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Sample records for model linking clinical

  1. Validity of Quinpirole Sensitization Rat Model of OCD: Linking Evidence from Animal and Clinical Studies

    PubMed Central

    Stuchlik, Ales; Radostová, Dominika; Hatalova, Hana; Vales, Karel; Nekovarova, Tereza; Koprivova, Jana; Svoboda, Jan; Horacek, Jiri

    2016-01-01

    Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with 1–3% prevalence. OCD is characterized by recurrent thoughts (obsessions) and repetitive behaviors (compulsions). The pathophysiology of OCD remains unclear, stressing the importance of pre-clinical studies. The aim of this article is to critically review a proposed animal model of OCD that is characterized by the induction of compulsive checking and behavioral sensitization to the D2/D3 dopamine agonist quinpirole. Changes in this model have been reported at the level of brain structures, neurotransmitter systems and other neurophysiological aspects. In this review, we consider these alterations in relation to the clinical manifestations in OCD, with the aim to discuss and evaluate axes of validity of this model. Our analysis shows that some axes of validity of quinpirole sensitization model (QSM) are strongly supported by clinical findings, such as behavioral phenomenology or roles of brain structures. Evidence on predictive validity is contradictory and ambiguous. It is concluded that this model is useful in the context of searching for the underlying pathophysiological basis of the disorder because of the relatively strong biological similarities with OCD. PMID:27833539

  2. 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

  3. A domain analysis model for eIRB systems: addressing the weak link in clinical research informatics.

    PubMed

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

    2014-12-01

    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.

  4. School-Based and School-Linked Clinics. Update 1991.

    ERIC Educational Resources Information Center

    Waszak, Cynthia; Neidell, Shara

    Since 1986, the Center for Population Options (CPO)/Support Center for School-Based Clinics (SBCs) has conducted an annual survey. Over time the SBC has become a prototype for other adolescent health service models. Perhaps the oldest is the school-linked clinic (SLC), a free-standing adolescent health clinic. Located away from the school campus,…

  5. Modelling health care processes for eliciting user requirements: a way to link a quality paradigm and clinical information system design.

    PubMed

    Staccini, P; Joubert, M; Quaranta, J F; Fieschi, D; Fieschi, M

    2001-12-01

    Healthcare institutions are looking at ways to increase their efficiency by reducing costs while providing care services with a high level of safety. Thus, hospital information systems have to support quality improvement objectives. The elicitation of the requirements has to meet users' needs in relation to both the quality (efficacy, safety) and the monitoring of all health care activities (traceability). Information analysts need methods to conceptualise clinical information systems that provide actors with individual benefits and guide behavioural changes. A methodology is proposed to elicit and structure users' requirements using a process-oriented analysis, and it is applied to the blood transfusion process. An object-oriented data model of a process has been defined in order to organise the data dictionary. Although some aspects of activity, such as 'where', 'what else', and 'why' are poorly represented by the data model alone, this method of requirement elicitation fits the dynamic of data input for the process to be traced. A hierarchical representation of hospital activities has to be found for the processes to be interrelated, and for their characteristics to be shared, in order to avoid data redundancy and to fit the gathering of data with the provision of care.

  6. X linked mental retardation: a clinical guide.

    PubMed

    Raymond, F L

    2006-03-01

    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.

  7. Clinical Science-linking basic science to disease mechanisms.

    PubMed

    Touyz, Rhian M

    2017-04-01

    For more than 50 years, Clinical Science has been at the interface linking basic science to disease mechanisms. Here, Rhian Touyz, the Editor-in-Chief, describes the journal, its aims and scope, and recent developments.

  8. An Integrated Approach to Falls Prevention: A Model for Linking Clinical and Community Interventions through the Massachusetts Prevention and Wellness Trust Fund

    PubMed Central

    Coe, Laura J.; St. John, Julie Ann; Hariprasad, Santhi; Shankar, Kalpana N.; MacCulloch, Patricia A.; Bettano, Amy L.; Zotter, Jean

    2017-01-01

    Older adult falls continue to be a public health priority across the United States—Massachusetts (MA) being no exception. The MA Prevention and Wellness Trust Fund (PWTF) program within the MA Department of Public Health aims to reduce the physical and economic burdens of chronic health conditions by linking evidence-based clinical care with community intervention programs. The PWTF partnerships that focused on older adult falls prevention integrated the Centers for Disease Control and Prevention’s Stopping Elderly Accidents, Death and Injuries toolkit into clinical settings. Partnerships also offer referrals for home safety assessments, Tai Chi, and Matter of Balance programs. This paper describes the PWTF program implementation process involving 49 MA organizations, while highlighting the successes achieved and lessons learned. With the unprecedented expansion of the U.S. Medicare beneficiary population, and the escalating incidence of falls, widespread adoption of effective prevention strategies will become increasingly important for both public health and for controlling healthcare costs. The lessons learned from this PWTF initiative offer insights and recommendations for future falls prevention program development and implementation. PMID:28321393

  9. X-linked creatine transporter deficiency: clinical aspects and pathophysiology.

    PubMed

    van de Kamp, Jiddeke M; Mancini, Grazia M; Salomons, Gajja S

    2014-09-01

    Creatine transporter deficiency was discovered in 2001 as an X-linked cause of intellectual disability characterized by cerebral creatine deficiency. This review describes the current knowledge regarding creatine metabolism, the creatine transporter and the clinical aspects of creatine transporter deficiency. The condition mainly affects the brain while other creatine requiring organs, such as the muscles, are relatively spared. Recent studies have provided strong evidence that creatine synthesis also occurs in the brain, leading to the intriguing question of why cerebral creatine is deficient in creatine transporter deficiency. The possible mechanisms explaining the cerebral creatine deficiency are discussed. The creatine transporter knockout mouse provides a good model to study the disease. Over the past years several treatment options have been explored but no treatment has been proven effective. Understanding the pathogenesis of creatine transporter deficiency is of paramount importance in the development of an effective treatment.

  10. 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.

  11. Optical Performance Models for FDDI Links

    NASA Astrophysics Data System (ADS)

    Kimball, Robert M.

    1990-01-01

    A loss budget model to predict optical performance of Fiber Distributed Data Interface (FDDI) type networks in the premises distribution environment has been developed. This model tailors existing statistical loss budget models to the FDDI standard. It is expected that as FDDI becomes popular, fiber based distribution systems will become common. When designing a fiber distribution system it is important to understand the constraints placed on link performance by the cable plant. To determine these constraints, the model is examined numerically using a large range of initial conditions. The total link length is used as the dependent variable. This set of initial conditions corresponds to an ensemble of possible link configurations. These link configurations are studied in the context of the premises distribution environment. The model is extended to include the use of optical bypass switches. Laboratory measurement data is presented to verify the accuracy of the bypass switch model. The extended model, including the bypass switch, is examined numerically for a similar set of initial conditions. These constraints are applied to the use of bypass switches in wiring closets, between floors, and at the work location. Distance limitations are determined for FDDI links utilizing optical bypass switches.

  12. Clinical evidence for Japanese population based on prospective studies--linking clinical trials and clinical practice.

    PubMed

    Ogawa, Hisao; Kojima, Sunao

    2009-10-01

    "Evidence-based medicine (EBM)" implies effective and high quality practice for patients based on well-grounded medical science. The success of clinical trials in Japan is essential to build original evidence specific for Japanese patients. Based on this concept, we have performed several large-scale clinical trials to provide EBM, including the Japanese Antiplatelets Myocardial Infarction Study [JAMIS; clinical improvement in acute myocardial infarction (AMI) patients with antiplatelet therapy], the Japanese beta-Blockers and Calcium Antagonists Myocardial Infarction (JBCMI; comparison of the effects of beta-blockers and calcium antagonists on cardiovascular events in post-AMI patients), a multicenter study for aggressive lipid-lowering strategy by HMG-CoA reductase inhibitors in patients with AMI (MUSASHI; effects of statin therapy on cardiovascular events in patients with AMI), and the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD trial; efficacy of low-dose aspirin therapy for primary prevention of atherosclerotic events in type 2 diabetic patients). The results of these prospective studies were directly linked with clinical practice. We have acquired the know-how of large-scale clinical trials; an important point is to have passion for "buildup evidence specific for the Japanese" and to recruit subjects for enrollment after explaining the significance of "clinical trials for the Japanese".

  13. Clinical fracture of cross-linked UHMWPE acetabular liners.

    PubMed

    Furmanski, Jevan; Anderson, Martin; Bal, Sonny; Greenwald, A Seth; Halley, David; Penenberg, Brad; Ries, Michael; Pruitt, Lisa

    2009-10-01

    Highly cross-linked ultrahigh molecular weight polyethylene (UHMWPE) is increasingly used as a bearing material in total hip replacements. Cross-linking of UHMWPE has been shown to increase wear resistance but decrease its fracture resistance. We analyzed the clinical fracture failure of four cross-linked UHMWPE total hip replacement components of four different designs via microscopic observation of the fracture surfaces, and found that in all cases fractures initiated at stress concentrations in an unsupported region of the component (termed the elevated rim). Finite element analyses (FEA) of each individual implant design were then conducted. Results from this analysis demonstrated that the predicted magnitude and orientation of maximum principal stress due to mechanical loading of the elevated rim was sufficient to propagate initiated fatigue cracks in each case. FEA also predicted that cracks may arrest after some amount of growth due to a steep stress gradient near the initiation site. Further, while anatomical positioning of the implant and material properties affect the risk of fracture, we examined whether these failures are strongly related to the notched elevated rim design feature that is common to the four failed cases presented here. We believe that cross-linked UHMWPE remains an excellent bearing material for total hip replacements but that designs employing this material should mitigate stress concentrations or other design features that increase the risk of fracture.

  14. 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.

  15. A clinical and educational telemedicine link between Bulgaria and Greece.

    PubMed

    Anogianakis, George; Ilonidis, George; Anogeianaki, Antonia; Milliaras, Spyros; Klisarova, Anelia; Temelkov, Temel; Vlachakis-Milliaras, Emmanuel

    2003-01-01

    During its transition to a market economy, Bulgaria benefited from foreign aid provided by Greece. One of the projects was the clinical and educational telemedicine link between the Medical University of Varna in Bulgaria and the Faculty of Medicine of Aristotle University of Thessaloniki in Greece. This began in 1997. In terms of the educational activities, the Bulgarian side of the network supports: an electronic classroom equipped with personal workstations, multimedia projectors and videoconference facilities; electronic design and publishing activities; Web hosting and mail server activities; and satellite communications. Communications are via ISDN. The main clinical experience has been remote consultations in immunology. This experience (admittedly limited) demonstrates that telemedicine can be used to provide assistance to remote colleagues. In addition, the use of telemedicine can greatly improve the quality of care available to travellers and migrant workers in cases where the patient cannot communicate with the attending physician because of a language barrier.

  16. 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.

  17. Nephrolithiasis and hypertension: possible links and clinical implications.

    PubMed

    Cupisti, Adamasco; D'Alessandro, Claudia; Samoni, Sara; Meola, Mario; Egidi, Maria Francesca

    2014-10-01

    A definite epidemiological association exists between kidney stone disease and arterial hypertension, but the pathophysiological mechanisms are still not fully understood. Hypercalciuria or inflammation and oxidative stress have been proposed as possible links. However, there is more convincing evidence that the association between nephrolithiasis and hypertension may be considered as a part of the association between kidney stone disease, metabolic syndrome and atherosclerosis. From a clinical point of view, this association represents a crucial aspect of the clinical management of patients affected by kidney stone disease. In order to implement early prevention and treatment of cardiovascular and/or renal damage physicians should be encouraged to assess individual cardiovascular risk factors in any adult with kidney stones. Consequently, patients with kidney stones need a comprehensive approach rather than an intervention limited to the urinary tract and focused on stone resolution and recurrence prevention. It is time to view kidney stone disease as a systemic disorder, associated to or predictive of hypertension, chronic kidney disease, bone and cardiovascular damage. All these conditions negatively affect patient prognosis. This multi-systemic approach could increase the clinical impact of the kidney stone clinic.

  18. X linked adrenoleukodystrophy: clinical presentation, diagnosis, and therapy

    PubMed Central

    van Geel, B. M; Assies, J.; Wanders, R.; Barth, P.

    1997-01-01

    X linked adrenoleukodystrophy (X-ALD) is an inherited disorder of peroxisomal metabolism, biochemically characterised by accumulation of saturated very long chain fatty acids. Accumulation of these fatty acids is associated with cerebral demyelination, peripheral nerve abnormalities, and adrenocortical and testicular insufficiency. The lowest estimated birth incidence is one per 100 000. At least six phenotypes can be distinguished, of which the two most frequent are childhood cerebral ALD and adrenomyeloneuropathy. The X-ALD gene has been identified, but thus far no relation between genotype and phenotype has been found. Diagnosis is relatively easy and can be confirmed reliably, and prenatal testing is possible in affected families. Several therapeutic options, some with promising perspectives, are available. Neurologists and other physicians seem not to be familiar with the many facets of X-ALD. In this review, the clinical presentation, the relative frequencies of the different phenotypes, and the diagnostic and therapeutic options are presented.

 PMID:9221959

  19. A clinical and educational telemedicine link between Bulgaria and Greece.

    PubMed

    Anogianakis, George; Ilonidis, George; Anogeianaki, Antonia; Milliaras, Spyros; Klisarova, Anelia; Temelkov, Temel; Vlachakis-Milliaras, Emmanuel

    2004-01-01

    During its transition to a free economy, Bulgaria benefited from foreign aid provided by Greece. One of the projects was the clinical and educational telemedicine link between the Medical University of Varna in Bulgaria and the Faculty of Medicine of Aristotle University of Thessaloniki in Greece. This began in 1997. In terms of the educational activities, the Bulgarian side of the network supports (a) electronic design and publishing activities, (b) web hosting and mail server activities and (c) satellite communications. In addition it supports an electronic classroom equipped with personal workstations, multimedia projectors and videoconference facilities. Communications are via the ISDN network. In terms of its telemedicine activities, the network provides remote medical assistance to "language handicapped" travellers and to migrant workers in both countries. The main clinical experience is remote consultations in immunology. This admittedly limited experience demonstrates that telemedicine can be used to provide assistance to remote colleagues. In cases where the patient cannot communicate with the attending physician, the use of telemedicine can greatly improve the quality of care available to travellers and migrant workers.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. X-linked dystonia parkinsonism: clinical phenotype, genetics and therapeutics.

    PubMed

    Rosales, Raymond L

    2010-10-01

    The clinical phenotype of X-Linked Dystonia Parkinsonism (XDP) is typically one that involves a Filipino adult male whose ancestry is mostly traced in the Philippine island of Panay. Dystonia usually starts focally in the lower limbs or oromandibular regions, then spreads to become generalized eventually. Parkinsonism sets in later into the disease and usually in combination with dystonia. /DYT3/ and /TAF1/ are the two genes associated with XDP. An SVA retrotransposon insertion in an intron of /TAF1/ may reduce neuron-specific expression of the /TAF1/ isoform in the caudate nucleus, and subsequently interfere with the transcription of many neuronal genes. Polypharmacy with oral benzodiazepines, anticholinergic agents and muscle relaxants leaves much to be desired in terms of efficacy. The medications to date that may appear beneficial, especially in disabling dystonias, are zolpidem, muscle afferent block with lidocaine-ethanol and botulinum toxin type A. Despite the few cases undergoing deep brain stimulation, this functional surgery has shown the greatest promise in XDP. An illustrative case of XDP in a family depicts the variable course of illness, including a bout of "status dystonicus," challenges in therapy, reckoning with the social impact of the disease, and eventual patient demise. Indeed, there remains some gaps in understanding some phenomenological, genetic and treatment aspects of XDP, the areas upon which future research directions may be worthwhile.

  5. Precision and negative predictive value of links between ClinicalTrials.gov and PubMed.

    PubMed

    Huser, Vojtech; Cimino, James J

    2012-01-01

    One of the goals of translational science is to shorten the time from discovery to clinical use. Clinical trial registries were established to increase transparency in completed and ongoing clinical trials, and they support linking trials with resulting publications. We set out to investigate precision and negative predictive value (NPV) of links between ClinicalTrials.gov (CT.gov) and PubMed. CT.gov has been established to increase transparency in clinical trials and the link to PubMed is crucial for supporting a number of important functions, including ascertaining publication bias. We drew a random sample of trials downloaded from CT.gov and performed manual review of retrieved publications. We characterize two types of links between trials and publications (NCT-link originating from MEDLINE and PMID-link originating from CT.gov).The link precision is different based on type (NCT-link: 100%; PMID-link: 63% to 96%). In trials with no linked publication, we were able to find publications 44% of the time (NPV=56%) by searching PubMed. This low NPV shows that there are potentially numerous publications that should have been formally linked with the trials. Our results indicate that existing trial registry and publisher policies may not be fully enforced. We suggest some automated methods for improving link quality.

  6. 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

  7. Optogenetically inspired deep brain stimulation: linking basic with clinical research.

    PubMed

    Lüscher, Christian; Pollak, Pierre

    2016-01-01

    In the last decade, optogenetics has revolutionised the neurosciences. The technique, which allows for cell-type specific excitation and inhibition of neurons in the brain of freely moving rodents, has been used to tighten the links of causality between neural activity and behaviour. Optogenetics is also enabling an unprecedented characterisation of circuits and their dysfunction in a number of brain diseases, above all those conditions that are not caused by neurodegeneration. Notable progress has been made in addiction, depression and obsessive-compulsive disorders, as well as other anxiety disorders. By extension, the technique has also been used to propose blueprints for innovative rational treatment of these diseases. The goal is to design manipulations that disrupt pathological circuit function or restore normal activity. This can be achieved by targeting specific projections in order to apply specific stimulation protocols validated by ex-vivo analysis of the mechanisms underlying the dysfunction. In a number of cases, specific forms of pathological synaptic plasticity have been implicated. For example, addictive drugs via strong increase of dopamine trigger a myriad of alterations of glutamate and γ-aminobutyric acid transmission, also called drug-evoked synaptic plasticity. This opens the way to the design of optogenetic reversal protocols, which might restore normal transmission with the hope to abolish the pathological behaviour. Several proof of principle studies for this approach have recently been published. However, for many reasons, optogenetics will not be translatable to human applications in the near future. Here, we argue that an intermediate step is novel deep brain stimulation (DBS) protocols that emulate successful optogenetic approaches in animal models. We provide a roadmap for a translational path to rational, optogenetically inspired DBS protocols to refine existing approaches and expand to novel indications.

