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Sample records for model linking clinical

  1. The Union Health Center: a working model of clinical care linked to preventive occupational health services.

    PubMed

    Herbert, R; Plattus, B; Kellogg, L; Luo, J; Marcus, M; Mascolo, A; Landrigan, P J

    1997-03-01

    As health care provision in the United States shifts to primary care settings, it is vital that new models of occupational health services be developed that link clinical care to prevention. The model program described in this paper was developed at the Union Health Center (UHC), a comprehensive health care center supported by the International Ladies Garment Workers Union (now the Union of Needletrades, Industrial and Textile Employees) serving a population of approximately 50,000 primarily minority, female garment workers in New York City. The objective of this paper is to describe a model occupational medicine program in a union-based comprehensive health center linking accessible clinical care with primary and secondary disease prevention efforts. To assess the presence of symptoms suggestive of occupational disease, a health status questionnaire was administered to female workers attending the UHC for routine health maintenance. Based on the results of this survey, an occupational medicine clinic was developed that integrated direct clinical care with worker and employer education and workplace hazard abatement. To assess the success of this new approach, selected cases of sentinel health events were tracked and a chart review was conducted after 3 years of clinic operation. Prior to initiation of the occupational medicine clinic, 64% (648) of the workers surveyed reported symptoms indicative of occupational illnesses. However, only 42 (4%) reported having been told by a physician that they had an occupational illness and only 4 (.4%) reported having field a workers' compensation claim for an occupational disease. In the occupational medicine clinic established at the UHC, a health and safety specialist acts as a case manager, coordinating worker and employer education as well as workplace hazard abatement focused on disease prevention, ensuring that every case of occupational disease is treated as a potential sentinel health event. As examples of the success

  2. A model linking clinical workforce skill mix planning to health and health care dynamics

    PubMed Central

    2010-01-01

    Background In an attempt to devise a simpler computable tool to assist workforce planners in determining what might be an appropriate mix of health service skills, our discussion led us to consider the implications of skill mixing and workforce composition beyond the 'stock and flow' approach of much workforce planning activity. Methods Taking a dynamic systems approach, we were able to address the interactions, delays and feedbacks that influence the balance between the major components of health and health care. Results We linked clinical workforce requirements to clinical workforce workload, taking into account the requisite facilities, technologies, other material resources and their funding to support clinical care microsystems; gave recognition to productivity and quality issues; took cognisance of policies, governance and power concerns in the establishment and operation of the health care system; and, going back to the individual, gave due attention to personal behaviour and biology within the socio-political family environment. Conclusion We have produced the broad endogenous systems model of health and health care which will enable human resource planners to operate within real world variables. We are now considering the development of simple, computable national versions of this model. PMID:20433720

  3. The role of rumination in illness trajectories in youth: linking trans-diagnostic processes with clinical staging models.

    PubMed

    Grierson, A B; Hickie, I B; Naismith, S L; Scott, J

    2016-09-01

    Research in developmental psychopathology and clinical staging models has increasingly sought to identify trans-diagnostic biomarkers or neurocognitive deficits that may play a role in the onset and trajectory of mental disorders and could represent modifiable treatment targets. Less attention has been directed at the potential role of cognitive-emotional regulation processes such as ruminative response style. Maladaptive rumination (toxic brooding) is a known mediator of the association between gender and internalizing disorders in adolescents and is increased in individuals with a history of early adversity. Furthermore, rumination shows moderate levels of genetic heritability and is linked to abnormalities in neural networks associated with emotional regulation and executive functioning. This review explores the potential role of rumination in exacerbating the symptoms of alcohol and substance misuse, and bipolar and psychotic disorders during the peak age range for illness onset. Evidence shows that rumination not only amplifies levels of distress and suicidal ideation, but also extends physiological responses to stress, which may partly explain the high prevalence of physical and mental co-morbidity in youth presenting to mental health services. In summary, the normative developmental trajectory of rumination and its role in the evolution of mental disorders and physical illness demonstrates that rumination presents a detectable, modifiable trans-diagnostic risk factor in youth. PMID:27352637

  4. A Domain Analysis Model for eIRB Systems: Addressing the Weak Link in Clinical Research Informatics

    PubMed Central

    He, Shan; Narus, Scott P.; Facelli, Julio C.; Lau, Lee Min; Botkin, Jefferey R.; Hurdle, John F.

    2014-01-01

    Institutional Review Boards (IRBs) are a critical component of clinical research and can become a significant bottleneck due to the dramatic increase, in both volume and complexity of clinical research. Despite the interest in developing clinical research informatics (CRI) systems and supporting data standards to increase clinical research efficiency and interoperability, informatics research in the IRB domain has not attracted much attention in the scientific community. The lack of standardized and structured application forms across different IRBs causes inefficient and inconsistent proposal reviews and cumbersome workflows. These issues are even more prominent in multi-institutional clinical research that is rapidly becoming the norm. This paper proposes and evaluates a domain analysis model for electronic IRB (eIRB) systems, paving the way for streamlined clinical research workflow via integration with other CRI systems and improved IRB application throughput via computer-assisted decision support. PMID:24929181

  5. LARGE ANIMAL MODELS OF HEART FAILURE: A CRITICAL LINK IN THE TRANSLATION OF BASIC SCIENCE TO CLINICAL PRACTICE

    PubMed Central

    Dixon, Jennifer A.; Spinale, Francis G.

    2009-01-01

    Congestive heart failure (HF) is a clinical syndrome, with hallmarks of fatigue and dyspnea, which continues to be highly prevalent and morbid. Due to the growing burden of HF as the population ages, the need to develop new pharmacologic treatments and therapeutic interventions is of paramount importance. Common pathophysiologic features of HF include changes in left ventricle (LV) structure, function, and neurohormonal activation. The recapitulation of the HF phenotype in large animal models can allow for the translation of basic science discoveries into clinical therapies. Models of myocardial infarction/ischemia, ischemic cardiomyopathy, ventricular pressure and volume overload, and pacing induced dilated cardiomyopathy have been created in dogs, pigs, and sheep for the investigation of HF and potential therapies. Large animal models recapitulating the clinical HF phenotype and translating basic science to clinical applications have successfully traveled the journey from bench to bedside. Undoubtedly, large animal models of HF will continue to play a crucial role in the elucidation of biologic pathways involved in HF and the development and refinement of HF therapies. PMID:19808348

  6. Linking community health improvement with clinical strategies.

    PubMed

    Hattis, P; Matheny, P

    2001-01-01

    In most health care organizations, there is a separation between community health improvement (CHI) efforts and other strategic goals--in particular, clinical care strategies. By carefully managing their approach to CHI, health care organizations can successfully link these areas and reap significant tangible and intangible rewards, including cost savings and better outcomes of care. PMID:11372277

  7. Linking Item Response Model Parameters.

    PubMed

    van der Linden, Wim J; Barrett, Michelle D

    2016-09-01

    With a few exceptions, the problem of linking item response model parameters from different item calibrations has been conceptualized as an instance of the problem of test equating scores on different test forms. This paper argues, however, that the use of item response models does not require any test score equating. Instead, it involves the necessity of parameter linking due to a fundamental problem inherent in the formal nature of these models-their general lack of identifiability. More specifically, item response model parameters need to be linked to adjust for the different effects of the identifiability restrictions used in separate item calibrations. Our main theorems characterize the formal nature of these linking functions for monotone, continuous response models, derive their specific shapes for different parameterizations of the 3PL model, and show how to identify them from the parameter values of the common items or persons in different linking designs. PMID:26155754

  8. A model-based cluster analysis of social experiences in clinically anxious youth: links to emotional functioning.

    PubMed

    Suveg, Cynthia; Jacob, Marni L; Whitehead, Monica; Jones, Anna; Kingery, Julie Newman

    2014-01-01

    Social difficulties are commonly associated with anxiety disorders in youth, yet are not well specified in the literature. The aim of this study was to identify patterns of social experiences in clinically anxious children and examine the associations with indices of emotional functioning. A model-based cluster analysis was conducted on parent-, teacher-, and child-reports of social experiences with 64 children, ages 7-12 years (M = 8.86 years, SD = 1.59 years; 60.3% boys; 85.7% Caucasian) with a primary diagnosis of separation anxiety disorder, social phobia, and/or generalized anxiety disorder. Follow-up analyses examined cluster differences on indices of emotional functioning. Findings yielded three clusters of social experiences that were unrelated to diagnosis: (1) Unaware Children (elevated scores on parent- and teacher-reports of social difficulties but relatively low scores on child-reports, n = 12), (2) Average Functioning (relatively average scores across all informants, n = 44), and (3) Victimized and Lonely (elevated child-reports of overt and relational victimization and loneliness and relatively low scores on parent- and teacher-reports of social difficulties, n = 8). Youth in the Unaware Children cluster were rated as more emotionally dysregulated by teachers and had a greater number of diagnoses than youth in the Average Functioning group. In contrast, the Victimized and Lonely group self-reported greater frequency of negative affect and reluctance to share emotional experiences than the Average Functioning cluster. Overall, this study demonstrates that social maladjustment in clinically anxious children can manifest in a variety of ways and assessment should include multiple informants and methods. PMID:24506348

  9. Links between clinical audit and contracting systems.

    PubMed

    Lord, J; Littlejohns, P

    1995-01-01

    In 1989, a programme of clinical audit was introduced throughout the UK National Health Service (NHS), in an attempt to improve care through the application of quality methodology to clinical issues. However, the role of clinical audit in the new NHS "internal market" is unclear. Reviews evidence on the development of audit and concludes that it has operated largely in isolation, under professional control. Central policy is now advocating greater purchaser and provider management involvement in audit, enabling feedback from and to service provision and management decisions. Where there are constructive local relationships the opening up of audit should be beneficial, but these do not always exist. Discusses a range of models for the interaction of clinical audit with wider NHS management systems. Recommends a split system of professionally controlled background audit and collaborative shared audits to balance conflicting goals. PMID:10143993

  10. X linked mental retardation: a clinical guide

    PubMed Central

    Raymond, F L

    2006-01-01

    Mental retardation is more common in males than females in the population, assumed to be due to mutations on the X chromosome. The prevalence of the 24 genes identified to date is low and less common than expansions in FMR1, which cause Fragile X syndrome. Systematic screening of all other X linked genes in X linked families with mental retardation is currently not feasible in a clinical setting. The phenotypes of genes causing syndromic and non‐syndromic mental retardation (NLGN3, NLGN4, RPS6KA3(RSK2), OPHN1, ATRX, SLC6A8, ARX, SYN1, AGTR2, MECP2, PQBP1, SMCX, and SLC16A2) are first discussed, as these may be the focus of more targeted mutation analysis. Secondly, the relative prevalence of genes causing only non‐syndromic mental retardation (IL1RAPL1, TM4SF2, ZNF41, FTSJ1, DLG3, FACL4, PAK3, ARHGEF6, FMR2, and GDI) is summarised. Thirdly, the problem of recurrence risk where a molecular genetics diagnosis has not been made and what proportion of the male excess of mental retardation is due to monogenic disorders of the X chromosome are discussed. PMID:16118346

  11. Patient Education and Health Promotion: Clinical Health Promotion--The Conceptual Link.

    ERIC Educational Resources Information Center

    Caraher, Martin

    1998-01-01

    Presents a model linking health promotion, health education, and patient education. The bases for distinctions between health education, patient education, and clinical health promotion are examined. The linking elements of the model are patient role, relationships adopted, and focus of the encounter; i.e., disease process vs. disease management.…

  12. Open loop model for WDM links

    NASA Astrophysics Data System (ADS)

    D, Meena; Francis, Fredy; T, Sarath K.; E, Dipin; Srinivas, T.; K, Jayasree V.

    2014-10-01

    Wavelength Division Multiplexing (WDM) techniques overfibrelinks helps to exploit the high bandwidth capacity of single mode fibres. A typical WDM link consisting of laser source, multiplexer/demultiplexer, amplifier and detectoris considered for obtaining the open loop gain model of the link. The methodology used here is to obtain individual component models using mathematical and different curve fitting techniques. These individual models are then combined to obtain the WDM link model. The objective is to deduce a single variable model for the WDM link in terms of input current to system. Thus it provides a black box solution for a link. The Root Mean Square Error (RMSE) associated with each of the approximated models is given for comparison. This will help the designer to select the suitable WDM link model during a complex link design.

  13. Reconceptualizing the Linked Courses Model

    ERIC Educational Resources Information Center

    Baxter, Mary

    2008-01-01

    To help students meet the demands of society, the University of Houston is using the framework of learning communities and constructivism to create a cross-disciplinary approach to teaching to provide media-rich thematically linked courses to engage a diverse student population. A case study investigated three semesters of thematically linked…

  14. Concept maps: linking nursing theory to clinical nursing practice.

    PubMed

    Daley, B J

    1996-01-01

    The purpose of this article is to offer a different methodology for teaching and learning in continuing nursing education and staff development. This article describes a qualitative research study that analyzed how linkages are made between theoretical material and clinical nursing practice. Findings indicate that nursing students did not link the elements of nursing process together, that clinical preparation was not linked to theoretical material, that the meaning students made of the information was different than the instructors' and that concepts from the basic sciences were not incorporated into student meaning structures. Implications for the use of concept maps as an educational strategy in continuing nursing education are drawn. PMID:8576492

  15. Clinical professional governance for detailed clinical models.

    PubMed

    Goossen, William; Goossen-Baremans, Anneke

    2013-01-01

    This chapter describes the need for Detailed Clinical Models for contemporary Electronic Health Systems, data exchange and data reuse. It starts with an explanation of the components related to Detailed Clinical Models with a brief summary of knowledge representation, including terminologies representing clinic relevant "things" in the real world, and information models that abstract these in order to let computers process data about these things. Next, Detailed Clinical Models are defined and their purpose is described. It builds on existing developments around the world and accumulates in current work to create a technical specification at the level of the International Standards Organization. The core components of properly expressed Detailed Clinical Models are illustrated, including clinical knowledge and context, data element specification, code bindings to terminologies and meta-information about authors, versioning among others. Detailed Clinical Models to date are heavily based on user requirements and specify the conceptual and logical levels of modelling. It is not precise enough for specific implementations, which requires an additional step. However, this allows Detailed Clinical Models to serve as specifications for many different kinds of implementations. Examples of Detailed Clinical Models are presented both in text and in Unified Modelling Language. Detailed Clinical Models can be positioned in health information architectures, where they serve at the most detailed granular level. The chapter ends with examples of projects that create and deploy Detailed Clinical Models. All have in common that they can often reuse materials from earlier projects, and that strict governance of these models is essential to use them safely in health care information and communication technology. Clinical validation is one point of such governance, and model testing another. The Plan Do Check Act cycle can be applied for governance of Detailed Clinical Models

  16. Semantically linking in silico cancer models.

    PubMed

    Johnson, David; Connor, Anthony J; McKeever, Steve; Wang, Zhihui; Deisboeck, Thomas S; Quaiser, Tom; Shochat, Eliezer

    2014-01-01

    Multiscale models are commonplace in cancer modeling, where individual models acting on different biological scales are combined within a single, cohesive modeling framework. However, model composition gives rise to challenges in understanding interfaces and interactions between them. Based on specific domain expertise, typically these computational models are developed by separate research groups using different methodologies, programming languages, and parameters. This paper introduces a graph-based model for semantically linking computational cancer models via domain graphs that can help us better understand and explore combinations of models spanning multiple biological scales. We take the data model encoded by TumorML, an XML-based markup language for storing cancer models in online repositories, and transpose its model description elements into a graph-based representation. By taking such an approach, we can link domain models, such as controlled vocabularies, taxonomic schemes, and ontologies, with cancer model descriptions to better understand and explore relationships between models. The union of these graphs creates a connected property graph that links cancer models by categorizations, by computational compatibility, and by semantic interoperability, yielding a framework in which opportunities for exploration and discovery of combinations of models become possible. PMID:25520553

  17. Semantically Linking In Silico Cancer Models

    PubMed Central

    Johnson, David; Connor, Anthony J; McKeever, Steve; Wang, Zhihui; Deisboeck, Thomas S; Quaiser, Tom; Shochat, Eliezer

    2014-01-01

    Multiscale models are commonplace in cancer modeling, where individual models acting on different biological scales are combined within a single, cohesive modeling framework. However, model composition gives rise to challenges in understanding interfaces and interactions between them. Based on specific domain expertise, typically these computational models are developed by separate research groups using different methodologies, programming languages, and parameters. This paper introduces a graph-based model for semantically linking computational cancer models via domain graphs that can help us better understand and explore combinations of models spanning multiple biological scales. We take the data model encoded by TumorML, an XML-based markup language for storing cancer models in online repositories, and transpose its model description elements into a graph-based representation. By taking such an approach, we can link domain models, such as controlled vocabularies, taxonomic schemes, and ontologies, with cancer model descriptions to better understand and explore relationships between models. The union of these graphs creates a connected property graph that links cancer models by categorizations, by computational compatibility, and by semantic interoperability, yielding a framework in which opportunities for exploration and discovery of combinations of models become possible. PMID:25520553

  18. Models for transition clinics.

    PubMed

    Carrizosa, Jaime; An, Isabelle; Appleton, Richard; Camfield, Peter; Von Moers, Arpad

    2014-08-01

    Transition is a purposeful, planned process that addresses the medical, psychosocial, educational, and vocational needs of adolescents and young adults with chronic medical conditions, as they advance from a pediatric and family-centered to an adult, individual focused health care provider. This article describes some of the models for transition clinics or services for epilepsy in five countries (Canada, France, Colombia, Germany, and the United Kingdom). These models include joint adult and pediatric clinics, algorithm-driven service, and a check list system in the context of pediatric care. Evaluation of these models is limited, and it is not possible to choose an optimal program. The attitude and motivation of health care providers may be the most important elements. PMID:25209087

  19. Key-linked on-line databases for clinical research.

    PubMed

    Müller, Thomas H

    2012-01-01

    Separating patient identification data from clinical data and/or information about biomaterial samples is an effective data protection measure, especially in clinical research employing "on-line", i.e., web-based, data capture. In this paper, we show that this specialised technique can be generalised into a network architecture of interconnected on-line databases potentially serving a variety of purposes. The basic idea of this approach consists of maintaining logical links, i.e., common record keys, between corresponding data structures in pairs of databases while keeping the actual key values hidden from clients. For client systems, simultaneous access to corresponding records is mediated by temporary access tokens. At the relational level, these links are represented by arbitrary unique record keys common to both databases. This architecture allows for integration of related data in different databases without replicating or permanently sharing this data in one place. Each participating on-line database can determine the degree of integration by specifying linkage keys only for those data structures that may be logically connected to other data. Logical links can de designed for specific use cases. In addition, each database controls user access by enforcing its own authorisation scheme. Another advantage is that individual database owners retain considerable leeway in adapting to changing local requirements without compromising the integration into the network. Beyond protecting individual subject identification data, this architecture permits splitting a cooperatively used data pool to achieve many kinds of objectives. Application examples could be clinical registries needing subject contact information for follow-up, biomaterial banks with or without genetic information, and automatic or assisted integration of data from electronic medical records into research data. PMID:22874246

  20. Multi-level slip-link modeling

    NASA Astrophysics Data System (ADS)

    Schieber, Jay

    2014-03-01

    That the dynamics of concentrated, high-molecular-weight polymers are largely governed by entanglements is now widely accepted, and typically understood by the tube model. Although the original idea for slip-links was proposed at the same time as tubes, only recently have detailed, quantitative mathematical models arisen based on this picture. We argue here for the use of a slip-link model that has strong connections to atomistic, multichain levels of description, agrees with non-equilibrium thermodynamics, applies to any chain architecture and can be used in linear or non-linear rheology. We present a hierarchy of slip-link models that are connected to each other through successive coarse graining. One might choose a particular member of the hierarchy depending on the problem at hand, in order to minimize computational effort. In particular, the most detailed level of description has four parameters, three of which can be determined directly from atomistic simulations. The least-detailed member is suitable for predicting non-linear, non-uniform flow fields. We will show how using this hierarchy of slip-link models we can make predictions about the nonlinear rheology of monodisperse homopolymer melts, polydisperse melts, or blends of different architectures.

  1. Linking Essential Tremor to the Cerebellum: Clinical Evidence.

    PubMed

    Benito-León, Julián; Labiano-Fontcuberta, Andrés

    2016-06-01

    Essential tremor (ET) might be a family of diseases unified by the presence of kinetic tremor, but also showing etiological, pathological, and clinical heterogeneity. In this review, we will describe the most significant clinical evidence, which suggests that ET is linked to the cerebellum. Data for this review were identified by searching PUBMED (January 1966 to May 2015) crossing the terms "essential tremor" (ET) and "cerebellum," which yielded 201 entries, 11 of which included the term "cerebellum" in the article title. This was supplemented by articles in the author's files that pertained to this topic. The wide spectrum of clinical features of ET that suggest that it originates as a cerebellar or cerebellar outflow problem include the presence of intentional tremor, gait and balance abnormalities, subtle features of dysarthria, and oculomotor abnormalities, as well as deficits in eye-hand coordination, motor learning deficits, incoordination during spiral drawing task, abnormalities in motor timing and visual reaction time, impairment of social abilities, improvement in tremor after cerebellar stroke, efficacy of deep brain stimulation (which blocks cerebellar outflow), and cognitive dysfunction. It is unlikely, however, that cerebellar dysfunction, per se, fully explains ET-associated dementia, because the cognitive deficits that have been described in patients with cerebellar lesions are generally mild. Overall, a variety of clinical findings suggest that in at least a sizable proportion of patients with ET, there is an underlying abnormality of the cerebellum and/or its pathways. PMID:26521074

  2. [X-linked agammaglobulinemia in adults. Clinical evolution].

    PubMed

    Giorgetti, Orlando B; Paolini, María V; Oleastro, Matías M; Fernández Romero, Diego S

    2016-01-01

    X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels and clinically by extracellular bacterial infections which mainly compromise the respiratory tract as well as recurrent diarrheas. The mainstay of treatment is gammaglobulin replacement therapy, which allows most patients to reach adulthood with high quality of life. We analyzed the clinical features of 14 patients over 18 years of age with XLA diagnosis that received treatment in our unit from the year 2003, the date the first patient was derived, until 2015. The average age at which patients were referred was 20.4 years old; age at the last consult was 25.5. The average follow-up time was 59.8 months. Previously to being diagnosed all patients had suffered infections, most frequently respiratory. After diagnosis all were started on intravenous gammaglobulin replacement treatment and in spite of infections being reduced in severity and frequency, there were cases of severe disease with long term sequelae. At the beginning of our follow-up 35.7% presented impaired respiratory function with only one case being severe. In no cases during this period did the respiratory function worsen, nor were there severe clinical complications. Three patients were switched to subcutaneous immunoglobulin treatment with good tolerance. The number of XLA cases is increasing, as most reach the second decade of life without serious complications and remain free of severe infectious disease and further impairment of their respiratory functions with the treatment. PMID:27135842

  3. Caries assessment: establishing mathematical link of clinical and benchtop method

    NASA Astrophysics Data System (ADS)

    Amaechi, Bennett T.

    2009-02-01

    It is well established that the development of new technologies for early detection and quantitative monitoring of dental caries at its early stage could provide health and economic benefits ranging from timely preventive interventions to reduction of the time required for clinical trials of anti-caries agents. However, the new technologies currently used in clinical setting cannot assess and monitor caries using the actual mineral concentration within the lesion, while a laboratory-based microcomputed tomography (MCT) has been shown to possess this capability. Thus we envision the establishment of mathematical equations relating the measurements of each of the clinical technologies to that of MCT will enable the mineral concentration of lesions detected and assessed in clinical practice to be extrapolated from the equation, and this will facilitate preventitive care in dentistry to lower treatment cost. We utilize MCT and the two prominent clinical caries assessment devices (Quantitative Light-induced Fluorescence [QLF] and Diagnodent) to longitudinally monitor the development of caries in a continuous flow mixed-organisms biofilm model (artificial mouth), and then used the collected data to establish mathematical equation relating the measurements of each of the clinical technologies to that of MCT. A linear correlation was observed between the measurements of MicroCT and that of QLF and Diagnodent. Thus mineral density in a carious lesion detected and measured using QLF or Diagnodent can be extrapolated using the developed equation. This highlights the usefulness of MCT for monitoring the progress of an early caries being treated with therapeutic agents in clinical practice or trials.

  4. Linking Doses with Clinical Scores of Hematopoietic Acute Radiation Syndrome.

    PubMed

    Hu, Shaowen

    2016-10-01

    In radiation accidents, determining the radiation dose the victim received is a key step for medical decision making and patient prognosis. To reconstruct and evaluate the absorbed dose, researchers have developed many physical devices and biological techniques during the last decades. However, using the physical parameter "absorbed dose" alone is not sufficient to predict the clinical development of the various organs injured in an individual patient. In operational situations for radiation accidents, medical responders need more urgently to classify the severity of the radiation injury based on the signs and symptoms of the patient. In this work, the author uses a unified hematopoietic model to describe dose-dependent dynamics of granulocytes, lymphocytes, and platelets, and the corresponding clinical grading of hematopoietic acute radiation syndrome. This approach not only visualizes the time course of the patient's probable outcome in the form of graphs but also indirectly gives information of the remaining stem and progenitor cells, which are responsible for the autologous recovery of the hematopoietic system. Because critical information on the patient's clinical evolution can be provided within a short time after exposure and only peripheral cell counts are required for the simulation, these modeling tools will be useful to assess radiation exposure and injury in human-involved radiation accident/incident scenarios. PMID:27575346

  5. X-linked acrogigantism syndrome: clinical profile and therapeutic responses.

    PubMed

    Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H; Bours, Vincent; Liu, Pengfei; W de Herder, Wouter; Pellegata, Natalia; Lupski, James R; Daly, Adrian F; Stratakis, Constantine A

    2015-06-01

    X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. PMID:25712922

  6. Feature-Linking Model for Image Enhancement.

    PubMed

    Zhan, Kun; Teng, Jicai; Shi, Jinhui; Li, Qiaoqiao; Wang, Mingying

    2016-06-01

    Inspired by gamma-band oscillations and other neurobiological discoveries, neural networks research shifts the emphasis toward temporal coding, which uses explicit times at which spikes occur as an essential dimension in neural representations. We present a feature-linking model (FLM) that uses the timing of spikes to encode information. The first spiking time of FLM is applied to image enhancement, and the processing mechanisms are consistent with the human visual system. The enhancement algorithm achieves boosting the details while preserving the information of the input image. Experiments are conducted to demonstrate the effectiveness of the proposed method. Results show that the proposed method is effective. PMID:26942747

  7. GROUNDWATER MODELING LINKS (SUBSURFACE PROTECTION AND REMEDIATION DIVISION, NRMRL)

    EPA Science Inventory

    From this site, the viewer will be able to access Groundwater Modeling Software Links as well as Groundwater Professionals Links. For the viewer's benefit, the site includes both USEPA and non-EPA links.To view and link to these sites, visit the website at http://www.epa.gov/ad...

  8. Common data link (CDL) interference model

    NASA Astrophysics Data System (ADS)

    Cerasoli, Caramen; Zhao, Wiley; Santapietro, John J.; McAlinden, R. E.; Smith, B. F.; Jacyk, P. A.

    2002-07-01

    The increasing use of airwaves for military communication and surveillance and commercial applications places burdens on spectrum use. This crowding of the spectrum presents two broad problem categories. The first is "co-site interference" where numerous transmitters and receivers are physically located in a small area and share a given portion of the spectrum. Under these conditions, a receiver can be "victim" to a co-located transmitter. The second category involves numerous transmitters (typically airborne) well separated from each other but communicating to receivers placed in a relatively small area. The Common Data Link (CDL) refers to a standard protocol for military data delivery and communication. Surveillance platforms such as Tactical Unmanned Aerial Vehicles (TUAV), JSTARS, U2's, Global Hawks will stream high rate surveillance data (radar, visual and/or infrared imagery, etc.) down to ground terminals. As such, bandwidths are wide (100's MHz) and the potential exists for ground receivers to be victim to signals from airborne transmitters other than its desired source. MITRE has developed a CDL Interference Model to assess potential problems in realistic tactical surveillance scenarios. This paper documents the physical basis of the CDL Interference Model as well as the visualization software architecture that integrates the model with ModSAF/OneSAF.

  9. Platform links clinical data with electronic health records

    Cancer.gov

    To make data gathered from patients in clinical trials available for use in standard care, NCI has created a new computer tool to support interoperability between clinical research and electronic health record systems. This new software represents an inno

  10. Links between Disorganized Attachment Classification and Clinical Symptoms in School-Aged Children

    ERIC Educational Resources Information Center

    Borelli, Jessica L.; David, Daryn H.; Crowley, Michael J.; Mayes, Linda C.

    2010-01-01

    Research examining the links between disorganized attachment and clinical symptoms largely has neglected middle childhood due to lack of available measurement tools. The few studies that have examined these links in other developmental phases have found higher clinical symptoms in disorganized individuals. Our study extended this research by using…

  11. Role Modeling for Clinical Educators.

    ERIC Educational Resources Information Center

    Ettinger, Ellen Richter

    1991-01-01

    To become better role models, higher educators in institutions of clinical education should be conscious of the behaviors they demonstrate and the broad range of activities and attitudes that students observe and emulate, including clinical competence, professional demeanor, doctor-patient interactions, ethical values, and social consciousness.…

  12. An Investigation of Linking Methods under the Graded Response Model.

    ERIC Educational Resources Information Center

    Cohen, Allan S.; Kim, Seock-Ho

    1998-01-01

    Studied results from five linking methods under the graded-response model using simulated data. Results show that differences in the linking coefficients are small. The five methods yielded similar results for longer common-item links with large sample sizes and when the distribution of item-location parameters matched the underlying trait…

  13. Ocular cytokinome is linked to clinical characteristics in ocular toxoplasmosis

    PubMed Central

    de-la-Torre, Alejandra; Pfaff, Alexander W.; Grigg, Michael E.; Villard, Odile; Candolfi, Ermanno; Gomez-Marin, Jorge E.

    2016-01-01

    Purpose To determine the cytokine levels in aqueous humor (AH) of Colombian patients with active ocular toxoplasmosis (OT), and to correlate them with their clinical characteristics. Methods 27 Cytokines/chemokines were assayed in 15 AH samples (nine patients with diagnosis of OT biologically-confirmed and six controls that underwent cataract surgery). Correlations were assessed between cytokine/chemokine levels, type of inflammatory response (Th1, Th2, Th17, Treg), and clinical characteristics. Results Th2 predominant response was related to more severe clinical features. The presence of VEGF and IL-5 was related to higher number of recurrences. Growth factors (VEGF, FGF, PDGF-β), were related to higher number of lesions. Patients infected by type-I/III strains had a particular intraocular cytokine-pattern. Conclusions Th2 response was related to more severe clinical characteristics in patients infected by Type I/III strains. IL-5 and VEGF were associated with recurrences. We correlate for the first time, specific cytokine-patterns with clinical characteristics and with the infecting Toxoplasma strain. PMID:24787053

  14. Pharmacokinetics of Melatonin: The Missing Link in Clinical Efficacy?

    PubMed

    Andersen, Lars Peter Holst; Gögenur, Ismail; Rosenberg, Jacob; Reiter, Russel J

    2016-09-01

    Despite widespread clinical application of melatonin, several unanswered questions remain regarding the pharmacokinetics of this drug. This lack of knowledge may contribute to the inconsistency of results in previous clinical studies. Currently, a t max value of 30-45 min and a t ½elimination of 45 min are well established. Several questions relate to what constitutes a clinically effective plasma concentration, the choice of ideal administration route, and the optimal method of analysis. Furthermore, investigations of melatonin metabolites in humans are urgently needed in order to characterize their biological functions and the metabolic fates of these derivatives. Finally, pharmacokinetics in patients should be investigated further in order to reduce the risk of potential adverse effects, such as daytime sleepiness or unintended sedation. PMID:27000757

  15. Translational Bioinformatics: Linking the Molecular World to the Clinical World

    PubMed Central

    Altman, RB

    2014-01-01

    Translational bioinformatics represents the union of translational medicine and bioinformatics. Translational medicine moves basic biological discoveries from the research bench into the patient-care setting and uses clinical observations to inform basic biology. It focuses on patient care, including the creation of new diagnostics, prognostics, prevention strategies, and therapies based on biological discoveries. Bioinformatics involves algorithms to represent, store, and analyze basic biological data, including DNA sequence, RNA expression, and protein and small-molecule abundance within cells. Translational bioinformatics spans these two fields; it involves the development of algorithms to analyze basic molecular and cellular data with an explicit goal of affecting clinical care. PMID:22549287

  16. Glutaraldehyde-cross-linked meniscal allografts: clinical, gross, and histological results.

    PubMed

    Powers, D L; Davenport, M E; Wisnewski, P J

    1988-01-01

    Osteoarthritic changes in the knee are often a late result of total meniscectomy. In cases of total resection, availability of a prosthetic meniscus might limit development of these changes. The objective of this research was to evaluate a glutaraldehyde-cross-linked medial meniscus as a morphologically and biologically compatible prosthesis in a canine model. Medial and lateral menisci were harvested from donor dogs, frozen in saline, and cross-linked with glutaraldehyde. Five host animals were selected and matched with donors. Glutaraldehyde-cross-linked medial menisci were implanted bilaterally in the stifle joints and one glutaraldehyde cross-linked lateral meniscus was implanted subcutaneously. Clinical results showed asymptomatic limb and joint usage during the 12 postoperative weeks. Gross and histological evaluations indicated acceptable biocompatibility. The subcutaneous implants were encapsulated with a thin fibrous tissue capsule that was only mildly inflamed. Within the joints, the anterior attachment and periphery were maintained in position by their sutures; however, there was dehiscence of the posterior suture in all cases. The articulating surfaces of the implants were intact. There was an initial loss in the quantity of proteoglycans following glutaraldehyde treatment, with significant recovery after implantation into the joints. There were significant degenerative changes (loss of proteoglycans and fibrillation) in the articular cartilage on the femoral condyle and tibial plateau most likely a result of the posterior attachment failure. It was concluded that glutaraldehyde-cross-linked meniscal allografts showed an acceptable degree of histocompatibility. However, failure of the posterior attachment interfered with testing the efficacy of the prosthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3155294

  17. Computational Medicine: Translating Models to Clinical Care

    PubMed Central

    Winslow, Raimond L.; Trayanova, Natalia; Geman, Donald; Miller, Michael I.

    2013-01-01

    Because of the inherent complexity of coupled nonlinear biological systems, the development of computational models is necessary for achieving a quantitative understanding of their structure and function in health and disease. Statistical learning is applied to high-dimensional biomolecular data to create models that describe relationships between molecules and networks. Multiscale modeling links networks to cells, organs, and organ systems. Computational approaches are used to characterize anatomic shape and its variations in health and disease. In each case, the purposes of modeling are to capture all that we know about disease and to develop improved therapies tailored to the needs of individuals. We discuss advances in computational medicine, with specific examples in the fields of cancer, diabetes, cardiology, and neurology. Advances in translating these computational methods to the clinic are described, as well as challenges in applying models for improving patient health. PMID:23115356

  18. [Families and psychiatry: models and evolving links].

    PubMed

    Frankhauser, Adeline

    2016-01-01

    The role of the families of persons with severe psychiatric disorders (schizophrenia in particular) in the care of their relatives has recently evolved: once seen as pathogenic to be kept at a distance, the family is now recognised by professionals as a partner in the care process. The links between families and psychiatric institutions remain complex and marked by ambivalence and paradoxes. PMID:27157191

  19. The palliative care clinical nurse consultant: an essential link.

    PubMed

    O'Connor, Margaret; Chapman, Ysanne

    2008-01-01

    This study describes the role of acute hospital palliative care nurse consultants and makes recommendations about future directions for the role development of this role. While the palliative care nurse consultant role is accepted in the acute setting there is little evidence or literature about what contributes to the success of this role. A three-phase study was undertaken to describe the role of palliative care nurse consultants in acute hospitals in Melbourne, Australia. The first phase of the three-phase study, involving in-depth qualitative interviews with the palliative care nurse consultants, is reported in this article. Using open-ended semi-structured questions, 10 palliative care nurse consultants were interviewed using open-ended questions about aspects of their role and the interviews were thematically analysed. Four main themes were identified that clarified the role; being the internal link; being the lynch pin; being responsive and being challenged. The palliative care nurse consultants were the first point of introduction to palliative care and thus they saw a significant role in introducing the concept of palliative care to those requiring palliative care, their families and others. They are an important link between the settings of care required by people accessing palliative care-acute, in-patient palliative care and community care. The palliative care nurse consultants saw themselves in leadership positions that in some ways defy boundaries, because of the inherent complexity and diversity of the role. The palliative care nurse consultants' role appears to be pivotal in providing expert advice to staff and people requiring palliative care, and connecting palliative care services both within the hospital and to external services. PMID:19112925

  20. [Clinical aspects of the link between diabetes and depression].

    PubMed

    Nagy, Géza; Rosta, Klára; Szémán, Barbara; Sasvári-Székely, Mária; Somogyi, Anikó

    2011-03-27

    Diabetes mellitus and depression are public health concerns of the present and, as predicted, also the future. The observation that depression is seen more frequently in diabetic patients compared to the non-diabetic population has been proven by several recent studies. The co-occurrence carries further risks for the affected patients, as depression in diabetics may affect sufficient treatment of diabetes and enhance the development of diabetic complications. These may further worsen depressive symptoms causing a vicious cycle in these patients. In the present paper authors discuss in detail the theoretic and practical issues of the complex two directional relationships between diabetes and depression. Their goal is to draw attention to depression as co-morbidity of diabetes that may interfere with the optimization of diabetic patient's carbohydrate metabolism. If sufficient glycaemic control is not achieved using routine clinical methods depression should be evaluated as a probable cause. If needed, depression should be treated to improve the medical outcomes and quality of life of diabetic patients. PMID:21398210

  1. Linking models and data on vegetation structure

    NASA Astrophysics Data System (ADS)

    Hurtt, G. C.; Fisk, J.; Thomas, R. Q.; Dubayah, R.; Moorcroft, P. R.; Shugart, H. H.

    2010-06-01

    For more than a century, scientists have recognized the importance of vegetation structure in understanding forest dynamics. Now future satellite missions such as Deformation, Ecosystem Structure, and Dynamics of Ice (DESDynI) hold the potential to provide unprecedented global data on vegetation structure needed to reduce uncertainties in terrestrial carbon dynamics. Here, we briefly review the uses of data on vegetation structure in ecosystem models, develop and analyze theoretical models to quantify model-data requirements, and describe recent progress using a mechanistic modeling approach utilizing a formal scaling method and data on vegetation structure to improve model predictions. Generally, both limited sampling and coarse resolution averaging lead to model initialization error, which in turn is propagated in subsequent model prediction uncertainty and error. In cases with representative sampling, sufficient resolution, and linear dynamics, errors in initialization tend to compensate at larger spatial scales. However, with inadequate sampling, overly coarse resolution data or models, and nonlinear dynamics, errors in initialization lead to prediction error. A robust model-data framework will require both models and data on vegetation structure sufficient to resolve important environmental gradients and tree-level heterogeneity in forest structure globally.

  2. Links between soil modelling and proximal sensing

    NASA Astrophysics Data System (ADS)

    Aitkenhead, Matt; McBratney, Alex; Minasny, Budiman

    2015-04-01

    Proximal sensing of soils can provide valuable information for soil modelling, by providing baseline data and validating model predictions through direct observation of soil characteristics. A wide range of soil parameters can be estimated using proximal sensing of soils (PSS), often simultaneously using single hand-held systems, of which there are many types. The benefits for soil modelling include direct observation of modelled parameters, rapid assessment in field conditions and digital data acquisition, making the transfer of information to soil models relatively straightforward. This is an active area of development, with research into improved methods of field-based capture of soil parameters directly relevant for soil modelling. A number of challenges exist, including the removal of or accounting for the effects of field conditions (e.g. soil moisture and structure), and the development of libraries of data that will allow calibration models to be produced. We present an overview of PSS as it relates to soil modelling, including equipment types, calibration approaches, cloud-based processing, soil parameters and processes estimated using PSS, and opportunities and challenges for the future. We also identify and discuss the possibilities for integration of modelling and proximal sensing within precision agriculture/precision land management.

  3. A VGI data integration framework based on linked data model

    NASA Astrophysics Data System (ADS)

    Wan, Lin; Ren, Rongrong

    2015-12-01

    This paper aims at the geographic data integration and sharing method for multiple online VGI data sets. We propose a semantic-enabled framework for online VGI sources cooperative application environment to solve a target class of geospatial problems. Based on linked data technologies - which is one of core components of semantic web, we can construct the relationship link among geographic features distributed in diverse VGI platform by using linked data modeling methods, then deploy these semantic-enabled entities on the web, and eventually form an interconnected geographic data network to support geospatial information cooperative application across multiple VGI data sources. The mapping and transformation from VGI sources to RDF linked data model is presented to guarantee the unique data represent model among different online social geographic data sources. We propose a mixed strategy which combined spatial distance similarity and feature name attribute similarity as the measure standard to compare and match different geographic features in various VGI data sets. And our work focuses on how to apply Markov logic networks to achieve interlinks of the same linked data in different VGI-based linked data sets. In our method, the automatic generating method of co-reference object identification model according to geographic linked data is discussed in more detail. It finally built a huge geographic linked data network across loosely-coupled VGI web sites. The results of the experiment built on our framework and the evaluation of our method shows the framework is reasonable and practicable.

  4. COMPARING AND LINKING PLUMES ACROSS MODELING APPROACHES

    EPA Science Inventory

    River plumes carry many pollutants, including microorganisms, into lakes and the coastal ocean. The physical scales of many stream and river plumes often lie between the scales for mixing zone plume models, such as the EPA Visual Plumes model, and larger-sized grid scales for re...

  5. Multi-Scale Modeling of Cross-Linked Nanotube Materials

    NASA Technical Reports Server (NTRS)

    Frankland, S. J. V.; Odegard, G. M.; Herzog, M. N.; Gates, T. S.; Fay, C. C.

    2005-01-01

    The effect of cross-linking single-walled carbon nanotubes on the Young's modulus of a nanotube-reinforced composite is modeled with a multi-scale method. The Young's modulus is predicted as a function of nanotube volume fraction and cross-link density. In this method, the constitutive properties of molecular representative volume elements are determined using molecular dynamics simulation and equivalent-continuum modeling. The Young's modulus is subsequently calculated for cross-linked nanotubes in a matrix which consists of the unreacted cross-linking agent. Two different cross-linking agents are used in this study, one that is short and rigid (Molecule A), and one that is long and flexible (Molecule B). Direct comparisons between the predicted elastic constants are made for the models in which the nanotubes are either covalently bonded or not chemically bonded to the cross-linking agent. At a nanotube volume fraction of 10%, the Young's modulus of Material A is not affected by nanotube crosslinking, while the Young's modulus of Material B is reduced by 64% when the nanotubes are cross-linked relative to the non-cross-linked material with the same matrix.

  6. Linking Models and Data on Vegetation Structure

    NASA Astrophysics Data System (ADS)

    Hurtt, G. C.; Fisk, J.; Thomas, R.; Dubayah, R.; Moorcroft, P.; Shugart, H.

    2008-12-01

    Forested ecosystems consist of a dynamic mosaic of patches on the landscape at different stages of recovery from disturbances. Recent studies have addressed this heterogeneity by combining remotely sensed measurements of vegetation structure, and advanced ecological models that track the dynamics of vegetation structure, to produce accurate estimates of both carbon stocks and fluxes at a set of important study sites. Now future satellite missions such as DESDYNI hold the potential to provide key data on vegetation structure needed to reduce uncertainties in terrestrial carbon dynamics globally. Here, we developed and analyzed a set of models to quantify the effects of limited sampling and/or coarse resolution averaging of structure measurements on model predictions. Generally, both limited sampling and coarse resolution averaging caused model initialization error, and led to subsequent prediction uncertainty and error. In cases with representative sampling, sufficient resolution, and linear dynamics, errors in initialization tended to compensate at larger scales. However, with inadequate sampling, overly coarse resolution data, and non-linear dynamics, errors in initialization led to bias. This study provides a generalized framework for assessing the tradeoffs between the quantity and quality of data on vegetation structure, and the science from models which depend on it.

  7. Binge eating in pre-clinical models.

    PubMed

    Rospond, Bartłomiej; Szpigiel, Joanna; Sadakierska-Chudy, Anna; Filip, Małgorzata

    2015-06-01

    Obesity is a globally widespread disease. Approximately 35% of world population has the problem of inappropriate body weight due to sedentary lifestyle, excessive food consumption and the lack of physical activity. In the course of many years, several pharmacological anti-obesity drugs have been discovered. Most of them, however, possess severe side effects. Recent findings suggest that disturbed functioning of the reward system can be involved in the development of obesity. The data coming from clinical and animal studies provide new evidence that links excessive food consumption with compulsive behavior that can lead to binge eating disease occurrence. In this review we discuss most commonly used animal models of binge eating such as restriction/refeeding, limited access and stress schedule model, and related to them neurobiological findings as well. We also present new, anti-obesity drugs, which are characterized by central mechanism of action. PMID:25933962

  8. Extended model of restricted beam for FSO links

    NASA Astrophysics Data System (ADS)

    Poliak, Juraj; Wilfert, Otakar

    2012-10-01

    Modern wireless optical communication systems in many aspects overcome wire or radio communications. Their advantages are license-free operation and broad bandwidth that they offer. The medium in free-space optical (FSO) links is the atmosphere. Operation of outdoor FSO links struggles with many atmospheric phenomena that deteriorate phase and amplitude of the transmitted optical beam. This beam originates in the transmitter and is affected by its individual parts, especially by the lens socket and the transmitter aperture, where attenuation and diffraction effects take place. Both of these phenomena unfavourable influence the beam and cause degradation of link availability, or its total malfunction. Therefore, both of these phenomena should be modelled and simulated, so that one can judge the link function prior to the realization of the system. Not only the link availability and reliability are concerned, but also economic aspects. In addition, the transmitted beam is not, generally speaking, circularly symmetrical, what makes the link simulation more difficult. In a comprehensive model, it is necessary to take into account the ellipticity of the beam that is restricted by circularly symmetrical aperture where then the attenuation and diffraction occur. General model is too computationally extensive; therefore simplification of the calculations by means of analytical and numerical approaches will be discussed. Presented model is not only simulated using computer, but also experimentally proven. One can then deduce the ability of the model to describe the reality and to estimate how far can one go with approximations, i.e. limitations of the model are discussed.

  9. Clinical genomics information management software linking cancer genome sequence and clinical decisions.

    PubMed

    Watt, Stuart; Jiao, Wei; Brown, Andrew M K; Petrocelli, Teresa; Tran, Ben; Zhang, Tong; McPherson, John D; Kamel-Reid, Suzanne; Bedard, Philippe L; Onetto, Nicole; Hudson, Thomas J; Dancey, Janet; Siu, Lillian L; Stein, Lincoln; Ferretti, Vincent

    2013-09-01

    Using sequencing information to guide clinical decision-making requires coordination of a diverse set of people and activities. In clinical genomics, the process typically includes sample acquisition, template preparation, genome data generation, analysis to identify and confirm variant alleles, interpretation of clinical significance, and reporting to clinicians. We describe a software application developed within a clinical genomics study, to support this entire process. The software application tracks patients, samples, genomic results, decisions and reports across the cohort, monitors progress and sends reminders, and works alongside an electronic data capture system for the trial's clinical and genomic data. It incorporates systems to read, store, analyze and consolidate sequencing results from multiple technologies, and provides a curated knowledge base of tumor mutation frequency (from the COSMIC database) annotated with clinical significance and drug sensitivity to generate reports for clinicians. By supporting the entire process, the application provides deep support for clinical decision making, enabling the generation of relevant guidance in reports for verification by an expert panel prior to forwarding to the treating physician. PMID:23603536

  10. Precise numerical modeling of next generation multimode fiber based links

    NASA Astrophysics Data System (ADS)

    Maksymiuk, L.; Stepniak, G.

    2015-12-01

    In order to numerically model modern multimode fiber based links we are required to take into account modal and chromatic dispersion, profile dispersion and spectral dependent coupling. In this paper we propose a complete numerical model which not only is precise but also versatile. Additionally to the detailed mathematical description of the model we provide also a bunch of numerical calculations performed with the use of the model.

  11. Clinical Psychology: A Research and Development Model.

    ERIC Educational Resources Information Center

    Broskowski, Anthony

    The purpose of this paper is to present a clinical research and development (R and D) model along with the rationale for its implementation and a sample training program for clinical psychologists. Although it may be possible to correct some problems by a clearer restatement of the scientist-professional model, a new model of clinical R and D has…

  12. Link Prediction in Weighted Networks: A Weighted Mutual Information Model

    PubMed Central

    Zhu, Boyao; Xia, Yongxiang

    2016-01-01

    The link-prediction problem is an open issue in data mining and knowledge discovery, which attracts researchers from disparate scientific communities. A wealth of methods have been proposed to deal with this problem. Among these approaches, most are applied in unweighted networks, with only a few taking the weights of links into consideration. In this paper, we present a weighted model for undirected and weighted networks based on the mutual information of local network structures, where link weights are applied to further enhance the distinguishable extent of candidate links. Empirical experiments are conducted on four weighted networks, and results show that the proposed method can provide more accurate predictions than not only traditional unweighted indices but also typical weighted indices. Furthermore, some in-depth discussions on the effects of weak ties in link prediction as well as the potential to predict link weights are also given. This work may shed light on the design of algorithms for link prediction in weighted networks. PMID:26849659

  13. Link Prediction in Weighted Networks: A Weighted Mutual Information Model.

    PubMed

    Zhu, Boyao; Xia, Yongxiang

    2016-01-01

    The link-prediction problem is an open issue in data mining and knowledge discovery, which attracts researchers from disparate scientific communities. A wealth of methods have been proposed to deal with this problem. Among these approaches, most are applied in unweighted networks, with only a few taking the weights of links into consideration. In this paper, we present a weighted model for undirected and weighted networks based on the mutual information of local network structures, where link weights are applied to further enhance the distinguishable extent of candidate links. Empirical experiments are conducted on four weighted networks, and results show that the proposed method can provide more accurate predictions than not only traditional unweighted indices but also typical weighted indices. Furthermore, some in-depth discussions on the effects of weak ties in link prediction as well as the potential to predict link weights are also given. This work may shed light on the design of algorithms for link prediction in weighted networks. PMID:26849659

  14. [Clinical and molecular study in a child with X-linked hypohidrotic ectodermal dysplasia].

    PubMed

    Callea, Michele; Yavuz, Izzet; Clarich, Gabriella; Cammarata-Scalisi, Francisco

    2015-12-01

    Ectodermal dysplasia encompasses more than 200 clinically distinct entities, which affect at least two structures derived from the ectoderm, including the skin, hair, nails, teeth, sweat glands, and sebaceous glands. X-linked hypohidrotic ectodermal dysplasia is the most common type and is caused by mutation of the EDA gene that encodes Ectodysplasin-A. It occurs in less than 1 in 100 000 individuals and is clinically characterized by hypodontia, hypohidrosis, hypotrichosis, and eye dis orders. We present a child evaluated in a multidisciplinary manner with clinical and molecular diagnosis of X-linked hypohidrotic ectodermal dysplasia with type missense mutation c.1133C> T; p.T378M in EDA gene. PMID:26593813

  15. Linking Output from regional Climat Models with Cryosphere Models

    NASA Astrophysics Data System (ADS)

    Winter, S.

    2003-04-01

    This study has the objective of linking the results of a low-resolution regional climate model (RCM) with high-resolution cryosphere models in order to determine the manner in which Alpine snow, ice and permafrost is likely to respond to enhanced atmospheric warming resulting from an increase in anthropogenic greenhouse gases. There are several constraints that need to be overcome prior to applying solutions to this problem. Firstly, as a result of the long response time of glaciers and alpine permafrost to climate change, long-term simulations of at least 30 years are required. Secondly, the smallest possible spatial resolution of current RCM still remains quite coarse (~ 50 km) because of the complex mathematical equations to be resolved in the RCM, the limited computer performance and the above mentioned long simulation period. On the other hand, cryosphere models used in the present study require gridded input climate variables with a typical mesh width of 50 m. The proposed solution consists in combining climate change data based on RCM scenarios with meteorological data of high elevation Alpine stations measured during a reference period. A RCM control run matching this reference period is required in order to quantify the expected change for each climate parameter. This approach allows breaking down the initial downscaling problem into two separate steps. First, the quantified change derived from RCM-control and scenario simulations is used to predict change for meteorological stations. Second, data sets of predicted change and meteorological measures of these stations are summed and then regionalized for the study area based on advanced algorithms and GIS techniques. Selecting a case study area close to one or more meteorological stations should minimize the associated regionalization error. A pilot study for a small area at Piz Corvatsch in the Eastern Swiss Alps has been designed. The A2 scenario of the IPCC (Intergovernmental Panel on Climate Change

  16. Link community detection using generative model and nonnegative matrix factorization.

    PubMed

    He, Dongxiao; Jin, Di; Baquero, Carlos; Liu, Dayou

    2014-01-01

    Discovery of communities in complex networks is a fundamental data analysis problem with applications in various domains. While most of the existing approaches have focused on discovering communities of nodes, recent studies have shown the advantages and uses of link community discovery in networks. Generative models provide a promising class of techniques for the identification of modular structures in networks, but most generative models mainly focus on the detection of node communities rather than link communities. In this work, we propose a generative model, which is based on the importance of each node when forming links in each community, to describe the structure of link communities. We proceed to fit the model parameters by taking it as an optimization problem, and solve it using nonnegative matrix factorization. Thereafter, in order to automatically determine the number of communities, we extend the above method by introducing a strategy of iterative bipartition. This extended method not only finds the number of communities all by itself, but also obtains high efficiency, and thus it is more suitable to deal with large and unexplored real networks. We test this approach on both synthetic benchmarks and real-world networks including an application on a large biological network, and compare it with two highly related methods. Results demonstrate the superior performance of our approach over competing methods for the detection of link communities. PMID:24489803

  17. Link Community Detection Using Generative Model and Nonnegative Matrix Factorization

    PubMed Central

    He, Dongxiao; Jin, Di; Baquero, Carlos; Liu, Dayou

    2014-01-01

    Discovery of communities in complex networks is a fundamental data analysis problem with applications in various domains. While most of the existing approaches have focused on discovering communities of nodes, recent studies have shown the advantages and uses of link community discovery in networks. Generative models provide a promising class of techniques for the identification of modular structures in networks, but most generative models mainly focus on the detection of node communities rather than link communities. In this work, we propose a generative model, which is based on the importance of each node when forming links in each community, to describe the structure of link communities. We proceed to fit the model parameters by taking it as an optimization problem, and solve it using nonnegative matrix factorization. Thereafter, in order to automatically determine the number of communities, we extend the above method by introducing a strategy of iterative bipartition. This extended method not only finds the number of communities all by itself, but also obtains high efficiency, and thus it is more suitable to deal with large and unexplored real networks. We test this approach on both synthetic benchmarks and real-world networks including an application on a large biological network, and compare it with two highly related methods. Results demonstrate the superior performance of our approach over competing methods for the detection of link communities. PMID:24489803

  18. Linking knowledge and action through mental models of sustainable agriculture.

    PubMed

    Hoffman, Matthew; Lubell, Mark; Hillis, Vicken

    2014-09-01

    Linking knowledge to action requires understanding how decision-makers conceptualize sustainability. This paper empirically analyzes farmer "mental models" of sustainability from three winegrape-growing regions of California where local extension programs have focused on sustainable agriculture. The mental models are represented as networks where sustainability concepts are nodes, and links are established when a farmer mentions two concepts in their stated definition of sustainability. The results suggest that winegrape grower mental models of sustainability are hierarchically structured, relatively similar across regions, and strongly linked to participation in extension programs and adoption of sustainable farm practices. We discuss the implications of our findings for the debate over the meaning of sustainability, and the role of local extension programs in managing knowledge systems. PMID:25157158

  19. Linking Goal-Oriented Requirements and Model-Driven Development

    NASA Astrophysics Data System (ADS)

    Pastor, Oscar; Giachetti, Giovanni

    In the context of Goal-Oriented Requirement Engineering (GORE) there are interesting modeling approaches for the analysis of complex scenarios that are oriented to obtain and represent the relevant requirements for the development of software products. However, the way to use these GORE models in an automated Model-Driven Development (MDD) process is not clear, and, in general terms, the translation of these models into the final software products is still manually performed. Therefore, in this chapter, we show an approach to automatically link GORE models and MDD processes, which has been elaborated by considering the experience obtained from linking the i * framework with an industrially applied MDD approach. The linking approach proposed is formulated by means of a generic process that is based on current modeling standards and technologies in order to facilitate its application for different MDD and GORE approaches. Special attention is paid to how this process generates appropriate model transformation mechanisms to automatically obtain MDD conceptual models from GORE models, and how it can be used to specify validation mechanisms to assure the correct model transformations.

  20. Link performance model for filter bank based multicarrier systems

    NASA Astrophysics Data System (ADS)

    Petrov, Dmitry; Oborina, Alexandra; Giupponi, Lorenza; Stitz, Tobias Hidalgo

    2014-12-01

    This paper presents a complete link level abstraction model for link quality estimation on the system level of filter bank multicarrier (FBMC)-based networks. The application of mean mutual information per coded bit (MMIB) approach is validated for the FBMC systems. The considered quality measure of the resource element for the FBMC transmission is the received signal-to-noise-plus-distortion ratio (SNDR). Simulation results of the proposed link abstraction model show that the proposed approach is capable of estimating the block error rate (BLER) accurately, even when the signal is propagated through the channels with deep and frequent fades, as it is the case for the 3GPP Hilly Terrain (3GPP-HT) and Enhanced Typical Urban (ETU) models. The FBMC-related results of link level simulations are compared with cyclic prefix orthogonal frequency division multiplexing (CP-OFDM) analogs. Simulation results are also validated through the comparison to reference publicly available results. Finally, the steps of link level abstraction algorithm for FBMC are formulated and its application for system level simulation of a professional mobile radio (PMR) network is discussed.

  1. Synthesis and characterization of new 5-linked pinoresinol lignin models.

    PubMed

    Yue, Fengxia; Lu, Fachuang; Sun, Runcang; Ralph, John

    2012-12-14

    Pinoresinol structures, featuring a β-β'-linkage between lignin monomer units, are important in softwood lignins and in dicots and monocots, particularly those that are downregulated in syringyl-specific genes. Although readily detected by NMR spectroscopy, pinoresinol structures largely escaped detection by β-ether-cleaving degradation analyses presumably due to the presence of the linkages at the 5 positions, in 5-5'- or 5-O-4'-structures. In this study, which is aimed at helping better understand 5-linked pinoresinol structures by providing the required data for NMR characterization, new lignin model compounds were synthesized through biomimetic peroxidase-mediated oxidative coupling reactions between pre-formed (free-phenolic) coniferyl alcohol 5-5'- or 5-O-4'-linked dimers and a coniferyl alcohol monomer. It was found that such dimers containing free-phenolic coniferyl alcohol moieties can cross-couple with the coniferyl alcohol producing pinoresinol-containing trimers (and higher oligomers) in addition to other homo- and cross-coupled products. Eight new lignin model compounds were obtained and characterized by NMR spectroscopy, and one tentatively identified cross-coupled β-O-4'-product was formed from a coniferyl alcohol 5-O-4'-linked dimer. It was demonstrated that the 5-5'- and 5-O-4'-linked pinoresinol structures could be readily differentiated by using heteronuclear multiple-bond correlation (HMBC) NMR spectroscopy. With appropriate modification (etherification or acetylation) to the newly obtained model compounds, it would be possible to identify the 5-5'- or 5-O-4'-linked pinoresinol structures in softwood lignins by 2D HMBC NMR spectroscopic methods. Identification of the cross-coupled dibenzodioxocin from a coniferyl alcohol 5-5'-linked moiety suggested that thioacidolysis or derivatization followed by reductive cleavage (DFRC) could be used to detect and identify whether the coniferyl alcohol itself undergoes 5-5'-cross-linking during

  2. Phase Diagram of the Bose Hubbard Model with Weak Links

    NASA Astrophysics Data System (ADS)

    Hettiarachchilage, Kalani; Rousseau, Valy; Tam, Ka-Ming; Moreno, Juana; Jarrell, Mark; Sheehy, Daniel

    2012-02-01

    We study the ground state phase diagram of strongly interacting ultracold Bose gas in a one-dimensional optical lattice with a tunable weak link, by means of Quantum Monte Carlo simulation. This model contains an on-site repulsive interaction (U) and two different near-neighbor hopping terms, J and t, for the weak link and the remainder of the chain, respectively. We show that by reducing the strength of J, a novel intermediate phase develops which is compressible and non-superfluid. This novel phase is identified as a Normal Bose Liquid (NBL) which does not appear in the phase diagram of the homogeneous bosonic Hubbard model. Further, we find a linear variation of the phase boundary of Normal Bose Liquid (NBL) to SuperFluid (SF) as a function of the strength of the weak link. These results may provide a new path to design advanced atomtronic devices in the future.

  3. The Link between the Appendix and Ulcerative Colitis: Clinical Relevance and Potential Immunological Mechanisms.

    PubMed

    Sahami, S; Kooij, I A; Meijer, S L; Van den Brink, G R; Buskens, C J; Te Velde, A A

    2016-02-01

    The human appendix has long been considered as a vestigial organ, an organ that has lost its function during evolution. In recent years, however, reports have emerged that link the appendix to numerous immunological functions in humans. Evidence has been presented for an important role of the appendix in maintaining intestinal health. This theory suggests that the appendix may be a reservoir or 'safe house' from which the commensal gut flora can rapidly be reestablished if it is eradicated from the colon. However, the appendix may also have a role in the development of inflammatory bowel disease (IBD). Several large epidemiological cohort studies have demonstrated the preventive effect of appendectomy on the development of ulcerative colitis, a finding that has been confirmed in murine colitis models. In addition, current studies are examining the possible therapeutic effect of an appendectomy to modulate disease course in patients with ulcerative colitis. This literature review assesses the current knowledge about the clinical and immunological aspects of the vermiform appendix in IBD and suggests that the idea of the appendix as a vestigial remnant should be discarded. PMID:26416189

  4. Studying Links between Hormones and Negative Affect: Models and Measures.

    ERIC Educational Resources Information Center

    Brooks-Gunn, Jeanne; And Others

    1994-01-01

    Considers eight models for the study of pubertal change that explore possible links between hormones and negative affective experiences, such as depression and aggression. Notes that hormonal effects, though small, have demonstrated stability and have interacted with psychological and social factors, implicating hormonal changes in the development…

  5. A Model Linking the Learning Organization and Performance Job Satisfaction

    ERIC Educational Resources Information Center

    Dirani, Khalil M.

    2006-01-01

    The underlying theories of learning and performance are quite complex. This paper proposes a model that links the learning organization theory as a process with job satisfaction as a performance theory outcome. The literature reviewed considered three process levels of learning within the learning organization and three outcome levels of job…

  6. Linking Academic Entitlement and Student Incivility Using Latent Means Modeling

    ERIC Educational Resources Information Center

    Kopp, Jason P.; Finney, Sara J.

    2013-01-01

    Academic entitlement has been theoretically linked with uncivil student behavior; however, this relationship has not been tested. To address this gap in the literature, the authors used latent means modeling to estimate the relationship between the Academic Entitlement Questionnaire and uncivil student behavior. The authors gathered scores on the…

  7. Single photon time transfer link model for GNSS satellites

    NASA Astrophysics Data System (ADS)

    Vacek, Michael; Michalek, Vojtech; Peca, Marek; Prochazka, Ivan; Blazej, Josef

    2015-05-01

    The importance of optical time transfer serving as a complement to traditional microwave links, has been attested for GNSSes and for scientific missions. Single photon time transfer (SPTT) is a process, allowing to compare (subtract) time readings of two distant clocks. Such a comparison may be then used to synchronize less accurate clock to a better reference, to perform clock characterization and calibration, to calculate mean time out of ensemble of several clocks, displaced in space. The single-photon time transfer is well established in field of space geodesy, being supported by passive retro-reflectors within space segment of five known GNSSes. A truly two-way, active terminals work aboard of Jason-2 (T2L2) - multiphoton operation, GNSS Beidou (Compass) - SPTT, and are going to be launched within recent ACES project (ELT) - SPTT, and GNSS GLONASS - multiphoton operation. However, there is still missing comprehensive theoretical model of two-way (using satellite receiver and retroreflector) SPTT link incorporating all crucial parameters of receiver (both ground and space segment receivers), transmitter, atmosphere effects on uplink and downlink path, influence of retroreflector. The input to calculation of SPTT link performance will be among others: link budget (distance, power, apertures, beam divergence, attenuation, scattering), propagating medium (atmosphere scintillation, beam wander, etc.), mutual Tx/Rx velocity, wavelength. The SPTT model will be evaluated without the properties of real components. These will be added in the further development. The ground-to-space SPTT link performance of typical scenarios are modeled. This work is a part of the ESA study "Comparison of optical time-transfer links."

  8. Monogenic mouse models of autism spectrum disorders: Common mechanisms and missing links.

    PubMed

    Hulbert, S W; Jiang, Y-H

    2016-05-01

    Autism spectrum disorders (ASDs) present unique challenges in the fields of genetics and neurobiology because of the clinical and molecular heterogeneity underlying these disorders. Genetic mutations found in ASD patients provide opportunities to dissect the molecular and circuit mechanisms underlying autistic behaviors using animal models. Ongoing studies of genetically modified models have offered critical insight into possible common mechanisms arising from different mutations, but links between molecular abnormalities and behavioral phenotypes remain elusive. The challenges encountered in modeling autism in mice demand a new analytic paradigm that integrates behavioral assessment with circuit-level analysis in genetically modified models with strong construct validity. PMID:26733386

  9. Linking Gap Model with MODIS Biophysical Products for Biomass Estimation

    NASA Astrophysics Data System (ADS)

    Wang, D.; Sun, G.; Cai, Y.; Guo, Z.; Fu, A.; Ni, W.; Liu, D.

    With the development of earth observation technology and data processing technology biophysical data from remote sensing means such as MODIS LAI and NPP are accessible now However it is still difficult for direct measurement of biomass from remote sensors One possibility for overcoming this problem is using ecological models to link the vegetation parameters currently available from remote sensing to biomass In this paper a combined work is done for estimating forest biomass A calibrated gap model ZELIG was run to simulate the forest development in a temperate forested area in NE China The output relationship between age and biomass was linked to registered MODIS LAI NPP and land cover type images of the same area From the above work forest age or biomass was estimated from existing remote sensed data Obviously there is a lot of work to be done such as optimal combination of biophysical parameters to improve the linkage between MODIS product and ecological modeling

  10. The Clinical Model in Rehabilitation and Alternatives.

    ERIC Educational Resources Information Center

    Woods, Diane E., Ed.; And Others

    This book is a compilation of responses and reactions to a position paper by Dr. Joseph Stubbins entitled "The Clinical Model in Rehabilitation and Alternatives." The text of the position paper is presented along with a brief summary of the main points he made in it pertaining to the clinical model and the systems model. Also included in the…

  11. UAS Modeling of the Communication Links Study Results

    NASA Technical Reports Server (NTRS)

    Birr, Richard B.; Girgis, Nancy; Murray, Jennifer

    2011-01-01

    The Federal Aviation Administration (FAA) is the authority that grants access into, and operations within, the National Airspace System (NAS) for all aircraft, including Unmanned Aircraft Systems (UAS). The safe operation of UAS in the NAS must be assured if the full potential of UAS is to be realized and supported by the public and Congress. This report analyzed the communication systems that are needed for the safe operations of UAS in the NAS. Safe operations can be defined as the availability of the required links to carry the information to control the UAS and the return links to allow controllers to know where the UAS is at any given moment as well as how it is performing. This report is the end result of work performed jointly between the FAA and National Aeronautics and Space Administration (NASA)/Kennedy Space Center (NASA KSC). The work was done in support of the Radio Technical Commission for Aeronautics (RTCA) Special Committee 203 (SC-203) Control and Communications Working Group. The RTCA is a federal advisory committee to the FAA. Though the work was not under the direction of the working group, a large part of the specific values used in the simulations came from the working group. Specifically, all of the radio links were modeled based on the formulation completed by the working group. This report analyzed three scenarios from RTCA SC-203 that represent how a UAS would operate in the NAS. Each scenario was created using the Satellite Tool Kit (STK) modeling and simulation tool. The flight paths of the UAS were generated and the UAS dynamics were likewise modeled. Then each communication asset such as transmitters, receivers, and antennas were modeled and placed on the appropriate UAS, satellite, or Control Station (CS). After that, the radio links were analyzed for signal strength and antenna blockage, and the overall link performance was analyzed in detail. The goal was to obtain 99.9% availability on all of the radio communication links. In order

  12. Promoting professional nursing practice: linking a professional practice model to performance expectations.

    PubMed

    Murphy, Marcia; Hinch, Barbara; Llewellyn, Jane; Dillon, Paula J; Carlson, Elizabeth

    2011-03-01

    Professional practice models (PPMs) provide the conceptual framework for establishing professional nursing practice. Integrating a PPM requires complex organizational change. One strategy for integrating a PPM is to directly link the PPM with performance expectations to ensure that underlying beliefs are integrated into everyday practice. This article describes the development, implementation, and successful outcomes of a clinical advancement system that was aligned with a PPM. PMID:21320662

  13. An Optometric Clinical Practicum Examination Model.

    ERIC Educational Resources Information Center

    Eskridge, Jess B.

