WorldWideScience

Sample records for underlying complex disease

  1. Worms under stress: C. elegans stress response and its relevance to complex human disease and aging

    NARCIS (Netherlands)

    Rodriguez Sanchez, M.; Snoek, L.B.; Bono, de M.; Kammenga, J.E.

    2013-01-01

    Many organisms have stress response pathways, components of which share homology with players in complex human disease pathways. Research on stress response in the nematode worm Caenorhabditis elegans has provided detailed insights into the genetic and molecular mechanisms underlying complex human

  2. Assessing the impact of vaccination programmes on burden of disease: Underlying complexities and statistical methods.

    Science.gov (United States)

    Mealing, Nicole; Hayen, Andrew; Newall, Anthony T

    2016-06-08

    It is important to assess the impact a vaccination programme has on the burden of disease after it is implemented. For example, this may reveal herd immunity effects or vaccine-induced shifts in the incidence of disease or in circulating strains or serotypes of the pathogen. In this article we summarise the key features of infectious diseases that need to be considered when trying to detect any changes in the burden of diseases at a population level as a result of vaccination efforts. We outline the challenges of using routine surveillance databases to monitor infectious diseases, such as the identification of diseased cases and the availability of vaccination status for cases. We highlight the complexities in modelling the underlying patterns in infectious disease rates (e.g. presence of autocorrelation) and discuss the main statistical methods that can be used to control for periodicity (e.g. seasonality) and autocorrelation when assessing the impact of vaccination programmes on burden of disease (e.g. cosinor terms, generalised additive models, autoregressive processes and moving averages). For some analyses, there may be multiple methods that can be used, but it is important for authors to justify the method chosen and discuss any limitations. We present a case study review of the statistical methods used in the literature to assess the rotavirus vaccination programme impact in Australia. The methods used varied and included generalised linear models and descriptive statistics. Not all studies accounted for autocorrelation and seasonality, which can have a major influence on results. We recommend that future analyses consider the strength and weakness of alternative statistical methods and justify their choice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Genetics of complex diseases

    DEFF Research Database (Denmark)

    Mellerup, Erling; Møller, Gert Lykke; Koefoed, Pernille

    2012-01-01

    A complex disease with an inheritable component is polygenic, meaning that several different changes in DNA are the genetic basis for the disease. Such a disease may also be genetically heterogeneous, meaning that independent changes in DNA, i.e. various genotypes, can be the genetic basis...... for the disease. Each of these genotypes may be characterized by specific combinations of key genetic changes. It is suggested that even if all key changes are found in genes related to the biology of a certain disease, the number of combinations may be so large that the number of different genotypes may be close...

  4. Complex Interfaces Under Change

    DEFF Research Database (Denmark)

    Rosbjerg, Dan

    The hydrosphere is dynamic across the major compartments of the Earth system: the atmosphere, the oceans and seas, the land surface water, and the groundwater within the strata below the two last compartments. The global geography of the hydrosphere essentially depends on thermodynamic and mechan...... these interfaces and interfaced compartments and processes. Climate, sea-level, oceanographic currents and hydrological processes are all affected, while anthropogenic changes are often intense in the geographic settings corresponding to such interfaces.......The hydrosphere is dynamic across the major compartments of the Earth system: the atmosphere, the oceans and seas, the land surface water, and the groundwater within the strata below the two last compartments. The global geography of the hydrosphere essentially depends on thermodynamic...... and mechanical processes that develop within this structure. Water-related processes at the interfaces between the compartments are complex, depending both on the interface itself, and on the characteristics of the interfaced compartments. Various aspects of global change directly or indirectly impact...

  5. Medical biostatistics for complex diseases

    National Research Council Canada - National Science Library

    Emmert-Streib, Frank; Dehmer, Matthias

    2010-01-01

    ... and factors that may all act together to lead to a frank disorder in the individual patient. Based on this assumption, the evaluation of such complex diseases with respect to the affected cells and cell systems by appropriate biostatistical analysis, including high capacity assays and highly developed multi-parameter evaluation-assays, is a clear me...

  6. Complex Plasma Research Under Extreme Conditions

    International Nuclear Information System (INIS)

    Ishihara, Osamu

    2008-01-01

    Complex plasma research under extreme conditions is described. The extreme conditions include low-dimensionality for self-organized structures of dust particles, dust magnetization in high magnetic field, criticality in phase transition, and cryogenic environment for Coulomb crystals and dust dynamics.

  7. Complex liver cysts in Autosomal Dominant Polycystic Kidney Disease.

    Science.gov (United States)

    Farooq, Zerwa; Behzadi, Ashkan Heshmatzadeh; Blumenfeld, Jon D; Zhao, Yize; Prince, Martin R

    To determine prevalence of complex liver cysts in Autosomal Dominant Polycystic Kidney Disease (ADPKD). Abdominal MRI in 186 ADPKD subjects were evaluated by two independent observers to determine prevalence of complex liver cysts. 23 (12%) of subjects, had at least 1 complex cyst. Only 8 (4%) were reported to have a complex cyst prospectively, representing an under-reporting rate of 65%. Median total cyst volume was 66-times greater for subjects with complex cysts compared to subjects without (p<0.0001). Complex hepatic cysts were observed in 12% of ADPKD cases, occurring more frequently in livers with extensive cystic involvement. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Network-based analysis of complex diseases.

    Science.gov (United States)

    Liu, Z-P; Wang, Y; Zhang, X-S; Chen, L

    2012-02-01

    Complex diseases are commonly believed to be caused by the breakdown of several correlated genes rather than individual genes. The availability of genome-wide data of high-throughput experiments provides us with new opportunity to explore this hypothesis by analysing the disease-related biomolecular networks, which are expected to bridge genotypes and disease phenotypes and further reveal the biological mechanisms of complex diseases. In this study, the authors review the existing network biology efforts to study complex diseases, such as breast cancer, diabetes and Alzheimer's disease, using high-throughput data and computational tools. Specifically, the authors categorise these existing methods into several classes based on the research topics, that is, disease genes, dysfunctional pathways, network signatures and drug-target networks. The authors also summarise the pros and cons of those methods from both computation and application perspectives, and further discuss research trends and future topics of this promising field.

  9. Phototaxis of Cyanobacteria under Complex Light Environments

    Directory of Open Access Journals (Sweden)

    Minsu Kim

    2017-04-01

    Full Text Available Photosynthetic bacteria are capable of producing their own food via photosynthesis. Unsurprisingly, they evolved the ability to move toward better light conditions (i.e., phototaxis. In a recent article in mBio, Chau et al. tuned the wavelength, flux, direction, and timing of light input and characterized the motility of the unicellular cyanobacterium Synechocystis sp. strain PCC6803 (R. M. W. Chau, D. Bhaya, and K. C. Huang, mBio 8:e02330-16, 2017, https://doi.org/10.1128/mBio.02330-16. The results revealed an intricate dependence of the motility on various light inputs, laying the fundamental groundwork toward understanding phototaxis under complex and dynamic light environments.

  10. Complex networks under dynamic repair model

    Science.gov (United States)

    Chaoqi, Fu; Ying, Wang; Kun, Zhao; Yangjun, Gao

    2018-01-01

    Invulnerability is not the only factor of importance when considering complex networks' security. It is also critical to have an effective and reasonable repair strategy. Existing research on network repair is confined to the static model. The dynamic model makes better use of the redundant capacity of repaired nodes and repairs the damaged network more efficiently than the static model; however, the dynamic repair model is complex and polytropic. In this paper, we construct a dynamic repair model and systematically describe the energy-transfer relationships between nodes in the repair process of the failure network. Nodes are divided into three types, corresponding to three structures. We find that the strong coupling structure is responsible for secondary failure of the repaired nodes and propose an algorithm that can select the most suitable targets (nodes or links) to repair the failure network with minimal cost. Two types of repair strategies are identified, with different effects under the two energy-transfer rules. The research results enable a more flexible approach to network repair.

  11. Bioenergetic Origins of Complexity and Disease

    Science.gov (United States)

    Wallace, D.C.

    2015-01-01

    The organizing power of energy flow is hypothesized to be the origin of biological complexity and its decline the basis of “complex” diseases and aging. Energy flow through organic systems creates nucleic acids, which store information, and the annual accumulation of information generates today's complexity. Energy flow through our bodies is mediated by the mitochondria, symbiotic bacteria whose genomes encompass the mitochondrial DNA (mtDNA) and more than 1000 nuclear genes. Inherited and/or epigenomic variation of the mitochondrial genome determines our initial energetic capacity, but the age-related accumulation of somatic cell mtDNA mutations further erodes energy flow, leading to disease. This bioenergetic perspective on disease provides a unifying pathophysiological and genetic mechanism for neuropsychiatric diseases such as Alzheimer and Parkinson Disease, metabolic diseases such as diabetes and obesity, autoimmune diseases, aging, and cancer. PMID:22194359

  12. Epigenetic alterations underlying autoimmune diseases.

    Science.gov (United States)

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein

    2016-01-01

    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases.

  13. Epigenetic Epidemiology of Complex Diseases Using Twins

    DEFF Research Database (Denmark)

    Tan, Qihua

    2013-01-01

    through multiple epigenetic mechanisms. This paper reviews the new developments in using twins to study disease-related epigenetic alterations, links them to lifetime environmental exposure with a focus on the discordant twin design and proposes novel data-analytical approaches with the aim of promoting...... a more efficient use of twins in epigenetic studies of complex human diseases....

  14. Chronic Venous Disease under pressure

    NARCIS (Netherlands)

    S.W.I. Reeder (Suzan)

    2013-01-01

    textabstractIn chapter 1 we provide a general introduction of this thesis. Chronic venous disease (CVD) is a common medical condition that affects 2-64% of the worldwide population and leads to leg ulcers in 1% of the Western population. Venous leg ulceration (VLU) has an unfavorable prognosis with

  15. Complexity, fractals, disease time, and cancer.

    Science.gov (United States)

    Spillman, W B; Robertson, J L; Huckle, W R; Govindan, B S; Meissner, K E

    2004-12-01

    Despite many years of research, a method to precisely and quantitatively determine cancer disease state remains elusive. Current practice for characterizing solid tumors involves the use of varying systems of tumor grading and staging and thus leaves diagnosis and clinical staging dependent on the experience and skill of the physicians involved. Although numerous disease markers have been identified, no combination of them has yet been found that produces a quantifiable and reliable measure of disease state. Newly developed genomic markers and other measures based on the developing sciences of complexity offer promise that this situation may soon be changed for the better. In this paper, we examine the potential of two measures of complexity, fractal dimension and percolation, for use as components of a yet to be determined "disease time" vector that more accurately quantifies disease state. The measures are applied to a set of micrographs of progressive rat hepatoma and analyzed in terms of their correlation with cell differentiation, ratio of tumor weight to rat body weight and tumor growth time. The results provide some support for the idea that measures of complexity could be important elements of any future cancer "disease time" vector.

  16. Complexity of Propositional Proofs Under a Promise

    Czech Academy of Sciences Publication Activity Database

    Dershowitz, N.; Tzameret, Iddo

    2010-01-01

    Roč. 11, č. 3 (2010), s. 1-29 ISSN 1529-3785 Institutional research plan: CEZ:AV0Z10190503 Keywords : theory * promise problems * propositional proof complexity * random 3CNF * resolution Subject RIV: BA - General Mathematics Impact factor: 1.391, year: 2010 http://dl.acm.org/ citation .cfm?doid=1740582.1740586

  17. Complexity of Propositional Proofs Under a Promise

    Czech Academy of Sciences Publication Activity Database

    Dershowitz, N.; Tzameret, Iddo

    2010-01-01

    Roč. 11, č. 3 (2010), s. 1-29 ISSN 1529-3785 Institutional research plan: CEZ:AV0Z10190503 Keywords : theory * promise problems * propositional proof complexity * random 3CNF * resolution Subject RIV: BA - General Mathematics Impact factor: 1.391, year: 2010 http://dl.acm.org/citation.cfm?doid=1740582.1740586

  18. Nephronophthisis and medullary cystic kidney disease complex

    Directory of Open Access Journals (Sweden)

    Stanišić Marijana

    2005-01-01

    Full Text Available Background. Nephronophthisis and medullary cystic kidney disease complex refers to the genetic heterogeneous group of inherited tubulointerstital nephritis. Nephronophthisis comprises at last 3 clinical manifestations, has the autosomal recessive pattern of inheritance, appears early in life and is the most frequent inherited kidney disease that causes terminal renal failure in childhood, while medullary cystic kidney disease has the autosomal dominant pattern of inheritance, is less frequent, and terminal renal failure appears later in life. These two forms have similar clinical and morphological findings but extrarenal manifestations, the median ages of occurrence of terminal renal failure, and siblings presence help us distinguish these diseases. Case report. In this article we illustrated the case of a 20- years old patient with the suspicion of having complex nephornophthisis and medullary cystic kidney disease based upon mild renal failure, seen in routinely taken laboratory findings and bilateral cysts in corticomedullary region of the kidneys verified on abdominal ultrasound examination. Conclusion. This disease should rise suspicion in children or adolescents with progressive renal failure, a typical clinical manifestation, blood and urine samples results, bilateral cysts in the corticomedullary region of the kidneys seen during ultrasound examination of the kidneys and family inheritance.

  19. Endocrine autoimmune disease: genetics become complex.

    Science.gov (United States)

    Wiebolt, Janneke; Koeleman, Bobby P C; van Haeften, Timon W

    2010-12-01

    The endocrine system is a frequent target in pathogenic autoimmune responses. Type 1 diabetes and autoimmune thyroid disease are the prevailing examples. When several diseases cluster together in one individual, the phenomenon is called autoimmune polyglandular syndrome. Progress has been made in understanding the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases such as autoimmune polyglandular syndrome type 1, immunodysregulation, polyendocrinopathy, enteropathy, X-linked and primary immune deficiencies helped uncover the role of key regulators in the preservation of immune tolerance. Alleles of the major histocompatibility complex have been known to contribute to the susceptibility to most forms of autoimmunity for more than 3 decades. Furthermore, sequencing studies revealed three non-major histocompatibility complex loci and some disease specific loci, which control T lymphocyte activation or signalling. Recent genome-wide association studies (GWAS) have enabled acceleration in the identification of novel (non-HLA) loci and hence other relevant immune response pathways. Interestingly, several loci are shared between autoimmune diseases, and surprisingly some work in opposite direction. This means that the same allele which predisposes to a certain autoimmune disease can be protective in another. Well powered GWAS in type 1 diabetes has led to the uncovering of a significant number of risk variants with modest effect. These studies showed that the innate immune system may also play a role in addition to the adaptive immune system. It is anticipated that next generation sequencing techniques will uncover other (rare) variants. For other autoimmune disease (such as autoimmune thyroid disease) GWAS are clearly needed. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.

  20. Coeliac disease : investigation of the genetic factors underlying coeliac disease

    NARCIS (Netherlands)

    Belzen, M.J. (Martine Juliana) van

    2003-01-01

    Coeliac disease is a common food intolerance with a complex genetic aetiology. It is caused by ingestion of gluten peptides from wheat and related proteins from barley and rye in genetically susceptible individuals. The disease affects the small intestine and leads to abnormalities ranging from the

  1. Barrier experiment: Shock initiation under complex loading

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-01-12

    The barrier experiments are a variant of the gap test; a detonation wave in a donor HE impacts a barrier and drives a shock wave into an acceptor HE. The question we ask is: What is the trade-off between the barrier material and threshold barrier thickness to prevent the acceptor from detonating. This can be viewed from the perspective of shock initiation of the acceptor subject to a complex pressure drive condition. Here we consider key factors which affect whether or not the acceptor undergoes a shock-to-detonation transition. These include the following: shock impedance matches for the donor detonation wave into the barrier and then the barrier shock into the acceptor, the pressure gradient behind the donor detonation wave, and the curvature of detonation front in the donor. Numerical simulations are used to illustrate how these factors affect the reaction in the acceptor.

  2. Complex social contagion makes networks more vulnerable to disease outbreaks

    Science.gov (United States)

    Campbell, Ellsworth; Salathé, Marcel

    2013-01-01

    Social network analysis is now widely used to investigate the dynamics of infectious disease spread. Vaccination dramatically disrupts disease transmission on a contact network, and indeed, high vaccination rates can potentially halt disease transmission altogether. Here, we build on mounting evidence that health behaviors - such as vaccination, and refusal thereof - can spread across social networks through a process of complex contagion that requires social reinforcement. Using network simulations that model health behavior and infectious disease spread, we find that under otherwise identical conditions, the process by which the health behavior spreads has a very strong effect on disease outbreak dynamics. This dynamic variability results from differences in the topology within susceptible communities that arise during the health behavior spreading process, which in turn depends on the topology of the overall social network. Our findings point to the importance of health behavior spread in predicting and controlling disease outbreaks. PMID:23712758

  3. Network biology concepts in complex disease comorbidities

    DEFF Research Database (Denmark)

    Hu, Jessica Xin; Thomas, Cecilia Engel; Brunak, Søren

    2016-01-01

    The co-occurrence of diseases can inform the underlying network biology of shared and multifunctional genes and pathways. In addition, comorbidities help to elucidate the effects of external exposures, such as diet, lifestyle and patient care. With worldwide health transaction data now often being...

  4. Unravelling metal mobility under complex contaminant signatures.

    Science.gov (United States)

    de Souza Machado, Anderson Abel; Spencer, Kate L; Zarfl, Christiane; O'Shea, Francis T

    2018-05-01

    Metals are concerning pollutants in estuaries, where contamination can undergo significant remobilisation driven by physico-chemical forcing. Environmental concentrations of metals in estuarine sediments are often higher than natural backgrounds, but show no contiguity to potential sources. Thus, better understanding the metal mobility in estuaries is essential to improve identification of pollution sources and their accountability for environmental effects. This study aims to identify the key biogeochemical drivers of metal mobilisation on contaminated estuarine sediments through (1) evaluation of the potential mobilisation under controlled conditions, and (2) investigation of the relevance of metal mobilisation for in situ pollution levels in an area with multiple contaminant sources. Sediments from a saltmarsh adjacent to a coastal landfill, a marina, and a shipyard on the Thames Estuary (Essex, UK) were exposed in the laboratory (24h, N=96, 20°C) to water under various salinity, pH, and redox potential. Major cations, Fe(II), and trace metal concentrations were analysed in the leachate and sediment. Salinity, pH and redox had a significant effect on metal mobilisation (pmetal spatial distribution. However, physicochemical parameters explained up to 97% of geochemically normalized metal concentrations in sediments. Organic matter and pH were dominant factors for most of the metal concentrations at the sediment surface. At subsurface, major cations (Ca, Na, Mg and K) were determinant predictors of metal concentrations. Applying the empirical model obtained in the laboratory to geochemical conditions of the studied saltmarsh it was possible to demonstrate that Fe mobilisation regulates the fate of this (and other) metal in that area. Thus, present results highlight the importance of metal mobility to control sediment pollution and estuarine fate of metals. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A Non-Degenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    OpenAIRE

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.; Bearden, Charles F.; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V.; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H.; Grossman, Robert L.; Cox, Nancy J.

    2013-01-01

    Whereas countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. Here, we examine the extent to which Mendelian variation contributes to complex disease risk by mining the medical records of over 110 million patients. We detect thousands of associations between Mendelian and complex diseases, revealing a non-degenerate, phenotypic code that links each complex disorder to a unique collection...

  6. Pathway-based analysis tools for complex diseases: a review.

    Science.gov (United States)

    Jin, Lv; Zuo, Xiao-Yu; Su, Wei-Yang; Zhao, Xiao-Lei; Yuan, Man-Qiong; Han, Li-Zhen; Zhao, Xiang; Chen, Ye-Da; Rao, Shao-Qi

    2014-10-01

    Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehensive understanding of the molecular mechanisms underlying complex diseases. Extensive studies utilizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods-the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available pathway-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are discussed. This review will provide a useful guide to dissect complex diseases. Copyright © 2014 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

  7. A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk.

    Science.gov (United States)

    Blair, David R; Lyttle, Christopher S; Mortensen, Jonathan M; Bearden, Charles F; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H; Grossman, Robert L; Cox, Nancy J; White, Kevin P; Rzhetsky, Andrey

    2013-09-26

    Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this "Mendelian code." Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. A Non-Degenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    Science.gov (United States)

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.; Bearden, Charles F.; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V.; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H.; Grossman, Robert L.; Cox, Nancy J.; White, Kevin P.; Rzhetsky, Andrey

    2013-01-01

    Summary Whereas countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. Here, we examine the extent to which Mendelian variation contributes to complex disease risk by mining the medical records of over 110 million patients. We detect thousands of associations between Mendelian and complex diseases, revealing a non-degenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this “Mendelian code.” Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute non-additively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. PMID:24074861

  9. Major histocompatibility complex genomics and human disease.

    Science.gov (United States)

    Trowsdale, John; Knight, Julian C

    2013-01-01

    Over several decades, various forms of genomic analysis of the human major histocompatibility complex (MHC) have been extremely successful in picking up many disease associations. This is to be expected, as the MHC region is one of the most gene-dense and polymorphic stretches of human DNA. It also encodes proteins critical to immunity, including several controlling antigen processing and presentation. Single-nucleotide polymorphism genotyping and human leukocyte antigen (HLA) imputation now permit the screening of large sample sets, a technique further facilitated by high-throughput sequencing. These methods promise to yield more precise contributions of MHC variants to disease. However, interpretation of MHC-disease associations in terms of the functions of variants has been problematic. Most studies confirm the paramount importance of class I and class II molecules, which are key to resistance to infection. Infection is likely driving the extreme variation of these genes across the human population, but this has been difficult to demonstrate. In contrast, many associations with autoimmune conditions have been shown to be specific to certain class I and class II alleles. Interestingly, conditions other than infections and autoimmunity are also associated with the MHC, including some cancers and neuropathies. These associations could be indirect, owing, for example, to the infectious history of a particular individual and selective pressures operating at the population level.

  10. Forward-time simulations of human populations with complex diseases.

    Directory of Open Access Journals (Sweden)

    Bo Peng

    2007-03-01

    Full Text Available Due to the increasing power of personal computers, as well as the availability of flexible forward-time simulation programs like simuPOP, it is now possible to simulate the evolution of complex human diseases using a forward-time approach. This approach is potentially more powerful than the coalescent approach since it allows simulations of more than one disease susceptibility locus using almost arbitrary genetic and demographic models. However, the application of such simulations has been deterred by the lack of a suitable simulation framework. For example, it is not clear when and how to introduce disease mutants-especially those under purifying selection-to an evolving population, and how to control the disease allele frequencies at the last generation. In this paper, we introduce a forward-time simulation framework that allows us to generate large multi-generation populations with complex diseases caused by unlinked disease susceptibility loci, according to specified demographic and evolutionary properties. Unrelated individuals, small or large pedigrees can be drawn from the resulting population and provide samples for a wide range of study designs and ascertainment methods. We demonstrate our simulation framework using three examples that map genes associated with affection status, a quantitative trait, and the age of onset of a hypothetical cancer, respectively. Nonadditive fitness models, population structure, and gene-gene interactions are simulated. Case-control, sibpair, and large pedigree samples are drawn from the simulated populations and are examined by a variety of gene-mapping methods.

  11. Robustness of Dengue Complex Network under Targeted versus Random Attack

    Directory of Open Access Journals (Sweden)

    Hafiz Abid Mahmood Malik

    2017-01-01

    Full Text Available Dengue virus infection is one of those epidemic diseases that require much consideration in order to save the humankind from its unsafe impacts. According to the World Health Organization (WHO, 3.6 billion individuals are at risk because of the dengue virus sickness. Researchers are striving to comprehend the dengue threat. This study is a little commitment to those endeavors. To observe the robustness of the dengue network, we uprooted the links between nodes randomly and targeted by utilizing different centrality measures. The outcomes demonstrated that 5% targeted attack is equivalent to the result of 65% random assault, which showed the topology of this complex network validated a scale-free network instead of random network. Four centrality measures (Degree, Closeness, Betweenness, and Eigenvector have been ascertained to look for focal hubs. It has been observed through the results in this study that robustness of a node and links depends on topology of the network. The dengue epidemic network presented robust behaviour under random attack, and this network turned out to be more vulnerable when the hubs of higher degree have higher probability to fail. Moreover, representation of this network has been projected, and hub removal impact has been shown on the real map of Gombak (Malaysia.

  12. Privatization of Land Plot Under Integral Real Estate Complex

    Directory of Open Access Journals (Sweden)

    Maruchek A. A.

    2014-10-01

    Full Text Available The article deals with the questions concerning the privatization of a land plot under integral real estate complex. The authors come to conclusion that a number of legislation norms relating to privatization of a land plot do not take into account the construction of an integral real estate complex that could cause some problems in the realization of the right to privatization of the land plot

  13. Mobile hyper spectral optical complex for under satellite ocean research

    Science.gov (United States)

    Nagorniy, Ivan G.; Mayor, Alexander Y.; Salyuk, Pavel A.; Krikun, Vladimir A.

    2015-11-01

    This paper presents the mobile complex to perform continuous measurements of chlorophyll-A concentrations and dissolved organic matter by the laser induced fluorescence method. The obtained data allow evaluating the state of the photosynthetic system of phytoplankton cells. In addition, the complex allows recording the CO2 gas analyzer data, the sea water saltiness sensors, pH, temperature, and solar illumination meter. The mobility this complex ensures a possibility working on different ships and under stationary conditions. The configuration of the complex can be promptly changed for solving the current problem by promptly adding or replacing various devices and sensors. The developed software integrates all devices into the complex. The enclosure of system allows use of conventional laboratory equipment, which is resistant to vibration, but not protected from the effects of the marine environment. Results of in situ measurements performed in Sea of Japan (Peter the Great Bay) by experimental setup are given.

  14. On Perturbative Cubic Nonlinear Schrodinger Equations under Complex Nonhomogeneities and Complex Initial Conditions

    Directory of Open Access Journals (Sweden)

    Magdy A. El-Tawil

    2009-01-01

    Full Text Available A perturbing nonlinear Schrodinger equation is studied under general complex nonhomogeneities and complex initial conditions for zero boundary conditions. The perturbation method together with the eigenfunction expansion and variational parameters methods are used to introduce an approximate solution for the perturbative nonlinear case for which a power series solution is proved to exist. Using Mathematica, the symbolic solution algorithm is tested through computing the possible approximations under truncation procedures. The method of solution is illustrated through case studies and figures.

  15. Alloimmunization in multitransfused liver disease patients: Impact of underlying disease

    Directory of Open Access Journals (Sweden)

    Meenu Bajpai

    2016-01-01

    Full Text Available Introduction: Transfusion support is vital to the management of patients with liver diseases. Repeated transfusions are associated with many risks such as transfusion-transmitted infection, transfusion immunomodulation, and alloimmunization. Materials and Methods: A retrospective data analysis of antibody screening and identification was done from February 2012 to February 2014 to determine the frequency and specificity of irregular red-cell antibodies in multitransfused liver disease patients. The clinical and transfusion records were reviewed. The data was compiled, statistically analyzed, and reviewed. Results: A total of 842 patients were included in our study. Alloantibodies were detected in 5.22% of the patients. Higher rates of alloimmunization were seen in patients with autoimmune hepatitis, cryptogenic liver disease, liver damage due to drugs/toxins, and liver cancer patients. Patients with alcoholic liver disease had a lower rate of alloimmunization. The alloimmunization was 12.7% (23/181 in females and 3.17% (21/661 in males. Antibodies against the Rh system were the most frequent with 27 of 44 alloantibodies (61.36%. The most common alloantibody identified was anti-E (11/44 cases, 25%, followed by anti-C (6/44 cases, 13.63%. Conclusion: Our findings suggest that alloimmunization rate is affected by underlying disease. Provision of Rh and Kell phenotype-matched blood can significantly reduce alloimmunization.

  16. Displacement defect formation in complex oxide crystals under irradiation

    NARCIS (Netherlands)

    Ubizskii, SB; Matkovskii, AO; Mironova-Ulmane, N; Skvortsova, [No Value; Suchocki, A; Zhydachevskii, YA; Potera, P

    The work is devoted to an analysis of formation processes of the radiation displacement defects (RDDs) and colour centres (CCs) in complex oxide crystals under irradiation. The calculation results on: the displacement process simulation as well as an analysis of the RDD and CC accumulation kinetics

  17. Epigenetic mechanisms underlying nervous system diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2018-01-01

    Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene-gene and gene-environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization; noncoding RNA regulation; and RNA editing. These mechanisms are intimately involved in executing fundamental genomic programs, including gene transcription, posttranscriptional RNA processing and transport, translation, X-chromosome inactivation, genomic imprinting, retrotransposon regulation, DNA replication, and DNA repair and the maintenance of genomic stability. For the nervous system, epigenetics offers a novel and robust framework for explaining how brain development and aging occur, neural cellular diversity is generated, synaptic and neural network connectivity and plasticity are mediated, and complex cognitive and behavioral phenotypes are inherited transgenerationally. Epigenetic factors and processes are, not surprisingly, implicated in nervous system disease pathophysiology through several emerging paradigms - mutations and genetic variation in genes encoding epigenetic factors; impairments in epigenetic factor expression, localization, and function; epigenetic mechanisms modulating disease-associated factors and pathways; and the presence of deregulated epigenetic profiles in central and peripheral tissues. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. 9 CFR 381.82 - Diseases of the leukosis complex.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Diseases of the leukosis complex. 381.82 Section 381.82 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... Carcasses and Parts § 381.82 Diseases of the leukosis complex. Carcasses of poultry affected with any one or...

  19. Modeling the Propagation of Mobile Phone Virus under Complex Network

    OpenAIRE

    Yang, Wei; Wei, Xi-liang; Guo, Hao; An, Gang; Guo, Lei; Yao, Yu

    2014-01-01

    Mobile phone virus is a rogue program written to propagate from one phone to another, which can take control of a mobile device by exploiting its vulnerabilities. In this paper the propagation model of mobile phone virus is tackled to understand how particular factors can affect its propagation and design effective containment strategies to suppress mobile phone virus. Two different propagation models of mobile phone viruses under the complex network are proposed in this paper. One is intende...

  20. Central Hypogonadotropic Hypogonadism: Genetic Complexity of a Complex Disease

    Directory of Open Access Journals (Sweden)

    Marco Marino

    2014-01-01

    Full Text Available Central hypogonadotropic hypogonadism (CHH is an emerging pathological condition frequently associated with overweight, metabolic syndrome, diabetes, and midline defects. The genetic mechanisms involve mutations in at least twenty-four genes regulating GnRH neuronal migration, secretion, and activity. So far, the mechanisms underlying CHH, both in prepubertal and in adulthood onset forms, remain unknown in most of the cases. Indeed, all detected gene variants may explain a small proportion of the affected patients (43%, indicating that other genes or epigenetic mechanisms are involved in the onset of CHH. The aim of this review is to summarize the current knowledge on genetic background of CHH, organizing the large amount of data present in the literature in a clear and concise manner, to produce a useful guide available for researchers and clinicians.

  1. Central Hypogonadotropic Hypogonadism: Genetic Complexity of a Complex Disease

    Science.gov (United States)

    2014-01-01

    Central hypogonadotropic hypogonadism (CHH) is an emerging pathological condition frequently associated with overweight, metabolic syndrome, diabetes, and midline defects. The genetic mechanisms involve mutations in at least twenty-four genes regulating GnRH neuronal migration, secretion, and activity. So far, the mechanisms underlying CHH, both in prepubertal and in adulthood onset forms, remain unknown in most of the cases. Indeed, all detected gene variants may explain a small proportion of the affected patients (43%), indicating that other genes or epigenetic mechanisms are involved in the onset of CHH. The aim of this review is to summarize the current knowledge on genetic background of CHH, organizing the large amount of data present in the literature in a clear and concise manner, to produce a useful guide available for researchers and clinicians. PMID:25254043

  2. Molecular diagnostics for the Sigatoka disease complex of banana

    NARCIS (Netherlands)

    Arzanlou, M.; Abeln, E.C.A.; Kema, G.H.J.; Waalwijk, C.; Carlier, J.; Crous, P.W.

    2007-01-01

    The Sigatoka disease complex of banana involves three related ascomycetous fungi, Mycosphaerella fijiensis, M. musicola, and M. eumusae. The exact distribution of these three species and their disease epidemiology remain unclear, because their symptoms and life cycles are rather similar. Disease

  3. A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    DEFF Research Database (Denmark)

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.

    2013-01-01

    with complex diseases are enriched in the genes indicated by this ‘‘Mendelian code.’’ Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset......Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes...... to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated...

  4. Neural correlates underlying micrographia in Parkinson's disease.

    Science.gov (United States)

    Wu, Tao; Zhang, Jiarong; Hallett, Mark; Feng, Tao; Hou, Yanan; Chan, Piu

    2016-01-01

    Micrographia is a common symptom in Parkinson's disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Complexity theory in the management of communicable diseases.

    Science.gov (United States)

    Simmons, Mike

    2003-06-01

    In nature, apparently complex behavioural patterns are the result of repetitive simple rules. Complexity science studies the application of these rules and looks for applications in society. Complexity management opportunities have developed from this science and are providing a revolutionary approach in the constantly changing workplace. This article discusses how complexity management techniques have already been applied to communicable disease management in Wales and suggests further developments. A similar approach is recommended to others in the field, while complexity management probably has wider applications in the NHS, not least in relation to the developing managed clinical networks.

  6. Results of complex treatment of Hodgkin's disease

    International Nuclear Information System (INIS)

    Kolygin, B.A.; Lebedev, S.V.; Borodina, A.F.; Kochurova, N.V.; Malinin, A.P.; Safonova, S.A.; Punanov, Yu.A.

    2000-01-01

    The evaluation of remote results of the complex treatment (polychemotherapy plus radiotherapy) for identification of the forecasting factor which may be applied, by stratification into the risk groups, is carried out. The group of 334 children up to 15 years with lymphogranulomatosis, subjected to not less than 2 cycles of inductive polychemotherapy and consolidating radiotherapy, is analyzed. The irradiation was conducted at the radiotherapeutic devices ROCUS LUE-25 and LUEV-15 M1. The complete remission after the treatment program was fixed by 95.1% of the patients the partial remission-by 6.3%; no effect was noted by 0.6% of the patients. Actuarial 10-year survival constituted 85.9%, the frequency of nonrelapsing flow - 74.3% [ru

  7. Analysis and Reduction of Complex Networks Under Uncertainty.

    Energy Technology Data Exchange (ETDEWEB)

    Ghanem, Roger G [University of Southern California

    2014-07-31

    This effort was a collaboration with Youssef Marzouk of MIT, Omar Knio of Duke University (at the time at Johns Hopkins University) and Habib Najm of Sandia National Laboratories. The objective of this effort was to develop the mathematical and algorithmic capacity to analyze complex networks under uncertainty. Of interest were chemical reaction networks and smart grid networks. The statements of work for USC focused on the development of stochastic reduced models for uncertain networks. The USC team was led by Professor Roger Ghanem and consisted of one graduate student and a postdoc. The contributions completed by the USC team consisted of 1) methodology and algorithms to address the eigenvalue problem, a problem of significance in the stability of networks under stochastic perturbations, 2) methodology and algorithms to characterize probability measures on graph structures with random flows. This is an important problem in characterizing random demand (encountered in smart grid) and random degradation (encountered in infrastructure systems), as well as modeling errors in Markov Chains (with ubiquitous relevance !). 3) methodology and algorithms for treating inequalities in uncertain systems. This is an important problem in the context of models for material failure and network flows under uncertainty where conditions of failure or flow are described in the form of inequalities between the state variables.

  8. Comprehension of Complex Discourse in Different Stages of Huntington's Disease

    Science.gov (United States)

    Saldert, Charlotta; Fors, Angelika; Stroberg, Sofia; Hartelius, Lena

    2010-01-01

    Background: Huntington's disease not only affects motor speech control, but also may have an impact on the ability to produce and understand language in communication. Aims: The ability to comprehend basic and complex discourse was investigated in three different stages of Huntington's disease. Methods & Procedures: In this experimental group…

  9. Analysis and Reduction of Complex Networks Under Uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    Knio, Omar M

    2014-04-09

    This is a collaborative proposal that aims at developing new methods for the analysis and reduction of complex multiscale networks under uncertainty. The approach is based on combining methods of computational singular perturbation (CSP) and probabilistic uncertainty quantification. In deterministic settings, CSP yields asymptotic approximations of reduced-dimensionality “slow manifolds” on which a multiscale dynamical system evolves. Introducing uncertainty raises fundamentally new issues, particularly concerning its impact on the topology of slow manifolds, and means to represent and quantify associated variability. To address these challenges, this project uses polynomial chaos (PC) methods to reformulate uncertain network models, and to analyze them using CSP in probabilistic terms. Specific objectives include (1) developing effective algorithms that can be used to illuminate fundamental and unexplored connections among model reduction, multiscale behavior, and uncertainty, and (2) demonstrating the performance of these algorithms through applications to model problems.

  10. Final Report. Analysis and Reduction of Complex Networks Under Uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    Marzouk, Youssef M. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Coles, T. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Spantini, A. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Tosatto, L. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2013-09-30

    The project was a collaborative effort among MIT, Sandia National Laboratories (local PI Dr. Habib Najm), the University of Southern California (local PI Prof. Roger Ghanem), and The Johns Hopkins University (local PI Prof. Omar Knio, now at Duke University). Our focus was the analysis and reduction of large-scale dynamical systems emerging from networks of interacting components. Such networks underlie myriad natural and engineered systems. Examples important to DOE include chemical models of energy conversion processes, and elements of national infrastructure—e.g., electric power grids. Time scales in chemical systems span orders of magnitude, while infrastructure networks feature both local and long-distance connectivity, with associated clusters of time scales. These systems also blend continuous and discrete behavior; examples include saturation phenomena in surface chemistry and catalysis, and switching in electrical networks. Reducing size and stiffness is essential to tractable and predictive simulation of these systems. Computational singular perturbation (CSP) has been effectively used to identify and decouple dynamics at disparate time scales in chemical systems, allowing reduction of model complexity and stiffness. In realistic settings, however, model reduction must contend with uncertainties, which are often greatest in large-scale systems most in need of reduction. Uncertainty is not limited to parameters; one must also address structural uncertainties—e.g., whether a link is present in a network—and the impact of random perturbations, e.g., fluctuating loads or sources. Research under this project developed new methods for the analysis and reduction of complex multiscale networks under uncertainty, by combining computational singular perturbation (CSP) with probabilistic uncertainty quantification. CSP yields asymptotic approximations of reduceddimensionality “slow manifolds” on which a multiscale dynamical system evolves. Introducing

  11. Mitochondrial dysfunction underlying outer retinal diseases

    DEFF Research Database (Denmark)

    Lefevere, Evy; Toft-Kehler, Anne Katrine; Vohra, Rupali

    2017-01-01

    Dysfunction of photoreceptors, retinal pigment epithelium (RPE) or both contribute to the initiation and progression of several outer retinal disorders. Disrupted Müller glia function might additionally subsidize to these diseases. Mitochondrial malfunctioning is importantly associated with outer...... of mitochondrial dysfunction, indicating that mitochondria represent a weak link in the antioxidant defenses of outer retinal cells....

  12. Understanding Parkinson Disease: A Complex and Multifaceted Illness.

    Science.gov (United States)

    Gopalakrishna, Apoorva; Alexander, Sheila A

    2015-12-01

    Parkinson disease is an incredibly complex and multifaceted illness affecting millions of people in the United States. Parkinson disease is characterized by progressive dopaminergic neuronal dysfunction and loss, leading to debilitating motor, cognitive, and behavioral symptoms. Parkinson disease is an enigmatic illness that is still extensively researched today to search for a better understanding of the disease, develop therapeutic interventions to halt or slow progression of the disease, and optimize patient outcomes. This article aims to examine in detail the normal function of the basal ganglia and dopaminergic neurons in the central nervous system, the etiology and pathophysiology of Parkinson disease, related signs and symptoms, current treatment, and finally, the profound impact of understanding the disease on nursing care.

  13. Immune evasion by pathogens of bovine respiratory disease complex.

    Science.gov (United States)

    Srikumaran, Subramaniam; Kelling, Clayton L; Ambagala, Aruna

    2007-12-01

    Bovine respiratory tract disease is a multi-factorial disease complex involving several viruses and bacteria. Viruses that play prominent roles in causing the bovine respiratory disease complex include bovine herpesvirus-1, bovine respiratory syncytial virus, bovine viral diarrhea virus and parinfluenza-3 virus. Bacteria that play prominent roles in this disease complex are Mannheimia haemolytica and Mycoplasma bovis. Other bacteria that infect the bovine respiratory tract of cattle are Histophilus (Haemophilus) somni and Pasteurella multocida. Frequently, severe respiratory tract disease in cattle is associated with concurrent infections of these pathogens. Like other pathogens, the viral and bacterial pathogens of this disease complex have co-evolved with their hosts over millions of years. As much as the hosts have diversified and fine-tuned the components of their immune system, the pathogens have also evolved diverse and sophisticated strategies to evade the host immune responses. These pathogens have developed intricate mechanisms to thwart both the innate and adaptive arms of the immune responses of their hosts. This review presents an overview of the strategies by which the pathogens suppress host immune responses, as well as the strategies by which the pathogens modify themselves or their locations in the host to evade host immune responses. These immune evasion strategies likely contribute to the failure of currently-available vaccines to provide complete protection to cattle against these pathogens.

  14. Hyperhemolysis Syndrome without Underlying Hematologic Disease

    Directory of Open Access Journals (Sweden)

    Lauren Anne Eberly

    2015-01-01

    Full Text Available Introduction. Hyperhemolysis is characterized by a life-threatening hemolytic transfusion reaction, with hemoglobin (Hb and hematocrit (Hct dropping markedly lower than before transfusion. This phenomenon, commonly described in sickle cell disease, is a rare occurrence in patients without hemoglobinopathies. Case Report. A 55-year-old male presented to the hospital after a motorcycle crash and received 10 units of cross-matched blood for active bleeding. The patient was blood group O, with a negative antibody screen. Ten days later, he represented complaining of dyspnea and was found to have a hematocrit of 12%. The direct antiglobulin test was positive for anti-immunoglobin G and complement. Indirect antiglobulin test was positive for anti-Jka alloantibodies. The presence of Jka antigen was revealed in one unit of previously transfused blood; patient’s RBCs were negative for the Jka antigen. Laboratory data demonstrated findings consistent with DHTR, as well as reticulopenia and elevated ferritin levels. He continued to show signs of active hemolysis, requiring a total of 4 subsequent units of pRBCs. Each transfusion precipitated a drop in Hb and Hct to levels lower than before transfusion; once transfusions were held, the patient slowly recovered. Discussion. Hyperhemolysis in the setting of a DHTR can occur in patients without hematologic disease.

  15. Enhancement of FSO communications links under complex environment

    Science.gov (United States)

    Alnajjar, Satea H.; Noori, Ammar A.; Moosa, Arwa A.

    2017-06-01

    Free space optical communication is a line-of-sight (LOS) technology that uses lasers to provide optical bandwidth connections. Potential disturbance arising from the weather condition is one of the most effective factors that influence the bi-directional free space optics (FSO) performance. The complex weather condition in the Middle East region and Arabian Gulf has been dominated by dust storms activities. Dust storms directly affect the characteristics of FSO and consequently lead to an increase in the bit error rate (BER) and deterioration Q-factor to bad levels due to the high attenuation factor. In this research, the authors compare the differences between two bi-directional FSOs. One is the traditional link, and the other has been developed to enhance the system performance under the dust storms condition. The proposed design consists of dual FSO channels, and each one includes erbium-doped fiber amplifier (EDFA) optical amplifiers. This design has demonstrated the proficiency in addressing the attenuation that occurs due to weather stickers. The results prove there is an improvement in performance by measuring the Q-factor. In addition, BER can be significantly improved, and further communicating distance can be achieved by utilizing 1550 nm with multiple channels and EDFA.

  16. Modeling the Propagation of Mobile Phone Virus under Complex Network

    Directory of Open Access Journals (Sweden)

    Wei Yang

    2014-01-01

    Full Text Available Mobile phone virus is a rogue program written to propagate from one phone to another, which can take control of a mobile device by exploiting its vulnerabilities. In this paper the propagation model of mobile phone virus is tackled to understand how particular factors can affect its propagation and design effective containment strategies to suppress mobile phone virus. Two different propagation models of mobile phone viruses under the complex network are proposed in this paper. One is intended to describe the propagation of user-tricking virus, and the other is to describe the propagation of the vulnerability-exploiting virus. Based on the traditional epidemic models, the characteristics of mobile phone viruses and the network topology structure are incorporated into our models. A detailed analysis is conducted to analyze the propagation models. Through analysis, the stable infection-free equilibrium point and the stability condition are derived. Finally, considering the network topology, the numerical and simulation experiments are carried out. Results indicate that both models are correct and suitable for describing the spread of two different mobile phone viruses, respectively.

  17. Modeling the propagation of mobile phone virus under complex network.

    Science.gov (United States)

    Yang, Wei; Wei, Xi-liang; Guo, Hao; An, Gang; Guo, Lei; Yao, Yu

    2014-01-01

    Mobile phone virus is a rogue program written to propagate from one phone to another, which can take control of a mobile device by exploiting its vulnerabilities. In this paper the propagation model of mobile phone virus is tackled to understand how particular factors can affect its propagation and design effective containment strategies to suppress mobile phone virus. Two different propagation models of mobile phone viruses under the complex network are proposed in this paper. One is intended to describe the propagation of user-tricking virus, and the other is to describe the propagation of the vulnerability-exploiting virus. Based on the traditional epidemic models, the characteristics of mobile phone viruses and the network topology structure are incorporated into our models. A detailed analysis is conducted to analyze the propagation models. Through analysis, the stable infection-free equilibrium point and the stability condition are derived. Finally, considering the network topology, the numerical and simulation experiments are carried out. Results indicate that both models are correct and suitable for describing the spread of two different mobile phone viruses, respectively.

  18. Spread of Epidemic on Complex Networks Under Voluntary Vaccination Mechanism

    Science.gov (United States)

    Xue, Shengjun; Ruan, Feng; Yin, Chuanyang; Zhang, Haifeng; Wang, Binghong

    Under the assumption that the decision of vaccination is a voluntary behavior, in this paper, we use two forms of risk functions to characterize how susceptible individuals estimate the perceived risk of infection. One is uniform case, where each susceptible individual estimates the perceived risk of infection only based on the density of infection at each time step, so the risk function is only a function of the density of infection; another is preferential case, where each susceptible individual estimates the perceived risk of infection not only based on the density of infection but only related to its own activities/immediate neighbors (in network terminology, the activity or the number of immediate neighbors is the degree of node), so the risk function is a function of the density of infection and the degree of individuals. By investigating two different ways of estimating the risk of infection for susceptible individuals on complex network, we find that, for the preferential case, the spread of epidemic can be effectively controlled; yet, for the uniform case, voluntary vaccination mechanism is almost invalid in controlling the spread of epidemic on networks. Furthermore, given the temporality of some vaccines, the waves of epidemic for two cases are also different. Therefore, our work insight that the way of estimating the perceived risk of infection determines the decision on vaccination options, and then determines the success or failure of control strategy.

  19. Modeling the Propagation of Mobile Phone Virus under Complex Network

    Science.gov (United States)

    Yang, Wei; Wei, Xi-liang; Guo, Hao; An, Gang; Guo, Lei

    2014-01-01

    Mobile phone virus is a rogue program written to propagate from one phone to another, which can take control of a mobile device by exploiting its vulnerabilities. In this paper the propagation model of mobile phone virus is tackled to understand how particular factors can affect its propagation and design effective containment strategies to suppress mobile phone virus. Two different propagation models of mobile phone viruses under the complex network are proposed in this paper. One is intended to describe the propagation of user-tricking virus, and the other is to describe the propagation of the vulnerability-exploiting virus. Based on the traditional epidemic models, the characteristics of mobile phone viruses and the network topology structure are incorporated into our models. A detailed analysis is conducted to analyze the propagation models. Through analysis, the stable infection-free equilibrium point and the stability condition are derived. Finally, considering the network topology, the numerical and simulation experiments are carried out. Results indicate that both models are correct and suitable for describing the spread of two different mobile phone viruses, respectively. PMID:25133209

  20. Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases.

    Science.gov (United States)

    Bauer-Mehren, Anna; Bundschus, Markus; Rautschka, Michael; Mayer, Miguel A; Sanz, Ferran; Furlong, Laura I

    2011-01-01

    Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases. The

  1. Coupled disease-behavior dynamics on complex networks: A review

    Science.gov (United States)

    Wang, Zhen; Andrews, Michael A.; Wu, Zhi-Xi; Wang, Lin; Bauch, Chris T.

    2015-12-01

    It is increasingly recognized that a key component of successful infection control efforts is understanding the complex, two-way interaction between disease dynamics and human behavioral and social dynamics. Human behavior such as contact precautions and social distancing clearly influence disease prevalence, but disease prevalence can in turn alter human behavior, forming a coupled, nonlinear system. Moreover, in many cases, the spatial structure of the population cannot be ignored, such that social and behavioral processes and/or transmission of infection must be represented with complex networks. Research on studying coupled disease-behavior dynamics in complex networks in particular is growing rapidly, and frequently makes use of analysis methods and concepts from statistical physics. Here, we review some of the growing literature in this area. We contrast network-based approaches to homogeneous-mixing approaches, point out how their predictions differ, and describe the rich and often surprising behavior of disease-behavior dynamics on complex networks, and compare them to processes in statistical physics. We discuss how these models can capture the dynamics that characterize many real-world scenarios, thereby suggesting ways that policy makers can better design effective prevention strategies. We also describe the growing sources of digital data that are facilitating research in this area. Finally, we suggest pitfalls which might be faced by researchers in the field, and we suggest several ways in which the field could move forward in the coming years.

  2. Coupled disease-behavior dynamics on complex networks: A review.

    Science.gov (United States)

    Wang, Zhen; Andrews, Michael A; Wu, Zhi-Xi; Wang, Lin; Bauch, Chris T

    2015-12-01

    It is increasingly recognized that a key component of successful infection control efforts is understanding the complex, two-way interaction between disease dynamics and human behavioral and social dynamics. Human behavior such as contact precautions and social distancing clearly influence disease prevalence, but disease prevalence can in turn alter human behavior, forming a coupled, nonlinear system. Moreover, in many cases, the spatial structure of the population cannot be ignored, such that social and behavioral processes and/or transmission of infection must be represented with complex networks. Research on studying coupled disease-behavior dynamics in complex networks in particular is growing rapidly, and frequently makes use of analysis methods and concepts from statistical physics. Here, we review some of the growing literature in this area. We contrast network-based approaches to homogeneous-mixing approaches, point out how their predictions differ, and describe the rich and often surprising behavior of disease-behavior dynamics on complex networks, and compare them to processes in statistical physics. We discuss how these models can capture the dynamics that characterize many real-world scenarios, thereby suggesting ways that policy makers can better design effective prevention strategies. We also describe the growing sources of digital data that are facilitating research in this area. Finally, we suggest pitfalls which might be faced by researchers in the field, and we suggest several ways in which the field could move forward in the coming years. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Can data repositories help find effective treatments for complex diseases?

    Science.gov (United States)

    Farber, Gregory K

    2017-05-01

    There are many challenges to developing treatments for complex diseases. This review explores the question of whether it is possible to imagine a data repository that would increase the pace of understanding complex diseases sufficiently well to facilitate the development of effective treatments. First, consideration is given to the amount of data that might be needed for such a data repository and whether the existing data storage infrastructure is enough. Several successful data repositories are then examined to see if they have common characteristics. An area of science where unsuccessful attempts to develop a data infrastructure is then described to see what lessons could be learned for a data repository devoted to complex disease. Then, a variety of issues related to sharing data are discussed. In some of these areas, it is reasonably clear how to move forward. In other areas, there are significant open questions that need to be addressed by all data repositories. Using that baseline information, the question of whether data archives can be effective in understanding a complex disease is explored. The major goal of such a data archive is likely to be identifying biomarkers that define sub-populations of the disease. Published by Elsevier Ltd.

  4. Streptococcus bovis bacteremia and underlying gastrointestinal disease.

    Science.gov (United States)

    Murray, H W; Roberts, R B

    1978-07-01

    Twenty-six adults with Streptococcus bovis endocarditis and ten with bacteremia alone were studied to determine possible portals of entry. Of 36 patients (17 with endocarditis, eight with bacteremia alone), 25 had gastrointestinal lesions or manipulation. In 22, the gastrointestinal tract appeared to be the source of S bovis bacteremia. Four patients had either carcinoma of the colon (two) or potentially malignant villous adenomas (two) when first seen because of S bovis bacteremia. None of these, nor two other patients with benign colonic polyps, had bowel-related symptoms or signs prior to admission. Since S bovis is a normal intestinal tract inhabitant, bacteremia may frequently be associated with bowel lesions. Streptococcus bovis bacteremia may provide an early clue to the presence of serious and clinically unexpected gastrointestinal disease. Gastrointestinal tract evaluation should be part of S bovis bacteremia patient management, with or without endocarditis.

  5. The impact of the human genome project on complex disease.

    Science.gov (United States)

    Bailey, Jessica N Cooke; Pericak-Vance, Margaret A; Haines, Jonathan L

    2014-07-16

    In the decade that has passed since the initial release of the Human Genome, numerous advancements in science and technology within and beyond genetics and genomics have been encouraged and enhanced by the availability of this vast and remarkable data resource. Progress in understanding three common, complex diseases: age-related macular degeneration (AMD), Alzheimer's disease (AD), and multiple sclerosis (MS), are three exemplars of the incredible impact on the elucidation of the genetic architecture of disease. The approaches used in these diseases have been successfully applied to numerous other complex diseases. For example, the heritability of AMD was confirmed upon the release of the first genome-wide association study (GWAS) along with confirmatory reports that supported the findings of that state-of-the art method, thus setting the foundation for future GWAS in other heritable diseases. Following this seminal discovery and applying it to other diseases including AD and MS, the genetic knowledge of AD expanded far beyond the well-known APOE locus and now includes more than 20 loci. MS genetics saw a similar increase beyond the HLA loci and now has more than 100 known risk loci. Ongoing and future efforts will seek to define the remaining heritability of these diseases; the next decade could very well hold the key to attaining this goal.

  6. genetic variability for tuber yield, quality, and virus disease complex ...

    African Journals Online (AJOL)

    Administrator

    GENETIC VARIABILITY FOR TUBER YIELD, QUALITY, AND VIRUS DISEASE. COMPLEX TRAITS IN UGANDA SWEETPOTATO GERMPLASM. E. GASURA, A.B. MASHINGAIDZE1 and S.B. MUKASA. Department of Crop Science, Makerere University, P. O. Box 7062 Kampala, Uganda. 1Department of Crop Science, ...

  7. DW complexes and their underlying topological spaces | Ntumba ...

    African Journals Online (AJOL)

    The naïve concept of a DW complex is that of a differential space that can be built up from cells and whose differential structure is defined in terms of differential structures on Euclidean unit closed balls. This concept stems from an analogue in the category of topological spaces: the so-called CW complex. The paper goes as ...

  8. Complex anxiety disorders : Risk factors, underlying mechanisms, and treatment enhancement

    NARCIS (Netherlands)

    Klein Hofmeijer-Sevink, M.

    2016-01-01

    This thesis aims to address lacunas in the current knowledge of complex anxiety disorders. This is an important topic since complex anxiety disorders tend to develop a chronic course and because current guidelines are incomplete. In this thesis, several studies are presented regarding the various

  9. Ecotoxicology of waters under the influence of a petrochemical complex

    Energy Technology Data Exchange (ETDEWEB)

    Noll, R.; Zandonai, V.; Ries, M.A. [CORSAN-SITEL, Triunfo, RS (Brazil). Polo Petrquimico do Sul

    1993-12-31

    This work summarizes the regular monitoring and studies conducted by SITEL - The Integrated Wastewater Treatment System of South Petrochemical Complex (South Brazil) - in order to evaluate the full environmental impact on waters in the area of influence of the effluents of the above mentioned Complex. 8 refs., 1 fig., 5 tabs.

  10. The dichotomy between disease phenotype databases and the implications for understanding complex diseases involving the major histocompatibility complex.

    Science.gov (United States)

    Clark, P M; Kunkel, M; Monos, D S

    2015-12-01

    Many genes related to innate and adaptive immunity reside within the major histocompatibility complex (MHC) and have been associated with a multitude of complex, immune-related disorders. Despite years of genetic study, this region has seen few causative determinants discovered for immune-mediated diseases. Reported associations have been curated in various databases including the Genetic Association Database, NCBI database of clinically relevant variants (ClinVar) and the Human Gene Mutation Database and together capture genetic associations and annotated pathogenic loci within the MHC and across the genome for a variety of complex, immune-mediated diseases. A review of these three distinct databases reveals disparate annotations between associated genes and pathogenic loci, alluding to the polygenic, multifactorial nature of immune-mediated diseases and the pleiotropic character of genes within the MHC. The technical limitations and inherent biases imposed by current approaches and technologies in studying the MHC create a strong case for the need to perform targeted deep sequencing of the MHC and other immunologically relevant loci in order to fully elucidate and study the causative elements of complex immune-mediated diseases. © 2015 The Authors. International Journal of Immunogenetics Published by John Wiley & Sons Ltd.

  11. Does a carpal tunnel syndrome predict an underlying disease?

    NARCIS (Netherlands)

    M.C. de Rijk (Maarten); F.H. Vermeij (Frederique); M. Suntjens (Maartje); P.A. van Doorn (Pieter)

    2007-01-01

    textabstractCarpal tunnel syndrome (CTS) may be the presenting symptom of an underlying disease such as diabetes mellitus, hypothyroidism or connective tissue disease (CTD). It was investigated whether additional blood tests (glucose level, thyroid-stimulating hormone level and erythrocyte

  12. Unraveling the mechanisms underlying postural instability in Parkinson's disease using dynamic posturography

    NARCIS (Netherlands)

    Nonnekes, J.H.; Kam, D. de; Geurts, A.C.; Weerdesteijn, V.G.M.; Bloem, B.R.

    2013-01-01

    Postural instability, one of the cardinal symptoms of Parkinson's disease (PD), has devastating consequences for affected patients. Better strategies to prevent falls are needed, but this calls for an improved understanding of the complex mechanisms underlying postural instability. We must also

  13. Increasing mortality burden among adults with complex congenital heart disease.

    Science.gov (United States)

    Greutmann, Matthias; Tobler, Daniel; Kovacs, Adrienne H; Greutmann-Yantiri, Mehtap; Haile, Sarah R; Held, Leonhard; Ivanov, Joan; Williams, William G; Oechslin, Erwin N; Silversides, Candice K; Colman, Jack M

    2015-01-01

    Progress in management of congenital heart disease has shifted mortality largely to adulthood. However, adult survivors with complex congenital heart disease are not cured and remain at risk of premature death as young adults. Thus, our aim was to describe the evolution and mortality risk of adult patient cohorts with complex congenital heart disease. Among 12,644 adults with congenital heart disease followed at a single center from 1980 to 2009, 176 had Eisenmenger syndrome, 76 had unrepaired cyanotic defects, 221 had atrial switch operations for transposition of the great arteries, 158 had congenitally corrected transposition of the great arteries, 227 had Fontan palliation, and 789 had repaired tetralogy of Fallot. We depict the 30-year evolution of these 6 patient cohorts, analyze survival probabilities in adulthood, and predict future number of deaths through 2029. Since 1980, there has been a steady increase in numbers of patients followed, except in cohorts with Eisenmenger syndrome and unrepaired cyanotic defects. Between 1980 and 2009, 308 patients in the study cohorts (19%) died. At the end of 2009, 85% of survivors were younger than 50 years. Survival estimates for all cohorts were markedly lower than for the general population, with important differences between cohorts. Over the upcoming two decades, we predict a substantial increase in numbers of deaths among young adults with subaortic right ventricles, Fontan palliation, and repaired tetralogy of Fallot. Anticipatory action is needed to prepare clinical services for increasing numbers of young adults at risk of dying from complex congenital heart disease. © 2014 The Authors. Congenital Heart Disease Published by Wiley Periodicals, Inc.

  14. Systems genetics of complex diseases using RNA-sequencing methods

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Kogelman, Lisette; Suravajhala, Prashanth

    2015-01-01

    non-coding RNAs (ncRNAs). The integration of transcriptomics data with genomic data in a systems genetics context represents a valuable possibility to go deep into the causal and regulatory mechanisms that generate complex traits and diseases. However RNA-Seq data have to be treated carefully......Next generation sequencing technologies have enabled the generation of huge quantities of biological data, and nowadays extensive datasets at different ‘omics levels have been generated. Systems genetics is a powerful approach that allows to integrate different ‘omics level and understand...... the biological mechanisms behind complex diseases or traits. In the recent past, transcriptomic studies with microarrays have been replaced with the new powerful RNA-seq technologies. This has led to detection of novel gene transcripts, novel regulatory mechanisms, allele specific gene expression and numerous...

  15. Several Indicators of Critical Transitions for Complex Diseases Based on Stochastic Analysis.

    Science.gov (United States)

    Wang, Gang; Li, Yuanyuan; Zou, Xiufen

    2017-01-01

    Many complex diseases (chronic disease onset, development and differentiation, self-assembly, etc.) are reminiscent of phase transitions in a dynamical system: quantitative changes accumulate largely unnoticed until a critical threshold is reached, which causes abrupt qualitative changes of the system. Understanding such nonlinear behaviors is critical to dissect the multiple genetic/environmental factors that together shape the genetic and physiological landscape underlying basic biological functions and to identify the key driving molecules. Based on stochastic differential equation (SDE) model, we theoretically derive three statistical indicators, that is, coefficient of variation (CV), transformed Pearson's correlation coefficient (TPC), and transformed probability distribution (TPD), to identify critical transitions and detect the early-warning signals of the phase transition in complex diseases. To verify the effectiveness of these early-warning indexes, we use high-throughput data for three complex diseases, including influenza caused by either H3N2 or H1N1 and acute lung injury, to extract the dynamical network biomarkers (DNBs) responsible for catastrophic transition into the disease state from predisease state. The numerical results indicate that the derived indicators provide a data-based quantitative analysis for early-warning signals for critical transitions in complex diseases or other dynamical systems.

  16. genetic variability for tuber yield, quality, and virus disease complex

    African Journals Online (AJOL)

    Administrator

    improvement of yield and quality attributes. Cultivar Munyeera displayed the highest level of SPVD resistance followed by New Kawogo and Polyster as exhibited by relative area under disease progress curves following natural field infection and graft inoculation with SPVD causing viruses, Sweet potato chlorotic stunt virus ...

  17. Gene-Disease Network Analysis Reveals Functional Modules in Mendelian, Complex and Environmental Diseases

    Science.gov (United States)

    Bauer-Mehren, Anna; Bundschus, Markus; Rautschka, Michael; Mayer, Miguel A.; Sanz, Ferran; Furlong, Laura I.

    2011-01-01

    Background Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. Principal Findings We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. Conclusions For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors

  18. Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases.

    Directory of Open Access Journals (Sweden)

    Anna Bauer-Mehren

    Full Text Available BACKGROUND: Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. PRINCIPAL FINDINGS: We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. CONCLUSIONS: For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and

  19. Worms under stress: unravelling genetic complex traits through perturbation

    NARCIS (Netherlands)

    Rodriguez Sanchez, M.

    2014-01-01

    The genetic architecture of an organism could be considered ‘the most amazing piece of engineering’ existing in nature. Looking from a certain distance, the genetic complexity of an organism could be described as an immense jigsaw puzzle. As in a real jigsaw, the connection between two pieces

  20. Relation of ventricular premature beats to underlying heart disease.

    Science.gov (United States)

    Uretz, E F; Denes, P; Ruggie, N; Vasilomanolakis, E; Messer, J V

    1984-03-01

    The relation between ventricular premature beats (VPBs) and physiologic disease was investigated in 305 patients who had 24-hour Holter monitoring tests, cardiac catheterization and angiography. Both frequency and Lown class of VPBs were measured. Analyses showed that occurrence of VPBs at an average frequency of more than 2 per hour or occurrence of complex VPBs (Lown class greater than 2) have the highest association with the presence and severity of cardiac disease. Using these criteria, VPB severity was then compared with extent of ventricular wall motion abnormality (right anterior oblique projection segments), ejection fraction, end-diastolic pressure, category of disease (normal, coronary artery disease [CAD], valvular heart disease, dilated cardiomyopathy), age and severity of CAD (major coronary arteries with greater than 75% diameter reduction). Severe VPBs defined either by complexity or frequency were significantly correlated with extent of wall motion abnormality, ejection fraction, category of disease and age. Severe VPBs were not significantly correlated with end-diastolic pressure or severity of CAD. Discriminant analysis then showed that in addition to wall motion abnormality and ejection fraction, category of disease and age are independently correlated with VPB severity.

  1. Ebola Virus Disease Candidate Vaccines Under Evaluation in Clinical Trials

    Science.gov (United States)

    Martins, Karen A.; Jahrling, Peter B.; Bavari, Sina; Kuhn, Jens H.

    2016-01-01

    Summary Filoviruses are the etiological agents of two human illnesses: Ebola virus disease and Marburg virus disease. Until 2013, medical countermeasure development against these afflictions was limited to only a few research institutes worldwide as both infections were considered exotic due to very low case numbers. Together with the high case-fatality rate of both diseases, evaluation of any candidate countermeasure in properly controlled clinical trials seemed impossible. However, in 2013, Ebola virus was identified as the etiological agent of a large disease outbreak in Western Africa including almost 30,000 infections and more than 11,000 deaths, including case exportations to Europe and North America. These large case numbers resulted in medical countermeasure development against Ebola virus disease becoming a global public-health priority. This review summarizes the status quo of candidate vaccines against Ebola virus disease, with a focus on those that are currently under evaluation in clinical trials. PMID:27160784

  2. Spiral instabilities in media supporting complex oscillations under periodic forcing

    Science.gov (United States)

    Gao, Qingyu; Li, Jun; Zhang, Kailong; Epstein, Irving R.

    2009-09-01

    The periodically forced Brusselator model displays temporal mixed-mode and quasiperiodic oscillations, period doubling, and chaos. We explore the behavior of such media as reaction-diffusion systems for investigating spiral instabilities. Besides near-core breakup and far-field breakup resulting from unstable modes in the radial direction or Doppler-induced instability (destabilization of the core's location), the observed complex phenomena include backfiring, spiral regeneration, and amplitude modulation from line defects. Amplitude modulation of spirals can evolve to chambered spirals resembling those found in nature, such as pine cones and sunflowers. When the forcing amplitude is increased, the spiral-tip meander evolves from simple rotation to complex petals, corresponding to transformation of the local dynamics from simple oscillations to mixed-mode, period-2, and quasiperiodic oscillations. The number of petals is related to the complexity of the mixed-mode oscillations. Spiral turbulence, standing waves, and homogeneous synchronization permeate the entire system when the forcing amplitude is further increased.

  3. A genomic pathway approach to a complex disease: axon guidance and Parkinson disease.

    Directory of Open Access Journals (Sweden)

    Timothy G Lesnick

    2007-06-01

    Full Text Available While major inroads have been made in identifying the genetic causes of rare Mendelian disorders, little progress has been made in the discovery of common gene variations that predispose to complex diseases. The single gene variants that have been shown to associate reproducibly with complex diseases typically have small effect sizes or attributable risks. However, the joint actions of common gene variants within pathways may play a major role in predisposing to complex diseases (the paradigm of complex genetics. The goal of this study was to determine whether polymorphism in a candidate pathway (axon guidance predisposed to a complex disease (Parkinson disease [PD]. We mined a whole-genome association dataset and identified single nucleotide polymorphisms (SNPs that were within axon-guidance pathway genes. We then constructed models of axon-guidance pathway SNPs that predicted three outcomes: PD susceptibility (odds ratio = 90.8, p = 4.64 x 10(-38, survival free of PD (hazards ratio = 19.0, p = 5.43 x 10(-48, and PD age at onset (R(2 = 0.68, p = 1.68 x 10(-51. By contrast, models constructed from thousands of random selections of genomic SNPs predicted the three PD outcomes poorly. Mining of a second whole-genome association dataset and mining of an expression profiling dataset also supported a role for many axon-guidance pathway genes in PD. These findings could have important implications regarding the pathogenesis of PD. This genomic pathway approach may also offer insights into other complex diseases such as Alzheimer disease, diabetes mellitus, nicotine and alcohol dependence, and several cancers.

  4. The role of protein complexes in a complex disease: molecular mechanisms of ALS

    NARCIS (Netherlands)

    Blokhuis, A.M.

    2016-01-01

    Amyotrophic Lateral Sclerosis is a devastating neurodegenerative diease caused by the selective loss of motor neurons. The pathogenic mechanism underlying the disease is largely unknown but a number of genes, proteins and cellular processes have been implicated. In this thesis we aimed to identify

  5. Multimodal cues improve prey localization under complex environmental conditions

    NARCIS (Netherlands)

    Rhebergen, F.; Taylor, R.C.; Ryan, M.J.; Page, R.A.; Halfwerk, W.H.

