishing and maintaining a child restraint loan program for children with special needs are outlined to encourage replication of this effort.

Reassessment of osteoporosis-related femoral fractures and economic burden in Saudi Arabia.

PubMed

Sadat-Ali, Mir; Al-Dakheel, Dakheel A; Azam, Md Q; Al-Bluwi, Mohammed T; Al-Farhan, Mohammed F; AlAmer, Hussein A; Al-Meer, Zakaria; Al-Mohimeed, Abdallah; Tabash, Ibrahim K; Karry, Maher O; Rassasy, Yaseen M; Baragaba, Mohammed A; Amer, Ahmed S; AlJawder, Abdallah; Al-Bouri, Kamil M; ElTinay, Mohammed; Badawi, Hamed A; Al-Othman, Abdallah A; Tayara, Badar K; Al-Faraidy, Moaad H; Amin, Ahmed H

2015-01-01

The current study reassesses the prevalence of fragility fractures and lifetime costs in the Eastern Province of Saudi Arabia. Forty-two percent (391) of the fractures were at the neck of the femur, and 38.6 % (354) were inter-trochanteric fractures. The overall incidence was assessed to be 7528 (1,300,336 population 55 years or older) with the direct cost of SR564.75 million ($150.60 million). A National Fracture Registry and osteoporosis awareness programs are recommended. Proximal femur fragility fractures are reported to be increasing worldwide due to increased life expectancy. The current study is carried out to assess the incidence of such fractures in the Eastern Province of Saudi Arabia and to assess the costs incurred in managing them annually. Finally, by extrapolating the data, the study can calculate the overall economic burden in Saudi Arabia. The data of fragility proximal femur fractures was collected from 24 of 28 hospitals in the Eastern Province. The data included age, sex, mode of injury, type of fracture, prescribed drug (and its cost), and length of hospital stay. Population statistics were obtained from the Department of Statistics of the Saudi Arabian government Web site. Twenty-four hospitals (85 %) participated in the study. A total of 780 fractures were sustained by 681 patients. Length of stay in the hospital averaged 23.28 ± 13.08 days. The projected fracture rate from all the hospitals would be 917 (an incidence of 5.81/1000), with a total cost of SR68.77 million. Further extrapolation showed that the overall incidence could be 7528 (1,300,336 population 55 years or older) with the direct cost of SR564.75 million ($150.60 million). Osteoporosis-related femoral fractures in Saudi Arabia are significant causes of morbidity besides incurring economic burden. We believe that a National Fracture Registry needs to be established, and osteoporosis awareness programs should be instituted in every part of Saudi Arabia so that these patients can be diagnosed early and treated appropriately to reduce both the number of fractures and the economic burden of the fractures.

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

USGS Publications Warehouse

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.

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

NASA Astrophysics Data System (ADS)

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.

Hippocampal dysfunction and cognitive impairment in Fragile-X Syndrome.

PubMed

Bostrom, Crystal; Yau, Suk-Yu; Majaess, Namat; Vetrici, Mariana; Gil-Mohapel, Joana; Christie, Brian R

2016-09-01

Fragile-X Syndrome (FXS) is the most common form of inherited intellectual disability and the leading genetic cause of autism spectrum disorder. FXS is caused by transcriptional silencing of the Fragile X Mental Retardation 1 (Fmr1) gene due to a CGG repeat expansion, resulting in the loss of Fragile X Mental Retardation Protein (FMRP). FMRP is involved in transcriptional regulation and trafficking of mRNA from the nucleus to the cytoplasm and distal sites both in pre- and post-synaptic terminals. Consequently, FXS is a multifaceted disorder associated with impaired synaptic plasticity. One region of the brain that is significantly impacted by the loss of FMRP is the hippocampus, a structure that plays a critical role in the regulation of mood and cognition. This review provides an overview of the neuropathology of Fragile-X Syndrome, highlighting how structural and synaptic deficits in hippocampal subregions, including the CA1 exhibiting exaggerated metabotropic glutamate receptor dependent long-term depression and the dentate gyrus displaying hypofunction of N-methyl-d-aspartate receptors, contribute to cognitive impairments associated with this neurodevelopmental disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease.

PubMed

Chavassieux, P; Seeman, E; Delmas, P D

2007-04-01

Minimal trauma fractures in bone diseases are the result of bone fragility. Rather than considering bone fragility as being the result of a reduced amount of bone, we recognize that bone fragility is the result of changes in the material and structural properties of bone. A better understanding of the contribution of each component of the material composition and structure and how these interact to maintain whole bone strength is obtained by the study of metabolic bone diseases. Disorders of collagen (osteogenesis imperfecta and Paget's disease of bone), mineral content, composition and distribution (fluorosis and osteomalacia); diseases of high remodeling (postmenopausal osteoporosis, hyperparathyroidism, and hyperthyroidism) and low remodeling (osteopetrosis, pycnodysostosis); and other diseases (idiopathic male osteoporosis, corticosteroid-induced osteoporosis) produce abnormalities in the material composition and structure that lead to bone fragility. Observations in patients and in animal models provide insights on the biomechanical consequences of these illnesses and the nature of the qualities of bone that determine its strength.

Mathematics learning disability in girls with Turner syndrome or fragile X syndrome.

PubMed

Murphy, Melissa M; Mazzocco, Michèle M M; Gerner, Gwendolyn; Henry, Anne E

2006-07-01

Two studies were carried out to examine the persistence (Study 1) and characteristics (Study 2) of mathematics learning disability (MLD) in girls with Turner syndrome or fragile X during the primary school years (ages 5-9 years). In Study 1, the rate of MLD for each syndrome group exceeded the rate observed in a grade-matched comparison group, although the likelihood of MLD persisting through the primary school years was comparable for all three groups. In Study 2, formal and informal math skills were compared across the syndrome groups, a normative group, and children from the normative group who had MLD. Few differences were observed between the Turner syndrome and normative groups. Despite having rote counting and number representation skills comparable to those in the normative group, girls with fragile X had difficulty with counting rules (e.g., cardinality, number constancy). However, this difficulty did not distingush them from the MLD group. Overall, counting skills appear to distinguish the Turner syndrome and fragile X groups, suggesting that the specificity of math deficits emerges earlier for fragile X than Turner syndrome.

Behavioral intervention for problem behavior in children with fragile X syndrome.

PubMed

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

2011-11-01

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 families. A multiple baseline design was used to demonstrate intervention effects for specific high-priority contexts (i.e., bedtime, running errands, and toileting). A multicomponent intervention plan was developed to teach the parents and child to effectively cope with the particular context. After intervention, there were substantial improvements in problem behavior and family quality of life within the given contexts. Results of this study demonstrated the effectiveness of behavioral intervention for children with fragile X syndrome.

Lack of significant association between spina bifida and the fragile X syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schiano, C.M.; Demb, H.B.; Brown, W.T.

1995-12-04

Folic acid is involved in two common disorders associated with developmental disabilities. Spina bifida is a malformation that may be associated with mental retardation, learning disabilities, and epilepsy. Its incidence can be reduced by the ingestion of folic acid before, and at the time of, conception. The fragile X syndrome is a genetic disorder which is the most common form of inherited mental retardation. This disorder can be diagnosed by the induction of fragile sites on the X chromosome which is cultured in a medium deficient in folic acid. In several studies, folic acid was reported to alleviate some ofmore » the developmental and behavioral manifestations associated in the fragile X syndrome, while in others, it has no effect. 9 refs.« less

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

PubMed Central

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

2012-01-01

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 revealed that an interaction between diagnosis and nonverbal mental age predicted narrative microstructure (e.g., complex syntax) but not macrostructure (e.g., thematic maintenance). Correlations with FMR1-related variation were investigated in children with Fragile X syndrome. While CGG repeat length was associated with many language characteristics, nonverbal IQ appeared to mediate these relationships. These findings are an important step toward understanding narrative abilities in boys with and without the FMR1 mutation. PMID:23464607

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

PubMed Central

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

The pathophysiology of fragile X (and what it teaches us about synapses).

PubMed

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

2012-01-01

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.

Mechanism-based approaches to treating fragile X.

PubMed

Dölen, Gül; Carpenter, Randall L; Ocain, Timothy D; Bear, Mark F

2010-07-01

Fragile X is the leading inherited cause of mental retardation and autism. Recent advances in our mechanistic understanding of the disease have led to the identification of the metabotropic glutamate receptor (mGluR) as a therapeutic target for the disease. These studies have revealed that core defects in multiple animal models can be corrected by down regulation of mGluR5 signaling. Although it remains to be seen if mGluR5 antagonists or related approaches will succeed in humans with fragile X, the progress in fragile X stands as a strong testament to the power of applying knowledge of basic neurobiology to understand pathophysiology in a genetically validated model of human psychiatric disease. These breakthroughs and several of the resulting drug development efforts are reviewed. (c) 2010 Elsevier Inc. All rights reserved.

Race and the Fragility of the Legal Distinction between Juveniles and Adults

PubMed Central

Rattan, Aneeta; Levine, Cynthia S.; Dweck, Carol S.; Eberhardt, Jennifer L.

2012-01-01

Legal precedent establishes juvenile offenders as inherently less culpable than adult offenders and thus protects juveniles from the most severe of punishments. But how fragile might these protections be? In the present study, simply bringing to mind a Black (vs. White) juvenile offender led participants to view juveniles in general as significantly more similar to adults in their inherent culpability and to express more support for severe sentencing. Indeed, these differences in participants’ perceptions of this foundational legal precedent distinguishing between juveniles and adults accounted for their greater support for severe punishment. These results highlight the fragility of protections for juveniles when race is in play. Furthermore, we suggest that this fragility may have broad implications for how juveniles are seen and treated in the criminal justice system. PMID:22649496

Race and the fragility of the legal distinction between juveniles and adults.

PubMed

Rattan, Aneeta; Levine, Cynthia S; Dweck, Carol S; Eberhardt, Jennifer L

2012-01-01

Legal precedent establishes juvenile offenders as inherently less culpable than adult offenders and thus protects juveniles from the most severe of punishments. But how fragile might these protections be? In the present study, simply bringing to mind a Black (vs. White) juvenile offender led participants to view juveniles in general as significantly more similar to adults in their inherent culpability and to express more support for severe sentencing. Indeed, these differences in participants' perceptions of this foundational legal precedent distinguishing between juveniles and adults accounted for their greater support for severe punishment. These results highlight the fragility of protections for juveniles when race is in play. Furthermore, we suggest that this fragility may have broad implications for how juveniles are seen and treated in the criminal justice system.

The Rise, Removal, and Return of Women: Gender Representations in Primary-Level Textbooks in Afghanistan, 1980-2010

ERIC Educational Resources Information Center

Sarvarzade, Somaye; Wotipka, Christine Min

2017-01-01

Nearly four decades of instability and fragility have led to many changes in the status of women and girls in Afghanistan. Yet, little research focuses on these changes within the education system. To understand the country's stance toward gender issues in formal practice, we examine gender representations in Afghan primary-level Dari language…

Open for Business: On What Terms? An Analysis of 12 Collaborations between Canadian Universities and Corporations, Donors and Governments

ERIC Educational Resources Information Center

Canadian Association of University Teachers, 2013

2013-01-01

The distinctive role of the university in society is always fragile and always in jeopardy. At its core, that role is primarily extending and deepening human understanding through research, scholarship, and teaching. This report presents an analysis of the following 12 collaborations between Canadian Universities and corporations, donors, and…

It Happened in Antarctica. A Collection of Observations Requiring Scientific Explanations.

ERIC Educational Resources Information Center

Yaxley, Murray

There are many reasons for studying Antarctica. It is the key element in the world's climate. Some of the secrets of the earth's past are locked beneath its icecap. It has a fascinating physical environment and a unique and fragile ecosystem. It is a frontier of scientific research and technological development. Its history is an important and…

Behavioural Phenotypes in the Classroom: A Qualitative Study of Parental and Teacher Knowledge of Classroom Guidelines and Teacher Views on Best Practices

ERIC Educational Resources Information Center

Reilly, Colin; Murtagh, Lelia; Senior, Joyce

2016-01-01

Research suggests that genetic syndromes associated with intellectual disability often have specific cognitive and behavioural profiles. It has been suggested that educational approaches need to reflect these profiles. Parents (n = 381) and teachers (n = 204) of children with one of four syndromes, fragile X syndrome, Prader-Willi syndrome,…

Toward a virtual reconstruction of an antique three-dimensional marble puzzle

NASA Astrophysics Data System (ADS)

Benamar, Fatima Zahra; Fauvet, Eric; Hostein, Antony; Laligant, Olivier; Truchetet, Frederic

2017-01-01

The reconstruction of broken objects is an important field of research for many applications, such as art restoration, surgery, forensics, and solving puzzles. In archaeology, the reconstruction of broken artifacts is a very time-consuming task due to the handling of fractured objects, which are generally fragile. However, it can now be supported by three-dimensional (3-D) data acquisition devices and computer processing. Those techniques are very useful in this domain because they allow the remote handling of very accurate models of fragile parts, they permit the extensive testing of reconstruction solutions, and they provide access to the parts for the entire research community. An interesting problem has recently been proposed by archaeologists in the form of a huge puzzle composed of a thousand fragments of Pentelic marble of different sizes found in Autun (France), and all attempts to reconstruct the puzzle during the last two centuries have failed. Archaeologists are sure that some fragments are missing and that some of the ones we have come from different slabs. We propose an inexpensive transportable system for 3-D acquisition setup and a 3-D reconstruction method that is applied to this Roman inscription but is also relevant to other applications.