    1979-01-01

    A practical clinical examination model for use by state board examiners in optometry is described including purpose, format, examination design, procedures, evaluation examples and administration. (JMF)

  14. How to Establish Clinical Prediction Models

    PubMed Central

    Bang, Heejung

    2016-01-01

    A clinical prediction model can be applied to several challenging clinical scenarios: screening high-risk individuals for asymptomatic disease, predicting future events such as disease or death, and assisting medical decision-making and health education. Despite the impact of clinical prediction models on practice, prediction modeling is a complex process requiring careful statistical analyses and sound clinical judgement. Although there is no definite consensus on the best methodology for model development and validation, a few recommendations and checklists have been proposed. In this review, we summarize five steps for developing and validating a clinical prediction model: preparation for establishing clinical prediction models; dataset selection; handling variables; model generation; and model evaluation and validation. We also review several studies that detail methods for developing clinical prediction models with comparable examples from real practice. After model development and vigorous validation in relevant settings, possibly with evaluation of utility/usability and fine-tuning, good models can be ready for the use in practice. We anticipate that this framework will revitalize the use of predictive or prognostic research in endocrinology, leading to active applications in real clinical practice. PMID:26996421

  15. How to Establish Clinical Prediction Models.

    PubMed

    Lee, Yong Ho; Bang, Heejung; Kim, Dae Jung

    2016-03-01

    A clinical prediction model can be applied to several challenging clinical scenarios: screening high-risk individuals for asymptomatic disease, predicting future events such as disease or death, and assisting medical decision-making and health education. Despite the impact of clinical prediction models on practice, prediction modeling is a complex process requiring careful statistical analyses and sound clinical judgement. Although there is no definite consensus on the best methodology for model development and validation, a few recommendations and checklists have been proposed. In this review, we summarize five steps for developing and validating a clinical prediction model: preparation for establishing clinical prediction models; dataset selection; handling variables; model generation; and model evaluation and validation. We also review several studies that detail methods for developing clinical prediction models with comparable examples from real practice. After model development and vigorous validation in relevant settings, possibly with evaluation of utility/usability and fine-tuning, good models can be ready for the use in practice. We anticipate that this framework will revitalize the use of predictive or prognostic research in endocrinology, leading to active applications in real clinical practice. PMID:26996421

  16. Clinical and mutational features of X-linked agammaglobulinemia in Mexico.

    PubMed

    García-García, E; Staines-Boone, A T; Vargas-Hernández, A; González-Serrano, M E; Carrillo-Tapia, E; Mogica-Martínez, D; Berrón-Ruíz, L; Segura-Mendez, N H; Espinosa-Rosales, F J; Yamazaki-Nakashimada, M A; Santos-Argumedo, L; López-Herrera, G

    2016-04-01

    X-linked agammaglobulinemia (XLA) is caused by BTK mutations, patients typically show <2% of peripheral B cells and reduced levels of all immunoglobulins; they suffer from recurrent infections of bacterial origin; however, viral infections, autoimmune-like diseases, and an increased risk of developing gastric cancer are also reported. In this work, we report the BTK mutations and clinical features of 12 patients diagnosed with XLA. Furthermore, a clinical revision is also presented for an additional cohort of previously reported patients with XLA. Four novel mutations were identified, one of these located in the previously reported mutation refractory SH3 domain. Clinical data support previous reports accounting for frequent respiratory, gastrointestinal tract infections and other symptoms such as the occurrence of reactive arthritis in 19.2% of the patients. An equal proportion of patients developed septic arthritis; missense mutations and mutations in SH1, SH2 and PH domains predominated in patients who developed arthritis. PMID:26960951

  17. The antibiotic resistance “mobilome”: searching for the link between environment and clinic

    PubMed Central

    Perry, Julie A.; Wright, Gerard D.

    2013-01-01

    Antibiotic resistance is an ancient problem, owing to the co-evolution of antibiotic-producing and target organisms in the soil and other environments over millennia. The environmental “resistome” is the collection of all genes that directly or indirectly contribute to antibiotic resistance. Many of these resistance determinants originate in antibiotic-producing organisms (where they serve to mediate self-immunity), while others become resistance determinants only when mobilized and over-expressed in non-native hosts (like plasmid-encoded β-lactamases). The modern environmental resistome is under selective pressure from human activities such as agriculture, which may influence the composition of the local resistome and lead to gene transfer events. Beyond the environment, we are challenged in the clinic by the rise in both frequency and diversity of antibiotic resistant pathogens. We assume that clinical resistance originated in the environment, but few examples of direct gene exchange between the environmental resistome and the clinical resistome have been documented. Strong evidence exists to suggest that clinical aminoglycoside and vancomycin resistance enzymes, the extended-spectrum β-lactamase CTX-M and the quinolone resistance gene qnr have direct links to the environmental resistome. In this review, we highlight recent advances in our understanding of horizontal gene transfer of antibiotic resistance genes from the environment to the clinic. Improvements in sequencing technologies coupled with functional metagenomic studies have revealed previously underappreciated diversity in the environmental resistome, and also established novel genetic links to the clinic. Understanding mechanisms of gene exchange becomes vital in controlling the future dissemination of antibiotic resistance. PMID:23755047

  18. Use of cross-linked carboxymethyl cellulose for soft-tissue augmentation: preliminary clinical studies

    PubMed Central

    Leonardis, Mauro; Palange, Andrea; Dornelles, Rodrigo FV; Hund, Felipe

    2010-01-01

    Purpose: The continual search for new products for soft-tissue augmentation has in recent years led to the introduction of long lasting alternatives to hyaluronic acids and collagen that are composed of other polymers able to improve clinical persistence over time. This is the first report in which sodium carboxymethyl cellulose (CMC) has been chemically treated by the cross-linking process and thus used as a hydrogel for soft-tissue augmentation through injection with thin needles. The study evaluates, from a clinical point of view, the behavior of cross-linked carboxymethyl cellulose hydrogel used in the aesthetic field and its side effects so as to check the safety and performance of the polymer following intradermal injections. Patients and methods: This work shows the preliminary results of an ongoing clinical study conducted between 2006 and 2009, performed on 84 healthy volunteers (62 females, 22 males) aged between 18 and 72 years, for the treatment of 168 nasolabial folds, 45 perioral wrinkles, and 39 lip volume. Results: Study results show an excellent correction of facial defects. Tolerance and aesthetic quality of the correction obtained indicate considerable safety features and absence of side effects. From a clinical point of view, hydrogel is gradually absorbed into the injection site without migration issues. Conclusion: Cross-linked CMC hydrogel proves to be an ideal agent for soft tissue augmentation with regard to safety and ease of application. It did not cause infection, extrusion, migration, or adverse reactions in the patients who have been followed for two years. Delayed aesthetic results on facial wrinkles were very satisfactory. PMID:21228896

  19. Linking Mind, Brain, and Education to Clinical Practice: A Proposal for Transdisciplinary Collaboration

    ERIC Educational Resources Information Center

    Ronstadt, Katie; Yellin, Paul B.

    2010-01-01

    It has been suggested that the field of Mind, Brain, and Education (MBE) requires a stable infrastructure for translating research into practice. Hinton and Fischer (2008) point to the academic medical center as a model for similar translational work and suggest a similar approach for linking scientists to research schools. We propose expanding…

  20. Improving nonlinear modeling capabilities of functional link adaptive filters.

    PubMed

    Comminiello, Danilo; Scarpiniti, Michele; Scardapane, Simone; Parisi, Raffaele; Uncini, Aurelio

    2015-09-01

    The functional link adaptive filter (FLAF) represents an effective solution for online nonlinear modeling problems. In this paper, we take into account a FLAF-based architecture, which separates the adaptation of linear and nonlinear elements, and we focus on the nonlinear branch to improve the modeling performance. In particular, we propose a new model that involves an adaptive combination of filters downstream of the nonlinear expansion. Such combination leads to a cooperative behavior of the whole architecture, thus yielding a performance improvement, particularly in the presence of strong nonlinearities. An advanced architecture is also proposed involving the adaptive combination of multiple filters on the nonlinear branch. The proposed models are assessed in different nonlinear modeling problems, in which their effectiveness and capabilities are shown. PMID:26057613

  1. Theoretical Basis, Laboratory Evidence, and Clinical Research of Chemical Surgery of the Cornea: Cross-Linking

    PubMed Central

    da Paz, Amanda C.; Bersanetti, Patrícia A.; Salomão, Marcella Q.; Ambrósio, Renato; Schor, Paulo

    2014-01-01

    Corneal cross-linking (CXL) is increasingly performed in ophthalmology with high success rates for progressive keratoconus and other types of ectasia. Despite being an established procedure, some molecular and clinical aspects still require additional studies. This review presents a critical analysis of some established topics and others that are still controversial. In addition, this review examines new technologies and techniques (transepithelial and ultrafast CXL), uses of corneal CXL including natural products and biomolecules as CXL promoters, and evidence for in vitro and in vivo indirect effectiveness. PMID:25215226

  2. A systematic review of evidence on the links between patient experience and clinical safety and effectiveness

    PubMed Central

    Doyle, Cathal; Lennox, Laura; Bell, Derek

    2013-01-01

    Objective To explore evidence on the links between patient experience and clinical safety and effectiveness outcomes. Design Systematic review. Setting A wide range of settings within primary and secondary care including hospitals and primary care centres. Participants A wide range of demographic groups and age groups. Primary and secondary outcome measures A broad range of patient safety and clinical effectiveness outcomes including mortality, physical symptoms, length of stay and adherence to treatment. Results This study, summarising evidence from 55 studies, indicates consistent positive associations between patient experience, patient safety and clinical effectiveness for a wide range of disease areas, settings, outcome measures and study designs. It demonstrates positive associations between patient experience and self-rated and objectively measured health outcomes; adherence to recommended clinical practice and medication; preventive care (such as health-promoting behaviour, use of screening services and immunisation); and resource use (such as hospitalisation, length of stay and primary-care visits). There is some evidence of positive associations between patient experience and measures of the technical quality of care and adverse events. Overall, it was more common to find positive associations between patient experience and patient safety and clinical effectiveness than no associations. Conclusions The data presented display that patient experience is positively associated with clinical effectiveness and patient safety, and support the case for the inclusion of patient experience as one of the central pillars of quality in healthcare. It supports the argument that the three dimensions of quality should be looked at as a group and not in isolation. Clinicians should resist sidelining patient experience as too subjective or mood-oriented, divorced from the ‘real’ clinical work of measuring safety and effectiveness. PMID:23293244

  3. Defining Scenarios: Linking Integrated Models, Regional Concerns, and Stakeholders

    NASA Astrophysics Data System (ADS)

    Hartmann, H. C.; Stewart, S.; Liu, Y.; Mahmoud, M.

    2007-05-01

    Scenarios are important tools for long-term planning, and there is great interest in using integrated models in scenario studies. However, scenario definition and assessment are creative, as well as scientific, efforts. Using facilitated creative processes, we have worked with stakeholders to define regionally significant scenarios that encompass a broad range of hydroclimatic, socioeconomic, and institutional dimensions. The regional scenarios subsequently inform the definition of local scenarios that work with context-specific integrated models that, individually, can address only a subset of overall regional complexity. Based on concerns of stakeholders in the semi-arid US Southwest, we prioritized three dimensions that are especially important, yet highly uncertain, for long-term planning: hydroclimatic conditions (increased variability, persistent drought), development patterns (urban consolidation, distributed rural development), and the nature of public institutions (stressed, proactive). Linking across real-world decision contexts and integrated modeling efforts poses challenges of creatively connecting the conceptual models held by both the research and stakeholder communities.

  4. Groundwater Pollution Source Identification using Linked ANN-Optimization Model

    NASA Astrophysics Data System (ADS)

    Ayaz, Md; Srivastava, Rajesh; Jain, Ashu

    2014-05-01

    Groundwater is the principal source of drinking water in several parts of the world. Contamination of groundwater has become a serious health and environmental problem today. Human activities including industrial and agricultural activities are generally responsible for this contamination. Identification of groundwater pollution source is a major step in groundwater pollution remediation. Complete knowledge of pollution source in terms of its source characteristics is essential to adopt an effective remediation strategy. Groundwater pollution source is said to be identified completely when the source characteristics - location, strength and release period - are known. Identification of unknown groundwater pollution source is an ill-posed inverse problem. It becomes more difficult for real field conditions, when the lag time between the first reading at observation well and the time at which the source becomes active is not known. We developed a linked ANN-Optimization model for complete identification of an unknown groundwater pollution source. The model comprises two parts- an optimization model and an ANN model. Decision variables of linked ANN-Optimization model contain source location and release period of pollution source. An objective function is formulated using the spatial and temporal data of observed and simulated concentrations, and then minimized to identify the pollution source parameters. In the formulation of the objective function, we require the lag time which is not known. An ANN model with one hidden layer is trained using Levenberg-Marquardt algorithm to find the lag time. Different combinations of source locations and release periods are used as inputs and lag time is obtained as the output. Performance of the proposed model is evaluated for two and three dimensional case with error-free and erroneous data. Erroneous data was generated by adding uniformly distributed random error (error level 0-10%) to the analytically computed concentration

  5. Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

    PubMed Central

    Zielinski, Daniel C.; Filipp, Fabian V.; Bordbar, Aarash; Jensen, Kasper; Smith, Jeffrey W.; Herrgard, Markus J.; Mo, Monica L.; Palsson, Bernhard O.

    2015-01-01

    Drug side effects cause a significant clinical and economic burden. However, mechanisms of drug action underlying side effect pathogenesis remain largely unknown. Here, we integrate pharmacogenomic and clinical data with a human metabolic network and find that non-pharmacokinetic metabolic pathways dysregulated by drugs are linked to the development of side effects. We show such dysregulated metabolic pathways contain genes with sequence variants affecting side effect incidence, play established roles in pathophysiology, have significantly altered activity in corresponding diseases, are susceptible to metabolic inhibitors and are effective targets for therapeutic nutrient supplementation. Our results indicate that metabolic dysregulation represents a common mechanism underlying side effect pathogenesis that is distinct from the role of metabolism in drug clearance. We suggest that elucidating the relationships between the cellular response to drugs, genetic variation of patients and cell metabolism may help managing side effects by personalizing drug prescriptions and nutritional intervention strategies. PMID:26055627

  6. Optimization model for UV-Riboflavin corneal cross-linking

    NASA Astrophysics Data System (ADS)

    Schumacher, S.; Wernli, J.; Scherrer, S.; Bueehler, M.; Seiler, T.; Mrochen, M.

    2011-03-01

    Nowadays UV-cross-linking is an established method for the treatment of keraectasia. Currently a standardized protocol is used for the cross-linking treatment. We will now present a theoretical model which predicts the number of induced crosslinks in the corneal tissue, in dependence of the Riboflavin concentration, the radiation intensity, the pre-treatment time and the treatment time. The model is developed by merging the difussion equation, the equation for the light distribution in dependence on the absorbers in the tissue and a rate equation for the polymerization process. A higher concentration of Riboflavin solution as well as a higher irradiation intensity will increase the number of induced crosslinks. However, performed stress-strain experiments which support the model showed that higher Riboflavin concentrations (> 0.125%) do not result in a further increase in stability of the corneal tissue. This is caused by the inhomogeneous distribution of induced crosslinks throughout the cornea due to the uneven absorption of the UV-light. The new model offers the possibility to optimize the treatment individually for every patient depending on their corneal thickness in terms of efficiency, saftey and treatment time.

  7. Modeling of Long-Range Atmospheric Lasercom Links Between Static and Mobile Platforms

    SciTech Connect

    Scharlemann, E T; Breitfeller, E F; Henderson, J R; Kallman, J S; Morris, J R; Ruggiero, A J

    2003-07-29

    We describe modeling and simulation of long-range terrestrial laser communications links between static and mobile platforms. Atmospheric turbulence modeling, along with pointing, tracking and acquisition models are combined to provide an overall capability to estimate communications link performance.

  8. Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

    SciTech Connect

    Mullan, M.; Bennett, C.; Figueredo, C.; Crawford, F.

    1995-02-27

    Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.

  9. Solanaceae—A Model for Linking Genomics With Biodiversity

    PubMed Central

    Bohs, Lynn; Nee, Michael; Spooner, David M.

    2004-01-01

    Recent progress in understanding the phylogeny of the economically important plant family Solanaceae makes this an ideal time to develop models for linking the new data on plant genomics with the huge diversity of naturally occurring species in the family. Phylogenetics provides the framework with which to investigate these linkages but, critically, good species-level descriptive resources for the Solanaceae community are currently missing. Phylogeny in the family as a whole is briefly reviewed, and the new NSF Planetary Biodiversity Inventories project ‘PBI: Solanum—a worldwide treatment’ is described. The aims of this project are to provide species-level information across the global scope of the genus Solanum and to make this available over the Internet. The project is in its infancy, but will make available nomenclatural information, descriptions, keys and illustrative material for all of the approximately 1500 species of Solanum. With this project, the opportunity of linking valid, up-to-date taxonomic information about wild species of Solanum with the genomic information being generated about the economically important species of the genus (potato, tomato and eggplant) can be realized. The phylogenetic framework in which the PBI project is set is also of enormous potential benefit to other workers on Solanum. The community of biologists working with Solanaceae has a unique opportunity to effectively link genomics and taxonomy for better understanding of this important family, taking plant biology to a new level for the next century. PMID:18629162

  10. X-linked myotubular myopathy: clinical observations in ten additional cases.

    PubMed

    Joseph, M; Pai, G S; Holden, K R; Herman, G

    1995-11-01

    X-linked myotubular myopathy (XLMTM) is a recessively inherited disorder, lethal to males in the first months of life. Since the first report in 1969, at least 90 cases have been described in the literature. Diagnosis is confirmed by muscle biopsy. Linkage studies have localized the disorder to the Xq28 region, close to the loci for X-linked hydrocephalus and MASA syndrome. We report on 10 additional cases of XLMTM from six different families. In addition to classic clinical features of XLMTM, our patients showed interesting associated findings which included birth length > 90th centile and large head circumference with or without hydrocephalus in 70%, narrow, elongated face in 80%, and slender, long digits in 60% of cases. There was concordance in the occurrence and severity of hydrocephalus in most sib pairs. These features in a "floppy" male infant serve as clues for early clinical diagnosis of XLMTM, which can then be confirmed by muscle biopsy. Development of polyhydramnios was observed in the third trimester of an at-risk dizygotic twin gestation monitored by serial sonography with confirmation of XLMTM at birth. PMID:8588581

  11. Linking Murine and Human Plasmodium falciparum Challenge Models in a Translational Path for Antimalarial Drug Development

    PubMed Central

    McCarthy, James S.; Marquart, Louise; Sekuloski, Silvana; Trenholme, Katharine; Elliott, Suzanne; Griffin, Paul; Rockett, Rebecca; O'Rourke, Peter; Sloots, Theo; Angulo-Barturen, Iñigo; Ferrer, Santiago; Jiménez-Díaz, María Belén; Martínez, María-Santos; Duparc, Stephan; Leroy, Didier; Wells, Timothy N. C.; Baker, Mark

    2016-01-01

    Effective progression of candidate antimalarials is dependent on optimal dosing in clinical studies, which is determined by a sound understanding of pharmacokinetics and pharmacodynamics (PK/PD). Recently, two important translational models for antimalarials have been developed: the NOD/SCID/IL2Rγ−/− (NSG) model, whereby mice are engrafted with noninfected and Plasmodium falciparum-infected human erythrocytes, and the induced blood-stage malaria (IBSM) model in human volunteers. The antimalarial mefloquine was used to directly measure the PK/PD in both models, which were compared to previously published trial data for malaria patients. The clinical part was a single-center, controlled study using a blood-stage Plasmodium falciparum challenge inoculum in volunteers to characterize the effectiveness of mefloquine against early malaria. The study was conducted in three cohorts (n = 8 each) using different doses of mefloquine. The characteristic delay in onset of action of about 24 h was seen in both NSG and IBSM systems. In vivo 50% inhibitory concentrations (IC50s) were estimated at 2.0 μg/ml and 1.8 μg/ml in the NSG and IBSM models, respectively, aligning with 1.8 μg/ml reported previously for patients. In the IBSM model, the parasite reduction ratios were 157 and 195 for the 10- and 15-mg/kg doses, within the range of previously reported clinical data for patients but significantly lower than observed in the mouse model. Linking mouse and human challenge models to clinical trial data can accelerate the accrual of critical data on antimalarial drug activity. Such data can guide large clinical trials required for development of urgently needed novel antimalarial combinations. (This trial was registered at the Australian New Zealand Clinical Trials Registry [http://anzctr.org.au] under registration number ACTRN12612000323820.) PMID:27044554

  12. Linking Murine and Human Plasmodium falciparum Challenge Models in a Translational Path for Antimalarial Drug Development.

    PubMed

    McCarthy, James S; Marquart, Louise; Sekuloski, Silvana; Trenholme, Katharine; Elliott, Suzanne; Griffin, Paul; Rockett, Rebecca; O'Rourke, Peter; Sloots, Theo; Angulo-Barturen, Iñigo; Ferrer, Santiago; Jiménez-Díaz, María Belén; Martínez, María-Santos; Hooft van Huijsduijnen, Rob; Duparc, Stephan; Leroy, Didier; Wells, Timothy N C; Baker, Mark; Möhrle, Jörg J

    2016-06-01

    Effective progression of candidate antimalarials is dependent on optimal dosing in clinical studies, which is determined by a sound understanding of pharmacokinetics and pharmacodynamics (PK/PD). Recently, two important translational models for antimalarials have been developed: the NOD/SCID/IL2Rγ(-/-) (NSG) model, whereby mice are engrafted with noninfected and Plasmodium falciparum-infected human erythrocytes, and the induced blood-stage malaria (IBSM) model in human volunteers. The antimalarial mefloquine was used to directly measure the PK/PD in both models, which were compared to previously published trial data for malaria patients. The clinical part was a single-center, controlled study using a blood-stage Plasmodium falciparum challenge inoculum in volunteers to characterize the effectiveness of mefloquine against early malaria. The study was conducted in three cohorts (n = 8 each) using different doses of mefloquine. The characteristic delay in onset of action of about 24 h was seen in both NSG and IBSM systems. In vivo 50% inhibitory concentrations (IC50s) were estimated at 2.0 μg/ml and 1.8 μg/ml in the NSG and IBSM models, respectively, aligning with 1.8 μg/ml reported previously for patients. In the IBSM model, the parasite reduction ratios were 157 and 195 for the 10- and 15-mg/kg doses, within the range of previously reported clinical data for patients but significantly lower than observed in the mouse model. Linking mouse and human challenge models to clinical trial data can accelerate the accrual of critical data on antimalarial drug activity. Such data can guide large clinical trials required for development of urgently needed novel antimalarial combinations. (This trial was registered at the Australian New Zealand Clinical Trials Registry [http://anzctr.org.au] under registration number ACTRN12612000323820.). PMID:27044554

  13. Linking the Weather Generator with Regional Climate Model

    NASA Astrophysics Data System (ADS)

    Dubrovsky, Martin; Farda, Ales; Skalak, Petr; Huth, Radan

    2013-04-01

    One of the downscaling approaches, which transform the raw outputs from the climate models (GCMs or RCMs) into data with more realistic structure, is based on linking the stochastic weather generator with the climate model output. The present contribution, in which the parametric daily surface weather generator (WG) M&Rfi is linked to the RCM output, follows two aims: (1) Validation of the new simulations of the present climate (1961-1990) made by the ALADIN-Climate Regional Climate Model at 25 km resolution. The WG parameters are derived from the RCM-simulated surface weather series and compared to those derived from weather series observed in 125 Czech meteorological stations. The set of WG parameters will include statistics of the surface temperature and precipitation series (including probability of wet day occurrence). (2) Presenting a methodology for linking the WG with RCM output. This methodology, which is based on merging information from observations and RCM, may be interpreted as a downscaling procedure, whose product is a gridded WG capable of producing realistic synthetic multivariate weather series for weather-ungauged locations. In this procedure, WG is calibrated with RCM-simulated multi-variate weather series in the first step, and the grid specific WG parameters are then de-biased by spatially interpolated correction factors based on comparison of WG parameters calibrated with gridded RCM weather series and spatially scarcer observations. The quality of the weather series produced by the resultant gridded WG will be assessed in terms of selected climatic characteristics (focusing on characteristics related to variability and extremes of surface temperature and precipitation). Acknowledgements: The present experiment is made within the frame of projects ALARO-Climate (project P209/11/2405 sponsored by the Czech Science Foundation), WG4VALUE (project LD12029 sponsored by the Ministry of Education, Youth and Sports of CR) and VALUE (COST ES 1102

  14. A note on some common diffraction link loss models

    NASA Astrophysics Data System (ADS)

    Pogorzelski, R. J.

    1982-12-01

    A tropospheric propagation path obstructed by transverse obstacles is considered. The obstacles are modeled as perfectly absorbing half planes. Propagation loss relative to the unobstructed path is calculated by means of the method of Epstein and Peterson and the method of Deygout. These results are compared with those predicted by spectral diffraction theory. The comparison is made entirely outside the transition regions surrounding the shadow boundaries, permitting simplification of the spectral theory to the familiar geometrical theory of diffraction. The comparisons are used to explain the apparent superiority of the Deygout method over that of Epstein and Peterson in predicting the link loss.

  15. A Drosophila XPD model links cell cycle coordination with neuro-development and suggests links to cancer

    PubMed Central

    Stettler, Karin; Li, Xiaoming; Sandrock, Björn; Braga-Lagache, Sophie; Heller, Manfred; Dümbgen, Lutz; Suter, Beat

    2015-01-01

    XPD functions in transcription, DNA repair and in cell cycle control. Mutations in human XPD (also known as ERCC2) mainly cause three clinical phenotypes: xeroderma pigmentosum (XP), Cockayne syndrome (XP/CS) and trichothiodystrophy (TTD), and only XP patients have a high predisposition to developing cancer. Hence, we developed a fly model to obtain novel insights into the defects caused by individual hypomorphic alleles identified in human XP-D patients. This model revealed that the mutations that displayed the greatest in vivo UV sensitivity in Drosophila did not correlate with those that led to tumor formation in humans. Immunoprecipitations followed by targeted quantitative MS/MS analysis showed how different xpd mutations affected the formation or stability of different transcription factor IIH (TFIIH) subcomplexes. The XP mutants most clearly linked to high cancer risk, Xpd R683W and R601L, showed a reduced interaction with the core TFIIH and also an abnormal interaction with the Cdk-activating kinase (CAK) complex. Interestingly, these two XP alleles additionally displayed high levels of chromatin loss and free centrosomes during the rapid nuclear division phase of the Drosophila embryo. Finally, the xpd mutations showing defects in the coordination of cell cycle timing during the Drosophila embryonic divisions correlated with those human mutations that cause the neurodevelopmental abnormalities and developmental growth defects observed in XP/CS and TTD patients. PMID:25431422

  16. A model for reflection for good clinical practice.

    PubMed

    Balla, John I; Heneghan, Carl; Glasziou, Paul; Thompson, Matthew; Balla, Margaret E

    2009-12-01

    Rationale and aim The rapidly changing knowledge base of clinical practice highlights the need to keep abreast of knowledge changes that are most relevant for the practitioner. We aimed to develop a model for reflection on clinical practice that identified the key elements of medical knowledge needed for good medical practice. Method The dual theory of cognition, an integration of intuitive and analytic processes, provided the framework for the study. The design looked at the congruence between the clinical thinking process and the dual theory. A one-year study was conducted in general practice clinics in Oxfordshire, UK. Thirty-five general practitioners participated in 20-minute interviews to discuss how they worked through recently seen clinical cases. Over a one-year period 72 cases were recorded from 35 interviews. These were categorized according to emerging themes, which were manually coded and substantiated with verbatim quotations. Results There was a close fit between the dual theory and participants' clinical thinking processes. This included instant problem framing, consistent with automatic intuitive thinking, focusing on the risk and urgency of the case. Salient features accounting for these choices were recognizable. There was a second reflective phase, leading to the review of initial judgements. Conclusions The proposed model highlights the critical steps in decision making. This allows regular recalibration of knowledge that is most critical at each of these steps. In line with good practice, the model also links the crucial knowledge used in decision making, to value judgments made in relation to the patient. PMID:20367693

  17. Modeling Clinical Context: Rediscovering the Social History and Evaluating Language from the Clinic to the Wards

    PubMed Central

    Walsh, Colin; Elhadad, Noémie

    2014-01-01

    Social, behavioral, and cultural factors are clearly linked to health and disease outcomes. The medical social history is a critical evaluation of these factors performed by healthcare providers with patients in both inpatient and outpatient care settings. Physicians learn the topics covered in the social history through education and practice, but the topics discussed and documented in real-world clinical narrative have not been described at scale. This study applies large-scale automated topic modeling techniques to discover common topics discussed in social histories, to compare those topics to the medical textbook representation of those histories, and to compare topics between clinical settings to illustrate differences of clinical context on narrative content. Language modeling techniques are used to consider the extent to which inpatient and outpatient social histories share in their language use. Our findings highlight the fact that clinical context and setting are distinguishing factors for social history documentation, as the language of the hospital wards is not the same as that of the ambulatory clinic. Moreover, providers receive little feedback on the quality of their documentation beyond that needed for billing processes. The findings in this study demonstrate a number of topics described in textbooks – schooling, religion, alternative health practices, stressors, for example - do not appear in social histories in either clinical setting. PMID:25717417

  18. Clinical characteristics and genetic profiles of 174 patients with X-linked agammaglobulinemia

    PubMed Central

    Chen, Xia-Fang; Wang, Wei-Fan; Zhang, Yi-Dan; Zhao, Wei; Wu, Jing; Chen, Tong-Xin

    2016-01-01

    Abstract X-linked agammaglobulinemia (XLA) is a humoral primary immunodeficiency. XLA patients typically present with very low numbers of peripheral B cells and a profound deficiency of all immunoglobulin isotypes. Most XLA patients carry mutations in Bruton tyrosine kinase (BTK) gene. The genetic background and clinical features of 174 Chinese patients with XLA were investigated. The relationship between specific BTK gene mutations and severity of clinical manifestations was also examined. Mutations were graded from mild to severe based on structural and functional prediction through bioinformatics analysis. One hundred twenty-seven mutations were identified in 142 patients from 124 families, including 45 novel mutations and 82 recurrent mutations that were distributed over the entire BTK gene sequence. Variation in phenotypes was observed, and there was a tendency of association between genotype and age of disease onset. This report constitutes the largest group of patients with BTK mutations in China. A genotype–phenotype correlation was observed in this study. Early diagnosis of congenital agammaglobulinemia should be based on clinical symptoms, family history, and molecular analysis of the BTK gene. PMID:27512878

  19. Model of Atmospheric Links on Optical Communications from High Altitude

    NASA Technical Reports Server (NTRS)

    Subich, Christopher

    2004-01-01

    Optical communication links have the potential to solve many of the problems of current radio and microwave links to satellites and high-altitude aircraft. The higher frequency involved in optical systems allows for significantly greater signal bandwidth, and thus information transfer rate, in excess of 10 Gbps, and the highly directional nature of laser-based signals eliminates the need for frequency-division multiplexing seen in radio and microwave links today. The atmosphere, however, distorts an optical signal differently than a microwave signal. While the ionosphere is one of the most significant sources of noise and distortion in a microwave or radio signal, the lower atmosphere affects an optical signal more significantly. Refractive index fluctuations, primarily caused by changes in atmospheric temperature and density, distort the incoming signal in both deterministic and nondeterministic ways. Additionally, suspended particles, such as those in haze or rain, further corrupt the transmitted signal. To model many of the atmospheric effects on the propagating beam, we use simulations based on the beam-propagation method. This method, developed both for simulation of signals in waveguides and propagation in atmospheric turbulence, separates the propagation into a diffraction and refraction problem. The diffraction step is an exact solution, within the limits of numerical precision, to the problem of propagation in free space, and the refraction step models the refractive index variances over a segment of the propagation path. By applying refraction for a segment of the propagation path, then diffracting over that same segment, this method forms a good approximation to true propagation through the atmospheric medium. Iterating over small segments of the total propagation path gives a good approximation to the problem of propagation over the entire path. Parameters in this model, such as initial beam profile and atmospheric constants, are easily modified in a

  20. Integrative modelling reveals mechanisms linking productivity and plant species richness

    NASA Astrophysics Data System (ADS)

    Grace, James B.; Anderson, T. Michael; Seabloom, Eric W.; Borer, Elizabeth T.; Adler, Peter B.; Harpole, W. Stanley; Hautier, Yann; Hillebrand, Helmut; Lind, Eric M.; Pärtel, Meelis; Bakker, Jonathan D.; Buckley, Yvonne M.; Crawley, Michael J.; Damschen, Ellen I.; Davies, Kendi F.; Fay, Philip A.; Firn, Jennifer; Gruner, Daniel S.; Hector, Andy; Knops, Johannes M. H.; MacDougall, Andrew S.; Melbourne, Brett A.; Morgan, John W.; Orrock, John L.; Prober, Suzanne M.; Smith, Melinda D.

    2016-01-01

    How ecosystem productivity and species richness are interrelated is one of the most debated subjects in the history of ecology. Decades of intensive study have yet to discern the actual mechanisms behind observed global patterns. Here, by integrating the predictions from multiple theories into a single model and using data from 1,126 grassland plots spanning five continents, we detect the clear signals of numerous underlying mechanisms linking productivity and richness. We find that an integrative model has substantially higher explanatory power than traditional bivariate analyses. In addition, the specific results unveil several surprising findings that conflict with classical models. These include the isolation of a strong and consistent enhancement of productivity by richness, an effect in striking contrast with superficial data patterns. Also revealed is a consistent importance of competition across the full range of productivity values, in direct conflict with some (but not all) proposed models. The promotion of local richness by macroecological gradients in climatic favourability, generally seen as a competing hypothesis, is also found to be important in our analysis. The results demonstrate that an integrative modelling approach leads to a major advance in our ability to discern the underlying processes operating in ecological systems.

  1. Integrative modelling reveals mechanisms linking productivity and plant species richness.

    PubMed

    Grace, James B; Anderson, T Michael; Seabloom, Eric W; Borer, Elizabeth T; Adler, Peter B; Harpole, W Stanley; Hautier, Yann; Hillebrand, Helmut; Lind, Eric M; Pärtel, Meelis; Bakker, Jonathan D; Buckley, Yvonne M; Crawley, Michael J; Damschen, Ellen I; Davies, Kendi F; Fay, Philip A; Firn, Jennifer; Gruner, Daniel S; Hector, Andy; Knops, Johannes M H; MacDougall, Andrew S; Melbourne, Brett A; Morgan, John W; Orrock, John L; Prober, Suzanne M; Smith, Melinda D

    2016-01-21

    How ecosystem productivity and species richness are interrelated is one of the most debated subjects in the history of ecology. Decades of intensive study have yet to discern the actual mechanisms behind observed global patterns. Here, by integrating the predictions from multiple theories into a single model and using data from 1,126 grassland plots spanning five continents, we detect the clear signals of numerous underlying mechanisms linking productivity and richness. We find that an integrative model has substantially higher explanatory power than traditional bivariate analyses. In addition, the specific results unveil several surprising findings that conflict with classical models. These include the isolation of a strong and consistent enhancement of productivity by richness, an effect in striking contrast with superficial data patterns. Also revealed is a consistent importance of competition across the full range of productivity values, in direct conflict with some (but not all) proposed models. The promotion of local richness by macroecological gradients in climatic favourability, generally seen as a competing hypothesis, is also found to be important in our analysis. The results demonstrate that an integrative modelling approach leads to a major advance in our ability to discern the underlying processes operating in ecological systems. PMID:26760203

  2. Mediators of the link between autistic traits and relationship satisfaction in a non-clinical sample.

    PubMed

    Pollmann, Monique M H; Finkenauer, Catrin; Begeer, Sander

    2010-04-01

    People with ASD have deficits in their social skills and may therefore experience lower relationship satisfaction. This study investigated possible mechanisms to explain whether and how autistic traits, measured with the AQ, influence relationship satisfaction in a non-clinical sample of 195 married couples. More autistic traits were associated with lower relationship satisfaction for husbands but not for wives. Multiple mediation analyses revealed that husbands' responsiveness towards their wives, trust, and intimacy mediated this link between autistic traits and relationship satisfaction. These findings suggest that autistic traits may hamper men's relationship satisfaction because they impede relationship-specific feelings and behavior. There was no partner-effect of autistic traits, indicating that more autistic traits do not necessarily influence the partner's perceptions of relationship satisfaction. PMID:19885724

  3. Susceptibility of Austrian Clinical Klebsiella and Enterobacter Isolates Linked to Patient-Related Data

    PubMed Central

    Badura, Alexandra; Pregartner, Gudrun; Holzer, Judith C.; Feierl, Gebhard; Grisold, Andrea J.

    2016-01-01

    The aim of the study was to analyze the antimicrobial susceptibility of Austrian clinical Klebsiella sp. and Enterobacter sp. isolates linked to patient-related data over a time period from 1998 to 2014. The main findings of this study were (i) a marked difference of antibiotic susceptibility rates between different infection sites for both Klebsiella sp. and Enterobacter sp., (ii) significantly greater percentages of resistant isolates among both Klebsiella sp. and Enterobacter sp. in male patients compared to female patients and (iii) significantly greater percentages of resistant isolates among both Klebsiella sp. and Enterobacter sp. from hospital-derived samples compared to samples from the community. In conclusion, our statistical data analysis clearly indicated a strong association of patient-related data and Klebsiella sp. and Enterobacter sp. susceptibility profiles. PMID:26903953

  4. Clinical presentations of X-linked retinoschisis in Taiwanese patients confirmed with genetic sequencing

    PubMed Central

    Liu, Laura; Chen, Ho-Min; Tsai, Shawn; Chang, Tsong-Chi; Tsai, Tzu-Hsun; Yang, Chung-May; Chao, An-Ning; Chen, Kuan-Jen; Kao, Ling-Yuh; Yeung, Ling; Yeh, Lung-Kun; Hwang, Yih-Shiou; Wu, Wei-Chi; Lai, Chi-Chun

    2015-01-01

    Purpose To investigate the clinical characteristics of X-linked retinoschisis (XLRS) and identify genetic mutations in Taiwanese patients with XLRS. Methods This study included 23 affected males from 16 families with XLRS. Fundus photography, spectral domain optical coherent tomography (SD-OCT), fundus autofluorescence (FAF), and full-field electroretinograms (ERGs) were performed. The coding regions of the RS1 gene that encodes retinoschisin were sequenced. Results The median age at diagnosis was 18 years (range 4–58 years). The best-corrected visual acuity ranged from no light perception to 20/25. The typical spoke-wheel pattern in the macula was present in 61% of the patients (14/23) while peripheral retinoschisis was present in 43% of the patients (10/23). Four eyes presented with vitreous hemorrhage, and two eyes presented with leukocoria that mimics Coats’ disease. Macular schisis was identified with SD-OCT in 82% of the eyes (31/38) while foveal atrophy was present in 18% of the eyes (7/38). Concentric area of high intensity was the most common FAF abnormality observed. Seven out of 12 patients (58%) showed electronegative ERG findings. Sequencing of the RS1 gene identified nine mutations, six of which were novel. The mutations are all located in exons 4–6, including six missense mutations, two nonsense mutations, and one deletion-caused frameshift mutation. Conclusions XLRS is a clinically heterogeneous disease with profound phenotypic inter- and intrafamiliar variability. Genetic sequencing is valuable as it allows a definite diagnosis of XLRS to be made without the classical clinical features and ERG findings. This study showed the variety of clinical features of XLRS and reported novel mutations. PMID:25999676

  5. The Linked Dual Representation model of vocal perception and production

    PubMed Central

    Hutchins, Sean; Moreno, Sylvain

    2013-01-01

    The voice is one of the most important media for communication, yet there is a wide range of abilities in both the perception and production of the voice. In this article, we review this range of abilities, focusing on pitch accuracy as a particularly informative case, and look at the factors underlying these abilities. Several classes of models have been posited describing the relationship between vocal perception and production, and we review the evidence for and against each class of model. We look at how the voice is different from other musical instruments and review evidence about both the association and the dissociation between vocal perception and production abilities. Finally, we introduce the Linked Dual Representation (LDR) model, a new approach which can account for the broad patterns in prior findings, including trends in the data which might seem to be countervailing. We discuss how this model interacts with higher-order cognition and examine its predictions about several aspects of vocal perception and production. PMID:24204360

  6. Linking geophysics and soil function modelling - biomass production

    NASA Astrophysics Data System (ADS)

    Krüger, J.; Franko, U.; Werban, U.; Fank, J.

    2012-04-01

    The iSOIL project aims at reliable mapping of soil properties and soil functions with various methods including geophysical, spectroscopic and monitoring techniques. The general procedure contains three steps (i) geophysical monitoring, (ii) generation of soil property maps and (iii) process modelling. The objective of this work is to demonstrate the mentioned procedure with a focus on process modelling. It deals with the dynamics of soil water and the direct influence on crop biomass production. The new module PLUS extends CANDY to simulate crop biomass production based on environmental influences. A soil function modelling with an adapted model parameterisation based on data of ground penetration radar (GPR) and conductivity (EM38) was realized. This study shows an approach to handle heterogeneity of soil properties with geophysical data used for biomass production modelling. The Austrian field site Wagna is characterised by highly heterogenic soil with fluvioglacial gravel sediments. The variation of thickness of topsoil above a sandy subsoil with gravels strongly influences the soil water balance. EM38, mounted on a mobile platform, enables to rapidly scan large areas whereas GPR requires a greater logistical effort. However, GPR can detect exact soil horizon depth between topsoil and subsoil, the combination of both results in a detailed large scale soil map. The combined plot-specific GPR and field site EM38 measurements extends the soil input data and improves the model performance of CANDY PLUS for plant biomass production (Krüger et al. 2011). The example demonstrates how geophysics provides a surplus of data for agroecosystem modelling which identifies and contributes alternative options for agricultural management decisions. iSOIL - "Interactions between soil related sciences - Linking geophysics, soil science and digital soil mapping" is a Collaborative Project (Grant Agreement number 211386) co-funded by the Research DG of the European Commission

  7. Linking genome-scale metabolic modeling and genome annotation

    PubMed Central

    Blais, Edik M.; Chavali, Arvind K.; Papin, Jason A.

    2014-01-01

    Summary Genome-scale metabolic network reconstructions, assembled from annotated genomes, serve as a platform for integrating data from heterogeneous sources and generating hypotheses for further experimental validation. Implementing constraint-based modeling techniques such as Flux Balance Analysis (FBA) on network reconstructions allow for interrogating metabolism at a systems-level, which aids in identifying and rectifying gaps in knowledge. With genome sequences for various organisms from prokaryotes to eukaryotes becoming increasingly available, a significant bottleneck lies in the structural and functional annotation of these sequences. Using topologically-based and biologically-inspired metabolic network refinement, we can better characterize enzymatic functions present in an organism and link annotation of these functions to candidate transcripts, both steps that can be experimentally validated. PMID:23417799

  8. Clinical and linkage study of a large family with simple ectopia lentis linked to FBN1

    SciTech Connect

    Edwards, M.J.; Roberts, J.; Partington, M.W.; Colley, P.W.; Hollway, G.E.; Kozman, H.M.; Mulley, J.C.

    1994-10-15

    Simple ectopia lentis (EL) was studied in a large family, by clinical examination and analysis of linkage to markers in the region of FBN1, the gene for fibrillin which causes Marfan syndrome on chromosome 15. No patient had clinical or echocardiographic evidence of Marfan syndrome, although there was a trend towards relatively longer measurements of height; lower segment; arm span; middle finger, hand, and foot length in the affected members of the family, compared with unaffected sibs of the same sex. Analysis of linkage to intragenic FBN1 markers was inconclusive because they were relatively uninformative. Construction of a multipoint background map from the CEPH reference families identified microsatellite markers linked closely to FBN1 which could demonstrate linkage of EL in this family to the FBN1 region. LINKMAP analysis detected a multipoint lod score of 5.68 at D15S119, a marker approximately 6 cM distal to FBN1, and a multipoint lod score of 5.04 at FBN1. The EL gene in this family is likely to be allelic to Marfan syndrome, and molecular characterization of the FBN1 mutation should now be possible. 25 refs., 6 figs., 2 tabs.

  9. Clinical diversity and chromosomal localization of X-linked cone dystrophy (COD1).

    PubMed Central

    Hong, H. K.; Ferrell, R. E.; Gorin, M. B.

    1994-01-01

    X-linked progressive cone dystrophy (COD1) causes progressive deterioration of visual acuity, deepening of central scotomas, macular changes, and bull's-eye lesions. The cone electroretinography (ERG) is variably abnormal in affected males, and the rod ERG may also be abnormal. The clinical picture of heterozygous females ranges from asymptomatic to a widespread spectrum of cone-mediated dysfunction. A prior linkage study demonstrated linkage between the COD1 locus and the marker locus DXS84, assigned to Xp21.1, with no recombination. In the present study, we have clinically characterized a large four-generation family with COD1 and have performed a linkage analysis using seven polymorphic markers on the short arm of the X chromosome. No recombination was observed between the disease and the marker loci DXS7 and MAOA, suggesting that the location of COD1 is in the region Xp11.3, distal to DXS84 and proximal to ARAF1. Images Figure 2 PMID:7977377

  10. Effects of linking a soil-water-balance model with a groundwater-flow model

    USGS Publications Warehouse

    Stanton, Jennifer S.; Ryter, Derek W.; Peterson, Steven M.

    2013-01-01

    A previously published regional groundwater-flow model in north-central Nebraska was sequentially linked with the recently developed soil-water-balance (SWB) model to analyze effects to groundwater-flow model parameters and calibration results. The linked models provided a more detailed spatial and temporal distribution of simulated recharge based on hydrologic processes, improvement of simulated groundwater-level changes and base flows at specific sites in agricultural areas, and a physically based assessment of the relative magnitude of recharge for grassland, nonirrigated cropland, and irrigated cropland areas. Root-mean-squared (RMS) differences between the simulated and estimated or measured target values for the previously published model and linked models were relatively similar and did not improve for all types of calibration targets. However, without any adjustment to the SWB-generated recharge, the RMS difference between simulated and estimated base-flow target values for the groundwater-flow model was slightly smaller than for the previously published model, possibly indicating that the volume of recharge simulated by the SWB code was closer to actual hydrogeologic conditions than the previously published model provided. Groundwater-level and base-flow hydrographs showed that temporal patterns of simulated groundwater levels and base flows were more accurate for the linked models than for the previously published model at several sites, particularly in agricultural areas.

  11. Linking Geomechanical Models with Observations of Microseismicity during CCS Operations

    NASA Astrophysics Data System (ADS)

    Verdon, J.; Kendall, J.; White, D.

    2012-12-01

    During CO2 injection for the purposes of carbon capture and storage (CCS), injection-induced fracturing of the overburden represents a key risk to storage integrity. Fractures in a caprock provide a pathway along which buoyant CO2 can rise and escape the storage zone. Therefore the ability to link field-scale geomechanical models with field geophysical observations is of paramount importance to guarantee secure CO2 storage. Accurate location of microseismic events identifies where brittle failure has occurred on fracture planes. This is a manifestation of the deformation induced by CO2 injection. As the pore pressure is increased during injection, effective stress is decreased, leading to inflation of the reservoir and deformation of surrounding rocks, which creates microseismicity. The deformation induced by injection can be simulated using finite-element mechanical models. Such a model can be used to predict when and where microseismicity is expected to occur. However, typical elements in a field scale mechanical models have decameter scales, while the rupture size for microseismic events are typically of the order of 1 square meter. This means that mapping modeled stress changes to predictions of microseismic activity can be challenging. Where larger scale faults have been identified, they can be included explicitly in the geomechanical model. Where movement is simulated along these discrete features, it can be assumed that microseismicity will occur. However, microseismic events typically occur on fracture networks that are too small to be simulated explicitly in a field-scale model. Therefore, the likelihood of microseismicity occurring must be estimated within a finite element that does not contain explicitly modeled discontinuities. This can be done in a number of ways, including the utilization of measures such as closeness on the stress state to predetermined failure criteria, either for planes with a defined orientation (the Mohr-Coulomb criteria) for

  12. Towards linking patients and clinical information: detecting UMLS concepts in e-mail.

    PubMed

    Brennan, Patricia Flatley; Aronson, Alan R

    2003-01-01

    The purpose of this project is to explore the feasibility of detecting terms within the electronic messages of patients that could be used to effectively search electronic knowledge resources and bring health information resources into the hands of patients. Our team is exploring the application of the natural language processing (NLP) tools built within the Lister Hill Center at the National Library of Medicine (NLM) to the challenge of detecting relevant concepts from the Unified Medical Language System (UMLS) within the free text of lay people's electronic messages (e-mail). We obtained a sample of electronic messages sent by patients participating in a randomized field evaluation of an internet-based home care support service to the project nurse, and we subjected elements of these messages to a series of analyses using several vocabularies from the UMLS Metathesaurus and the selected NLP tools. The nursing vocabularies provide an excellent starting point for this exercise because their domain encompasses patient's responses to health challenges. In successive runs we augmented six nursing vocabularies (NANDA Nursing Diagnosis, Nursing Interventions Classification, Nursing Outcomes Classification, Home Health Classification, Omaha System, and the Patient Care Data Set) with selected sets of clinical terminologies (International Classification of Primary Care; International Classification of Primary Care- American English; Micromedex DRUGDEX; National Drug Data File; Thesaurus of Psychological Terms; WHO Adverse Drug Reaction Terminology) and then additionally with either Medical Subject Heading (MeSH) or SNOMED International terms. The best performance was obtained when the nursing vocabularies were complemented with selected clinical terminologies. These findings have implications not only for facilitating lay people's access to electronic knowledge resources but may also be of assistance in developing new tools to aid in linking free text (e.g., clinical

  13. Exploring the clinical and epidemiological complexity of GJB2-linked deafness.

    PubMed

    Gualandi, F; Ravani, A; Berto, A; Sensi, A; Trabanelli, C; Falciano, F; Trevisi, P; Mazzoli, M; Tibiletti, M G; Cristofari, E; Burdo, S; Ferlini, A; Martini, A; Calzolari, E

    2002-09-15

    GJB2 mutation analysis was performed in 179 unrelated subjects with sporadic or familial hearing loss (HL). Among 57 families, 18 showed a vertical transmission of HL, the disease being present in two or three generations. Besides 155 nonsyndromic cases, 24 patients presenting with extra-auditory clinical signs were included in the molecular study. GJB2 mutation analysis was also performed in 19 subjects with an anamnestic history of perinatal risks factors for acquired HL. The 35delG mutation accounted for 22.1% of analyzed chromosomes in sporadic cases and 39.4% in familial cases; 35delG prevalence reached 41% in autosomal recessive and 44.4% in pseudodominant pedigrees. Two novel GJB2 mutations were identified in compound heterozygosity with 35delG allele (D159V, 284ins/dup[CACGT]). Two 35delG homozygous subjects were identified among HL cases classified as environmental in origin. Four patients 35delG heterozygous (35delG/V95M, 35delG/L90P, 35delG/167delT, and 35delG/?) and two homozygous presented with extra-auditory clinical signs involving different organs (skin, vascular system, hemopoietic lineages, and thyroid). In a high proportion of 35delG heterozygous HL patients (52%), no second GJB2 mutation was detected. The reported data highlight the complexity of the genetic epidemiology of GJB2-linked deafness, further enlarging the spectrum of situations in which GJB2 mutation analysis should be performed. The presence of extra-auditory signs in a significant portion of GJB2-mutated patients suggests the possibility that GJB2 loss of function could contribute to clinical phenotypes presenting in association with deafness. This hypothesis deserves further investigation. The failure to identify a presumed partnering GJB2 mutation in a high proportion of deaf patients remains a challenging problem to be clarified. PMID:12239718

  14. Linking geophysics and soil function modelling - two examples

    NASA Astrophysics Data System (ADS)

    Krüger, J.; Franko, U.; Werban, U.; Dietrich, P.; Behrens, T.; Schmidt, K.; Fank, J.; Kroulik, M.

    2011-12-01

    iSOIL - "Interactions between soil related sciences - Linking geophysics, soil science and digital soil mapping" is a Collaborative Project (Grant Agreement number 211386) co-funded by the Research DG of the European Commission within the RTD activities of the FP7 Thematic Priority Environment. The iSOIL project aims at reliable mapping of soil properties and soil functions with various methods including geophysical, spectroscopic and monitoring techniques. The general procedure contains three steps (i) geophysical monitoring, (ii) generation of soil property maps and (iii) process modelling. The objective of this work is to demonstrate the methodological procedure on two different examples. Example A focuses on the turnover conditions for soil organic matter (SOM) since many soil functions in a direct or indirect way depend on SOM and SOM depletion is amongst the worst soil threats. Example B deals with the dynamics of soil water and the direct influence on crop biomass production. The applied CANDY model (Franko et al. 1995) was developed to describe dynamics of soil organic matter and mineral nitrogen as well as soil water and temperature. The new module PLUS extends CANDY to simulate crop biomass production based on environmental influences (Krüger et al. 2011). The methodological procedure of example A illustrates a model application for a field site in the Czech Republic using generated soil maps from combined geophysical data. Modelling requires a complete set of soil parameters. Combining measured soil properties and data of geophysical measurements (electrical conductivity and gamma spectrometry) is the basis for digital soil mapping which provided data about clay, silt and sand as well as SOC content. With these data pedotransfer functions produce detailed soil input data (e.g. bulk and particle density, field capacity, wilting point, saturated conductivity) for the rooted soil profile. CANDY calculated different indicators for SOM and gave hints about

  15. Modeling to link regional myocardial work, metabolism and blood flows

    PubMed Central

    Bassingthwaighte, James B.; Beard, Daniel A; Carlson, Brian E.; Dash, Ranjan K.; Vinnakota, Kalyan

    2012-01-01

    Given the mono-functional, highly coordinated processes of cardiac excitation and contraction, the observations that regional myocardial blood flows, rMBF, are broadly heterogeneous has provoked much attention, but a clear explanation has not emerged. In isolated and in vivo heart studies the total coronary flow is found to be proportional to the rate-pressure product (systolic mean blood pressure times heart rate), a measure of external cardiac work. The same relationship might be expected on a local basis: more work requires more flow. The validity of this expectation has never been demonstrated experimentally. In this article we review the concepts linking cellular excitation and contractile work to cellular energetics and ATP demand, substrate utilization, oxygen demand, vasoregulation, and local blood flow. Mathematical models of these processes are now rather well developed. We propose that the construction of an integrated model encompassing the biophysics, biochemistry and physiology of cardiomyocyte contraction, then combined with a detailed three-dimensional structuring of the fiber bundle and sheet arrangements of the heart as a whole will frame an hypothesis that can be quantitatively evaluated to settle the prime issue: Does local work drive local flow in a predictable fashion that explains the heterogeneity? While in one sense one can feel content that work drives flow is irrefutable, there are no cardiac contractile models that demonstrate the required heterogeneity in local strain-stress-work; quite the contrary, cardiac contraction models have tended toward trying to show that work should be uniform. The object of this review is to argue that uniformity of work does not occur, and is impossible in any case, and that further experimentation and analysis are necessary to test the hypothesis. PMID:22915334

  16. Implementation of a vibrationally linked chemical reaction model for DSMC

    NASA Technical Reports Server (NTRS)

    Carlson, A. B.; Bird, Graeme A.

    1994-01-01

    A new procedure closely linking dissociation and exchange reactions in air to the vibrational levels of the diatomic molecules has been implemented in both one- and two-dimensional versions of Direct Simulation Monte Carlo (DSMC) programs. The previous modeling of chemical reactions with DSMC was based on the continuum reaction rates for the various possible reactions. The new method is more closely related to the actual physics of dissociation and is more appropriate to the particle nature of DSMC. Two cases are presented: the relaxation to equilibrium of undissociated air initially at 10,000 K, and the axisymmetric calculation of shuttle forebody heating during reentry at 92.35 km and 7500 m/s. Although reaction rates are not used in determining the dissociations or exchange reactions, the new method produces rates which agree astonishingly well with the published rates derived from experiment. The results for gas properties and surface properties also agree well with the results produced by earlier DSMC models, equilibrium air calculations, and experiment.

  17. Network modeling links breast cancer susceptibility and centrosome dysfunction.

    PubMed

    Pujana, Miguel Angel; Han, Jing-Dong J; Starita, Lea M; Stevens, Kristen N; Tewari, Muneesh; Ahn, Jin Sook; Rennert, Gad; Moreno, Víctor; Kirchhoff, Tomas; Gold, Bert; Assmann, Volker; Elshamy, Wael M; Rual, Jean-François; Levine, Douglas; Rozek, Laura S; Gelman, Rebecca S; Gunsalus, Kristin C; Greenberg, Roger A; Sobhian, Bijan; Bertin, Nicolas; Venkatesan, Kavitha; Ayivi-Guedehoussou, Nono; Solé, Xavier; Hernández, Pilar; Lázaro, Conxi; Nathanson, Katherine L; Weber, Barbara L; Cusick, Michael E; Hill, David E; Offit, Kenneth; Livingston, David M; Gruber, Stephen B; Parvin, Jeffrey D; Vidal, Marc

    2007-11-01

    Many cancer-associated genes remain to be identified to clarify the underlying molecular mechanisms of cancer susceptibility and progression. Better understanding is also required of how mutations in cancer genes affect their products in the context of complex cellular networks. Here we have used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. Starting with four known genes encoding tumor suppressors of breast cancer, we combined gene expression profiling with functional genomic and proteomic (or 'omic') data from various species to generate a network containing 118 genes linked by 866 potential functional associations. This network shows higher connectivity than expected by chance, suggesting that its components function in biologically related pathways. One of the components of the network is HMMR, encoding a centrosome subunit, for which we demonstrate previously unknown functional associations with the breast cancer-associated gene BRCA1. Two case-control studies of incident breast cancer indicate that the HMMR locus is associated with higher risk of breast cancer in humans. Our network modeling strategy should be useful for the discovery of additional cancer-associated genes. PMID:17922014

  18. Phosphoinositide system-linked serotonin receptor subtypes and their pharmacological properties and clinical correlates.

    PubMed Central

    Pandey, S C; Davis, J M; Pandey, G N

    1995-01-01

    Serotonergic neurotransmission represents a complex mechanism involving pre- and post-synaptic events and distinct 5-HT receptor subtypes. Serotonin (5-HT) receptors have been classified into several categories, and they are termed as 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 type receptors. 5-HT1 receptors have been further subdivided into 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F. 5-HT2 receptors have been divided into 5-HT2A, 5-HT2B and 5-HT2C receptors. All 5-HT2 receptor subtypes are linked to the multifunctional phosphoinositide (PI) signalling system. 5-HT3 receptors are considered ion-gated receptors and are also linked to the PI signalling system by an unknown mechanism. The 5-HT2A receptor subtype is the most widely studied of the 5-HT receptors in psychiatric disorders (for example, suicide, depression and schizophrenia) as well as in relation to the mechanism of action of antidepressant drugs. The roles of 5-HT2C and 5-HT3 receptors in psychiatric disorders are less clear. These 5-HT receptors also play an important role in alcoholism. It has been shown that 5-HT2A, 5-HT2C and 5-HT3 antagonists cause attenuation of alcohol intake in animals and humans. However, the exact mechanisms are unknown. The recent cloning of the cDNAs for 5-HT2A, 5-HT2C and 5-HT3 receptors provides the opportunity to explore the molecular mechanisms responsible for the alterations in these receptors during illness as well as pharmacotherapy. This review article will focus on the current research into the pharmacological properties, molecular biology, and clinical correlates of 5-HT2A, 5-HT2C and 5-HT3 receptors. PMID:7786883

  19. Prime time: 18-month violence outcomes of a clinic-linked intervention.

    PubMed

    Sieving, Renee E; McMorris, Barbara J; Secor-Turner, Molly; Garwick, Ann W; Shlafer, Rebecca; Beckman, Kara J; Pettingell, Sandra L; Oliphant, Jennifer A; Seppelt, Ann M

    2014-08-01

    Prime Time, a youth development intervention, aims to reduce multiple risk behaviors among adolescent girls seeking clinic services who are at high risk for pregnancy. The purpose of the current study was to examine whether Prime Time involvement produced changes in relational aggression, physical violence, and related psychosocial and behavioral outcomes. Qualitative case exemplars illustrated social contexts of intervention participants with differing longitudinal patterns of relational aggression and physical violence. Data were from a randomized efficacy trial with 13-17 year-old girls (n = 253) meeting specified risk criteria. Intervention participants were involved in Prime Time and usual clinic services for 18 months, control participants received usual clinic services. Participants in the current study completed self-report surveys at baseline and 18 months following enrollment. Outcomes analyses revealed significantly lower levels of relational aggression perpetration in the intervention group versus controls. In contrast, Prime Time involvement did not result in significant reductions in physical violence. Exploratory dose-response analyses indicated that reductions in relational aggression may have been most pronounced among girls actively involved in Prime Time case management and peer leadership activities. Qualitative findings suggested that the intervention's emphasis on modeling and building supportive relationships contributed to reductions in relational aggression. This study contributes to what has been a very limited evidence base regarding effective approaches to preventing violence among high-risk adolescent girls. Findings suggest that offering youth development interventions through clinic settings hold promise in reducing violence risk among vulnerable youth. PMID:23543359

  20. Prime Time: 18-Month Violence Outcomes of a Clinic-Linked Intervention

    PubMed Central

    Sieving, Renee E.; McMorris, Barbara J.; Secor-Turner, Molly; Garwick, Ann W.; Shlafer, Rebecca; Beckman, Kara J.; Pettingell, Sandra L.; Oliphant, Jennifer A.; Seppelt, Ann M.

    2013-01-01

    Prime Time, a youth development intervention, aims to reduce multiple risk behaviors among adolescent girls seeking clinic services who are at high risk for pregnancy. The purpose of the current study was to examine whether Prime Time involvement produced changes in relational aggression, physical violence and related psychosocial and behavioral outcomes. Qualitative case exemplars illustrated social contexts of intervention participants with differing longitudinal patterns of relational aggression and physical violence. Data were from a randomized efficacy trial with 13–17 year old girls (n=253) meeting specified risk criteria. Intervention participants were involved in Prime Time and usual clinic services for 18 months, control participants received usual clinic services. Participants in the current study completed self-report surveys at baseline and 18 months following enrollment. Outcomes analyses revealed significantly lower levels of relational aggression perpetration in the intervention group versus controls. In contrast, Prime Time involvement did not result in significant reductions in physical violence. Exploratory dose-response analyses indicated that reductions in relational aggression may have been most pronounced among girls actively involved in Prime Time case management and peer leadership activities. Qualitative findings suggested that the intervention’s emphasis on modeling and building supportive relationships contributed to reductions in relational aggression. This study contributes to a very limited evidence base regarding effective approaches to preventing violence among high-risk adolescent girls. Findings suggest that offering youth development interventions through clinic settings hold promise in reducing violence risk among vulnerable youth. PMID:23543359

  1. Characterizing cognitive aging in humans with links to animal models

    PubMed Central

    Alexander, Gene E.; Ryan, Lee; Bowers, Dawn; Foster, Thomas C.; Bizon, Jennifer L.; Geldmacher, David S.; Glisky, Elizabeth L.

    2012-01-01

    With the population of older adults expected to grow rapidly over the next two decades, it has become increasingly important to advance research efforts to elucidate the mechanisms associated with cognitive aging, with the ultimate goal of developing effective interventions and prevention therapies. Although there has been a vast research literature on the use of cognitive tests to evaluate the effects of aging and age-related neurodegenerative disease, the need for a set of standardized measures to characterize the cognitive profiles specific to healthy aging has been widely recognized. Here we present a review of selected methods and approaches that have been applied in human research studies to evaluate the effects of aging on cognition, including executive function, memory, processing speed, language, and visuospatial function. The effects of healthy aging on each of these cognitive domains are discussed with examples from cognitive/experimental and clinical/neuropsychological approaches. Further, we consider those measures that have clear conceptual and methodological links to tasks currently in use for non-human animal studies of aging, as well as those that have the potential for translation to animal aging research. Having a complementary set of measures to assess the cognitive profiles of healthy aging across species provides a unique opportunity to enhance research efforts for cross-sectional, longitudinal, and intervention studies of cognitive aging. Taking a cross-species, translational approach will help to advance cognitive aging research, leading to a greater understanding of associated neurobiological mechanisms with the potential for developing effective interventions and prevention therapies for age-related cognitive decline. PMID:22988439

  2. A communications model for an ISAS to NASA span link

    NASA Technical Reports Server (NTRS)

    Green, James L.; Mcguire, Robert E.; Lopez-Swafford, Brian

    1987-01-01

    The authors propose that an initial computer-to-computer communication link use the public packet switched networks (PPSN) Venus-P in Japan and TELENET in the U.S. When the traffic warrants it, this link would then be upgraded to a dedicated leased line that directly connects into the Space Physics Analysis Network (SPAN). The proposed system of hardware and software will easily support migration to such a dedicated link. It therefore provides a cost effective approach to the network problem. Once a dedicated line becomes operation it is suggested that the public networks link and continue to coexist, providing a backup capability.

  3. Clinical ethics support services: an evolving model.

    PubMed

    Schlairet, Maura C; Kiser, Ken; Norris, Stephen

    2012-01-01

    Ethical issues arising in clinical practice are complex and clinicians must be able to manage the needs of ethically vulnerable patients and families. This paper describes a model for providing Clinical Ethics Support Services as a broad spectrum of care for management of conflict and ethically difficult situations in health care and describes how an ethics consultation process was transformed to a Holistic Care Continuum for managing the needs of ethically vulnerable patients. During a 4-year journey at a regional medical center, a Family Support Team played a central role in identification of ethically vulnerable patients/family, interdisciplinary connectivity, and iterative engagement in the clinical milieu. Concepts of professional advocacy and interdisciplinary perspectives resulted in a model for ethically sound patient care promoting communication among patients/family, staff, and professionals; clarification of interdisciplinary roles and responsibilities; establishment of mutually derived goals and shared solutions; and implementation of interventions maximizing institutional resources. PMID:22357314

  4. X-linked Acrogigantism (X-LAG) Syndrome: Clinical Profile and Therapeutic Responses

    PubMed Central

    Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J.; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H.; Bours, Vincent; Liu, Pengfei; De Herder, Wouter; Pellegata, Natalia; Lupski, James R.; Daly, Adrian F.; Stratakis, Constantine A.

    2015-01-01

    X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and a microduplication in chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in 2 families was dominant with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2–3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight SDS score of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF-1 and prolactin, usually due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high somatostatin receptor subtype-2 expression in tumor tissue. Postoperative adjuvant pegvisomant achieved control of IGF-1 all 5 cases in which it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. PMID:25712922

  5. Local degree blocking model for link prediction in complex networks.

    PubMed

    Liu, Zhen; Dong, Weike; Fu, Yan

    2015-01-01

    Recovering and reconstructing networks by accurately identifying missing and unreliable links is a vital task in the domain of network analysis and mining. In this article, by studying a specific local structure, namely, a degree block having a node and its all immediate neighbors, we find it contains important statistical features of link formation for complex networks. We therefore propose a parameter-free local blocking (LB) predictor to quantitatively detect link formation in given networks via local link density calculations. The promising experimental results performed on six real-world networks suggest that the new index can outperform other traditional local similarity-based methods on most of tested networks. After further analyzing the scores' correlations between LB and two other methods, we find that LB index simultaneously captures the features of both PA index and short-path-based index, which empirically verifies that LB index is a multiple-mechanism-driven link predictor. PMID:25637926

  6. {open_quotes}Unspecific{close_quotes} X-linked mental retardation: Clinical, genetic and molecular studies

    SciTech Connect

    Ropers, H.H.; Maacel, S. van der; Knoers, N.

    1994-09-01

    Previous linkage studies have assigned a gene for non-syndromic X-linked mental retardation (XMR) to at least 8 different regions on the X-chromosome. The fragile X-syndrome (FRAXA) does not account for more than 40% of all cases; in most XMR families early diagnosis and prevention is not possible. As part of a systematic study into {open_quotes}unspecific{close_quotes} XMR involving more than 30 non-FRAXA families, linkage studies have enabled us to map the respective genes in 4 families to the Xp11.4-q12 interval with peak lod scores around the ALAS2 locus. In three other families, the gene defect could be assigned to the KAL-DMD, DXS424-FRAXAC2 and DSX52-Xqter intervals, respectively. In one of these families, small stature due to growth hormone deficiency was observed as a distinctive clinical feature. Molecular cloning of the breakpoint in a mentally retarded girl with a balanced t(Xq13;13q) translocation has enabled us to isolate an X-chromosomal gene which is disrupted in this patient and is highly expressed in brain. YAC cloning strategies are being employed to clone another XMR gene, which has been identified previously in the vicinity of the CHM locus and genes involved in mentally retarded patients with two different inversions, inv(X)(q21p11) and inv(X)(p21q24), respectively.