    2015-01-01

    Predators often eavesdrop on sexual displays of their prey. These displays can provide multimodal cues that aid predators, but the benefits in attending to them should depend on the environmental sensory conditions under which they forage. We assessed whether bats hunting for frogs use multimodal

  6. Complex systems of biological interest stability under ionising radiations

    International Nuclear Information System (INIS)

    Maclot, Sylvain

    2014-01-01

    This PhD work presents the study of stability of molecular systems of biological interest in the gas phase after interaction with ionising radiations. The use of ionising radiation can probe the physical chemistry of complex systems at the molecular scale and thus consider their intrinsic properties. Beyond the fundamental aspect, this work is part of the overall understanding of radiation effects on living organisms and in particular the use of ionizing radiation in radiotherapy. Specifically, this study focused on the use of low-energy multiply charged ions (tens of keV) provided by the GANIL (Caen), which includes most of the experiments presented. In addition, experiments using VUV photons were also conducted at synchrotron ELETTRA (Trieste, Italy). The bio-molecular systems studied are amino acids and nucleic acid constituents. Using an experimental crossed beams device allows interaction between biomolecules and ionising radiation leads mainly to the ionization and fragmentation of the system. The study of its relaxation dynamics is by time-of-flight mass spectrometry coupled to a coincidences measurements method. It is shown that an approach combining experiment and theory allows a detailed study of the fragmentation dynamics of complex systems. The results indicate that fragmentation is generally governed by the Coulomb repulsion but the intramolecular rearrangements involve specific relaxation mechanisms. (author) [fr

  7. Molecular diagnostics for the sigatoka disease complex of banana.

    Science.gov (United States)

    Arzanlou, Mahdi; Abeln, Edwin C A; Kema, Gert H J; Waalwijk, Cees; Carlier, Jean; Vries, Ineke de; Guzmán, Mauricio; Crous, Pedro W

    2007-09-01

    ABSTRACT The Sigatoka disease complex of banana involves three related ascomycetous fungi, Mycosphaerella fijiensis, M. musicola, and M. eumusae. The exact distribution of these three species and their disease epidemiology remain unclear, because their symptoms and life cycles are rather similar. Disease diagnosis in the Mycosphaerella complex of banana is based on the presence of host symptoms and fungal fruiting structures, which hamper preventive management strategies. In the present study, we have developed rapid and robust species-specific molecular-based diagnostic tools for detection and quantification of M. fijiensis, M. musicola, and M. eumusae. Conventional species-specific polymerase chain reaction (PCR) primers were developed based on the actin gene that detected DNA at as little as 100, 1, and 10 pg/mul from M. fijiensis, M. musicola, and M. eumusae, respectively. Furthermore, TaqMan real-time quantitative PCR assays were developed based on the beta-tubulin gene and detected quantities of DNA as low as 1 pg/mul for each Mycosphaerella sp. from pure cultures and DNA at 1.6 pg/mul per milligram of dry leaf tissue for M. fijiensis that was validated using naturally infected banana leaves.

  8. Mycobacterium avium complex pulmonary disease: characteristics and treatment in an Irish patient cohort.

    LENUS (Irish Health Repository)

    Judge, EP

    2016-04-01

    The prevalence of Mycobacterium avium complex (MAC) pulmonary disease is increasing globally. However, reliable national and international data relating to its epidemiology and management is lacking. During the period 2003-2014, MAC was isolated from the pulmonary samples of 75 patients at the Irish Mycobacteria Reference Laboratory (IMRL). Most patients (42, 56%) had underlying pulmonary disease, and 37 (49%) had clinical\\/radiographic characteristics consistent with MAC pulmonary disease. However, only 18 patients (24%) fulfilled internationally accepted criteria for diagnosis\\/treatment of this disease. Treatment was started in 13 (72%) of these cases, which is similar to internationally published treatment rates. The diagnosis of significant MAC pulmonary disease can be difficult, and treatment is not always warranted even when diagnostic criteria are met.

  9. Genomic risk prediction of complex human disease and its clinical application.

    Science.gov (United States)

    Abraham, Gad; Inouye, Michael

    2015-08-01

    Recent advances in genome-wide association studies have stimulated interest in the genomic prediction of disease risk, potentially enabling individual-level risk estimates for early intervention and improved diagnostic procedures. Here, we review recent findings and approaches to genomic prediction model construction and performance, then contrast the potential benefits of such models in two complex human diseases, aiding diagnosis in celiac disease and prospective risk prediction for cardiovascular disease. Early indications are that optimal application of genomic risk scores will differ substantially for each disease depending on underlying genetic architecture as well as current clinical and public health practice. As costs decline, genomic profiles become common, and popular understanding of risk and its communication improves, genomic risk will become increasingly useful for the individual and the clinician. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Nye Lecture: Water Under Ice: Curiosities, Complexities, and Catastrophes

    Science.gov (United States)

    Clarke, G. K.

    2006-12-01

    flood occurring 4 km below the surface of the East Antarctic Ice Sheet has reignited interest in this important question. Complexity is the hallmark of nonlinear systems and the coupled subglacial interactions of ice, water, and sediment systems are certain to be nonlinear and complex. This complexity may account for the lack of agreement concerning the processes that govern subglacial landform genesis and which, for the most part, remain challenging and mysterious.

  11. Energy profile of nanobody–GFP complex under force

    International Nuclear Information System (INIS)

    Klamecka, Kamila; Severin, Philip M; Milles, Lukas F; Gaub, Hermann E; Leonhardt, Heinrich

    2015-01-01

    Nanobodies (Nbs)—the smallest known fully functional and naturally occuring antigen-binding fragments—have attracted a lot of attention throughout the last two decades. Exploring their potential beyond the current use requires more detailed characterization of their binding forces as those cannot be directly derived from the binding affinities. Here we used atomic force microscope to measure rupture force of the Nb–green fluorescent protein (GFP) complex in various pulling geometries and derived the energy profile characterizing the interaction along the direction of the pulling force. We found that—despite identical epitopes—the Nb binds stronger (41–56 pN) to enhanced GFP than to wild-type GFP (28–45 pN). Measured forces make the Nb–GFP pair a potent reference for investigating molecular forces in living systems both in and ex vivo. (paper)

  12. Energy profile of nanobody-GFP complex under force

    Science.gov (United States)

    Klamecka, Kamila; Severin, Philip M.; Milles, Lukas F.; Gaub, Hermann E.; Leonhardt, Heinrich

    2015-10-01

    Nanobodies (Nbs)—the smallest known fully functional and naturally occuring antigen-binding fragments—have attracted a lot of attention throughout the last two decades. Exploring their potential beyond the current use requires more detailed characterization of their binding forces as those cannot be directly derived from the binding affinities. Here we used atomic force microscope to measure rupture force of the Nb-green fluorescent protein (GFP) complex in various pulling geometries and derived the energy profile characterizing the interaction along the direction of the pulling force. We found that—despite identical epitopes—the Nb binds stronger (41-56 pN) to enhanced GFP than to wild-type GFP (28-45 pN). Measured forces make the Nb-GFP pair a potent reference for investigating molecular forces in living systems both in and ex vivo.

  13. Pacing and Defibrillators in Complex Congenital Heart Disease

    Science.gov (United States)

    Chubb, Henry; O’Neill, Mark; Rosenthal, Eric

    2016-01-01

    Device therapy in the complex congenital heart disease (CHD) population is a challenging field. There is a myriad of devices available, but none designed specifically for the CHD patient group, and a scarcity of prospective studies to guide best practice. Baseline cardiac anatomy, prior surgical and interventional procedures, existing tachyarrhythmias and the requirement for future intervention all play a substantial role in decision making. For both pacing systems and implantable cardioverter defibrillators, numerous factors impact on the merits of system location (endovascular versus non-endovascular), lead positioning, device selection and device programming. For those with Fontan circulation and following the atrial switch procedure there are also very specific considerations regarding access and potential complications. This review discusses the published guidelines, device indications and the best available evidence for guidance of device implantation in the complex CHD population. PMID:27403295

  14. Declining Prevalence of Disease Vectors Under Climate Change

    Science.gov (United States)

    Escobar, Luis E.; Romero-Alvarez, Daniel; Leon, Renato; Lepe-Lopez, Manuel A.; Craft, Meggan E.; Borbor-Cordova, Mercy J.; Svenning, Jens-Christian

    2016-12-01

    More than half of the world population is at risk of vector-borne diseases including dengue fever, chikungunya, zika, yellow fever, leishmaniasis, chagas disease, and malaria, with highest incidences in tropical regions. In Ecuador, vector-borne diseases are present from coastal and Amazonian regions to the Andes Mountains; however, a detailed characterization of the distribution of their vectors has never been carried out. We estimate the distribution of 14 vectors of the above vector-borne diseases under present-day and future climates. Our results consistently suggest that climate warming is likely threatening some vector species with extinction, locally or completely. These results suggest that climate change could reduce the burden of specific vector species. Other vector species are likely to shift and constrain their geographic range to the highlands in Ecuador potentially affecting novel areas and populations. These forecasts show the need for development of early prevention strategies for vector species currently absent in areas projected as suitable under future climate conditions. Informed interventions could reduce the risk of human exposure to vector species with distributional shifts, in response to current and future climate changes. Based on the mixed effects of future climate on human exposure to disease vectors, we argue that research on vector-borne diseases should be cross-scale and include climatic, demographic, and landscape factors, as well as forces facilitating disease transmission at fine scales.

  15. Sustainable design of complex industrial and energy systems under uncertainty

    Science.gov (United States)

    Liu, Zheng

    Depletion of natural resources, environmental pressure, economic globalization, etc., demand seriously industrial organizations to ensure that their manufacturing be sustainable. On the other hand, the efforts of pursing sustainability also give raise to potential opportunities for improvements and collaborations among various types of industries. Owing to inherent complexity and uncertainty, however, sustainability problems of industrial and energy systems are always very difficult to deal with, which has made industrial practice mostly experience based. For existing research efforts on the study of industrial sustainability, although systems approaches have been applied in dealing with the challenge of system complexity, most of them are still lack in the ability of handling inherent uncertainty. To overcome this limit, there is a research need to develop a new generation of systems approaches by integrating techniques and methods for handling various types of uncertainties. To achieve this objective, this research introduced series of holistic methodologies for sustainable design and decision-making of industrial and energy systems. The introduced methodologies are developed in a systems point of view with the functional components involved in, namely, modeling, assessment, analysis, and decision-making. For different methodologies, the interval-parameter-based, fuzzy-logic-based, and Monte Carlo based methods are selected and applied respectively for handling various types of uncertainties involved, and the optimality of solutions is guaranteed by thorough search or system optimization. The proposed methods are generally applicable for any types of industrial systems, and their efficacy had been successfully demonstrated by the given case studies. Beyond that, a computational tool was designed, which provides functions on the industrial sustainability assessment and decision-making through several convenient and interactive steps of computer operation. This

  16. [Magnetic therapy for complex treatment of chronic periodontal disease].

    Science.gov (United States)

    P'yanzina, A V

    The aim of the study was to elaborate the methodology of magnetic therapy for complex treatment of chronic periodontal disease (CPD). The study included 60 patients aged 35 to 65 years with moderate CPD divided in 2 groups. Patients in group 1 (controls) received impulse carbonate irrigation for 12 min №10, group 2 additionally received magnetic therapy for 5 min №10 in maxillary and mandibular areas. periodontal and rheological indices proved magnetic therapy to be useful tool for eradication of inflammation, periodontal tissue functional recovery and stabilization.

  17. Understanding complexity in neurodegenerative diseases: in silico reconstruction of emergence

    Directory of Open Access Journals (Sweden)

    Alexey eKolodkin

    2012-07-01

    Full Text Available Healthy functioning is an emergent property of the network of interacting biomolecules that comprise an organism. It follows that disease (a network shift that causes malfunction is also an emergent property, emerging from a perturbation of the network. On one hand, the biomolecular network of every individual is unique and this is evident when similar disease-producing agents cause different individual pathologies. Consequently, a personalized model and approach for every patient may be required for therapies to become effective across mankind. On the other hand, diverse combinations of internal and external perturbation factors may cause a similar shift in network functioning. We offer this as an explanation for the multi-factorial nature of most diseases: they are ‘systems biology diseases’, or ‘network diseases’. Here we focus on neurodegenerative diseases, like Parkinson’s disease, as an example. Because of the inherent complexity of these networks, it is difficult to understand multi-factorial diseases using simply our ‘naked brain’. When describing interactions between biomolecules through mathematical equations and integrating those equations into a mathematical model, we try to reconstruct the emergent properties of the system in silico. The reconstruction of emergence from interactions between huge numbers of macromolecules is one of the aims of systems biology. Systems biology approaches enable us to break through the limitation of the human brain to perceive the extraordinarily large number of interactions, but this also means that we delegate the understanding of reality to the computer. We no longer recognize all those essences in the system’s design crucial for important physiological behavior (the so-called ‘design principles’ of the system. In this paper we review evidence that by using more abstract approaches and by experimenting in silico, one may still be able to discover and understand the design

  18. Understanding complex clinical reasoning in infectious diseases for improving clinical decision support design.

    Science.gov (United States)

    Islam, Roosan; Weir, Charlene R; Jones, Makoto; Del Fiol, Guilherme; Samore, Matthew H

    2015-11-30

    Clinical experts' cognitive mechanisms for managing complexity have implications for the design of future innovative healthcare systems. The purpose of the study is to examine the constituents of decision complexity and explore the cognitive strategies clinicians use to control and adapt to their information environment. We used Cognitive Task Analysis (CTA) methods to interview 10 Infectious Disease (ID) experts at the University of Utah and Salt Lake City Veterans Administration Medical Center. Participants were asked to recall a complex, critical and vivid antibiotic-prescribing incident using the Critical Decision Method (CDM), a type of Cognitive Task Analysis (CTA). Using the four iterations of the Critical Decision Method, questions were posed to fully explore the incident, focusing in depth on the clinical components underlying the complexity. Probes were included to assess cognitive and decision strategies used by participants. The following three themes emerged as the constituents of decision complexity experienced by the Infectious Diseases experts: 1) the overall clinical picture does not match the pattern, 2) a lack of comprehension of the situation and 3) dealing with social and emotional pressures such as fear and anxiety. All these factors contribute to decision complexity. These factors almost always occurred together, creating unexpected events and uncertainty in clinical reasoning. Five themes emerged in the analyses of how experts deal with the complexity. Expert clinicians frequently used 1) watchful waiting instead of over- prescribing antibiotics, engaged in 2) theory of mind to project and simulate other practitioners' perspectives, reduced very complex cases into simple 3) heuristics, employed 4) anticipatory thinking to plan and re-plan events and consulted with peers to share knowledge, solicit opinions and 5) seek help on patient cases. The cognitive strategies to deal with decision complexity found in this study have important

  19. Poverty, Disease, and the Ecology of Complex Systems

    Science.gov (United States)

    Pluciński, Mateusz M.; Murray, Megan B.; Farmer, Paul E.; Barrett, Christopher B.; Keenan, Donald C.

    2014-01-01

    Understanding why some human populations remain persistently poor remains a significant challenge for both the social and natural sciences. The extremely poor are generally reliant on their immediate natural resource base for subsistence and suffer high rates of mortality due to parasitic and infectious diseases. Economists have developed a range of models to explain persistent poverty, often characterized as poverty traps, but these rarely account for complex biophysical processes. In this Essay, we argue that by coupling insights from ecology and economics, we can begin to model and understand the complex dynamics that underlie the generation and maintenance of poverty traps, which can then be used to inform analyses and possible intervention policies. To illustrate the utility of this approach, we present a simple coupled model of infectious diseases and economic growth, where poverty traps emerge from nonlinear relationships determined by the number of pathogens in the system. These nonlinearities are comparable to those often incorporated into poverty trap models in the economics literature, but, importantly, here the mechanism is anchored in core ecological principles. Coupled models of this sort could be usefully developed in many economically important biophysical systems—such as agriculture, fisheries, nutrition, and land use change—to serve as foundations for deeper explorations of how fundamental ecological processes influence structural poverty and economic development. PMID:24690902

  20. Epigenetic mechanisms underlying the pathogenesis of neurogenetic diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2014-10-01

    There have been considerable advances in uncovering the complex genetic mechanisms that underlie nervous system disease pathogenesis, particularly with the advent of exome and whole genome sequencing techniques. The emerging field of epigenetics is also providing further insights into these mechanisms. Here, we discuss our understanding of the interplay that exists between genetic and epigenetic mechanisms in these disorders, highlighting the nascent field of epigenetic epidemiology-which focuses on analyzing relationships between the epigenome and environmental exposures, development and aging, other health-related phenotypes, and disease states-and next-generation research tools (i.e., those leveraging synthetic and chemical biology and optogenetics) for examining precisely how epigenetic modifications at specific genomic sites affect disease processes.

  1. Technology for planning and scheduling under complex constraints

    Science.gov (United States)

    Alguire, Karen M.; Pedro Gomes, Carla O.

    1997-02-01

    Within the context of law enforcement, several problems fall into the category of planning and scheduling under constraints. Examples include resource and personnel scheduling, and court scheduling. In the case of court scheduling, a schedule must be generated considering available resources, e.g., court rooms and personnel. Additionally, there are constraints on individual court cases, e.g., temporal and spatial, and between different cases, e.g., precedence. Finally, there are overall objectives that the schedule should satisfy such as timely processing of cases and optimal use of court facilities. Manually generating a schedule that satisfies all of the constraints is a very time consuming task. As the number of court cases and constraints increases, this becomes increasingly harder to handle without the assistance of automatic scheduling techniques. This paper describes artificial intelligence (AI) technology that has been used to develop several high performance scheduling applications including a military transportation scheduler, a military in-theater airlift scheduler, and a nuclear power plant outage scheduler. We discuss possible law enforcement applications where we feel the same technology could provide long-term benefits to law enforcement agencies and their operations personnel.

  2. Glomerular diseases and cancer: evaluation of underlying malignancy.

    Science.gov (United States)

    Pani, Antonello; Porta, Camillo; Cosmai, Laura; Melis, Patrizia; Floris, Matteo; Piras, Doloretta; Gallieni, Maurizio; Rosner, Mitchell; Ponticelli, Claudio

    2016-04-01

    Onconephrology is an emerging medical subspecialty focused on the numerous interconnections between cancer and kidney diseases. Patient with malignancies commonly experience kidney problems including acute kidney injury, tumor lysis syndrome, fluid and electrolyte disorders and chronic kidney disease, often as a consequence of the anti-cancer treatment. Conversely, a number of glomerulopathies, tubulopathies and vascular renal diseases can early signal the presence of an underlying cancer. Furthermore, the administration of immunosuppressive drugs, especially cytotoxic drugs and calcineurin inhibitors, may strongly impair the immune response increasing the risk of cancer. The objective of this review article is to: (i) discuss paraneoplastic glomerular disease, (ii) review cancer as an adverse effect of immunosuppressive agents used to treat glomerulopathies, and (iii) in the absence of international approved guidelines, propose a screening program based on expert opinion aimed at guiding nephrologists to early detect malignancies during their clinical practice.

  3. OEIS complex with glomerulocystic kidney disease: a case report.

    Science.gov (United States)

    Hong, Ran; Lim, Sung-Chul; Jang, Jung-Whan; Suh, Chae-Hong; Jeon, Ho-Jong; Lee, Mi-Ja; Kim, Youn-Shin

    2007-01-01

    We present a case of OEIS complex (omphalocele, exstrophy of bladder, imperforated anus, spinal defect) combined with colonic agenesis and glomerulocystic kidney disease (GCKD). The baby was born at 35.2 weeks of gestational age, weighing 2.51 kg. A prenatal ultrasound examination showed spina bifida, hydroureter, and a unilateral polycystic kidney. The postdelivery examination, which included a physical examination, simple X-ray, and pelvic MRI, showed a lower abdominal wall defect through which a small pouch with a segment of bowel protruded, imperforated anus, ambiguous external genitalia, spina bifida with meningomyelocele at the lumbosacral junction, and nonunion of pubic symphysis. The baby underwent surgery, including nephrectomy, colostomy, and repair of the abdominal wall defect. In addition to the abnormalities mentioned, a tailgut as a result of colonic agenesis and 2 appendices were identified in the course of surgery. The result of histopathological examination confirmed the polycystic kidney identified as GCKD. These radiological, surgical, and histopathologic findings are consistent with the OEIS complex. The postoperative course was uneventful during a period of 4 months of follow up. We herein report a case of the very rare OEIS complex in a newborn male baby and review the available literature.

  4. Employment characteristics of a complex adult congenital heart disease cohort.

    Science.gov (United States)

    Pickup, L; Gaffey, T; Clift, P; Bowater, S; Thorne, S; Hudsmith, L

    2017-08-01

    Due to advances in surgical techniques and subsequent management, there have been remarkable improvements in the survival of patients with congenital heart disease. In particular, larger numbers of patients with complex disease are now living into adulthood and are entering the workforce. To establish the types of employment complex adult congenital heart disease (ACHD) patients are engaged in, based on the largest cohort of patients with a single-ventricle circulation in the UK. Records of all patients with a univentricular (Fontan) circulation at the Queen Elizabeth Hospital were reviewed. Employment status was categorized according to the Standard Occupational Classification criteria (2010). A total of 210 patient records were reviewed. There was the same proportion of professionals in our cohort compared to the rest of the UK (20% versus 20%). There were greater proportions working in the caring, leisure and other service occupations (15% versus 9%), the elementary occupations (17% versus 11%), sales and customer service occupations (14% versus 8%) and administrative and secretarial occupations (12% versus 11%). The reverse trend was observed for associate professions and technical occupations (7% versus 14%), skilled trades (10% versus 11%), process, plant and machine operatives (3% versus 6%) and managers, directors and senior officials (2% versus 10%). The data show that ACHD patients with a single ventricle are engaged in a diverse range of occupations. It is essential that early education and employment advice are given to this cohort to maximize future employment potential. © The Author 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  5. NOX Activation by Subunit Interaction and Underlying Mechanisms in Disease.

    Science.gov (United States)

    Rastogi, Radhika; Geng, Xiaokun; Li, Fengwu; Ding, Yuchuan

    2016-01-01

    Nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (NOX) is an enzyme complex with the sole function of producing superoxide anion and reactive oxygen species (ROS) at the expense of NADPH. Vital to the immune system as well as cellular signaling, NOX is also involved in the pathologies of a wide variety of disease states. Particularly, it is an integral player in many neurological diseases, including stroke, TBI, and neurodegenerative diseases. Pathologically, NOX produces an excessive amount of ROS that exceed the body's antioxidant ability to neutralize them, leading to oxidative stress and aberrant signaling. This prevalence makes it an attractive therapeutic target and as such, NOX inhibitors have been studied and developed to counter NOX's deleterious effects. However, recent studies of NOX have created a better understanding of the NOX complex. Comprised of independent cytosolic subunits, p47- phox , p67- phox , p40- phox and Rac , and membrane subunits, gp91- phox and p22- phox , the NOX complex requires a unique activation process through subunit interaction. Of these subunits, p47- phox plays the most important role in activation, binding and translocating the cytosolic subunits to the membrane and anchoring to p22- phox to organize the complex for NOX activation and function. Moreover, these interactions, particularly that between p47- phox and p22- phox , are dependent on phosphorylation initiated by upstream processes involving protein kinase C (PKC). This review will look at these interactions between subunits and with PKC. It will focus on the interaction involving p47- phox with p22- phox , key in bringing the cytosolic subunits to the membrane. Furthermore, the implication of these interactions as a target for NOX inhibitors such as apocynin will be discussed as a potential avenue for further investigation, in order to develop more specific NOX inhibitors based on the inhibition of NOX assembly and activation.

  6. On Impact Dynamics under Complex or Extreme Conditions

    KAUST Repository

    Kouraytem, Nadia

    2016-11-01

    The impact of a spherical object onto a surface of a liquid, solid or granular material, is a configuration which occurs in numerous industrial and natural phenomena. The resulting dynamics can produce complex outcomes and often occur on very short time-scales. Their study thereby requires high-speed video imaging, as is done herein. This three-part dissertation investigates widely disparate but kindred impact configurations, where the impacting object is a solid steel sphere, or a molten metal droplet. The substrate, on the other hand, is either granular material, a liquid, or solid ice. Therefore both fluid mechanics and thermodynamics play a key role in some of these dynamics. Part I, investigates the penetration depth of a steel sphere which impacts onto a granular bed containing a mixture of grains of two different sizes. The addition of smaller grains within a bed of larger grains can promote a “lubrication” effect and deeper penetration of the sphere. However, there needs to be enough mass fraction of the smaller grains so that they get lodged between the larger grains and are not simply like isolated rattlers inside the voids between the larger grains. This lubrication occurs even though the addition of the small grains increases the overall packing fraction of the bed. We compare the enhanced penetration for the mixtures to a simple interpolative model based on the results for monodispersed media of the constitutive sizes. The strongest lubrication is observed for large irregular shaped Ottawa sand grains, which are seeded with small spherical glass beads. Part II, tackles the topic of a molten metal drop impacting onto a pool of water. When the drop temperature is far above the boiling temperature of water, a continuous vapor layer can form at the interface between the metal and water, in what is called the Leidenfrost phenomenon. This vapor layer can become unstable forming what is called a vapor explosion, which can break up the molten metal drop

  7. Polypharmacy and enteral nutrition in patients with complex chronic diseases

    Science.gov (United States)

    Romero Jiménez, Rosa Mª; Ortega Navarro, Cristina; Cuerda Compés, Cristina

    2017-05-08

    Oral medications are often administered through enteral feeding tubes in patients with complex chronic diseases. It is important to consider possible interactions between drugs and enteral nutrition that might lead to unsuccessful treatment or tube occlusion. These patients become subjects for higher risk of problems and errors such as drug incompatibility with enteral nutrition and inappropriate dosage form selection. It is possible to minimize the risk of tube occlusion and incompatibilities problems by recognizing potential medication errors, selecting the most appropriate drug and dosage form and using appropriate administration techniques. In this context, high-alert medications for patients with chronic diseases deserve special attention. Furthermore, risk exposure should be considered among healthcare professionals and patient caregivers handling hazardous drugs. Therefore, main incompatibility problems between drugs and enteral nutrition have been reviewed, including general recommendations for administration of oral medications through enteral feeding tubes and safe handling of hazardous drugs. Specific recommendations for administration of high-alert medications for patients with chronic diseases are also included.

  8. Unintended consequences of conservation actions: managing disease in complex ecosystems.

    Directory of Open Access Journals (Sweden)

    Aliénor L M Chauvenet

    Full Text Available Infectious diseases are increasingly recognised to be a major threat to biodiversity. Disease management tools such as control of animal movements and vaccination can be used to mitigate the impact and spread of diseases in targeted species. They can reduce the risk of epidemics and in turn the risks of population decline and extinction. However, all species are embedded in communities and interactions between species can be complex, hence increasing the chance of survival of one species can have repercussions on the whole community structure. In this study, we use an example from the Serengeti ecosystem in Tanzania to explore how a vaccination campaign against Canine Distemper Virus (CDV targeted at conserving the African lion (Panthera leo, could affect the viability of a coexisting threatened species, the cheetah (Acinonyx jubatus. Assuming that CDV plays a role in lion regulation, our results suggest that a vaccination programme, if successful, risks destabilising the simple two-species system considered, as simulations show that vaccination interventions could almost double the probability of extinction of an isolated cheetah population over the next 60 years. This work uses a simple example to illustrate how predictive modelling can be a useful tool in examining the consequence of vaccination interventions on non-target species. It also highlights the importance of carefully considering linkages between human-intervention, species viability and community structure when planning species-based conservation actions.

  9. Proteomic profile of circulating immune complexes in chronic Chagas disease.

    Science.gov (United States)

    Ohyama, K; Huy, N T; Yoshimi, H; Kishikawa, N; Nishizawa, J E; Roca, Y; Revollo Guzmán, R J; Velarde, F U G; Kuroda, N; Hirayama, K

    2016-10-01

    Immune complexes (ICs) are the direct and real-time products of humoral immune responses. The identification of constituent foreign or autoantigens within ICs might bring new insights into the pathology of infectious diseases. We applied immune complexome analysis of plasma to the study of Chagas disease caused by Trypanosoma cruzi. Twenty seropositive plasma samples including cardiac and/or megacolon determinate patients (n = 11) and indeterminate (n = 9) were analysed along with 10 seronegative individuals to characterize the antigens bound to circulating ICs. We identified 39 T. cruzi antigens and 114 human autoantigens specific to patients with Chagas. Among those antigens, two T. cruzi antigens (surface protease GP63, glucose-6-isomerase) and six human autoantigens (CD180 antigen, ceruloplasmin, fibrinogen beta chain, fibrinogen beta chain isoform 2 preprotein, isoform gamma-A of fibrinogen γ-chain, serum paraoxonase) were detected in more than 50% of the patients tested. Human isoform short of complement factor H-related protein 2 and trans-sialidase of T. cruzi were more frequently found in the indeterminate (5/9 for both) compared with in the determinate Chagas (0/11, P = 0·046 for human, 1/11, P = 0·0498 for T. cruzi). The immune complexome could illustrate the difference of immune status between clinical forms of chronic Chagas disease. © 2016 John Wiley & Sons Ltd.

  10. A new conceptual framework for investigating complex genetic disease

    Directory of Open Access Journals (Sweden)

    Shobbir eHussain

    2015-11-01

    Full Text Available Some common diseases are known to have an inherited component, however their population- and familial-incidence patterns do not conform to any known monogenic Mendelian pattern of inheritance and instead they are currently much better explained if an underlying polygenic architecture is posited. Studies that have attempted to identify the causative genetic factors have been designed on this polygenic framework, but so far the yield has been largely unsatisfactory. Based on accumulating recent observations concerning the roles of somatic mosaicism in disease, in this article a second framework which posits a single gene-two hit model which can be modulated by a mutator/anti-mutator genetic background is suggested. I discuss whether such a model can be considered a viable alternative based on current knowledge, its advantages over the current polygenic framework, and describe practical routes via which the new framework can be investigated.

  11. Patient access to complex chronic disease records on the Internet.

    Science.gov (United States)

    Bartlett, Cherry; Simpson, Keith; Turner, A Neil

    2012-08-06

    Access to medical records on the Internet has been reported to be acceptable and popular with patients, although most published evaluations have been of primary care or office-based practice. We tested the feasibility and acceptability of making unscreened results and data from a complex chronic disease pathway (renal medicine) available to patients over the Internet in a project involving more than half of renal units in the UK. Content and presentation of the Renal PatientView (RPV) system was developed with patient groups. It was designed to receive information from multiple local information systems and to require minimal extra work in units. After piloting in 4 centres in 2005 it was made available more widely. Opinions were sought from both patients who enrolled and from those who did not in a paper survey, and from staff in an electronic survey. Anonymous data on enrollment and usage were extracted from the webserver. By mid 2011 over 17,000 patients from 47 of the 75 renal units in the UK had registered. Users had a wide age range (90 yrs) but were younger and had more years of education than non-users. They were enthusiastic about the concept, found it easy to use, and 80% felt it gave them a better understanding of their disease. The most common reason for not enrolling was being unaware of the system. A minority of patients had security concerns, and these were reduced after enrolling. Staff responses were also strongly positive. They reported that it aided patient concordance and disease management, and increased the quality of consultations with a neutral effect on consultation length. Neither patient nor staff responses suggested that RPV led to an overall increase in patient anxiety or to an increased burden on renal units beyond the time required to enroll each patient. Patient Internet access to secondary care records concerning a complex chronic disease is feasible and popular, providing an increased sense of empowerment and understanding, with no

  12. Patient access to complex chronic disease records on the Internet

    Directory of Open Access Journals (Sweden)

    Bartlett Cherry

    2012-08-01

    Full Text Available Abstract Background Access to medical records on the Internet has been reported to be acceptable and popular with patients, although most published evaluations have been of primary care or office-based practice. We tested the feasibility and acceptability of making unscreened results and data from a complex chronic disease pathway (renal medicine available to patients over the Internet in a project involving more than half of renal units in the UK. Methods Content and presentation of the Renal PatientView (RPV system was developed with patient groups. It was designed to receive information from multiple local information systems and to require minimal extra work in units. After piloting in 4 centres in 2005 it was made available more widely. Opinions were sought from both patients who enrolled and from those who did not in a paper survey, and from staff in an electronic survey. Anonymous data on enrolments and usage were extracted from the webserver. Results By mid 2011 over 17,000 patients from 47 of the 75 renal units in the UK had registered. Users had a wide age range (90 yrs but were younger and had more years of education than non-users. They were enthusiastic about the concept, found it easy to use, and 80% felt it gave them a better understanding of their disease. The most common reason for not enrolling was being unaware of the system. A minority of patients had security concerns, and these were reduced after enrolling. Staff responses were also strongly positive. They reported that it aided patient concordance and disease management, and increased the quality of consultations with a neutral effect on consultation length. Neither patient nor staff responses suggested that RPV led to an overall increase in patient anxiety or to an increased burden on renal units beyond the time required to enrol each patient. Conclusions Patient Internet access to secondary care records concerning a complex chronic disease is feasible and popular

  13. Tuberous sclerosis complex and polycystic kidney disease contiguous gene syndrome with Moyamoya disease.

    Science.gov (United States)

    Lai, Jonathan; Modi, Lopa; Ramai, Daryl; Tortora, Matthew

    2017-04-01

    Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are two diseases sharing close genetic loci on chromosome 16. Due to contiguous gene syndrome, also known as contiguous gene deletion syndrome, the proximity of TSC2 and PKD1 genes increases the risk of co-deletion resulting in a shared clinical presentation. Furthermore, Moyamoya disease (MMD) is a rare vaso-occlusive disease in the circle of Willis. We present the first case of TSC2/PKD1 contiguous gene syndrome in a patient with MMD along with detailed histopathologic, radiologic, and cytogenetic analyses. We also highlight the clinical presentation and surgical complications in this case. Copyright © 2017 Elsevier GmbH. All rights reserved.

  14. Underlying diseases in syncope of children in China

    Science.gov (United States)

    Li, Chen; Cheng, Wang; Hongwei, Wang; Hong, Tian; Chaoshu, Tang; Hongfang, Jin; Junbao, Du

    2011-01-01

    Summary Background Syncope accounts for about 1–2% of emergency department visits, but the etiology in many patients with syncope is unclear. Recently, with the use of the head-up tilt test (HUT), the number of patients with unexplained syncope (UPS) has been decreasing; however, the spectrum of underlying diseases of syncope in children is unclear. This retrospective study aimed to analyze the spectrum of underlying diseases in children with syncope. Material/Methods This multi-center clinical study consisted of 888 children (417 males, 471 females, aged 5–18 yrs, median age 12.0±3.0 yrs) with syncope who came from Beijing city, Hunan province, Hubei province and Shanghai from August 1999 to March 2009. The clinical and laboratory data of children were studied and the spectrum of underlying diseases in children with syncope was analyzed. Results In 888 children with syncope, 175 (19.7%) had vasovagal syncope (VVS) with vasoinhibitory response, 35 (3.9%) had VVS with cardioinhibitory response, 73 (8.2%) had VVS with mixed response, 286 (32.2%) had postural orthostatic tachycardia syndrome (POTS), 19 (2.1%) had orthostatic hypotension, 7 (0.9%) had situational syncope, 13 (1.5%) had cardiogenic syncope, and 280 (31.5%) had unexplained syncope. Conclusions The data suggest that neurally-mediated syncope was the most common cause in children with syncope. POTS and VVS were the most common hemodynamic patterns of neurally-mediated syncope. PMID:21629199

  15. Visualizing the indefinable: three-dimensional complexity of 'infectious diseases'.

    Directory of Open Access Journals (Sweden)

    Gabriel Leitner

    Full Text Available The words 'infection' and 'inflammation' lack specific definitions. Here, such words are not defined. Instead, the ability to visualize host-microbial interactions was explored.Leukocyte differential counts and four bacterial species (Staphylococcus aureus, Streptococcus dysgalactiae, Staphylococcus chromogenes, and Escherichia coli were determined or isolated in a cross-sectional and randomized study conducted with 611 bovine milk samples. Two paradigms were evaluated: (i the classic one, which measures non-structured (count or percent data; and (ii a method that, using complex data structures, detects and differentiates three-dimensional (3D interactions among lymphocytes (L, macrophages (M, and neutrophils (N.Classic analyses failed to differentiate bacterial-positive (B+ from -negative (B- observations: B- and B+ data overlapped, even when statistical significance was achieved. In contrast, the alternative approach showed distinct patterns, such as perpendicular data inflections, which discriminated microbial-negative/mononuclear cell-predominating (MCP from microbial-positive/phagocyte-predominating (PP subsets. Two PP subcategories were distinguished, as well as PP/culture-negative (false-negative and MCP/culture-positive (false-positive observations. In 3D space, MCP and PP subsets were perpendicular to one another, displaying ≥ 91% specificity or sensitivity. Findings supported five inferences: (i disease is not always ruled out by negative bacterial tests; (ii low total cell counts can coexist with high phagocyte percents; (iii neither positive bacterial isolation nor high cell counts always coincide with PP profiles; (iv statistical significance is not synonymous with discrimination; and (v hidden relationships cannot be detected when simple (non-structured data formats are used and statistical analyses are performed before data subsets are identified, but can be uncovered when complexity is investigated.Pattern recognition

  16. Bioresorbable vascular scaffold in patients with complex coronary artery disease.

    Science.gov (United States)

    Tamburino, Claudia I; Capranzano, Piera; Longo, Giovanni; Immè, Sebastiano; Tamburino, Giacomo; Scalia, Matteo; Condorelli, Antonio; Francaviglia, Bruno; LA Manna, Alessio; Sgroi, Carmelo; Grasso, Carmelo; DI Salvo, Maria E; Capodanno, Davide; Tamburino, Corrado

    2016-08-01

    The advent of fully bioresorbable stent technology is heralded as breakthrough technology in the current era of percutaneous coronary interventions (PCI). Bioresorbable scaffolds (BRS) have the potential to introduce a paradigm shift in interventional cardiology, representing an anatomical and functional "vascular restoration" therapy instead of an artificial stiff tube encased by persistent metallic foreign body. Among BRS, the everolimus-eluting scaffold (ABSORB, Abbott Vascular, Santa Clara, CA, USA) has been the most extensively investigated in clinical studies. The use of ABSORB in the treatment of relatively simple lesions appears to provide a similar degree of safety and efficacy compared with metallic drug-eluting stent (DES) treated under randomized trials conditions, but patients treated in real-world practice are far more complex than those included in randomized trials. Therefore, several ABSORB all-comers registries dealing with real world conditions are being performed. Their currently available results are summarized in the present overview.

  17. Under-ascertainment, under-reporting and timeliness of Iranian communicable disease surveillance system for zoonotic diseases.

    Science.gov (United States)

    Kazerooni, P A; Fararouei, M; Nejat, M; Akbarpoor, M; Sedaghat, Z

    2018-01-01

    The important steps in controlling infectious diseases are fast detection, proper treatment and on-time reporting of cases to the appropriate authorities. This study was conducted to evaluate the quality of Iranian communicable diseases surveillance system (CDSS) for zoonotic diseases in rural areas of Fars province (Iran's third largest province). The three most important evaluation indices of CDSS, namely under-ascertainment, under-reporting and timeliness, for the three most common zoonotic diseases were measured using independent data source obtained from door-to-door interviews and patients' medical records. Interviews were conducted with 48,771 households in rural areas of Fars province from April 2014 to March 2015. The medical and registration data were obtained from the CDSS and medical or health centres. Under-ascertainment, total under-reporting and timeliness (delay from the time of onset of symptoms to the time of visiting a medical or health centre, to the time of reporting visited cases to the highest level of CDSS) for leishmaniasis were 19.6%, 42.5% and 81.61 days (48.95 due to system delay), respectively. The corresponding indices for brucellosis were 0%, 41.8% and 56.5 days (22 due to system delay), respectively. For animal bite, the corresponding indices were 7.83%, 13.07% and less than 72 h, respectively (no system delay). Although the status of case reporting and timeliness of surveillance system in public sectors providing medical services are clearly better than those of the private sectors, the indices are far from the level needed by CDSS to be able to detect and handle epidemics on time. Training health personnel, especially physicians, from public and private sectors to secure their cooperation along with routine and indebt evaluation are necessary to improve CDSS in Iran. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  18. Micro RNA, A Review: Pharmacogenomic drug targets for complex diseases

    Directory of Open Access Journals (Sweden)

    Sandhya Bawa

    2010-01-01

    differentially expressed in malignant cells compared to normal cells altering the regulation of expression of many important genes. MiRNA expression has been used for prognosis and early diagnosis of these complex diseases.  The present paper focuses on the role of miRNAs in various complex diseases, which will help in improving the drug discovery process and personalized medicines.

     

  • Understanding the Fatigue Behavior of FML Structures and Materials under Complex Variable Amplitude Loading

    NARCIS (Netherlands)

    Alderdiesten, R.; Benedictus, R.; Khan, S.

    2009-01-01

    This paper presents various failure mechanisms in FMLs, highlights the presence or absence of interaction effects, and describes how the failure mechanisms can be described for predicting damage growth under arbitrary complex load spectra.

  • pincer complex in Suzuki–Miyaura cross-coupling reaction under ...

    Indian Academy of Sciences (India)

    high catalytic activity in Suzuki–Miyaura cross coupling reaction under microwave irradiation for a variety of aryl bromides and aryl boronic acids. The complex showed the same efficiency for gram scale reactions. Keywords. Pincer complex; bisphosphomide; Suzuki–Miyaura coupling; microwave irradiation; palladium(II). 1.

    1. The treatment of complex airway diseases with inverted Y-shaped self-expandable metal stent

      International Nuclear Information System (INIS)

      Li Jianming; Jia Guangzhi

      2011-01-01

      Objective: To investigate the application and therapeutic effects of inverted Y-shaped self-expandable metal airway stent in treating complex airway diseases (stenosis or fistula). Methods: According to the distinctive anatomic structure and the pathological changes of complex airway stenosis or fistula, the inverted y-shaped self-expandable metal airway stent was designed. Under fluoroscopic monitoring, a total of 12 inverted Y-shaped self-expandable metal stents were implanted in 12 patients with complex airway diseases. Results: Stent placement in the trachea-bronchial tree was technically successful in all patients. After the operation, the symptom of dyspnea was immediately relieved and the bucking following food intake disappeared. The general physical condition and living quality were much improved in all patients. Conclusion: The use of inverted Y-shaped self-expandable metal airway stent for the management of complex airway stenosis involving the tracheal carina was a simple and safe procedure and it has satisfactory short-term clinical results. (authors)

    2. Impact of asymptomatic infection on coupled disease-behavior dynamics in complex networks

      Science.gov (United States)

      Zhang, Hai-Feng; Xie, Jia-Rong; Chen, Han-Shuang; Liu, Can; Small, Michael

      2016-05-01

      Studies on how to model the interplay between diseases and behavioral responses (so-called coupled disease-behavior interaction) have attracted increasing attention. Owing to the lack of obvious clinical evidence of diseases, or the incomplete information related to the disease, the risks of infection cannot be perceived and may lead to inappropriate behavioral responses. Therefore, how to quantitatively analyze the impacts of asymptomatic infection on the interplay between diseases and behavioral responses is of particular importance. In this letter, under the complex network framework, we study the coupled disease-behavior interaction model by dividing infectious individuals into two states: U-state (without evident clinical symptoms, labelled as U) and I-state (with evident clinical symptoms, labelled as I). A susceptible individual can be infected by U- or I-nodes, however, since the U-nodes cannot be easily observed, susceptible individuals take behavioral responses only when they contact I-nodes. The mechanism is considered in the improved Susceptible-Infected-Susceptible (SIS) model and the improved Susceptible-Infected-Recovered (SIR) model, respectively. Then, one of the most concerned problems in spreading dynamics: the epidemic thresholds for the two models are given by two methods. The analytic results quantitatively describe the influence of different factors, such as asymptomatic infection, the awareness rate, the network structure, and so forth, on the epidemic thresholds. Moreover, because of the irreversible process of the SIR model, the suppression effect of the improved SIR model is weaker than the improved SIS model.

    3. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

      DEFF Research Database (Denmark)

      Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S

      2018-01-01

      Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns...... the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes...... in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely...

    4. Fatigue analysis of assembled marine floating platform for special purposes under complex water environments

      Science.gov (United States)

      Ma, Guang-ying; Yao, Yun-long

      2018-03-01

      In this paper, the fatigue lives of a new type of assembled marine floating platform for special purposes were studied. Firstly, by using ANSYS AQWA software, the hydrodynamic model of the platform was established. Secondly, the structural stresses under alternating change loads were calculated under complex water environments, such as wind, wave, current and ice. The minimum fatigue lives were obtained under different working conditions. The analysis results showed that the fatigue life of the platform structure can meet the requirements

    5. Phenome-wide association study maps new diseases to the human major histocompatibility complex region.

      Science.gov (United States)

      Liu, Jixia; Ye, Zhan; Mayer, John G; Hoch, Brian A; Green, Clayton; Rolak, Loren; Cold, Christopher; Khor, Seik-Soon; Zheng, Xiuwen; Miyagawa, Taku; Tokunaga, Katsushi; Brilliant, Murray H; Hebbring, Scott J

      2016-10-01

      Over 160 disease phenotypes have been mapped to the major histocompatibility complex (MHC) region on chromosome 6 by genome-wide association study (GWAS), suggesting that the MHC region as a whole may be involved in the aetiology of many phenotypes, including unstudied diseases. The phenome-wide association study (PheWAS), a powerful and complementary approach to GWAS, has demonstrated its ability to discover and rediscover genetic associations. The objective of this study is to comprehensively investigate the MHC region by PheWAS to identify new phenotypes mapped to this genetically important region. In the current study, we systematically explored the MHC region using PheWAS to associate 2692 MHC-linked variants (minor allele frequency ≥0.01) with 6221 phenotypes in a cohort of 7481 subjects from the Marshfield Clinic Personalized Medicine Research Project. Findings showed that expected associations previously identified by GWAS could be identified by PheWAS (eg, psoriasis, ankylosing spondylitis, type I diabetes and coeliac disease) with some having strong cross-phenotype associations potentially driven by pleiotropic effects. Importantly, novel associations with eight diseases not previously assessed by GWAS (eg, lichen planus) were also identified and replicated in an independent population. Many of these associated diseases appear to be immune-related disorders. Further assessment of these diseases in 16 484 Marshfield Clinic twins suggests that some of these diseases, including lichen planus, may have genetic aetiologies. These results demonstrate that the PheWAS approach is a powerful and novel method to discover SNP-disease associations, and is ideal when characterising cross-phenotype associations, and further emphasise the importance of the MHC region in human health and disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

    6. Social contact networks and disease eradicability under voluntary vaccination.

      Directory of Open Access Journals (Sweden)

      Ana Perisic

      2009-02-01

      Full Text Available Certain theories suggest that it should be difficult or impossible to eradicate a vaccine-preventable disease under voluntary vaccination: Herd immunity implies that the individual incentive to vaccinate disappears at high coverage levels. Historically, there have been examples of declining coverage for vaccines, such as MMR vaccine and whole-cell pertussis vaccine, that are consistent with this theory. On the other hand, smallpox was globally eradicated by 1980 despite voluntary vaccination policies in many jurisdictions. Previous modeling studies of the interplay between disease dynamics and individual vaccinating behavior have assumed that infection is transmitted in a homogeneously mixing population. By comparison, here we simulate transmission of a vaccine-preventable SEIR infection through a random, static contact network. Individuals choose whether to vaccinate based on infection risks from neighbors, and based on vaccine risks. When neighborhood size is small, rational vaccinating behavior results in rapid containment of the infection through voluntary ring vaccination. As neighborhood size increases (while the average force of infection is held constant, a threshold is reached beyond which the infection can break through partially vaccinated rings, percolating through the whole population and resulting in considerable epidemic final sizes and a large number vaccinated. The former outcome represents convergence between individually and socially optimal outcomes, whereas the latter represents their divergence, as observed in most models of individual vaccinating behavior that assume homogeneous mixing. Similar effects are observed in an extended model using smallpox-specific natural history and transmissibility assumptions. This work illustrates the significant qualitative differences between behavior-infection dynamics in discrete contact-structured populations versus continuous unstructured populations. This work also shows how disease

    7. Identification of susceptible genes for complex chronic diseases based on disease risk functional SNPs and interaction networks.

      Science.gov (United States)

      Li, Wan; Zhu, Lina; Huang, Hao; He, Yuehan; Lv, Junjie; Li, Weimin; Chen, Lina; He, Weiming

      2017-10-01

      Complex chronic diseases are caused by the effects of genetic and environmental factors. Single nucleotide polymorphisms (SNPs), one common type of genetic variations, played vital roles in diseases. We hypothesized that disease risk functional SNPs in coding regions and protein interaction network modules were more likely to contribute to the identification of disease susceptible genes for complex chronic diseases. This could help to further reveal the pathogenesis of complex chronic diseases. Disease risk SNPs were first recognized from public SNP data for coronary heart disease (CHD), hypertension (HT) and type 2 diabetes (T2D). SNPs in coding regions that were classified into nonsense and missense by integrating several SNP functional annotation databases were treated as functional SNPs. Then, regions significantly associated with each disease were screened using random permutations for disease risk functional SNPs. Corresponding to these regions, 155, 169 and 173 potential disease susceptible genes were identified for CHD, HT and T2D, respectively. A disease-related gene product interaction network in environmental context was constructed for interacting gene products of both disease genes and potential disease susceptible genes for these diseases. After functional enrichment analysis for disease associated modules, 5 CHD susceptible genes, 7 HT susceptible genes and 3 T2D susceptible genes were finally identified, some of which had pleiotropic effects. Most of these genes were verified to be related to these diseases in literature. This was similar for disease genes identified from another method proposed by Lee et al. from a different aspect. This research could provide novel perspectives for diagnosis and treatment of complex chronic diseases and susceptible genes identification for other diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

    8. Bone disease in patients with chronic kidney disease under conservative management

      Directory of Open Access Journals (Sweden)

      Carlos Perez Gomes

      Full Text Available CONTEXT AND OBJECTIVE: Few studies have focused on bone disease in patients with chronic kidney disease under conservative treatment. The objective was to evaluate bone disease in patients with chronic kidney disease. DESIGN AND SETTING: Case series, at the Nephrology Division, Hospital Universitário Pedro Ernesto. METHODS: 131 patients with creatinine clearance from 10 to 60 ml/min/1.73 m² were followed up for at least one year. Serum creatinine, albumin, calcium, phosphorus, alkaline phosphatase, total CO2 (tCO2, intact parathyroid hormone (iPTH, and alkaline phosphatase were measured. Creatinine clearance was calculated from 24-hour urine creatinine measurements and protein ingestion estimates from urea assays. RESULTS: Patients presenting creatinine clearance 144 pg/ml showed osteitis fibrosa (4, mild lesion (4 and high turnover (1. CONCLUSION: The present data suggest the importance of early control for iPTH and metabolic acidosis, among patients under conservative management for chronic kidney disease, in order to prevent complications related to bone disease.

    9. Antennal phenotype of Mexican haplogroups of the Triatoma dimidiata complex, vectors of Chagas disease.

      Science.gov (United States)

      May-Concha, Irving; Guerenstein, Pablo G; Ramsey, Janine M; Rojas, Julio C; Catalá, Silvia

      2016-06-01

      Triatoma dimidiata (Latreille) is a species complex that spans North, Central, and South America and which is a key vector of all known discrete typing units (DTU) of Trypanosoma cruzi, the etiologic agent of Chagas disease. Morphological and genetic studies indicate that T. dimidiata is a species complex with three principal haplogroups (hg) in Mexico. Different markers and traits are still inconclusive regarding if other morphological differentiation may indicate probable behavioral and vectorial divergences within this complex. In this paper we compared the antennae of three Mexican haplogroups (previously verified by molecular markers ND4 and ITS-2) and discussed possible relationships with their capacity to disperse and colonized new habitats. The abundance of each type of sensillum (bristles, basiconics, thick- and thin-walled trichoids) on the antennae of the three haplogroups, were measured under light microscopy and compared using Kruskal-Wallis non-parametric and multivariate non-parametric analyses. Discriminant analyses indicate significant differences among the antennal phenotype of haplogroups either for adults and some nymphal stages, indicating consistency of the character to analyze intraspecific variability within the complex. The present study shows that the adult antennal pedicel of the T. dimidiata complex have abundant chemosensory sensilla, according with good capacity for dispersal and invasion of different habitats also related to their high capacity to adapt to conserved as well as modified habitats. However, the numerical differences among the haplogroups are suggesting variations in that capacity. The results here presented support the evidence of T. dimidiata as a species complex but show females and males in a different way. Given the close link between the bug's sensory system and its habitat and host-seeking behavior, AP characterization could be useful to complement genetic, neurological and ethological studies of the closely

    10. Degradation of the mitochondrial complex I assembly factor TMEM126B under chronic hypoxia.

      Science.gov (United States)

      Fuhrmann, Dominik C; Wittig, Ilka; Dröse, Stefan; Schmid, Tobias; Dehne, Nathalie; Brüne, Bernhard

      2018-02-20

      Cell stress such as hypoxia elicits adaptive responses, also on the level of mitochondria, and in part is mediated by the hypoxia-inducible factor (HIF) 1α. Adaptation of mitochondria towards acute hypoxic conditions is reasonably well understood, while regulatory mechanisms, especially of respiratory chain assembly factors, under chronic hypoxia remains elusive. One of these assembly factors is transmembrane protein 126B (TMEM126B). This protein is part of the mitochondrial complex I assembly machinery. We identified changes in complex I abundance under chronic hypoxia, in association with impaired substrate-specific mitochondrial respiration. Complexome profiling of isolated mitochondria of the human leukemia monocytic cell line THP-1 revealed HIF-1α-dependent deficits in complex I assembly and mitochondrial complex I assembly complex (MCIA) abundance. Of all mitochondrial MCIA members, we proved a selective HIF-1-dependent decrease of TMEM126B under chronic hypoxia. Mechanistically, HIF-1α induces the E3-ubiquitin ligase F-box/WD repeat-containing protein 1A (β-TrCP1), which in turn facilitates the proteolytic degradation of TMEM126B. Attenuating a functional complex I assembly appears critical for cellular adaptation towards chronic hypoxia and is linked to destruction of the mitochondrial assembly factor TMEM126B.

    11. Mechanisms Underlying HIV-Associated Noninfectious Lung Disease.

      Science.gov (United States)

      Presti, Rachel M; Flores, Sonia C; Palmer, Brent E; Atkinson, Jeffrey J; Lesko, Catherine R; Lau, Bryan; Fontenot, Andrew P; Roman, Jesse; McDyer, John F; Twigg, Homer L

      2017-11-01

      Pulmonary disease remains a primary source of morbidity and mortality in persons living with HIV (PLWH), although the advent of potent combination antiretroviral therapy has resulted in a shift from predominantly infectious to noninfectious pulmonary complications. PLWH are at high risk for COPD, pulmonary hypertension, and lung cancer even in the era of combination antiretroviral therapy. The underlying mechanisms of this are incompletely understood, but recent research in both human and animal models suggests that oxidative stress, expression of matrix metalloproteinases, and genetic instability may result in lung damage, which predisposes PLWH to these conditions. Some of the factors that drive these processes include tobacco and other substance use, direct HIV infection and expression of specific HIV proteins, inflammation, and shifts in the microbiome toward pathogenic and opportunistic organisms. Further studies are needed to understand the relative importance of these factors to the development of lung disease in PLWH. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

    12. Histiocytoid Sweet Syndrome in a Child without Underlying Systemic Disease.

      Science.gov (United States)

      Yeom, Seung Dohn; Ko, Hye Soo; Moon, Jong Hyuk; Kang, Min Ji; Byun, Ji Won; Choi, Gwang Seong; Shin, Jeonghyun

      2017-10-01

      Sweet syndrome (acute, febrile, neutrophilic dermatosis) is characterized by the acute onset of an eruption of painful nodules or erythematous or violaceous plaques on the limbs, face and neck. These symptoms are accompanied by fever. The diagnostic features include histopathological findings of dermal neutrophilic infiltration without leukocytoclastic vasculitis or peripheral blood leukocytosis. Sweet syndrome is associated with infection, malignancies, autoimmune disease, pregnancy, and drugs. Patients with Sweet syndrome demonstrate a complete and rapid response to systemic steroid administration. Recently, a distinct variant of Sweet syndrome was reported, termed "histiocytoid Sweet syndrome", in which the infiltration of myeloperoxidase-positive histiocytoid mononuclear cells are observed (in contrast to the infiltration of neutrophils). The other clinical features are similar to those of classic Sweet syndrome. Pediatric Sweet syndrome is uncommon, and the histiocytoid type is even rarer. To date, four cases of histiocytoid Sweet syndrome have been reported in children. Herein, we describe a case of histiocytoid Sweet syndrome in an otherwise healthy 10-year-old boy with no underlying systemic disease in whom non-steroidal, anti-inflammatory drug treatment was successful.

    13. Transcriptional regulatory networks underlying gene expression changes in Huntington's disease.

      Science.gov (United States)

      Ament, Seth A; Pearl, Jocelynn R; Cantle, Jeffrey P; Bragg, Robert M; Skene, Peter J; Coffey, Sydney R; Bergey, Dani E; Wheeler, Vanessa C; MacDonald, Marcy E; Baliga, Nitin S; Rosinski, Jim; Hood, Leroy E; Carroll, Jeffrey B; Price, Nathan D

      2018-03-26

      Transcriptional changes occur presymptomatically and throughout Huntington's disease (HD), motivating the study of transcriptional regulatory networks (TRNs) in HD We reconstructed a genome-scale model for the target genes of 718 transcription factors (TFs) in the mouse striatum by integrating a model of genomic binding sites with transcriptome profiling of striatal tissue from HD mouse models. We identified 48 differentially expressed TF-target gene modules associated with age- and CAG repeat length-dependent gene expression changes in Htt CAG knock-in mouse striatum and replicated many of these associations in independent transcriptomic and proteomic datasets. Thirteen of 48 of these predicted TF-target gene modules were also differentially expressed in striatal tissue from human disease. We experimentally validated a specific model prediction that SMAD3 regulates HD-related gene expression changes using chromatin immunoprecipitation and deep sequencing (ChIP-seq) of mouse striatum. We found CAG repeat length-dependent changes in the genomic occupancy of SMAD3 and confirmed our model's prediction that many SMAD3 target genes are downregulated early in HD. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

    14. Action Memorandum for Decommissioning the Engineering Test Reactor Complex under the Idaho Cleanup Project

      International Nuclear Information System (INIS)

      A. B. Culp

      2007-01-01

      This Action Memorandum documents the selected alternative for decommissioning of the Engineering Test Reactor at the Idaho National Laboratory under the Idaho Cleanup Project. Since the missions of the Engineering Test Reactor Complex have been completed, an engineering evaluation/cost analysis that evaluated alternatives to accomplish the decommissioning of the Engineering Test Reactor Complex was prepared and released for public comment. The scope of this Action Memorandum is to encompass the final end state of the Complex and disposal of the Engineering Test Reactor vessel. The selected removal action includes removing and disposing of the vessel at the Idaho CERCLA Disposal Facility and demolishing the reactor building to ground surface

    15. Galectin-9: From cell biology to complex disease dynamics

      Indian Academy of Sciences (India)

      Author Affiliations. SEBASTIAN JOHN1 RASHMI MISHRA1. Department of Neurobiology and Genetics, Division of Disease Biology, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram 695014, India ...

    16. Independent Role of Underlying Kidney Disease on Renal Prognosis of Patients with Chronic Kidney Disease under Nephrology Care.

      Directory of Open Access Journals (Sweden)

      Luca De Nicola

      Full Text Available Primary kidney disease is suggested to affect renal prognosis of CKD patients; however, whether nephrology care modifies this association is unknown. We studied patients with CKD stage I-IV treated in a renal clinic and with established diagnosis of CKD cause to evaluate whether the risk of renal event (composite of end-stage renal disease and eGFR decline ≥ 40% linked to the specific diagnosis is modified by the achievement or maintenance in the first year of nephrology care of therapeutic goals for hypertension (BP ≤ 130/80 mmHg in patients with proteinuria ≥ 1 50 mg/24h and/or diabetes and ≤ 140/90 in those with proteinuria <150 mg/24h and without diabetes anemia (hemoglobin, Hb ≥ 11 g/dL, and proteinuria (≤ 0.5 g/24h. Survival analysis started after first year of nephrology care. We studied 729 patients (age 64 ± 15 y; males 59.1%; diabetes 34.7%; cardiovascular disease (CVD 44.9%; hypertensive nephropathy, HTN 53.8%; glomerulonephritis, GN 17.3%; diabetic nephropathy, DN 15.9%; tubule-interstitial nephropathy, TIN 9.5%; polycystic kidney disease, PKD 3.6%. During first year of Nephrology care, therapy was overall intensified in most patients and prevalence of main therapeutic goals generally improved. During subsequent follow up (median 3.3 years, IQR 1.9-5.1, 163 renal events occurred. Cox analysis disclosed a higher risk for PKD (Hazard Ratio 5.46, 95% Confidence Intervals 2.28-10.6 and DN (1.28,2.99-3.05, versus HTN (reference, independently of age, gender, CVD, BMI, eGFR or CKD stage, use of RAS inhibitors and achievement or maintenance in the first year of nephrology care of each of the three main therapeutic goals. No interaction was found on the risk of CKD progression between diagnostic categories and month-12 eGFR (P=0.737, as with control of BP (P=0.374, Hb (P=0.248 or proteinuria (P=0.590. Therefore, in CKD patients under nephrology care, diagnosis of kidney disease should be considered in conjunction with the main

    17. Independent Role of Underlying Kidney Disease on Renal Prognosis of Patients with Chronic Kidney Disease under Nephrology Care.

      Science.gov (United States)

      De Nicola, Luca; Provenzano, Michele; Chiodini, Paolo; Borrelli, Silvio; Garofalo, Carlo; Pacilio, Mario; Liberti, Maria Elena; Sagliocca, Adelia; Conte, Giuseppe; Minutolo, Roberto

      2015-01-01

      Primary kidney disease is suggested to affect renal prognosis of CKD patients; however, whether nephrology care modifies this association is unknown. We studied patients with CKD stage I-IV treated in a renal clinic and with established diagnosis of CKD cause to evaluate whether the risk of renal event (composite of end-stage renal disease and eGFR decline ≥ 40%) linked to the specific diagnosis is modified by the achievement or maintenance in the first year of nephrology care of therapeutic goals for hypertension (BP ≤ 130/80 mmHg in patients with proteinuria ≥ 1 50 mg/24h and/or diabetes and ≤ 140/90 in those with proteinuria nephrology care. We studied 729 patients (age 64 ± 15 y; males 59.1%; diabetes 34.7%; cardiovascular disease (CVD) 44.9%; hypertensive nephropathy, HTN 53.8%; glomerulonephritis, GN 17.3%; diabetic nephropathy, DN 15.9%; tubule-interstitial nephropathy, TIN 9.5%; polycystic kidney disease, PKD 3.6%). During first year of Nephrology care, therapy was overall intensified in most patients and prevalence of main therapeutic goals generally improved. During subsequent follow up (median 3.3 years, IQR 1.9-5.1), 163 renal events occurred. Cox analysis disclosed a higher risk for PKD (Hazard Ratio 5.46, 95% Confidence Intervals 2.28-10.6) and DN (1.28,2.99-3.05), versus HTN (reference), independently of age, gender, CVD, BMI, eGFR or CKD stage, use of RAS inhibitors and achievement or maintenance in the first year of nephrology care of each of the three main therapeutic goals. No interaction was found on the risk of CKD progression between diagnostic categories and month-12 eGFR (P=0.737), as with control of BP (P=0.374), Hb (P=0.248) or proteinuria (P=0.590). Therefore, in CKD patients under nephrology care, diagnosis of kidney disease should be considered in conjunction with the main risk factors to refine renal risk stratification.

    18. Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiology

      OpenAIRE

      Spataro, Nino, 1984-; Rodríguez, Juan Antonio; Navarro i Cuartiellas, Arcadi, 1969-; Bosch Fusté, Elena

      2017-01-01

      Abstract Do genes presenting variation that has been linked to human disease have different biological properties than genes that have never been related to disease? What is the relationship between disease and fitness? Are the evolutionary pressures that affect genes linked to Mendelian diseases the same to those acting on genes whose variation contributes to complex disorders? The answers to these questions could shed light on the architecture of human genetic disorders and may have relevan...

    19. Properties of human disease genes and the role of genes linked to Mendelian disorders in complex disease aetiology.

      Science.gov (United States)

      Spataro, Nino; Rodríguez, Juan Antonio; Navarro, Arcadi; Bosch, Elena

      2017-02-01

      Do genes presenting variation that has been linked to human disease have different biological properties than genes that have never been related to disease? What is the relationship between disease and fitness? Are the evolutionary pressures that affect genes linked to Mendelian diseases the same to those acting on genes whose variation contributes to complex disorders? The answers to these questions could shed light on the architecture of human genetic disorders and may have relevant implications when designing mapping strategies in future genetic studies. Here we show that, relative to non-disease genes, human disease (HD) genes have specific evolutionary profiles and protein network properties. Additionally, our results indicate that the mutation-selection balance renders an insufficient account of the evolutionary history of some HD genes and that adaptive selection could also contribute to shape their genetic architecture. Notably, several biological features of HD genes depend on the type of pathology (complex or Mendelian) with which they are related. For example, genes harbouring both causal variants for Mendelian disorders and risk factors for complex disease traits (Complex-Mendelian genes), tend to present higher functional relevance in the protein network and higher expression levels than genes associated only with complex disorders. Moreover, risk variants in Complex-Mendelian genes tend to present higher odds ratios than those on genes associated with the same complex disorders but with no link to Mendelian diseases. Taken together, our results suggest that genetic variation at genes linked to Mendelian disorders plays an important role in driving susceptibility to complex disease. © The Author 2017. Published by Oxford University Press.

    20. Thyroid functional disease: an under-recognized cardiovascular risk factor in kidney disease patients

      Science.gov (United States)

      Rhee, Connie M.; Brent, Gregory A.; Kovesdy, Csaba P.; Soldin, Offie P.; Nguyen, Danh; Budoff, Matthew J.; Brunelli, Steven M.; Kalantar-Zadeh, Kamyar

      2015-01-01

      Thyroid functional disease, and in particular hypothyroidism, is highly prevalent among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In the general population, hypothyroidism is associated with impaired cardiac contractility, endothelial dysfunction, atherosclerosis and possibly higher cardiovascular mortality. It has been hypothesized that hypothyroidism is an under-recognized, modifiable risk factor for the enormous burden of cardiovascular disease and death in CKD and ESRD, but this has been difficult to test due to the challenge of accurate thyroid functional assessment in uremia. Low thyroid hormone levels (i.e. triiodothyronine) have been associated with adverse cardiovascular sequelae in CKD and ESRD patients, but these metrics are confounded by malnutrition, inflammation and comorbid states, and hence may signify nonthyroidal illness (i.e. thyroid functional test derangements associated with underlying ill health in the absence of thyroid pathology). Thyrotropin is considered a sensitive and specific thyroid function measure that may more accurately classify hypothyroidism, but few studies have examined the clinical significance of thyrotropin-defined hypothyroidism in CKD and ESRD. Of even greater uncertainty are the risks and benefits of thyroid hormone replacement, which bear a narrow therapeutic-to-toxic window and are frequently prescribed to CKD and ESRD patients. In this review, we discuss mechanisms by which hypothyroidism adversely affects cardiovascular health; examine the prognostic implications of hypothyroidism, thyroid hormone alterations and exogenous thyroid hormone replacement in CKD and ESRD; and identify areas of uncertainty related to the interplay between hypothyroidism, cardiovascular disease and kidney disease requiring further investigation. PMID:24574542

    1. [Influence of different iron compounds on lipid complex of vitamin fortified wheat flour under storage].

      Science.gov (United States)

      Vorob'eva, I S; Baĭkov, V G; Vorob'eva, V M; Shatniuk, L N

      2009-01-01

      Influence of different iron compounds at combined vitamin fortification on hygienic and biochemical properties of freshly grounded first-class wheat flour under storage was studied. It proved, that more intensive oxidative and hydrolytic processes take place in the lipid complex of the flour, fortified with ferrous sulfate heptahydrate.

    2. L2 Speaking Development during Study Abroad: Fluency, Accuracy, Complexity, and Underlying Cognitive Factors

      Science.gov (United States)

      Leonard, Karen Ruth; Shea, Christine E.

      2017-01-01

      We take a multidimensional perspective on the development of second language (L2) speaking ability and examine how changes in the underlying cognitive variables of linguistic knowledge and processing speed interact with complexity, fluency, and accuracy over the course of a 3-month Spanish study abroad session. Study abroad provides a unique…

    3. Simplified reactive power management strategy for complex power grids under stochastic operation and incomplete information

      DEFF Research Database (Denmark)

      Vlachogiannis, Ioannis (John)

      2009-01-01

      grids is a major issue for system operators. Under these circumstances an online reactive power management strategy with minimum risk concerning all uncertain and stochastic parameters is proposed. Therefore, new concepts such as reactive power-weighted node-to-node linking and reactive power control......In the current released energy market, the large-scale complex transmission networks and the distribution ones with dispersed energy sources and "intelligent" components operate under uncertainties, stochastic and prior incomplete information. A safe and reliable operation of such complex power...... capability are introduced. A distributed and interconnected stochastic learning automata system is implemented to manage, in a unified and unique way, the reactive power in complex power grids with stochastic reactive power demand and detect the vulnerable part. The proposed simplified strategy can also...

    4. Microwave Synthesis Under Solvent-Free Conditions and Spectral Studies of Some Mesoporphyrinic Complexes

      Directory of Open Access Journals (Sweden)

      Rica Boscencu

      2012-05-01

      Full Text Available A series of A3B and A4 type mesoporphyrinic complexes were synthesized with superior yields using microwave irradiation under solvent-free conditions. The structures of the complexes were confirmed using elemental analysis, FT-IR, UV-Vis, EPR and NMR spectral data. The influence of environmental polarity on spectral properties of the mesoporphyrinic complexes was investigated. The obtained results indicate that the shape of absorption and fluorescence spectra does not depend on the solvent polarity under the experimental conditions used. The small shifts of the absorption and emission maximums that occur by increasing of solvent polarity reflects the physical interaction between the porphyrinic substituents and the solvent molecules.

    5. The Impact of Evolutionary Driving Forces on Human Complex Diseases: A Population Genetics Approach

      Directory of Open Access Journals (Sweden)

      Amr T. M. Saeb

      2016-01-01

      Full Text Available Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases.

    6. Tumour necrosis factor gene complex polymorphisms in chronic obstructive pulmonary disease.

      Science.gov (United States)

      Ruse, Charlotte E; Hill, Maureen C; Tobin, Martin; Neale, Natalie; Connolly, Martin J; Parker, Stuart G; Wardlaw, Andrew J

      2007-02-01

      We aimed to examine the role of tumour necrosis factor gene complex polymorphisms in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that individuals possessing polymorphic variants associated with higher tumour necrosis factor (TNF) secretion would be more susceptible to and/or have more severe disease. Patients with COPD and population controls underwent detailed clinical phenotyping. Genotyping for the tumour necrosis factor-308 and the lymphotoxin alpha NcoI (LTalpha polymorphisms was carried out by 'blinded' laboratory staff. Three hundred and sixty one individuals (220 cases and 141 controls) were recruited. We showed an association between the LTalphaNcol polymorphism and forced vital capacity (FVC) in a population of older adults with and without COPD. The LTalphaNcol*2 allele was associated with poorer lung function, under a codominant model, with a fall in FVC (expressed as a percentage of its predicted value) of 3.7% for each copy of the LTalphaNcol*2 allele possessed (for FVC, regression coefficient (95% CI)=-3.73(-7.01 to -0.44), P=0.026; for FEV(1) regression coefficient=-3.56(-7.80 to 0.70), P=0.101. However, there was no difference in genotype distribution between the case and control populations. This study adds weight to the suggestion that the TNF gene complex is involved in physiological alterations (FVC) that may affect the development and severity of COPD. The absence of a significant association between the TNF gene-complex polymorphisms in this study does not rule out a modest effect of these polymorphisms on the risk of COPD, as much larger studies are needed to detect modest gene effects on binary disease endpoints.