Programming social behavior by the maternal fragile X protein.

PubMed

Zupan, B; Sharma, A; Frazier, A; Klein, S; Toth, M

2016-07-01

The developing fetus and neonate are highly sensitive to maternal environment. Besides the well-documented effects of maternal stress, nutrition and infections, maternal mutations, by altering the fetal, perinatal and/or early postnatal environment, can impact the behavior of genetically normal offspring. Mutation/premutation in the X-linked FMR1 (encoding the translational regulator FMRP) in females, although primarily responsible for causing fragile X syndrome (FXS) in their children, may also elicit such maternal effects. We showed that a deficit in maternal FMRP in mice results in hyperactivity in the genetically normal offspring. To test if maternal FMRP has a broader intergenerational effect, we measured social behavior, a core dimension of neurodevelopmental disorders, in offspring of FMRP-deficient dams. We found that male offspring of Fmr1(+/-) mothers, independent of their own Fmr1 genotype, exhibit increased approach and reduced avoidance toward conspecific strangers, reminiscent of 'indiscriminate friendliness' or the lack of stranger anxiety, diagnosed in neglected children and in patients with Asperger's and Williams syndrome. Furthermore, social interaction failed to activate mesolimbic/amygdala regions, encoding social aversion, in these mice, providing a neurobiological basis for the behavioral abnormality. This work identifies a novel role for FMRP that extends its function beyond the well-established genetic function into intergenerational non-genetic inheritance/programming of social behavior and the corresponding neuronal circuit. As FXS premutation and some psychiatric conditions that can be associated with reduced FMRP expression are more prevalent in mothers than full FMR1 mutation, our findings potentially broaden the significance of FMRP-dependent programming of social behavior beyond the FXS population. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

ValuedCare program: a population health model for the delivery of evidence-based care across care continuum for hip fracture patients in Eastern Singapore.

PubMed

Mittal, Chikul; Lee, Hsien Chieh Daniel; Goh, Kiat Sern; Lau, Cheng Kiang Adrian; Tay, Leeanna; Siau, Chuin; Loh, Yik Hin; Goh, Teck Kheng Edward; Sandi, Chit Lwin; Lee, Chien Earn

2018-05-30

To test a population health program which could, through the application of process redesign, implement multiple evidence-based practices across the continuum of care in a functionally integrated health delivery system and deliver highly reliable and consistent evidence-based surgical care for patients with fragility hip fractures in an acute tertiary general hospital. The ValuedCare (VC) program was developed in three distinct phases as an ongoing collaboration between the Geisinger Health System (GHS), USA, and Changi General Hospital (CGH), Singapore, modelled after the GHS ProvenCare® Fragile Hip Fracture Program. Clinical outcome data on consecutive hip fracture patients seen in 12 months pre-intervention were then compared with the post-intervention group. Both pre- and post-intervention groups were followed up across the continuum of care for a period of 12 months. VC patients showed significant improvement in median time to surgery (97 to 50.5 h), as well as proportion of patients operated within 48 h from hospital admission (48% from 18.8%) as compared to baseline pre-intervention data. These patients also had significant reduction (p value < 0.001) of acute inpatient complications such as delirium, pneumonia, urinary tract infections, and pressure sores. VC program has shown significant reduction in median length of stay for acute hospital (13 to 9 days) as well as median combined length of stay for acute and sub-acute rehabilitation hospital (46 to 39 days), thus reducing the total duration of hospitalization and saving total hospital bed days. Operative and inpatient mortality, together with readmission rates, remained low and comparable to international Geriatric Fracture Centers (GFCs). The implementation of VC methodology has enabled consistent delivery of high-quality, reliable and comprehensive evidence-based care for hip fracture patients at Changi General Hospital. This has also reflected successful change management and interdisciplinary collaboration within the organization through the program. There is potential for testing this methodology as a quality improvement framework replicable to other disease groups in a functionally integrated healthcare system.

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

PubMed

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.

Using Helical CT to Predict Stone Fragility in Shock Wave Lithotripsy (SWL)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, James C. Jr.; Zarse, Chad A.; Jackson, Molly E.

2007-04-05

Great variability exists in the response of urinary stones to SWL, and this is true even for stones composed of the same mineral. Efforts have been made to predict stone fragility to shock waves using computed tomography (CT) patient images, but most work to date has focused on the use of stone CT number (i.e., Hounsfield units). This is an easy number to measure on a patient stone, but its value depends on a number of factors, including the relationship of the size of the stone to me resolution (i.e., the slicewidth) of the CT scan. Studies that have shownmore » a relationship between stone CT number and failure in SWL are reviewed, and all are shown to suffer from error due to stone size, which was not accounted for in the use of Hounsfield unit values. Preliminary data are then presented for a study of calcium oxalate monohydrate (COM) stones, in which stone structure-rather than simple CT number values-is shown to correlate with fragility to shock waves. COM stones that were observed to have structure by micro CT (e.g., voids, apatite regions, unusual shapes) broke to completion in about half the number of shock waves required for COM stones that were observed to be homogeneous in structure by CT. This result suggests another direction for the use of CT in predicting success of SWL: the use of CT to view stone structure, rather than simply measuring stone CT number. Viewing stone structure by CT requires the use of different viewing windows than those typically used for examining patient scans, but much research to date indicates that stone structure can be observed in the clinical setting. Future clinical studies will need to be done to verify the relationship between stone structure observed by CT and stone fragility in SWL.« less

Effects of a social stimulus on gene expression in a mouse model of fragile X syndrome.

PubMed

Rogers, Tiffany D; Anacker, Allison M J; Kerr, Travis M; Forsberg, C Gunnar; Wang, Jing; Zhang, Bing; Veenstra-VanderWeele, Jeremy

2017-01-01

People with fragile X syndrome (FXS) often have deficits in social behavior, and a substantial portion meet criteria for autism spectrum disorder. Though the genetic cause of FXS is known to be due to the silencing of FMR1 , and the Fmr1 null mouse model representing this lesion has been extensively studied, the contributions of this gene and its protein product, FMRP, to social behavior are not well understood. Fmr1 null mice and wildtype littermates were exposed to a social or non-social stimulus. In one experiment, subjects were assessed for expression of the inducible transcription factor c-Fos in response to the stimulus, to detect brain regions with social-specific activity. In a separate experiment, tissue was taken from those brain regions showing differential activity, and RNA sequencing was performed. Immunohistochemistry revealed a significantly greater number of c-Fos-positive cells in the lateral amygdala and medial amygdala in the brains of mice exposed to a social stimulus, compared to a non-social stimulus. In the prelimbic cortex, there was no significant effect of social stimulus; although the number of c-Fos-positive cells was lower in the social condition compared to the non-social condition, and negatively correlated with c-Fos in the amygdala. RNA sequencing revealed differentially expressed genes enriched for molecules known to interact with FMRP and also for autism-related genes identified in the Simons Foundation Autism Research Initiative gene database. Ingenuity Pathway Analysis detected enrichment of differentially expressed genes in networks and pathways related to neuronal development, intracellular signaling, and inflammatory response. Using the Fmr1 null mouse model of fragile X syndrome, we have identified brain regions, gene networks, and molecular pathways responsive to a social stimulus. These findings, and future experiments following up on the role of specific gene networks, may shed light on the neural mechanisms underlying dysregulated social behaviors in fragile X syndrome and more broadly.

Fragility fractures and bone mineral density in HIV positive women: a case-control population-based study.

PubMed

Prior, J; Burdge, D; Maan, E; Milner, R; Hankins, C; Klein, M; Walmsley, S

2007-10-01

This Canadian study of bone health showed that HIV+ women were more likely to have had fragility fractures (OR 1.7) but had BMD values that were not different than women from a national population-based cohort. Given that 17.5 million women globally are HIV-infected and living longer on anti-retroviral therapy (ART+), it is essential to determine whether they are at risk for osteoporosis as is currently assumed. Assessment of osteoporosis risk factors and lifetime low-trauma (fragility) fracture history used a common interviewer-administered questionnaire and phantom-adjusted bone mineral density (BMD). This study compared HIV+ Canadian women with age- and region-matched control women (1:3) from a national population-based study of osteoporosis. One hundred and thirty-eight HIV+ women (100 ART+, 38 ART-) were compared with 402 controls. There were no differences in age (37.7 vs. 38.0 years), BMI (25.0 vs. 26.2), family history of osteoporosis, exercise history, alcohol or calcium intakes, age at menarche, oral contraceptive use or parity. HIV+ cases included more Aboriginal and Black women (12.5% and 16.2 vs. 2% and 1%, respectively), smoked and used injection drugs (53%) more, were more often treated with glucocorticoids, had oligomenorrhea, and reported 10-kg weight cycling. Significantly more HIV+ women reported lifetime fragility fractures (26.1% vs. 17.3; OR 1.7, 95% CI 1.1, 2.6). HIV+ and control women did not differ in BMD: spine 1.0 +/- 0.12 vs.1.0 +/- 0.14 g/cm(2) (diff. 0.0, 95% CI -0.27, 0.27) or total femur 0.91 +/- 0.15 vs. 0.93 +/- 0.12 g/cm(2) (diff 0.02, 95% CI +0.005, -0.045). HIV+ women reported significantly more past osteoporotic fractures than population-based controls despite normal BMD. Research is needed to assess bone microarchitecture and develop a reliable fracture risk assessment tool for HIV+ women.

New mechanisms and targets in the treatment of bone fragility.

PubMed

Martin, T John; Seeman, Ego

2007-01-01

Bone modelling and remodelling are cell-mediated processes responsible for the construction and reconstruction of the skeleton throughout life. These processes are chiefly mediated by locally generated cytokines and growth factors that regulate the differentiation, activation, work and life span of osteoblasts and osteoclasts, the cells that co-ordinate the volumes of bone resorbed and formed. In this way, the material composition and structural design of bone is regulated in accordance with its loading requirements. Abnormalities in this regulatory system compromise the material and structural determinants of bone strength producing bone fragility. Understanding the intercellular control processes that regulate bone modelling and remodelling is essential in planning therapeutic approaches to prevention and treatment of bone fragility. A great deal has been learnt in the last decade. Clinical trials carried out exclusively with drugs that inhibit bone resorption have identified the importance of reducing the rate of bone remodelling and so the progression of bone fragility to achieved fracture reductions of approx. 50%. These trials have also identified limitations that should be placed upon interpretation of bone mineral density changes in relation to treatment. New resorption inhibitors are being developed, based on mechanisms of action that are different from existing drugs. Some of these might offer resorption inhibition without reducing bone formation. More recent research has provided the first effective anabolic therapy for bone reconstruction. Daily injections of PTH (parathyroid hormone)-(1-34) have been shown in preclinical studies and in a large clinical trial to increase bone tissue mass and reduce the risk of fractures. The action of PTH differs from that of the resorption inhibitors, but whether it is more effective in fracture reduction is not known. Understanding the cellular and molecular mechanisms of PTH action, particularly its interactions with other pathways in determining bone formation, is likely to lead to new therapeutic developments. The recent discovery through mouse genetics that PTHrP (PTH-related protein) is a crucial bone-derived paracrine regulator of remodelling offers new and interesting therapeutic targets.

Practical pathology of aging mice

PubMed Central

Pettan-Brewer, Christina; Treuting, Piper M.

2011-01-01

Old mice will have a subset of lesions as part of the progressive decline in organ function that defines aging. External and palpable lesions will be noted by the research, husbandry, or veterinary staff during testing, cage changing, or physical exams. While these readily observable lesions may cause alarm, not all cause undue distress or are life-threatening. In aging research, mice are maintained until near end of life that, depending on strain and genetic manipulation, can be upwards of 33 months. Aging research has unique welfare issues related to age-related decline, debilitation, fragility, and associated pain of chronic diseases. An effective aging research program includes the collaboration and education of the research, husbandry, and veterinary staff, and of the members of the institution animal care and use committee. This collaborative effort is critical to humanely maintaining older mice and preventing excessive censorship due to non-lethal diseases. Part of the educational process is becoming familiar with how old mice appear clinically, at necropsy and histopathologically. This baseline knowledge is important in making the determination of humane end points, defining health span, contributing causes of death and effects of interventions. The goal of this paper is to introduce investigators to age-associated diseases and lesion patterns in mice from clinical presentation to pathologic assessment. To do so, we present and illustrate the common clinical appearances, necropsy and histopathological lesions seen in subsets of the aging colonies maintained at the University of Washington. PMID:22953032

A case study of the Australian Plague Locust Commission and environmental due diligence: why mere legislative compliance is no longer sufficient for environmentally responsible locust control in Australia.