  8. 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…

  9. 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.

  10. 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...

  11. Design and modelling of a link monitoring mechanism for the Common Data Link (CDL)

    NASA Astrophysics Data System (ADS)

    Eichelberger, John W., III

    1994-09-01

    The Common Data Link (CDL) is a full duplex, point-to-point microwave communications system used in imagery and signals intelligence collection systems. It provides a link between two remote Local Area Networks (LAN's) aboard collection and surface platforms. In a hostile environment, there is an overwhelming need to dynamically monitor the link and thus, limit the impact of jamming. This work describes steps taken to design, model, and evaluate a link monitoring system suitable for the CDL. The monitoring system is based on features and monitoring constructs of the Link Control Protocol (LCP) in the Point-to-Point Protocol (PPP) suite. The CDL model is based on a system of two remote Fiber Distributed Data Interface (FDDI) LAN's. In particular, the policies and mechanisms associated with monitoring are described in detail. An implementation of the required mechanisms using the OPNET network engineering tool is described. Performance data related to monitoring parameters is reported. Finally, integration of the FDDI-CDL model with the OPNET Internet model is described.

  12. Shuttle/TDRSS modelling and link simulation study

    NASA Technical Reports Server (NTRS)

    Braun, W. R.; Mckenzie, T. M.; Biederman, L.; Lindsey, W. C.

    1979-01-01

    A Shuttle/TDRSS S-band and Ku-band link simulation package called LinCsim was developed for the evaluation of link performance for specific Shuttle signal designs. The link models were described in detail and the transmitter distortion parameters or user constraints were carefully defined. The overall link degradation (excluding hardware degradations) relative to an ideal BPSK channel were given for various sets of user constraint values. The performance sensitivity to each individual user constraint was then illustrated. The effect of excessive Spacelab clock jitter on the return link BER performance was also investigated as was the problem of subcarrier recovery for the K-band Shuttle return link signal.

  13. 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.

  14. 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.

  15. Manipulators with flexible links: A simple model and experiments

    NASA Technical Reports Server (NTRS)

    Shimoyama, Isao; Oppenheim, Irving J.

    1989-01-01

    A simple dynamic model proposed for flexible links is briefly reviewed and experimental control results are presented for different flexible systems. A simple dynamic model is useful for rapid prototyping of manipulators and their control systems, for possible application to manipulator design decisions, and for real time computation as might be applied in model based or feedforward control. Such a model is proposed, with the further advantage that clear physical arguments and explanations can be associated with its simplifying features and with its resulting analytical properties. The model is mathematically equivalent to Rayleigh's method. Taking the example of planar bending, the approach originates in its choice of two amplitude variables, typically chosen as the link end rotations referenced to the chord (or the tangent) motion of the link. This particular choice is key in establishing the advantageous features of the model, and it was used to support the series of experiments reported.

  16. Characterizing nanoparticle interactions: Linking models to experiments

    SciTech Connect

    Ramakrishnan, S.; Zukoski, C. F.

    2000-07-15

    Self-assembly of nanoparticles involves manipulating particle interactions such that attractions are on the order of the average thermal energy in the system. If the self-assembly is to result in an ordered packing, an understanding of their phase behavior is necessary. Here we test the ability of simple pair potentials to characterize the interactions and phase behavior of silico tungstic acid (STA), a 1.2 nm particle. The strength of interaction is controlled by dispersing STA in different background salt concentrations. The experimental variables used in characterizing the interactions are the osmotic compressibility (d{pi}/d{rho}), the second virial coefficient (B{sub 2}), relative solution viscosity ({eta}/{eta}{sub c}), and the solubility ({rho}{sigma}{sup 3}){sub sat}. Various techniques are then developed to extract the parameters of square well, the adhesive hard sphere (AHS), and the Yukawa pair potentials that best describe the experimental data. The AHS model describes the solution thermodynamic behavior only where the system is weakly attractive but, as would be expected, fails when long range repulsions or nonmonotonic pair potentials become important. Model free representations are presented which offer the opportunity to extract pair potential parameters. (c) 2000 American Institute of Physics.

  17. PIPELINEs: Creating Comparable Clinical Knowledge Efficiently by Linking Trial Platforms

    PubMed Central

    Shrier, AA; Antonijevic, Z; Beckman, RA; Campbell, RK; Chen, C; Flaherty, KT; Loewy, J; Lacombe, D; Madhavan, S; Selker, HP; Esserman, LJ

    2016-01-01

    Adaptive, seamless, multisponsor, multitherapy clinical trial designs executed as large scale platforms, could create superior evidence more efficiently than single‐sponsor, single‐drug trials. These trial PIPELINEs also could diminish barriers to trial participation, increase the representation of real‐world populations, and create systematic evidence development for learning throughout a therapeutic life cycle, to continually refine its use. Comparable evidence could arise from multiarm design, shared comparator arms, and standardized endpoints—aiding sponsors in demonstrating the distinct value of their innovative medicines; facilitating providers and patients in selecting the most appropriate treatments; assisting regulators in efficacy and safety determinations; helping payers make coverage and reimbursement decisions; and spurring scientists with translational insights. Reduced trial times and costs could enable more indications, reduced development cycle times, and improved system financial sustainability. Challenges to overcome range from statistical to operational to collaborative governance and data exchange. PMID:27643536

  18. Targeting cancer epigenetics: Linking basic biology to clinical medicine.

    PubMed

    Shinjo, Keiko; Kondo, Yutaka

    2015-12-01

    Recent studies provide compelling evidence that epigenetic dysregulation is involved in almost every step of tumor development and progression. Differences in tumor behavior, which ultimately reflects clinical outcome, can be explained by variations in gene expression patterns generated by epigenetic mechanisms, such as DNA methylation. Therefore, epigenetic abnormalities are considered potential biomarkers and therapeutic targets. DNA methylation is stable at certain specific loci in cancer cells and predominantly reflects the characteristic clinicopathological features. Thus, it is an ideal biomarker for cancer screening, classification and prognostic purposes. Epigenetic treatment for cancers is based on the pharmacologic targeting of various core transcriptional programs that sustains cancer cell identity. Therefore, targeting aberrant epigenetic modifiers may be effective for multiple processes compared with using a selective inhibitor of aberrant single signaling pathway. This review provides an overview of the epigenetic alterations in human cancers and discusses about novel therapeutic strategies targeting epigenetic alterations.

  19. The Clinical Evidence Linking Helicobacter pylori to Gastric Cancer.

    PubMed

    Moss, Steven F

    2017-03-01

    Gastric cancer has long been recognized to be accompanied and preceded by chronic gastritis, lasting decades. Arguably, the most important development in our understanding of gastric cancer pathogenesis over the past 50 years has been the realization that, for most cases of gastric cancer, Helicobacter pylori is the cause of the underlying gastritis. Gastritis can promote gastric carcinogenesis, typically via the Correa cascade of atrophic gastritis, intestinal metaplasia, and dysplasia. Nested case-control studies have shown that H pylori infection increases the risk of gastric cancer significantly, both of the intestinal and diffuse subtypes, and that H pylori is responsible for approximately 90% of the world's burden of noncardia gastric cancer. Based largely on randomized studies in high gastric cancer prevalence regions in East Asia, it appears that primary and tertiary intervention to eradicate H pylori can halve the risk of gastric cancer. Some public health authorities now are starting screening and treatment programs to reduce the burden of gastric cancer in these high-risk areas. However, there is currently much less enthusiasm for initiating similar attempts in the United States. This is partially because gastric cancer is a relatively less frequent cause of cancer in the United States, and in addition there are concerns about theoretical downsides of H pylori eradication, principally because of the consistent inverse relationship noted between H pylori and esophageal adenocarcinoma. Nevertheless, establishing a link between chronic H pylori infection and gastric cancer has led to novel insights into cancer biology, the gastrointestinal microbiome, and on individual and population-based gastric cancer prevention strategies.

  20. A novel fibre-ensemble level constitutive model for exogenous cross-linked collagenous tissues

    PubMed Central

    Sacks, Michael S.; Wognum, Silvia

    2016-01-01

    Exogenous cross-linking of soft collagenous tissues is a common method for biomaterial development and medical therapies. To enable improved applications through computational methods, physically realistic constitutive models are required. Yet, despite decades of research, development and clinical use, no such model exists. In this study, we develop the first rigorous full structural model (i.e. explicitly incorporating various features of the collagen fibre architecture) for exogenously cross-linked soft tissues. This was made possible, in-part, with the use of native to cross-linked matched experimental datasets and an extension to the collagenous structural constitutive model so that the uncross-linked collagen fibre responses could be mapped to the cross-linked configuration. This allowed us to separate the effects of cross-linking from kinematic changes induced in the cross-linking process, which in turn allowed the non-fibrous tissue matrix component and the interaction effects to be identified. It was determined that the matrix could be modelled as an isotropic material using a modified Yeoh model. The most novel findings of this study were that: (i) the effective collagen fibre modulus was unaffected by cross-linking and (ii) fibre-ensemble interactions played a large role in stress development, often dominating the total tissue response (depending on the stress component and loading path considered). An important utility of the present model is its ability to separate the effects of exogenous cross-linking on the fibres from changes due to the matrix. Applications of this approach include the utilization in the design of novel chemical treatments to produce specific mechanical responses and the study of fatigue damage in bioprosthetic heart valve biomaterials. PMID:26855761

  1. A novel fibre-ensemble level constitutive model for exogenous cross-linked collagenous tissues.

    PubMed

    Sacks, Michael S; Zhang, Will; Wognum, Silvia

    2016-02-06

    Exogenous cross-linking of soft collagenous tissues is a common method for biomaterial development and medical therapies. To enable improved applications through computational methods, physically realistic constitutive models are required. Yet, despite decades of research, development and clinical use, no such model exists. In this study, we develop the first rigorous full structural model (i.e. explicitly incorporating various features of the collagen fibre architecture) for exogenously cross-linked soft tissues. This was made possible, in-part, with the use of native to cross-linked matched experimental datasets and an extension to the collagenous structural constitutive model so that the uncross-linked collagen fibre responses could be mapped to the cross-linked configuration. This allowed us to separate the effects of cross-linking from kinematic changes induced in the cross-linking process, which in turn allowed the non-fibrous tissue matrix component and the interaction effects to be identified. It was determined that the matrix could be modelled as an isotropic material using a modified Yeoh model. The most novel findings of this study were that: (i) the effective collagen fibre modulus was unaffected by cross-linking and (ii) fibre-ensemble interactions played a large role in stress development, often dominating the total tissue response (depending on the stress component and loading path considered). An important utility of the present model is its ability to separate the effects of exogenous cross-linking on the fibres from changes due to the matrix. Applications of this approach include the utilization in the design of novel chemical treatments to produce specific mechanical responses and the study of fatigue damage in bioprosthetic heart valve biomaterials.

  2. 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

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

    PubMed

    Hoffman, Matthew; Lubell, Mark; Hillis, Vicken

    2014-09-09

    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.

  4. 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.

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

    PubMed Central

    Hoffman, Matthew; Lubell, Mark; Hillis, Vicken

    2014-01-01

    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

  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. Model selection for athermal cross-linked fiber networks.

    PubMed

    Shahsavari, A; Picu, R C

    2012-07-01

    Athermal random fiber networks are usually modeled by representing each fiber as a truss, a Euler-Bernoulli or a Timoshenko beam, and, in the case of cross-linked networks, each cross-link as a pinned, rotating, or welded joint. In this work we study the effect of these various modeling options on the dependence of the overall network stiffness on system parameters. We conclude that Timoshenko beams can be used for the entire range of density and beam stiffness parameters, while the Euler-Bernoulli model can be used only at relatively low network densities. In the high density-high bending stiffness range, strain energy is stored predominantly in the axial and shear deformation modes, while in the other extreme range of parameters, the energy is stored in the bending mode. The effect of the model size on the network stiffness is also discussed.

  8. 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."

  9. A mathematical model of N-linked glycoform biosynthesis.

    PubMed

    Umaña, P; Bailey, J E

    1997-09-20

    Metabolic engineering of N-linked oligosaccharide biosynthesis to produce novel glycoforms or glycoform distributions of a recombinant glycoprotein can potentially lead to an improved therapeutic performance of the glycoprotein product. Effective engineering of this pathway to maximize the fractions of beneficial glycoforms within the glycoform population of a target glycoprotein can be aided by a mathematical model of the N-linked glycosylation process. A mathematical model is presented here, whose main function is to calculate the expected qualitative trends in the N-linked oligosaccharide distribution resulting from changes in the levels of one or more enzymes involved in the network of enzyme-catalyzed reactions that accomplish N-linked oligosaccharide biosynthesis. It consists of mass balances for 33 different oligosaccharide species N-linked to a specified protein that is being transported through the different compartments of the Golgi complex. Values of the model parameters describing Chinese hamster ovary (CHO) cells were estimated from literature information. A basal set of kinetic parameters for the enzyme-catalyzed reactions acting on free oligosaccharide substrates was also obtained from the literature. The solution of the system for this basal set of parameters gave a glycoform distribution consisting mainly of complex-galactosylated oligosaccharides distributed in structures with different numbers of antennae in a fashion similar to that observed for various recombinant proteins produced in CHO cells. Other simulations indicate that changes in the oligosaccharide distribution could easily result from alteration in glycoprotein productivity within the range currently attainable in industry. The overexpression of N-acetylglucosaminyltransferase III in CHO cells was simulated under different conditions to test the main function of the model. These simulations allow a comparison of different strategies, such as simultaneous overexpression of several

  10. Model updating in flexible-link multibody systems

    NASA Astrophysics Data System (ADS)

    Belotti, R.; Caneva, G.; Palomba, I.; Richiedei, D.; Trevisani, A.

    2016-09-01

    The dynamic response of flexible-link multibody systems (FLMSs) can be predicted through nonlinear models based on finite elements, to describe the coupling between rigid- body and elastic behaviour. Their accuracy should be as high as possible to synthesize controllers and observers. Model updating based on experimental measurements is hence necessary. By taking advantage of the experimental modal analysis, this work proposes a model updating procedure for FLMSs and applies it experimentally to a planar robot. Indeed, several peculiarities of the model of FLMS should be carefully tackled. On the one hand, nonlinear models of a FLMS should be linearized about static equilibrium configurations. On the other, the experimental mode shapes should be corrected to be consistent with the elastic displacements represented in the model, which are defined with respect to a fictitious moving reference (the equivalent rigid link system). Then, since rotational degrees of freedom are also represented in the model, interpolation of the experimental data should be performed to match the model displacement vector. Model updating has been finally cast as an optimization problem in the presence of bounds on the feasible values, by also adopting methods to improve the numerical conditioning and to compute meaningful updated inertial and elastic parameters.

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

    PubMed

    Hulbert, S W; Jiang, Y-H

    2016-05-03

    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.

  13. Mutual information model for link prediction in heterogeneous complex networks

    PubMed Central

    Shakibian, Hadi; Moghadam Charkari, Nasrollah

    2017-01-01

    Recently, a number of meta-path based similarity indices like PathSim, HeteSim, and random walk have been proposed for link prediction in heterogeneous complex networks. However, these indices suffer from two major drawbacks. Firstly, they are primarily dependent on the connectivity degrees of node pairs without considering the further information provided by the given meta-path. Secondly, most of them are required to use a single and usually symmetric meta-path in advance. Hence, employing a set of different meta-paths is not straightforward. To tackle with these problems, we propose a mutual information model for link prediction in heterogeneous complex networks. The proposed model, called as Meta-path based Mutual Information Index (MMI), introduces meta-path based link entropy to estimate the link likelihood and could be carried on a set of available meta-paths. This estimation measures the amount of information through the paths instead of measuring the amount of connectivity between the node pairs. The experimental results on a Bibliography network show that the MMI obtains high prediction accuracy compared with other popular similarity indices. PMID:28344326

  14. 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.

  15. Clinical liaison nurse model in a community hospital: a unique academic-practice partnership that strengthens clinical nursing education.

    PubMed

    Lovecchio, Catherine P; DiMattio, Mary Jane K; Hudacek, Sharon

    2012-11-01

    The necessity to help baccalaureate nursing students transition to clinical practice in a health care environment governed by change has compelled nurse educators to investigate alternative clinical instruction models that nurture academic-practice partnerships and facilitate student clinical learning. This article describes an academic-practice partnership in a community hospital using the Clinical Liaison Nurse (CLN) model as a link between students and clinical faculty and reports results of a quasi-experimental study that compared perceptions of the clinical learning environment between students participating in the CLN model (experimental group) and those in a traditional, instructor-led clinical model (control group). Students assigned to the CLN model had statistically significantly higher individualization, satisfaction, and task orientation scores on the Clinical Learning Environment Inventory. The findings provide evidence that academic-practice partnerships can be successful in community hospital settings and enhance students' perceptions in the clinical learning environment.

  16. Clinical consequences of urea cycle enzyme deficiencies and potential links to arginine and nitric oxide metabolism.

    PubMed

    Scaglia, Fernando; Brunetti-Pierri, Nicola; Kleppe, Soledad; Marini, Juan; Carter, Susan; Garlick, Peter; Jahoor, Farook; O'Brien, William; Lee, Brendan

    2004-10-01

    Urea cycle disorders (UCD) are human conditions caused by the dysregulation of nitrogen transfer from ammonia nitrogen into urea. The biochemistry and the genetics of these disorders were well elucidated. Earlier diagnosis and improved treatments led to an emerging, longer-lived cohort of patients. The natural history of some of these disorders began to point to pathophysiological processes that may be unrelated to the primary cause of acute morbidity and mortality, i.e., hyperammonemia. Carbamyl phosphate synthetase I single nucleotide polymorphisms may be associated with altered vascular resistance that becomes clinically relevant when specific environmental stressors are present. Patients with argininosuccinic aciduria due to a deficiency of argininosuccinic acid lyase are uniquely prone to chronic hepatitis, potentially leading to cirrhosis. Moreover, our recent observations suggest that there may be an increased prevalence of essential hypertension. In contrast, hyperargininemia found in patients with arginase 1 deficiency is associated with pyramidal tract findings and spasticity, without significant hyperammonemia. An intriguing potential pathophysiological link is the dysregulation of intracellular arginine availability and its potential effect on nitric oxide (NO) metabolism. By combining detailed natural history studies with the development of tissue-specific null mouse models for urea cycle enzymes and measurement of nitrogen flux through the cycle to urea and NO in UCD patients, we may begin to dissect the contribution of different sources of arginine to NO production and the consequences on both rare genetic and common multifactorial diseases.