    7. A Systemic Analysis of Transcriptomic and Epigenomic Data To Reveal Regulation Patterns for Complex Disease.

      Science.gov (United States)

      Xu, Chao; Zhang, Ji-Gang; Lin, Dongdong; Zhang, Lan; Shen, Hui; Deng, Hong-Wen

      2017-07-05

      Integrating diverse genomics data can provide a global view of the complex biological processes related to the human complex diseases. Although substantial efforts have been made to integrate different omics data, there are at least three challenges for multi-omics integration methods: (i) How to simultaneously consider the effects of various genomic factors, since these factors jointly influence the phenotypes; (ii) How to effectively incorporate the information from publicly accessible databases and omics datasets to fully capture the interactions among (epi)genomic factors from diverse omics data; and (iii) Until present, the combination of more than two omics datasets has been poorly explored. Current integration approaches are not sufficient to address all of these challenges together. We proposed a novel integrative analysis framework by incorporating sparse model, multivariate analysis, Gaussian graphical model, and network analysis to address these three challenges simultaneously. Based on this strategy, we performed a systemic analysis for glioblastoma multiforme (GBM) integrating genome-wide gene expression, DNA methylation, and miRNA expression data. We identified three regulatory modules of genomic factors associated with GBM survival time and revealed a global regulatory pattern for GBM by combining the three modules, with respect to the common regulatory factors. Our method can not only identify disease-associated dysregulated genomic factors from different omics, but more importantly, it can incorporate the information from publicly accessible databases and omics datasets to infer a comprehensive interaction map of all these dysregulated genomic factors. Our work represents an innovative approach to enhance our understanding of molecular genomic mechanisms underlying human complex diseases. Copyright © 2017 Xu et al.

    8. A novel approach to simulate gene-environment interactions in complex diseases

      Directory of Open Access Journals (Sweden)

      Nicodemi Mario

      2010-01-01

      Full Text Available Abstract Background Complex diseases are multifactorial traits caused by both genetic and environmental factors. They represent the major part of human diseases and include those with largest prevalence and mortality (cancer, heart disease, obesity, etc.. Despite a large amount of information that has been collected about both genetic and environmental risk factors, there are few examples of studies on their interactions in epidemiological literature. One reason can be the incomplete knowledge of the power of statistical methods designed to search for risk factors and their interactions in these data sets. An improvement in this direction would lead to a better understanding and description of gene-environment interactions. To this aim, a possible strategy is to challenge the different statistical methods against data sets where the underlying phenomenon is completely known and fully controllable, for example simulated ones. Results We present a mathematical approach that models gene-environment interactions. By this method it is possible to generate simulated populations having gene-environment interactions of any form, involving any number of genetic and environmental factors and also allowing non-linear interactions as epistasis. In particular, we implemented a simple version of this model in a Gene-Environment iNteraction Simulator (GENS, a tool designed to simulate case-control data sets where a one gene-one environment interaction influences the disease risk. The main aim has been to allow the input of population characteristics by using standard epidemiological measures and to implement constraints to make the simulator behaviour biologically meaningful. Conclusions By the multi-logistic model implemented in GENS it is possible to simulate case-control samples of complex disease where gene-environment interactions influence the disease risk. The user has full control of the main characteristics of the simulated population and a Monte

    9. Neural correlates underlying micrographia in Parkinson’s disease

      Science.gov (United States)

      Zhang, Jiarong; Hallett, Mark; Feng, Tao; Hou, Yanan; Chan, Piu

      2016-01-01

      Micrographia is a common symptom in Parkinson’s disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks. PMID:26525918

    10. Functional abnormalities underlying pathological gambling in Parkinson disease.

      Science.gov (United States)

      Cilia, Roberto; Siri, Chiara; Marotta, Giorgio; Isaias, Ioannis U; De Gaspari, Danilo; Canesi, Margherita; Pezzoli, Gianni; Antonini, Angelo

      2008-12-01

      Pathological gambling (PG) may develop in patients with Parkinson disease (PD) during dopamine replacement therapy, but the underlying neural correlates are still unclear. To investigate resting state brain perfusion in PD patients with active PG compared with matched PD controls and healthy controls. Case-control study. Outpatient tertiary clinic. Eleven right-handed PD patients with active PG according to Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria, 40 matched PD controls, and 29 age-matched healthy controls. All the participants underwent resting state brain perfusion single-photon emission computed tomography using technetium TC 99m ethylcysteinate dimer bicisate. All PD subjects were taking dopaminergic medication. Statistical Parametric Mapping was used for data analysis (P<.005, false discovery rate corrected). PD patients with PG showed resting state overactivity in a right hemisphere network that included the orbitofrontal cortex, the hippocampus, the amygdala, the insula, and the ventral pallidum. No areas of perfusion reduction were detected. We found that PD patients with PG have abnormal resting state dysfunction of the mesocorticolimbic network possibly associated with a drug-induced overstimulation of relatively preserved reward-related neuronal systems. These findings support the concept that PG is a "behavioral" addictive disorder.

    11. Bromodomain Inhibitors Correct Bioenergetic Deficiency Caused by Mitochondrial Disease Complex I Mutations.

      Science.gov (United States)

      Barrow, Joeva J; Balsa, Eduardo; Verdeguer, Francisco; Tavares, Clint D J; Soustek, Meghan S; Hollingsworth, Louis R; Jedrychowski, Mark; Vogel, Rutger; Paulo, Joao A; Smeitink, Jan; Gygi, Steve P; Doench, John; Root, David E; Puigserver, Pere

      2016-10-06

      Mitochondrial diseases comprise a heterogeneous group of genetically inherited disorders that cause failures in energetic and metabolic function. Boosting residual oxidative phosphorylation (OXPHOS) activity can partially correct these failures. Herein, using a high-throughput chemical screen, we identified the bromodomain inhibitor I-BET 525762A as one of the top hits that increases COX5a protein levels in complex I (CI) mutant cybrid cells. In parallel, bromodomain-containing protein 4 (BRD4), a target of I-BET 525762A, was identified using a genome-wide CRISPR screen to search for genes whose loss of function rescues death of CI-impaired cybrids grown under conditions requiring OXPHOS activity for survival. We show that I-BET525762A or loss of BRD4 remodeled the mitochondrial proteome to increase the levels and activity of OXPHOS protein complexes, leading to rescue of the bioenergetic defects and cell death caused by mutations or chemical inhibition of CI. These studies show that BRD4 inhibition may have therapeutic implications for the treatment of mitochondrial diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

    12. Amputation effects on the underlying complexity within transtibial amputee ankle motion

      Energy Technology Data Exchange (ETDEWEB)

      Wurdeman, Shane R., E-mail: shanewurdeman@gmail.com [Nebraska Biomechanics Core Facility, University of Nebraska at Omaha, Omaha, Nebraska 68182 (United States); Advanced Prosthetics Center, Omaha, Nebraska 68134 (United States); Myers, Sara A. [Nebraska Biomechanics Core Facility, University of Nebraska at Omaha, Omaha, Nebraska 68182 (United States); Stergiou, Nicholas [Nebraska Biomechanics Core Facility, University of Nebraska at Omaha, Omaha, Nebraska 68182 (United States); College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska 68198 (United States)

      2014-03-15

      The presence of chaos in walking is considered to provide a stable, yet adaptable means for locomotion. This study examined whether lower limb amputation and subsequent prosthetic rehabilitation resulted in a loss of complexity in amputee gait. Twenty-eight individuals with transtibial amputation participated in a 6 week, randomized cross-over design study in which they underwent a 3 week adaptation period to two separate prostheses. One prosthesis was deemed “more appropriate” and the other “less appropriate” based on matching/mismatching activity levels of the person and the prosthesis. Subjects performed a treadmill walking trial at self-selected walking speed at multiple points of the adaptation period, while kinematics of the ankle were recorded. Bilateral sagittal plane ankle motion was analyzed for underlying complexity through the pseudoperiodic surrogation analysis technique. Results revealed the presence of underlying deterministic structure in both prostheses and both the prosthetic and sound leg ankle (discriminant measure largest Lyapunov exponent). Results also revealed that the prosthetic ankle may be more likely to suffer loss of complexity than the sound ankle, and a “more appropriate” prosthesis may be better suited to help restore a healthy complexity of movement within the prosthetic ankle motion compared to a “less appropriate” prosthesis (discriminant measure sample entropy). Results from sample entropy results are less likely to be affected by the intracycle periodic dynamics as compared to the largest Lyapunov exponent. Adaptation does not seem to influence complexity in the system for experienced prosthesis users.

    13. Amputation effects on the underlying complexity within transtibial amputee ankle motion

      Science.gov (United States)

      Wurdeman, Shane R.; Myers, Sara A.; Stergiou, Nicholas

      2014-03-01

      The presence of chaos in walking is considered to provide a stable, yet adaptable means for locomotion. This study examined whether lower limb amputation and subsequent prosthetic rehabilitation resulted in a loss of complexity in amputee gait. Twenty-eight individuals with transtibial amputation participated in a 6 week, randomized cross-over design study in which they underwent a 3 week adaptation period to two separate prostheses. One prosthesis was deemed "more appropriate" and the other "less appropriate" based on matching/mismatching activity levels of the person and the prosthesis. Subjects performed a treadmill walking trial at self-selected walking speed at multiple points of the adaptation period, while kinematics of the ankle were recorded. Bilateral sagittal plane ankle motion was analyzed for underlying complexity through the pseudoperiodic surrogation analysis technique. Results revealed the presence of underlying deterministic structure in both prostheses and both the prosthetic and sound leg ankle (discriminant measure largest Lyapunov exponent). Results also revealed that the prosthetic ankle may be more likely to suffer loss of complexity than the sound ankle, and a "more appropriate" prosthesis may be better suited to help restore a healthy complexity of movement within the prosthetic ankle motion compared to a "less appropriate" prosthesis (discriminant measure sample entropy). Results from sample entropy results are less likely to be affected by the intracycle periodic dynamics as compared to the largest Lyapunov exponent. Adaptation does not seem to influence complexity in the system for experienced prosthesis users.

    14. Amputation effects on the underlying complexity within transtibial amputee ankle motion

      International Nuclear Information System (INIS)

      Wurdeman, Shane R.; Myers, Sara A.; Stergiou, Nicholas

      2014-01-01

      The presence of chaos in walking is considered to provide a stable, yet adaptable means for locomotion. This study examined whether lower limb amputation and subsequent prosthetic rehabilitation resulted in a loss of complexity in amputee gait. Twenty-eight individuals with transtibial amputation participated in a 6 week, randomized cross-over design study in which they underwent a 3 week adaptation period to two separate prostheses. One prosthesis was deemed “more appropriate” and the other “less appropriate” based on matching/mismatching activity levels of the person and the prosthesis. Subjects performed a treadmill walking trial at self-selected walking speed at multiple points of the adaptation period, while kinematics of the ankle were recorded. Bilateral sagittal plane ankle motion was analyzed for underlying complexity through the pseudoperiodic surrogation analysis technique. Results revealed the presence of underlying deterministic structure in both prostheses and both the prosthetic and sound leg ankle (discriminant measure largest Lyapunov exponent). Results also revealed that the prosthetic ankle may be more likely to suffer loss of complexity than the sound ankle, and a “more appropriate” prosthesis may be better suited to help restore a healthy complexity of movement within the prosthetic ankle motion compared to a “less appropriate” prosthesis (discriminant measure sample entropy). Results from sample entropy results are less likely to be affected by the intracycle periodic dynamics as compared to the largest Lyapunov exponent. Adaptation does not seem to influence complexity in the system for experienced prosthesis users

    15. Amputation effects on the underlying complexity within transtibial amputee ankle motion.

      Science.gov (United States)

      Wurdeman, Shane R; Myers, Sara A; Stergiou, Nicholas

      2014-03-01

      The presence of chaos in walking is considered to provide a stable, yet adaptable means for locomotion. This study examined whether lower limb amputation and subsequent prosthetic rehabilitation resulted in a loss of complexity in amputee gait. Twenty-eight individuals with transtibial amputation participated in a 6 week, randomized cross-over design study in which they underwent a 3 week adaptation period to two separate prostheses. One prosthesis was deemed "more appropriate" and the other "less appropriate" based on matching/mismatching activity levels of the person and the prosthesis. Subjects performed a treadmill walking trial at self-selected walking speed at multiple points of the adaptation period, while kinematics of the ankle were recorded. Bilateral sagittal plane ankle motion was analyzed for underlying complexity through the pseudoperiodic surrogation analysis technique. Results revealed the presence of underlying deterministic structure in both prostheses and both the prosthetic and sound leg ankle (discriminant measure largest Lyapunov exponent). Results also revealed that the prosthetic ankle may be more likely to suffer loss of complexity than the sound ankle, and a "more appropriate" prosthesis may be better suited to help restore a healthy complexity of movement within the prosthetic ankle motion compared to a "less appropriate" prosthesis (discriminant measure sample entropy). Results from sample entropy results are less likely to be affected by the intracycle periodic dynamics as compared to the largest Lyapunov exponent. Adaptation does not seem to influence complexity in the system for experienced prosthesis users.

    16. Forest pathogens and diseases under changing climate-A review

      International Nuclear Information System (INIS)

      Raza, M. M.; Khan, M. A.; Aslam, H. M. U.; Riaz, K.

      2015-01-01

      Changing climate threatens tree health by affecting the likelihood, frequency of occurrence, types and severity of forest diseases caused by diverse pests, resultantly altering the forest ecosystems. The present review covers the relationship between climate and diverse cases of forest diseases and potential shocks of climate change on pathogens and diseases. Biotic diseases, cankers, decays, declines, foliar diseases, root diseases and stem rust of pine have been reviewed with some illustrations of potential disease effects with predicted changing climate. The impact of changing climate on host, pathogen, and their interaction will have frequent and mostly unsympathetic outcomes to forest ecosystems. By employing the proactive and modern scientific management strategies like monitoring, modeling prediction, risk rating, planning, genetic diversity and facilitated migration, genetic protection and breeding for disease resistance and relating results to forest policy, planning as well as decision making, the suspicions innate to climate change effects can be minimized. (author)

    17. Declining Prevalence of Disease Vectors Under Climate Change

      DEFF Research Database (Denmark)

      Escobar, Luis E.; Romero-Alvarez, Daniel; Leon, Renato

      2016-01-01

      More than half of the world population is at risk of vector-borne diseases including dengue fever, chikungunya, zika, yellow fever, leishmaniasis, chagas disease, and malaria, with highest incidences in tropical regions. In Ecuador, vector-borne diseases are present from coastal and Amazonian reg...

    18. Declining Prevalence of Disease Vectors Under Climate Change

      DEFF Research Database (Denmark)

      Escobar, Luis E.; Romero-Alvarez, Daniel; Leon, Renato

      2016-01-01

      More than half of the world population is at risk of vector-borne diseases including dengue fever, chikungunya, zika, yellow fever, leishmaniasis, chagas disease, and malaria, with highest incidences in tropical regions. In Ecuador, vector-borne diseases are present from coastal and Amazonian...

    19. An archaeal tRNA-synthetase complex that enhances aminoacylation under extreme conditions

      DEFF Research Database (Denmark)

      Godinic-Mikulcic, Vlatka; Jaric, Jelena; Hausmann, Corinne D

      2011-01-01

      Aminoacyl-tRNA synthetases (aaRSs) play an integral role in protein synthesis, functioning to attach the correct amino acid with its cognate tRNA molecule. AaRSs are known to associate into higher-order multi-aminoacyl-tRNA synthetase complexes (MSC) involved in archaeal and eukaryotic translatio...... of a complex between MtSerRS and MtArgRS provides a means by which methanogenic archaea can optimize an early step in translation under a wide range of extreme environmental conditions....

    20. Water oxidation catalysis with nonheme iron complexes under acidic and basic conditions: homogeneous or heterogeneous?

      Science.gov (United States)

      Hong, Dachao; Mandal, Sukanta; Yamada, Yusuke; Lee, Yong-Min; Nam, Wonwoo; Llobet, Antoni; Fukuzumi, Shunichi

      2013-08-19

      Thermal water oxidation by cerium(IV) ammonium nitrate (CAN) was catalyzed by nonheme iron complexes, such as Fe(BQEN)(OTf)2 (1) and Fe(BQCN)(OTf)2 (2) (BQEN = N,N'-dimethyl-N,N'-bis(8-quinolyl)ethane-1,2-diamine, BQCN = N,N'-dimethyl-N,N'-bis(8-quinolyl)cyclohexanediamine, OTf = CF3SO3(-)) in a nonbuffered aqueous solution; turnover numbers of 80 ± 10 and 20 ± 5 were obtained in the O2 evolution reaction by 1 and 2, respectively. The ligand dissociation of the iron complexes was observed under acidic conditions, and the dissociated ligands were oxidized by CAN to yield CO2. We also observed that 1 was converted to an iron(IV)-oxo complex during the water oxidation in competition with the ligand oxidation. In addition, oxygen exchange between the iron(IV)-oxo complex and H2(18)O was found to occur at a much faster rate than the oxygen evolution. These results indicate that the iron complexes act as the true homogeneous catalyst for water oxidation by CAN at low pHs. In contrast, light-driven water oxidation using [Ru(bpy)3](2+) (bpy = 2,2'-bipyridine) as a photosensitizer and S2O8(2-) as a sacrificial electron acceptor was catalyzed by iron hydroxide nanoparticles derived from the iron complexes under basic conditions as the result of the ligand dissociation. In a buffer solution (initial pH 9.0) formation of the iron hydroxide nanoparticles with a size of around 100 nm at the end of the reaction was monitored by dynamic light scattering (DLS) in situ and characterized by X-ray photoelectron spectra (XPS) and transmission electron microscope (TEM) measurements. We thus conclude that the water oxidation by CAN was catalyzed by short-lived homogeneous iron complexes under acidic conditions, whereas iron hydroxide nanoparticles derived from iron complexes act as a heterogeneous catalyst in the light-driven water oxidation reaction under basic conditions.

    1. Neural mechanisms underlying cognitive inflexibility in Parkinson's disease.

      Science.gov (United States)

      Lange, Florian; Seer, Caroline; Loens, Sebastian; Wegner, Florian; Schrader, Christoph; Dressler, Dirk; Dengler, Reinhard; Kopp, Bruno

      2016-12-01

      Cognitive inflexibility is a hallmark of executive dysfunction in Parkinson's disease (PD). This deficit consistently manifests itself in a PD-related increase in the number of perseverative errors committed on the Wisconsin Card Sorting Test (WCST). However, the neural processes underlying perseverative WCST performance in PD are still largely unknown. The present study is the first to investigate the event-related potential (ERP) correlates of cognitive inflexibility on the WCST in PD patients. Thirty-two PD patients and 35 matched control participants completed a computerized version of the WCST while the electroencephalogram (EEG) was recorded. Behavioral results revealed the expected increase in perseverative errors in patients with PD. ERP analysis focused on two established indicators of executive processes: the fronto-central P3a as an index of attentional orienting and the sustained parietal positivity (SPP) as an index of set-shifting processes. In comparison to controls, P3a amplitudes were significantly attenuated in PD patients. Regression analysis further revealed that P3a and SPP amplitudes interactively contributed to the prediction of perseverative errors in PD patients: The number of perseverative errors was only increased when both ERP amplitudes were attenuated. Notably, the two ERP markers of executive processes accounted for more than 40% of the variance in perseverative errors in PD patients. We conclude that cognitive inflexibility in PD occurs when the neural bases of multiple executive processes are affected by the pathophysiology of PD. The combined measurement of P3a and SPP might yield an electrophysiological marker of cognitive inflexibility in PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

    2. Multiple systemic embolism in infective endocarditis underlying in Barlow's disease.

      Science.gov (United States)

      Yu, Ziqing; Fan, Bing; Wu, Hongyi; Wang, Xiangfei; Li, Chenguang; Xu, Rende; Su, Yangang; Ge, Junbo

      2016-08-11

      Systemic embolism, especially septic embolism, is a severe complication of infective endocarditis (IE). However, concurrent embolism to the brain, coronary arteries, and spleen is very rare. Because of the risk of hemorrhage or visceral rupture, anticoagulants are recommended only if an indication is present, e.g. prosthetic valve. Antiplatelet therapy in IE is controversial, but theoretically, this therapy has the potential to prevent and treat thrombosis and embolism in IE. Unfortunately, clinical trial results have been inconclusive. We describe a previously healthy 50-year-old man who presented with dysarthria secondary to bacterial endocarditis with multiple cerebral, coronary, splenic, and peripheral emboli; antibiotic therapy contributed to the multiple emboli. Emergency splenectomy was performed, with subsequent mitral valve repair. Pathological examination confirmed mucoid degeneration and mitral valve prolapse (Barlow's disease) as the underlying etiology of the endocardial lesion. Continuous antibiotics were prescribed, postoperatively. Transthoracic echocardiography at 1.5, 3, and 6 months after the onset of his illness showed no severe regurgitation, and there was no respiratory distress, fever, or lethargy during follow-up. Although antibiotic use in IE carries a risk of septic embolism, these drugs have bactericidal and antithrombotic benefits. It is important to consider that negative blood culture and symptom resolution do not confirm complete elimination of bacteria. However, vegetation size and Staphylococcus aureus infection accurately predict embolization. It is also important to consider that bacteria can be segregated from the microbicide when embedded in platelets and fibrin. Therefore, antimicrobial therapy with concurrent antiplatelet therapy should be considered carefully.

    3. Galectin-9: From cell biology to complex disease dynamics

      Indian Academy of Sciences (India)

      Galectins is a family of non-classically secreted, β-galactoside-binding proteins that has recently received considerableattention in the spatio-temporal regulation of surface 'signal lattice' organization, membrane dynamics, cell-adhesionand disease therapeutics. Galectin-9 is a unique member of this family, with two ...

    4. Complex lipid trafficking in Niemann-Pick disease type C.

      Science.gov (United States)

      Vanier, Marie T

      2015-01-01

      Niemann-Pick disease type C (NPC) is an atypical lysosomal storage disease resulting from mutations in one of two genes, either NPC1 or NPC2. Although a neurovisceral disorder, it is above all a neurodegenerative disease in the vast majority of patients. Not an enzyme deficiency, it is currently conceived as a lipid trafficking disorder. Impaired egress of cholesterol from the late endosomal/lysosomal (LE/L) compartment is a specific and key element of the pathogenesis, but other lipids, more specially sphingolipids, are also involved, and there are indications for further abnormalities. The full function of the NPC1 and NPC2 proteins is still unclear. This review provides a reappraisal of lipid storage and lysosomal enzymes activities in tissues/cells from NPC patients and animal models. It summarizes the current knowledge on the NPC1 and NPC2 proteins and their function in transport of cholesterol within the late endosomal-lysosomal compartment, with emphasis on differences between systemic organs and the brain; it also discusses regulation by membrane lipids of the NPC2-mediated cholesterol trafficking, interplay between cholesterol and sphingomyelin, the metabolic origin of glycosphingolipids stored in brain, and the putative role of free sphingoid bases in pathogenesis. Brief mention is finally made of diseases affecting other genes that were very recently shown to impact the "NPC pathway".

    5. Understanding complexity in neurodegenerative diseases: in silico reconstruction of emergence.

      NARCIS (Netherlands)

      Kolodkin, A.; Simeonidis, E.; Balling, R.; Westerhoff, H.V.

      2012-01-01

      Healthy functioning is an emergent property of the network of interacting biomolecules that comprise an organism. It follows that disease (a network shift that causes malfunction) is also an emergent property, emerging from a perturbation of the network. On the one hand, the biomolecular network of

    6. Hyperparathyroidism in chronic kidney disease: complexities within the commonplace.

      Science.gov (United States)

      Cai, Michael M; McMahon, Lawrence P; Smith, Edward R; Williams, David S; Holt, Stephen G

      2012-08-01

      Secondary hyperparathyroidism in patients with chronic kidney disease (CKD) is common and usually caused by associated metabolic abnormalities, in particular, hypocalcaemia and hyperphosphataemia. Nevertheless, other causes of hyperparathyroidism can exist concurrently with CKD, challenging diagnostic interpretation and therapeutic intervention. We present four cases of hyperparathyroidism in patients with CKD that highlight some of these dilemmas.

    7. The Crystal Structure and Behavior of Fenamic Acid-Acridine Complex Under High Pressure.

      Science.gov (United States)

      Jerzykiewicz, Lucjan; Sroka, Adam; Majerz, Irena

      2016-12-01

      The crystal structure of fenamic acid-acridine complex is determined by X-ray diffraction. The strong OHN hydrogen bond linking the complex components and other interactions responsible for packing of the molecules into a crystal are investigated within the Quantum Theory of Atom in Molecule theory. The crystal structure is compared with the structure optimized at B3LYP/6-311++G** level and with the theoretical structures optimized under systematically changed pressure. Analysis of the lattice constants, hydrogen bond lengths, and angles of the inter- and intramolecular hydrogen bond under compression is performed. The structural transformation observed at 5 GPa is connected with a change in the intermolecular OHN hydrogen bond. The proton shifts to acceptor and a new interaction in the crystal appears. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

    8. Accurate and Autonomous Star Acquisition Method for Star Sensor under Complex Conditions

      Directory of Open Access Journals (Sweden)

      Hao Zhang

      2017-01-01

      Full Text Available Star sensor is a preferred attitude measurement device for its extremely high accuracy. Star acquisition is the essential and critical procedure, which is aiming at acquiring accurate star areas. However, degenerated acquisition results under complex conditions become one of the major restrictions for modern star sensor. In this paper, an accurate and autonomous star acquisition method is proposed. Mathematical morphology and variable thresholding are combined for accurate star extraction; motion PSF is estimated in frequency domain and nonlinear filter is adopted for star restoration. Accurate star acquisition can be achieved based on only one star image. Simulations and laboratory experiments are conducted for verification. Several existing methods are also reproduced for comparison. Acquisition results demonstrate that the proposed method is effective and an excellent performance can be achieved autonomously under complex conditions, along with more detected stars and improved acquisition accuracy.

    9. An integer programming framework for inferring disease complexes from network data.

      Science.gov (United States)

      Mazza, Arnon; Klockmeier, Konrad; Wanker, Erich; Sharan, Roded

      2016-06-15

      Unraveling the molecular mechanisms that underlie disease calls for methods that go beyond the identification of single causal genes to inferring larger protein assemblies that take part in the disease process. Here, we develop an exact, integer-programming-based method for associating protein complexes with disease. Our approach scores proteins based on their proximity in a protein-protein interaction network to a prior set that is known to be relevant for the studied disease. These scores are combined with interaction information to infer densely interacting protein complexes that are potentially disease-associated. We show that our method outperforms previous ones and leads to predictions that are well supported by current experimental data and literature knowledge. The datasets we used, the executables and the results are available at www.cs.tau.ac.il/roded/disease_complexes.zip roded@post.tau.ac.il. © The Author 2016. Published by Oxford University Press.

    10. The forgotten D : challenges of addressing forest degradation in complex mosaic landscapes under REDD

      OpenAIRE

      Mertz, O.; Muller, D.; Sikor, T.; Hett, C.; Heinimann, A.; Castella, Jean-Christophe; Lestrelin, Guillaume; Ryan, C. M.; Reay, D. S.; Schmidt-Vogt, D.; Danielsen, F.; Theilade, I.; van Noordwijk, M.; Verchot, L. V.; Burgess, N. D.

      2012-01-01

      International climate negotiations have stressed the importance of considering emissions from forest degradation under the planned REDD+ (Reducing Emissions from Deforestation and forest Degradation + enhancing forest carbon stocks) mechanism. However, most research, pilot-REDD+ projects and carbon certification agencies have focused on deforestation and there appears to be a gap in knowledge on complex mosaic landscapes containing degraded forests, smallholder agriculture, agroforestry and p...

    11. Highly efficient photocatalytic hydrogen evolution from nickel quinolinethiolate complexes under visible light irradiation

      Science.gov (United States)

      Rao, Heng; Yu, Wen-Qian; Zheng, Hui-Qin; Bonin, Julien; Fan, Yao-Ting; Hou, Hong-Wei

      2016-08-01

      Earth-abundant metal complexes have emerged as promising surrogates of platinum for catalyzing the hydrogen evolution reaction (HER). In this study, we report the design and synthesis of two novel nickel quinolinethiolate complexes, namely [Ni(Hqt)2(4, 4‧-Z-2, 2‧-bpy)] (Hqt = 8-quinolinethiol, Z = sbnd H [1] or sbnd CH3 [2], bpy = bipyridine). An efficient three-component photocatalytic homogeneous system for hydrogen generation working under visible light irradiation was constructed by using the target complexes as catalysts, triethylamine (TEA) as sacrificial electron donor and xanthene dyes as photosensitizer. We obtain turnover numbers (TON, vs. catalyst) for H2 evolution of 5923/7634 under the optimal conditions with 5.0 × 10-6 M complex 1/2 respectively, 1.0 × 10-3 M fluorescein and 5% (v/v) TEA at pH 12.3 in EtOH/H2O (1:1, v/v) mixture after 8 h irradiation (λ > 420 nm). We discuss the mechanism of H2 evolution in the homogeneous photocatalytic system based on fluorescence spectrum and cyclic voltammetry data.

    12. Using advanced surface complexation models for modelling soil chemistry under forests: Solling forest, Germany

      International Nuclear Information System (INIS)

      Bonten, Luc T.C.; Groenenberg, Jan E.; Meesenburg, Henning; Vries, Wim de

      2011-01-01

      Various dynamic soil chemistry models have been developed to gain insight into impacts of atmospheric deposition of sulphur, nitrogen and other elements on soil and soil solution chemistry. Sorption parameters for anions and cations are generally calibrated for each site, which hampers extrapolation in space and time. On the other hand, recently developed surface complexation models (SCMs) have been successful in predicting ion sorption for static systems using generic parameter sets. This study reports the inclusion of an assemblage of these SCMs in the dynamic soil chemistry model SMARTml and applies this model to a spruce forest site in Solling Germany. Parameters for SCMs were taken from generic datasets and not calibrated. Nevertheless, modelling results for major elements matched observations well. Further, trace metals were included in the model, also using the existing framework of SCMs. The model predicted sorption for most trace elements well. - Highlights: → Surface complexation models can be well applied in field studies. → Soil chemistry under a forest site is adequately modelled using generic parameters. → The model is easily extended with extra elements within the existing framework. → Surface complexation models can show the linkages between major soil chemistry and trace element behaviour. - Surface complexation models with generic parameters make calibration of sorption superfluous in dynamic modelling of deposition impacts on soil chemistry under nature areas.

    13. A neural network underlying intentional emotional facial expression in neurodegenerative disease

      Directory of Open Access Journals (Sweden)

      Kelly A. Gola

      2017-01-01

      Full Text Available Intentional facial expression of emotion is critical to healthy social interactions. Patients with neurodegenerative disease, particularly those with right temporal or prefrontal atrophy, show dramatic socioemotional impairment. This was an exploratory study examining the neural and behavioral correlates of intentional facial expression of emotion in neurodegenerative disease patients and healthy controls. One hundred and thirty three participants (45 Alzheimer's disease, 16 behavioral variant frontotemporal dementia, 8 non-fluent primary progressive aphasia, 10 progressive supranuclear palsy, 11 right-temporal frontotemporal dementia, 9 semantic variant primary progressive aphasia patients and 34 healthy controls were video recorded while imitating static images of emotional faces and producing emotional expressions based on verbal command; the accuracy of their expression was rated by blinded raters. Participants also underwent face-to-face socioemotional testing and informants described participants' typical socioemotional behavior. Patients' performance on emotion expression tasks was correlated with gray matter volume using voxel-based morphometry (VBM across the entire sample. We found that intentional emotional imitation scores were related to fundamental socioemotional deficits; patients with known socioemotional deficits performed worse than controls on intentional emotion imitation; and intentional emotional expression predicted caregiver ratings of empathy and interpersonal warmth. Whole brain VBMs revealed a rightward cortical atrophy pattern homologous to the left lateralized speech production network was associated with intentional emotional imitation deficits. Results point to a possible neural mechanisms underlying complex socioemotional communication deficits in neurodegenerative disease patients.

    14. A neural network underlying intentional emotional facial expression in neurodegenerative disease.

      Science.gov (United States)

      Gola, Kelly A; Shany-Ur, Tal; Pressman, Peter; Sulman, Isa; Galeana, Eduardo; Paulsen, Hillary; Nguyen, Lauren; Wu, Teresa; Adhimoolam, Babu; Poorzand, Pardis; Miller, Bruce L; Rankin, Katherine P

      2017-01-01

      Intentional facial expression of emotion is critical to healthy social interactions. Patients with neurodegenerative disease, particularly those with right temporal or prefrontal atrophy, show dramatic socioemotional impairment. This was an exploratory study examining the neural and behavioral correlates of intentional facial expression of emotion in neurodegenerative disease patients and healthy controls. One hundred and thirty three participants (45 Alzheimer's disease, 16 behavioral variant frontotemporal dementia, 8 non-fluent primary progressive aphasia, 10 progressive supranuclear palsy, 11 right-temporal frontotemporal dementia, 9 semantic variant primary progressive aphasia patients and 34 healthy controls) were video recorded while imitating static images of emotional faces and producing emotional expressions based on verbal command; the accuracy of their expression was rated by blinded raters. Participants also underwent face-to-face socioemotional testing and informants described participants' typical socioemotional behavior. Patients' performance on emotion expression tasks was correlated with gray matter volume using voxel-based morphometry (VBM) across the entire sample. We found that intentional emotional imitation scores were related to fundamental socioemotional deficits; patients with known socioemotional deficits performed worse than controls on intentional emotion imitation; and intentional emotional expression predicted caregiver ratings of empathy and interpersonal warmth. Whole brain VBMs revealed a rightward cortical atrophy pattern homologous to the left lateralized speech production network was associated with intentional emotional imitation deficits. Results point to a possible neural mechanisms underlying complex socioemotional communication deficits in neurodegenerative disease patients.

    15. Chronic obstructive pulmonary disease: a complex comorbidity of lung cancer

      OpenAIRE

      Grose, Derek; Milroy, Robert

      2011-01-01

      Chronic obstructive pulmonary disease (COPD) is a major burden throughout the world. It is associated with a significantly increased incidence of lung cancer and may influence treatment options and outcome. Impaired lung function confirming COPD is an independent risk factor for lung cancer. Oxidative stress and inflammation may be a key link between COPD and lung cancer, with numerous molecular markers being analysed to attempt to understand the pathway of lung cancer development. COPD negat...

    16. Analysis of altered complexity of gait dynamics with aging and Parkinson’s disease using ternary Lempel–Ziv complexity

      Directory of Open Access Journals (Sweden)

      Chandrakar Kamath

      2016-12-01

      Full Text Available Fluctuations in stride interval series show complex dynamical behavior in healthy young adults. Hypothesizing that these stride interval complexity changes would be altered by changes in neurological function associated with aging and certain disease states, we aimed to develop a tool to facilitate clinical judgments to assess the complex dynamical behavior in the stride series in discerning young, elderly, and Parkinson’s disease (PD classes. This novel approach, which employs a new variant of coarse-graining in conjunction with Lempel–Ziv complexity measure, yields useful, reliable, and predictive results. We also show the presence of nonlinear deterministic structures in the stride time series and appropriateness of the application of our nonlinear approach through surrogate data analysis. The findings show that the fluctuations are more complex/random in elderly and PD classes than those in young class. These findings may add to the growing body of literature supporting the clinical utility of this new approach to stride time series.

    17. Infectious disease outbreaks and increased complexity of care.

      Science.gov (United States)

      Musau, J; Baumann, A; Kolotylo, C; O'Shea, T; Bialachowski, A

      2015-09-01

      This study examined the effects of healthcare-associated infectious disease outbreaks on nurses' work in a large acute care hospital in Ontario, Canada. The incidence of healthcare-associated infections has increased. Previous research focuses on epidemiology, healthcare systems, and the economic burden of outbreaks. Few published studies focus on the impact of outbreaks on nurses' work in acute care facilities. Since the severe acute respiratory syndrome epidemic in 2003, combating infectious diseases has become a key issue. Hospitals have implemented measures related to healthcare-associated infections. However, nurses experience challenges in preventing, controlling, and contending with outbreaks. A retrospective exploratory case study approach was used. Data were collected over a 4-month period in 2012. The incidence rates of site-specific HAIs were analysed, and individual interviews were held with 23 bedside nurses and five nurse managers. Five themes emerged from the interviews: comparison of healthcare-associated infections outbreaks; the nature of nurses' work; impact of outbreaks on patient care; innovation and quality control in clinical practice; and increased and expanded IPAC measures. The incidence rates of methicillin-resistant Staphylococcus aureus, Clostridium difficile and vancomycin-resistant enterococci at the study site decreased, but remained above provincial benchmarks. Nurses experienced workload challenges, time pressures and psychological effects stemming from outbreaks and developed various innovations in response. Patient care was also affected. Nurses' work has been impacted by healthcare-associated infectious disease outbreaks. Nursing workloads should be quantified to facilitate the development of guidelines for optimum nurse-patient ratio during outbreaks. A strong evidence-based policy framework is required to address healthcare-associated infectious disease outbreaks. Infection prevention and control guidelines and procedures

    18. An Intelligent Complex Event Processing with D Numbers under Fuzzy Environment

      Directory of Open Access Journals (Sweden)

      Fuyuan Xiao

      2016-01-01

      Full Text Available Efficient matching of incoming mass events to persistent queries is fundamental to complex event processing systems. Event matching based on pattern rule is an important feature of complex event processing engine. However, the intrinsic uncertainty in pattern rules which are predecided by experts increases the difficulties of effective complex event processing. It inevitably involves various types of the intrinsic uncertainty, such as imprecision, fuzziness, and incompleteness, due to the inability of human beings subjective judgment. Nevertheless, D numbers is a new mathematic tool to model uncertainty, since it ignores the condition that elements on the frame must be mutually exclusive. To address the above issues, an intelligent complex event processing method with D numbers under fuzzy environment is proposed based on the Technique for Order Preferences by Similarity to an Ideal Solution (TOPSIS method. The novel method can fully support decision making in complex event processing systems. Finally, a numerical example is provided to evaluate the efficiency of the proposed method.

    19. Mechanisms underlying disease transmission between spatially separated animals

      NARCIS (Netherlands)

      Bunnik, van B.A.D.

      2014-01-01

      Transmission of infections between spatially separated hosts is a common problem, not only during major outbreaks of livestock diseases, but also in many other settings such as the transmission of infectious diseases between plants and crops or in healthcare settings. During the last

    20. Disassembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients

      Directory of Open Access Journals (Sweden)

      Adler Charles

      2009-07-01

      Full Text Available Abstract Correction to Nural H, He P, Beach T, Sue L, Xia W, Shen Y. Disassembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients Molecular Neurodegeneration 2009, 4:23.

    1. An Ocular Protein Triad Can Classify Four Complex Retinal Diseases

      Science.gov (United States)

      Kuiper, J. J. W.; Beretta, L.; Nierkens, S.; van Leeuwen, R.; Ten Dam-van Loon, N. H.; Ossewaarde-van Norel, J.; Bartels, M. C.; de Groot-Mijnes, J. D. F.; Schellekens, P.; de Boer, J. H.; Radstake, T. R. D. J.

      2017-01-01

      Retinal diseases generally are vision-threatening conditions that warrant appropriate clinical decision-making which currently solely dependents upon extensive clinical screening by specialized ophthalmologists. In the era where molecular assessment has improved dramatically, we aimed at the identification of biomarkers in 175 ocular fluids to classify four archetypical ocular conditions affecting the retina (age-related macular degeneration, idiopathic non-infectious uveitis, primary vitreoretinal lymphoma, and rhegmatogenous retinal detachment) with one single test. Unsupervised clustering of ocular proteins revealed a classification strikingly similar to the clinical phenotypes of each disease group studied. We developed and independently validated a parsimonious model based merely on three proteins; interleukin (IL)-10, IL-21, and angiotensin converting enzyme (ACE) that could correctly classify patients with an overall accuracy, sensitivity and specificity of respectively, 86.7%, 79.4% and 92.5%. Here, we provide proof-of-concept for molecular profiling as a diagnostic aid for ophthalmologists in the care for patients with retinal conditions.

    2. Postoperative management in patients with complex congenital heart disease.

      Science.gov (United States)

      Tweddell, James S; Hoffman, George M

      2002-01-01

      Life-threatening problems occur in the neonate and infant after cardiac surgery because of the interplay of diminished cardiac output (CO), increased metabolic demand, inflammatory responses to cardiopulmonary bypass, and maladaptive responses to stress. Therefore, the postoperative management of patients with complex congenital heart defects is directed at optimization of oxygen delivery to maintain end-organ function and promote wound healing. Traditionally, assessment of circulation in the postoperative congenital heart patient has depended on indirect assessment of CO using parameters such as blood pressure, pulses, capillary refill, and urine output. Because of the limitations of indirect and observer-dependent assessment of CO, we rely on objective measures of tissue oxygen levels for the complex postoperative patient. We have found that continuous monitoring of the mixed venous saturation (SvO2) allows for identification of acute changes in systemic oxygen delivery and frequently precedes other indicators of decreased CO. The postoperative patient can be expected to have a period of decreasing CO, and the need for intervention should be anticipated because critical low output syndrome will develop in a subset of patients. Strategies for postoperative care are developed based on the diagnosis and procedure, but optimizing SvO2 is a consistent goal. A uniform approach to airway maintenance, vascular access, and drug infusions, all universal concerns during the perioperative period, minimizes the potential for these predictable and necessary interventions to result in morbidity or mortality. Management of the postoperative single ventricle patient targets stabilization of the systemic vascular resistance through the use of vasodilators to improve systemic perfusion and simplify ventilator management. Management of any individual patient should be driven by objective analysis of available data and must include efforts to re-evaluate the treatment plan as well as

    3. Deconstruction of Vulnerability to Complex Diseases: Enhanced Effect Sizes and Power of Intermediate Phenotypes

      Directory of Open Access Journals (Sweden)

      David Goldman

      2007-01-01

      Full Text Available The deconstruction of vulnerability to complex disease with the help of intermediate phenotypes, including the heritable and disease-associated endophenotypes, is a legacy of Henri Begleiter. Systematic searches for genes influencing complex disorders, including bipolar disorder, have recently been completed using whole genome association (WGA, identifying a series of validated loci. Using this information, it is possible to compare effect sizes of disease loci discovered in very large samples to the effect sizes of replicated functional loci determining intermediate phenotypes that are of essential interest in psychiatric disorders. It is shown that the genes influencing intermediate phenotypes tend to have a larger effect size. Furthermore, the WGA results reveal that the number of loci of large effect size for complex diseases is limited, and yet multiple functional loci have already been identified for intermediate phenotypes relevant to psychiatric diseases, and without the benefit of WGA.

    4. [Advances on pharmacokinetics of traditional Chinese medicine under disease states].

      Science.gov (United States)

      Gong, Zi-peng; Chen, Ying; Zhang, Rui-jie; Yang, Qing; Zhu, Xiao-xin

      2015-01-01

      In recent years, more and more research shows that the pharmacokinetic parameter of traditional Chinese medicine can be affected by the disease states. It's possible that drug metabolic enzymes, transporters, cell membrane permeability and the change of microbes group could be interfered with physiological and pathological changes, which enables the pharmacokinetics of traditional Chinese medicine in the body to be altered, including the process of absorption, distribution, metabolism and excretion, and then the pharmacokinetic parameters of traditional chinese medicine are altered. It's found that investigating the pharmacokinetic of traditional Chinese medicine in the pathological state is more useful than that of in normal state because the great part of traditional Chinese medicine is mainly used to treat disease. This article reflects the latest research on the pharmacokinetic of traditional Chinese medicine in the disease state such as diabete, cerebral ischemia, liver injury, inflammatory disease, nervous system disorders and fever in order to provide certain reference for clinicians designing reasonable administration dose.

    5. Review of the complexation of tetravalent actinides by ISA and gluconate under alkaline to hyperalkaline conditions.

      Science.gov (United States)

      Gaona, X; Montoya, V; Colàs, E; Grivé, M; Duro, L

      2008-12-12

      Isosaccharinic (ISA) and gluconic acids (GLU) are polyhydroxy carboxylic compounds showing a high affinity to metal complexation. Both organic ligands are expected in the cementitious environments usually considered for the disposal of low- and intermediate-level radioactive wastes. The hyperalkaline conditions imposed by cementitious materials contribute to the formation of ISA through cellulose degradation, whereas GLU is commonly used as a concrete additive. Despite the high stability attributed to ISA/GLU complexes of tetravalent actinides, the number and reliability of available experimental studies is still limited. This work aims at providing a general and comprehensive overview of the state of the art regarding Th, U(IV), Np(IV), and Pu(IV) complexes with ISA and GLU. In the presence of ISA/GLU concentrations in the range 10(-5)-10(-2) M and absence of calcium, An(IV)(OH)x(L)y complexes (An(IV)=Th, U(IV), Np(IV), Pu(IV); L=ISA, GLU) are expected to dominate the aqueous speciation of tetravalent actinides in the alkaline pH range. There is a moderate agreement among their stability, although the stoichiometry of certain An(IV)-GLU complexes is still ill-defined. Under hyperalkaline conditions and presence of calcium, the species CaTh(OH)4(L)2(aq) has been described for both ISA and GLU, and similar complexes may be expected to form with other tetravalent actinides. In the present work, the available thermodynamic data for An(IV)-ISA/GLU complexes have been reviewed and re-calculated to ensure the internal consistency of the stability constants assessed. Further modelling exercises, estimations based on Linear Free-Energy Relationships (LFER) among tetravalent actinides, as well as direct analogies between ISA and GLU complexes have also been performed. This approach has led to the definition of a speciation scheme for the complexes of Th, U(IV), Np(IV) and Pu(IV) with ISA and GLU forming in alkaline to hyperalkaline pH conditions, both in the absence and

    6. Therapeutical approaches under investigation for treatment of Chagas disease.

      Science.gov (United States)

      Bahia, Maria Terezinha; Diniz, Lívia de Figueiredo; Mosqueira, Vanessa Carla Furtado

      2014-09-01

      A century after its discovery, American trypanosomiasis or Chagas disease remains a serious health problem in Latin America, where it affects around 7 - 8 million people. The prevalence of Chagas disease in the poorer parts of the world has meant that it has largely been neglected with limited progress that made in identifying new drugs for the treatment. The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available for Chagas disease with limitations that include variable efficacy, long treatment courses and toxicity. This review focuses on different therapeutic strategies that have been used for the discovery of new treatments for Chagas disease. These include combination chemotherapy, drug repositioning, re-dosing regimens for current drugs and the identification of new drugs with specified target profiles. There are currently several reasons for a more optimistic view about chemotherapy with Chagas disease. However, despite some progress being made in preclinical studies, there is yet to be an ideal drug or formulation for human treatment. One major drawback in the evaluation of potential Chagas disease therapeutics is the lack of tools available to perform the said evaluation. Indeed, there is a great need to discover a better biomarker that could determine the efficacy of potential chemotherapeutics in treated patients.

    7. Paget's disease of bone: evidence for complex pathogenetic interactions.

      Science.gov (United States)

      Chung, Pui Yan Jenny; Van Hul, Wim

      2012-04-01

      Paget's disease of bone (PDB), with a prevalence of 2 to 5% in Caucasians >55 years, is the second most frequent metabolic bone disease, after osteoporosis. PDB characteristics are bone lesions with an imbalanced bone remodeling, resulting in disorganized and nonfully fledged new bone. PDB etiology is not completely understood. In this review, current views on the etiology, clinical aspects, and PDB treatment are summarized and discussed. The PubMed database was searched using the keywords PDB, sequestosome1 (SQSTM1), valosin-containing protein (VCP), receptor activator of nuclear factor-κB (RANK), osteoprotegerin (OPG), RANK ligand (RANKL), mutation, genetic variants, virus, osteosarcoma, bisphosphonates, and denosumab. Environmental evidence (e.g. viruses) and also genetic risk factors have been found for PDB. Until now, SQSTM1 was the only PDB-causing gene identified. However, PDB patients without SQSTM1 mutations seem to have susceptibility genetic polymorphisms in regions containing the CaSR, ESR1, TNFRSF11B (OPG), TNFRSF11A (RANK), CSF1 (M-CSF), OPTN, TM7SF4 (DC-STAMP), VCP, NUP205, RIN3, PML, and GOLGA6A genes, resulting in an increased risk of developing PDB. The nature of these genes indicates that the regulation of osteoclastogenesis is a key process in PDB pathogenesis. Furthermore, with the involvement of SQSTM1 and VCP in autophagy and in forming protein aggregates, this might also indicate that a disturbance of these processes might be a risk factor. Unraveling the PDB genetic background is instrumental to understanding the PDB pathogenesis and the role of slow viruses. Furthermore, it might make early detection and subsequently treatment of risk individuals possible. Copyright © 2012 Elsevier Inc. All rights reserved.

    8. Simplified reactive power management strategy for complex power grids under stochastic operation and incomplete information

      International Nuclear Information System (INIS)

      Vlachogiannis, John G.

      2009-01-01

      In the current released energy market, the large-scale complex transmission networks and the distribution ones with dispersed energy sources and 'intelligent' components operate under uncertainties, stochastic and prior incomplete information. A safe and reliable operation of such complex power grids is a major issue for system operators. Under these circumstances an online reactive power management strategy with minimum risk concerning all uncertain and stochastic parameters is proposed. Therefore, new concepts such as reactive power-weighted node-to-node linking and reactive power control capability are introduced. A distributed and interconnected stochastic learning automata system is implemented to manage, in a unified and unique way, the reactive power in complex power grids with stochastic reactive power demand and detect the vulnerable part. The proposed simplified strategy can also consider more stochastic aspects such as variable grid's topology. Results of the proposed strategy obtained on the networks of IEEE 30-bus and IEEE 118-bus systems demonstrate the effectiveness of the proposed strategy.

    9. Systems Pharmacology Dissecting Holistic Medicine for Treatment of Complex Diseases: An Example Using Cardiocerebrovascular Diseases Treated by TCM.

      Science.gov (United States)

      Wang, Yonghua; Zheng, Chunli; Huang, Chao; Li, Yan; Chen, Xuetong; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Zhang, Boli

      2015-01-01

      Holistic medicine is an interdisciplinary field of study that integrates all types of biological information (protein, small molecules, tissues, organs, external environmental signals, etc.) to lead to predictive and actionable models for health care and disease treatment. Despite the global and integrative character of this discipline, a comprehensive picture of holistic medicine for the treatment of complex diseases is still lacking. In this study, we develop a novel systems pharmacology approach to dissect holistic medicine in treating cardiocerebrovascular diseases (CCDs) by TCM (traditional Chinese medicine). Firstly, by applying the TCM active ingredients screened out by a systems-ADME process, we explored and experimentalized the signed drug-target interactions for revealing the pharmacological actions of drugs at a molecule level. Then, at a/an tissue/organ level, the drug therapeutic mechanisms were further investigated by a target-organ location method. Finally, a translational integrating pathway approach was applied to extract the diseases-therapeutic modules for understanding the complex disease and its therapy at systems level. For the first time, the feature of the drug-target-pathway-organ-cooperations for treatment of multiple organ diseases in holistic medicine was revealed, facilitating the development of novel treatment paradigm for complex diseases in the future.

    10. High-utilizing Crohn's disease patients under psychosomatic therapy*

      Science.gov (United States)

      Deter, Hans-Christian; von Wietersheim, Jörn; Jantschek, Günther; Burgdorf, Friederike; Blum, Brigitta; Keller, Wolfram

      2008-01-01

      Objective Few studies have been published on health care utilization in Crohn's disease and the influence of psychological treatment on high utilizers. Methods The present sub study of a prospective multi center investigation conducted in 87 of 488 consecutive Crohn's disease (CD) patients was designed to investigate the influence of the course of Crohn's disease on health care utilization (hospital days (HD) and sick leave days (SLD) collected by German insurance companies) and to examine the conditions of high-utilizing patients. Predictors of health care utilization should be selected. Based on a standardized somatic treatment, high health care utilizing patients of the psychotherapy and control groups should be compared before and after a one-year treatment. Results Multivariate regression analysis identified disease activity at randomization as an important predictor of the clinical course (r2 = 0.28, p < 0.01). Health care utilization correlated with duration of disease (p < 0.04), but the model was not significant (r2 = 0.15, p = 0.09). The patients' level of anxiety, depression and lack of control at randomization predicted their health-related quality of life at the end of the study (r2 = 0.51, p < 0.00001). Interestingly, steroid intake and depression (t1) predicted the combined outcome measure (clinical course, HRQL, health care utilization) of Crohn's disease at the end of the study (r2 = 0.22, p < 0.001). Among high utilizers, a significantly greater drop in HD (p < 0.03) and in mean in SLD were found in the treatment compared to the control group. Conclusion The course of Crohn's disease is influenced by psychological as well as somatic factors; especially depression seems important here. A significant drop of health care utilization demonstrates the benefit of psychological treatment in the subgroup of high-utilizing CD patients. Further studies are needed to replicate the findings of the clinical outcome in this CD subgroup. PMID:18851749

    11. Exploring the genetics underlying autoimmune diseases with network analysis and link prediction

      KAUST Repository

      Alanis Lobato, Gregorio

      2014-02-01

      Ever since the first Genome Wide Association Study (GWAS) was carried out we have seen an important number of discoveries of biological and clinical relevance. However, there are some scientists that consider that these research outcomes and their utility are far from what was expected from this experimental design. We instead believe that the thousands of genetic variants associated with complex disorders by means of GWASs are an extremely valuable source of information that needs to be mined in a different way. Based on this philosophy, we followed a holistic perspective to analyze GWAS data and explored the structural properties of the network representation of one of these datasets with the aim to advance our understanding of the genetic intricacies underlying autoimmune human diseases. The simplicity, computational efficiency and precision of the tools proposed in this paper represent a new means to address GWAS data and contribute to the better exploitation of these rich sources of information. © 2014 IEEE.

    12. Researchers and stakeholders shape advances in management of tree and vine trunk-disease complexes

      Science.gov (United States)

      The grapevine trunk-disease complex limits grape production and vineyard longevity worldwide. Every vineyard in California eventually is infected by one or more trunk diseases. The causal fungi, which are taxonomically unrelated Ascomycetes, infect and then degrade the permanent woody structure of t...

    13. Complex Nonlinear Dynamic System of Oligopolies Price Game with Heterogeneous Players Under Noise

      Science.gov (United States)

      Liu, Feng; Li, Yaguang

      A nonlinear four oligopolies price game with heterogeneous players, that are boundedly rational and adaptive, is built using two different special demand costs. Based on the theory of complex discrete dynamical system, the stability and the existing equilibrium point are investigated. The complex dynamic behavior is presented via bifurcation diagrams, the Lyapunov exponents to show equilibrium state, bifurcation and chaos with the variation in parameters. As disturbance is ubiquitous in economic systems, this paper focuses on the analysis of delay feedback control method under noise circumstances. Stable dynamics is confirmed to depend mainly on the low price adjustment speed, and if all four players have limited opportunities to stabilize the market, the new adaptive player facing profits of scale are found to be higher than the incumbents of bounded rational.

    14. On the origin of dust vortices in complex plasmas under microgravity conditions

      Energy Technology Data Exchange (ETDEWEB)

      Bockwoldt, Tim, E-mail: bockwoldt@physik.uni-kiel.de; Arp, Oliver; Piel, Alexander [IEAP, Christian-Albrechts-Universität zu Kiel, D–24098 Kiel (Germany); Menzel, Kristoffer Ole [ABB Switzerland Ltd., Corporate Research Center, 5405 Dättwil (Switzerland)

      2014-10-15

      Under microgravity conditions, microparticles in a radio-frequency plasma form an extended dust cloud. In such clouds, self-excited large-scale vortices are observed. New experimental observations are reported, which exhibit a simple double vortex structure or a more complex quadrupole-like topology. Modeling the fields of the main acting forces, namely, the electric field force and the ion drag force, and calculating the curl of these forces reveal their non-conservative character and the possible driving mechanism of the vortices. It is shown that the curl of the ion drag force and of the electric field force has opposite sign and the combination could thus lead to the complex structures, also found in the observations.

    15. Non-random biodiversity loss underlies predictable increases in viral disease prevalence.

      Science.gov (United States)

      Lacroix, Christelle; Jolles, Anna; Seabloom, Eric W; Power, Alison G; Mitchell, Charles E; Borer, Elizabeth T

      2014-03-06

      Disease dilution (reduced disease prevalence with increasing biodiversity) has been described for many different pathogens. Although the mechanisms causing this phenomenon remain unclear, the disassembly of communities to predictable subsets of species, which can be caused by changing climate, land use or invasive species, underlies one important hypothesis. In this case, infection prevalence could reflect the competence of the remaining hosts. To test this hypothesis, we measured local host species abundance and prevalence of four generalist aphid-vectored pathogens (barley and cereal yellow dwarf viruses) in a ubiquitous annual grass host at 10 sites spanning 2000 km along the North American West Coast. In laboratory and field trials, we measured viral infection as well as aphid fecundity and feeding preference on several host species. Virus prevalence increased as local host richness declined. Community disassembly was non-random: ubiquitous hosts dominating species-poor assemblages were among the most competent for vector production and virus transmission. This suggests that non-random biodiversity loss led to increased virus prevalence. Because diversity loss is occurring globally in response to anthropogenic changes, such work can inform medical, agricultural and veterinary disease research by providing insights into the dynamics of pathogens nested within a complex web of environmental forces.

    16. Bacterial pathogens of the bovine respiratory disease complex.

      Science.gov (United States)

      Griffin, Dee; Chengappa, M M; Kuszak, Jennifer; McVey, D Scott

      2010-07-01

      Pneumonia caused by the bacterial pathogens discussed in this article is the most significant cause of morbidity and mortality of the BRDC. Most of these infectious bacteria are not capable of inducing significant disease without the presence of other predisposing environmental factors, physiologic stressors, or concurrent infections. Mannheimia haemolytica is the most common and serious of these bacterial agents and is therefore also the most highly characterized. There are other important bacterial pathogens of BRD, such as Pasteurella multocida, Histophulus somni, and Mycoplasma bovis. Mixed infections with these organisms do occur. These pathogens have unique and common virulence factors but the resulting pneumonic lesions may be similar. Although the amount and quality of research associated with BRD has increased, vaccination and therapeutic practices are not fully successful. A greater understanding of the virulence mechanisms of the infecting bacteria and pathogenesis of pneumonia, as well as the characteristics of the organisms that allow tissue persistence, may lead to improved management, therapeutics, and vaccines. Copyright 2010 Elsevier Inc. All rights reserved.

    17. Contrasting regional architectures of schizophrenia and other complex diseases using fast variance components analysis

      DEFF Research Database (Denmark)

      Loh, Po-Ru; Bhatia, Gaurav; Gusev, Alexander

      2015-01-01

      Heritability analyses of genome-wide association study (GWAS) cohorts have yielded important insights into complex disease architecture, and increasing sample sizes hold the promise of further discoveries. Here we analyze the genetic architectures of schizophrenia in 49,806 samples from the PGC...... and nine complex diseases in 54,734 samples from the GERA cohort. For schizophrenia, we infer an overwhelmingly polygenic disease architecture in which ≥71% of 1-Mb genomic regions harbor ≥1 variant influencing schizophrenia risk. We also observe significant enrichment of heritability in GC-rich regions...... and in higher-frequency SNPs for both schizophrenia and GERA diseases. In bivariate analyses, we observe significant genetic correlations (ranging from 0.18 to 0.85) for several pairs of GERA diseases; genetic correlations were on average 1.3 tunes stronger than the correlations of overall disease liabilities...

    18. Under-through levator complex plication for correction of mild to moderate congenital ptosis.

      Science.gov (United States)

      Hong, Sung Pyo; Song, Seung Yong; Cho, In Chang

      2014-01-01

      Congenital ptosis is most commonly of mild to moderate severity, with good to fair levator function. The appropriate procedures for this condition are levator resection or levator aponeurosis approaches. Among the latter, the levator plication method has received little attention because of a relatively high rate of ptosis recurrence secondary to weak adhesion. In this study, the authors described and retrospectively analyzed the results of an alternative plication technique, the "under-through levator complex plication" method. This method differs from conventional levator plication primarily by the posterior part of the levator complex being advanced to the tarsal plate to produce strong adhesion. Five hundred and ten eyelids of 255 consecutive patients who underwent the under-through levator complex plication for congenital bilateral symmetrical ptosis were included in this study. Final outcomes were assessed at more than 5 months after surgery. The mean preoperative and postoperative marginal reflex distance 1 (MRD1) were 1.73 and 3.71 mm, respectively, and the mean amount of levator plication for every 1-mm increase in MRD1 was 3.31 mm. After the levator complex was plicated by the amount planned preoperatively, 65.1% of eyelids were at the target height. After subsequent intraoperative adjustments of the amount of plication, the overall surgery success rate was 94.5%. Recurrent ptosis due to relapse was not observed. The newly described surgical technique has overcome the limitations of conventional levator plication, by increasing the success rate and markedly reducing the relapse rate, while preserving the advantages of the conventional technique.

    19. Still's Disease and Recurrent Complex Regional Pain Syndrome Type-I: The First Description

      Science.gov (United States)

      Faillace, César; de Carvalho, Jozélio Freire

      2012-01-01

      Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder characterized by neuropathic pain associated with local edema and changes suggestive of autonomic involvement such as altered sweating, skin color, and skin temperature of the affected region. CRPS was described associated with several diseases, such as trauma, psychiatric conditions, and cancer. However, no case associated with Still's disease has been previously described. In this paper, the authors describe the first case of CRPS associated with Still's disease. PMID:22162802

    20. Hydrodynamic analysis of floating platform for special purposes under complex water environment

      Science.gov (United States)

      Ma, Guang-ying; Yao, Yun-long

      2018-03-01

      This article studied a new floating offshore platform for special purposes, which was assembled by standard floating modules. By using ANSYS AQWA software, the hydrodynamic model of the platform was established. The time history responses of the platform motions and the cable tension forces were calculate under complex water environments, such as wind, wave, current and mooring. The results showed that the tension of the four cables are far less than the breaking tension of the cable, so that the cable will not break. This study can be referenced by the relevant researchers and engineers.

    1. [Role of environment in complex diseases: air pollution and food contaminants].

      Science.gov (United States)

      Scheen, A J; Giet, D

      2012-01-01

      Our polluted environment exposes human beings, along their life, to various toxic compounds that could trigger and aggravate different complex diseases. Such a phenomenon is well recognized for cardiovascular diseases, respiratory diseases and cancers, but other chronic inflammatory disorders may also been implicated. The most common factors, but also the most toxic, and thereby the most extensively investigated, are air pollutants (both indoor and outdoor pollution) and various contaminants present in drinking water and food (organic compounds, chemical products, heavy metals, ...). The complex interrelationships between food and pollutants, on the one hand, and between gene and environmental pollutants, including the influence of epigenetics, on the other hand, deserve further careful studies.

    2. Heterogeneity of mitochondrial diseases caused by defects in mitochondrial respiratory chain complex I

      Directory of Open Access Journals (Sweden)

      E. A. Nikolaeva

      2015-01-01

      Full Text Available The common cause of mitochondrial diseases is hereditary defects in mitochondrial respiratory chain complex I, which account for about 30% of the cases of mitochondrial diseases in children. Complex I is the largest and most complicated enzyme complex of the respiratory electron chain. The function of Complex I is controlled by both nuclear and mitochondrial genomes and it seems to be determined by at least 300 genes. Complex I is comprised of 45 subunits: 7 of them are encoded by mitochondrial DNA, the others are by nuclear DNA. Besides, there are additional factors that are located outside Complex I, but determine its stability and activity. The paper analyzes the clinical forms of Complex I deficiency-induced diseases; the most common of them is Leigh syndrome. The diseases are generally characterized by an early onset, severe involvement of the nervous, muscular, and cardiovascular systems. If the treatment is ineffective, it is particularly important to identify a gene mutation to verify the diagnosis, as well as antenatal diagnosis. 

    3. Getting Under the Skin: The Inscription of Dermatological Disease ...

      African Journals Online (AJOL)

      8; Papadopoulos, Bor & Legg, 1999, p. 107). Chronic cutaneous disease is often visible to others so that social factors in coping and adjustment are thus highly relevant (Papadopoulos, et al., 1999, p. 107). Psychological factors tend, however, to be overlooked in the dermatological treatment domain when the skin problem ...

    4. Yellow Vein Mosaic disease in kenaf ( Hibiscus cannabinus l.) under ...

      African Journals Online (AJOL)

      Nucleic acid spot hybridization (NASH) was used to confirm the disease and the results revealed that Begomovirus was present in kenaf sowm in the two locations during the period of the three months except in kenaf sown in July at Ilora. The results of this study revealed the importance of sowing dates on the occurrence of ...

    5. Underlying congenital heart disease in Nigerian children with ...

      African Journals Online (AJOL)

      EB

      2013-09-03

      Sep 3, 2013 ... Abstract. Background: Pneumonia is a common cause of childhood morbidity and mortality globally. Some congenital heart disease. (CHD) may predispose their sufferer to bronchopneumonia. Objective: To evaluate the contribution of CHD to pneumonia in children seen in a tertiary hospital. Methods: Over ...

    6. Underlying congenital heart disease in Nigerian children with ...

      African Journals Online (AJOL)

      Background: Pneumonia is a common cause of childhood morbidity and mortality globally. Some congenital heart disease(CHD) may predispose their sufferer to bronchopneumonia. Objective: To evaluate the contribution of CHD to pneumonia in children seen in a tertiary hospital. Methods: Over a year, consecutive ...

    7. High-utilizing Crohn's disease patients under psychosomatic therapy*

      Directory of Open Access Journals (Sweden)

      Jantschek Günther

      2008-10-01

      Full Text Available Abstract Objective Few studies have been published on health care utilization in Crohn's disease and the influence of psychological treatment on high utilizers. Methods The present sub study of a prospective multi center investigation conducted in 87 of 488 consecutive Crohn's disease (CD patients was designed to investigate the influence of the course of Crohn's disease on health care utilization (hospital days (HD and sick leave days (SLD collected by German insurance companies and to examine the conditions of high-utilizing patients. Predictors of health care utilization should be selected. Based on a standardized somatic treatment, high health care utilizing patients of the psychotherapy and control groups should be compared before and after a one-year treatment. Results Multivariate regression analysis identified disease activity at randomization as an important predictor of the clinical course (r2 = 0.28, p 2 = 0.15, p = 0.09. The patients' level of anxiety, depression and lack of control at randomization predicted their health-related quality of life at the end of the study (r2 = 0.51, p 2 = 0.22, p Among high utilizers, a significantly greater drop in HD (p Conclusion The course of Crohn's disease is influenced by psychological as well as somatic factors; especially depression seems important here. A significant drop of health care utilization demonstrates the benefit of psychological treatment in the subgroup of high-utilizing CD patients. Further studies are needed to replicate the findings of the clinical outcome in this CD subgroup.

    8. BRISENT: An Entropy-Based Model for Bridge-Pier Scour Estimation under Complex Hydraulic Scenarios

      Directory of Open Access Journals (Sweden)

      Alonso Pizarro

      2017-11-01

      Full Text Available The goal of this paper is to introduce the first clear-water scour model based on both the informational entropy concept and the principle of maximum entropy, showing that a variational approach is ideal for describing erosional processes under complex situations. The proposed bridge–pier scour entropic (BRISENT model is capable of reproducing the main dynamics of scour depth evolution under steady hydraulic conditions, step-wise hydrographs, and flood waves. For the calibration process, 266 clear-water scour experiments from 20 precedent studies were considered, where the dimensionless parameters varied widely. Simple formulations are proposed to estimate BRISENT’s fitting coefficients, in which the ratio between pier-diameter and sediment-size was the most critical physical characteristic controlling scour model parametrization. A validation process considering highly unsteady and multi-peaked hydrographs was carried out, showing that the proposed BRISENT model reproduces scour evolution with high accuracy.

    9. Transitional dispersive scenarios driven by mesoscale flows on complex terrain under strong dry convective conditions

      Directory of Open Access Journals (Sweden)

      J. L. Palau

      2009-01-01

      Full Text Available By experimentation and modelling, this paper analyses the atmospheric dispersion of the SO2 emissions from a power plant on complex terrain under strong convective conditions, describing the main dispersion features as an ensemble of "stationary dispersive scenarios" and reformulating some "classical" dispersive concepts to deal with the systematically monitored summer dispersive scenarios in inland Spain. The results and discussions presented arise from a statistically representative study of the physical processes associated with the multimodal distribution of pollutants aloft and around a 343-m-tall chimney under strong dry convective conditions in the Iberian Peninsula. This paper analyses the importance of the identification and physical implications of transitional periods for air quality applications. The indetermination of a transversal plume to the preferred transport direction during these transitional periods implies a small (or null physical significance of the classical definition of horizontal standard deviation of the concentration distribution.

    10. Structural Vibration of A Flexible Complex System Under A Harmonic Oscillation Moving Force

      Science.gov (United States)

      Rusin, Jarosław

      2017-10-01

      This paper focuses on the free and forced transverse vibration of a double-string complex system with elastic interlayer under a harmonic oscillation moving force. The paper includes the study of a dynamic behaviour of a finite, simply supported double-string flexible complex system subject to harmonic force moving with a constant velocity on the top string. The strings are identical, parallel one upon the other. The elastic interlayer is described by the Winkler’s model consists of a Hookean resilient spring distributed in parallel. The classical solution of the response of complex systems subjected to harmonic oscillation force moving with a constant velocity has a form of an infinite series. But also, it is possible to show that in the considered case part of the solution can be presented in a closed, analytical form instead of an infinite series. The presented method to search for a solution in a closed-form is based on the observation that the solution of the system of partial differential equations in the form of an infinite series is also a solution of an appropriate system of ordinary differential equations. The double string connected in parallel by linear elastic elements can be studied as a theoretical model of composite structure in which impact of layer interaction, interlayer coupling effects and transverse wave effects is taken into account.