PubMed

Story, Paul G; Walker, Paul W; McRae, Heath; Hamilton, John G

2005-07-01

The Australian Plague Locust Commission (APLC) manages locust populations across 2 million square kilometers of eastern Australia using the aerial application of chemical and biological control agents to protect agricultural production. This occurs via a preventative control strategy involving ultralow-volume spray equipment to distribute small droplets of control agent over a target area. The economic costs of, and potential gains stemming from, locust control are well documented. The application of insecticides, however, to fragile arid and semiarid ecosystems is a task that brings with it both real and perceived environmental issues. The APLC is proactive in addressing these issues through a combination of targeted environmental operational research, an ISO-14001-aligned Environmental Management System (EMS), and links with environmental regulatory and research institutions. Increasing due diligence components within Australian environmental legislation dictate that mere legislative compliance is no longer sufficient for industries to ensure that they meet their environmental obligations. The development of external research links and the formulation of an EMS for locust control have enabled the APLC to identify environmental issues and trends, quantify objective environmental targets and strategies, and facilitate continuous improvement in its environmental performance, while maintaining stakeholder support. This article outlines the environmental issues faced by the APLC, the research programs in place to address these issues, and the procedures in place to incorporate research findings into the organization's operational structure.

Primary Ovarian Insufficiency

MedlinePlus

... POI. For example, women Fragile X syndrome or Turner syndrome are at higher risk. Certain diseases, such as ... Genetic disorders such as Fragile X syndrome and Turner syndrome A low number of follicles Autoimmune diseases, including ...

Fragile X-Associated Primary Ovarian Insufficiency (FXPOI)

MedlinePlus

Donate Contact PS3G Home About About Us Finances 2016 Annual Impact Report Learn Fragile X Syndrome FXS Resources by Age Group Clinical Practice Consensus Documents FXPOI FXTAS Newly Diagnosed Premutation Carriers ...

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

PubMed Central

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

Clinical, molecular, and pharmacological aspects of FMR1 related disorders.

PubMed

Pugin, A; Faundes, V; Santa María, L; Curotto, B; Aliaga, S; Salas, I; Soto, P; Bravo, P; Peña, M I; Alliende, M A

2017-05-01

Fragile X syndrome, the most common inherited cause of intellectual disability, is associated with a broad spectrum of disorders across different generations of a single family. This study reviews the clinical manifestations of fragile X-associated disorders as well as the spectrum of mutations of the fragile X mental retardation 1 gene (FMR1) and the neurobiology of the fragile X mental retardation protein (FMRP), and also provides an overview of the potential therapeutic targets and genetic counselling. This disorder is caused by expansion of the CGG repeat (>200 repeats) in the 5 prime untranslated region of FMR1, resulting in a deficit or absence of FMRP. FMRP is an RNA-binding protein that regulates the translation of several genes that are important in synaptic plasticity and dendritic maturation. It is believed that CGG repeat expansions in the premutation range (55 to 200 repeats) elicit an increase in mRNA levels of FMR1, which may cause neuronal toxicity. These changes manifest clinically as developmental problems such as autism and learning disabilities as well as neurodegenerative diseases including fragile X-associated tremor/ataxia syndrome (FXTAS). Advances in identifying the molecular basis of fragile X syndrome may help us understand the causes of neuropsychiatric disorders, and they will probably contribute to development of new and specific treatments. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Fragile Sites of ‘Valencia’ Sweet Orange (Citrus sinensis) Chromosomes Are Related with Active 45s rDNA

PubMed Central

Lan, Hong; Chen, Chun-Li; Miao, Yin; Yu, Chang-Xiu; Guo, Wen-Wu; Xu, Qiang; Deng, Xiu-Xin

2016-01-01

Citrus sinensis chromosomes present a morphological differentiation of bands after staining by the fluorochromes CMA and DAPI, but there is still little information on its chromosomal characteristics. In this study, the chromosomes in ‘Valencia’ C. sinensis were analyzed by fluorescence in situ hybridization (FISH) using telomere DNA and the 45S rDNA gene as probes combining CMA/DAPI staining, which showed that there were two fragile sites in sweet orange chromosomes co-localizing at distended 45S rDNA regions, one proximally locating on B-type chromosome and the other subterminally locating on D-type chromosome. While the chromosomal CMA banding and 45S rDNA FISH mapping in the doubled haploid line of ‘Valencia’ C. sinensis indicated six 45S rDNA regions, four were identified as fragile sites as doubled comparing its parental line, which confirmed the cytological heterozygosity and chromosomal heteromorphisms in sweet orange. Furthermore, Ag-NOR identified two distended 45S rDNA regions to be active nucleolar organizing regions (NORs) in diploid ‘Valencia’ C. sinensis. The occurrence of quadrivalent in meiosis of pollen mother cells (PMCs) in ‘Valencia’ sweet orange further confirmed it was a chromosomal reciprocal translocation line. We speculated this chromosome translocation was probably related to fragile sites. Our data provide insights into the chromosomal characteristics of the fragile sites in ‘Valencia’ sweet orange and are expected to facilitate the further investigation of the possible functions of fragile sites. PMID:26977938

Fragile Sites of 'Valencia' Sweet Orange (Citrus sinensis) Chromosomes Are Related with Active 45s rDNA.

PubMed

Lan, Hong; Chen, Chun-Li; Miao, Yin; Yu, Chang-Xiu; Guo, Wen-Wu; Xu, Qiang; Deng, Xiu-Xin

2016-01-01

Citrus sinensis chromosomes present a morphological differentiation of bands after staining by the fluorochromes CMA and DAPI, but there is still little information on its chromosomal characteristics. In this study, the chromosomes in 'Valencia' C. sinensis were analyzed by fluorescence in situ hybridization (FISH) using telomere DNA and the 45S rDNA gene as probes combining CMA/DAPI staining, which showed that there were two fragile sites in sweet orange chromosomes co-localizing at distended 45S rDNA regions, one proximally locating on B-type chromosome and the other subterminally locating on D-type chromosome. While the chromosomal CMA banding and 45S rDNA FISH mapping in the doubled haploid line of 'Valencia' C. sinensis indicated six 45S rDNA regions, four were identified as fragile sites as doubled comparing its parental line, which confirmed the cytological heterozygosity and chromosomal heteromorphisms in sweet orange. Furthermore, Ag-NOR identified two distended 45S rDNA regions to be active nucleolar organizing regions (NORs) in diploid 'Valencia' C. sinensis. The occurrence of quadrivalent in meiosis of pollen mother cells (PMCs) in 'Valencia' sweet orange further confirmed it was a chromosomal reciprocal translocation line. We speculated this chromosome translocation was probably related to fragile sites. Our data provide insights into the chromosomal characteristics of the fragile sites in 'Valencia' sweet orange and are expected to facilitate the further investigation of the possible functions of fragile sites.

[Diet and polymer standard vs. standard in the nutritional status of elderly patients with fragility].

PubMed

Luna-Ramos, Gissel Karelly; Pedraza-Zárate, Miguel Ángel; Franco-Álvarez, Nubia; González-Velázquez, Felipe

2016-01-01

The elderly patients with fragility show different physiological changes, so they are given polymeric diets to maintain and/or alter their nutritional status. The aim of this paper is to demonstrate the effect of changing a standard polymeric diet and a standard diet on nutritional status in elderly patients with fragility. Clinical randomized controlled trial in 23 elderly patients, 70 years of age or older, with fragility, hospitalized in a Internal Medicine Unity in a period from July to December 2014. Nutritional status was determined through Minimum Nutritional Consulting (MNA) and body mass index (BMI). Descriptive statistics, Chi square, Student t test and McNemar. In the G1: 12 patients were in the G2 and 11, a positive change was observed in the nutritional status G1 initially being 14.00 (malnutrition) and end 22.75 (risk of malnutrition). According to BMI (kg/m2) was evident at the beginning 25 % of patients (3) with mild malnutrition, but the final results show figures with a zero percentage of malnourished patients. The use of standard polymeric diet increases body weight, BMI and nutritional status in elderly patients with fragility.

A Comparison of Pragmatic Language in Boys with Autism and Fragile X Syndrome

PubMed Central

Klusek, Jessica; Martin, Gary E.; Losh, Molly

2014-01-01

Purpose Impaired pragmatic language (i.e., language use for social interaction) is a hallmark feature of both autism spectrum disorder (ASD) and fragile X syndrome (FXS), the most common known monogenic disorder associated with ASD. However, few cross-population comparisons of ASD and FXS have been conducted, and it is unclear whether pragmatic language profiles in these conditions overlap. Method This study used semi-naturalistic and standardized assessment methods to characterize pragmatic language abilities of 29 school-aged boys with idiopathic ASD, 38 with FXS and comorbid ASD, 16 with FXS without ASD, 20 with Down syndrome and 20 with typical development. Results Similar severity of pragmatic language deficits was observed in both of the groups with ASD (idiopathic and fragile X-associated). ASD comorbidity had a detrimental effect on the pragmatic language skills of boys with FXS. Some different patterns emerged across the two pragmatic assessment tools, with more robust group differences observed in pragmatics assessed in a semi-naturalistic conversational context. Conclusions These findings have implications for pragmatic language assessment and intervention, as well as for understanding the potential role of the fragile X gene, Fragile X Mental Retardation-1, in the pragmatic language phenotype of ASD. PMID:24686468

Autism Is Associated with the Fragile-X Syndrome.

ERIC Educational Resources Information Center

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)

Genetics Home Reference: fragile XE syndrome

MedlinePlus

... are so mild that the individuals function normally. Learning disabilities are the most common sign of impaired cognitive function in people with fragile XE syndrome . The learning disabilities are likely a result of communication and behavioral ...

Intellectual Property Rights and International Trade

DTIC Science & Technology

2007-12-20

to maintain its secrecy.1 Examples of trade secrets include blueprints, customer lists, and pricing information. While protection of patents and...is fragile or if the area of research is highly competitive . Copyright. Protection of copyrights in the United States is based on the Copyright Act...as Louis Vuitton bags or Rolex watches, or fake pharmaceutical products, such as popular brand -name prescription medicines. A related issue is the

Fragile Identities: Exploring Learner Identity, Learner Autonomy and Motivation through Young Learners' Voices

ERIC Educational Resources Information Center

Lamb, Terry Eric

2011-01-01

Recent research in the fields of motivation and learner autonomy in language learning has begun to explore their relationships to the construct of identity. This article builds on this through the voices of a group of six learners of French or German in a secondary school in England, over a two-year period. These young learners initially reveal a…

How do health workers experience and cope with shocks? Learning from four fragile and conflict-affected health systems in Uganda, Sierra Leone, Zimbabwe and Cambodia.

PubMed

Witter, Sophie; Wurie, Haja; Chandiwana, Pamela; Namakula, Justine; So, Sovannarith; Alonso-Garbayo, Alvaro; Ssengooba, Freddie; Raven, Joanna

2017-11-01

This article is grounded in a research programme which set out to understand how to rebuild health systems post-conflict. Four countries were studied-Uganda, Sierra Leone, Zimbabwe and Cambodia-which were at different distances from conflict and crisis, as well as having unique conflict stories. During the research process, the Ebola epidemic broke out in West Africa. Zimbabwe has continued to face a profound economic crisis. Within our research on health worker incentives, we captured insights from 128 life histories and in-depth interviews with a variety of staff that had remained in service. This article aims to draw together lessons from these contexts which can provide lessons for enhancing staff and therefore health system resilience in future, especially in similarly fragile and conflict-affected contexts. We examine the reported effects, both personal and professional, of the three different types of shock (conflicts, epidemics and prolonged political-economic crises), and how staff coped. We find that the impact of shocks and coping strategies are similar between conflict/post-conflict and epidemic contexts-particularly in relation to physical threats and psychosocial threats-while all three contexts create challenges and staff responses for working conditions and remuneration. Health staff showed considerable inventiveness and resilience, and also benefited from external assistance of various kinds, but there are important gaps which point to ways in which they should be better protected and supported in the future. Health systems are increasingly fragile and conflict-prone, and shocks are often prolonged or repeated. Resilience should not be taken for granted or used as an excuse for abandoning frontline health staff. Strategies should be in place at local, national and international levels to prepare for predictable crises of various sorts, rather than waiting for them to occur and responding belatedly, or relying on personal sacrifices by staff to keep services functioning. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

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.

Non-marfan idiopathic medionecrosis (cystic medial necrosis) presenting with multiple visceral artery aneurysms and diffuse connective tissue fragility: Two brothers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kubota, Jun; Tsunemura, Mami; Amano, Shigeko

1997-05-15

Two brothers with multiple visceral artery aneurysms or dilatations and diffuse connective tissue fragility who did not have clinical features of Marfan syndrome are reported. One presented with retroperitoneal hemorrhage during angiography, and idiopathic medionecrosis was proved by resection of the aneurysms. These cases belong to the heterogeneous group of Marfan syndrome. The angiographical features (multiple dilation of visceral arteries) suggests fragility of connective tissue and is predictive of hazards during and after a catheterization and operation.