  17. 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.

  18. A FAULT MODEL FOR ONTOLOGY MAPPING, ALIGNMENT, AND LINKING SYSTEMS

    PubMed Central

    JOHNSON, HELEN L.; COHEN, K. BRETONNEL; HUNTER, LAWRENCE

    2008-01-01

    There has been much work devoted to the mapping, alignment, and linking of ontologies (MALO), but little has been published about how to evaluate systems that do this. A fault model for conducting fine-grained evaluations of MALO systems is proposed, and its application to the system described in Johnson et al. [15] is illustrated. Two judges categorized errors according to the model, and inter-judge agreement was calculated by error category. Overall inter-judge agreement was 98% after dispute resolution, suggesting that the model is consistently applicable. The results of applying the model to the system described in [15] reveal the reason for a puzzling set of results in that paper, and also suggest a number of avenues and techniques for improving the state of the art in MALO, including the development of biomedical domain specific language processing tools, filtering of high frequency matching results, and word sense disambiguation. PMID:17990495

  19. 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.

  20. Curing critical links in oscillator networks as power flow models

    NASA Astrophysics Data System (ADS)

    Rohden, Martin; Witthaut, Dirk; Timme, Marc; Meyer-Ortmanns, Hildegard

    2017-01-01

    Modern societies crucially depend on the robust supply with electric energy so that blackouts of power grids can have far reaching consequences. Typically, large scale blackouts take place after a cascade of failures: the failure of a single infrastructure component, such as a critical transmission line, results in several subsequent failures that spread across large parts of the network. Improving the robustness of a network to prevent such secondary failures is thus key for assuring a reliable power supply. In this article we analyze the nonlocal rerouting of power flows after transmission line failures for a simplified AC power grid model and compare different strategies to improve network robustness. We identify critical links in the grid and compute alternative pathways to quantify the grid’s redundant capacity and to find bottlenecks along the pathways. Different strategies are developed and tested to increase transmission capacities to restore stability with respect to transmission line failures. We show that local and nonlocal strategies typically perform alike: one can equally well cure critical links by providing backup capacities locally or by extending the capacities of bottleneck links at remote locations.

  1. 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

  2. A mathematical model of N-linked glycosylation.

    PubMed

    Krambeck, Frederick J; Betenbaugh, Michael J

    2005-12-20

    Metabolic engineering of N-linked oligosaccharide biosynthesis to produce novel glycoforms or glycoform distributions of a recombinant glycoprotein can potentially lead to an improved therapeutic performance of the glycoprotein product. A mathematical model for the initial stages of this process, up to the first galactosylation of an oligosaccharide, was previously developed by Umana and Bailey (1997) (UB1997). Building on this work, an extended model is developed to include further galactosylation, fucosylation, extension of antennae by N-acetyllactosamine repeats, and sialylation. This allows many more structural features to be predicted. A number of simplifying assumptions are also relaxed to incorporate more variables for the control of glycoforms. The full model generates 7565 oligosaccharide structures in a network of 22,871 reactions. Methods for solving the model for the complete product distribution and adjusting the parameters to match experimental data are also developed. A basal set of kinetic parameters for the enzyme-catalyzed reactions acting on free oligosaccharide substrates is obtained from the previous model and existing literature. Enzyme activities are adjusted to match experimental glycoform distributions for Chinese Hamster Ovary (CHO). The model is then used to predict the effect of increasing expression of a target glycoprotein on the product glycoform distribution and evaluate appropriate metabolic engineering strategies to return the glycoform profile to its original distribution pattern. This model may find significant utility in the future to predict glycosylation patterns and direct glycoengineering projects to optimize glycoform distributions.

  3. 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…

  4. 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

  5. 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.

  6. 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

  7. 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)

  8. 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

  9. Molecular genetic and clinical evaluation of three Chinese families with X-linked ocular albinism.

    PubMed

    Zou, Xuan; Li, Hui; Yang, Lizhu; Sun, Zixi; Yuan, Zhisheng; Li, Huajin; Sui, Ruifang

    2017-02-17

    X-linked ocular albinism (OA1) is an X-linked inherited disease characterized by hypopigmentation of the fundus and nystagmus. Our study performed mutation analysis of the G protein-coupled receptor 143 gene (GPR143) and assessed the clinical characteristics of OA1 in three Chinese families. Three novel mutations, c.333_360+14del42insCTT, c.276G>A (p.W92X), and c.793C>T (p.R265X), were identified in GPR143 by PCR followed by Sanger sequencing in these families. All affected individuals presented with nystagmus, photophobia, poor visual acuity, foveal hypoplasia and varying degrees of hypopigmentation of the fundus. The fundus of female carriers showed pigmented streaks alternating with hypopigmented streaks. These results allowed us to expand the spectrum of mutations in GPR143 and phenotypes associated with ocular albinism.

  10. Molecular genetic and clinical evaluation of three Chinese families with X-linked ocular albinism

    PubMed Central

    Zou, Xuan; Li, Hui; Yang, Lizhu; Sun, Zixi; Yuan, Zhisheng; Li, Huajin; Sui, Ruifang

    2017-01-01

    X-linked ocular albinism (OA1) is an X-linked inherited disease characterized by hypopigmentation of the fundus and nystagmus. Our study performed mutation analysis of the G protein-coupled receptor 143 gene (GPR143) and assessed the clinical characteristics of OA1 in three Chinese families. Three novel mutations, c.333_360+14del42insCTT, c.276G>A (p.W92X), and c.793C>T (p.R265X), were identified in GPR143 by PCR followed by Sanger sequencing in these families. All affected individuals presented with nystagmus, photophobia, poor visual acuity, foveal hypoplasia and varying degrees of hypopigmentation of the fundus. The fundus of female carriers showed pigmented streaks alternating with hypopigmented streaks. These results allowed us to expand the spectrum of mutations in GPR143 and phenotypes associated with ocular albinism. PMID:28211458

  11. 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

  12. Linking electronic medical records to large-scale simulation models: can we put rapid learning on turbo?

    PubMed

    Eddy, David M

    2007-01-01

    One method for rapid learning is to use data from electronic medical records (EMRs) to help build and validate large-scale, physiology-based simulation models. These models can than be used to help answer questions that cannot be addressed directly from the EMR data. Their potential uses include analyses of physiological pathways; simulation and design of clinical trials; and analyses of clinical management tools such as guidelines, performance measures, priority setting, and cost-effectiveness. Linking the models to EMR data also facilitates tailoring analyses to specific populations. The models' power and accuracy can be improved by linkage to comprehensive, person-specific, longitudinal data from EMRs.

  13. 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.

  14. Linking GIS and storm water modeling for emergency risk assessment

    SciTech Connect

    Newkirk, R.T.

    1995-12-31

    Many emergencies involve the deposition of chemical contaminants on land either as a direct event or as a secondary byproduct. GIS can be useful in estimating the initial deposition area. Chemical product attribute data bases can be accessed to determine the degree that the contaminants might be transportable in a water medium. An important issue is to estimate the potential impact of the deposition on surface and subsurface water flows. This particularly important since millions of people rely on subsurface ground water as their main source of potable water. Thus, a modeling system is needed by planners and emergency managers to assess the potential for short and long term risks to communities due to storm water transport of deposited contaminants. GIS itself cannot provide the complete analysis. A prototype system to assist in estimating the flows of contaminants related to an emergency has been developed by linking an Arc/Info database, Digital Terrain Model, and SWMM the storm water management modeling system. This system also has important planning applications in assessing alternative land development plans for their impact on ground water recharge and management of storm water.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Linking Geomagentic Data to Dynamo Models via Variational Data Assimilation

    NASA Astrophysics Data System (ADS)

    Dimitrova, L. L.; Egbert, G. D.; Kuang, W.; Jiang, W.; Tangborn, A.

    2011-12-01

    The increased resolution and accuracy of both the geomagnetic field models and observations in recent years has resulted in increased efforts to link theory to data via data assimilation (DA) techniques similar to those previously developed in the atmospheric and oceanic communities . If applied to the geomagnetic field, DA has potential to improve both models and observations: geodynamics models can be assessed and improved based on observational constraints to better understand the physics of the core dynamics; the improved models can then be used to (1)constrain "hidden" components of the state of the geodynamo that are not directly observable, (2)more accurately forecast the geomagnetic fields and (3) hindcast and improve past geomagnetic field models. DA methods can be broadly divided into two approaches: sequential and variational. In sequential DA, observations are combined with the current model state to produce a new state estimate, which is then used as the initial state for the next model forecast. As such, sequential DA leads to discontinuous model state, and observations can influence only the future model state. Variational DA differs from sequential DA in that the goal is a global adjustment of the model trajectory to fit simultaneously all the data. Thus in the variational approach, observations at a later time could influence the model solution at an earlier time. Both sequential and variational DA has been applied to simplified dynamic models (e.g.Sun et al. [2007], Fournier et al. [2007]), and sequential DA has been applied to full dynamo models (e.g. Liu et al. [2007], Kuang et al. [2008]). However, since the best data is from recent years, sequential schemes can't readily project this data backwards in time. We present an update to our ongoing efforts to implement modern variational DA methods (based on theory of representers, potentially allowing for weak constraint DA) for the Modular Scalable Self-consistent Three-dimensional (Mo

  20. X-linked intellectual disability type Nascimento is a clinically distinct, probably underdiagnosed entity

    PubMed Central

    2013-01-01

    X-linked intellectual disability type Nascimento (MIM #300860), caused by mutations in UBE2A (MIM *312180), is characterized by craniofacial dysmorphism (synophrys, prominent supraorbital ridges, deep-set, almond-shaped eyes, depressed nasal bridge, prominent columella, hypoplastic alae nasi, and macrostomia), skin anomalies (hirsutism, myxedematous appearance, onychodystrophy), micropenis, moderate to severe intellectual disability (ID), motor delay, impaired/absent speech, and seizures. Hitherto only five familial point mutations and four different deletions including UBE2A have been reported in the literature. We present eight additional individuals from five families with UBE2A associated ID - three males from a consanguineous family, in whom we identified a small deletion of only 7.1 kb encompassing the first three exons of UBE2A, two related males with a UBE2A missense mutation in exon 4, a patient with a de novo nonsense mutation in exon 6, and two sporadic males with larger deletions including UBE2A. All affected male individuals share the typical clinical phenotype, all carrier females are unaffected and presented with a completely skewed X inactivation in blood. We conclude that 1.) X-linked intellectual disability type Nascimento is a clinically very distinct entity that might be underdiagnosed to date. 2.) So far, all females carrying a familial UBE2A aberration have a completely skewed X inactivation and are clinically unaffected. This should be taken in to account when counselling those families. 3.) The coverage of an array should be checked carefully prior to analysis since not all arrays have a sufficient resolution at specific loci, or alternative quantitative methods should be applied not to miss small deletions. PMID:24053514

  1. 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.

  2. FSO and radio link attenuation: meteorological models verified by experiment

    NASA Astrophysics Data System (ADS)

    Brazda, Vladimir; Fiser, Ondrej; Svoboda, Jaroslav

    2011-09-01

    Institute of Atmospheric Physics of Czech Academy measures atmospheric attenuation on 60 m experimental FSO link on 830 and 1550 nm for more than three years. Visibility sensors and two 3D sonic anemometers on both transmitting and receiving site, rain gauge and many sensors enabling the refractivity index computation are spaced along the optical link. Meteorological visibility, wind turbulent energy, sonic temperature, structure index and rain rate are correlated with measured attenuation. FSO link attenuation dependence on the above mentioned parameters is analyzed. The paper shows also basic statistical behavior of the long-term FSO signal level and also the simulation of hybrid link techniques.

  3. 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

  4. Alternative Methodologies in Research Literature Review: Links between Clinical Work and MFT Effectiveness.

    ERIC Educational Resources Information Center

    Addison, Shelia M.; Sandberg, Jonathan G.; Corby, Joy; Robila, Mihaela; Platt, Jason J.

    2002-01-01

    Reviews 15 years of clinical research in three family therapy (FT) journals that provide evidence for the effectiveness of marriage and family therapy. Considers designs that are being utilized in reports on the effectiveness of various models of FT. Makes connections between research and the everyday work of clinicians to make the work more…

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. A proposed model of psychodynamic psychotherapy linked to Erik Erikson's eight stages of psychosocial development.

    PubMed

    Knight, Zelda Gillian

    2017-01-25

    Just as Freud used stages of psychosexual development to ground his model of psychoanalysis, it is possible to do the same with Erik Erikson's stages of development with regards to a model of psychodynamic psychotherapy. This paper proposes an eight-stage model of psychodynamic psychotherapy linked to Erik Erikson's eight stages of psychosocial development. Various suggestions are offered. One such suggestion is that as each of Erikson's developmental stages is triggered by a crisis, in therapy it is triggered by the client's search. The resolution of the search often leads to the development of another search, which implies that the therapy process comprises a series of searches. This idea of a series of searches and resolutions leads to the understanding that identity is developmental and therapy is a space in which a new sense of identity may emerge. The notion of hope is linked to Erikson's stage of Basic Trust and the proposed model of therapy views hope and trust as essential for the therapy process. Two clinical vignettes are offered to illustrate these ideas.

  11. 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.

  12. Genetic analysis and clinical features of X-linked retinoschisis in Chinese patients

    PubMed Central

    Hu, Qin-rui; Huang, Lv-zhen; Chen, Xiao-li; Xia, Hui-ka; Li, Tian-qi; Li, Xiao-xin

    2017-01-01

    Many mutations in the retinoschisis (RS1) gene have been identified, but there are limited clinical data relating to the different genotypes. This study investigated the genotype, clinical phenotype and therapies for X-linked juvenile retinoschisis (XLRS) patients in China to evaluate the effects of gene mutations and therapies on the prognosis of the disease. Thirty patients were recruited in the study. Genetic examination identified 8 novel RS1 gene mutations. Twenty-four patients were identified as missense mutation, which was the most common gene mutation in XLRS patients. Amino acids 102 and 209 were the most common mutation areas, accounting for a total 35.7% of all patients. Mutations affecting amino acid 102 were associated with poor results on the flash electroretinogram (ERG). Sixteen patients had various complications. Anti-vascular endothelial growth factor (VEGF) drugs were given to four patients with hemorrhage or other complications, and serious adverse events did not occur. Our outcome demonstrates that missense mutation was the leading cause of XLRS and more than half of the patients with this missense had various complications. Anti-VEGF drugs may be an effective and safe way to prevent deterioration of XLRS with certain complications. There is wide genotypic and phenotypic variability in Chinese patients with XLRS. PMID:28272453

  13. 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.

  14. 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

  15. A Typology for Modeling Processes in Clinical Guidelines and Protocols

    NASA Astrophysics Data System (ADS)

    Tu, Samson W.; Musen, Mark A.

    We analyzed the graphical representations that are used by various guideline-modeling methods to express process information embodied in clinical guidelines and protocols. From this analysis, we distilled four modeling formalisms and the processes they typically model: (1) flowcharts for capturing problem-solving processes, (2) disease-state maps that link decision points in managing patient problems over time, (3) plans that specify sequences of activities that contribute toward a goal, (4) workflow specifications that model care processes in an organization. We characterized the four approaches and showed that each captures some aspect of what a guideline may specify. We believe that a general guideline-modeling system must provide explicit representation for each type of process.

  16. A physiologically based pharmacokinetic model linking plasma protein binding interactions with drug disposition.

    PubMed

    Buur, J L; Baynes, R E; Smith, G W; Riviere, J E

    2009-04-01

    Combination drug therapy increases the chance for an adverse drug reactions due to drug-drug interactions. Altered disposition for sulfamethazine (SMZ) when concurrently administered with flunixin meglumine (FLU) in swine could lead to increased tissue residues. There is a need for a pharmacokinetic modeling technique that can predict the consequences of possible drug interactions. A physiologically based pharmacokinetic model was developed that links plasma protein binding interactions to drug disposition for SMZ and FLU in swine. The model predicted a sustained decrease in total drug and a temporary increase in free drug concentration. An in vivo study confirmed the presence of a drug interaction. Neither the model nor the in vivo study revealed clinically significant changes that alter tissue disposition. This novel linkage approach has use in the prediction of the clinical impact of plasma protein binding interactions. Ultimately it could be used in the design of dosing regimens and in the protection of the food supply through prediction and minimization of tissue residues.

  17. Investigating the productivity model for clinical nurses.

    PubMed

    Dehghan Nayeri, Nahid; Hooshmand Bahabadi, Abbas; Kazemnejad, Anoshirvan

    2014-01-01

    One of the main objectives of quantitative researches is assessment of models developed by qualitative studies. Models validation through their testing implies that the designed model is representative of the existed facts. Hence, this study was conducted to assess the clinical nurses' productivity model presented for Iranian nurses' productivity. The sample of the study consisted of 360 nurses of Tehran University of Medical Sciences. The research tool was a questionnaire for measuring the components of clinical nurses' productivity. After completing all steps of instrument psychometric and getting answers from the participants, the factors introduced in the questionnaire were named and then Lisrel Path Analysis tests were performed to analyze the components of the model. The results of the model test revealed there is an internal relationship among different components of the model. Regression Analysis showed that each increasing unit in components of the model was to be added to central variable of productivity model -human resource. Model components altogether explained 20 % of clinical nurses' productivity variance. This study found that the important component of productivity is human resources that are reciprocally related to other components of the model. Therefore, it can be stated that the managers can promote the productivity by using efficient strategies to correct human resource patterns.