    11. A framework for modelling the complexities of food and water security under globalisation

      Science.gov (United States)

      Dermody, Brian J.; Sivapalan, Murugesu; Stehfest, Elke; van Vuuren, Detlef P.; Wassen, Martin J.; Bierkens, Marc F. P.; Dekker, Stefan C.

      2018-01-01

      We present a new framework for modelling the complexities of food and water security under globalisation. The framework sets out a method to capture regional and sectoral interdependencies and cross-scale feedbacks within the global food system that contribute to emergent water use patterns. The framework integrates aspects of existing models and approaches in the fields of hydrology and integrated assessment modelling. The core of the framework is a multi-agent network of city agents connected by infrastructural trade networks. Agents receive socio-economic and environmental constraint information from integrated assessment models and hydrological models respectively and simulate complex, socio-environmental dynamics that operate within those constraints. The emergent changes in food and water resources are aggregated and fed back to the original models with minimal modification of the structure of those models. It is our conviction that the framework presented can form the basis for a new wave of decision tools that capture complex socio-environmental change within our globalised world. In doing so they will contribute to illuminating pathways towards a sustainable future for humans, ecosystems and the water they share.

    12. C sub 6 sub 0 fullerene and its molecular complexes under axial and shear deformation

      CERN Document Server

      Spitsina, N G; Bashkin, I V; Meletov, K P

      2002-01-01

      We have studied the pristine C sub 6 sub 0 and its molecular complexes with the organic donors bis(ethylenedithio) tetrathiafulvalene (BEDT-TTF or ET) and tetramethyltetraselenafulvalene (TMTSF) by means of ESR and Raman spectroscopy at high pressure. The important changes in the ESR signal of C sub 6 sub 0 were observed under axial pressure combined with shear deformation. It is shown that the treatment at a anisotropic pressure of 4 GPa results in a reduction in the symmetry of the C sub 6 sub 0 molecule and the formation of radicals. Treatment of the molecular complex of (ET) sub 2 centre dot C sub 6 sub 0 at a pressure of approx 4.5 GPa and a temperature of 150 deg. C leads to the formation of C sub 6 sub 0 dimers. The Raman spectra of the molecular complex C sub 6 sub 0 centre dot TMTSF centre dot 2(CS sub 2) were measured in situ at ambient temperature and pressures up to 9.5 GPa. The pressure behaviour of the Raman peaks reveals singularity at 5.0 +- 0.5 GPa related to the softening and splitting of so...

    13. Modeling of the Human - Operator in a Complex System Functioning Under Extreme Conditions

      Science.gov (United States)

      Getzov, Peter; Hubenova, Zoia; Yordanov, Dimitar; Popov, Wiliam

      2013-12-01

      Problems, related to the explication of sophisticated control systems of objects, operating under extreme conditions, have been examined and the impact of the effectiveness of the operator's activity on the systems as a whole. The necessity of creation of complex simulation models, reflecting operator's activity, is discussed. Organizational and technical system of an unmanned aviation complex is described as a sophisticated ergatic system. Computer realization of main subsystems of algorithmic system of the man as a controlling system is implemented and specialized software for data processing and analysis is developed. An original computer model of a Man as a tracking system has been implemented. Model of unmanned complex for operators training and formation of a mental model in emergency situation, implemented in "matlab-simulink" environment, has been synthesized. As a unit of the control loop, the pilot (operator) is simplified viewed as an autocontrol system consisting of three main interconnected subsystems: sensitive organs (perception sensors); central nervous system; executive organs (muscles of the arms, legs, back). Theoretical-data model of prediction the level of operator's information load in ergatic systems is proposed. It allows the assessment and prediction of the effectiveness of a real working operator. Simulation model of operator's activity in takeoff based on the Petri nets has been synthesized.

    14. A framework for modelling the complexities of food and water security under globalisation

      Directory of Open Access Journals (Sweden)

      B. J. Dermody

      2018-01-01

      Full Text Available We present a new framework for modelling the complexities of food and water security under globalisation. The framework sets out a method to capture regional and sectoral interdependencies and cross-scale feedbacks within the global food system that contribute to emergent water use patterns. The framework integrates aspects of existing models and approaches in the fields of hydrology and integrated assessment modelling. The core of the framework is a multi-agent network of city agents connected by infrastructural trade networks. Agents receive socio-economic and environmental constraint information from integrated assessment models and hydrological models respectively and simulate complex, socio-environmental dynamics that operate within those constraints. The emergent changes in food and water resources are aggregated and fed back to the original models with minimal modification of the structure of those models. It is our conviction that the framework presented can form the basis for a new wave of decision tools that capture complex socio-environmental change within our globalised world. In doing so they will contribute to illuminating pathways towards a sustainable future for humans, ecosystems and the water they share.

    15. MPPT Control Strategy of PV Based on Improved Shuffled Frog Leaping Algorithm under Complex Environments

      Directory of Open Access Journals (Sweden)

      Xiaohua Nie

      2017-01-01

      Full Text Available This work presents a maximum power point tracking (MPPT based on the particle swarm optimization (PSO improved shuffled frog leaping algorithm (PSFLA. The swarm intelligence algorithm (SIA has vast computing ability. The MPPT control strategies of PV array based on SIA are attracting considerable interests. Firstly, the PSFLA was proposed by adding the inertia weight factor w of PSO in standard SFLA to overcome the defect of falling into the partial optimal solutions and slow convergence speed. The proposed PSFLA algorithm increased calculation speed and excellent global search capability of MPPT. Then, the PSFLA was applied to MPPT to solve the multiple extreme point problems of nonlinear optimization. Secondly, for the problems of MPPT under complex environments, a new MPPT strategy of the PSFLA combined with recursive least square filtering was proposed to overcome the measurement noise effects on MPPT accuracy. Finally, the simulation comparisons between PSFLA and SFLA algorithm were developed. The experiment and comparison between PSLFA and PSO algorithm under complex environment were executed. The simulation and experiment results indicate that the proposed MPPT control strategy based on PSFLA can suppress the measurement noise effects effectively and improve the PV array efficiency.

    16. Study of Polymeric Luminescent Blend (PC/PMMA) Doped with Europium Complex under Gamma-Iradiation

      International Nuclear Information System (INIS)

      Parra, D. F.

      2006-01-01

      Spectroscopic properties of blends formed by bisphenol-A polycarbonate (PC) and poly(methyl methacrylate) (PMMA) doped with europium in organic complex were studied. Polymeric luminescent blends are potential materials for many applications; however, little information has been reported concerning the stability under thermal and radiation conditions. Luminescent films were synthesized from europium thenoyltrifluoroacetonate at different concentrations doped in PC/PMMA blends. Films produced of the luminescent polymer blend were irradiated in a 60 C o source. Their luminescent properties, in the solid state, as well as, the thermal oxidative resistance after gamma irradiation was investigated. These systems were characterized by elemental analysis, thermogravimetry (TGA), differential scanning calorimetry (DSC) and infrared spectroscopy (FTIR). Based on TGA data, the thermal stability of PC/PMMA:(tta)3 system is higher than the polymer blend. The DSC results indicated that those new systems are chemically stables. The emission spectra of the Eu 3 +-tta complex doped in the PC/PMMA recorded at 298 and 77 K exhibited the characteristic bands arising from the 5 D 0 →7 F J transitions (J = 0-6). The luminescence intensity decreases with increasing of precursor concentration in the doped polymer obtained by chemical reaction. This result is different from that of samples obtained by physical method in melting doping. The blend was irradiated under ionizing radiation of 60 C o source. After irradiation of the luminescent films the physical properties of luminescence, thermal and oxidative stability were evaluated.(Fapesp and Cnpq financial support)

    17. Ethnographic study of diarrhoeal diseases among under-five ...

      African Journals Online (AJOL)

      A cross-sectional design was employed to identify the local cosmology of childhood diarrhoea and its local treatment procedures. A total of 848 under-five children were identified by a quick inventory of randomly selected kebeles. Trained enumerators administered a pre-tested questionnaire in order to identify the ...

    18. Applying nonlinear MODM model to supply chain management with quantity discount policy under complex fuzzy environment

      Directory of Open Access Journals (Sweden)

      Zhe Zhang

      2014-06-01

      Full Text Available Purpose: The aim of this paper is to deal with the supply chain management (SCM with quantity discount policy under the complex fuzzy environment, which is characterized as the bi-fuzzy variables. By taking into account the strategy and the process of decision making, a bi-fuzzy nonlinear multiple objective decision making (MODM model is presented to solve the proposed problem.Design/methodology/approach: The bi-fuzzy variables in the MODM model are transformed into the trapezoidal fuzzy variables by the DMs's degree of optimism ?1 and ?2, which are de-fuzzified by the expected value index subsequently. For solving the complex nonlinear model, a multi-objective adaptive particle swarm optimization algorithm (MO-APSO is designed as the solution method.Findings: The proposed model and algorithm are applied to a typical example of SCM problem to illustrate the effectiveness. Based on the sensitivity analysis of the results, the bi-fuzzy nonlinear MODM SCM model is proved to be sensitive to the possibility level ?1.Practical implications: The study focuses on the SCM under complex fuzzy environment in SCM, which has a great practical significance. Therefore, the bi-fuzzy MODM model and MO-APSO can be further applied in SCM problem with quantity discount policy.Originality/value: The bi-fuzzy variable is employed in the nonlinear MODM model of SCM to characterize the hybrid uncertain environment, and this work is original. In addition, the hybrid crisp approach is proposed to transferred to model to an equivalent crisp one by the DMs's degree of optimism and the expected value index. Since the MODM model consider the bi-fuzzy environment and quantity discount policy, so this paper has a great practical significance.

    19. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

      Science.gov (United States)

      Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S; Clohisey, Sara; Gray, Alan; Neyton, Lucile P A; Barrett, Jeffrey; Stahl, Eli A; Tenesa, Albert; Andersson, Robin; Brown, J Ben; Faulkner, Geoffrey J; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Itoh, Masayoshi; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Mole, Damian; Bajic, Vladimir B; Heutink, Peter; Rehli, Michael; Kawaji, Hideya; Sandelin, Albin; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A; Hacohen, Nir; Freeman, Thomas C; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Hume, David A

      2018-03-01

      Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

    20. Periodontal and inflammatory bowel diseases: Is there evidence of complex pathogenic interactions?

      Science.gov (United States)

      Lira-Junior, Ronaldo; Figueredo, Carlos Marcelo

      2016-09-21

      Periodontal disease and inflammatory bowel disease (IBD) are both chronic inflammatory diseases. Their pathogenesis is mediated by a complex interplay between a dysbiotic microbiota and the host immune-inflammatory response, and both are influenced by genetic and environmental factors. This review aimed to provide an overview of the evidence dealing with a possible pathogenic interaction between periodontal disease and IBD. There seems to be an increased prevalence of periodontal disease in patients with IBD when compared to healthy controls, probably due to changes in the oral microbiota and a higher inflammatory response. Moreover, the induction of periodontitis seems to result in gut dysbiosis and altered gut epithelial cell barrier function, which might contribute to the pathogenesis of IBD. Considering the complexity of both periodontal disease and IBD, it is very challenging to understand the possible pathways involved in their coexistence. In conclusion, this review points to a complex pathogenic interaction between periodontal disease and IBD, in which one disease might alter the composition of the microbiota and increase the inflammatory response related to the other. However, we still need more data derived from human studies to confirm results from murine models. Thus, mechanistic studies are definitely warranted to clarify this possible bidirectional association.

    1. Aloe QDM complex enhances specific cytotoxic T lymphocyte killing in vivo in metabolic disease mice.

      Science.gov (United States)

      Lee, Youngjoo; Kim, Jiyeon; An, Jinho; Lee, Heetae; Kong, Hyunseok; Song, Youngcheon; Shin, Eunju; Do, Seon-Gil; Lee, Chong-Kil; Kim, Kyungjae

      2017-03-01

      We developed spontaneous diet-induced metabolic disease in mice by feeding them a high-fat diet for 23 weeks and administered Aloe QDM complex for 16 weeks to examine its restorative effect on immune disorders and metabolic syndrome. A series of immune functional assays indicated Aloe QDM complex enhanced lymphocyte proliferation and antigen-specific immunity as determined by the restored functions of cytotoxic T lymphocytes (CTL) and IgG production. The elevated serum TNF-α level was also regulated by Aloe QDM complex treatment, which suggested its complex therapeutic potential. As for metabolic phenotypes, oral administration of Aloe QDM complex significantly improved diabetic symptoms, including high fasting glucose levels and glucose tolerance, and distinctly alleviated lipid accumulation in adipose and hepatic tissue. The simultaneous restoration of Aloe QDM complex on metabolic syndrome and host immune dysfunction, especially on the specific CTL killing was first elucidated in our study.

    2. Diagnosis of rare diseases under focus: impacts for Canadian patients.

      Science.gov (United States)

      Esquivel-Sada, Daphne; Nguyen, Minh Thu

      2018-01-01

      This paper presents an in-depth qualitative analysis of the impact of diagnosis on the lives of rare disease (RD) patients. While diagnosis may be described as a watershed step for RD patients, no extensive account of non-medical outcomes following a RD diagnosis exists within the literature. This study aims to fill this knowledge gap through an analysis of the impact of diagnosis on the lives of RD patients according to their personal experiences. Qualitative research was conducted in three provinces across Canada, with a total of 23 participants, both adult and parents of children with RD, diagnosed and not yet diagnosed. A thematic approach guided the analysis of the transcripts. The results reveal that the impacts of a RD diagnosis for both adults and paediatric patients are multifold, ranging from social to personal and medical impacts (including cases where etiological treatments for the diseases are non-existent). Furthermore, the results shed light on distinct factors that affect the scope of impacts of a diagnosis.

    3. Physiological consequences of complex II inhibition for aging, disease, and the mKATP channel.

      Science.gov (United States)

      Wojtovich, Andrew P; Smith, C Owen; Haynes, Cole M; Nehrke, Keith W; Brookes, Paul S

      2013-05-01

      In recent years, it has become apparent that there exist several roles for respiratory complex II beyond metabolism. These include: (i) succinate signaling, (ii) reactive oxygen species (ROS) generation, (iii) ischemic preconditioning, (iv) various disease states and aging, and (v) a role in the function of the mitochondrial ATP-sensitive K(+) (mKATP) channel. This review will address the involvement of complex II in each of these areas, with a focus on how complex II regulates or may be involved in the assembly of the mKATP. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease. Copyright © 2012. Published by Elsevier B.V.

    4. A Thermal Infrared and Visible Images Fusion Based Approach for Multitarget Detection under Complex Environment

      Directory of Open Access Journals (Sweden)

      Xinnan Fan

      2015-01-01

      Multitarget detection. However, there are some limitations of the general D-S belief theory under complex environment. For example, the basic belief assignment is difficult to establish, and the subjective factors will influence the update process of evidence. In this paper, a new Multitarget detection approach based on thermal infrared and visible images fusion is proposed. To easily characterize the defected heterogeneous image, a basic belief assignment based on the distance distribution function of heterogeneous characteristics is presented. Furthermore, to improve the discrimination and effectiveness of the Multitarget detection, a concept of comprehensive credibility is introduced into the proposed approach and a new update rule of evidence is designed. Finally, some experiments are carried out and the experimental results show the efficiency and effectiveness of the proposed approach in the Multitarget detection task.

    5. Examination of atmospheric dynamic model's performance over complex terrain under temporally changing synoptic meteorological conditions

      International Nuclear Information System (INIS)

      Nagai, Haruyasu; Yamazawa, Hiromi

      1995-01-01

      The mesoscale atmospheric dynamic model, a submodel of the numerical atmospheric dispersion model named PHYSIC, was improved and its performance was examined in a coastal area with a complex terrain. To introduce temporally changing synoptic meteorological conditions into the model, the initial and boundary conditions were improved. Moreover, land surface temperature calculations were modified to apply the model to snow-covered areas. These improvements worked effectively in the model simulation of four series of the observations during winter and summer in 1992. The model successfully simulated the wind fields and its temporal variations under the condition of strong westerlies and a land and sea breeze. Limitation of model's performance caused by the temporal and spatial resolutions of input data was also discussed. (author)

    6. Complex network analysis of phase dynamics underlying oil-water two-phase flows

      Science.gov (United States)

      Gao, Zhong-Ke; Zhang, Shan-Shan; Cai, Qing; Yang, Yu-Xuan; Jin, Ning-De

      2016-01-01

      Characterizing the complicated flow behaviors arising from high water cut and low velocity oil-water flows is an important problem of significant challenge. We design a high-speed cycle motivation conductance sensor and carry out experiments for measuring the local flow information from different oil-in-water flow patterns. We first use multivariate time-frequency analysis to probe the typical features of three flow patterns from the perspective of energy and frequency. Then we infer complex networks from multi-channel measurements in terms of phase lag index, aiming to uncovering the phase dynamics governing the transition and evolution of different oil-in-water flow patterns. In particular, we employ spectral radius and weighted clustering coefficient entropy to characterize the derived unweighted and weighted networks and the results indicate that our approach yields quantitative insights into the phase dynamics underlying the high water cut and low velocity oil-water flows. PMID:27306101

    7. Wear Behavior of Uncoated and Coated Tools under Complex Loading Conditions

      Directory of Open Access Journals (Sweden)

      M. Wieland

      2012-03-01

      Full Text Available In automotive industry crash relevant structures of the body in white are manufactured using the direct hot stamping process. Due to the high temperature difference between the hot blank and the cold tool surfaces and the relative movement between the blank and the tool surfaces during the forming operation, high thermal and mechanical loads are applied on the tool leading to excessive wear in terms of adhesion on the tool surfaces. One possibility to reduce wear of hot stamping tools is the application of tool coating systems. In the scope of this work uncoated and coated tools are characterized under complex loading conditions with respect to adhesive layer build-up.

    8. Relevance of Chronic Lyme Disease to Family Medicine as a Complex Multidimensional Chronic Disease Construct: A Systematic Review

      Directory of Open Access Journals (Sweden)

      Liesbeth Borgermans

      2014-01-01

      Full Text Available Lyme disease has become a global public health problem and a prototype of an emerging infection. Both treatment-refractory infection and symptoms that are related to Borrelia burgdorferi infection remain subject to controversy. Because of the absence of solid evidence on prevalence, causes, diagnostic criteria, tools and treatment options, the role of autoimmunity to residual or persisting antigens, and the role of a toxin or other bacterial-associated products that are responsible for the symptoms and signs, chronic Lyme disease (CLD remains a relatively poorly understood chronic disease construct. The role and performance of family medicine in the detection, integrative treatment, and follow-up of CLD are not well studied either. The purpose of this paper is to describe insights into the complexity of CLD as a multidimensional chronic disease construct and its relevance to family medicine by means of a systematic literature review.

    9. FUNCTION OF MALATDEHYDROGENASE COMPLEX OF MAIZE MESOPHYLL AND BUNDLE SHEATH CELLS UNDER SALT STRESS CONDITION

      Directory of Open Access Journals (Sweden)

      Еprintsev А.Т.

      2006-12-01

      Full Text Available Salt-induced changes in malatdehydrogenase system activity make the essential contribution to cell adaptation to stress condition. The enzyme systems of C4-plants are most interesting due to their ability for adaptation to environment conditions. The role of separate components of malatdehydrogenase complex of mesophyll and bundle sheath cells of corn in formation of adaptive reaction in stressful conditions is investigated in presented work.The activation of all enzymes of malatdehydrogenase system and the subsequent decrease in their activity was observed in mesophyll durring the first stage of adaptation to salt influence. In bundle sheath cells such parameters are differed from control less essentially. Fast accumulation of piruvate in cells and malate in both investigated tissues was induced. The further salinity led to falling of concentration this intermediate. The concentration of piruvate was below control level, and it was raised by the end of an exposition.The results show that sodium chloride causes induction of Krebs-cycle in mesophyll and bundle sheath cells of corn and intensification of Hatch-Slack cycle. The described differences in function malatdehydrogenase systems of mesophyll and bundle sheath cells of leaves of corn under salinity mainly consist of the activity of enzymes of a studied complex in bundle sheath cells is subject to the minimal changes in comparison with mesophyll. Role of this enzymesystem in mechanisms of adaptive reaction of various tissues of corn to salt stress is discussed.

    10. Core regulatory network motif underlies the ocellar complex patterning in Drosophila melanogaster

      Science.gov (United States)

      Aguilar-Hidalgo, D.; Lemos, M. C.; Córdoba, A.

      2015-03-01

      During organogenesis, developmental programs governed by Gene Regulatory Networks (GRN) define the functionality, size and shape of the different constituents of living organisms. Robustness, thus, is an essential characteristic that GRNs need to fulfill in order to maintain viability and reproducibility in a species. In the present work we analyze the robustness of the patterning for the ocellar complex formation in Drosophila melanogaster fly. We have systematically pruned the GRN that drives the development of this visual system to obtain the minimum pathway able to satisfy this pattern. We found that the mechanism underlying the patterning obeys to the dynamics of a 3-nodes network motif with a double negative feedback loop fed by a morphogenetic gradient that triggers the inhibition in a French flag problem fashion. A Boolean modeling of the GRN confirms robustness in the patterning mechanism showing the same result for different network complexity levels. Interestingly, the network provides a steady state solution in the interocellar part of the patterning and an oscillatory regime in the ocelli. This theoretical result predicts that the ocellar pattern may underlie oscillatory dynamics in its genetic regulation.

    11. Detecting the tipping points in a three-state model of complex diseases by temporal differential networks

      Directory of Open Access Journals (Sweden)

      Pei Chen

      2017-10-01

      Full Text Available Abstract Background The progression of complex diseases, such as diabetes and cancer, is generally a nonlinear process with three stages, i.e., normal state, pre-disease state, and disease state, where the pre-disease state is a critical state or tipping point immediately preceding the disease state. Traditional biomarkers aim to identify a disease state by exploiting the information of differential expressions for the observed molecules, but may fail to detect a pre-disease state because there are generally little significant differences between the normal and pre-disease states. Thus, it is challenging to signal the pre-disease state, which actually implies the disease prediction. Methods In this work, by exploiting the information of differential associations among the observed molecules between the normal and pre-disease states, we propose a temporal differential network based computational method to accurately signal the pre-disease state or predict the occurrence of severe disease. The theoretical foundation of this work is the quantification of the critical state using dynamical network biomarkers. Results Considering that there is one stationary Markov process before reaching the tipping point, a novel index, inconsistency score (I-score, is proposed to quantitatively measure the change of the stationary processes from the normal state so as to detect the onset of pre-disease state. In other words, a drastic increase of I-score implies the high inconsistency with the preceding stable state and thus signals the upcoming critical transition. This approach is applied to the simulated and real datasets of three diseases, which demonstrates the effectiveness of our method for predicting the deterioration into disease states. Both functional analysis and pathway enrichment also validate the computational results from the perspectives of both molecules and networks. Conclusions At the molecular network level, this method provides a

    12. Disease course and management strategy of pouch neoplasia in patients with underlying inflammatory bowel diseases.

      Science.gov (United States)

      Wu, Xian-Rui; Remzi, Feza H; Liu, Xiu-Li; Lian, Lei; Stocchi, Luca; Ashburn, Jean; Shen, Bo

      2014-11-01

      To evaluate the disease course and management strategy for pouch neoplasia. Patients undergoing ileal pouch surgery for underlying ulcerative colitis who developed low-grade dysplasia (LGD), high-grade dysplasia, or adenocarcinoma in the pouch were identified. All eligible 44 patients were evaluated. Of the 22 patients with initial diagnosis of pouch LGD, 6 (27.3%) had persistence or progression after a median follow-up of 9.5 (4.1-17.6) years. Family history of colorectal cancer was shown to be a risk factor associated with persistence or progression of LGD (P = 0.03). Of the 12 patients with pouch high-grade dysplasia, 5 (41.7%) had a history of (n = 2, 16.7%) or synchronous (n = 4, 33.3%) pouch LGD. Pouch high-grade dysplasia either persisted or progressed in 3 patients (25.0%) after the initial management, during a median time interval of 5.4 (2.2-9.2) years. Of the 14 patients with pouch adenocarcinoma, 12 (85.7%) had a history of (n = 2, 14.3%) or synchronous dysplasia (n = 12, 85.7%). After a median follow-up of 2.1 (0.6-5.2) years, 6 patients with pouch cancer (42.9%) died. Comparison of patients with a final diagnosis of pouch adenocarcinoma (14, 32.6%), and those with dysplasia (29, 67.4%) showed that patients with adenocarcinoma were older (P = 0.04) and had a longer duration from IBD diagnosis or pouch construction to the detection of pouch neoplasia (P = 0.007 and P = 0.0013). The risk for progression of pouch dysplasia can be stratified. The presence of family history of colorectal cancer seemed to increase the risk for persistence or progression for patients with pouch LGD. The prognosis for pouch adenocarcinoma was poor.

    13. [Autosomal recessive polycystic kidney disease and complex nephronophtisis medullary cystic disease].

      Science.gov (United States)

      2008-12-01

      Reseach during the past decade has led to the discovery that defects in some proteins that localize to primary cilia or the basal body are the main contributors to renal cyst development. Autosomal recessive polycystic disease and nephronophthisis- medullary cystic kidney disease are named ciliopathies. The cilium is a microtubule-based organelle that is found on most mammalian cells. Cilia-mediated hypothesis has evolved into the concept of cystogenesis, cilia bend by fluid initiate a calcium influx that prevents cyst formation. Cilia might sense stimuli in the cell enviroment and control cell polarity and mitosis. A new set of pathogenic mechanisms in renal cystic disease defined new therapeutic targets, control of intracellular calcium, inhibition of cAMP and down regulation cannonical Wnt signaling.

    14. Leadless pacemaker implantation in a patient with complex congenital heart disease and limited vascular access

      Directory of Open Access Journals (Sweden)

      Paolo Ferrero

      2016-11-01

      Full Text Available Management of rhythm related issues might be particularly challenging in patients with congenital heart disease due to complex anatomy and restricted vascular access. The leadless technology appears a suitable and attractive alternative for this population. We describe a patient with single ventricle physiology who successfully underwent implantation of a leadless pacemaker.

    15. Intervention Fidelity for a Complex Behaviour Change Intervention in Community Pharmacy Addressing Cardiovascular Disease Risk

      Science.gov (United States)

      McNamara, K. P.; O'Reilly, S. L.; George, J.; Peterson, G. M.; Jackson, S. L.; Duncan, G.; Howarth, H.; Dunbar, J. A.

      2015-01-01

      Background: Delivery of cardiovascular disease (CVD) prevention programs by community pharmacists appears effective and enhances health service access. However, their capacity to implement complex behavioural change processes during patient counselling remains largely unexplored. This study aims to determine intervention fidelity by pharmacists…

    16. Lessons from model organisms: phenotypic robustness and missing heritability in complex disease.

      Directory of Open Access Journals (Sweden)

      Christine Queitsch

      Full Text Available Genetically tractable model organisms from phages to mice have taught us invaluable lessons about fundamental biological processes and disease-causing mutations. Owing to technological and computational advances, human biology and the causes of human diseases have become accessible as never before. Progress in identifying genetic determinants for human diseases has been most remarkable for Mendelian traits. In contrast, identifying genetic determinants for complex diseases such as diabetes, cancer, and cardiovascular and neurological diseases has remained challenging, despite the fact that these diseases cluster in families. Hundreds of variants associated with complex diseases have been found in genome-wide association studies (GWAS, yet most of these variants explain only a modest amount of the observed heritability, a phenomenon known as "missing heritability." The missing heritability has been attributed to many factors, mainly inadequacies in genotyping and phenotyping. We argue that lessons learned about complex traits in model organisms offer an alternative explanation for missing heritability in humans. In diverse model organisms, phenotypic robustness differs among individuals, and those with decreased robustness show increased penetrance of mutations and express previously cryptic genetic variation. We propose that phenotypic robustness also differs among humans and that individuals with lower robustness will be more responsive to genetic and environmental perturbations and hence susceptible to disease. Phenotypic robustness is a quantitative trait that can be accurately measured in model organisms, but not as yet in humans. We propose feasible approaches to measure robustness in large human populations, proof-of-principle experiments for robustness markers in model organisms, and a new GWAS design that takes differences in robustness into account.

    17. Robust Satisficing Decision Making for Unmanned Aerial Vehicle Complex Missions under Severe Uncertainty.

      Directory of Open Access Journals (Sweden)

      Xiaoting Ji

      Full Text Available This paper presents a robust satisficing decision-making method for Unmanned Aerial Vehicles (UAVs executing complex missions in an uncertain environment. Motivated by the info-gap decision theory, we formulate this problem as a novel robust satisficing optimization problem, of which the objective is to maximize the robustness while satisfying some desired mission requirements. Specifically, a new info-gap based Markov Decision Process (IMDP is constructed to abstract the uncertain UAV system and specify the complex mission requirements with the Linear Temporal Logic (LTL. A robust satisficing policy is obtained to maximize the robustness to the uncertain IMDP while ensuring a desired probability of satisfying the LTL specifications. To this end, we propose a two-stage robust satisficing solution strategy which consists of the construction of a product IMDP and the generation of a robust satisficing policy. In the first stage, a product IMDP is constructed by combining the IMDP with an automaton representing the LTL specifications. In the second, an algorithm based on robust dynamic programming is proposed to generate a robust satisficing policy, while an associated robustness evaluation algorithm is presented to evaluate the robustness. Finally, through Monte Carlo simulation, the effectiveness of our algorithms is demonstrated on an UAV search mission under severe uncertainty so that the resulting policy can maximize the robustness while reaching the desired performance level. Furthermore, by comparing the proposed method with other robust decision-making methods, it can be concluded that our policy can tolerate higher uncertainty so that the desired performance level can be guaranteed, which indicates that the proposed method is much more effective in real applications.

    18. Robust Satisficing Decision Making for Unmanned Aerial Vehicle Complex Missions under Severe Uncertainty.

      Science.gov (United States)

      Ji, Xiaoting; Niu, Yifeng; Shen, Lincheng

      2016-01-01

      This paper presents a robust satisficing decision-making method for Unmanned Aerial Vehicles (UAVs) executing complex missions in an uncertain environment. Motivated by the info-gap decision theory, we formulate this problem as a novel robust satisficing optimization problem, of which the objective is to maximize the robustness while satisfying some desired mission requirements. Specifically, a new info-gap based Markov Decision Process (IMDP) is constructed to abstract the uncertain UAV system and specify the complex mission requirements with the Linear Temporal Logic (LTL). A robust satisficing policy is obtained to maximize the robustness to the uncertain IMDP while ensuring a desired probability of satisfying the LTL specifications. To this end, we propose a two-stage robust satisficing solution strategy which consists of the construction of a product IMDP and the generation of a robust satisficing policy. In the first stage, a product IMDP is constructed by combining the IMDP with an automaton representing the LTL specifications. In the second, an algorithm based on robust dynamic programming is proposed to generate a robust satisficing policy, while an associated robustness evaluation algorithm is presented to evaluate the robustness. Finally, through Monte Carlo simulation, the effectiveness of our algorithms is demonstrated on an UAV search mission under severe uncertainty so that the resulting policy can maximize the robustness while reaching the desired performance level. Furthermore, by comparing the proposed method with other robust decision-making methods, it can be concluded that our policy can tolerate higher uncertainty so that the desired performance level can be guaranteed, which indicates that the proposed method is much more effective in real applications.

    19. Binge eating under a complex reading: Subsidies for the praxis of food and nutrition education

      Directory of Open Access Journals (Sweden)

      Maria Lúcia Magalhães BOSI

      Full Text Available ABSTRACT Binge eating disorder is characterized by the consumption of large amounts of food in a short time, accompanied by the feeling of lack of control, remorse and guilt. binge eating disorder has a close interface with the obesity problem, a matter of great dimensions for health services, especially for the high comorbidity. Although this disorder is closely linked to obesity, a matter of great dimensions for healthcare, especially due to it high comorbidity, this disorder is still poorly known in its symbolic dimension, compromising actions directed to this dimension, among them those included in the scope of food and nutrition education. The purpose of this article is to delimitate the issue of binge eating disorder, under a lens based on complex thinking, in order to discuss and support the scope of the nutritional eating education, illustrating, with life experiences, the multidimensionality inherent to eating disorders. The analysis aims to highlight the challenge of working in educational practices focused on these complex disorders. Therefore, we articulated the theoretical with the empirical levels, revisiting, through a reflexive exercise, the discursive material obtained in a broad research carried out by the authors, guided by phenomenological-hermeneutics approach focusing on the understanding of binge eating disorder, with obese women who have also received this diagnosis. The analysis highlights binge eating disorder as an intense experience of suffering, which compromises the ability to innovate and reinvent behavior, in which food operates as an emotional cushion. In this context, healing requires taking an active and engaged place, feeling an active part in the self-transformation process. Thus, food and nutritional education should be conceived in the scope of a comprehensive care, as a fundamental and strategic space due to the specific nature of the practice, in potential terms.

    20. The power of gene-based rare variant methods to detect disease-associated variation and test hypotheses about complex disease.

      Directory of Open Access Journals (Sweden)

      Loukas Moutsianas

      2015-04-01

      Full Text Available Genome and exome sequencing in large cohorts enables characterization of the role of rare variation in complex diseases. Success in this endeavor, however, requires investigators to test a diverse array of genetic hypotheses which differ in the number, frequency and effect sizes of underlying causal variants. In this study, we evaluated the power of gene-based association methods to interrogate such hypotheses, and examined the implications for study design. We developed a flexible simulation approach, using 1000 Genomes data, to (a generate sequence variation at human genes in up to 10K case-control samples, and (b quantify the statistical power of a panel of widely used gene-based association tests under a variety of allelic architectures, locus effect sizes, and significance thresholds. For loci explaining ~1% of phenotypic variance underlying a common dichotomous trait, we find that all methods have low absolute power to achieve exome-wide significance (~5-20% power at α = 2.5 × 10(-6 in 3K individuals; even in 10K samples, power is modest (~60%. The combined application of multiple methods increases sensitivity, but does so at the expense of a higher false positive rate. MiST, SKAT-O, and KBAC have the highest individual mean power across simulated datasets, but we observe wide architecture-dependent variability in the individual loci detected by each test, suggesting that inferences about disease architecture from analysis of sequencing studies can differ depending on which methods are used. Our results imply that tens of thousands of individuals, extensive functional annotation, or highly targeted hypothesis testing will be required to confidently detect or exclude rare variant signals at complex disease loci.

    1. Computer Simulation of Complex Power System Faults under various Operating Conditions

      International Nuclear Information System (INIS)

      Khandelwal, Tanuj; Bowman, Mark

      2015-01-01

      A power system is normally treated as a balanced symmetrical three-phase network. When a fault occurs, the symmetry is normally upset, resulting in unbalanced currents and voltages appearing in the network. For the correct application of protection equipment, it is essential to know the fault current distribution throughout the system and the voltages in different parts of the system due to the fault. There may be situations where protection engineers have to analyze faults that are more complex than simple shunt faults. One type of complex fault is an open phase condition that can result from a fallen conductor or failure of a breaker pole. In the former case, the condition is often accompanied by a fault detectable with normal relaying. In the latter case, the condition may be undetected by standard line relaying. The effect on a generator is dependent on the location of the open phase and the load level. If an open phase occurs between the generator terminals and the high-voltage side of the GSU in the switchyard, and the generator is at full load, damaging negative sequence current can be generated. However, for the same operating condition, an open conductor at the incoming transmission lines located in the switchyard can result in minimal negative sequence current. In 2012, a nuclear power generating station (NPGS) suffered series or open phase fault due to insulator mechanical failure in the 345 kV switchyard. This resulted in both reactor units tripping offline in two separate incidents. Series fault on one of the phases resulted in voltage imbalance that was not detected by the degraded voltage relays. These under-voltage relays did not initiate a start signal to the emergency diesel generators (EDG) because they sensed adequate voltage on the remaining phases exposing a design vulnerability. This paper is intended to help protection engineers calculate complex circuit faults like open phase condition using computer program. The impact of this type of

    2. Complex Fibroadenoma and Breast Cancer Risk: A Mayo Clinic Benign Breast Disease Cohort Studya

      Science.gov (United States)

      Nassar, Aziza; Visscher, Daniel W.; Degnim, Amy C.; Frank, Ryan D.; Vierkant, Robert A.; Frost, Marlene; Radisky, Derek C.; Vachon, Celine M.; Kraft, Ruth A.; Hartmann, Lynn C.; Ghosh, Karthik

      2015-01-01

      Purpose To examine the breast cancer risk overall among women with simple fibroadenoma or complex fibroadenoma and to examine the association of complex fibroadenoma with breast cancer through stratification of other breast cancer risks. Methods The study included women aged 18 to 85 years from the Mayo Clinic Benign Breast Disease Cohort who underwent excisional breast biopsy from 1967 through 1991. Within this cohort, women who had fibroadenoma were compared to women who did not have fibroadenoma. Breast cancer risk (observed vs expected) across fibroadenoma levels was assessed through standardized incidence ratios (SIRs) by using age- and calendar-stratified incidence rates from the Iowa Surveillance, Epidemiology, and End Results registry. Analyses were performed overall, within subgroups of involution status, with other demographic characteristics (age, year of biopsy, indication for biopsy, and family history), and with histologic characteristics, including overall impression (nonproliferative disease, proliferative disease without atypia [PDWA], or atypical hyperplasia). Results Fibroadenoma was identified in 2,136 women (noncomplex, 1,835 [85.9%]; complex, 301 [14.1%]). SIR for noncomplex fibroadenoma was 1.49 (95% CI, 1.26–1.74); for complex fibroadenoma, it was 2.27 (95% CI, 1.63–3.10) (test for heterogeneity in SIR, P=.02). However, women with complex fibroadenoma were more likely to have other, concomitant high-risk histologic characteristics (eg, incomplete involution and PDWA). In analyses stratified by involution status and PDWA, complex fibroadenoma was not an independent risk marker for breast cancer. Conclusions Complex fibroadenoma does not confer increased breast cancer risk beyond other established histologic characteristics. PMID:26264469

    3. Complex fibroadenoma and breast cancer risk: a Mayo Clinic Benign Breast Disease Cohort Study.

      Science.gov (United States)

      Nassar, Aziza; Visscher, Daniel W; Degnim, Amy C; Frank, Ryan D; Vierkant, Robert A; Frost, Marlene; Radisky, Derek C; Vachon, Celine M; Kraft, Ruth A; Hartmann, Lynn C; Ghosh, Karthik

      2015-09-01

      The purpose of this study is to examine the breast cancer risk overall among women with simple fibroadenoma or complex fibroadenoma and to examine the association of complex fibroadenoma with breast cancer through stratification of other breast cancer risks. The study included women aged 18-85 years from the Mayo Clinic Benign Breast Disease Cohort who underwent excisional breast biopsy from 1967 through 1991. Within this cohort, women who had fibroadenoma were compared to women who did not have fibroadenoma. Breast cancer risk (observed versus expected) across fibroadenoma levels was assessed through standardized incidence ratios (SIRs) by using age- and calendar-stratified incidence rates from the Iowa Surveillance, Epidemiology, and End Results registry. Analyses were performed overall, within subgroups of involution status, with other demographic characteristics (age, year of biopsy, indication for biopsy, and family history), and with histologic characteristics, including overall impression [nonproliferative disease, proliferative disease without atypia (PDWA), or atypical hyperplasia]. Fibroadenoma was identified in 2136 women [noncomplex, 1835 (85.9%); complex, 301 (14.1%)]. SIR for noncomplex fibroadenoma was 1.49 (95% CI 1.26-1.74); for complex fibroadenoma, it was 2.27 (95% CI 1.63-3.10) (test for heterogeneity in SIR, P = .02). However, women with complex fibroadenoma were more likely to have other, concomitant high-risk histologic characteristics (e.g., incomplete involution and PDWA). In analyses stratified by involution status and PDWA, complex fibroadenoma was not an independent risk marker for breast cancer. Complex fibroadenoma does not confer increased breast cancer risk beyond other established histologic characteristics.

    4. Waste management under multiple complexities: Inexact piecewise-linearization-based fuzzy flexible programming

      International Nuclear Information System (INIS)

      Sun Wei; Huang, Guo H.; Lv Ying; Li Gongchen

      2012-01-01

      Highlights: ► Inexact piecewise-linearization-based fuzzy flexible programming is proposed. ► It’s the first application to waste management under multiple complexities. ► It tackles nonlinear economies-of-scale effects in interval-parameter constraints. ► It estimates costs more accurately than the linear-regression-based model. ► Uncertainties are decreased and more satisfactory interval solutions are obtained. - Abstract: To tackle nonlinear economies-of-scale (EOS) effects in interval-parameter constraints for a representative waste management problem, an inexact piecewise-linearization-based fuzzy flexible programming (IPFP) model is developed. In IPFP, interval parameters for waste amounts and transportation/operation costs can be quantified; aspiration levels for net system costs, as well as tolerance intervals for both capacities of waste treatment facilities and waste generation rates can be reflected; and the nonlinear EOS effects transformed from objective function to constraints can be approximated. An interactive algorithm is proposed for solving the IPFP model, which in nature is an interval-parameter mixed-integer quadratically constrained programming model. To demonstrate the IPFP’s advantages, two alternative models are developed to compare their performances. One is a conventional linear-regression-based inexact fuzzy programming model (IPFP2) and the other is an IPFP model with all right-hand-sides of fussy constraints being the corresponding interval numbers (IPFP3). The comparison results between IPFP and IPFP2 indicate that the optimized waste amounts would have the similar patterns in both models. However, when dealing with EOS effects in constraints, the IPFP2 may underestimate the net system costs while the IPFP can estimate the costs more accurately. The comparison results between IPFP and IPFP3 indicate that their solutions would be significantly different. The decreased system uncertainties in IPFP’s solutions demonstrate

    5. The theory and method of variable frequency directional seismic wave under the complex geologic conditions

      Science.gov (United States)

      Jiang, T.; Yue, Y.

      2017-12-01

      It is well known that the mono-frequency directional seismic wave technology can concentrate seismic waves into a beam. However, little work on the method and effect of variable frequency directional seismic wave under complex geological conditions have been done .We studied the variable frequency directional wave theory in several aspects. Firstly, we studied the relation between directional parameters and the direction of the main beam. Secondly, we analyzed the parameters that affect the beam width of main beam significantly, such as spacing of vibrator, wavelet dominant frequency, and number of vibrator. In addition, we will study different characteristics of variable frequency directional seismic wave in typical velocity models. In order to examine the propagation characteristics of directional seismic wave, we designed appropriate parameters according to the character of direction parameters, which is capable to enhance the energy of the main beam direction. Further study on directional seismic wave was discussed in the viewpoint of power spectral. The results indicate that the energy intensity of main beam direction increased 2 to 6 times for a multi-ore body velocity model. It showed us that the variable frequency directional seismic technology provided an effective way to strengthen the target signals under complex geological conditions. For concave interface model, we introduced complicated directional seismic technology which supports multiple main beams to obtain high quality data. Finally, we applied the 9-element variable frequency directional seismic wave technology to process the raw data acquired in a oil-shale exploration area. The results show that the depth of exploration increased 4 times with directional seismic wave method. Based on the above analysis, we draw the conclusion that the variable frequency directional seismic wave technology can improve the target signals of different geologic conditions and increase exploration depth with little

    6. Soybean (Glycine max L. Merr.) Sprouts Germinated under Red Light Irradiation Induce Disease Resistance against Bacterial Rotting Disease

      OpenAIRE

      Dhakal, Radhika; Park, Euiho; Lee, Se-Weon; Baek, Kwang-Hyun

      2015-01-01

      Specific wavelengths of light can exert various physiological changes in plants, including effects on responses to disease incidence. To determine whether specific light wavelength had effects on rotting disease caused by Pseudomonas putida 229, soybean sprouts were germinated under a narrow range of wavelengths from light emitting diodes (LEDs), including red (650-660), far red (720-730) and blue (440-450 nm) or broad range of wavelength from daylight fluorescence bulbs. The controls were co...

    7. Characteristics of Lipoprotein(a)-Containing Circulating Immune Complexes as Markers of Coronary Heart Disease.

      Science.gov (United States)

      Klesareva, E A; Afanas'eva, O I; Donskikh, V V; Adamova, I Yu; Pokrovskii, S N

      2016-12-01

      We studied the composition of circulating immune complexes precipitated in the presence of various concentrations of polyethylene glycol in patients with coronary heart disease (CHD) and high concentration of lipoprotein(a) - Lp(a). Precipitation of highly purified Lp(a) preparation with polyethylene glycol was evaluated. The contents of Lp(a), autoantibodies to Lp(a), IgG, and IgM in circulating immune complexes isolated from the sera of donors and CHD patients with normal and high levels of Lp(a) were measured. Circulating immune complexes containing Lp(a) were detected in the plasma of CHD patients with high Lp(a) concentrations. The presence of high concentrations of Lp(a), autoantibodies to Lp(a), and circulating immune complexes in CHD patients suggests that immunological factor contributes to high atherothrombogenicity of Lp(a).

    8. Transantral, endoscopically guided balloon dilatation of the ostiomeatal complex for chronic rhinosinusitis under local anesthesia.

      Science.gov (United States)

      Stankiewicz, James; Tami, Thomas; Truitt, Theodore; Atkins, James; Liepert, Douglas; Winegar, Bradford

      2009-01-01

      A multicenter study (BREATHE I - Entellus Medical, Inc.) was performed to assess the safety and outcomes of a new, less invasive system that uses direct endoscopic visualization to facilitate balloon dilation of the maxillary sinus ostia and ethmoid infundibulum. General anesthesia was avoided in most subjects to assess feasibility of performing transantral ostial dilatation in an office setting. Subjects with chronic rhinosinusitis of the maxillary sinuses alone or maxillary and anterior ethmoid sinuses underwent baseline evaluation including CT imaging and symptom assessment using the Sino-Nasal Outcome Test (SNOT 20). Subjects underwent transantral balloon dilation and follow-up evaluation at 1 week, 3 months, and 6 months post-procedure. Thirty subjects were treated at three centers. Fifty-five of 58 maxillary ostia were successfully treated for a procedural completion rate of 94.8%. Ninety-seven percent of the procedures were completed under local anesthesia with or without minimal intravenous sedation. There were no device-related serious adverse events or unanticipated adverse device effects. The mean overall SNOT 20 score at baseline was 2.9 +/- 1.0. Mean overall SNOT 20 scores at 1-week, 3-month, and 6-month follow-up were 0.8 +/- 0.8, 0.7 +/- 0.8, and 0.8 +/- 0.9 respectively. Patency at 3-months as confirmed by CT imaging was 95.8%. These results indicate that transantral balloon dilation of the ostiomeatal complex under local anesthesia appears to be a safe technique for managing isolated maxillary or maxillary and anterior ethmoid sinusitis and can potentially be performed safely in an office setting.

    9. Identifying driving gene clusters in complex diseases through critical transition theory

      Science.gov (United States)

      Wolanyk, Nathaniel; Wang, Xujing; Hessner, Martin; Gao, Shouguo; Chen, Ye; Jia, Shuang

      A novel approach of looking at the human body using critical transition theory has yielded positive results: clusters of genes that act in tandem to drive complex disease progression. This cluster of genes can be thought of as the first part of a large genetic force that pushes the body from a curable, but sick, point to an incurable diseased point through a catastrophic bifurcation. The data analyzed is time course microarray blood assay data of 7 high risk individuals for Type 1 Diabetes who progressed into a clinical onset, with an additional larger study requested to be presented at the conference. The normalized data is 25,000 genes strong, which were narrowed down based on statistical metrics, and finally a machine learning algorithm using critical transition metrics found the driving network. This approach was created to be repeatable across multiple complex diseases with only progression time course data needed so that it would be applicable to identifying when an individual is at risk of developing a complex disease. Thusly, preventative measures can be enacted, and in the longer term, offers a possible solution to prevent all Type 1 Diabetes.

    10. Gene-Environment Interactions in the Development of Complex Disease Phenotypes

      Directory of Open Access Journals (Sweden)

      Kenneth Olden

      2008-03-01

      Full Text Available The lack of knowledge about the earliest events in disease development is due to the multi-factorial nature of disease risk. This information gap is the consequence of the lack of appreciation for the fact that most diseases arise from the complex interactions between genes and the environment as a function of the age or stage of development of the individual. Whether an environmental exposure causes illness or not is dependent on the efficiency of the so-called “environmental response machinery” (i.e., the complex of metabolic pathways that can modulate response to environmental perturbations that one has inherited. Thus, elucidating the causes of most chronic diseases will require an understanding of both the genetic and environmental contribution to their etiology. Unfortunately, the exploration of the relationship between genes and the environment has been hampered in the past by the limited knowledge of the human genome, and by the inclination of scientists to study disease development using experimental models that consider exposure to a single environmental agent. Rarely in the past were interactions between multiple genes or between genes and environmental agents considered in studies of human disease etiology. The most critical issue is how to relate exposure-disease association studies to pathways and mechanisms. To understand how genes and environmental factors interact to perturb biological pathways to cause injury or disease, scientists will need tools with the capacity to monitor the global expression of thousands of genes, proteins and metabolites simultaneously. The generation of such data in multiple species can be used to identify conserved and functionally significant genes and pathways involved in geneenvironment interactions. Ultimately, it is this knowledge that will be used to guide agencies such as the U.S. Department of Health and Human Services in decisions regarding biomedical research funding

    11. Evaluation of the Aristotle complexity models in adult patients with congenital heart disease.

      Science.gov (United States)

      Hörer, Jürgen; Vogt, Manfred; Wottke, Michael; Cleuziou, Julie; Kasnar-Samprec, Jelena; Lange, Rüdiger; Schreiber, Christian

      2013-01-01

      The adult congenital heart disease (CHD) population has surpassed the paediatric CHD population. Half of all mortality caused by CHD occurs in adulthood; in some patients, it occurs during surgery. We sought to assess the potential risk factors for adverse outcome after cardiac operations in adults with CHD, and to evaluate the predictive power of the Aristotle score models for hospital mortality. Procedure-dependent and independent factors, as well as the outcome factors of all consecutive patients aged 16 or more who underwent surgery for CHD between 2005 and 2008 at our institution were evaluated according to the European Association for Cardio-Thoracic Surgery Congenital Database nomenclature. An Aristotle basic complexity (ABC) and an Aristotle comprehensive complexity (ACC) score were assigned to each operation. The discriminatory power of the scores was assessed using the area under the receiver operating characteristics (AuROC) curve. During 542 operations, 773 procedures were performed. The early mortality rate was 2.4%, and the early complication rate was 53.7%. Tricuspid valve replacement (P = 0.009), mitral valve replacement (P < 0.001), elevated lung resistances (P = 0.002), hypothyroidism (P = 0.002) and redosternotomy (P = 0.003) emerged as risk factors for 30-day mortality. Tricuspid valve replacement (P < 0.001), tricuspid valvuloplasty (P = 0.006), mitral valve replacement (P = 0.003), shunt implantation (P = 0.009), surgical ablation (P = 0.024), myocardial dysfunction (P = 0.014), elevated lung resistances (P = 0.004), hypothyroidism (P = 0.002) and redosternotomy (P < 0.001) emerged as risk factors for complications. Mean ABC and ACC scores were 6.6 ± 2.3, and 9.0 ± 3.7, respectively. The AuROCs of the ABC and the ACC scores for 30-day mortality were 0.663 (P = 0.044), and 0.755 (P = 0.002), respectively. The AuROCs of the ABC and the ACC scores for complications were 0.634 (P < 0.001), and 0.670 (P < 0.001), respectively. Surgery for adults

    12. Soybean (Glycine max L. Merr.) sprouts germinated under red light irradiation induce disease resistance against bacterial rotting disease.

      Science.gov (United States)

      Dhakal, Radhika; Park, Euiho; Lee, Se-Weon; Baek, Kwang-Hyun

      2015-01-01

      Specific wavelengths of light can exert various physiological changes in plants, including effects on responses to disease incidence. To determine whether specific light wavelength had effects on rotting disease caused by Pseudomonas putida 229, soybean sprouts were germinated under a narrow range of wavelengths from light emitting diodes (LEDs), including red (650-660), far red (720-730) and blue (440-450 nm) or broad range of wavelength from daylight fluorescence bulbs. The controls were composed of soybean sprouts germinated in darkness. After germination under different conditions for 5 days, the soybean sprouts were inoculated with P. putida 229 and the disease incidence was observed for 5 days. The sprouts exposed to red light showed increased resistance against P. putida 229 relative to those grown under other conditions. Soybean sprouts germinated under red light accumulated high levels of salicylic acid (SA) accompanied with up-regulation of the biosynthetic gene ICS and the pathogenesis- related (PR) gene PR-1, indicating that the resistance was induced by the action of SA via de novo synthesis of SA in the soybean sprouts by red light irradiation. Taken together, these data suggest that only the narrow range of red light can induce disease resistance in soybean sprouts, regulated by the SA-dependent pathway via the de novo synthesis of SA and up-regulation of PR genes.

    13. Soybean (Glycine max L. Merr. sprouts germinated under red light irradiation induce disease resistance against bacterial rotting disease.

      Directory of Open Access Journals (Sweden)

      Radhika Dhakal

      Full Text Available Specific wavelengths of light can exert various physiological changes in plants, including effects on responses to disease incidence. To determine whether specific light wavelength had effects on rotting disease caused by Pseudomonas putida 229, soybean sprouts were germinated under a narrow range of wavelengths from light emitting diodes (LEDs, including red (650-660, far red (720-730 and blue (440-450 nm or broad range of wavelength from daylight fluorescence bulbs. The controls were composed of soybean sprouts germinated in darkness. After germination under different conditions for 5 days, the soybean sprouts were inoculated with P. putida 229 and the disease incidence was observed for 5 days. The sprouts exposed to red light showed increased resistance against P. putida 229 relative to those grown under other conditions. Soybean sprouts germinated under red light accumulated high levels of salicylic acid (SA accompanied with up-regulation of the biosynthetic gene ICS and the pathogenesis- related (PR gene PR-1, indicating that the resistance was induced by the action of SA via de novo synthesis of SA in the soybean sprouts by red light irradiation. Taken together, these data suggest that only the narrow range of red light can induce disease resistance in soybean sprouts, regulated by the SA-dependent pathway via the de novo synthesis of SA and up-regulation of PR genes.

    14. On rational complex of investigation methods in prophylactic examination of patients with chronic kidney diseases

      International Nuclear Information System (INIS)

      Yazykov, A.S.; Telichko, F.F.

      1989-01-01

      A retrospective evaluation of the total quantity of X-ray procedures and the radiation degree in 310 patients with chronic kidney diseases is given. It is ascertained that only account of integral absorbed dose in the organ tissues, comprising the doses of X-ray examinations of other organs during the patient lifetime, can serve as the main condition for developing well-grounded recommendations concerning rational complex of examination methods during prophylactic examination of patients with chronic kidney disease. 9 refs.; 4 figs

    15. Forecasting the future risk of Barmah Forest virus disease under climate change scenarios in Queensland, Australia.

      Directory of Open Access Journals (Sweden)

      Suchithra Naish

      Full Text Available BACKGROUND: Mosquito-borne diseases are climate sensitive and there has been increasing concern over the impact of climate change on future disease risk. This paper projected the potential future risk of Barmah Forest virus (BFV disease under climate change scenarios in Queensland, Australia. METHODS/PRINCIPAL FINDINGS: We obtained data on notified BFV cases, climate (maximum and minimum temperature and rainfall, socio-economic and tidal conditions for current period 2000-2008 for coastal regions in Queensland. Grid-data on future climate projections for 2025, 2050 and 2100 were also obtained. Logistic regression models were built to forecast the otential risk of BFV disease distribution under existing climatic, socio-economic and tidal conditions. The model was applied to estimate the potential geographic distribution of BFV outbreaks under climate change scenarios. The predictive model had good model accuracy, sensitivity and specificity. Maps on potential risk of future BFV disease indicated that disease would vary significantly across coastal regions in Queensland by 2100 due to marked differences in future rainfall and temperature projections. CONCLUSIONS/SIGNIFICANCE: We conclude that the results of this study demonstrate that the future risk of BFV disease would vary across coastal regions in Queensland. These results may be helpful for public health decision making towards developing effective risk management strategies for BFV disease control and prevention programs in Queensland.

    16. Forecasting the future risk of Barmah Forest virus disease under climate change scenarios in Queensland, Australia.

      Science.gov (United States)

      Naish, Suchithra; Mengersen, Kerrie; Hu, Wenbiao; Tong, Shilu

      2013-01-01

      Mosquito-borne diseases are climate sensitive and there has been increasing concern over the impact of climate change on future disease risk. This paper projected the potential future risk of Barmah Forest virus (BFV) disease under climate change scenarios in Queensland, Australia. We obtained data on notified BFV cases, climate (maximum and minimum temperature and rainfall), socio-economic and tidal conditions for current period 2000-2008 for coastal regions in Queensland. Grid-data on future climate projections for 2025, 2050 and 2100 were also obtained. Logistic regression models were built to forecast the otential risk of BFV disease distribution under existing climatic, socio-economic and tidal conditions. The model was applied to estimate the potential geographic distribution of BFV outbreaks under climate change scenarios. The predictive model had good model accuracy, sensitivity and specificity. Maps on potential risk of future BFV disease indicated that disease would vary significantly across coastal regions in Queensland by 2100 due to marked differences in future rainfall and temperature projections. We conclude that the results of this study demonstrate that the future risk of BFV disease would vary across coastal regions in Queensland. These results may be helpful for public health decision making towards developing effective risk management strategies for BFV disease control and prevention programs in Queensland.

    17. Distributional potential of the Triatoma brasiliensis species complex at present and under scenarios of future climate conditions

      Science.gov (United States)

      2014-01-01

      Background The Triatoma brasiliensis complex is a monophyletic group, comprising three species, one of which includes two subspecific taxa, distributed across 12 Brazilian states, in the caatinga and cerrado biomes. Members of the complex are diverse in terms of epidemiological importance, morphology, biology, ecology, and genetics. Triatoma b. brasiliensis is the most disease-relevant member of the complex in terms of epidemiology, extensive distribution, broad feeding preferences, broad ecological distribution, and high rates of infection with Trypanosoma cruzi; consequently, it is considered the principal vector of Chagas disease in northeastern Brazil. Methods We used ecological niche models to estimate potential distributions of all members of the complex, and evaluated the potential for suitable adjacent areas to be colonized; we also present first evaluations of potential for climate change-mediated distributional shifts. Models were developed using the GARP and Maxent algorithms. Results Models for three members of the complex (T. b. brasiliensis, N = 332; T. b. macromelasoma, N = 35; and T. juazeirensis, N = 78) had significant distributional predictivity; however, models for T. sherlocki and T. melanica, both with very small sample sizes (N = 7), did not yield predictions that performed better than random. Model projections onto future-climate scenarios indicated little broad-scale potential for change in the potential distribution of the complex through 2050. Conclusions This study suggests that T. b. brasiliensis is the member of the complex with the greatest distributional potential to colonize new areas: overall; however, the distribution of the complex appears relatively stable. These analyses offer key information to guide proactive monitoring and remediation activities to reduce risk of Chagas disease transmission. PMID:24886587

    18. Broncho-pleural fistula with hydropneumothorax at CT: Diagnostic implications in mycobacterium avium complex lung disease with pleural involvement

      Energy Technology Data Exchange (ETDEWEB)

      Yoon, Hyun Jung; Chung, Myung Jin; Lee, Kyung Soo; Park, Hye Yun; Koh, Won Jung [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Jung Soo [Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of)

      2016-04-15

      To determine the patho-mechanism of pleural effusion or hydropneumothorax in Mycobacterium avium complex (MAC) lung disease through the computed tomographic (CT) findings. We retrospectively collected data from 5 patients who had pleural fluid samples that were culture-positive for MAC between January 2001 and December 2013. The clinical findings were investigated and the radiological findings on chest CT were reviewed by 2 radiologists. The 5 patients were all male with a median age of 77 and all had underlying comorbid conditions. Pleural fluid analysis revealed a wide range of white blood cell counts (410-100690/µL). The causative microorganisms were determined as Mycobacterium avium and Mycobacterium intracellulare in 1 and 4 patients, respectively. Radiologically, the peripheral portion of the involved lung demonstrated fibro-bullous changes or cavitary lesions causing lung destruction, reflecting the chronic, insidious nature of MAC lung disease. All patients had broncho-pleural fistulas (BPFs) and pneumothorax was accompanied with pleural effusion. In patients with underlying MAC lung disease who present with pleural effusion, the presence of BPFs and pleural air on CT imaging are indicative that spread of MAC infection is the cause of the effusion.

    19. Broncho-pleural fistula with hydropneumothorax at CT: Diagnostic implications in mycobacterium avium complex lung disease with pleural involvement

      International Nuclear Information System (INIS)

      Yoon, Hyun Jung; Chung, Myung Jin; Lee, Kyung Soo; Park, Hye Yun; Koh, Won Jung; Kim, Jung Soo

      2016-01-01

      To determine the patho-mechanism of pleural effusion or hydropneumothorax in Mycobacterium avium complex (MAC) lung disease through the computed tomographic (CT) findings. We retrospectively collected data from 5 patients who had pleural fluid samples that were culture-positive for MAC between January 2001 and December 2013. The clinical findings were investigated and the radiological findings on chest CT were reviewed by 2 radiologists. The 5 patients were all male with a median age of 77 and all had underlying comorbid conditions. Pleural fluid analysis revealed a wide range of white blood cell counts (410-100690/µL). The causative microorganisms were determined as Mycobacterium avium and Mycobacterium intracellulare in 1 and 4 patients, respectively. Radiologically, the peripheral portion of the involved lung demonstrated fibro-bullous changes or cavitary lesions causing lung destruction, reflecting the chronic, insidious nature of MAC lung disease. All patients had broncho-pleural fistulas (BPFs) and pneumothorax was accompanied with pleural effusion. In patients with underlying MAC lung disease who present with pleural effusion, the presence of BPFs and pleural air on CT imaging are indicative that spread of MAC infection is the cause of the effusion

    20. Metabolic Networks Underlying Cognitive Reserve in Prodromal Alzheimer Disease: A European Alzheimer Disease Consortium Project

      NARCIS (Netherlands)

      Morbelli, S.; Perneczky, R.; Drzezga, A.; Frisoni, G. B.; Caroli, A.; van Berckel, B.N.M.; Ossenkoppele, R.; Guedj, E.; Didic, M.; Brugnolo, A.; Naseri, M.; Sambuceti, G.; Pagani, M.; Nobili, F.

      2013-01-01

      This project aimed to investigate the metabolic basis for resilience to neurodegeneration (cognitive reserve) in highly educated patients with prodromal Alzheimer disease (AD). Methods: Sixty-four patients with amnestic mild cognitive impairment who later converted to AD dementia during follow-up,

    1. Steady-state configuration and tension calculations of marine cables under complex currents via separated particle swarm optimization

      Science.gov (United States)

      Xu, Xue-song

      2014-12-01

      Under complex currents, the motion governing equations of marine cables are complex and nonlinear, and the calculations of cable configuration and tension become difficult compared with those under the uniform or simple currents. To obtain the numerical results, the usual Newton-Raphson iteration is often adopted, but its stability depends on the initial guessed solution to the governing equations. To improve the stability of numerical calculation, this paper proposed separated the particle swarm optimization, in which the variables are separated into several groups, and the dimension of search space is reduced to facilitate the particle swarm optimization. Via the separated particle swarm optimization, these governing nonlinear equations can be solved successfully with any initial solution, and the process of numerical calculation is very stable. For the calculations of cable configuration and tension of marine cables under complex currents, the proposed separated swarm particle optimization is more effective than the other particle swarm optimizations.

    2. Neural mechanisms underlying migrating motor complex formation in mouse isolated colon

      Science.gov (United States)

      Brierley, Stuart M; Nichols, Kim; Grasby, Dallas J; Waterman, Sally A

      2001-01-01

      Little is known about the intrinsic enteric reflex pathways associated with migrating motor complex (MMC) formation. Acetylcholine (ACh) mediates the rapid component of the MMC, however a non-cholinergic component also exists. The present study investigated the possible role of endogenous tachykinins (TKs) in the formation of colonic MMCs and the relative roles of excitatory and inhibitory pathways.MMCs were recorded from the circular muscle at four sites (proximal, proximal-mid, mid-distal and distal) along the mouse colon using force transducers.The tachykinin (NK1 and NK2) receptor antagonists SR-140 333 (250 nM) and SR-48 968 (250 nM) reduced the amplitude of MMCs at all recording sites, preferentially abolishing the long duration contraction. Residual MMCs were abolished by the subsequent addition of atropine (1 μM).The neuronal nitric oxide synthase inhibitor, Nωnitro-L-arginine (L-NOARG, 100 μM), increased MMC amplitude in the distal region, whilst reducing the amplitude in the proximal region. In preparations where MMCs did not migrate to the distal colon, addition of L-NOARG resulted in the formation of MMCs. Subsequent addition of apamin (250 nM) or suramin (100 μM) further increased MMC amplitude in the distal region, whilst suramin increased MMC amplitude in the mid-distal region. Apamin but not suramin reduced MMC amplitude in the proximal region. Subsequent addition of SR-140 333 and SR-48 968 reduced MMC amplitude at all sites. Residual MMCs were abolished by atropine (1 μM).In conclusion, TKs, ACh, nitric oxide (NO) and ATP are involved in the neural mechanisms underlying the formation of MMCs in the mouse colon. Tachykinins mediate the long duration component of the MMC via NK1 and NK2 receptors. Inhibitory pathways may be involved in determining whether MMCs are formed. PMID:11159701

    3. Photodegradation of orange I in the heterogeneous iron oxide-oxalate complex system under UVA irradiation

      International Nuclear Information System (INIS)

      Lei, Jing; Liu Chengshuai; Li Fangbai; Li Xiaomin; Zhou Shungui; Liu Tongxu; Gu Minghua; Wu Qitang

      2006-01-01

      To understand the photodegradation of azo dyes in natural aquatic environment, a novel photo-Fenton-like system, the heterogeneous iron oxide-oxalate complex system was set up with the existence of iron oxides and oxalate. Five iron oxides, including γ-FeOOH, IO-250, IO-320, IO-420 and IO-520, were prepared and their adsorption capacity was investigated in the dark. The results showed that the saturated adsorption amount (Γ max ) was ranked the order of IO-250>IO-320>γ-FeOOH>IO-420>IO-520 and the adsorption equilibrium constant (K a ) followed the order of IO-250>IO-520>γ-FeOOH>IO-420>IO-320. The effect of initial pH value, the initial concentrations of oxalate and orange I on the photodegradation of orange I were also investigated in different iron oxide-oxalate systems. The results showed that the photodegradation of orange I under UVA irradiation could be enhanced greatly in the presence of oxalate. And the optimal oxalate concentrations (C ox 0 ) for γ-FeOOH, IO-250, IO-320, IO-420 and IO-520 were 1.8, 1.6, 3.5, 3.0 and 0.8mM, respectively. The photodegradation of orange I in the presence of optimal C ox 0 was ranked as the order of γ-FeOOH>IO-250>IO-320>IO-420>IO-520. The optimal range of initial pH was at about 3-4. The first-order kinetic constant for the degradation of orange I decreased with the increase in the initial concentration of orange I. Furthermore, the variation of pH, the concentrations of Fe 3+ and Fe 2+ during the photoreaction were also strongly dependent on the C ox 0 and iron oxides

    4. Framework for Smart Electronic Health Record- Linked Predictive Models to Optimize Care for Complex Digestive Diseases

      Science.gov (United States)

      2015-03-01

      INTRODUCTION: Complex disorders result from the interaction of genetic, metabolic and environmental factors that may not produce disease themselves but...constructed using demographic (age>55yrs, Race, Gender, BMI, Tobacco use, Alcohol Use), lab values (BUN, Creatinine , Lipids, WBC, Hemaglobin, AST, Calcium...lead to us to look more closely at those CD patients with concomitant mood disorders and irritable bowel syndrome (IBS). We found that patients with

    5. Antagonism between phytohormone signalling underlies the variation in disease susceptibility of tomato plants under elevated CO2.