Thermalization as an invisibility cloak for fragile quantum superpositions

NASA Astrophysics Data System (ADS)

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.

The cyclic AMP cascade is altered in the fragile X nervous system.

PubMed

Kelley, Daniel J; Davidson, Richard J; Elliott, Jamie L; Lahvis, Garet P; Yin, Jerry C P; Bhattacharyya, Anita

2007-09-26

Fragile X syndrome (FX), the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP). Although research efforts have focused on FMRP's impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 3', 5'-monophosphate (cAMP) cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in platelets and in brains of fmr1 knockout mice are substantially reduced. Cyclic AMP induction is also significantly reduced in human FX neural cells. Furthermore, cAMP production is decreased in the heads of FX Drosophila and this defect can be rescued by reintroduction of the dfmr gene. Our results indicate that a robust defect in cAMP production in FX is conserved across species and suggest that cAMP metabolism may serve as a useful biomarker in the human disease population. Reduced cAMP induction has implications for the underlying causes of FX and autism spectrum disorders. Pharmacological agents known to modulate the cAMP cascade may be therapeutic in FX patients and can be tested in these models, thus supplementing current efforts centered on mGluR signaling.

Grain size of recall practice for lengthy text material: fragile and mysterious effects on memory.

PubMed

Wissman, Kathryn T; Rawson, Katherine A

2015-03-01

The current research evaluated the extent to which the grain size of recall practice for lengthy text material affects recall during practice and subsequent memory. The grain size hypothesis states that a smaller vs. larger grain size will increase retrieval success during practice that in turn will enhance subsequent memory for lengthy text material. Participants were prompted to recall directly after studying each section (section recall) or after all sections had been studied (whole-text recall) during practice, and then all participants completed a final test after a delay. Results across 7 experiments (including 587 participants and 1,394 recall protocols) partially disconfirmed the predictions of the grain size hypothesis: Although the smaller grain size produced sizable recall advantages during practice as expected (ds from 1.02 to 1.87 across experiments), the advantage was substantially or completely attenuated across a delay. Experiments 2-7 falsified several plausible methodological and theoretical explanations for the fragility of the effect, indicating that it was not due to particular text materials, retrieval from working memory during practice, the length of the retention interval, the spacing between study and practice recall, a disproportionate increase in recall of unimportant details, or a deficit in integration of ideas across text sections. In sum, results conclusively establish an initially sizable but mysteriously fragile effect of grain size, for which an explanation remains elusive. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Consensus and controversy regarding osteoporosis in the pediatric population.

PubMed

Bachrach, Laura Keyes

2007-09-01

To review current consensus and controversy surrounding the diagnosis and treatment of osteoporosis in childhood and adolescence. The medical literature was reviewed with emphasis on the importance of early skeletal health, risk factors for bone fragility, and the diagnosis and management of children at risk for osteoporosis. Childhood and adolescence are critical periods for optimizing bone growth and mineral accrual. Bone strength is determined by bone size, geometry, quality, and mass-variables that are influenced by genetic factors, activity, nutrition, and hormones. For children with genetic skeletal disorders or chronic disease, bone growth and mineral accrual may be compromised, increasing the lifetime risk of osteoporosis. The goal for the clinician is to identify children at greatest risk for future fragility fracture. Bone densitometry and turnover markers are challenging to interpret in children. Prevention and treatment of bone fragility in children are less well established than in adults. Optimizing nutrition and activity may not restore bone health, but the drug armamentarium is limited. Sex steroid replacement has not proven effective in restoring bone mass in patients with anorexia nervosa or exercise-associated amenorrhea. Bisphosphonates can increase bone mass and may reduce bone pain and fractures, most convincingly in patients with osteogenesis imperfecta. Further studies are needed to establish the safety, efficacy, and optimal drug, duration, and dosage in pediatric patients. Bone health during the first 2 decades contributes to the lifetime risk of osteoporosis. Further research is needed to develop evidence-based recommendations for the diagnosis and treatment of osteoporosis in childhood.

Friendships and social participation as markers of quality of life of adolescents and adults with fragile X syndrome and autism.

PubMed

DaWalt, Leann Smith; Usher, Lauren V; Greenberg, Jan S; Mailick, Marsha R

2017-12-01

Friendships and social participation are key domains of quality of life for individuals with intellectual disabilities. This study examined the friendships, social and recreational activities, and family social networks of individuals with intellectual disabilities from two distinct diagnostic groups: individuals diagnosed with fragile X syndrome (n = 81) compared with those diagnosed with autistic disorder (n = 226). Within each diagnostic group, individuals in two developmental stages were compared: adolescence and adulthood. Quality of life in friendships and social participation domains was notably low for individuals with fragile X and those with autism. Individuals with fragile X had more friendships and a less negative social impact on the family than individuals with autism. Across both groups, adolescents spent less time with friends and neighbors, and more time in exercising, than did adults.

Fragile X syndrome: A review of clinical management

PubMed Central

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

Repurposing available drugs for neurodevelopmental disorders: The fragile X experience.

PubMed

Tranfaglia, Michael R; Thibodeaux, Clare; Mason, Daniel J; Brown, David; Roberts, Ian; Smith, Richard; Guilliams, Tim; Cogram, Patricia

2018-05-04

Many available drugs have been repurposed as treatments for neurodevelopmental disorders. In the specific case of fragile X syndrome, many clinical trials of available drugs have been conducted with the goal of disease modification. In some cases, detailed understanding of basic disease mechanisms has guided the choice of drugs for clinical trials, and several notable successes in fragile X clinical trials have led to common use of drugs such as minocycline in routine medical practice. Newer technologies like Disease-Gene Expression Matching (DGEM) may allow for more rapid identification of promising repurposing candidates. A DGEM study predicted that sulindac could be therapeutic for fragile X, and subsequent preclinical validation studies have shown promising results. The use of combinations of available drugs and nutraceuticals has the potential to greatly expand the options for repurposing, and may even be a viable business strategy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fragile Families in the American Welfare State

PubMed Central

Garfinkel, Irwin; Zilanawala, Afshin

2016-01-01

The proportion of children born out of wedlock is now over 40 percent. At birth, about half of these parents are co-habiting. This paper examines data from the Fragile Families and Child Wellbeing study (N = 4,271) to describe for the first time the role of welfare state benefits in the economic lives of married, cohabiting, and single parent families with young children. Surprisingly, total welfare state benefits received by the three family types are relatively similar. Nearly half of the full incomes of fragile families come from welfare state transfers. For single parent families the proportion is slightly more than two thirds. Though aggregate welfare state transfers are approximately equal across family type and thus change very little as marital status changes, these transfers and the taxes required to finance them cushion family status changes and substantially narrow the gap in full income between married and fragile families. PMID:27114616

Frailty syndrome and socioeconomic and health characteristics among older adults

PubMed Central

de Freitas Corrêa, Thais Aline; Dias, Flavia Aparecida; dos Santos Ferreira, Pollyana Cristina; Sousa Pegorari, Maycon

2017-01-01

Abstract Objective: To investigate the association of frailty syndrome with socioeconomic and health variables among older adults. Methods: This is a cross-sectional, observational and analytical household research conducted with a sample of 1,609 urban elderly. We used: semi-structured questionnaire, scales (Katz, Lawton and shortened version of Geriatric Depression Scale) and Fragility Phenotype proposed by Fried. Descriptive analysis was performed along with a bivariate and multinomial logistic regression model (p <0.05). Results: The prevalence of pre-frailty condition was 52.0% and the fragility corresponded to 13.6%. Pre-frailty and frailty associated factors were, respectively: age range between 70-79 years and ≥80 years; one to four morbidities and five or more morbidities categories; functional disability for basic and instrumental activities of daily life and depression indicative; whilst lack of a companion or income and female gender were only associated to pre-frailty. Conclusion: The conditions of pre-frailty and frailty levels were elevated with negative effects on the health of the elderly. PMID:29213155

MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome

PubMed Central

Siew, Wei-Hong; Tan, Kai-Leng; Babaei, Maryam Abbaspour; Cheah, Pike-See; Ling, King-Hwa

2013-01-01

Intellectual disability (ID) is one of the many features manifested in various genetic syndromes leading to deficits in cognitive function among affected individuals. ID is a feature affected by polygenes and multiple environmental factors. It leads to a broad spectrum of affected clinical and behavioral characteristics among patients. Until now, the causative mechanism of ID is unknown and the progression of the condition is poorly understood. Advancement in technology and research had identified various genetic abnormalities and defects as the potential cause of ID. However, the link between these abnormalities with ID is remained inconclusive and the roles of many newly discovered genetic components such as non-coding RNAs have not been thoroughly investigated. In this review, we aim to consolidate and assimilate the latest development and findings on a class of small non-coding RNAs known as microRNAs (miRNAs) involvement in ID development and progression with special focus on Down syndrome (DS) and X-linked ID (XLID) [including Fragile X syndrome (FXS)]. PMID:23596395

Genome-wide Control of Heterochromatin Replication by the Telomere Capping Protein TRF2.

PubMed

Mendez-Bermudez, Aaron; Lototska, Liudmyla; Bauwens, Serge; Giraud-Panis, Marie-Josèphe; Croce, Olivier; Jamet, Karine; Irizar, Agurtzane; Mowinckel, Macarena; Koundrioukoff, Stephane; Nottet, Nicolas; Almouzni, Genevieve; Teulade-Fichou, Mare-Paule; Schertzer, Michael; Perderiset, Mylène; Londoño-Vallejo, Arturo; Debatisse, Michelle; Gilson, Eric; Ye, Jing

2018-05-03

Hard-to-replicate regions of chromosomes (e.g., pericentromeres, centromeres, and telomeres) impede replication fork progression, eventually leading, in the event of replication stress, to chromosome fragility, aging, and cancer. Our knowledge of the mechanisms controlling the stability of these regions is essentially limited to telomeres, where fragility is counteracted by the shelterin proteins. Here we show that the shelterin subunit TRF2 ensures progression of the replication fork through pericentromeric heterochromatin, but not centromeric chromatin. In a process involving its N-terminal basic domain, TRF2 binds to pericentromeric Satellite III sequences during S phase, allowing the recruitment of the G-quadruplex-resolving helicase RTEL1 to facilitate fork progression. We also show that TRF2 is required for the stability of other heterochromatic regions localized throughout the genome, paving the way for future research on heterochromatic replication and its relationship with aging and cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

ESR evidence for 2 coexisting liquid phases in deeply supercooled bulk water

PubMed Central

Banerjee, D.; Bhat, S. N.; Bhat, S. V.; Leporini, D.

2009-01-01

Using electron spin resonance spectroscopy (ESR), we measure the rotational mobility of probe molecules highly diluted in deeply supercooled bulk water and negligibly constrained by the possible ice fraction. The mobility increases above the putative glass transition temperature of water, Tg = 136 K, and smoothly connects to the thermodynamically stable region by traversing the so called “no man's land” (the range 150–235 K), where it is believed that the homogeneous nucleation of ice suppresses the liquid water. Two coexisting fractions of the probe molecules are evidenced. The 2 fractions exhibit different mobility and fragility; the slower one is thermally activated (low fragility) and is larger at low temperatures below a fragile-to-strong dynamic cross-over at ≈225 K. The reorientation of the probe molecules decouples from the viscosity below ≈225 K. The translational diffusion of water exhibits a corresponding decoupling at the same temperature [Chen S-H, et al. (2006) The violation of the Stokes–Einstein relation in supercooled water. Proc Natl Acad Sci USA 103:12974–12978]. The present findings are consistent with key issues concerning both the statics and the dynamics of supercooled water, namely the large structural fluctuations [Poole PH, Sciortino F, Essmann U, Stanley HE (1992) Phase behavior of metastable water. Nature 360:324–328] and the fragile-to-strong dynamic cross-over at ≈228 K [Ito K, Moynihan CT, Angell CA (1999) Thermodynamic determination of fragility in liquids and a fragile-to-strong liquid transition in water. Nature 398:492–494]. PMID:19556546

TARGETED TREATMENTS IN AUTISM AND FRAGILE X SYNDROME

PubMed Central

Gürkan, C. Kağan; Hagerman, Randi J.