  7. X-linked hypophosphatemic rickets: enamel abnormalities and oral clinical findings.

    PubMed

    Cremonesi, Ilaria; Nucci, Cesare; D'Alessandro, Giovanni; Alkhamis, Nadia; Marchionni, Silvia; Piana, Gabriela

    2014-01-01

    X-linked hypophosphatemia (XLH) is a genetic disorder related to alterations in bones and teeth formation, due to low levels of phosphate in blood. Oral findings in XLH have been enamel and dentine abnormalities, high pulp horns, large pulp chambers, and some cases of periapical abscesses related to teeth without caries or traumatic injuries. The aim of our study was to assess the presence of enamel alterations, such as microclefts and/or structure defects in patients with XLH and give guidelines of prevention of XLH dental complications. History taking, oral clinical and radiological examination in 10 young patients affected by XLH (average age of 9) and in 6 patients without XLH (average age of 8). Impressions were performed on the vestibular surfaces of teeth in order to obtain replicas. The replicas were analyzed using scanning electron microscope (SEM) and compared to replicas of control group. The images of replicas of XLH patients showed deep microclefts and irregular enamel surface structure compared to replicas of control group. The replica of a patient with spontaneous periapical abscesses showed numerous enamel crater-shaped depressions and deep microcleavages penetrating into the enamel thickness. In absence of caries or fractures, the abscesses pathogenesis may be related to microcleavages of the enamel and dentin, which allow bacterial invasion of the pulp. There could be a relationship between XLH disease and enamel abnormalities. PMID:24677288

  8. Role modeling excellence in clinical nursing practice.

    PubMed

    Perry, R N Beth

    2009-01-01

    Role modeling excellence in clinical nursing practice is the focus of this paper. The phenomenological research study reported involved a group of 8 nurses identified by their colleagues as exemplary. The major theme revealed in this study was that these exemplary nurses were also excellent role models in the clinical setting. This paper details approaches used by these nurses that made them excellent role models. Specifically, the themes of attending to the little things, making connections, maintaining a light-hearted attitude, modeling, and affirming others are presented. These themes are discussed within the framework of Watson [Watson, J., 1989. Human caring and suffering: a subjective model for health services. In: Watson, J., Taylor, R. (Eds.), They Shall Not Hurt: Human Suffering and Human Caring. Colorado University, Boulder, CO] "transpersonal caring" and [Bandura, A., 1997. Social Learning Theory. Prentice Hall, Englewood Cliffs, NJ] "Social Learning Theory." Particular emphasis in the discussion is on how positive role modeling by exemplary practitioners can contribute to the education of clinical nurses in the practice setting. PMID:18590978

  9. A cell-based model system links chromothripsis with hyperploidy

    PubMed Central

    Mardin, Balca R; Drainas, Alexandros P; Waszak, Sebastian M; Weischenfeldt, Joachim; Isokane, Mayumi; Stütz, Adrian M; Raeder, Benjamin; Efthymiopoulos, Theocharis; Buccitelli, Christopher; Segura-Wang, Maia; Northcott, Paul; Pfister, Stefan M; Lichter, Peter; Ellenberg, Jan; Korbel, Jan O

    2015-01-01

    A remarkable observation emerging from recent cancer genome analyses is the identification of chromothripsis as a one-off genomic catastrophe, resulting in massive somatic DNA structural rearrangements (SRs). Largely due to lack of suitable model systems, the mechanistic basis of chromothripsis has remained elusive. We developed an integrative method termed “complex alterations after selection and transformation (CAST),” enabling efficient in vitro generation of complex DNA rearrangements including chromothripsis, using cell perturbations coupled with a strong selection barrier followed by massively parallel sequencing. We employed this methodology to characterize catastrophic SR formation processes, their temporal sequence, and their impact on gene expression and cell division. Our in vitro system uncovered a propensity of chromothripsis to occur in cells with damaged telomeres, and in particular in hyperploid cells. Analysis of primary medulloblastoma cancer genomes verified the link between hyperploidy and chromothripsis in vivo. CAST provides the foundation for mechanistic dissection of complex DNA rearrangement processes. PMID:26415501

  10. The oral-systemic personalized medicine model at Marshfield Clinic.

    PubMed

    Glurich, I; Acharya, A; Shukla, S K; Nycz, G R; Brilliant, M H

    2013-01-01

    Periodontal disease and diabetes, two diseases that have achieved epidemic status, share a bidirectional relationship driven by micro-inflammatory processes. The present review frames the current understanding of the pathological processes that appear to link these diseases and advances the hypothesis that reversal of the epidemic is possible through application of interdisciplinary intervention and advancement of oral-systemic personalized medicine. An overview of how Marshfield Clinic's unique clinical, informatics and bio-repository resources and infrastructures are being aligned to advance oral-systemic personalized medicine is presented as an interventional model with the potential to reverse the epidemic trends seen for these two chronic diseases over the past several decades. The overall vision is to engineer a transformational shift in paradigm from 'personalized medicine' to 'personalized health'. PMID:22458294

  11. Linking the M&Rfi Weather Generator with Agrometeorological Models

    NASA Astrophysics Data System (ADS)

    Dubrovsky, Martin; Trnka, Miroslav

    2015-04-01

    Realistic meteorological inputs (representing the present and/or future climates) for the agrometeorological model simulations are often produced by stochastic weather generators (WGs). This contribution presents some methodological issues and results obtained in our recent experiments. We also address selected questions raised in the synopsis of this session. The input meteorological time series for our experiments are produced by the parametric single site weather generator (WG) Marfi, which is calibrated from the available observational data (or interpolated from surrounding stations). To produce meteorological series representing the future climate, the WG parameters are modified by climate change scenarios, which are prepared by the pattern scaling method: the standardised scenarios derived from Global or Regional Climate Models are multiplied by the change in global mean temperature (ΔTG) determined by the simple climate model MAGICC. The presentation will address following questions: (i) The dependence of the quality of the synthetic weather series and impact results on the WG settings. An emphasis will be put on an effect of conditioning the daily WG on monthly WG (presently being one of our hot topics), which aims at improvement of the reproduction of the low-frequency weather variability. Comparison of results obtained with various WG settings is made in terms of climatic and agroclimatic indices (including extreme temperature and precipitation characteristics and drought indices). (ii) Our methodology accounts for the uncertainties coming from various sources. We will show how the climate change impact results are affected by 1. uncertainty in climate modelling, 2. uncertainty in ΔTG, and 3. uncertainty related to the complexity of the climate change scenario (focusing on an effect of inclusion of changes in variability into the climate change scenarios). Acknowledgements: This study was funded by project "Building up a multidisciplinary scientific

  12. Brief Report: Examining the Link between Autistic Traits and Compulsive Internet Use in a Non-Clinical Sample

    ERIC Educational Resources Information Center

    Finkenauer, Catrin; Pollmann, Monique M. H.; Begeer, Sander; Kerkhof, Peter

    2012-01-01

    Individuals with autism spectrum disorders or autistic traits may profit from Internet and computer-mediated interactions, but there is concern about their Internet use becoming compulsive. This study investigated the link between autistic traits and Internet use in a 2-wave longitudinal study with a non-clinical community sample (n = 390). As…

  13. Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

    PubMed Central

    Crampton, Steve P.; Morawski, Peter A.; Bolland, Silvia

    2014-01-01

    Systemic lupus erythematosus (SLE) represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS) and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease. PMID:25147296

  14. Modelling and Decision Support of Clinical Pathways

    NASA Astrophysics Data System (ADS)

    Gabriel, Roland; Lux, Thomas

    The German health care market is under a rapid rate of change, forcing especially hospitals to provide high-quality services at low costs. Appropriate measures for more effective and efficient service provision are process orientation and decision support by information technology of clinical pathway of a patient. The essential requirements are adequate modelling of clinical pathways as well as usage of adequate systems, which are capable of assisting the complete path of a patient within a hospital, and preferably also outside of it, in a digital way. To fulfil these specifications the authors present a suitable concept, which meets the challenges of well-structured clinical pathways as well as rather poorly structured diagnostic and therapeutic decisions, by interplay of process-oriented and knowledge-based hospital information systems.

  15. Super High Frequency (SHF) Link Analysis Model (SLAM) for nonsatellite applications

    NASA Astrophysics Data System (ADS)

    James, R. R.; Rockway, J. W.

    1990-06-01

    A point-to-point link analysis model has been developed for the Super High Frequency (SHF) band. It was developed to evaluate ship-to-ship and ship-to-air links. The SHF Link Analysis Model (SLAM) evaluates a communication link and determines system margin. The link margin is determined after a user defines the transmitter subsystem, the receiver subsystem, the specified level of system performance, and the propagation channel. The propagation channel incorporates the Engineer's Refractive Effects Prediction System (EREPS) and includes the effects of the evaporation duct. A rain model developed by NASA is also included in the channel. SLAM provides a detailed discussion of the link equation, the propagation effects, the rain model, and the antenna characteristics. In addition, a detailed explanation of the operation of the SLAM computer program is given. Two communication links are evaluated and these examples are used to demonstrate the computer program's capabilities.

  16. Improving Power System Modeling. A Tool to Link Capacity Expansion and Production Cost Models

    SciTech Connect

    Diakov, Victor; Cole, Wesley; Sullivan, Patrick; Brinkman, Gregory; Margolis, Robert

    2015-11-01

    Capacity expansion models (CEM) provide a high-level long-term view at the prospects of the evolving power system. In simulating the possibilities of long-term capacity expansion, it is important to maintain the viability of power system operation in the short-term (daily, hourly and sub-hourly) scales. Production-cost models (PCM) simulate routine power system operation on these shorter time scales using detailed load, transmission and generation fleet data by minimizing production costs and following reliability requirements. When based on CEM 'predictions' about generating unit retirements and buildup, PCM provide more detailed simulation for the short-term system operation and, consequently, may confirm the validity of capacity expansion predictions. Further, production cost model simulations of a system that is based on capacity expansion model solution are 'evolutionary' sound: the generator mix is the result of logical sequence of unit retirement and buildup resulting from policy and incentives. The above has motivated us to bridge CEM with PCM by building a capacity expansion - to - production cost model Linking Tool (CEPCoLT). The Linking Tool is built to onset capacity expansion model prescriptions onto production cost model inputs. NREL's ReEDS and Energy Examplar's PLEXOS are the capacity expansion and the production cost models, respectively. Via the Linking Tool, PLEXOS provides details of operation for the regionally-defined ReEDS scenarios.

  17. Emotion regulation strategies in trauma-related disorders: pathways linking neurobiology and clinical manifestations.

    PubMed

    Del Río-Casanova, Lucía; González, Anabel; Páramo, Mario; Van Dijke, Annemiek; Brenlla, Julio

    2016-06-01

    Emotion regulation impairments with traumatic origins have mainly been studied from posttraumatic stress disorder (PTSD) models by studying cases of adult onset and single-incident trauma exposure. The effects of adverse traumatic experiences, however, go beyond the PTSD. Different authors have proposed that PTSD, borderline personality, dissociative, conversive and somatoform disorders constitute a full spectrum of trauma-related conditions. Therefore, a comprehensive review of the neurobiological findings covering this posttraumatic spectrum is needed in order to develop an all-encompassing model for trauma-related disorders with emotion regulation at its center. The present review has sought to link neurobiology findings concerning cortico-limbic function to the field of emotion regulation. In so doing, trauma-related disorders have been placed in a continuum between under- and over-regulation of affect strategies. Under-regulation of affect was predominant in borderline personality disorder, PTSD with re-experiencing symptoms and positive psychoform and somatoform dissociative symptoms. Over-regulation of affect was more prevalent in somatoform disorders and pathologies characterized by negative psychoform and somatoform symptoms. Throughout this continuum, different combinations between under- and over-regulation of affect strategies were also found. PMID:26812780

  18. Linking international clinical research with stateless populations to justice in global health

    PubMed Central

    2014-01-01

    working with refugees and migrants. Obstructive factors included the research funding environment and staff turnover due to resettlement or migration. Conclusions Our findings show that obligations for selecting research targets, research capacity strengthening, and post-trial benefits that link clinical trials to justice in global health can be upheld by external research actors from high-income countries when working with stateless populations in LMICs. However, meeting certain framework requirements for long-term collaborations may not be entirely feasible. PMID:24969638

  19. X-linked lethal infantile spinal muscular atrophy: From clinical description to molecular mapping

    SciTech Connect

    Baumbach, L.; Schiavi, A.

    1994-09-01

    The proximal spinal muscular atrophies (PSMA), one of the most common forms of lower motor neuron disease in children, are characterized by progressive muscle weakness due to loss of anterior horn cells. All three autosomal recessive forms have been mapped to chromosome 5q11.2-11.3, implying an allelic association between these disorders. Recent evidence from our laboratories, as well as others, suggests that a distinct form of lethal neonatal spinal muscular atrophy, associated with early onset contractures, is determined by a gene on the X chromosome. We report our efforts in mapping this disease locus. Our original studies have focused on two unrelated multigenerational families with similar clinical presentations of severe hypotonia, muscle weakness, and a disease course similar to Werdnig Hoffman except for the additional finding of congenital or early onset contractures. Muscle biopsy and/or autopsy were indicative of anterior horn cell loss in affected males. Disease occurrence in each of the families was consistent with an X-linked recessive mode of inheritance. Subsequently, two additional families have been identified, as well as several sporadic male cases. Linkage analysis has been completed in one of these families using highly polymorphic repeats dispersed 10 cM on the X chromosome. Interpretation of results was achieved using an automated data acquisition program. Analysis of over 300 haplotypes generated using PCR-based DNA markers have identified two 16 cM regions on Xp with complete concordance to the disease phenotype. Our currents efforts are focused on the region surrounding the Kallman gene, in attempts to better define a candidate region, as well as analyze possible candidate genes within this region.

  20. Linking Student Retention Model with Institutional Planning: The Benefits and Limitations of a Student Matrix Model.

    ERIC Educational Resources Information Center

    Schartman, Laura; Rhee, Byung-Shik

    This study explored the possibility of linking the Luna (1999) student flow matrix model with institutional planning at a comprehensive state institution, investigating how student flow environments were associated with student characteristics such as race, gender, citizenship, class level, entry type, and cumulative grade point average. The study…

  1. UAS Modeling of the Communication Links Study Results

    NASA Technical Reports Server (NTRS)

    Birr, Richard; Murray, Jennifer; Girgis, nancy

    2011-01-01

    There were many links calculated for this and the other scenarios. The rain was analyzed for 99.9% availability with rain rated of none, 20 mm/hr and 90 mm/hr at a height of 5 km out to 25 NM. This was done for each scenario for LOS and for BLOS links for Scenario 5 and 6. Scenario 1 was a LOS-only scenario. Use of two 3 dB Antennas on both ends. The CS2 was unable to maintain a control RF Link during the flight. The largest access gap periods between object top and bottom UA antennae were caused by terrain (ridges and hills). The CS Antenna was changed to High Gain Directional Antenna, all three CS maintained lock on vehicle. There were RF dropouts between the top and bottom UA antennae caused by aircraft obstructions (fuselage, wings, wheel assembles, etc.). Note that for this study antenna locations were placed on top and bottom center of the UA body. Future study should include actual UA antenna locations on the aircraft providing manufactures are willing to provide information. The importance of CS location(s) was demonstrated for primary or backup CS. With a second backup CS placed in a suitable location the UA was able to maintain an overall RF link. The actual location of both backup CSs required the antenna location to be place 150 ft above ground in order to establish a RF link between the UA and CS.

  2. [Use of animal models of clinical pain].

    PubMed

    Guilbaud, G

    1990-11-01

    For a better understanding of clinical pain, several groups involved in the study of basic pain mechanisms have proposed the use of various experimental models close to clinical situations. They are based either on neurogenic or inflammatory processes. Data obtained with three of these models will be developed in the paper: rats rendered arthritic by Freund's adjuvant injection into the tail, rats with an intraplantar injection of carrageenin in one hind-paw, rats with a moderate ligature of one common sciatic nerve. The various pharmacological approaches revealed dramatic changes of the analgesic effects of morphine and other opioid substances, and a spectacular modification of the endogenous opioid reactivity. A further enhancement of the initial hyperalgesia was observed with high doses (1-3 mg/kg iv) of naloxone (known as an antagonist of morphine), contrasting with the paradoxical analgesia induced with the low dose (peaking up for 3 micrograms/kg iv). Electrophysiological studies emphasized dramatic changes of neuronal responsiveness in structures involved in the transmission of the nociceptive messages. In each of these models, electrophysiological data provide new insights on the physiopathological mechanisms of the related clinical pain. PMID:2092200

  3. Clinical role modelling: uncovering hidden knowledge.

    PubMed

    Davies, E

    1993-04-01

    Those responsible for the education of nurses are well aware of the need to reconcile the art and science of nursing so that future practitioners can be prepared to offer a humanistic and professional service to society. One way to assist students in this integration is to provide them with opportunities for role modelling as a means of discovering the knowledge embedded in clinical practice. A study of first-year undergraduate students undertaking a course which provides such opportunities in a number of practice settings was carried out to determine whether the observation of clinical role models does lead to knowledge discovery. The study, which used a grounded theory approach, indicated that the major aspect of nursing uncovered by the students through observation of clinical role models was that of provision of direct care. They articulated their values in relation to 'good' and 'bad' care and identified those attributes of nurses which they considered contributed to these care positions. In addition, they were able to recognize creativity and flexibility in practitioners and to relate these attributes to the ability to provide individualized, context-specific care. There was some uncovering of aspects of the nurse's role in maintaining their own professional competence, socializing neophytes into the profession and collaborating with the members of the multi-disciplinary health care team. PMID:8496511

  4. Coaching Model + Clinical Playbook = Transformative Learning.

    PubMed

    Fletcher, Katherine A; Meyer, Mary

    2016-01-01

    Health care employers demand that workers be skilled in clinical reasoning, able to work within complex interprofessional teams to provide safe, quality patient-centered care in a complex evolving system. To this end, there have been calls for radical transformation of nursing education including the development of a baccalaureate generalist nurse. Based on recommendations from the American Association of Colleges of Nursing, faculty concluded that clinical education must change moving beyond direct patient care by applying the concepts associated with designer, manager, and coordinator of care and being a member of a profession. To accomplish this, the faculty utilized a system of focused learning assignments (FLAs) that present transformative learning opportunities that expose students to "disorienting dilemmas," alternative perspectives, and repeated opportunities to reflect and challenge their own beliefs. The FLAs collected in a "Playbook" were scaffolded to build the student's competencies over the course of the clinical experience. The FLAs were centered on the 6 Quality and Safety Education for Nurses competencies, with 2 additional concepts of professionalism and systems-based practice. The FLAs were competency-based exercises that students performed when not assigned to direct patient care or had free clinical time. Each FLA had a lesson plan that allowed the student and faculty member to see the competency addressed by the lesson, resources, time on task, student instructions, guide for reflection, grading rubric, and recommendations for clinical instructor. The major advantages of the model included (a) consistent implementation of structured learning experiences by a diverse teaching staff using a coaching model of instruction; (b) more systematic approach to present learning activities that build upon each other; (c) increased time for faculty to interact with students providing direct patient care; (d) guaranteed capture of selected transformative

  5. Model-based auditability of clinical trial recruitment.

    PubMed

    Curcin, Vasa; Lim Choi Keung, Sarah N; Danger, Roxana; Rossiter, James; Zhao, Lei; Arvanitis, Theodoros N

    2013-01-01

    Detailed insight into the recruitment parameters of a clinical trial is crucial to interpretation of its results, and reasons for its success or failure. Such recruitment is increasingly done through specialized software tools, sometimes linked to Electronic Health Record (EHR) systems, enabling automated capture of audit logs. However, in the absence of shared semantic models underpinning these logs, gathered data remains insular and opaque. We propose a standardized syntactical representation to capture the provenance of the recruitment task, and ground it in CRIM, a variant of the established PCROM information model for research in primary care. The method has been successfully prototyped in the EU FP7 TRANSFoRm project, where the recruitment eligibility query module has been integrated with a provenance capture infrastructure, resulting in the full reproducibility of the study design process. PMID:23920997

  6. FG syndrome, an X-linked multiple congenital anomaly syndrome: The clinical phenotype and an algorithm for diagnostic testing

    PubMed Central

    Clark, Robin Dawn; Graham, John M.; Friez, Michael J.; Hoo, Joe J.; Jones, Kenneth Lyons; McKeown, Carole; Moeschler, John B.; Raymond, F. Lucy; Rogers, R. Curtis; Schwartz, Charles E.; Battaglia, Agatino; Lyons, Michael J.; Stevenson, Roger E.

    2014-01-01

    FG syndrome is a rare X-linked multiple congenital anomaly-cognitive impairment disorder caused by the p.R961W mutation in the MED12 gene. We identified all known patients with this mutation to delineate their clinical phenotype and devise a clinical algorithm to facilitate molecular diagnosis. We ascertained 23 males with the p.R961W mutation in MED12 from 9 previously reported FG syndrome families and 1 new family. Six patients are reviewed in detail. These 23 patients were compared with 48 MED12 mutation-negative patients, who had the clinical diagnosis of FG syndrome. Traits that best discriminated between these two groups were chosen to develop an algorithm with high sensitivity and specificity for the p.R961W MED12 mutation. FG syndrome has a recognizable dysmorphic phenotype with a high incidence of congenital anomalies. A family history of X-linked mental retardation, deceased male infants, and/or multiple fetal losses was documented in all families. The algorithm identifies the p.R961W MED12 mutation-positive group with 100% sensitivity and 90% spec-ificity. The clinical phenotype of FG syndrome defines a recognizable pattern of X-linked multiple congenital anomalies and cognitive impairment. This algorithm can assist the clinician in selecting the patients for testing who are most likely to have the recurrent p.R961W MED12 mutation. PMID:19938245

  7. A 2-year clinical evaluation of a diphenylphosphorylazide-cross-linked collagen membrane for the treatment of buccal gingival recession.

    PubMed

    Zahedi, S; Bozon, C; Brunel, G

    1998-09-01

    To retard collagen membrane enzymatic degradation and to increase its mechanical strength, the diphenylphosphorylazide (DPPA) technique has been demonstrated to achieve natural cross-links between peptide chains of collagen without leaving any foreign product in the cross-linked molecule. In the present prospective clinical trial, the potential of a DPPA-cross-linked type I bovine collagen membrane was evaluated in the healing of 15 buccal soft tissue recessions in 15 patients according to the biological concept of guided tissue regeneration. The recession decreased from 3.7 mm (SD 1.4) at baseline to 0.8 mm (SD 1.2) at 2 years postsurgery, corresponding to a mean root coverage of 82.2% (P <0.0001). Concurrently, the clinical attachment level decreased from 5.4 mm (SD 1.6) at baseline to 1.9 mm (SD 1.2) 2 years postsurgery, corresponding to an average clinical attachment gain of 3.5 mm (SD 1.3) (P <0.0001). The 2-year postsurgical width of the keratinized tissue was not significantly different from baseline values. More than half (53%) of the treated sites showed complete root coverage and about two-thirds (73%) of the total cases showed a 75% to 100% disappearance of the mucogingival defect. The present investigation demonstrated that the use of DPPA-cross-linked collagen membranes in the treatment of human buccal soft tissue recessions results in predictable amounts of root coverage and clinical attachment gain. Long-term randomization controlled clinical trials of this material are needed to fully evaluate its potential for treating periodontal recession. PMID:9776025

  8. A novel animal model linking adiposity to altered circadian rhythms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Researchers have provided evidence for a link between obesity and altered circadian rhythms (e.g., shift work, disrupted sleep), but the mechanism for this association is still unknown. Adipocytes possess an intrinsic circadian clock, and circadian rhythms in adipocytokines and adipose tissue metab...

  9. Modeling and Simulation of a Slider Crank Mechanism with a Flexible Extensible Link

    NASA Astrophysics Data System (ADS)

    Dupac, M.; Noroozi, S.

    In this paper the modelling of a slider-crank mechanism with an extensible flexible link is presented and its dynamical behaviour analyzed. The link flexibility is modelled using extensible rigid links and rotational springs. The equations of motion with and without slider clearance are written. Accurate simulation of the extensible mechanism is performed to study its possible performance and behaviour under the combined effect of different parameters. A dynamic analysis is carried out in order to understand its behaviour under motion reconfiguration.

  10. Dynamic link between ECG and clinical data by a CORBA-based query engine and temporal mapping.

    PubMed Central

    Wang, C.; Ohe, K.; Kaihara, S.

    1997-01-01

    It is important to create a dynamic link method to link distributed patient data across multiple hospitals on an "as needed" basis because the pre-defined links (an item of data has a character or group of characters that indicates the storage of another item of data) are difficult to be managed, or can only be established in part, or are not necessary to be pre-defined in many cases, especially in linking the descriptive data such as history data with the corresponding examination data across multiple hospitals. A method of linking electrocardiogram (ECG) with clinical data dynamically in a Common Object Request Broker Architecture (CORBA) environment has been achieved and verified in a real computing environment to approach to this goal. By this method, distributed patient data can be linked dynamically by a CORBA-based query engine and temporal mapping no matter where they are located on the Internet. The necessary temporal information is provided by either computing or human being. Since multiple time-axes for different databases are involved in, some temporal reasoning methods (such as mapping occurrences across temporal contexts and determining bounds for absolute occurrences, etc.) are applied to this study, and a series of temporal mappings including the first mapping, the secondary mapping, the contextual mapping, the extended mapping, the previous mapping and the next mapping are created. In comparison with the pre-defined link, the major strengths of this method are the dynamic link on an "as needed" basis, no limitation of institutional boundaries, easy creation, simplifying the data storage, and the high flexibility, etc. PMID:9357582

  11. Deregulation of the lysyl hydroxylase matrix cross-linking system in experimental and clinical bronchopulmonary dysplasia.

    PubMed

    Witsch, Thilo J; Turowski, Pawel; Sakkas, Elpidoforos; Niess, Gero; Becker, Simone; Herold, Susanne; Mayer, Konstantin; Vadász, István; Roberts, Jesse D; Seeger, Werner; Morty, Rory E

    2014-02-01

    Bronchopulmonary dysplasia (BPD) is a common and serious complication of premature birth, characterized by a pronounced arrest of alveolar development. The underlying pathophysiological mechanisms are poorly understood although perturbations to the maturation and remodeling of the extracellular matrix (ECM) are emerging as candidate disease pathomechanisms. In this study, the expression and regulation of three members of the lysyl hydroxylase family of ECM remodeling enzymes (Plod1, Plod2, and Plod3) in clinical BPD, as well as in an experimental animal model of BPD, were addressed. All three enzymes were localized to the septal walls in developing mouse lungs, with Plod1 also expressed in the vessel walls of the developing lung and Plod3 expressed uniquely at the base of developing septa. The expression of plod1, plod2, and plod3 was upregulated in the lungs of mouse pups exposed to 85% O2, an experimental animal model of BPD. Transforming growth factor (TGF)-β increased plod2 mRNA levels and activated the plod2 promoter in vitro in lung epithelial cells and in lung fibroblasts. Using in vivo neutralization of TGF-β signaling in the experimental animal model of BPD, TGF-β was identified as the regulator of aberrant plod2 expression. PLOD2 mRNA expression was also elevated in human neonates who died with BPD or at risk for BPD, compared with neonates matched for gestational age at birth or chronological age at death. These data point to potential roles for lysyl hydroxylases in normal lung development, as well as in perturbed late lung development associated with BPD. PMID:24285264

  12. Deregulation of the lysyl hydroxylase matrix cross-linking system in experimental and clinical bronchopulmonary dysplasia

    PubMed Central

    Witsch, Thilo J.; Turowski, Paweł; Sakkas, Elpidoforos; Niess, Gero; Becker, Simone; Herold, Susanne; Mayer, Konstantin; Vadász, István; Roberts, Jesse D.; Seeger, Werner

    2013-01-01

    Bronchopulmonary dysplasia (BPD) is a common and serious complication of premature birth, characterized by a pronounced arrest of alveolar development. The underlying pathophysiological mechanisms are poorly understood although perturbations to the maturation and remodeling of the extracellular matrix (ECM) are emerging as candidate disease pathomechanisms. In this study, the expression and regulation of three members of the lysyl hydroxylase family of ECM remodeling enzymes (Plod1, Plod2, and Plod3) in clinical BPD, as well as in an experimental animal model of BPD, were addressed. All three enzymes were localized to the septal walls in developing mouse lungs, with Plod1 also expressed in the vessel walls of the developing lung and Plod3 expressed uniquely at the base of developing septa. The expression of plod1, plod2, and plod3 was upregulated in the lungs of mouse pups exposed to 85% O2, an experimental animal model of BPD. Transforming growth factor (TGF)-β increased plod2 mRNA levels and activated the plod2 promoter in vitro in lung epithelial cells and in lung fibroblasts. Using in vivo neutralization of TGF-β signaling in the experimental animal model of BPD, TGF-β was identified as the regulator of aberrant plod2 expression. PLOD2 mRNA expression was also elevated in human neonates who died with BPD or at risk for BPD, compared with neonates matched for gestational age at birth or chronological age at death. These data point to potential roles for lysyl hydroxylases in normal lung development, as well as in perturbed late lung development associated with BPD. PMID:24285264

  13. Self-management support interventions that are clinically linked and technology enabled: can they successfully prevent and treat diabetes?

    PubMed

    Kaufman, Neal D; Woodley, Paula D Patnoe

    2011-05-01

    Patients with diabetes need a complex set of services and supports. The challenge of integrating these services into the diabetes regimen can be successfully overcome through self-management support interventions that are clinically linked and technology enabled: self-management support because patients need help mastering the knowledge, attitudes, skills, and behaviors so necessary for good outcomes; interventions because comprehensive theory-based, evidence-proven, long-term, longitudinal interventions work better than direct-to-consumer or nonplanned health promotion approaches; clinically linked because patients are more likely to adopt new behaviors when the approach is in the context of a trusted therapeutic relationship and within an effective medical care system; and technology enabled because capitalizing on the amazing power of information technology leads to the delivery of cost-effective, scalable, engaging solutions that prevent and manage diabetes. PMID:21722596

  14. Covalent cross-links in polyampholytic chitosan fibers enhances bone regeneration in a rabbit model.

    PubMed

    Ghosh, Paulomi; Rameshbabu, Arun Prabhu; Das, Dipankar; Francis, Nimmy K; Pawar, Harpreet Singh; Subramanian, Bhuvaneshwaran; Pal, Sagar; Dhara, Santanu

    2015-01-01

    Chitosan fibers were prepared in citric acid bath, pH 7.4 and NaOH solution at pH 13, to form ionotropically cross-linked and uncross-linked fibers, respectively. The fibers formed in citric acid bath were further cross-linked via carbodiimide chemistry; wherein the pendant carboxyl moieties of citric acid were used for new amide bond formation. Moreover, upon covalent cross-linking in the ionically gelled citrate-chitosan fibers, incomplete conversion of the ion pairs to amide linkages took place resulting in the formation of a dual network structure. The dual cross-linked fibers displayed improved mechanical property, higher stability against enzymatic degradation, hydrophobicity and superior bio-mineralization compared to the uncross-linked and native citrate cross-linked fibers. Additionally, upon cyclic loading, the ion pairs in the dual cross-linked fibers dissociated by dissipating energy and reformed during the relaxation period. The twin property of elasticity and energy dissipation mechanism makes the dual cross-linked fiber unique under dynamic mechanical conditions. The differences in the physico-chemical characteristics were reflected in protein adsorption, which in turn influenced the cellular activities on the fibers. Compared to the uncross-linked and ionotropically cross-linked fibers, the dual cross-linked fibers demonstrated higher proliferation and osteogenic differentiation of the MSCs in vitro as well as better osseous tissue regeneration in a rabbit model. PMID:25483844

  15. Expanding clinical applications of population pharmacodynamic modelling

    PubMed Central

    Minto, Charles; Schnider, Thomas

    1998-01-01

    Population pharmacokinetics or pharmacodynamics is the study of the variability in drug concentration or pharmacological effect between individuals when standard dosage regimens are administered. We provide an overview of pharmacokinetic models, pharmacodynamic models, population models and residual error models. We outline how population modelling approaches seek to explain interpatient variability with covariate analysis, and, in some approaches, to characterize the unexplained interindividual variability. The interpretation of the results of population modelling approaches is facilitated by shifting the emphasis from the perspective of the modeller to the perspective of the clinician. Both the explained and unexplained interpatient variability should be presented in terms of their impact on the dose–response relationship. Clinically relevant questions relating to the explained and unexplained variability in the population can be posed to the model, and confidence intervals can be obtained for the fraction of the population that is estimated to fall within a specific therapeutic range given a certain dosing regimen. Such forecasting can be used to develop optimal initial dosing guidelines. The development of population models (with random effects) permits the application of Bayes’s formula to obtain improved estimates of an individual’s pharmacokinetic and pharmacodynamic parameters in the light of observed responses. An important challenge to clinical pharmacology is to identify the drugs that might benefit from such adaptive-control-with-feedback dosing strategies. Drugs used for life threatening diseases with a proven pharmacokinetic-pharmacodynamic relationship, a small therapeutic range, large interindividual variability, small interoccasion variability and severe adverse effects are likely to be good candidates. Rapidly evolving changes in health care economics and consumer expectations make it unlikely that traditional drug development approaches

  16. First six months of clinical usage of an ATM network link between two Veterans Affairs Medical Centers

    NASA Astrophysics Data System (ADS)

    Duerinckx, Andre J.; Gentili, Amilcare; El-Saden, Suzie; Harmon, Craig; Kenagy, John J.; Grant, Edward G.

    1998-07-01

    Purpose/Background: Asynchronous transfer mode (ATM) network technology has recently been used for high speed transmission of radiological images between hospitals and inside hospitals. However, the number of clinical sites which routinely use this technology is limited. The purpose of this study was to analyze the very early impact of an ATM link between a large tertiary referral center and small peripheral clinic on cost and clinical practice. Methodology: An ATM link using 155 bps (OC3) technology was installed between the West Los Angeles VA Medical Center and the Sepulveda VA, a large outpatient facility which provides full service radiological services. The West Los Angeles VA Medical Center is a large tertiary referral center with sub-specialist radiologist. The clinical impact of this ATM link between a large full-scale DICOM-3 compliant PACS system at the West LA VA on a smaller PACS system at the Sepulveda VA was evaluated. Results: The ability to freely exchange complicated MRI and CT studies between a tertiary referral center and a clinic could have a direct impact on patient care. Over the last six months, all and CT studies from Sepulveda VA were readily available via the ATM connection to all radiologists at the West LA VA. On average the workload at the Sepulveda VA in CT and MRI was about one tenth of the same workload at West LA VA, thus creating interesting possibilities for sharing or radiologist resources. Conclusions: Although our preliminary data and work loads have been too limited to draw any final conclusions yet, we feel that future results will show that the ability to provide immediate and fast interactive consultation between general radiologists in a large outpatient facility and sub- specialists at a tertiary referral center can have an impact upon the quality of patient care.

  17. Clinical models of cardiovascular regulation after weightlessness

    NASA Technical Reports Server (NTRS)

    Robertson, D.; Jacob, G.; Ertl, A.; Shannon, J.; Mosqueda-Garcia, R.; Robertson, R. M.; Biaggioni, I.

    1996-01-01

    After several days in microgravity, return to earth is attended by alterations in cardiovascular function. The mechanisms underlying these effects are inadequately understood. Three clinical disorders of autonomic function represent possible models of this abnormal cardiovascular function after spaceflight. They are pure autonomic failure, baroreflex failure, and orthostatic intolerance. In pure autonomic failure, virtually complete loss of sympathetic and parasympathetic function occurs along with profound and immediate orthostatic hypotension. In baroreflex failure, various degrees of debuffering of blood pressure occur. In acute and complete baroreflex failure, there is usually severe hypertension and tachycardia, while with less complete and more chronic baroreflex impairment, orthostatic abnormalities may be more apparent. In orthostatic intolerance, blood pressure fall is minor, but orthostatic symptoms are prominent and tachycardia frequently occurs. Only careful autonomic studies of human subjects in the microgravity environment will permit us to determine which of these models most closely reflects the pathophysiology brought on by a period of time in the microgravity environment.

  18. Clinical relevance of animal models of schizophrenia.

    PubMed

    Koch, Michael

    2013-01-01

    Animal models and endophenotypes of mental disorders are regarded as preclinical heuristic approaches aiming at understanding the etiopathogenesis of these diseases, and at developing drug treatment strategies. A frequently used translational model of sensorimotor gating and its deficits in some neuropsychiatric disorders is prepulse inhibition (PPI) of startle. PPI is reduced in schizophrenia patients, but the exact relationship between symptoms and reduced PPI is still unclear. Recent findings suggest that the levels of PPI in humans and animals may be predictive of certain cognitive functions. Hence, this simple measure of reflex suppression may be of use for clinical research. PPI is the reduction of the acoustic startle response that occurs when a weak prestimulus is presented shortly prior to a startling noise pulse. It is considered a measure of sensorimotor gating and is regulated by a cortico-limbic striato-pallidal circuit. However, PPI does not only occur in the domain of startle. PPI of alpha, gamma, and theta oscillations at frontal and central locations has been found, suggesting a relationship between PPI and cognitive processes. In fact, levels of PPI in healthy subjects and in animals predict their performance in cognitive tasks mainly mediated by the frontal cortex. Taken together, PPI might reflect a more general filtering performance leading to gating of intrusive sensory, motor, and cognitive input, thereby improving cognitive function. Hence, PPI might be used in clinical settings to predict the impact of drugs or psychotherapy on cognitive performance in neuropsychiatric patients. PMID:24053035

  19. Mathematical modeling of cross-linking monomer elution from resin-based dental composites.

    PubMed

    Manojlovic, Dragica; Radisic, Marina; Lausevic, Mila; Zivkovic, Slavoljub; Miletic, Vesna

    2013-01-01

    Elution of potentially toxic substances, including monomers, from resin-based dental composites may affect the biocompatibility of these materials in clinical conditions. In addition to the amounts of eluted monomers, mathematical modeling of elution kinetics reveals composite restorations as potential chronic sources of leachable monomers. The aim of this work was to experimentally quantify elution of main cross-linking monomers from four commercial composites and offer a mathematical model of elution kinetics. Composite samples (n = 7 per group) of Filtek Supreme XT (3M ESPE), Tetric EvoCeram (Ivoclar Vivadent), Admira (Voco), and Filtek Z250 (3M ESPE) were prepared in 2-mm thick Teflon moulds and cured with halogen or light-emitting diode light. Monomer elution in ethanol and water was analyzed using high-performance liquid chromatography up to 28 days postimmersion. The mathematical model was expressed as a sum of two exponential regression functions representing the first-order kinetics law. Elution kinetics in all cases followed the same mathematical model though differences in rate constants as well as the extent of monomer elution were material-, LCU-, medium-dependent. The proposed mechanisms of elution indicate fast elution from surface and subsurface layers and up to 100 times slower monomer extraction from the bulk polymer. PMID:22997145

  20. “Youth friendly” clinics: Considerations for linking and engaging HIV-infected adolescents into care

    PubMed Central

    Tanner, Amanda E.; Philbin, Morgan M.; Duval, Anna; Ellen, Jonathan; Kapogiannis, Bill; Fortenberry, J. Dennis

    2014-01-01

    Linkage and engagement in care are critical corollaries to the health of HIV-infected adolescents. The adolescent HIV epidemic and adolescents’ unique barriers to care necessitates innovation in the provision of care, including the consideration of the clinical experience. Little research has addressed how “youth friendly” clinics may influence care retention for HIV-infected youth. We conducted 124 interviews with providers, outreach workers, and case managers, at 15 Adolescent Medicine Trials Network clinics. Photographs of each clinic documented the characteristics of the physical space. Constant comparison and content and visual narrative methods were utilized for data analysis. Three elements of youth friendliness were identified for clinics serving HIV-infected youth, including: (1) role of target population (e.g., pediatric, adolescent, HIV); (2) clinics’ physical environment; and (3) clinics’ social environment. Working to create ‘youth friendly’ clinics through changes in physical (e.g., space, entertainment, and educational materials) and social (e.g., staff training related to development, gender, sexual orientation) environments may help reduce HIV-infected adolescents’ unique barriers to care engagement. The integration of clinic design and staff training within the organization of a clinical program is helpful in meeting the specialized needs of HIV-infected youth. PMID:23782040

  1. Circuit-level simulation of transistor lasers and its application to modelling of microwave photonic links

    NASA Astrophysics Data System (ADS)

    Iezekiel, Stavros; Christou, Andreas

    2015-03-01

    Equivalent circuit models of a transistor laser are used to investigate the suitability of this relatively new device for analog microwave photonic links. The three-terminal nature of the device enables transistor-based circuit design techniques to be applied to optoelectronic transmitter design. To this end, we investigate the application of balanced microwave amplifier topologies in order to enable low-noise links to be realized with reduced intermodulation distortion and improved RF impedance matching compared to conventional microwave photonic links.

  2. Automatic generation of computable implementation guides from clinical information models.

    PubMed

    Boscá, Diego; Maldonado, José Alberto; Moner, David; Robles, Montserrat

    2015-06-01

    Clinical information models are increasingly used to describe the contents of Electronic Health Records. Implementation guides are a common specification mechanism used to define such models. They contain, among other reference materials, all the constraints and rules that clinical information must obey. However, these implementation guides typically are oriented to human-readability, and thus cannot be processed by computers. As a consequence, they must be reinterpreted and transformed manually into an executable language such as Schematron or Object Constraint Language (OCL). This task can be difficult and error prone due to the big gap between both representations. The challenge is to develop a methodology for the specification of implementation guides in such a way that humans can read and understand easily and at the same time can be processed by computers. In this paper, we propose and describe a novel methodology that uses archetypes as basis for generation of implementation guides. We use archetypes to generate formal rules expressed in Natural Rule Language (NRL) and other reference materials usually included in implementation guides such as sample XML instances. We also generate Schematron rules from NRL rules to be used for the validation of data instances. We have implemented these methods in LinkEHR, an archetype editing platform, and exemplify our approach by generating NRL rules and implementation guides from EN ISO 13606, openEHR, and HL7 CDA archetypes. PMID:25910958

  3. Correlation between connexin 32 gene mutations and clinical phenotype in X-linked dominant Charcot-Marie-Tooth neuropathy

    SciTech Connect

    Ionasescu, V.; Ionasescu, R.; Searby, C.

    1996-06-14

    We studied the relationship between the genotype and clinical phenotype in 27 families with dominant X-linked Charcot-Marie-Tooth (CMTX1) neuropathy. Twenty-two families showed mutations in the coding region of the connexin32 (cx32) gene. The mutations include four nonsense mutations, eight missense mutations, two medium size deletions, and one insertion. Most missense mutations showed a mild clinical phenotype (five out of eight), whereas all nonsense mutations, the larger of the two deletions, and the insertion that produced frameshifts showed severe phenotypes. Five CMTX1 families with mild clinical phenotype showed no point mutations of the cx32 gene coding region. Three of these families showed positive genetic linkage with the markers of the Xq13.1 region. The genetic linkage of the remaining two families could not be evaluated because of their small size. 25 refs., 1 fig., 1 tab.

  4. The mental health clinic: a new model

    PubMed Central

    FAVA, GIOVANNI A.; PARK, SEUGN K.; DUBOVSKY, STEVEN

    2008-01-01

    The role of psychiatrists into public mental health clinics has been hampered by a perceived restriction of the psychiatrist's role to prescribing and sign-ing forms, limiting opportunities to engage in the kind of integrated care that attracted many physicians to this specialty. We propose a revision of the current model in a direction that maximizes the expertise of this specialist as well as other clinicians in the health care team. The basic unit would consist of a psychiatrist (with adequate background both in psychopharmacology and psychotherapy), an internist and four clinical psychotherapists, who may provide evidence-based treatment after the initial evaluation of the psychiatrist. Its functioning would emphasize repeated assessments, sequential combi-nation of treatments, and close coordination of team members. Re-invigorating the role of the psychiatrist in the context of a team in which role assign-ments are clear could result in better outcomes and enhanced recruitment of psychiatrists into the public sector. PMID:18836544

  5. Clinical Trials Reference Materials and Related Links | Division of Cancer Prevention

    Cancer.gov

    Agreements Clinical Trials Agreement Confidential Disclosure Agreements Cooperative Research and Development Agreement (CRADA) - Research Plan Financial and Staffing Contribution of the Parties Exception or Modifications to the CRADA Human Subject Protection/Informed Consent Tutorials (or Education) |

  6. Modeling and control of a hydraulically actuated flexible-prismatic link robot

    SciTech Connect

    Love, L.; Kress, R.; Jansen, J.

    1996-12-01

    Most of the research related to flexible link manipulators to date has focused on single link, fixed length, single plane of vibration test beds. In addition, actuation has been predominantly based upon electromagnetic motors. Ironically, these elements are rarely found in the existing industrial long reach systems. This manuscript describes a new hydraulically actuated, long reach manipulator with a flexible prismatic link at Oak Ridge National Laboratory (ORNL). Focus is directed towards both modeling and control of hydraulic actuators as well as flexible links that have variable natural frequencies.

  7. Theory and Practice: An Integrative Model Linking Class and Field

    ERIC Educational Resources Information Center

    Lesser, Joan Granucci; Cooper, Marlene

    2006-01-01

    Social work has evolved over the years taking on the challenges of the times. The profession now espouses a breadth of theoretical approaches and treatment modalities. We have developed a model to help graduate social work students master the skill of integrating theory and social work practice. The Integrative Model has five components: (l) The…

  8. Tools and Algorithms to Link Horizontal Hydrologic and Vertical Hydrodynamic Models and Provide a Stochastic Modeling Framework

    NASA Astrophysics Data System (ADS)

    Salah, Ahmad M.; Nelson, E. James; Williams, Gustavious P.

    2010-04-01

    We present algorithms and tools we developed to automatically link an overland flow model to a hydrodynamic water quality model with different spatial and temporal discretizations. These tools run the linked models which provide a stochastic simulation frame. We also briefly present the tools and algorithms we developed to facilitate and analyze stochastic simulations of the linked models. We demonstrate the algorithms by linking the Gridded Surface Subsurface Hydrologic Analysis (GSSHA) model for overland flow with the CE-QUAL-W2 model for water quality and reservoir hydrodynamics. GSSHA uses a two-dimensional horizontal grid while CE-QUAL-W2 uses a two-dimensional vertical grid. We implemented the algorithms and tools in the Watershed Modeling System (WMS) which allows modelers to easily create and use models. The algorithms are general and could be used for other models. Our tools create and analyze stochastic simulations to help understand uncertainty in the model application. While a number of examples of linked models exist, the ability to perform automatic, unassisted linking is a step forward and provides the framework to easily implement stochastic modeling studies.

  9. Defining Nursing Information System Requirements: A Linked Model

    PubMed Central

    Gassert, Carole A.

    1989-01-01

    There is increasing opportunity for nurses to make decisions about information systems. The purpose of this study was: to develop a model that provides nurses with a guiding framework for deriving nursing information system requirements needed to select, evaluate, enhance or design nursing information systems (NISs); and to test the model's completeness and usefulness. Five model elements were identified from the nursing informatics literature. Structured analysis was then used to identify sub-elements and to produce a graphic model. The Model for Defining Nursing Information System Requirements (MDNISR) was tested by surveying a purposive sample of 75 registered nurses who had made decisions about NISs in hospital settings. Findings support MDNISR as a complete and useful tool for defining requirements for nursing information systems.

  10. X-linked ichthyosis without STS deficiency: Clinical, genetical, and molecular studies

    SciTech Connect

    Robledo, R.; Melis, P.; Schillinger, E.; Siniscalco, M.

    1995-11-06

    We report on a Sardinian pedigree with congenital ichthyosis associated with normal levels of steroid sulfatase and a normal molecular pattern, as detectable with a cDNA probe for the steroid sulfatase (STS) gene. Though the pattern of transmission of the disease is consistent with X-linked recessive inheritance, this form of ichthyosis was found to segregate independently of genetic polymorphisms detected by probes of the region Xp22.3, where the STS locus has been mapped. The search for close genetic linkages with other polymorphic markers scattered along the entire X chromosome has so far been fruitless. For the time being, the main conclusion derived from these data is that STS deficiency is not a sine qua non for X-linked ichthyosis which may also result from a mutational event at an X-chromosomal site genetically unlinked to the STS locus. 16 refs., 4 figs.

  11. Linking Hydrology and Atmospheric Sciences in Continental Water Dynamics Modeling

    NASA Astrophysics Data System (ADS)

    David, C. H.; Gochis, D. J.; Maidment, D. R.; Wilhelmi, O.

    2006-12-01

    Atmospheric observation and model output datasets as well as hydrologic datasets are increasingly becoming available on a continental scale. Although the availability of these datasets could allow large-scale water dynamics modeling, the different objects and semantics used in atmospheric science and hydrology set barriers to their interoperability. Recent work has demonstrated the feasibility for modeling terrestrial water dynamics for the continental United States of America. Continental water dynamics defines the interaction of the hydrosphere, the land surface and subsurface at spatial scales ranging from point to continent. The improved version of the National Hydrographic Dataset (NHDPlus, an integrated suite of geospatial datasets stored in a vector and raster GIS format) was used as hydrologic and elevation data input to the Noah community Land Surface Model, developed at NCAR. Noah was successfully run on a watershed in the Ohio River Basin with NHDPlus inputs. The use of NHDPlus as input data for Noah is a crucial improvement for community modeling efforts allowing users to by-pass much of the time consumed in Digital Elevation Model and hydrological network processing. Furthermore, the community Noah land surface model, in its hydrologically-enhanced configuration, is capable of providing flow inputs for a river dynamics model. Continued enhancement of Noah will, as a consequence, be beneficial to the atmospheric science community as well as to the hydrologic community. Ongoing research foci include using a diversity of weather drivers as an input to Noah, and investigation of how to use land surface model outputs for river forecasting, using both the ArcHydro and OpenMI frameworks.

  12. A model integration framework for linking SWAT and MODFLOW

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydrological response and transport phenomena are driven by atmospheric, surface and subsurface processes. These complex processes occur at different spatiotemporal scales requiring comprehensive modeling to assess the impact of anthropogenic activity on hydrology and fate and transport of chemical ...

  13. Cooperative modeling: linking science, communication, and ground water planning.

    PubMed

    Tidwell, Vincent C; van den Brink, Cors

    2008-01-01

    Equitable allocation of ground water resources is a growing challenge due to both the increasing demand for water and the competing values placed on its use. While scientists can contribute to a technically defensible basis for water resource planning, this framework must be cast in a broader societal and environmental context. Given the complexity and often contentious nature of resource allocation, success requires a process for inclusive and transparent sharing of ideas complemented by tools to structure, quantify, and visualize the collective understanding and data, providing an informed basis of dialogue, exploration, and decision making. Ideally, a process that promotes shared learning leading to cooperative and adaptive planning decisions. While variously named, mediated modeling, group modeling, cooperative modeling, shared vision planning, or computer-mediated collaborative decision making are similar approaches aimed at meeting these objectives. In this paper, we frame "cooperative modeling" in the context of ground water planning and illustrate the process with two brief examples. PMID:18194321

  14. Linking Time and Space Scales in Distributed Hydrological Modelling - a case study for the VIC model

    NASA Astrophysics Data System (ADS)

    Melsen, Lieke; Teuling, Adriaan; Torfs, Paul; Zappa, Massimiliano; Mizukami, Naoki; Clark, Martyn; Uijlenhoet, Remko

    2015-04-01

    One of the famous paradoxes of the Greek philosopher Zeno of Elea (~450 BC) is the one with the arrow: If one shoots an arrow, and cuts its motion into such small time steps that at every step the arrow is standing still, the arrow is motionless, because a concatenation of non-moving parts does not create motion. Nowadays, this reasoning can be refuted easily, because we know that motion is a change in space over time, which thus by definition depends on both time and space. If one disregards time by cutting it into infinite small steps, motion is also excluded. This example shows that time and space are linked and therefore hard to evaluate separately. As hydrologists we want to understand and predict the motion of water, which means we have to look both in space and in time. In hydrological models we can account for space by using spatially explicit models. With increasing computational power and increased data availability from e.g. satellites, it has become easier to apply models at a higher spatial resolution. Increasing the resolution of hydrological models is also labelled as one of the 'Grand Challenges' in hydrology by Wood et al. (2011) and Bierkens et al. (2014), who call for global modelling at hyperresolution (~1 km and smaller). A literature survey on 242 peer-viewed articles in which the Variable Infiltration Capacity (VIC) model was used, showed that the spatial resolution at which the model is applied has decreased over the past 17 years: From 0.5 to 2 degrees when the model was just developed, to 1/8 and even 1/32 degree nowadays. On the other hand the literature survey showed that the time step at which the model is calibrated and/or validated remained the same over the last 17 years; mainly daily or monthly. Klemeš (1983) stresses the fact that space and time scales are connected, and therefore downscaling the spatial scale would also imply downscaling of the temporal scale. Is it worth the effort of downscaling your model from 1 degree to 1

  15. A simple model linking galaxy and dark matter evolution

    SciTech Connect

    Birrer, Simon; Lilly, Simon; Amara, Adam; Paranjape, Aseem; Refregier, Alexandre E-mail: simon.lilly@phys.ethz.ch

    2014-09-20

    We construct a simple phenomenological model for the evolving galaxy population by incorporating predefined baryonic prescriptions into a dark matter hierarchical merger tree. The model is based on the simple gas-regulator model introduced by Lilly et al., coupled with the empirical quenching rules of Peng et al. The simplest model already does quite well in reproducing, without re-adjusting the input parameters, many observables, including the main sequence sSFR-mass relation, the faint end slope of the galaxy mass function, and the shape of the star forming and passive mass functions. Similar to observations and/or the recent phenomenological model of Behroozi et al., which was based on epoch-dependent abundance-matching, our model also qualitatively reproduces the evolution of the main sequence sSFR(z) and SFRD(z) star formation rate density relations, the M{sub s} – M{sub h} stellar-to-halo mass relation, and the SFR – M{sub h} relation. Quantitatively the evolution of sSFR(z) and SFRD(z) is not steep enough, the M{sub s} – M{sub h} relation is not quite peaked enough, and, surprisingly, the ratio of quenched to star forming galaxies around M* is not quite high enough. We show that these deficiencies can simultaneously be solved by ad hoc allowing galaxies to re-ingest some of the gas previously expelled in winds, provided that this is done in a mass-dependent and epoch-dependent way. These allow the model galaxies to reduce an inherent tendency to saturate their star formation efficiency, which emphasizes how efficient galaxies around M* are in converting baryons into stars and highlights the fact that quenching occurs at the point when galaxies are rapidly approaching the maximum possible efficiency of converting baryons into stars.

  16. A Simple Model Linking Galaxy and Dark Matter Evolution

    NASA Astrophysics Data System (ADS)

    Birrer, Simon; Lilly, Simon; Amara, Adam; Paranjape, Aseem; Refregier, Alexandre

    2014-09-01

    We construct a simple phenomenological model for the evolving galaxy population by incorporating predefined baryonic prescriptions into a dark matter hierarchical merger tree. The model is based on the simple gas-regulator model introduced by Lilly et al., coupled with the empirical quenching rules of Peng et al. The simplest model already does quite well in reproducing, without re-adjusting the input parameters, many observables, including the main sequence sSFR-mass relation, the faint end slope of the galaxy mass function, and the shape of the star forming and passive mass functions. Similar to observations and/or the recent phenomenological model of Behroozi et al., which was based on epoch-dependent abundance-matching, our model also qualitatively reproduces the evolution of the main sequence sSFR(z) and SFRD(z) star formation rate density relations, the Ms - Mh stellar-to-halo mass relation, and the SFR - Mh relation. Quantitatively the evolution of sSFR(z) and SFRD(z) is not steep enough, the Ms - Mh relation is not quite peaked enough, and, surprisingly, the ratio of quenched to star forming galaxies around M* is not quite high enough. We show that these deficiencies can simultaneously be solved by ad hoc allowing galaxies to re-ingest some of the gas previously expelled in winds, provided that this is done in a mass-dependent and epoch-dependent way. These allow the model galaxies to reduce an inherent tendency to saturate their star formation efficiency, which emphasizes how efficient galaxies around M* are in converting baryons into stars and highlights the fact that quenching occurs at the point when galaxies are rapidly approaching the maximum possible efficiency of converting baryons into stars.

  17. Linking Essential Tremor to the Cerebellum-Animal Model Evidence.

    PubMed

    Handforth, Adrian

    2016-06-01

    In this review, we hope to stimulate interest in animal models as opportunities to understand tremor mechanisms within the cerebellar system. We begin by considering the harmaline model of essential tremor (ET), which has ET-like anatomy and pharmacology. Harmaline induces the inferior olive (IO) to burst fire rhythmically, recruiting rhythmic activity in Purkinje cells (PCs) and deep cerebellar nuclei (DCN). This model has fostered the IO hypothesis of ET, which postulates that factors that promote excess IO, and hence PC complex spike synchrony, also promote tremor. In contrast, the PC hypothesis postulates that partial PC cell loss underlies tremor of ET. We describe models in which chronic partial PC loss is associated with tremor, such as the Weaver mouse, and others with PC loss that do not show tremor, such as the Purkinje cell degeneration mouse. We postulate that partial PC loss with tremor is associated with terminal axonal sprouting. We then discuss tremor that occurs with large lesions of the cerebellum in primates. This tremor has variable frequency and is an ataxic tremor not related to ET. Another tremor type that is not likely related to ET is tremor in mice with mutations that cause prolonged synaptic GABA action. This tremor is probably due to mistiming within cerebellar circuitry. In the final section, we catalog tremor models involving neurotransmitter and ion channel perturbations. Some appear to be related to the IO hypothesis of ET, while in others tremor may be ataxic or due to mistiming. In summary, we offer a tentative framework for classifying animal action tremor, such that various models may be considered potentially relevant to ET, subscribing to IO or PC hypotheses, or not likely relevant, as with mistiming or ataxic tremor. Considerable further research is needed to elucidate the mechanisms of tremor in animal models. PMID:26660708

  18. Proportional exponentiated link transformed hazards (ELTH) models for discrete time survival data with application

    PubMed Central

    Joeng, Hee-Koung; Chen, Ming-Hui; Kang, Sangwook

    2015-01-01

    Discrete survival data are routinely encountered in many fields of study including behavior science, economics, epidemiology, medicine, and social science. In this paper, we develop a class of proportional exponentiated link transformed hazards (ELTH) models. We carry out a detailed examination of the role of links in fitting discrete survival data and estimating regression coefficients. Several interesting results are established regarding the choice of links and baseline hazards. We also characterize the conditions for improper survival functions and the conditions for existence of the maximum likelihood estimates under the proposed ELTH models. An extensive simulation study is conducted to examine the empirical performance of the parameter estimates under the Cox proportional hazards model by treating discrete survival times as continuous survival times, and the model comparison criteria, AIC and BIC, in determining links and baseline hazards. A SEER breast cancer dataset is analyzed in details to further demonstrate the proposed methodology. PMID:25772374

  19. Linking plate reconstructions with deforming lithosphere to geodynamic models

    NASA Astrophysics Data System (ADS)

    Müller, R. D.; Gurnis, M.; Flament, N.; Seton, M.; Spasojevic, S.; Williams, S.; Zahirovic, S.

    2011-12-01

    While global computational models are rapidly advancing in terms of their capabilities, there is an increasing need for assimilating observations into these models and/or ground-truthing model outputs. The open-source and platform independent GPlates software fills this gap. It was originally conceived as a tool to interactively visualize and manipulate classical rigid plate reconstructions and represent them as time-dependent topological networks of editable plate boundaries. The user can export time-dependent plate velocity meshes that can be used either to define initial surface boundary conditions for geodynamic models or alternatively impose plate motions throughout a geodynamic model run. However, tectonic plates are not rigid, and neglecting plate deformation, especially that of the edges of overriding plates, can result in significant misplacing of plate boundaries through time. A new, substantially re-engineered version of GPlates is now being developed that allows an embedding of deforming plates into topological plate boundary networks. We use geophysical and geological data to define the limit between rigid and deforming areas, and the deformation history of non-rigid blocks. The velocity field predicted by these reconstructions can then be used as a time-dependent surface boundary condition in regional or global 3-D geodynamic models, or alternatively as an initial boundary condition for a particular plate configuration at a given time. For time-dependent models with imposed plate motions (e.g. using CitcomS) we incorporate the continental lithosphere by embedding compositionally distinct crust and continental lithosphere within the thermal lithosphere. We define three isostatic columns of different thickness and buoyancy based on the tectonothermal age of the continents: Archean, Proterozoic and Phanerozoic. In the fourth isostatic column, the oceans, the thickness of the thermal lithosphere is assimilated using a half-space cooling model. We also

  20. Modeling photosynthesis of discontinuous plant canopies by linking Geometric Optical Radiative Transfer model with biochemical processes

    NASA Astrophysics Data System (ADS)

    Xin, Q.; Gong, P.; Li, W.

    2015-02-01

    Modeling vegetation photosynthesis is essential for understanding carbon exchanges between terrestrial ecosystems and the atmosphere. The radiative transfer process within plant canopies is one of the key drivers that regulate canopy photosynthesis. Most vegetation cover consists of discrete plant crowns, of which the physical observation departs from the underlying assumption of a homogenous and uniform medium in classic radiative transfer theory. Here we advance the Geometric Optical Radiative Transfer (GORT) model to simulate photosynthesis activities for discontinuous plant canopies. We separate radiation absorption into two components that are absorbed by sunlit and shaded leaves, and derive analytical solutions by integrating over the canopy layer. To model leaf-level and canopy-level photosynthesis, leaf light absorption is then linked to the biochemical process of gas diffusion through leaf stomata. The canopy gap probability derived from GORT differs from classic radiative transfer theory, especially when the leaf area index is high, due to leaf clumping effects. Tree characteristics such as tree density, crown shape, and canopy length affect leaf clumping and regulate radiation interception. Modeled gross primary production (GPP) for two deciduous forest stands could explain more than 80% of the variance of flux tower measurements at both near hourly and daily time scales. We also demonstrate that the ambient CO2 concentration influences daytime vegetation photosynthesis, which needs to be considered in state-of-the-art biogeochemical models. The proposed model is complementary to classic radiative transfer theory and shows promise in modeling the radiative transfer process and photosynthetic activities over discontinuous forest canopies.

  1. X-linked creatine transporter defect: A report on two unrelated boys with a severe clinical phenotype

    PubMed Central

    Anselm, I. M.; Alkuraya, F. S.; Salomons, G. S.; Jakobs, C.; Fulton, A. B.; Mazumdar, M.; Rivkin, M.; Frye, R.; Poussaint, T. Young; Marsden, D.

    2008-01-01

    Summary We report two unrelated boys with the X-linked creatine transporter defect (CRTR) and clinical features more severe than those previously described with this disorder. These two boys presented at ages 12 and 30 months with severe mental retardation, absent speech development, hypotonia, myopathy and extra-pyramidal movement disorder. One boy has seizures and some dysmorphic features; he also has evidence of an oxidative phosphorylation defect. They both had classical absence of creatine peak on brain magnetic resonance spectroscopy (MRS). In one, however, this critical finding was overlooked in the initial interpretation and was discovered upon subsequent review of the MRS. PMID:16601897

  2. Links between fluid mechanics and quantum mechanics: a model for information in economics?

    PubMed

    Haven, Emmanuel

    2016-05-28

    This paper tallies the links between fluid mechanics and quantum mechanics, and attempts to show whether those links can aid in beginning to build a formal template which is usable in economics models where time is (a)symmetric and memory is absent or present. An objective of this paper is to contemplate whether those formalisms can allow us to model information in economics in a novel way. PMID:27091173

  3. Knowledge of risk factors and the periodontal disease-systemic link in dental students' clinical decisions.

    PubMed

    Friesen, Lynn Roosa; Walker, Mary P; Kisling, Rebecca E; Liu, Ying; Williams, Karen B

    2014-09-01

    This study evaluated second-, third-, and fourth-year dental students' ability to identify systemic conditions associated with periodontal disease, risk factors most important for referral, and medications with an effect on the periodontium and their ability to apply this knowledge to make clinical decisions regarding treatment and referral of periodontal patients. A twenty-one question survey was administered at one U.S. dental school in the spring semester of 2012 to elicit the students' knowledge and confidence regarding clinical reasoning. The response rate was 86 percent. Periodontal risk factors were accurately selected by at least 50 percent of students in all three classes; these were poorly controlled diabetes, ≥6 mm pockets posteriorly, and lack of response to previous non-surgical therapy. Confidence in knowledge, knowledge of risk factors, and knowledge of medications with an effect on the periodontium improved with training and were predictive of better referral decision making. The greatest impact of training was seen on the students' ability to make correct decisions about referral and treatment for seven clinical scenarios. Although the study found a large increase in the students' abilities from the second through fourth years, the mean of 4.6 (out of 7) for the fourth-year students shows that, on average, those students missed correct treatment or referral on more than two of seven clinical cases. These results suggest that dental curricula should emphasize more critical decision making with respect to referral and treatment criteria in managing the periodontal patient. PMID:25179920

  4. The CAEP Standards and Research on Educator Preparation Programs: Linking Clinical Partnerships with Program Impact

    ERIC Educational Resources Information Center

    Heafner, Tina; McIntyre, Ellen; Spooner, Melba

    2014-01-01

    Responding to the challenge of more rigorous and outcome-oriented program evaluation criteria of the Council for the Accreditation of Educator Preparation (CAEP), authors take a critical look at the intersection of two standards: Clinical Partnerships and Practice (Standard 2) and Program Impact (Standard 4). Illustrating one aspect of a secondary…

  5. Shuttle Communications and Tracking Systems Modeling and TDRSS Link Simulations Studies

    NASA Technical Reports Server (NTRS)

    Chie, C. M.; Dessouky, K.; Lindsey, W. C.; Tsang, C. S.; Su, Y. T.

    1985-01-01

    An analytical simulation package (LinCsim) which allows the analytical verification of data transmission performance through TDRSS satellites was modified. The work involved the modeling of the user transponder, TDRS, TDRS ground terminal, and link dynamics for forward and return links based on the TDRSS performance specifications (4) and the critical design reviews. The scope of this effort has recently been expanded to include the effects of radio frequency interference (RFI) on the bit error rate (BER) performance of the S-band return links. The RFI environment and the modified TDRSS satellite and ground station hardware are being modeled in accordance with their description in the applicable documents.

  6. Linking Models: Reasoning from Patterns to Tables and Equations

    ERIC Educational Resources Information Center

    Switzer, J. Matt

    2013-01-01

    Patterns are commonly used in middle years mathematics classrooms to teach students about functions and modelling with tables, graphs, and equations. Grade 6 students are expected to, "continue and create sequences involving whole numbers, fractions and decimals," and "describe the rule used to create the sequence." (Australian…

  7. An integrative model linking feedback environment and organizational citizenship behavior.

    PubMed

    Peng, Jei-Chen; Chiu, Su-Fen

    2010-01-01

    Past empirical evidence has suggested that a positive supervisor feedback environment may enhance employees' organizational citizenship behavior (OCB). In this study, we aim to extend previous research by proposing and testing an integrative model that examines the mediating processes underlying the relationship between supervisor feedback environment and employee OCB. Data were collected from 259 subordinate-supervisor dyads across a variety of organizations in Taiwan. We used structural equation modeling to test our hypotheses. The results demonstrated that supervisor feedback environment influenced employees' OCB indirectly through (1) both positive affective-cognition and positive attitude (i.e., person-organization fit and organizational commitment), and (2) both negative affective-cognition and negative attitude (i.e., role stressors and job burnout). Theoretical and practical implications are discussed. PMID:21166326

  8. Linking agent-based models and stochastic models of financial markets.

    PubMed

    Feng, Ling; Li, Baowen; Podobnik, Boris; Preis, Tobias; Stanley, H Eugene

    2012-05-29

    It is well-known that financial asset returns exhibit fat-tailed distributions and long-term memory. These empirical features are the main objectives of modeling efforts using (i) stochastic processes to quantitatively reproduce these features and (ii) agent-based simulations to understand the underlying microscopic interactions. After reviewing selected empirical and theoretical evidence documenting the behavior of traders, we construct an agent-based model to quantitatively demonstrate that "fat" tails in return distributions arise when traders share similar technical trading strategies and decisions. Extending our behavioral model to a stochastic model, we derive and explain a set of quantitative scaling relations of long-term memory from the empirical behavior of individual market participants. Our analysis provides a behavioral interpretation of the long-term memory of absolute and squared price returns: They are directly linked to the way investors evaluate their investments by applying technical strategies at different investment horizons, and this quantitative relationship is in agreement with empirical findings. Our approach provides a possible behavioral explanation for stochastic models for financial systems in general and provides a method to parameterize such models from market data rather than from statistical fitting. PMID:22586086

  9. Linking agent-based models and stochastic models of financial markets

    PubMed Central

    Feng, Ling; Li, Baowen; Podobnik, Boris; Preis, Tobias; Stanley, H. Eugene

    2012-01-01

    It is well-known that financial asset returns exhibit fat-tailed distributions and long-term memory. These empirical features are the main objectives of modeling efforts using (i) stochastic processes to quantitatively reproduce these features and (ii) agent-based simulations to understand the underlying microscopic interactions. After reviewing selected empirical and theoretical evidence documenting the behavior of traders, we construct an agent-based model to quantitatively demonstrate that “fat” tails in return distributions arise when traders share similar technical trading strategies and decisions. Extending our behavioral model to a stochastic model, we derive and explain a set of quantitative scaling relations of long-term memory from the empirical behavior of individual market participants. Our analysis provides a behavioral interpretation of the long-term memory of absolute and squared price returns: They are directly linked to the way investors evaluate their investments by applying technical strategies at different investment horizons, and this quantitative relationship is in agreement with empirical findings. Our approach provides a possible behavioral explanation for stochastic models for financial systems in general and provides a method to parameterize such models from market data rather than from statistical fitting. PMID:22586086

  10. Microbial Life in Soil - Linking Biophysical Models with Observations

    NASA Astrophysics Data System (ADS)

    Or, D.; Tecon, R.; Ebrahimi, A.; Kleyer, H.; Ilie, O.; Wang, G.

    2014-12-01

    Microbial life in soil occurs within fragmented aquatic habitats in complex pore spaces where motility is restricted to short hydration windows (e.g., following rainfall). The limited range of self-dispersion and physical confinement promote spatial association among trophically interdepended microbial species. Competition and preferences for different nutrient resources and byproducts and their diffusion require high level of spatial organization to sustain the functioning of multispecies communities. We report mechanistic modeling studies of competing multispecies microbial communities grown on hydrated surfaces and within artificial soil aggregates (represented by 3-D pore network). Results show how trophic dependencies and cell-level interactions within patchy diffusion fields promote spatial self-organization of motile microbial cells. The spontaneously forming patterns of segregated, yet coexisting species were robust to spatial heterogeneities and to temporal perturbations (hydration dynamics), and respond primarily to the type of trophic dependencies. Such spatially self-organized consortia may reflect ecological templates that optimize substrate utilization and could form the basic architecture for more permanent surface-attached microbial colonies. Hydration dynamics affect structure and spatial arrangement of aerobic and anaerobic microbial communities and their biogeochemical functions. Experiments with well-characterized artificial soil microbial assemblies grown on porous surfaces provide access to community dynamics during wetting and drying cycles detected through genetic fingerprinting. Experiments for visual observations of spatial associations of tagged bacterial species with known trophic dependencies on model porous surfaces are underway. Biophysical modeling provide a means for predicting hydration-mediated critical separation distances for activation of spatial self-organization. The study provides new modeling and observational tools that

  11. Microbial Life in Soil - Linking Biophysical Models with Observations

    NASA Astrophysics Data System (ADS)

    Or, Dani; Tecon, Robin; Ebrahimi, Ali; Kleyer, Hannah; Ilie, Olga; Wang, Gang

    2015-04-01

    Microbial life in soil occurs within fragmented aquatic habitats formed in complex pore spaces where motility is restricted to short hydration windows (e.g., following rainfall). The limited range of self-dispersion and physical confinement promote spatial association among trophically interdepended microbial species. Competition and preferences for different nutrient resources and byproducts and their diffusion require high level of spatial organization to sustain the functioning of multispecies communities. We report mechanistic modeling studies of competing multispecies microbial communities grown on hydrated surfaces and within artificial soil aggregates (represented by 3-D pore network). Results show how trophic dependencies and cell-level interactions within patchy diffusion fields promote spatial self-organization of motile microbial cells. The spontaneously forming patterns of segregated, yet coexisting species were robust to spatial heterogeneities and to temporal perturbations (hydration dynamics), and respond primarily to the type of trophic dependencies. Such spatially self-organized consortia may reflect ecological templates that optimize substrate utilization and could form the basic architecture for more permanent surface-attached microbial colonies. Hydration dynamics affect structure and spatial arrangement of aerobic and anaerobic microbial communities and their biogeochemical functions. Experiments with well-characterized artificial soil microbial assemblies grown on porous surfaces provide access to community dynamics during wetting and drying cycles detected through genetic fingerprinting. Experiments for visual observations of spatial associations of tagged bacterial species with known trophic dependencies on model porous surfaces are underway. Biophysical modeling provide a means for predicting hydration-mediated critical separation distances for activation of spatial self-organization. The study provides new modeling and observational tools

  12. Cross Linking and Degradation Mechanisms in Model Sealant Candidates

    NASA Technical Reports Server (NTRS)

    Paciorek, K. L.; Kaufman, J.; Ito, T. I.; Nakahara, J. H.; Kratzer, R. H.

    1977-01-01

    Model compounds were investigated as to which type of heterocyclic ring is the most advantageous for curing sealants based on perfluoroalkylether chains. The relative thermal, thermal oxidative, hydrolytic, and fuel stability of potential crosslinks were determined. Specifically substituted materials were synthesized and evaluation of their stabilities in air, inert atmosphere, water, and Jet-A fuel at 235 and 325 C was made. Three heterocyclic ring systems were considered, namely, triazine, 1,2,4- and 1,3,4-oxadiazoles.