      Science.gov (United States)

      Zhang, Shuai; Li, Xin; Sun, Zenghui; Shao, Shujun; Hu, Lingfei; Ye, Meng; Zhou, Yanhong; Xia, Xiaojian; Yu, Jingquan; Shi, Kai

      2015-04-01

      Increasing CO2 concentrations ([CO2]) have the potential to disrupt plant-pathogen interactions in natural and agricultural ecosystems, but the research in this area has often produced conflicting results. Variations in phytohormone salicylic acid (SA) and jasmonic acid (JA) signalling could be associated with variations in the responses of pathogens to plants grown under elevated [CO2]. In this study, interactions between tomato plants and three pathogens with different infection strategies were compared. Elevated [CO2] generally favoured SA biosynthesis and signalling but repressed the JA pathway. The exposure of plants to elevated [CO2] revealed a lower incidence and severity of disease caused by tobacco mosaic virus (TMV) and by Pseudomonas syringae, whereas plant susceptibility to necrotrophic Botrytis cinerea increased. The elevated [CO2]-induced and basal resistance to TMV and P. syringae were completely abolished in plants in which the SA signalling pathway nonexpressor of pathogenesis-related genes 1 (NPR1) had been silenced or in transgenic plants defective in SA biosynthesis. In contrast, under both ambient and elevated [CO2], the susceptibility to B. cinerea highly increased in plants in which the JA signalling pathway proteinase inhibitors (PI) gene had been silenced or in a mutant affected in JA biosynthesis. However, plants affected in SA signalling remained less susceptible to this disease. These findings highlight the modulated antagonistic relationship between SA and JA that contributes to the variation in disease susceptibility under elevated [CO2]. This information will be critical for investigating how elevated CO2 may affect plant defence and the dynamics between plants and pathogens in both agricultural and natural ecosystems. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

    6. Antagonism between phytohormone signalling underlies the variation in disease susceptibility of tomato plants under elevated CO2

      Science.gov (United States)

      Zhang, Shuai; Li, Xin; Sun, Zenghui; Shao, Shujun; Hu, Lingfei; Ye, Meng; Zhou, Yanhong; Xia, Xiaojian; Yu, Jingquan; Shi, Kai

      2015-01-01

      Increasing CO2 concentrations ([CO2]) have the potential to disrupt plant–pathogen interactions in natural and agricultural ecosystems, but the research in this area has often produced conflicting results. Variations in phytohormone salicylic acid (SA) and jasmonic acid (JA) signalling could be associated with variations in the responses of pathogens to plants grown under elevated [CO2]. In this study, interactions between tomato plants and three pathogens with different infection strategies were compared. Elevated [CO2] generally favoured SA biosynthesis and signalling but repressed the JA pathway. The exposure of plants to elevated [CO2] revealed a lower incidence and severity of disease caused by tobacco mosaic virus (TMV) and by Pseudomonas syringae, whereas plant susceptibility to necrotrophic Botrytis cinerea increased. The elevated [CO2]-induced and basal resistance to TMV and P. syringae were completely abolished in plants in which the SA signalling pathway nonexpressor of pathogenesis-related genes 1 (NPR1) had been silenced or in transgenic plants defective in SA biosynthesis. In contrast, under both ambient and elevated [CO2], the susceptibility to B. cinerea highly increased in plants in which the JA signalling pathway proteinase inhibitors (PI) gene had been silenced or in a mutant affected in JA biosynthesis. However, plants affected in SA signalling remained less susceptible to this disease. These findings highlight the modulated antagonistic relationship between SA and JA that contributes to the variation in disease susceptibility under elevated [CO2]. This information will be critical for investigating how elevated CO2 may affect plant defence and the dynamics between plants and pathogens in both agricultural and natural ecosystems. PMID:25657213

    7. Complexity of the HVR-1 quasispecies and disease activity in patients with hepatitis C.

      Science.gov (United States)

      Kumagai, N; Kaneko, F; Tsunematsu, S; Tsuchimoto, K; Tada, S; Saito, H; Hibi, T

      2007-07-01

      Hepatitis C virus (HCV) easily undergoes genomic changes, especially in the hypervariable region (HVR) in the N-terminus of the E2/NS1 region. The quasispecies nature of HCV may have important biological implications in relation to viral persistence; however, the relationship between disease activity of chronic HCV infection and development of the genomic complexity have yielded conflicting results. We explored the changes in the complexity of the HVR-1 in the natural course of chronic HCV infection with and without elevation of serum alanine transaminase (ALT) levels. Ten patients with chronic hepatitis C proven by liver biopsy, who showed persistent elevation of the serum ALT levels, and 15 patients with chronic HCV infection and persistently normal serum ALT levels (PNAL) were enrolled in this study. The number of the HCV quasispecies was determined twice for each patient at an interval of mean 2.5 years by fluorescence single-strand conformation polymorphism and sequence analysis. There was no significant difference in the changes in the number of quasispecies during the follow-up period between chronic hepatitis C and PNAL. There was also no significant difference in the change in the number of variable nucleotides sites between the two groups. In these patients, the number of quasispecies and the diversity of HVR-1 were correlated with platelet counts and serum hyaluronic acid levels previously shown to be associated with disease progression. Our results suggested that the disease activity is not always related to the generation of the HVR-1 quasispecies complexity.

    8. Systems Genetics as a Tool to Identify Master Genetic Regulators in Complex Disease.

      Science.gov (United States)

      Moreno-Moral, Aida; Pesce, Francesco; Behmoaras, Jacques; Petretto, Enrico

      2017-01-01

      Systems genetics stems from systems biology and similarly employs integrative modeling approaches to describe the perturbations and phenotypic effects observed in a complex system. However, in the case of systems genetics the main source of perturbation is naturally occurring genetic variation, which can be analyzed at the systems-level to explain the observed variation in phenotypic traits. In contrast with conventional single-variant association approaches, the success of systems genetics has been in the identification of gene networks and molecular pathways that underlie complex disease. In addition, systems genetics has proven useful in the discovery of master trans-acting genetic regulators of functional networks and pathways, which in many cases revealed unexpected gene targets for disease. Here we detail the central components of a fully integrated systems genetics approach to complex disease, starting from assessment of genetic and gene expression variation, linking DNA sequence variation to mRNA (expression QTL mapping), gene regulatory network analysis and mapping the genetic control of regulatory networks. By summarizing a few illustrative (and successful) examples, we highlight how different data-modeling strategies can be effectively integrated in a systems genetics study.

    9. Mechanisms underlying neurodegeneration in Huntington disease: applications to novel disease-modifying therapies.

      Science.gov (United States)

      Ross, Christopher A; Kronenbuerger, Martin; Duan, Wenzhen; Margolis, Russell L

      2017-01-01

      The CAG repeat expansion mutation that causes Huntington Disease (HD) was discovered more than 20 years ago, yet no treatment has yet been developed to stop the relentless course of the disease. Nonetheless, substantial progress has been made in understanding HD pathogenesis. We review insights that have been gleaned from HD genetics, metabolism, and pathology; HD mouse and cell models; the structure, function and post-translational modification of normal and mutant huntingtin (htt) protein; gene expression profiles in HD cells and tissue; the neurotoxicy of mutant htt RNA; and the expression of an antisense transcript from the HD locus. We conclude that rationale therapeutics for HD is within sight, though many questions remain to be answered. Copyright © 2017 Elsevier B.V. All rights reserved.

    10. Symptoms of main Callistephus chinensis L. Nees. diseases under Ukrainian urban ecosystem conditions of the forest-steppe zone

      Directory of Open Access Journals (Sweden)

      Marchenko Alla

      2017-12-01

      Full Text Available Phytopathological monitoring of C. chinensis (L. Nees. has proven withering and root rot to be the dominating diseases in agrobiocenoses under Ukrainian urban ecosystem conditions of the forest-steppe zone. Their spread was 5,1 and 4 times more than one of spotting. The complex of plant pathogenic overground and underground microflora consists of 24 causative agents. B. cinerea, F. oxysporum, V. albo-atrum have been found on all the vegetative and reproductive parts of Callistephus chinensis (L. Nees., , Ph. cactorum – on plant overground and underground parts, Rh. solani – on underground parts and seeds, A. zinniae – on overground parts and seeds. The main C. chinensis (L. Nees. disease symptoms have been diagnosed (leaf spots, powdery mildew, verticillium wilt, rust, ramularia spot, septoria spots, botrytis blight, grey mold rot, late blight, fusarium blight, black stem.

    11. Identification of chromatophore membrane protein complexes formed under different nitrogen availability conditions in Rhodospirillum rubrum

      DEFF Research Database (Denmark)

      Selao, Tiago Toscano; Branca, Rui; Chae, Pil Seok

      2011-01-01

      of two-dimensional Blue Native/SDS-PAGE and NSI-LC-LTQ-Orbitrap mass spectrometry. We have identified several membrane protein complexes, including components of the ATP synthase, reaction center, light harvesting, and NADH dehydrogenase complexes. Additionally, we have identified differentially...

    12. Comparison of family history and SNPs for predicting risk of complex disease.

      Directory of Open Access Journals (Sweden)

      Chuong B Do

      Full Text Available The clinical utility of family history and genetic tests is generally well understood for simple Mendelian disorders and rare subforms of complex diseases that are directly attributable to highly penetrant genetic variants. However, little is presently known regarding the performance of these methods in situations where disease susceptibility depends on the cumulative contribution of multiple genetic factors of moderate or low penetrance. Using quantitative genetic theory, we develop a model for studying the predictive ability of family history and single nucleotide polymorphism (SNP-based methods for assessing risk of polygenic disorders. We show that family history is most useful for highly common, heritable conditions (e.g., coronary artery disease, where it explains roughly 20%-30% of disease heritability, on par with the most successful SNP models based on associations discovered to date. In contrast, we find that for diseases of moderate or low frequency (e.g., Crohn disease family history accounts for less than 4% of disease heritability, substantially lagging behind SNPs in almost all cases. These results indicate that, for a broad range of diseases, already identified SNP associations may be better predictors of risk than their family history-based counterparts, despite the large fraction of missing heritability that remains to be explained. Our model illustrates the difficulty of using either family history or SNPs for standalone disease prediction. On the other hand, we show that, unlike family history, SNP-based tests can reveal extreme likelihood ratios for a relatively large percentage of individuals, thus providing potentially valuable adjunctive evidence in a differential diagnosis.

    13. Cyclic plastic material behavior leading to crack initiation in stainless steel under complex fatigue loading conditions

      International Nuclear Information System (INIS)

      Facheris, G.

      2014-01-01

      The improvement of the reliability and of the safety in the design of components belonging to the primary cooling circuit of a light water nuclear reactor is nowadays one of the most important research topics in nuclear industry. One of the most important damage mechanisms leading the crack initiation in this class of components is the low cycle fatigue (LCF) driven by thermal strain fluctuations caused by the complex thermo-mechanical loading conditions typical for the primary circuit (e.g. operating thermal transients, thermal stratification, turbulent mixing of cold and hot water flows, etc.). The cyclic application of the resulting plastic deformation to the steel grades commonly used for the fabrication of piping parts (e.g. austenitic stainless steels) is associated with a continuous evolution of the mechanical response of the material. As an additional complication, the cyclic behavior of stainless steels is influenced by temperature, strain amplitude and cyclic accumulation of inelastic strain (i.e. ratcheting). The accurate prediction of the structural response of components belonging to the primary cooling circuit requires the development of a reliable constitutive model that must be characterized by a reduced complexity to allow its application in an industrial context. In this framework, the main goal of the current dissertation is to formulate, calibrate and implement in a commercial Finite Element code, a constitutive model that is suitable for the stainless stain grade 316L subjected to complex loading conditions. As a first task, a characterization of the mechanical behavior of 316L subjected to uniaxial and multiaxial strain-controlled conditions (including LCF and ratcheting) is carried out performing several tests in the laboratories of the Paul Scherrer Institute (PSI, Villigen, Switzerland) and of Politecnico di Milano (Italy). The uniaxial experiments demonstrate that, prescribing a strain-controlled ratcheting path, a harder material response

    14. Spatial statistical analysis of basal stem root disease under natural field epidemic of oil palm

      Science.gov (United States)

      Kamu, Assis; Phin, Chong Khim; Seman, Idris Abu; Wan, Hoong Hak; Mun, Ho Chong

      2015-02-01

      Oil palm or scientifically known as Elaeis guineensis Jacq. is the most important commodity crop in Malaysia and has greatly contributed to the economy growth of the country. As far as disease is concerned in the industry, Basal Stem Rot (BSR) caused by Ganoderma boninence remains the most important disease. BSR disease is the most widely studied with information available for oil palm disease in Malaysia. However, there is still limited study on the spatial as well as temporal pattern or distribution of the disease especially under natural field epidemic condition in oil palm plantation. The objective of this study is to spatially identify the pattern of BSR disease under natural field epidemic using two geospatial analytical techniques, which are quadrat analysis for the first order properties of partial pattern analysis and nearest-neighbor analysis (NNA) for the second order properties of partial pattern analysis. Two study sites were selected with different age of tree. Both sites are located in Tawau, Sabah and managed by the same company. The results showed that at least one of the point pattern analysis used which is NNA (i.e. the second order properties of partial pattern analysis) has confirmed the disease is complete spatial randomness. This suggests the spread of the disease is not from tree to tree and the age of palm does not play a significance role in determining the spatial pattern of the disease. From the spatial pattern of the disease, it would help in the disease management program and for the industry in the future. The statistical modelling is expected to help in identifying the right model to estimate the yield loss of oil palm due to BSR disease in the future.

    15. Density functional study of Cu(2+)-phenylalanine complex under micro-solvation environment.

      Science.gov (United States)

      Ganesan, Aravindhan; Dreyer, Jens; Wang, Feng; Akola, Jaakko; Larrucea, Julen

      2013-09-01

      We present an atomistic study carried out using density functional calculations including structural relaxations and Car-Parrinello Molecular Dynamics (CPMD) simulations, aiming to investigate the structures of phenylalanine-copper (II) ([Phe-Cu](2+)) complexes and their micro-solvation processes. The structures of the [Phe-Cu](2+) complex with up to four water molecules are optimized using the B3LYP/6-311++G** model in gas phase to identify the lowest energy structures at each degree of solvation (n=0-4). It is found that the phenylalanine appears to be in the neutral form in isolated and mono-hydrated complexes, but in the zwitterionic form in other hydrated complexes (with n≥2). The most stable structures of the complexes suggest that the Cu(2+)-π interactions are not dominant in the [Phe-Cu](2+) complexes. The present CPMD simulations of the lowest energy micro-hydrated [Phe-Cu](2+) complexes also reveal that the maximum coordination of Cu(2+) in the presence of the Phe ligand does not exceed four: the oxygen atoms from three water molecules and one carboxyl oxygen atom of Phe. Any excess water molecules will migrate to the second solvation shell. Moreover a unique structural motif, (N)H···O(3)···H2O-Cu(2+) is present in the lowest energy complexes, which is recognized to be significant in stabilizing the structures of the complexes. Extensively rich information of the structures, energetics, hydrogen bonds and dynamics of the lowest energy complexes are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

    16. Ocean warming and acidification have complex interactive effects on the dynamics of a marine fungal disease

      Science.gov (United States)

      Williams, Gareth J.; Price, Nichole N.; Ushijima, Blake; Aeby, Greta S.; Callahan, Sean M.; Davy, Simon K.; Gove, Jamison M.; Johnson, Maggie D.; Knapp, Ingrid S.; Shore-Maggio, Amanda; Smith, Jennifer E.; Videau, Patrick; Work, Thierry M.

      2014-01-01

      Diseases threaten the structure and function of marine ecosystems and are contributing to the global decline of coral reefs. We currently lack an understanding of how climate change stressors, such as ocean acidification (OA) and warming, may simultaneously affect coral reef disease dynamics, particularly diseases threatening key reef-building organisms, for example crustose coralline algae (CCA). Here, we use coralline fungal disease (CFD), a previously described CCA disease from the Pacific, to examine these simultaneous effects using both field observations and experimental manipulations. We identify the associated fungus as belonging to the subphylum Ustilaginomycetes and show linear lesion expansion rates on individual hosts can reach 6.5 mm per day. Further, we demonstrate for the first time, to our knowledge, that ocean-warming events could increase the frequency of CFD outbreaks on coral reefs, but that OA-induced lowering of pH may ameliorate outbreaks by slowing lesion expansion rates on individual hosts. Lowered pH may still reduce overall host survivorship, however, by reducing calcification and facilitating fungal bio-erosion. Such complex, interactive effects between simultaneous extrinsic environmental stressors on disease dynamics are important to consider if we are to accurately predict the response of coral reef communities to future climate change.

    17. Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases

      Directory of Open Access Journals (Sweden)

      Min Kyung Sung

      2014-12-01

      Full Text Available Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE data: type 2 diabetes mellitus (DM, hypertension (HT, and coronary artery disease (CAD. We showed that epistatic single-nucleotide polymorphisms (SNPs were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012, which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE. Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.

    18. Entropy-based complexity measures for gait data of patients with Parkinson's disease

      Science.gov (United States)

      Afsar, Ozgur; Tirnakli, Ugur; Kurths, Juergen

      2016-02-01

      Shannon, Kullback-Leibler, and Klimontovich's renormalized entropies are applied as three different complexity measures on gait data of patients with Parkinson's disease (PD) and healthy control group. We show that the renormalized entropy of variability of total reaction force of gait is a very efficient tool to compare patients with respect to disease severity. Moreover, it is a good risk predictor such that the sensitivity, i.e., the percentage of patients with PD who are correctly identified as having PD, increases from 25% to 67% while the Hoehn-Yahr stage increases from 2.5 to 3.0 (this stage goes from 0 to 5 as the disease severity increases). The renormalized entropy method for stride time variability of gait is found to correctly identify patients with a sensitivity of 80%, while the Shannon entropy and the Kullback-Leibler relative entropy can do this with a sensitivity of only 26.7% and 13.3%, respectively.

    19. Effects of eHealth physical activity encouragement in adolescents with complex congenital heart disease

      DEFF Research Database (Denmark)

      Klausen, Susanne Hwiid; Andersen, Lars L; Søndergaard, Lars

      2016-01-01

      OBJECTIVE: To assess benefit and harms of adding an eHealth intervention to health education and individual counseling in adolescents with congenital heart disease. DESIGN: Randomized clinical trial. SETTING: Denmark. PATIENTS: A total of 158 adolescents aged 13-16years with no physical activity...... restrictions after repaired complex congenital heart disease. INTERVENTIONS: PReVaiL consisted of individually tailored eHealth encouragement physical activity for 52weeks. All patients received 45min of group-based health education and 15min of individual counseling involving patients' parents. OUTCOMES......·kg(-1)·min(-1) (95% CI -2.66 to 1.36). Between-group differences at 1year in physical activity, generic health-related quality of life, and disease-specific quality of life were not statistically significant. CONCLUSIONS: Adding a tailored eHealth intervention to health education and individual...

    20. Ring chromosome in myeloid neoplasms is associated with complex karyotype and disease progression.

      Science.gov (United States)

      Rosenbaum, Matthew W; Pozdnyakova, Olga; Geyer, Julia T; Dal Cin, Paola; Hasserjian, Robert P

      2017-10-01

      Ring chromosome (RC) is a poorly understood genetic anomaly seen in myeloid neoplasms. This study aims to shed light on the clinical significance of this finding. We identified 96 cases of myeloid neoplasms with RC from 3 academic hospitals. Clinicopathologic features and overall (OS) and leukemia-free survival were reviewed and compared to cases of myeloid neoplasms lacking RC. We identified 59 acute myeloid leukemias (AML-RC) and 37 myelodysplastic syndromes (MDS-RC) with RC identified on routine karyotyping. Seventy-five percent of AML-RC and 97% of MDS-RC had complex (>3 independent cytogenetic abnormalities) karyotypes. The median OS of AML-RC with complex karyotype was significantly shorter than AML-RC patients with a non-complex (≤3 independent cytogenetic abnormalities) karyotype (P=.001), but similar to AML patients with complex karyotype lacking RC (P=not significant). Compared to complex-karyotype MDS lacking RC, MDS-RC patients had shorter leukemia-free survival (P=.016) and a trend for shorter OS (P=.10). RCs were sometimes lost after therapy or appeared during disease relapse, suggesting that they may be associated with genetic instability. Copyright © 2017 Elsevier Inc. All rights reserved.

    1. Multidisciplinary management of pregnancy in complex congenital heart disease: a model for coordination of care.

      Science.gov (United States)

      Harris, Rachel C; Fries, Melissa H; Boyle, Annelee; Adeniji-Adele, Hassan; Cherian, Zacharia; Klein, Nancy; John, Anitha S

      2014-01-01

      With advancements in medical care, many women with complex congenital heart disease (CHD) are now living into adulthood and childbearing years. The strains of pregnancy and parturition can be dangerous in such patients, and careful interdisciplinary plans must be made to optimize maternal and fetal health through this process. Several large studies have been published regarding risk prediction and medical management of pregnancy in complex CHD, though few case studies detailing clinical care plans have been published. The objective of this report is to describe the process of developing a detailed pregnancy and delivery care plan for three women with complex CHD, including perspectives from the multidisciplinary specialists involved in the process. This article demonstrates that collaboration between specialists in the fields of cardiology, anesthesiology, high-risk obstetrics, maternal fetal medicine, and neonatology results in clinically successful individualized treatment plans for the management of pregnancy in complex CHD. Multidisciplinary collaboration is a crucial element in the management of pregnancy in complex CHD. We provide a template used in three cases which can serve as a model for the design of future care plans. © 2014 Wiley Periodicals, Inc.

    2. Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

      Science.gov (United States)

      Bousquet, Jean; Jorgensen, Christian; Dauzat, Michel; Cesario, Alfredo; Camuzat, Thierry; Bourret, Rodolphe; Best, Nicolas; Anto, Josep M; Abecassis, Frederic; Aubas, Pierre; Avignon, Antoine; Badin, Melanie; Bedbrook, Anna; Blain, Hubert; Bourdin, Arnaud; Bringer, Jacques; Camu, William; Cayla, Guilhaume; Costa, David J; Courtet, Philippe; Cristol, Jean-Paul; Demoly, Pascal; de la Coussaye, Jean-Emmanuel; Fesler, Pierre; Gouzi, Fares; Gris, Jean-Christophe; Guillot, Bernard; Hayot, Maurice; Jeandel, Claude; Jonquet, Olivier; Journot, Laurent; Lehmann, Sylvain; Mathieu, Gwenaelle; Morel, Jacques; Ninot, Gregory; Pelissier, Jacques; Picot, Marie-Christine; Radier-Pontal, Francoise; Robine, Jean-Marie; Rodier, Michel; Roubille, Francois; Sultan, Ariane; Wojtusciszyn, Anne; Auffray, Charles; Balling, Rudi; Barbara, Cristina; Cambon-Thomsen, Anne; Chavannes, Niels H; Chuchalin, Alexander; Crooks, George; Dedeu, Antoni; Fabbri, Leonardo M; Garcia-Aymerich, Judith; Hajjam, Jawad; Melo Gomes, Elisabete; Palkonen, Susana; Piette, Francois; Pison, Christophe; Price, David; Samolinski, Boleslaw; Schunemann, Holger J; Sterk, Peter J; Yiallouros, Panayiotis; Roca, Josep; Van de Perre, Philippe; Mercier, Jacques

      2014-01-01

      Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing).

    3. The complexity, relative value, and financial worth of curbside consultations in an academic infectious diseases unit.

      Science.gov (United States)

      Grace, Christopher; Alston, W Kemper; Ramundo, Mary; Polish, Louis; Kirkpatrick, Beth; Huston, Christopher

      2010-09-15

      Curbside consultations are common in clinical practice. The complexity, relative value, and revenue loss associated with curbside consultations are not well defined. Curbside consultations performed during a 1-year period were studied. Each curbside consultation was assigned a Current Procedural Terminology (CPT) code on the basis of the inpatient versus outpatient status of the patient, initial versus subsequent care, and clinical complexity. On the basis of the CPT code, the physician work component of the relative value unit (wRVU) was assigned for each curbside consultation. The 2005 Centers for Medicaid and Medicare Services conversion factor of $37.89 per wRVU was used for cost estimates. Comparisons were made with formal consultations performed during the same time period. A total of 1001 curbside consultations were fielded: 66% involved outpatients, and 97% were coded as initial consultations. A total of 78% of curbside consultations were considered complex in nature, being assigned a CPT code of level 4-5, including 84% of the inpatient and 75% of the outpatient curbside consultations. These curbside consultations would have generated 2480 wRVUs. During the same period, formal consultations generated 12,121 wRVUs. Thus, curbside consultations represented 17% (2480/14,601) of the clinical work value of the infectious diseases unit. If the infectious diseases unit had performed these curbside consultations as formal consultations, an additional $93,979 in revenue would have been generated. Curbside consultations are common and complex. The curbside consultation should be incorporated into measures of infectious diseases providers' productivity and compensation.

    4. Analyzing Student Motivation at the Confluence of Achievement Goals and Their Underlying Reasons: An Investigation of Goal Complexes

      Science.gov (United States)

      Hodis, Flaviu A.; Tait, Carolyn; Hodis, Georgeta M.; Hodis, Monica A.; Scornavacca, Eusebio

      2016-01-01

      This research investigated the interrelations among achievement goals and the underlying reasons for pursuing them. To do so, it utilized the framework of goal complexes, which are regulatory constructs defined at the intersection of aims and reasons. Data from two independent large samples of New Zealand university students showed that across…

    5. DEVELOPMENT OF COMPLEX OILING COMPONENT ON THE BASIS OF SILICONE POLYMERS FOR MOLDS FOR CASTING UNDER PRESSURE

      Directory of Open Access Journals (Sweden)

      A. M. Mihaltsov

      2008-01-01

      Full Text Available The receipt of complex oiling component, used for greasing of moulds for casting under pressure of aluminiun alloys on the basis of high-molecular organosilicon polymers with addition of soap stocks of light vegetable oils as filling agent and stabilizer of emulsion is examined.

    6. Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease

      Science.gov (United States)

      van der Crabben, Saskia N.; Hennus, Marije P.; McGregor, Grant A.; Ritter, Deborah I.; Nagamani, Sandesh C.S.; Wells, Owen S.; Harakalova, Magdalena; Chinn, Ivan K.; Alt, Aaron; Vondrova, Lucie; Hochstenbach, Ron; van Montfrans, Joris M.; Terheggen-Lagro, Suzanne W.; van Lieshout, Stef; van Roosmalen, Markus J.; Renkens, Ivo; Duran, Karen; Nijman, Isaac J.; Kloosterman, Wigard P.; Hennekam, Eric; van Hasselt, Peter M.; Wheeler, David A.; Palecek, Jan J.; Lehmann, Alan R.; Oliver, Antony W.; Pearl, Laurence H.; Plon, Sharon E.; Murray, Johanne M.

      2016-01-01

      The structural maintenance of chromosomes (SMC) family of proteins supports mitotic proliferation, meiosis, and DNA repair to control genomic stability. Impairments in chromosome maintenance are linked to rare chromosome breakage disorders. Here, we have identified a chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died of severe pulmonary disease during infancy following viral pneumonia with evidence of combined T and B cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in the NSMCE3 (also known as NDNL2) gene, which encodes a subunit of the SMC5/6 complex that is essential for DNA damage response and chromosome segregation. The NSMCE3 mutations disrupted interactions within the SMC5/6 complex, leading to destabilization of the complex. Patient cells showed chromosome rearrangements, micronuclei, sensitivity to replication stress and DNA damage, and defective homologous recombination. This work associates missense mutations in NSMCE3 with an autosomal recessive chromosome breakage syndrome that leads to defective T and B cell function and acute respiratory distress syndrome in early childhood. PMID:27427983

    7. The microglial NADPH oxidase complex as a source of oxidative stress in Alzheimer's disease

      Directory of Open Access Journals (Sweden)

      Landreth Gary E

      2006-11-01

      Full Text Available Abstract Alzheimer's disease is the most common cause of dementia in the elderly, and manifests as progressive cognitive decline and profound neuronal loss. The principal neuropathological hallmarks of Alzheimer's disease are the senile plaques and the neurofibrillary tangles. The senile plaques are surrounded by activated microglia, which are largely responsible for the proinflammatory environment within the diseased brain. Microglia are the resident innate immune cells in the brain. In response to contact with fibrillar beta-amyloid, microglia secrete a diverse array of proinflammatory molecules. Evidence suggests that oxidative stress emanating from activated microglia contribute to the neuronal loss characteristic of this disease. The source of fibrillar beta-amyloid induced reactive oxygen species is primarily the microglial nicotinamide adenine dinucleotide phosphate (NADPH oxidase. The NADPH oxidase is a multicomponent enzyme complex that, upon activation, produces the highly reactive free radical superoxide. The cascade of intracellular signaling events leading to NADPH oxidase assembly and the subsequent release of superoxide in fibrillar beta-amyloid stimulated microglia has recently been elucidated. The induction of reactive oxygen species, as well as nitric oxide, from activated microglia can enhance the production of more potent free radicals such as peroxynitrite. The formation of peroxynitrite causes protein oxidation, lipid peroxidation and DNA damage, which ultimately lead to neuronal cell death. The elimination of beta-amyloid-induced oxidative damage through the inhibition of the NADPH oxidase represents an attractive therapeutic target for the treatment of Alzheimer's disease.

    8. Tedizolid is highly bactericidal in the treatment of pulmonary Mycobacterium avium complex disease.

      Science.gov (United States)

      Deshpande, Devyani; Srivastava, Shashikant; Pasipanodya, Jotam G; Lee, Pooi S; Gumbo, Tawanda

      2017-09-01

      To determine if tedizolid is effective for pulmonary Mycobacterium avium complex (MAC) disease, and to use pharmacokinetics/pharmacodynamics to design optimal doses. We performed an exposure-response experiment in the hollow-fibre system model of intracellular MAC (HFS-MAC). We mimicked the tedizolid concentration-time profiles achieved in the lungs of patients treated once daily for 28 days. The HFS-MAC was sampled at intervals to determine the tedizolid pharmacokinetics and MAC intracellular burden. We identified the 0-24 h area under the concentration-time curves to MIC (AUC0-24/MIC) ratios associated with the following targets: 80% of maximal kill (EC80), bacteriostasis, and 1.0 and 2.0 log10 cfu/mL kill. We then performed 10 000 patient Monte Carlo simulations to identify the optimal dose for each of the exposure targets. Tedizolid achieved the feat of 2.0 log10 cfu/mL kill below initial bacterial burden, an effect not seen before in this model with other antibiotics. The tedizolid exposure associated with 1.0 log10 cfu/mL kill was a non-protein bound AUC0-24/MIC ratio of 23.46, while that associated with 2.0 log10 cfu/mL kill was 37.50, and the EC80 was 21.71. The clinical dose of 200 mg achieved each of these targets in ∼100% of the 10 000 patients, except the 2.0 log10 cfu/mL kill which required 300 mg/day. A tedizolid susceptibility MIC breakpoint of 1 mg/L is proposed. Tedizolid, at standard clinical doses, is expected to be bactericidal, and even achieved an unprecedented 2.0 log10 cfu/mL kill of MAC as monotherapy. We propose it as the backbone of short-course anti-MAC chemotherapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

    9. Three viruses of the bovine respiratory disease complex apply different strategies to initiate infection.

      Science.gov (United States)

      Kirchhoff, Jana; Uhlenbruck, Sabine; Goris, Katherina; Keil, Günther M; Herrler, Georg

      2014-02-18

      Bovine respiratory disease complex (BRDC) is the major cause of serious respiratory tract infections in calves. The disease is multifactorial, with either stress or reduced immunity allowing several pathogens to emerge. We investigated the susceptibility of bovine airway epithelial cells (BAEC) to infection by the three major viruses associated with the BRDC: bovine respiratory syncytial virus (BRSV), bovine herpesvirus type 1 (BHV-1) and bovine parainfluenza virus type 3 (BPIV3). For this purpose, two culture systems for well-differentiated BAEC were used: the air-liquid interface (ALI) system, where filter-grown BAEC differentiate into a pseudostratified respiratory epithelium and precision-cut lung slices (PCLS) where BAEC are maintained in the original tissue organisation. Comparative infection studies demonstrated that entry and release of BPIV3 occurred specifically via the apical membrane with ciliated cells being the major target cells. By contrast, airway epithelial cells were largely resistant to infection by BHV-1. When the epithelial barrier was abolished by opening tight junctions or by injuring the cell monolayer, BHV-1 infected mainly basal cells. Respiratory epithelial cells were also refractory to infection by BRSV. However, this virus infected neither differentiated epithelial cells nor basal cells when the integrity of the epithelial barrier was destroyed. In contrast to cells of the airway epithelium, subepithelial cells were susceptible to infection by BRSV. Altogether, these results indicate that the three viruses of the same disease complex follow different strategies to interact with the airway epithelium. Possible entry mechanisms are discussed.

    10. Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling

      Directory of Open Access Journals (Sweden)

      Jay S. Coggan

      2015-09-01

      Full Text Available Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of multiple sclerosis, for example, there is no unanimity among researchers about the cause or even which system or cell type could be ground zero. This situation precludes the development and strategic application of mechanism-based therapies. We will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism. By making testable predictions and revealing critical gaps in existing knowledge, such models can help direct research and will provide a rigorous framework in which to integrate new data as they are collected. Nowadays, there is no shortage of data; the challenge is to make sense of it all. In that respect, computational modeling is an invaluable tool that could, ultimately, transform how we understand, diagnose, and treat demyelinating diseases.

    11. AN INTEGRATED NETWORK APPROACH TO IDENTIFYING BIOLOGICAL PATHWAYS AND ENVIRONMENTAL EXPOSURE INTERACTIONS IN COMPLEX DISEASES.

      Science.gov (United States)

      Darabos, Christian; Qiu, Jingya; Moore, Jason H

      2016-01-01

      Complex diseases are the result of intricate interactions between genetic, epigenetic and environmental factors. In previous studies, we used epidemiological and genetic data linking environmental exposure or genetic variants to phenotypic disease to construct Human Phenotype Networks and separately analyze the effects of both environment and genetic factors on disease interactions. To better capture the intricacies of the interactions between environmental exposure and the biological pathways in complex disorders, we integrate both aspects into a single "tripartite" network. Despite extensive research, the mechanisms by which chemical agents disrupt biological pathways are still poorly understood. In this study, we use our integrated network model to identify specific biological pathway candidates possibly disrupted by environmental agents. We conjecture that a higher number of co-occurrences between an environmental substance and biological pathway pair can be associated with a higher likelihood that the substance is involved in disrupting that pathway. We validate our model by demonstrating its ability to detect known arsenic and signal transduction pathway interactions and speculate on candidate cell-cell junction organization pathways disrupted by cadmium. The validation was supported by distinct publications of cell biology and genetic studies that associated environmental exposure to pathway disruption. The integrated network approach is a novel method for detecting the biological effects of environmental exposures. A better understanding of the molecular processes associated with specific environmental exposures will help in developing targeted molecular therapies for patients who have been exposed to the toxicity of environmental chemicals.

    12. The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

      Science.gov (United States)

      Astle, William J; Elding, Heather; Jiang, Tao; Allen, Dave; Ruklisa, Dace; Mann, Alice L; Mead, Daniel; Bouman, Heleen; Riveros-Mckay, Fernando; Kostadima, Myrto A; Lambourne, John J; Sivapalaratnam, Suthesh; Downes, Kate; Kundu, Kousik; Bomba, Lorenzo; Berentsen, Kim; Bradley, John R; Daugherty, Louise C; Delaneau, Olivier; Freson, Kathleen; Garner, Stephen F; Grassi, Luigi; Guerrero, Jose; Haimel, Matthias; Janssen-Megens, Eva M; Kaan, Anita; Kamat, Mihir; Kim, Bowon; Mandoli, Amit; Marchini, Jonathan; Martens, Joost H A; Meacham, Stuart; Megy, Karyn; O'Connell, Jared; Petersen, Romina; Sharifi, Nilofar; Sheard, Simon M; Staley, James R; Tuna, Salih; van der Ent, Martijn; Walter, Klaudia; Wang, Shuang-Yin; Wheeler, Eleanor; Wilder, Steven P; Iotchkova, Valentina; Moore, Carmel; Sambrook, Jennifer; Stunnenberg, Hendrik G; Di Angelantonio, Emanuele; Kaptoge, Stephen; Kuijpers, Taco W; Carrillo-de-Santa-Pau, Enrique; Juan, David; Rico, Daniel; Valencia, Alfonso; Chen, Lu; Ge, Bing; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yang, Ying; Guigo, Roderic; Beck, Stephan; Paul, Dirk S; Pastinen, Tomi; Bujold, David; Bourque, Guillaume; Frontini, Mattia; Danesh, John; Roberts, David J; Ouwehand, Willem H; Butterworth, Adam S; Soranzo, Nicole

      2016-11-17

      Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal. Copyright © 2016 Elsevier Inc. All rights reserved.

    13. Role of angiocardiography in the diagnosis and management of complex/complicated congenital heart disease

      International Nuclear Information System (INIS)

      Ling Jian; Liu Yuqing

      2006-01-01

      Objective: To evaluate the role of angiocadiography (ACG) in the diagnosis and management of complex/complicated congenital heart disease (CHD). Methods: A retrospective study of ACG findings in 360 cases with complex/complicated CHD was performed with a comparision to that of echocardiography (Echo) and related clinical examination. Results: The present series of CHD cases included pulmonary atresia with ventricular septal defect in 75 cases, double outlet of right ventricle in 62 cases, Fallot's tetralogy in 60 cases, single ventricle in 52 cases, transposition of the great arteries in 42 cases, tricuspid valve atresia in 15 cases, coronary abnormality in 6 eases, total abnormal pulmonary venous connection in 5 cases, total endocardial cushion defect in 5 cases, persistent truncus arteriosus in 4 cases, pulmonary atresia with normal ventricular septum in 3 cases, other disorders in 7 eases, and postsurgical operation in 24 cases. ACG was superior to that of Echo in demonstrating the abnormalities of systemic, pulmonary, and coronary arteries and their branches of complex/complicated CHD as well as measuring the pressure of pulmonary artery, vein, and systemic-pulmonary collateral vessels. Conclusion: In the diagnosis and differential diagnosis of knotty cases with complex and complicated CHD, particularly in the demonstration of full view of systemic, pulmonary, and coronary arterial branches and accurate measurement of' pulmonary arterial pressure/resistance, and atrial, ventricular, and systemic arterial pressure, ACG (including DSA) still plays an important and irreplaceable role. (authors)

    14. Coral reef structural complexity provides important coastal protection from waves under rising sea levels

      Science.gov (United States)

      Harris, Daniel L.; Rovere, Alessio; Casella, Elisa; Power, Hannah; Canavesio, Remy; Collin, Antoine; Pomeroy, Andrew; Webster, Jody M.; Parravicini, Valeriano

      2018-01-01

      Coral reefs are diverse ecosystems that support millions of people worldwide by providing coastal protection from waves. Climate change and human impacts are leading to degraded coral reefs and to rising sea levels, posing concerns for the protection of tropical coastal regions in the near future. We use a wave dissipation model calibrated with empirical wave data to calculate the future increase of back-reef wave height. We show that, in the near future, the structural complexity of coral reefs is more important than sea-level rise in determining the coastal protection provided by coral reefs from average waves. We also show that a significant increase in average wave heights could occur at present sea level if there is sustained degradation of benthic structural complexity. Our results highlight that maintaining the structural complexity of coral reefs is key to ensure coastal protection on tropical coastlines in the future. PMID:29503866

    15. Coral reef structural complexity provides important coastal protection from waves under rising sea levels.

      Science.gov (United States)

      Harris, Daniel L; Rovere, Alessio; Casella, Elisa; Power, Hannah; Canavesio, Remy; Collin, Antoine; Pomeroy, Andrew; Webster, Jody M; Parravicini, Valeriano

      2018-02-01

      Coral reefs are diverse ecosystems that support millions of people worldwide by providing coastal protection from waves. Climate change and human impacts are leading to degraded coral reefs and to rising sea levels, posing concerns for the protection of tropical coastal regions in the near future. We use a wave dissipation model calibrated with empirical wave data to calculate the future increase of back-reef wave height. We show that, in the near future, the structural complexity of coral reefs is more important than sea-level rise in determining the coastal protection provided by coral reefs from average waves. We also show that a significant increase in average wave heights could occur at present sea level if there is sustained degradation of benthic structural complexity. Our results highlight that maintaining the structural complexity of coral reefs is key to ensure coastal protection on tropical coastlines in the future.

    16. Analysis on complex structure stability under different bar angle with BIM technology

      Directory of Open Access Journals (Sweden)

      Wang Xiongjue

      2016-03-01

      Full Text Available Sun Valley, the landmark building of World Expo in Shanghai, which has free surface with single-layer reticulated shell structure, is a typical complex structure. CAD/CAM integrated information system to design is used for the complex structure; however, it is a very rigorous process to be used widely. The relevant technology of the Sun Valley is not open to the public at present, so we try to use BIM technology to model the Sun Valley, including architecture modelling and structure analysis. By analysis of the Sun Valley structure using this method, it is proved that the problems in modelling may be solved by writing some script codes in Rhino software and the stability of the model can also be analyzed. The new approach is viable and effective in combination with different softwares such as Rhino, Revit, and Midas in solution of the complex shaped surfaces’ structure for modelling and calculation.

    17. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

      DEFF Research Database (Denmark)

      Gluud, C; Jans, H

      1982-01-01

      the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence......A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...

    18. Relation of ABO blood groups to coronary lesion complexity in patients with stable coronary artery disease.

      Science.gov (United States)

      Kaya, Ahmet; Tanboğa, İbrahim Halil; Kurt, Mustafa; Işık, Turgay; Kaya, Yasemin; Günaydın, Zeki Yüksel; Aksakal, Enbiya

      2014-02-01

      We aimed to investigate the relationship between ABO blood groups and complexity of coronary lesions assessed by SYNTAX score (SS) in stable coronary artery disease (CAD) patients. Our cross-sectional and observational study population consisted of 559 stable CAD patients. From all patients, ABO blood group was determined and the SS was calculated as low SYNTAX score (0-22), intermediate SYNTAX (23-32) score and high SYNTAX score (>32). Statistical analysis was performed using Student's t-test or Mann-Whitney U test, ANOVA, or Kruskal-Wallis test and chi-square test. Multiple logistic regression analysis was used to identify the independent predictors of high SS. The analysis between the SS tertiles revealed that the frequency of non-O blood group was significantly higher in the upper SS tertiles (56.2% vs. 75.9 vs. 80.2%, pABO blood groups and complexity of angiographic CAD.

    19. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

      DEFF Research Database (Denmark)

      Gluud, C; Jans, H

      1982-01-01

      A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...... the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence...

    20. Reflex sympathetic dystrophy: complex regional pain syndrome type I in children with mitochondrial disease and maternal inheritance.

      Science.gov (United States)

      Higashimoto, T; Baldwin, E E; Gold, J I; Boles, R G

      2008-05-01

      Complex regional pain syndrome type I (CRPS-I), previously known as reflex sympathetic dystrophy (RSD), is an idiopathic condition characterised by localised, abnormally intense and prolonged pain, allodynia and autonomic nervous system changes (ie, swelling, skin colour and temperature changes and altered perspiration) that usually appear following a "noxious" trigger such as trauma or surgery. The objective of this report is to demonstrate that children with CRPS-I can have additional dysautonomic conditions secondary to an underlying maternally inherited mitochondrial disease, an association not previously published. Medical records of about 500 patients seen by one paediatric metabolic geneticist were reviewed to identify children meeting established CRPS diagnostic criteria. CRPS-I was present in eight children in seven families, each of which also had additional functional/dysautonomic conditions, the most common (> or = 4 cases per condition) being gastrointestinal dysmotility, migraine, cyclic vomiting and chronic fatigue. All seven probands studied met Nijmegen (2002) diagnostic criteria for definite mitochondrial disease on the basis of the clinical signs and symptoms and biochemical analyses. Six of the seven families met our pedigree-based criteria for probable maternal inheritance. In one tertiary-care paediatric genetics practice, children meeting the CRPS-I diagnostic criteria frequently had additional autonomic-related conditions secondary to maternally inherited mitochondrial disease, suggesting that mitochondrial DNA sequence variants can predispose children towards the development of CRPS-I and other dysautonomias. CRPS-I should be considered in patients with mitochondrial disease who complain of idiopathic pain. Maternally inherited mitochondrial disease may not be a rare cause of CRPS-I, especially in children who present with other manifestations of dysautonomia.

    1. Design considerations for massively parallel sequencing studies of complex human disease.

      Directory of Open Access Journals (Sweden)

      Bing-Jian Feng

      Full Text Available Massively Parallel Sequencing (MPS allows sequencing of entire exomes and genomes to now be done at reasonable cost, and its utility for identifying genes responsible for rare Mendelian disorders has been demonstrated. However, for a complex disease, study designs need to accommodate substantial degrees of locus, allelic, and phenotypic heterogeneity, as well as complex relationships between genotype and phenotype. Such considerations include careful selection of samples for sequencing and a well-developed strategy for identifying the few "true" disease susceptibility genes from among the many irrelevant genes that will be found to harbor rare variants. To examine these issues we have performed simulation-based analyses in order to compare several strategies for MPS sequencing in complex disease. Factors examined include genetic architecture, sample size, number and relationship of individuals selected for sequencing, and a variety of filters based on variant type, multiple observations of genes and concordance of genetic variants within pedigrees. A two-stage design was assumed where genes from the MPS analysis of high-risk families are evaluated in a secondary screening phase of a larger set of probands with more modest family histories. Designs were evaluated using a cost function that assumes the cost of sequencing the whole exome is 400 times that of sequencing a single candidate gene. Results indicate that while requiring variants to be identified in multiple pedigrees and/or in multiple individuals in the same pedigree are effective strategies for reducing false positives, there is a danger of over-filtering so that most true susceptibility genes are missed. In most cases, sequencing more than two individuals per pedigree results in reduced power without any benefit in terms of reduced overall cost. Further, our results suggest that although no single strategy is optimal, simulations can provide important guidelines for study design.

    2. Emergency Department Processes for the Evaluation and Management of Persons Under Investigation for Ebola Virus Disease.

      Science.gov (United States)

      Wadman, Michael C; Schwedhelm, Shelly S; Watson, Suzanne; Swanhorst, John; Gibbs, Shawn G; Lowe, John J; Iwen, Peter C; Hayes, A Kim; Needham, Susie; Johnson, Daniel W; Kalin, Daniel J; Zeger, Wesley G; Muelleman, Robert L

      2015-09-01

      Due to the recent Ebola virus outbreak in West Africa, patients with epidemiologic risk for Ebola virus disease and symptoms consistent with Ebola virus disease are presenting to emergency departments (EDs) and clinics in the United States. These individuals, identified as a person under investigation for Ebola virus disease, are initially screened using a molecular assay for Ebola virus. If this initial test is negative and the person under investigation has been symptomatic for Ebola virus disease or some other etiology, may require further investigation to direct appropriate therapy. ED administrators, physicians, and nurses proposed processes to provide care that is consistent with other ED patients. Biocontainment unit administrators, industrial hygienists, laboratory directors, physicians, and other medical personnel examined the ED processes and offered biocontainment unit personal protective equipment and process strategies designed to ensure safety for providers and patients. ED processes for the safe and timely evaluation and management of the person under investigation for Ebola virus disease are presented with the ultimate goals of protecting providers and ensuring a consistent level of care while confirmatory testing is pending. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

    3. Epidemiology of the Diseases of Wheat under Different Strategies of Supplementary Irrigation

      Directory of Open Access Journals (Sweden)

      Roberto P. Marano

      2012-01-01

      Full Text Available Wheat (Triticum aestivum L. is one of the most important and highly productive crops grown under supplementary irrigation in the central region of Santa Fe. However, its production is limited by the presence of diseases in the main stages for yield definition. The objective of this work was to assess wheat health in response to different supplementary irrigation strategies under greenhouse and field conditions. The field experiment included three treatments: dry (D, controlled deficit irrigation (CDI, and total irrigation (TI using the central pivot method. Disease incidence from stem elongation and severity in flag leaf and the leaf below the flag leaf were measured. Leaf area index (LAI, harvest index, air biomass, and yield components were determined. In greenhouse the treatments were TI and CDI, with evaluations similar to the field. The major leaf diseases observed were tan spot, leaf rust, and septoria leaf blotch. Significant differences in disease burden, LAI and yield components were observed in the different treatments. Under greenhouse conditions, only tan spot was observed. The results of this study indicated that the application of supplemental irrigation in wheat improved the yield, without increasing the incidence and severity of foliar diseases.

    4. Cyclopentadienyl molybdenum(II/VI) N-heterocyclic carbene complexes: Synthesis, structure, and reactivity under oxidative conditions

      KAUST Repository

      Li, Shenyu

      2010-04-26

      A series of N-heterocyclic carbene (NHC) complexes CpMo(CO) 2(NHC)X (NHC = IMe = 1,3-dimethylimidazol-2-ylidene, X = Br, 1; NHC = 1,3-dipropylimidazol-2-ylidene, X = Br, 2; NHC = IMes = 1,3-bis(2,4,6- trimethylphenyl)imidazol-2-ylidene, X = Br, 3; NHC = IBz = 1,3-dibenzylimidazol- 2-ylidene, X = Br, 4a, and X = Cl, 4b; NHC = 1-methyl-3-propylimidazol-2- ylidene, X = Br, 5) and [CpMo(CO)2(IMes)(CH3CN)][BF 4] (6) have been synthesized and fully characterized. The stability of metal-NHC ligand bonds in these compounds under oxidative conditions has been investigated. The thermally stable Mo(VI) dioxo NHC complex [CpMoO 2(IMes)][BF4] (9) has been isolated by the oxidation of the ionic complex 6 by TBHP (tert-butyl hydrogen peroxide). Complex 6 can be applied as a very active (TOFs up to 3400 h-1) and selective olefin epoxidation catalyst. While under oxidative conditions (in the presence of TBHP), compounds 1-5 decompose into imidazolium bromide and imidazolium polyoxomolybdate. The formation of polyoxomolybdate as oxidation products had not been observed in a similar epoxidation catalyzed by Mo(II) and Mo(VI) complexes. DFT studies suggest that the presence of Br- destabilizes the CpMo(VI) oxo NHC carbene species, consistent with the experimental observations. © 2010 American Chemical Society.

    5. Tracking energy transfer between light harvesting complex 2 and 1 in photosynthetic membranes grown under high and low illumination.

      Science.gov (United States)

      Lüer, Larry; Moulisová, Vladimíra; Henry, Sarah; Polli, Dario; Brotosudarmo, Tatas H P; Hoseinkhani, Sajjad; Brida, Daniele; Lanzani, Guglielmo; Cerullo, Giulio; Cogdell, Richard J

      2012-01-31

      Energy transfer (ET) between B850 and B875 molecules in light harvesting complexes LH2 and LH1/RC (reaction center) complexes has been investigated in membranes of Rhodopseudomonas palustris grown under high- and low-light conditions. In these bacteria, illumination intensity during growth strongly affects the type of LH2 complexes synthesized, their optical spectra, and their amount of energetic disorder. We used a specially built femtosecond spectrometer, combining tunable narrowband pump with broadband white-light probe pulses, together with an analytical method based on derivative spectroscopy for disentangling the congested transient absorption spectra of LH1 and LH2 complexes. This procedure allows real-time tracking of the forward (LH2 → LH1) and backward (LH2←LH1) ET processes and unambiguous determination of the corresponding rate constants. In low-light grown samples, we measured lower ET rates in both directions with respect to high-light ones, which is explained by reduced spectral overlap between B850 and B875 due to partial redistribution of oscillator strength into a higher energetic exciton transition. We find that the low-light adaptation in R. palustris leads to a reduced elementary backward ET rate, in accordance with the low probability of two simultaneous excitations reaching the same LH1/RC complex under weak illumination. Our study suggests that backward ET is not just an inevitable consequence of vectorial ET with small energetic offsets, but is in fact actively managed by photosynthetic bacteria.

    6. Effects of solution pH and complexing reagents on uranium and thorium desorption under saturated equilibrium conditions

      International Nuclear Information System (INIS)

      Wang, Yug-Yea; Yu, C.

      1992-01-01

      Three contaminated bulk surface soils were used for investigating the effect of solution pH and complexing reagents on uranium and thorium desorption. At a low solution pH, the major chemical species of uranium and thorium, uranyl UO 2 +2 , thorium dihydroxide Th(OH) 2 +2 , and thorium hydroxide Th(OH) +3 , tend to form complexes with acetates in the solution phase, which increases the fractions of uranium and thorium desorbed into this phase. At a high solution pH, important uranium and thorium species such as uranyl tricarbonate complex UO 2 (CO) 33 -4 and thorium tetrahydroxide complex Th(OH) 4 tend to resist complexation with acetates. The presence of complexing reagents in solution can release radionuclides such as uranium and/or thorium from the soil to the solution by forming soluble complexes. Sodium bicarbonate (NaHCO 3 ) and diethylenetriaminepentaacetic acid (DTPA) are strong complex formers that released 38% to 62% of total uranium activity and 78% to 86% of total thorium activity, respectively, from the soil samples investigated. Solutions of 0.1 molar sodium nitrate (NaNO 3 ) and 0.1 molar sodium sulfate (Na 2 SO 4 ) were not effective complex formers with uranium and thorium under the experimental conditions. Fractions of uranium and thorium desorbed by 0.15g/200ml humic acid ranged from 4.62% to 6.17% and 1.59% to 7.09%, respectively. This work demonstrates the importance of a knowledge of solution chemistry in investigating the desorption of radionuclides

    7. [Change of paradigms in the surgical treatment of complex thoracic aortic disease].

      Science.gov (United States)

      Herold, Ulf; Tsagakis, Konstantinos; Kamler, Markus; Massoudy, Parwis; Assenmacher, Eva; Eggebrecht, Holger; Buck, Thomas; Jakob, Heinz

      2006-08-01

      One of the main issues in complex thoracic aortic disease, requiring the replacement of the ascending aorta, the entire aortic arch and the descending aorta, is the vast amount of surgery necessary to cure the patient. Though one-stage repair is feasible by a clamshell thoracotomy, the associated surgical trauma and perioperative morbidity limit this approach to younger patients only. Classic surgical repair consist of a two-stage strategy, whereby, in the first step, the ascending aorta and the aortic arch are replaced via a midline sternotomy. In the second step, via a lateral thoracotomy, the descending aorta is replaced. The two stages may sum up to a mortality of 20%; furthermore, the waiting period between the stages is associated with a mortality rate of 10% of its own. Additionally, the two-stage strategy has an inherent limitation, due to the comorbidity and advanced age of the majority of patients. Therefore, the second stage cannot be offered to up to 30% of patients. New developments and improvements in aortic surgery were introduced to overcome these shortcomings and to simplify the surgical repair. The "elephant trunk" principle, introduced by Borst et al. in 1983, was an important step to facilitate surgical repair, but still required the second step. With the introduction of endovascular repair of thoracic aortic disease with stent grafts implanted retrograde via the femoral artery, new therapeutic concepts emerged. In the late 1990s, two Japanese groups reported first trials to stabilize the free-floating "elephant trunk" prosthesis by implantation of nitinol stent grafts into the vascular graft. The applied devices were purely custom-made and nonstandardized. The availability of industrially made and CE-marked stent-graft devices raised the possibility to apply them in open aortic arch surgery. The experience with stent-graft devices implanted antegrade into the descending aorta (Medtronic Talent) was reported first by the Essen and the Vienna

    8. Understanding the Role of GPCR Heteroreceptor Complexes in Modulating the Brain Networks in Health and Disease.

      Science.gov (United States)

      Borroto-Escuela, Dasiel O; Carlsson, Jens; Ambrogini, Patricia; Narváez, Manuel; Wydra, Karolina; Tarakanov, Alexander O; Li, Xiang; Millón, Carmelo; Ferraro, Luca; Cuppini, Riccardo; Tanganelli, Sergio; Liu, Fang; Filip, Malgorzata; Diaz-Cabiale, Zaida; Fuxe, Kjell

      2017-01-01

      The introduction of allosteric receptor-receptor interactions in G protein-coupled receptor (GPCR) heteroreceptor complexes of the central nervous system (CNS) gave a new dimension to brain integration and neuropsychopharmacology. The molecular basis of learning and memory was proposed to be based on the reorganization of the homo- and heteroreceptor complexes in the postjunctional membrane of synapses. Long-term memory may be created by the transformation of parts of the heteroreceptor complexes into unique transcription factors which can lead to the formation of specific adapter proteins. The observation of the GPCR heterodimer network (GPCR-HetNet) indicated that the allosteric receptor-receptor interactions dramatically increase GPCR diversity and biased recognition and signaling leading to enhanced specificity in signaling. Dysfunction of the GPCR heteroreceptor complexes can lead to brain disease. The findings of serotonin (5-HT) hetero and isoreceptor complexes in the brain over the last decade give new targets for drug development in major depression. Neuromodulation of neuronal networks in depression via 5-HT, galanin peptides and zinc involve a number of GPCR heteroreceptor complexes in the raphe-hippocampal system: GalR1-5-HT1A, GalR1-5-HT1A-GPR39, GalR1-GalR2, and putative GalR1-GalR2-5-HT1A heteroreceptor complexes. The 5-HT1A receptor protomer remains a receptor enhancing antidepressant actions through its participation in hetero- and homoreceptor complexes listed above in balance with each other. In depression, neuromodulation of neuronal networks in the raphe-hippocampal system and the cortical regions via 5-HT and fibroblast growth factor 2 involves either FGFR1-5-HT1A heteroreceptor complexes or the 5-HT isoreceptor complexes such as 5-HT1A-5-HT7 and 5-HT1A-5-HT2A. Neuromodulation of neuronal networks in cocaine use disorder via dopamine (DA) and adenosine signals involve A2AR-D2R and A2AR-D2R-Sigma1R heteroreceptor complexes in the dorsal and

    9. pincer complex in Suzuki–Miyaura cross-coupling reaction under

      Indian Academy of Sciences (India)

      in microwave-assisted Suzuki–Miyaura cross-coupling. ∗. For correspondence reactions of aryl and heteroaryl halides (figure 1). To the best of our knowledge, this is the first report of a pin- cer complex employed in microwave-assisted catalytic reactions. 2. Experimental. All bromo compounds and boronic acid derivatives.

    10. The calcium-paracaseinate-phosphate-complex under conditions similar to those in cheese

      NARCIS (Netherlands)

      Monib, A.M.M.F.

      1962-01-01

      The complex of calcium-paracaseinate-phosphate is the matrix substance of cheese. The changes it undergoes during maturing determines many characteristics of the finished product.

      The preliminary studies of the effect of pH and sodium chloride on the swelling and solubility of the

    11. The value of extended pedigrees for next-generation analysis of complex disease in the rhesus macaque.

      Science.gov (United States)

      Vinson, Amanda; Prongay, Kamm; Ferguson, Betsy

      2013-01-01

      Complex diseases (e.g., cardiovascular disease and type 2 diabetes, among many others) pose the biggest threat to human health worldwide and are among the most challenging to investigate. Susceptibility to complex disease may be caused by multiple genetic variants (GVs) and their interaction, by environmental factors, and by interaction between GVs and environment, and large study cohorts with substantial analytical power are typically required to elucidate these individual contributions. Here, we discuss the advantages of both power and feasibility afforded by the use of extended pedigrees of rhesus macaques (Macaca mulatta) for genetic studies of complex human disease based on next-generation sequence data. We present these advantages in the context of previous research conducted in rhesus macaques for several representative complex diseases. We also describe a single, multigeneration pedigree of Indian-origin rhesus macaques and a sample biobank we have developed for genetic analysis of complex disease, including power of this pedigree to detect causal GVs using either genetic linkage or association methods in a variance decomposition approach. Finally, we summarize findings of significant heritability for a number of quantitative traits that demonstrate that genetic contributions to risk factors for complex disease can be detected and measured in this pedigree. We conclude that the development and application of an extended pedigree to analysis of complex disease traits in the rhesus macaque have shown promising early success and that genome-wide genetic and higher order -omics studies in this pedigree are likely to yield useful insights into the architecture of complex human disease.

    12. PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex.

      Science.gov (United States)

      Kiefer, Florian W; Winhofer, Yvonne; Iacovazzo, Donato; Korbonits, Márta; Wolfsberger, Stefan; Knosp, Engelbert; Trautinger, Franz; Höftberger, Romana; Krebs, Michael; Luger, Anton; Gessl, Alois

      2017-08-01

      Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the PRKAR1A gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC. Here, we describe the first case of a patient with CNC and adrenocorticotropic hormone (ACTH)-dependent Cushing disease due to a pituitary corticotroph adenoma. Loss-of-heterozygosity analysis of the pituitary tumour revealed loss of the wild-type copy of PRKAR1A , suggesting a role of this gene in the pituitary adenoma development. PRKAR1A loss-of-function mutations can rarely lead to ACTH-secreting pituitary adenomas in CNC patients. Pituitary-dependent disease should be considered in the differential diagnosis of Cushing syndrome in CNC patients. © 2017 European Society of Endocrinology.

    13. Importance of reciprocal balance of T cell immunity in Mycobacterium abscessus complex lung disease.

      Directory of Open Access Journals (Sweden)

      Su-Young Kim

      Full Text Available Little is known about the nature of the host immune response to Mycobacterium abscessus complex (MABC infection. The aim of the present study was to investigate whether alterations in serum immunomolecule levels after treating MABC lung disease patients with antibiotics can reflect the disease-associated characteristics.A total of 22 immunomolecules in 24 MABC lung disease patients before and after antibiotic therapy were quantitatively analyzed using a multiplex bead-based system.In general, the pre-treatment levels of T helper type 1 (Th1-related cytokines, i.e., interferon (IFN-γ and interleukin (IL-12, and Th2-related cytokines, i.e., IL-4 and IL-13, were significantly decreased in patients compared with control subjects. In contrast, the pre-treatment levels of Th17-related cytokines, i.e., IL-17 and IL-23, were significantly increased in MABC patients. Interestingly, significantly higher levels of IFN-γ-induced protein (IP-10 and monokine induced by IFN-γ protein (MIG were detected in patients with failure of sputum conversion at post-treatment compared to patients with successful sputum conversion.Reduced Th1 and Th2 responses and enhanced Th17 responses in patients may perpetuate MABC lung disease, and the immunomolecules IP-10 and MIG, induced through IFN-γ, may serve as key markers for indicating the treatment outcome.

    14. [Variability of diarrheal diseases in children under 5 living in an urban setting: observations in Rufisque, Senegal].

      Science.gov (United States)

      Sy, I; Handschumacher, P; Wyss, K; Cisse, G; Lo, B; Piermay, J L; Tanner, M

      2010-02-01

      Rapid urbanization has created numerous health risks in developing countries, but the exact impact on many diseases in function of living conditions is unclear. For insight into this complex relationship, a study on diarrheal diseases was carried out to obtain knowledge about the distribution of health risks in an urban setting. An epidemiological survey with a combined longitudinal and transverse design was conducted in Rufisque, Senegal, from April 2002 to March 2003 in a sample including households with children less than 5-years-old living in four areas presenting different levels of hygiene. Results showed a high overall incidence of diarrhea (6.5 episodes/child/year) but there were major discrepancies between the four study areas in direct relation with level of hygiene. The annual incidence per child was lower in the low-cost housing project (fair hygiene, 3.4 episodes) than in the Castors area (poor hygiene, 6.8 episodes), Diokoul Wague area (very poor hygiene, 7.3 episodes) and Goufe Aldiana area (no hygiene, 8.4 episodes). The study showed only a slight seasonal effect on diarrheal disease in the different areas. However, the differences observed between areas during the cold and hot dry seasons were considerably attenuated in the rainy season. This variability in the incidence rate that underlines the diversity of urban living conditions depends on a variety of risk factors (such as age and number of children) that may interact, although hygiene level remains critical. For issues usually given priority at the national level, multiplying studies aimed at fine analysis of factors underlying disease transmission is useful since this approach can improve understanding of public health policy in city environments characterized by the complex conditions (density and diversity) created by urbanization.

    15. Can transcriptomics provide insight into the underlying chemopreventive mechanisms of complex mixtures of phytochemicals in humans?

      NARCIS (Netherlands)

      Breda, van S.G.; Wilms, L.C.; Gaj, S.; Briedé, J.J.; Helsper, J.P.F.G.; Kleinjans, J.C.; Kok, de T.M.

      2014-01-01

      Blueberries contain relatively large amounts of different phytochemicals which are suggested to have chemopreventive properties, but little information is available on the underlying molecular modes of action. This study investigates whole genome gene expression changes in lymphocytes of 143 humans

    16. Infectious Bursal disease virus: ribonucleoprotein complexes of a double-stranded RNA virus.

      Science.gov (United States)

      Luque, Daniel; Saugar, Irene; Rejas, María Teresa; Carrascosa, José L; Rodríguez, José F; Castón, José R

      2009-02-27

      Genome-binding proteins with scaffolding and/or regulatory functions are common in living organisms and include histones in eukaryotic cells, histone-like proteins in some double-stranded DNA (dsDNA) viruses, and the nucleocapsid proteins of single-stranded RNA viruses. dsRNA viruses nevertheless lack these ribonucleoprotein (RNP) complexes and are characterized by sharing an icosahedral T=2 core involved in the metabolism and insulation of the dsRNA genome. The birnaviruses, with a bipartite dsRNA genome, constitute a well-established exception and have a single-shelled T=13 capsid only. Moreover, as in many negative single-stranded RNA viruses, the genomic dsRNA is bound to a nucleocapsid protein (VP3) and the RNA-dependent RNA polymerase (VPg). We used electron microscopy and functional analysis to characterize these RNP complexes of infectious bursal disease virus, the best characterized member of the Birnaviridae family. Mild disruption of viral particles revealed that VP3, the most abundant core protein, present at approximately 450 copies per virion, is found in filamentous material tightly associated with the dsRNA. We developed a method to purify RNP and VPg-dsRNA complexes. Analysis of these complexes showed that they are linear molecules containing a constant amount of protein. Sensitivity assays to nucleases indicated that VP3 renders the genomic dsRNA less accessible for RNase III without introducing genome compaction. Additionally, we found that these RNP complexes are functionally competent for RNA synthesis in a capsid-independent manner, in contrast to most dsRNA viruses.

    17. Balloon Angioplasty as a Modality to Treat Children with Pulmonary Stenosis Secondary to Complex Congenital Heart Diseases

      Directory of Open Access Journals (Sweden)

      Yan Gu

      2017-01-01

      Conclusions: Balloon angioplasty was proven to be a safe and useful modality in children with complex congenital heart diseases and postoperative pulmonary stenosis, which should be the initial therapeutic modality in selected patients.

    18. Modelling fast spreading patterns of airborne infectious diseases using complex networks

      Science.gov (United States)

      Brenner, Frank; Marwan, Norbert; Hoffmann, Peter

      2017-04-01

      The pandemics of SARS (2002/2003) and H1N1 (2009) have impressively shown the potential of epidemic outbreaks of infectious diseases in a world that is strongly connected. Global air travelling established an easy and fast opportunity for pathogens to migrate globally in only a few days. This made epidemiological prediction harder. By understanding this complex development and its link to climate change we can suggest actions to control a part of global human health affairs. In this study we combine the following data components to simulate the outbreak of an airborne infectious disease that is directly transmitted from human to human: em{Global Air Traffic Network (from openflights.org) with information on airports, airport location, direct flight connection, airplane type} em{Global population dataset (from SEDAC, NASA)} em{Susceptible-Infected-Recovered (SIR) compartmental model to simulate disease spreading in the vicinity of airports. A modified Susceptible-Exposed-Infected-Recovered (SEIR) model to analyze the impact of the incubation period.} em{WATCH-Forcing-Data-ERA-Interim (WFDEI) climate data: temperature, specific humidity, surface air pressure, and water vapor pressure} These elements are implemented into a complex network. Nodes inside the network represent airports. Each single node is equipped with its own SIR/SEIR compartmental model with node specific attributes. Edges between those nodes represent direct flight connections that allow infected individuals to move between linked nodes. Therefore the interaction of the set of unique SIR models creates the model dynamics we will analyze. To better figure out the influence on climate change on disease spreading patterns, we focus on Influenza-like-Illnesses (ILI). The transmission rate of ILI has a dependency on climate parameters like humidity and temperature. Even small changes of environmental variables can trigger significant differences in the global outbreak behavior. Apart from the direct

    19. Transfer of skill engendered by complex task training under conditions of variable priority.

      Science.gov (United States)

      Boot, Walter R; Basak, Chandramallika; Erickson, Kirk I; Neider, Mark; Simons, Daniel J; Fabiani, Monica; Gratton, Gabriele; Voss, Michelle W; Prakash, Ruchika; Lee, HyunKyu; Low, Kathy A; Kramer, Arthur F

      2010-11-01

      We explored the theoretical underpinnings of a commonly used training strategy by examining issues of training and transfer of skill in the context of a complex video game (Space Fortress, Donchin, 1989). Participants trained using one of two training regimens: Full Emphasis Training (FET) or Variable Priority Training (VPT). Transfer of training was assessed with a large battery of cognitive and psychomotor tasks ranging from basic laboratory paradigms measuring reasoning, memory, and attention to complex real-world simulations. Consistent with previous studies, VPT accelerated learning and maximized task mastery. However, the hypothesis that VPT would result in broader transfer of training received limited support. Rather, transfer was most evident in tasks that were most similar to the Space Fortress game itself. Results are discussed in terms of potential limitations of the VPT approach. Copyright © 2010 Elsevier B.V. All rights reserved.

    20. Molecular Mechanisms Underlying the Epileptogenesis and Seizure Progression in Tuberous Sclerosis Complex 1 Deficient Mouse Models

      Science.gov (United States)

      2016-10-01

      in different subtypes of brain cells , including neurons, glia or progenitor cells , all cause spontaneous seizures in animal models, suggesting that...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT We seek to understand four basic questions related to epileptogenesis: 1) What is the role of mTOR...mutations in the TSC1 or TSC2 genes, which form a regulatory complex responsible for limiting the activity of an important intracellular regulator of cell

    1. Supersonic particle in a low damped complex plasma under microgravity conditions

      Science.gov (United States)

      Zaehringer, E.; Zhdanov, S.; Schwabe, M.; Mohr, D. P.; Knapek, C. A.; Huber, P.; Semenov, I.; Thomas, H. M.

      2018-01-01

      We discuss the diagnostics of a complex plasma cloud recorded in experiments performed in the framework of the Ekoplasma project. A supersonic extra particle is used as a probe of the cloud dynamics. A fine-structured Mach cone behind the supersonic particle is observed. We investigate the spatial and temporal development of the Mach cone with a computer based measurement to determine the speed of sound of the particle cloud. Also time and position dependent characteristics of the velocity field are recorded.

    2. Modern methods of surveyor observations in opencast mining under complex hydrogeological conditions.

      Science.gov (United States)

      Usoltseva, L. A.; Lushpei, V. P.; Mursin, VA

      2017-10-01

      The article considers the possibility of linking the modern methods of surveying security of open mining works to improve industrial safety in the Primorsky Territory, as well as their use in the educational process. Industrial Safety in the management of Surface Mining depends largely on the applied assessment methods and methods of stability of pit walls and slopes of dumps in the complex mining and hydro-geological conditions.

    3. Nursing care of the patient with lymfedema under the treatment of Complex decongestive therapy

      OpenAIRE

      Šertlerová, Kateřina

      2017-01-01

      In the theoretical part of my theses I have dealt with lymphedema from the point of wiew of etiology and pathofyziology. I have described the lymph origin and transport, the lymphatics structure, the drenage of body parts to the corresponding regional lymphatic nodes and the lymphatic watershed. This basic theoretical knowledge is necessary for the understanding of the Complex decongestive therapy method, that is described in the practical part. Next I have described lymphedema clasification,...

    4. Complex Plasmas under free fall conditions aboard the International Space Station

      Science.gov (United States)

      Konopka, Uwe; Thomas, Edward, Jr.; Funk, Dylan; Doyle, Brandon; Williams, Jeremiah; Knapek, Christina; Thomas, Hubertus

      2017-10-01

      Complex Plasmas are dynamically dominated by massive, highly negatively charged, micron-sized particles. They are usually strongly coupled and as a result can show fluid-like behavior or undergo phase transitions to form crystalline structures. The dynamical time scale of these systems is easily accessible in experiments because of the relatively high mass/inertia of the particles. However, the high mass also leads to sedimentation effects and as a result prevents the conduction of large scale, fully three dimensional experiments that are necessary to utilize complex plasmas as model systems in the transition to continuous media. To reduce sedimentation influences it becomes necessary to perform experiments in a free-fall (``microgravity'') environment, such as the ISS based experiment facility ``Plasma-Kristall-4'' (``PK-4''). In our paper we will present our recently started research activities to investigate the basic properties of complex plasmas by utilizing the PK-4 experiment facility aboard the ISS. We further give an overview of developments towards the next generation experiment facility ``Ekoplasma'' (formerly named ``PlasmaLab'') and discuss potential additional small-scale space-based experiment scenarios. This work was supported by the JPL/NASA (JPL-RSA 1571699), the US Dept. of Energy (DE-SC0016330) and the NSF (PHY-1613087).