2012-01-01

Autism is a neurodevelopmental disorder consisting of a constellation of symptoms that sometimes occur as part of a complex disorder characterized by impairments in social interaction, communication and behavioral domains. It is a highly disabling disorder and there is a need for treatment targeting the core symptoms. Although autism is accepted as highly heritable, there is no genetic cure at this time. Autism is shown to be linked to several genes and is a feature of some complex genetic disorders, including fragile X syndrome (FXS), fragile X premutation involvement, tuberous sclerosis and Rett syndrome. The term autism spectrum disorders (ASDs) covers autism, Asperger syndrome and pervasive developmental disorders (PDD-NOS) and the etiologies are heterogeneous. In recent years, targeted treatments have been developed for several disorders that have a known specific genetic cause leading to autism. Since there are significant molecular and neurobiological overlaps among disorders, targeted treatments developed for a specific disorder may be helpful in ASD of unknown etiology. Examples of this are two drug classes developed to treat FXS, Arbaclofen, a GABAB agonist, and mGluR5 antagonists, and both may be helpful in autism without FXS. The mGluR5 antagonists are also likely to have a benefit in the aging problems of fragile X premutation carriers, the fragile X –associated tremor ataxia syndrome (FXTAS) and the Parkinsonism that can occur in aging patients with fragile X syndrome. Targeted treatments in FXS which has a well known genetic etiology may lead to new targeted treatments in autism. PMID:23162607

Adverse Housing Conditions and Early-Onset Delinquency.

PubMed

Jackson, Dylan B; Newsome, Jamie; Lynch, Kellie R

2017-09-01

Housing constitutes an important health resource for children. Research has revealed that, when housing conditions are unfavorable, they can interfere with child health, academic performance, and cognition. Little to no research, however, has considered whether adverse housing conditions and early-onset delinquency are significantly associated with one another. This study explores the associations between structural and non-structural housing conditions and delinquent involvement during childhood. Data from the Fragile Families and Child Wellbeing Study (FFCWS) were employed in this study. Each adverse housing condition was significantly associated with early-onset delinquency. Even so, disarray and deterioration were only significantly linked to early delinquent involvement in the presence of health/safety hazards. The predicted probability of early-onset delinquency among children exposed to housing risks in the presence of health/safety hazards was nearly three times as large as the predicted probability of early-onset delinquency among children exposed only to disarray and/or deterioration, and nearly four times as large as the predicted probability of early-onset delinquency among children exposed to none of the adverse housing conditions. The findings suggest that minimizing housing-related health/safety hazards among at-risk subsets of the population may help to alleviate other important public health concerns-particularly early-onset delinquency. Addressing household health/safety hazards may represent a fruitful avenue for public health programs aimed at the prevention of early-onset delinquency. © Society for Community Research and Action 2017.

Fragile X syndrome

MedlinePlus

Martin-Bell syndrome; Marker X syndrome ... Fragile X syndrome is caused by a change in a gene called FMR1 . A small part of the gene ... repeated several times in one area of the X chromosome. The more repeats, the more likely the ...

The gendered health workforce: mixed methods analysis from four fragile and post-conflict contexts.

PubMed

Witter, Sophie; Namakula, Justine; Wurie, Haja; Chirwa, Yotamu; So, Sovanarith; Vong, Sreytouch; Ros, Bandeth; Buzuzi, Stephen; Theobald, Sally

2017-12-01

It is well known that the health workforce composition is influenced by gender relations. However, little research has been done which examines the experiences of health workers through a gender lens, especially in fragile and post-conflict states. In these contexts, there may not only be opportunities to (re)shape occupational norms and responsibilities in the light of challenges in the health workforce, but also threats that put pressure on resources and undermine gender balance, diversity and gender responsive human resources for health (HRH). We present mixed method research on HRH in four fragile and post-conflict contexts (Sierra Leone, Zimbabwe, northern Uganda and Cambodia) with different histories to understand how gender influences the health workforce. We apply a gender analysis framework to explore access to resources, occupations, values, decision-making and power. We draw largely on life histories with male and female health workers to explore their lived experiences, but complement the analysis with evidence from surveys, document reviews, key informant interviews, human resource data and stakeholder mapping. Our findings shed light on patterns of employment: in all contexts women predominate in nursing and midwifery cadres, are under-represented in management positions and are clustered in lower paying positions. Gendered power relations shaped by caring responsibilities at the household level, affect attitudes to rural deployment and women in all contexts face challenges in accessing both pre- and in-service training. Coping strategies within conflict emerged as a key theme, with experiences here shaped by gender, poverty and household structure. Most HRH regulatory frameworks did not sufficiently address gender concerns. Unless these are proactively addressed post-crisis, health workforces will remain too few, poorly distributed and unable to meet the health needs of vulnerable populations. Practical steps need to be taken to identify gender barriers proactively and engage staff and communities on best approaches for change. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Dietary Considerations in Autism Spectrum Disorders: The Potential Role of Protein Digestion and Microbial Putrefaction in the Gut-Brain Axis

PubMed Central

Sanctuary, Megan R.; Kain, Jennifer N.; Angkustsiri, Kathleen; German, J. Bruce

2018-01-01

Children with autism spectrum disorders (ASD), characterized by a range of behavioral abnormalities and social deficits, display high incidence of gastrointestinal (GI) co-morbidities including chronic constipation and diarrhea. Research is now increasingly able to characterize the “fragile gut” in these children and understand the role that impairment of specific GI functions plays in the GI symptoms associated with ASD. This mechanistic understanding is extending to the interactions between diet and ASD, including food structure and protein digestive capacity in exacerbating autistic symptoms. Children with ASD and gut co-morbidities exhibit low digestive enzyme activity, impaired gut barrier integrity and the presence of antibodies specific for dietary proteins in the peripheral circulation. These findings support the hypothesis that entry of dietary peptides from the gut lumen into the vasculature are associated with an aberrant immune response. Furthermore, a subset of children with ASD exhibit high concentrations of metabolites originating from microbial activity on proteinaceous substrates. Taken together, the combination of specific protein intakes poor digestion, gut barrier integrity, microbiota composition and function all on a background of ASD represents a phenotypic pattern. A potential consequence of this pattern of conditions is that the fragile gut of some children with ASD is at risk for GI symptoms that may be amenable to improvement with specific dietary changes. There is growing evidence that shows an association between gut dysfunction and dysbiosis and ASD symptoms. It is therefore urgent to perform more experimental and clinical research on the “fragile gut” in children with ASD in order to move toward advancements in clinical practice. Identifying those factors that are of clinical value will provide an evidence-based path to individual management and targeted solutions; from real time sensing to the design of diets with personalized protein source/processing, all to improve GI function in children with ASD. PMID:29868601

The gendered health workforce: mixed methods analysis from four fragile and post-conflict contexts

PubMed Central

Witter, Sophie; Namakula, Justine; Wurie, Haja; Chirwa, Yotamu; So, Sovanarith; Vong, Sreytouch; Ros, Bandeth; Buzuzi, Stephen; Theobald, Sally

2017-01-01

Abstract It is well known that the health workforce composition is influenced by gender relations. However, little research has been done which examines the experiences of health workers through a gender lens, especially in fragile and post-conflict states. In these contexts, there may not only be opportunities to (re)shape occupational norms and responsibilities in the light of challenges in the health workforce, but also threats that put pressure on resources and undermine gender balance, diversity and gender responsive human resources for health (HRH). We present mixed method research on HRH in four fragile and post-conflict contexts (Sierra Leone, Zimbabwe, northern Uganda and Cambodia) with different histories to understand how gender influences the health workforce. We apply a gender analysis framework to explore access to resources, occupations, values, decision-making and power. We draw largely on life histories with male and female health workers to explore their lived experiences, but complement the analysis with evidence from surveys, document reviews, key informant interviews, human resource data and stakeholder mapping. Our findings shed light on patterns of employment: in all contexts women predominate in nursing and midwifery cadres, are under-represented in management positions and are clustered in lower paying positions. Gendered power relations shaped by caring responsibilities at the household level, affect attitudes to rural deployment and women in all contexts face challenges in accessing both pre- and in-service training. Coping strategies within conflict emerged as a key theme, with experiences here shaped by gender, poverty and household structure. Most HRH regulatory frameworks did not sufficiently address gender concerns. Unless these are proactively addressed post-crisis, health workforces will remain too few, poorly distributed and unable to meet the health needs of vulnerable populations. Practical steps need to be taken to identify gender barriers proactively and engage staff and communities on best approaches for change. PMID:29244105

Dietary Considerations in Autism Spectrum Disorders: The Potential Role of Protein Digestion and Microbial Putrefaction in the Gut-Brain Axis.

PubMed

Sanctuary, Megan R; Kain, Jennifer N; Angkustsiri, Kathleen; German, J Bruce

2018-01-01

Children with autism spectrum disorders (ASD), characterized by a range of behavioral abnormalities and social deficits, display high incidence of gastrointestinal (GI) co-morbidities including chronic constipation and diarrhea. Research is now increasingly able to characterize the "fragile gut" in these children and understand the role that impairment of specific GI functions plays in the GI symptoms associated with ASD. This mechanistic understanding is extending to the interactions between diet and ASD, including food structure and protein digestive capacity in exacerbating autistic symptoms. Children with ASD and gut co-morbidities exhibit low digestive enzyme activity, impaired gut barrier integrity and the presence of antibodies specific for dietary proteins in the peripheral circulation. These findings support the hypothesis that entry of dietary peptides from the gut lumen into the vasculature are associated with an aberrant immune response. Furthermore, a subset of children with ASD exhibit high concentrations of metabolites originating from microbial activity on proteinaceous substrates. Taken together, the combination of specific protein intakes poor digestion, gut barrier integrity, microbiota composition and function all on a background of ASD represents a phenotypic pattern. A potential consequence of this pattern of conditions is that the fragile gut of some children with ASD is at risk for GI symptoms that may be amenable to improvement with specific dietary changes. There is growing evidence that shows an association between gut dysfunction and dysbiosis and ASD symptoms. It is therefore urgent to perform more experimental and clinical research on the "fragile gut" in children with ASD in order to move toward advancements in clinical practice. Identifying those factors that are of clinical value will provide an evidence-based path to individual management and targeted solutions; from real time sensing to the design of diets with personalized protein source/processing, all to improve GI function in children with ASD.

Investigation of Mineral Transformations in Wet Supercritical CO2 by Electron Microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arey, Bruce W.; Kovarik, Libor; Wang, Zheming

2011-10-10

The capture and storage of carbon dioxide and other greenhouse gases in deep geologic formations represents one of the most promising options for mitigating the impacts of greenhouse gases on global warming. In this regard, mineral-fluid interactions are of prime importance since such reactions can result in the long term sequestration of CO2 by trapping in mineral phases. Recently it has been recognized that interactions with neat to water-saturated non-aqueous fluids are of prime importance in understanding mineralization reactions since the introduced CO2 is likely to contain water initially or soon after injection and the supercritical CO2 (scCO2) is lessmore » dense than the aqueous phase which can result in a buoyant scCO2 plume contacting the isolating caprock. As a result, unraveling the molecular/microscopic mechanisms of mineral transformation in neat to water saturated scCO2 has taken on an added important. In this study, we are examining the interfacial reactions of the olivine mineral forsterite (Mg2SiO4) over a range of water contents up to and including complete water saturation in scCO2. The surface precipitates that form on the reacted forsterite grains are extremely fragile and difficult to experimentally characterize. In order to address this issue we have developed experimental protocols for preparing and imaging electron-transparent samples from fragile structures. These electron-transparent samples are then examined using a combination of STEM/EDX, FIB-TEM, and helium ion microscope (HIM) imaging (Figures 1-3). This combination of capabilities has provided unique insight into the geochemical processes that occur on scCO2 reacted mineral surfaces. The experimental procedures and protocols that have been developed also have useful applications for examining fragile structures on a wide variety of materials. This research was performed using EMSL, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research located at Pacific Northwest National Laboratory.« less

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

NASA Astrophysics Data System (ADS)

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 probabilistic hazard maps. Through the GPS and embedded calculation function based on the aforementioned fragility results, these applications can be used in the field for a quick estimation of possible building damage, as well as a decision support system for fishermen (whether or not they should move their boats to the deep sea upon tsunami arrival).

How Mean is the Mean?

PubMed Central

Speelman, Craig P.; McGann, Marek

2013-01-01

In this paper we voice concerns about the uncritical manner in which the mean is often used as a summary statistic in psychological research. We identify a number of implicit assumptions underlying the use of the mean and argue that the fragility of these assumptions should be more carefully considered. We examine some of the ways in which the potential violation of these assumptions can lead us into significant theoretical and methodological error. Illustrations of alternative models of research already extant within Psychology are used to explore methods of research less mean-dependent and suggest that a critical assessment of the assumptions underlying its use in research play a more explicit role in the process of study design and review. PMID:23888147

Fragile X Syndrome: Genetic Predisposition to Psychopathology.

ERIC Educational Resources Information Center

Bregman, Joel D.; And Others

1988-01-01

Psychiatric evaluation of 14 males (ages 3-27 years) with the fragile X syndrome found pervasive hyperactivity, impulsivity, and attentional deficits, and a significant degree of anxiety. However, diagnostic criteria for persistent pervasive developmental disorder and autism were not met. (Author/DB)

76 FR 13621 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel; Teleconference

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

... Announcement (FOA) DD11-004, and Pilot Longitudinal Data Collection to Inform Public Health--Fragile X Syndrome... Collection to Inform Public Health--Fragile X Syndrome, FOA DD11-007.'' Contact Person for More Information...