  13. Modeling Prairie Pothole Lakes: Linking Satellite Observation and Calibration (Invited)

    NASA Astrophysics Data System (ADS)

    Schwartz, F. W.; Liu, G.; Zhang, B.; Yu, Z.

    2009-12-01

    This paper examines the response of a complex lake wetland system to variations in climate. The focus is on the lakes and wetlands of the Missouri Coteau, which is part of the larger Prairie Pothole Region of the Central Plains of North America. Information on lake size was enumerated from satellite images, and yielded power law relationships for different hydrological conditions. More traditional lake-stage data were made available to us from the USGS Cottonwood Lake Study Site in North Dakota. A Probabilistic Hydrologic Model (PHM) was developed to simulate lake complexes comprised of tens-of-thousands or more individual closed-basin lakes and wetlands. What is new about this model is a calibration scheme that utilizes remotely-sensed data on lake area as well as stage data for individual lakes. Some ¼ million individual data points are used within a Genetic Algorithm to calibrate the model by comparing the simulated results with observed lake area-frequency power law relationships derived from Landsat images and water depths from seven individual lakes and wetlands. The simulated lake behaviors show good agreement with the observations under average, dry, and wet climatic conditions. The calibrated model is used to examine the impact of climate variability on a large lake complex in ND, in particular, the “Dust Bowl Drought” 1930s. This most famous drought of the 20th Century devastated the agricultural economy of the Great Plains with health and social impacts lingering for years afterwards. Interestingly, the drought of 1930s is unremarkable in relation to others of greater intensity and frequency before AD 1200 in the Great Plains. Major droughts and deluges have the ability to create marked variability of the power law function (e.g. up to one and a half orders of magnitude variability from the extreme Dust Bowl Drought to the extreme 1993-2001 deluge). This new probabilistic modeling approach provides a novel tool to examine the response of the

  14. Linking continuous and discrete intervertebral disc models through homogenisation.

    PubMed

    Karajan, N; Röhrle, O; Ehlers, W; Schmitt, S

    2013-06-01

    At present, there are two main numerical approaches that are frequently used to simulate the mechanical behaviour of the human spine. Researchers with a continuum-mechanical background often utilise the finite-element method (FEM), where the involved biological soft and hard tissues are modelled on a macroscopic (continuum) level. In contrast, groups associated with the science of human movement usually apply discrete multi-body systems (MBS). Herein, the bones are modelled as rigid bodies, which are connected by Hill-type muscles and non-linear rheological spring-dashpot models to represent tendons and cartilaginous connective tissue like intervertebral discs (IVD). A possibility to benefit from both numerical methods is to couple them and use each approach, where it is most appropriate. Herein, the basic idea is to utilise MBS in simulations of the overall body and apply the FEM only to selected regions of interest. In turn, the FEM is used as homogenisation tool, which delivers more accurate non-linear relationships describing the behaviour of the IVD in the multi-body dynamics model. The goal of this contribution is to present an approach to couple both numerical methods without the necessity to apply a gluing algorithm in the context of a co-simulation. Instead, several pre-computations of the intervertebral disc are performed offline to generate an approximation of the homogenised finite-element (FE) result. In particular, the discrete degrees of freedom (DOF) of the MBS, that is, three displacements and three rotations, are applied to the FE model of the IVD, and the resulting homogenised forces and moments are recorded. Moreover, a polynomial function is presented with the discrete DOF of the MBS as variables and the discrete forces an moments as function values. For the sake of a simple verification, the coupling method is applied to a simplified motion segment of the spine. Herein, two stiff cylindrical vertebrae with an interjacent homogeneous

  15. LINKING THE CMAQ AND HYSPLIT MODELING SYSTEM INTERFACE PROGRAM AND EXAMPLE APPLICATION

    EPA Science Inventory

    A new software tool has been developed to link the Eulerian-based Community Multiscale Air Quality (CMAQ) modeling system with the Lagrangian-based HYSPLIT (HYbrid Single-Particle Lagrangian Integrated Trajectory) model. Both models require many of the same hourly meteorological...

  16. A Dual-Process Model of the Alcohol-Behavior Link for Social Drinking

    ERIC Educational Resources Information Center

    Moss, Antony C.; Albery, Ian P.

    2009-01-01

    A dual-process model of the alcohol-behavior link is presented, synthesizing 2 of the major social-cognitive approaches: expectancy and myopia theories. Substantial evidence has accrued to support both of these models, and recent neurocognitive models of the effects of alcohol on thought and behavior have provided evidence to support both as well.…

  17. Comorbidity and high viral load linked to clinical presentation of respiratory human bocavirus infection.

    PubMed

    Ghietto, Lucía María; Majul, Diego; Ferreyra Soaje, Patricia; Baumeister, Elsa; Avaro, Martín; Insfrán, Constanza; Mosca, Liliana; Cámara, Alicia; Moreno, Laura Beatriz; Adamo, Maria Pilar

    2015-01-01

    Human bocavirus (HBoV) is a new parvovirus associated with acute respiratory tract infection (ARTI). In order to evaluate HBoV significance as an agent of acute respiratory disease, we screened 1,135 respiratory samples from children and adults with and without symptoms during two complete calendar years. HBoV1 prevalence in patients with ARTI was 6.33 % in 2011 and 11.64 % in 2012, including neonatal and adult patients. HBoV1 was also detected in 3.77 % of asymptomatic individuals. The co-detection rate was 78.1 %. Among children, 87 % were clinically diagnosed with lower respiratory infection (no significant differences between patients with and without coinfection), and 31 % exhibited comorbidities. Pediatric patients with comorbidities were significantly older than patients without comorbidities. Patients with ARTI had either high or low viral load, while controls had only low viral load, but there were no clinical differences between patients with high or low viral load. In conclusion, we present evidence of the pathogenic potential of HBoV1 in young children with ARTI. Since patients with HBoV1-single infection are not significantly different from those with coinfection with respect to clinical features, the virus can be as pathogenic by itself as other respiratory agents are. Furthermore, an association between high HBoV1 load and disease could not be demonstrated in this study, but all asymptomatic individuals had low viral loads. Also, children with comorbidities are susceptible to HBoV1 infection at older ages than previously healthy children. Thus, the clinical presentation of infection may occur depending on both viral load and the particular interaction between the HBoV1 and the host. PMID:25269520

  18. AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT): Rationale, Design, and Baseline Characteristics

    PubMed Central

    Smurzynski, Marlene; Collier, Ann C.; Koletar, Susan L.; Bosch, Ronald J.; Wu, Kunling; Bastow, Barbara; Benson, Constance A.

    2009-01-01

    Purpose ALLRT is a longitudinal cohort study of HIV-infected subjects prospectively randomized into selected clinical trials for antiretroviral (ARV) treatment-naïve and ARV treatment-experienced individuals conducted by the AIDS Clinical Trials Group (ACTG). We describe the rationale, design, and baseline characteristics of the ALLRT cohort and its potential to address important research questions related to ARV therapy. Method Standardized visits occur every 16 weeks to evaluate long-term clinical, virologic, and immunologic outcomes associated with ARV treatment. Results A total of 4,371 subjects enrolled in ALLRT from January 2000 through June 2007. Of these, 3,146 (72%) were ARV naïve at parent study entry (18% female, 44% white, 32% black, 21% Hispanic; median age 37 years, CD4 count 218 cells/μL, follow-up 3.6 years; 343 [11%] followed ≥8 years) and 1,225 (28%) were treatment experienced (13% female, 59% white, 20% black, 17% Hispanic; median age 42 years, CD4 count 325 cells/μL, follow-up 5.7 years). Conclusions ALLRT provides the opportunity to understand long-term ramifications of therapeutic ARV choices and determine whether these vary by treatment regimen, timing of treatment initiation, or treatment changes over long-term follow-up. Investigations based on uniform data and specimen collection in the context of randomized ARV treatments will be critical to developing more successful long-term therapeutic strategies for HIV treatment. PMID:18753121

  19. Developments of mass spectrometry-based technologies for effective drug development linked with clinical proteomes.

    PubMed

    Nakayama, Noboru; Bando, Yasuhiko; Fukuda, Tetsuya; Kawamura, Takeshi; Nakamura, Haruhiko; Marko-Varga, György; Nishimura, Toshihide

    2016-02-01

    A strong demand in drug discovery and development today is to overcome "Big Gaps" encountered by differences in species and races, to accelerate effective developments in cost and time, and to meet medical needs. Moreover, drugs of various types have emerged which cover middle-size molecules and polymers rather than conventional small molecules. Upon those challenges, mass spectrometry (MS)-based technologies, which will be described in this paper, will play an increasingly important role, among which the liquid chromatography-tandem mass spectrometry (LC/MS/MS) platform will be powerful as rapid and molecule-based analysis more than ever. nanoPore Optical Interferometry (nPOI) newly introduced can detect even weak interactions in protein-protein and protein-compound, and can be connected directly to LC/MS/MS for identification of binding molecular species, which will be quite useful for affinity ranking and high-throughput interaction screening. Imaging MS provides the molecular information and spatial distribution of targeted molecules within a tissue specimen. MS-based clinical proteomics utilizing clinical specimens and empowered by advanced bioinformatics can attain both key protein-protein interaction (PPI) networks with major protein players responsible for functional mechanisms of a disease subtype. An integration of those MS-based technologies will deliver a seamless platform of drug development from molecules identified in human clinical specimens. PMID:26782309

  20. Model analysis of the link between interest rates and crashes

    NASA Astrophysics Data System (ADS)

    Broga, Kristijonas M.; Viegas, Eduardo; Jensen, Henrik Jeldtoft

    2016-09-01

    We analyse the effect of distinct levels of interest rates on the stability of the financial network under our modelling framework. We demonstrate that banking failures are likely to emerge early on under sustained high interest rates, and at much later stage-with higher probability-under a sustained low interest rate scenario. Moreover, we demonstrate that those bank failures are of a different nature: high interest rates tend to result in significantly more bankruptcies associated to credit losses whereas lack of liquidity tends to be the primary cause of failures under lower rates.

  1. Linking seasonal climate forecasts with crop models in Iberian Peninsula

    NASA Astrophysics Data System (ADS)

    Capa, Mirian; Ines, Amor; Baethgen, Walter; Rodriguez-Fonseca, Belen; Han, Eunjin; Ruiz-Ramos, Margarita

    2015-04-01

    Translating seasonal climate forecasts into agricultural production forecasts could help to establish early warning systems and to design crop management adaptation strategies that take advantage of favorable conditions or reduce the effect of adverse conditions. In this study, we use seasonal rainfall forecasts and crop models to improve predictability of wheat yield in the Iberian Peninsula (IP). Additionally, we estimate economic margins and production risks associated with extreme scenarios of seasonal rainfall forecast. This study evaluates two methods for disaggregating seasonal climate forecasts into daily weather data: 1) a stochastic weather generator (CondWG), and 2) a forecast tercile resampler (FResampler). Both methods were used to generate 100 (with FResampler) and 110 (with CondWG) weather series/sequences for three scenarios of seasonal rainfall forecasts. Simulated wheat yield is computed with the crop model CERES-wheat (Ritchie and Otter, 1985), which is included in Decision Support System for Agrotechnology Transfer (DSSAT v.4.5, Hoogenboom et al., 2010). Simulations were run at two locations in northeastern Spain where the crop model was calibrated and validated with independent field data. Once simulated yields were obtained, an assessment of farmer's gross margin for different seasonal climate forecasts was accomplished to estimate production risks under different climate scenarios. This methodology allows farmers to assess the benefits and risks of a seasonal weather forecast in IP prior to the crop growing season. The results of this study may have important implications on both, public (agricultural planning) and private (decision support to farmers, insurance companies) sectors. Acknowledgements Research by M. Capa-Morocho has been partly supported by a PICATA predoctoral fellowship of the Moncloa Campus of International Excellence (UCM-UPM) and MULCLIVAR project (CGL2012-38923-C02-02) References Hoogenboom, G. et al., 2010. The Decision

  2. Clinical Forms and Animal Models of Hypophosphatasia.

    PubMed

    Salles, Jean Pierre

    2015-01-01

    Hypophosphatasia (HPP) is due to mutations of the tissue non-specific alkaline phosphatase (TNAP) gene expressed in the liver, kidney, and bone. TNAP substrates include inorganic pyrophosphate cleaved into inorganic phosphate (Pi) in bone, pyridoxal-5'-phosphate (PLP), the circulating form of vitamin B6, and phosphoethanolamine (PEA). As an autosomal recessive or dominant disease, HPP results in a range of clinical forms. Its hallmarks are low alkaline phosphatase (AP) and elevated PLP and PEA levels. Perinatal HPP may cause early death with respiratory insufficiency and hypomineralization resulting in deformed limbs and sometimes near-absence of bones and skull. Infantile HPP is diagnosed before 6 months of life. Respiratory failure, rib fractures and seizures due to vitamin B6 deficiency in the brain indicate poor prognosis. Craniosynostosis is frequent. Unlike in other forms of rickets, calcium and phosphorus are not decreased, resulting in hypercalciuria and nephrocalcinosis. Hypercalcemic crisis may occur. Failure to thrive and growth retardation are concerns. In infantile and adult forms of HPP, non-traumatic fractures may be the prominent manifestation, with otherwise unexplained chronic pain. Progressive myopathy has been described. Dental manifestations with early loss of teeth are usual in HPP and in a specific form, odontohypophosphatasia. HPP has been studied in knock-out mice models which mimic its severe form. Animal models have made a major contribution to the development of an original enzyme therapy for human infantile HPP, which is however essentially targeted at mineralized tissues. Better knowledge of its extraskeletal manifestations, including pain and neurological symptoms, is therefore required. PMID:26219704

  3. Familial X-linked mental retardation and isolated growth hormone deficiency: Clinical and molecular findings

    SciTech Connect

    Hamel, B.C.J.; Smits, A.P.T.; Helm, B. van den

    1996-07-12

    We report on several members of a family with varying degrees of X-linked mental retardation (XLMR), isolated growth hormone deficiency (IGHD), and infantile behavior but without other consistent phenotypic abnormalities. Male patients continued to grow until well into their twenties and reached a height ranging from 135 to 159 cm. Except one, all female carriers were mentally normal; their adult height ranged from 159 to 168 cm. By linkage studies we have assigned the underlying genetic defect to the Xq24-q27.3 region, with a maximum lod score of Z = 3.26 at {theta} = 0.0 for the DXS294 locus. The XLMR-IGHD phenotype in these patients may be due to pleiotropic effects of a single gene or it may represent a contiguous gene syndrome. 18 refs., 6 figs., 3 tabs.

  4. Modelling Optimal Control of Cholera in Communities Linked by Migration.

    PubMed

    Njagarah, J B H; Nyabadza, F

    2015-01-01

    A mathematical model for the dynamics of cholera transmission with permissible controls between two connected communities is developed and analysed. The dynamics of the disease in the adjacent communities are assumed to be similar, with the main differences only reflected in the transmission and disease related parameters. This assumption is based on the fact that adjacent communities often have different living conditions and movement is inclined toward the community with better living conditions. Community specific reproduction numbers are given assuming movement of those susceptible, infected, and recovered, between communities. We carry out sensitivity analysis of the model parameters using the Latin Hypercube Sampling scheme to ascertain the degree of effect the parameters and controls have on progression of the infection. Using principles from optimal control theory, a temporal relationship between the distribution of controls and severity of the infection is ascertained. Our results indicate that implementation of controls such as proper hygiene, sanitation, and vaccination across both affected communities is likely to annihilate the infection within half the time it would take through self-limitation. In addition, although an infection may still break out in the presence of controls, it may be up to 8 times less devastating when compared with the case when no controls are in place. PMID:26246850

  5. Modelling Optimal Control of Cholera in Communities Linked by Migration

    PubMed Central

    Njagarah, J. B. H.; Nyabadza, F.

    2015-01-01

    A mathematical model for the dynamics of cholera transmission with permissible controls between two connected communities is developed and analysed. The dynamics of the disease in the adjacent communities are assumed to be similar, with the main differences only reflected in the transmission and disease related parameters. This assumption is based on the fact that adjacent communities often have different living conditions and movement is inclined toward the community with better living conditions. Community specific reproduction numbers are given assuming movement of those susceptible, infected, and recovered, between communities. We carry out sensitivity analysis of the model parameters using the Latin Hypercube Sampling scheme to ascertain the degree of effect the parameters and controls have on progression of the infection. Using principles from optimal control theory, a temporal relationship between the distribution of controls and severity of the infection is ascertained. Our results indicate that implementation of controls such as proper hygiene, sanitation, and vaccination across both affected communities is likely to annihilate the infection within half the time it would take through self-limitation. In addition, although an infection may still break out in the presence of controls, it may be up to 8 times less devastating when compared with the case when no controls are in place. PMID:26246850

  6. Harmonising and linking biomedical and clinical data across disparate data archives to enable integrative cross-biobank research

    PubMed Central

    Spjuth, Ola; Krestyaninova, Maria; Hastings, Janna; Shen, Huei-Yi; Heikkinen, Jani; Waldenberger, Melanie; Langhammer, Arnulf; Ladenvall, Claes; Esko, Tõnu; Persson, Mats-Åke; Heggland, Jon; Dietrich, Joern; Ose, Sandra; Gieger, Christian; Ried, Janina S; Peters, Annette; Fortier, Isabel; de Geus, Eco JC; Klovins, Janis; Zaharenko, Linda; Willemsen, Gonneke; Hottenga, Jouke-Jan; Litton, Jan-Eric; Karvanen, Juha; Boomsma, Dorret I; Groop, Leif; Rung, Johan; Palmgren, Juni; Pedersen, Nancy L; McCarthy, Mark I; van Duijn, Cornelia M; Hveem, Kristian; Metspalu, Andres; Ripatti, Samuli; Prokopenko, Inga; Harris, Jennifer R

    2016-01-01

    A wealth of biospecimen samples are stored in modern globally distributed biobanks. Biomedical researchers worldwide need to be able to combine the available resources to improve the power of large-scale studies. A prerequisite for this effort is to be able to search and access phenotypic, clinical and other information about samples that are currently stored at biobanks in an integrated manner. However, privacy issues together with heterogeneous information systems and the lack of agreed-upon vocabularies have made specimen searching across multiple biobanks extremely challenging. We describe three case studies where we have linked samples and sample descriptions in order to facilitate global searching of available samples for research. The use cases include the ENGAGE (European Network for Genetic and Genomic Epidemiology) consortium comprising at least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetes tools) consortium and a pilot for data integration between a Swedish clinical health registry and a biobank. We used the Sample avAILability (SAIL) method for data linking: first, created harmonised variables and then annotated and made searchable information on the number of specimens available in individual biobanks for various phenotypic categories. By operating on this categorised availability data we sidestep many obstacles related to privacy that arise when handling real values and show that harmonised and annotated records about data availability across disparate biomedical archives provide a key methodological advance in pre-analysis exchange of information between biobanks, that is, during the project planning phase. PMID:26306643

  7. Harmonising and linking biomedical and clinical data across disparate data archives to enable integrative cross-biobank research.

    PubMed

    Spjuth, Ola; Krestyaninova, Maria; Hastings, Janna; Shen, Huei-Yi; Heikkinen, Jani; Waldenberger, Melanie; Langhammer, Arnulf; Ladenvall, Claes; Esko, Tõnu; Persson, Mats-Åke; Heggland, Jon; Dietrich, Joern; Ose, Sandra; Gieger, Christian; Ried, Janina S; Peters, Annette; Fortier, Isabel; de Geus, Eco J C; Klovins, Janis; Zaharenko, Linda; Willemsen, Gonneke; Hottenga, Jouke-Jan; Litton, Jan-Eric; Karvanen, Juha; Boomsma, Dorret I; Groop, Leif; Rung, Johan; Palmgren, Juni; Pedersen, Nancy L; McCarthy, Mark I; van Duijn, Cornelia M; Hveem, Kristian; Metspalu, Andres; Ripatti, Samuli; Prokopenko, Inga; Harris, Jennifer R

    2016-04-01

    A wealth of biospecimen samples are stored in modern globally distributed biobanks. Biomedical researchers worldwide need to be able to combine the available resources to improve the power of large-scale studies. A prerequisite for this effort is to be able to search and access phenotypic, clinical and other information about samples that are currently stored at biobanks in an integrated manner. However, privacy issues together with heterogeneous information systems and the lack of agreed-upon vocabularies have made specimen searching across multiple biobanks extremely challenging. We describe three case studies where we have linked samples and sample descriptions in order to facilitate global searching of available samples for research. The use cases include the ENGAGE (European Network for Genetic and Genomic Epidemiology) consortium comprising at least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetes tools) consortium and a pilot for data integration between a Swedish clinical health registry and a biobank. We used the Sample avAILability (SAIL) method for data linking: first, created harmonised variables and then annotated and made searchable information on the number of specimens available in individual biobanks for various phenotypic categories. By operating on this categorised availability data we sidestep many obstacles related to privacy that arise when handling real values and show that harmonised and annotated records about data availability across disparate biomedical archives provide a key methodological advance in pre-analysis exchange of information between biobanks, that is, during the project planning phase. PMID:26306643

  8. Horizontal gene transfer in eukaryotes: The weak-link model

    PubMed Central

    Huang, Jinling

    2013-01-01

    The significance of horizontal gene transfer (HGT) in eukaryotic evolution remains controversial. Although many eukaryotic genes are of bacterial origin, they are often interpreted as being derived from mitochondria or plastids. Because of their fixed gene pool and gene loss, however, mitochondria and plastids alone cannot adequately explain the presence of all, or even the majority, of bacterial genes in eukaryotes. Available data indicate that no insurmountable barrier to HGT exists, even in complex multicellular eukaryotes. In addition, the discovery of both recent and ancient HGT events in all major eukaryotic groups suggests that HGT has been a regular occurrence throughout the history of eukaryotic evolution. A model of HGT is proposed that suggests both unicellular and early developmental stages as likely entry points for foreign genes into multicellular eukaryotes. PMID:24037739

  9. Linking Air Quality and Watershed Models for Environmental Assessments: Analysis of the Effects of Model-Specific Precipitation Estimates on Calculated Water Flux

    EPA Science Inventory

    Directly linking air quality and watershed models could provide an effective method for estimating spatially-explicit inputs of atmospheric contaminants to watershed biogeochemical models. However, to adequately link air and watershed models for wet deposition estimates, each mod...

  10. Simulating the link between ENSO and summer drought in Southern Africa using regional climate models

    NASA Astrophysics Data System (ADS)

    Meque, Arlindo; Abiodun, Babatunde J.

    2015-04-01

    This study evaluates the capability of regional climate models (RCMs) in simulating the link between El Niño Southern Oscillation (ENSO) and Southern African droughts. It uses the Standardized Precipitation-Evapotranspiration Index (SPEI, computed using rainfall and temperature data) to identify 3-month drought over Southern Africa, and compares the observed and simulated correlation between ENSO and SPEI. The observation data are from the Climate Research Unit, while the simulation data are from ten RCMs (ARPEGE, CCLM, HIRHAM, RACMO, REMO, PRECIS, RegCM3, RCA, WRF, and CRCM) that participated in the regional climate downscaling experiment (CORDEX) project. The study analysed the rainy season (December-February) data for 19 years (1989-2008). The results show a strong link between ENSO and droughts (SPEI) over Southern Africa. The link is owing to the influence of ENSO on both rainfall and temperature fields, but the correlation between ENSO and temperature is stronger than the correlation between ENSO and rainfall. Hence, using only rainfall to monitor droughts in Southern Africa may underestimate the influence of ENSO on the droughts. Only few CORDEX RCMs simulate the influence of ENSO on Southern African drought as observed. In this regard, the ARPEGE model shows the best simulation, while CRCM shows the worst. The different in the performance may be due to their lateral boundary conditions. The RCA-simulated link between ENSO and Southern African droughts is sensitive to the global dataset used as the lateral boundary conditions. In some cases, using RCA to downscale global circulation models (GCM) simulations adds value to the simulated link between ENSO and the droughts, but in other cases the downscaling adds no value to the link. The added value of RCA to the simulated link decreases as the capability of the GCM to simulate the link increases. This study suggests that downscaling GCM simulations with RCMs over Southern Africa may improve or depreciate the

  11. Linking personality disorders and clinical syndromes on the MCMI-III.

    PubMed

    Haddy, Christopher; Strack, Stephen; Choca, James P

    2005-04-01

    We examined the relationship between personality disorders (PDs) and clinical syndromes (CSs) as measured by the Millon Clinical Multiaxial Inventory-III (MCMI-III; Millon, 1997) in a large, heterogeneous sample of psychiatric patients (N = 2,366) who completed the instrument as part of routine assessment following presentation for treatment. Using separate sets of base rate (BR) and nonoverlapping scale scores, we factor analyzed the PD and CS scales together and then separately. We correlated results from the latter analyses to determine how trait dimensions were associated with syndrome dimensions. We also studied co-occurrence at the scale level by examining CS score profiles of patients who were grouped according to their highest PD scale elevation > or = BR75. Results for the two score sets were very similar and were consistent with previous research on the MCMI-III and its predecessors that identified 3 underlying dimensions loading both PD and CS scales. Three fourths (76.2%) of the sample had a highest PD scale > or = BR75, and among these, 90% had at least 1 CS scale > or = BR75, whereas 62.4% had 3 or more CS scales above this elevation. Findings underscore the substantial overlap between PDs and CSs along 3 dimensions that resemble Horney's (1945) tripartite interpersonal distinction of moving toward, away, and against, as well as Eysenck's (1994) higher order factors of neuroticism, extraversion, and psychoticism. PMID:15799894

  12. A model linking biology, behavior and psychiatric diagnoses in perpetrators of domestic violence.

    PubMed

    George, David T; Phillips, Monte J; Doty, Linda; Umhau, John C; Rawlings, Robert R

    2006-01-01

    Research indicates that perpetrators of domestic violence have abnormalities in central serotonin and testosterone metabolism, an increased sensitivity to anxiogenic stimuli, and an impaired neuro-connection between their cortex and the amygdala. Clinical evaluations show that perpetrators of domestic violence also have a distinguishing set of behaviors and diagnoses related to anxiety, depression, intermittent explosive disorder, and borderline personality disorder. In this paper we propose a model to understand how the biological abnormalities can potentially explain the behaviors and diagnoses exhibited by the perpetrators. Changes in the perpetrator's neurotransmitters lead to a heightened sensitivity to environmental stimuli, anxiety, and conditioned fear. Lack of cortical input to the amygdala impairs the perpetrator's ability to extinguish anxiety and/or conditioned fear and gives rise to either innate behaviors (e.g., fight, flight, and shut down) or learned fear avoidant behaviors designed to avoid anxiety (e.g., alcohol consumption, self-injurious acts, and obsessive behaviors). Linking conditioned fear and fear avoidance to the behaviors and psychiatric diagnoses will serve to change the way the medical community perceives and treats perpetrators of domestic violence. PMID:16580153

  13. Modelling soil nitrogen: the MAGIC model with nitrogen retention linked to carbon turnover using decomposer dynamics.

    PubMed

    Oulehle, F; Cosby, B J; Wright, R F; Hruška, J; Kopáček, J; Krám, P; Evans, C D; Moldan, F

    2012-06-01

    We present a new formulation of the acidification model MAGIC that uses decomposer dynamics to link nitrogen (N) cycling to carbon (C) turnover in soils. The new model is evaluated by application to 15-30 years of water chemistry data at three coniferous-forested sites in the Czech Republic where deposition of sulphur (S) and N have decreased by >80% and 40%, respectively. Sulphate concentrations in waters have declined commensurately with S deposition, but nitrate concentrations have shown much larger decreases relative to N deposition. This behaviour is inconsistent with most conceptual models of N saturation, and with earlier versions of MAGIC which assume N retention to be a first-order function of N deposition and/or controlled by the soil C/N ratio. In comparison with earlier versions, the new formulation more correctly simulates observed short-term changes in nitrate leaching, as well as long-term retention of N in soils. The model suggests that, despite recent deposition reductions and recovery, progressive N saturation will lead to increased future nitrate leaching, ecosystem eutrophication and re-acidification. PMID:22459669

  14. Convective rain cell modelling from radar data and their linking with a hydrological model

    NASA Astrophysics Data System (ADS)

    Morin, E.; Yakir, H.

    2009-04-01

    The technology of weather radar systems enables a detailed view of rainstorms over watersheds with high spatial and temporal resolution that was never available before. Nevertheless, the utilization of radar rainfall data in hydrological models has not brought a significant improvement in understanding rainfall-runoff processes, and in prediction capability of watershed responses. There is a need to develop new ways to exploit essential information about spatio-temporal rain structures, and gain greater insights into rainfall and subsequent watershed response behavior. The current study suggests an innovative approach to the above challenge. We emphasize as a key issue the structure in which the data are represented in the hydrological models. Whereas in the standard approach, radar data are utilized in a grid structure, we propose to represent the rainfall data in a model-structure that takes into account the known behavior and properties of the rain system. The spatial and temporal characteristics of the rain system are thus explicitly represented and are linked directly to hydrological responses. The basic distinction between the grid and the currently suggested data model-structures is the presence of a-priori knowledge about the represented system incorporated into the model. The above approach was applied in the analysis of a large flood event in a semi-arid catchment in southern Israel. A model representing the spatio-temporal structure of the derived rain cells was developed and fitted to the radar data. The hydrological model was then fed by the rain cell information rather than the gridded radar data. Using this direct linkage between rain cell features and hydrological features the main controls of the generated flood were determined.

  15. An information-theoretic model for link prediction in complex networks

    NASA Astrophysics Data System (ADS)

    Zhu, Boyao; Xia, Yongxiang

    2015-09-01

    Various structural features of networks have been applied to develop link prediction methods. However, because different features highlight different aspects of network structural properties, it is very difficult to benefit from all of the features that might be available. In this paper, we investigate the role of network topology in predicting missing links from the perspective of information theory. In this way, the contributions of different structural features to link prediction are measured in terms of their values of information. Then, an information-theoretic model is proposed that is applicable to multiple structural features. Furthermore, we design a novel link prediction index, called Neighbor Set Information (NSI), based on the information-theoretic model. According to our experimental results, the NSI index performs well in real-world networks, compared with other typical proximity indices.

  16. An information-theoretic model for link prediction in complex networks

    PubMed Central

    Zhu, Boyao; Xia, Yongxiang

    2015-01-01

    Various structural features of networks have been applied to develop link prediction methods. However, because different features highlight different aspects of network structural properties, it is very difficult to benefit from all of the features that might be available. In this paper, we investigate the role of network topology in predicting missing links from the perspective of information theory. In this way, the contributions of different structural features to link prediction are measured in terms of their values of information. Then, an information-theoretic model is proposed that is applicable to multiple structural features. Furthermore, we design a novel link prediction index, called Neighbor Set Information (NSI), based on the information-theoretic model. According to our experimental results, the NSI index performs well in real-world networks, compared with other typical proximity indices. PMID:26335758

  17. [X-linked hyper-IGM syndrome associated to sclerosing cholangitis and gallbladder neoplasm: clinical case].

    PubMed

    Rodríguez, Cristián; Carrión, Flavio; Marinovic, María Angélica; Chávez, Eduardo; Preisler, Jessica; Pooley, Francisco; Futatani, Takeshi; Ochs, Hans D

    2003-03-01

    We report a 11 years old male diagnosed as a X-linked hyper-IgM syndrome that presented with recurrent infections and sclerosing cholangitis and later developed a gallbladder cancer. Immunological evaluation showed decreased levels of serum IgG and IgA with elevated levels of IgM. Study of CD40 ligand expression on mitogen activated peripheral blood mononuclear cells revealed total absence of this marker on T lymphocytes. Molecular analysis detected, in the patient and his mother, a nonsense mutation in exon 1 of the transmembrane segment of the CD40 ligand. He also presented elevation of alkaline phosphatases and mild elevation of liver enzymes. Liver biopsy demonstrated the presence of idiopathic sclerosing cholangitis. The patient was started on monthly IVIG therapy at 400 mg/kg, as well as ursodeoxycholic acid and vitamin E, with normalization of his IgG and IgM levels a decrease in the incidence of infections and normalization of liver function. Three years after diagnosis, we detected the presence of polyps inside the gallbladder that were reported at biopsy as adenocarcinoma. He underwent hepatic bisegmentectomy (VI B-V) and local lymphadenectomy. PMID:12790080

  18. A methodology for linking 2D overland flow models with the sewer network model SWMM 5.1 based on dynamic link libraries.

    PubMed

    Leandro, Jorge; Martins, Ricardo

    2016-01-01

    Pluvial flooding in urban areas is characterized by a gradually varying inundation process caused by surcharge of the sewer manholes. Therefore urban flood models need to simulate the interaction between the sewer network and the overland flow in order to accurately predict the flood inundation extents. In this work we present a methodology for linking 2D overland flow models with the storm sewer model SWMM 5. SWMM 5 is a well-known free open-source code originally developed in 1971. The latest major release saw its structure re-written in C ++ allowing it to be compiled as a command line executable or through a series of calls made to function inside a dynamic link library (DLL). The methodology developed herein is written inside the same DLL in C + +, and is able to simulate the bi-directional interaction between both models during simulation. Validation is done in a real case study with an existing urban flood coupled model. The novelty herein is that the new methodology can be added to SWMM without the need for editing SWMM's original code. Furthermore, it is directly applicable to other coupled overland flow models aiming to use SWMM 5 as the sewer network model. PMID:27332848

  19. HIV research in Australia: linking basic research findings with clinical and public health outcomes

    PubMed Central

    Lewin, Sharon R; Kaldor, John M; Cooper, David A

    2006-01-01

    Despite a population of only 20 million and sustained low prevalence of HIV infection in Australia, Australian researchers have provided many substantial original findings to the fields of HIV pathogenesis, treatment and prevention. More recently, Australian clinicians and scientists have turned their attention to assisting other countries in developing effective responses, particularly within the Asia-Pacific region. It is therefore fitting that the 4th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention will be held in Sydney in July 2007. The meeting is expected to attract over 5000 participants and will have a dynamic and innovative programme within the three major themes of HIV basic science, clinical research and biomedical prevention. PMID:17140433

  20. Prime Time: Long-Term Sexual Health Outcomes of a Clinic-Linked Intervention

    PubMed Central

    Sieving, Renee E.; McRee, Annie-Laurie; Secor-Turner, Molly; Garwick, Ann W.; Bearinger, Linda H.; Beckman, Kara J.; McMorris, Barbara J.; Resnick, Michael D.

    2015-01-01

    CONTEXT Evidence about long-term effects of preventive health services for youth with complex needs is lacking. Prime Time, a youth development intervention, aims to reduce pregnancy risk among vulnerable adolescent females seeking clinic services. METHODS In a randomized trial, 253 sexually active females aged 13–17 who were at high risk for pregnancy were assigned to the Prime Time intervention or usual clinic services. The 18-month intervention, initiated in 2007–2008, comprised regular meetings with case managers and participation in youth leadership groups. Trial participants completed surveys at baseline and 30 months. Regression analyses were used to evaluate differences between groups in sexual and psychosocial outcomes at follow-up. RESULTS At 30 months, the intervention group reported more months of consistent condom use (adjusted means, 1.8 vs. 1.1) and dual contraceptive use (0.9 vs. 0.3) in the past seven months than did controls. The intervention was most effective in promoting consistent use among participants with relatively high levels of connectedness to family or school. Fifteen percent of intervention participants, but only 6% of controls, reported having abstained from sex in the past six months (adjusted odds ratio, 2.9). Moreover, among high school graduates, those in the intervention group were more likely than those in the control group to have enrolled in college or technical school (72% vs. 37%; odds ratio, 4.5). CONCLUSION Health services grounded in a youth development framework can lead to reductions in sexual risk among vulnerable youth that are evident one year following conclusion of services. PMID:24650164

  1. Computer modeling and analysis of thermal link performance for an optical refrigerator

    NASA Astrophysics Data System (ADS)

    Byram, Kevin; Mar, David; Parker, John; Von der Porten, Steven; Hankinson, John; Lee, Chris; Mayeda, Kai; Haskell, Richard C.; Yang, Qimin; Greenfield, Scott R.; Epstein, Richard I.

    2008-02-01

    We have used the thermal modeling tool in COMSOL Multiphysics to investigate factors that affect the thermal performance of the optical refrigerator. Assuming an ideal cooling element and a non-absorptive dielectric trapping mirror, the three dominant heating factors are blackbody radiation from the surrounding environment, conductive heat transfer through mechanical supports, and the absorption of fluoresced photons transmitted through the thermal link. Laboratory experimentation coupled with computer modeling using Code V optical software have resulted in link designs capable of reducing the transmission to 0.04% of the fluoresced photons emitted toward the thermal link. The ideal thermal link will have minimal surface area, provide complete optical isolation for the load, and possess high thermal conductivity. Modeling results imply that a 1cm 3 load can be chilled to 102 K with currently available cooling efficiencies using a 100 W pump laser on a YB:ZBLANP system, and using an ideal link that has minimal surface area and no optical transmission. We review the simulated steady-state cooling temperatures reached by the heat load for several link designs and system configurations as a comparative measure of how well particular configurations perform.

  2. The Hillman Rotation: An External Clinic Model.

    ERIC Educational Resources Information Center

    Sears, Joan M.; Veith, Jack

    2000-01-01

    Describes the external optometric education program at the Sidney Hillman Health Centre (Chicago, Illinois). Discusses the history of the clinic, its administrative and educational philosophy, and its affiliation with two prominent hospitals and the Illinois College of Optometry. (DB)

  3. A Simple Forecasting Model Linking Macroeconomic Policy to Industrial Employment Demand.

    ERIC Educational Resources Information Center

    Malley, James R.; Hady, Thomas F.

    A study detailed further a model linking monetary and fiscal policy to industrial employment in metropolitan and nonmetropolitan areas of four United States regions. The model was used to simulate the impacts on area and regional employment of three events in the economy: changing real gross national product (GNP) via monetary policy, holding the…

  4. Reproduction of links between circulation types and precipitation in Central Europe in regional climate model simulations

    NASA Astrophysics Data System (ADS)

    Plavcová, Eva; Kyselý, Jan; Štěpánek, Petr

    2014-05-01

    The study evaluates relationships between large-scale atmospheric circulation (represented by circulation indices and circulation types derived from gridded mean sea level pressure) and daily precipitation amounts over three regions in the Czech Republic (Central Europe) with different precipitation regimes. We examine how ENSEMBLES regional climate model (RCM) simulations driven by re-analysis reproduce the observed links and capture differences in the links between the regions (lowlands vs. highlands) and seasons. We study the links of circulation to (i) mean precipitation over the regions, (ii) probability of wet days, and (iii) probability of extreme daily precipitation (exceeding threshold defined by a high quantile of precipitation distribution in a given season). Relatively strong links between atmospheric circulation and the precipitation characteristics are found in the observed data. The links are generally more pronounced for highland than lowland regions. More wet days and higher precipitation amounts are found for cyclonic and stronger flows, and for westerly and north-easterly flows. The RCMs are generally able to capture basic features of the links; nevertheless, they have difficulties to reproduce some more specific features and differences in the links between the regions. The results also suggest that good performance in some precipitation characteristics may be due to compensating errors rather than model's perfection. Reference: Plavcová E., Kyselý J., Štěpánek P., 2014: Links between circulation types and precipitation in Central Europe in the observed data and regional climate model simulations. International Journal of Climatology, doi 10.1002/joc.3882.

  5. Ferroportin diseases: functional studies, a link between genetic and clinical phenotype.

    PubMed

    Détivaud, Lénaïck; Island, Marie-Laure; Jouanolle, Anne-Marie; Ropert, Martine; Bardou-Jacquet, Edouard; Le Lan, Caroline; Mosser, Annick; Leroyer, Patricia; Deugnier, Yves; David, Véronique; Brissot, Pierre; Loréal, Olivier

    2013-11-01

    Ferroportin (FPN) mediates iron export from cells and this function is modulated by serum hepcidin. Mutations in the FPN gene (SLC40A1) lead to autosomal dominant iron overload diseases related either to loss or to gain of function, and usually characterized by normal or low transferrin saturation versus elevated transferrin saturation, respectively. However, for the same mutation, the phenotypic expression may vary from one patient to another. Using in vitro overexpression of wild-type or mutant FPN proteins, we characterized the functional impact of five recently identified FPN gene mutations regarding FPN localization, cell iron status, and hepcidin sensitivity. Our aim was to integrate functional results and biological findings in probands and relatives. We show that while the p.Arg371Gln (R371Q) mutation had no impact on studied parameters, the p.Trp158Leu (W158L), p.Arg88Gly (R88G), and p.Asn185Asp (N185D) mutations caused an iron export defect and were classified as loss-of-function mutations. The p.Gly204Ser (G204S) mutation induced a gain of FPN function. Functional studies are useful to determine whether or not a FPN gene mutation found in an iron overloaded patient is deleterious and to characterize its biological impact, especially when family studies are not fully informative and/or additional confounding factors may affect bio-clinical expression. PMID:23943237

  6. Oxidative stress and the use of antioxidants in diabetes: Linking basic science to clinical practice

    PubMed Central

    Johansen, Jeanette Schultz; Harris, Alex K; Rychly, David J; Ergul, Adviye

    2005-01-01

    Cardiovascular complications, characterized by endothelial dysfunction and accelerated atherosclerosis, are the leading cause of morbidity and mortality associated with diabetes. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Overproduction and/or insufficient removal of these free radicals result in vascular dysfunction, damage to cellular proteins, membrane lipids and nucleic acids. Despite overwhelming evidence on the damaging consequences of oxidative stress and its role in experimental diabetes, large scale clinical trials with classic antioxidants failed to demonstrate any benefit for diabetic patients. As our understanding of the mechanisms of free radical generation evolves, it is becoming clear that rather than merely scavenging reactive radicals, a more comprehensive approach aimed at preventing the generation of these reactive species as well as scavenging may prove more beneficial. Therefore, new strategies with classic as well as new antioxidants should be implemented in the treatment of diabetes. PMID:15862133

  7. The clinical practice developmental model: the transition process.

    PubMed

    Nuccio, S A; Lingen, D; Burke, L J; Kramer, A; Ladewig, N; Raaum, J; Shearer, B

    1996-12-01

    The authors report their hospital's experience in replicating Benner's novice-to-expert clinical nursing practice model, called the Clinical Practice Developmental Model. The authors describe the outcomes of an exploratory, qualitative study conducted to understand staff nurses' perceptions of their transition experience from a traditional clinical ladder for advancement and recognition to the theoretically based clinical practice developmental model. The findings of this study identify critical factors that influenced nurses' perceptions and describe positive and negative outcomes of transition. Specific recommendations to facilitate organizational changes for the nurse executive and the individual nurse are discussed. PMID:8968322

  8. Integration of Evidence into a Detailed Clinical Model-based Electronic Nursing Record System

    PubMed Central

    Park, Hyeoun-Ae; Jeon, Eunjoo; Chung, Eunja

    2012-01-01

    Objectives The purpose of this study was to test the feasibility of an electronic nursing record system for perinatal care that is based on detailed clinical models and clinical practice guidelines in perinatal care. Methods This study was carried out in five phases: 1) generating nursing statements using detailed clinical models; 2) identifying the relevant evidence; 3) linking nursing statements with the evidence; 4) developing a prototype electronic nursing record system based on detailed clinical models and clinical practice guidelines; and 5) evaluating the prototype system. Results We first generated 799 nursing statements describing nursing assessments, diagnoses, interventions, and outcomes using entities, attributes, and value sets of detailed clinical models for perinatal care which we developed in a previous study. We then extracted 506 recommendations from nine clinical practice guidelines and created sets of nursing statements to be used for nursing documentation by grouping nursing statements according to these recommendations. Finally, we developed and evaluated a prototype electronic nursing record system that can provide nurses with recommendations for nursing practice and sets of nursing statements based on the recommendations for guiding nursing documentation. Conclusions The prototype system was found to be sufficiently complete, relevant, useful, and applicable in terms of content, and easy to use and useful in terms of system user interface. This study has revealed the feasibility of developing such an ENR system. PMID:22844649

  9. Cumulative t-link threshold models for the genetic analysis of calving ease scores

    PubMed Central

    Kizilkaya, Kadir; Carnier, Paolo; Albera, Andrea; Bittante, Giovanni; Tempelman, Robert J

    2003-01-01

    In this study, a hierarchical threshold mixed model based on a cumulative t-link specification for the analysis of ordinal data or more, specifically, calving ease scores, was developed. The validation of this model and the Markov chain Monte Carlo (MCMC) algorithm was carried out on simulated data from normally and t4 (i.e. a t-distribution with four degrees of freedom) distributed populations using the deviance information criterion (DIC) and a pseudo Bayes factor (PBF) measure to validate recently proposed model choice criteria. The simulation study indicated that although inference on the degrees of freedom parameter is possible, MCMC mixing was problematic. Nevertheless, the DIC and PBF were validated to be satisfactory measures of model fit to data. A sire and maternal grandsire cumulative t-link model was applied to a calving ease dataset from 8847 Italian Piemontese first parity dams. The cumulative t-link model was shown to lead to posterior means of direct and maternal heritabilities (0.40 ± 0.06, 0.11 ± 0.04) and a direct maternal genetic correlation (-0.58 ± 0.15) that were not different from the corresponding posterior means of the heritabilities (0.42 ± 0.07, 0.14 ± 0.04) and the genetic correlation (-0.55 ± 0.14) inferred under the conventional cumulative probit link threshold model. Furthermore, the correlation (> 0.99) between posterior means of sire progeny merit from the two models suggested no meaningful rerankings. Nevertheless, the cumulative t-link model was decisively chosen as the better fitting model for this calving ease data using DIC and PBF. PMID:12939202

  10. Links between the spatial structure of weather generator and hydrological modeling

    NASA Astrophysics Data System (ADS)

    Li, Zhi; Lü, Zhemin; Li, Jingjing; Shi, Xiaoping

    2015-12-01

    Impacts of the spatial structure of weather generators on hydrological modeling have been largely qualitatively discussed; however, their links have been rarely quantified. The precipitation occurrence and amount were respectively generated with Markov chain and the mixed exponential distribution for single sites, and then the procedures were extended to multi-site simulation according to Wilks (1998). In the multi-site model, precipitation amounts were respectively generated with untapered or tapered mixed exponential scale parameters. The generated precipitation series were used as inputs of Soil and Water Assessment Tool (SWAT) to interpret the links between the spatial structure of weather generators and hydrological modeling. The single-site and multi-site model using untapered scale parameters gave similar averages for monthly and annual streamflow; however, the untapered multi-site model was superior to simulating hydrological variability. The single-site model underestimated the maxima and variances while overestimated the minima of streamflow; therefore, the use of single-site models for hydrological variability simulation should be cautious. The multi-site model using tapered scale parameters greatly overestimated the averages, extremes, and variances of streamflow. The Wilks model for multi-site precipitation simulation using tapered scale parameters is not appropriate for hydrological modeling, and the untapered version is thus recommended. Overall, the spatial structure of weather generators has significant impacts on hydrological modeling, especially for hydrological variability simulation; therefore, the links between them should be paid great attentions.

  11. Model-driven CDA Clinical Document Development Framework.

    PubMed

    Li, Jingdong; Lincoln, Michael J

    2007-01-01

    The Health Level 7 (HL7) Clinical Document Architecture, Release 2 (CDA R2) standardizes the structure and semantics of clinical documents in order to permit interchange. We have applied this standard to generate a platform independent CDA model and write a toolset that permits model specialization, generation of XML implementation artifacts, and provides an interface for clinical data managers. The resulting work was tested using US Department of Veterans Affairs Operative Note templates. PMID:18694129

  12. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management

    PubMed Central

    2012-01-01

    X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. The disease is caused by mutations in the ABCD1 gene that encodes the peroxisomal membrane protein ALDP which is involved in the transmembrane transport of very long-chain fatty acids (VLCFA; ≥C22). A defect in ALDP results in elevated levels of VLCFA in plasma and tissues. The clinical spectrum in males with X-ALD ranges from isolated adrenocortical insufficiency and slowly progressive myelopathy to devastating cerebral demyelination. The majority of heterozygous females will develop symptoms by the age of 60 years. In individual patients the disease course remains unpredictable. This review focuses on the diagnosis and management of patients with X-ALD and provides a guideline for clinicians that encounter patients with this highly complex disorder. PMID:22889154

  13. Blood Group O-Dependent Cellular Responses to Cholera Toxin: Parallel Clinical and Epidemiological Links to Severe Cholera.

    PubMed

    Kuhlmann, F Matthew; Santhanam, Srikanth; Kumar, Pardeep; Luo, Qingwei; Ciorba, Matthew A; Fleckenstein, James M

    2016-08-01

    Because O blood group has been associated with more severe cholera infections, it has been hypothesized that cholera toxin (CT) may bind non-O blood group antigens of the intestinal mucosae, thereby preventing efficient interaction with target GM1 gangliosides required for uptake of the toxin and activation of cyclic adenosine monophosphate (cAMP) signaling in target epithelia. Herein, we show that after exposure to CT, human enteroids expressing O blood group exhibited marked increase in cAMP relative to cells derived from blood group A individuals. Likewise, using CRISPR/Cas9 engineering, a functional group O line (HT-29-A(-/-)) was generated from a parent group A HT-29 line. CT stimulated robust cAMP responses in HT-29-A(-/-) cells relative to HT-29 cells. These findings provide a direct molecular link between blood group O expression and differential cellular responses to CT, recapitulating clinical and epidemiologic observations. PMID:27162272

  14. African American Women's Perceptions and Attitudes Regarding Participation in Medical Research: The Mayo Clinic/The Links, Incorporated Partnership

    PubMed Central

    Brewer, LaPrincess C.; Parker, Monica W.; Balls-Berry, Joyce E.; Halyard, Michele Y.; Pinn, Vivian W.; Radecki Breitkopf, Carmen

    2014-01-01

    Abstract Objective: To examine perceptions and attitudes toward health-related research participation among professional African American women. Methods: Participants were members of an African American women's service organization, The Links, Incorporated. Data were collected via self-administered questionnaires at The Links, Incorporated 2012 National Assembly. Sociodemographics, prior research experience, intention to participate (ITP), willingness to participate (WTP) in a variety of research studies and attitudes about research participation were measured. Results: A total of 381 surveys were analyzed. A majority of respondents were married (66%), employed (69%), and college educated (96%). Median age was 59; 38% reported prior research participation. Overall, 78% agreed with the statement, “Participation in research will mean better care,” 24% agreed “Participation in research is risky” and 3% agreed “Scientists cannot be trusted.” Fifty-two percent agreed with the statement, “Research conducted in the U.S. is ethical.” Mean ITP in research was 4.9±1.7 on a rating scale of 1 (“definitely no”) to 7 (“definitely yes”). WTP was highest for an interview study and providing a blood sample, and lowest for clinical trial and medical record review. Conclusion: Attitudes toward research participation were generally favorable among professional African American women; many expressed WTP in a variety of research study types. PMID:25046058

  15. Modeling Flowsheet Data for Clinical Research.

    PubMed

    Johnson, Steven G; Byrne, Matthew D; Christie, Beverly; Delaney, Connie W; LaFlamme, Anne; Park, Jung In; Pruinelli, Lisiane; Sherman, Suzan G; Speedie, Stuart; Westra, Bonnie L

    2015-01-01

    Health care data included in clinical data repositories (CDRs) are increasingly used for quality reporting, business analytics and research; however, extended clinical data from interprofessional practice are seldom included. With the increasing emphasis on care coordination across settings, CDRs need to include data from all clinicians and be harmonized to understand the impact of their collaborative efforts on patient safety, effectiveness and efficiency. This study characterizes the extended clinical data derived from EHR flowsheet data that is available in the University of Minnesota's CDR and describes a process for creating an ontology that organizes that data so that it is more useful and accessible to researchers. The process is illustrated using a pressure ulcer ontology and compares ease of finding concepts in i2b2 for different data organization approaches. The challenges of the manual process and difficulties combining similar concepts are discussed. PMID:26306244

  16. Modeling Flowsheet Data for Clinical Research

    PubMed Central

    Johnson, Steven G.; Byrne, Matthew D.; Christie, Beverly; Delaney, Connie W.; LaFlamme, Anne; Park, Jung In; Pruinelli, Lisiane; Sherman, Suzan G.; Speedie, Stuart; Westra, Bonnie L.

    2015-01-01

    Health care data included in clinical data repositories (CDRs) are increasingly used for quality reporting, business analytics and research; however, extended clinical data from interprofessional practice are seldom included. With the increasing emphasis on care coordination across settings, CDRs need to include data from all clinicians and be harmonized to understand the impact of their collaborative efforts on patient safety, effectiveness and efficiency. This study characterizes the extended clinical data derived from EHR flowsheet data that is available in the University of Minnesota’s CDR and describes a process for creating an ontology that organizes that data so that it is more useful and accessible to researchers. The process is illustrated using a pressure ulcer ontology and compares ease of finding concepts in i2b2 for different data organization approaches. The challenges of the manual process and difficulties combining similar concepts are discussed. PMID:26306244

  17. Venous Thrombosis and Cancer: from Mouse Models to Clinical Trials

    PubMed Central

    Hisada, Y.; Geddings, J. E.; Ay, C.; Mackman, N.

    2015-01-01

    Cancer patients have a ~4 fold increased risk of venous thromboembolism (VTE) compared with the general population and this is associated with significant morbidity and mortality. This review summarizes our current knowledge of VTE and cancer from mouse models to clinical studies. Notably, risk of VTE varies depending on the type and stage of cancer. For instance, pancreatic and brain cancer patients have a higher risk of VTE than breast and prostate cancer patients. Moreover, patients with metastatic disease have a higher risk than those with localized tumors. Tumor-derived procoagulant factors and growth factors may directly and indirectly enhance VTE. For example, increased levels of circulating tumor-derived, tissue factor-positive microvesicles may trigger VTE. In a mouse model of ovarian cancer, tumor-derived IL-6 and hepatic thrombopoietin has been linked to increased platelet production and thrombosis. In addition, mouse models of mammary and lung cancer showed that tumor-derived granulocyte colony-stimulating factor causes neutrophilia and activation of neutrophils. Activated neutrophils can release neutrophil extracellular traps (NETs) that enhance thrombosis. Cell-free DNA in the blood derived from cancer cells, NETs and treatment with cytotoxic drugs can activate the clotting cascade. These studies suggest that there are multiple mechanisms for VTE in patients with different types of cancer. Preventing and treating VTE in cancer patients is challenging; the current recommendations are to use low molecular weight heparin. Understanding the underlying mechanisms may allow the development of new therapies to safely prevent VTE in cancer patients. PMID:25988873

  18. Unscheduled-Return-Visits after an Emergency Department (ED) Attendance and Clinical Link between Both Visits in Patients Aged 75 Years and Over: A Prospective Observational Study

    PubMed Central

    Pereira, Laurent; Choquet, Christophe; Perozziello, Anne; Wargon, Mathias; Juillien, Gaelle; Colosi, Luisa; Hellmann, Romain; Ranaivoson, Michel; Casalino, Enrique

    2015-01-01

    Background Predictors of unscheduled return visits (URV), best time-frame to evaluate URV rate and clinical relationship between both visits have not yet been determined for the elderly following an ED visit. Methods We conducted a prospective-observational study including 11,521 patients aged ≥75-years and discharged from ED (5,368 patients (53.5%)) or hospitalized after ED visit (6,153 patients). Logistic Regression and time-to-failure analyses including Cox proportional model were performed. Results Mean time to URV was 17 days; 72-hour, 30-day and 90-day URV rates were 1.8%, 6.1% and 10% respectively. Multivariate analysis indicates that care-pathway and final disposition decisions were significantly associated with a 30-day URV. Thus, we evaluated predictors of 30-day URV rates among non-admitted and hospitalized patient groups. By using the Cox model we found that, for non-admitted patients, triage acuity and diagnostic category and, for hospitalized patients, that visit time (day, night) and diagnostic categories were significant predictors (p<0.001). For URV, we found that 25% were due to closely related-clinical conditions. Time lapses between both visits constituted the strongest predictor of closely related-clinical conditions. Conclusion Our study shows that a decision of non-admission in emergency departments is linked with an accrued risk of URV, and that some diagnostic categories are also related for non-admitted and hospitalized subjects alike. Our study also demonstrates that the best time frame to evaluate the URV rate after an ED visit is 30 days, because this is the time period during which most URVs and cases with close clinical relationships between two visits are concentrated. Our results suggest that URV can be used as an indicator or quality. PMID:25853822

  19. Cognitive vulnerability to depression: A comparison of the weakest link, keystone and additive models

    PubMed Central

    Reilly, Laura C.; Ciesla, Jeffrey A.; Felton, Julia W.; Weitlauf, Amy S.; Anderson, Nicholas L.

    2014-01-01

    Multiple theories of cognitive vulnerability to depression have been proposed, each focusing on different aspects of negative cognition and utilising different measures of risk. Various methods of integrating such multiple indices of risk have been examined in the literature, and each demonstrates some promise. Yet little is known about the interrelations among these methods, or their incremental validity in predicting changes in depression. The present study compared three integrative models of cognitive vulnerability: the additive, weakest link, and keystone models. Support was found for each model as predictive of depression over time, but only the weakest link model demonstrated incremental utility in predicting changes in depression over the other models. We also explore the correlation between these models and each model’s unique contribution to predicting onset of depressive symptoms. PMID:21851251

  20. Predictive oncology: multidisciplinary, multi-scale in-silico modeling linking phenotype, morphology and growth

    PubMed Central

    Sanga, Sandeep; Frieboes, Hermann B.; Zheng, Xiaoming; Gatenby, Robert; Bearer, Elaine L.; Cristini, Vittorio

    2007-01-01

    Empirical evidence and theoretical studies suggest that the phenotype, i.e., cellular- and molecular-scale dynamics, including proliferation rate and adhesiveness due to microenvironmental factors and gene expression that govern tumor growth and invasiveness, also determine gross tumor-scale morphology. It has been difficult to quantify the relative effect of these links on disease progression and prognosis using conventional clinical and experimental methods and observables. As a result, successful individualized treatment of highly malignant and invasive cancers, such as glioblastoma, via surgical resection and chemotherapy cannot be offered and outcomes are generally poor. What is needed is a deterministic, quantifiable method to enable understanding of the connections between phenotype and tumor morphology. Here, we critically review advantages and disadvantages of recent computational modeling efforts (e.g., continuum, discrete, and cellular automata models) that have pursued this understanding. Based on this assessment, we propose and discuss a multi-scale, i.e., from the molecular to the gross tumor scale, mathematical and computational “first-principle” approach based on mass conservation and other physical laws, such as employed in reaction-diffusion systems. Model variables describe known characteristics of tumor behavior, and parameters and functional relationships across scales are informed from in vitro, in vivo and ex vivo biology. We demonstrate that this methodology, once coupled to tumor imaging and tumor biopsy or cell culture data, should enable prediction of tumor growth and therapy outcome through quantification of the relation between the underlying dynamics and morphological characteristics. In particular, morphologic stability analysis of this mathematical model reveals that tumor cell patterning at the tumor-host interface is regulated by cell proliferation, adhesion and other phenotypic characteristics: histopathology information of

  1. Selection and mutation in X-linked recessive diseases epidemiological model.

    PubMed

    Verrilli, Francesca; Kebriaei, Hamed; Glielmo, Luigi; Corless, Martin; Del Vecchio, Carmen

    2015-08-01

    To describe the epidemiology of X-linked recessive diseases we developed a discrete time, structured, non linear mathematical model. The model allows for de novo mutations (i.e. affected sibling born to unaffected parents) and selection (i.e., distinct fitness rates depending on individual's health conditions). Applying Lyapunov direct method we found the domain of attraction of model's equilibrium point and studied the convergence properties of the degenerate equilibrium where only affected individuals survive. PMID:26737169

  2. Depressive behavior and vascular dysfunction: a link between clinical depression and vascular disease?

    PubMed Central

    d'Audiffret, Alexandre C.; Frisbee, Stephanie J.; Stapleton, Phoebe A.; Goodwill, Adam G.; Isingrini, Elsa

    2010-01-01

    As chronic stress and depression have become recognized as significant risk factors for peripheral vascular disease in patients with no prior history of vasculopathy, we interrogated this relationship utilizing an established mouse model of chronic stress/depressive symptoms from behavioral research. Male mice were exposed to 8 wk of unpredictable chronic mild stress (UCMS; e.g., wet bedding, predator sound/smell, random disruption of light/dark cycle), with indexes of depressive behavior (coat status, grooming, and mobility) becoming exacerbated vs. controls. In vascular rings, constrictor (phenylephrine) and endothelium-independent dilator (sodium nitroprusside) responses were not different between groups, although endothelium-dependent dilation (methacholine) was attenuated with UCMS. Nitric oxide synthase (NOS) inhibition was without effect in UCMS but nearly abolished reactivity in controls, while cyclooxygenase inhibition blunted dilation in both. Combined blockade abolished reactivity in controls, although a significant dilation remained in UCMS that was abolished by catalase. Arterial NO production was attenuated by UCMS, although H2O2 production was increased. UCMS mice demonstrated an increased, although variable, insulin resistance and inflammation. However, while UCMS-induced vascular impairments were consistent, the predictive power of aggregate plasma levels of insulin, TNF-α, IL-1β, and C-reactive peptide were limited. However, when separated into tertiles with regard to vascular outcomes, insulin resistance and hypertension were predictive of the most severe vascular impairments. Taken together, these data suggest that aggregate insulin resistance, inflammation, and hypertension in UCMS mice are not robust predictors of vascular dysfunction, suggesting that unidentified mechanisms may be superior predictors of poor vascular outcomes in this model. PMID:20167667

  3. Linking rainfall and irrigation to clinically reported malaria cases in some villages in Chikhwawa District, Malawi

    NASA Astrophysics Data System (ADS)

    Kalinga-Chirwa, Ruth; Ngongondo, Cosmo; Kalanda-Joshua, Miriam; Kazembe, Lawrence; Pemba, Dylo; Kululanga, Elina

    Irrigation is a major coping strategy in many areas experiencing unreliable rainfall distribution and pattern for rain fed agriculture. The benefits of irrigation may however be challenged by its potential to increase malaria incidences through creating breeding grounds for malaria vectors. This study compared malaria trends from archived malaria records in the rainy season and the dry season in Mbewe Extension Planning Area (EPA) in Chikhwawa District, Malawi. This is an area where irrigation has been intensified as a means of coping with floods and drought effects, which often result in crop destruction and failure. Data of monthly incidences of malaria from 2002 to 2009 from Ndakwera Health Centre in the area were used. Rainfall data for the area from 1971 to 2008 were also used. Mwanza River discharge from 1951 to 1992 was considered. Rainfall data were lagged to four months taking into consideration the breeding period of malaria vectors and the incubation period for malaria in human host. We assessed correlation between rainfall and malaria using data of 2004-2009, by fitting a generalised linear model to the data via an over-dispersed Poisson model. The highest malaria cases corresponded with the rain season. Malaria cases in the dry season, when irrigation is implemented, were low. The Pearson correlation coefficient for the monthly rainfall and discharge was not statistically significant at 0.34 ( p > 0.05). The results suggest that direct contribution of the rainfall to flooding in the area is minimal and the floods experienced are generated in the upstream areas. Further, the malaria pattern was mainly associated with the rain season flooding and not irrigation.

  4. Enzyme-linked immunosorbent assay for serological diagnosis of Nocardia brasiliensis and clinical correlation with mycetoma infections.

    PubMed Central

    Salinas-Carmona, M C; Welsh, O; Casillas, S M

    1993-01-01

    We previously identified three immunodominant antigens obtained from a Nocardia brasiliensis cell extract and recognized by sera from mycetoma patients (M. C. Salinas-Carmona, L. Vera, O. Welsh, and M. Rodríguez, Zentralbl. Bakteriol. 276:390-397, 1992). In the present work, we obtained a crude extract from a mass culture of N. brasiliensis HUJEG-1 and purified two immunodominant antigens, the 26- and 24-kDa proteins, by using simple physiochemical techniques. With these antigens, we developed a conventional solid-phase enzyme-linked immunosorbent assay and tested 30 serum samples from mycetoma patients, 29 from tuberculosis patients, 24 from a leprosy group, and 31 from healthy individuals. Our results show for the first time statistically significant differences in serology among these groups. All mycetoma patients with a positive culture for N. brasiliensis had absorbance values higher than 0.3. On the other hand, the mycobacterium-infected patients as well as the healthy individuals all had absorbance values below that level. Moreover, we found a close correlation between the clinical condition of the mycetoma patients and the anti-26- and anti-24-kDa protein antibody concentrations. We therefore propose the use of this assay in routine clinical laboratories to confirm the diagnosis of N. brasiliensis infection in human mycetoma cases. In addition, the possible application of this assay in the serodiagnosis of Nocardia asteroides infection is also discussed. Images PMID:8263174

  5. An approximate closed-form link loss model for non-line-of-sight ultraviolet communication in noncoplanar geometry.

    PubMed

    Wang, Leijie; Xu, Zhengyuan; Sadler, Brian M

    2011-04-01

    Non-line-of-sight UV communication link path loss models have been explored for both coplanar and noncoplanar geometries, and these typically require numerical evaluation. In this Letter, we propose a closed-form and easily applied model to describe link behavior, applicable to noncoplanar geometry. The model is compared with a recently reported analytical model and shows good agreement. PMID:21479037

  6. Clinical features of X linked juvenile retinoschisis in Chinese families associated with novel mutations in the RS1 gene

    PubMed Central

    Ma, Xiang; Tao, Yong

    2007-01-01

    Purpose To describe the clinical phenotype of X linked juvenile retinoschisis (XLRS) in 12 Chinese families with 11 different mutations in the XLRS1 (RS1) gene. Methods Complete ophthalmic examinations were carried out in 29 affected males (12 probands), 38 heterozygous females carriers, and 100 controls. The coding regions of the RS1 gene that encodes retinoschisin were amplified by polymerase chain reaction and directly sequenced. Results Of the 29 male participants, 28 (96.6%) displayed typical foveal schisis. Eleven different RS1 mutations were identified in 12 families; four of these mutations, two frameshift mutations (26 del T of exon 1 and 488 del G of exon 5), and two missense mutations (Asp145His and Arg156Gly) of exon 5, had not been previously described. One non-disease-related polymorphism (NSP): 576C to T (Pro192Pro) change was also newly reported herein. We compared genotypes and observed more severe clinical features in families with the following mutations: frameshift mutation (26 del T) of exon 1, the splice donor site mutation (IVS1+2T to C),or Arg102Gln, Arg209His, and Arg213Gln mutations. Conclusions Severe XLRS phenotypes are associated with the frameshift mutation 26 del T, splice donor site mutation (IVS1+2T to C), and Arg102Gln, Asp145His, Arg209His, and Arg213Gln mutations. The wide variability in the phenotype in Chinese patients with XLRS and different mutations in the RS1 gene is described. Identification of mutations in the RS1 gene and expanded information on clinical manifestations will facilitate early diagnosis, appropriate early therapy, and genetic counseling regarding the prognosis of XLRS. PMID:17615541

  7. Bayesian inference in an item response theory model with a generalized student t link function

    NASA Astrophysics Data System (ADS)

    Azevedo, Caio L. N.; Migon, Helio S.

    2012-10-01

    In this paper we introduce a new item response theory (IRT) model with a generalized Student t-link function with unknown degrees of freedom (df), named generalized t-link (GtL) IRT model. In this model we consider only the difficulty parameter in the item response function. GtL is an alternative to the two parameter logit and probit models, since the degrees of freedom (df) play a similar role to the discrimination parameter. However, the behavior of the curves of the GtL is different from those of the two parameter models and the usual Student t link, since in GtL the curve obtained from different df's can cross the probit curves in more than one latent trait level. The GtL model has similar proprieties to the generalized linear mixed models, such as the existence of sufficient statistics and easy parameter interpretation. Also, many techniques of parameter estimation, model fit assessment and residual analysis developed for that models can be used for the GtL model. We develop fully Bayesian estimation and model fit assessment tools through a Metropolis-Hastings step within Gibbs sampling algorithm. We consider a prior sensitivity choice concerning the degrees of freedom. The simulation study indicates that the algorithm recovers all parameters properly. In addition, some Bayesian model fit assessment tools are considered. Finally, a real data set is analyzed using our approach and other usual models. The results indicate that our model fits the data better than the two parameter models.