    5. Magnetic resonance imaging of complex congenital heart disease in aduits; Magnetresonanztomographie komplexer kongenitaler Herzerkrankungen beim Erwachsenen

      Energy Technology Data Exchange (ETDEWEB)

      Bremerich, J. [San Francisco Univ, CA (United States). Dept. of Radiology]|[Universitaetsklinik Basel (Switzerland). Abt. fuer Medizinische Radiologie; Wyttenbach, R.; Higgins, C.B. [San Francisco Univ, CA (United States). Dept. of Radiology; Buser, P. [Universitaetsklinik Basel (Switzerland). Abt. fuer Kardiologie; Steinbrich, W. [Universitaetsklinik Basel (Switzerland). Abt. fuer Medizinische Radiologie

      1999-04-01

      An increasing number of patients with complex congenital heart disease reaches adulthood, because treatment and patient outcome have improved considerably in recent years. Monitoring of these patients requires both definition of cardiac anatomy and assessment of function with good reproducibility. Complications after surgical repair such as restenoses of pulmonary arteries after surgical repair of Tetralogy of Fallot, ventricular hypertrophy, stenoses or leakage of baffles, or stenosis and aneurysms of anastomoses have to be detected at an early stage. Magnetic Resonance Imaging (MRI) is an excellent tool to monitor these patients because of its noninvasive nature, its good interstudy and interobserver reproducibility, and because it allows assessment of both cardiac anatomy and function. This paper reviews the current applications of MRI in complex congenital heart disease in adults. (orig.) [Deutsch] Durch Verbesserungen in der Diagnose und Therapie komplexer kongenitaler Herzerkrankungen kann eine zunehmende Anzahl von betroffenen Patienten das Erwachsenenalter erreichen. Diese Patienten benoetigen regelmaessige postoperative Verlaufskontrollen, um Komplikationen wie z.B. Restenosen der grossen Arterien, Stenosen, Lecks und Aneurysmata von Anastomosen, Ventrikelhypertrophie und -dilatation oder Klappendysfunktionen fruehzeitig zu erkennen und zu behandeln. Fuer nichtinvasive regelmaessige Verlaufskontrollen bietet sich die Magnetresonanztomographie (MRT) des Herzens an, da sie eine umfassende Untersuchung sowohl der Morphologie als auch der Funktion des Herzens mit guter Reproduzierbarkeit erlaubt. Die gegenwaertigen klinischen Anwendungen der MRT bei komplexen kongenitalen Herzerkrankungen beim Erwachsenen werden in dieser Uebersicht beschrieben. (orig.)

    6. Transmission of sexually transmitted disease in complex network of the Penna model

      Science.gov (United States)

      Chen, Feng; Li, Chunguang

      2007-04-01

      The Penna model is a computational model which can encompass the inheritance, mutation, evolution and ageing phenomena of population successfully. Some researchers considered social interactions in an asexual Penna model, got a complex network and found some interesting properties. We consider a sexual Penna model to study the transmission of sexually transmitted diseases (STD). Our model can also generate a complex network and we observed some properties in real networks, such as small-world and assortative mixing. In the real world, the fatality of STD is changing with the advancing of medicine and it can affect our life. In this paper, we uncover the effect induced by the fatality of STD. We found that fatality plays an important role in the transmission of STD because whether the STD will disappear or continue to exist depends on the fatality of STD. Also, the fatality of STD can affect the evolution of inherited diseases and average life span. Some properties found in the model should be useful for the prevention and control of STD.

    7. Deep sequencing of the MHC region in the Chinese population contributes to studies of complex disease.

      Science.gov (United States)

      Zhou, Fusheng; Cao, Hongzhi; Zuo, Xianbo; Zhang, Tao; Zhang, Xiaoguang; Liu, Xiaomin; Xu, Ricong; Chen, Gang; Zhang, Yuanwei; Zheng, Xiaodong; Jin, Xin; Gao, Jinping; Mei, Junpu; Sheng, Yujun; Li, Qibin; Liang, Bo; Shen, Juan; Shen, Changbing; Jiang, Hui; Zhu, Caihong; Fan, Xing; Xu, Fengping; Yue, Min; Yin, Xianyong; Ye, Chen; Zhang, Cuicui; Liu, Xiao; Yu, Liang; Wu, Jinghua; Chen, Mengyun; Zhuang, Xuehan; Tang, Lili; Shao, Haojing; Wu, Longmao; Li, Jian; Xu, Yu; Zhang, Yijie; Zhao, Suli; Wang, Yu; Li, Ge; Xu, Hanshi; Zeng, Lei; Wang, Jianan; Bai, Mingzhou; Chen, Yanling; Chen, Wei; Kang, Tian; Wu, Yanyan; Xu, Xun; Zhu, Zhengwei; Cui, Yong; Wang, Zaixing; Yang, Chunjun; Wang, Peiguang; Xiang, Leihong; Chen, Xiang; Zhang, Anping; Gao, Xinghua; Zhang, Furen; Xu, Jinhua; Zheng, Min; Zheng, Jie; Zhang, Jianzhong; Yu, Xueqing; Li, Yingrui; Yang, Sen; Yang, Huanming; Wang, Jian; Liu, Jianjun; Hammarström, Lennart; Sun, Liangdan; Wang, Jun; Zhang, Xuejun

      2016-07-01

      The human major histocompatibility complex (MHC) region has been shown to be associated with numerous diseases. However, it remains a challenge to pinpoint the causal variants for these associations because of the extreme complexity of the region. We thus sequenced the entire 5-Mb MHC region in 20,635 individuals of Han Chinese ancestry (10,689 controls and 9,946 patients with psoriasis) and constructed a Han-MHC database that includes both variants and HLA gene typing results of high accuracy. We further identified multiple independent new susceptibility loci in HLA-C, HLA-B, HLA-DPB1 and BTNL2 and an intergenic variant, rs118179173, associated with psoriasis and confirmed the well-established risk allele HLA-C*06:02. We anticipate that our Han-MHC reference panel built by deep sequencing of a large number of samples will serve as a useful tool for investigating the role of the MHC region in a variety of diseases and thus advance understanding of the pathogenesis of these disorders.

    8. Characterization of complexity in the electroencephalograph activity of Alzheimer's disease based on fuzzy entropy.

      Science.gov (United States)

      Cao, Yuzhen; Cai, Lihui; Wang, Jiang; Wang, Ruofan; Yu, Haitao; Cao, Yibin; Liu, Jing

      2015-08-01

      In this paper, experimental neurophysiologic recording and statistical analysis are combined to investigate the nonlinear characteristic and the cognitive function of the brain. Fuzzy approximate entropy and fuzzy sample entropy are applied to characterize the model-based simulated series and electroencephalograph (EEG) series of Alzheimer's disease (AD). The effectiveness and advantages of these two kinds of fuzzy entropy are first verified through the simulated EEG series generated by the alpha rhythm model, including stronger relative consistency and robustness. Furthermore, in order to detect the abnormality of irregularity and chaotic behavior in the AD brain, the complexity features based on these two fuzzy entropies are extracted in the delta, theta, alpha, and beta bands. It is demonstrated that, due to the introduction of fuzzy set theory, the fuzzy entropies could better distinguish EEG signals of AD from that of the normal than the approximate entropy and sample entropy. Moreover, the entropy values of AD are significantly decreased in the alpha band, particularly in the temporal brain region, such as electrode T3 and T4. In addition, fuzzy sample entropy could achieve higher group differences in different brain regions and higher average classification accuracy of 88.1% by support vector machine classifier. The obtained results prove that fuzzy sample entropy may be a powerful tool to characterize the complexity abnormalities of AD, which could be helpful in further understanding of the disease.

    9. Alzheimer's Disease as Subcellular `Cancer' --- The Scale-Invariant Principles Underlying the Mechanisms of Aging ---

      Science.gov (United States)

      Murase, M.

      1996-01-01

      with self-organization, has been thought to underlie `creative' aspects of biological phenomena such as the origin of life, adaptive evolution of viruses, immune recognition and brain function. It therefore must be surprising to find that the same principles will also underlie `non-creative' aspects, for example, the development of cancer and the aging of complex organisms. Although self-organization has extensively been studied in nonliving things such as chemical reactions and laser physics, it is undoubtedly true that the similar sources of the order are available to living things at different levels and scales. Several paradigm shifts are, however, required to realize how the general principles of natural selection can be extensible to non-DNA molecules which do not possess the intrinsic nature of self-reproduction. One of them is, from the traditional, genetic inheritance view that DNA (or RNA) molecules are the ultimate unit of heritable variations and natural selection at any organization level, to the epigenetic (nongenetic) inheritance view that any non-DNA molecule can be the target of heritable variations and molecular selection to accumulate in certain biochemical environment. Because they are all enriched with a β-sheet content, ready to mostly interact with one another, different denatured proteins like β-amyloid, PHF and prions can individually undergo self-templating or self-aggregating processes out of gene control. Other paradigm shifts requisite for a break-through in the etiology of neurodegenerative disorders will be discussed. As it is based on the scale-invariant principles, the present theory also predicts plausible mechanisms underlying quite different classes of disorders such as amyotrophic lateral sclerosis (ALS), atherosclerosis, senile cataract and many other symptoms of aging. The present theory, thus, provides the consistent and comprehensive account to the origin of aging by means of natural selection and self-organization.

    10. Measurement of the speed of sound by observation of the Mach cones in a complex plasma under microgravity conditions

      Energy Technology Data Exchange (ETDEWEB)

      Zhukhovitskii, D. I., E-mail: dmr@ihed.ras.ru; Fortov, V. E.; Molotkov, V. I.; Lipaev, A. M.; Naumkin, V. N. [Joint Institute of High Temperatures, Russian Academy of Sciences, Izhorskaya 13, Bd. 2, 125412 Moscow (Russian Federation); Thomas, H. M. [Research Group Complex Plasma, DLR, Oberpfaffenhofen, 82234 Wessling (Germany); Ivlev, A. V.; Morfill, G. E. [Max-Planck-Institut für extraterrestrische Physik, Giessenbachstrasse, 85748 Garching (Germany); Schwabe, M. [Department of Chemical and Biomolecular Engineering, Graves Lab, D75 Tan Hall, University of California, Berkeley, CA 94720 (United States)

      2015-02-15

      We report the first observation of the Mach cones excited by a larger microparticle (projectile) moving through a cloud of smaller microparticles (dust) in a complex plasma with neon as a buffer gas under microgravity conditions. A collective motion of the dust particles occurs as propagation of the contact discontinuity. The corresponding speed of sound was measured by a special method of the Mach cone visualization. The measurement results are incompatible with the theory of ion acoustic waves. The estimate for the pressure in a strongly coupled Coulomb system and a scaling law for the complex plasma make it possible to derive an evaluation for the speed of sound, which is in a reasonable agreement with the experiments in complex plasmas.

    11. CO Cleavage and CO2 Functionalization under Mild Conditions by a Multimetallic CsU2 Nitride Complex.

      Science.gov (United States)

      Falcone, Marta; Chatelain, Lucile; Scopelliti, Rosario; Mazzanti, Marinella

      2017-04-26

      Novel efficient chemical processes involving cheap and widely accessible carbon dioxide or carbon monoxide under mild conditions for the production of valuable chemical products are highly desirable in the current energetic context. Uranium nitride materials act as high activity catalysts in the Haber-Bosch process but the reactivity of molecular nitride compounds remains unexplored. Here we review recent results obtained in our group showing that a multimetallic nitride complex [Cs{[U(OSi(OtBu)3)3]2(μ-N)}] (1) with a CsUIV-N-UIV core, is able to promote N-C bond formation due to its strong nucleophile behaviour. In particular, complex 1, in the presence of excess CO2 leads to a remarkable dicarbamate product. The multimetallic CsUIV-N-UIV nitride also readily cleaves the C≡O bond under mild conditions.

    12. Variations in cardiovascular disease under-diagnosis in England: national cross-sectional spatial analysis

      Directory of Open Access Journals (Sweden)

      Walford Hannah

      2011-03-01

      Full Text Available Abstract Background There is under-diagnosis of cardiovascular disease (CVD in the English population, despite financial incentives to encourage general practices to register new cases. We compared the modelled (expected and diagnosed (observed prevalence of three cardiovascular conditions- coronary heart disease (CHD, hypertension and stroke- at local level, their geographical variation, and population and healthcare predictors which might influence diagnosis. Methods Cross-sectional observational study in all English local authorities (351 and general practices (8,372 comparing model-based expected prevalence with diagnosed prevalence on practice disease registers. Spatial analyses were used to identify geographic clusters and variation in regression relationships. Results A total of 9,682,176 patients were on practice CHD, stroke and transient ischaemic attack, and hypertension registers. There was wide spatial variation in observed: expected prevalence ratios for all three diseases, with less than five per cent of expected cases diagnosed in some areas. London and the surrounding area showed statistically significant discrepancies in observed: expected prevalence ratios, with observed prevalence much lower than the epidemiological models predicted. The addition of general practitioner supply as a variable yielded stronger regression results for all three conditions. Conclusions Despite almost universal access to free primary healthcare, there may be significant and highly variable under-diagnosis of CVD across England, which can be partially explained by persistent inequity in GP supply. Disease management studies should consider the possible impact of under-diagnosis on population health outcomes. Compared to classical regression modelling, spatial analytic techniques can provide additional information on risk factors for under-diagnosis, and can suggest where healthcare resources may be most needed.

    13. Association of red complex, A. actinomycetemcomitans and non-oral bacteria with periodontal diseases.

      Science.gov (United States)

      da Silva-Boghossian, Carina Maciel; do Souto, Renata Martins; Luiz, Ronir R; Colombo, Ana Paula Vieira

      2011-09-01

      Pathogens related to systemic infections have been detected in the periodontal microbiota. The relationship amongst these pathogens, periodontal bacteria and periodontal clinical status is poorly understood. This study evaluated the association amongst red complex, A. actinomycetemcomitans (A.a) and non-oral pathogenic bacteria in subjects with good periodontal health (PH), gingivitis (G), chronic (CP) and aggressive (AP) periodontitis. Subgingival biofilm samples were obtained from 51 PH, 42 G, 219 CP and 90 AP subjects. The presence and levels of A.a, red complex (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola), Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus were determined by DNA probes and DNA-DNA hybridization technique. CP and AP subjects presented significantly higher prevalence and levels of A.a, red complex and A. baumannii than G and PH individuals (pperiodontal disease (pperiodontal pathogens and non-oral bacteria alone or in association were strongly associated with periodontitis. Copyright © 2011 Elsevier Ltd. All rights reserved.

    14. [The X+ chronic granulomatous disease as a fabulous model to study the NADPH oxidase complex activation].

      Science.gov (United States)

      Stasia, Marie-José

      2007-05-01

      Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes lack NADPH oxidase activity. Patients with CGD suffer from recurrent bacterial and fungal infections because of the absence of superoxide anions (O2- degrees ) generatingsystem. The NADPH oxidase complex is composed of a membranous cytochrome b558, cytosolic proteins p67phox, p47phox, p40phox and two small GTPases Rac2 and Rap1A. Cytochrome b558 consists of two sub-units gp91phox and p22phox. The most common form of CGD is due to mutations in CYBB gene encoding gp91phox. In some rare cases, the mutated gp91phox is normally expressed but is devoided of oxidase activity. These variants called X+ CGD, have provided interesting informations about oxidase activation mechanisms. However modelization of such variants is necessary to obtain enough biological material for studies at the molecular level. A cellular model (knock-out PLB-985 cells) has been developed for expressing recombinant mutated gp91phox for functional analysis of the oxidase complex. Recent works demonstrated that this cell line genetically deficient in gp91phox is a powerful tool for functional analysis of the NADPH oxidase complex activation.

    15. Health-related fitness profiles in adolescents with complex congenital heart disease.

      Science.gov (United States)

      Klausen, Susanne Hwiid; Wetterslev, Jørn; Søndergaard, Lars; Andersen, Lars L; Mikkelsen, Ulla Ramer; Dideriksen, Kasper; Zoffmann, Vibeke; Moons, Philip

      2015-04-01

      This study investigates whether subgroups of different health-related fitness (HrF) profiles exist among girls and boys with complex congenital heart disease (ConHD) and how these are associated with lifestyle behaviors. We measured the cardiorespiratory fitness, muscle strength, and body composition of 158 adolescents aged 13-16 years with previous surgery for a complex ConHD. Data on lifestyle behaviors were collected concomitantly between October 2010 and April 2013. A cluster analysis was conducted to identify profiles with similar HrF. For comparisons between clusters, multivariate analyses of covariance were used to test the differences in lifestyle behaviors. Three distinct profiles were formed: (1) Robust (43, 27%; 20 girls and 23 boys); (2) Moderately Robust (85, 54%; 37 girls and 48 boys); and (3) Less robust (30, 19%; 9 girls and 21 boys). The participants in the Robust clusters reported leading a physically active lifestyle and participants in the Less robust cluster reported leading a sedentary lifestyle. Diagnoses were evenly distributed between clusters. The cluster analysis attributed some of the variability in cardiorespiratory fitness among adolescents with complex ConHD to lifestyle behaviors and physical activity. Profiling of HrF offers a valuable new option in the management of person-centered health promotion. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

    16. Decreased Complexity in Alzheimer's Disease: Resting-State fMRI Evidence of Brain Entropy Mapping

      Directory of Open Access Journals (Sweden)

      Bin Wang

      2017-11-01

      Full Text Available Alzheimer's disease (AD is a frequently observed, irreversible brain function disorder among elderly individuals. Resting-state functional magnetic resonance imaging (rs-fMRI has been introduced as an alternative approach to assessing brain functional abnormalities in AD patients. However, alterations in the brain rs-fMRI signal complexities in mild cognitive impairment (MCI and AD patients remain unclear. Here, we described the novel application of permutation entropy (PE to investigate the abnormal complexity of rs-fMRI signals in MCI and AD patients. The rs-fMRI signals of 30 normal controls (NCs, 33 early MCI (EMCI, 32 late MCI (LMCI, and 29 AD patients were obtained from the Alzheimer's disease Neuroimaging Initiative (ADNI database. After preprocessing, whole-brain entropy maps of the four groups were extracted and subjected to Gaussian smoothing. We performed a one-way analysis of variance (ANOVA on the brain entropy maps of the four groups. The results after adjusting for age and sex differences together revealed that the patients with AD exhibited lower complexity than did the MCI and NC controls. We found five clusters that exhibited significant differences and were distributed primarily in the occipital, frontal, and temporal lobes. The average PE of the five clusters exhibited a decreasing trend from MCI to AD. The AD group exhibited the least complexity. Additionally, the average PE of the five clusters was significantly positively correlated with the Mini-Mental State Examination (MMSE scores and significantly negatively correlated with Functional Assessment Questionnaire (FAQ scores and global Clinical Dementia Rating (CDR scores in the patient groups. Significant correlations were also found between the PE and regional homogeneity (ReHo in the patient groups. These results indicated that declines in PE might be related to changes in regional functional homogeneity in AD. These findings suggested that complexity analyses using PE

    17. Congenital heart disease: interrelation between German diagnosis-related groups system and Aristotle complexity score.

      Science.gov (United States)

      Sinzobahamvya, Nicodème; Photiadis, Joachim; Arenz, Claudia; Kopp, Thorsten; Hraska, Viktor; Asfour, Boulos

      2010-06-01

      The Disease-Related Groups (DRGs) system postulates that inpatient stays with similar levels of clinical complexity are expected to consume similar amounts of resources. This, applied to surgery of congenital heart disease, suggests that the higher the complexity of procedures as estimated by the Aristotle complexity score, the higher hospital reimbursement should be. This study analyses how much case-mix index (CMI) generated by German DRG 2009 version correlates with Aristotle score. A total of 456 DRG cases of year 2008 were regrouped according to German DRG 2009 and related cost-weight values and overall CMI evaluated. Corresponding Aristotle basic and comprehensive complexity scores (ABC and ACC) and levels were determined. Associated surgical performance (Aristotle score times hospital survival) was estimated. Spearman 'r' correlation coefficients were calculated between Aristotle scores and cost-weights. Goodness of fit 'r(2)' from derived regression was determined. Correlation was estimated to be optimal if Spearman 'r' and derived goodness of fit 'r(2)' approached 1 value. CMI was 8.787 while mean ABC and ACC scores were 7.64 and 9.27, respectively. Hospital survival was 98.5%: therefore, surgical performance attained 7.53 (ABC score) and 9.13 (ACC score). ABC and ACC scores and levels positively correlated with cost-weights. With Spearman 'r' of 1 and goodness of fit 'r(2)' of 0.9790, scores of the six ACC levels correlated at best. The equation was y = 0.5591 + 0.939x, in which y stands for cost-weight (CMI) and x for score of ACC level. ACC score correlates almost perfectly with corresponding cost-weights (CMI) generated by the German DRG 2009. It could therefore be used as the basis for hospital reimbursement to compensate in conformity with procedures' complexity. Extrapolated CMI in this series would be 9.264. Modulation of reimbursement according to surgical performance could be established and thus 'reward' quality in congenital heart surgery

    18. Genomic screening for dissection of a complex disease: The multiple sclerosis phenotype

      Energy Technology Data Exchange (ETDEWEB)

      Haines, J.L.; Bazyk, A.; Gusella, J.F. [Massachusetts General Hospital, Boston, MA (United States)] [and others

      1994-09-01

      Application of positional cloning to diseases with a complex etiology is fraught with problems. These include undefined modes of inheritance, heterogeneity, and epistasis. Although microsatellite markers now make genotyping the genome a straightforward task, no single analytical method is available to efficiently and accurately use these data for a complex disease. We have developed a multi-stage genomic screening strategy which uses a combination of non-parametric approaches (Affected Pedigree Member (APM) linkage analysis and robust sib pair analysis (SP)), and the parametric lod score approach (using four different genetic models). To warrant follow-up, a marker must have two or more of: a nominal P value of 0.05 or less on the non-parametric tests, or a lod score greater than 1.0 for any model. Two adjacent markers each fulfilling one criterion are also considered for follow-up. These criteria were determined both by simulation studies and our empirical experience in screening a large number of other disorders. We applied this approach to multiple sclerosis (MS), a complex neurological disorder with a strong but ill-defined genetic component. Analysis of the first 91 markers from our screen of 55 multiplex families found 5 markers which met the SP criteria, 13 markers which met the APM criteria, and 8 markers which met the lod score criteria. Five regions (on chromosomes 2, 4, 7, 14, and 19) met our overall criteria. However, no single method identified all of these regions, suggesting that each method is sensitive to various (unknown) influences. The chromosome 14 results were not supported by follow-up typing and analysis of markers in that region, but the chromosome 19 results remain well supported. Updated screening results will be presented.

    19. [Children's medically complex diseases unit. A model required in all our hospitals].

      Science.gov (United States)

      Climent Alcalá, Francisco José; García Fernández de Villalta, Marta; Escosa García, Luis; Rodríguez Alonso, Aroa; Albajara Velasco, Luis Adolfo

      2018-01-01

      The increase in survival of children with severe diseases has led to the rise of children with chronic diseases, sometimes with lifelong disabilities. In 2008, a unit for the specific care of medically complex children (MCC) was created in Hospital La Paz. To describe the work and care activities of this Unit. Patients and methods An analysis was performed on all discharge reports of the Unit between January 2014 and July 2016. The MCC Unit has 6 beds and daily outpatient clinic. A total of 1,027 patients have been treated since the creation of the unit, with 243 from 2014. The median age was 24.2 months (IQ: 10.21-84.25). The large majority (92.59%) have multiple diseases, the most frequent chronic conditions observed were neurological (76.95%), gastrointestinal (63.78%), and respiratory diseases (61.72%). More than two-thirds (69.54%) of MCC are dependent on technology, 53.49% on respiratory support, and 35.80% on nutritional support. Hospital admission rates have increased annually. There have been 403 admissions since 2014, of which 8.93% were re-admissions within 30 days of hospital discharge. The median stay during 2014-2016 was 6 days (IQ: 3-14). The occupancy rate has been above 100% for this period. Currently, 210 patients remain on follow-up (86.42%), and 11 children (4.53%) were discharged to their referral hospitals. The mortality rate is 9.05% (22 deaths). The main condition of these 22 patients was neurological (9 patients). Infectious diseases were the leading cause of death. MCC should be treated in specialized units in tertiary or high-level hospitals. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

    20. Simulation study of the mechanisms underlying outbreaks of clinical disease caused by Actinobacillus pleuropneumoniae in finishing pigs

      NARCIS (Netherlands)

      Klinkenberg, D; Tobias, T J; Bouma, A; van Leengoed, L A M G; Stegeman, J A

      2014-01-01

      Actinobacillus pleuropneumoniae is a major cause of respiratory disease in pigs. Many farms are endemically infected without apparent disease, but occasionally severe outbreaks of pleuropneumonia occur. To prevent and control these outbreaks without antibiotics, the underlying mechanisms of these

    1. On Advice Complexity of the k-server Problem under Sparse Metrics

      DEFF Research Database (Denmark)

      Gupta, S.; Kamali, S.; López-Ortiz, A.

      2013-01-01

      We consider the k-Server problem under the advice model of computation when the underlying metric space is sparse. On one side, we introduce Θ (1)-competitive algorithms for a wide range of sparse graphs, which require advice of (almost) linear size. Namely, we show that for graphs of size N...... for the 2-server problem on a path metric of size N ≥ 5. Through another lower bound argument, we show that at least n/2 (log α - 1.22) bits of advice is required to obtain an optimal solution for metric spaces of treewidth α, where 4 ≤ α

    2. Complex genetic architecture of cardiac disease in a wild type inbred strain of Drosophila melanogaster.

      Directory of Open Access Journals (Sweden)

      Zhi Zhang

      Full Text Available Natural populations of the fruit fly, Drosophila melanogaster, segregate genetic variation that leads to cardiac disease phenotypes. One nearly isogenic line from a North Carolina peach orchard, WE70, is shown to harbor two genetically distinct heart phenotypes: elevated incidence of arrhythmias, and a dramatically constricted heart diameter in both diastole and systole, with resemblance to restrictive cardiomyopathy in humans. Assuming the source to be rare variants of large effect, we performed Bulked Segregant Analysis using genomic DNA hybridization to Affymetrix chips to detect single feature polymorphisms, but found that the mutant phenotypes are more likely to have a polygenic basis. Further mapping efforts revealed a complex architecture wherein the constricted cardiomyopathy phenotype was observed in individual whole chromosome substitution lines, implying that variants on both major autosomes are sufficient to produce the phenotype. A panel of 170 Recombinant Inbred Lines (RIL was generated, and a small subset of mutant lines selected, but these each complemented both whole chromosome substitutions, implying a non-additive (epistatic contribution to the "disease" phenotype. Low coverage whole genome sequencing was also used to attempt to map chromosomal regions contributing to both the cardiomyopathy and arrhythmia, but a polygenic architecture had to be again inferred to be most likely. These results show that an apparently simple rare phenotype can have a complex genetic basis that would be refractory to mapping by deep sequencing in pedigrees. We present this as a cautionary tale regarding assumptions related to attempts to map new disease mutations on the assumption that probands carry a single causal mutation.

    3. Large-Scale Association Study Confirms Genetic Complexity Underlying Type 2 Diabetes

      OpenAIRE

      Barroso, Inês; Luan, Jian'an; Middelberg, Rita P. S; Harding, Anne-Helen; Franks, Paul W; Jakes, Rupert W; Clayton, David; Schafer, Alan J; O'Rahilly, Stephen; Wareham, Nicholas J

      2003-01-01

      Type 2 diabetes is an increasingly common, serious metabolic disorder with a substantial inherited component. It is characterised by defects in both insulin secretion and action. Progress in identification of specific genetic variants predisposing to the disease has been limited. To complement ongoing positional cloning efforts, we have undertaken a large-scale candidate gene association study. We examined 152 SNPs in 71 candidate genes for association with diabetes status and related phenoty...

    4. Susceptibility genes for lung diseases in the major histocompatibility complex revealed by lung expression quantitative trait loci analysis

      NARCIS (Netherlands)

      Lamontagne, Maxime; Joubert, Philippe; Timens, Wim; Postma, Dirkje S.; Hao, Ke; Nickle, David; Sin, Don D.; Pare, Peter D.; Laviolette, Michel; Bosse, Yohan

      The major histocompatibility complex (MHC) has been linked with hundreds of diseases [1]. The MHC is one of the most complex regions of the human genome, because of the high gene density, extended linkage disequilibrium (LD) and sequence diversity [2]. Recent genome-wide association studies (GWAS)

    5. Functional Connectivity under Optogenetic Control Allows Modeling of Human Neuromuscular Disease.

      Science.gov (United States)

      Steinbeck, Julius A; Jaiswal, Manoj K; Calder, Elizabeth L; Kishinevsky, Sarah; Weishaupt, Andreas; Toyka, Klaus V; Goldstein, Peter A; Studer, Lorenz

      2016-01-07

      Capturing the full potential of human pluripotent stem cell (PSC)-derived neurons in disease modeling and regenerative medicine requires analysis in complex functional systems. Here we establish optogenetic control in human PSC-derived spinal motorneurons and show that co-culture of these cells with human myoblast-derived skeletal muscle builds a functional all-human neuromuscular junction that can be triggered to twitch upon light stimulation. To model neuromuscular disease we incubated these co-cultures with IgG from myasthenia gravis patients and active complement. Myasthenia gravis is an autoimmune disorder that selectively targets neuromuscular junctions. We saw a reversible reduction in the amplitude of muscle contractions, representing a surrogate marker for the characteristic loss of muscle strength seen in this disease. The ability to recapitulate key aspects of disease pathology and its symptomatic treatment suggests that this neuromuscular junction assay has significant potential for modeling of neuromuscular disease and regeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

    6. Studying the Laws of the Thermoviscoplastic Deformation of a Solid Under Nonisothermal Complex Loading. Part 2

      Science.gov (United States)

      Shevchenko, Yu. N.; Terekhov, R. G.

      2001-06-01

      The studies made at the thermoplasticity department of the S. P. Timoshenko Institute of Mechanics are analyzed. These studies involve experimental validations of the kinematic equation of creep damage and the constitutive equations describing simple thermoviscoelastoplastic loading, with history, of isotropic and transversally isotropic bodies, for elastoviscoplastic deformation of bodies along slightly curved paths, for complex loading along arbitrary paths lying either in a plane arbitrarily oriented in the five-dimensional space of stresses or in one coordinate plane, and for elastoplastic deformation of a body's elements along paths of moderate curvature and small torsion

    7. Home-based interval training increases endurance capacity in adults with complex congenital heart disease.

      Science.gov (United States)

      Sandberg, Camilla; Hedström, Magnus; Wadell, Karin; Dellborg, Mikael; Ahnfelt, Anders; Zetterström, Anna-Klara; Öhrn, Amanda; Johansson, Bengt

      2017-12-04

      The beneficial effects of exercise training in acquired heart failure and coronary artery disease are well known and have been implemented in current treatment guidelines. Knowledge on appropriate exercise training regimes for adults with congenital heart disease is limited, thus further studies are needed. The aim of this study was to examine the effect of home-based interval exercise training on maximal endurance capacity and peak exercise capacity. Randomized controlled trial. Twenty-six adults with complex congenital heart disease were recruited from specialized units for adult congenital heart disease. Patients were randomized to either an intervention group-12 weeks of home-based interval exercise training on a cycle ergometer (n = 16), or a control group (n = 10). The latter was instructed to maintain their habitual physical activities. An incremental cardiopulmonary exercise test and a constant work rate cardiopulmonary exercise test at 75% of peak workload were performed preintervention and postintervention. Twenty-three patients completed the protocol and were followed (intervention n = 13, control n = 10). Postintervention exercise time at constant work rate cardiopulmonary exercise test increased in the intervention group compared to controls (median[range] 12[-4 to 52]min vs 0[-4 to 5]min, P = .001). At incremental cardiopulmonary exercise test, peak VO 2 increased 15% within the intervention group (P = .019) compared to 2% within the control group (P = .8). However, in comparison between the groups no difference was found (285[-200 to 535] ml/min vs 17[-380 to 306] ml/min, P = .10). In addition, peak workload at incremental cardiopulmonary exercise test increased in the intervention group compared to controls (20[-10 to 70]W vs 0[-20 to 15]W, P = .003). Home-based interval exercise training increased endurance capacity and peak exercise capacity in adults with complex congenital heart disease. Aerobic endurance

    8. Cellular immune responses to ESAT-6 discriminate between patients with pulmonary disease due to Mycobacterium avium complex and those with pulmonary disease due to Mycobacterium tuberculosis

      DEFF Research Database (Denmark)

      Lein, A D; von Reyn, C F; Ravn, P

      1999-01-01

      ESAT-6 (for 6-kDa early secreted antigenic target) is a secreted antigen found almost exclusively in organisms of the Mycobacterium tuberculosis complex. We compared in vitro gamma interferon (IFN-gamma) responses by peripheral blood mononuclear cells to this antigen in patients with pulmonary...... disease due to either Mycobacterium avium complex (MAC) or Mycobacterium tuberculosis with those in healthy, skin test-negative, control subjects. Significant IFN-gamma responses to ESAT-6 were detected in 16 (59%) of 27 M. tuberculosis pulmonary disease patients, 0 (0%) of 8 MAC disease patients, and 0...

    9. Consequence of Mycobacterium avium complex pulmonary disease judging from the change of the chest CT image

      International Nuclear Information System (INIS)

      Fujiwara, Kiyohiro

      2008-01-01

      The long term consequence of the disease in Mycobacterium avium complex pulmonary disease (MACPD) is scarcely reported. This paper describes consequences of CT images and clinical symptoms in MACPD patients with rather poorer prognosis than usual during chemotherapy for one or more years in authors' hospital until May 2007. Subjects are 17 patients (average age 65.3 y, M 6/F 11) diagnosed as MACPD by the criteria by Jap. Soc. Tuberculosis (2003), whose follow up period is 14-105 (av. 58.1) months, and are classified in tuberculoid type (tt, 2 cases), bronchiectasis post surgery (2) and bronchia type (bt, 13, mostly primary MACPD). Chemotherapy is done with clarithromycin (CAM)+ethambutol (EB)+rifampicin (RHP) (+streptomycin (SM) for progression). Consequences of typical chest CT images are presented for each classification in this paper. Cavitation is seen even in bt as well as in tt and, if observed, the disease tends to deteriorate. In the secondary MACPD post surgery, the exacerbation of clinical symptom is often more severe despite slow changes in CT finding than in bt. Thus, careful follow up is necessary for the two cases above. (R.T.)

    10. Tissue Tropism in Host Transcriptional Response to Members of the Bovine Respiratory Disease Complex.

      Science.gov (United States)

      Behura, Susanta K; Tizioto, Polyana C; Kim, JaeWoo; Grupioni, Natalia V; Seabury, Christopher M; Schnabel, Robert D; Gershwin, Laurel J; Van Eenennaam, Alison L; Toaff-Rosenstein, Rachel; Neibergs, Holly L; Regitano, Luciana C A; Taylor, Jeremy F

      2017-12-20

      Bovine respiratory disease (BRD) is the most common infectious disease of beef and dairy cattle and is characterized by a complex infectious etiology that includes a variety of viral and bacterial pathogens. We examined the global changes in mRNA abundance in healthy lung and lung lesions and in the lymphoid tissues bronchial lymph node, retropharyngeal lymph node, nasopharyngeal lymph node and pharyngeal tonsil collected at the peak of clinical disease from beef cattle experimentally challenged with either bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Mannheimia haemolytica or Mycoplasma bovis. We identified signatures of tissue-specific transcriptional responses indicative of tropism in the coordination of host's immune tissue responses to infection by viral or bacterial infections. Furthermore, our study shows that this tissue tropism in host transcriptional response to BRD pathogens results in the activation of different networks of response genes. The differential crosstalk among genes expressed in lymphoid tissues was predicted to be orchestrated by specific immune genes that act as 'key players' within expression networks. The results of this study serve as a basis for the development of innovative therapeutic strategies and for the selection of cattle with enhanced resistance to BRD.

    11. The Impact of Organo-Mineral Complexation on Mineral Weathering in the Soil Zone under Unsaturated Conditions

      Science.gov (United States)

      Michael, H. A.; Tan, F.; Yoo, K.; Imhoff, P. T.

      2017-12-01

      While organo-mineral complexes can protect organic matter (OM) from biodegradation, their impact on soil mineral weathering is not clear. Previous bench-scale experiments that focused on specific OM and minerals showed that the adsorption of OM to mineral surfaces accelerates the dissolution of some minerals. However, the impact of natural organo-mineral complexes on mineral dissolution under unsaturated conditions is not well known. In this study, soil samples prepared from an undisturbed forest site were used to determine mineral weathering rates under differing conditions of OM sorption to minerals. Two types of soil samples were generated: 1) soil with OM (C horizon soil from 84-100cm depth), and 2) soil without OM (the same soil as in 1) but with OM removed by heating to 350°for 24 h). Soil samples were column-packed and subjected to intermittent infiltration and drainage to mimic natural rainfall events. Each soil sample type was run in duplicate. The unsaturated condition was created by applying gas pressure to the column, and the unsaturated chemical weathering rates during each cycle were calculated from the effluent concentrations. During a single cycle, when applying the same gas pressure, soils with OM retained more moisture than OM-removed media, indicating increased water retention capacity under the impact of OM. This is consistent with the water retention data measured by evaporation experiments (HYPROP) and the dew point method (WP4C Potential Meter). Correspondingly, silicon (Si) denudation rates indicated that dissolution of silicate minerals was 2-4 times higher in OM soils, suggesting that organo-mineral complexes accelerate mineral dissolution under unsaturated conditions. When combining data from all cycles, the results showed that Si denudation rates were positively related to soil water content: denundation rate increased with increasing water content. Therefore, natural mineral chemical weathering under unsaturated conditions, while

    12. Bacteria of the Burkholderia cepacia complex are cyanogenic under biofilm and colonial growth conditions

      Directory of Open Access Journals (Sweden)

      Hoshino Saiko

      2008-06-01

      Full Text Available Abstract Background The Burkholderia cepacia complex (Bcc is a collection of nine genotypically distinct but phenotypically similar species. They show wide ecological diversity and include species that are used for promoting plant growth and bio-control as well species that are opportunistic pathogens of vulnerable patients. Over recent years the Bcc have emerged as problematic pathogens of the CF lung. Pseudomonas aeruginosa is another important CF pathogen. It is able to synthesise hydrogen cyanide (HCN, a potent inhibitor of cellular respiration. We have recently shown that HCN production by P. aeruginosa may have a role in CF pathogenesis. This paper describes an investigation of the ability of bacteria of the Bcc to make HCN. Results The genome of Burkholderia cenocepacia has 3 putative HCN synthase encoding (hcnABC gene clusters. B. cenocepacia and all 9 species of the Bcc complex tested were able to make cyanide at comparable levels to P. aeruginosa, but only when grown surface attached as colonies or during biofilm growth on glass beads. In contrast to P. aeruginosa and other cyanogenic bacteria, cyanide was not detected during planktonic growth of Bcc strains. Conclusion All species in the Bcc are cyanogenic when grown as surface attached colonies or as biofilms.

    13. A Socio-Institutional Approach to Brighten Complexity under Agricultural Pest Invasion Conditions

      Directory of Open Access Journals (Sweden)

      David Romero Manrique de Lara

      2016-06-01

      Full Text Available This study illustrates the inherent complexity and uncertainties surrounding the Guatemalan potato moth pest on Tenerife that has affected potato crops for several decades using a Socio-Institutional methodology and a farmers’ focus group. It focuses on detecting major socioeconomic and environmental impacts caused by the pest. It identifies the stakeholders and historical decisions involved as well as systemic uncertainties. This methodology generates socially robust knowledge and introduces new variables into future decision-making processes. The results show that the efforts made so far to control the pest, based on technical and scientific knowledge, have not been commensurate with the enormous complexity of the issue. Novel alternatives to eliminate the plague and new recommendations have emerged after the application of the methodology. These alternatives and recommendations are related to breaking the reproduction cycle of the moth; promoting agro-ecological strategies and participatory processes; and dealing with uncertainties such as climate change or loss of agro-biodiversity on the island.

    14. Neuronal complex I deficiency occurs throughout the Parkinson's disease brain, but is not associated with neurodegeneration or mitochondrial DNA damage.

      Science.gov (United States)

      Flønes, Irene H; Fernandez-Vizarra, Erika; Lykouri, Maria; Brakedal, Brage; Skeie, Geir Olve; Miletic, Hrvoje; Lilleng, Peer K; Alves, Guido; Tysnes, Ole-Bjørn; Haugarvoll, Kristoffer; Dölle, Christian; Zeviani, Massimo; Tzoulis, Charalampos

      2018-03-01

      Mitochondrial complex I deficiency occurs in the substantia nigra of individuals with Parkinson's disease. It is generally believed that this phenomenon is caused by accumulating mitochondrial DNA damage in neurons and that it contributes to the process of neurodegeneration. We hypothesized that if these theories are correct, complex I deficiency should extend beyond the substantia nigra to other affected brain regions in Parkinson's disease and correlate tightly with neuronal mitochondrial DNA damage. To test our hypothesis, we employed a combination of semiquantitative immunohistochemical analyses, Western blot and activity measurements, to assess complex I quantity and function in multiple brain regions from an extensively characterized population-based cohort of idiopathic Parkinson's disease (n = 18) and gender and age matched healthy controls (n = 11). Mitochondrial DNA was assessed in single neurons from the same areas by real-time PCR. Immunohistochemistry showed that neuronal complex I deficiency occurs throughout the Parkinson's disease brain, including areas spared by the neurodegenerative process such as the cerebellum. Activity measurements in brain homogenate confirmed a moderate decrease of complex I function, whereas Western blot was less sensitive, detecting only a mild reduction, which did not reach statistical significance at the group level. With the exception of the substantia nigra, neuronal complex I loss showed no correlation with the load of somatic mitochondrial DNA damage. Interestingly, α-synuclein aggregation was less common in complex I deficient neurons in the substantia nigra. We show that neuronal complex I deficiency is a widespread phenomenon in the Parkinson's disease brain which, contrary to mainstream theory, does not follow the anatomical distribution of neurodegeneration and is not associated with the neuronal load of mitochondrial DNA mutation. Our findings suggest that complex I deficiency in Parkinson's disease can

    15. The challenge for genetic epidemiologists: how to analyze large numbers of SNPs in relation to complex diseases

      NARCIS (Netherlands)

      Heidema, A.G.; Boer, J.M.A.; Nagelkerke, N.; Mariman, E.C.M.; A, van der D.L.; Feskens, E.J.M.

      2006-01-01

      Genetic epidemiologists have taken the challenge to identify genetic polymorphisms involved in the development of diseases. Many have collected data on large numbers of genetic markers but are not familiar with available methods to assess their association with complex diseases. Statistical methods

    16. Assembly factors as a new class of disease genes for mitochondrial complex I deficiency: cause, pathology and treatment options.

      NARCIS (Netherlands)

      Nouws, J.; Nijtmans, L.G.J.; Smeitink, J.A.M.; Vogel, R.O.

      2012-01-01

      Complex I deficiency is the most frequent cause of oxidative phosphorylation disorders. The disease features a large diversity of clinical symptoms often leading to progressive encephalomyopathies with a fatal outcome. There is currently no cure, and although disease-causing mutations have been

    17. Challenges of malaria diagnosis in clinical settings and disease surveillance under reduced malaria burden in Tanzania

      Directory of Open Access Journals (Sweden)

      Donath Samuel Tarimo

      2017-01-01

      Full Text Available Febrile illnesses that are caused by malaria and other infectious diseases are a major cause of morbidity and mortality in sub-Saharan Africa. In malaria endemic countries, malaria is considered as one of the most serious febrile illnesses. Over the last two decades, major investment in malaria control has witnessed a major achievement in decline of malaria burden, however, other causes of febrile illnesses have remained prevalent. The decline in malaria burden poses challenges for the diagnosis of malaria in clinical settings, research and disease surveillance. This review highlights the challenges facing the diagnosis of malarial and nonmalarial fevers under reduced malaria burden from the perspectives of parasite diagnosis and interpretations of the diagnoses of malarial and non-malarial fevers, and the possible approaches to address the challenges for a better understanding of the dynamics of febrile illnesses under reduced malaria burden.

    18. Modeling of agent-based complex network under cyber-violence

      Science.gov (United States)

      Huang, Chuanchao; Hu, Bin; Jiang, Guoyin; Yang, Ruixian

      2016-09-01

      Public opinion reversal arises frequently in modern society, due to the continual interactions between individuals and their surroundings. To explore the underlying mechanism of the interesting social phenomenon, we introduce here a new model which takes the relationship between the individual cognitive bias and their corresponding choice behavior into account. Experimental results show that the proposed model can provide an accurate description of the entire process of public opinion reversal under the internet environment and the distribution of cognitive bias plays the role of a measure for the reversal probability. In particular, the application to cyber violence, a typical example of public opinion reversal, suggests that public opinion is prone to be seriously affected by the spread of misleading and harmful information. Furthermore, our model is very robust and thus can be employed to other empirical studies that concern the sudden change of public and personal opinion on internet.

    19. Temperate mountain forest biodiversity under climate change: compensating negative effects by increasing structural complexity.

      Science.gov (United States)

      Braunisch, Veronika; Coppes, Joy; Arlettaz, Raphaël; Suchant, Rudi; Zellweger, Florian; Bollmann, Kurt

      2014-01-01

      Species adapted to cold-climatic mountain environments are expected to face a high risk of range contractions, if not local extinctions under climate change. Yet, the populations of many endothermic species may not be primarily affected by physiological constraints, but indirectly by climate-induced changes of habitat characteristics. In mountain forests, where vertebrate species largely depend on vegetation composition and structure, deteriorating habitat suitability may thus be mitigated or even compensated by habitat management aiming at compositional and structural enhancement. We tested this possibility using four cold-adapted bird species with complementary habitat requirements as model organisms. Based on species data and environmental information collected in 300 1-km2 grid cells distributed across four mountain ranges in central Europe, we investigated (1) how species' occurrence is explained by climate, landscape, and vegetation, (2) to what extent climate change and climate-induced vegetation changes will affect habitat suitability, and (3) whether these changes could be compensated by adaptive habitat management. Species presence was modelled as a function of climate, landscape and vegetation variables under current climate; moreover, vegetation-climate relationships were assessed. The models were extrapolated to the climatic conditions of 2050, assuming the moderate IPCC-scenario A1B, and changes in species' occurrence probability were quantified. Finally, we assessed the maximum increase in occurrence probability that could be achieved by modifying one or multiple vegetation variables under altered climate conditions. Climate variables contributed significantly to explaining species occurrence, and expected climatic changes, as well as climate-induced vegetation trends, decreased the occurrence probability of all four species, particularly at the low-altitudinal margins of their distribution. These effects could be partly compensated by modifying

    20. Temperate mountain forest biodiversity under climate change: compensating negative effects by increasing structural complexity.

      Directory of Open Access Journals (Sweden)

      Veronika Braunisch

      Full Text Available Species adapted to cold-climatic mountain environments are expected to face a high risk of range contractions, if not local extinctions under climate change. Yet, the populations of many endothermic species may not be primarily affected by physiological constraints, but indirectly by climate-induced changes of habitat characteristics. In mountain forests, where vertebrate species largely depend on vegetation composition and structure, deteriorating habitat suitability may thus be mitigated or even compensated by habitat management aiming at compositional and structural enhancement. We tested this possibility using four cold-adapted bird species with complementary habitat requirements as model organisms. Based on species data and environmental information collected in 300 1-km2 grid cells distributed across four mountain ranges in central Europe, we investigated (1 how species' occurrence is explained by climate, landscape, and vegetation, (2 to what extent climate change and climate-induced vegetation changes will affect habitat suitability, and (3 whether these changes could be compensated by adaptive habitat management. Species presence was modelled as a function of climate, landscape and vegetation variables under current climate; moreover, vegetation-climate relationships were assessed. The models were extrapolated to the climatic conditions of 2050, assuming the moderate IPCC-scenario A1B, and changes in species' occurrence probability were quantified. Finally, we assessed the maximum increase in occurrence probability that could be achieved by modifying one or multiple vegetation variables under altered climate conditions. Climate variables contributed significantly to explaining species occurrence, and expected climatic changes, as well as climate-induced vegetation trends, decreased the occurrence probability of all four species, particularly at the low-altitudinal margins of their distribution. These effects could be partly compensated

    1. Designing automation for complex work environments under different levels of stress.

      Science.gov (United States)

      Sauer, Juergen; Nickel, Peter; Wastell, David

      2013-01-01

      This article examines the effectiveness of different forms of static and adaptable automation under low- and high-stress conditions. Forty participants were randomly assigned to one of four experimental conditions, comparing three levels of static automation (low, medium and high) and one level of adaptable automation, with the environmental stressor (noise) being varied as a within-subjects variable. Participants were trained for 4 h on a simulation of a process control environment, called AutoCAMS, followed by a 2.5-h testing session. Measures of performance, psychophysiology and subjective reactions were taken. The results showed that operators preferred higher levels of automation under noise than under quiet conditions. A number of parameters indicated negative effects of noise exposure, such as performance impairments, physiological stress reactions and higher mental workload. It also emerged that adaptable automation provided advantages over low and intermediate static automation, with regard to mental workload, effort expenditure and diagnostic performance. The article concludes that for the design of automation a wider range of operational scenarios reflecting adverse as well as ideal working conditions needs to be considered. Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.

    2. A Portable Kit for Rapid Diagnosis of Infectious Diseases under Field Conditions

      Science.gov (United States)

      1980-08-14

      counter Wallis, C. & Melnick , J. L. (1971). Enhanced detection current immunoelectrophoresis. Singapore Medical of Australia antigen in serum hepatitis...RESEARC CEWlE iir.’c.rpro~net~. P. 0. BOX 85122 ’i’J v’il bz la blact &Z SAN DIEGO, CALIFORNIA 92138 NAVAL MEDICAL RESEARCH AND) DEVELOPMENT COMMAND...DIAGNOSIS of INFECTIOUS DISEASES under FIELD CONDITIONS I / Warren R. Sanborn Head, Microbiology Branch Biological Sciences Division Naval Health

    3. Limited value of transbronchial lung biopsy for diagnosing Mycobacterium avium complex lung disease.

      Science.gov (United States)

      Sekine, Akimasa; Saito, Takefumi; Satoh, Hiroaki; Morishita, Yukio; Tsunoda, Yoshiya; Tanaka, Toru; Yatagai, Yohei; Lin, Shih-Yuen; Miyazaki, Kunihiko; Miura, Yukiko; Hayashihara, Kenji

      2017-11-01

      It remains unclear whether transbronchial lung biopsy (TBLB) is useful for diagnosing Mycobacterium avium complex (MAC) lung disease. Thirty-eight consecutive patients with MAC lung disease, who were evaluated with TBLB tissue culture between June 2006 and May 2010, were included. Bronchial washing (BW) and histopathological evaluation were performed in all patients. The positivity rates of BW and TBLB tissue culture, and typical histopathological findings for MAC disease were investigated. Furthermore, all patients were divided into two groups according to the presence of intrabronchial purulent or mucopurulent secretion and the clinical, bacteriological and pathological characteristics were compared between the two groups. The positive culture rates of BW and TBLB specimens for MAC were 100% (38 patients) and 28.9% (11 patients). BW materials were much more sensitive for culture positivity than TBLB specimens (P present in the TBLB specimens of only 11 patients (28.9%). Intrabronchial secretion was identified in 15 patients (39.5%, secretion-positive group) and absent in 23 patients (60.5%, secretion-negative group). Typical histopathological findings for MAC disease were more common in the secretion-positive group than in the secretion-negative group (53.3% vs 13.0%, P = 0.01), although the radiological classification and smear positivity of BW were not different between the two groups. TBLB for pathological and bacterial investigations would provide only a limited value for MAC diagnosis. Moreover, the presence of intrabronchial secretion may be an important manifestation of ongoing airway damage, which would require early treatment. © 2016 John Wiley & Sons Ltd.

    4. A complex protein derivative acts as biogenic elicitor of grapevine resistance against powdery mildew under field conditions

      Directory of Open Access Journals (Sweden)

      Andrea eNesler

      2015-09-01

      Full Text Available Powdery mildew caused by Erysiphe necator is one of the most important grapevine diseases in several viticulture areas, and high fungicide input is required to control it. However, numerous synthetic chemical pesticides are under scrutiny due to concerns about their impact on human health and the environment. Biopesticides, such as biogenic elicitors, are a promising alternative to chemical fungicides. Although several studies have reported on effective elicitors against grapevine diseases, their efficacy under field conditions has not been investigated extensively or has occurred at rather limited levels. Our goal was to examine the efficacy of a protein-based composition, namely nutrient broth (NB, against powdery mildew under field conditions and to characterize its mechanism of action. Weekly treatments with NB was highly effective in controlling powdery mildew on grapevine across seasons with different disease pressures. The level of disease control achieved with NB was comparable to standard fungicide treatments both on leaves and bunches across three different years. NB has no direct toxic effect on the germination of E. necator conidia, and it activates plant resistance with both systemic and translaminar effect in experiments with artificial inoculation under controlled conditions. NB induced the expression of defense-related genes in grapevine, demonstrating stimulation of plant defense mechanisms, prior to and in the early stages of pathogen infection. NB is a natural derivative from meat and yeast, substances that tend not to raise concerns about toxicological and ecotoxicological properties. NB represents a valid control tool for integrated plant protection programs against powdery mildew, to reduce the use of synthetic pesticides on grapevine.

    5. Non-linear increase of respiratory diseases and their costs under severe air pollution.

      Science.gov (United States)

      Shen, Ying; Wu, Yiyun; Chen, Guangdi; Van Grinsven, Hans J M; Wang, Xiaofeng; Gu, Baojing; Lou, Xiaoming

      2017-05-01

      China is experiencing severe and persistent air pollution, with concentrations of fine particulate matters (PM 2.5 ) reaching unprecedentedly high levels in many cities. Quantifying the detrimental effects on health and their costs derived from high PM 2.5 levels is crucial because of the unsolved challenges to mitigate air pollution in the following decades. Using the daily monitoring data on PM 2.5 concentrations and clinic visits, we found a non-linear increase of respiratory diseases, but not for other diseases (e.g., digestive diseases) under severe air pollution. We found an increase of respiratory diseases by 1% for each 10 μg m -3 increase in PM 2.5 when the annual average daily PM 2.5 concentration was less than 50 μg m -3 ; while this ratio was doubled (around 2%) with the daily PM 2.5 concentration larger than 50 μg m -3 . Under severe air pollution (PM 2.5 concentration >150 μg m -3 ), the respiratory diseases increased by over 50% compared to that in clean days. Children are more sensitive to the severe air pollution. The increase of clinic visits, especially for adults, was observed mainly in bigger (>500 beds) hospitals. Re-allocating medical resources (e.g., doctors) from big hospitals to community hospitals can benefit the respiratory patients due to air pollution. The total medical cost of clinic visits of respiratory diseases derived from PM 2.5 pollution was estimated at 17.2-57.0 billion Yuan in 2014 in China, accounting for 0.5-1.6% of national total health expenditure. Because these medical costs only represent a small part of total health cost derived from air pollution, the reduction of associated health costs would be an important co-benefit of implementation of air pollution preventive strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

    6. Modeling infectious disease dynamics in the complex landscape of global health

      Science.gov (United States)

      Heesterbeek, Hans; Anderson, Roy; Andreasen, Viggo; Bansal, Shweta; De Angelis, Daniela; Dye, Chris; Eames, Ken; Edmunds, John; Frost, Simon; Funk, Sebastian; Hollingsworth, Deirdre; House, Thomas; Isham, Valerie; Klepac, Petra; Lessler, Justin; Lloyd-Smith, James; Metcalf, Jessica; Mollison, Denis; Pellis, Lorenzo; Pulliam, Juliet; Roberts, Mick; Viboud, Cecile

      2015-01-01

      Despite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of infections play out on a wide range of interconnected temporal, organizational and spatial scales, which even within a single pathogen often span hours to months, cellular to ecosystem levels, and local to pandemic spread. Some pathogens are directly transmitted between individuals of a single species, while others circulate among multiple hosts, need arthropod vectors, or can survive in environmental reservoirs. Many factors, including increasing antimicrobial resistance, increased human connectivity, and dynamic human behavior, raise prevention and control from formerly national to international issues. In the face of this complexity, mathematical models offer essential tools for synthesizing information to understand epidemiological patterns, and for developing the quantitative evidence base for decision-making in global health. PMID:25766240

    7. Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex.

      Directory of Open Access Journals (Sweden)

      Laurel J Gershwin

      Full Text Available Bovine respiratory disease complex (BRDC is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus, which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described.

    8. Global Dynamics of Infectious Disease with Arbitrary Distributed Infectious Period on Complex Networks

      Directory of Open Access Journals (Sweden)

      Xiaoguang Zhang

      2014-01-01

      Full Text Available Most of the current epidemic models assume that the infectious period follows an exponential distribution. However, due to individual heterogeneity and epidemic diversity, these models fail to describe the distribution of infectious periods precisely. We establish a SIS epidemic model with multistaged progression of infectious periods on complex networks, which can be used to characterize arbitrary distributions of infectious periods of the individuals. By using mathematical analysis, the basic reproduction number R0 for the model is derived. We verify that the R0 depends on the average distributions of infection periods for different types of infective individuals, which extend the general theory obtained from the single infectious period epidemic models. It is proved that if R0<1, then the disease-free equilibrium is globally asymptotically stable; otherwise the unique endemic equilibrium exists such that it is globally asymptotically attractive. Finally numerical simulations hold for the validity of our theoretical results is given.

    9. Genetics of graft-versus-host disease: the major histocompatibility complex.

      Science.gov (United States)

      Petersdorf, Effie W

      2013-01-01

      Graft-versus-host disease (GVHD) is a potentially life-threatening complication of allogeneic hematopoietic cell transplantation. Many genes are presumed to be involved in GVHD, but the best characterized genetic system is that of the human major histocompatibility complex (MHC) located on chromosome 6. Among the hundreds of genes located within the MHC region, the best known and characterized are the classical HLA genes, HLA-A, C, B, DRB1, DQB1, and DPB1. They play a fundamental role in T cell immune responses, and HLA-A, C, and B also function as ligands for the natural killer cell immunoglobulin-like receptors involved in innate immunity. This review highlights the state-of-the art in the field of histocompatibility and immunogenetics of the MHC with respect to genetic risk factors for GVHD. Copyright © 2012 Elsevier Ltd. All rights reserved.

    10. The major histocompatibility complex: a model for understanding graft-versus-host disease.

      Science.gov (United States)

      Petersdorf, Effie W

      2013-09-12

      Acute graft-versus-host disease (GVHD) afflicts as much as 80% of all patients who receive an unrelated donor hematopoietic cell transplant (HCT) for the treatment of blood disorders, even with optimal donor HLA matching and use of prophylactic immunosuppressive agents. Of patients who develop acute GVHD, many are at risk for chronic GVHD and bear the burden of considerable morbidity and lowered quality of life years after transplantation. The immunogenetic basis of GVHD has been the subject of intensive investigation, with the classic HLA genetic loci being the best-characterized determinants. Recent information on the major histocompatibility complex (MHC) region of chromosome 6 as an important source of untyped genetic variation has shed light on novel GVHD determinants. These data open new paradigms for understanding the genetic basis of GVHD.

    11. Evolution in health and medicine Sackler colloquium: Consanguinity, human evolution, and complex diseases.

      Science.gov (United States)

      Bittles, A H; Black, M L

      2010-01-26

      There is little information on inbreeding during the critical early years of human existence. However, given the small founding group sizes and restricted mate choices it seems inevitable that intrafamilial reproduction occurred and the resultant levels of inbreeding would have been substantial. Currently, couples related as second cousins or closer (F >or= 0.0156) and their progeny account for an estimated 10.4% of the global population. The highest rates of consanguineous marriage occur in north and sub-Saharan Africa, the Middle East, and west, central, and south Asia. In these regions even couples who regard themselves as unrelated may exhibit high levels of homozygosity, because marriage within clan, tribe, caste, or biraderi boundaries has been a long-established tradition. Mortality in first-cousin progeny is approximately 3.5% higher than in nonconsanguineous offspring, although demographic, social, and economic factors can significantly influence the outcome. Improving socioeconomic conditions and better access to health care will impact the effects of consanguinity, with a shift from infant and childhood mortality to extended morbidity. At the same time, a range of primarily social factors, including urbanization, improved female education, and smaller family sizes indicate that the global prevalence of consanguineous unions will decline. This shift in marriage patterns will initially result in decreased homozygosity, accompanied by a reduction in the expression of recessive single-gene disorders. Although the roles of common and rare gene variants in the etiology of complex disease remain contentious, it would be expected that declining consanguinity would also be reflected in reduced prevalence of complex diseases, especially in population isolates.

    12. Sero-diagnosis of Mycobacterium avium complex lung disease using serum immunoglobulin A antibody against glycopeptidolipid antigen in Taiwan.

      Directory of Open Access Journals (Sweden)

      Chin-Chung Shu

      Full Text Available BACKGROUND: Lung disease (LD due to non-tuberculous mycobacteria is an important clinical concern. Mycobacterium avium complex (MAC is one of the most common causative agents but the diagnosis of MAC-LD remains challenging. Detection of serum IgA antibody against MAC glycopeptidolipid (GPL has recently been shown to improve the diagnosis of MAC-LD, but has yet to be validated worldwide. METHODS: This prospective study was conducted in a tertiary referral center in northern Taiwan and enrolled patients with MAC-LD, MAC contamination, other lung diseases, and control subjects. Serum immunoglobulin A (IgA antibody against MAC-GPL was detected in the participants and its specificity and sensitivity was assessed. RESULTS: There were 56 patients with MAC-LD, 11 with MAC contamination, 13 M. kansasii-LD, 26 LD due to rapidly-growing mycobacteria (RGM, 48 pulmonary tuberculosis, and 42 household contacts of patients with TB. Patients with MAC-LD were older and 32% of them had an underlying co-morbidity. By logistic regression, serum MAC-GPL IgA level was an independent predictor of MAC-LD among the study subjects and those with culture-positive specimens for MAC. By the receiver operating characteristic curve, serum MAC-GPL IgA had a good power to discriminate MAC-LD from MAC contamination. Under the optimal cut-off value of 0.73 U/mL, its sensitivity and specificity were 60% and 91%, respectively. Among MAC-LD patients, presence of co-morbidity was associated with MAC-GPL <0.73 U/ml in logistic regression analysis. CONCLUSIONS: Measurement of serum anti-MAC-GPL IgA level is useful for the diagnosis of MAC-LD. However, its implement in clinical practice for immuno-compromised hosts needs careful consideration.

    13. A Markov random walk under constraint for discovering overlapping communities in complex networks

      International Nuclear Information System (INIS)

      Jin, Di; Yang, Bo; Liu, Dayou; He, Dongxiao; Liu, Jie; Baquero, Carlos

      2011-01-01

      The detection of overlapping communities in complex networks has motivated recent research in relevant fields. Aiming to address this problem, we propose a Markov-dynamics-based algorithm, called UEOC, which means 'unfold and extract overlapping communities'. In UEOC, when identifying each natural community that overlaps, a Markov random walk method combined with a constraint strategy, which is based on the corresponding annealed network (degree conserving random network), is performed to unfold the community. Then, a cutoff criterion with the aid of a local community function, called conductance, which can be thought of as the ratio between the number of edges inside the community and those leaving it, is presented to extract this emerged community from the entire network. The UEOC algorithm depends on only one parameter whose value can be easily set, and it requires no prior knowledge of the hidden community structures. The proposed UEOC has been evaluated both on synthetic benchmarks and on some real-world networks, and has been compared with a set of competing algorithms. The experimental result has shown that UEOC is highly effective and efficient for discovering overlapping communities

    14. 28-Homobrassinolide Modulate Antenna Complexes and Carbon Skeleton of Brassica juncea L. under Temperature Stress

      Directory of Open Access Journals (Sweden)

      Harpreet Kaur

      2014-08-01

      Full Text Available The aim of present study was to explore the ameliorative impact of 28-homoBL on morpho-physiological attributes, photosynthetic pigments and sugars of Brassica juncea L. exposed to oxidative stress caused by extreme temperatures (4 and 44 °C. For this, experiments were carried out at the Plant Physiology Laboratory, Department of Botany, Punjabi University, Patiala. Effect of different degrees of temperature (4 and 44 °C taking 24 °C as control was studied. 28-homoBL (10-6, 10-9 and 10-12M primed and unprimed seeds of B. juncea L. in terms of antenna complexes and end products of photosynthesis that is total carbohydrates and total soluble sugars was investigated. All concentrations of 28-homoBL used in present study showed different effects on morphology and light quenching pigments. All concentrations of 28-homoBL showed promoting effect on growth and light quenching pigments. The carbon makeup ameliorated positively in stressed and non-stressed components of photosynthetic machinery and 10-9 M 28-homoBL showed best results. In conclusion 28-homoBL showed great potential in protecting the reaction centre of photosynthetic machinery from oxidative stress caused by extreme low and high temperatures but in very dose dependent manner and thus modulate the carbon skeleton of the plant.

    15. Model for Sulfate Diffusion Depth in Concrete under Complex Aggressive Environments and Its Experimental Verification

      Directory of Open Access Journals (Sweden)

      Yingwu Zhou

      2015-01-01

      Full Text Available Sulfate attack is one of the most important factors that lead to the performance deterioration of concrete materials. The progress of the sulfate diffusion depth in concrete is an important index that quantitatively characterizes the rate of concrete damage, cracking, and spalling due to sulfate attacks. The progress of the diffusion depth of concrete to sulfate attack is systematically investigated in this paper by both theoretical and experimental study. A newly time-varying model of the diffusion depth is developed, which has comprehensively considered a mass of parameter of complex environments for the first time. On this basis, a method is further proposed for effectively predicting the residual life of in-service concrete structures subject to sulfate attack. Integrating the data from the self-designed high-temperature dry-wet accelerated corrosion test and a large amount of experimental data reported in the existing literatures, the effectiveness and accuracy of the time-varying model of the diffusion depth by sulfates are finally verified.

    16. Difficult Geotechnical Conditions Under the Palace Complex, Case Study from Cianowice, Near Krakow, Poland

      Science.gov (United States)

      Gil-Mastalerczyk, Joanna; Gil, Regina

      2016-10-01

      The palace complex in Cianowice near Krakow (Lesser Poland, Poland) built around 1890, after 1945 ceased to function as a residential, so the whole building underwent successive devastation. Military activities, ad hoc repairs and long-term shortage of funds in Poland, led to the destruction of the magnificent assumptions. Since 2006. Palace remained completely unsecured and unattended. Performed in 2012-2015 modernization of the historic palace with the expansion of the basement (for residential building multigenerational) has become the occasion for a thorough diagnosis of the prevailing geotechnical conditions and the state of preservation of threads stone and brick walls and vaults chambers basement. Difficult ground conditions, water penetration, lack of insulation of horizontal and vertical has become one of the main causes of the destruction of the foundations and walls of basements. Moisture from the ground, rising damp in the walls (with dissolved salts in it), evaporate causing erosion of the walls. The result it led to the weakening of the structural and breakout layers of walls. The phenomenon has become particularly clear after the geotechnical surveys, excavations and complete discovery of the basement walls. The conducted works related to general technical renovation and restoration, included foundations (lining and insulation), walls, floors and roof. The assumption palace in Cianowice, through appropriate interference with the use of modern and introduction of a new substance, in any manner that emphasizes value and historical monument became possible to restore the important significance of the object and place.

    17. Reduced-order modeling of piezoelectric energy harvesters with nonlinear circuits under complex conditions

      Science.gov (United States)

      Xiang, Hong-Jun; Zhang, Zhi-Wei; Shi, Zhi-Fei; Li, Hong

      2018-04-01

      A fully coupled modeling approach is developed for piezoelectric energy harvesters in this work based on the use of available robust finite element packages and efficient reducing order modeling techniques. At first, the harvester is modeled using finite element packages. The dynamic equilibrium equations of harvesters are rebuilt by extracting system matrices from the finite element model using built-in commands without any additional tools. A Krylov subspace-based scheme is then applied to obtain a reduced-order model for improving simulation efficiency but preserving the key features of harvesters. Co-simulation of the reduced-order model with nonlinear energy harvesting circuits is achieved in a system level. Several examples in both cases of harmonic response and transient response analysis are conducted to validate the present approach. The proposed approach allows to improve the simulation efficiency by several orders of magnitude. Moreover, the parameters used in the equivalent circuit model can be conveniently obtained by the proposed eigenvector-based model order reduction technique. More importantly, this work establishes a methodology for modeling of piezoelectric energy harvesters with any complicated mechanical geometries and nonlinear circuits. The input load may be more complex also. The method can be employed by harvester designers to optimal mechanical structures or by circuit designers to develop novel energy harvesting circuits.