  18. Clinical HBSE Concentration: A Transactional Model.

    ERIC Educational Resources Information Center

    Farmer, Rosemary L.

    1999-01-01

    Outlines a transactional model for addressing the underrepresentation of key areas in advanced clinical courses in human behavior in the social environment (HBSE), looking at social work's understanding of the biological and spiritual aspects of human beings. The transactional model is distinguished from other reductionist or interactionist models…

  19. 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.

  20. Clinical governance in Scotland: an educational model.

    PubMed Central

    Lough, Murray; Kelly, Diane; Taylor, Mike; Snadden, David; Patterson, Bill; McNamara, Iain; Murray, Stuart

    2002-01-01

    The concepts underpinning clinical governance are similar throughout the United Kingdom but models for its implementation will differ widely. This model aims to enable practices to identify areas for further learning and development against specific outcomes. Criteria sets and standards are suggested and a governance plan is used to allow practices to prioritise their objectives. Resourcing will always be a major issue and such a model should be fully evaluated. PMID:11942453

  1. Infertility etiologies are genetically and clinically linked with other diseases in single meta-diseases.

    PubMed

    Tarín, Juan J; García-Pérez, Miguel A; Hamatani, Toshio; Cano, Antonio

    2015-04-15

    linked with other diseases in single meta-diseases. This finding opens new insights for clinicians and reproductive biologists to treat infertility problems using a phenomic approach instead of considering infertility as an isolated and exclusive disease of the reproductive system/hypothalamic-pituitary-gonadal axis. In agreement with a previous validation analysis of the utility of DiseaseConnect web server, the present study does not show a univocal correspondence between common gene expression and clinical comorbid relationship. Further work is needed to untangle the potential genetic, epigenetic and phenotypic relationships that may be present among different infertility etiologies, morbid conditions and physical/cognitive traits.

  2. 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.

  3. 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...

  4. Phenotypic characterization of X-linked retinoschisis: Clinical, electroretinography, and optical coherence tomography variables

    PubMed Central

    Neriyanuri, Srividya; Dhandayuthapani, Sudha; Arunachalam, Jayamuruga Pandian; Raman, Rajiv

    2016-01-01

    Aims: To study the phenotypic characteristics of X-linked retinoschisis (XLRS) and report the clinical, electroretinogram (ERG), and optical coherence tomography (OCT) variables in Indian eyes. Design: A retrospective study. Materials and Methods: Medical records of 21 patients with retinoschisis who were genetically confirmed to have RS1 mutation were reviewed. The phenotype characterization included the age of onset, best-corrected visual acuity, refractive error, fundus findings, OCT, and ERG. Statistical Analysis Used: Data from both the eyes were used for analysis. A P < 0.05 was set as statistical significance. Data were not normally distributed (P < 0.05, Shapiro wilk); hence, nonparametric tests were used for statistical analysis. Results: All were males whose mean age of presentation was 9 years. Visual acuity was moderately impaired (median 0.6 logMAR, interquartile range: 0.47, 1) in these eyes with a hyperopic refractive error of median +1.75 Ds (interquartile range: +0.50 Ds, +4.25 Ds). About 54.7% of the eyes had both foveal and peripheral schisis, isolated foveal schisis was seen in 28.5% of the eyes, and schisis with retinal detachment was seen in 16.6% of the eyes. The inner nuclear layer was found to be commonly involved in the schisis, followed by outer nuclear and plexiform layers as evident on OCT. On ERG, a- and b-wave amplitudes were significantly reduced in eyes with foveal and peripheral schisis when compared to the eyes with only foveal schisis (P < 0.05). Conclusions: XLRS has phenotypic heterogeneity as evident on OCT, ERG, and clinical findings. PMID:27609164

  5. Mutations in the gene for X-linked adrenoleukodystrophy in patients with different clinical phenotypes

    SciTech Connect

    Braun, A.; Ambach, H.; Kammerer, S.; Rolinski, B.; Roscher, A.; Rabl, W.; Stoeckler, S.; Gaertner, J.; Zierz, S.

    1995-04-01

    Recently, the gene for the most common peroxisomal disorder, X-linked adrenoleukodystrophy (X-ALD), has been described encoding a peroxisomal membrane transporter protein. We analyzed the entire protein-coding sequence of this gene by reverse-transcription PCR, SSCP, and DNA sequencing in five patients with different clinical expressions were cerebral childhood ALD, adrenomyecloneuropathy (AMN), and {open_quotes}Addison disease only{close_quotes} (AD) phenotype. In the three patients exhibiting the classical picture of severe childhood ALD we identified in the 5{prime} portion of the X-ALD gene a 38-bp deletion that causes a frameshift mutation, a 3-bp deletion leading to a deletion of an amino acid in the ATP-binding domain of the ALD protein, and a missense mutation. In the patient with the clinical phenotype of AMN, a nonsense mutation in codon 212, along with a second site mutation at codon 178, was observed. Analysis of the patient with the ADO phenotype revealed a further missense mutation at a highly conserved position in the ALDP/PMP70 comparison. The disruptive nature of two mutations (i.e., the frameshift and the nonsense mutation) in patients with biochemically proved childhood ALD and AMN further strongly supports the hypothesis that alterations in this gene play a crucial role in the pathogenesis of X-ALD. Since the current biochemical techniques for X-ALD carrier detection in affected families lack sufficient reliability, our procedure described for systematic mutation scanning is also capable of improving genetic counseling and prenatal diagnosis. 19 refs., 6 figs., 3 tabs.

  6. 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

  7. Links between respiratory syncytial virus bronchiolitis and childhood asthma: clinical and research approaches.

    PubMed

    Openshaw, Peter J; Dean, Gillian S; Culley, Fiona J

    2003-02-01

    This review examines the relationship between severe pulmonary disease caused by respiratory syncytial virus (RSV) infection in infancy and later development of asthma or reactive airway disease (RAD). RSV infection accounts for 70% or greater of all cases of infantile bronchiolitis and has been linked to subsequent asthma or RAD, either directly or through a shared common predisposition. Several studies suggest that RSV bronchiolitis is an important factor in the development of asthma and possibly atopy, although the association is lost by the age of 13 years. The mechanism is as yet unclear, but murine models of RSV disease have identified many plausible causal explanations. Further study is necessary to determine the relative roles of RSV infection and genetic predisposition in explaining the association between RSV infection and asthma/RAD.

  8. Clinical safety and wear resistance of the phospholipid polymer-grafted highly cross-linked polyethylene liner.

    PubMed

    Moro, Toru; Takatori, Yoshio; Tanaka, Sakae; Ishihara, Kazuhiko; Oda, Hiromi; Kim, Yoon Taek; Umeyama, Takashige; Fukatani, Eisei; Ito, Hideya; Kyomoto, Masayuki; Oshima, Hirofumi; Tanaka, Takeyuki; Kawaguchi, Hiroshi; Nakamura, Kozo

    2016-11-03

    To reduce the production of wear particles and subsequent aseptic loosening, we created a human articular cartilage-mimicked surface for a highly cross-linked polyethylene liner, whose surface grafted layer consisted of a biocompatible phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine). Although our previous in vitro findings showed that poly(2-methacryloyloxyethyl phosphorylcholine)-grafted particles were biologically inert and caused no subsequent bone resorptive responses, and poly(2-methacryloyloxyethyl phosphorylcholine) grafting markedly decreased wear in hip joint simulator tests, the clinical safety, and in vivo wear resistance of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners remained open to question. Therefore, in the present study, we evaluated clinical and radiographic outcomes of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners 5 years subsequent to total hip replacement in 68 consecutive patients. No reoperation was required for any reason, and no adverse events were associated with the implanted liners. The average Harris Hip Score increased from 38.6 preoperatively to 96.5 5 years postoperatively, and health-related quality of life, as indicated by the Short Form 36 Health Survey, improved. Radiographic analyses showed no periprosthetic osteolysis or implant migration. Between 1 and 5 years postoperatively, the mean steady-state wear rate was 0.002 mm/year, which represented a marked reduction relative to other highly cross-linked polyethylene liners, and appeared to be unaffected by patient-related or surgical factors. Although longer follow up is required, poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners improved mid-term clinical outcomes. The clinical safety and wear-resistance results are encouraging with respect to the improvement of long-term clinical outcomes with poly(2

  9. {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.

  10. From Molecules to the Clinic: Linking Schizophrenia and Metabolic Syndrome through Sphingolipids Metabolism.

    PubMed

    Castillo, Rolando I; Rojo, Leonel E; Henriquez-Henriquez, Marcela; Silva, Hernán; Maturana, Alejandro; Villar, María J; Fuentes, Manuel; Gaspar, Pablo A

    2016-01-01

    Metabolic syndrome (MS) is a prevalent and severe comorbidity observed in schizophrenia (SZ). The exact nature of this association is controversial and very often accredited to the effects of psychotropic medications and disease-induced life-style modifications, such as inactive lifestyle, poor dietary choices, and smoking. However, drug therapy and disease-induced lifestyle factors are likely not the only factors contributing to the observed converging nature of these conditions, since an increased prevalence of MS is also observed in first episode and drug-naïve psychosis populations. MS and SZ share common intrinsic susceptibility factors and etiopathogenic mechanisms, which may change the way we approach clinical management of SZ patients. Among the most relevant common pathogenic pathways of SZ and MS are alterations in the sphingolipids (SLs) metabolism and SLs homeostasis. SLs have important structural functions as they participate in the formation of membrane "lipid rafts." SLs also play physiological roles in cell differentiation, proliferation, and inflammatory processes, which might be part of MS/SZ common pathophysiological processes. In this article we review a plausible mechanism to explain the link between MS and SZ through a disruption in SL homeostasis. Additionally, we provide insights on how this hypothesis can lead to the developing of new diagnostic/therapeutic technologies for SZ patients.

  11. From Molecules to the Clinic: Linking Schizophrenia and Metabolic Syndrome through Sphingolipids Metabolism

    PubMed Central

    Castillo, Rolando I.; Rojo, Leonel E.; Henriquez-Henriquez, Marcela; Silva, Hernán; Maturana, Alejandro; Villar, María J.; Fuentes, Manuel; Gaspar, Pablo A.

    2016-01-01

    Metabolic syndrome (MS) is a prevalent and severe comorbidity observed in schizophrenia (SZ). The exact nature of this association is controversial and very often accredited to the effects of psychotropic medications and disease-induced life-style modifications, such as inactive lifestyle, poor dietary choices, and smoking. However, drug therapy and disease-induced lifestyle factors are likely not the only factors contributing to the observed converging nature of these conditions, since an increased prevalence of MS is also observed in first episode and drug-naïve psychosis populations. MS and SZ share common intrinsic susceptibility factors and etiopathogenic mechanisms, which may change the way we approach clinical management of SZ patients. Among the most relevant common pathogenic pathways of SZ and MS are alterations in the sphingolipids (SLs) metabolism and SLs homeostasis. SLs have important structural functions as they participate in the formation of membrane “lipid rafts.” SLs also play physiological roles in cell differentiation, proliferation, and inflammatory processes, which might be part of MS/SZ common pathophysiological processes. In this article we review a plausible mechanism to explain the link between MS and SZ through a disruption in SL homeostasis. Additionally, we provide insights on how this hypothesis can lead to the developing of new diagnostic/therapeutic technologies for SZ patients. PMID:27877101

  12. Clinical and mutational features of Vietnamese children with X-linked agammaglobulinemia

    PubMed Central

    2014-01-01

    Background X-linked agammaglobulinemia (XLA) is a primary immune deficiency characterized by recurrent bacterial infections and profoundly depressed serum immunoglobulin levels and circulating mature B cells. It is caused by mutations of the Bruton tyrosine kinase (BTK) gene and is the most common form of inherited antibody deficiency. To our knowledge, this is the first report of XLA from Vietnam. Methods We investigated the BTK gene mutations and clinical features of four unrelated Vietnamese children. Results The mean ages at onset and at diagnosis were 2.5 and 8 years, respectively. All patients had a medical history of otitis media, pneumonia, and septicemia at the time of diagnosis. Other infections reported included sinusitis, bronchiectasis, arthritis, skin infections, meningitis, and recurrent diarrhea. We identified one previously reported mutation (c.441G >A) and three novel mutations: two frameshifts (c.1770delG and c.1742 delG), and one nonsense (c.1249A >T). Conclusions The delayed diagnosis may be attributable to insufficient awareness of this rare disease on the background of frequent infections even in the immunocompetent pediatric population in Vietnam. Our results further support the importance of molecular genetic testing in diagnosis of XLA. PMID:24885015

  13. BR 07-2 THE LINKING IN THE HUMAN (OBSERVATIONAL AND CLINICAL STUDY).

    PubMed

    Nilsson, Peter

    2016-09-01

    patterns in the household during childhood and adolescence due to cohabitation. It is hypothesized that microbiota profile as well as dietary intake patterns may cluster within families. Recently it was discovered that there is also a specific serum biomarker, the pro-atherosclerotic metabolite, trimethylamine-N-oxide (TMAO) that is able to reflect the gut microbiome and predict cardiovascular events [2]. TMAO can also predict prognosis in patients with congestive heart failure. Interventions to change the microbiota have provided promising results [3] and been described as a potential treatment target for cardio-metabolic disease. Such interventions should be based on the wider use of designed and tested functional food products as part of a healthy lifestyle in general. New findings hypertensive experimental animals and in human patients has revealed a special pattern of different microbiota patterns (dysbiosis) that differs from normotensive controls [4]. This could be linked to early life influences of other factors related to lifestyle in adult life. One idea is to test the influence of antibiotic treatment in these hypertensive individuals to see if vascular function can be improved and blood pressure lowered. We have to learn more about the gastrointestinal tract as potential initial organ of metabolic hypertension, as recently suggested [5].In summary, the family clustering of cardiometabolic disorders is a well-known clinical observation, but still not fully understood. Genetic factors, even put together in a risk score, can explain just a minor proportion of the increased family risk. New discoveries linking gut microbiota to obesity and cardiometabolic risk conditions, including hypertension, could explain some of this increased clustering. Gut microbiota could potentially be influenced by functional food products and healthy lifestyle, providing a link to cardiovascular and metabolic prevention.

  14. Multilevel and Latent Variable Modeling with Composite Links and Exploded Likelihoods

    ERIC Educational Resources Information Center

    Rabe-Hesketh, Sophia; Skrondal, Anders

    2007-01-01

    Composite links and exploded likelihoods are powerful yet simple tools for specifying a wide range of latent variable models. Applications considered include survival or duration models, models for rankings, small area estimation with census information, models for ordinal responses, item response models with guessing, randomized response models,…

  15. Exploring Links between Genotypes, Phenotypes, and Clinical Predictors of Response to Early Intensive Behavioral Intervention in Autism Spectrum Disorder

    PubMed Central

    Eapen, Valsamma; Črnčec, Rudi; Walter, Amelia

    2013-01-01

    Autism spectrum disorder (ASD) is amongst the most familial of psychiatric disorders. Twin and family studies have demonstrated a monozygotic concordance rate of 70–90%, dizygotic concordance of around 10%, and more than a 20-fold increase in risk for first-degree relatives. Despite major advances in the genetics of autism, the relationship between different aspects of the behavioral and cognitive phenotype and their underlying genetic liability is still unclear. This is complicated by the heterogeneity of autism, which exists at both genetic and phenotypic levels. Given this heterogeneity, one method to find homogeneous entities and link these with specific genotypes would be to pursue endophenotypes. Evidence from neuroimaging, eye tracking, and electrophysiology studies supports the hypothesis that, building on genetic vulnerability, ASD emerges from a developmental cascade in which a deficit in attention to social stimuli leads to impaired interactions with primary caregivers. This results in abnormal development of the neurocircuitry responsible for social cognition, which in turn adversely affects later behavioral and functional domains dependent on these early processes, such as language development. Such a model begets a heterogeneous clinical phenotype, and is also supported by studies demonstrating better clinical outcomes with earlier treatment. Treatment response following intensive early behavioral intervention in ASD is also distinctly variable; however, relatively little is known about specific elements of the clinical phenotype that may predict response to current behavioral treatments. This paper overviews the literature regarding genotypes, phenotypes, and predictors of response to behavioral intervention in ASD and presents suggestions for future research to explore linkages between these that would enable better identification of, and increased treatment efficacy for, ASD. PMID:24062668

  16. 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…

  17. Linking mechanistic models of tree physiology with models of forest dynamics: Problems of temporal scale

    SciTech Connect

    King, A.W.; Emanuel, W.R.; O'Neill, R.V.

    1988-01-01

    The individual-based forest gap models are a potential resource in the study of forest growth responses to environmental stress acting on physiological processes. This approach is currently limited by the lack of physiological detail in the gap models and by the temporal scales separating tree physiology and the annual tree growth simulated by the gap models. We describe a general procedure that integrates process-based models of tree physiology with forest gap models. The procedure involves (1) a link between a physiological model and a gap model provided by the simulation of annual wood production (AWP), (2) a factorial execution of a physiological model to generate AWP, (3) a response-surface model describing the relationship between AWP and driving variables appropriate to the annual time scale of a gap model, and (4) a revised gap model that includes a rescaled physiological model. The modified gap model can be used to simulate the impact of environmental stress on forest growth and succession. 18 refs., 2 figs.

  18. Global land-use allocation model linked to an integrated assessment model.

    PubMed

    Hasegawa, Tomoko; Fujimori, Shinichiro; Ito, Akihiko; Takahashi, Kiyoshi; Masui, Toshihiko

    2017-02-15

    We developed a global land-use allocation model that can be linked to integrated assessment models (IAMs) with a coarser spatial resolution. Using the model, we performed a downscaling of the IAMs' regional aggregated land-use projections to obtain a spatial land-use distribution, which could subsequently be used by Earth system models for global environmental assessments of ecosystem services, food security, and climate policies. Here we describe the land-use allocation model, discuss the verification of the downscaling technique, and explain the influences of the downscaling on estimates of land-use carbon emissions. A comparison of the emissions estimated with and without downscaling suggested that the land-use downscaling would help capture the spatial distribution of carbon stock density and regional heterogeneity of carbon emissions caused by cropland and pasture land expansion.