  8. Clinical Utility of an Enzyme-Linked Immunosorbent Assay for Detecting Anti-Melanoma Differentiation-Associated Gene 5 Autoantibodies

    PubMed Central

    Sato, Shinji; Murakami, Akihiro; Kuwajima, Akiko; Takehara, Kazuhiko; Mimori, Tsuneyo; Kawakami, Atsushi; Mishima, Michiaki; Suda, Takafumi; Seishima, Mariko; Fujimoto, Manabu; Kuwana, Masataka

    2016-01-01

    Objective Autoantibodies to melanoma differentiation-associated gene 5 (MDA5) are specifically expressed in patients with dermatomyositis (DM) and are associated with a subset of DM patients with rapidly progressive interstitial lung disease (RP-ILD). Here, we examined the clinical utility of a newly developed enzyme-linked immunosorbent assay (ELISA) system for detecting these antibodies. Methods Here we developed an improved ELISA for detecting anti-MDA5 antibodies. We then performed a multicenter clinical study involving 8 medical centers and enrolled 242 adult patients with polymyositis (PM)/DM, 190 with non-PM/DM connective tissue disease (CTD), 154 with idiopathic interstitial pneumonia (IIP), and 123 healthy controls. Anti-MDA5 antibodies in the patients’ serum samples were quantified using our newly developed ELISA, and the results were compared to those obtained using the gold-standard immunoprecipitation (IP) assay. In addition, correlations between the ELISA-quantified anti-MDA5 antibodies and clinical characteristics were evaluated. Results In patients with PM/DM, the anti-MDA5 antibody measurements obtained from the ELISA and IP assay were highly concordant; the ELISA exhibited an analytical sensitivity of 98.2%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 99.5% (compared to the IP assay). Anti-MDA5 antibodies were detected in 22.7% of the DM patients, but not in any of the patients with PM, non-PM/DM CTD, or IIP. Clinically amyopathic DM, RP-ILD, arthritis, and fever were more prevalent in DM patients who were anti-MDA5 antibody-positive than in those who were antibody-negative (P ≤ 0.0002 for all comparisons). In addition, anti-MDA5 antibody-positive patients with RP-ILD exhibited higher antibody levels than those without RP-ILD (P = 0.006). Conclusion Our newly developed ELISA can detect anti-MDA5 antibodies as efficiently as the gold standard IP assay and has the potential to facilitate the routine

  9. Nursing students in clinical practice--developing a model for clinical supervision.

    PubMed

    Häggman-Laitila, Arja; Elina, Eriksson; Riitta, Meretoja; Kirsi, Sillanpää; Leena, Rekola

    2007-11-01

    The aim of this study was to develop a model for clinical supervision to promote the clinical practice of nursing students. The study was implemented in Finland and it was carried out in three phases. Firstly, data were collected by means of a literature review and focus group interviews. Secondly, the data were analysed and described in expert groups, and finally the model itself was evaluated by 23 nursing experts. The data of literature review and focus group interviews consisted of 27 studies and four groups from three organisations: nurses (n=7), managers (n=6), teachers (n=8) and students (n=6). The data were analysed by qualitative content analysis. The model devolved from the study includes the concepts describing prerequisites, content and influence of clinical supervision. The prerequisites are nursing skills, a holistic view of the nursing curriculum, pedagogical, organisational, development, cooperation and interaction competence and decision-making skills. The content of clinical supervision includes support of professional development, pedagogical competence, research and development activities and collaborative working. Clinical supervision has influence on students' professional and personal development and conception of the future of nursing profession, students' preparedness for career planning and the teacher's and preceptor's professional development. The model could unify the notions of all parties concerned of the prerequisites, content and influence of clinical supervision. Furthermore, the entire supervision process and its control could be clarified. The model may be utilised in selecting and educating preceptors and evaluating the quality of clinical supervision. PMID:17936544

  10. Linking Education and Industry in Preparing Students for Nontraditional Jobs. Project Model. Final Report.

    ERIC Educational Resources Information Center

    Smith, Armenia

    The Ysleta Schools Vocational Equity Project was implemented to develop and test methods to link education and industry in preparing students for nontraditional jobs. Both factual and attitudinal data were collected from educators, students, employers, and employees to accomplish the following project objectives: identify successful role models to…

  11. Experimental validation of an analytical model for nonlinear propagation in uncompensated optical links.

    PubMed

    Torrengo, E; Cigliutti, R; Bosco, G; Carena, A; Curri, V; Poggiolini, P; Nespola, A; Zeolla, D; Forghieri, F

    2011-12-12

    Link design for optical communication systems requires accurate modeling of nonlinear propagation in fibers. This topic has been widely analyzed in last decades with partial successes in special conditions, but without a comprehensive solution. Since the introduction of coherent detection with electronic signal processing the scenario completely changed because this category of systems shows better performances in links without in-line dispersion management. This change to uncompensated transmission allowed to modify the approach in the study of nonlinear fiber propagation and in recent years a series of promising analytical models have been proposed. In this paper, we present an experimental validation over different fiber types of an analytical model for nonlinear propagation over uncompensated optical transmission links. Considering an ultra-dense WDM system, we transmitted ten 120-Gb/s PM-QPSK signals over a multi-span system probing different fiber types: SSMF, PSCF and NZDSF. A good matching was found in all cases showing the potential of the analytical model for accurate performance estimation that could lead to powerful tools for link design. PMID:22274104

  12. The Gender-Linked Language Effect: An Empirical Test of a General Process Model

    ERIC Educational Resources Information Center

    Mulac, Anthony; Giles, Howard; Bradac, James J.; Palomares, Nicholas A.

    2013-01-01

    The gender-linked language effect (GLLE) is a phenomenon in which transcripts of female communicators are rated higher on Socio-Intellectual Status and Aesthetic Quality and male communicators are rated higher on Dynamism. This study proposed and tested a new general process model explanation for the GLLE, a central mediating element of which…

  13. PILOT STUDY LINKING AIR AND WATER MODELS FOR MERCURY IN THE EVERGLADES

    EPA Science Inventory

    A major goal of the Everglades Pilot Study is to demonstrate the technical feasibility of linking atmospheric and aquatic system models to calculate an atmospherically-driven total maximum daily load (TMDL) for mercury, given the current state of knowledge of mercury cycling in t...

  14. Multiscale Modeling for Linking Growth, Microstructure, and Properties of Inorganic Microporous Films

    NASA Technical Reports Server (NTRS)

    Vlachos, Dion G.

    2002-01-01

    The focus of this presentation is on multiscale modeling in order to link processing, microstructure, and properties of materials. Overview of problems we study includes: Growth mechanisms in chemical and physical vapor epitaxy; thin films of zeolites for separation and sensing; thin Pd films for hydrogen separation and pattern formation by self-regulation routes.

  15. The Chain-Link Fence Model: A Framework for Creating Security Procedures

    ERIC Educational Resources Information Center

    Houghton, Robert F.

    2013-01-01

    A long standing problem in information technology security is how to help reduce the security footprint. Many specific proposals exist to address specific problems in information technology security. Most information technology solutions need to be repeatable throughout the course of an information systems lifecycle. The Chain-Link Fence Model is…

  16. Exploring Alternative Characteristic Curve Approaches to Linking Parameter Estimates from the Generalized Partial Credit Model.

    ERIC Educational Resources Information Center

    Roberts, James S.; Bao, Han; Huang, Chun-Wei; Gagne, Phill

    Characteristic curve approaches for linking parameters from the generalized partial credit model were examined for cases in which common (anchor) items are calibrated separately in two groups. Three of these approaches are simple extensions of the test characteristic curve (TCC), item characteristic curve (ICC), and operating characteristic curve…

  17. Entangled polymer dynamics in equilibrium and flow modeled through slip links.

    PubMed

    Schieber, Jay D; Andreev, Marat

    2014-01-01

    The idea that the dynamics of concentrated, high-molecular weight polymers are largely governed by entanglements is now widely accepted and typically understood through the tube model. Here we review alternative approaches, slip-link models, that share some similarities to and offer some advantages over tube models. Although slip links were proposed at the same time as tubes, only recently have detailed, quantitative mathematical models arisen based on this picture. In this review, we focus on these models, with most discussion limited to mathematically well-defined objects that conform to state-of-the-art beyond-equilibrium thermodynamics. These models are connected to each other through successive coarse graining, using nonequilibrium thermodynamics along the way, and with a minimal parameter set. In particular, the most detailed level of description has four parameters, three of which can be determined directly from atomistic simulations. Once the remaining parameter is determined for any system, all parameters for all members of the hierarchy are determined. We show how, using this hierarchy of slip-link models combined with atomistic simulations, we can make predictions about the nonlinear rheology of monodisperse homopolymer melts, polydisperse melts, or blends of different architectures. Mathematical details are given elsewhere, so these are limited here, and physical ideas are emphasized. We conclude with an outlook on remaining challenges that might be tackled successfully using this approach, including complex flow fields and polymer blends. PMID:24655135

  18. Lessons learned in detailed clinical modeling at Intermountain Healthcare

    PubMed Central

    Oniki, Thomas A; Coyle, Joseph F; Parker, Craig G; Huff, Stanley M

    2014-01-01

    Background and objective Intermountain Healthcare has a long history of using coded terminology and detailed clinical models (DCMs) to govern storage of clinical data to facilitate decision support and semantic interoperability. The latest iteration of DCMs at Intermountain is called the clinical element model (CEM). We describe the lessons learned from our CEM efforts with regard to subjective decisions a modeler frequently needs to make in creating a CEM. We present insights and guidelines, but also describe situations in which use cases conflict with the guidelines. We propose strategies that can help reconcile the conflicts. The hope is that these lessons will be helpful to others who are developing and maintaining DCMs in order to promote sharing and interoperability. Methods We have used the Clinical Element Modeling Language (CEML) to author approximately 5000 CEMs. Results Based on our experience, we have formulated guidelines to lead our modelers through the subjective decisions they need to make when authoring models. Reported here are guidelines regarding precoordination/postcoordination, dividing content between the model and the terminology, modeling logical attributes, and creating iso-semantic models. We place our lessons in context, exploring the potential benefits of an implementation layer, an iso-semantic modeling framework, and ontologic technologies. Conclusions We assert that detailed clinical models can advance interoperability and sharing, and that our guidelines, an implementation layer, and an iso-semantic framework will support our progress toward that goal. PMID:24993546

  19. E-health stakeholders experiences with clinical modelling and standardizations.

    PubMed

    Gøeg, Kirstine Rosenbeck; Elberg, Pia Britt; Højen, Anne Randorff

    2015-01-01

    Stakeholders in e-health such as governance officials, health IT-implementers and vendors have to co-operate to achieve the goal of a future-proof interoperable e-health infrastructure. Co-operation requires knowledge on the responsibility and competences of stakeholder groups. To increase awareness on clinical modeling and standardization we conducted a workshop for Danish and a few Norwegian e-health stakeholders' and made them discuss their views on different aspects of clinical modeling using a theoretical model as a point of departure. Based on the model, we traced stakeholders' experiences. Our results showed there was a tendency that stakeholders were more familiar with e-health requirements than with design methods, clinical information models and clinical terminology as they are described in the scientific literature. The workshop made it possible for stakeholders to discuss their roles and expectations to each other. PMID:25991150

  20. Team Preceptorship Model: A Solution for Students' Clinical Experience

    PubMed Central

    Cooper Brathwaite, Angela; Lemonde, Manon

    2011-01-01

    There is a shortage of registered nurses in developed countries, and this shortage is due to the aging nursing workforce, demand for healthcare services, and shortage of nursing professors to teach students. In order to increase the number of clinical placements for nursing students, the authors developed and implemented a collaborative preceptorship model between a Canadian University and Public Health Department to facilitate the clinical experiences of Bachelor of Science of Nursing (BScN) students. This paper describes the Team Preceptorship Model which guided the clinical experience of nine students and 14 preceptors. It also highlights the model's evaluation, strengths, and limitations. PMID:21994893

  1. Linking Parameters Estimated with the Generalized Graded Unfolding Model: A Comparison of the Accuracy of Characteristic Curve Methods

    ERIC Educational Resources Information Center

    Anderson Koenig, Judith; Roberts, James S.

    2007-01-01

    Methods for linking item response theory (IRT) parameters are developed for attitude questionnaire responses calibrated with the generalized graded unfolding model (GGUM). One class of IRT linking methods derives the linking coefficients by comparing characteristic curves, and three of these methods---test characteristic curve (TCC), item…

  2. Joint modeling of progression-free survival and death in advanced cancer clinical trials.

    PubMed

    Dejardin, David; Lesaffre, Emmanuel; Verbeke, Geert

    2010-07-20

    Progression-related endpoints (such as time to progression or progression-free survival) and time to death are common endpoints in cancer clinical trials. It is of interest to study the link between progression-related endpoints and time to death (e.g. to evaluate the degree of surrogacy). However, current methods ignore some aspects of the definitions of progression-related endpoints. We review those definitions and investigate their impact on modeling the joint distribution. Further, we propose a multi-state model in which the association between the endpoints is modeled through a frailty term. We also argue that interval-censoring needs to be taken into account to more closely match the latent disease evolution. The joint distribution and an expression for Kendall's tau are derived. The model is applied to data from a clinical trial in advanced metastatic ovarian cancer. PMID:20572123

  3. Challenges in linking preclinical anti-microbial research strategies with clinical outcomes for device-associated infections.

    PubMed

    Moriarty, T F; Grainger, D W; Richards, R G

    2014-01-01

    Infections related to implanted medical devices have become a significant health care issue in recent decades. Increasing numbers of medical devices are in use, often in an aging population, and these devices are implanted against a background of increasing antibiotic-resistant bacterial populations. Progressively more antibiotic resistant infections, requiring ever more refined treatment options, are therefore predicted to emerge with greater frequency in the coming decades. Improvements in the prevention, diagnosis and treatment of these device-associated infections will remain priority targets both for clinicians and the translational research community charged with addressing these challenges. Preclinical strategies, predictive of ultimate clinical efficacy, should serve as a control point for effective translation of new technologies to clinical applications. The development of new anti-infective medical devices requires a validated preclinical testing protocol; however, reliable validation of experimental and preclinical antimicrobial methodologies currently suffers from a variety of technical limitations. These include the lack of agreement or standardisation of experimental protocols, a general lack of correlation between in vitro and in vivo preclinical results and lack of validation between in vivo preclinical implant infection models and clinical (human) results. Device-associated infections pose additional challenges to practicing clinicians concerning diagnosis and treatment, both of which are complicated by the biofilms formed on the medical device. The critical challenges facing both preclinical research and clinical laboratories in improving both diagnosis and treatment of medical device-associated infections are the focus of this review. PMID:25214018

  4. The rise and fall of a psychiatric antenatal clinic: development of a perinatal psychiatric service linked directly to the provision of antenatal care

    PubMed Central

    Shah, N; Musters, C; Selwood, A; Ellis, D

    2010-01-01

    Usual referral pathways to psychiatric services can miss opportunities for timely intervention in maternal perinatal psychiatric ill health. Psychiatric illness leading to suicide is a significant factor in at least 10% of maternal deaths. Despite Royal College of Psychiatry and National Institute for Health and Clinical Excellence recommendations for specialist provision of perinatal mental health services, this remains sporadic and insufficient. We set out to develop a new integrated antenatal–psychiatric direct referral pathway and present a year of experience using this service model. The psychiatric service was delivered from within the antenatal clinic setting with a direct health-care professional (HCP) led referral pathway between 2003 and 2004. The service comprised one session per week of a senior psychiatric specialist registrar and provided three new patients and two follow-up appointments per week. During this period, a total of 75 referrals to the service were made with 57 individuals attending for an appointment. There was a range of diagnoses among the women who attended, with only 24% meeting eligibility criteria for referral to secondary psychiatric services. The majority diagnosis was depression. More severely ill women were not referred to this clinic by obstetric HCPs. In conclusion, this model for developing and delivering a specialist perinatal psychiatric service using direct links to antenatal medical care was not successful despite requiring minimal funding. Nevertheless, it has been used to inform development of a new perinatal service in keeping with the Royal College of Psychiatrists' recommendations and incorporating enhanced training of HCPs responsible for the referral pathway.

  5. Rainfall retrieval in urban areas using commercial microwave links from mobile networks: A modelling feasibility study

    NASA Astrophysics Data System (ADS)

    Zohidov, Bahtiyor; Andrieu, Hervé; Servières, Myriam; Normand, Nicolas

    2014-05-01

    Rainfall is usually measured by networks of rain gauges and weather radars. Many cities worldwide are not supplied with these devices; however, they are generally equipped with mobile telecommunication networks. Mobile networks use atmospheric Hyper-Frequency (HF) links whose transmitted signal power is attenuated by rainfall. Measuring that signal attenuation along each link could allow the measurement of path-averaged rainfall [Leijnse et al 2007, Overeem et al 2013, Messer et al 2006, Guili et al 1991, Zinevich et al 2008, Cuccoli et al 2011]. As HF links are concentrated in cities, these networks could constitute a self-sufficient approach to monitoring rainfall in urban areas. We adopt a simulation approach in order to study the feasibility of mapping rainfall fields at the city scale by means of existing HF links. Our domain of study is the central part of the city of Nantes, France, where the density of cellular networks is greatest. As a basis, we use a data set consisting of hundreds of weather radar images recorded by the Météo-France C band weather radar at high spatial (250m x 250m) and temporal (5 minute) resolutions located about 10 km north of the center of Nantes. We convert these images into rainfall maps using the Z-R relation and consider them as reference rainfall fields. The simulation is performed as follows. First, we simulate the measurement of total attenuation along each HF link using a rain-attenuation model based on Mie theory and a known drop size distribution in a continental temperate climate. This procedure is applied for 256 real radio links operating at different frequencies (18, 23, 38 GHz) with lengths ranging from 0.4 to 16 km. This helps us to substitute the attenuation data for the signal power received from microwave links. Error sources affecting measurement accuracy are introduced as a zero-mean Gaussian distributed random variable with variance of 10% of total attenuation. The retrieval of the rainfield is performed by a

  6. Preclinical Murine Models for Lung Cancer: Clinical Trial Applications

    PubMed Central

    Kellar, Amelia; Egan, Cay; Morris, Don

    2015-01-01

    Murine models for the study of lung cancer have historically been the backbone of preliminary preclinical data to support early human clinical trials. However, the availability of multiple experimental systems leads to debate concerning which model, if any, is best suited for a particular therapeutic strategy. It is imperative that these models accurately predict clinical benefit of therapy. This review provides an overview of the current murine models used to study lung cancer and the advantages and limitations of each model, as well as a retrospective evaluation of the uses of each model with respect to accuracy in predicting clinical benefit of therapy. A better understanding of murine models and their uses, as well as their limitations may aid future research concerning the development and implementation of new targeted therapies and chemotherapeutic agents for lung cancer. PMID:26064932

  7. Clinical Predictive Modeling Development and Deployment through FHIR Web Services

    PubMed Central

    Khalilia, Mohammed; Choi, Myung; Henderson, Amelia; Iyengar, Sneha; Braunstein, Mark; Sun, Jimeng

    2015-01-01

    Clinical predictive modeling involves two challenging tasks: model development and model deployment. In this paper we demonstrate a software architecture for developing and deploying clinical predictive models using web services via the Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) standard. The services enable model development using electronic health records (EHRs) stored in OMOP CDM databases and model deployment for scoring individual patients through FHIR resources. The MIMIC2 ICU dataset and a synthetic outpatient dataset were transformed into OMOP CDM databases for predictive model development. The resulting predictive models are deployed as FHIR resources, which receive requests of patient information, perform prediction against the deployed predictive model and respond with prediction scores. To assess the practicality of this approach we evaluated the response and prediction time of the FHIR modeling web services. We found the system to be reasonably fast with one second total response time per patient prediction. PMID:26958207

  8. Clinical Predictive Modeling Development and Deployment through FHIR Web Services.

    PubMed

    Khalilia, Mohammed; Choi, Myung; Henderson, Amelia; Iyengar, Sneha; Braunstein, Mark; Sun, Jimeng

    2015-01-01

    Clinical predictive modeling involves two challenging tasks: model development and model deployment. In this paper we demonstrate a software architecture for developing and deploying clinical predictive models using web services via the Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) standard. The services enable model development using electronic health records (EHRs) stored in OMOP CDM databases and model deployment for scoring individual patients through FHIR resources. The MIMIC2 ICU dataset and a synthetic outpatient dataset were transformed into OMOP CDM databases for predictive model development. The resulting predictive models are deployed as FHIR resources, which receive requests of patient information, perform prediction against the deployed predictive model and respond with prediction scores. To assess the practicality of this approach we evaluated the response and prediction time of the FHIR modeling web services. We found the system to be reasonably fast with one second total response time per patient prediction. PMID:26958207

  9. [AGIKO (Clinical Research Fellow); a training model aimed at enhancement of clinical scientific research].

    PubMed

    van Rees-Wortelboer, M M; Lamberts, S W; Klasen, E C

    1997-06-21

    The enhancement of clinical scientific research in the Netherlands is being stimulated to a substantial extent by the introduction and stimulation of a training model aimed at the combined training of physicians to both a general practitioner or specialist and a clinical researcher, the AGIKO (Clinical Research Fellow). The model has been recognized by the Central College for Recognition and Registration of Medical Specialists. Extra stimulation by the section Medical Sciences of the Netherlands Organization for Scientific Research (MW-NWO) makes it possible to appoint AGIKOs on second or third flows of funds but also within the first flow of funds. During the last two years, 25 AGIKO applications from ten medical specialisms have been approved. The AGIKO model may help to meet (expected) needs for future clinical-medical research workers in specific research areas. PMID:9380169

  10. Indication of CPAP in Patients with Suspected Obstructive Sleep Apnea, Based on Clinical Parameters and a Novel Two-Channel Recording Device (ApneaLink): A Pilot Study

    PubMed Central

    Nigro, Carlos Alberto; Dibur, Eduardo; Grandval, Sofía; Nogueira, Facundo

    2012-01-01

    Objective. To evaluate the accuracy and reliability of the medical decision based on the results of the hand scoring from a two-channel recording device (ApneaLink) plus clinical data for the prescription of a CPAP assay in patients with suspected OSA. Methods. 39 subjects were assessed in the sleep laboratory with polysomnography and ApneaLink. The patients completed the Epworth sleepiness scale and a clinical history. Two blinded independent observers decided to prescribe CPAP according to the results of the PSG (gold standard, observer A), ApneaLink (alternative method, observer B), and the clinical parameters. Sensitivity and specificity of observer B on the indication of CPAP were calculated. The interobserver agreement for the indication of CPAP was assessed using kappa statistics. Results. 38 subjects were included (26 men, mean age 47.5, mean RDI 28.7, mean BMI 31.4 kg/m2). The prevalence of OSA was 84%. The sensitivity and specificity of observer B to initiate a CPAP trial were 90.6% and 100%, respectively. The interrater agreement for the prescription of CPAP was good (kappa: 0.75). Conclusion. This study has shown that the use of ApneaLink plus clinical data has made it possible to indicate CPAP reliably in most patients with high-clinical pretest for OSA. PMID:23470904

  11. Mathematical Modeling and the Redesign of a Teaching Ambulatory Clinic

    ERIC Educational Resources Information Center

    Baker, Duke H.; Mamlin, Joseph

    1976-01-01

    Mathematical modeling was utilized in the planning and decision-making process involved in reorganizing a teaching clinic to effect continuity of care. The model interrelated physicians, time, and space, facilitating value judgments and decisions. The reorganization was successful and the outcomes remarkably similar to model predictions.…

  12. Experimental scleral cross-linking increases glaucoma damage in a mouse model

    PubMed Central

    Kimball, Elizabeth C.; Nguyen, Cathy; Steinhart, Matthew R.; Nguyen, Thao D.; Pease, Mary E.; Oglesby, Ericka N.; Oveson, Brian C.; Quigley, Harry A.

    2014-01-01

    The purpose of this study was to assess the effect of a scleral cross-linking agent on susceptibility to glaucoma damage in a mouse model. CD1 mice underwent 3 subconjunctival injections of 0.5 M glyceraldehyde (GA) in 1 week, then had elevated intraocular pressure (IOP) induced by bead injection. Degree of cross-linking was measured by enzyme-linked immunosorbent assay (ELISA), scleral permeability was measured by fluorescence recovery after photobleaching (FRAP), and the mechanical effects of GA exposure were measured by inflation testing. Control mice had buffer injection or no injection in 2 separate glaucoma experiments. IOP was monitored by Tonolab and retinal ganglion cell (RGC) loss was measured by histological axon counting. To rule out undesirable effects of GA, we performed electroretinography and detailed histology of the retina. GA exposure had no detectable effects on RGC number, retinal structure or function either histologically or electrophysiologically. GA increased cross-linking of sclera by 37% in an ELISA assay, decreased scleral permeability (FRAP, p = 0.001), and produced a steeper pressure—strain behavior by in vitro inflation testing. In two experimental glaucoma experiments, GA-treated eyes had greater RGC axon loss from elevated IOP than either buffer-injected or control eyes, controlling for level of IOP exposure over time (p = 0.01, and 0.049, multivariable regression analyses). This is the first report that experimental alteration of the sclera, by cross-linking, increases susceptibility to RGC damage in mice. PMID:25285424

  13. Dynamic modelling and link mechanism design of four-legged mobile robot

    NASA Astrophysics Data System (ADS)

    Park, Sung-Ho

    In order to apply the advanced biological phenomena to the leg design of mobile robots, the structural and locomotive characteristics of several selected animals and insects are studied, and the four-legged mobile robot which can cover all existing leg arrangements and locomotion patterns is modeled by a rigid multibody system consisting of links and joints. The model is simulated to prove that the given structure or locomotive conditions satisfy the requirement of minimum energy expenditure. According to the first simulation, there exist ideal forward and backward stroke distances for each pair leg. Therefore, the walking volume and link lengths of existing legged mobile robots should be modified. Also, for other structural and locomotive characteristics which have been used by living creatures, the model is simulated to determine whether or not the actual or possible biological phenomena can be applied to the leg mechanism design of mobile robot.

  14. Linear DNA-linked colloidal chains: a model to visualize polymer dynamics

    NASA Astrophysics Data System (ADS)

    Biswal, Sibani; Byrom, Julie; Du, Daniel

    2012-02-01

    We present the development of synthetic materials consisting of chains of DNA-linked paramagnetic colloids that have rigidity and length specificity. These chains have demonstrated capability for folding and self-assembly. This is classic bead-spring-bead model can be a model system to visualize polymer dynamics. Here, I will describe the formation mechanism and stability of these DNA-linked magnetic particle chains. I will also describe a model that describes the total energy landscape that describes the inter-particle interactions and provides a workable theory toward the optimization of experimental parameters in synthesizing more stable and reliable colloidal assemblies. In addition to stability, we will also present the use of a colloidal worm-like chain (WLC) model system to describe chain dynamics. We measure bending rigidity by monitoring the thermal fluctuations of the chains. We show that the persistence length of the chains can be tuned from 1 to 50 mm (L/LP = 0.002 - 0.1), by changing the length of the DNA used to link adjacent particles from 75 to 15 bases. We also will show that the bending relaxation dynamics of these chains, which match well with theoretical predictions, further supporting the validity of using these colloidal chains as models for semiflexible polymer systems in both equilibrium and dynamic studies.

  15. Efficient estimation and prediction for the Bayesian binary spatial model with flexible link functions.

    PubMed

    Roy, Vivekananda; Evangelou, Evangelos; Zhu, Zhengyuan

    2016-03-01

    Spatial generalized linear mixed models (SGLMMs) are popular models for spatial data with a non-Gaussian response. Binomial SGLMMs with logit or probit link functions are often used to model spatially dependent binomial random variables. It is known that for independent binomial data, the robit regression model provides a more robust (against extreme observations) alternative to the more popular logistic and probit models. In this article, we introduce a Bayesian spatial robit model for spatially dependent binomial data. Since constructing a meaningful prior on the link function parameter as well as the spatial correlation parameters in SGLMMs is difficult, we propose an empirical Bayes (EB) approach for the estimation of these parameters as well as for the prediction of the random effects. The EB methodology is implemented by efficient importance sampling methods based on Markov chain Monte Carlo (MCMC) algorithms. Our simulation study shows that the robit model is robust against model misspecification, and our EB method results in estimates with less bias than full Bayesian (FB) analysis. The methodology is applied to a Celastrus Orbiculatus data, and a Rhizoctonia root data. For the former, which is known to contain outlying observations, the robit model is shown to do better for predicting the spatial distribution of an invasive species. For the latter, our approach is doing as well as the classical models for predicting the disease severity for a root disease, as the probit link is shown to be appropriate. Though this article is written for Binomial SGLMMs for brevity, the EB methodology is more general and can be applied to other types of SGLMMs. In the accompanying R package geoBayes, implementations for other SGLMMs such as Poisson and Gamma SGLMMs are provided. PMID:26331903

  16. Clinical trade-offs in cross-linked ultrahigh-molecular-weight polyethylene used in total joint arthroplasty.

    PubMed

    Pruitt, Lisa A; Ansari, Farzana; Kury, Matt; Mehdizah, Amir; Patten, Elias W; Huddlestein, James; Mickelson, Dayne; Chang, Jennifer; Hubert, Kim; Ries, Michael D

    2013-04-01

    Highly cross-linked formulations of ultrahigh-molecular-weight polyethylene (XLPE) offer exceptional wear resistance for total joint arthroplasty but are offset with a reduction in postyield and fatigue fracture properties in comparison to conventional ultrahigh-molecular-weight polyethylene (UHMWPE). Oxidation resistance is also an important property for the longevity of total joint replacements (TJRs) as formulations of UHMWPE or XLPE utilizing radiation methods are susceptible to free radical generation and subsequent embrittlement. The balance of oxidation, wear, and fracture properties is an enduring concern for orthopedic polymers used as the bearing surface in total joint arthroplasty. Optimization of material properties is further challenged in designs that make use of locking mechanisms, notches, or other stress concentrations that can render the polymer susceptible to fracture due to elevated local stresses. Clinical complications involving impingements, dislocations, or other biomechanical overloads can exacerbate stresses and negate benefits of improved wear resistance provided by XLPE. This work examines trade-offs that factor into the use of XLPE in TJR implants. PMID:23436567

  17. Linking acknowledgement to action: closing the loop on non-urgent, clinically significant test results in the electronic health record.

    PubMed

    Dalal, Anuj K; Pesterev, Bailey M; Eibensteiner, Katyuska; Newmark, Lisa P; Samal, Lipika; Rothschild, Jeffrey M

    2015-07-01

    Failure to follow-up nonurgent, clinically significant test results (CSTRs) is an ambulatory patient safety concern. Tools within electronic health records (EHRs) may facilitate test result acknowledgment, but their utility with regard to nonurgent CSTRs is unclear. We measured use of an acknowledgment tool by 146 primary care physicians (PCPs) at 13 network-affiliated practices that use the same EHR. We then surveyed PCPs to assess use of, satisfaction with, and desired enhancements to the acknowledgment tool. The rate of acknowledgment of non-urgent CSTRs by PCPs was 78%. Of 73 survey respondents, 72 reported taking one or more actions after reviewing a CSTR; fewer (40-75%) reported that using the acknowledgment tool was helpful for a specific purpose. Forty-six (64%) were satisfied with the tool. Both satisfied and nonsatisfied PCPs reported that enhancements linking acknowledgment to routine actions would be useful. EHR vendors should consider enhancements to acknowledgment functionality to ensure follow-up of nonurgent CSTRs. PMID:25796594

  18. Incidence and clinical features of X-linked Cornelia de Lange syndrome due to SMC1L1 mutations.

    PubMed

    Borck, Guntram; Zarhrate, Mohamed; Bonnefont, Jean-Paul; Munnich, Arnold; Cormier-Daire, Valérie; Colleaux, Laurence

    2007-02-01

    Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder characterized by facial dysmorphism, growth and mental retardation, microcephaly, and various malformations. Heterozygous mutations in the NIPBL gene have been detected in approximately 45% of affected individuals. Recently, a second CdLS gene, mapping to the X chromosome, has been identified: SMC1L1 (structural maintenance of chromosomes 1-like 1; or SMC1A). In order to estimate the incidence and refine the clinical presentation of X-linked CdLS, we have screened a series of 11 CdLS boys carrying no NIPBL anomaly. We have identified two novel de novo SMC1L1 missense mutations (c.587G>A [p.Arg196His] and c.3254A>G [p.Tyr1085Cys]). Our results confirm that SMC1L1 mutations cause CdLS and support the view that SMC1L1 accounts for a significant fraction of boys with unexplained CdLS. Furthermore, we suggest that SMC1L1 mutations have milder effects than NIPBL mutations with respect to pre- and postnatal growth retardation and associated malformations. If confirmed, these data may have important implications for directing mutation screening in CdLS. PMID:17221863

  19. Clinical Model for Suicide Risk Assessment.

    ERIC Educational Resources Information Center

    Kral, Michael J.; Sakinofsky, Isaac

    1994-01-01

    Presents suicide risk assessment in a two-tiered model comprising background/contextual factors and subjectivity. The subjectivity portion is formulated around Shneidman's concepts of perturbation and lethality. Discusses decision of hospital admission versus ambulatory care. Suggests that theoretically informed approach should serve both…

  20. Markers, Models, and Measurement Error: Exploring the Links Between Attention Deficits and Language Impairments

    PubMed Central

    2016-01-01

    Purpose The empirical record regarding the expected co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and specific language impairment is confusing and contradictory. A research plan is presented that has the potential to untangle links between these 2 common neurodevelopmental disorders. Method Data from completed and ongoing research projects examining the relative value of different clinical markers for separating cases of specific language impairment from ADHD are presented. Results The best option for measuring core language impairments in a manner that does not potentially penalize individuals with ADHD is to focus assessment on key grammatical and verbal memory skills. Likewise, assessment of ADHD symptoms through standardized informant rating scales is optimized when they are adjusted for overlapping language and academic symptoms. Conclusion As a collection, these clinical metrics set the stage for further examination of potential linkages between attention deficits and language impairments. PMID:26501406

  1. Linked Clinical Trials – The Development of New Clinical Learning Studies in Parkinson’s Disease Using Screening of Multiple Prospective New Treatments

    PubMed Central

    Brundin, Patrik; Barker, Roger A.; Conn, P. Jeffrey; Dawson, Ted M.; Kieburtz, Karl; Lees, Andrew J.; Schwarzschild, Michael A.; Tanner, Caroline M.; Isaacs, Tom; Duffen, Joy; Matthews, Helen; Wyse, Richard K.H.

    2015-01-01

    Finding new therapies for Parkinson’s disease (PD) is a slow process. We assembled an international committee of experts to examine drugs potentially suitable for repurposing to modify PD progression. This committee evaluated multiple drugs currently used, or being developed, in other therapeutic areas, as well as considering several natural, non-pharmaceutical compounds. The committee prioritized which of these putative treatments were most suited to move immediately into pilot clinical trials. Aspects considered included known modes of action, safety, blood-brain-barrier penetration, preclinical data in animal models of PD and the possibility to monitor target engagement in the brain. Of the 26 potential interventions, 10 were considered worth moving forward into small, parallel ‘learning’ clinical trials in PD patients. These trials could be funded in a multitude of ways through support from industry, research grants and directed philanthropic donations. The committee-based approach to select the candidate compounds might help rapidly identify new potential PD treatment strategies for use in clinical trials. PMID:24018336

  2. Computational modeling of mechanical response of dual cross-linked polymer grafted nanoparticle networks

    NASA Astrophysics Data System (ADS)

    v S, Balaji; Yashin, Victor; Salib, Isaac; Kowalewski, Tomasz; Matyjaszewski, Krzystof; Balazs, Anna; Anna Balazs Collaboration; Krzystof Matyjaszewski Collaboration

    2013-03-01

    We develop a hybrid computational model for the behavior of a network of cross-linked polymer-grafted nanoparticles (PGNs). The individual nanoparticles are composed of a rigid core and a corona of grafted polymers that encompass reactive end groups. With the overlap of the coronas on adjacent particles, the reactive end groups can form permanent or labile bonds, which lead to the formation of a ``dual cross-linked'' network. To capture these multi-scale interactions, our approach integrates the essential structural features of the polymer grafted nanoparticles, the interactions between the overlapping coronas, and the kinetics of bond formation and rupture between the reactive groups on the chain ends. We investigate the mechanical response of the dual-cross linked network to an applied tensile deformation. We find that the response depends on the bond energies of the labile bonds, the fraction of permanent bonds in the network, and thickness of the corona. This model provides a powerful tool for the computational design of dual cross-linked PGN's by predicting how the structural features of the system affect the mechanical performance.

  3. The clinical nurse specialist's role as coach in a clinical practice development model.

    PubMed

    Lewis, C K

    1996-06-01

    Over the past 5 years, nursing leadership at St. Luke's Medical Center in Milwaukee has been considering various mechanisms in response to recurrent comments from nursing staff regarding our career ladder. A lack of satisfaction with our career ladder led to the adoption of a new model for nursing. This shift from a career ladder to a clinical ladder has taken place over many years. In April 1994 all staff nurses were staged and transitioned to a clinical practice development model (CPDM). The CPDM is based solely on nursing practice. Our new model was developed from more than 100 narratives of clinical practice submitted by nurses at St. Luke's. Narratives are first-person accounts of an actual clinical experience. The model is based on research conducted by Patricia Benner, PhD, RN, which focused on how nurses acquired their clinical skills and what characteristics are embedded in nurses' practice. This article describes the clinical nurse specialist (CNS) role as a "coach" in facilitating nursing staff transition from a career ladder to a CPDM. The CNS is in a unique position to contribute directly to quality patient care, and also indirectly by fostering professional growth and development of staff nurses. CPDM supports staff development along a continuum. The challenge for the CNS role is to further develop the coaching role to move staff along the continuum. PMID:8900771

  4. A linked hydrodynamic and water quality model for the Salton Sea

    USGS Publications Warehouse

    Chung, E.G.; Schladow, S.G.; Perez-Losada, J.; Robertson, D.M.

    2008-01-01

    A linked hydrodynamic and water quality model was developed and applied to the Salton Sea. The hydrodynamic component is based on the one-dimensional numerical model, DLM. The water quality model is based on a new conceptual model for nutrient cycling in the Sea, and simulates temperature, total suspended sediment concentration, nutrient concentrations, including PO4-3, NO3-1 and NH4+1, DO concentration and chlorophyll a concentration as functions of depth and time. Existing water temperature data from 1997 were used to verify that the model could accurately represent the onset and breakup of thermal stratification. 1999 is the only year with a near-complete dataset for water quality variables for the Salton Sea. The linked hydrodynamic and water quality model was run for 1999, and by adjustment of rate coefficients and other water quality parameters, a good match with the data was obtained. In this article, the model is fully described and the model results for reductions in external phosphorus load on chlorophyll a distribution are presented. ?? 2008 Springer Science+Business Media B.V.

  5. Influence of atmospheric turbulence on OAM-based FSO system with use of realistic link model

    NASA Astrophysics Data System (ADS)

    Li, Ming; Yu, Zhongyuan; Cvijetic, Milorad

    2016-04-01

    We study the influence of atmospheric turbulence on OAM-based free-space optical (FSO) communication by using the Pump turbulence spectrum model which accurately characterizes the realistic FSO link. A comprehensive comparison is made between the Pump and Kolmogorov spectrum models with respect to the turbulence impact. The calculated results show that obtained turbulence-induced crosstalk is lower, which means that a higher channel capacity is projected when the realistic Pump spectrum is used instead of the Kolmogorov spectrum. We believe that our results prove that performance of practical OAM-based FSO is better than one predicted by using the original Kolmogorov turbulence model.

  6. Link functions in multi-locus genetic models: implications for testing, prediction, and interpretation.

    PubMed

    Clayton, David

    2012-05-01

    "Complex" diseases are, by definition, influenced by multiple causes, both genetic and environmental, and statistical work on the joint action of multiple risk factors has, for more than 40 years, been dominated by the generalized linear model (GLM). In genetics, models for dichotomous traits have traditionally been approached via the model of an underlying, normally distributed, liability. This corresponds to the GLM with binomial errors and a probit link function. Elsewhere in epidemiology, however, the logistic regression model, a GLM with logit link function, has been the tool of choice, largely because of its convenient properties in case-control studies. The choice of link function has usually been dictated by mathematical convenience, but it has some important implications in (a) the choice of association test statistic in the presence of existing strong risk factors, (b) the ability to predict disease from genotype given its heritability, and (c) the definition, and interpretation of epistasis (or epistacy). These issues are reviewed, and a new association test proposed. PMID:22508388

  7. Towards Controlling the Glycoform: A Model Framework Linking Extracellular Metabolites to Antibody Glycosylation

    PubMed Central

    Jedrzejewski, Philip M.; del Val, Ioscani Jimenez; Constantinou, Antony; Dell, Anne; Haslam, Stuart M.; Polizzi, Karen M.; Kontoravdi, Cleo

    2014-01-01

    Glycoproteins represent the largest group of the growing number of biologically-derived medicines. The associated glycan structures and their distribution are known to have a large impact on pharmacokinetics. A modelling framework was developed to provide a link from the extracellular environment and its effect on intracellular metabolites to the distribution of glycans on the constant region of an antibody product. The main focus of this work is the mechanistic in silico reconstruction of the nucleotide sugar donor (NSD) metabolic network by means of 34 species mass balances and the saturation kinetics rates of the 60 metabolic reactions involved. NSDs are the co-substrates of the glycosylation process in the Golgi apparatus and their simulated dynamic intracellular concentration profiles were linked to an existing model describing the distribution of N-linked glycan structures of the antibody constant region. The modelling framework also describes the growth dynamics of the cell population by means of modified Monod kinetics. Simulation results match well to experimental data from a murine hybridoma cell line. The result is a modelling platform which is able to describe the product glycoform based on extracellular conditions. It represents a first step towards the in silico prediction of the glycoform of a biotherapeutic and provides a platform for the optimisation of bioprocess conditions with respect to product quality. PMID:24637934

  8. Gene correction of induced pluripotent stem cells derived from a murine model of X-linked chronic granulomatous disorder.

    PubMed

    Mukherjee, Sayandip; Thrasher, Adrian J

    2014-01-01

    Gene therapy presents an attractive alternative to allogeneic haematopoietic stem cell transplantation (HSCT) for treating patients suffering from primary immunodeficiency disorder (PID). The conceptual advantage of gene correcting a patient's autologous HSCs lies in minimizing or completely avoiding immunological complications arising from allogeneic transplantation while conferring the same benefits of immune reconstitution upon long-term engraftment. Clinical trials targeting X-linked chronic granulomatous disorder (X-CGD) have shown promising results in this context. However, long-term clinical benefits in these patients have been limited by issues of poor engraftment of gene-transduced cells coupled with transgene silencing and vector induced clonal proliferation. Novel vectors incorporating safety features such as self-inactivating (SIN) mutations in the long terminal repeats (LTRs) along with synthetic promoters driving lineage-restricted sustainable expression of the gp91phox transgene are expected to resolve the current pitfalls and require rigorous preclinical testing. In this chapter, we have outlined a protocol in which X-CGD mouse model derived induced pluripotent stem cells (iPSCs) have been utilized to develop a platform for investigating the efficacy and safety profiles of novel vectors prior to clinical evaluation. PMID:24557920

  9. Nursing preceptors' experiences of two clinical education models.

    PubMed

    Mamhidir, Anna-Greta; Kristofferzon, Marja-Leena; Hellström-Hyson, Eva; Persson, Elisabeth; Mårtensson, Gunilla

    2014-08-01

    Preceptors play an important role in the process of developing students' knowledge and skills. There is an ongoing search for the best learning and teaching models in clinical education. Little is known about preceptors' perspectives on different models. The aim of the study was to describe nursing preceptors' experiences of two clinical models of clinical education: peer learning and traditional supervision. A descriptive design and qualitative approach was used. Eighteen preceptors from surgical and medical departments at two hospitals were interviewed, ten representing peer learning (student work in pairs) and eight traditional supervision (one student follows a nurse during a shift). The findings showed that preceptors using peer learning created room for students to assume responsibility for their own learning, challenged students' knowledge by refraining from stepping in and encouraged critical thinking. Using traditional supervision, the preceptors' individual ambitions influenced the preceptorship and their own knowledge was empathized as being important to impart. They demonstrated, observed and gradually relinquished responsibility to the students. The choice of clinical education model is important. Peer learning seemed to create learning environments that integrate clinical and academic skills. Investigation of pedagogical models in clinical education should be of major concern to managers and preceptors. PMID:24512652

  10. Space Station communications and tracking systems modeling and RF link simulation

    NASA Technical Reports Server (NTRS)

    Tsang, Chit-Sang; Chie, Chak M.; Lindsey, William C.

    1986-01-01

    In this final report, the effort spent on Space Station Communications and Tracking System Modeling and RF Link Simulation is described in detail. The effort is mainly divided into three parts: frequency division multiple access (FDMA) system simulation modeling and software implementation; a study on design and evaluation of a functional computerized RF link simulation/analysis system for Space Station; and a study on design and evaluation of simulation system architecture. This report documents the results of these studies. In addition, a separate User's Manual on Space Communications Simulation System (SCSS) (Version 1) documents the software developed for the Space Station FDMA communications system simulation. The final report, SCSS user's manual, and the software located in the NASA JSC system analysis division's VAX 750 computer together serve as the deliverables from LinCom for this project effort.

  11. Simulink models for performance analysis of high speed DQPSK modulated optical link

    NASA Astrophysics Data System (ADS)

    Sharan, Lucky; Rupanshi, Chaubey, V. K.

    2016-03-01

    This paper attempts to present the design approach for development of simulation models to study and analyze the transmission of 10 Gbps DQPSK signal over a single channel Peer to Peer link using Matlab Simulink. The simulation model considers the different optical components used in link design with their behavior represented initially by theoretical interpretation, including the transmitter topology, Mach Zehnder Modulator(MZM) module and, the propagation model for optical fibers etc. thus allowing scope for direct realization in experimental configurations. It provides the flexibility to incorporate the various photonic components as either user-defined or fixed and, can also be enhanced or removed from the model as per the design requirements. We describe the detailed operation and need of every component model and its representation in Simulink blocksets. Moreover the developed model can be extended in future to support Dense Wavelength Division Multiplexing (DWDM) system, thereby allowing high speed transmission with N × 40 Gbps systems. The various compensation techniques and their influence on system performance can be easily investigated by using such models.

  12. Modeling and tachometer feedback in the control of an experimental single link flexible structure

    NASA Technical Reports Server (NTRS)

    Garcia, Ephrahim; Inman, Daniel J.

    1990-01-01

    In this work a formulation for the modeling of a single link flexible structure will be introduced that includes the effects of dynamic interaction between the actuator and structure. These effects are the rotational modal participation factors for the structure's vibratory motion that occurs at the slewing axis. It will be shown, both theoretically and experimentally, that this dynamic interaction can be advantageous for vibration suppression of the flexible modes of the system during slewing positioning maneuvers.

  13. Learning Adaptive Forecasting Models from Irregularly Sampled Multivariate Clinical Data

    PubMed Central

    Liu, Zitao; Hauskrecht, Milos

    2016-01-01

    Building accurate predictive models of clinical multivariate time series is crucial for understanding of the patient condition, the dynamics of a disease, and clinical decision making. A challenging aspect of this process is that the model should be flexible and adaptive to reflect well patient-specific temporal behaviors and this also in the case when the available patient-specific data are sparse and short span. To address this problem we propose and develop an adaptive two-stage forecasting approach for modeling multivariate, irregularly sampled clinical time series of varying lengths. The proposed model (1) learns the population trend from a collection of time series for past patients; (2) captures individual-specific short-term multivariate variability; and (3) adapts by automatically adjusting its predictions based on new observations. The proposed forecasting model is evaluated on a real-world clinical time series dataset. The results demonstrate the benefits of our approach on the prediction tasks for multivariate, irregularly sampled clinical time series, and show that it can outperform both the population based and patient-specific time series prediction models in terms of prediction accuracy. PMID:27525189

  14. Clinical Trials: Spline Modeling is Wonderful for Nonlinear Effects.

    PubMed

    Cleophas, Ton J

    2016-01-01

    Traditionally, nonlinear relationships like the smooth shapes of airplanes, boats, and motor cars were constructed from scale models using stretched thin wooden strips, otherwise called splines. In the past decades, mechanical spline methods have been replaced with their mathematical counterparts. The objective of the study was to study whether spline modeling can adequately assess the relationships between exposure and outcome variables in a clinical trial and also to study whether it can detect patterns in a trial that are relevant but go unobserved with simpler regression models. A clinical trial assessing the effect of quantity of care on quality of care was used as an example. Spline curves consistent of 4 or 5 cubic functions were applied. SPSS statistical software was used for analysis. The spline curves of our data outperformed the traditional curves because (1) unlike the traditional curves, they did not miss the top quality of care given in either subgroup, (2) unlike the traditional curves, they, rightly, did not produce sinusoidal patterns, and (3) unlike the traditional curves, they provided a virtually 100% match of the original values. We conclude that (1) spline modeling can adequately assess the relationships between exposure and outcome variables in a clinical trial; (2) spline modeling can detect patterns in a trial that are relevant but may go unobserved with simpler regression models; (3) in clinical research, spline modeling has great potential given the presence of many nonlinear effects in this field of research and given its sophisticated mathematical refinement to fit any nonlinear effect in the mostly accurate way; and (4) spline modeling should enable to improve making predictions from clinical research for the benefit of health decisions and health care. We hope that this brief introduction to spline modeling will stimulate clinical investigators to start using this wonderful method. PMID:23689089

  15. Translational approaches to obsessive-compulsive disorder: from animal models to clinical treatment

    PubMed Central

    Fineberg, NA; Chamberlain, SR; Hollander, E; Boulougouris, V; Robbins, TW

    2011-01-01

    Obsessive-compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence links these conditions with underlying dysregulation of fronto-striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of ‘false alarms’ for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted. LINKED ARTICLES This article is part of a themed issue on Translational

  16. A cybrid cell model for the assessment of the link between mitochondrial deficits and sporadic Parkinson's disease.

    PubMed

    Arduíno, Daniela M; Esteves, A Raquel; Swerdlow, Russell H; Cardoso, Sandra M

    2015-01-01

    Parkinson's disease (PD) is a multifactorial and clinically complex age-related movement disorder. The cause of its most common form (sporadic PD, sPD) is unknown, but one prominent causal factor is mitochondrial dysfunction. Although several genetic- and toxin-based models have been developed along the last decades to mimic the pathological cascade of PD, cellular models that reliably recapitulate the pathological features of the neurons that degenerate in PD are scarce.We describe here the generation of cytoplasmic hybrid cells (or cybrids) as a cellular model of sPD. This approach consists on the fusion of platelets harboring mtDNA from sPD patients with cells in which the endogenous mtDNA has been depleted (Rho0 cells).The sPD cybrid model has been successful in recapitulating most of the hallmarks of sPD, constituting now a validated model for addressing the link between mitochondrial dysfunction and sPD pathology. PMID:25634293

  17. A Cybrid Cell Model for the Assessment of the Link Between Mitochondrial Deficits and Sporadic Parkinson’s Disease

    PubMed Central

    Arduíno, Daniela M.; Esteves, A. Raquel; Swerdlow, Russell H.; Cardoso, Sandra M.

    2015-01-01

    Parkinson’s disease (PD) is a multifactorial and clinically complex age-related movement disorder. The cause of its most common form (sporadic PD, sPD) is unknown, but one prominent causal factor is mitochondrial dysfunction. Although several genetic- and toxin-based models have been developed along the last decades to mimic the pathological cascade of PD, cellular models that reliably recapitulate the pathological features of the neurons that degenerate in PD are scarce. We describe here the generation of cytoplasmic hybrid cells (or cybrids) as a cellular model of sPD. This approach consists on the fusion of platelets harboring mtDNA from sPD patients with cells in which the endogenous mtDNA has been depleted (Rho0 cells). The sPD cybrid model has been successful in recapitulating most of the hallmarks of sPD, constituting now a validated model for addressing the link between mitochondrial dysfunction and sPD pathology. PMID:25634293

  18. Animated-simulation modeling facilitates clinical-process costing.

    PubMed

    Zelman, W N; Glick, N D; Blackmore, C C

    2001-09-01

    Traditionally, the finance department has assumed responsibility for assessing process costs in healthcare organizations. To enhance process-improvement efforts, however, many healthcare providers need to include clinical staff in process cost analysis. Although clinical staff often use electronic spreadsheets to model the cost of specific processes, PC-based animated-simulation tools offer two major advantages over spreadsheets: they allow clinicians to interact more easily with the costing model so that it more closely represents the process being modeled, and they represent cost output as a cost range rather than as a single cost estimate, thereby providing more useful information for decision making. PMID:11552586

  19. The integration of a nurse model to increase clinical excellence.

    PubMed

    Harris, Karen; Spinweber, Carol; Doherty, Marie; Milligan, Lorraine; Addy, Linda; Hydo, Beverly

    2007-01-01

    The purpose of this article is to describe the integration of a nurse model into practice. The goal of the model was to formulate a well-developed professional self-concept, enabling nurses to articulate the facets of nursing. The facets provide a basis for evaluations and a foundation for clinical nurse specialists to use for professional development during rounds and inservice programs. Various activities were conducted to ensure a comprehensive model that was effective, thereby creating an environment of clinical excellence. PMID:17259815

  20. [Management models in clinical nutrition: weaknesses and strengths].

    PubMed

    García de Lorenzo, A; Alvarez, J; Burgos, R; Cabrerizo, L; Farrer, K; García Almeida, J M; García Luna, P P; García Peris, P; Llano, J Del; Planas, M; Piñeiro, G

    2009-01-01

    At the 6th Abbott-SENPE Debate Forum a multidisciplinary and multiprofessional discussion was established in order to seek for the model or the models of clinical management most appropriate for Clinical Nutrition and Dietetics Units (CNAD) in Spain. The weaknesses and strengths as well as opportunities for the current systems were assessed concluding that a certain degree of disparity was observed not only due to regional differences but also to different hospital types. It was proposed, from SENPE, the creation of a working group helping to standardize the models and promote the culture of Integral Control and Change Management. PMID:19593481

  1. Do mouse models of allergic asthma mimic clinical disease?

    PubMed

    Epstein, Michelle M

    2004-01-01

    Experimental mouse models of allergic asthma established almost 10 years ago offered new opportunities to study disease pathogenesis and to develop new therapeutics. These models focused on the factors governing the allergic immune response, on modeling clinical behavior of allergic asthma, and led to insights into pulmonary pathophysiology. Although mouse models rarely completely reproduce all the features of human disease, after sensitization and respiratory tract challenges with antigen, wild-type mice develop a clinical syndrome that closely resembles allergic asthma, characterized by eosinophilic lung inflammation, airway hyperresponsiveness (AHR), increased IgE, mucus hypersecretion, and eventually, airway remodeling. There are, however, differences between mouse and human physiology that threaten to limit the value of mouse models. Three examples of such differences relate to both clinical manifestations of disease and underlying pathogenesis. First, in contrast to patients who have increased methacholine-induced AHR even when they are symptom-free, mice exhibit only transient methacholine-induced AHR following allergen exposure. Second, chronic allergen exposure in patients leads to chronic allergic asthma, whereas repeated exposures in sensitized mice causes suppression of disease. Third, IgE and mast cells, in humans, mediate early- and late-phase allergic responses, though both are unnecessary for the generation of allergic asthma in mice. Taken together, these observations suggest that mouse models of allergic asthma are not exact replicas of human disease and thus, question the validity of these models. However, observations from mouse models of allergic asthma support many existing paradigms, although some novel discoveries in mice have yet to be verified in patients. This review presents an overview of the clinical aspects of disease in mouse models of allergic asthma emphasizing (1). the factors influencing the pathophysiological responses during

  2. A clinically relevant canine lung cancer model

    SciTech Connect

    Benfield, J.R.; Shors, E.C.; Hammond, W.G.; Paladugu, R.R.; Cohen, A.H.; Jensen, T.; Fu, P.C.; Pak, H.Y.; Teplitz, R.L.

    1981-12-01

    Research on early human lung cancer is difficult; we have sought a canine correlate. Regimens included endobronchial submucosal injections and topical focal applications of benzo(a)pyrene, nitrosomethylurea, dimethylbenzanthracene, and methylcholanthrene, singly or in combinations. Sustained-release discs were placed into lung parenchyma or sutured into major bronchi. Tracheal segments were isolated as cervical pedicle grafts. Gross and histological evolution was reproducible. Columnar and basal hyperplasia and squamous metaplasia were early changes. Atypia occurred within 6 weeks and was found in all dogs within 16 to 18 weeks. Invasive cancers occurred within 8 to 65 months. No tracheal graft developed cancer. Of 15 dogs with parenchymal sustained-release implants, 1 to date has developed cancer in 8 months. Four endobronchial regimens have produced 16 cancers in 56 lungs at risk for 18 to 65 months. No cancers developed in 23 lungs at risk from eight other regimens. Of 10 dogs at risk for unilateral endobronchial cancer, 5 have had cancer. Of 23 dogs with both lungs at risk, 9 developed cancer. We have shown focal carcinogenesis with well-defined pathogenesis and an extended preneoplastic period at predictable sites in a lung cancer model.

  3. Modelling the multidimensional niche by linking functional traits to competitive performance.

    PubMed

    Maynard, Daniel S; Leonard, Kenneth E; Drake, John M; Hall, David W; Crowther, Thomas W; Bradford, Mark A

    2015-07-22

    Linking competitive outcomes to environmental conditions is necessary for understanding species' distributions and responses to environmental change. Despite this importance, generalizable approaches for predicting competitive outcomes across abiotic gradients are lacking, driven largely by the highly complex and context-dependent nature of biotic interactions. Here, we present and empirically test a novel niche model that uses functional traits to model the niche space of organisms and predict competitive outcomes of co-occurring populations across multiple resource gradients. The model makes no assumptions about the underlying mode of competition and instead applies to those settings where relative competitive ability across environments correlates with a quantifiable performance metric. To test the model, a series of controlled microcosm experiments were conducted using genetically related strains of a widespread microbe. The model identified trait microevolution and performance differences among strains, with the predicted competitive ability of each organism mapped across a two-dimensional carbon and nitrogen resource space. Areas of coexistence and competitive dominance between strains were identified,and the predicted competitive outcomes were validated in approximately 95% of the pairings. By linking trait variation to competitive ability, our work demonstrates a generalizable approach for predicting and modelling competitive outcomes across changing environmental contexts. PMID:26136444

  4. A NEW GHOST-NODE METHOD FOR LINKING DIFFERENT MODELS WITH VARIED GRID REFINEMENT

    SciTech Connect

    J. dickinson; S.C. James; S. Mehl; M.C. Hill; S. Leake; G.A. Zyvoloski

    2005-10-18

    A flexible, robust method for linking grids of locally refined models that may be constructed using different types of numerical methods is needed to address a variety of hydrologic problems. This work outlines and tests a new ghost-node model-linking method based on the iterative method of Mehl and Hill (2002, 2004). It is applicable to steady-state solutions for ground-water flow. Tests are presented for a homogeneous two-dimensional system that facilitates clear analysis of typical problems. The coupled grids are simulated using the finite-difference and finite-element models MODFLOW and FEHM. Results indicate that when the grids are matched spatially so that nodes and control volume boundaries are aligned, the new coupling technique has approximately twice the error as coupling using two MODFLOW models. When the grids are non-matching; model accuracy is slightly increased over matching grid cases. Overall, results indicate that the ghost-node technique is a viable means to accurately couple distinct models.

  5. NEW GHOST-NODE METHOD FOR LINKING DIFFERENT MODELS WITH VARIED GRID REFINEMENT

    SciTech Connect

    S.C. James; J.E. Dickinson; S.W. Mehl; M.C. Hill; S.A. Leake; G.A. zyvoloski; A. Eddebbarh

    2006-02-15

    A flexible, robust method for linking grids of locally refined models constructed with different numerical methods is needed to address a variety of hydrologic problems. This work outlines and tests a new ghost-node model-linking method for a refined ''child'' model that is contained within a larger and coarser ''parent'' model that is based on the iterative method of Mehl and Hill (2002, 2004). The method is applicable to steady-state solutions for ground-water flow. Tests are presented for a homogeneous two-dimensional system that has either matching grids (parent cells border an integer number of child cells; Figure 2a) or non-matching grids (parent cells border a non-integer number of child cells; Figure 2b). The coupled grids are simulated using the finite-difference and finite-element models MODFLOW and FEHM, respectively. The simulations require no alteration of the MODFLOW or FEHM models and are executed using a batch file on Windows operating systems. Results indicate that when the grids are matched spatially so that nodes and child cell boundaries are aligned, the new coupling technique has error nearly equal to that when coupling two MODFLOW models (Mehl and Hill, 2002). When the grids are non-matching, model accuracy is slightly increased over matching-grid cases. Overall, results indicate that the ghost-node technique is a viable means to accurately couple distinct models because the overall error is less than if only the regional model was used to simulate flow in the child model's domain.

  6. New Ghost-node method for linking different models with varied grid refinement.

    SciTech Connect

    Mehl, Steffen W.; Hill, Mary Catherine.; James, Scott Carlton; Leake, Stanley A.; Zyvoloski, George A.; Dickinson, Jesse E.; Eddebbarh, Al A.

    2006-01-01

    A flexible, robust method for linking grids of locally refined models constructed with different numerical methods is needed to address a variety of hydrologic problems. This work outlines and tests a new ghost-node model-linking method for a refined 'child' model that is contained within a larger and coarser 'parent' model that is based on the iterative method of Mehl and Hill (2002, 2004). The method is applicable to steady-state solutions for ground-water flow. Tests are presented for a homogeneous two-dimensional system that has either matching grids (parent cells border an integer number of child cells; Figure 2a) or non-matching grids (parent cells border a non-integer number of child cells; Figure 2b). The coupled grids are simulated using the finite-difference and finite-element models MODFLOW and FEHM, respectively. The simulations require no alteration of the MODFLOW or FEHM models and are executed using a batch file on Windows operating systems. Results indicate that when the grids are matched spatially so that nodes and child cell boundaries are aligned, the new coupling technique has error nearly equal to that when coupling two MODFLOW models (Mehl and Hill, 2002). When the grids are non-matching, model accuracy is slightly increased over matching-grid cases. Overall, results indicate that the ghost-node technique is a viable means to accurately couple distinct models because the overall error is less than if only the regional model was used to simulate flow in the child model's domain.

  7. New ghost-node method for linking different models with varied grid refinement

    USGS Publications Warehouse

    James, S.C.; Dickinson, J.E.; Mehl, S.W.; Hill, M.C.; Leake, S.A.; Zyvoloski, G.A.; Eddebbarh, A.-A.

    2006-01-01

    A flexible, robust method for linking grids of locally refined ground-water flow models constructed with different numerical methods is needed to address a variety of hydrologic problems. This work outlines and tests a new ghost-node model-linking method for a refined "child" model that is contained within a larger and coarser "parent" model that is based on the iterative method of Steffen W. Mehl and Mary C. Hill (2002, Advances in Water Res., 25, p. 497-511; 2004, Advances in Water Res., 27, p. 899-912). The method is applicable to steady-state solutions for ground-water flow. Tests are presented for a homogeneous two-dimensional system that has matching grids (parent cells border an integer number of child cells) or nonmatching grids. The coupled grids are simulated by using the finite-difference and finite-element models MODFLOW and FEHM, respectively. The simulations require no alteration of the MODFLOW or FEHM models and are executed using a batch file on Windows operating systems. Results indicate that when the grids are matched spatially so that nodes and child-cell boundaries are aligned, the new coupling technique has error nearly equal to that when coupling two MODFLOW models. When the grids are nonmatching, model accuracy is slightly increased compared to that for matching-grid cases. Overall, results indicate that the ghost-node technique is a viable means to couple distinct models because the overall head and flow errors relative to the analytical solution are less than if only the regional coarse-grid model was used to simulate flow in the child model's domain.

  8. X-Linked Hereditary Nephropathy in Navasota Dogs: Clinical Pathology, Morphology, and Gene Expression During Disease Progression.

    PubMed

    Benali, S L; Lees, G E; Nabity, M B; Aricò, A; Drigo, M; Gallo, E; Giantin, M; Aresu, L

    2016-07-01

    X-linked hereditary nephropathy (XLHN) in Navasota dogs is a spontaneously occurring disease caused by a mutation resulting in defective production of type IV collagen and juvenile-onset renal failure. The study was aimed at examining the evolution of renal damage and the expression of selected molecules potentially involved in the pathogenesis of XLHN. Clinical data and renal samples were obtained in 10 XLHN male dogs and 5 controls at 4 (T0), 6 (T1), and 9 (T2) months of age. Glomerular and tubulointerstitial lesions were scored by light microscopy, and the expression of 21 molecules was investigated by quantitative real-time polymerase chain reaction with selected proteins evaluated by immunohistochemistry. No significant histologic lesions or clinicopathologic abnormalities were identified in controls at any time-point. XLHN dogs had progressive proteinuria starting at T0. At T1, XLHN dogs had a mesangioproliferative glomerulopathy with glomerular loss, tubular necrosis, and interstitial fibrosis. At T2, glomerular and tubulointerstitial lesions were more severe, particularly glomerular loss, interstitial fibrosis, and inflammation. At T0, transforming growth factor β, connective tissue growth factor, and platelet-derived growth factor α mRNA were overexpressed in XLHN dogs compared with controls. Clusterin and TIMP1 transcripts were upregulated in later stages of the disease. Transforming growth factor β, connective tissue growth factor, and platelet-derived growth factor α should be considered as key players in the initial events of XHLN. Clusterin and TIMP1 appear to be more associated with the progression rather than initiation of tubulointerstitial damage in chronic renal disease. PMID:26917550

  9. Influence of gender constancy and social power on sex-linked modeling.

    PubMed

    Bussey, K; Bandura, A

    1984-12-01

    Competing predictions derived from cognitive-developmental theory and social learning theory concerning sex-linked modeling were tested. In cognitive-developmental theory, gender constancy is considered a necessary prerequisite for the emulation of same-sex models, whereas according to social learning theory, sex-role development is promoted through a vast system of social influences with modeling serving as a major conveyor of sex role information. In accord with social learning theory, even children at a lower level of gender conception emulated same-sex models in preference to opposite-sex ones. Level of gender constancy was associated with higher emulation of both male and female models rather than operating as a selective determinant of modeling. This finding corroborates modeling as a basic mechanism in the sex-typing process. In a second experiment we explored the limits of same-sex modeling by pitting social power against the force of collective modeling of different patterns of behavior by male and female models. Social power over activities and rewarding resources produced cross-sex modeling in boys, but not in girls. This unexpected pattern of cross-sex modeling is explained by the differential sex-typing pressures that exist for boys and girls and socialization experiences that heighten the attractiveness of social power for boys. PMID:6527216

  10. A Refined Model for the TSG-6 Link Module in Complex with Hyaluronan

    PubMed Central

    Higman, Victoria A.; Briggs, David C.; Mahoney, David J.; Blundell, Charles D.; Sattelle, Benedict M.; Dyer, Douglas P.; Green, Dixy E.; DeAngelis, Paul L.; Almond, Andrew; Milner, Caroline M.; Day, Anthony J.

    2014-01-01

    Tumor necrosis factor-stimulated gene-6 (TSG-6) is an inflammation-associated hyaluronan (HA)-binding protein that contributes to remodeling of HA-rich extracellular matrices during inflammatory processes and ovulation. The HA-binding domain of TSG-6 consists solely of a Link module, making it a prototypical member of the superfamily of proteins that interacts with this high molecular weight polysaccharide composed of repeating disaccharides of d-glucuronic acid and N-acetyl-d-glucosamine (GlcNAc). Previously we modeled a complex of the TSG-6 Link module in association with an HA octasaccharide based on the structure of the domain in its HA-bound conformation. Here we have generated a refined model for a HA/Link module complex using novel restraints identified from NMR spectroscopy of the protein in the presence of 10 distinct HA oligosaccharides (from 4- to 8-mers); the model was then tested using unique sugar reagents, i.e. chondroitin/HA hybrid oligomers and an octasaccharide in which a single sugar ring was 13C-labeled. The HA chain was found to make more extensive contacts with the TSG-6 surface than thought previously, such that a d-glucuronic acid ring makes stacking and ionic interactions with a histidine and lysine, respectively. Importantly, this causes the HA to bend around two faces of the Link module (resembling the way that HA binds to CD44), potentially providing a mechanism for how TSG-6 can reorganize HA during inflammation. However, the HA-binding site defined here may not play a role in TSG-6-mediated transfer of heavy chains from inter-α-inhibitor onto HA, a process known to be essential for ovulation. PMID:24403066

  11. A local-world heterogeneous model of wireless sensor networks with node and link diversity

    NASA Astrophysics Data System (ADS)

    Li, Shudong; Li, Lixiang; Yang, Yixian

    2011-03-01

    In this paper, we present a novel local-world model of wireless sensor networks (WSN) with two kinds of nodes: sensor nodes and sink nodes, which is different from other models with identical nodes and links. The model balances energy consumption by limiting the connectivity of sink nodes to prolong the life of the network. How the proportion of sink nodes, different energy distribution and the local-world scale would affect the topological structure and network performance are investigated. We find that, using mean-field theory, the degree distribution is obtained as an integral with respect to the proportion of sink nodes and energy distribution. We also show that, the model exhibits a mixed connectivity correlation which is greatly distinct from general networks. Moreover, from the perspective of the efficiency and the average hops for data processing, we find some suitable range of the proportion p of sink nodes would make the network model have optimal performance for data processing.

  12. Models and estimation methods for clinical HIV-1 data

    NASA Astrophysics Data System (ADS)

    Verotta, Davide

    2005-12-01

    Clinical HIV-1 data include many individual factors, such as compliance to treatment, pharmacokinetics, variability in respect to viral dynamics, race, sex, income, etc., which might directly influence or be associated with clinical outcome. These factors need to be taken into account to achieve a better understanding of clinical outcome and mathematical models can provide a unifying framework to do so. The first objective of this paper is to demonstrate the development of comprehensive HIV-1 dynamics models that describe viral dynamics and also incorporate different factors influencing such dynamics. The second objective of this paper is to describe alternative estimation methods that can be applied to the analysis of data with such models. In particular, we consider: (i) simple but effective two-stage estimation methods, in which data from each patient are analyzed separately and summary statistics derived from the results, (ii) more complex nonlinear mixed effect models, used to pool all the patient data in a single analysis. Bayesian estimation methods are also considered, in particular: (iii) maximum posterior approximations, MAP, and (iv) Markov chain Monte Carlo, MCMC. Bayesian methods incorporate prior knowledge into the models, thus avoiding some of the model simplifications introduced when the data are analyzed using two-stage methods, or a nonlinear mixed effect framework. We demonstrate the development of the models and the different estimation methods using real AIDS clinical trial data involving patients receiving multiple drugs regimens.

  13. Successes and Challenges in Linking Observations and Modeling of Marine and Terrestrial Cryospheric Processes

    NASA Astrophysics Data System (ADS)

    Herzfeld, U. C.; Hunke, E. C.; Trantow, T.; Greve, R.; McDonald, B.; Wallin, B.

    2014-12-01

    Understanding of the state of the cryosphere and its relationship to other components of the Earth system requires both models of geophysical processes and observations of geophysical properties and processes, however linking observations and models is far from trivial. This paper looks at examples from sea ice and land ice model-observation linkages to examine some approaches, challenges and solutions. In a sea-ice example, ice deformation is analyzed as a key process that indicates fundamental changes in the Arctic sea ice cover. Simulation results from the Los Alamos Sea-Ice Model CICE, which is also the sea-ice component of the Community Earth System Model (CESM), are compared to parameters indicative of deformation as derived from mathematical analysis of remote sensing data. Data include altimeter, micro-ASAR and image data from manned and unmanned aircraft campaigns (NASA OIB and Characterization of Arctic Sea Ice Experiment, CASIE). The key problem to linking data and model results is the derivation of matching parameters on both the model and observation side.For terrestrial glaciology, we include an example of a surge process in a glacier system and and example of a dynamic ice sheet model for Greenland. To investigate the surge of the Bering Bagley Glacier System, we use numerical forward modeling experiments and, on the data analysis side, a connectionist approach to analyze crevasse provinces. In the Greenland ice sheet example, we look at the influence of ice surface and bed topography, as derived from remote sensing data, on on results from a dynamic ice sheet model.

  14. A link-segment model of upright human posture for analysis of head-trunk coordination

    NASA Technical Reports Server (NTRS)

    Nicholas, S. C.; Doxey-Gasway, D. D.; Paloski, W. H.

    1998-01-01

    Sensory-motor control of upright human posture may be organized in a top-down fashion such that certain head-trunk coordination strategies are employed to optimize visual and/or vestibular sensory inputs. Previous quantitative models of the biomechanics of human posture control have examined the simple case of ankle sway strategy, in which an inverted pendulum model is used, and the somewhat more complicated case of hip sway strategy, in which multisegment, articulated models are used. While these models can be used to quantify the gross dynamics of posture control, they are not sufficiently detailed to analyze head-trunk coordination strategies that may be crucial to understanding its underlying mechanisms. In this paper, we present a biomechanical model of upright human posture that extends an existing four mass, sagittal plane, link-segment model to a five mass model including an independent head link. The new model was developed to analyze segmental body movements during dynamic posturography experiments in order to study head-trunk coordination strategies and their influence on sensory inputs to balance control. It was designed specifically to analyze data collected on the EquiTest (NeuroCom International, Clackamas, OR) computerized dynamic posturography system, where the task of maintaining postural equilibrium may be challenged under conditions in which the visual surround, support surface, or both are in motion. The performance of the model was tested by comparing its estimated ground reaction forces to those measured directly by support surface force transducers. We conclude that this model will be a valuable analytical tool in the search for mechanisms of balance control.