75 FR 78997 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Pilot...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-17

... Collection To Inform Public Health--Fragile X Syndrome, DD11-007, Initial Review In accordance with Section... Collection to Inform Public Health--Fragile X Syndrome, DD11-007, initial review.'' Contact Person for More...

Metadata for selecting or submitting generic seismic vulnerability functions via GEM's vulnerability database

USGS Publications Warehouse

Jaiswal, Kishor

2013-01-01

This memo lays out a procedure for the GEM software to offer an available vulnerability function for any acceptable set of attributes that the user specifies for a particular building category. The memo also provides general guidelines on how to submit the vulnerability or fragility functions to the GEM vulnerability repository, stipulating which attributes modelers must provide so that their vulnerability or fragility functions can be queried appropriately by the vulnerability database. An important objective is to provide users guidance on limitations and applicability by providing the associated modeling assumptions and applicability of each vulnerability or fragility function.

Tuning the fragility of a glass-forming liquid by curving space.

PubMed

Sausset, François; Tarjus, Gilles; Viot, Pascal

2008-10-10

We investigate the influence of space curvature, and of the associated frustration, on the dynamics of a model glass former: a monatomic liquid on the hyperbolic plane. We find that the system's fragility, i.e., the sensitivity of the relaxation time to temperature changes, increases as one decreases the frustration. As a result, curving space provides a way to tune fragility and make it as large as wanted. We also show that the nature of the emerging "dynamic heterogeneities", another distinctive feature of slowly relaxing systems, is directly connected to the presence of frustration-induced topological defects.

Clinical aspects of the fragile X syndrome.

PubMed

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.

Effect of tailored educational intervention to improve self-care maintenance and quality of life in postmenopausal osteoporotic women after a fragility fracture: the Guardian Angel® study.

PubMed

Basilici Zannetti, Emanuela; D'Agostino, Fabio; Cittadini, Noemi; Feola, Maurizio; Pennini, Annalisa; Rao, Cecilia; Vellone, Ercole; Tarantino, Umberto; Alvaro, Rosaria

2017-01-01

Osteoporosis has a significant impact on affected patients. Healthcare providers should encourage postmenopausal women to improve self-care maintenance behaviors and quality of life following a fragility fracture. The aims of this study were to a) develop two new instruments for measuring, respectively, self-care maintenance and quality of life, in postmenopausal women with osteoporosis; b) evaluate the effectiveness of a tailored educational intervention to improve self-care maintenance and quality of life after a fragility fracture in postmenopausal women. For the first aim, a cross-sectional study will be performed; for the second aim, a multicenter, quasi-experimental, interventional design will be used. A convenience sample of postmenopausal women admitted to 44 hospitals in Italy with a diagnosis of bone fragility fracture will be enrolled and surveyed at 7, 30, 60 and 180 days after discharge. Trained nurses will conduct the educational intervention. The new instruments will allow the measurement of self-care and quality of life in postmenopausal women following a fragility fracture. Through tailored educational interventions, women can be helped to take their medications correctly, adopt a healthy lifestyle, reduce the occurrence of bone fractures, and have a better quality of life.

Development of hazard-compatible building fragility and vulnerability models

USGS Publications Warehouse

Karaca, E.; Luco, N.

2008-01-01

We present a methodology for transforming the structural and non-structural fragility functions in HAZUS into a format that is compatible with conventional seismic hazard analysis information. The methodology makes use of the building capacity (or pushover) curves and related building parameters provided in HAZUS. Instead of the capacity spectrum method applied in HAZUS, building response is estimated by inelastic response history analysis of corresponding single-degree-of-freedom systems under a large number of earthquake records. Statistics of the building response are used with the damage state definitions from HAZUS to derive fragility models conditioned on spectral acceleration values. Using the developed fragility models for structural and nonstructural building components, with corresponding damage state loss ratios from HAZUS, we also derive building vulnerability models relating spectral acceleration to repair costs. Whereas in HAZUS the structural and nonstructural damage states are treated as if they are independent, our vulnerability models are derived assuming "complete" nonstructural damage whenever the structural damage state is complete. We show the effects of considering this dependence on the final vulnerability models. The use of spectral acceleration (at selected vibration periods) as the ground motion intensity parameter, coupled with the careful treatment of uncertainty, makes the new fragility and vulnerability models compatible with conventional seismic hazard curves and hence useful for extensions to probabilistic damage and loss assessment.

Mosaicism for the FMR1 gene influences adaptive skills development in fragile X-affected males

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, I.L.; Sudhalter, V.; Nolin, S.L.

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 developmentmore » 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.« less

Ebselen exhibits glycation-inhibiting properties and protects against osmotic fragility of human erythrocytes in vitro.

PubMed

Soares, Julio C M; Folmer, Vanderlei; Da Rocha, João B T; Nogueira, Cristina W

2014-05-01

Diabetic status is associated with an increase on oxidative stress markers in humans and animal models. We have investigated the in vitro effects of high concentrations of glucose on the profile of oxidative stress and osmotic fragility of blood from control and diabetic patients; we considered whether its antioxidant properties could afford some protection against glucose-induced osmotic fragility, and whether ebselen could act as an inhibitor of hemoglobin glycation. Raising blood glucose to 5-100 mmol/L resulted in a concentration-dependent increase of glycated hemoglobin (HbA1c; P < 0.001) and thiobarbituric acid reactive species (TBA-RS) content (P < 0.004). Non-protein SH groups (NPSH) also increased significantly as the concentration of glucose increased up to 30 mmol/L (P < 0.001). The osmotic fragility was more pronounced in blood of uncontrolled diabetic patients than in these non-diabetic subjects. Ebselen significantly reduced the glucose-induced increase in osmotic fragility and inhibited HbA1c formation (P < 0.0001). These results indicate that blood from patients with uncontrolled diabetes are more sensitive to osmotic shock than from patients with controlled diabetes and control subjects in relation to increased production of free radicals in vivo. © 2014 International Federation for Cell Biology.

Fragility and super-strong character of non-stoichiometric chalcogenides: implications on melt homogenization

NASA Astrophysics Data System (ADS)

Ravindren, Sriram; Gunasekera, Kapila; Boolchand, Punit; Micoulaut, Matthieu

2014-03-01

The kinetics of homogenization of binary AsxSe100-x melts in the As concentration range 0%

Alterations of amino acids and monoamine metabolism in male Fmr1 knockout mice: a putative animal model of the human fragile X mental retardation syndrome.

PubMed

Gruss, M; Braun, K

2001-01-01

The Fragile X syndrome, a common form of mental retardation in humans, is caused by silencing the fragile X mental retardation (FMR1) gene leading to the absence of the encoded fragile X mental retardation protein 1 (FMRP). We describe morphological and behavioral abnormalities for both affected humans and Fmr1 knockout mice, a putative animal model for the human Fragile X syndrome. The aim of the present study was to identify possible neurochemical abnormalities in Fmr1 knockout mice, with particular focus on neurotransmission. Significant region-specific differences of basal neurotransmitter and metabolite levels were found between wildtype and Fmr1 knockout animals, predominantly in juveniles (post-natal days 28 to 31). Adults (postnatal days 209 to 221) showed only few abnormalities as compared with the wildtype. In juvenile knockout mice, aspartate and taurine were especially increased in cortical regions, striatum, hippocampus, cerebellum, and brainstem. In addition, juveniles showed an altered balance between excitatory and inhibitory amino acids in the caudal cortex, hippocampus, and brainstem. We detected very few differences in monoamine turnover in both age stages. The results presented here provide the first evidence that lack of FMRP expression in FMRP knockout mice is accompanied by age-dependent, region-specific alterations in neurotransmission.

Pragmatic Language Features of Mothers With the FMR1 Premutation Are Associated With the Language Outcomes of Adolescents and Young Adults With Fragile X Syndrome.

PubMed

Klusek, Jessica; McGrath, Sara E; Abbeduto, Leonard; Roberts, Jane E

2016-02-01

Pragmatic language difficulties have been documented as part of the FMR1 premutation phenotype, yet the interplay between these features in mothers and the language outcomes of their children with fragile X syndrome is unknown. This study aimed to determine whether pragmatic language difficulties in mothers with the FMR1 premutation are related to the language development of their children. Twenty-seven mothers with the FMR1 premutation and their adolescent/young adult sons with fragile X syndrome participated. Maternal pragmatic language violations were rated from conversational samples using the Pragmatic Rating Scale (Landa et al., 1992). Children completed standardized assessments of vocabulary, syntax, and reading. Maternal pragmatic language difficulties were significantly associated with poorer child receptive vocabulary and expressive syntax skills, with medium effect sizes. This work contributes to knowledge of the FMR1 premutation phenotype and its consequences at the family level, with the goal of identifying modifiable aspects of the child's language-learning environment that may promote the selection of treatments targeting the specific needs of families affected by fragile X. Findings contribute to our understanding of the multifaceted environment in which children with fragile X syndrome learn language and highlight the importance of family-centered intervention practices for this group.

Making metadata usable in a multi-national research setting.

PubMed

Ellul, Claire; Foord, Joanna; Mooney, John

2013-11-01

SECOA (Solutions for Environmental Contrasts in Coastal Areas) is a multi-national research project examining the effects of human mobility on urban settlements in fragile coastal environments. This paper describes the setting up of a SECOA metadata repository for non-specialist researchers such as environmental scientists and tourism experts. Conflicting usability requirements of two groups - metadata creators and metadata users - are identified along with associated limitations of current metadata standards. A description is given of a configurable metadata system designed to grow as the project evolves. This work is of relevance for similar projects such as INSPIRE. Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Understanding fragile X syndrome from a mother's perspective: Challenges and resilience

PubMed Central

Weber, Chantel Lynette

2016-01-01

The purpose of this study is to communicate findings from a case study on a South African mother with three children diagnosed with full mutation fragile X syndrome (FXS). The participant is an unaffected carrier of FXS. Research has shown that mothers of children with FXS often experience high levels of parenting stress and low levels of psychological well-being. However, observations made have piqued curiosity about their positivity and determination to carry on each day raising children diagnosed with FXS. The aim is to develop a better understanding of the manner in which a mother of children with FXS make sense of her situation, to gain further insight into the specific resilience processes she acquired. A qualitative case study approach was followed, gathering data through semi-structured interviews based on open-ended questions. The findings offer new insights into a South African mother's life raising children with FXS. Even though there is very limited support and little awareness of FXS in South Africa, she still found ways to seek help, and find solutions to every day challenges. The study conclusions discourage blind stereotyping of mothers of children with FXS as vulnerable only. Future research should concentrate on promoting awareness, education, advocacy, and support for individuals with FXS in South Africa. PMID:27104339

Elevated occupational transportation fatalities among older workers in Oregon: an empirical investigation.

PubMed

Walters, Jaime K; Olson, Ryan; Karr, Justin; Zoller, Erika; Cain, Daniel; Douglas, Jae P

2013-04-01

Older workers have an elevated risk of being killed on the job, and transportation incidents involving vehicles or mobile machinery are especially deadly for this group. The present study was designed to address the research gap in understanding contributing factors to these incidents and recommend evidence-based guidelines for interventions. We gathered and analyzed data from several sources, including the Oregon Fatality Assessment and Control Evaluation program, the Oregon Workers' Compensation system, the Census of Fatal Occupational Injuries, the Bureau of Labor Statistics, and peer reviewed research literatures. Rates and rate ratios (RR) were used to evaluate excess risk among groups. The results of this study show that older workers in Oregon have an elevated risk of fatality both in all events (RR=3.0, 95% CI 2.2-4.0) and transportation events (RR=3.6, 95% CI 2.4-5.4). Additional analyses and extant literature supports our hypotheses that multiple risk factors contribute to the phenomenon, including (a) hazard exposure, (b) organization of work, (c) physical fragility, and (d) normative cognitive, sensory, and psychomotor changes that occur with age. The evidence-based framework proposed may provide valuable guidance for developing safety interventions that protect older workers. Copyright © 2013 Elsevier Ltd. All rights reserved.