  19. 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

  20. 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.

  1. Mutations, Clinical Findings and Survival Estimates in South American Patients with X-Linked Adrenoleukodystrophy

    PubMed Central

    Pereira, Fernanda dos Santos; Matte, Ursula; Habekost, Clarissa Troller; de Castilhos, Raphael Machado; El Husny, Antonette Souto; Lourenço, Charles Marques; Vianna-Morgante, Angela M.; Giuliani, Liane; Galera, Marcial Francis; Honjo, Rachel; Kim, Chong Ae; Politei, Juan; Vargas, Carmen Regla; Jardim, Laura Bannach

    2012-01-01

    In this study, we analyzed the ABCD1 gene in X-linked adrenoleukodystrophy (X-ALD) patients and relatives from 38 unrelated families from South America, as well as phenotypic proportions, survival estimates, and the potential effect of geographical origin in clinical characteristics. Methods X- ALD patients from Brazil, Argentina and Uruguay were invited to participate in molecular studies to determine their genetic status, characterize the mutations and improve the genetic counseling of their families. All samples were screened by SSCP analysis of PCR fragments, followed by automated DNA sequencing to establish the specific mutation in each family. Age at onset and at death, male phenotypes, genetic status of women, and the effect of family and of latitude of origin were also studied. Results We identified thirty-six different mutations (twelve novel). This population had an important allelic heterogeneity, as only p.Arg518Gln was repeatedly found (three families). Four cases carried de novo mutations. Intra-familiar phenotype variability was observed in all families. Out of 87 affected males identified, 65% had the cerebral phenotype (CALD). The mean (95% CI) ages at onset and at death of the CALD were 10.9 (9.1–12.7) and 24.7 (19.8–29.6) years. No association was found between phenotypic manifestations and latitude of origin. One index-case was a girl with CALD who carried an ABCD1 mutation, and had completely skewed X inactivation. Conclusions This study extends the spectrum of mutations in X-ALD, confirms the high rates of de novo mutations and the absence of common mutations, and suggests a possible high frequency of cerebral forms in our population. PMID:22479560

  2. Gait Characteristics in a Canine Model of X-linked Myotubular Myopathy

    PubMed Central

    Goddard, Melissa A.; Burlingame, Emily; Beggs, Alan H.; Buj-Bello, Anna; Childers, Martin K.; Marsh, Anthony P.; Kelly, Valerie E.

    2014-01-01

    X-linked myotubular myopathy (XLMTM) is a fatal pediatric disease where affected boys display profound weakness of the skeletal muscles. Possible therapies are under development but robust outcome measures in animal models are required for effective translation to human patients. We established a naturally-occuring canine model, where XLMTM dogs display clinical symptoms similar to those observed in humans. The aim of this study was to determine potential endpoints for the assessment of future treatments in this model. Video-based gait analysis was selected, as it is a well-established method of assessing limb function in neuromuscular disease and measures have been correlated to patient quality of life. XLMTM dogs (N=3) and their true littermate wild type controls (N=3) were assessed at 4–5 time points, beginning at 10 weeks and continuing through 17 weeks. Motion capture and an instrumented carpet were used separately to evaluate spatiotemporal and kinematic changes over time. XLMTM dogs walk more slowly and with shorter stride lengths than wild type dogs, and these differences became greater over time. However, there was no clear difference in angular measures between affected and unaffected dogs. These data demonstrate that spatiotemporal parameters capture functional changes in gait in an XLMTM canine model and support their utility in future therapeutic trials. PMID:25281397

  3. Quantitative Modeling of Entangled Polymer Rheology: Experiments, Tube Models and Slip-Link Simulations

    NASA Astrophysics Data System (ADS)

    Desai, Priyanka Subhash

    Rheology properties are sensitive indicators of molecular structure and dynamics. The relationship between rheology and polymer dynamics is captured in the constitutive model, which, if accurate and robust, would greatly aid molecular design and polymer processing. This dissertation is thus focused on building accurate and quantitative constitutive models that can help predict linear and non-linear viscoelasticity. In this work, we have used a multi-pronged approach based on the tube theory, coarse-grained slip-link simulations, and advanced polymeric synthetic and characterization techniques, to confront some of the outstanding problems in entangled polymer rheology. First, we modified simple tube based constitutive equations in extensional rheology and developed functional forms to test the effect of Kuhn segment alignment on a) tube diameter enlargement and b) monomeric friction reduction between subchains. We, then, used these functional forms to model extensional viscosity data for polystyrene (PS) melts and solutions. We demonstrated that the idea of reduction in segmental friction due to Kuhn alignment is successful in explaining the qualitative difference between melts and solutions in extension as revealed by recent experiments on PS. Second, we compiled literature data and used it to develop a universal tube model parameter set and prescribed their values and uncertainties for 1,4-PBd by comparing linear viscoelastic G' and G" mastercurves for 1,4-PBds of various branching architectures. The high frequency transition region of the mastercurves superposed very well for all the 1,4-PBds irrespective of their molecular weight and architecture, indicating universality in high frequency behavior. Therefore, all three parameters of the tube model were extracted from this high frequency transition region alone. Third, we compared predictions of two versions of the tube model, Hierarchical model and BoB model against linear viscoelastic data of blends of 1,4-PBd

  4. Plantar Fasciitis and the Windlass Mechanism: A Biomechanical Link to Clinical Practice

    PubMed Central

    Malone, Terry R.

    2004-01-01

    Objective: Plantar fasciitis is a prevalent problem, with limited consensus among clinicians regarding the most effective treatment. The purpose of this literature review is to provide a systematic approach to the treatment of plantar fasciitis based on the windlass mechanism model. Data Sources: We searched MEDLINE, SPORT Discus, and CINAHL from 1966 to 2003 using the key words plantar fasciitis, windlass mechanism, pronation, heel pain, and heel spur. Data Synthesis: We offer a biomechanical application for the evaluation and treatment of plantar fasciitis based on a review of the literature for the windlass mechanism model. This model provides a means for describing plantar fasciitis conditions such that clinicians can formulate a potential causal relationship between the conditions and their treatments. Conclusions/Recommendations: Clinicians' understanding of the biomechanical causes of plantar fasciitis should guide the decision-making process concerning the evaluation and treatment of heel pain. Use of this approach may improve clinical outcomes because intervention does not merely treat physical symptoms but actively addresses the influences that resulted in the condition. Principles from this approach might also provide a basis for future research investigating the efficacy of plantar fascia treatment. PMID:16558682

  5. Generalized Modelling of the Stabilizer Link and Static Simulation Using FEM

    NASA Astrophysics Data System (ADS)

    Cofaru, Nicolae Florin; Roman, Lucian Ion; Oleksik, Valentin; Pascu, Adrian

    2016-12-01

    This paper proposes an organological approach of one of the components of front suspension, namely anti-roll power link. There will be realized a CAD 3D modelling of this power link. 3D modelling is generalized and there were used the powers of Catia V5R20 software. Parameterized approach provides a high flexibility in the design, meaning that dimensional and shape changes of the semi-power link are very easy to perform just by changing some parameters. Several new versions are proposed for the anti-roll power link body. At the end of the work, it is made a static analysis of the semi-power link model used in the suspension of vehicles OPEL ASTRA G, ZAFIRA, MERIVA, and constructive optimization of its body.

  6. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench.

    PubMed

    Diaz, Patricia I; Strausbaugh, Linda D; Dongari-Bagtzoglou, Anna

    2014-01-01

    High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

  7. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench

    PubMed Central

    Diaz, Patricia I.; Strausbaugh, Linda D.; Dongari-Bagtzoglou, Anna

    2014-01-01

    High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases. PMID:25120959

  8. Design-oriented analytic model of phase and frequency modulated optical links

    NASA Astrophysics Data System (ADS)

    Monsurrò, Pietro; Saitto, Antonio; Tommasino, Pasquale; Trifiletti, Alessandro; Vannucci, Antonello; Cimmino, Rosario F.

    2016-07-01

    An analytic design-oriented model of phase and frequency modulated microwave optical links has been developed. The models are suitable for design of broadband high dynamic range optical links for antenna remoting and optical beamforming, where noise and linearity of the subsystems are a concern Digital filter design techniques have been applied to the design of optical filters working as frequency discriminator, that are the bottleneck in terms of linearity for these systems. The models of frequency modulated, phase modulated, and coherent I/Q link have been used to compare performance of the different architectures in terms of linearity and SFDR.

  9. 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…

  10. A Tiered Model for Linking Students to the Community

    ERIC Educational Resources Information Center

    Meyer, Laura Landry; Gerard, Jean M.; Sturm, Michael R.; Wooldridge, Deborah G.

    2016-01-01

    A tiered practice model (introductory, pre-internship, and internship) embedded in the curriculum facilitates community engagement and creates relevance for students as they pursue a professional identity in Human Development and Family Studies. The tiered model integrates high-impact teaching practices (HIP) and student engagement pedagogies…

  11. 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.

  12. Derivation of free energy expressions for tube models from coarse-grained slip-link models

    NASA Astrophysics Data System (ADS)

    Steenbakkers, Rudi J. A.; Schieber, Jay D.

    2012-07-01

    We present the free energy of a single-chain mean-field model for polymer melt dynamics, which uses a continuous (tube-like) approximation to the discrete entanglements with surrounding chains, but, in contrast to previous tube models, includes fluctuations in the number density of Kuhn steps along the primitive path and in the degree of entanglement. The free energy is obtained from that of the slip-link model with fluctuating entanglement positions [J. D. Schieber and K. Horio, J. Chem. Phys. 132, 074905 (2010)], 10.1063/1.3314727 by taking the continuous limit of (functions of) the discrete Kuhn-step numbers and end-to-end vectors of the strands between entanglements. This coarse-graining from a more-detailed level of description has the advantage that no ad hoc arguments need to be introduced. Moreover, the thermodynamic consistency of the slip-link model [J. D. Schieber, J. Non-Equilib. Thermodyn. 28, 179 (2003)], 10.1515/JNETDY.2003.010 can be preserved. Fluctuations in the positions of entanglements lead to a harmonic bending term in the free energy of the continuous chain, similar to that derived by Read et al. [Macromolecules 41, 6843 (2008)], 10.1021/ma8009855 starting from a modified GLaMM model [R. S. Graham, A. E. Likhtman, T. C. B. McLeish, and S. T. Milner, J. Rheol. 47, 1171 (2003)], 10.1122/1.1595099. If these fluctuations are set to zero, the free energy becomes purely Gaussian and corresponds to the continuous limit of the original slip-link model, with affinely moving entanglements [J. D. Schieber, J. Chem. Phys. 118, 5162 (2003)], 10.1063/1.1553764. The free energy reduces to that of Read et al. under their assumptions of a homogeneous Kuhn-step number density and a constant degree of entanglement. Finally, we show how a transformation of the primitive-path coordinate can be applied to make the degree of entanglement an outcome of the model instead of a variable. In summary, this paper constitutes a first step towards a unified mathematical

  13. Development of a clinical preceptor model.

    PubMed

    Blum, Cynthia Ann

    2009-01-01

    To reflect contemporary nursing care, the practicing nurse is in an ideal position to shape the clinical experience for student nurses. Although nurse preceptors are frequently used to assist in practice education of nursing students, their contribution to the creation of these programs has not been explored. The author discusses the results of a participatory action research study with the aim of creating a preceptor-guided practice education model for use throughout an undergraduate bachelor of science in nursing curriculum.

  14. Strengthening the weak link: Built Environment modelling for loss analysis

    NASA Astrophysics Data System (ADS)

    Millinship, I.

    2012-04-01

    Methods to analyse insured losses from a range of natural perils, including pricing by primary insurers and catastrophe modelling by reinsurers, typically lack sufficient exposure information. Understanding the hazard intensity in terms of spatial severity and frequency is only the first step towards quantifying the risk of a catastrophic event. For any given event we need to know: Are any structures affected? What type of buildings are they? How much damaged occurred? How much will the repairs cost? To achieve this, detailed exposure information is required to assess the likely damage and to effectively calculate the resultant loss. Modelling exposures in the Built Environment therefore plays as important a role in understanding re/insurance risk as characterising the physical hazard. Across both primary insurance books and aggregated reinsurance portfolios, the location of a property (a risk) and its monetary value is typically known. Exactly what that risk is in terms of detailed property descriptors including structure type and rebuild cost - and therefore its vulnerability to loss - is often omitted. This data deficiency is a primary source of variations between modelled losses and the actual claims value. Built Environment models are therefore required at a high resolution to describe building attributes that relate vulnerability to property damage. However, national-scale household-level datasets are often not computationally practical in catastrophe models and data must be aggregated. In order to provide more accurate risk analysis, we have developed and applied a methodology for Built Environment modelling for incorporation into a range of re/insurance applications, including operational models for different international regions and different perils and covering residential, commercial and industry exposures. Illustrated examples are presented, including exposure modelling suitable for aggregated reinsurance analysis for the UK and bespoke high resolution

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

    PubMed

    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.

  16. 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

  17. 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 ...

  18. 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

  19. 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.

  20. Linking Meteorology, Air Quality Models and Observations to ...

    EPA Pesticide Factsheets

    Epidemiologic studies are critical in establishing the association between exposure to air pollutants and adverse health effects. Results of epidemiologic studies are used by U.S. EPA in developing air quality standards to protect the public from the health effects of air pollutants. A major challenge in environmental epidemiology is adequate exposure characterization. Numerous health studies have used measurements from a few central-site ambient monitors to characterize air pollution exposures. Relying solely on central-site ambient monitors does not account for the spatial-heterogeneity of ambient air pollution patterns, the temporal variability in ambient concentrations, nor the influence of infiltration and indoor sources. Central-site monitoring becomes even more problematic for certain air pollutants that exhibit significant spatial heterogeneity. Statistical interpolation techniques and passive monitoring methods can provide additional spatial resolution in ambient concentration estimates. In addition, spatio-temporal models, which integrate GIS data and other factors, such as meteorology, have also been developed to produce more resolved estimates of ambient concentrations. Models, such as the Community Multi-Scale Air Quality (CMAQ) model, estimate ambient concentrations by combining information on meteorology, source emissions, and chemical-fate and transport. Hybrid modeling approaches, which integrate regional scale models with local scale dispersion

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. Conceptual Processes for Linking Eutrophication and Network Models

    DTIC Science & Technology

    2006-08-01

    for improvements. Submerged Aquatic Vegetation (SAV). SAV biomass values from ICM (identified as SAV in Table 3) are two to three times lower...Dorothy H. Tillman, Dr. Carl F. Cerco, and Mr. Mark R. Noel of the Water Quality and Contaminant Modeling Branch, Enviromental Laboratory (EL

  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. 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.

  8. Modeling water quality, temperature, and flow in Link River, south-central Oregon

    USGS Publications Warehouse

    Sullivan, Annett B.; Rounds, Stewart A.

    2016-09-09

    The 2.1-km (1.3-mi) Link River connects Upper Klamath Lake to the Klamath River in south-central Oregon. A CE-QUAL-W2 flow and water-quality model of Link River was developed to provide a connection between an existing model of the upper Klamath River and any existing or future models of Upper Klamath Lake. Water-quality sampling at six locations in Link River was done during 2013–15 to support model development and to provide a better understanding of instream biogeochemical processes. The short reach and high velocities in Link River resulted in fast travel times and limited water-quality transformations, except for dissolved oxygen. Reaeration through the reach, especially at the falls in Link River, was particularly important in moderating dissolved oxygen concentrations that at times entered the reach at Link River Dam with marked supersaturation or subsaturation. This reaeration resulted in concentrations closer to saturation downstream at the mouth of Link River.

  9. 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.

  10. 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

  11. 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.

  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. 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

  14. 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

  15. Neurophysiological Measures and Alcohol Use Disorder (AUD): Hypothesizing Links between Clinical Severity Index and Molecular Neurobiological Patterns

    PubMed Central

    Vitali, Mario; Napolitano, Carmen; Berman, Marlene Oscar; Minuto, Simona Flamminii; Battagliese, Gemma; Attilia, Maria Luisa; Braverman, Eric R; Romeo, Marina; Blum, Kenneth; Ceccanti, Mauro

    2016-01-01

    Background In 1987, Cloninger proposed a clinical description and classification of different personality traits genetically defined and independent from each other. Moreover, he elaborated a specific test the TCI to investigate these traits/states. The study of craving in Alcohol Use Disorder (AUD) assumed a greater significance, since ever more data seems to suggest a direct correlation between high levels of craving and a higher risk of relapse in alcoholics. Thus, our study aim is to explore the possible correlations among TCI linked molecular neurobiological pattern (s), craving and alcohol addiction severity measures in a sample of Italian alcoholics. Materials and Methods 191 alcoholics were recruited in a Day Hospital (DH) setting at the Alcohol Addiction Program Latium Region Referral Center, Sapienza University of Rome. After 7 days detoxification treatment a psychodiagnostic protocol was administered, including TCI, VAS-C, ASI and SADQ. All patients signed an Institutional Review Board (IRB) approved informed consent. Results Principally, we detected a significant positive correlation between HA-scale scores and the VAS scale: increasing in HA-scale corresponds to an increase in craving perception for both intensity (r=0.310; p ≤ 0.001) and frequency (r=0.246; p ≤ 0.001). Moreover, perception of dependence severity, measured with SADQ was also found to be significantly associated positively to both HA-scale (r=0.246; p ≤ 0.001) and NS-scale (r=0.224; p ≤ 0.01). While, for character scales, Persistence (r=−0.195; p=.008) and Self-directedness (r=−0.294; p ≤ 0.001) was negatively associated with ASI linked to alcohol problems. Self-directedness was also negatively correlated with ASI linked to family and social problems (r=−0.349; p ≤ 0.001), employment and support problems (r=−0.220; p=0.003) and psychiatric problems (r=−0.358; p ≤ 0.001). Cooperativeness was a negative correlate with Legal Problems (r=−0.173; p=0.019). and Self

  16. "Youth friendly" clinics: considerations for linking and engaging HIV-infected adolescents into care.

    PubMed

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

    2014-02-01

    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.

  17. 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

  18. 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...

  19. 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.…

  20. 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.