    18. A multi-protein receptor-ligand complex underlies combinatorial dendrite guidance choices in C. elegans

      Science.gov (United States)

      Zou, Wei; Shen, Ao; Dong, Xintong; Tugizova, Madina; Xiang, Yang K; Shen, Kang

      2016-01-01

      Ligand receptor interactions instruct axon guidance during development. How dendrites are guided to specific targets is less understood. The C. elegans PVD sensory neuron innervates muscle-skin interface with its elaborate dendritic branches. Here, we found that LECT-2, the ortholog of leukocyte cell-derived chemotaxin-2 (LECT2), is secreted from the muscles and required for muscle innervation by PVD. Mosaic analyses showed that LECT-2 acted locally to guide the growth of terminal branches. Ectopic expression of LECT-2 from seam cells is sufficient to redirect the PVD dendrites onto seam cells. LECT-2 functions in a multi-protein receptor-ligand complex that also contains two transmembrane ligands on the skin, SAX-7/L1CAM and MNR-1, and the neuronal transmembrane receptor DMA-1. LECT-2 greatly enhances the binding between SAX-7, MNR-1 and DMA-1. The activation of DMA-1 strictly requires all three ligands, which establishes a combinatorial code to precisely target and pattern dendritic arbors. DOI: http://dx.doi.org/10.7554/eLife.18345.001 PMID:27705746

    19. Functional proteomics of light-harvesting complex proteins under varying light-conditions in diatoms.

      Science.gov (United States)

      Büchel, Claudia; Wilhelm, Christian; Wagner, Volker; Mittag, Maria

      2017-10-01

      Comparative proteome analysis of subcellular compartments like thylakoid membranes and their associated supercomplexes can deliver important in-vivo information on the molecular basis of physiological functions which go far beyond to that what can be learnt from transcriptional-based gene expression studies. For instance, the finding that light intensity influences mainly the relative stoichiometry of subunits could be obtained only by high resolution proteome analysis. The high sensitivity of LC-ESI-MS/MS based proteome analysis allows the determination of proteins in very small subfractions along with their non-labeled semi quantitative analysis. This provides insights in the protein-protein interactions of supercomplexes that are the operative units in intact cells. Here, we have focused on functional proteome approaches for the identification of microalgal light-harvesting complex proteins in chloroplasts and the eyespot in general and in detail for those of diatoms that are exposed to varying light conditions. Copyright © 2017 Elsevier GmbH. All rights reserved.

    20. IMMUNOMODULATORY ACTION OF MYELOPIDUM UNDER ITS INCLUSION IN COMPLEX THERAPY OF PATIENTS WITH PENETRATING OCULAR INJURIES

      Directory of Open Access Journals (Sweden)

      T. V. Gavrilova

      2008-01-01

      Full Text Available Abstract. Examination of immunomodulatory actions and clinical efficiency of myelopidum when included into complex therapy that was carried out in 24 male patients with severe (stage 3 penetrating eye injury in the course of trauma treatment. The levels of C-reactive protein, lactoferrin, interleukin (IL-1β, IL-6, and activity of complement system were measured in peripheral blood, and concentrations of lactoferrin and IL-8 were determined in tears. An increase in lactoferrin, C-reactive protein, IL-1β, IL-8, and C5 complement component levels was detected during early post-traumatic period, as compared with data from the control group. As compared to effects of steroid and non-steroid anti-inflammatory drugs included into standard therapy, treatment with myelopidum has led to a more favorable clinical course of traumatic process, and resulted into more pronounced anti-inflammatory effect that was manifested by decrease in lactoferrin and C-reactive protein levels, reduction of IL-1β concentration, and C5 complement component activity. (Med. Immunol., 2008, vol. 10, N 2-3, pp 239-244.

    1. From 'omics' to complex disease: a systems biology approach to gene-environment interactions in cancer

      Directory of Open Access Journals (Sweden)

      Knox Sarah S

      2010-04-01

      Full Text Available Abstract Background Cancer is a complex disease that involves a sequence of gene-environment interactions in a progressive process that cannot occur without dysfunction in multiple systems, including DNA repair, apoptotic and immune functions. Epigenetic mechanisms, responding to numerous internal and external cues in a dynamic ongoing exchange, play a key role in mediating environmental influences on gene expression and tumor development. Hypothesis The hypothesis put forth in this paper addresses the limited success of treatment outcomes in clinical oncology. It states that improvement in treatment efficacy requires a new paradigm that focuses on reversing systemic dysfunction and tailoring treatments to specific stages in the process. It requires moving from a reductionist framework of seeking to destroy aberrant cells and pathways to a transdisciplinary systems biology approach aimed at reversing multiple levels of dysfunction. Conclusion Because there are many biological pathways and multiple epigenetic influences working simultaneously in the expression of cancer phenotypes, studying individual components in isolation does not allow an adequate understanding of phenotypic expression. A systems biology approach using new modeling techniques and nonlinear mathematics is needed to investigate gene-environment interactions and improve treatment efficacy. A broader array of study designs will also be required, including prospective molecular epidemiology, immune competent animal models and in vitro/in vivo translational research that more accurately reflects the complex process of tumor initiation and progression.

    2. Social ecosystem health: confronting the complexity and emergence of infectious diseases

      Directory of Open Access Journals (Sweden)

      Cristina de Albuquerque Possas

      2001-02-01

      Full Text Available The emergence and re-emergence of infectious diseases and their rapid dissemination worldwide are challenging national health systems, particularly in developing countries affected by extreme poverty and environmental degradation. The expectations that new vaccines and drugs and global surveillance would help reverse these trends have been frustrated thus far by the complexity of the epidemiological transition, despite promising prospects for the near future in biomolecular research and genetic engineering. This impasse raises crucial issues concerning conceptual frameworks supporting priority-setting, risk anticipation, and the transfer of science and technology's results to society. This article discusses these issues and the limitations of social and economic sciences on the one hand and ecology on the other as the main theoretical references of the health sciences in confronting the complexity of these issues on their own. The tension between these historically dissociated paradigms is discussed and a transdisciplinary approach is proposed, that of social ecosystem health, incorporating these distinct perspectives into a comprehensive framework.

    3. Synonymous codon usage of genes in polymerase complex of Newcastle disease virus.

      Science.gov (United States)

      Kumar, Chandra Shekhar; Kumar, Sachin

      2017-06-01

      Newcastle disease virus (NDV) is pathogenic to both avian and non-avian species but extensively finds poultry as its primary host and causes heavy economic losses in the poultry industry. In this study, a total of 186 polymerase complex comprising of nucleoprotein (N), phosphoprotein (P), and large polymerase (L) genes of NDV was analyzed for synonymous codon usage. The relative synonymous codon usage and effective number of codons (ENC) values were used to estimate codon usage variation in each gene. Correspondence analysis (COA) was used to study the major trend in codon usage variation. Analyzing the ENC plot values against GC3s (at synonymous third codon position) we concluded that mutational pressure was the main factor determining codon usage bias than translational selection in NDV N, P, and L genes. Moreover, correlation analysis indicated, that aromaticity of N, P, and L genes also influenced the codon usage variation. The varied distribution of pathotypes for N, P, and L gene clearly suggests that change in codon usage for NDV is pathotype specific. The codon usage preference similarity in N, P, and L gene might be detrimental for polymerase complex functioning. The study represents a comprehensive analysis to date of N, P, and L genes codon usage pattern of NDV and provides a basic understanding of the mechanisms for codon usage bias. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

    4. Segregation analysis suggests that keratoconus is a complex non-mendelian disease.

      Science.gov (United States)

      Kriszt, Agnes; Losonczy, Gergely; Berta, András; Vereb, György; Takács, Lili

      2014-11-01

      Complex segregation analysis of 60 unrelated sporadic keratoconus (KC) families was performed to reveal the presumed mode of inheritance in our dataset. Sixty probands, 212 family members and 212 age and gender matched healthy controls underwent clinical and videokeratographic examination. Family aggregation and distribution of videokeratography parameters were examined. Segregation of KSI, KISA and 6mm Fourier asymmetry alone or in covariate analysis with gender or the presence of Fleischer ring, exploring mendelian and non-mendelian models of inheritance was tested using complex segregation analysis with the S.A.G.E. program package. In 145 relatives of probands, the estimated prevalence of manifest KC was 7.6% (95% CI: 3.3-11.9) based on KISA index, indicating strong familial aggregation. All examined videokeratography indices were able to differentiate between KC and non-KC family members as well as normal controls (anova p 0.1) for all indices indicated the presence of a non-mendelian major gene effect (MG). Inclusion of Fleischer ring as covariate improved the fit of MG models. Mendelian, Sporadic and polygenic models were consistently rejected. Complex segregation analysis indicates a strong genetic contribution to the transmission of keratoconus. Inheritance is most probably due to a non-mendelian major gene effect. Low genotype-phenotype correlation in sporadic KC families can make linkage studies difficult, thus genome wide association studies, epigenetic and pathway analyses may provide more information on disease pathogenesis in non-familial keratoconus. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

    5. Towards structural systems pharmacology to study complex diseases and personalized medicine.

      Directory of Open Access Journals (Sweden)

      Lei Xie

      2014-05-01

      Full Text Available Genome-Wide Association Studies (GWAS, whole genome sequencing, and high-throughput omics techniques have generated vast amounts of genotypic and molecular phenotypic data. However, these data have not yet been fully explored to improve the effectiveness and efficiency of drug discovery, which continues along a one-drug-one-target-one-disease paradigm. As a partial consequence, both the cost to launch a new drug and the attrition rate are increasing. Systems pharmacology and pharmacogenomics are emerging to exploit the available data and potentially reverse this trend, but, as we argue here, more is needed. To understand the impact of genetic, epigenetic, and environmental factors on drug action, we must study the structural energetics and dynamics of molecular interactions in the context of the whole human genome and interactome. Such an approach requires an integrative modeling framework for drug action that leverages advances in data-driven statistical modeling and mechanism-based multiscale modeling and transforms heterogeneous data from GWAS, high-throughput sequencing, structural genomics, functional genomics, and chemical genomics into unified knowledge. This is not a small task, but, as reviewed here, progress is being made towards the final goal of personalized medicines for the treatment of complex diseases.

    6. Osteomeatal complex obstruction is not associated with adjacent sinus disease in chronic rhinosinusitis with polyps.

      Science.gov (United States)

      Leung, Randy M; Kern, Robert C; Conley, David B; Tan, Bruce K; Chandra, Rakesh K

      2011-01-01

      It is universally accepted that osteomeatal complex (OMC) disease is linked to the subsequent development of chronic rhinosinusitis without nasal polyps (CRSsNPs) via postobstructive mechanisms. The role of OMC obstruction in the pathogenesis of CRSwNPs is less clear. This study was designed to identify if there is an association between OMC obstruction and inflammation of the adjacent sinuses, when patients are stratified by polyp status. This is a follow-up and expanded series of a previous pilot study from our group. CT scans of 144 patients with CRSsNPs and 123 patients with CRS with nasal polyps (CRSwNPs) were evaluated for each sinus and OMC. Patients had no previous surgeries for NPs. CT scans were obtained after a trial of maximal medical therapy. Increasing OMC involvement was associated with increasing Lund-Mackay score for both CRSsNPs and CRSwNPs. In CRSsNP patients, OMC status significantly correlated with adjacent sinus status (p OMC status does not correlate with adjacent sinus status (p = 0.328). OMC obstruction in the setting of CRSwNP may be a barometer of the overall disease process, but in this scenario, paranasal sinus inflammation can not be classified as a postobstructive phenomenon. These findings question the role of minimally invasive procedures in the management of CRSwNPs.

    7. The synergy factor: a statistic to measure interactions in complex diseases

      Directory of Open Access Journals (Sweden)

      Combarros Onofre

      2009-06-01

      Full Text Available Abstract Background One challenge in understanding complex diseases lies in revealing the interactions between susceptibility factors, such as genetic polymorphisms and environmental exposures. There is thus a need to examine such interactions explicitly. A corollary is the need for an accessible method of measuring both the size and the significance of interactions, which can be used by non-statisticians and with summarised, e.g. published data. The lack of such a readily available method has contributed to confusion in the field. Findings The synergy factor (SF allows assessment of binary interactions in case-control studies. In this paper we describe its properties and its novel characteristics, e.g. in calculating the power to detect a synergistic effect and in its application to meta-analyses. We illustrate these functions with real examples in Alzheimer's disease, e.g. a meta-analysis of the potential interaction between a BACE1 polymorphism and APOE4: SF = 2.5, 95% confidence interval: 1.5–4.2; p = 0.0001. Conclusion Synergy factors are easy to use and clear to interpret. Calculations may be performed through the Excel programmes provided within this article. Unlike logistic regression analysis, the method can be applied to datasets of any size, however small. It can be applied to primary or summarised data, e.g. published data. It can be used with any type of susceptibility factor, provided the data are dichotomised. Novel features include power estimation and meta-analysis.

    8. Passive Immunotherapy for Retroviral Disease: Influence of Major Histocompatibility Complex Type and T-Cell Responsiveness

      Science.gov (United States)

      Hasenkrug, Kim J.; Brooks, Diane M.; Chesebro, Bruce

      1995-11-01

      Administration of virus-specific antibodies is known to be an effective early treatment for some viral infections. Such immunotherapy probably acts by antibody-mediated neutralization of viral infectivity and is often thought to function independently of T-cell-mediated immune responses. In the present experiments, we studied passive antibody therapy using Friend murine leukemia virus complex as a model for an immunosuppressive retroviral disease in adult mice. The results showed that antibody therapy could induce recovery from a well-established retroviral infection. However, the success of therapy was dependent on the presence of both CD4^+ and CD8^+ T lymphocytes. Thus, cell-mediated responses were required for recovery from infection even in the presence of therapeutic levels of antibody. The major histocompatibility type of the mice was also an important factor determining the relative success of antibody therapy in this system, but it was less critical for low-dose than for high-dose infections. Our results imply that limited T-cell responsiveness as dictated by major histocompatibility genes and/or stage of disease may have contributed to previous immunotherapy failures in AIDS patients. Possible strategies to improve the efficacy of future therapies are discussed.

    9. Arabidopsis CML38, a Calcium Sensor That Localizes to Ribonucleoprotein Complexes under Hypoxia Stress1[OPEN

      Science.gov (United States)

      McClintock, Carlee; Li, Tian

      2016-01-01

      During waterlogging and the associated oxygen deprivation stress, plants respond by the induction of adaptive programs, including the redirected expression of gene networks toward the synthesis of core hypoxia-response proteins. Among these core response proteins in Arabidopsis (Arabidopsis thaliana) is the calcium sensor CML38, a protein related to regulator of gene silencing calmodulin-like proteins (rgsCaMs). CML38 transcripts are up-regulated more than 300-fold in roots within 6 h of hypoxia treatment. Transfer DNA insertional mutants of CML38 show an enhanced sensitivity to hypoxia stress, with lowered survival and more severe inhibition of root and shoot growth. By using yellow fluorescent protein (YFP) translational fusions, CML38 protein was found to be localized to cytosolic granule structures similar in morphology to hypoxia-induced stress granules. Immunoprecipitation of CML38 from the roots of hypoxia-challenged transgenic plants harboring CML38pro::CML38:YFP followed by liquid chromatography-tandem mass spectrometry analysis revealed the presence of protein targets associated with messenger RNA ribonucleoprotein (mRNP) complexes including stress granules, which are known to accumulate as messenger RNA storage and triage centers during hypoxia. This finding is further supported by the colocalization of CML38 with the mRNP stress granule marker RNA Binding Protein 47 (RBP47) upon cotransfection of Nicotiana benthamiana leaves. Ruthenium Red treatment results in the loss of CML38 signal in cytosolic granules, suggesting that calcium is necessary for stress granule association. These results confirm that CML38 is a core hypoxia response calcium sensor protein and suggest that it serves as a potential calcium signaling target within stress granules and other mRNPs that accumulate during flooding stress responses. PMID:26634999

    10. Arabidopsis CML38, a Calcium Sensor That Localizes to Ribonucleoprotein Complexes under Hypoxia Stress.

      Science.gov (United States)

      Lokdarshi, Ansul; Conner, W Craig; McClintock, Carlee; Li, Tian; Roberts, Daniel M

      2016-02-01

      During waterlogging and the associated oxygen deprivation stress, plants respond by the induction of adaptive programs, including the redirected expression of gene networks toward the synthesis of core hypoxia-response proteins. Among these core response proteins in Arabidopsis (Arabidopsis thaliana) is the calcium sensor CML38, a protein related to regulator of gene silencing calmodulin-like proteins (rgsCaMs). CML38 transcripts are up-regulated more than 300-fold in roots within 6 h of hypoxia treatment. Transfer DNA insertional mutants of CML38 show an enhanced sensitivity to hypoxia stress, with lowered survival and more severe inhibition of root and shoot growth. By using yellow fluorescent protein (YFP) translational fusions, CML38 protein was found to be localized to cytosolic granule structures similar in morphology to hypoxia-induced stress granules. Immunoprecipitation of CML38 from the roots of hypoxia-challenged transgenic plants harboring CML38pro::CML38:YFP followed by liquid chromatography-tandem mass spectrometry analysis revealed the presence of protein targets associated with messenger RNA ribonucleoprotein (mRNP) complexes including stress granules, which are known to accumulate as messenger RNA storage and triage centers during hypoxia. This finding is further supported by the colocalization of CML38 with the mRNP stress granule marker RNA Binding Protein 47 (RBP47) upon cotransfection of Nicotiana benthamiana leaves. Ruthenium Red treatment results in the loss of CML38 signal in cytosolic granules, suggesting that calcium is necessary for stress granule association. These results confirm that CML38 is a core hypoxia response calcium sensor protein and suggest that it serves as a potential calcium signaling target within stress granules and other mRNPs that accumulate during flooding stress responses. © 2016 American Society of Plant Biologists. All Rights Reserved.

    11. Lyme disease as an underlying cause of supraspinatus tendinopathy in an overhead athlete.

      Science.gov (United States)

      Coulon, Christian L; Landin, Dennis

      2012-05-01

      Supraspinatus tendinopathy is a common cause of shoulder pain seen in overhead athletes, but there appear to be no published cases that present Lyme disease as the underlying cause of tendinopathy. Lyme disease is diagnosed primarily by clinical signs and symptoms and then supported by laboratory tests, including enzyme-linked immunosorbant assay (ELISA) and Western blot testing. This case demonstrates the importance of a physical therapist's input and clinical role in reaching the correct diagnosis in an athlete with Lyme disease who had a diagnosis of rotator cuff impingement and tendinitis. A 34-year-old male tennis player was seen for physical therapy for right shoulder impingement and tendinitis diagnosed by an orthopedic surgeon. He was unable to participate in sporting activities due to impairments in strength and pain. Initial examination revealed distal supraspinatus impingement and tendinopathy. The patient was not progressing with commonly accepted interventions and began to have "arthritis-like" shoulder pain in the uninvolved left shoulder. Suspicious of an underlying condition, the physical therapist informed the physician of the patient's updated status and referred the patient to the physician to discuss the current symptoms in therapy. After testing, the patient was diagnosed with chronic Lyme disease and underwent antibiotic therapy. Many active patients spend time in the outdoors, increasing their risk of exposure to a vector for Borrelia burgdorferi. Physical therapists spend a larger portion of time with patients than other health care professionals and due to this extended contact and musculoskeletal knowledge are able to recognize atypical musculoskeletal disorders or musculoskeletal manifestations of unusual pathologies, including Lyme disease.

    12. Multivariate dimensionality reduction approaches to identify gene-gene and gene-environment interactions underlying multiple complex traits.

      Science.gov (United States)

      Xu, Hai-Ming; Sun, Xi-Wei; Qi, Ting; Lin, Wan-Yu; Liu, Nianjun; Lou, Xiang-Yang

      2014-01-01

      The elusive but ubiquitous multifactor interactions represent a stumbling block that urgently needs to be removed in searching for determinants involved in human complex diseases. The dimensionality reduction approaches are a promising tool for this task. Many complex diseases exhibit composite syndromes required to be measured in a cluster of clinical traits with varying correlations and/or are inherently longitudinal in nature (changing over time and measured dynamically at multiple time points). A multivariate approach for detecting interactions is thus greatly needed on the purposes of handling a multifaceted phenotype and longitudinal data, as well as improving statistical power for multiple significance testing via a two-stage testing procedure that involves a multivariate analysis for grouped phenotypes followed by univariate analysis for the phenotypes in the significant group(s). In this article, we propose a multivariate extension of generalized multifactor dimensionality reduction (GMDR) based on multivariate generalized linear, multivariate quasi-likelihood and generalized estimating equations models. Simulations and real data analysis for the cohort from the Study of Addiction: Genetics and Environment are performed to investigate the properties and performance of the proposed method, as compared with the univariate method. The results suggest that the proposed multivariate GMDR substantially boosts statistical power.

    13. Multivariate dimensionality reduction approaches to identify gene-gene and gene-environment interactions underlying multiple complex traits.

      Directory of Open Access Journals (Sweden)

      Hai-Ming Xu

      Full Text Available The elusive but ubiquitous multifactor interactions represent a stumbling block that urgently needs to be removed in searching for determinants involved in human complex diseases. The dimensionality reduction approaches are a promising tool for this task. Many complex diseases exhibit composite syndromes required to be measured in a cluster of clinical traits with varying correlations and/or are inherently longitudinal in nature (changing over time and measured dynamically at multiple time points. A multivariate approach for detecting interactions is thus greatly needed on the purposes of handling a multifaceted phenotype and longitudinal data, as well as improving statistical power for multiple significance testing via a two-stage testing procedure that involves a multivariate analysis for grouped phenotypes followed by univariate analysis for the phenotypes in the significant group(s. In this article, we propose a multivariate extension of generalized multifactor dimensionality reduction (GMDR based on multivariate generalized linear, multivariate quasi-likelihood and generalized estimating equations models. Simulations and real data analysis for the cohort from the Study of Addiction: Genetics and Environment are performed to investigate the properties and performance of the proposed method, as compared with the univariate method. The results suggest that the proposed multivariate GMDR substantially boosts statistical power.

    14. Dissection of a Complex Disease Susceptibility Region Using a Bayesian Stochastic Search Approach to Fine Mapping.

      Directory of Open Access Journals (Sweden)

      Chris Wallace

      2015-06-01

      Full Text Available Identification of candidate causal variants in regions associated with risk of common diseases is complicated by linkage disequilibrium (LD and multiple association signals. Nonetheless, accurate maps of these variants are needed, both to fully exploit detailed cell specific chromatin annotation data to highlight disease causal mechanisms and cells, and for design of the functional studies that will ultimately be required to confirm causal mechanisms. We adapted a Bayesian evolutionary stochastic search algorithm to the fine mapping problem, and demonstrated its improved performance over conventional stepwise and regularised regression through simulation studies. We then applied it to fine map the established multiple sclerosis (MS and type 1 diabetes (T1D associations in the IL-2RA (CD25 gene region. For T1D, both stepwise and stochastic search approaches identified four T1D association signals, with the major effect tagged by the single nucleotide polymorphism, rs12722496. In contrast, for MS, the stochastic search found two distinct competing models: a single candidate causal variant, tagged by rs2104286 and reported previously using stepwise analysis; and a more complex model with two association signals, one of which was tagged by the major T1D associated rs12722496 and the other by rs56382813. There is low to moderate LD between rs2104286 and both rs12722496 and rs56382813 (r2 ≃ 0:3 and our two SNP model could not be recovered through a forward stepwise search after conditioning on rs2104286. Both signals in the two variant model for MS affect CD25 expression on distinct subpopulations of CD4+ T cells, which are key cells in the autoimmune process. The results support a shared causal variant for T1D and MS. Our study illustrates the benefit of using a purposely designed model search strategy for fine mapping and the advantage of combining disease and protein expression data.

    15. Integrating genome-wide association study summaries and element-gene interaction datasets identified multiple associations between elements and complex diseases.

      Science.gov (United States)

      He, Awen; Wang, Wenyu; Prakash, N Tejo; Tinkov, Alexey A; Skalny, Anatoly V; Wen, Yan; Hao, Jingcan; Guo, Xiong; Zhang, Feng

      2018-03-01

      Chemical elements are closely related to human health. Extensive genomic profile data of complex diseases offer us a good opportunity to systemically investigate the relationships between elements and complex diseases/traits. In this study, we applied gene set enrichment analysis (GSEA) approach to detect the associations between elements and complex diseases/traits though integrating element-gene interaction datasets and genome-wide association study (GWAS) data of complex diseases/traits. To illustrate the performance of GSEA, the element-gene interaction datasets of 24 elements were extracted from the comparative toxicogenomics database (CTD). GWAS summary datasets of 24 complex diseases or traits were downloaded from the dbGaP or GEFOS websites. We observed significant associations between 7 elements and 13 complex diseases or traits (all false discovery rate (FDR) elements and complex diseases. © 2017 WILEY PERIODICALS, INC.

    16. A Joint Positioning and Attitude Solving Method for Shearer and Scraper Conveyor under Complex Conditions

      Directory of Open Access Journals (Sweden)

      Jiacheng Xie

      2017-01-01

      Full Text Available In a fully mechanized coal-mining face, the positioning and attitude of the shearer and scraper conveyor are inaccurate. To overcome this problem, a joint positioning and attitude solving method that considers the effect of an uneven floor is proposed. In addition, the real-time connection and coupling relationship between the two devices is analyzed. Two types of sensors, namely, the tilt sensor and strapdown inertial navigation system (SINS, are used to measure the shearer body pitch angle and the scraper conveyor shape, respectively. To improve the accuracy, two pieces of information are fused using the adaptive information fusion algorithm. It is observed that, using a marking strategy, the shearer body pitch angle can be reversely mapped to the real-time shape of the scraper conveyor. Then, a virtual-reality (VR software that can visually simulate this entire operation process under different conditions is developed. Finally, experiments are conducted on a prototype experimental platform. The positioning error is found to be less than 0.38 times the middle trough length; moreover, no accumulated error is detected. This method can monitor the operation of the shearer and scraper conveyor in a highly dynamic and precise manner and provide strong technical support for safe and efficient operation of a fully mechanized coal-mining face.

    17. Delamination monitoring in CFRP laminated plates under noisy conditions using complex-wavelet 2D curvature mode shapes

      Science.gov (United States)

      Xu, Wei; Cao, Maosen; Li, Ximing; Radzieński, Maciej; Ostachowicz, Wiesław; Bai, Runbo

      2017-10-01

      Delamination monitoring in carbon fiber reinforced polymer (CFRP) laminated plates is crucial to ensure the integrity and safety of the structures that accommodate the plates. To identify delaminations in CFRP laminated plates, the two-dimensional (2D) curvature mode shape method is a prevailing method that features instant and simultaneous determination of the presence and location of the delamination. However, this method has two noticeable deficiencies in characterizing incipient small-sized delaminations, namely lack of damage sensitivity and inadequate noise robustness. To this end, this study proposes a new dynamics feature of the complex-wavelet 2D curvature mode shape to discriminate small-sized delaminations. This feature is delicately formulated based on the integration of the 2D curvature mode shape with the complex wavelet. The complex-wavelet 2D curvature mode shape is superior to the 2D curvature mode shape by virtue of its stronger damage sensitivity and noise robustness. These merits can be attributed to the adjustable localization and the multi-scale properties of the second-order Gabor wavelet, respectively. Proof of concept of the complex-wavelet 2D curvature mode shape is numerically undertaken in a finite-element laminated CFRP plate with a small-sized delamination, with emphasis on sensitivity to damage and robustness against noise. The applicability of the feature is experimentally validated on a CFRP laminated plate with a small-sized delamination, whose mode shapes are acquired via the non-contact measurement using a scanning laser vibrometer. The numerical and experimental results show that the complex-wavelet 2D curvature mode shape can effectively designate the presence and location of the delaminations in CFRP laminated plates under noisy conditions.

    18. Effect of Maize Hybrid and Foliar Fungicides on Yield Under Low Foliar Disease Severity Conditions.

      Science.gov (United States)

      Mallowa, Sally O; Esker, Paul D; Paul, Pierce A; Bradley, Carl A; Chapara, Venkata R; Conley, Shawn P; Robertson, Alison E

      2015-08-01

      Foliar fungicide use in the U.S. Corn Belt increased in the last decade; however, questions persist pertaining to its value and sustainability. Multistate field trials were established from 2010 to 2012 in Illinois, Iowa, Ohio, and Wisconsin to examine how hybrid and foliar fungicide influenced disease intensity and yield. The experimental design was in a split-split plot with main plots consisting of hybrids varying in resistance to gray leaf spot (caused by Cercospora zeae-maydis) and northern corn leaf blight (caused by Setosphaera turcica), subplots corresponding to four application timings of the fungicide pyraclostrobin, and sub-subplots represented by inoculations with either C. zeae-maydis, S. turcica, or both at two vegetative growth stages. Fungicide application (VT/R1) significantly reduced total disease severity relative to the control in five of eight site-years (P<0.05). Disease was reduced by approximately 30% at Wisconsin in 2011, 20% at Illinois in 2010, 29% at Iowa in 2010, and 32 and 30% at Ohio in 2010 and 2012, respectively. These disease severities ranged from 0.2 to 0.3% in Wisconsin in 2011 to 16.7 to 22.1% in Illinois in 2010. The untreated control had significantly lower yield (P<0.05) than the fungicide-treated in three site-years. Fungicide application increased the yield by approximately 6% at Ohio in 2010, 5% at Wisconsin in 2010 and 6% in 2011. Yield differences ranged from 8,403 to 8,890 kg/ha in Wisconsin 2011 to 11,362 to 11,919 kg/ha in Wisconsin 2010. Results suggest susceptibility to disease and prevailing environment are important drivers of observed differences. Yield increases as a result of the physiological benefits of plant health benefits under low disease were not consistent.

    19. Alveolar bone loss associated to periodontal disease in lead intoxicated rats under environmental hypoxia.

      Science.gov (United States)

      Terrizzi, Antonela R; Fernandez-Solari, Javier; Lee, Ching M; Bozzini, Clarisa; Mandalunis, Patricia M; Elverdin, Juan C; Conti, María Ines; Martínez, María Pilar

      2013-10-01

      Previously reported studies from this laboratory revealed that rats chronically intoxicated with lead (Pb) under hypoxic conditions (HX) impaired growth parameters and induced damages on femoral and mandibular bones predisposing to fractures. We also described periodontal inflammatory processes under such experimental conditions. Periodontitis is characterised by inflammation of supporting tissues of the teeth that result in alveolar bone loss. The existence of populations living at high altitudes and exposed to lead contamination aimed us to establish the macroscopic, biochemical and histological parameters consistent with a periodontal disease in the same rat model with or without experimental periodontitis (EP). Sixty female rats were divided into: Control; Pb (1000ppm of lead acetate in drinking water); HX (506mbar) and PbHX (both treatments simultaneously). EP was induced by placing ligatures around the molars of half of the rats during the 14 days previous to the autopsy. Hemi-mandibles were extracted to evaluate bone loss by histomorphometrical techniques. TNFα plasmatic concentration was greater (plead intoxication under hypoxic environment enhanced not only alveolar bone loss but also systemic and oral tissues inflammatory parameters, which could aggravate the physiopathological alterations produced by periodontal disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

    20. Molecular Processes Underlying the Structure and Assembly of Thin Films and Nanoparticles at Complex interfaces

      Energy Technology Data Exchange (ETDEWEB)

      Richmond, Geraldine [Univ. of Oregon, Eugene, OR (United States)

      2016-06-03

      Since 1995 we have pursued a number of different studies that are quite diverse in nature but with the common theme of using novel laser based methods to study important processes at buried interfaces. Studies of Corrosion, Passivation on n-GaAs(100)Methanol Photoelectrochemical Cell In these studies we have used picosecond photoluminescence and electrochemical studies to understand the GaAs/methanol interface. In our most extensive set of studies we conducted photo-illumination and XPS experiments to understand the chemistry occurring in the GaAs/methanol photoelectrochemical during photoexcitation. An important distinction between photocorrosion and photoetching of GaAs is elucidated by these studies. The dependence of GaAs photocorrosion on light intensity has been explored to better understand intrinsic differences between the lamplight studies and the picosecond photoluminescence studies. The effect of coating the GaAs with a sulfide layer prior to immersion in the cell has also been explored. This last result has led us to examine n-GaAs as a function of crystallographic orientation after exposure to aqueous Na2S containing solutions has been studied as a function of crystallographic orientation of the GaAs surface. The (100) and (110) surfaces are relatively similar, with significant amounts of As-S species present at the interface. The (111)B surface lacks this constituent, but shows significant amounts of metallic As. The XPS results have been correlated with the results of previous photocorrosion and passivation studies conducted in a photoelectrochemical cell. The studies indicate that the metallic As present at (111)B surface contributes strongly to the large surface recombination velocity found there, and to the inability of Na2S to passivate the (111)B surface. SAMS Under Water: Water Molecular Structure and Bonding at Hydrophobic Surfaces In these DOE sponsored studies we have been interested in learning the similarities and

    1. Eddy-correlation measurements of benthic fluxes under complex flow conditions: Effects of coordinate transformations and averaging time scales

      DEFF Research Database (Denmark)

      Lorke, Andreas; McGinnis, Daniel F.; Maeck, Andreas

      2013-01-01

      hours of continuous eddy-correlation measurements of sediment oxygen fluxes in an impounded river, we demonstrate that rotation of measured current velocities into streamline coordinates can be a crucial and necessary step in data processing under complex flow conditions in non-flat environments......Eddy-correlation measurements of sediment oxygen uptake rates in aquatic systems are increasingly used to obtain areal-averaged fluxes with a high temporal resolution. Here we discuss the effects of coordinate rotation and averaging time scale for Reynolds decomposition on flux estimates. Using 119...... in the context of the theoretical concepts underlying eddy-correlation measurements and a set of recommendations for planning and analyses of flux measurements are derived....

    2. [Achieving pathogenesis understanding of ocular diseases by deciphering the underlying molecular pathways].

      Science.gov (United States)

      Huang, Qian

      2005-10-01

      The field of ophthalmology research has experienced a revolution since the 1970's, when molecular biology techniques were gradually and widely adopted. Many of the developments generated impact that went far beyond the field of ophthalmology. A classic case was the identification and characterization of the Retinoblastoma susceptibility gene (Rb), whose impact went far beyond the rare and obscure disease, as it provides key evidence for the concept of tumor suppressor gene and the "two hit" theory of tumor formation. The identification of scores of genes involved in retinitis pigmentosum (pigmentosa), on the other hand, show cases the complexity of multi-factorial diseases. Ophthalmology researchers in China have been quick in integrating these novel tools into their research. However, the field still lags behind in the effective use of these technologies to carry out in-depth inquiries into key disease mechanisms. The advent of "omics" technologies heralded a new era in biomedical research that allows for the global and rapid survey of genetic and biochemical profiles. Effective integration of these novel technologies into ophthalmology research will have far-reaching impact for the whole field.

    3. Creutzfeldt-Jakob Disease-Like Periodic Sharp Wave Complexes in Voltage-Gated Potassium Channel-Complex Antibodies Encephalitis: A Case Report.

      Science.gov (United States)

      Savard, Martin; Irani, Sarosh R; Guillemette, Annie; Gosselin-Lefebvre, Stéphanie; Geschwind, Michael; Jansen, Gerard H; Gould, Peter V; Laforce, Robert

      2016-02-01

      Voltage-gated potassium channel-complex antibodies (VGKC-cAbs) encephalitis, a treatable autoantibody encephalopathy, has been previously reported to clinically mimic sporadic Creutzfeldt-Jakob disease. Among available clinical clues to distinguish them, periodic sharp wave complexes, a typical finding in sporadic Creutzfeldt-Jakob disease, have never been reported in association with VGKC-cAbs encephalitis. A 76-year-old man was transferred to a tertiary neurology center with a clinical history of 6-month weight loss, cognitive disturbance, and nonspecific generalized weakness. He had two seizures the month before transfer and then evolved to severe encephalopathy, requiring mechanical ventilation. Periodic sharp wave complexes every 1 to 2 seconds over slowed background were found on EEG, and MRI showed cerebellar and bifrontal cortical T2/FLAIR/DWI hypersignal without restricted diffusion on ADC mapping. Pancorporal positron emission tomography scan was negative. An immunotherapy trial did not improve the patient condition. Therefore, he died after life support withdrawal. Brain autopsy revealed mononuclear neocortex infiltrate without significant spongiosis, and the anti-VGKC test showed a seropositivity of 336 pmol/L (normal, 0-31), 3 month after the patient deceased. This is the first reported case of VGKC-cAbs encephalitis associated with periodic sharp wave complexes on EEG, which further confuse the differential diagnosis with sporadic Creutzfeldt-Jakob disease. However, the cortical DWI hypersignal without restriction seems to remain a way to discriminate these two entities appropriately, when present. These clues are of paramount importance because VGKC-cAbs encephalitis is a treatable disease.

    4. Turbulent dispersivity under conditions relevant to airborne disease transmission between laboratory animals

      Science.gov (United States)

      Halloran, Siobhan; Wexler, Anthony; Ristenpart, William

      2014-11-01

      Virologists and other researchers who test pathogens for airborne disease transmissibility often place a test animal downstream from an inoculated animal and later determine whether the test animal became infected. Despite the crucial role of the airflow in modulating the pathogen transmission, to date the infectious disease community has paid little attention to the effect of airspeed or turbulence intensity on the probability of transmission. Here we present measurements of the turbulent dispersivity under conditions relevant to experimental tests of airborne disease transmissibility between laboratory animals. We used time lapse photography to visualize the downstream transport and turbulent dispersion of smoke particulates released from a point source downstream of a standard axial fan, thus mimicking the release and transport of expiratory aerosols exhaled by an inoculated animal. We demonstrate that the fan speed counterintuitively has no effect on the downstream plume width, a result replicated with a variety of different fan types and configurations. The results point toward a useful simplification in modeling of airborne disease transmission via fan-generated flows.

    5. Are the educational differences in incidence of cardiovascular disease explained by underlying familial factors?

      DEFF Research Database (Denmark)

      Madsen, Mia; Andersen, Per K; Gerster, Mette

      2014-01-01

      To isolate the effect of education from the influence of potential underlying factors, we investigated the association of education with the risk of cardiovascular disease (CVD) and ischemic heart disease (IHD) using twin data to adjust for familial factors shared within twins, including genetic...... make-up and childhood environment. The study was based on data from the Danish Twin Registry linked to administrative and heath registers in Statistics Denmark. A total of 11,968 monozygotic and 20,464 dizygotic same sexed twins were followed from 1980 to 2009, including more than 8000 events of CVD....... Unpaired and intra-pair analyses were compared. In the unpaired analyses, an inverse educational gradient in CVD- and IHD risk was observed. This association was not replicated in the intra-pair analyses that control for shared familial factors exploiting that twins share their intrauterine- and childhood...

    6. The effect of the physical activity on polymorphic premature ventricular complexes in chronic kidney disease

      Directory of Open Access Journals (Sweden)

      Márcio G. Kiuchi

      2017-06-01

      Full Text Available Background: Polymorphic premature ventricular complexes (PVCs are very common, appearing most frequently in patients with hypertension, obesity, sleep apnea, and structural heart disease. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of ventricular arrhythmias. Endurance exercise training clearly lowers sympathetic activity in sympatho-excitatory disease states and may be tolerated by patients with chronic kidney disease (CKD. Methods: We assessed 40 CKD patients with hypertension with polymorphic PVCs. Patients underwent a complete medical history and physical examination. We evaluated the effectiveness of β blocker only or β blocker + exercise during 12 months of follow-up regarding the changes of the numbers of PVCs and mean heart rate (HR by 24-hour-Holter. Results: We observed in the β blocker group a significant decrease in the number of polymorphic PVCs from baseline 36,515 ± 3,518 to 3, 6, 9 and 12 months of follow-up, 28,314 ± 2,938, 23,709 ± 1,846, 22,564 ± 1,673, and 22,725 ± 1,415, respectively (P < 0.001. In the β blocker + exercise group a significant decrease in the number of polymorphic PVCs also occurred from baseline 36,091 ± 3,327 to 3, 6, 9 and 12 months of follow-up, 29,252 ± 3,211, 20,948 ± 2,386, 14,238 ± 3,338, and 6,225 ± 2,319, respectively (P < 0.001. Comparisons between the two groups at the same time point showed differences from the sixth month onwards: the 6th (Δ = −2,761, P = 0.045, 9th (Δ = −8,325, P < 0.001 and 12th (Δ = −16,500, P < 0.001 months. There was an improvement during the 12 months of follow-up vs. baseline, after the β blocker or β blocker + exercise in mean 24-hour HR Holter monitoring, creatinine values, eGFR, and ACR. Conclusion: Polymorphic PVCs may be modifiable by physical activity in CKD patients with hypertension without structural heart disease.

    7. HYBRID TREATMENT OF COMPLEX COMBINED CORONARY AND VALVE DISEASE FOR PATIENTS WITH HIGH LEVEL OF OPERATIONAL RISK

      Directory of Open Access Journals (Sweden)

      G. V. Aniskevich

      2011-01-01

      Full Text Available The analysis of results of hybrid treatment of complex combined coronary and valve disease at patients with high level of operational risk between January 2005 and December 2010. The hybrid treatment of complex combined coronary and valve disease, provides performance of percutaneous coronary interventions (PCI in a combinati- on valve surgery. 118 patients, with a median age 64.4 ± 8.9 years, are included in research. 2 approaches of a hy- brid method of treatment – 2-Staged (n = 86 and a method «1-stop» (n = 32 are applied. The оperative mortality has made 4.2%. On the basis of the received results were the conclusion is drawn that at high-risk patients with complex combined coronary and valve disease the hybrid method of treatment allows to lower risk of operation. 

    8. Evaluating Safety Culture Under the Socio-Technical Complex Systems Perspective

      International Nuclear Information System (INIS)

      Lemos, F. L. de

      2016-01-01

      itself as a quality of a social system, the proposed approach integrates the safety culture traits into the control structure of a broader system, the socio-technical complex system. A practical example, based on the Davis-Besse Nuclear Power Plant head degradation event, is presented. (author)

    9. Exploring the molecular mechanisms underlying the potentiation of exogenous growth hormone on alcohol-induced fatty liver diseases in mice

      Directory of Open Access Journals (Sweden)

      Tian Ya-ping

      2010-11-01

      Full Text Available Abstract Background Growth hormone (GH is an essential regulator of intrahepatic lipid metabolism by activating multiple complex hepatic signaling cascades. Here, we examined whether chronic exogenous GH administration (via gene therapy could ameliorate liver steatosis in animal models of alcoholic fatty liver disease (AFLD and explored the underlying molecular mechanisms. Methods Male C57BL/6J mice were fed either an alcohol or a control liquid diet with or without GH therapy for 6 weeks. Biochemical parameters, liver histology, oxidative stress markers, and serum high molecular weight (HMW adiponectin were measured. Quantitative real-time PCR and western blotting were also conducted to determine the underlying molecular mechanism. Results Serum HMW adiponectin levels were significantly higher in the GH1-treated control group than in the control group (3.98 ± 0.71 μg/mL vs. 3.07 ± 0.55 μg/mL; P P P P P Conclusions GH therapy had positive effects on AFLD and may offer a promising approach to prevent or treat AFLD. These beneficial effects of GH on AFLD were achieved through the activation of the hepatic adiponectin-SIRT1-AMPK and PPARα-AMPK signaling systems.

    10. Music and Memory in Alzheimer's Disease and The Potential Underlying Mechanisms.

      Science.gov (United States)

      Peck, Katlyn J; Girard, Todd A; Russo, Frank A; Fiocco, Alexandra J

      2016-01-01

      With population aging and a projected exponential expansion of persons diagnosed with Alzheimer's disease (AD), the development of treatment and prevention programs has become a fervent area of research and discovery. A growing body of evidence suggests that music exposure can enhance memory and emotional function in persons with AD. However, there is a paucity of research that aims to identify specific underlying neural mechanisms associated with music's beneficial effects in this particular population. As such, this paper reviews existing anecdotal and empirical evidence related to the enhancing effects of music exposure on cognitive function and further provides a discussion on the potential underlying mechanisms that may explain music's beneficial effect. Specifically, this paper will outline the potential role of the dopaminergic system, the autonomic nervous system, and the default network in explaining how music may enhance memory function in persons with AD.

    11. Laparoscopic cholecystectomy performed under regional anesthesia in patients with chronic obstructive pulmonary disease.

      Science.gov (United States)

      Gramatica, L; Brasesco, O E; Mercado Luna, A; Martinessi, V; Panebianco, G; Labaque, F; Rosin, D; Rosenthal, R J; Gramatica, L

      2002-03-01

      Laparoscopic cholecystectomy has been successfully performed using epidural anesthesia. We evaluated our experience with this surgical approach in high-risk patients. We present the results of 29 patients with gallstones who, between 1998 and 1999, underwent laparoscopic cholecystectomy with epidural anesthesia. All but 1 patient had chronic obstructive pulmonary disease. All 29 surgeries were successfully completed via laparoscopy and with the patients under epidural anesthesia. No patient required endotracheal intubation during surgery or pain medication afterward. Postoperatively, 1 patient developed a wound infection and 3 patients developed urinary retention. At last follow-up (12 months postop), all patients were in good health. In this series, laparoscopic cholecystectomy was feasible under epidural anesthesia and it eliminated the need for postoperative analgesia. We believe that this approach should be considered for patients who require biliary surgery but who are not good candidates for general anesthesia due to cardiorespiratory problems.

    12. Management of chronic obstructive pulmonary disease exacerbations at the Nasser Medical Complex: a clinical audit.

      Science.gov (United States)

      Al-Faqawi, Maha; Abuowda, Yousef; Elmassry, Alaa Eldeen; Böttcher, Bettina

      2018-02-21

      The frequency and severity of chronic obstructive pulmonary disease (COPD) exacerbations are the most important determinants of prognosis in COPD. The aim of this study was to assess the management of patients presenting with COPD exacerbations at the Nasser Medical Complex in the Gaza Strip and to compare the management with the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD 2015). We reviewed the medical records of all patients admitted to Nasser Medical Complex and diagnosed with COPD exacerbation between Jan 1, 2014, and Dec 31, 2016. Clinical practice was compared with GOLD guidelines. Ethical approval was obtained from the General Directorate of Human Resources. 55 patient records were reviewed. The mean age was 66·4 years (SD 8·5), and 54 (98%) patients were male. All patients received inhaled bronchodilators. 36 (65%) patients received short-acting β agonists (SABA), 43 (78%) received short-acting muscarinic agonists (SAMA), 13 (24%) received long-acting muscarinic agonists (LAMA), one (2%) received long-acting beta-agonists (LABA), and 22 (40%) received both SABA and SAMA. 53 (96%) patients received systemic corticosteroids. 43 (78%) patients took more than the recommended 40 mg prednisolone daily. Only 12 (22%) patients received prednisolone as the recommended 5 day treatment course, whereas most patients received a shorter course. Other treatments included oxygen (51 [93%] patients), antibiotics (55 [100%]), antiviral medication (three [6%]), and theophylline (two [4%]). Overall adherence to guidelines was moderately good. All patients received antibiotics, and most patients received oxygen, which are both recommended for all patients. Less useful therapies were rarely prescribed. However, more patients received SAMA than SABA, although SABA is more effective and therefore the first-line treatment for COPD exacerbation. The dose of the most prescribed drug (prednisolone) exceeded the recommended dose. Generally, awareness and

    13. A Model of Compound Heterozygous, Loss-of-Function Alleles Is Broadly Consistent with Observations from Complex-Disease GWAS Datasets.

      Directory of Open Access Journals (Sweden)

      Jaleal S Sanjak

      2017-01-01

      Full Text Available The genetic component of complex disease risk in humans remains largely unexplained. A corollary is that the allelic spectrum of genetic variants contributing to complex disease risk is unknown. Theoretical models that relate population genetic processes to the maintenance of genetic variation for quantitative traits may suggest profitable avenues for future experimental design. Here we use forward simulation to model a genomic region evolving under a balance between recurrent deleterious mutation and Gaussian stabilizing selection. We consider multiple genetic and demographic models, and several different methods for identifying genomic regions harboring variants associated with complex disease risk. We demonstrate that the model of gene action, relating genotype to phenotype, has a qualitative effect on several relevant aspects of the population genetic architecture of a complex trait. In particular, the genetic model impacts genetic variance component partitioning across the allele frequency spectrum and the power of statistical tests. Models with partial recessivity closely match the minor allele frequency distribution of significant hits from empirical genome-wide association studies without requiring homozygous effect sizes to be small. We highlight a particular gene-based model of incomplete recessivity that is appealing from first principles. Under that model, deleterious mutations in a genomic region partially fail to complement one another. This model of gene-based recessivity predicts the empirically observed inconsistency between twin and SNP based estimated of dominance heritability. Furthermore, this model predicts considerable levels of unexplained variance associated with intralocus epistasis. Our results suggest a need for improved statistical tools for region based genetic association and heritability estimation.

    14. THE POLYPEPTIDE STIMULATOR APPLICATION IN COMPLEX TREATMENT OF COGNITIVE DISORDERS IN CHILDREN WITH DISEASES OF THE CENTRAL NERVOUS SYSTEM

      Directory of Open Access Journals (Sweden)

      S. A. Nemkova

      2012-01-01

      Full Text Available The results of the review of studies on the polypeptide nootropic neurometabolic stimulator in a complex correction of cognitive impairment in children with diseases of the central nervous system are given in the article. It is shown that cognitive-modulating effect is the leading feature of the drug, and in a combination with nootropic, neurotrophic, neuroprotective, reparative and anticonvulsive effects, as well as antioxidant, anti-stress and metabolic actions, which determines its high therapeutic efficacy in a complex correction of cognitive impairment in various central nervous system diseases in children.

    15. The 'sialo-microbial-dental complex' in oral health and disease.

      Science.gov (United States)

      Kaidonis, John; Townsend, Grant

      2016-01-01

      Biofilms are naturally found in all wet environments including the oral structures of nearly all species. Human oral biofilms have existed since our earliest ancestors and have evolved symbiotically with the dentition over many millennia within a Palaeolithic, hunter-gatherer setting. Irrespective of the plant-animal ratio, it can be argued that the Palaeolithic diet was essentially acidic, and acted as a selective force for much of the evolution of the stomatognathic system. The relationship between saliva, biofilm and teeth, the 'sialo-microbial-dental complex', provides oral health benefits and offers a different perspective to the old dental paradigm that only associated oral biofilms (plaque) with disease (caries). This new paradigm emphasises that oral biofilms are essential for the 'mineral maintenance' of teeth. Oral biofilms provide physical protection from dietary acid and together with bacterial metabolic acids cause the resting pH of the biofilm to fall below neutral. This is then followed by the re-establishment of a neutral environment by chemical interactions mediated by the saliva within the biofilm. Such pH fluctuations are often responsible for the cyclic demineralisation, then remineralisation of teeth, a process necessary for tooth maturation. However, since the advent of farming and especially since the industrial revolution, the increase in consumption of carbohydrates, refined sugars and acidic drinks has changed the ecology of biofilms. Biofilm biodiversity is significantly reduced together with a proliferation of acidogenic and aciduric organisms, tipping the balance of the 'demin-remin' cycle towards net mineral loss and hence caries. In addition, the consumption of acidic drinks in today's societies has removed the protective nature of the biofilm, leading to erosion. Erosion and caries are 'modern-day' diseases and reflect an imbalance within the oral biofilm resulting in the demineralisation of teeth. Copyright © 2015 The Authors

    16. Single ventricle, bicuspid aorta and interatrial wall aneurysm as a rare complex adult congenital heart disease: a case report

      OpenAIRE

      Berisha, Blerim; Krasniqi, Xhevdet; Thaqi, Agim; Gashi, Masar; Ko?inaj, Dardan

      2009-01-01

      Background Single ventricle, bicuspid aortic valve and interatrial wall aneurysm in adulthood are a rare and unique case in medical literature. This presented case with congenital heart disease has never been treated surgically and clinical consequences seriously presented in adulthood. Case presentation A 27 year old man with complex congenital heart disease presented. At the age of six, the single ventricle was ultrasonographly diagnosed, but at age 27 clinical consequences started to be se...

    17. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease.

      Science.gov (United States)

      Imhann, Floris; Vich Vila, Arnau; Bonder, Marc Jan; Fu, Jingyuan; Gevers, Dirk; Visschedijk, Marijn C; Spekhorst, Lieke M; Alberts, Rudi; Franke, Lude; van Dullemen, Hendrik M; Ter Steege, Rinze W F; Huttenhower, Curtis; Dijkstra, Gerard; Xavier, Ramnik J; Festen, Eleonora A M; Wijmenga, Cisca; Zhernakova, Alexandra; Weersma, Rinse K

      2018-01-01

      Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case-control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD. Stool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2 , CARD9 , ATG16L1 , IRGM and FUT2 . Strikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10 -13 ). We show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

    18. Delayed pneumothorax after laparoscopic sigmoid colectomy in a patient without underlying lung disease

      Directory of Open Access Journals (Sweden)

      Richie K Huynh

      2014-10-01

      Full Text Available We present an unusual case of a delayed pneumothorax occurring approximately 72 h post-operatively in a patient without any underlying lung disease who had undergone laparoscopic sigmoid colon resection. The patient was in her mid-40s with a body mass index of 28.0 and had no history of smoking. Her spontaneous pneumothorax manifested without any precipitating events or complications during recovery. There was no evidence of any infectious process. There were no central line attempts and all ports were placed intra-peritoneally, and there was no evidence of any subcutaneous emphysema. One possible mechanism of injury that we propose is barotrauma from an extended period of time in Trendelenburg position. Notably, the only abnormal finding throughout the entire post-operative period preceding the delayed pneumothorax was a PO 2 desaturation the day before. This case highlights the necessity to examine and investigate any desaturation post-operatively and deliberate its possible significance. Furthermore, it demonstrates that, even during a normal recovery period for a patient without any underlying lung disease or risk factors, spontaneous pneumothorax could still develop in a delayed fashion multiple days post-operatively from a laparoscopic procedure.

    19. [Case management and complex chronic diseases: concepts, models, evidence and uncertainties].

      Science.gov (United States)

      Morales-Asencio, José Miguel

      2014-01-01

      Chronic diseases are the greatest challenge for Health Care, but the conventional health care models have failed noticeably. Nurses are one of the main providers of the services developed to tackle this challenge, with special emphasis on case management, as one of the most common forms. But, one of the key problems is that case management is poorly conceptualized, and with the diversity of experience available, make its development and comparative evaluation difficult. An in-depth review on case management definition and concepts is presented in this article, with a description of the models, ingredients and the effectiveness reported in various studies. The remaining uncertainties in case management, such as the heterogeneity of designs and target populations, the weak description of the components, and the scarce use of research models for complex interventions, are also discussed. Finally, some key factors for a successful implementation of case management are detailed, such as a clear definition of accountability and roles, the existence of support to guarantee the competence of case managers, the use of valid mechanisms for case finding, adjusted caseload, accessible and team-shared record systems, or the integration of health and social services. Copyright © 2013 Elsevier España, S.L. All rights reserved.

    20. The complex and multifactorial relationship between testosterone deficiency (TD), obesity and vascular disease.

      Science.gov (United States)

      Traish, Abdulmaged M; Zitzmann, Michael

      2015-09-01

      Testosterone deficiency (TD) is a well-established and recognized medical condition that contributes to several co-morbidities, including metabolic syndrome, visceral obesity and cardiovascular disease (CVD). More importantly, obesity is thought to contribute to TD. This complex bidirectional interplay between TD and obesity promotes a vicious cycle, which further contributes to the adverse effects of TD and obesity and may increase the risk of CVD. Testosterone (T) therapy for men with TD has been shown to be safe and effective in ameliorating the components of the metabolic syndrome (Met S) and in contributiong to increased lean body mass and reduced fat mass and therefore contributes to weight loss. We believe that appropriate T therapy in obese men with TD is a novel medical approach to manage obesity in men with TD. Indeed, other measures of lifestyle and behavioral changes can be used to augment but not fully replace this effective therapeutic approach. It should be noted that concerns regarding the safety of T therapy remain widely unsubstantiated and considerable evidence exists supporting the benefits of T therapy. Thus, it is paramount that clinicians managing obese men with TD be made aware of this novel approach to treatment of obesity. In this review, we discuss the relationship between TD and obesity and highlight the contemporary advancement in management of obesity with pharmacological and surgical approaches, as well as utilization of T therapy and how this intervention may evolve as a novel approach to treatment of obesity in men with TD .

    1. Genetic architecture of the F7 gene in a Spanish population: implication for mapping complex diseases and for functional assays.

      Science.gov (United States)

      Sabater-Lleal, M; Almasy, L; Martínez-Marchán, E; Martínez-Sánchez, E; Souto, R; Blangero, J; Souto, Jc; Fontcuberta, J; Soria, J M

      2006-05-01

      Delineating the genetic variability of loci coding for complex diseases helps to understand the individual variation in disease susceptibility and drug response. We present the allelic architecture of the F7 gene. This gene is the major determinant of FVII plasma levels, and these plasma levels constitute an important intermediate risk factor for cardiovascular disease. As part of the Genetic Analysis of Idiopathic Thrombophila Project, we completely re-sequenced the F7 locus (promoter, exons, introns, and 3'-untranslated region) in 40 unrelated individuals. We found 49 polymorphisms with only two amino acid changes suggesting that regulatory non-coding and intronic variants are responsible for the FVII variability. These results are important for mapping susceptibility alleles of complex diseases, because differences in pair-wise linkage disequilibrium patterns between DNA variants and haplotype frequency distributions may help to detect disease-associated alleles. In addition, we present the results of an in silico search that established genomic comparisons among different species. In conclusion, our study of the F7 DNA sequence variations is an example of a strategy for analyzing the genetic architecture of a quantitative trait locus. Furthermore, it provides a model for future analyses of genetic factors that contribute to the susceptibility of complex diseases in humans.

    2. Transcriptomic Analysis and the Expression of Disease-Resistant Genes in Oryza meyeriana under Native Condition.

      Directory of Open Access Journals (Sweden)

      Bin He

      Full Text Available Oryza meyeriana (O. meyeriana, with a GG genome type (2n = 24, accumulated plentiful excellent characteristics with respect to resistance to many diseases such as rice shade and blast, even immunity to bacterial blight. It is very important to know if the diseases-resistant genes exist and express in this wild rice under native conditions. However, limited genomic or transcriptomic data of O. meyeriana are currently available. In this study, we present the first comprehensive characterization of the O. meyeriana transcriptome using RNA-seq and obtained 185,323 contigs with an average length of 1,692 bp and an N50 of 2,391 bp. Through differential expression analysis, it was found that there were most tissue-specifically expressed genes in roots, and next to stems and leaves. By similarity search against protein databases, 146,450 had at least a significant alignment to existed gene models. Comparison with the Oryza sativa (japonica-type Nipponbare and indica-type 93-11 genomes revealed that 13% of the O. meyeriana contigs had not been detected in O. sativa. Many diseases-resistant genes, such as bacterial blight resistant, blast resistant, rust resistant, fusarium resistant, cyst nematode resistant and downy mildew gene, were mined from the transcriptomic database. There are two kinds of rice bacterial blight-resistant genes (Xa1 and Xa26 differentially or specifically expressed in O. meyeriana. The 4 Xa1 contigs were all only expressed in root, while three of Xa26 contigs have the highest expression level in leaves, two of Xa26 contigs have the highest expression profile in stems and one of Xa26 contigs was expressed dominantly in roots. The transcriptomic database of O. meyeriana has been constructed and many diseases-resistant genes were found to express under native condition, which provides a foundation for future discovery of a number of novel genes and provides a basis for studying the molecular mechanisms associated with disease

    3. Impact Assessment of Pollutant Emissions in the Atmosphere from a Power Plant over a Complex Terrain and under Unsteady Winds

      Directory of Open Access Journals (Sweden)

      Grazia Ghermandi

      2017-11-01

      Full Text Available The development of a natural gas-fired tri-generation power plant (520 MW Combined Cycle Gas Turbines + 58 MW Tri-generation in the Republic of San Marino, a small independent country in Northern Italy, is under assessment. This work investigates the impact of atmospheric emissions of NOx by the plant, under the Italian and European regulatory framework. The impact assessment was performed by the means of the Aria Industry package, including the 3D Lagrangian stochastic particle dispersion model SPRAY, the diagnostic meteorological model SWIFT, and the turbulence model SURFPRO (Aria Technologies, France, and Arianet, Italy. The Republic of San Marino is almost completely mountainous, 10 km west of the Adriatic Sea and affected by land-sea breeze circulation. SPRAY is suitable for simulations under non-homogenous and non-stationary conditions, over a complex topography. The emission scenario included both a worst-case meteorological condition and three 10-day periods representative of typical atmospheric conditions for 2014. The simulated NOx concentrations were compared with the regulatory air quality limits. Notwithstanding the high emission rate, the simulation showed a spatially confined environmental impact, with only a single NOx peak at ground where the plume hits the hillside of the Mount Titano (749 m a.s.l., 5 km west of the future power plant.

    4. Complex Interfaces Under Change

      DEFF Research Database (Denmark)

      Rosbjerg, Dan

      The hydrosphere is dynamic across the major compartments of the Earth system: the atmosphere, the oceans and seas, the land surface water, and the groundwater within the strata below the two last compartments. The global geography of the hydrosphere essentially depends on thermodynamic and mechan......The hydrosphere is dynamic across the major compartments of the Earth system: the atmosphere, the oceans and seas, the land surface water, and the groundwater within the strata below the two last compartments. The global geography of the hydrosphere essentially depends on thermodynamic...... these interfaces and interfaced compartments and processes. Climate, sea-level, oceanographic currents and hydrological processes are all affected, while anthropogenic changes are often intense in the geographic settings corresponding to such interfaces....

    5. Chagas disease: national survey of seroprevalence in children under five years of age conducted in 2008

      Directory of Open Access Journals (Sweden)

      Graciela Russomando

      Full Text Available BACKGROUND Since the early 1990s, programs to control Chagas disease in South America have focused on eradicating domiciliary Triatoma infestans, the main vector. Seroprevalence studies of the chagasic infection are included as part of the vector control programs; they are essential to assess the impact of vector control measures and to monitor the prevention of vector transmission. OBJECTIVE To assess the interruption of domiciliary vector transmission of Chagas disease by T. infestans in Paraguay by evaluating the current state of transmission in rural areas. METHODS A survey of seroprevalence of Chagas disease was carried out in a representative sample group of Paraguayans aged one to five years living in rural areas of Paraguay in 2008. Blood samples collected on filter paper from 12,776 children were tested using an enzyme-linked immunosorbent assay. Children whose serology was positive or undetermined (n = 41 were recalled to donate a whole blood sample for retesting. Their homes were inspected for current triatomine infestation. Blood samples from their respective mothers were also collected and tested to check possible transmission of the disease by a congenital route. FINDINGS A seroprevalence rate of 0.24% for Trypanosoma cruzi infection was detected in children under five years of age among the country’s rural population. Our findings indicate that T. cruzi was transmitted to these children vertically. The total number of infected children, aged one to five years living in these departments, was estimated at 1,691 cases with an annual incidence of congenital transmission of 338 cases per year. MAIN CONCLUSION We determined the impact of vector control in the transmission of T. cruzi, following uninterrupted vector control measures employed since 1999 in contiguous T. infestans-endemic areas of Paraguay, and this allowed us to estimate the degree of risk of congenital transmission in the country.

    6. Chagas disease: national survey of seroprevalence in children under five years of age conducted in 2008.

      Science.gov (United States)

      Russomando, Graciela; Cousiño, Blanca; Sanchez, Zunilda; Franco, Laura X; Nara, Eva M; Chena, Lilian; Martínez, Magaly; Galeano, María E; Benitez, Lucio

      2017-05-01

      Since the early 1990s, programs to control Chagas disease in South America have focused on eradicating domiciliary Triatoma infestans, the main vector. Seroprevalence studies of the chagasic infection are included as part of the vector control programs; they are essential to assess the impact of vector control measures and to monitor the prevention of vector transmission. To assess the interruption of domiciliary vector transmission of Chagas disease by T. infestans in Paraguay by evaluating the current state of transmission in rural areas. A survey of seroprevalence of Chagas disease was carried out in a representative sample group of Paraguayans aged one to five years living in rural areas of Paraguay in 2008. Blood samples collected on filter paper from 12,776 children were tested using an enzyme-linked immunosorbent assay. Children whose serology was positive or undetermined (n = 41) were recalled to donate a whole blood sample for retesting. Their homes were inspected for current triatomine infestation. Blood samples from their respective mothers were also collected and tested to check possible transmission of the disease by a congenital route. A seroprevalence rate of 0.24% for Trypanosoma cruzi infection was detected in children under five years of age among the country's rural population. Our findings indicate that T. cruzi was transmitted to these children vertically. The total number of infected children, aged one to five years living in these departments, was estimated at 1,691 cases with an annual incidence of congenital transmission of 338 cases per year. We determined the impact of vector control in the transmission of T. cruzi, following uninterrupted vector control measures employed since 1999 in contiguous T. infestans-endemic areas of Paraguay, and this allowed us to estimate the degree of risk of congenital transmission in the country.

    7. Chagas disease: national survey of seroprevalence in children under five years of age conducted in 2008

      Science.gov (United States)

      Russomando, Graciela; Cousiño, Blanca; Sanchez, Zunilda; Franco, Laura X; Nara, Eva M; Chena, Lilian; Martínez, Magaly; Galeano, María E; Benitez, Lucio

      2017-01-01

      BACKGROUND Since the early 1990s, programs to control Chagas disease in South America have focused on eradicating domiciliary Triatoma infestans, the main vector. Seroprevalence studies of the chagasic infection are included as part of the vector control programs; they are essential to assess the impact of vector control measures and to monitor the prevention of vector transmission. OBJECTIVE To assess the interruption of domiciliary vector transmission of Chagas disease by T. infestans in Paraguay by evaluating the current state of transmission in rural areas. METHODS A survey of seroprevalence of Chagas disease was carried out in a representative sample group of Paraguayans aged one to five years living in rural areas of Paraguay in 2008. Blood samples collected on filter paper from 12,776 children were tested using an enzyme-linked immunosorbent assay. Children whose serology was positive or undetermined (n = 41) were recalled to donate a whole blood sample for retesting. Their homes were inspected for current triatomine infestation. Blood samples from their respective mothers were also collected and tested to check possible transmission of the disease by a congenital route. FINDINGS A seroprevalence rate of 0.24% for Trypanosoma cruzi infection was detected in children under five years of age among the country’s rural population. Our findings indicate that T. cruzi was transmitted to these children vertically. The total number of infected children, aged one to five years living in these departments, was estimated at 1,691 cases with an annual incidence of congenital transmission of 338 cases per year. MAIN CONCLUSION We determined the impact of vector control in the transmission of T. cruzi, following uninterrupted vector control measures employed since 1999 in contiguous T. infestans-endemic areas of Paraguay, and this allowed us to estimate the degree of risk of congenital transmission in the country. PMID:28443980

    8. Stenting and overdilating small Gore-Tex vascular grafts in complex congenital heart disease.

      Science.gov (United States)

      Penford, Gemma; Quandt, Daniel; Mehta, Chetan; Bhole, Vinay; Dhillon, Rami; Seale, Anna; Stumper, Oliver

      2018-01-01

      Gore-Tex ® grafts are integral in the management of congenital heart disease. Issues of graft stenosis or somatic outgrowth may precipitate high-risk early surgery, and catheter intervention is a relatively under-reported management option. To assess efficacy, safety, and outcomes of stenting and overdilating small Gore-Tex ® vascular grafts with the aim of optimizing surgical timing. Retrospective analysis of single-center, 13-year experience of 93 graft stenting interventions or reintervention in 80 patients, with the aim of relieving stenosis ± overdilation, to depose surgical graft revision or optimize surgical timing and candidacy. Median preintervention graft diameter was 52% (IQR 43-63) of nominal size, postintervention this increased to median 102% (IQR 96-120) [P Gore-Tex ® vascular grafts can be stented effectively and expanded beyond nominal diameters by around +26%. This improves oxygen saturations, providing excellent palliation and optimized surgical timing. Adverse events are most frequent in precavopulmonary shunt patients. Gore-Tex ® grafts are widely used in the palliation of cyanotic congenital heart disease. Grafts may become stenosed and do not allow for somatic growth. Over a 13 year period, graft stenting was performed in 80 patients (93 technically successful interventions, 4 unsuccessful.) Median internal lumen change was +50% (of nominal graft size), mean oxygen saturation change +13%. Over-dilation was performed in more than half of the cohort, with a median gain of +26% on nominal graft size. In precavopulmonary shunt patients, there was a moderate incidence of serious complications. Clinically useful deferral of surgery was achieved for the majority. © 2018 Wiley Periodicals, Inc.

    9. Identifying improvements to complex pathways: evidence synthesis and stakeholder engagement in infant congenital heart disease.

      Science.gov (United States)

      Crowe, Sonya; Knowles, Rachel; Wray, Jo; Tregay, Jenifer; Ridout, Deborah A; Utley, Martin; Franklin, Rodney; Bull, Catherine L; Brown, Katherine L

      2016-06-06

      Many infants die in the year following discharge from hospital after surgical or catheter intervention for congenital heart disease (3-5% of discharged infants). There is considerable variability in the provision of care and support in this period, and some families experience barriers to care. We aimed to identify ways to improve discharge and postdischarge care for this patient group. A systematic evidence synthesis aligned with a process of eliciting the perspectives of families and professionals from community, primary, secondary and tertiary care. UK. A set of evidence-informed recommendations for improving the discharge and postdischarge care of infants following intervention for congenital heart disease was produced. These address known challenges with current care processes and, recognising current resource constraints, are targeted at patient groups based on the number of patients affected and the level and nature of their risk of adverse 1-year outcome. The recommendations include: structured discharge documentation, discharging certain high-risk patients via their local hospital, enhanced surveillance for patients with certain (high-risk) cardiac diagnoses and an early warning tool for parents and community health professionals. Our recommendations set out a comprehensive, system-wide approach for improving discharge and postdischarge services. This approach could be used to address challenges in delivering care for other patient populations that can fall through gaps between sectors and organisations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

    10. Plasma levels of nucleosomes and nucleosome-autoantibody complexes in murine lupus: effects of disease progression and lipopolyssacharide administration.

      NARCIS (Netherlands)

      Licht, R.; Bruggen, M.C.J. van; Oppers-Walgreen, B.; Rijke, T.P.M.; Berden, J.H.M.

      2001-01-01

      OBJECTIVE: To evaluate the effect of disease progression and lipopolysaccharide (LPS) administration on the presence of nucleosomes, antinucleosome reactivity, and nucleosome-Ig complexes in the circulation of MRL and control mice. METHODS: Plasma samples from lupus-prone (MRL/lpr and MRL/+) and

    11. Local immune-complexes and inflammatory response in patients with chronic interstitial pulmonary disorders associated with collagen vascular diseases

      NARCIS (Netherlands)

      Jansen, H. M.; Schutte, A. J. H.; Elema, J. D.; van der Giessen, M.; Reig, R. P.; van Leeuwen, M. A.; Sluiter, H. J.; The, T. Hauw

      Evidence is accumulating that the lung injury in collagen vascular diseases (CVD) is triggered by immune complexes (IC). These reactions are neutrophil- and complement-dependent. The direct, in vivo phagocytosis of IC by bronchoalveolar lavage polymorphonuclear leucocytes (BAL-PMN), was studied in

    12. Health related quality of life and health status in adult survivors with previously operated complex congenital heart disease

      NARCIS (Netherlands)

      Kamphuis, M.; Ottenkamp, J.; Vliegen, H. W.; Vogels, T.; Zwinderman, K. H.; Kamphuis, R. P.; Verloove-Vanhorick, S. P.