  15. Identification of Unknown Groundwater Pollution Source Using Linked ANN-Optimization Model

    NASA Astrophysics Data System (ADS)

    Ayaz, M.; Srivastava, R.

    2011-12-01

    Identification of groundwater pollution sources is a major step in groundwater pollution remediation, particularly for assigning fractions of the remediation cost to different polluters. Identification of unknown groundwater pollution source is an inverse problem which is generally ill-posed. A pollution source is said to be identified completely when its source characteristics (location, strength and release period) are known. In practice, the lag time between the first reading at observation well and the time at which the source becomes active is not known. For such cases, pollution source identification problem becomes more difficult. We propose a linked ANN-Optimization model for complete identification of unknown groundwater pollution sources. Spatial and temporal data of observed and simulated concentration is used to formulate the objective function. An optimization model is then used to minimize the objective function. We define the lag time as the time from the start of the pollutant release to the peak of the breakthrough curve observed at a monitoring well. Lag time for a particular monitoring well is then dependent only on the source location and release period. An ANN model is trained for different source locations and release periods as input data to determine the lag time for breakthrough curve. In the proposed model, the ANN model is linked externally with the optimization model to identify the pollution sources. The main advantage of the proposed model is to identify the unique solution for pollution sources when lag time is not known. The performance of the model is evaluated for a one dimensional case with error-free and erroneous data. The measurement errors incorporated in the data vary from 0% to 10% of the analytically computed values. The results indicate that the proposed linked ANN-Optimization model is able to predict the source parameters quite well for the error-free data. For the observations subjected to random measurement errors, the

  16. The Clinical Learning Dyad Model: An Innovation in Midwifery Education.

    PubMed

    Cohen, Susanna R; Thomas, Celeste R; Gerard, Claudia

    2015-01-01

    There is a national shortage of women's health and primary care providers in the United States, including certified nurse-midwives and certified midwives. This shortage is directly related to how many students can be trained within the existing system. The current model of midwifery clinical training is based on apprenticeship, with one-on-one interaction between a student and preceptor. Thus, the number of newly trained midwifery providers is limited by the number of available and willing preceptors. The clinical learning dyad model (CLDM), which pairs 2 beginning midwifery students with one preceptor in a busy practice, addresses this problem. In addition, this model brings in a senior midwife student as a near-peer mentor when the students are first oriented into outpatient clinical practice. The model began as a pilot project to improve the quality of training and increase available student spots in clinical education. This article discusses the origins of the model, the specifics of its design, and the results of a midterm and one-year postintervention survey. Students and preceptors involved in this model identified several advantages to the program, including increased student accountability, enhanced socialization into the profession, improved learning, and reduced teaching burden on preceptors. An additional benefit of the CLDM is that students form a learning community and collaborate with preceptors to care for women in busy clinical settings. Challenges of the model will also be discussed. Further research is needed to evaluate the effectiveness of the CLDM. This article is part of a special series of articles that address midwifery innovations in clinical practice, education, interprofessional collaboration, health policy, and global health. PMID:26605990

  17. Evidence of TAF1 dysfunction in peripheral models of X-linked dystonia-parkinsonism.

    PubMed

    Domingo, Aloysius; Amar, David; Grütz, Karen; Lee, Lillian V; Rosales, Raymond; Brüggemann, Norbert; Jamora, Roland Dominic; Cutiongco-Dela Paz, Eva; Rolfs, Arndt; Dressler, Dirk; Walter, Uwe; Krainc, Dimitri; Lohmann, Katja; Shamir, Ron; Klein, Christine; Westenberger, Ana

    2016-08-01

    The molecular dysfunction in X-linked dystonia-parkinsonism is not completely understood. Thus far, only noncoding alterations have been found in genetic analyses, located in or nearby the TATA-box binding protein-associated factor 1 (TAF1) gene. Given that this gene is ubiquitously expressed and is a critical component of the cellular transcription machinery, we sought to study differential gene expression in peripheral models by performing microarray-based expression profiling in blood and fibroblasts, and comparing gene expression in affected individuals vs. ethnically matched controls. Validation was performed via quantitative polymerase chain reaction in discovery and independent replication sets. We observed consistent downregulation of common TAF1 transcripts in samples from affected individuals in gene-level and high-throughput experiments. This signal was accompanied by a downstream effect in the microarray, reflected by the dysregulation of 307 genes in the disease group. Gene Ontology and network analyses revealed enrichment of genes involved in RNA polymerase II-dependent transcription, a pathway relevant to TAF1 function. Thus, the results converge on TAF1 dysfunction in peripheral models of X-linked dystonia-parkinsonism, and provide evidence of altered expression of a canonical gene in this disease. Furthermore, our study illustrates a link between the previously described genetic alterations and TAF1 dysfunction at the transcriptome level. PMID:26879577

  18. Artificial neural network modeling using clinical and knowledge independent variables predicts salt intake reduction behavior

    PubMed Central

    Isma’eel, Hussain A.; Sakr, George E.; Almedawar, Mohamad M.; Fathallah, Jihan; Garabedian, Torkom; Eddine, Savo Bou Zein

    2015-01-01

    Background High dietary salt intake is directly linked to hypertension and cardiovascular diseases (CVDs). Predicting behaviors regarding salt intake habits is vital to guide interventions and increase their effectiveness. We aim to compare the accuracy of an artificial neural network (ANN) based tool that predicts behavior from key knowledge questions along with clinical data in a high cardiovascular risk cohort relative to the least square models (LSM) method. Methods We collected knowledge, attitude and behavior data on 115 patients. A behavior score was calculated to classify patients’ behavior towards reducing salt intake. Accuracy comparison between ANN and regression analysis was calculated using the bootstrap technique with 200 iterations. Results Starting from a 69-item questionnaire, a reduced model was developed and included eight knowledge items found to result in the highest accuracy of 62% CI (58-67%). The best prediction accuracy in the full and reduced models was attained by ANN at 66% and 62%, respectively, compared to full and reduced LSM at 40% and 34%, respectively. The average relative increase in accuracy over all in the full and reduced models is 82% and 102%, respectively. Conclusions Using ANN modeling, we can predict salt reduction behaviors with 66% accuracy. The statistical model has been implemented in an online calculator and can be used in clinics to estimate the patient’s behavior. This will help implementation in future research to further prove clinical utility of this tool to guide therapeutic salt reduction interventions in high cardiovascular risk individuals. PMID:26090333

  19. Women and work in rural Taiwan: building a contextual model linking employment and health.

    PubMed

    Gallin, R S

    1989-12-01

    This paper is based on ethnographic research in a rural Taiwanese village in which married women with children are a major source of labor for local industry. Responsibility for job and home exposes these women to repeated stressors that can increase their susceptibility to illness. Existing explanatory models linking employment and women's health, however, do not explain adequately the women's response to their wage labor and the consequences of the social aspects of their work on their health. This paper describes women's work and its meaning, and discusses the way in which micro phenomena such as meanings and health states are linked to macro phenomena such as national political-economic processes and the world capitalist system. PMID:2689508

  20. Clinical use of the five-factor model: an introduction.

    PubMed

    Costa, P T

    1991-12-01

    In the past decade, clinical psychologists have developed a renewed appreciation of the value of assessment. At the same time, personality psychologists have come to agree on a fundamental taxonomy of personality traits, the five-factor model. Articles in this special series describe the model and its measurement and discuss applications in three different settings: general clinical practice, a sexual behaviors consultation unit, and a behavioral medicine clinic. This introduction raises questions about the use of personality profiles in psychodiagnosis, the range of applicability of the five-factor model, the utility of personality feedback in psychotherapy, the stability of personality scores among psychotherapy patients, and the feasibility of using personality scores to select optimal forms of treatment. This special series is intended to stimulate research on such topics. PMID:1757867

  1. Identification of Multiple QTLs Linked to Neuropathology in the Engrailed-1 Heterozygous Mouse Model of Parkinson's Disease.

    PubMed

    Kurowska, Zuzanna; Jewett, Michael; Brattås, Per Ludvik; Jimenez-Ferrer, Itzia; Kenéz, Xuyian; Björklund, Tomas; Nordström, Ulrika; Brundin, Patrik; Swanberg, Maria

    2016-01-01

    Motor symptoms in Parkinson's disease are attributed to degeneration of midbrain dopaminergic neurons (DNs). Heterozygosity for Engrailed-1 (En1), one of the key factors for programming and maintenance of DNs, results in a parkinsonian phenotype featuring progressive degeneration of DNs in substantia nigra pars compacta (SNpc), decreased striatal dopamine levels and swellings of nigro-striatal axons in the SwissOF1-En1+/- mouse strain. In contrast, C57Bl/6-En1+/- mice do not display this neurodegenerative phenotype, suggesting that susceptibility to En1 heterozygosity is genetically regulated. Our goal was to identify quantitative trait loci (QTLs) that regulate the susceptibility to PD-like neurodegenerative changes in response to loss of one En1 allele. We intercrossed SwissOF1-En1+/- and C57Bl/6 mice to obtain F2 mice with mixed genomes and analyzed number of DNs in SNpc and striatal axonal swellings in 120 F2-En1+/- 17 week-old male mice. Linkage analyses revealed 8 QTLs linked to number of DNs (p = 2.4e-09, variance explained = 74%), 7 QTLs linked to load of axonal swellings (p = 1.7e-12, variance explained = 80%) and 8 QTLs linked to size of axonal swellings (p = 7.0e-11, variance explained = 74%). These loci should be of prime interest for studies of susceptibility to Parkinson's disease-like damage in rodent disease models and considered in clinical association studies in PD. PMID:27550741

  2. Identification of Multiple QTLs Linked to Neuropathology in the Engrailed-1 Heterozygous Mouse Model of Parkinson’s Disease

    PubMed Central

    Kurowska, Zuzanna; Jewett, Michael; Brattås, Per Ludvik; Jimenez-Ferrer, Itzia; Kenéz, Xuyian; Björklund, Tomas; Nordström, Ulrika; Brundin, Patrik; Swanberg, Maria

    2016-01-01

    Motor symptoms in Parkinson’s disease are attributed to degeneration of midbrain dopaminergic neurons (DNs). Heterozygosity for Engrailed-1 (En1), one of the key factors for programming and maintenance of DNs, results in a parkinsonian phenotype featuring progressive degeneration of DNs in substantia nigra pars compacta (SNpc), decreased striatal dopamine levels and swellings of nigro-striatal axons in the SwissOF1-En1+/− mouse strain. In contrast, C57Bl/6-En1+/− mice do not display this neurodegenerative phenotype, suggesting that susceptibility to En1 heterozygosity is genetically regulated. Our goal was to identify quantitative trait loci (QTLs) that regulate the susceptibility to PD-like neurodegenerative changes in response to loss of one En1 allele. We intercrossed SwissOF1-En1+/− and C57Bl/6 mice to obtain F2 mice with mixed genomes and analyzed number of DNs in SNpc and striatal axonal swellings in 120 F2-En1+/− 17 week-old male mice. Linkage analyses revealed 8 QTLs linked to number of DNs (p = 2.4e-09, variance explained = 74%), 7 QTLs linked to load of axonal swellings (p = 1.7e-12, variance explained = 80%) and 8 QTLs linked to size of axonal swellings (p = 7.0e-11, variance explained = 74%). These loci should be of prime interest for studies of susceptibility to Parkinson’s disease-like damage in rodent disease models and considered in clinical association studies in PD. PMID:27550741

  3. Links between circulation indices and precipitation in the Mediterranean in an ensemble of regional climate models

    NASA Astrophysics Data System (ADS)

    Beranová, Romana; Kyselý, Jan

    2016-02-01

    Spatial and temporal variability of precipitation in the Mediterranean is related to atmospheric circulation patterns such as the North Atlantic Oscillation (NAO), the Mediterranean Oscillation (MO) and the Western Mediterranean Oscillation (WeMO). This study examines ability of an ensemble of 12 regional climate model (RCM) simulations to reproduce observed links between these circulation indices and precipitation, as well as how these links may change in the late twenty-first century. We focus on the winter season and differences in precipitation amounts on the highest and lowest 25 % of days according to a given index. The relationships are evaluated against the E-OBS data set for 1961-1990. The observed pattern of differences in precipitation between positive and negative phases is generally similar for MO and NAO, which relates to the high correlation between these indices. Most regional climate models (RCMs) simulate links between the circulation indices and precipitation over most of the Mediterranean area reasonably well, especially for the MO and WeMO indices. The RCM with the largest deficiencies in reproducing the links is HadRM for all indices. The spatial patterns of differences in daily precipitation under positive and negative phases of the circulation indices for the future scenario (2070-2099) are similar to those for the control climate for all indices. This suggests that NAO, MO and WeMO are likely to play similar roles in affecting precipitation in the Mediterranean also in the future. However, increased NAO and decreased WeMO index, projected in most examined RCMs for the late twenty-first century in winter, may affect overall precipitation patterns.

  4. Kinematic modeling of mobile robot with rocker-bogie link structure

    NASA Astrophysics Data System (ADS)

    Gang, Taig-Gi; Yi, Soo-Yeong

    2005-12-01

    A method for kinematic modeling of a mobile robot with rocker-bogie link mechanism was described. By using the well-known concept of the instantaneous coordinates, it derives the kinematic model for the full six degree of freedom motion including the x, y, and z motions and the pitch, roll, and yaw rotations. The kinematic model here implies both of the forward and the inverse kinematic equations. The forward kinematic equation with the wheel Jacobian matrices can be used to obtain the robot position and orientation from the measured wheel velocities and the rocker-bogie joint angles. On the contrary, the inverse kinematic equation implies a resulting robot motions consisting of body velocity and turning rate from the individual wheel velocities. Through the computer simulation, the kinematic model of the mobile robot was verified.

  5. Global sensitivity analysis, probabilistic calibration, and predictive assessment for the data assimilation linked ecosystem carbon model

    NASA Astrophysics Data System (ADS)

    Safta, C.; Ricciuto, D. M.; Sargsyan, K.; Debusschere, B.; Najm, H. N.; Williams, M.; Thornton, P. E.

    2015-07-01

    In this paper we propose a probabilistic framework for an uncertainty quantification (UQ) study of a carbon cycle model and focus on the comparison between steady-state and transient simulation setups. A global sensitivity analysis (GSA) study indicates the parameters and parameter couplings that are important at different times of the year for quantities of interest (QoIs) obtained with the data assimilation linked ecosystem carbon (DALEC) model. We then employ a Bayesian approach and a statistical model error term to calibrate the parameters of DALEC using net ecosystem exchange (NEE) observations at the Harvard Forest site. The calibration results are employed in the second part of the paper to assess the predictive skill of the model via posterior predictive checks.

  6. TESTING POPULATION-SPECIFIC QUANTITATIVE TRAIT ASSOCIATIONS FOR CLINICAL OUTCOME RELEVANCE IN A BIOREPOSITORY LINKED TO ELECTRONIC HEALTH RECORDS: LPA AND MYOCARDIAL INFARCTION IN AFRICAN AMERICANS

    PubMed Central

    Dumitrescu, Logan; Diggins, Kirsten E.; Goodloe, Robert; Crawford, Dana C.

    2015-01-01

    Previous candidate gene and genome-wide association studies have identified common genetic variants in LPA associated with the quantitative trait Lp(a), an emerging risk factor for cardiovascular disease. These associations are population-specific and many have not yet been tested for association with the clinical outcome of interest. To fill this gap in knowledge, we accessed the epidemiologic Third National Health and Nutrition Examination Surveys (NHANES III) and BioVU, the Vanderbilt University Medical Center biorepository linked to de-identified electronic health records (EHRs), including billing codes (ICD-9-CM) and clinical notes, to test population-specific Lp(a)-associated variants for an association with myocardial infarction (MI) among African Americans. We performed electronic phenotyping among African Americans in BioVU ≥40 years of age using billing codes. At total of 93 cases and 522 controls were identified in NHANES III and 265 cases and 363 controls were identified in BioVU. We tested five known Lp(a)-associated genetic variants (rs1367211, rs41271028, rs6907156, rs10945682, and rs1652507) in both NHANES III and BioVU for association with myocardial infarction. We also tested LPA rs3798220 (I4399M), previously associated with increased levels of Lp(a), MI, and coronary artery disease in European Americans, in BioVU. After meta-analysis, tests of association using logistic regression assuming an additive genetic model revealed no significant associations (p<0.05) for any of the five LPA variants previously associated with Lp(a) levels in African Americans. Also, I4399M rs3798220 was not associated with MI in African Americans (odds ratio = 0.51; 95% confidence interval: 0.16 – 1.65; p=0.26) despite strong, replicated associations with MI and coronary artery disease in European American genome-wide association studies. These data highlight the challenges in translating quantitative trait associations to clinical outcomes in diverse populations

  7. TESTING POPULATION-SPECIFIC QUANTITATIVE TRAIT ASSOCIATIONS FOR CLINICAL OUTCOME RELEVANCE IN A BIOREPOSITORY LINKED TO ELECTRONIC HEALTH RECORDS: LPA AND MYOCARDIAL INFARCTION IN AFRICAN AMERICANS.

    PubMed

    Dumitrescu, Logan; Diggins, Kirsten E; Goodloe, Robert; Crawford, Dana C

    2016-01-01

    Previous candidate gene and genome-wide association studies have identified common genetic variants in LPA associated with the quantitative trait Lp(a), an emerging risk factor for cardiovascular disease. These associations are population-specific and many have not yet been tested for association with the clinical outcome of interest. To fill this gap in knowledge, we accessed the epidemiologic Third National Health and Nutrition Examination Surveys (NHANES III) and BioVU, the Vanderbilt University Medical Center biorepository linked to de-identified electronic health records (EHRs), including billing codes (ICD-9-CM) and clinical notes, to test population-specific Lp(a)-associated variants for an association with myocardial infarction (MI) among African Americans. We performed electronic phenotyping among African Americans in BioVU≥40 years of age using billing codes. At total of 93 cases and 522 controls were identified in NHANES III and 265 cases and 363 controls were identified in BioVU. We tested five known Lp(a)-associated genetic variants (rs1367211, rs41271028, rs6907156, rs10945682, and rs1652507) in both NHANES III and BioVU for association with myocardial infarction. We also tested LPA rs3798220 (I4399M), previously associated with increased levels of Lp(a), MI, and coronary artery disease in European Americans, in BioVU. After meta-analysis, tests of association using logistic regression assuming an additive genetic model revealed no significant associations (p<0.05) for any of the five LPA variants previously associated with Lp(a) levels in African Americans. Also, I4399M rs3798220 was not associated with MI in African Americans (odds ratio = 0.51; 95% confidence interval: 0.16 - 1.65; p=0.26) despite strong, replicated associations with MI and coronary artery disease in European American genome-wide association studies. These data highlight the challenges in translating quantitative trait associations to clinical outcomes in diverse populations

  8. Exposure–Response Modeling of Clinical End Points Using Latent Variable Indirect Response Models

    PubMed Central

    Hu, C

    2014-01-01

    Exposure–response modeling facilitates effective dosing regimen selection in clinical drug development, where the end points are often disease scores and not physiological variables. Appropriate models need to be consistent with pharmacology and identifiable from the time courses of available data. This article describes a general framework of applying mechanism-based models to various types of clinical end points. Placebo and drug model parameterization, interpretation, and assessment are discussed with a focus on the indirect response models. PMID:24897307

  9. Full Scale Rotor Aeroacoustic Predictions and the Link to Model Scale Rotor Data

    NASA Technical Reports Server (NTRS)

    Boyd, D. Douglas, Jr.; Burley, Casey L.; Conner, David A.

    2004-01-01

    The NASA Aeroacoustic Prediction System (NAPS) is used to establish a link between model-scale and full-scale rotor predictions and is partially validated against measured wind tunnel and flight aeroacoustic data. The prediction approach of NAPS couples a comprehensive rotorcraft analysis with acoustic source noise and propagation codes. The comprehensive analysis selected for this study is CAMRAD-II, which provides the performance/trim/wake solution for a given rotor or flight condition. The post-trim capabilities of CAMRAD-II are used to compute high-resolution sectional airloads for the acoustic tone noise analysis, WOPMOD. The tone noise is propagated to observers on the ground with the propagation code, RNM (Rotor Noise Model). Aeroacoustic predictions are made with NAPS for an isolated rotor and compared to results of the second Harmonic Aeroacoustic Rotor Test (HART-II) program, which tested a 40% dynamically and Mach-scaled BO-105 main rotor at the DNW. The NAPS is validated with comparisons for three rotor conditions: a baseline condition and two Higher Harmonic Control (HHC) conditions. To establish a link between model and full-scale rotor predictions, a full-scale BO-105 main rotor input deck for NAPS is created from the 40% scale rotor input deck. The full-scale isolated rotor predictions are then compared to the model predictions. The comparisons include aerodynamic loading, acoustic levels, and acoustic pressure time histories for each of the three conditions. With this link established, full-scale predictions are made for a range of descent flight conditions and compared with measured trends from the recent Rotorcraft Operational Noise Abatement Procedures (RONAP) flight test conducted by DLR and ONERA. Additionally, the effectiveness of two HHC conditions from the HART-II program is demonstrated for the full-scale rotor in flight.

  10. Latent constructs model explaining the attachment-linked variation in autobiographical remembering.

    PubMed

    Öner, Sezin; Gülgöz, Sami

    2016-01-01

    In the current study, we proposed a latent constructs model to characterise the qualitative aspects of autobiographical remembering and investigated the structural relations in the model that may vary across individuals. Primarily, we focused on the memories of romantic relationships and argued that attachment anxiety and avoidance would be reflected in the ways that individuals encode, rehearse, or remember autobiographical memories in close relationships. Participants reported two positive and two negative relationship-specific memories and rated the characteristics for each memory. As predicted, the basic memory model yielded appropriate fit, indicating that event characteristics (EC) predicted the frequency of rehearsal (RC) and phenomenology at retrieval (PC). When attachment variables were integrated, the model showed that rehearsal mediated the link between anxiety and PC, especially for negative memories. On the other hand, for avoidance EC was the key factor mediating the link between avoidance and RC, as well as PC. Findings were discussed with respect to autobiographical memory functions emphasising a systematically, integrated framework. PMID:25716295

  11. Linked Hydrologic-Hydrodynamic Model Framework to Forecast Impacts of Rivers on Beach Water Quality

    NASA Astrophysics Data System (ADS)

    Anderson, E. J.; Fry, L. M.; Kramer, E.; Ritzenthaler, A.

    2014-12-01

    The goal of NOAA's beach quality forecasting program is to use a multi-faceted approach to aid in detection and prediction of bacteria in recreational waters. In particular, our focus has been on the connection between tributary loads and bacteria concentrations at nearby beaches. While there is a clear link between stormwater runoff and beach water quality, quantifying the contribution of river loadings to nearshore bacterial concentrations is complicated due to multiple processes that drive bacterial concentrations in rivers as well as those processes affecting the fate and transport of bacteria upon exiting the rivers. In order to forecast potential impacts of rivers on beach water quality, we developed a linked hydrologic-hydrodynamic water quality framework that simulates accumulation and washoff of bacteria from the landscape, and then predicts the fate and transport of washed off bacteria from the watershed to the coastal zone. The framework includes a watershed model (IHACRES) to predict fecal indicator bacteria (FIB) loadings to the coastal environment (accumulation, wash-off, die-off) as a function of effective rainfall. These loadings are input into a coastal hydrodynamic model (FVCOM), including a bacteria transport model (Lagrangian particle), to simulate 3D bacteria transport within the coastal environment. This modeling system provides predictive tools to assist local managers in decision-making to reduce human health threats.

  12. A linked simulation-optimization model for solving the unknown groundwater pollution source identification problems.

    PubMed

    Ayvaz, M Tamer

    2010-09-20

    This study proposes a linked simulation-optimization model for solving the unknown groundwater pollution source identification problems. In the proposed model, MODFLOW and MT3DMS packages are used to simulate the flow and transport processes in the groundwater system. These models are then integrated with an optimization model which is based on the heuristic harmony search (HS) algorithm. In the proposed simulation-optimization model, the locations and release histories of the pollution sources are treated as the explicit decision variables and determined through the optimization model. Also, an implicit solution procedure is proposed to determine the optimum number of pollution sources which is an advantage of this model. The performance of the proposed model is evaluated on two hypothetical examples for simple and complex aquifer geometries, measurement error conditions, and different HS solution parameter sets. Identified results indicated that the proposed simulation-optimization model is an effective way and may be used to solve the inverse pollution source identification problems. PMID:20633952

  13. Making interprofessional education real: a university clinic model.

    PubMed

    Copley, Jodie A; Allison, Heather D; Hill, Anne E; Moran, Monica C; Tait, Judy A; Day, Toni

    2007-08-01

    Interprofessional education (IPE) is an emerging focus in the professional training of allied health students. To date, IPE has occurred in classroom teaching or case simulations, rather than in the provision of client services. At the University of Queensland, students in occupational therapy, speech pathology and music therapy participate in both on-campus and community-based IPE clinics conducted by university staff. These clinics are planned and implemented to promote interprofessional learning for students, and to provide integrated service provision for children and young people in the community. An adapted version of Bronstein's model of interdisciplinary collaboration is used to guide IPE processes, including team orientation, joint goal-setting and intervention planning, and integrated delivery of therapy sessions. The development and implementation of these IPE clinics is described, together with challenges to clinical IPE in the university context. PMID:17669056

  14. Collagen cross-linking effect on progressive keratoconus in patients younger than 18 years of age: A clinical trial

    PubMed Central

    Peyman, Alireza; Kamali, Ali; Khushabi, Maral; Nasrollahi, Kobra; Kargar, Neda; Taghaodi, Maryam; Razmjoo, Hasan; Fazel, Farhad; Salesi, Asiyeh

    2015-01-01

    Background: Keratoconus is a bilateral non-inflammatory corneal disease. Collagen cross-linking (CXL) is a new treatment option for the disease that uses ultraviolet A light irradiation and riboflavin administration. The aim of this study is to evaluate the effect of CXL on corneal topographic and refractive values in patients with keratoconus younger than 18 years of age. Materials and Methods: For the clinical trial study, 37 patients (64 eyes) younger than 18 years of age with progressive keratoconus were included. Age, sex, family history of keratoconus, and history of allergic disorders and eye rubbing were recorded. Refractive, topographic, and topometric indices were evaluated before and 12 months after the CXL with 3mW for 30 minutes. Results: Mean age (±SD) of the patients was 15.83 ± 1.53 years; 26 (70.3%) of the 37 patients were male. Fourteen (37.8%) had positive family history of keratoconus, 11 (29.7%) had history of allergic disorders, and 15 (40.5%) had positive history of eye rubbing. Of the refractive values, cylinder value decreased significantly from −4.50 ± 0.29 to −4.11 ± 0.28 (P = 0.001). Also, the logarithm of minimal angle of resolution (logMAR) uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) improved significantly 12 months after CXL (P = 0.012 and 0.001, respectively). Maximum keratometry before and after the operation was 53.82 ± 0.72 and 53.33 ± 0.72, respectively (P = 0.018). Differences for simulated K values, the thinnest cornea pachymetry, keratoconus index (KI), index of highest asymmetry (IHA), and index of highest decentration (IHD) before and 12 months after the CXL were statistically significant (P = 0.015, 0.034, <0.001, 0.017, 0.019, and 0.004, respectively). Conclusion: CXL improves the refractory, topographic, and topometric indices in patients with keratoconus younger than 18 years of age. PMID:26693470

  15. Multicountry prospective clinical evaluation of two enzyme-linked immunosorbent assays and two rapid diagnostic tests for diagnosing dengue fever.

    PubMed

    Pal, Subhamoy; Dauner, Allison L; Valks, Andrea; Forshey, Brett M; Long, Kanya C; Thaisomboonsuk, Butsaya; Sierra, Gloria; Picos, Victor; Talmage, Sara; Morrison, Amy C; Halsey, Eric S; Comach, Guillermo; Yasuda, Chadwick; Loeffelholz, Michael; Jarman, Richard G; Fernandez, Stefan; An, Ung Sam; Kochel, Tadeusz J; Jasper, Louis E; Wu, Shuenn-Jue L

    2015-04-01

    We evaluated four dengue diagnostic devices from Alere, including the SD Bioline Dengue Duo (nonstructural [NS] 1 Ag and IgG/IgM), the Panbio Dengue Duo Cassette (IgM/IgG) rapid diagnostic tests (RDTs), and the Panbio dengue IgM and IgG capture enzyme-linked immunosorbent assays (ELISAs) in a prospective, controlled, multicenter study in Peru, Venezuela, Cambodia, and the United States, using samples from 1,021 febrile individuals. Archived, well-characterized samples from an additional 135 febrile individuals from Thailand were also used. Reference testing was performed on all samples using an algorithm involving virus isolation, in-house IgM and IgG capture ELISAs, and plaque reduction neutralization tests (PRNT) to determine the infection status of the individual. The primary endpoints were the clinical sensitivities and specificities of these devices. The SD Bioline Dengue Duo had an overall sensitivity of 87.3% (95% confidence interval [CI], 84.1 to 90.2%) and specificity of 86.8% (95% CI, 83.9 to 89.3%) during the first 14 days post-symptom onset (p.s.o.). The Panbio Dengue Duo Cassette demonstrated a sensitivity of 92.1% (87.8 to 95.2%) and specificity of 62.2% (54.5 to 69.5%) during days 4 to 14 p.s.o. The Panbio IgM capture ELISA had a sensitivity of 87.6% (82.7 to 91.4%) and specificity of 88.1% (82.2 to 92.6%) during days 4 to 14 p.s.o. Finally, the Panbio IgG capture ELISA had a sensitivity of 69.6% (62.1 to 76.4%) and a specificity of 88.4% (82.6 to 92.8%) during days 4 to 14 p.s.o. for identification of secondary dengue infections. This multicountry prospective study resulted in reliable real-world performance data that will facilitate data-driven laboratory test choices for managing patient care during dengue outbreaks. PMID:25588659

  16. Multicountry Prospective Clinical Evaluation of Two Enzyme-Linked Immunosorbent Assays and Two Rapid Diagnostic Tests for Diagnosing Dengue Fever

    PubMed Central

    Dauner, Allison L.; Valks, Andrea; Forshey, Brett M.; Long, Kanya C.; Thaisomboonsuk, Butsaya; Sierra, Gloria; Picos, Victor; Talmage, Sara; Morrison, Amy C.; Halsey, Eric S.; Comach, Guillermo; Yasuda, Chadwick; Loeffelholz, Michael; Jarman, Richard G.; Fernandez, Stefan; An, Ung Sam; Kochel, Tadeusz J.; Jasper, Louis E.; Wu, Shuenn-Jue L.

    2015-01-01

    We evaluated four dengue diagnostic devices from Alere, including the SD Bioline Dengue Duo (nonstructural [NS] 1 Ag and IgG/IgM), the Panbio Dengue Duo Cassette (IgM/IgG) rapid diagnostic tests (RDTs), and the Panbio dengue IgM and IgG capture enzyme-linked immunosorbent assays (ELISAs) in a prospective, controlled, multicenter study in Peru, Venezuela, Cambodia, and the United States, using samples from 1,021 febrile individuals. Archived, well-characterized samples from an additional 135 febrile individuals from Thailand were also used. Reference testing was performed on all samples using an algorithm involving virus isolation, in-house IgM and IgG capture ELISAs, and plaque reduction neutralization tests (PRNT) to determine the infection status of the individual. The primary endpoints were the clinical sensitivities and specificities of these devices. The SD Bioline Dengue Duo had an overall sensitivity of 87.3% (95% confidence interval [CI], 84.1 to 90.2%) and specificity of 86.8% (95% CI, 83.9 to 89.3%) during the first 14 days post-symptom onset (p.s.o.). The Panbio Dengue Duo Cassette demonstrated a sensitivity of 92.1% (87.8 to 95.2%) and specificity of 62.2% (54.5 to 69.5%) during days 4 to 14 p.s.o. The Panbio IgM capture ELISA had a sensitivity of 87.6% (82.7 to 91.4%) and specificity of 88.1% (82.2 to 92.6%) during days 4 to 14 p.s.o. Finally, the Panbio IgG capture ELISA had a sensitivity of 69.6% (62.1 to 76.4%) and a specificity of 88.4% (82.6 to 92.8%) during days 4 to 14 p.s.o. for identification of secondary dengue infections. This multicountry prospective study resulted in reliable real-world performance data that will facilitate data-driven laboratory test choices for managing patient care during dengue outbreaks. PMID:25588659

  17. Application of cross-linked and hydrolyzed arabinoxylans in baking of model rye bread.

    PubMed

    Buksa, Krzysztof; Nowotna, Anna; Ziobro, Rafał

    2016-02-01

    The role of water extractable arabinoxylan with varying molar mass and structure (cross-linked vs. hydrolyzed) in the structure formation of rye bread was examined using a model bread. Instead of the normal flour, the dough contained starch, arabinoxylan and protein, which were isolated from rye wholemeal. It was observed that the applied mixes of these constituents result in a product closely resembling typical rye bread, even if arabinoxylan was modified (by cross-linking or hydrolysis). The levels of arabinoxylan required for bread preparation depended on its modification and mix composition. At 3% protein, the maximum applicable level of poorly soluble cross-linked arabinoxylan was 3%, as higher amounts of this preparation resulted in an extensively viscous dough and diminished bread volume. On the other hand highly soluble, hydrolyzed arabinoxylan could be used at a higher level (6%) together with larger amounts of rye protein (3% or 6%). Further addition of arabinoxylan leads to excessive water absorption, resulting in a decreased viscosity of the dough during baking and insufficient gas retention. PMID:26304439

  18. An atomistic model for cross-linked HNBR elastomers used in seals

    NASA Astrophysics Data System (ADS)

    Molinari, Nicola; Sutton, Adrian; Stevens, John; Mostofi, Arash

    2015-03-01

    Hydrogenated nitrile butadiene rubber (HNBR) is one of the most common elastomeric materials used for seals in the oil and gas industry. These seals sometimes suffer ``explosive decompression,'' a costly problem in which gases permeate a seal at the elevated temperatures and pressures pertaining in oil and gas wells, leading to rupture when the seal is brought back to the surface. The experimental evidence that HNBR and its unsaturated parent NBR have markedly different swelling properties suggests that cross-linking may occur during hydrogenation of NBR to produce HNBR. We have developed a code compatible with the LAMMPS molecular dynamics package to generate fully atomistic HNBR configurations by hydrogenating initial NBR structures. This can be done with any desired degree of cross-linking. The code uses a model of atomic interactions based on the OPLS-AA force-field. We present calculations of the dependence of a number of bulk properties on the degree of cross-linking. Using our atomistic representations of HNBR and NBR, we hope to develop a better molecular understanding of the mechanisms that result in explosive decompression.

  19. LERC-SLAM - THE NASA LEWIS RESEARCH CENTER SATELLITE LINK ATTENUATION MODEL PROGRAM (MACINTOSH VERSION)

    NASA Technical Reports Server (NTRS)

    Manning, R. M.

    1994-01-01

    The frequency and intensity of rain attenuation affecting the communication between a satellite and an earth terminal is an important consideration in planning satellite links. The NASA Lewis Research Center Satellite Link Attenuation Model Program (LeRC-SLAM) provides a static and dynamic statistical assessment of the impact of rain attenuation on a communications link established between an earth terminal and a geosynchronous satellite. The program is designed for use in the specification, design and assessment of satellite links for any terminal location in the continental United States. The basis for LeRC-SLAM is the ACTS Rain Attenuation Prediction Model, which uses a log-normal cumulative probability distribution to describe the random process of rain attenuation on satellite links. The derivation of the statistics for the rainrate process at the specified terminal location relies on long term rainfall records compiled by the U.S. Weather Service during time periods of up to 55 years in length. The theory of extreme value statistics is also utilized. The user provides 1) the longitudinal position of the satellite in geosynchronous orbit, 2) the geographical position of the earth terminal in terms of latitude and longitude, 3) the height above sea level of the terminal site, 4) the yearly average rainfall at the terminal site, and 5) the operating frequency of the communications link (within 1 to 1000 GHz, inclusive). Based on the yearly average rainfall at the terminal location, LeRC-SLAM calculates the relevant rain statistics for the site using an internal data base. The program then generates rain attenuation data for the satellite link. This data includes a description of the static (i.e., yearly) attenuation process, an evaluation of the cumulative probability distribution for attenuation effects, and an evaluation of the probability of fades below selected fade depths. In addition, LeRC-SLAM calculates the elevation and azimuth angles of the terminal

  20. LERC-SLAM - THE NASA LEWIS RESEARCH CENTER SATELLITE LINK ATTENUATION MODEL PROGRAM (IBM PC VERSION)

    NASA Technical Reports Server (NTRS)

    Manning, R. M.

    1994-01-01

    The frequency and intensity of rain attenuation affecting the communication between a satellite and an earth terminal is an important consideration in planning satellite links. The NASA Lewis Research Center Satellite Link Attenuation Model Program (LeRC-SLAM) provides a static and dynamic statistical assessment of the impact of rain attenuation on a communications link established between an earth terminal and a geosynchronous satellite. The program is designed for use in the specification, design and assessment of satellite links for any terminal location in the continental United States. The basis for LeRC-SLAM is the ACTS Rain Attenuation Prediction Model, which uses a log-normal cumulative probability distribution to describe the random process of rain attenuation on satellite links. The derivation of the statistics for the rainrate process at the specified terminal location relies on long term rainfall records compiled by the U.S. Weather Service during time periods of up to 55 years in length. The theory of extreme value statistics is also utilized. The user provides 1) the longitudinal position of the satellite in geosynchronous orbit, 2) the geographical position of the earth terminal in terms of latitude and longitude, 3) the height above sea level of the terminal site, 4) the yearly average rainfall at the terminal site, and 5) the operating frequency of the communications link (within 1 to 1000 GHz, inclusive). Based on the yearly average rainfall at the terminal location, LeRC-SLAM calculates the relevant rain statistics for the site using an internal data base. The program then generates rain attenuation data for the satellite link. This data includes a description of the static (i.e., yearly) attenuation process, an evaluation of the cumulative probability distribution for attenuation effects, and an evaluation of the probability of fades below selected fade depths. In addition, LeRC-SLAM calculates the elevation and azimuth angles of the terminal

  1. Probing the Lipid-Protein Interface Using Model Transmembrane Peptides with a Covalently Linked Acyl Chain

    PubMed Central

    Nyholm, Thomas K.M.; van Duyl, Bianca; Rijkers, Dirk T.S.; Liskamp, Rob M.J.; Killian, J. Antoinette

    2011-01-01

    The aim of this study was to gain insight into how interactions between proteins and lipids in membranes are sensed at the protein-lipid interface. As a probe to analyze this interface, we used deuterium-labeled acyl chains that were covalently linked to a model transmembrane peptide. First, a perdeuterated palmitoyl chain was coupled to the Trp-flanked peptide WALP23 (Ac-CGWW(LA)8LWWA-NH2), and the deuterium NMR spectrum was analyzed in di-C18:1-phosphatidylcholine (PC) bilayers. We found that the chain order of this peptide-linked chain is rather similar to that of a noncovalently coupled perdeuterated palmitoyl chain, except that it exhibits a slightly lower order. Similar results were obtained when site-specific deuterium labels were used and when the palmitoyl chain was attached to the more-hydrophobic model peptide WLP23 (Ac-CGWWL17WWA-NH2) or to the Lys-flanked peptide KALP23 (Ac-CGKK(LA)8LKKA-NH2). The experiments showed that the order of both the peptide-linked chains and the noncovalently coupled palmitoyl chains in the phospholipid bilayer increases in the order KALP23 < WALP23 < WLP23. Furthermore, changes in the bulk lipid bilayer thickness caused by varying the lipid composition from di-C14:1-PC to di-C18:1-PC or by including cholesterol were sensed rather similarly by the covalently coupled chain and the noncovalently coupled palmitoyl chains. The results indicate that the properties of lipids adjacent to transmembrane peptides mostly reflect the properties of the surrounding lipid bilayer, and hence that (at least for the single-span model peptides used in this study) annular lipids do not play a highly specific role in protein-lipid interactions. PMID:22004750

  2. LINKING ETA MODEL WITH THE COMMUNITY MULTISCALE AIR QUALITY (CMAQ) MODELING SYSTEM: OZONE BOUNDARY CONDITIONS

    EPA Science Inventory

    A prototype surface ozone concentration forecasting model system for the Eastern U.S. has been developed. The model system is consisting of a regional meteorological and a regional air quality model. It demonstrated a strong prediction dependence on its ozone boundary conditions....

  3. The Repeated Insertion Model for Rankings: Missing Link between Two Subset Choice Models

    ERIC Educational Resources Information Center

    Doignon, Jean-Paul; Pekec, Aleksandar; Regenwetter, Michel

    2004-01-01

    Several probabilistic models for subset choice have been proposed in the literature, for example, to explain approval voting data. We show that Marley et al.'s latent scale model is subsumed by Falmagne and Regenwetter's size-independent model, in the sense that every choice probability distribution generated by the former can also be explained by…

  4. The Cleveland Clinic: a distinctive model of American medicine

    PubMed Central

    2014-01-01

    The Cleveland Clinic is a large healthcare system based in Cleveland, Ohio (USA) with an extensive American (throughout Northeast Ohio; Weston, Florida; and Las Vegas, Nevada) and global presence (in Abu Dhabi, UAE; and with training alumni in >70 countries). Cleveland Clinic was founded in 1921 as a distinctive medical model with a tripartite mission of “better care of the sick, investigation of their problems, and more teaching of those who serve” which has been vibrantly maintained. Distinctive aspects of the Clinic include its being a closed staff, salaried, group practice which is physician-led and which features 1-year faculty appointments and a vigorous annual review process for all physicians and leaders. Regarding its tripartite mission, the Clinic has demonstrated longstanding clinical excellence, e.g., with consistent ranking as first in cardiovascular care in U.S. News and World Report and top-10 rankings in at least 12 other specialties. A longstanding tradition of research has contributed landmark discoveries, including performance of the first coronary revascularization procedure, the first intra-coronary angiogram, the world’s third face transplant, ongoing development of a breast cancer vaccine, etc. Regarding education, the Clinic serves many educational audiences excellently through its Education Institute. These audiences include medical students, graduate medical trainees, faculty physicians, nurses, and allied health providers (both within the Cleveland Clinic and from other institutions worldwide), and patients. The Education Institute also includes the Cleveland Clinic Academy, which offers training in leadership competencies to physicians, nurses, and healthcare administrators both within the Cleveland Clinic and to visitors from abroad (through the Executive Visitors Program and the Samson Global Leadership Academy for Healthcare Executives). The latter program is an intensive 2-week residential leadership development course for

  5. Excitonic Coupling and Femtosecond Relaxation of Zinc Porphyrin Oligomers Linked with Triazole Bridge: Dynamics and Modeling.

    PubMed

    Bukreev, Alexey; Mikhailov, Konstantin; Shelaev, Ivan; Gostev, Fedor; Polevaya, Yuliya; Tyurin, Vladimir; Beletskaya, Irina; Umansky, Stanislav; Nadtochenko, Victor

    2016-03-31

    The synthesis of new zinc porphyrin oligomers linked by a triazole bridge was carried out via "click" reaction. A split in the porphyrin oligomer B-band was observed. It was considered as evidence of exciton-excitonic coupling. The relaxation of excited states in Q-band porphyrin oligomers was studied by the femtosecond laser spectroscopy technique with a 20 fs pump pulse. The transient oscillations of two B-band excitonic peaks have a π-radian shift. For explanation of the coherent oscillation, a theoretical model was developed. The model considered the combination of the exciton-excitonic coupling between porphyrin rings in dimer and weak exciton-vibronic coupling in one porphyrin ring. By varying the values of the structural parameters of porphyrins (the strength values of this couplings and measure of symmetry breaking), we obtained correspondence between the experimental data (phase shift and amplitudes of the spectrum oscillations) and the predictions of the model developed here. PMID:26935579

  6. Two Allergen Model Reveals Complex Relationship Between IgE Cross-Linking and Degranulation

    PubMed Central

    Handlogten, Michael W.; Deak, Peter E.; Bilgicer, Basar

    2014-01-01

    Summary Allergy is an immune response to complex mixtures of multiple allergens yet current models use a single synthetic allergen. Multiple allergens were modeled using two well-defined tetravalent allergens each specific for a distinct IgE thus enabling a systematic approach to evaluate the effect of each allergen and percent of allergen specific IgE on mast cell degranulation. We found the overall degranulation response caused by two allergens is additive for low allergen concentrations or low percent specific IgE, does not change for moderate allergen concentrations with moderate to high percent specific IgE, and is reduced for high allergen concentrations with moderate to high percent specific IgE. These results provide further evidence that supra-optimal IgE cross-linking decreases the degranulation response and establishes the two allergen model as a relevant experimental system to elucidate mast cell degranulation mechanisms. PMID:25308278

  7. Modeling framework to link climate, hydrology and flood hazards: An application to Sacramento, California

    NASA Astrophysics Data System (ADS)

    Kim, B.; David, C. H.; Druffel-Rodriguez, R.; Sanders, B. F.; Famiglietti, J. S.

    2013-12-01

    The City of Sacramento and the broader delta region may be the most flood vulnerable urbanized area in the United States. Management of flood risk here and elsewhere requires an understanding of flooding hazards, which is in turn linked to California hydrology, climate, development and flood control infrastructure. A modeling framework is presented here to make predictions of flooding hazards (e.g., depth and velocity) at the household scale (personalized flood risk information), and to study how these predictions could change under different climate change, land-use change, and infrastructure adaptation scenarios. The framework couples a statewide hydrologic model (RAPID) that predicts runoff and streamflow to a city-scale hydrodynamic model (BreZo) capable of predicting levee-breach flows and overland flows into urbanized lowlands. Application of the framework to the Sacramento area is presented here, with a focus on data needs, computational demands, results and hazard communication strategies, for selected flooding scenarios.

  8. Link between hopping models and percolation scaling laws for charge transport in mixtures of small molecules

    NASA Astrophysics Data System (ADS)

    Ha, Dong-Gwang; Kim, Jang-Joo; Baldo, Marc A.

    2016-04-01

    Mixed host compositions that combine charge transport materials with luminescent dyes offer superior control over exciton formation and charge transport in organic light emitting devices (OLEDs). Two approaches are typically used to optimize the fraction of charge transport materials in a mixed host composition: either an empirical percolative model, or a hopping transport model. We show that these two commonly-employed models are linked by an analytic expression which relates the localization length to the percolation threshold and critical exponent. The relation is confirmed both numerically and experimentally through measurements of the relative conductivity of Tris(4-carbazoyl-9-ylphenyl)amine (TCTA) :1,3-bis(3,5-dipyrid-3-yl-phenyl)benzene (BmPyPb) mixtures with different concentrations, where the TCTA plays a role as hole conductor and the BmPyPb as hole insulator. The analytic relation may allow the rational design of mixed layers of small molecules for high-performance OLEDs.

  9. Linking Slow Dynamics and Local Structure in Simple Models of Glass-Forming Liquids

    NASA Astrophysics Data System (ADS)

    Coslovich, D.; Pastore, G.

    2008-07-01

    Establishing a relation between the dynamical features of supercooled liquids, their structural properties and the nature of intermolecular interactions is a key issue in the description of the glass transition. To investigate this point we perform molecular dynamics simulations for three model glass-forming liquids with different types of local order. Our results show that the roughness of the energy landscape, estimated from the amplitude of average energy barriers, and the localization of unstable modes provide useful means to rationalize the link between structure and dynamics in glass-forming liquids.

  10. Modeling channel interference in an orbital angular momentum-multiplexed laser link

    NASA Astrophysics Data System (ADS)

    Anguita, Jaime A.; Neifeld, Mark A.; Vasic, Bane V.

    2009-08-01

    We study the effects of optical turbulence on the energy crosstalk among constituent orbital angular momentum (OAM) states in a vortex-based multi-channel laser communication link and determine channel interference in terms of turbulence strength and OAM state separation. We characterize the channel interference as a function of C2n and transmit OAM state, and propose probability models to predict the random fluctuations in the received signals for such architecture. Simulations indicate that turbulence-induced channel interference is mutually correlated across receive channels.

  11. The clinical adoption meta-model: a temporal meta-model describing the clinical adoption of health information systems

    PubMed Central

    2014-01-01

    Health information systems (HISs) hold the promise to transform health care; however, their adoption is challenged. We have developed the Clinical Adoption Meta-Model (CAMM) to help describe processes and possible challenges with clinical adoption. The CAMM, developed through an action research study to evaluate a provincial HIS, is a temporal model with four dimensions: availability, use, behaviour changes, and outcome changes. Seven CAMM archetypes are described, illustrating classic trajectories of adoption of HISs over time. Each archetype includes an example from the literature. The CAMM and its archetypes can support HIS implementers, evaluators, learners, and researchers. PMID:24884588

  12. The clinical adoption meta-model: a temporal meta-model describing the clinical adoption of health information systems.

    PubMed

    Price, Morgan; Lau, Francis

    2014-01-01

    Health information systems (HISs) hold the promise to transform health care; however, their adoption is challenged. We have developed the Clinical Adoption Meta-Model (CAMM) to help describe processes and possible challenges with clinical adoption. The CAMM, developed through an action research study to evaluate a provincial HIS, is a temporal model with four dimensions: availability, use, behaviour changes, and outcome changes. Seven CAMM archetypes are described, illustrating classic trajectories of adoption of HISs over time. Each archetype includes an example from the literature. The CAMM and its archetypes can support HIS implementers, evaluators, learners, and researchers. PMID:24884588

  13. Modeling Clinical Radiation Responses in the IMRT Era

    NASA Astrophysics Data System (ADS)

    Schwartz, J. L.; Murray, D.; Stewart, R. D.; Phillips, M. H.

    2014-03-01

    The purpose of this review is to highlight the critical issues of radiobiological models, particularly as they apply to clinical radiation therapy. Developing models of radiation responses has a long history that continues to the present time. Many different models have been proposed, but in the field of radiation oncology, the linear-quadratic (LQ) model has had the most impact on the design of treatment protocols. Questions have been raised as to the value of the LQ model given that the biological assumption underlying it has been challenged by molecular analyses of cell and tissue responses to radiation. There are also questions as to use of the LQ model for hypofractionation, especially for high dose treatments using a single fraction. While the LQ model might over-estimate the effects of large radiation dose fractions, there is insufficient information to fully justify the adoption of alternative models. However, there is increasing evidence in the literature that non-targeted and other indirect effects of radiation sometimes produce substantial deviations from LQ-like dose-response curves. As preclinical and clinical hypofractionation studies accumulate, new or refined dose-response models that incorporate high-dose/fraction non-targeted and indirect effects may be required, but for now the LQ model remains a simple, useful tool to guide the design of treatment protocols.

  14. Clinical laboratory as an economic model for business performance analysis

    PubMed Central

    Buljanović, Vikica; Patajac, Hrvoje; Petrovečki, Mladen

    2011-01-01

    Aim To perform SWOT (strengths, weaknesses, opportunities, and threats) analysis of a clinical laboratory as an economic model that may be used to improve business performance of laboratories by removing weaknesses, minimizing threats, and using external opportunities and internal strengths. Methods Impact of possible threats to and weaknesses of the Clinical Laboratory at Našice General County Hospital business performance and use of strengths and opportunities to improve operating profit were simulated using models created on the basis of SWOT analysis results. The operating profit as a measure of profitability of the clinical laboratory was defined as total revenue minus total expenses and presented using a profit and loss account. Changes in the input parameters in the profit and loss account for 2008 were determined using opportunities and potential threats, and economic sensitivity analysis was made by using changes in the key parameters. The profit and loss account and economic sensitivity analysis were tools for quantifying the impact of changes in the revenues and expenses on the business operations of clinical laboratory. Results Results of simulation models showed that operational profit of €470 723 in 2008 could be reduced to only €21 542 if all possible threats became a reality and current weaknesses remained the same. Also, operational gain could be increased to €535 804 if laboratory strengths and opportunities were utilized. If both the opportunities and threats became a reality, the operational profit would decrease by €384 465. Conclusion The operational profit of the clinical laboratory could be significantly reduced if all threats became a reality and the current weaknesses remained the same. The operational profit could be increased by utilizing strengths and opportunities as much as possible. This type of modeling may be used to monitor business operations of any clinical laboratory and improve its financial situation by

  15. Linking nutrient loading and oxygen in the coastal ocean: A new global scale model

    NASA Astrophysics Data System (ADS)

    Reed, Daniel C.; Harrison, John A.

    2016-03-01

    Recent decades have witnessed an exponential spread of low-oxygen regions in the coastal ocean due at least in-part to enhanced terrestrial nutrient inputs. As oxygen deprivation is a major stressor on marine ecosystems, there is a great need to quantitatively link shifts in nutrient loading with changes in oxygen concentrations. To this end, we have developed and here describe, evaluate, and apply the Coastal Ocean Oxygen Linked to Benthic Exchange And Nutrient Supply (COOLBEANS) model, a first-of-its-kind, spatially explicit (with 152 coastal segments) model, global model of coastal oxygen and nutrient dynamics. In COOLBEANS, benthic oxygen demand (BOD) is calculated using empirical models for aerobic respiration, iron reduction, and sulfate reduction, while oxygen supply is represented by a simple parameterization of exchange between surface and bottom waters. A nutrient cycling component translates shifts in riverine nutrient inputs into changes in organic matter delivery to sediments and, ultimately, oxygen uptake. Modeled BOD reproduces observations reasonably well (Nash-Sutcliffe efficiency = 0.71), and estimates of exchange between surface and bottom waters correlate with stratification. The model examines sensitivity of bottom water oxygen to changes in nutrient inputs and vertical exchange between surface and bottom waters, highlighting the importance of this vertical exchange in defining the susceptibility of a system to oxygen depletion. These sensitivities along with estimated maximum hypoxic areas that are supported by present day nutrient loads are consistent with existing hypoxic regions. Sensitivities are put into context by applying historic changes in nitrogen loading observed in the Gulf of Mexico to the global coastal ocean, demonstrating that such loads would drive many systems anoxic or even sulfidic.

  16. The MOSART Database: Linking the SART CORS Clinical Database to the Population-Based Massachusetts PELL Reproductive Public Health Data System

    PubMed Central

    Hoang, Lan; Stern, Judy E.; Diop, Hafsatou; Belanoff, Candice; Declercq, Eugene

    2015-01-01

    Although Assisted Reproductive Technology (ART) births make up 1.6 % of births in the US, the impact of ART on subsequent infant and maternal health is not well understood. Clinical ART treatment records linked to population data would be a powerful tool to study long term outcomes among those treated or not by ART. This paper describes the development of a database intended to accomplish this task. We constructed the Massachusetts Outcomes Study of Assisted Reproductive Technology (MOSART) database by linking the Society of Assisted Reproductive Technologies Clinical Outcomes Reporting System (SART CORS) and the Massachusetts (MA) Pregnancy to Early Life Longitudinal (PELL) data systems for children born to MA resident women at MA hospitals between July 2004 and December 2008. PELL data representing 282,971 individual women and their 334,152 deliveries and 342,035 total births were linked with 48,578 cycles of ART treatment in SART CORS delivered to MA residents or women receiving treatment in MA clinics, representing 18,439 eligible women of whom 9,326 had 10,138 deliveries in this time period. A deterministic five phase linkage algorithm methodology was employed. Linkage results, accuracy, and concordance analyses were examined. We linked 9,092 (89.7 %) SART CORS outcome records to PELL delivery records overall, including 95.0 % among known MA residents treated in MA clinics; 70.8 % with full exact matches. There were minimal differences between matched and unmatched delivery records, except for unknown residency and out-of-state ART site. There was very low concordance of reported use of ART treatment between SART CORS and PELL (birth certificate) data. A total of 3.4 % of MA children (11,729) were identified from ART assisted pregnancies (6,556 singletons; 5,173 multiples). The MOSART linked database provides a strong basis for further longitudinal ART outcomes studies and supports the continued development of potentially powerful linked clinical-public health

  17. Liver regeneration - mechanisms and models to clinical application.

    PubMed

    Forbes, Stuart J; Newsome, Philip N

    2016-08-01

    Liver regeneration has been studied for many decades and the mechanisms underlying regeneration of the normal liver following resection or moderate damage are well described. A large number of factors extrinsic (such as bile acids and circulating growth factors) and intrinsic to the liver interact to initiate and regulate liver regeneration. Less well understood, and more clinically relevant, are the factors at play when the abnormal liver is required to regenerate. Fatty liver disease, chronic scarring, prior chemotherapy and massive liver injury can all inhibit the normal programme of regeneration and can lead to liver failure. Understanding these mechanisms could enable the rational targeting of specific therapies to either reduce the factors inhibiting regeneration or directly stimulate liver regeneration. Although animal models of liver regeneration have been highly instructive, the clinical relevance of some models could be improved to bridge the gap between our in vivo model systems and the clinical situation. Likewise, modern imaging techniques such as spectroscopy will probably improve our understanding of whole-organ metabolism and how this predicts the liver's regenerative capacity. This Review describes briefly the mechanisms underpinning liver regeneration, the models used to study this process, and discusses areas in which failed or compromised liver regeneration is clinically relevant. PMID:27353402

  18. Applications of the psychotherapy phase model to clinically significant deterioration.

    PubMed

    Swift, Joshua K; Callahan, Jennifer L; Heath, Christopher J; Herbert, Gregory L; Levine, Jason C

    2010-06-01

    While previous research on deterioration has focused on identifying individuals at risk for negative outcomes, little is known about the nature or pattern by which deterioration occurs. The problem of deterioration is especially salient in training clinics; a setting in which higher deterioration rates have been reported. Two studies were designed to test the applicability of the phase model to deterioration in a training clinic and to replicate the model with a training clinic referral-base sample. In Study 1, the course of therapy was monitored for 135 clients. For the 38 clients who deteriorated during therapy, a model where increased symptoms (demediation) reliably preceded both decreased functioning (dehabilitation) and decreased well-being (demoralization) was found. In Study 2, the same three phases were prospectively monitored for 914 undergraduate students on a weekly basis throughout a single semester. For the 158 individuals who deteriorated during this time, a model where demediation reliably preceded dehabilitation, which preceded demoralization was found. These results have clinical implications for the use of tailored intervention strategies focusing on the deterioration phases. PMID:22402050

  19. Clinical Reasoning in Athletic Training Education: Modeling Expert Thinking

    ERIC Educational Resources Information Center

    Geisler, Paul R.; Lazenby, Todd W.

    2009-01-01

    Objective: To address the need for a more definitive approach to critical thinking during athletic training educational experiences by introducing the clinical reasoning model for critical thinking. Background: Educators are aware of the need to teach students how to think critically. The multiple domains of athletic training are comprehensive and…

  20. A model integration approach linking signalling and gene-regulatory logic with kinetic metabolic models.

    PubMed

    Ryll, A; Bucher, J; Bonin, A; Bongard, S; Gonçalves, E; Saez-Rodriguez, J; Niklas, J; Klamt, S

    2014-10-01

    Systems biology has to increasingly cope with large- and multi-scale biological systems. Many successful in silico representations and simulations of various cellular modules proved mathematical modelling to be an important tool in gaining a solid understanding of biological phenomena. However, models spanning different functional layers (e.g. metabolism, signalling and gene regulation) are still scarce. Consequently, model integration methods capable of fusing different types of biological networks and various model formalisms become a key methodology to increase the scope of cellular processes covered by mathematical models. Here we propose a new integration approach to couple logical models of signalling or/and gene-regulatory networks with kinetic models of metabolic processes. The procedure ends up with an integrated dynamic model of both layers relying on differential equations. The feasibility of the approach is shown in an illustrative case study integrating a kinetic model of central metabolic pathways in hepatocytes with a Boolean logical network depicting the hormonally induced signal transduction and gene regulation events involved. In silico simulations demonstrate the integrated model to qualitatively describe the physiological switch-like behaviour of hepatocytes in response to nutritionally regulated changes in extracellular glucagon and insulin levels. A simulated failure mode scenario addressing insulin resistance furthermore illustrates the pharmacological potential of a model covering interactions between signalling, gene regulation and metabolism. PMID:25063553

  1. Ensuring Congruency in Multiscale Modeling: Towards Linking Agent Based and Continuum Biomechanical Models of Arterial Adaptation

    PubMed Central

    Hayenga, Heather N.; Thorne, Bryan C.; Peirce, Shayn M.; Humphrey, Jay D.

    2011-01-01

    There is a need to develop multiscale models of vascular adaptations to understand tissue level manifestations of cellular level mechanisms. Continuum based biomechanical models are well suited for relating blood pressures and flows to stress-mediated changes in geometry and properties, but less so for describing underlying mechanobiological processes. Discrete stochastic agent based models are well suited for representing biological processes at a cellular level, but not for describing tissue level mechanical changes. We present here a conceptually new approach to facilitate the coupling of continuum and agent based models. Because of ubiquitous limitations in both the tissue- and cell-level data from which one derives constitutive relations for continuum models and rule-sets for agent based models, we suggest that model verification should enforce congruency across scales. That is, multiscale model parameters initially determined from data sets representing different scales should be refined, when possible, to ensure that common outputs are consistent. Potential advantages of this approach are illustrated by comparing simulated aortic responses to a sustained increase in blood pressure predicted by continuum and agent based models both before and after instituting a genetic algorithm to refine 16 objectively bounded model parameters. We show that congruency-based parameter refinement not only yielded increased consistency across scales, it also yielded predictions that are closer to in vivo observations. PMID:21809144

  2. Predictive statistical models linking antecedent meteorological conditions and waterway bacterial contamination in urban waterways.

    PubMed

    Farnham, David J; Lall, Upmanu

    2015-06-01

    Although the relationships between meteorological conditions and waterway bacterial contamination are being better understood, statistical models capable of fully leveraging these links have not been developed for highly urbanized settings. We present a hierarchical Bayesian regression model for predicting transient fecal indicator bacteria contamination episodes in urban waterways. Canals, creeks, and rivers of the New York City harbor system are used to examine the model. The model configuration facilitates the hierarchical structure of the underlying system with weekly observations nested within sampling sites, which in turn were nested inside of the harbor network. Models are compared using cross-validation and a variety of Bayesian and classical model fit statistics. The uncertainty of predicted enterococci concentration values is reflected by sampling from the posterior predictive distribution. Issuing predictions with the uncertainty reasonably reflected allows a water manager or a monitoring agency to issue warnings that better reflect the underlying risk of exposure. A model using only antecedent meteorological conditions is shown to correctly classify safe and unsafe levels of enterococci with good accuracy. The hierarchical Bayesian regression approach is most valuable where transient fecal indicator bacteria contamination is problematic and drainage network data are scarce. PMID:25813489

  3. A generalized linear mixed model for longitudinal binary data with a marginal logit link function

    PubMed Central

    Parzen, Michael; Ghosh, Souparno; Lipsitz, Stuart; Sinha, Debajyoti; Fitzmaurice, Garrett M.; Mallick, Bani K.; Ibrahim, Joseph G.

    2010-01-01

    Summary Longitudinal studies of a binary outcome are common in the health, social, and behavioral sciences. In general, a feature of random effects logistic regression models for longitudinal binary data is that the marginal functional form, when integrated over the distribution of the random effects, is no longer of logistic form. Recently, Wang and Louis (2003) proposed a random intercept model in the clustered binary data setting where the marginal model has a logistic form. An acknowledged limitation of their model is that it allows only a single random effect that varies from cluster to cluster. In this paper, we propose a modification of their model to handle longitudinal data, allowing separate, but correlated, random intercepts at each measurement occasion. The proposed model allows for a flexible correlation structure among the random intercepts, where the correlations can be interpreted in terms of Kendall’s τ. For example, the marginal correlations among the repeated binary outcomes can decline with increasing time separation, while the model retains the property of having matching conditional and marginal logit link functions. Finally, the proposed method is used to analyze data from a longitudinal study designed to monitor cardiac abnormalities in children born to HIV-infected women. PMID:21532998

  4. Burden of disease in adults admitted to hospital in a rural region of coastal Kenya: an analysis of data from linked clinical and demographic surveillance systems

    PubMed Central

    Etyang, Anthony O; Munge, Kenneth; Bunyasi, Erick W; Matata, Lena; Ndila, Carolyne; Kapesa, Sailoki; Owiti, Maureen; Khandwalla, Iqbal; Brent, Andrew J; Tsofa, Benjamin; Kabibu, Pamela; Morpeth, Susan; Bauni, Evasius; Otiende, Mark; Ojal, John; Ayieko, Philip; Knoll, Maria D; Smeeth, Liam; Williams, Thomas N; Griffiths, Ulla K; Scott, J Anthony G

    2014-01-01

    Summary Background Estimates of the burden of disease in adults in sub-Saharan Africa largely rely on models of sparse data. We aimed to measure the burden of disease in adults living in a rural area of coastal Kenya with use of linked clinical and demographic surveillance data. Methods We used data from 18 712 adults admitted to Kilifi District Hospital (Kilifi, Kenya) between Jan 1, 2007, and Dec 31, 2012, linked to 790 635 person-years of observation within the Kilifi Health and Demographic Surveillance System, to establish the rates and major causes of admission to hospital. These data were also used to model disease-specific disability-adjusted life-years lost in the population. We used geographical mapping software to calculate admission rates stratified by distance from the hospital. Findings The main causes of admission to hospital in women living within 5 km of the hospital were infectious and parasitic diseases (303 per 100 000 person-years of observation), pregnancy-related disorders (239 per 100 000 person-years of observation), and circulatory illnesses (105 per 100 000 person-years of observation). Leading causes of hospital admission in men living within 5 km of the hospital were infectious and parasitic diseases (169 per 100 000 person-years of observation), injuries (135 per 100 000 person-years of observation), and digestive system disorders (112 per 100 000 person-years of observation). HIV-related diseases were the leading cause of disability-adjusted life-years lost (2050 per 100 000 person-years of observation), followed by non-communicable diseases (741 per 100 000 person-years of observation). For every 5 km increase in distance from the hospital, all-cause admission rates decreased by 11% (95% CI 7–14) in men and 20% (17–23) in women. The magnitude of this decline was highest for endocrine disorders in women (35%; 95% CI 22–46) and neoplasms in men (30%; 9–45). Interpretation Adults in rural Kenya face a combined

  5. Multiscale Modeling in the Clinic: Drug Design and Development.

    PubMed

    Clancy, Colleen E; An, Gary; Cannon, William R; Liu, Yaling; May, Elebeoba E; Ortoleva, Peter; Popel, Aleksander S; Sluka, James P; Su, Jing; Vicini, Paolo; Zhou, Xiaobo; Eckmann, David M

    2016-09-01

    A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multiscale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multiscale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multiscale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical and computational techniques employed for multiscale modeling approaches used in pharmacometric and systems pharmacology models in drug development and present several examples illustrating the current state-of-the-art models for (1) excitable systems and applications in cardiac disease; (2) stem cell driven complex biosystems; (3) nanoparticle delivery, with applications to angiogenesis and cancer therapy; (4) host-pathogen interactions and their use in metabolic disorders, inflammation and sepsis; and (5) computer-aided design of nanomedical systems. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multiscale models. PMID:26885640

  6. Model Comparison for Breast Cancer Prognosis Based on Clinical Data

    PubMed Central

    Boughorbel, Sabri; Al-Ali, Rashid; Elkum, Naser

    2016-01-01

    We compared the performance of several prediction techniques for breast cancer prognosis, based on AU-ROC performance (Area Under ROC) for different prognosis periods. The analyzed dataset contained 1,981 patients and from an initial 25 variables, the 11 most common clinical predictors were retained. We compared eight models from a wide spectrum of predictive models, namely; Generalized Linear Model (GLM), GLM-Net, Partial Least Square (PLS), Support Vector Machines (SVM), Random Forests (RF), Neural Networks, k-Nearest Neighbors (k-NN) and Boosted Trees. In order to compare these models, paired t-test was applied on the model performance differences obtained from data resampling. Random Forests, Boosted Trees, Partial Least Square and GLMNet have superior overall performance, however they are only slightly higher than the other models. The comparative analysis also allowed us to define a relative variable importance as the average of variable importance from the different models. Two sets of variables are identified from this analysis. The first includes number of positive lymph nodes, tumor size, cancer grade and estrogen receptor, all has an important influence on model predictability. The second set incudes variables related to histological parameters and treatment types. The short term vs long term contribution of the clinical variables are also analyzed from the comparative models. From the various cancer treatment plans, the combination of Chemo/Radio therapy leads to the largest impact on cancer prognosis. PMID:26771838

  7. A Model of Placebo Response in Antidepressant Clinical Trials

    PubMed Central

    Rutherford, Bret R; Roose, Steven P.