The influences of LuxX in Escherichia coli biofilm formation and improving teacher quality through the Bio-Bus Program

NASA Astrophysics Data System (ADS)

Robbins, Chandan Morris

The objectives of this work are: (1) to agarose-stabilize fragile biofilms for quantitative structure analysis; (2) to understand the influences of LuxS on biofilm formation; (3) to improve teacher quality by preparing Georgia's middle school science teachers to integrate inquiry-based, hands-on research modules in the classroom. Quantitative digital image analysis demonstrated the effectiveness of the agarose stabilization technique for generating reproducible measurements of three dimensional biofilm structure. The described method will also benefit researchers who transport their flow cell-cultivated biofilms to a core facility for imaging. AI-2-dependent and independent effects of LuxS on biofilm-related phenotypes were revealed, suggesting that LuxS is a versatile enzyme, possessing multiple functions in E. coli ecology that could assist E. coli in adapting to diverse conditions. Overall, the work presented in this dissertation supported the concept that QS, biofilm formation, and cell adhesion are largely related. Additionally, through this project, teachers enhanced content knowledge and confidence levels, mastered innovative teaching strategies and integrated inquiry-based, inter-disciplinary, hands-on activities in the classroom. As a result, student learning was enhanced, and Georgia's students are better equipped to become tomorrow's leaders. INDEX WORDS: Biofilm, Escherichia coli, Quorum sensing, LuxS, Autoinducer-2, Microbial ecology

Cardiac Autonomic Regulation in Autism and Fragile X Syndrome: A Review

PubMed Central

Klusek, Jessica; Roberts, Jane E.; Losh, Molly

2014-01-01

Despite the significance of efforts to understand the biological basis of autism, progress in this area has been hindered, in part, by the considerable heterogeneity in the disorder. Fragile X syndrome (FXS), a monogenic condition associated with high risk for autism, may pave the way for the dissection of biological heterogeneity within idiopathic autism. This paper adopts a cross-syndrome biomarker approach to evaluate potentially overlapping profiles of cardiac arousal dysregulation (and broader autonomic dysfunction) in autism and FXS. Approaches such as this, aimed at delineating shared mechanisms across genetic syndromes, hold great potential for improving diagnostic precision, promoting earlier identification, and uncovering key systems that can be targeted in pharmaceutical/behavioral interventions. Biomarker approaches may be vital to deconstructing complex psychiatric disorders, and are currently promoted as such by major research initiatives such as the NIMH Research Domain Criteria (RDoC). Evidence reviewed here supports physiological dysregulation in a subset of individuals with autism, as evidenced by patterns of hyperarousal and dampened parasympathetic vagal tone, which overlap with the well-documented physiological profile of FXS. Moreover, there is growing support for a link between aberrant cardiac activity and core deficits associated with autism, such as communication and social impairment. The delineation of physiological mechanisms common to autism and FXS could lend insight into relationships between genetic etiology and behavioral endstates, highlighting FMR1 as a potential candidate gene. Research gaps and potential pitfalls are discussed to inform timely, well-controlled biomarker research that will ultimately promote better diagnosis and treatment of autism and associated conditions. PMID:25420222

Leaving no one behind: lessons on rebuilding health systems in conflict- and crisis-affected states.

PubMed

Martineau, Tim; McPake, Barbara; Theobald, Sally; Raven, Joanna; Ensor, Tim; Fustukian, Suzanne; Ssengooba, Freddie; Chirwa, Yotamu; Vong, Sreytouch; Wurie, Haja; Hooton, Nick; Witter, Sophie

2017-01-01

Conflict and fragility are increasing in many areas of the world. This context has been referred to as the 'new normal' and affects a billion people. Fragile and conflict-affected states have the worst health indicators and the weakest health systems. This presents a major challenge to achieving universal health coverage. The evidence base for strengthening health systems in these contexts is very weak and hampered by limited research capacity, challenges relating to insecurity and apparent low prioritisation of this area of research by funders. This article reports on findings from a multicountry consortium examining health systems rebuilding post conflict/crisis in Sierra Leone, Zimbabwe, northern Uganda and Cambodia. Across the ReBUILD consortium's interdisciplinary research programme, three cross-cutting themes have emerged through our analytic process: communities, human resources for health and institutions. Understanding the impact of conflict/crisis on the intersecting inequalities faced by households and communities is essential for developing responsive health policies. Health workers demonstrate resilience in conflict/crisis, yet need to be supported post conflict/crisis with appropriate policies related to deployment and incentives that ensure a fair balance across sectors and geographical distribution. Postconflict/crisis contexts are characterised by an influx of multiple players and efforts to support coordination and build strong responsive national and local institutions are critical. The ReBUILD evidence base is starting to fill important knowledge gaps, but further research is needed to support policy makers and practitioners to develop sustainable health systems, without which disadvantaged communities in postconflict and postcrisis contexts will be left behind in efforts to promote universal health coverage.

Health Policy, Health Systems Research and Analysis Capacity Assessment of the School of Public Health, University of Ghana.

PubMed

Agyepong, I A; Anniah, K; Aikins, M; Akweongo, P; Esena, R; Mirzoev, T

2015-09-01

Health Policy and Systems Research and Analysis (HPSR&A) is an applied science that deals with complexity as it tries to provide lessons, tools and methods to understand and improve health systems and health policy. It is defined by the kinds of questions asked rather than a particular methodology. Our objective was to assess capacity and capacity strengthening needs for HPSR&A conduct and teaching in the University of Ghana School of Public Health (UG-SPH). We conceptualized dynamically inter-related levels of capacity as contextual, institutional and individual. The study had a cross sectional, mixed methods design. Data collection involved desk review, ,an in-depth interview, focus group discussions (FGD) and an interviewer administered questionnaire with closed and open ended items. Netmap was used as a tool in the FGD. At all levels, HPSR&A capacity exists in Ghana but is somewhat fragile. The fragility reflects in part contextual challenges related to national income and priorities as well as the fact that globally HPSR&A remains an emerging field. At the contextual level, Institutions involved in some way or other in HPSR&A were part of larger organizations with broader mandates. Only a handful of SPH staff indicated that they specifically do teaching and /or research related to HPSR&A. There is a need to raise awareness of the field of HPSR&A and its potential contributions to health sector development; build upon already existing contextual, institutional and individual capacity; and also attract and develop the next generation of researchers and teachers.

Characteristics of seismic and tsunami fragility of industries, revealed by the 2011 Tohoku-oki earthquake

NASA Astrophysics Data System (ADS)

Kuwahara, Y.; Hasegawa, I.; Yoshimi, M.; Namegaya, Y.; Horikawa, H.; Nakai, M.; Masuda, S.

2013-12-01

We have developed seismic and tsunami fragility curves of industries by using damage data of industrial companies, estimated strong motions and estimated tsunami heights of the 2011 Tohoku-oki earthquake. The damage data were obtained from 7,019 industrial companies, which responded to an inquiry survey to 30,000 companies carried out by the Regional Innovation Research Center of Tohoku University. As a damage level indicator for each company, we introduced a ratio of an economical damage of physical fixed assets excluding lands to previous balance of the physical fixed assets. The estimated strong motions of the 2011 Tohoku-oki earthquake at all the sites of the companies were from the database of the so-called QuiQuake system (Quick estimation system for earthquake maps triggered by observation records) operated by the National Institute of Advanced Industrial Science and Technology (AIST). It is noted that the estimated data were obtained by taking account of seismic local site effects and the actually observed ones. The tsunami height data at each site of the company were obtained by interpolating the confirmed data compiled by the 2011 Tohoku Earthquake Tsunami Joint Survey Group (2013). A frequency-damage level distribution for each seismic intensity is well correlated with a binominal distribution where the only parameter characterizing the distribution is an average value of the damage levels in each seismic intensity. The averaged damage levels of all the data for respective seismic intensity scales are 0.016 for SIj 5 lower, 0.042 for SIj 5 upper, 0.067 for SIj 6 lower, 0.092 for SIj 6 upper, and 0.16 for SIj 7, where SIj stands for the Japanese seismic intensity scale. The data were sorted into several classified industries and fragility curve for each classified industry is found to have a different character from each other. The tsunami fragilities are also obtained as a function of the tsunami height in the same way. The averaged damage levels of all the data for respective tsunami height are 0.051 for less than 3m, 0.23 for 0.3-1 m, 0.27 for 1-2 m, 0.43 for 2-3 m, and 0.50 for higher than 3m, respectively. These fragility curves can be useful not only to estimate economic damages for future huge earthquakes, but also to rapidly assess the damage just after earthquakes.

Pathways for diffusion in the potential energy landscape of the network glass former SiO2

NASA Astrophysics Data System (ADS)

Niblett, S. P.; Biedermann, M.; Wales, D. J.; de Souza, V. K.

2017-10-01

We study the dynamical behaviour of a computer model for viscous silica, the archetypal strong glass former, and compare its diffusion mechanism with earlier studies of a fragile binary Lennard-Jones liquid. Three different methods of analysis are employed. First, the temperature and time scale dependence of the diffusion constant is analysed. Negative correlation of particle displacements influences transport properties in silica as well as in fragile liquids. We suggest that the difference between Arrhenius and super-Arrhenius diffusive behaviour results from competition between the correlation time scale and the caging time scale. Second, we analyse the dynamics using a geometrical definition of cage-breaking transitions that was proposed previously for fragile glass formers. We find that this definition accurately captures the bond rearrangement mechanisms that control transport in open network liquids, and reproduces the diffusion constants accurately at low temperatures. As the same method is applicable to both strong and fragile glass formers, we can compare correlation time scales in these two types of systems. We compare the time spent in chains of correlated cage breaks with the characteristic caging time and find that correlations in the fragile binary Lennard-Jones system persist for an order of magnitude longer than those in the strong silica system. We investigate the origin of the correlation behaviour by sampling the potential energy landscape for silica and comparing it with the binary Lennard-Jones model. We find no qualitative difference between the landscapes, but several metrics suggest that the landscape of the fragile liquid is rougher and more frustrated. Metabasins in silica are smaller than those in binary Lennard-Jones and contain fewer high-barrier processes. This difference probably leads to the observed separation of correlation and caging time scales.

Fragility and hysteretic creep in frictional granular jamming.

PubMed

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)<φ<φ(2)) and exhibits simultaneous exponential rise in pressure and exponential decrease in 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.

Thermal and fragility aspects of microwave synthesized glasses containing transition metal ions and heavy metal ions

NASA Astrophysics Data System (ADS)

Renuka, C.; Viswanatha, R.; Reddy, C. Narayana

2017-02-01

A simple, clean and energy efficient microwave heating route is used to prepare glasses in the systems xMnO-33(0.09PbCl2:0.91PbO)-(67-x) NaPO3 and xPbCl2-33PbO-(67-x) NaPO3 where 0.1 ≤ x ≤ 4 (mol%). Thermal data extracted from differential scanning calorimetry (DSC) thermograms are used to study the composition dependence of glass transition temperature (Tg), heat capacity, thermal stability and fragility. The decrease in glass transition temperature with modifier oxide (Na2O + MnO) content can be ascribed to network degradation and the volume increasing effect caused by PbCl2. The change in heat capacity of MnPb glass being greater than that of PbNP glass, suggests that MnPb glasses are more covalent than PbNP glasses. DSC thermograms taken at different heating rates (φ) reveal the dependence of Tg on φ, and the thermal stability of the glass increases due to MnO addition. Fragility aspects have also been studied by calculating the fragility functions ( {{Δ {{C}}_{{p}} }/{{{C}_{{pl}} }}{{and}}{[ {{NBO}} ]}/{{{V}_{{m}}3 {{T}}_{{g}} }}} ). Results obtained from both the fragility functions compare well and reveal the dependence of fragility functions on modifier content and PbCl2 mol%. Further, the decrease in Tg and Hv are suggested to be due to the increase in the number of non-bridging oxygens, which results in the lowering of stiffness and rigidity of the glass network. Analysis of the infrared spectra confirms that the glassy matrix is composed of P-O-P, P-O-Pb, P=O and P-O- bonding.

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

PubMed

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.

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

PubMed

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.

Identification of fragile X pre-mutation carriers in the Chinese obstetric population using a robust FMR1 polymerase chain reaction assay: implications for screening and prenatal diagnosis.

PubMed

Cheng, Y Ky; Lin, C Sw; Kwok, Y Ky; Chan, Y M; Lau, T K; Leung, T Y; Choy, K W

2017-04-01

There is significant morbidity associated with fragile X syndrome. Unfortunately, most maternal carriers are clinically silent during their reproductive years. Because of this, many experts have put forward the notion of preconception or prenatal fragile X carrier screening for females. This study aimed to determine the prevalence of fragile X syndrome pre-mutation and asymptomatic full-mutation carriers in a Chinese pregnant population, and the distribution of cytosine-guanine-guanine (CGG) repeat numbers using a robust fragile X mental retardation 1 (FMR1) polymerase chain reaction assay. This was a cross-sectional survey in prospectively recruited pregnant women from a university hospital in Hong Kong. Chinese pregnant women without a family history of fragile X syndrome were recruited between April 2013 and May 2015. A specific FMR1 polymerase chain reaction assay was performed on peripheral blood to determine the CGG repeat number of the FMR1 gene. Prenatal counselling was offered to full-mutation and pre-mutation carriers. In 2650 Chinese pregnant women, two individuals with pre-mutation alleles (0.08%, one in 1325) and one asymptomatic woman with full-mutation (0.04%, one in 2650) alleles were identified. The overall prevalence of pre-mutation and full-mutation alleles was 0.11% (1 in 883). Furthermore, 30 (1.1%) individuals with intermediate alleles were detected. In the 2617 women with normal CGG repeats, the most common CGG repeat allele was 30. The overall prevalence of pre-mutation and asymptomatic full-mutation carriers in the Chinese pregnant population was one in 883, detected by a new FMR1 polymerase chain reaction assay.