      2002-01-01

      To examine the impact of previously operated complex congenital heart disease on health related quality of life and subjective health status and to determine the relation between these parameters and physical status. Cross sectional; information on medical follow up was sought retrospectively.

    13. Wolves, dogs, rearing and reinforcement: complex interactions underlying species differences in training and problem-solving performance.

      Science.gov (United States)

      Frank, Harry

      2011-11-01

      Frank and Frank et al. (1982-1987) administered a series of age-graded training and problem-solving tasks to samples of Eastern timber wolf (C. lupus lycaon) and Alaskan Malamute (C. familiaris) pups to test Frank's (Zeitschrift für Tierpsychologie 53:389-399, 1980) model of the evolution of information processing under conditions of natural and artificial selection. Results confirmed the model's prediction that wolves should perform better than dogs on problem-solving tasks and that dogs should perform better than wolves on training tasks. Further data collected at the University of Connecticut in 1983 revealed a more complex and refined picture, indicating that species differences can be mediated by a number of factors influencing wolf performance, including socialization regimen (hand-rearing vs. mother-rearing), interactive effects of socialization on the efficacy of both rewards and punishments, and the flexibility to select learning strategies that experimenters might not anticipate.

    14. Stability and Complexity Analysis of a Dual-Channel Closed-Loop Supply Chain with Delayed Decision under Government Intervention

      Directory of Open Access Journals (Sweden)

      Daoming Dai

      2017-10-01

      Full Text Available This paper constructs a continuous dual-channel closed-loop supply chain (DCLSC model with delayed decision under government intervention. The existence conditions of the local stability of the equilibrium point are discussed. We analyze the influence of delay parameters, the adjustment speed of wholesale price, recovery rate of waste products, direct price, carbon quota subsidy, and carbon tax on the stability and complexity of model by using bifurcation diagram, entropy diagram, attractor, and time series diagram and so on. Besides, the delay feedback control method is adopted to control the unstable or chaotic system effectively. The main conclusions of this paper show that the variables mentioned above must be within a reasonable range. Otherwise, the model will lose stability or enter chaos. The government can effectively adjust manufacturers' profit through carbon tax and carbon quota subsidy, and encourage manufacturers to reduce carbon emissions and increase the remanufacturing of waste products.

    15. Control technique of spontaneous combustion in fully mechan ized stope during period of end caving under complex mining influence

      Science.gov (United States)

      Yuan, Benqing

      2018-01-01

      In view of the phenomenon of spontaneous combustion of coal seam occurring during the period of end caving under complex mining conditions, taking the 1116 (3) stope of Guqiao mine as the object of study, the causes of spontaneous combustion during the period of end caving are analyzed, according to the specific geological conditions of the stope to develop corresponding fire prevention measures, including the reduction of air supply and air leakage in goaf, reduce the amount of coal left, reasonable drainage, nitrogen injection for spontaneous combustion prevention, grouting for spontaneous combustion prevention and permanent closure, fundamentally eliminates the potential for spontaneous combustion during the period of 1116(3) stope end caving. The engineering practice shows that this kind of measure has reference value for the prevention and control of spontaneous combustion during the period of stope end caving.

    16. Mutation of C20orf7 Disrupts Complex I Assembly and Causes Lethal Neonatal Mitochondrial Disease

      NARCIS (Netherlands)

      Sugiana, Canny; Pagliarini, David J.; McKenzie, Matthew; Kirby, Denise M.; Salemi, Renato; Abu-Amero, Khaled K.; Dahl, Hans-Henrik M.; Hutchison, Wendy M.; Vascotto, Katherine A.; Smith, Stacey M.; Newbold, Robert F.; Christodoulou, John; Calvo, Sarah; Mootha, Vamsi K.; Ryan, Michael T.; Thorburn, David R.

      2008-01-01

      Complex I (NADH:ubiquinone oxidoreductase) is the first and largest multimeric complex of the mitochondrial respiratory chain. Human complex I comprises seven Subunits encoded by mitochondrial DNA and 38 nuclear-encoded subunits that are assembled together in a process that is only partially

    17. The human RNase MRP complex : composition, assembly and role in human disease

      NARCIS (Netherlands)

      Eenennaam, Hans van

      2002-01-01

      Not all RNA molecules in human cells are being translated into proteins. Some of them function in binding proteins, thereby forming so-called RNA-protein complexes. The RNase MRP complex is an example of such an RNA-protein complex. In this thesis two new protein components of the human RNase MRP

    18. A coupled remote sensing and the Surface Energy Balance with Topography Algorithm (SEBTA) to estimate actual evapotranspiration under complex terrain

      Science.gov (United States)

      Gao, Z. Q.; Liu, C. S.; Gao, W.; Chang, N. B.

      2010-07-01

      Evapotranspiration (ET) may be used as an ecological indicator to address the ecosystem complexity. The accurate measurement of ET is of great significance for studying environmental sustainability, global climate changes, and biodiversity. Remote sensing technologies are capable of monitoring both energy and water fluxes on the surface of the Earth. With this advancement, existing models, such as SEBAL, S_SEBI and SEBS, enable us to estimate the regional ET with limited temporal and spatial scales. This paper extends the existing modeling efforts with the inclusion of new components for ET estimation at varying temporal and spatial scales under complex terrain. Following a coupled remote sensing and surface energy balance approach, this study emphasizes the structure and function of the Surface Energy Balance with Topography Algorithm (SEBTA). With the aid of the elevation and landscape information, such as slope and aspect parameters derived from the digital elevation model (DEM), and the vegetation cover derived from satellite images, the SEBTA can fully account for the dynamic impacts of complex terrain and changing land cover in concert with some varying kinetic parameters (i.e., roughness and zero-plane displacement) over time. Besides, the dry and wet pixels can be recognized automatically and dynamically in image processing thereby making the SEBTA more sensitive to derive the sensible heat flux for ET estimation. To prove the application potential, the SEBTA was carried out to present the robust estimates of 24 h solar radiation over time, which leads to the smooth simulation of the ET over seasons in northern China where the regional climate and vegetation cover in different seasons compound the ET calculations. The SEBTA was validated by the measured data at the ground level. During validation, it shows that the consistency index reached 0.92 and the correlation coefficient was 0.87.

    19. Transcatheter radiofrequency ablation under the guidance of three-dimensional mapping for the treatment of complex cardiac arrhythmias

      International Nuclear Information System (INIS)

      Hong Lang; Wang Hong; Lai Hengli; Ying Qiulin; Chen Zhangqiang; Lu Linxiang; Qiu Yun; Xiao Chengwei

      2010-01-01

      Objective: To investigate the effectiveness and safety of transcatheter radiofrequency ablation guided by a three-dimensional mapping system (Ensite or Carto) for the treatment of complex cardiac arrhythmias. Methods: A cohort of 123 consecutive hospitalized inpatients during the period from February 2006 to December 2008 were selected for this study. These patients suffered from various arrhythmias, including paroxysmal atrial fibrillation (n = 58), persistent or permanent atrial fibrillation (n = 10), atrial flutter (n = 13), atrial tachycardia (n = 12) and ventricular tachycardia or frequent ventricular premature beats (n = 30). Transcatheter radiofrequency ablation for arrhythmias was performed under the guidance of an EnSite3000 / NavX or Array mapping system in 80 cases, and under the guidance of a CARTO mapping system in the remaining 43 cases. Results: Successful ablation of arrhythmias was obtained by single operation in 106 cases (86.18%), including 59 cases with atrial fibrillation, 11 cases with atrial flutter, 10 cases with atrial tachycardia, and 26 cases with ventricular tachycardia or premature ventricular beat.Ablation procedure was carried out and was successful in 10 cases with a successful rate of 94.31%, including 5 cases with atrial fibrillation, 1 case with recurred atrial flutter, 1 case with recurrent atrial tachycardia, and 3 cases with ventricular tachycardia or premature ventricular beat.After operation, complications occurred in 6 cases, including cardiac tamponade in 4 cases, distal embolism of the left anterior descending coronary artery in 1 case, and pulmonary embolism in 1 case. Conclusion: Three-dimensional mapping system can clearly and stereoscopically display the cardiac structures. Therefore, this technique is of great value in guiding the transcatheter radiofrequency ablation for complex arrhythmias, in improving the success rate of ablation and in increasing the safety of the procedure. (authors)

    20. ACCURACY EVALUATION FOR THE NON-CONTACT DEFECT AREA MEASUREMENT AT THE COMPLEX-SHAPE SURFACES UNDER VIDEOENDOSCOPIC CONTROL

      Directory of Open Access Journals (Sweden)

      A. V. Gorevoy

      2014-07-01

      Full Text Available The problem of non-contact surface defect area measurement at complex-shape objects under videoendoscopic control is considered. Major factors contributing to the measurement uncertainty are analyzed for the first time. The proposed method of accuracy analysis is based on the evaluation of 3D coordinates of surface points from 2D projections under assumption of projective camera model and Mahalanobis distance minimization in the image plane. Expressions for area measurement error caused by sum-of-triangles approximation are obtained analytically for practically important cases of cylindrical and spherical surfaces. It is shown that the magnitude of this error component for a single triangle does not exceed 1% for the real values of parameters of the endoscopic imaging system. Expressions are derived for area measurement uncertainty evaluation on arbitrary shape surfaces, caused by measurement errors of 3D coordinates of individual points with and without a priori information about surface shape. Verification of the obtained expressions with real experiment data showed that area measurement error for a complex figure, given by a set of points, is mainly caused by ignoring the fact that these points belong to the surface. It is proved that the use of a priori information about investigated surface shape, which is often available from the design documentation, in many cases would radically improve the accuracy of surface defects area measurement. The presented results are valid for stereoscopic, shadow and phase methods of video endoscopic measurements and can be effectively used in development of new non-contact measuring endoscopic systems and modernization of existing ones.

    1. Identification of Phytoplankton Blooms under the Index of Inherent Optical Properties (IOP Index in Optically Complex Waters

      Directory of Open Access Journals (Sweden)

      Jesús A. Aguilar-Maldonado

      2018-01-01

      Full Text Available Phytoplankton blooms are sporadic events in time and are isolated in space. This complex phenomenon is produced by a variety of both natural and anthropogenic causes. Early detection of this phenomenon, as well as the classification of a water body under conditions of bloom or non-bloom, remains an unresolved problem. This research proposes the use of Inherent Optical Properties (IOPs in optically complex waters to detect the bloom or non-bloom state of the phytoplankton community. An IOP index is calculated from the absorption coefficients of the colored dissolved organic matter (CDOM, the phytoplankton (phy and the detritus (d, using the wavelength (λ 443 nm. The effectiveness of this index is tested in five bloom events in different places and with different characteristics from Mexican seas: 1. Dzilam (Caribbean Sea, Atlantic Ocean, a diatom bloom (Rhizosolenia hebetata; 2. Holbox (Caribbean Sea, Atlantic Ocean, a mixed bloom of dinoflagellates (Scrippsiella sp. and diatoms (Chaetoceros sp.; 3. Campeche Bay in the Gulf of Mexico (Atlantic Ocean, a bloom of dinoflagellates (Karenia brevis; 4. Upper Gulf of California (UGC (Pacific Ocean, a diatom bloom (Coscinodiscus and Pseudo-nitzschia and 5. Todos Santos Bay, Ensenada (Pacific Ocean, a dinoflagellate bloom (Lingulodinium polyedrum. The diversity of sites show that the IOP index is a suitable method to determine the phytoplankton bloom conditions.

    2. Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus.

      Science.gov (United States)

      Sjöwall, C; Zapf, J; von Löhneysen, S; Magorivska, I; Biermann, M; Janko, C; Winkler, S; Bilyy, R; Schett, G; Herrmann, M; Muñoz, L E

      2015-05-01

      In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the

    3. Structural and Mechanical Properties of Intermediate Filaments under Extreme Conditions and Disease

      Science.gov (United States)

      Qin, Zhao

      Intermediate filaments are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that intermediate filament proteins play key roles to reinforce cells subjected to large-deformation as well as participate in signal transduction. However, it is still poorly understood how the nanoscopic structure, as well as the biochemical properties of these protein molecules contribute to their biomechanical functions. In this research we investigate the material function of intermediate filaments under various extreme mechanical conditions as well as disease states. We use a full atomistic model and study its response to mechanical stresses. Learning from the mechanical response obtained from atomistic simulations, we build mesoscopic models following the finer-trains-coarser principles. By using this multiple-scale model, we present a detailed analysis of the mechanical properties and associated deformation mechanisms of intermediate filament network. We reveal the mechanism of a transition from alpha-helices to beta-sheets with subsequent intermolecular sliding under mechanical force, which has been inferred previously from experimental results. This nanoscale mechanism results in a characteristic nonlinear force-extension curve, which leads to a delocalization of mechanical energy and prevents catastrophic fracture. This explains how intermediate filament can withstand extreme mechanical deformation of > 1 00% strain despite the presence of structural defects. We combine computational and experimental techniques to investigate the molecular mechanism of Hutchinson-Gilford progeria syndrome, a premature aging disease. We find that the mutated lamin tail .domain is more compact and stable than the normal one. This altered structure and stability may enhance the association of intermediate filaments with the nuclear membrane, providing a molecular mechanism of the disease. We study the nuclear membrane association

    4. EFFICIENCY OF INFLUENZA VACCINATION IN PATIENTS WITH CIRCULATORY SYSTEM DISEASES UNDER DISPENSARY OBSERVATION IN OUTPATIENT CLINICS: PROSPECTIVE FOLLOW-UP MONITORING DATA

      Directory of Open Access Journals (Sweden)

      S. A. Boytsov

      2016-01-01

      Full Text Available Aim. To estimate an efficiency of influenza vaccination in patients with circulatory system diseases diseases (CSD under 3-year follow-up in outpatient clinics.Methods. The efficiency of influenza vaccination was investigated in CSD patients followed up at 2Ivanovo outpatient clinics and 2Saratov ones. The investigation enrolled 817 people, including 367 patients who consented to Grippol Plus influenza vaccination and 450 who refused.Results. During 36-month follow-up after being included in the study the vaccinated group showed a significantly fewer influenza and acute respiratory viral infections than the non-vaccinated group (28 and 442; р<0.0001. The vaccinated group had fewer CSD worsening cases per patient (p=0.04 and CSD-associated hospitalization rates (p=0.006 than the non-vaccinated group. In the vaccinated group, the total number of cases of cerebral stroke, myocardial infarction, deaths from cardiovascular diseases (CVD was significantly less (17 compared with non-vaccinated (38, р=0.03. The risk of infectious diseases and acute cardiovascular event (myocardial infarction, stroke, death from CVD was significantly lower in the group of vaccinated patients: by 36% (p=0.001 and by 59% (p=0.008, respectively.Conclusion. Influenza vaccination, as an essential component of complex medical prevention, leads to reduction in incidence of infectious diseases and of CSD worsening including myocardial infarction, stroke, and death from CVD in patients under 3-year monitoring in outpatient clinics

    5. Complex Regional Pain Syndrome Caused by Lumbar Herniated Intervertebral Disc Disease.

      Science.gov (United States)

      Kim, Se Hee; Choi, Sang Sik; Lee, Mi Kyung; Kin, Jung Eun

      2016-07-01

      Most cases of complex regional pain syndrome (CRPS) occur after some inciting injury. There are a few cases of CRPS after an operation for disc disease. CRPS from a mild herniated intervertebral disc (HIVD) without surgical intervention is even rarer than CRPS after an operation for disc disease.A 22-year-old man was transferred to a pain clinic. He had continuously complained about back and right leg pain. He presented with a skin color change in the right lower leg, intermittent resting tremor, stiffness, and swelling in the right leg. He complained of a pulling sensation and numbness in his right buttock, posterior thigh, lateral calf, and ankle. This symptom was in accordance with L4/5 radiculopathy. Magnetic resonance imaging (MRI) also showed L4/5 HIVD that was central to the bilateral subarticular protrusion.He was diagnosed as having CRPS, which fits the revised International Association for the Study of Pain (IASP) criteria. He fulfilled 4 symptom categories (allodynia, temperature asymmetry and skin color change, sweating changes, decreased range of motion and motor dysfunction) and 3 of 4 sign categories (allodynia, temperature asymmetry and skin color changes, decreased range of motion and motor dysfunction). The bone scan and thermography also revealed CRPS.For the past 2 months, we have performed intensive treatments. But, he never became pain-free and walking for 5 minutes led to persistent leg pain. We decided to perform percutaneous nucleoplasty, which can directly decompress a HIVD. On the next day, he achieved dramatic symptom relief. The visual analog scale (VAS) score improved to 3, compared to the VAS score of 9 at the first visit. The skin color change, allodynia, and tremor in the right leg disappeared, and the temperature asymmetry normalized. Motor weakness of the right leg also recovered.We report an unusual case of CRPS that was caused by L4/5 HIVD without a history of trauma or surgery. It has a clear causal relationship between HIVD

    6. Potential distribution of pine wilt disease under future climate change scenarios.

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      Akiko Hirata

      Full Text Available Pine wilt disease (PWD constitutes a serious threat to pine forests. Since development depends on temperature and drought, there is a concern that future climate change could lead to the spread of PWD infections. We evaluated the risk of PWD in 21 susceptible Pinus species on a global scale. The MB index, which represents the sum of the difference between the mean monthly temperature and 15 when the mean monthly temperatures exceeds 15°C, was used to determine current and future regions vulnerable to PWD (MB ≥ 22. For future climate conditions, we compared the difference in PWD risks among four different representative concentration pathways (RCPs 2.6, 4.5, 6.0, and 8.5 and two time periods (2050s and 2070s. We also evaluated the impact of climate change on habitat suitability for each Pinus species using species distribution models. The findings were then integrated and the potential risk of PWD spread under climate change was discussed. Within the natural Pinus distribution area, southern parts of North America, Europe, and Asia were categorized as vulnerable regions (MB ≥ 22; 16% of the total Pinus distribution area. Representative provinces in which PWD has been reported at least once overlapped with the vulnerable regions. All RCP scenarios showed expansion of vulnerable regions in northern parts of Europe, Asia, and North America under future climate conditions. By the 2070s, under RCP 8.5, an estimated increase in the area of vulnerable regions to approximately 50% of the total Pinus distribution area was revealed. In addition, the habitat conditions of a large portion of the Pinus distribution areas in Europe and Asia were deemed unsuitable by the 2070s under RCP 8.5. Approximately 40% of these regions overlapped with regions deemed vulnerable to PWD, suggesting that Pinus forests in these areas are at risk of serious damage due to habitat shifts and spread of PWD.

    7. Potential distribution of pine wilt disease under future climate change scenarios.

      Science.gov (United States)

      Hirata, Akiko; Nakamura, Katsunori; Nakao, Katsuhiro; Kominami, Yuji; Tanaka, Nobuyuki; Ohashi, Haruka; Takano, Kohei Takenaka; Takeuchi, Wataru; Matsui, Tetsuya

      2017-01-01

      Pine wilt disease (PWD) constitutes a serious threat to pine forests. Since development depends on temperature and drought, there is a concern that future climate change could lead to the spread of PWD infections. We evaluated the risk of PWD in 21 susceptible Pinus species on a global scale. The MB index, which represents the sum of the difference between the mean monthly temperature and 15 when the mean monthly temperatures exceeds 15°C, was used to determine current and future regions vulnerable to PWD (MB ≥ 22). For future climate conditions, we compared the difference in PWD risks among four different representative concentration pathways (RCPs 2.6, 4.5, 6.0, and 8.5) and two time periods (2050s and 2070s). We also evaluated the impact of climate change on habitat suitability for each Pinus species using species distribution models. The findings were then integrated and the potential risk of PWD spread under climate change was discussed. Within the natural Pinus distribution area, southern parts of North America, Europe, and Asia were categorized as vulnerable regions (MB ≥ 22; 16% of the total Pinus distribution area). Representative provinces in which PWD has been reported at least once overlapped with the vulnerable regions. All RCP scenarios showed expansion of vulnerable regions in northern parts of Europe, Asia, and North America under future climate conditions. By the 2070s, under RCP 8.5, an estimated increase in the area of vulnerable regions to approximately 50% of the total Pinus distribution area was revealed. In addition, the habitat conditions of a large portion of the Pinus distribution areas in Europe and Asia were deemed unsuitable by the 2070s under RCP 8.5. Approximately 40% of these regions overlapped with regions deemed vulnerable to PWD, suggesting that Pinus forests in these areas are at risk of serious damage due to habitat shifts and spread of PWD.

    8. EFFICACY AND SAFETY OF IRRIGATION SPRAY APPLICATION FOR THE THROAT IN COMPLEX THERAPY OF INFLAMMATORY OROPHARYNX DISEASES IN CHILDREN

      Directory of Open Access Journals (Sweden)

      Yu.L. Soldatskiy

      2011-01-01

      Full Text Available Inflammatory diseases of the oropharynx manifested with pain or discomfort in the throat, is a frequent pathology in children. Traditionally, patients with acute and exacerbation of chronic tonsillitis and pharyngitis are prescribed gargarism. In recent years, the use of sea water-based throat sprays have been allowed for irrigation therapy. Their use as part of the complex treatment of inflammatory oropharynx diseases statistically reliably decreases the intensity of pain reaction on the 10th–24th day of treatment compared to conventional gargarism and is comparable with conventional therapy when assessing other clinical symptoms. It is therefore possible to recommend using sea water-based substance as a initial means of irrigation therapy in the complex treatment of inflammatory oropharynx diseases in children.Key words: pharyngitis, tonsillitis, throat pain, irrigation therapy, children.

    9. Complex disposition of methylthioninium redox forms determines efficacy in tau aggregation inhibitor therapy for Alzheimer's disease.

      Science.gov (United States)

      Baddeley, Thomas C; McCaffrey, Jennifer; Storey, John M D; Cheung, John K S; Melis, Valeria; Horsley, David; Harrington, Charles R; Wischik, Claude M

      2015-01-01

      Methylthioninium (MT) is a tau aggregation inhibitor with therapeutic potential in Alzheimer's disease (AD). MT exists in equilibrium between reduced [leucomethylthioninium (LMT)] and oxidized (MT(+)) forms; as a chloride salt [methylthioninium chloride (MTC), "methylene blue"], it is stabilized in its MT(+) form. Although the results of a phase 2 study of MTC in 321 mild/moderate AD subjects identified a 138-mg MT/day dose as the minimum effective dose on cognitive and imaging end points, further clinical development of MT was delayed pending resolution of the unexpected lack of efficacy of the 228-mg MT/day dose. We hypothesized that the failure of dose response may depend on differences known at the time in dissolution in simulated gastric and intestinal fluids of the 100-mg MTC capsules used to deliver the 228-mg dose and reflect previously unsuspected differences in redox processing of MT at different levels in the gut. The synthesis of a novel chemical entity, LMTX (providing LMT in a stable anhydrous crystalline form), has enabled a systematic comparison of the pharmacokinetic properties of MTC and LMTX in preclinical and clinical studies. The quantity of MT released in water or gastric fluid within 60 minutes proved in retrospect to be an important determinant of clinical efficacy. A further factor was a dose-dependent limitation in the ability to absorb MT in the presence of food when delivered in the MT(+) form as MTC. A model is presented to account for the complexity of MT absorption, which may have relevance for other similar redox molecules. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

    10. Efficacy of Oral Administration of Sodium Iodide to Prevent Bovine Respiratory Disease Complex.

      Science.gov (United States)

      Shoemake, B M; Vander Ley, B L; Newcomer, B W; Heller, M C

      2018-01-01

      The prevention of bovine respiratory disease complex (BRD) in beef cattle is important to maintaining health and productivity of calves in feeding operations. Determine whether BRD bacterial and viral pathogens are susceptible to the lactoperoxidase/hydrogen peroxide/iodide (LPO/H 2 O 2 /I - ) system in vitro and to determine whether the oral administration of sodium iodide (NaI) could achieve sufficient concentrations of iodine (I) in the respiratory secretions of weaned beef calves to inactivate these pathogens in vivo. Sixteen weaned, apparently healthy, commercial beef calves from the University of Missouri, College of Veterinary Medicine teaching herd. In vitro viral and bacterial assays were performed to determine susceptibility to the LPO/H 2 O 2 /I - system at varying concentrations of NaI. Sixteen randomly selected, healthy crossbred beef weanlings were administered 70 mg/kg NaI, or water, orally in a blinded, placebo-controlled trial. Blood and nasal secretions were collected for 72 hours and analyzed for I - concentration. Bovine herpesvirus-1, parainfluenza-3, Mannheimia haemolytica and Bibersteinia trehalosi were all inactivated or inhibited in vitro by the LPO/H 2 O 2 /I - reaction. Oral administration of NaI caused a marked increase in nasal fluid I concentration with a C max  = 181 (1,420 μM I), T 12 , a sufficient concentration to inactivate these pathogens in vitro. In vitro, the LPO/H 2 O 2 /I - system inactivates and inhibits common pathogens associated with BRD. The administration of oral NaI significantly increases the I concentration of nasal fluid indicating that this system might be useful in preventing bovine respiratory infections. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

    11. The care delivery experience of hospitalized patients with complex chronic disease.

      Science.gov (United States)

      Kuluski, Kerry; Hoang, Sylvia N; Schaink, Alexis K; Alvaro, Celeste; Lyons, Renee F; Tobias, Roy; Bensimon, Cécile M

      2013-12-01

      This study investigated what is important in care delivery from the perspective of hospital inpatients with complex chronic disease, a currently understudied population. One-on-one semi-structured interviews were conducted with inpatients at a continuing care/rehabilitation hospital (n = 116) in Canada between February and July 2011. The study design was mixed methods and reports on patient characteristics and care delivery experiences. Basic descriptive statistics were run using SPSS version 17, and thematic analysis on the transcripts was conducted using NVivo9 software. Patients had an average of 5 morbidities and several illness symptoms including activity of daily living impairments, physical pain and emotional disturbance. Three broad themes (each with one or more subthemes) were generated from the data representing important components of care delivery: components of the care plan (a comprehensive assessment, supported transitions and a bio-psycho-social care package); care capacity and quality (optimal staff to patient ratios, quicker response times, better patient-provider communication and consistency between providers) and the patient-provider relationships (characterized by respect and dignity). As health systems throughout the industrialized world move to sustain health budgets while optimizing quality of care, it is critical to better understand this population, so that appropriate metrics, services and policies can be developed. The study has generated a body of evidence on the important components of care delivery from the perspectives of a diverse group of chronically ill individuals who have spent a considerable amount of time in the health-care system. Moving forward, exploration around the appropriate funding models and skill mix is needed to move the evidence into changed practice. © 2013 John Wiley & Sons Ltd.

    12. Magnetic resonance imaging planning in children with complex congenital heart disease – A new approach

      Directory of Open Access Journals (Sweden)

      Israel Valverde

      2017-04-01

      Full Text Available Objectives To compare a standard sequential 2D Planning Method (2D-PM with a 3D offline Planning Method (3D-PM based on 3D contrast-enhanced magnetic resonance angiography (CE-MRA in children with congenital heart disease (CHD. Design In 14 children with complex CHD (mean: 2.6 years, range: 3 months to 7.6 years, axial and coronal cuts were obtained with single slice spin echo sequences to get the final double oblique longitudinal cut of the targeted anatomical structure (2D-PM, n = 31. On a separate workstation, similar maximal intensity projection (MIP images were generated offline from a 3D CE-MRA. MIP images were localizers for repeated targeted imaging using the previous spin echo sequence (3D-PM. Finally, image coverage, spatial orientation and acquisition time were compared for 2D-PM and 3D-PM. Main outcome measures 2D-PM and 3D-PM images were similar: both perfectly covered the selected anatomic regions and no spatial differences were found (p>0.05. The mean time for creation of the final imaging plane was 241 ± 31 s (2D-PM compared to 71 ± 18 s (3D-PM (p<0.05. Conclusions 3D-PM shows similar results compared to 2D-PM, but allows faster and offline planning thereby reducing the scan time significantly. As newly developed high-resolution 3D datasets can also be used further improvement of this technology is expected.

    13. The clinical efficacy of a clarithromycin-based regimen for Mycobacterium avium complex disease: A nationwide post-marketing study.

      Science.gov (United States)

      Kadota, Jun-Ichi; Kurashima, Atsuyuki; Suzuki, Katsuhiro

      2017-05-01

      The revised 2007 American Thoracic Society/Infectious Diseases Society of America statement recommend clarithromycin-based combination therapy for treatment of Mycobacterium avium complex lung disease and stipulates approximately 1 year of continuous treatment after bacilli negative conversion. However, supporting data are insufficient. Our objective was to obtain data on the clinical outcome of clarithromycin-based daily regimens by conducting a nationwide retrospective post-marketing study of M. avium complex lung disease. In accordance with the Japanese guidelines, patients were enrolled in this survey according to their chest radiographic findings and microbiologic test results. They were treated with a multidrug regimen including clarithromycin, rifampicin, and ethambutol (clarithromycin-based regimen) until bacilli negative conversion, and the treatment was continued for approximately 1 year after the initial conversion. Data were collected before administration, at the time of bacilli negative conversion, at the end of treatment, and at 6 months after the end of treatment. Of the 466 subjects enrolled in the study, 271 patients who received clarithromycin at 800 mg/day underwent evaluation for M. avium complex disease. The final bacilli negative conversion rate in those patients was 94.7%. The bacteriological relapse rate was 5.0% (5/100 patients). Bacteriological relapse was noted in patients treated for less than 15 months after conversion. No life-threatening or serious adverse drug reactions were observed. This study demonstrated that a clarithromycin-based daily regimen can yield a high bacteriological conversion rate in M. avium complex disease. After conversion, treatment for less than 15 months might be insufficient to prevent bacteriological relapse. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

    14. The Mechanisms of Traditional Chinese Medicine Underlying the Prevention and Treatment of Parkinson's Disease

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      Xiaoliang Li

      2017-09-01

      Full Text Available Parkinson's disease (PD, characterized with bradykinesia, static tremor, rigidity and disturbances in balance, is the second most common neurodegenerative disorder. Along with the largely aging population in the world, the incidence is increasing year by year, which imposes the negative impacts on patients, their families and the whole society. Traditional Chinese medicine (TCM has a positive prospect for the prevention and cure of PD due to its advantages of less side effects and multi-target effects. At present, the pathogenesis of PD is not yet fully discovered. This paper elaborates the mechanisms of TCM underlying the prevention and treatment of PD with regards to the inhibition of oxidative stress, the regulation of mitochondrial dysfunction, the reduction of toxic excitatory amino acids (EAA, the inhibition of neuroinflammation, the inhibition of neuronal apoptosis, and the inhibition of abnormal protein aggregation.

    15. Resistance Potential of Bread Wheat Genotypes Against Yellow Rust Disease Under Egyptian Climate.

      Science.gov (United States)

      Mahmoud, Amer F; Hassan, Mohamed I; Amein, Karam A

      2015-12-01

      Yellow rust (stripe rust), caused by Puccinia striiformis f. sp. tritici, is one of the most destructive foliar diseases of wheat in Egypt and worldwide. In order to identify wheat genotypes resistant to yellow rust and develop molecular markers associated with the resistance, fifty F8 recombinant inbred lines (RILs) derived from a cross between resistant and susceptible bread wheat landraces were obtained. Artificial infection of Puccinia striiformis was performed under greenhouse conditions during two growing seasons and relative resistance index (RRI) was calculated. Two Egyptian bread wheat cultivars i.e. Giza-168 (resistant) and Sakha-69 (susceptible) were also evaluated. RRI values of two-year trial showed that 10 RILs responded with RRI value >6 2 rust. However, further molecular analyses would be performed to confirm markers associated with the resistance and suitable for marker-assisted selection. Resistant RILs identified in the study could be efficiently used to improve the resistance to yellow rust in wheat.

    16. Production of Biomass-Degrading Multienzyme Complexes under Solid-State Fermentation of Soybean Meal Using a Bioreactor.

      Science.gov (United States)

      Vitcosque, Gabriela L; Fonseca, Rafael F; Rodríguez-Zúñiga, Ursula Fabiola; Bertucci Neto, Victor; Couri, Sonia; Farinas, Cristiane S

      2012-01-01

      Biomass-degrading enzymes are one of the most costly inputs affecting the economic viability of the biochemical route for biomass conversion into biofuels. This work evaluates the effects of operational conditions on biomass-degrading multienzyme production by a selected strain of Aspergillus niger. The fungus was cultivated under solid-state fermentation (SSF) of soybean meal, using an instrumented lab-scale bioreactor equipped with an on-line automated monitoring and control system. The effects of air flow rate, inlet air relative humidity, and initial substrate moisture content on multienzyme (FPase, endoglucanase, and xylanase) production were evaluated using a statistical design methodology. Highest production of FPase (0.55 IU/g), endoglucanase (35.1 IU/g), and xylanase (47.7 IU/g) was achieved using an initial substrate moisture content of 84%, an inlet air humidity of 70%, and a flow rate of 24 mL/min. The enzymatic complex was then used to hydrolyze a lignocellulosic biomass, releasing 4.4 g/L of glucose after 36 hours of saccharification of 50 g/L pretreated sugar cane bagasse. These results demonstrate the potential application of enzymes produced under SSF, thus contributing to generate the necessary technological advances to increase the efficiency of the use of biomass as a renewable energy source.

    17. Production of Biomass-Degrading Multienzyme Complexes under Solid-State Fermentation of Soybean Meal Using a Bioreactor

      Directory of Open Access Journals (Sweden)

      Gabriela L. Vitcosque

      2012-01-01

      Full Text Available Biomass-degrading enzymes are one of the most costly inputs affecting the economic viability of the biochemical route for biomass conversion into biofuels. This work evaluates the effects of operational conditions on biomass-degrading multienzyme production by a selected strain of Aspergillus niger. The fungus was cultivated under solid-state fermentation (SSF of soybean meal, using an instrumented lab-scale bioreactor equipped with an on-line automated monitoring and control system. The effects of air flow rate, inlet air relative humidity, and initial substrate moisture content on multienzyme (FPase, endoglucanase, and xylanase production were evaluated using a statistical design methodology. Highest production of FPase (0.55 IU/g, endoglucanase (35.1 IU/g, and xylanase (47.7 IU/g was achieved using an initial substrate moisture content of 84%, an inlet air humidity of 70%, and a flow rate of 24 mL/min. The enzymatic complex was then used to hydrolyze a lignocellulosic biomass, releasing 4.4 g/L of glucose after 36 hours of saccharification of 50 g/L pretreated sugar cane bagasse. These results demonstrate the potential application of enzymes produced under SSF, thus contributing to generate the necessary technological advances to increase the efficiency of the use of biomass as a renewable energy source.

    18. Underlying mechanism of antimicrobial activity of chitosan microparticles and implications for the treatment of infectious diseases.

      Directory of Open Access Journals (Sweden)

      Soo Jin Jeon

      Full Text Available The emergence of antibiotic resistant microorganisms is a great public health concern and has triggered an urgent need to develop alternative antibiotics. Chitosan microparticles (CM, derived from chitosan, have been shown to reduce E. coli O157:H7 shedding in a cattle model, indicating potential use as an alternative antimicrobial agent. However, the underlying mechanism of CM on reducing the shedding of this pathogen remains unclear. To understand the mode of action, we studied molecular mechanisms of antimicrobial activity of CM using in vitro and in vivo methods. We report that CM are an effective bactericidal agent with capability to disrupt cell membranes. Binding assays and genetic studies with an ompA mutant strain demonstrated that outer membrane protein OmpA of E. coli O157:H7 is critical for CM binding, and this binding activity is coupled with a bactericidal effect of CM. This activity was also demonstrated in an animal model using cows with uterine diseases. CM treatment effectively reduced shedding of intrauterine pathogenic E. coli (IUPEC in the uterus compared to antibiotic treatment. Since Shiga-toxins encoded in the genome of bacteriophage is often overexpressed during antibiotic treatment, antibiotic therapy is generally not recommended because of high risk of hemolytic uremic syndrome. However, CM treatment did not induce bacteriophage or Shiga-toxins in E. coli O157:H7; suggesting that CM can be a potential candidate to treat infections caused by this pathogen. This work establishes an underlying mechanism whereby CM exert antimicrobial activity in vitro and in vivo, providing significant insight for the treatment of diseases caused by a broad spectrum of pathogens including antibiotic resistant microorganisms.

    19. Hygiene and sanitation risk factors of diarrhoeal disease among under-five children in Ibadan, Nigeria.

      Science.gov (United States)

      Oloruntoba, Elizabeth Omoladun; Folarin, Taiwo Bukola; Ayede, Adejumoke Idowu

      2014-12-01

      Diarrhoea diseases are among the leading causes of morbidity and mortality in under-five-children (U-5C) in Nigeria. Inadequate safe water, sanitation, and hygiene account for the disease burden. Cases of diarrhoea still occur in high proportion in the study area despite government-oriented interventions. To determine the hygiene and sanitation risk factors predisposing U-5C to diarrhoea in Ibadan, Nigeria. Two hundred and twenty pairs of children, matched on age, were recruited as cases and controls over a period of 5 months in Ibadan. Questionnaire and observation checklist were used to obtain information on hygiene practices from caregivers/mothers and sanitation conditions in the households of 30% of the consenting mothers/caregivers. Data were analysed using descriptive and inferential statistics. Caregivers/mothers' mean ages were 31.3 ±7.5 (cases) and 30.6 ±6.0(controls) years. The risk of diarrhoea was significantly higher among children whose mothers did not wash hands with soap before food preparation (OR=3.0, psanitation conditions within households were risk factors for diarrhoea. This study revealed the feasibility of developing and implementing an adequate model to establish intervention priorities in sanitation in Ibadan, Nigeria.

    20. Effect of multidisciplinary disease management for hospitalized heart failure under a national health insurance programme.

      Science.gov (United States)

      Mao, Chun-Tai; Liu, Min-Hui; Hsu, Kuang-Hung; Fu, Tieh-Cheng; Wang, Jong-Shyan; Huang, Yu-Yen; Yang, Ning-I; Wang, Chao-Hung

      2015-09-01

      Multidisciplinary disease management programmes (MDPs) for heart failure have been shown to be effective in Western countries. However, it is not known whether they improve outcomes in a high population density country with a national health insurance programme. In total, 349 patients hospitalized because of heart failure were randomized into control and MDP groups. All-cause death and re-hospitalization related to heart failure were analyzed. The median follow-up period was approximately 2 years. Mean patient age was 60 years; 31% were women; and 50% of patients had coronary artery disease. MDP was associated with fewer all-cause deaths [hazard ratio (HR) = 0.49, 95% confidence interval (CI) = 0.27-0.91, P = 0.02] and heart failure-related re-hospitalizations (HR = 0.44, 95% CI = 0.25-0.77, P = 0.004). MDP was still associated with better outcomes for all-cause death (HR = 0.53, 95% CI = 0.29-0.98, P = 0.04) and heart failure-related re-hospitalization (HR = 0.46, 95% CI = 0.26-0.81, P = 0.007), after adjusting for age, diuretics, diabetes mellitus, chronic kidney disease, hypertension, sodium, and albumin. However, MDPs' effect on all-cause mortality and heart failure-related re-hospitalization was significantly attenuated after adjusting for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers or β-blockers. A stratified analysis showed that MDP combined with guideline-based medication had synergistic effects. MDP is effective in lowering all-cause mortality and re-hospitalization rates related to heart failure under a national health insurance programme. MDP synergistically improves the effectiveness of guidelines-based medications for heart failure.

    1. Perspectives of experimental and theoretical studies of self-organized dust structures in complex plasmas under microgravity conditions

      International Nuclear Information System (INIS)

      Tsytovich, V N

      2015-01-01

      We review research aimed at understanding the phenomena occurring in a complex plasma under microgravity conditions. Some aspects of the work already performed are considered that have not previously been given sufficient attention but which are potentially crucial for future work. These aspects, in particular, include the observation of compact dust structures that are estimated to be capable of confining all components of a dust plasma in a bounded spatial volume; experimental evidence of the nonlinear screening of dust particles; and experimental evidence of the excitation of collective electric fields. In theoretical terms, novel collective attraction processes between likely charged dust particles are discussed and all schemes of the shadowy attraction between dust particles used earlier, including in attempts to interpret observations, are reviewed and evaluated. Dust structures are considered from the standpoint of the current self-organization theory. It is emphasized that phase transitions between states of self-organized systems differ significantly from those in homogeneous states and that the phase diagrams should be constructed in terms of the parameters of a self-organized structure and cannot be constructed in terms of the temperature and density or similar parameters of homogeneous structures. Using the existing theoretical approaches to modeling self-organized structures in dust plasmas, the parameter distribution of a structure is recalculated for a simpler model that includes the quasineutrality condition and neglects diffusion. These calculations indicate that under microgravity conditions, any self-organized structure can contain a limited number of dust particles and is finite in size. The maximum possible number of particles in a structure determines the characteristic inter-grain distance in dust crystals that can be created under microgravity conditions. Crystallization criteria for the structures are examined and the quasispherical

    2. Detection of immune complexes in sera of dogs with rheumatic and neoplastic diseases by 125I-Clq binding test

      International Nuclear Information System (INIS)

      Terman, D.S.; Moore, D.; Collins, J.; Johnston, B.; Person, D.; Templeton, J.; Poser, R.; Quinby, F.

      1979-01-01

      Some canine rheumatic and neoplastic diseases bear a striking clinical and serological resemblance to their counterparts in man. In the present study, human 125 I-Clq was employed in a radioimmunoassay for detection of immune complexes in sera of normal dogs and those with rheumatic and neoplastic diseases. Human 125 I-Clq showed binding of 16.7 +- 5.73% in a group of normal dog sera with binding of 32.5 +- 17.3% and 43.0 +- 16.0% in sera of dogs with rheumatic and neoplastic diseases. respectively. Human 125 I-Clq bound similar quantities of heat-aggregated canine and human gamma-globulin over a broad range of concentrations and human 125 I-Clq binding in canine sera was effectively inhibited by similar quantities of heat aggregated canine and human gamma-globulin. Seven of 12 dogs with elevated levels of Clq binding had active clinical and serological rheumatic disease (SLE or rheumatoid arthritis), while none of 7 dogs with values within the normal range had active clinical disease. All 5 dogs with widespread osteogenic sarcoma and all 4 dogs with high grade adenocarcinoma of the mammary gland had elevated Clq binding values while 2 animals with low grade malignancies without evident metastases did not. Thus, it appears that human 125 I-Clq may be employed to assay immune complexes in canine sera and may be a valuable technique for the study of dogs with various rheumatic and neoplastic diseases. (author)

    3. Properties and modeling of GWAS when complex disease risk is due to non-complementing, deleterious mutations in genes of large effect.

      Directory of Open Access Journals (Sweden)

      Kevin R Thornton

      Full Text Available Current genome-wide association studies (GWAS have high power to detect intermediate frequency SNPs making modest contributions to complex disease, but they are underpowered to detect rare alleles of large effect (RALE. This has led to speculation that the bulk of variation for most complex diseases is due to RALE. One concern with existing models of RALE is that they do not make explicit assumptions about the evolution of a phenotype and its molecular basis. Rather, much of the existing literature relies on arbitrary mapping of phenotypes onto genotypes obtained either from standard population-genetic simulation tools or from non-genetic models. We introduce a novel simulation of a 100-kilobase gene region, based on the standard definition of a gene, in which mutations are unconditionally deleterious, are continuously arising, have partially recessive and non-complementing effects on phenotype (analogous to what is widely observed for most Mendelian disorders, and are interspersed with neutral markers that can be genotyped. Genes evolving according to this model exhibit a characteristic GWAS signature consisting of an excess of marginally significant markers. Existing tests for an excess burden of rare alleles in cases have low power while a simple new statistic has high power to identify disease genes evolving under our model. The structure of linkage disequilibrium between causative mutations and significantly associated markers under our model differs fundamentally from that seen when rare causative markers are assumed to be neutral. Rather than tagging single haplotypes bearing a large number of rare causative alleles, we find that significant SNPs in a GWAS tend to tag single causative mutations of small effect relative to other mutations in the same gene. Our results emphasize the importance of evaluating the power to detect associations under models that are genetically and evolutionarily motivated.

    4. Determination of immune complexes in sera from dogs with various diseases by mastocytoma cell assay.

      OpenAIRE

      Targowski, S

      1982-01-01

      Canine immunoglobulin G complexed with particulate or soluble antigen can bind to the Fc receptors on the mastocytoma cells. Attachment of immune complexes composed of immunoglobulin G and soluble antigen (ovalbumin) to mastocytoma cells was detected by an inhibition of rosette formation with indicator cells (sensitized sheep erythrocytes). Therefore, canine circulating immune complexes may also attach to mastocytoma cells and inhibit rosette formation (mastocytoma cell assay). Sera from 326 ...

    5. Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease

      KAUST Repository

      Vangone, Anna

      2014-07-30

      Anti-idiotype antibodies have potential therapeutic applications in many fields, including autoimmune diseases. Herein we report the isolation and characterization of AIM2, an anti-idiotype antibody elicited in a mouse model upon expression of the celiac disease-specific autoantibody MB2.8 (directed against the main disease autoantigen type 2 transglutaminase, TG2). To characterize the interaction between the two antibodies, a 3D model of the MB2.8-AIM2 complex has been obtained by molecular docking. Analysis and selection of the different obtained docking solutions was based on the conservation within them of the inter-residue contacts. The selected model is very well representative of the different solutions found and its stability is confirmed by molecular dynamics simulations. Furthermore, the binding mode it adopts is very similar to that observed in most of the experimental structures available for idiotype-anti-idiotype antibody complexes. In the obtained model, AIM2 is directed against the MB2.8 CDR region, especially on its variable light chain. This makes the concurrent formation of the MB2.8-AIM2 complex and of the MB2.8-TG2 complex incompatible, thus explaining the experimentally observed inhibitory effect on the MB2.8 binding to TG2. © 2014 Vangone et al.

    6. Herd Immunity Against Foot-and-Mouth Disease Under Different Vaccination Practices in India.

      Science.gov (United States)

      Sharma, G K; Mahajan, S; Matura, R; Biswal, J K; Ranjan, R; Subramaniam, S; Misri, J; Bambal, R G; Pattnaik, B

      2017-08-01

      A systematic vaccination programme is ongoing in India to control the three prevailing serotypes (A, O, Asia1) of foot-and-mouth disease (FMD) virus. Under the programme, more than 120 million bovine (term bovine applicable to both cattle and buffalo in this study) population of 221 of the 666 districts in the country are being bi-annually vaccinated with trivalent vaccine since 2010. Although clinical disease has reduced in these districts because of the systematic vaccinations, an abrupt increase in the number of FMD cases was recorded in 2013. Hence, a longitudinal field study was conducted in the year 2014 to estimate the serological herd immunity level in bovines, the impact of systematic vaccinations and field efficacy of the vaccines used. Serum samples (n = 115 963) collected from 295 districts of the 18 states of the country were analysed to estimate antibody titres against structural proteins of the three serotypes. The efficacy of the vaccine was demonstrated in the control group (group-D) where animals of the group were identified by ear tags for the purpose of repeated sampling after vaccination. Progressive building of the herd immunity in the field after systematic vaccination was demonstrated. The mean antibody titre against the serotypes O, A and Asia1 was estimated as log 10 1.93 (95% CI 1.92-1.93), 2.02 (2.02-2.02) and 2.02 (2.02-2.02), respectively, in the states covered under the control programme. However, in other states herd immunity was significantly low [mean titre log 10 1.68 (95% CI 1.67-1.69), 1.77 (1.76-1.78) and 1.85 (1.84-1.86) against the three serotypes]. Inverse relationship between the herd immunity and FMD incidences was observed the states following different vaccination practices. The study helped in demarcation of FMD risk zones in the country with low herd immunity. Estimation of herd immunity kinetics in the field helped in refining the vaccination schedule under the control programme. © 2016 Blackwell Verlag GmbH.

    7. Do heart failure disease management programs make financial sense under a bundled payment system?

      Science.gov (United States)

      Eapen, Zubin J; Reed, Shelby D; Curtis, Lesley H; Hernandez, Adrian F; Peterson, Eric D

      2011-05-01

      Policy makers have proposed bundling payments for all heart failure (HF) care within 30 days of an HF hospitalization in an effort to reduce costs. Disease management (DM) programs can reduce costly HF readmissions but have not been economically attractive for caregivers under existing fee-for-service payment. Whether a bundled payment approach can address the negative financial impact of DM programs is unknown. Our study determined the cost-neutral point for the typical DM program and examined whether published HF DM programs can be cost saving under bundled payment programs. We used a decision analytic model using data from retrospective cohort studies, meta-analyses, 5 randomized trials evaluating DM programs, and inpatient claims for all Medicare beneficiaries discharged with an HF diagnosis from 2001 to 2004. We determined the costs of DM programs and inpatient care over 30 and 180 days. With a baseline readmission rate of 22.9%, the average cost for readmissions over 30 days was $2,272 per patient. Under base-case assumptions, a DM program that reduced readmissions by 21% would need to cost $477 per patient to be cost neutral. Among evaluated published DM programs, 2 of the 5 would increase provider costs (+$15 to $283 per patient), whereas 3 programs would be cost saving (-$241 to $347 per patient). If bundled payments were broadened to include care over 180 days, then program saving estimates would increase, ranging from $419 to $1,706 per patient. Proposed bundled payments for HF admissions provide hospitals with a potential financial incentive to implement DM programs that efficiently reduce readmissions. Copyright © 2011 Mosby, Inc. All rights reserved.

    8. Evaluation of cardiovascular risk in patients with Parkinson disease under levodopa treatment.

      Science.gov (United States)

      Günaydın, Zeki Yüksel; Özer, Fahriye Feriha; Karagöz, Ahmet; Bektaş, Osman; Karataş, Mehmet Baran; Vural, Aslı; Bayramoğlu, Adil; Çelik, Abdullah; Yaman, Mehmet

      2016-01-01

      Levodopa is the indispensable choice of medial therapy in patients with Parkinson disease (PD). Since L-dopa treatment was shown to increase serum homocysteine levels, a well-known risk factor for cardiovascular disorders, the patients with PD under L-dopa treatment will be at increased risk for future cardiovascular events. The objective of this study is to evaluate cardiovascular risk in patients with PD under levodopa treatment. The study population consisted of 65 patients with idiopathic PD under L-dopa treatment. The control group included 32 age and gender matched individuals who had no cognitive decline. Echocardiographic measurements, serum homocysteine levels and elastic parameters of the aorta were compared between the patients with PD and controls. As an expected feature of L-dopa therapy, the Parkinson group had significantly higher homocystein levels (15.1 ± 3.9 µmol/L vs. 11.5 ± 3.2 µmol/L, P = 0.02). Aortic distensibility was significantly lower in the patients with PD when compared to controls (4.8 ± 1.5 dyn/cm(2) vs. 6.2 ± 1.9 dyn/cm(2), P = 0.016). Additionally, the patients with PD had higher aortic strain and aortic stiffness index (13.4% ± 6.4% vs. 7.4% ± 3.6%, P homocysteine levels were found to be positively correlated with aortic stiffness index and there was a negative correlation between aortic distensibility and levels of serum homocysteine (r = 0.674, P homocysteine levels may be a possible pathophysiological mechanism.

    9. Effectiveness of bronchoscopy in the diagnosis of bronchial-type mycobacterium avium-intracellulare complex pulmonary disease

      International Nuclear Information System (INIS)

      Sato, Kazuhiro; Kourakata, Hiroyo

      2004-01-01

      Mycobacterium avium-intracellulare complex (MAC) pulmonary disease with associated nodules and bronchiectasis is an increasingly prevalent condition. This condition is often difficult to diagnose in the early stages of the disease, because of the limited effectiveness of sputum culture cytology. The effectiveness of bronchoscopy in the isolation and diagnosis of MAC in respiratory secretions is still unclear. Over a three-year period, we examined the effectiveness of bronchoscopy in 45 non-HIV-infected patients who had clusters of small peripheral lung nodules. These nodules were associated with changes of the draining bronchi detected by high-resolution CT (HRCT). A total of 22 of 45 patients (48.9%) had cultures positive for MAC. In the MAC-positive group, 10 patients tested positive for disease in sputum and 22 tested positive for disease in bronchial washings. A total of 13 of 45 patients (28.9%) fulfilled the American Thoracic Society criteria for pulmonary MAC disease, and 9 (20.0%) others with cultures positive for MAC did not fulfill the criteria. Radiographic measures and sputum cultures of 13 of 16 patients (81.3%) with negative cultures revealed no further disease progression. We found that HRCT was a useful technique in the diagnosis of MAC-pulmonary disease. We also found that bronchoscopy was a more sensitive diagnostic technique than sputum culture, analysis in the differential diagnosis of MAC pulmonary diseases. (author)

    10. Under-Expression of Chemosensory Genes in Domiciliary Bugs of the Chagas Disease Vector Triatoma brasiliensis.

      Science.gov (United States)

      Marchant, Axelle; Mougel, Florence; Jacquin-Joly, Emmanuelle; Costa, Jane; Almeida, Carlos Eduardo; Harry, Myriam

      2016-10-01

      In Latin America, the bloodsucking bugs Triatominae are vectors of Trypanosoma cruzi, the parasite that causes Chagas disease. Chemical elimination programs have been launched to control Chagas disease vectors. However, the disease persists because native vectors from sylvatic habitats are able to (re)colonize houses-a process called domiciliation. Triatoma brasiliensis is one example. Because the chemosensory system allows insects to interact with their environment and plays a key role in insect adaption, we conducted a descriptive and comparative study of the chemosensory transcriptome of T. brasiliensis samples from different ecotopes. In a reference transcriptome built using de novo assembly, we found transcripts encoding 27 odorant-binding proteins (OBPs), 17 chemosensory proteins (CSPs), 3 odorant receptors (ORs), 5 transient receptor potential channel (TRPs), 1 sensory neuron membrane protein (SNMPs), 25 takeout proteins, 72 cytochrome P450s, 5 gluthatione S-transferases, and 49 cuticular proteins. Using protein phylogenies, we showed that most of the OBPs and CSPs for T. brasiliensis had well supported orthologs in the kissing bug Rhodnius prolixus. We also showed a higher number of these genes within the bloodsucking bugs and more generally within all Hemipterans compared to the other species in the super-order Paraneoptera. Using both DESeq2 and EdgeR software, we performed differential expression analyses between samples of T. brasiliensis, taking into account their environment (sylvatic, peridomiciliary and domiciliary) and sex. We also searched clusters of co-expressed contigs using HTSCluster. Among differentially expressed (DE) contigs, most were under-expressed in the chemosensory organs of the domiciliary bugs compared to the other samples and in females compared to males. We clearly identified DE genes that play a role in the chemosensory system. Chemosensory genes could be good candidates for genes that contribute to adaptation or plastic

    11. Under-Expression of Chemosensory Genes in Domiciliary Bugs of the Chagas Disease Vector Triatoma brasiliensis.

      Directory of Open Access Journals (Sweden)

      Axelle Marchant

      2016-10-01

      Full Text Available In Latin America, the bloodsucking bugs Triatominae are vectors of Trypanosoma cruzi, the parasite that causes Chagas disease. Chemical elimination programs have been launched to control Chagas disease vectors. However, the disease persists because native vectors from sylvatic habitats are able to (recolonize houses-a process called domiciliation. Triatoma brasiliensis is one example. Because the chemosensory system allows insects to interact with their environment and plays a key role in insect adaption, we conducted a descriptive and comparative study of the chemosensory transcriptome of T. brasiliensis samples from different ecotopes.In a reference transcriptome built using de novo assembly, we found transcripts encoding 27 odorant-binding proteins (OBPs, 17 chemosensory proteins (CSPs, 3 odorant receptors (ORs, 5 transient receptor potential channel (TRPs, 1 sensory neuron membrane protein (SNMPs, 25 takeout proteins, 72 cytochrome P450s, 5 gluthatione S-transferases, and 49 cuticular proteins. Using protein phylogenies, we showed that most of the OBPs and CSPs for T. brasiliensis had well supported orthologs in the kissing bug Rhodnius prolixus. We also showed a higher number of these genes within the bloodsucking bugs and more generally within all Hemipterans compared to the other species in the super-order Paraneoptera. Using both DESeq2 and EdgeR software, we performed differential expression analyses between samples of T. brasiliensis, taking into account their environment (sylvatic, peridomiciliary and domiciliary and sex. We also searched clusters of co-expressed contigs using HTSCluster. Among differentially expressed (DE contigs, most were under-expressed in the chemosensory organs of the domiciliary bugs compared to the other samples and in females compared to males. We clearly identified DE genes that play a role in the chemosensory system.Chemosensory genes could be good candidates for genes that contribute to adaptation or

    12. Under-Expression of Chemosensory Genes in Domiciliary Bugs of the Chagas Disease Vector Triatoma brasiliensis

      Science.gov (United States)

      Marchant, Axelle; Mougel, Florence; Jacquin-Joly, Emmanuelle; Costa, Jane; Almeida, Carlos Eduardo; Harry, Myriam

      2016-01-01

      Background In Latin America, the bloodsucking bugs Triatominae are vectors of Trypanosoma cruzi, the parasite that causes Chagas disease. Chemical elimination programs have been launched to control Chagas disease vectors. However, the disease persists because native vectors from sylvatic habitats are able to (re)colonize houses—a process called domiciliation. Triatoma brasiliensis is one example. Because the chemosensory system allows insects to interact with their environment and plays a key role in insect adaption, we conducted a descriptive and comparative study of the chemosensory transcriptome of T. brasiliensis samples from different ecotopes. Methodology/Principal Finding In a reference transcriptome built using de novo assembly, we found transcripts encoding 27 odorant-binding proteins (OBPs), 17 chemosensory proteins (CSPs), 3 odorant receptors (ORs), 5 transient receptor potential channel (TRPs), 1 sensory neuron membrane protein (SNMPs), 25 takeout proteins, 72 cytochrome P450s, 5 gluthatione S-transferases, and 49 cuticular proteins. Using protein phylogenies, we showed that most of the OBPs and CSPs for T. brasiliensis had well supported orthologs in the kissing bug Rhodnius prolixus. We also showed a higher number of these genes within the bloodsucking bugs and more generally within all Hemipterans compared to the other species in the super-order Paraneoptera. Using both DESeq2 and EdgeR software, we performed differential expression analyses between samples of T. brasiliensis, taking into account their environment (sylvatic, peridomiciliary and domiciliary) and sex. We also searched clusters of co-expressed contigs using HTSCluster. Among differentially expressed (DE) contigs, most were under-expressed in the chemosensory organs of the domiciliary bugs compared to the other samples and in females compared to males. We clearly identified DE genes that play a role in the chemosensory system. Conclusion/Significance Chemosensory genes could be good

    13. Hypoxic Challenge Testing (Fitness to Fly) in children with complex congenital heart disease.

      Science.gov (United States)

      Naqvi, Nitha; Doughty, Victoria L; Starling, Luke; Franklin, Rodney C; Ward, Simon; Daubeney, Piers E F; Balfour-Lynn, Ian M

      2018-02-14

      Commercial airplanes fly with an equivalent cabin fraction of inspired oxygen of 0.15, leading to reduced oxygen saturation (SpO 2 ) in passengers. How this affects children with complex congenital heart disease (CHD) is unknown. We conducted Hypoxic Challenge Testing (HCT) to assess need for inflight supplemental oxygen. Children aged <16 years had a standard HCT. They were grouped as (A) normal versus abnormal baseline SpO 2 (≥95% vs <95%) and (B) absence versus presence of an actual/potential right-to-left (R-L) shunt. We measured SpO 2 , heart rate, QT interval corrected for heart rate and partial pressure of carbon dioxide measured transcutaneously (PtcCO 2 ). A test failed when children with (1) normal baseline SpO 2 desaturated to 85%, (2) baseline SpO 2 85%-94% desaturated by 15% of baseline; and (3) baseline SpO 2 75%-84% desaturated to 70%. There were 68 children, mean age 3.3 years (range 10 weeks-14.5 years). Children with normal (n=36) baseline SpO 2 desaturated from median 99% to 91%, P<0.0001, and 3/36 (8%) failed the test. Those with abnormal baseline SpO 2 (n=32) desaturated from median 84% to 76%, P<0.0001, and 5/32 (16%) failed (no significant difference between groups). Children with no R-L shunt (n=25) desaturated from median 99% to 93%, P<0.0001, but 0/25 failed. Those with an actual/potential R-L shunt (n=43) desaturated from median 87% to 78%, P<0.0001, and 8/43 (19%) failed (difference between groups P<0.02). PtcCO 2 , heart rate and QT interval corrected for heart rate were unaffected by the hypoxic state. This is the first evidence to help guide which children with CHD need a preflight HCT. We suggest all children with an actual or potential R-L shunt should be tested. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

    14. [Terminal complement complex (TCC) levels in urine in patients with renal diseases].

      Science.gov (United States)

      Yasuda, K

      2001-03-01

      The terminal complement complex (TCC) has been reported to play an important role in the pathogenesis of proteinuria not only in experimental nephritis but also in human glomerulonephritis. In order to clarify the clinical significance of TCC, the author investigated a total of 129 pediatric patients with the following glomerular diseases: idiopathic nephrotic syndrome (INS; 40 cases), IgA nephropathy (IgAN; 48 cases), mesangio-capillary glomerulonephritis (MPGN; 16 cases), lupus nephritis (LN; 16 cases), purpura nephritis (5 cases) and membranous nephritis (4 cases). Results were analyzed in relation to the responsiveness to steroid treatment in INS and the degree of proteinuria and histopathologic severity in glonerulonephritis groups. In 40 patients who underwent renal biopsy, the localizations of vitronectin and clusterin, both of which are regulatory proteins for TCC, were examined by immunofluorescence microscopy in conjunction with that of TCC for the study of the mechanism of local defense in glomerulonephritis. The urinary TCC levels were elevated in 9 (90%) of 10 patients with steroid-resistant INS, while they were elevated only in 2 of 30 steroid-responsive patients. In glomerulonephritis groups, urinary TCC levels were elevated in 13 of 48 patients with IgAN, 6 of 16 with MPGN, 8 of 16 with LN, 2 of 5 purpural nephritis and 1 of 4 with membranous nephritis. Urinary TCC levels correlated with histological severity in IgAN and showed a reciprocal relation to C3 levels in MPGN and LN. Immunofluorescence findings showed that localization of TCC was quite similar to that of C3 in glomerulonephritis groups. Vitronectin and clusterin were also demonstrated to deposit in similar pattern to TCC. These results suggest that in INS urinary TCC levels could predict the responsiveness to steroid therapy and might be useful as a non-invasive diagnostic method in differential diagnosis of INS. In IgAN, urinary TCC could be a useful marker of histologic severity. The

    15. Therapeutic application of new holmium-166 chitosan complex in malignant and benign diseases

      International Nuclear Information System (INIS)

      Park, K.B.; Kim, Y.M.; Shin, B.C.; Kim, J.R.; Ryu, J.M.; Lim, S.M.

      1998-01-01

      The new holmium-166 chitosan complex ( 166 Ho-CHICO, DW- 166 HC) was prepared by reacting the aqueous acidic solution of chitosan with 166 Ho(NO 3 ) 3 at room temperature with quantitative labelling yield. The progress of the reaction and labelling yield were determined by instant this layer chromatography using silicic acid impregnated glass fiber (ITLC-SA) and developing solvent of MeOH:H 2 O:HAC (49:49:2). The high labelling yield of more than 99% was obtained by reacting chitosan solution (35 mg/4 ml) with 166 Ho(NO 3 ) 3 in which 7 mg of 165 Ho+ 166 Ho were contained as a maximum content. The labelling yield was highly dependent on the pH of the chitosan solution. The optimal labelling could be obtained at pH 2.5∼3.5 The characteristics of 166 Ho-CHICO were similar to those of chitosan, which is biocompatible, biodegradable, non-toxic, soluble and viscous in acidic condition but geltatinuous at pH 6.0 and precipitating in alkaline conditions. 166 Ho-CHICO can be easily prepared by reconstituting freeze-dried chitosan (kit A) with 166 Ho(NO 3 ) 3 solution (kit B) just prior to use. After intrahepatic administration of 166 Ho-CHICO to male rats, the radioactivity concentrations in blood were low and the cumulative urinary and fecal excretion over a period of 0 to 72 hours were 0.53% and 0.54%, respectively. the radioactivity concentration in tissues and the whole-body autoradiography images showed that most of the administered radioactivity was localized at the administered site, and only slight radioactivity was detected from the liver, spleen, lungs, and bones. An autoradiograph after intratumoral administration of 166 Ho-CHICO showed that radioactivity was localized at the administered site of the lesion without distribution to other organs and tissues. A biodistribution study in normal rabbits with 166 Ho-CHICO showed that most of the radioactivities were retained in the knee joint with negligible extra leakage at 72 hours after intra

    16. [Extramammary Paget's disease of the scrotum with underlying sweat gland adenocarcinoma: a report of six cases with literature review].

      Science.gov (United States)

      Tu, Hua; Han, Hui; Zhou, Fang-Jian; Li, Yong-Hong; Qin, Zi-Ke; Liu, Zhuo-Wei

      2009-08-01

      Extramammary Paget's disease (EMPD) of the scrotum with sweat gland adenocarcinoma is a rare malignant tumor. This study was to summarize the clinicopathologic characteristics of scrotum Paget's disease with underlying sweat gland adenocarcinoma, and analyze the treatment outcome. Clinical data of six scrotum Paget's disease patients with sweat gland adenocarcinoma, treated in Sun Yat-sen University Cancer Center from 1964 to 2004, were analyzed with literature review. The typical manifestation of scrotum Paget's disease with sweat gland adenocarcinoma was eczematoid-like skin changes. All patients underwent primary lesion resection plus uni-inguinal lymphadenectomy, one patient underwent rectus abdominis pedicle flap transplantation. Three patients died of tumor at 15, 26, 38 months after operation, respectively. Other three patients were followed up for 48, 50, 55 months, respectively, and were alive without tumor. The primary lesion resection plus uni-inguinal lymphadenectomy is the major treatment for scrotum Paget's disease with underlying sweat gland adenocarcinoma.

    17. Complex self-management interventions in chronic disease unravelled: a review of lessons learned from an individual patient data meta-analysis.

      Science.gov (United States)

      Jonkman, Nini H; Groenwold, Rolf H H; Trappenburg, Jaap C A; Hoes, Arno W; Schuurmans, Marieke J

      2017-03-01

      Meta-analyses using individual patient data (IPD) rather than aggregated data are increasingly applied to analyze sources of heterogeneity between trials and have only recently been applied to unravel multicomponent, complex interventions. This study reflects on methodological challenges encountered in two IPD meta-analyses on self-management interventions in patients with heart failure or chronic obstructive pulmonary disease. Critical reflection on prior IPD meta-analyses and discussion of literature. Experience from two IPD meta-analyses illustrates methodological challenges. Despite close collaboration with principal investigators, assessing the effect of characteristics of complex interventions on the outcomes of trials is compromised by lack of sufficient details on intervention characteristics and limited data on fidelity and adherence. Furthermore, trials collected baseline variables in a highly diverse way, limiting the possibilities to study subgroups of patients in a consistent manner. Possible solutions are proposed based on lessons learnt from the methodological challenges. Future researchers of complex interventions should pay considerable attention to the causal mechanism underlying the intervention and conducting process evaluations. Future researchers on IPD meta-analyses of complex interventions should carefully consider their own causal assumptions and availability of required data in eligible trials before undertaking such resource-intensive IPD meta-analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

    18. Under-reporting of notifiable infectious disease hospitalizations in a health board region in Ireland: room for improvement?

      LENUS (Irish Health Repository)

      Brabazon, E D

      2008-02-01

      Rapid notification of infectious diseases is essential for prompt public health action and for monitoring of these diseases in the Irish population at both a local and national level. Anecdotal evidence suggests, however, that the occurrence of notifiable infectious diseases is seriously underestimated. This study aims to assess the level of hospitalization for notifiable infectious diseases for a 6-year period in one health board region in Ireland and to assess whether or not there was any under-reporting during this period. All hospital in-patient admissions from 1997 to 2002 inclusive with a principal diagnosis relating to \\'infectious and parasitic diseases\\' (ICD codes 001-139) of residents from a health board region in Ireland were extracted from the Hospital In-Patient Enquiry System (HIPE). All notifiable infectious diseases were identified based on the 1981 Irish Infectious Disease Regulations and the data were analysed in the statistical package, JMP. These data were compared with the corresponding notification data. Analysis of the hospital in-patient admission data revealed a substantial burden associated with notifiable infectious diseases in this health board region: there were 2758 hospitalizations by 2454 residents, 17,034 bed days and 33 deaths. The statutory notification data comprises both general practitioner and hospital clinician reports of infectious disease. Therefore, only in cases where there are more hospitalizations than notifications can under-reporting be demonstrated. This occurred in nine out of 22 notifiable diseases and amounted to an additional 18% of notifications (or 572 cases) which were \\'missed\\' due to hospital clinician under-reporting. The majority of these under-reported cases were for viral meningitis (45%), infectious mononucleosis (27%), viral hepatitis C unspecified (15%) and acute encephalitis (5.8%). This study has highlighted the extent of under-reporting of hospitalized notifiable infectious diseases, in a

    19. One-year experience of a regional service model of teleconsultation for planning and treatment of complex thoracoabdominal aortic disease.

      Science.gov (United States)

      Chisci, Emiliano; de Donato, Gianmarco; Fargion, Aaron; Ventoruzzo, Giorgio; Parlani, Gianbattista; Setacci, Carlo; Ercolini, Leonardo; Michelagnoli, Stefano

      2018-03-01

      The objective of this study was to report the methodology and 1-year experience of a regional service model of teleconsultation for planning and treatment of complex thoracoabdominal aortic disease (TAAD). Complex TAADs without a feasible conventional surgical repair were prospectively evaluated by vascular surgeons of the same public health service (National Health System) located in a huge area of 22,994 km 2 with 3.7 million inhabitants and 11 tertiary hospitals. Surgeons evaluated computed tomography scans and clinical details that were placed on a web platform (Google Drive; Google, Mountain View, Calif) and shared by all surgeons. Patients gave informed consent for the teleconsultation. The surgeon who submits a case discusses in detail his or her case a