    2012-01-01

    Placebo response in clinical trials of antidepressant medications is substantial and increasing. High placebo response rates hamper efforts to detect signals of efficacy for new antidepressant medications, contributing to more failed trials and delaying the delivery of new treatments to market. Media reports seize upon increasing placebo response and modest advantages for active drugs as reasons to question the value of antidepressant medication, which may further stigmatize treatments for depression and dissuade patients from accessing mental health care. Conversely, enhancing the factors responsible for placebo response may represent a strategy for improving available treatments for Major Depressive Disorder. A conceptual framework describing the causes of placebo response is needed in order to develop strategies for minimizing placebo response in clinical trials, maximizing placebo response in clinical practice, and talking with depressed patients about the risks and benefits of antidepressant medications. This review examines contributors to placebo response in antidepressant clinical trials and proposes an explanatory model. Research aimed at reducing placebo response should focus on limiting patient expectancy and the intensity of therapeutic contact in antidepressant clinical trials, while the optimal strategy in clinical practice may be to combine active medication with a presentation and level of therapeutic contact that enhances treatment response. PMID:23318413

  8. Comprehensive transgender healthcare: the gender affirming clinical and public health model of Fenway Health.

    PubMed

    Reisner, Sari L; Bradford, Judith; Hopwood, Ruben; Gonzalez, Alex; Makadon, Harvey; Todisco, David; Cavanaugh, Timothy; VanDerwarker, Rodney; Grasso, Chris; Zaslow, Shayne; Boswell, Stephen L; Mayer, Kenneth

    2015-06-01

    This report describes the evolution of a Boston community health center's multidisciplinary model of transgender healthcare, research, education, and dissemination of best practices. This process began with the development of a community-based approach to care that has been refined over almost 20 years where transgender patients have received tailored services through the Transgender Health Program. The program began as a response to unmet clinical needs and has grown through recognition that our local culturally responsive approach that links clinical care with biobehavioral and health services research, education, training, and advocacy promotes social justice and health equity for transgender people. Fenway Health's holistic public health efforts recognize the key role of gender affirmation in the care and well-being of transgender people worldwide. PMID:25779756

  9. A multivariate approach linking reported side effects of clinical antidepressant and antipsychotic trials to in vitro binding affinities

    PubMed Central

    Michl, Johanna; Scharinger, Christian; Zauner, Miriam; Kasper, Siegfried; Freissmuth, Michael; Sitte, Harald H.; Ecker, Gerhard F.; Pezawas, Lukas

    2015-01-01

    The vast majority of approved antidepressants and antipsychotics exhibit a complex pharmacology. The mechanistic understanding of how these psychotropic medications are related to adverse drug reactions (ADRs) is crucial for the development of novel drug candidates and patient adherence. This study aims to associate in vitro assessed binding affinity profiles (39 compounds, 24 molecular drug targets) and ADRs (n=22) reported in clinical trials of antidepressants and antipsychotics (n>59.000 patients) by the use of robust multivariate statistics. Orthogonal projection to latent structures (O-PLS) regression models with reasonable predictability were found for several frequent ADRs such as nausea, diarrhea, hypotension, dizziness, headache, insomnia, sedation, sleepiness, increased sweating, and weight gain. Results of the present study support many well-known pharmacological principles such as the association of hypotension and dizziness with α1-receptor or sedation with H1-receptor antagonism. Moreover, the analyses revealed novel or hardly investigated mechanisms for common ADRs including the potential involvement of 5-HT6-antagonism in weight gain, muscarinic receptor antagonism in dizziness, or 5-HT7-antagonism in sedation. To summarize, the presented study underlines the feasibility and value of a multivariate data mining approach in psychopharmacological development of antidepressants and antipsychotics. PMID:25044049

  10. Curative haploidentical BMT in a murine model of X-linked chronic granulomatous disease.

    PubMed

    Takeuchi, Yasuo; Takeuchi, Emiko; Ishida, Takashi; Onodera, Masafumi; Nakauchi, Hiromitsu; Otsu, Makoto

    2015-07-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by defective microbial killing in phagocytes. Long-term prognosis for CGD patients is generally poor, highlighting the need to develop minimally toxic, curative therapeutic approaches. We here describe the establishment of a mouse model in which X-linked CGD can be cured by allogeneic bone marrow transplantation. Using a combination of non-myeloablative-dose total body irradiation and a single injection of anti-CD40 ligand monoclonal antibody, transplantation of whole bone marrow cells achieved long-lasting mixed chimerism in X-linked CGD mice in a haploidentical transplantation setting. Stable mixed chimerism was maintained for up to 1 year even at a low range (<20 % donor cells), indicating induction of donor-specific tolerance. The regimen induced mild myelosuppression without severe acute complications. Stable chimerism was therapeutic, as it suppressed cutaneous granuloma formation in an in vivo test suited for evaluation of treatment efficacy in murine CGD models. These results warrant future development of a simplified allogeneic hematopoietic cell transplantation regimen that would benefit CGD patients by allowing the use of haploidentical donor grafts without serious concerns of severe treatment-related toxicity. PMID:25921405

  11. The reinstatement model and relapse prevention: a clinical perspective

    PubMed Central

    Preston, Kenzie L

    2005-01-01

    Objectives This commentary assesses the degree to which the reinstatement model is homologous to the human experience of relapse. Results A review of the literature suggests that the relationship is less clear than is often assumed, largely due to a lack of prospective data on the precipitants and process of relapse (especially relapse to heroin or cocaine abuse). However, reinstatement does not need to resemble relapse to have immediate clinical value; predictive validity as a medication screen would be sufficient. Whether the model has predictive validity is unknown, because, to date, very few clinical trials have tested medications that are effective in the reinstatement model, and even fewer have used designs comparable to those of reinstatement experiments. A clinical trial comparable to a reinstatement experiment would enroll participants who are already abstinent, and its main outcome measure would be propensity to undergo a specific type of relapse (e.g., relapse induced by stress or cues). Conclusions Until clinical and preclinical work are more comparable, criticisms of the reinstatement model’s presumed shortcomings are premature. PMID:12721778

  12. Condensation transitions in a model for a directed network with weighted links

    NASA Astrophysics Data System (ADS)

    Angel, A. G.; Hanney, T.; Evans, M. R.

    2006-01-01

    An exactly solvable model for the rewiring dynamics of weighted, directed networks is introduced. Simulations indicate that the model exhibits two types of condensation: (i) a phase in which, for each node, a finite fraction of its total out-strength condenses onto a single link; (ii) a phase in which a finite fraction of the total weight in the system is directed into a single node. A virtue of the model is that its dynamics can be mapped onto those of a zero-range process with many species of interacting particles—an exactly solvable model of particles hopping between the sites of a lattice. This mapping, which is described in detail, guides the analysis of the steady state of the network model and leads to theoretical predictions for the conditions under which the different types of condensation may be observed. A further advantage of the mapping is that, by exploiting what is known about exactly solvable generalizations of the zero-range process, one can infer a number of generalizations of the network model and dynamics which remain exactly solvable.

  13. Linking Statistically- and Physically-Based Models for Improved Streamflow Simulation in Gaged and Ungaged Areas

    NASA Astrophysics Data System (ADS)

    Lafontaine, J.; Hay, L.; Archfield, S. A.; Farmer, W. H.; Kiang, J. E.

    2014-12-01

    The U.S. Geological Survey (USGS) has developed a National Hydrologic Model (NHM) to support coordinated, comprehensive and consistent hydrologic model development, and facilitate the application of hydrologic simulations within the continental US. The portion of the NHM located within the Gulf Coastal Plains and Ozarks Landscape Conservation Cooperative (GCPO LCC) is being used to test the feasibility of improving streamflow simulations in gaged and ungaged watersheds by linking statistically- and physically-based hydrologic models. The GCPO LCC covers part or all of 12 states and 5 sub-geographies, totaling approximately 726,000 km2, and is centered on the lower Mississippi Alluvial Valley. A total of 346 USGS streamgages in the GCPO LCC region were selected to evaluate the performance of this new calibration methodology for the period 1980 to 2013. Initially, the physically-based models are calibrated to measured streamflow data to provide a baseline for comparison. An enhanced calibration procedure then is used to calibrate the physically-based models in the gaged and ungaged areas of the GCPO LCC using statistically-based estimates of streamflow. For this application, the calibration procedure is adjusted to address the limitations of the statistically generated time series to reproduce measured streamflow in gaged basins, primarily by incorporating error and bias estimates. As part of this effort, estimates of uncertainty in the model simulations are also computed for the gaged and ungaged watersheds.

  14. A computer model for unconscious spread of anxiety-linked inhibition in cognitive networks.

    PubMed

    Blum, G S

    1989-01-01

    Unconscious inhibitory processes, triggered by a potential anxiety reaction, are reviewed in the context of an emerging rapprochement between psychodynamic and cognitive approaches in experimental psychology. Conditions underlying spread of inhibitory action to other cognitive networks are first explored in three tachistoscopic experiments utilizing words posthypnotically tied to a potential anxiety, pleasure, or neutral reaction. Response times of subjects, instructed to ignore those words while naming pictures or solving anagrams as quickly as possible, reveal a highly differentiated pattern of circumstances governing likelihood of inhibitory spread from anxiety-linked words to target stimuli. Next a computer model is constructed to simulate cognitive processes from onset of display to eventual response, and the model is then tested for its fit to the empirical data. Finally, an illustrative study shows that a subset of computer-generated predictions for spread of inhibitory action is verifiable experimentally. PMID:2920005

  15. Individual-based modeling of fish: Linking to physical models and water quality.

    SciTech Connect

    Rose, K.A.

    1997-08-01

    The individual-based modeling approach for the simulating fish population and community dynamics is gaining popularity. Individual-based modeling has been used in many other fields, such as forest succession and astronomy. The popularity of the individual-based approach is partly a result of the lack of success of the more aggregate modeling approaches traditionally used for simulating fish population and community dynamics. Also, recent recognition that it is often the atypical individual that survives has fostered interest in the individual-based approach. Two general types of individual-based models are distribution and configuration. Distribution models follow the probability distributions of individual characteristics, such as length and age. Configuration models explicitly simulate each individual; the sum over individuals being the population. DeAngelis et al (1992) showed that, when distribution and configuration models were formulated from the same common pool of information, both approaches generated similar predictions. The distribution approach was more compact and general, while the configuration approach was more flexible. Simple biological changes, such as making growth rate dependent on previous days growth rates, were easy to implement in the configuration version but prevented simple analytical solution of the distribution version.

  16. Channel modelling for free-space optical inter-HAP links using adaptive ARQ transmission

    NASA Astrophysics Data System (ADS)

    Parthasarathy, S.; Giggenbach, D.; Kirstädter, A.

    2014-10-01

    Free-space optical (FSO) communication systems have seen significant developments in recent years due to growing need for very high data rates and tap-proof communication. The operation of an FSO link is suited to diverse variety of applications such as satellites, High Altitude Platforms (HAPs), Unmanned Aerial Vehicles (UAVs), aircrafts, ground stations and other areas involving both civil and military situations. FSO communication systems face challenges due to different effects of the atmospheric channel. FSO channel primarily suffers from scintillation effects due to Index of Refraction Turbulence (IRT). In addition, acquisition and pointing becomes more difficult because of the high directivity of the transmitted beam: Miss-pointing of the transmitted beam and tracking errors at the receiver generate additional fading of the optical signal. High Altitude Platforms (HAPs) are quasi-stationary vehicles operating in the stratosphere. The slowly varying but precisely determined time-of-flight of the Inter-HAP channel adds to its characteristics. To propose a suitable ARQ scheme, proper theoretical understanding of the optical atmospheric propagation and modeling of a specific scenario FSO channel is required. In this paper, a bi-directional symmetrical Inter-HAP link has been selected and modeled. The Inter-HAP channel model is then investigated via simulations in terms of optical scintillation induced by IRT and in presence of pointing error. The performance characteristic of the model is then quantified in terms of fading statistics from which the Packet Error Probability (PEP) is calculated. Based on the PEP characteristics, we propose suitable ARQ schemes.

  17. On linking an Earth system model to the equilibrium carbon representation of an economically optimizing land use model

    SciTech Connect

    Bond-Lamberty, Benjamin; Calvin, Katherine V.; Jones, Andrew D.; Mao, Jiafu; Patel, Pralit L.; Shi, Xiaoying; Thomson, Allison M.; Thornton, Peter E.; Zhou, Yuyu

    2014-01-01

    Human activities are significantly altering biogeochemical cycles at the global scale, posing a significant problem for earth system models (ESMs), which may incorporate static land-use change inputs but do not actively simulate policy or economic forces. One option to address this problem is a to couple an ESM with an economically oriented integrated assessment model. Here we have implemented and tested a coupling mechanism between the carbon cycles of an ESM (CLM) and an integrated assessment (GCAM) model, examining the best proxy variables to share between the models, and quantifying our ability to distinguish climate- and land-use-driven flux changes. CLM’s net primary production and heterotrophic respiration outputs were found to be the most robust proxy variables by which to manipulate GCAM’s assumptions of long-term ecosystem steady state carbon, with short-term forest production strongly correlated with long-term biomass changes in climate-change model runs. By leveraging the fact that carbon-cycle effects of anthropogenic land-use change are short-term and spatially limited relative to widely distributed climate effects, we were able to distinguish these effects successfully in the model coupling, passing only the latter to GCAM. By allowing climate effects from a full earth system model to dynamically modulate the economic and policy decisions of an integrated assessment model, this work provides a foundation for linking these models in a robust and flexible framework capable of examining two-way interactions between human and earth system processes.

  18. Assessment of dehydrothermally cross‐linked collagen membrane for guided bone regeneration around peri-implant dehiscence defects: a randomized single-blinded clinical trial

    PubMed Central

    2015-01-01

    Purpose The aim of this study was to determine the clinical feasibility of using dehydrothermally cross‐linked collagen membrane (DCM) for bone regeneration around peri-implant dehiscence defects, and compare it with non-cross-linked native collagen membrane (NCM). Methods Dehiscence defects were investigated in twenty-eight patients. Defect width and height were measured by periodontal probe immediately following implant placement (baseline) and 16 weeks afterward. Membrane manipulation and maintenance were clinically assessed by means of the visual analogue scale score at baseline. Changes in horizontal thickness at 1 mm, 2 mm, and 3 mm below the top of the implant platform and the average bone density were assessed by cone-beam computed tomography at 16 weeks. Degradation of membrane was histologically observed in the soft tissue around the implant prior to re-entry surgery. Results Five defect sites (two sites in the NCM group and three sites in the DCM group) showed soft-tissue dehiscence defects and membrane exposure during the early healing period, but there were no symptoms or signs of severe complications during the experimental postoperative period. Significant clinical and radiological improvements were found in all parameters with both types of collagen membrane. Partially resorbed membrane leaflets were only observed histologically in the DCM group. Conclusions These findings suggest that, compared with NCM, DCM has a similar clinical expediency and possesses more stable maintenance properties. Therefore, it could be used effectively in guided bone regeneration around dehiscence-type defects. PMID:26732806

  19. Stabilizing PID controllers for a single-link biomechanical model with position, velocity, and force feedback.

    PubMed

    Iqbal, Kamran; Roy, Anindo

    2004-12-01

    In this paper we address the problem of PID stabilization of a single-link inverted pendulum-based biomechanical model with force feedback, two levels of position and velocity feedback, and with delays in all the feedback loops. The novelty of the proposed model lies in its physiological relevance, whereby both small and medium latency sensory feedbacks from muscle spindle (MS), and force feedback from Golgi tendon organ (GTO) are included in the formulation. The biomechanical model also includes active and passive viscoelastic feedback from Hill-type muscle model and a second-order low-pass function for muscle activation. The central nervous system (CNS) regulation of postural movement is represented by a proportional-integral-derivative (PID) controller. Padé approximation of delay terms is employed to arrive at an overall rational transfer function of the biomechanical model. The Hermite-Biehler theorem is then used to derive stability results, leading to the existence of stabilizing PID controllers. An algorithm for selection of stabilizing feedback gains is developed using the linear matrix inequality (LMI) approach. PMID:15796343

  20. Evaluating a model linking assessed parent factors to four domains of youth risky driving.

    PubMed

    Schmidt, Sarah; Morrongiello, Barbara A; Colwell, Scott R

    2014-08-01

    Motor vehicle collisions are the leading cause of death in youth aged 15-19. Research has consistently shown that driver education programs do not result in safer youth driving. Indeed, the biggest predictor of collisions involving youth is parental history of collisions. The current study examined how parental modeling of and teaching about risky driving behaviors related to youth practices within four domains of risky driving (aggressive, substance use, distracted, moving violations), and evaluated whether the Prototype-Willingness Model explains links from parent to teen driving practices. Participants (N=432) were undergraduate students (mean age 18 years, age range 17-22 years) who had obtained their G2 driver's license within the past year; the G2 driver's license allows youth to drive alone on all municipal roads, with some restrictions on their blood alcohol level and the number of passengers they can carry. Results revealed that parental modeling was more predictive than parental teaching for all domains of risky driving examined. Youth whose parents modeled risky driving behaviors were found to be more likely to have engaged in those risky driving behaviors in the past, as well as to be more willing to engage in the behaviors in the future. The Prototype-Willingness Model was not a good fit to explain these relations. Findings from this study highlight the role parents play in the development of youth risky driving practices. PMID:24797085

  1. Development of conceptual ecological models linking management of the Missouri River to pallid sturgeon population dynamics

    USGS Publications Warehouse

    Jacobson, Robert B.; Parsley, Michael J.; Annis, Mandy L.; Colvin, Michael E.; Welker, Timothy L.; James, Daniel A.

    2015-01-01

    This report documents the process of developing and refining conceptual ecological models (CEMs) for linking river management to pallid sturgeon (Scaphirhynchus albus) population dynamics in the Missouri River. The refined CEMs are being used in the Missouri River Pallid Sturgeon Effects Analysis to organize, document, and formalize an understanding of pallid sturgeon population responses to past and future management alternatives. The general form of the CEMs, represented by a population-level model and component life-stage models, was determined in workshops held in the summer of 2013. Subsequently, the Missouri River Pallid Sturgeon Effects Analysis team designed a general hierarchical structure for the component models, refined the graphical structure, and reconciled variation among the components and between models developed for the upper river (Upper Missouri & Yellowstone Rivers) and the lower river (Missouri River downstream from Gavins Point Dam). Importance scores attributed to the relations between primary biotic characteristics and survival were used to define a candidate set of working dominant hypotheses about pallid sturgeon population dynamics. These CEMs are intended to guide research and adaptive-management actions to benefit pallid sturgeon populations in the Missouri River.

  2. A dynamical systems analysis of the data assimilation linked ecosystem carbon (DALEC) models

    NASA Astrophysics Data System (ADS)

    Chuter, Anna M.; Aston, Philip J.; Skeldon, Anne C.; Roulstone, Ian

    2015-03-01

    Changes in our climate and environment make it ever more important to understand the processes involved in Earth systems, such as the carbon cycle. There are many models that attempt to describe and predict the behaviour of carbon stocks and stores but, despite their complexity, significant uncertainties remain. We consider the qualitative behaviour of one of the simplest carbon cycle models, the Data Assimilation Linked Ecosystem Carbon (DALEC) model, which is a simple vegetation model of processes involved in the carbon cycle of forests, and consider in detail the dynamical structure of the model. Our analysis shows that the dynamics of both evergreen and deciduous forests in DALEC are dependent on a few key parameters and it is possible to find a limit point where there is stable sustainable behaviour on one side but unsustainable conditions on the other side. The fact that typical parameter values reside close to this limit point highlights the difficulty of predicting even the correct trend without sufficient data and has implications for the use of data assimilation methods.

  3. Linking Formal and Informal Science Education: A Successful Model using Libraries, Volunteers and NASA Resources

    NASA Astrophysics Data System (ADS)

    Race, M. S.; Lafayette Library; Learning Center Foundation (Lllcf)

    2011-12-01

    In these times of budget cuts, tight school schedules, and limited opportunities for student field trips and teacher professional development, it is especially difficult to expose elementary and middle school students to the latest STEM information-particularly in the space sciences. Using our library as a facilitator and catalyst, we built a volunteer-based, multi-faceted, curriculum-linked program for students and teachers in local middle schools (Grade 8) and showcased new astronomical and planetary science information using mainly NASA resources and volunteer effort. The project began with the idea of bringing free NASA photo exhibits (FETTU) to the Lafayette and Antioch Libraries for public display. Subsequently, the effort expanded by adding layers of activities that brought space and science information to teachers, students and the pubic at 5 libraries and schools in the 2 cities, one of which serves a diverse, underserved community. Overall, the effort (supported by a pilot grant from the Bechtel Foundation) included school and library based teacher workshops with resource materials; travelling space museum visits with hands-on activities (Chabot-to-Go); separate powerpoint presentations for students and adults at the library; and concurrent ancillary space-related themes for young children's programs at the library. This pilot project, based largely on the use of free government resources and online materials, demonstrated that volunteer-based, standards-linked STEM efforts can enhance curriculum at the middle school, with libraries serving a special role. Using this model, we subsequently also obtained a small NASA-Space Grant award to bring star parties and hand-on science activities to three libraries this Fall, linking with numerous Grade 5 teachers and students in two additional underserved areas of our county. It's not necessary to reinvent the wheel, you just collect the pieces and build on what you already have.

  4. A Model of Clinical Alarm Errors in Hospital.

    PubMed

    Busch-Vishniac, Ilene

    2015-01-01

    Although there has been much attention paid recently to clinical alarms, research has primarily focused on particular aspects of the clinical alarm problem, such as how to reduce nuisance alarms. This paper takes a broad view of clinical alarms and develops a model of errors in alarm handling and how they affect patients directly. Based on reports in the literature, I estimate that alarms that should sound by current standards do not sound about 9% of the time. Additionally, about 3% of alarms that are clinically significant are ignored, either intentionally or because they were inaudible. However, these errors produce a very low rate of reported alarm-related deaths and other adverse effects (on the order of a couple adverse effects per 10 million alarm errors). While it is not yet possible to estimate the probabilities of clinical alarms having an adverse impact on patients other than the patient whose alarm is sounding, such indirect adverse effects likely occur at a low level as a result of disruption of staff workflow, creation of a noisy hospital environment, and contribution to communication difficulties. Consideration of alarms should include not only the patient connected to the device that is sounding, but also the impact of the alarm on other patients in the vicinity. PMID:26196919

  5. Underestimation of boreal soil carbon stocks by mathematical soil carbon models linked to soil nutrient status

    NASA Astrophysics Data System (ADS)

    Ťupek, Boris; Ortiz, Carina A.; Hashimoto, Shoji; Stendahl, Johan; Dahlgren, Jonas; Karltun, Erik; Lehtonen, Aleksi

    2016-08-01

    Inaccurate estimate of the largest terrestrial carbon pool, soil organic carbon (SOC) stock, is the major source of uncertainty in simulating feedback of climate warming on ecosystem-atmosphere carbon dioxide exchange by process-based ecosystem and soil carbon models. Although the models need to simplify complex environmental processes of soil carbon sequestration, in a large mosaic of environments a missing key driver could lead to a modeling bias in predictions of SOC stock change.We aimed to evaluate SOC stock estimates of process-based models (Yasso07, Q, and CENTURY soil sub-model v4) against a massive Swedish forest soil inventory data set (3230 samples) organized by a recursive partitioning method into distinct soil groups with underlying SOC stock development linked to physicochemical conditions.For two-thirds of measurements all models predicted accurate SOC stock levels regardless of the detail of input data, e.g., whether they ignored or included soil properties. However, in fertile sites with high N deposition, high cation exchange capacity, or moderately increased soil water content, Yasso07 and Q models underestimated SOC stocks. In comparison to Yasso07 and Q, accounting for the site-specific soil characteristics (e. g. clay content and topsoil mineral N) by CENTURY improved SOC stock estimates for sites with high clay content, but not for sites with high N deposition.Our analysis suggested that the soils with poorly predicted SOC stocks, as characterized by the high nutrient status and well-sorted parent material, indeed have had other predominant drivers of SOC stabilization lacking in the models, presumably the mycorrhizal organic uptake and organo-mineral stabilization processes. Our results imply that the role of soil nutrient status as regulator of organic matter mineralization has to be re-evaluated, since correct SOC stocks are decisive for predicting future SOC change and soil CO2 efflux.

  6. LINKING AIR TOXIC CONCENTRATIONS FROM CMAQ TO THE HAPEM5 EXPOSURE MODEL AT NEIGHORHOOD SCALES FOR THE PHILADELPHIA AREA

    EPA Science Inventory

    This paper provides a preliminary demonstration of the EPA neighborhood scale modeling paradigm for air toxics by linking concentration from the Community Multi-scale Air Quality (CMAQ) modeling system to the fifth version of the Hazardous Pollutant Exposure Model (HAPEM5). For ...

  7. Commentary: models of academic-clinical partnerships: goods, better, best.

    PubMed

    Pardes, Herbert; Pincus, Harold Alan

    2010-08-01

    Elsewhere in this issue, Ovseiko and colleagues discuss organizational models for emerging academic health science centers (AHSCs) in England. In this commentary, the authors consider the advantages, or "goods," to organizing educational, clinical, and research missions within the AHSC model. Cultivating relationships among the three central missions of academic medicine yields good results for clinicians, trainees, patients, researchers, and communities, but it can also inspire all stakeholders to strive for better results. After outlining some of these benefits of current AHSC models, like those common in the United States, the authors discuss how close collaboration between U.S. and U.K. AHSC leaders could foster sharing of best practices and ultimately lead to better performance at AHSCs-emerging and established-in both nations. Providing excellent health care begins with developing the best organizational models for AHSCs, and identifying and pursuing such models should be a top priority. PMID:20671448

  8. Modeling the Biodegradation of Bacterial Community Assembly Linked Antibiotics in River Sediment Using a Deterministic-Stochastic Combined Model.

    PubMed

    Zhang, Wenlong; Li, Yi; Wang, Chao; Wang, Peifang; Hou, Jun; Yu, Zhongbo; Niu, Lihua; Wang, Linqiong; Wang, Jing

    2016-08-16

    To understand the interaction between bacterial community assembly and the assembly linked antibiotics biodegradation, a unique model framework containing a Monod kinetic, a logistic kinetic, and a stochastic item was established to describe the biodegradation of bacterial community assembly linked sulfamethoxazole (SMX) in river sediment. According to the modeling results, both deterministic and stochastic processes driving bacterial population variations played important roles in controlling SMX biodegradation, and the relative importance depended on the in situ concentration of SMX. A threshold concentration of SMX, which was biodegraded in the experimental river sediment depending on different processes, was obtained (i.e., 20 μg/kg). The higher introduced concentration of SMX (>20 μg/kg) was found to promote the acclimation of antibiotic degradation bacteria in microbial community through niche differentiation, which resulted in the specific microbial metabolization of SMX. In contrast, the lower introduced concentration of SMX (<20 μg/kg) was not able to lead to a significant increase of deterministic processes and resulted in the biodegradation of SMX through co-metabolism by the coexisting microorganisms. The developed model can be considered a useful tool for improving the technologies of water environmental protection and remediation. PMID:27428250

  9. Cross-linked hyaluronate hydrogel prevents adhesion formation and reformation in mouse uterine horn model.

    PubMed

    Sawada, T; Tsukada, K; Hasegawa, K; Ohashi, Y; Udagawa, Y; Gomel, V

    2001-02-01

    The aim of this study was to evaluate the efficacy of cross-linked hyaluronate hydrogel (HA gel) as an adjuvant for postoperative adhesion prevention, in a mouse uterine horn model. In experiment 1 uterine horns were abrased with iodine. HA gel was applied to the injured surface before closure in the treatment group. In experiment 2, after injuring the uterine horns, three stitches were placed at equal distances around the uterine horns to appose the injured medial surfaces of the two horns during healing. HA gel was inserted between the uterine horns in the treatment group. In experiment 3 prevention of adhesion reformation was assessed. After lysis of adhesions that were induced as in experiment 2, HA gel was introduced between the serosal surfaces of apposing uterine horns. Untreated animals served as controls in each experiment. Statistical analysis was carried out using Student's t-test. The adhesion score was significantly lower in the HA gel group on the 14th day compared with controls in all the experiments: in experiment 1, 0.3 +/- 0.4 versus 1.7 +/- 1.2; in experiment 2, 0.9 +/- 1.0 versus 2.6 +/- 0.5; and in experiment 3, 1.5 +/- 0.9 versus 2.2 +/- 0.6 respectively. Cross-linked HA gel significantly reduced de-novo adhesions (P< 0.03) and adhesion reformation (P < 0.03). PMID:11157833

  10. A model for preparing faculty to teach model C clinical nurse leader students.

    PubMed

    Webb, Sherry; McKeon, Leslie

    2014-07-01

    Model C clinical nurse leader (CNL) programs are complex because they must meet the The Essentials of Baccalaureate Education for Professional Nursing Practice and The Essentials of Master's Education in Nursing, as well as the graduate level competencies outlined in the white paper Competencies and Curricular Expectations for Clinical Nurse Leader Education and Practice. Faculty assigned to teach in these programs may be experts in education or areas of clinical specialty, but they may not have a clear understanding of the CNL role to teach and mentor CNL students. This article describes a faculty development model that includes an introduction to the CNL role, course mapping of the essentials, integration of CNL professional values into clinical evaluation, consultation with practicing model C graduates, and participation in a comprehensive CNL certification review course. The model was effective in preparing faculty to teach and mentor students in a model C CNL program. PMID:24971734

  11. Bone fracture toughness and strength correlate with collagen cross-link maturity in a dose-controlled lathyrism mouse model

    PubMed Central

    McNerny, Erin M. B.; Gong, Bo; Morris, Michael D.; Kohn, David H.

    2014-01-01

    Collagen cross-linking is altered in many diseases of bone, and enzymatic collagen cross-links are important to bone quality as evidenced by losses of strength following lysyl oxidase inhibition (lathyrism). We hypothesized that cross-links also contribute directly to bone fracture toughness. A mouse model of lathyrism using subcutaneous injection of up to 500mg/kg β-aminopropionitrile (BAPN) was developed and characterized (60 animals across 4 dosage groups). Three weeks of 150 or 350 mg/kg BAPN treatment in young growing mice significantly reduced cortical bone fracture toughness, strength, and pyridinoline cross-link content. Ratios reflecting relative cross-link maturity were positive regressors of fracture toughness (HP/[DHLNL+HLNL] r2=0.208, p<0.05; [HP+LP]/[DHNL+HLNL] r2=0.196, p<0.1), whereas quantities of mature pyridinoline cross-links were significant positive regressors of tissue strength (lysyl pyridinoline r2=0.159, p=0.014; hydroxylysyl pyridinoline r2=0.112, p<0.05). Immature and pyrrole cross-links, which were not significantly reduced by BAPN, did not correlate with mechanical properties. The effect of BAPN treatment on mechanical properties was dose specific, with the greatest impact found at the intermediate (350mg/kg) dose. Calcein labeling was used to define locations of new bone formation, allowing for the identification of regions of normally cross-linked (preexisting) and BAPN treated (newly formed, cross-link-deficient) bone. Raman spectroscopy revealed spatial differences due to relative tissue age and effects of cross-link inhibition. Newly deposited tissues had lower mineral/matrix, carbonate/phosphate and Amide I cross-link (matrix maturity) ratios compared to preexisting tissues. BAPN treatment did not affect mineral measures, but significantly increased the cross-link (matrix maturity) ratio compared to newly formed control tissue. Our study reveals that spatially localized effects of short term BAPN cross-link inhibition can alter

  12. Entangled Cross-Linked Fibres for an Application as Core Material for Sandwich Structures - Part II: Analytical Model

    NASA Astrophysics Data System (ADS)

    Mezeix, L.; Poquillon, D.; Bouvet, C.

    2016-02-01

    Entangled cross-linked carbon, aramid and glass fibres were recently produced by epoxy spraying for an application as core material for sandwich panel. The Young's moduli in compression and tension have been previously measured and briefly summarized in this paper. To optimize the core structure, modelling of these properties has been achieved in the present paper. The cross-link fibres have a random orientation and the stiffness of the epoxy joint is modelled by a torsion spring. A parallel model is chosen for homogenisation. It was found that the experimentally estimated stiffness of these materials fits fairly well with the modelled ones.

  13. On model selections for repeated measurement data in clinical studies.

    PubMed

    Zou, Baiming; Jin, Bo; Koch, Gary G; Zhou, Haibo; Borst, Stephen E; Menon, Sandeep; Shuster, Jonathan J

    2015-05-10

    Repeated measurement designs have been widely used in various randomized controlled trials for evaluating long-term intervention efficacies. For some clinical trials, the primary research question is how to compare two treatments at a fixed time, using a t-test. Although simple, robust, and convenient, this type of analysis fails to utilize a large amount of collected information. Alternatively, the mixed-effects model is commonly used for repeated measurement data. It models all available data jointly and allows explicit assessment of the overall treatment effects across the entire time spectrum. In this paper, we propose an analytic strategy for longitudinal clinical trial data where the mixed-effects model is coupled with a model selection scheme. The proposed test statistics not only make full use of all available data but also utilize the information from the optimal model deemed for the data. The performance of the proposed method under various setups, including different data missing mechanisms, is evaluated via extensive Monte Carlo simulations. Our numerical results demonstrate that the proposed analytic procedure is more powerful than the t-test when the primary interest is to test for the treatment effect at the last time point. Simulations also reveal that the proposed method outperforms the usual mixed-effects model for testing the overall treatment effects across time. In addition, the proposed framework is more robust and flexible in dealing with missing data compared with several competing methods. The utility of the proposed method is demonstrated by analyzing a clinical trial on the cognitive effect of testosterone in geriatric men with low baseline testosterone levels. PMID:25645442

  14. Modeling photosynthesis of discontinuous plant canopies by linking the Geometric Optical Radiative Transfer model with biochemical processes

    NASA Astrophysics Data System (ADS)

    Xin, Q.; Gong, P.; Li, W.

    2015-06-01

    Modeling vegetation photosynthesis is essential for understanding carbon exchanges between terrestrial ecosystems and the atmosphere. The radiative transfer process within plant canopies is one of the key drivers that regulate canopy photosynthesis. Most vegetation cover consists of discrete plant crowns, of which the physical observation departs from the underlying assumption of a homogenous and uniform medium in classic radiative transfer theory. Here we advance the Geometric Optical Radiative Transfer (GORT) model to simulate photosynthesis activities for discontinuous plant canopies. We separate radiation absorption into two components that are absorbed by sunlit and shaded leaves, and derive analytical solutions by integrating over the canopy layer. To model leaf-level and canopy-level photosynthesis, leaf light absorption is then linked to the biochemical process of gas diffusion through leaf stomata. The canopy gap probability derived from GORT differs from classic radiative transfer theory, especially when the leaf area index is high, due to leaf clumping effects. Tree characteristics such as tree density, crown shape, and canopy length affect leaf clumping and regulate radiation interception. Modeled gross primary production (GPP) for two deciduous forest stands could explain more than 80% of the variance of flux tower measurements at both near hourly and daily timescales. We demonstrate that ambient CO2 concentrations influence daytime vegetation photosynthesis, which needs to be considered in biogeochemical models. The proposed model is complementary to classic radiative transfer theory and shows promise in modeling the radiative transfer process and photosynthetic activities over discontinuous forest canopies.

  15. A mouse model of X-linked intellectual disability associated with impaired removal of histone methylation

    PubMed Central

    Iwase, Shigeki; Brookes, Emily; Agarwal, Saurabh; Badeaux, Aimee I; Ito, Hikaru; Vallianatos, Christina N; Tomassy, Giulio Srubek; Kasza, Tomas; Lin, Grace; Thompson, Andrew; Gu, Lei; Kwan, Kenneth Y.; Chen, Chinfei; Sartor, Maureen A.; Egan, Brian; Xu, Jun; Shi, Yang

    2015-01-01

    Mutations in a number of chromatin modifiers are associated with human neurological disorders. KDM5C, a histone H3 lysine 4 di- and tri-methyl (H3K4me2/3)-specific demethylase, is frequently mutated in X-linked intellectual disability (XLID) patients. Here, we report that disruption of the mouse Kdm5c gene recapitulates adaptive and cognitive abnormalities observed in XLID, including impaired social behavior and memory, and aggression. Kdm5c-knockout brains exhibit impaired dendritic arborization, spine abnormalities, and altered transcriptomes. In neurons, Kdm5c is recruited to promoters that harbor CpG islands decorated with high levels of H3K4me3, where it fine-tunes H3K4me3 levels. Kdm5c predominantly represses these genes, which include members of key pathways that regulate the development and function of neuronal circuitries. In summary, our mouse behavioral data strongly suggests that KDM5C mutations are causal to XLID. Furthermore, our findings suggest that loss of KDM5C function may impact gene expression in multiple regulatory pathways relevant to the clinical phenotypes. PMID:26804915

  16. A Mouse Model of X-linked Intellectual Disability Associated with Impaired Removal of Histone Methylation.

    PubMed

    Iwase, Shigeki; Brookes, Emily; Agarwal, Saurabh; Badeaux, Aimee I; Ito, Hikaru; Vallianatos, Christina N; Tomassy, Giulio Srubek; Kasza, Tomas; Lin, Grace; Thompson, Andrew; Gu, Lei; Kwan, Kenneth Y; Chen, Chinfei; Sartor, Maureen A; Egan, Brian; Xu, Jun; Shi, Yang

    2016-02-01

    Mutations in a number of chromatin modifiers are associated with human neurological disorders. KDM5C, a histone H3 lysine 4 di- and tri-methyl (H3K4me2/3)-specific demethylase, is frequently mutated in X-linked intellectual disability (XLID) patients. Here, we report that disruption of the mouse Kdm5c gene recapitulates adaptive and cognitive abnormalities observed in XLID, including impaired social behavior, memory deficits, and aggression. Kdm5c-knockout brains exhibit abnormal dendritic arborization, spine anomalies, and altered transcriptomes. In neurons, Kdm5c is recruited to promoters that harbor CpG islands decorated with high levels of H3K4me3, where it fine-tunes H3K4me3 levels. Kdm5c predominantly represses these genes, which include members of key pathways that regulate the development and function of neuronal circuitries. In summary, our mouse behavioral data strongly suggest that KDM5C mutations are causal to XLID. Furthermore, our findings suggest that loss of KDM5C function may impact gene expression in multiple regulatory pathways relevant to the clinical phenotypes. PMID:26804915

  17. Pathophysiology of white-nose syndrome in bats: a mechanistic model linking wing damage to mortality.

    PubMed

    Warnecke, Lisa; Turner, James M; Bollinger, Trent K; Misra, Vikram; Cryan, Paul M; Blehert, David S; Wibbelt, Gudrun; Willis, Craig K R

    2013-08-23

    White-nose syndrome is devastating North American bat populations but we lack basic information on disease mechanisms. Altered blood physiology owing to epidermal invasion by the fungal pathogen Geomyces destructans (Gd) has been hypothesized as a cause of disrupted torpor patterns of affected hibernating bats, leading to mortality. Here, we present data on blood electrolyte concentration, haematology and acid-base balance of hibernating little brown bats, Myotis lucifugus, following experimental inoculation with Gd. Compared with controls, infected bats showed electrolyte depletion (i.e. lower plasma sodium), changes in haematology (i.e. increased haematocrit and decreased glucose) and disrupted acid-base balance (i.e. lower CO2 partial pressure and bicarbonate). These findings indicate hypotonic dehydration, hypovolaemia and metabolic acidosis. We propose a mechanistic model linking tissue damage to altered homeostasis and morbidity/mortality. PMID:23720520

  18. Pathophysiology of white-nose syndrome in bats: a mechanistic model linking wing damage to mortality

    USGS Publications Warehouse

    Warnecke, Lisa; Turner, James M.; Bollinger, Trent K.; Misra, Vikram; Cryan, Paul M.; Blehert, David S.; Wibbelt, Gudrun; Willis, Craig K.R.

    2013-01-01

    White-nose syndrome is devastating North American bat populations but we lack basic information on disease mechanisms. Altered blood physiology owing to epidermal invasion by the fungal pathogen Geomyces destructans (Gd) has been hypothesized as a cause of disrupted torpor patterns of affected hibernating bats, leading to mortality. Here, we present data on blood electrolyte concentration, haematology and acid–base balance of hibernating little brown bats, Myotis lucifugus, following experimental inoculation with Gd. Compared with controls, infected bats showed electrolyte depletion (i.e. lower plasma sodium), changes in haematology (i.e. increased haematocrit and decreased glucose) and disrupted acid–base balance (i.e. lower CO2 partial pressure and bicarbonate). These findings indicate hypotonic dehydration, hypovolaemia and metabolic acidosis. We propose a mechanistic model linking tissue damage to altered homeostasis and morbidity/mortality.

  19. Static and dynamic properties of model elastomer with various cross-linking densities: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Liu, Jun; Cao, Dapeng; Zhang, Liqun

    2009-07-01

    The effects of the cross-linking density on the static and dynamic properties of polymer networks are examined by using a molecular dynamics simulation based on a simple elastomer model. Simulation results indicate that the introduced cross-linking junctions show almost no effect on the static structure factor. The glass transition temperature Tg increases slightly with the cross-linking density. By analyzing the mean square displacement of the monomers, the chain diffusion, and the incoherent intermediate dynamic structure factor ϕqs(t) at the chain and segmental length scales, it is found that the mobilities of the monomers and chains are retarded and the relaxation behavior is hindered by the cross linking of polymers. Furthermore, the spatial localization of the monomers is also observed at a long time period for a highly cross-linked system. For the cross-linked system, the time-temperature superposition principle is valid at the segmental length scale but breaks down at the chain length scale. The effect of the cross-linking density on the terminal relaxation is investigated by the end-to-end vector correlation, which is well fitted to the Kohlrauch-William-Watts (KWW) or modified KWW functions. The characteristic relaxation time shows an approximately linear relationship with the cross-linking density. It is demonstrated that the relaxation behavior tends to broaden, attributed to the stronger intermolecular coupling or cooperativity induced by the cross linking, suggesting that the system with a higher cross-linking degree becomes more fragile. For the dynamic properties, the bond orientation and the end-to-end distance along the deformed direction, which is an indicator of the entropic change, and the nonbonded energy are examined during the deformation and relaxation processes, respectively. The results explore the molecular mechanism accounting for the residual stress in the stress relaxation of cross-linked elastomer networks.

  20. Static and dynamic properties of model elastomer with various cross-linking densities: a molecular dynamics study.

    PubMed

    Liu, Jun; Cao, Dapeng; Zhang, Liqun

    2009-07-21

    The effects of the cross-linking density on the static and dynamic properties of polymer networks are examined by using a molecular dynamics simulation based on a simple elastomer model. Simulation results indicate that the introduced cross-linking junctions show almost no effect on the static structure factor. The glass transition temperature T(g) increases slightly with the cross-linking density. By analyzing the mean square displacement of the monomers, the chain diffusion, and the incoherent intermediate dynamic structure factor phi(q)(s)(t) at the chain and segmental length scales, it is found that the mobilities of the monomers and chains are retarded and the relaxation behavior is hindered by the cross linking of polymers. Furthermore, the spatial localization of the monomers is also observed at a long time period for a highly cross-linked system. For the cross-linked system, the time-temperature superposition principle is valid at the segmental length scale but breaks down at the chain length scale. The effect of the cross-linking density on the terminal relaxation is investigated by the end-to-end vector correlation, which is well fitted to the Kohlrauch-William-Watts (KWW) or modified KWW functions. The characteristic relaxation time shows an approximately linear relationship with the cross-linking density. It is demonstrated that the relaxation behavior tends to broaden, attributed to the stronger intermolecular coupling or cooperativity induced by the cross linking, suggesting that the system with a higher cross-linking degree becomes more fragile. For the dynamic properties, the bond orientation and the end-to-end distance along the deformed direction, which is an indicator of the entropic change, and the nonbonded energy are examined during the deformation and relaxation processes, respectively. The results explore the molecular mechanism accounting for the residual stress in the stress relaxation of cross-linked elastomer networks. PMID:19624229

  1. Coupled variable selection for regression modeling of complex treatment patterns in a clinical cancer registry.

    PubMed

    Schmidtmann, I; Elsäßer, A; Weinmann, A; Binder, H

    2014-12-30

    For determining a manageable set of covariates potentially influential with respect to a time-to-event endpoint, Cox proportional hazards models can be combined with variable selection techniques, such as stepwise forward selection or backward elimination based on p-values, or regularized regression techniques such as component-wise boosting. Cox regression models have also been adapted for dealing with more complex event patterns, for example, for competing risks settings with separate, cause-specific hazard models for each event type, or for determining the prognostic effect pattern of a variable over different landmark times, with one conditional survival model for each landmark. Motivated by a clinical cancer registry application, where complex event patterns have to be dealt with and variable selection is needed at the same time, we propose a general approach for linking variable selection between several Cox models. Specifically, we combine score statistics for each covariate across models by Fisher's method as a basis for variable selection. This principle is implemented for a stepwise forward selection approach as well as for a regularized regression technique. In an application to data from hepatocellular carcinoma patients, the coupled stepwise approach is seen to facilitate joint interpretation of the different cause-specific Cox models. In conditional survival models at landmark times, which address updates of prediction as time progresses and both treatment and other potential explanatory variables may change, the coupled regularized regression approach identifies potentially important, stably selected covariates together with their effect time pattern, despite having only a small number of events. These results highlight the promise of the proposed approach for coupling variable selection between Cox models, which is particularly relevant for modeling for clinical cancer registries with their complex event patterns. PMID:25345575

  2. The clinical implications of mouse models of enhanced anxiety

    PubMed Central

    Sartori, Simone B; Landgraf, Rainer; Singewald, Nicolas

    2011-01-01

    Mice are increasingly overtaking the rat model organism in important aspects of anxiety research, including drug development. However, translating the results obtained in mouse studies into information that can be applied in clinics remains challenging. One reason may be that most of the studies so far have used animals displaying ‘normal’ anxiety rather than ‘psychopathological’ animal models with abnormal (elevated) anxiety, which more closely reflect core features and sensitivities to therapeutic interventions of human anxiety disorders, and which would, thus, narrow the translational gap. Here, we discuss manipulations aimed at persistently enhancing anxiety-related behavior in the laboratory mouse using phenotypic selection, genetic techniques and/or environmental manipulations. It is hoped that such models with enhanced construct validity will provide improved ways of studying the neurobiology and treatment of pathological anxiety. Examples of findings from mouse models of enhanced anxiety-related behavior will be discussed, as well as their relation to findings in anxiety disorder patients regarding neuroanatomy, neurobiology, genetic involvement and epigenetic modifications. Finally, we highlight novel targets for potential anxiolytic pharmacotherapeutics that have been established with the help of research involving mice. Since the use of psychopathological mouse models is only just beginning to increase, it is still unclear as to the extent to which such approaches will enhance the success rate of drug development in translating identified therapeutic targets into clinical trials and, thus, helping to introduce the next anxiolytic class of drugs. PMID:21901080

  3. Linking landscape characteristics to local grizzly bear abundance using multiple detection methods in a hierarchical model

    USGS Publications Warehouse

    Graves, T.A.; Kendall, K.C.; Royle, J. Andrew; Stetz, J.B.; Macleod, A.C.

    2011-01-01

    Few studies link habitat to grizzly bear Ursus arctos abundance and these have not accounted for the variation in detection or spatial autocorrelation. We collected and genotyped bear hair in and around Glacier National Park in northwestern Montana during the summer of 2000. We developed a hierarchical Markov chain Monte Carlo model that extends the existing occupancy and count models by accounting for (1) spatially explicit variables that we hypothesized might influence abundance; (2) separate sub-models of detection probability for two distinct sampling methods (hair traps and rub trees) targeting different segments of the population; (3) covariates to explain variation in each sub-model of detection; (4) a conditional autoregressive term to account for spatial autocorrelation; (5) weights to identify most important variables. Road density and per cent mesic habitat best explained variation in female grizzly bear abundance; spatial autocorrelation was not supported. More female bears were predicted in places with lower road density and with more mesic habitat. Detection rates of females increased with rub tree sampling effort. Road density best explained variation in male grizzly bear abundance and spatial autocorrelation was supported. More male bears were predicted in areas of low road density. Detection rates of males increased with rub tree and hair trap sampling effort and decreased over the sampling period. We provide a new method to (1) incorporate multiple detection methods into hierarchical models of abundance; (2) determine whether spatial autocorrelation should be included in final models. Our results suggest that the influence of landscape variables is consistent between habitat selection and abundance in this system. ?? 2011 The Authors. Animal Conservation ?? 2011 The Zoological Society of London.

  4. Clinical Strategies and Animal Models for Developing Senolytic Agents

    PubMed Central

    Kirkland, James L.; Tchkonia, Tamara

    2014-01-01

    Aging is associated with increasing predisposition to multiple chronic diseases. One fundamental aging process that is often operative at sites of the pathology underlying chronic age-related diseases is cellular senescence. Small molecule senolytic agents are being developed. For successful drug development: 1) appropriate animal models of human age-related diseases need to be devised. 2) Models have to be made in which it can be proven that beneficial phenotypic effects are actually caused through clearing senescent cells by putative senolytic agents, as opposed to “off-target” effects of these agents on non-senescent cells. 3) Models are needed to test efficacy of drugs and to uncover potential side effects of senolytic agents. Development of the optimal animal models and clinical trial paradigms for senolytic agents warrants an intensive effort, since senolytic agents, if successful in delaying, preventing, alleviating, or reversing age-related diseases as a group would be transformative. PMID:25446976

  5. Study of Clinical Practical Model of Urinary System Injury

    PubMed Central

    Li, Gang; Wu, Yuan-Yi; Fu, Wei-Jun; Jia, Ying-Xin; Zhang, Bing-Hong; Xu, Yong-De; Wang, Zhong-Xin; Shi, Jian-Guo; Tan, Hai-Song; Qian, Ye-Yong; Shi, Bin-Yi; Zhang, Chao-Hua; Wang, Xiao-Xiong

    2015-01-01

    Background: In order to improve the clinical treatment level of urinary system injury, it is necessary to build up an animal model of urinary system wound, which is not only analogous to real clinical practice, but also simple and practical. Methods: We have developed the third generation of firearm fragment wound generator based on the first and the second producer. The best explosive charge of the blank cartridge was selected by gradient powder loading experiments. The firearm fragment injuries were made to the bulbous urethra of 10 New Zealand male rabbits. One week preoperatively and 2, 4 and 8 weeks postoperatively, all the animals underwent urethroscopy and urethrography. At 2, 4 and 8 weeks postoperatively, two animals were randomly selected and killed, and the urethra was cut off for pathological examination. Results: The shooting distance of the third generation of firearm fragment wound generator is 2 cm. The best explosive charge of the blank cartridge is 1 g of nitrocotton. All rabbits survived the procedures and stayed alive until they were killed. Injuries were limited to bulbous urethra and distal urethra. Round damaged areas, 1–1.5 cm in length, on the ventral wall were observed. Ureteroscopy results showed that canal diameter gradually shrank by over 50% in 9 rabbits. The rate of success was 90%. Urethrography result noted that a 1–1.3 cm stricture was formed at the bulbous urethra. Histology results of injured stricture urethra showed that fibrous connective tissue hyperplasia and hyaline degeneration caused further stricture in the canal. Conclusions: The third generation of firearm fragment wound generator imitates the bullet firing process and is more accurate and repeatable. The corresponding rabbit model of traumatic complex urethral stricture simulates the real complex clinical conditions. This animal model provides a standardized platform for clinical researches on treating traumatic injuries to the urinary system. PMID:25836614

  6. Link between hopping models and percolation scaling laws for charge transport in mixtures of small molecules

    DOE PAGESBeta

    Ha, Dong -Gwang; Kim, Jang -Joo; Baldo, Marc A.

    2016-04-29

    Mixed host compositions that combine charge transport materials with luminescent dyes offer superior control over exciton formation and charge transport in organic light emitting devices (OLEDs). Two approaches are typically used to optimize the fraction of charge transport materials in a mixed host composition: either an empirical percolative model, or a hopping transport model. We show that these two commonly-employed models are linked by an analytic expression which relates the localization length to the percolation threshold and critical exponent. The relation is confirmed both numerically and experimentally through measurements of the relative conductivity of Tris(4-carbazoyl-9-ylphenyl) amine (TCTA) :1,3-bis(3,5-dipyrid-3-yl-phenyl) benzene (BmPyPb)more » mixtures with different concentrations, where the TCTA plays a role as hole conductor and the BmPyPb as hole insulator. Furthermore, the analytic relation may allow the rational design of mixed layers of small molecules for high-performance OLEDs.« less

  7. Linking genes to communities and ecosystems: Daphnia as an ecogenomic model.

    PubMed

    Miner, Brooks E; De Meester, Luc; Pfrender, Michael E; Lampert, Winfried; Hairston, Nelson G

    2012-05-22

    How do genetic variation and evolutionary change in critical species affect the composition and functioning of populations, communities and ecosystems? Illuminating the links in the causal chain from genes up to ecosystems is a particularly exciting prospect now that the feedbacks between ecological and evolutionary changes are known to be bidirectional. Yet to fully explore phenomena that span multiple levels of the biological hierarchy requires model organisms and systems that feature a comprehensive triad of strong ecological interactions in nature, experimental tractability in diverse contexts and accessibility to modern genomic tools. The water flea Daphnia satisfies these criteria, and genomic approaches capitalizing on the pivotal role Daphnia plays in the functioning of pelagic freshwater food webs will enable investigations of eco-evolutionary dynamics in unprecedented detail. Because its ecology is profoundly influenced by both genetic polymorphism and phenotypic plasticity, Daphnia represents a model system with tremendous potential for developing a mechanistic understanding of the relationship between traits at the genetic, organismal and population levels, and consequences for community and ecosystem dynamics. Here, we highlight the combination of traits and ecological interactions that make Daphnia a definitive model system, focusing on the additional power and capabilities enabled by recent molecular and genomic advances. PMID:22298849

  8. Linking genes to communities and ecosystems: Daphnia as an ecogenomic model

    PubMed Central

    Miner, Brooks E.; De Meester, Luc; Pfrender, Michael E.; Lampert, Winfried; Hairston, Nelson G.

    2012-01-01

    How do genetic variation and evolutionary change in critical species affect the composition and functioning of populations, communities and ecosystems? Illuminating the links in the causal chain from genes up to ecosystems is a particularly exciting prospect now that the feedbacks between ecological and evolutionary changes are known to be bidirectional. Yet to fully explore phenomena that span multiple levels of the biological hierarchy requires model organisms and systems that feature a comprehensive triad of strong ecological interactions in nature, experimental tractability in diverse contexts and accessibility to modern genomic tools. The water flea Daphnia satisfies these criteria, and genomic approaches capitalizing on the pivotal role Daphnia plays in the functioning of pelagic freshwater food webs will enable investigations of eco-evolutionary dynamics in unprecedented detail. Because its ecology is profoundly influenced by both genetic polymorphism and phenotypic plasticity, Daphnia represents a model system with tremendous potential for developing a mechanistic understanding of the relationship between traits at the genetic, organismal and population levels, and consequences for community and ecosystem dynamics. Here, we highlight the combination of traits and ecological interactions that make Daphnia a definitive model system, focusing on the additional power and capabilities enabled by recent molecular and genomic advances. PMID:22298849

  9. Modeling dynamic interactions and coherence between marine zooplankton and fishes linked to environmental variability

    NASA Astrophysics Data System (ADS)

    Liu, Hui; Fogarty, Michael J.; Hare, Jonathan A.; Hsieh, Chih-hao; Glaser, Sarah M.; Ye, Hao; Deyle, Ethan; Sugihara, George

    2014-03-01

    The dynamics of marine fishes are closely related to lower trophic levels and the environment. Quantitatively understanding ecosystem dynamics linking environmental variability and prey resources to exploited fishes is crucial for ecosystem-based management of marine living resources. However, standard statistical models typically grounded in the concept of linear system may fail to capture the complexity of ecological processes. We have attempted to model ecosystem dynamics using a flexible, nonparametric class of nonlinear forecasting models. We analyzed annual time series of four environmental indices, 22 marine copepod taxa, and four ecologically and commercially important fish species during 1977 to 2009 on Georges Bank, a highly productive and intensively studied area of the northeast U.S. continental shelf ecosystem. We examined the underlying dynamic features of environmental indices and copepods, quantified the dynamic interactions and coherence with fishes, and explored the potential control mechanisms of ecosystem dynamics from a nonlinear perspective. We found: (1) the dynamics of marine copepods and environmental indices exhibiting clear nonlinearity; (2) little evidence of complex dynamics across taxonomic levels of copepods; (3) strong dynamic interactions and coherence between copepods and fishes; and (4) the bottom-up forcing of fishes and top-down control of copepods coexisting as target trophic levels vary. These findings highlight the nonlinear interactions among ecosystem components and the importance of marine zooplankton to fish populations which point to two forcing mechanisms likely interactively regulating the ecosystem dynamics on Georges Bank under a changing environment.

  10. Linking riparian dynamics and groundwater: an ecohydrologic approach to modeling groundwater and riparian vegetation.

    PubMed

    Baird, Kathryn J; Stromberg, Juliet C; Maddock, Thomas

    2005-10-01

    The growing use of global freshwater supplies is increasing the need for improved modeling of the linkage between groundwater and riparian vegetation. Traditional groundwater models such as MODFLOW have been used to predict changes in regional groundwater levels, and thus riparian vegetation potential attributable to anthropogenic water use. This article describes an approach that improves on these modeling techniques through several innovations. First, evapotranspiration from riparian/wetland systems is modeled in a manner that more realistically reflects plant ecophysiology and vegetation complexity. In the authors' model programs (RIP-ET and PRE-RIP-ET), the single, monotonically increasing evapotranspiration flux curve in traditional groundwater models is replaced with a set of ecophysiologically based curves, one for each plant functional group present. For each group, the curve simulates transpiration declines that occur both as water levels decline below rooting depths and as waters rise to levels that produce anoxic soil conditions. Accuracy is further improved by more effective spatial handling of vegetation distribution, which allows modeling of surface elevation and depth to water for multiple vegetation types within each large model cell. The use of RIP-ET in groundwater models can improve the accuracy of basin scale estimates of riparian evapotranspiration rates, riparian vegetation water requirements, and water budgets. Two case studies are used to demonstrate that RIP-ET produces significantly different evapotranspiration estimates than the traditional method. When combined with vegetation mapping and a supporting program (RIP-GIS), RIP-ET also enables predictions of riparian vegetation response to water use and development scenarios. The RIP-GIS program links the head distribution from MODFLOW with surface digital elevation models, producing moderate- to high-resolution depth-to-groundwater maps. Together with information on plant rooting depths

  11. Linking environmental variability to village-scale malaria transmission using a simple immunity model

    PubMed Central

    2013-01-01

    constituting a mechanistic link between spatial and temporal environmental variability and village-scale malaria transmission. Incorporating acquired immunity into the model has allowed simulation of prevalence in the two villages, and isolation of the effects of acquired immunity in dampening the difference in prevalence between the two villages. Without these effects, the difference in prevalence between the two villages would have been significantly larger in response to the large differences in mosquito populations and the associated biting rates. PMID:23919581

  12. Beyond clinical engagement: a pragmatic model for quality improvement interventions, aligning clinical and managerial priorities.

    PubMed

    Pannick, Samuel; Sevdalis, Nick; Athanasiou, Thanos

    2016-09-01

    Despite taking advantage of established learning from other industries, quality improvement initiatives in healthcare may struggle to outperform secular trends. The reasons for this are rarely explored in detail, and are often attributed merely to difficulties in engaging clinicians in quality improvement work. In a narrative review of the literature, we argue that this focus on clinicians, at the relative expense of managerial staff, has proven counterproductive. Clinical engagement is not a universal challenge; moreover, there is evidence that managers-particularly middle managers-also have a role to play in quality improvement. Yet managerial participation in quality improvement interventions is often assumed, rather than proven. We identify specific factors that influence the coordination of front-line staff and managers in quality improvement, and integrate these factors into a novel model: the model of alignment. We use this model to explore the implementation of an interdisciplinary intervention in a recent trial, describing different participation incentives and barriers for different staff groups. The extent to which clinical and managerial interests align may be an important determinant of the ultimate success of quality improvement interventions. PMID:26647411

  13. Beyond clinical engagement: a pragmatic model for quality improvement interventions, aligning clinical and managerial priorities

    PubMed Central

    Athanasiou, Thanos

    2016-01-01

    Despite taking advantage of established learning from other industries, quality improvement initiatives in healthcare may struggle to outperform secular trends. The reasons for this are rarely explored in detail, and are often attributed merely to difficulties in engaging clinicians in quality improvement work. In a narrative review of the literature, we argue that this focus on clinicians, at the relative expense of managerial staff, has proven counterproductive. Clinical engagement is not a universal challenge; moreover, there is evidence that managers—particularly middle managers—also have a role to play in quality improvement. Yet managerial participation in quality improvement interventions is often assumed, rather than proven. We identify specific factors that influence the coordination of front-line staff and managers in quality improvement, and integrate these factors into a novel model: the model of alignment. We use this model to explore the implementation of an interdisciplinary intervention in a recent trial, describing different participation incentives and barriers for different staff groups. The extent to which clinical and managerial interests align may be an important determinant of the ultimate success of quality improvement interventions. PMID:26647411

  14. The use of statistical channel models, full-field propagation codes, and field data to predict link availability

    NASA Astrophysics Data System (ADS)

    Michael, Steven; Parenti, Ronald R.; Moores, John D.; Wilcox, William, Jr.; Yarnall, Timothy M.; Volpicelli, Alicia M.; Taylor, John A.

    2009-08-01

    The free-space communications community has only recently recognized the complexity of atmospheric channel interactions, which are highly dependent on the turbulence profile, beam propagation geometry, and transceiver design. The search for models that accurately describe link performance and overall availability is currently an active field of research. This paper describes a method for defining link availability based on statistical channel models, which can be derived from measured signal fluctuations during periods of stable atmospheric conditions. Measurements made during an extended communication link experiment conducted during the summer of 2008 indicate that the intervals of channel stability, which impact the length of link outages, can vary in duration from a few minutes to several hours. This work was sponsored by the Department of Defense, RRCO DDR&E, under Air Force Contract FA8721-05-C-0002. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the United States Government.

  15. Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence

    PubMed Central

    Krishnan, Neeraja; Gupta, Saurabh; Palve, Vinayak; Varghese, Linu; Pattnaik, Swetansu; Jain, Prach; Khyriem, Costerwell; Hariharan, Arun; Dhas, Kunal; Nair, Jayalakshmi; Pareek, Manisha; Prasad, Venkatesh; Siddappa, Gangotri; Suresh, Amritha; Kekatpure, Vikram; Kuriakose, Moni; Panda, Binay

    2015-01-01

    Oral tongue squamous cell carcinomas (OTSCC) are a homogeneous group of tumors characterized by aggressive behavior, early spread to lymph nodes and a higher rate of regional failure. Additionally, the incidence of OTSCC among younger population (<50yrs) is on the rise; many of whom lack the typical associated risk factors of alcohol and/or tobacco exposure. We present data on single nucleotide variations (SNVs), indels, regions with loss of heterozygosity (LOH), and copy number variations (CNVs) from fifty-paired oral tongue primary tumors and link the significant somatic variants with clinical parameters, epidemiological factors including human papilloma virus (HPV) infection and tumor recurrence. Apart from the frequent somatic variants harbored in TP53, CASP8, RASA1, NOTCH and CDKN2A genes, significant amplifications and/or deletions were detected in chromosomes 6-9, and 11 in the tumors. Variants in CASP8 and CDKN2A were mutually exclusive. CDKN2A, PIK3CA, RASA1 and DMD variants were exclusively linked to smoking, chewing, HPV infection and tumor stage. We also performed a whole-genome gene expression study that identified matrix metalloproteases to be highly expressed in tumors and linked pathways involving arachidonic acid and NF-k-B to habits and distant metastasis, respectively. Functional knockdown studies in cell lines demonstrated the role of CASP8 in a HPV-negative OTSCC cell line. Finally, we identified a 38-gene minimal signature that predicts tumor recurrence using an ensemble machine-learning method. Taken together, this study links molecular signatures to various clinical and epidemiological factors in a homogeneous tumor population with a relatively high HPV prevalence. PMID:26834999

  16. Statistical models for the control phase of clinical monitoring.

    PubMed

    Stevens, Richard J; Oke, Jason; Perera, Rafael

    2010-08-01

    The rise in the prevalence of chronic conditions means that these are now the leading causes of death and disability worldwide, accounting for almost 60% of all deaths and 43% of the global burden of disease. Management of chronic conditions requires both effective treatment and ongoing monitoring. Although costs related to monitoring are substantial, there is relatively little evidence on its effectiveness. Monitoring is inherently different to diagnosis in its use of regularly repeated tests, and increasing frequency can result in poorer rather than better statistical properties because of multiple testing in the presence of high variability. We present here a general framework for modelling the control phase of a monitoring programme, and for the estimation of quantities of potential clinical interest such as the ratio of false to true positive tests. We show how four recent clinical studies of monitoring cardiovascular disease, hypertension, diabetes and HIV infection can be thought as special cases of this framework; as well as using this framework to clarify the choice of estimation and calculation methods available. Noticeably, in each of the presented examples over-frequent monitoring appears to be a greater problem than under-frequent monitoring. We also present recalculations of results under alternative conditions, illustrating conceptual decisions about modelling the true or observed value of a clinical measure. PMID:20442195

  17. Linking near- and far-field hydrodynamic models for simulation of desalination plant brine discharges.

    PubMed

    Botelho, D A; Barry, M E; Collecutt, G C; Brook, J; Wiltshire, D

    2013-01-01

    A desalination plant is proposed to be the major water supply to the Olympic Dam Expansion Mining project. Located in the Upper Spencer Gulf, South Australia, the site was chosen due to the existence of strong currents and their likely advantages in terms of mixing and dilution of discharged return water. A high-resolution hydrodynamic model (Estuary, Lake and Coastal Ocean Model, ELCOM) was constructed and, through a rigorous review process, was shown to reproduce the intricate details of the Spencer Gulf dynamics, including those characterising the discharge site. Notwithstanding this, it was found that deploying typically adopted 'direct insertion' techniques to simulate the brine discharge within the hydrodynamic model was problematic. Specifically, it was found that in this study the direct insertion technique delivered highly conservative brine dilution predictions in and around the proposed site, and that these were grid and time-step dependent. To improve the predictive capability, a strategy to link validated computational fluid dynamics (CFD) predictions to hydrodynamic simulations was devised. In this strategy, environmental conditions from ELCOM were used to produce boundary conditions for execution of a suite of CFD simulations. In turn, the CFD simulations provided the brine dilutions and flow rates to be applied in ELCOM. In order to conserve mass in a system-wide sense, artificial salt sinks were introduced to the ELCOM model such that salt quantities were conserved. As a result of this process, ELCOM predictions were naturally very similar to CFD predictions near the diffuser, whilst at the same time they produced an area of influence (further afield) comparable to direct insertion methods. It was concluded that the linkage of the models, in comparison to direct insertion methods, constituted a more realistic and defensible alternative to predict the far-field dispersion of outfall discharges, particularly with regards to the estimation of brine

  18. Extending the RENO model: Clinical and ethical applications.

    PubMed

    Shaffer, Howard J; Ladouceur, Robert; Blaszczynski, Alex; Whyte, Keith

    2016-01-01

    The RENO Model, first published during 2004, described a science-based framework of responsible gambling principles for a range of industry operators, health service providers, community and consumer groups, and governments. These strategic principles serve as a guide for the adoption and implementation of responsible gambling and harm-minimization initiatives. This article extends the RENO Model core principles by describing how to apply these strategies to clinical practice. This discussion examines the central tenets of the model and includes a review of (a) the ethical principles that should guide the development, implementation, and practice of RENO Model responsible gambling activities; (b) a brief consideration of the various perspectives that influence the treatment of gambling-related problems; and (c) a discussion of key applied elements of responsible gambling programs. This article advances the argument that, to maximize positive outcomes and to avoid unintended harms, clinicians should apply science-based principles to rigorously evaluate the efficacy and impact of their clinical practice activities. (PsycINFO Database Record PMID:26569354

  19. Tectonic plates, difficulties for pupils to link models and scientific data.

    NASA Astrophysics Data System (ADS)

    David-Ameline, Jacques

    2014-05-01

    In a secondary school in the west of France, I teach Biology and Geology to young pupils from 12 to 15 years old. This poster deals with the difficulties that pupils have to link the scientific data concerning the plate tectonics and the models. I choose to reproduce for pupils some situations that faced some first scientific people as they discovered arguments for the plate tectonics. For example, they have to discover the thickness of the plates by studying the speed of the seismic waves regarding the deepness. That means that they have to construct a curve starting with a table and then to analyze it. The first step is linked to math lessons and is quite easy for them. But the second one needs to mix the curve with its signification. This point is particularly hard and as we correct it, it appears like one moment of « pure science » because they seem to discover something none did before, with the power of their brain ! The second work on this subject is to study the representations of the subduction at an oceanic trench and of the mid-ocean ridge. They first look for drawing explaining what happens for the plates in those places and then they look for proofs that permitted to create those drawings. They really need help to make the difference between scientific data (pictures, curves...) and other drawings similar to the one they choose. For this subject working with documents is not easy because pupils have to ask themselves « what kind of document is it ?» before going further into their thinking. Nevertheless, they often succeed in those works because the teacher helps them a little. Those subjects open their eyes on what science is for a geological theme. It's also a good method to make them having fun doing science and to make them being seduced by making science.

  20. Population pharmacokinetic–pharmacodynamic modelling in oncology: a tool for predicting clinical response

    PubMed Central

    Bender, Brendan C; Schindler, Emilie; Friberg, Lena E

    2015-01-01

    In oncology trials, overall survival (OS) is considered the most reliable and preferred endpoint to evaluate the benefit of drug treatment. Other relevant variables are also collected from patients for a given drug and its indication, and it is important to characterize the dynamic effects and links between these variables in order to improve the speed and efficiency of clinical oncology drug development. However, the drug-induced effects and causal relationships are often difficult to interpret because of temporal differences. To address this, population pharmacokinetic–pharmacodynamic (PKPD) modelling and parametric time-to-event (TTE) models are becoming more frequently applied. Population PKPD and TTE models allow for exploration towards describing the data, understanding the disease and drug action over time, investigating relevance of biomarkers, quantifying patient variability and in designing successful trials. In addition, development of models characterizing both desired and adverse effects in a modelling framework support exploration of risk-benefit of different dosing schedules. In this review, we have summarized population PKPD modelling analyses describing tumour, tumour marker and biomarker responses, as well as adverse effects, from anticancer drug treatment data. Various model-based metrics used to drive PD response and predict OS for oncology drugs and their indications are also discussed. PMID:24134068

  1. Pre-Clinical Models of Diffuse Intrinsic Pontine Glioma

    PubMed Central

    Misuraca, Katherine L.; Cordero, Francisco J.; Becher, Oren J.