  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. 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.

  3. Atempts to link Quanta & Atoms before the Bohr Atom model

    NASA Astrophysics Data System (ADS)

    Venkatesan, A.; Lieber, M.

    2005-03-01

    Attempts to quantize atomic phenomena before Bohr are hardly ever mentioned in elementary textbooks.This presentation will elucidate the contributions of A.Haas around 1910. Haas tried to quantize the Thomson atom model as an optical resonator made of positive and negative charges. The inherent ambiguity of charge distribution in the model made him choose a positive spherical distribution around which the electrons were distributed.He obtained expressions for the Rydberg constant and what is known today as the Bohr radius by balancing centrifugal energy with Coulomb energy and quantizing it with Planck's relation E=hν. We point out that Haas would have arrived at better estimates of these constants had he used the virial theorem apart from the fact that the fundamental constants were not well known. The crux of Haas's physical picture was to derive Planck's constant h from charge quantum e , mass of electron m and atomic radius. Haas faced severe criticism for applying thermodynamic concepts like Planck distribution to microscopic phenomena. We will try to give a flavor for how quantum phenomena were viewed at that time. It is of interest to note that the driving force behind Haas's work was to present a paper that would secure him a position as a Privatdozent in History of Physics. We end with comments by Bohr and Sommerfeld on Haas's work and with some brief biographical remarks.

  4. 4D human body posture estimation based on a motion capture system and a multi-rigid link model.

    PubMed

    Yoshikawa, Naoya; Suzuki, Yasuyuki; Ozaki, Wataru; Yamamoto, Tomohisa; Nomura, Taishin

    2012-01-01

    Human motion analysis in various fields such as neurophysiology, clinical medicine, and sports sciences utilizes a multi-rigid link model of a human body for considering kinetics by solving inverse dynamics of a motion, in which a motion capture system with reflective markers are often used to measure the motion, and then the obtained motion are mapped onto the multi-rigid link model. However, algorithms for such a mapping from spatio-temporal positions of the markers to the corresponding posture of the model are not always fully disclosed. Moreover, a common difficulty for such algorithms is an error caused by displacements of the markers attached on the body surface, referred to as the skin motion error. In this study, we developed a simple algorithm that maps positions of the markers to the corresponding posture of a rigid link model, and examined accuracy of the algorithm by evaluating quantitatively differences between the measured and the estimated posture. We also analyzed the skin motion error. It is shown that magnitude of the error was determined not only by the amplitude of the skin motion, but also by the direction of the marker displacement relative to the frame of reference attached to each segment of the body.

  5. Data Model Considerations for Clinical Effectiveness Researchers

    PubMed Central

    Kahn, Michael G.; Batson, Deborah; Schilling, Lisa M.

    2013-01-01

    Introduction Growing adoption of electronic health records and increased emphasis on the reuse and integration of clinical care and administration data require a robust informatics infrastructure to inform health care effectiveness in real-world settings. The Scalable Architecture for Federated Translational Inquiries Network (SAFTI Net) was one of 3 projects receiving Agency for Healthcare Quality and Research funds to create a scalable, distributed network to support Comparative Effectiveness Research. SAFTINet’s method of extracting and compiling data from disparate entities requires the use of a shared common data model. Data Models Focusing on the needs of CER investigators, in addition to other project considerations, we examined the suitability of several data models. Data modeling is the process of determining which data elements will be stored and how they will be stored, including their relationships and constraints. Addressing compromises between complexity and usability is critical to modeling decisions. Case Study The SAFTINet project provides the case study for describing data model evaluation. A sample use case defines a cohort of asthma subjects that illustrates the need to identify patients by age, diagnoses, and medication use while excluding those with diagnoses that may often be misdiagnosed as asthma. Discussion The SAFTINet team explored several data models against a set of technical and investigator requirements to select a data model that best fit its needs and was conducive to expansion with new research requirements. Although SAFTINet ultimately chose the Observation Medical Outcomes Partnership common data model, other valid options exist and prioritization of requirements is dependent upon many factors. PMID:22692260

  6. 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

  7. Horizontal gene transfer in eukaryotes: the weak-link model.

    PubMed

    Huang, Jinling

    2013-10-01

    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.

  8. 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...

  9. The Oral-Systemic Personalized Medicine Model at Marshfield Clinic

    PubMed Central

    Glurich, Ingrid; Acharya, Amit; Shukla, Sanjay K.; Nycz, Greg R; Brilliant, Murray H.

    2012-01-01

    Periodontal disease and diabetes, two diseases that have achieved epidemic status, share a bi-directional 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

  10. Clinical Scholar Model: providing excellence in clinical supervision of nursing students.

    PubMed

    Preheim, Gayle; Casey, Kathy; Krugman, Mary

    2006-01-01

    The Clinical Scholar Model (CSM) is a practice-education partnership focused on improving the outcomes of clinical nursing education by bridging the academic and service settings. An expert clinical nurse serves as a clinical scholar (CS) to coordinate, supervise, and evaluate the clinical education of nursing students in collaboration with school of nursing faculty. This article describes the model's evolution, how the model is differentiated from traditional clinical instruction roles and responsibilities, and the benefits to the collaborating clinical agency and school of nursing.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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 |

  18. [From clinical judgment to linear regression model.

    PubMed

    Palacios-Cruz, Lino; Pérez, Marcela; Rivas-Ruiz, Rodolfo; Talavera, Juan O

    2013-01-01

    When we think about mathematical models, such as linear regression model, we think that these terms are only used by those engaged in research, a notion that is far from the truth. Legendre described the first mathematical model in 1805, and Galton introduced the formal term in 1886. Linear regression is one of the most commonly used regression models in clinical practice. It is useful to predict or show the relationship between two or more variables as long as the dependent variable is quantitative and has normal distribution. Stated in another way, the regression is used to predict a measure based on the knowledge of at least one other variable. Linear regression has as it's first objective to determine the slope or inclination of the regression line: Y = a + bx, where "a" is the intercept or regression constant and it is equivalent to "Y" value when "X" equals 0 and "b" (also called slope) indicates the increase or decrease that occurs when the variable "x" increases or decreases in one unit. In the regression line, "b" is called regression coefficient. The coefficient of determination (R(2)) indicates the importance of independent variables in the outcome.

  19. 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.

  20. 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…

  1. An Extension of Least Squares Estimation of IRT Linking Coefficients for the Graded Response Model

    ERIC Educational Resources Information Center

    Kim, Seonghoon

    2010-01-01

    The three types (generalized, unweighted, and weighted) of least squares methods, proposed by Ogasawara, for estimating item response theory (IRT) linking coefficients under dichotomous models are extended to the graded response model. A simulation study was conducted to confirm the accuracy of the extended formulas, and a real data study was…

  2. Humanized mouse models of clinical disease

    PubMed Central

    Walsh, Nicole; Kenney, Laurie; Jangalwe, Sonal; Aryee, Ken-Edwin; Greiner, Dale L.; Brehm, Michael A.; Shultz, Leonard D.

    2017-01-01

    Immunodeficient mice engrafted with functional human cells and tissues, i.e., “humanized mice”, have become increasingly important as small pre-clinical animal models for the study of human diseases. Since the description of immunodeficient mice bearing mutations in the IL2 receptor common gamma chain (IL2rgnull) in the early 2000’s, investigators have been able to engraft murine recipients with human hematopoietic stem cells that develop into functional human immune systems. These mice can also be engrafted with human tissues such as islets, liver, skin, and most solid and hematologic cancers. Humanized mice are permitting significant progress in studies of human infectious disease, cancer, regenerative medicine, graft versus host disease, allergies, and immunity. Ultimately, use of humanized mice may lead to the implementation of truly “personalized” medicine in the clinic. This review discusses recent progress in the development and use of humanized mice, and highlights their utility for the study of human diseases. PMID:27959627

  3. Implicit and explicit stigma of mental illness: links to clinical care.

    PubMed

    Peris, Tara S; Teachman, Bethany A; Nosek, Brian A

    2008-10-01

    This study examined implicit and explicit measures of bias toward mental illness among people with different levels of mental health training, and investigated the influence of stigma on clinically-relevant decision-making. Participants (N = 1539) comprised of (1) mental health professionals and clinical graduate students, (2) other health care/social services specialists, (3) undergraduate students, and (4) the general public self-reported their attitudes toward people with mental illness, and completed implicit measures to assess mental illness evaluations that exist outside of awareness or control. In addition, participants predicted patient prognoses and assigned diagnoses after clinical vignettes. Compared with people without mental health training, individuals with mental health training demonstrated more positive implicit and explicit evaluations of people with mental illness. Further, explicit (but not implicit) biases predicted more negative patient prognoses, but implicit (and not explicit) biases predicted over-diagnosis, underscoring the value of using both implicit and explicit measures.

  4. Quality and safety of detailed clinical models.

    PubMed

    Ritz, Derek

    2013-01-01

    This chapter describes quality and safety risks related to the development and use of Detailed Clinical Models (DCM) and mechanisms which may be employed to mitigate such risks. The chapter begins with a brief discussion of DCMs and the role they can play in mitigating patient safety risk. There is then a brief description of the risks which DCMs themselves may introduce, followed by the introduction of a standards-based risk assessment method and the ways this assessment method may be applied to DCMs in particular. A general description is then made of the ISO 9000-based approach to quality management systems (QMS) and, specifically, how such an approach may be applied to DCM development, maintenance, deployment and use. The chapter concludes with a discussion of specific DCM quality and safety challenges and governance approaches which may be employed to help address these.

  5. 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.

  6. Mutations in chromatin regulators functionally link Cornelia de Lange syndrome and clinically overlapping phenotypes.

    PubMed

    Parenti, Ilaria; Teresa-Rodrigo, María E; Pozojevic, Jelena; Ruiz Gil, Sara; Bader, Ingrid; Braunholz, Diana; Bramswig, Nuria C; Gervasini, Cristina; Larizza, Lidia; Pfeiffer, Lutz; Ozkinay, Ferda; Ramos, Feliciano; Reiz, Benedikt; Rittinger, Olaf; Strom, Tim M; Watrin, Erwan; Wendt, Kerstin; Wieczorek, Dagmar; Wollnik, Bernd; Baquero-Montoya, Carolina; Pié, Juan; Deardorff, Matthew A; Gillessen-Kaesbach, Gabriele; Kaiser, Frank J

    2017-03-01

    The coordinated tissue-specific regulation of gene expression is essential for the proper development of all organisms. Mutations in multiple transcriptional regulators cause a group of neurodevelopmental disorders termed "transcriptomopathies" that share core phenotypical features including growth retardation, developmental delay, intellectual disability and facial dysmorphism. Cornelia de Lange syndrome (CdLS) belongs to this class of disorders and is caused by mutations in different subunits or regulators of the cohesin complex. Herein, we report on the clinical and molecular characterization of seven patients with features overlapping with CdLS who were found to carry mutations in chromatin regulators previously associated to other neurodevelopmental disorders that are frequently considered in the differential diagnosis of CdLS. The identified mutations affect the methyltransferase-encoding genes KMT2A and SETD5 and different subunits of the SWI/SNF chromatin-remodeling complex. Complementary to this, a patient with Coffin-Siris syndrome was found to carry a missense substitution in NIPBL. Our findings indicate that mutations in a variety of chromatin-associated factors result in overlapping clinical phenotypes, underscoring the genetic heterogeneity that should be considered when assessing the clinical and molecular diagnosis of neurodevelopmental syndromes. It is clear that emerging molecular mechanisms of chromatin dysregulation are central to understanding the pathogenesis of these clinically overlapping genetic disorders.

  7. Mediators of the Link between Autistic Traits and Relationship Satisfaction in a Non-Clinical Sample

    ERIC Educational Resources Information Center

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

    2010-01-01

    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…

  8. 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…

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

    PubMed

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

    2015-01-01

    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.

  10. Discovering link communities in complex networks by an integer programming model and a genetic algorithm.

    PubMed

    Li, Zhenping; Zhang, Xiang-Sun; Wang, Rui-Sheng; Liu, Hongwei; Zhang, Shihua

    2013-01-01

    Identification of communities in complex networks is an important topic and issue in many fields such as sociology, biology, and computer science. Communities are often defined as groups of related nodes or links that correspond to functional subunits in the corresponding complex systems. While most conventional approaches have focused on discovering communities of nodes, some recent studies start partitioning links to find overlapping communities straightforwardly. In this paper, we propose a new quantity function for link community identification in complex networks. Based on this quantity function we formulate the link community partition problem into an integer programming model which allows us to partition a complex network into overlapping communities. We further propose a genetic algorithm for link community detection which can partition a network into overlapping communities without knowing the number of communities. We test our model and algorithm on both artificial networks and real-world networks. The results demonstrate that the model and algorithm are efficient in detecting overlapping community structure in complex networks.

  11. Special conference of the American Association for Cancer Research on molecular imaging in cancer: linking biology, function, and clinical applications in vivo.

    PubMed

    Luker, Gary D

    2002-04-01

    The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.

  12. Enzyme-linked immunosorbent assay for detection of respiratory syncytial virus infection: application to clinical samples.

    PubMed Central

    McIntosh, K; Hendry, R M; Fahnestock, M L; Pierik, L T

    1982-01-01

    An enzyme-linked immunosorbent assay (ELISA) for respiratory syncytial virus antigens was applied to the rapid diagnosis of acute infections in children and was compared with viral culture and immunofluorescence tests. The ELISA test employed commercially available reagents and was run on a day-to-day basis as specimens were received in the laboratory. Sensitivity and specificity by ELISA were 82 and 95%, respectively, compared with culture. In the same specimens, the sensitivity and specificity by immunofluorescence were 86 and 96%, respectively. Nasopharyngeal aspirates were proven to be a better source of viral antigen than were nasopharyngeal swabs. ELISA-positive samples remained positive even when left unrefrigerated for a week or mailed to the laboratory in plastic containers. Respiratory syncytial virus ELISA, like culture, became negative as the disease progressed and showed no superiority over culture for diagnosis late in the illness. PMID:6749895

  13. Genetic analysis and clinical phenotype of two Indian families with X-linked choroideremia

    PubMed Central

    Battu, Rajani; Jeyabalan, Nallathambi; Murthy, Praveen; Reddy, Kavita S; Schouten, Jan SAG; Webers, Caroll A

    2016-01-01

    Purpose: This study aims to describe the phenotype and genotype of two Indian families affected with X-linked choroideremia (CHM). Materials and Methods: In these two families, the affected individuals and unaffected family members underwent a comprehensive ophthalmic examination including an optical coherence tomography (OCT) and electroretinogram. Blood samples were collected from the families for genetic analysis. Next generation sequencing (NGS) was done using a panel of 184 genes, which covered previously associated genes with retinal dystrophies. Sequencing data were analyzed for the CHM, RPGR, and RP2 genes that have been implicated in CHM and X-linked retinitis pigmentosa (XLRP), respectively. The identified variants were confirmed by Sanger sequencing in available individuals and unrelated controls. Results: In two unrelated male patients, NGS analysis revealed a previously reported 3’-splice site change c.820-1G>C in the CHM gene in the first family and hemizygous mutation c.653G>C (p.Ser218X) in the second family. The asymptomatic family members were carriers for these mutations. Spectral domain-OCT showed loss of outer retina, preservation of the inner retina, and choroidal thinning in the affected males and retinal pigment epithelial changes in the asymptomatic carriers. The identified mutations were not present in 100 controls of Indian origin. There were no potential mutations found in XLRP-associated (RPGR and RP2) genes. Conclusion: This report describes the genotype and phenotype findings in patients with CHM from India. The identified genetic mutation leads to lack of Rab escort protein-1 (REP-1) or affects the production of a REP-1 protein that is likely to cause retinal abnormalities in patients. PMID:28112135

  14. 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.

  15. Deletion analysis and clinical correlations in patients with Xp21 linked muscular dystrophy.

    PubMed

    Ulgenalp, Ayfer; Giray, Ozlem; Bora, Elçin; Hizli, Tülin; Kurul, Semra; Sağin-Saylam, Gül; Karasoy, Hatice; Uran, Nedret; Dizdarer, Gülşen; Tütüncüoğlu, Sarenur; Dirik, Eray; Ozkinay, Ferda; Erçal, Derya

    2004-01-01

    We carried out molecular deletion analysis on 142 patients with Duchenne/Becker muscular dystrophy which covered 25 exons of the dystrophin gene. We also evaluated the results by comparing with the clinical findings and examples in the literature. A deletion ratio of 63.7% was achieved. Exon 46 was the most frequently affected region. Interestingly we also observed four cases with muscle promoter (Mp) region deletions which have been rarely reported in the literature.

  16. 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

  17. 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.

  18. Proficiency testing linked to the national reference system for the clinical laboratory: a proposal for achieving accuracy.

    PubMed

    Lasky, F D

    1992-07-01

    I propose using proficiency testing (PT) to achieve one of the important goals of CLIA: accurate and reliable clinical testing. Routine methods for the clinical laboratory are traceable to Definitive (DM) or Reference Methods (RM) or to Methodological Principles (MP) through a modification of the National Reference System for the Clinical Laboratory. PT is the link used to monitor consistent field performance. Although PT has been effective as a relative measure of laboratory performance, the technical limitations of PT fluids and of routine methods currently in use make it unlikely that PT alone can be used as a reliable measure of laboratory accuracy. Instead, I recommend calibration of routine systems through correlation to DM, RM, or MP with use of patients' specimens. The manufacturer is in the best position to assume this responsibility because of also being responsible for consistent, reliable product. Analysis of different manufactured batches of reagent would be compared with predetermined goals for precision and accuracy, as illustrated with data from product testing of Kodak Ektachem clinical chemistry slides. Adoption of this proposal would give manufacturers of PT materials, manufacturers of analytical systems, PT providers, and government agencies time to understand and resolve sources of error that limit the utility of PT for the job required by law.