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

PubMed

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.

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

PubMed

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.

Dysregulation of mTOR signaling in fragile X syndrome.

PubMed

Sharma, Ali; Hoeffer, Charles A; Takayasu, Yukihiro; Miyawaki, Takahiro; McBride, Sean M; Klann, Eric; Zukin, R Suzanne

2010-01-13

Fragile X syndrome, the most common form of inherited mental retardation and leading genetic cause of autism, is caused by transcriptional silencing of the Fmr1 gene. The fragile X mental retardation protein (FMRP), the gene product of Fmr1, is an RNA binding protein that negatively regulates translation in neurons. The Fmr1 knock-out mouse, a model of fragile X syndrome, exhibits cognitive deficits and exaggerated metabotropic glutamate receptor (mGluR)-dependent long-term depression at CA1 synapses. However, the molecular mechanisms that link loss of function of FMRP to aberrant synaptic plasticity remain unclear. The mammalian target of rapamycin (mTOR) signaling cascade controls initiation of cap-dependent translation and is under control of mGluRs. Here we show that mTOR phosphorylation and activity are elevated in hippocampus of juvenile Fmr1 knock-out mice by four functional readouts: (1) association of mTOR with regulatory associated protein of mTOR; (2) mTOR kinase activity; (3) phosphorylation of mTOR downstream targets S6 kinase and 4E-binding protein; and (4) formation of eukaryotic initiation factor complex 4F, a critical first step in cap-dependent translation. Consistent with this, mGluR long-term depression at CA1 synapses of FMRP-deficient mice is exaggerated and rapamycin insensitive. We further show that the p110 subunit of the upstream kinase phosphatidylinositol 3-kinase (PI3K) and its upstream activator PI3K enhancer PIKE, predicted targets of FMRP, are upregulated in knock-out mice. Elevated mTOR signaling may provide a functional link between overactivation of group I mGluRs and aberrant synaptic plasticity in the fragile X mouse, mechanisms relevant to impaired cognition in fragile X syndrome.

The Efficacy of Melatonin for Sleep Problems in Children with Autism, Fragile X Syndrome, or Autism and Fragile X Syndrome

PubMed Central

Wirojanan, Juthamas; Jacquemont, Sebastien; Diaz, Rafael; Bacalman, Susan; Anders, Thomas F.; Hagerman, Randi J.; Goodlin-Jones, Beth L.

2009-01-01

Study Objective: To determine the efficacy of melatonin on sleep problems in children with autistic spectrum disorder (ASD) and fragile X syndrome (FXS). Methods: A 4-week, randomized, double blind, placebo-controlled, crossover design was conducted following a 1-week baseline period. Either melatonin, 3 mg, or placebo was given to participants for 2 weeks and then alternated for another 2 weeks. Sleep variables, including sleep duration, sleep-onset time, sleep-onset latency time, and the number of night awakenings, were recorded using an Actiwatch and from sleep diaries completed by parents. All participants had been thoroughly assessed for ASD and also had DNA testing for the diagnosis of FXS. Results: Data were successfully obtained from the 12 of 18 subjects who completed the study (11 males, age range 2 to 15.25 years, mean 5.47, SD 3.6). Five participants met diagnostic criteria for ASD, 3 for FXS alone, 3 for FXS and ASD, and 1 for fragile X premutation. Eight out of 12 had melatonin first. The conclusions from a nonparametric repeated-measures technique indicate that mean night sleep duration was longer on melatonin than placebo by 21 minutes (p = .02), mean sleep-onset latency was shorter by 28 minutes (p = .0001), and mean sleep-onset time was earlier by 42 minutes (p = .02). Conclusion: The results of this study support the efficacy and tolerability of melatonin treatment for sleep problems in children with ASD and FXS. Citation: Wirojanan J; Jacquemont S; Diaz R; Bacalman S; Anders TF; Hagerman RJ; Goodlin-Jones BL. The Efficacy of Melatonin for Sleep Problems in Children with Autism, Fragile X Syndrome, or Autism and Fragile X Syndrome. J Clin Sleep Med 2009;5(2):145-150. PMID:19968048

Lifetime prevalence of mood and anxiety disorders in fragile X premutation carriers.

PubMed

Bourgeois, James A; Seritan, Andreea L; Casillas, E Melina; Hessl, David; Schneider, Andrea; Yang, Ying; Kaur, Inderjeet; Cogswell, Jennifer B; Nguyen, Danh V; Hagerman, Randi J

2011-02-01

The authors studied the lifetime prevalence of DSM-IV-TR psychiatric disorders in a population of adults with the fragile X premutation. The Structured Clinical Interview for DSM-IV was conducted, from 2007-2008, in 85 individuals with the fragile X premutation, 47 with the fragile X-associated tremor/ataxia syndrome (FXTAS; 33 male, 14 female; mean age = 66 years) and 38 without FXTAS (16 male, 22 female; mean age = 52 years). Lifetime prevalence for mood and anxiety disorders among carriers with and without FXTAS was compared to available age-specific population estimates from the National Comorbidity Survey Replication (NCS-R). Among participants with FXTAS, 30 (65%) met lifetime DSM-IV-TR criteria for a mood disorder; 24 (52%) met lifetime DSM-IV-TR criteria for an anxiety disorder. Among the non-FXTAS participants, there were 15 instances of lifetime mood disorder (42%) and 18 of lifetime anxiety disorder (47%). When compared to age-specific NCS-R data, the lifetime prevalences of any mood disorder (P < .0001), major depressive disorder (P < .0001), any anxiety disorder (P < .0001), panic disorder (P = .006), specific phobia (P = .0003), and posttraumatic stress disorder (P = .004) were significantly higher in participants with FXTAS. The lifetime rates of social phobia in individuals with the premutation without FXTAS were significantly higher than NCS-R data (P = .001). This sample of carriers of the fragile X premutation had a notably high lifetime risk of mood and anxiety disorders. Mood and anxiety disorders may be part of the clinical phenotype of the fragile X premutation conditions, especially in carriers with FXTAS. Clinicians encountering these patients are advised to consider FXTAS as a neuropsychiatric syndrome as well as a neurologic disorder. © Copyright 2011 Physicians Postgraduate Press, Inc.

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

PubMed

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.

Fragility non-hip fracture patients are at risk.

PubMed

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.

Gulf of Mexico Deep-Sea Coral Ecosystem Studies, 2008-2011

USGS Publications Warehouse

Kellogg, Christina A.

2009-01-01

Most people are familiar with tropical coral reefs, located in warm, well-illuminated, shallow waters. However, corals also exist hundreds and even thousands of meters below the ocean surface, where it is cold and completely dark. These deep-sea corals, also known as cold-water corals, have become a topic of interest due to conservation concerns over the impacts of trawling, exploration for oil and gas, and climate change. Although the existence of these corals has been known since the 1800s, our understanding of their distribution, ecology, and biology is limited due to the technical difficulties of conducting deep-sea research. DISCOVRE (DIversity, Systematics, and COnnectivity of Vulnerable Reef Ecosystems) is a new U.S. Geological Survey (USGS) program focused on deep-water coral ecosystems in the Gulf of Mexico. This integrated, multidisciplinary, international effort investigates a variety of topics related to unique and fragile deep-sea coral ecosystems from the microscopic level to the ecosystem level, including components of microbiology, population genetics, paleoecology, food webs, taxonomy, community ecology, physical oceanography, and mapping.

Public Health Literature Review of Fragile X Syndrome

PubMed Central

Raspa, Melissa; Wheeler, Anne C.; Riley, Catharine

2017-01-01

OBJECTIVES The purpose of this systematic literature review is to describe what is known about fragile X syndrome (FXS) and to identify research gaps. The results can be used to help inform future public health research and provide pediatricians with up-to-date information about the implications of the condition for individuals and their families. METHODS An electronic literature search was conducted, guided by a variety of key words. The search focused on 4 areas of both clinical and public health importance: (1) the full mutation phenotype, (2) developmental trajectories across the life span, (3) available interventions and treatments, and (4) impact on the family. A total of 661 articles were examined and 203 were included in the review. RESULTS The information is presented in the following categories: developmental profile (cognition, language, functional skills, and transition to adulthood), social-emotional profile (cooccurring psychiatric conditions and behavior problems), medical profile (physical features, seizures, sleep, health problems, and physiologic features), treatment and interventions (educational/behavioral, allied health services, and pharmacologic), and impact on the family (family environment and financial impact). Research gaps also are presented. CONCLUSIONS The identification and treatment of FXS remains an important public health and clinical concern. The information presented in this article provides a more robust understanding of FXS and the impact of this complex condition for pediatricians. Despite a wealth of information about the condition, much work remains to fully support affected individuals and their families. PMID:28814537

Utility of the Hebb-Williams Maze Paradigm for Translational Research in Fragile X Syndrome: A Direct Comparison of Mice and Humans.

PubMed

Boutet, Isabelle; Collin, Charles A; MacLeod, Lindsey S; Messier, Claude; Holahan, Matthew R; Berry-Kravis, Elizabeth; Gandhi, Reno M; Kogan, Cary S

2018-01-01

To generate meaningful information, translational research must employ paradigms that allow extrapolation from animal models to humans. However, few studies have evaluated translational paradigms on the basis of defined validation criteria. We outline three criteria for validating translational paradigms. We then evaluate the Hebb-Williams maze paradigm (Hebb and Williams, 1946; Rabinovitch and Rosvold, 1951) on the basis of these criteria using Fragile X syndrome (FXS) as model disease. We focused on this paradigm because it allows direct comparison of humans and animals on tasks that are behaviorally equivalent (criterion #1) and because it measures spatial information processing, a cognitive domain for which FXS individuals and mice show impairments as compared to controls (criterion #2). We directly compared the performance of affected humans and mice across different experimental conditions and measures of behavior to identify which conditions produce comparable patterns of results in both species. Species differences were negligible for Mazes 2, 4, and 5 irrespective of the presence of visual cues, suggesting that these mazes could be used to measure spatial learning in both species. With regards to performance on the first trial, which reflects visuo-spatial problem solving, Mazes 5 and 9 without visual cues produced the most consistent results. We conclude that the Hebb-Williams mazes paradigm has the potential to be utilized in translational research to measure comparable cognitive functions in FXS humans and animals (criterion #3).

Public Health Literature Review of Fragile X Syndrome.

PubMed

Raspa, Melissa; Wheeler, Anne C; Riley, Catharine

2017-06-01

The purpose of this systematic literature review is to describe what is known about fragile X syndrome (FXS) and to identify research gaps. The results can be used to help inform future public health research and provide pediatricians with up-to-date information about the implications of the condition for individuals and their families. An electronic literature search was conducted, guided by a variety of key words. The search focused on 4 areas of both clinical and public health importance: (1) the full mutation phenotype, (2) developmental trajectories across the life span, (3) available interventions and treatments, and (4) impact on the family. A total of 661 articles were examined and 203 were included in the review. The information is presented in the following categories: developmental profile (cognition, language, functional skills, and transition to adulthood), social-emotional profile (cooccurring psychiatric conditions and behavior problems), medical profile (physical features, seizures, sleep, health problems, and physiologic features), treatment and interventions (educational/behavioral, allied health services, and pharmacologic), and impact on the family (family environment and financial impact). Research gaps also are presented. The identification and treatment of FXS remains an important public health and clinical concern. The information presented in this article provides a more robust understanding of FXS and the impact of this complex condition for pediatricians. Despite a wealth of information about the condition, much work remains to fully support affected individuals and their families. Copyright © 2017 by the American Academy of Pediatrics.

Social Approach and Emotion Recognition in Fragile X Syndrome

ERIC Educational Resources Information Center

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…

21 CFR 864.6600 - Osmotic fragility test.

Code of Federal Regulations, 2011 CFR

2011-04-01

... test. (a) Identification. An osmotic fragility test is a device used to determine the resistance of red blood cells to hemolysis (destruction) in varying concentrations of hypotonic saline solutions. (b) Classification. Class I (general controls). This device is exempt from the premarket notification procedures in...

21 CFR 864.6600 - Osmotic fragility test.

Code of Federal Regulations, 2012 CFR

2012-04-01

... test. (a) Identification. An osmotic fragility test is a device used to determine the resistance of red blood cells to hemolysis (destruction) in varying concentrations of hypotonic saline solutions. (b) Classification. Class I (general controls). This device is exempt from the premarket notification procedures in...

21 CFR 864.6600 - Osmotic fragility test.

Code of Federal Regulations, 2014 CFR

2014-04-01

... test. (a) Identification. An osmotic fragility test is a device used to determine the resistance of red blood cells to hemolysis (destruction) in varying concentrations of hypotonic saline solutions. (b) Classification. Class I (general controls). This device is exempt from the premarket notification procedures in...