    2015-01-01

    Diffuse intrinsic pontine glioma (DIPG) is a rare and incurable brain tumor that arises in the brainstem of children predominantly between the ages of 6 and 8. Its intricate morphology and involvement of normal pons tissue precludes surgical resection, and the standard of care today remains fractionated radiation alone. In the past 30 years, there have been no significant advances made in the treatment of DIPG. This is largely because we lack good models of DIPG and therefore have little biological basis for treatment. In recent years, however, due to increased biopsy and acquisition of autopsy specimens, research is beginning to unravel the genetic and epigenetic drivers of DIPG. Insight gleaned from these studies has led to improvements in approaches to both model these tumors in the lab and to potentially treat them in the clinic. This review will detail the initial strides toward modeling DIPG in animals, which included allograft and xenograft rodent models using non-DIPG glioma cells. Important advances in the field came with the development of in vitro cell and in vivo xenograft models derived directly from autopsy material of DIPG patients or from human embryonic stem cells. Finally, we will summarize the progress made in the development of genetically engineered mouse models of DIPG. Cooperation of studies incorporating all of these modeling systems to both investigate the unique mechanisms of gliomagenesis in the brainstem and to test potential novel therapeutic agents in a preclinical setting will result in improvement in treatments for DIPG patients. PMID:26258075

  2. Clinical application of the five-factor model.

    PubMed

    Widiger, Thomas A; Presnall, Jennifer Ruth

    2013-12-01

    The Five-Factor Model (FFM) has become the predominant dimensional model of general personality structure. The purpose of this paper is to suggest a clinical application. A substantial body of research indicates that the personality disorders included within the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM) can be understood as extreme and/or maladaptive variants of the FFM (the acronym "DSM" refers to any particular edition of the APA DSM). In addition, the current proposal for the forthcoming fifth edition of the DSM (i.e., DSM-5) is shifting closely toward an FFM dimensional trait model of personality disorder. Advantages of this shifting conceptualization are discussed, including treatment planning. PMID:22924994

  3. Clinical immersion: a residency model for nursing education.

    PubMed

    Diefenbeck, Cynthia A; Plowfield, Lisa Ann; Herrman, Judith W

    2006-01-01

    The education of future generations of nurses is in need of philosophic and programmatic transformation in keeping with the rapidly changing health care delivery system. The Nurse Residency Model is one baccalaureate nursing program's response to calls for reform. Rooted in a spirit of collegiality and lifelong learning, the three facets of its philosophy include enhanced socialization, improved transition to practice, and increased student accountability. Students gain increased competency and demonstrate increased accountability with each progressive semester in the program, which culminates in clinical immersion in the senior year. Unique programmatic features of this model include field experiences, the simulation lab, and a work requirement. Additional benefits include resource efficiency and patient safety. Implementation remains an ongoing process. Outcome indicators are expected to yield valuable data on which to develop an evidence base in support of the model. PMID:16733969

  4. The role of ecological models in linking ecological risk assessment to ecosystem services in agroecosystems.

    PubMed

    Galic, Nika; Schmolke, Amelie; Forbes, Valery; Baveco, Hans; van den Brink, Paul J

    2012-01-15

    Agricultural practices are essential for sustaining the human population, but at the same time they can directly disrupt ecosystem functioning. Ecological risk assessment (ERA) aims to estimate possible adverse effects of human activities on ecosystems and their parts. Current ERA practices, however, incorporate very little ecology and base the risk estimates on the results of standard tests with several standard species. The main obstacles for a more ecologically relevant ERA are the lack of clear protection goals and the inherent complexity of ecosystems that is hard to approach empirically. In this paper, we argue that the ecosystem services framework offers an opportunity to define clear and ecologically relevant protection goals. At the same time, ecological models provide the tools to address ecological complexity to the degree needed to link measurement endpoints and ecosystem services, and to quantify service provision and possible adverse effects from human activities. We focus on the ecosystem services relevant for agroecosystem functioning, including pollination, biocontrol and eutrophication effects and present modeling studies relevant for quantification of each of the services. The challenges of the ecosystem services approach are discussed as well as the limitations of ecological models in the context of ERA. A broad, multi-stakeholder dialog is necessary to aid the definition of protection goals in terms of services delivered by ecosystems and their parts. The need to capture spatio-temporal dynamics and possible interactions among service providers pose challenges for ecological models as a basis for decision making. However, we argue that both fields are advancing quickly and can prove very valuable in achieving more ecologically relevant ERA. PMID:21802704

  5. Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model.

    PubMed

    Bestas, Burcu; Moreno, Pedro M D; Blomberg, K Emelie M; Mohammad, Dara K; Saleh, Amer F; Sutlu, Tolga; Nordin, Joel Z; Guterstam, Peter; Gustafsson, Manuela O; Kharazi, Shabnam; Piątosa, Barbara; Roberts, Thomas C; Behlke, Mark A; Wood, Matthew J A; Gait, Michael J; Lundin, Karin E; El Andaloussi, Samir; Månsson, Robert; Berglöf, Anna; Wengel, Jesper; Smith, C I Edvard

    2014-09-01

    X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency that results from mutations within the gene encoding Bruton's tyrosine kinase (BTK). Many XLA-associated mutations affect splicing of BTK pre-mRNA and severely impair B cell development. Here, we assessed the potential of antisense, splice-correcting oligonucleotides (SCOs) targeting mutated BTK transcripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we engineered a transgenic mouse that harbors a BAC with an authentic, mutated, splice-defective human BTK gene. BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the orthologous mouse protein. Using this model, we determined that BTK-specific SCOs are able to correct aberrantly spliced BTK in B lymphocytes, including pro-B cells. Correction of BTK mRNA restored expression of functional protein, as shown both by enhanced lymphocyte survival and reestablished BTK activation upon B cell receptor stimulation. Furthermore, SCO treatment corrected splicing and restored BTK expression in primary cells from patients with XLA. Together, our data demonstrate that SCOs can restore BTK function and that BTK-targeting SCOs have potential as personalized medicine in patients with XLA. PMID:25105368

  6. Linking Fine-Scale Observations and Model Output with Imagery at Multiple Scales

    NASA Astrophysics Data System (ADS)

    Sadler, J.; Walthall, C. L.

    2014-12-01

    The development and implementation of a system for seasonal worldwide agricultural yield estimates is underway with the international Group on Earth Observations GeoGLAM project. GeoGLAM includes a research component to continually improve and validate its algorithms. There is a history of field measurement campaigns going back decades to draw upon for ways of linking surface measurements and model results with satellite observations. Ground-based, in-situ measurements collected by interdisciplinary teams include yields, model inputs and factors affecting scene radiation. Data that is comparable across space and time with careful attention to calibration is essential for the development and validation of agricultural applications of remote sensing. Data management to ensure stewardship, availability and accessibility of the data are best accomplished when considered an integral part of the research. The expense and logistical challenges of field measurement campaigns can be cost-prohibitive and because of short funding cycles for research, access to consistent, stable study sites can be lost. The use of a dedicated staff for baseline data needed by multiple investigators, and conducting measurement campaigns using existing measurement networks such as the USDA Long Term Agroecosystem Research network can fulfill these needs and ensure long-term access to study sites.

  7. Ecological-network models link diversity, structure and function in the plankton food-web

    PubMed Central

    D’Alelio, Domenico; Libralato, Simone; Wyatt, Timothy; Ribera d’Alcalà, Maurizio

    2016-01-01

    A planktonic food-web model including sixty-three functional nodes (representing auto- mixo- and heterotrophs) was developed to integrate most trophic diversity present in the plankton. The model was implemented in two variants - which we named ‘green’ and ‘blue’ - characterized by opposite amounts of phytoplankton biomass and representing, respectively, bloom and non-bloom states of the system. Taxonomically disaggregated food-webs described herein allowed to shed light on how components of the plankton community changed their trophic behavior in the two different conditions, and modified the overall functioning of the plankton food web. The green and blue food-webs showed distinct organizations in terms of trophic roles of the nodes and carbon fluxes between them. Such re-organization stemmed from switches in selective grazing by both metazoan and protozoan consumers. Switches in food-web structure resulted in relatively small differences in the efficiency of material transfer towards higher trophic levels. For instance, from green to blue states, a seven-fold decrease in phytoplankton biomass translated into only a two-fold decrease in potential planktivorous fish biomass. By linking diversity, structure and function in the plankton food-web, we discuss the role of internal mechanisms, relying on species-specific functionalities, in driving the ‘adaptive’ responses of plankton communities to perturbations. PMID:26883643

  8. Ecological-network models link diversity, structure and function in the plankton food-web.

    PubMed

    D'Alelio, Domenico; Libralato, Simone; Wyatt, Timothy; Ribera d'Alcalà, Maurizio

    2016-01-01

    A planktonic food-web model including sixty-three functional nodes (representing auto- mixo- and heterotrophs) was developed to integrate most trophic diversity present in the plankton. The model was implemented in two variants - which we named 'green' and 'blue' - characterized by opposite amounts of phytoplankton biomass and representing, respectively, bloom and non-bloom states of the system. Taxonomically disaggregated food-webs described herein allowed to shed light on how components of the plankton community changed their trophic behavior in the two different conditions, and modified the overall functioning of the plankton food web. The green and blue food-webs showed distinct organizations in terms of trophic roles of the nodes and carbon fluxes between them. Such re-organization stemmed from switches in selective grazing by both metazoan and protozoan consumers. Switches in food-web structure resulted in relatively small differences in the efficiency of material transfer towards higher trophic levels. For instance, from green to blue states, a seven-fold decrease in phytoplankton biomass translated into only a two-fold decrease in potential planktivorous fish biomass. By linking diversity, structure and function in the plankton food-web, we discuss the role of internal mechanisms, relying on species-specific functionalities, in driving the 'adaptive' responses of plankton communities to perturbations. PMID:26883643

  9. ON THE TRANSITIONAL DISK CLASS: LINKING OBSERVATIONS OF T TAURI STARS AND PHYSICAL DISK MODELS

    SciTech Connect

    Espaillat, C.; Andrews, S.; Qi, C.; Wilner, D.; Ingleby, L.; Calvet, N.; Hernandez, J.; Furlan, E.; D'Alessio, P.; Muzerolle, J. E-mail: sandrews@cfa.harvard.edu E-mail: dwilner@cfa.harvard.edu E-mail: ncalvet@umich.edu E-mail: Elise.Furlan@jpl.nasa.gov E-mail: muzerol@stsci.edu

    2012-03-10

    Two decades ago 'transitional disks' (TDs) described spectral energy distributions (SEDs) of T Tauri stars with small near-IR excesses, but significant mid- and far-IR excesses. Many inferred this indicated dust-free holes in disks possibly cleared by planets. Recently, this term has been applied disparately to objects whose Spitzer SEDs diverge from the expectations for a typical full disk (FD). Here, we use irradiated accretion disk models to fit the SEDs of 15 such disks in NGC 2068 and IC 348. One group has a 'dip' in infrared emission while the others' continuum emission decreases steadily at all wavelengths. We find that the former have an inner disk hole or gap at intermediate radii in the disk and we call these objects 'transitional disks' and 'pre-transitional disks' (PTDs), respectively. For the latter group, we can fit these SEDs with FD models and find that millimeter data are necessary to break the degeneracy between dust settling and disk mass. We suggest that the term 'transitional' only be applied to objects that display evidence for a radical change in the disk's radial structure. Using this definition, we find that TDs and PTDs tend to have lower mass accretion rates than FDs and that TDs have lower accretion rates than PTDs. These reduced accretion rates onto the star could be linked to forming planets. Future observations of TDs and PTDs will allow us to better quantify the signatures of planet formation in young disks.

  10. Playing the role of weak clique property in link prediction: A friend recommendation model

    NASA Astrophysics Data System (ADS)

    Ma, Chuang; Zhou, Tao; Zhang, Hai-Feng

    2016-07-01

    An important fact in studying link prediction is that the structural properties of networks have significant impacts on the performance of algorithms. Therefore, how to improve the performance of link prediction with the aid of structural properties of networks is an essential problem. By analyzing many real networks, we find a typical structural property: nodes are preferentially linked to the nodes with the weak clique structure (abbreviated as PWCS to simplify descriptions). Based on this PWCS phenomenon, we propose a local friend recommendation (FR) index to facilitate link prediction. Our experiments show that the performance of FR index is better than some famous local similarity indices, such as Common Neighbor (CN) index, Adamic-Adar (AA) index and Resource Allocation (RA) index. We then explain why PWCS can give rise to the better performance of FR index in link prediction. Finally, a mixed friend recommendation index (labelled MFR) is proposed by utilizing the PWCS phenomenon, which further improves the accuracy of link prediction.

  11. An analytical model applied to a multicenter pneumococcal enzyme-linked immunosorbent assay study.

    PubMed

    Plikaytis, B D; Goldblatt, D; Frasch, C E; Blondeau, C; Bybel, M J; Giebink, G S; Jonsdottir, I; Käyhty, H; Konradsen, H B; Madore, D V; Nahm, M H; Schulman, C A; Holder, P F; Lezhava, T; Elie, C M; Carlone, G M

    2000-06-01

    Pneumococcal conjugate vaccines will eventually be licensed after favorable results from phase III efficacy trials. After licensure of a conjugate vaccine for invasive pneumococcal disease in infants, new conjugate vaccines will likely be licensed primarily on the basis of immunogenicity data rather than clinical efficacy. Analytical methods must therefore be developed, evaluated, and validated to compare immunogenicity results accurately within and between laboratories for different vaccines. At present no analytical technique is uniformly accepted and used in vaccine evaluation studies to determine the acceptable level of agreement between a laboratory result and the assigned value for a given serum sample. This multicenter study describes the magnitude of agreement among 12 laboratories quantifying an identical series of 48 pneumococcal serum specimens from 24 individuals (quality-control sera) by a consensus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) developed for this study. After provisional or trial antibody concentrations were assigned to the quality-control serum samples for this study, four methods for comparison of a series of laboratory-determined values with the assigned concentrations were evaluated. The percent error between assigned values and laboratory-determined concentrations proved to be the most informative of the four methods. We present guidelines that a laboratory may follow to analyze a series of quality-control sera to determine if it can reproduce the assigned antibody concentrations within an acceptable level of tolerance. While this study focused on a pneumococcal IgG ELISA, the methods that we describe are easily generalizable to other immunological assays. PMID:10834951

  12. A Framework and Model for Evaluating Clinical Decision Support Architectures

    PubMed Central

    Wright, Adam; Sittig, Dean F.

    2008-01-01

    In this paper, we develop a four-phase model for evaluating architectures for clinical decision support that focuses on: defining a set of desirable features for a decision support architecture; building a proof-of-concept prototype; demonstrating that the architecture is useful by showing that it can be integrated with existing decision support systems and comparing its coverage to that of other architectures. We apply this framework to several well-known decision support architectures, including Arden Syntax, GLIF, SEBASTIAN and SAGE PMID:18462999

  13. The ADHD Clinic: a collaborative model of care.

    PubMed

    Campbell, Lisa; Allan, Carla

    2014-01-01

    Hyperactivity Disorder (ADHD) is a common chronic and often life-persistent neurobehavioral disorder. At Children's Mercy Hospital, collaboration between a developmental-behavioral pediatrician and a behavioral psychologist, both of whom specialize in ADHD, allows the use of both medication and behavior modification which are recommended by the American Academy of Pediatrics and which are equally effective as stand-alone therapies. Children who receive both of these treatment modalities also fare better than those who receive only medication in a number of areas. This article will describe our collaborative clinic model and will address considerations of parent preference about these therapeutic approaches. PMID:25011340

  14. The beginning of a beautiful friendship: Cross-linking/mass spectrometry and modelling of proteins and multi-protein complexes

    PubMed Central

    Rappsilber, Juri

    2011-01-01

    After more than a decade of method development, cross-linking in combination with mass spectrometry and bioinformatics is finally coming of age. This technology now provides improved opportunities for modelling by mapping structural details of functional complexes in solution. The structure of proteins or protein complexes is ascertained by identifying amino acid pairs that are positioned in close proximity to each other. The validity of this technique has recently been benchmarked for large multi-protein complexes, by comparing cross-link data with that from a crystal structure of RNA polymerase II. Here, the specific nature of this cross-linking data will be discussed to assess the technical challenges and opportunities for model building. We believe that once remaining technological challenges of cross-linking/mass spectrometry have been addressed and cross-linking/mass spectrometry data has been incorporated into modelling algorithms it will quickly become an indispensable companion of protein and protein complex modelling and a corner-stone of integrated structural biology. PMID:21029779

  15. Neuroradiologic correlates of clinical disability and progression in the X-Linked leukodystrophy Pelizaeus–Merzbacher disease

    PubMed Central

    Laukka, Jeremy J.; Stanley, Jeffrey A.; Garbern, James Y.; Trepanier, Angela; Hobson, Grace; Lafleur, Tori; Gow, Alexander; Kamholz, John

    2014-01-01

    Objective To determine whether quantitative measure of magnetic resonance imaging data from patients with the inherited leukodystrophy, Pelizaeus–Merzbacher disease (PMD) correlates with clinical severity or progression. Methods In our current work we have analyzed the clinical phenotypes and MRI scans of 51 male patients with PMD and 10 female carriers for whom the PLP1 genotype had been determined. In addition, we developed a 32-point functional disability scoring (FDS) system for PMD, and validated it for inter-rater reliability. Using conventional T1- and T2-weighted MRI images of the whole brain, we measured white matter and total brain volume (WMV and TBV), inter-caudate ratio (ICR), and corpus callosum area. Results There was a significant positive correlation of FDS with white matter fraction (WMV/TBV) and corpus callosum area. Also, when applying a median split based on FDS, patients with lower FDS showed reduced white matter fraction and corpus callosum area, and increased ICR compared to patients with relatively higher FDS, regardless of age. Conclusion Although this patient population is heterogeneous, with multiple genetic and molecular mechanisms causing PMD, these data imply that white matter atrophy is a major pathological determinant of the clinical disability in most patients. Development of reliable non-invasive quantitative biomarkers of disease activity would be useful not only for following the natural history of the disease, but also raising the potential for evaluating future therapies. PMID:24139698

  16. Poor symptom and performance validity in regularly referred Hospital outpatients: Link with standard clinical measures, and role of incentives.

    PubMed

    Dandachi-FitzGerald, Brechje; van Twillert, Björn; van de Sande, Peter; van Os, Yindee; Ponds, Rudolf W H M

    2016-05-30

    We investigated the frequency of symptom validity test (SVT) failure and its clinical correlates in a large, heterogeneous sample of hospital outpatients referred for psychological assessment for clinical purposes. We studied patients (N=469), who were regularly referred for assessment to the psychology departments of five hospitals. Background characteristics, including information about incentives, were obtained with a checklist completed by the clinician. As a measure of over-reporting, the Structured Inventory of Malingered Symptomatology (SIMS) was administered to all patients. The Amsterdam Short-Term Memory test (ASTM), a cognitive underperformance measure, was only administered to patients who were referred for a neuropsychological assessment. Symptom over-reporting occurred in a minority of patients, ranging from 12% to 19% in the main diagnostic patient groups. Patients with morbid obesity had a low rate of over-reporting (1%). The SIMS was positively associated with levels of self-reported psychological symptoms. Cognitive underperformance occurred in 29.3% of the neuropsychological assessments. The ASTM was negatively associated with memory test performance. We found no association between SVT failure and financial incentives. Our results support the recommendation to routinely evaluate symptom validity in clinical assessments of hospital patients. The dynamics behind invalid symptom reporting need to be further elucidated. PMID:27137961

  17. The future of monitoring in clinical research - a holistic approach: linking risk-based monitoring with quality management principles.

    PubMed

    Ansmann, Eva B; Hecht, Arthur; Henn, Doris K; Leptien, Sabine; Stelzer, Hans Günther

    2013-01-01

    Since several years risk-based monitoring is the new "magic bullet" for improvement in clinical research. Lots of authors in clinical research ranging from industry and academia to authorities are keen on demonstrating better monitoring-efficiency by reducing monitoring visits, monitoring time on site, monitoring costs and so on, always arguing with the use of risk-based monitoring principles. Mostly forgotten is the fact, that the use of risk-based monitoring is only adequate if all mandatory prerequisites at site and for the monitor and the sponsor are fulfilled.Based on the relevant chapter in ICH GCP (International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use - Good Clinical Practice) this publication takes a holistic approach by identifying and describing the requirements for future monitoring and the use of risk-based monitoring. As the authors are operational managers as well as QA (Quality Assurance) experts, both aspects are represented to come up with efficient and qualitative ways of future monitoring according to ICH GCP. PMID:23382708

  18. A life cycle model of continuous clinical process innovation.

    PubMed

    Savitz, L A; Kaluzny, A D; Kelly, D L

    2000-01-01

    The changing healthcare environment has created a sense of urgency for continuous innovation in clinical care processes. Managers and clinicians are investing unprecedented funds and energy in the development of various clinical process innovations (CPI) such as clinical pathways, electronic workstations, and various forms of information technology. While increasing attention has been paid to the development of such initiatives, our understanding of how best to disseminate and ensure their use is limited. In this first of two articles dealing with the dissemination and use of CPI in integrated delivery systems, we present a "life cycle" model of the dissemination process and suggest opportunities for managing CPI. The management of CPI requires more than just an understanding of the factors that may facilitate or impede its implementation and use. Managers require an understanding of the actual process so that they can assess the specific implementation stage at which the organization is presently operating, and design appropriate interventions that can affect the process. A future article will identify the factors that facilitate and inhibit the process and suggest some intervention strategies. PMID:11067423

  19. An Infinite Mixture Model for Coreference Resolution in Clinical Notes.

    PubMed

    Liu, Sijia; Liu, Hongfang; Chaudhary, Vipin; Li, Dingcheng

    2016-01-01

    It is widely acknowledged that natural language processing is indispensable to process electronic health records (EHRs). However, poor performance in relation detection tasks, such as coreference (linguistic expressions pertaining to the same entity/event) may affect the quality of EHR processing. Hence, there is a critical need to advance the research for relation detection from EHRs. Most of the clinical coreference resolution systems are based on either supervised machine learning or rule-based methods. The need for manually annotated corpus hampers the use of such system in large scale. In this paper, we present an infinite mixture model method using definite sampling to resolve coreferent relations among mentions in clinical notes. A similarity measure function is proposed to determine the coreferent relations. Our system achieved a 0.847 F-measure for i2b2 2011 coreference corpus. This promising results and the unsupervised nature make it possible to apply the system in big-data clinical setting. PMID:27595047

  20. An Infinite Mixture Model for Coreference Resolution in Clinical Notes

    PubMed Central

    Liu, Sijia; Liu, Hongfang; Chaudhary, Vipin; Li, Dingcheng

    2016-01-01

    It is widely acknowledged that natural language processing is indispensable to process electronic health records (EHRs). However, poor performance in relation detection tasks, such as coreference (linguistic expressions pertaining to the same entity/event) may affect the quality of EHR processing. Hence, there is a critical need to advance the research for relation detection from EHRs. Most of the clinical coreference resolution systems are based on either supervised machine learning or rule-based methods. The need for manually annotated corpus hampers the use of such system in large scale. In this paper, we present an infinite mixture model method using definite sampling to resolve coreferent relations among mentions in clinical notes. A similarity measure function is proposed to determine the coreferent relations. Our system achieved a 0.847 F-measure for i2b2 2011 coreference corpus. This promising results and the unsupervised nature make it possible to apply the system in big-data clinical setting. PMID:27595047

  1. Linking land use change to recreational fishery valuation with a spatially explicit behavior model: A case study from Tampa Bay, FL USA

    EPA Science Inventory

    Drawing a link between habitat change and production and delivery of ecosystem services is a priority in coastal estuarine ecosystems. This link is needed to fully understand how human communities can influence ecosystem sustainability. Mechanistic modeling tools are highly fun...

  2. Linking GIS-based models to value ecosystem services in an Alpine region.

    PubMed

    Grêt-Regamey, Adrienne; Bebi, Peter; Bishop, Ian D; Schmid, Willy A

    2008-11-01

    Planning frequently fails to include the valuation of public goods and services. This can have long-term negative economic consequences for a region. This is especially the case in mountainous regions such as the Alps, which depend on tourism and where land-use changes can negatively impact key ecosystem services and hence the economy. In this study, we develop a semi-automatic procedure to value ecosystem goods and services. Several existing process-based models linked to economic valuation methods are integrated into a geographic information system (GIS) platform. The model requires the input of a digital elevation model, a land-cover map, and a spatially explicit temperature dataset. These datasets are available for most regions in Europe. We illustrate the approach by valuing four ecosystem services: avalanche protection, timber production, scenic beauty, and habitat, which are supplied by the "Landschaft Davos", an administrative district in the Swiss Alps. We compare the impacts of a human development scenario and a climate scenario on the value of these ecosystem services. Urban expansion and tourist infrastructure developments have a negative impact on scenic beauty and habitats. These impacts outweigh the benefits of the developments in the long-term. Forest expansion, predictable under a climate change scenario, favours natural avalanche protection and habitats. In general, such non-marketed benefits provided by the case-study region more than compensate for the costs of forest maintenance. Finally, we discuss the advantages and disadvantages of the approach. Despite its limitations, we show how this approach could well help decision-makers balance the impacts of different planning options on the economic accounting of a region, and guide them in selecting sustainable and economically feasible development strategies. PMID:17825979

  3. Linking Human Diseases to Animal Models Using Ontology-Based Phenotype Annotation

    PubMed Central

    Mungall, Christopher J.; Ashburner, Michael; Westerfield, Monte; Lewis, Suzanna E.

    2009-01-01

    Scientists and clinicians who study genetic alterations and disease have traditionally described phenotypes in natural language. The considerable variation in these free-text descriptions has posed a hindrance to the important task of identifying candidate genes and models for human diseases and indicates the need for a computationally tractable method to mine data resources for mutant phenotypes. In this study, we tested the hypothesis that ontological annotation of disease phenotypes will facilitate the discovery of new genotype-phenotype relationships within and across species. To describe phenotypes using ontologies, we used an Entity-Quality (EQ) methodology, wherein the affected entity (E) and how it is affected (Q) are recorded using terms from a variety of ontologies. Using this EQ method, we annotated the phenotypes of 11 gene-linked human diseases described in Online Mendelian Inheritance in Man (OMIM). These human annotations were loaded into our Ontology-Based Database (OBD) along with other ontology-based phenotype descriptions of mutants from various model organism databases. Phenotypes recorded with this EQ method can be computationally compared based on the hierarchy of terms in the ontologies and the frequency of annotation. We utilized four similarity metrics to compare phenotypes and developed an ontology of homologous and analogous anatomical structures to compare phenotypes between species. Using these tools, we demonstrate that we can identify, through the similarity of the recorded phenotypes, other alleles of the same gene, other members of a signaling pathway, and orthologous genes and pathway members across species. We conclude that EQ-based annotation of phenotypes, in conjunction with a cross-species ontology, and a variety of similarity metrics can identify biologically meaningful similarities between genes by comparing phenotypes alone. This annotation and search method provides a novel and efficient means to identify gene candidates

  4. The hydrological calibration and validation of a complexly-linked watershed reservoir model for the Occoquan watershed, Virginia

    NASA Astrophysics Data System (ADS)

    Xu, Zhongyan; Godrej, Adil N.; Grizzard, Thomas J.

    2007-10-01

    SummaryRunoff models such as HSPF and reservoir models such as CE-QUAL-W2 are used to model water quality in watersheds. Most often, the models are independently calibrated to observed data. While this approach can achieve good calibration, it does not replicate the physically-linked nature of the system. When models are linked by using the model output from an upstream model as input to a downstream model, the physical reality of a continuous watershed, where the overland and waterbody portions are parts of the whole, is better represented. There are some additional challenges in the calibration of such linked models, because the aim is to simulate the entire system as a whole, rather than piecemeal. When public entities are charged with model development, one of the driving forces is to use public-domain models. This paper describes the use of two such models, HSPF and CE-QUAL-W2, in the linked modeling of the Occoquan watershed located in northern Virginia, USA. The description of the process is provided, and results from the hydrological calibration and validation are shown. The Occoquan model consists of six HSPF and two CE-QUAL-W2 models, linked in a complex way, to simulate two major reservoirs and the associated drainage areas. The overall linked model was calibrated for a three-year period and validated for a two-year period. The results show that a successful calibration can be achieved using the linked approach, with moderate additional effort. Overall flow balances based on the three-year calibration period at four stream stations showed agreement ranging from -3.95% to +3.21%. Flow balances for the two reservoirs, compared via the daily water surface elevations, also showed good agreement ( R2 values of 0.937 for Lake Manassas and 0.926 for Occoquan Reservoir), when missing (un-monitored) flows were included. Validation of the models ranged from poor to fair for the watershed models and excellent for the waterbody models, thus indicating that the

  5. Linking an economic model for European agriculture with a mechanistic model to estimate nitrogen losses from cropland soil in Europe

    NASA Astrophysics Data System (ADS)

    Leip, A.; Marchi, G.; Koeble, R.; Kempen, M.; Britz, W.; Li, C.

    2007-07-01

    For the comprehensive assessment of the policy impact on greenhouse gas emissions from agricultural soils both socio-economic aspects and the environmental heterogeneity of the landscape are important factors that must be considered. We developed a modelling framework that links the large-scale economic model for agriculture CAPRI with the bio-geochemistry model DNDC to simulate greenhouse gas fluxes, carbon stock changes and the nitrogen budget of agricultural soils in Europe. The framework allows the ex-ante simulation of agricultural or agri-environmental policy impacts on wide range of environmental problems such as climate change (greenhouse gas emissions), air pollution and groundwater pollution. Those environmental impacts can be analysed in the context of economic and social indicators as calculated by the economic model. The methodology consists in four steps (i) the definition of appropriate calculation units that can be considered as homogeneous in terms of economic behaviour and environmental response; (ii) downscaling of regional agricultural statistics and farm management information from a CAPRI simulation run into the spatial calculation units; (iii) setting up of environmental model scenarios and model runs; and finally (iv) aggregating results for interpretation. We show first results of the nitrogen budget in cropland for the area of fourteen countries of the European Union. These results, in terms of estimated nitrogen fluxes, must still be considered as illustrative as needs for improvements in input data (e.g. the soil map) and management data (yield estimates) have been identified and will be the focus of future work. Nevertheless, we highlight inter-dependencies between farmer's choices of land uses and the environmental impact of different cultivation systems.

  6. A conceptual model for translating omic data into clinical action

    PubMed Central

    Herr, Timothy M.; Bielinski, Suzette J.; Bottinger, Erwin; Brautbar, Ariel; Brilliant, Murray; Chute, Christopher G.; Denny, Joshua; Freimuth, Robert R.; Hartzler, Andrea; Kannry, Joseph; Kohane, Isaac S.; Kullo, Iftikhar J.; Lin, Simon; Pathak, Jyotishman; Peissig, Peggy; Pulley, Jill; Ralston, James; Rasmussen, Luke; Roden, Dan; Tromp, Gerard; Williams, Marc S.; Starren, Justin

    2015-01-01

    Genomic, proteomic, epigenomic, and other “omic” data have the potential to enable precision medicine, also commonly referred to as personalized medicine. The volume and complexity of omic data are rapidly overwhelming human cognitive capacity, requiring innovative approaches to translate such data into patient care. Here, we outline a conceptual model for the application of omic data in the clinical context, called “the omic funnel.” This model parallels the classic “Data, Information, Knowledge, Wisdom pyramid” and adds context for how to move between each successive layer. Its goal is to allow informaticians, researchers, and clinicians to approach the problem of translating omic data from bench to bedside, by using discrete steps with clearly defined needs. Such an approach can facilitate the development of modular and interoperable software that can bring precision medicine into widespread practice. PMID:26430534

  7. A conceptual model for translating omic data into clinical action.

    PubMed

    Herr, Timothy M; Bielinski, Suzette J; Bottinger, Erwin; Brautbar, Ariel; Brilliant, Murray; Chute, Christopher G; Denny, Joshua; Freimuth, Robert R; Hartzler, Andrea; Kannry, Joseph; Kohane, Isaac S; Kullo, Iftikhar J; Lin, Simon; Pathak, Jyotishman; Peissig, Peggy; Pulley, Jill; Ralston, James; Rasmussen, Luke; Roden, Dan; Tromp, Gerard; Williams, Marc S; Starren, Justin

    2015-01-01

    Genomic, proteomic, epigenomic, and other "omic" data have the potential to enable precision medicine, also commonly referred to as personalized medicine. The volume and complexity of omic data are rapidly overwhelming human cognitive capacity, requiring innovative approaches to translate such data into patient care. Here, we outline a conceptual model for the application of omic data in the clinical context, called "the omic funnel." This model parallels the classic "Data, Information, Knowledge, Wisdom pyramid" and adds context for how to move between each successive layer. Its goal is to allow informaticians, researchers, and clinicians to approach the problem of translating omic data from bench to bedside, by using discrete steps with clearly defined needs. Such an approach can facilitate the development of modular and interoperable software that can bring precision medicine into widespread practice. PMID:26430534

  8. Vibro-acoustic modelling of aircraft double-walls with structural links using Statistical Energy Analysis

    NASA Astrophysics Data System (ADS)

    Campolina, Bruno L.

    The prediction of aircraft interior noise involves the vibroacoustic modelling of the fuselage with noise control treatments. This structure is composed of a stiffened metallic or composite panel, lined with a thermal and acoustic insulation layer (glass wool), and structurally connected via vibration isolators to a commercial lining panel (trim). The goal of this work aims at tailoring the noise control treatments taking design constraints such as weight and space optimization into account. For this purpose, a representative aircraft double-wall is modelled using the Statistical Energy Analysis (SEA) method. Laboratory excitations such as diffuse acoustic field and point force are addressed and trends are derived for applications under in-flight conditions, considering turbulent boundary layer excitation. The effect of the porous layer compression is firstly addressed. In aeronautical applications, compression can result from the installation of equipment and cables. It is studied analytically and experimentally, using a single panel and a fibrous uniformly compressed over 100% of its surface. When compression increases, a degradation of the transmission loss up to 5 dB for a 50% compression of the porous thickness is observed mainly in the mid-frequency range (around 800 Hz). However, for realistic cases, the effect should be reduced since the compression rate is lower and compression occurs locally. Then the transmission through structural connections between panels is addressed using a four-pole approach that links the force-velocity pair at each side of the connection. The modelling integrates experimental dynamic stiffness of isolators, derived using an adapted test rig. The structural transmission is then experimentally validated and included in the double-wall SEA model as an equivalent coupling loss factor (CLF) between panels. The tested structures being flat, only axial transmission is addressed. Finally, the dominant sound transmission paths are

  9. Subgraph augmented non-negative tensor factorization (SANTF) for modeling clinical narrative text

    PubMed Central

    Xin, Yu; Hochberg, Ephraim; Joshi, Rohit; Uzuner, Ozlem; Szolovits, Peter

    2015-01-01

    Objective Extracting medical knowledge from electronic medical records requires automated approaches to combat scalability limitations and selection biases. However, existing machine learning approaches are often regarded by clinicians as black boxes. Moreover, training data for these automated approaches at often sparsely annotated at best. The authors target unsupervised learning for modeling clinical narrative text, aiming at improving both accuracy and interpretability. Methods The authors introduce a novel framework named subgraph augmented non-negative tensor factorization (SANTF). In addition to relying on atomic features (e.g., words in clinical narrative text), SANTF automatically mines higher-order features (e.g., relations of lymphoid cells expressing antigens) from clinical narrative text by converting sentences into a graph representation and identifying important subgraphs. The authors compose a tensor using patients, higher-order features, and atomic features as its respective modes. We then apply non-negative tensor factorization to cluster patients, and simultaneously identify latent groups of higher-order features that link to patient clusters, as in clinical guidelines where a panel of immunophenotypic features and laboratory results are used to specify diagnostic criteria. Results and Conclusion SANTF demonstrated over 10% improvement in averaged F-measure on patient clustering compared to widely used non-negative matrix factorization (NMF) and k-means clustering methods. Multiple baselines were established by modeling patient data using patient-by-features matrices with different feature configurations and then performing NMF or k-means to cluster patients. Feature analysis identified latent groups of higher-order features that lead to medical insights. We also found that the latent groups of atomic features help to better correlate the latent groups of higher-order features. PMID:25862765

  10. Multiscale modeling for clinical translation in neuropsychiatric disease

    PubMed Central

    Lytton, William W.; Neymotin, Samuel A.; Kerr, Cliff C.

    2015-01-01

    Multiscale modeling of neuropsychiatric illness bridges scales of clinical importance: from the highest scales (presentation of behavioral signs and symptoms), through intermediate scales (clinical testing and surgical intervention), down to the molecular scale of pharmacotherapy. Modeling of brain disease is difficult compared to modeling of other organs, because dysfunction manifests at scales where measurements are rudimentary due both to inadequate access (memory and cognition) and to complexity (behavior). Nonetheless, we can begin to explore these aspects through the use of information-theoretic measures as stand-ins for meaning at the top scales. We here describe efforts across five disorders: Parkinson’s, Alzheimer’s, stroke, schizophrenia, and epilepsy. We look at the use of therapeutic brain stimulation to replace lost neural signals, a loss that produces diaschisis, defined as activity changes in other brain areas due to missing inputs. These changes may in some cases be compensatory, hence beneficial, but in many cases a primary pathology, whether itself static or dynamic, sets in motion a series of dynamic consequences that produce further pathology. The simulations presented here suggest how diaschisis can be reversed by using a neuroprosthetic signal. Despite having none of the information content of the lost physiological signal, the simplified neuroprosthetic signal can restore a diaschitic area to near-normal patterns of activity. Computer simulation thus begins to explain the remarkable success of stimulation technologies - deep brain stimulation, transcranial magnetic stimulation, ultrasound stimulation, transcranial direct current stimulation - across an extremely broad range of pathologies. Multiscale modeling can help us to optimize and integrate these neuroprosthetic therapies by taking into consideration effects of different stimulation protocols, combinations of stimulation with neuropharmacological therapy, and interplay of these

  11. Modeling HIV Immune Response and Validation with Clinical Data

    PubMed Central

    Banks, H. T.; Davidian, M.; Hu, Shuhua; Kepler, Grace M.; Rosenberg, E.S.

    2009-01-01

    A system of ordinary differential equations is formulated to describe the pathogenesis of HIV infection, wherein certain features that have been shown to be important by recent experimental research are incorporated in the model. These include the role of CD4+ memory cells that serve as a major reservoir of latently infected cells, a critical role for T-helper cells in the generation of CD8 memory cells capable of efficient recall response, and stimulation by antigens other than HIV. A stability analysis illustrates the capability of this model in admitting multiple locally asymptotically stable (locally a.s.) off-treatment equilibria. We show that this more biologically-detailed model can exhibit the phenomenon of transient viremia experienced by some patients on therapy with viral load levels suppressed below the detection limit. We also show that the loss of CD4+ T-cell help in the generation of CD8+ memory cells leads to larger peak values for the viral load during transient viremia. Censored clinical data is used to obtain parameter estimates. We demonstrate that using a reduced set of 16 free parameters, obtained by fixing some parameters at their population averages, the model provides reasonable fits to the patient data and, moreover, that it exhibits good predictive capability. We further show that parameter values obtained for most clinical patients do not admit multiple locally a.s off-treatment equilibria. This suggests that treatment to move from a high viral load equilibrium state to an equilibrium state with a lower (or zero) viral load is not possible for these patients. PMID:19495424

  12. Patient safety's missing link: using clinical expertise to recognize, respond to and reduce risks at a population level

    PubMed Central

    Hibbert, Peter D.; Healey, Frances; Lamont, Tara; Marela, William M.; Warner, Bruce; Runciman, William B.

    2016-01-01

    Introduction Although incident reporting systems are widespread in health care as a strategy to reduce harm to patients, the focus has been on reporting incidents rather than responding to them. Systems containing large numbers of incidents are uniquely placed to raise awareness of, and then characterize and respond to infrequent, but significant risks. The aim of this paper is to outline a framework for the surveillance of such risks, their systematic analysis, and for the development and dissemination of population-based preventive and corrective strategies using clinical and human factors expertise. Requirements for a population-level response The framework outlines four system requirements: to report incidents; to aggregate them; to support and conduct a risk surveillance, review and response process; and to disseminate recommendations. Personnel requirements include a non-hierarchical multidisciplinary team comprising clinicians and subject-matter and human factors experts to provide interpretation and high-level judgement from a range of perspectives. The risk surveillance, review and response process includes searching of large incident and other databases for how and why things have gone wrong, narrative analysis by clinical experts, consultation with the health care sector, and development and pilot testing of corrective strategies. Criteria for deciding which incidents require a population-level response are outlined. Discussion The incremental cost of a population-based response function is modest compared with the ‘reporting’ element. Combining clinical and human factors expertise and a systematic approach underpins the creation of credible risk identification processes and the development of preventive and corrective strategies. PMID:26573789

  13. Gene Therapy Studies in a Canine Model of X-Linked Severe Combined Immunodeficiency

    PubMed Central

    De Ravin, Suk See; Malech, Harry L.; Sorrentino, Brian P.; Burtner, Christopher; Kiem, Hans-Peter

    2015-01-01

    Abstract Since the occurrence of T cell leukemias in the original human γ-retroviral gene therapy trials for X-linked severe combined immunodeficiency (XSCID), considerable effort has been devoted to developing safer vectors. This review summarizes gene therapy studies performed in a canine model of XSCID to evaluate the efficacy of γ-retroviral, lentiviral, and foamy viral vectors for treating XSCID and a novel method of vector delivery. These studies demonstrate that durable T cell reconstitution and thymopoiesis with no evidence of any serious adverse events and, in contrast to the human XSCID patients, sustained marking in myeloid cells and B cells with reconstitution of normal humoral immune function can be achieved for up to 5 years without any pretreatment conditioning. The presence of sustained levels of gene-marked T cells, B cells, and more importantly myeloid cells for almost 5 years is highly suggestive of transduction of either multipotent hematopoietic stem cells or very primitive committed progenitors. PMID:25603151

  14. Gene Therapy Model of X-linked Severe Combined Immunodeficiency Using a Modified Foamy Virus Vector

    PubMed Central

    Horino, Satoshi; Uchiyama, Toru; So, Takanori; Nagashima, Hiroyuki; Sun, Shu-lan; Sato, Miki; Asao, Atsuko; Haji, Yoichi; Sasahara, Yoji; Candotti, Fabio; Tsuchiya, Shigeru; Kure, Shigeo; Sugamura, Kazuo; Ishii, Naoto

    2013-01-01

    X-linked severe combined immunodeficiency (SCID-X1) is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc) gene, and characterized by a complete defect of T and natural killer (NK) cells. Gene therapy for SCID-X1 using conventional retroviral (RV) vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV) vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO) mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1. PMID:23990961

  15. An affine continuum mechanical model for cross-linked F-actin networks with compliant linker proteins.

    PubMed

    Holzapfel, Gerhard A; Unterberger, Michael J; Ogden, Ray W

    2014-10-01

    Cross-linked actin networks are important building blocks of the cytoskeleton. In order to gain deeper insight into the interpretation of experimental data on actin networks, adequate models are required. In this paper we introduce an affine constitutive network model for cross-linked F-actin networks based on nonlinear continuum mechanics, and specialize it in order to reproduce the experimental behavior of in vitro reconstituted model networks. The model is based on the elastic properties of single filaments embedded in an isotropic matrix such that the overall properties of the composite are described by a free-energy function. In particular, we are able to obtain the experimentally determined shear and normal stress responses of cross-linked actin networks typically observed in rheometer tests. In the present study an extensive analysis is performed by applying the proposed model network to a simple shear deformation. The single filament model is then extended by incorporating the compliance of cross-linker proteins and further extended by including viscoelasticity. All that is needed for the finite element implementation is the constitutive model for the filaments, the linkers and the matrix, and the associated elasticity tensor in either the Lagrangian or Eulerian formulation. The model facilitates parameter studies of experimental setups such as micropipette aspiration experiments and we present such studies to illustrate the efficacy of this modeling approach. PMID:25043658

  16. Echistatin prevents posterior capsule opacification in diabetic rabbit model via integrin linked kinase signaling pathway

    PubMed Central

    Lin, Fengbin; Chen, Yingying; Liang, Hao; Tan, Shaojian

    2015-01-01

    Purpose: To investigate the effect of disintegrin echistatin on integrin linked kinase (ILK) and subsequent PI3-K/Akt and ERK1/2 signaling pathways in the posterior capsule opacification (PCO) model of diabetic rabbit. Methods: 56 rabbits were injected alloxan to model diabetic. Then they accepted lens extraction surgery and randomly and intraoperatively injected distilled water (control group; n = 28) or 10.0 mg·L-1 echistatin (echistatin-treated group; n = 28) into the anterior chamber. Each group was subdivided into ten days group (n = 14) and six weeks group (n = 14) respectively. The PCO severity was evaluated with a slit lamp microscope and light microscope for 10 days and 6 weeks postoperatively. The levels of ILK in the posterior capsule were determined by Q-PCR, Western blotting and Immunohistochemistry. Akt and ERK1/2 phosphorylation were analyzed by Western blotting. Results: 10 days and 6 weeks after surgery, the grades of PCO in the echistatin-treated group were lower than the control group. The lens epithelial cells (LECs) in the posterior capsule of echistatin-treated eyes had decreased degrees of proliferation and migration than the control group. And no significant side effects appeared after treated with echistatin. Echistatin could significantly reduce the expression of ILK in terms of both mRNA and protein levels. The phosphorylation levels of Akt and ERK1/2 were decreased in the echistatin-treated group compared with the control group. Conclusions: Echistatin could inhibit postoperative PCO occurrence and development in diabetic rabbit eyes, which may be related to down-regulation the expression of ILK and inhibition the PI3-K/Akt and ERK1/2 pathways. PMID:26823745

  17. What Is Engagement? Proactivity as the Missing Link in the HEXACO Model of Personality.

    PubMed

    de Vries, Reinout E; Wawoe, Kilian W; Holtrop, Djurre

    2016-04-01

    We tested the hypothesis that proactivity represents the engagement vector in the HEXACO model of personality. Questionnaire data were obtained in five studies, three of which consisted (mostly) of students: Study 1 (N = 188, Mage  = 20.0, 89.4% women), Study 3 (N = 315, Mage  = 20.4, 80.6% women), and Study 4 (N = 309 self-ratings, Mage  = 20.0, 78.3% women; N = 307 other-ratings, Mage  = 24.5, 62.2% women). Participants in the other two studies came from an ISO-certified representative community panel: Study 2 (N = 525, Mage  = 51.2, 52.0% women) and Study 5 (N = 736, Mage  = 42.2, 48.0% women). Proactive Personality and Proactivity were positively related to Extraversion, Conscientiousness, and Openness to Experience, but only weakly related or unrelated to Honesty-Humility, Emotionality, and Agreeableness, supporting the alignment of Proactive Personality/Proactivity with the hypothesized HEXACO engagement vector. Additionally, Proactivity explained incremental variance in self-rated job performance on top of the HEXACO facets that were most closely associated with Proactive Personality/Proactivity, that is, Social Boldness (an Extraversion facet), Diligence (a Conscientiousness facet), and Creativity (an Openness to Experience facet), but not in entrepreneurship and intrapreneurship. Proactivity is the missing engagement link in the HEXACO model of personality. The results are discussed in light of higher-order factors (e.g., general factor of personality and Alpha and Beta) of personality and bandwidth-fidelity controversies. PMID:25403271

  18. On linking an Earth system model to the equilibrium carbon representation of an economically optimizing land use model

    NASA Astrophysics Data System (ADS)

    Bond-Lamberty, B.; Calvin, K.; Jones, A. D.; Mao, J.; Patel, P.; Shi, X. Y.; Thomson, A.; Thornton, P.; Zhou, Y.

    2014-11-01

    assessment model, this work will help link these models in a robust and flexible framework capable of examining two-way interactions between human and Earth system processes.

  19. Personalized-Detailed Clinical Model for Data Interoperability Among Clinical Standards

    PubMed Central

    Khan, Wajahat Ali; Hussain, Maqbool; Afzal, Muhammad; Amin, Muhammad Bilal; Saleem, Muhammad Aamir

    2013-01-01

    Abstract Objective: Data interoperability among health information exchange (HIE) systems is a major concern for healthcare practitioners to enable provisioning of telemedicine-related services. Heterogeneity exists in these systems not only at the data level but also among different heterogeneous healthcare standards with which these are compliant. The relationship between healthcare organization data and different heterogeneous standards is necessary to achieve the goal of data level interoperability. We propose a personalized-detailed clinical model (P-DCM) approach for the generation of customized mappings that creates the necessary linkage between organization-conformed healthcare standards concepts and clinical model concepts to ensure data interoperability among HIE systems. Materials and Methods: We consider electronic health record (EHR) standards, openEHR, and HL7 CDA instances transformation using P-DCM. P-DCM concepts associated with openEHR and HL7 CDA help in transformation of instances among these standards. We investigated two datasets: (1) data of 100 diabetic patients, including 50 each of type 1 and type 2, from a local hospital in Korea and (2) data of a single Alzheimer's disease patient. P-DCMs were created for both scenarios, which provided the basis for deriving instances for HL7 CDA and openEHR standards. Results: For proof of concept, we present case studies of encounter information for type 2 diabetes mellitus patients and monitoring of daily routine activities of an Alzheimer's disease patient. These reflect P-DCM-based customized mappings generation with openEHR and HL7 CDA standards. Customized mappings are generated based on the relationship of P-DCM concepts with CDA and openEHR concepts. Conclusions: The objective of this work is to achieve semantic data interoperability among heterogeneous standards. This would lead to effective utilization of resources and allow timely information exchange among healthcare systems. PMID:23875730

  20. Linking clinic and home: a randomized, controlled clinical effectiveness trial of real-time, wireless blood pressure monitoring for older patients with kidney disease and hypertension

    PubMed Central

    Rifkin, Dena E.; Abdelmalek, Joseph A.; Miracle, Cynthia M.; Low, Chai; Barsotti, Ryan; Rios, Phil; Stepnowsky, Carl; Agha, Zia

    2014-01-01

    Objective Older adults with chronic kidney disease have a high rate of uncontrolled hypertension. Home monitoring of blood pressure (BP) is an integral part of management, but requires that patients bring records to clinic visits. Telemonitoring interventions, however, have not targeted older, less technologically-skilled populations. Methods Veterans with stage 3 or greater chronic kidney disease and uncontrolled hypertension were randomized to a novel telemonitoring device pairing a Bluetooth-enabled BP cuff with an Internet-enabled hub, which wirelessly transmitted readings (n= 28), or usual care (n= 15). Home recordings were reviewed weekly and telemonitoring participants were contacted if BP was above goal. The prespecified primary endpoints were improved data exchange and device acceptability. Secondary endpoint was BP change. Results Forty-three participants (average age 68 years, 75% white) completed the 6-month study. Average start-of-study BP was 147/78mmHg. Those in the intervention arm had a median of 29 (IQR 22, 53) transmitted BP readings per month, with 78% continuing to use the device regularly, whereas only 20% of those in the usual care group brought readings to in-person visits. The median number of telephone contacts triggered by the wireless monitoring was 2 (IQR 1, 4) per patient. Both groups had a significant improvement in systolic BP (P< 0.05, for both changes); systolic BP fell a median of 13 mmHg in monitored participants compared with 8.5mmHg in usual care participants (P for comparison 0.31). Conclusion This low-cost wireless monitoring strategy led to greater sharing of data between patients and clinic and produced a trend toward improvements in BP control over usual care at 6 months. PMID:23275313

  1. Full-vector multi-mode fiber modeling for short reach serdes links of 112Gbps and beyond.

    PubMed

    Lu, Yu-Chun; Wong, Henry; Tonietto, Davide; Zang, Da-Jun; Zhai, Su-Ping; Li, Liang

    2016-07-11

    A rigorous full-vector multi-mode fiber (MMF) model is proposed. It is believed to be the first comparative study of vector and scalar MMF model in terms of differential mode delay (DMD), mode power distribution (MPD), transfer functions as well as eye diagrams. It shows that the vector nature of fiber modes cannot be ignored even though the refractive index difference can be as small as 1%. A standard-compliant methodology for MMF characterization is introduced. The impact of fiber parameters on bandwidth is studied. The statistical transfer function model of OM3 and OM4 fiber is provided. These transfer functions can be applied to the MMF link modeling. Rigorous full-vector MMF model is an essential tool for research and development of MMF link transceivers and standard development of 112Gbps and beyond. PMID:27410880

  2. Wireless local area networking for linking a PC reporting system and PACS: clinical feasibility in emergency reporting.

    PubMed

    Yoshihiro, Akiko; Nakata, Norio; Harada, Junta; Tada, Shimpei

    2002-01-01

    Although local area networks (LANs) are commonplace in hospital-based radiology departments today, wireless LANs are still relatively unknown and untried. A linked wireless reporting system was developed to improve work throughput and efficiency. It allows radiologists, physicians, and technologists to review current radiology reports and images and instantly compare them with reports and images from previous examinations. This reporting system also facilitates creation of teaching files quickly, easily, and accurately. It consists of a Digital Imaging and Communications in Medicine 3.0-based picture archiving and communication system (PACS), a diagnostic report server, and portable laptop computers. The PACS interfaces with magnetic resonance imagers, computed tomographic scanners, and computed radiography equipment. The same kind of functionality is achievable with a wireless LAN as with a wired LAN, with comparable bandwidth but with less cabling infrastructure required. This wireless system is presently incorporated into the operations of the emergency and radiology departments, with future plans calling for applications in operating rooms, outpatient departments, all hospital wards, and intensive care units. No major problems have been encountered with the system, which is in constant use and appears to be quite successful. PMID:12006700

  3. ASC provides a potential link between depression and inflammatory disorders: A clinical study of depressed Iranian medical students.

    PubMed

    Momeni, Mohammad; Ghorban, Khodayar; Dadmanesh, Maryam; Khodadadi, Hassan; Bidaki, Reza; Kazemi Arababadi, Mohammad; Kennedy, Derek

    2016-05-01

    Background and aims AIM2 is a component of inflammasomes which can activate caspase-1 via an adaptor protein (ASC) after pathogen-associated molecular pattern (PAMP) or danger-associated molecular pattern (DAMP) recognition. Activation of caspase-1 is a trigger for the induction of IL-1 and IL-18 which are important pro-inflammatory cytokines. Furthermore, IL-1β, which can regulate inflammatory responses, has also been associated with depression. Previous studies revealed that patients suffering from depression may also have altered immune responses, but the mechanisms underlying this correlation are unclear. Thus, the aim of this study was to determine the mRNA levels of AIM2 and ASC in the peripheral blood mononuclear cells (PBMCs) isolated from Iranian medical students suffering from depression. Materials and methods The participants used for the study included 38 Iranian medical students diagnosed with depression and 43 non-depressed students as a control group. The mRNA levels of AIM2 and ASC were evaluated by quantitative real-time polymerase chain reaction (PCR) using β-actin as a housekeeping gene for the normalization of expression. Results The results showed that mRNA levels of AIM2 were similar in both groups. However, ASC levels were significantly increased in PBMCs isolated from individuals with elevated depressive symptoms when compared to non-depressed participants. Conclusions Based on the current results, it appears that ASC transcript expression may be a surrogate marker for depression and may represent a link between depression and the altered immune responses observed in these categories of individuals with elevated depressive symptoms. PMID:26750863

  4. A Lean Neck Mass Clinic Model: Adding Value to Care

    PubMed Central

    Tillman, Brittny N.; Glazer, Tiffany A.; Ray, Amrita; Brenner, J. Chad; Spector, Matthew E.

    2016-01-01

    Objective To demonstrate that ultrasound guided fine needle aspiration (USFNA) with on-site cytopathologic analysis eliminates unnecessary diagnostic testing, return visits, repeat procedures and optimizes quality of care. Study Design Retrospective Cohort Methods 61 new patients (28 female; 33 male; age range 19-85) were seen in our dedicated neck mass clinic over a one-year period. All patients underwent USFNA of masses located in neck levels I-VI (40), parotid gland (20), or parapharyngeal space (1). Each patient underwent two USFNA passes followed by on-site cytopathologic analysis with additional passes if required for diagnosis. Results Diagnosis was made in 93.4% (57) of patients allowing for counseling and treatment planning at the first visit. In order to obtain a diagnosis, more than half (57.4%, 35) of our patients required additional passes which implies that they would have required an additional visit without on-site cytopathologic analysis. Treatment included: Observation in 42.6% (26) of patients, surgery in 32.8 % (20) of patients and nonsurgical treatment (chemotherapy, radiation, other) in 24.6% (15) of patients. The average time from check-in to checkout including the clinic visit, biopsy and treatment counseling was 103 minutes, and the average round trip mileage traveled per patient was 127.6 miles. Conclusion The adult neck mass is a commonly encountered scenario in otolaryngology. For the patient this can be a stressful situation in which timely and accurate diagnosis is critical. A dedicated lean neck mass clinic model with USFNA and on-site cytopathologic analysis can be both an efficient part of one's practice and a valuable addition to patient care. PMID:26256915

  5. Testing the Causal Links between School Climate, School Violence, and School Academic Performance: A Cross-Lagged Panel Autoregressive Model

    ERIC Educational Resources Information Center

    Benbenishty, Rami; Astor, Ron Avi; Roziner, Ilan; Wrabel, Stephani L.

    2016-01-01

    The present study explores the causal link between school climate, school violence, and a school's general academic performance over time using a school-level, cross-lagged panel autoregressive modeling design. We hypothesized that reductions in school violence and climate improvement would lead to schools' overall improved academic performance.…

  6. The spatial pattern of transition (spot): linking pattern, process, and scale to state-and-transition models

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Field implementation of conceptual state-and-transition models will benefit from explicit representations of spatial patterns of vegetation, soils and topography and the hydrological/eolian processes that link them. Here, we introduce the concept "spatial pattern of transition” (SPOT) as a means to ...

  7. Advances in Linked Air Quality, Farm Management and Biogeochemistry Models to Address Bidirectional Ammonia Flux in CMAQ

    EPA Science Inventory

    Recent increases in anthropogenic inputs of nitrogen to air, land and water media pose a growing threat to human health and ecosystems. Modeling of air-surface N flux is one area in need of improvement. Implementation of a linked air quality and cropland management system is de...

  8. "Advances in Linked Air Quality, Farm Management and Biogeochemistry Models to Address Bidrectional Ammonia Flux in CMAQ"

    EPA Science Inventory

    Recent increases in anthropogenic inputs of nitrogen to air, land and water media pose a growing threat to human health and ecosystems. Modeling of air-surface N flux is one area in need of improvement. Implementation of a linked air quality and cropland management system is de...

  9. What Works Clearinghouse Quick Review: "A Model for Success: CART's Linked Learning Program Increases College Enrollment"

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2012

    2012-01-01

    The study, "A Model for Success: CART's Linked Learning Program Increases College Enrollment" examined whether students who enrolled in courses at a high school that combined academics and technical education had higher college enrollment rates than students who did not. The research described in this report does not meet What Works…

  10. A Dynamic Reading-Linking-to-Writing Model for Problem Solving within a Constructive Hypermedia Learning Environment.

    ERIC Educational Resources Information Center

    Yang, Shu Ching

    1996-01-01

    A study of five undergraduates in an introductory course on Greek culture identified novice problem-solving patterns and cognitive processes when using Perseus, a Greek culture database. Discusses the Reading-Linking-to-Writing Model developed to capture procedural and systemic processes used in problem-solving tasks with hypermedia applications.…

  11. Experimental verification of a model of a two-link flexible, lightweight manipulator. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Huggins, James David

    1988-01-01

    Experimental verification is presented for an assumed modes model of a large, two link, flexible manipulator design and constructed in the School of Mechanical Engineering at Georgia Institute of Technology. The structure was designed to have typical characteristics of a lightweight manipulator.

  12. Adverse outcome pathways linked to population models as a methodology for investigating effects of chemical stressors

    EPA Science Inventory

    In addressing the complexity and toxicity of chemical contaminants in Great Lakes ecosystems, we describe an approach to link chemically induced alterations in molecular and biochemical endpoints to adverse outcomes in whole organisms and populations. Analysis of population impac...

  13. Models to study NK cell biology and possible clinical application

    PubMed Central

    Zamora, Anthony E.; Grossenbacher, Steven K.; Aguilar, Ethan G.; Murphy, William J.

    2016-01-01

    Natural killer (NK) cells are large granular lymphocytes of the innate immune system, responsible for direct targeting and killing of both virally infected and transformed cells. NK cells rapidly recognize and respond to abnormal cells in the absence of prior sensitization due to their wide array of germline-encoded inhibitory and activating receptors, which differs from the receptor diversity found in B and T lymphocytes resulting from the use of recombination-activation gene (RAG) enzymes. Although NK cells have traditionally been described as natural killers that provide a first line of defense prior to the induction of adaptive immunity, a more complex view of NK cells is beginning to emerge indicating they may also function in various immunoregulatory roles and have the capacity to shape adaptive immune responses. With the growing appreciation for the diverse functions of NK cells and recent technological advancements that allow for a more in-depth understanding of NK cell biology, we can now begin to explore new ways to manipulate NK cells to increase their clinical utility. In this overview unit, we introduce the reader to various aspects of NK cell biology by reviewing topics ranging from NK cell diversity and function, mouse models and the roles of NK cells in health and disease, to potential clinical applications. PMID:26237009

  14. Models to Study NK Cell Biology and Possible Clinical Application.

    PubMed

    Zamora, Anthony E; Grossenbacher, Steven K; Aguilar, Ethan G; Murphy, William J

    2015-01-01

    Natural killer (NK) cells are large granular lymphocytes of the innate immune system, responsible for direct targeting and killing of both virally infected and transformed cells. NK cells rapidly recognize and respond to abnormal cells in the absence of prior sensitization due to their wide array of germline-encoded inhibitory and activating receptors, which differs from the receptor diversity found in B and T lymphocytes that is due to the use of recombination-activation gene (RAG) enzymes. Although NK cells have traditionally been described as natural killers that provide a first line of defense prior to the induction of adaptive immunity, a more complex view of NK cells is beginning to emerge, indicating they may also function in various immunoregulatory roles and have the capacity to shape adaptive immune responses. With the growing appreciation for the diverse functions of NK cells, and recent technological advancements that allow for a more in-depth understanding of NK cell biology, we can now begin to explore new ways to manipulate NK cells to increase their clinical utility. In this overview unit, we introduce the reader to various aspects of NK cell biology by reviewing topics ranging from NK cell diversity and function, mouse models, and the roles of NK cells in health and disease, to potential clinical applications. © 2015 by John Wiley & Sons, Inc. PMID:26237009

  15. Playing the role of weak clique property in link prediction: A friend recommendation model

    PubMed Central

    Ma, Chuang; Zhou, Tao; Zhang, Hai-Feng

    2016-01-01

    An important fact in studying link prediction is that the structural properties of networks have significant impacts on the performance of algorithms. Therefore, how to improve the performance of link prediction with the aid of structural properties of networks is an essential problem. By analyzing many real networks, we find a typical structural property: nodes are preferentially linked to the nodes with the weak clique structure (abbreviated as PWCS to simplify descriptions). Based on this PWCS phenomenon, we propose a local friend recommendation (FR) index to facilitate link prediction. Our experiments show that the performance of FR index is better than some famous local similarity indices, such as Common Neighbor (CN) index, Adamic-Adar (AA) index and Resource Allocation (RA) index. We then explain why PWCS can give rise to the better performance of FR index in link prediction. Finally, a mixed friend recommendation index (labelled MFR) is proposed by utilizing the PWCS phenomenon, which further improves the accuracy of link prediction. PMID:27439697

  16. Exogenous collagen cross-linking recovers tendon functional integrity in an experimental model of partial tear.

    PubMed

    Fessel, Gion; Wernli, Jeremy; Li, Yufei; Gerber, Christian; Snedeker, Jess G

    2012-06-01

    We investigated the hypothesis that exogenous collagen cross-linking can augment intact regions of tendon to mitigate mechanical propagation of partial tears. We first screened the low toxicity collagen cross-linkers genipin, methylglyoxal and ultra-violet (UV) light for their ability to augment tendon stiffness and failure load in rat tail tendon fascicles (RTTF). We then investigated cross-linking effects in load bearing equine superficial digital flexor tendons (SDFT). Data indicated that all three cross-linking agents augmented RTTF mechanical properties but reduced native viscoelasticity. In contrast to effects observed in fascicles, methylglyoxal treatment of SDFT detrimentally affected tendon mechanical integrity, and in the case of UV did not alter tendon mechanics. As in the RTTF experiments, genipin cross-linking of SDFT resulted in increased stiffness, higher failure loads and reduced viscoelasticity. Based on this result we assessed the efficacy of genipin in arresting tendon tear propagation in cyclic loading to failure. Genipin cross-linking secondary to a mid-substance biopsy-punch significantly reduced tissue strains, increased elastic modulus and increased resistance to fatigue failure. We conclude that genipin cross-linking of injured tendons holds potential for arresting tendon tear progression, and that implications of the treatment on matrix remodeling in living tendons should now be investigated. PMID:22102295

  17. Playing the role of weak clique property in link prediction: A friend recommendation model.

    PubMed

    Ma, Chuang; Zhou, Tao; Zhang, Hai-Feng

    2016-01-01

    An important fact in studying link prediction is that the structural properties of networks have significant impacts on the performance of algorithms. Therefore, how to improve the performance of link prediction with the aid of structural properties of networks is an essential problem. By analyzing many real networks, we find a typical structural property: nodes are preferentially linked to the nodes with the weak clique structure (abbreviated as PWCS to simplify descriptions). Based on this PWCS phenomenon, we propose a local friend recommendation (FR) index to facilitate link prediction. Our experiments show that the performance of FR index is better than some famous local similarity indices, such as Common Neighbor (CN) index, Adamic-Adar (AA) index and Resource Allocation (RA) index. We then explain why PWCS can give rise to the better performance of FR index in link prediction. Finally, a mixed friend recommendation index (labelled MFR) is proposed by utilizing the PWCS phenomenon, which further improves the accuracy of link prediction. PMID:27439697

  18. Rain rate intensity model for communication link design across the Indian region

    NASA Astrophysics Data System (ADS)

    Kilaru, Aravind; Kotamraju, Sarat K.; Avlonitis, Nicholas; Sri Kavya, K. Ch.

    2016-07-01

    A study on rain statistical parameters such as one minute rain intensity, possible number of minute occurrences with respective percentage of time in a year has been evaluated for the purpose of communication link design at Ka, Q, V bands as well as at Free-Space Optical communication links (FSO). To understand possible outage period of a communication links due to rainfall and to investigate rainfall pattern, Automatic Weather Station (AWS) rainfall data is analysed due its ample presence across India. The climates of the examined AWS regions vary from desert to cold climate, heavy rainfall to variable rainfall regions, cyclone effective regions, mountain and coastal regions. In this way a complete and unbiased picture of the rainfall statistics for Indian region is evaluated. The analysed AWS data gives insight into yearly accumulated rainfall, maximum hourly accumulated rainfall, mean hourly accumulated rainfall, number of rainy days and number of rainy hours from 668 AWS locations. Using probability density function the one minute rainfall measurements at KL University is integrated with AWS measurements for estimating number of rain occurrences in terms of one minute rain intensity for annual rainfall accumulated between 100 mm and 5000 mm to give an insight into possible one minute accumulation pattern in an hour for comprehensive analysis of rainfall influence on a communication link for design engineers. So that low availability communications links at higher frequencies can be transformed into a reliable and economically feasible communication links for implementing High Throughput Services (HTS).

  19. A Clinically Translatable Mouse Model for Chemotherapy-Related Fatigue

    PubMed Central

    Zombeck, Jonathan A; Fey, Edward G; Lyng, Gregory D; Sonis, Stephen T

    2013-01-01

    Fatigue is a debilitating and pervasive complication of cancer and cancer care. Clinical research investigating potential therapies is hindered by variability in patient histories, different metrics for measuring fatigue, and environmental factors that may affect fatigue. The purpose of this study was to establish an animal model of chemotherapy-related fatigue. Female HSD:ICR mice were treated with doxorubicin (2.5 mg/kg) or saline in 2 cycles (days 1 through 3 and 10 through 12). After treatment, mice were individually housed in cages equipped with running wheels. Open-field activity and motor coordination were examined after each cycle of treatment and after each week of wheel running. In a separate cohort, modafinil (50 mg/kg) was assessed as a potential treatment for fatigue. Doxorubicin administration resulted in greater than 30% less wheel running compared with that of saline controls. Activity differences were specific to wheel running: neither distance traveled in the open field nor motor coordination according to the rotarod test differed between groups. Compared with control values, RBC counts in the doxorubicin group were decreased on days 15 and 22 but recovered to control levels by study completion. Modafinil was efficacious in increasing wheel running in the doxorubicin group. The current results establish an animal model of chemotherapy-related fatigue that recapitulates the physical symptoms of cancer-related fatigue as manifested as decreased voluntary activity. This model is sensitive to pharmaceutical intervention and can be used to screen potential treatments for fatigue. PMID:24326224

  20. Adjuvants for Leishmania vaccines: from models to clinical application

    PubMed Central

    Raman, Vanitha S.; Duthie, Malcolm S.; Fox, Christopher B.; Matlashewski, Greg; Reed, Steven G.

    2012-01-01

    Two million new cases of leishmaniasis occur every year, with the cutaneous leishmaniasis (CL) presentation accounting for approximately two-thirds of all cases. Despite the high incidence rates and geographic expansion of the disease, CL remains a neglected tropical disease without effective intervention strategies. Efforts to address this deficit have given rise to the experimental murine model of CL. By virtue of its simplicity and pliability, the CL model has been used to provide substantial information regarding cellular immunity, as well as in the discovery and evaluation of various vaccine adjuvants. The CL model has facilitated in vivo studies of the mechanism of action of many adjuvants, including the TLR4 agonist monophosphoryl lipid A, the TLR7/8 agonist imiquimod, the TLR9 agonist CpG, adenoviral vectors, and the immunostimulatory complexes. Together, these studies have helped to unveil the requirement for certain types of immune responses at specific stages of CL disease and provide a basis to aid the design of effective second-generation vaccines for human CL. This review focuses on adjuvants that have been tested in experimental CL, outlining how they have helped advance our understanding of the disease and ultimately, how they have performed when applied within clinical trials against human CL. PMID:22701453

  1. Quantitative Raman characterization of cross-linked collagen thin films as a model system for diagnosing early osteoarthritis

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Durney, Krista M.; Fomovsky, Gregory; Ateshian, Gerard A.; Vukelic, Sinisa

    2016-03-01

    The onset of osteoarthritis (OA)in articular cartilage is characterized by degradation of extracellular matrix (ECM). Specifically, breakage of cross-links between collagen fibrils in the articular cartilage leads to loss of structural integrity of the bulk tissue. Since there are no broadly accepted, non-invasive, label-free tools for diagnosing OA at its early stage, Raman spectroscopyis therefore proposed in this work as a novel, non-destructive diagnostic tool. In this study, collagen thin films were employed to act as a simplified model system of the cartilage collagen extracellular matrix. Cross-link formation was controlled via exposure to glutaraldehyde (GA), by varying exposure time and concentration levels, and Raman spectral information was collected to quantitatively characterize the cross-link assignments imparted to the collagen thin films during treatment. A novel, quantitative method was developed to analyze the Raman signal obtained from collagen thin films. Segments of Raman signal were decomposed and modeled as the sum of individual bands, providing an optimization function for subsequent curve fitting against experimental findings. Relative changes in the concentration of the GA-induced pyridinium cross-links were extracted from the model, as a function of the exposure to GA. Spatially resolved characterization enabled construction of spectral maps of the collagen thin films, which provided detailed information about the variation of cross-link formation at various locations on the specimen. Results showed that Raman spectral data correlate with glutaraldehyde treatment and therefore may be used as a proxy by which to measure loss of collagen cross-links in vivo. This study proposes a promising system of identifying onset of OA and may enable early intervention treatments that may serve to slow or prevent osteoarthritis progression.

  2. Linking e-health records, patient-reported symptoms and environmental exposure data to characterise and model COPD exacerbations: protocol for the COPE study

    PubMed Central

    Moore, Elizabeth; Chatzidiakou, Lia; Jones, Roderic L; Smeeth, Liam; Beevers, Sean; Kelly, Frank J; Barratt, Benjamin

    2016-01-01

    Introduction Relationships between exacerbations of chronic obstructive pulmonary disease (COPD) and environmental factors such as temperature, humidity and air pollution are not well characterised, due in part to oversimplification in the assignment of exposure estimates to individuals and populations. New developments in miniature environmental sensors mean that patients can now carry a personal air quality monitor for long periods of time as they go about their daily lives. This creates the potential for capturing a direct link between individual activities, environmental exposures and the health of patients with COPD. Direct associations then have the potential to be scaled up to population levels