  19. Summary goodness-of-fit statistics for binary generalized linear models with noncanonical link functions.

    PubMed

    Canary, Jana D; Blizzard, Leigh; Barry, Ronald P; Hosmer, David W; Quinn, Stephen J

    2016-05-01

    Generalized linear models (GLM) with a canonical logit link function are the primary modeling technique used to relate a binary outcome to predictor variables. However, noncanonical links can offer more flexibility, producing convenient analytical quantities (e.g., probit GLMs in toxicology) and desired measures of effect (e.g., relative risk from log GLMs). Many summary goodness-of-fit (GOF) statistics exist for logistic GLM. Their properties make the development of GOF statistics relatively straightforward, but it can be more difficult under noncanonical links. Although GOF tests for logistic GLM with continuous covariates (GLMCC) have been applied to GLMCCs with log links, we know of no GOF tests in the literature specifically developed for GLMCCs that can be applied regardless of link function chosen. We generalize the Tsiatis GOF statistic originally developed for logistic GLMCCs, (TG), so that it can be applied under any link function. Further, we show that the algebraically related Hosmer-Lemeshow (HL) and Pigeon-Heyse (J(2) ) statistics can be applied directly. In a simulation study, TG, HL, and J(2) were used to evaluate the fit of probit, log-log, complementary log-log, and log models, all calculated with a common grouping method. The TG statistic consistently maintained Type I error rates, while those of HL and J(2) were often lower than expected if terms with little influence were included. Generally, the statistics had similar power to detect an incorrect model. An exception occurred when a log GLMCC was incorrectly fit to data generated from a logistic GLMCC. In this case, TG had more power than HL or J(2) .

  20. 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…

  1. 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…

  2. 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…

  3. 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.

  4. 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…

  5. Targeting Carcinoembryonic Antigen with DNA Vaccination: On-Target Adverse Events Link with Immunological and Clinical Outcomes

    PubMed Central

    Chudley, Lindsey; Stasakova, Jana; Thirdborough, Stephen; King, Andrew; Lloyd-Evans, Paul; Buxton, Emily; Edwards, Ceri; Halford, Sarah; Bateman, Andrew; O’Callaghan, Ann; Clive, Sally; Anthoney, Alan; Jodrell, Duncan I.; Weinschenk, Toni; Simon, Petra; Sahin, Ugur; Thomas, Gareth J.; Stevenson, Freda K.; Ottensmeier, Christian H.

    2017-01-01

    Purpose We have clinically evaluated a DNA fusion vaccine to target the HLA-A*0201 binding peptide CAP-1 from carcinoembryonic antigen (CEA605–613) linked to an immunostimulatory domain (DOM) from fragment C of tetanus toxin. Experimental Design Twenty-seven patients with CEA-expressing carcinomas were recruited: 15 patients with measurable disease (Arm-I) and 12 patients without radiological evidence of disease (Arm-II). Six intramuscular vaccinations of naked DNA (1mg/dose) were administered up to week 12. Clinical and immunological follow-up was to week 64 or clinical/radiological disease. Results DOM-specific immune responses demonstrated successful vaccine delivery. All patients without measurable disease compared to 60% with advanced disease responded immunologically, while 58% and 20% expanded anti-CAP-1 CD8+ T-cells, respectively. CAP-1-specific T-cells were only detectable in the blood post-vaccination, but could also be identified in previously resected cancer tissue. The gastrointestinal adverse event diarrhea was reported by 48% of patients and linked to more frequent decreases in CEA (p<0.001) and improved global immunological responses (anti-DOM responses of greater magnitude (p<0.001), frequency (p=0.004) and duration) compared to patients without diarrhea. In advanced disease patients, decreases in CEA were associated with better overall survival (HR=0.14, p=0.017). CAP-1 peptide was detectable on MHC class I of normal bowel mucosa and primary colorectal cancer tissue by mass-spectrometry, offering a mechanistic explanation for diarrhea through CD8+ T-cell attack. Conclusions Our data suggest that DNA vaccination is able to overcome peripheral tolerance in normal and tumor tissue and warrants testing in combination studies, for example, by vaccinating in parallel to treatment with an anti-PD1 antibody. PMID:27091407

  6. Gene-based association studies report genetic links for clinical subtypes of frontotemporal dementia.

    PubMed

    Mishra, Aniket; Ferrari, Raffaele; Heutink, Peter; Hardy, John; Pijnenburg, Yolande; Posthuma, Danielle

    2017-04-05

    Genome-wide association studies in frontotemporal dementia showed limited success in identifying associated loci. This is possibly due to small sample size, allelic heterogeneity, small effect sizes of single genetic variants, and the necessity to statistically correct for testing millions of genetic variants. To overcome these issues, we performed gene-based association studies on 3348 clinically identified frontotemporal dementia cases and 9390 controls (discovery, replication and joint-cohort analyses). We report association of APOE and TOMM40 with behavioural variant frontotemporal dementia, and ARHGAP35 and SERPINA1 with progressive non-fluent aphasia. Further, we found the ɛ2 and ɛ4 alleles of APOE harbouring protective and risk increasing effects, respectively, in clinical subtypes of frontotemporal dementia against neurologically normal controls. The APOE-locus association with behavioural variant frontotemporal dementia indicates its potential risk-increasing role across different neurodegenerative diseases, whereas the novel genetic associations of ARHGAP35 and SERPINA1 with progressive non-fluent aphasia point towards a potential role of the stress-signalling pathway in its pathophysiology.

  7. Link of the mechanisms of action of glatiramer acetate to its long-term clinical data.

    PubMed

    Moreau, Thibault

    2009-02-01

    A consequence of the long-term nature of progression in multiple sclerosis is that treatment needs to be provided over the long term. Gathering evidence for long term clinical efficacy, safety and patient acceptance of immunomodulatory therapies is thus a critically important issue. However, pivotal trials, which generally last no more than two years, cannot address this issue. Glatiramer acetate is the only immunomodulatory treatment for which prospective data is available covering a treatment period of over a decade. In the long-term extension of the pivotal trial of glatiramer acetate, 108 patients have been followed for a mean treatment duration of 10.1 years. At the end of the treatment period, patients were experiencing a relapse only once every five years and 92% remained ambulatory throughout. Similar findings have been made in observational studies in the long-term follow-up of patients with relapsing remitting multiple sclerosis treated with glatiramer acetate under a compassionate use programme in France and in a patient registry in Argentina. Such data strongly suggest that a reduced risk of relapse represents a real long-term treatment effect. The cumulative evidence for the long-term clinical efficacy of glatiramer acetate is consistent with its dual mechanism of action, reassures the physician that glatiramer acetate can really help improve patient care over the long term, and may contribute to a more positive view of prognosis for patients with multiple sclerosis.

  8. Model of Host-Pathogen Interaction Dynamics Links In Vivo Optical Imaging and Immune Responses

    PubMed Central

    Ale, Angelique; Crepin, Valerie F.; Collins, James W.; Constantinou, Nicholas; Habibzay, Maryam; Babtie, Ann C.

    2016-01-01

    ABSTRACT Tracking disease progression in vivo is essential for the development of treatments against bacterial infection. Optical imaging has become a central tool for in vivo tracking of bacterial population development and therapeutic response. For a precise understanding of in vivo imaging results in terms of disease mechanisms derived from detailed postmortem observations, however, a link between the two is needed. Here, we develop a model that provides that link for the investigation of Citrobacter rodentium infection, a mouse model for enteropathogenic Escherichia coli (EPEC). We connect in vivo disease progression of C57BL/6 mice infected with bioluminescent bacteria, imaged using optical tomography and X-ray computed tomography, to postmortem measurements of colonic immune cell infiltration. We use the model to explore changes to both the host immune response and the bacteria and to evaluate the response to antibiotic treatment. The developed model serves as a novel tool for the identification and development of new therapeutic interventions. PMID:27821583

  9. ClinRefLink: Implementation of Infobutton-like Functionality in a Commercial Clinical Information System Incorporating Concepts From Textual Documents

    PubMed Central

    Oppenheim, Michael I.; Rand, Debra; Barone, Catherine; Hom, Richard

    2009-01-01

    Clinical information systems offer an opportunity to provide clinicians with medical reference materials during clinical encounters when the information is most beneficial. Implementation of this “Infobutton” concept has been described by a number of institutions with locally developed clinical information systems and electronic medical records. This article describes the development of an infobutton-like application called ClinRefLink embedded within a commercial clinical information system. ClinRefLink is somewhat unique in that it offers clinicians the option to perform reference searches based on clinical entities identified within narrative documents. In the first 30 days after implementation, 1018 reference searches were performed. The characteristics of the clinicians and the clinical context of the search terms are described. These data support the value of clinical term extraction from narrative documents as a component of an infobutton system. PMID:20351904

  10. 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…

  11. Dynamical modeling of serial manipulators with flexible links and joints using the method of kinematic influence

    NASA Technical Reports Server (NTRS)

    Graves, Philip L.

    1989-01-01

    A method of formulating the dynamical equations of a flexible, serial manipulator is presented, using the Method of Kinematic Influence. The resulting equations account for rigid body motion, structural motion due to link and joint flexibilities, and the coupling between these two motions. Nonlinear inertial loads are included in the equations. A finite order mode summation method is used to model flexibilities. The structural data may be obtained from experimental, finite element, or analytical methods. Nonlinear flexibilities may be included in the model.

  12. High Bandwidth Communications Links Between Heterogeneous Autonomous Vehicles Using Sensor Network Modeling and Extremum Control Approaches

    DTIC Science & Technology

    2008-12-01

    two- fold. First, a communication propagation model was developed to predict the signal-to-noise ( SNR ) ratio of the communication link, which is used...as a reference SNR signal for the UAVs. Second, the communication model was then integrated into a feedback control loop to formulate a new real-time...loitering path using SNR as the cost function. 15. NUMBER OF PAGES 75 14. SUBJECT TERMS Unmanned Aerial Vehicle, UAV, Extremum Seeking

  13. Allostatic Load as a Complex Clinical Construct: A Case-Based Computational Modeling Approach.

    PubMed

    Buckwalter, J Galen; Castellani, Brian; McEwen, Bruce; Karlamangla, Arun S; Rizzo, Albert A; John, Bruce; O'Donnell, Kyle; Seeman, Teresa

    2016-01-01

    Allostatic load (AL) is a complex clinical construct, providing a unique window into the cumulative impact of stress. However, due to its inherent complexity, AL presents two major measurement challenges to conventional statistical modeling (the field's dominant methodology): it is comprised of a complex causal network of bioallostatic systems, represented by an even larger set of dynamic biomarkers; and, it is situated within a web of antecedent socioecological systems, linking AL to differences in health outcomes and disparities. To address these challenges, we employed case-based computational modeling (CBM), which allowed us to make four advances: (1) we developed a multisystem, 7-factor (20 biomarker) model of AL's network of allostatic systems; (2) used it to create a catalog of nine different clinical AL profiles (causal pathways); (3) linked each clinical profile to a typology of 23 health outcomes; and (4) explored our results (post hoc) as a function of gender, a key socioecological factor. In terms of highlights, (a) the Healthy clinical profile had few health risks; (b) the pro-inflammatory profile linked to high blood pressure and diabetes; (c) Low Stress Hormones linked to heart disease, TIA/Stroke, diabetes, and circulation problems; and (d) high stress hormones linked to heart disease and high blood pressure. Post hoc analyses also found that males were overrepresented on the High Blood Pressure (61.2%), Metabolic Syndrome (63.2%), High Stress Hormones (66.4%), and High Blood Sugar (57.1%); while females were overrepresented on the Healthy (81.9%), Low Stress Hormones (66.3%), and Low Stress Antagonists (stress buffers) (95.4%) profiles.

  14. Pioglitazone halts axonal degeneration in a mouse model of X-linked adrenoleukodystrophy

    PubMed Central

    Morató, Laia; Galino, Jorge; Ruiz, Montserrat; Calingasan, Noel Ylagan; Starkov, Anatoly A.; Dumont, Magali; Naudí, Alba; Martínez, Juan José; Aubourg, Patrick; Portero-Otín, Manuel; Pamplona, Reinald; Galea, Elena; Beal, M. Flint; Ferrer, Isidre; Fourcade, Stéphane

    2013-01-01

    X-linked adrenoleukodystrophy is a neurometabolic disorder caused by inactivation of the peroxisomal ABCD1 transporter of very long-chain fatty acids. In mice, ABCD1 loss causes late onset axonal degeneration in the spinal cord in association with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. Increasing evidence indicates that oxidative stress and bioenergetic failure play major roles in the pathogenesis of X-linked adrenoleukodystrophy. In this study, we aimed to evaluate whether mitochondrial biogenesis is affected in X-linked adrenoleukodystrophy. We demonstrated that Abcd1 null mice show reduced mitochondrial DNA concomitant with downregulation of mitochondrial biogenesis pathway driven by PGC-1α/PPARγ and reduced expression of mitochondrial proteins cytochrome c, NDUFB8 and VDAC. Moreover, we show that the oral administration of pioglitazone, an agonist of PPARγ, restored mitochondrial content and expression of master regulators of biogenesis, neutralized oxidative damage to proteins and DNA, and reversed bioenergetic failure in terms of ATP levels, NAD+/NADH ratios, pyruvate kinase and glutathione reductase activities. Most importantly, the treatment halted locomotor disability and axonal damage in X-linked adrenoleukodystrophy mice. These results lend support to the use of pioglitazone in clinical trials with patients with adrenomyeloneuropathy and reveal novel molecular mechanisms of action of pioglitazone in neurodegeneration. Future studies should address the effects of this anti-diabetic drug on other axonopathies in which oxidative stress and mitochondrial dysfunction are contributing factors. PMID:23794606

  15. Model Development for A University-Based Learning Disability Clinic.

    ERIC Educational Resources Information Center

    Martin, Larry L.; And Others

    The report presents a model for appraisal and individualized educational programing for learning disabled children at the School of Education, Auburn University, Alabama. Descriptions by clinic staff of visitations to exemplary models and a summary of a regional conference on learning disabilities introduce the report. The clinic model is…

  16. A prosthesis-specific multi-link segment model of lower-limb amputee sprinting.

    PubMed

    Rigney, Stacey M; Simmons, Anne; Kark, Lauren

    2016-10-03

    Lower-limb amputees commonly utilize non-articulating energy storage and return (ESAR) prostheses for high impact activities such as sprinting. Despite these prostheses lacking an articulating ankle joint, amputee gait analysis conventionally features a two-link segment model of the prosthetic foot. This paper investigated the effects of the selected link segment model׳s marker-set and geometry on a unilateral amputee sprinter׳s calculated lower-limb kinematics, kinetics and energetics. A total of five lower-limb models of the Ottobock(®) 1E90 Sprinter were developed, including two conventional shank-foot models that each used a different version of the Plug-in-Gait (PiG) marker-set to test the effect of prosthesis ankle marker location. Two Hybrid prosthesis-specific models were then developed, also using the PiG marker-sets, with the anatomical shank and foot replaced by prosthesis-specific geometry separated into two segments. Finally, a Multi-link segment (MLS) model was developed, consisting of six segments for the prosthesis as defined by a custom marker-set. All full-body musculoskeletal models were tested using four trials of experimental marker trajectories within OpenSim 3.2 (Stanford, California, USA) to find the affected and unaffected hip, knee and ankle kinematics, kinetics and energetics. The geometry of the selected lower-limb prosthesis model was found to significantly affect all variables on the affected leg (p < 0.05), and the marker-set also significantly affected all variables on the affected leg, and none of the unaffected leg variables. The results indicate that the omission of prosthesis-specific spatial, inertial and elastic properties from full-body models significantly affects the calculated amputee gait characteristics, and we therefore recommend the implementation of a MLS model.

  17. Pex gene deletions in Gy and Hyp mice provide mouse models for X-linked hypophosphatemia.

    PubMed

    Strom, T M; Francis, F; Lorenz, B; Böddrich, A; Econs, M J; Lehrach, H; Meitinger, T

    1997-02-01

    X-linked hypophosphatemic rickets in humans is caused by mutations in the PEX gene which codes for a protein homologous to neutral endopeptidases. Hyp and Gy mice both have X-linked hypophosphatemic rickets, although genetic data and the different phenotypic spectra observed have previously suggested that two different genes are mutated. In addition to the metabolic disorder observed in Hyp mice, male Gy mice are sterile and show circling behavior and reduced viability. We now report the cloning of the mouse homolog of PEX which is highly conserved between man and mouse. The 3' end of this gene is deleted in Hyp mice. In Gy mice, the first three exons and the promotor region are deleted. Thus, Hyp and Gy are allelic mutations and both provide mouse models for X-linked hypophosphatemia.

  18. Analytical model and figures of merit for filtered Microwave Photonic Links.

    PubMed

    Gasulla, Ivana; Capmany, José

    2011-09-26

    The concept of filtered Microwave Photonic Links is proposed in order to provide the most general and versatile description of complex analog photonic systems. We develop a field propagation model where a global optical filter, characterized by its optical transfer function, embraces all the intermediate optical components in a linear link. We assume a non-monochromatic light source characterized by an arbitrary spectral distribution which has a finite linewidth spectrum and consider both intensity modulation and phase modulation with balanced and single detection. Expressions leading to the computation of the main figures of merit concerning the link gain, noise and intermodulation distortion are provided which, to our knowledge, are not available in the literature. The usefulness of this derivation resides in the capability to directly provide performance criteria results for complex links just by substituting in the overall closed-form formulas the numerical or measured optical transfer function characterizing the link. This theory is presented thus as a potential tool for a wide range of relevant microwave photonic application cases which is extendable to multiport radio over fiber systems.

  19. 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.

  20. Assessment of sea ice-atmosphere links in CMIP5 models

    NASA Astrophysics Data System (ADS)

    Boland, Emma J. D.; Bracegirdle, Thomas J.; Shuckburgh, Emily F.

    2016-09-01

    The Arctic is currently undergoing drastic changes in climate, largely thought to be due to so-called `Arctic amplification', whereby local feedbacks enhance global warming. Recently, a number of observational and modelling studies have questioned what the implications of this change in Arctic sea ice extent might be for weather in Northern Hemisphere midlatitudes, and in particular whether recent extremely cold winters such as 2009/10 might be consistent with an influence from observed Arctic sea ice decline. However, the proposed mechanisms for these links have not been consistently demonstrated. In a uniquely comprehensive cross-season and cross-model study, we show that the CMIP5 models provide no support for a relationship between declining Arctic sea ice and a negative NAM, or between declining Barents-Kara sea ice and cold European temperatures. The lack of evidence for the proposed links is consistent with studies that report a low signal-to-noise ratio in these relationships. These results imply that, whilst links may exist between declining sea ice and extreme cold weather events in the Northern Hemisphere, the CMIP5 model experiments do not show this to be a leading order effect in the long-term. We argue that this is likely due to a combination of the limitations of the CMIP5 models and an indication of other important long-term influences on Northern Hemisphere climate.

  1. The Link Between Mental Illness and Firearm Violence: Implications for Social Policy and Clinical Practice.

    PubMed

    Rozel, John S; Mulvey, Edward P

    2017-03-30

    The United States has substantially higher levels of firearm violence than most other developed countries. Firearm violence is a significant and preventable public health crisis. Mental illness is a weak risk factor for violence despite popular misconceptions reflected in the media and policy. That said, mental health professionals play a critical role in assessing their patients for violence risk, counseling about firearm safety, and guiding the creation of rational and evidence-based public policy that can be effective in mitigating violence risk without unnecessarily stigmatizing people with mental illness. This article summarizes existing evidence about the interplay among mental illness, violence, and firearms, with particular attention paid to the role of active symptoms, addiction, victimization, and psychosocial risk factors. The social and legal context of firearm ownership is discussed as a preface to exploring practical, evidence-driven, and behaviorally informed policy recommendations for mitigating firearm violence risk. Expected final online publication date for the Annual Review of Clinical Psychology Volume 13 is May 7, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  2. Air pollution, vascular disease and thrombosis: linking clinical data and pathogenic mechanisms.

    PubMed

    Franchini, M; Guida, A; Tufano, A; Coppola, A

    2012-12-01

    The public health burden of air pollution has been increasingly recognized over the last decades. Following the first assessed adverse effects on respiratory diseases and lung cancer, a large body of epidemiologic and clinical studies definitely documented an even stronger association of air pollution exposure with cardiovascular mortality and morbidity, particularly related to atherothrombotic (coronary and cerebrovascular) disease. Particulate matter (PM), mainly that with lower aerodynamic diameter (fine and ultrafine PM), is responsible for the most severe effects, due to its capacity to transport toxic substances deep into the lower airways. These effects have been shown to occur not only after short-term exposure to elevated concentrations of pollutants, but even after long-term relatively low levels of exposure. Vulnerable subjects (elderly persons and those with preexisting cardiopulmonary diseases) show the highest impact. Fewer and conflicting data also suggest an association with venous thromboembolism. Although not completely elucidated, a series of mechanisms have been hypothesized and tested in experimental settings. These phenomena, including vasomotor and cardiac autonomic dysfunction, hemostatic unbalance, oxidative stress and inflammatory response, have been shown to change over time and differently contribute to the short-term and long-term adverse effects of pollution exposure. Beyond environmental health policies, crucial for improving air quality and reducing the impact of such an elusive threat to public health, the recognition and assessment of the individual risk, together with specific advice, should be routinely implemented in the strategies of primary and secondary cardiovascular prevention.

  3. Discovery of Novel DNA Gyrase Inhibiting Spiropyrimidinetriones: Benzisoxazole Fusion with N-Linked Oxazolidinone Substituents Leading to a Clinical Candidate (ETX0914).

    PubMed

    Basarab, Gregory S; Doig, Peter; Galullo, Vincent; Kern, Gunther; Kimzey, Amy; Kutschke, Amy; Newman, Joseph P; Morningstar, Marshall; Mueller, John; Otterson, Linda; Vishwanathan, Karthick; Zhou, Fei; Gowravaram, Madhusudhan

    2015-08-13

    A novel class of bacterial type-II topoisomerase inhibitor displaying a spiropyrimidinetrione architecture fused to a benzisoxazole scaffold shows potent activity against Gram-positive and fastidious Gram-negative bacteria. Here, we describe a series of N-linked oxazolidinone substituents on the benzisoxazole that improve upon the antibacterial activity of initially described compounds of the class, show favorable PK properties, and demonstrate efficacy in an in vivo Staphylococcus aureus infection model. Inhibition of the topoisomerases DNA gyrase and topoisomerase IV from both Gram-positive and a Gram-negative organisms was demonstrated. Compounds showed a clean in vitro toxicity profile, including no genotoxicity and no bone marrow toxicity at the highest evaluated concentrations or other issues that have been problematic for some fluoroquinolones. Compound 1u was identified for advancement into human clinical trials for treatment of uncomplicated gonorrhea based on a variety of beneficial attributes including the potent activity and the favorable safety profile.

  4. Accelerated Corneal Collagen Cross-Linking Using Topography-Guided UV-A Energy Emission: Preliminary Clinical and Morphological Outcomes

    PubMed Central

    Mazzotta, Cosimo; Traversi, Claudio; Baiocchi, Stefano; Fontana, Luigi

    2016-01-01

    Purpose. To assess the clinical and morphological outcomes of topography-guided accelerated corneal cross-linking. Design. Retrospective case series. Methods. 21 eyes of 20 patients with progressive keratoconus were enrolled. All patients underwent accelerated cross-linking using an ultraviolet-A (UVA) exposure with an energy release varying from 7.2 J/cm2 up to 15 J/cm2, according to the topographic corneal curvature. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, topography, in vivo confocal microscopy (IVCM), and anterior segment optic coherence tomography (AS-OCT) were evaluated preoperatively and at the 1, 3, 6, and 12 months postoperatively. Results. 12 months after surgery UDVA and CDVA did not significantly vary from preoperative values. The average topographic astigmatism decreased from −4.61 ± 0.74 diopters (D) to −3.20 ± 0.81 D and coma aberration improved from 0.95 ± 0.03 μm to 0.88 ± 0.04 μm after surgery. AS-OCT and IVCM documented differential effects on the treated areas using different energies doses. The depths of demarcation line and keratocyte apoptosis were assessed. Conclusions. Preliminary results show correspondence between the energy dose applied and the microstructural stromal changes induced by the cross-linking at various depths in different areas of treated cornea. One year after surgery a significant reduction in the topographic astigmatism and comatic aberration was detected. None of the patients developed significant complications. PMID:28018671

  5. Evaluation of an enzyme-linked immunosorbent assay using purified, deglycosylated histoplasmin for different clinical manifestations of histoplasmosis

    PubMed Central

    Guimarães, Allan Jefferson; Pizzini, Claudia Vera; De Abreu Almeida, Marcos; Peralta, José Mauro; Nosanchuk, Joshua Daniel; Zancopé-Oliveira, Rosely Maria

    2010-01-01

    Diagnosis of invasive fungal diseases remains problematic, especially in undeveloped countries. We have developed an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to Histoplasma capsulatum using metaperiodate treated purified histoplasmin (ptHMIN). Our ELISA was validated comparing sera from patients with histoplasmosis, related mycoses, and healthy individuals. The overall test specificity was 96%, with sensitivities of 100% (8/8) in acute disease, 90% (9/10) in chronic disease, 89% (8/9) in disseminated infection in individuals without HIV infection, 86% (12/14) in disseminated disease in the setting of HIV infection and 100% (3/3) in mediastinal histoplasmosis. These parameters are superior to the use of untreated histoplasmin in diagnostic ELISAs. The high specificities, sensitivities, and simplicity of our ELISA support further development of a deglycosylated HMIN ELISA for clinical use and for monitoring the humoral immune response during therapy in patients with chronic and disseminated histoplasmosis. PMID:21691458

  6. 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

    2016-08-03

    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.

  7. Conceptual Models and Guidelines for Clinical Assessment of Financial Capacity.

    PubMed

    Marson, Daniel

    2016-09-01

    The ability to manage financial affairs is a life skill of critical importance, and neuropsychologists are increasingly asked to assess financial capacity across a variety of settings. Sound clinical assessment of financial capacity requires knowledge and appreciation of applicable clinical conceptual models and principles. However, the literature has presented relatively little conceptual guidance for clinicians concerning financial capacity and its assessment. This article seeks to address this gap. The article presents six clinical models of financial capacity : (1) the early gerontological IADL model of Lawton, (2) the clinical skills model and (3) related cognitive psychological model developed by Marson and colleagues, (4) a financial decision-making model adapting earlier decisional capacity work of Appelbaum and Grisso, (5) a person-centered model of financial decision-making developed by Lichtenberg and colleagues, and (6) a recent model of financial capacity in the real world developed through the Institute of Medicine. Accompanying presentation of the models is discussion of conceptual and practical perspectives they represent for clinician assessment. Based on the models, the article concludes by presenting a series of conceptually oriented guidelines for clinical assessment of financial capacity. In summary, sound assessment of financial capacity requires knowledge and appreciation of clinical conceptual models and principles. Awareness of such models, principles and guidelines will strengthen and advance clinical assessment of financial capacity.

  8. Molecular weight and galloylation affect grape seed extract constituents’ ability to cross-link dentin collagen in clinically relevant time

    PubMed Central

    Liu, Yi; Bai, Xinyan; Li, Shaohua; Liu, Ying; Keightley, Andrew; Wang, Yong

    2015-01-01

    Objective To investigate the relationship between the structures of polyphenolic compounds found in grape seed extract (GSE) and their activity in cross-linking dentin collagen in clinically relevant settings. Methods Representative monomeric and dimeric GSE constituents including (+)-catechin (pCT), (−)-catechin (CT), (−)-epicatechin (EC), (−)-epigallocatechin (EGC), (−)-epicatechin gallate (ECG), (−)-epigallocatechin gallate (EGCG), procyanidin B2 and a pCT-pCT dimer were purchased or synthesized. GSE was separated into low (PALM) and high molecular weight (PAHM) fractions. Human molars were processed into dentin films and beams. After demineralization, 11 groups of films (n=5) were treated for 1 min with the aforementioned reagents (1 wt% in 50/50 ethanol/water) and 1 group remained untreated. The films were studied by Fourier transform infrared spectroscopy (FTIR) followed by a quantitative mass spectroscopy-based digestion assay. Tensile properties of demineralized dentin beams were evaluated (n=7) after treatments (2h and 24h) with selective GSE species that were found to protect dentin collagen from collagenase. Results Efficacy of GSE constituents in cross-linking dentin collagen was dependent on molecular size and galloylation. Non-galloylated species with degree of polymerization up to two, including pCT, CT, EC, EGC, procyanidin B2 and pCT-pCT dimer were not active. Galloylated species were active starting from monomeric form, including ECG, EGCG, PALM, GSE and PAHM. PALM induced the best overall improvement in tensile properties of dentin collagen. Significance Identification under clinically relevant settings of structural features that contribute to GSE constituents’ efficacy in stabilizing demineralized dentin matrix has immediate impact on optimizing GSE’s use in dentin bonding. PMID:25958268

  9. 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.

  10. 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.

  11. 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)

  12. 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

  13. Equilibrium and kinetic modeling of adsorption of reactive dye on cross-linked chitosan beads.

    PubMed

    Chiou, Ming Shen; Li, Hsing Ya

    2002-07-22

    The adsorption of reactive dye (Reactive Red 189) from aqueous solutions on cross-linked chitosan beads was studied in a batch system. The equilibrium isotherms at different particle sizes (2.3-2.5, 2.5-2.7 and 3.5-3.8mm) and the kinetics of adsorption with respect to the initial dye concentration (4320, 5760 and 7286 g/m(3)), temperature (30, 40 and 50 degrees C), pH (1.0, 3.0, 6.0 and 9.0), and cross-linking ratio (cross-linking agent/chitosan weight ratio: 0.2, 0.5, 0.7 and 1.0) were investigated. Langmuir and Freundlich adsorption models were applied to describe the experimental isotherms and isotherm constants. Equilibrium data fitted very well to the Langmuir model in the entire saturation concentration range (0-1800 g/m(3)). The maximum monolayer adsorption capacities obtained from the Langmuir model are very large, which are 1936, 1686 and 1642 g/kg for small, mediumand large particle sizes, respectively, at pH 3.0, 30 degrees C, and the cross-linking ratio of 0.2. The pseudo first- and second-order kinetic models were used to describe the kinetic data, and the rate constants were evaluated. The experimental data fitted well to the second-order kinetic model, which indicates that the chemical sorption is the rate-limiting step, instead of mass transfer. The initial dye concentration and the solution pH both significantly affect the adsorption capacity, but the temperature and the cross-linking ratio are relatively minor factors. An increase in initial dye concentration results in the increase of adsorption capacity, which also increases with decreasing pH. The activation energy is 43.0 kJ/mol for the adsorption of the dye on the cross-linked chitosan beads at pH 3.0 and initial dye concentration 3768 g/m(3).

  14. 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

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

    DTIC Science & Technology

    2012-06-01

    Regueiro MD, Krasinskas AM, Saul M, Sapienza D, Binion DG, Hartman D. Mucosal IgG4 Cell Infiltration in Ulcerative Colitis (UC) is Linked to Disease ...Record-Linked Predictive Models to Optimize Care for Complex Digestive Diseases PRINCIPAL INVESTIGATOR: Michael A. Dunn, MD CONTRACTING...Framework for Smart Electronic Health Record-Linked Predictive Models to Optimize Care for Complex Digestive Diseases 5b. GRANT NUMBER W81XWH11-2

  16. 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

  17. Role of weakest links and system-size scaling in multiscale modeling of stochastic plasticity

    NASA Astrophysics Data System (ADS)

    Ispánovity, Péter Dusán; Tüzes, Dániel; Szabó, Péter; Zaiser, Michael; Groma, István

    2017-02-01

    Plastic deformation of crystalline and amorphous matter often involves intermittent local strain burst events. To understand the physical background of the phenomenon a minimal stochastic mesoscopic model was introduced, where details of the microstructure evolution are statistically represented in terms of a fluctuating local yield threshold. In the present paper we propose a method for determining the corresponding yield stress distribution for the case of crystal plasticity from lower scale discrete dislocation dynamics simulations which we combine with weakest link arguments. The success of scale linking is demonstrated by comparing stress-strain curves obtained from the resulting mesoscopic and the underlying discrete dislocation models in the microplastic regime. As shown by various scaling relations they are statistically equivalent and behave identically in the thermodynamic limit. The proposed technique is expected to be applicable to different microstructures and also to amorphous materials.

  18. 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.

  19. 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.

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

    PubMed

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

    1993-11-01

    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.

  1. 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

  2. X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options.

    PubMed

    Albert, Michael H; Bittner, Tanja C; Nonoyama, Shigeaki; Notarangelo, Lucia Dora; Burns, Siobhan; Imai, Kohsuke; Espanol, Teresa; Fasth, Anders; Pellier, Isabelle; Strauss, Gabriele; Morio, Tomohiro; Gathmann, Benjamin; Noordzij, Jeroen G; Fillat, Cristina; Hoenig, Manfred; Nathrath, Michaela; Meindl, Alfons; Pagel, Philipp; Wintergerst, Uwe; Fischer, Alain; Thrasher, Adrian J; Belohradsky, Bernd H; Ochs, Hans D

    2010-04-22

    A large proportion of patients with mutations in the Wiskott-Aldrich syndrome (WAS) protein gene exhibit the milder phenotype termed X-linked thrombocytopenia (XLT). Whereas stem cell transplantation at an early age is the treatment of choice for patients with WAS, therapeutic options for patients with XLT are controversial. In a retrospective multicenter study we defined the clinical phenotype of XLT and determined the probability of severe disease-related complications in patients older than 2 years with documented WAS gene mutations and mild-to-moderate eczema or mild, infrequent infections. Enrolled were 173 patients (median age, 11.5 years) from 12 countries spanning 2830 patient-years. Serious bleeding episodes occurred in 13.9%, life-threatening infections in 6.9%, autoimmunity in 12.1%, and malignancy in 5.2% of patients. Overall and event-free survival probabilities were not significantly influenced by the type of mutation or intravenous immunoglobulin or antibiotic prophylaxis. Splenectomy resulted in increased risk of severe infections. This analysis of the clinical outcome and molecular basis of patients with XLT shows excellent long-term survival but also a high probability of severe disease-related complications. These observations will allow better decision making when considering treatment options for individual patients with XLT.

  3. Constructing a Conceptual Model Linking Drivers and Ecosystem Services in Piedmont Streams

    DTIC Science & Technology

    2011-04-01

    CONSTRUCTING A CONCEPTUAL MODEL LINKING DRIVERS AND ECOSYSTEM SERVICES IN PIEDMONT STREAMS S . Kyle McKay1, Bruce A. Pruitt1, Christopher J...5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7...PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) U.S. Army Engineer Research and Development Center,Athens,GA,30606 8. PERFORMING ORGANIZATION REPORT NUMBER

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

    DTIC Science & Technology

    2013-08-01

    etc, disease location descriptors, Lupus , Thyroid disease, Rheumatoid arthritis, history of Appendectomy, psoriasis. The Crohn’s work is also...of a patient’s clinical history . This information is usually not rich enough to develop predictive models. To construct a useful patient profile...collaboration to achieve this goal given their history of successful development of informatics applications and our clinical research in complex GI

  5. AR intragenic deletions linked to androgen receptor splice variant expression and activity in models of prostate cancer progression.

    PubMed

    Li, Y; Hwang, T H; Oseth, L A; Hauge, A; Vessella, R L; Schmechel, S C; Hirsch, B; Beckman, K B; Silverstein, K A; Dehm, S M

    2012-11-08

    Reactivation of the androgen receptor (AR) during androgen depletion therapy (ADT) underlies castration-resistant prostate cancer (CRPCa). Alternative splicing of the AR gene and synthesis of constitutively active COOH-terminally truncated AR variants lacking the AR ligand-binding domain has emerged as an important mechanism of ADT resistance in CRPCa. In a previous study, we demonstrated that altered AR splicing in CRPCa 22Rv1 cells was linked to a 35-kb intragenic tandem duplication of AR exon 3 and flanking sequences. In this study, we demonstrate that complex patterns of AR gene copy number imbalances occur in PCa cell lines, xenografts and clinical specimens. To investigate whether these copy number imbalances reflect AR gene rearrangements that could be linked to splicing disruptions, we carried out a detailed analysis of AR gene structure in the LuCaP 86.2 and CWR-R1 models of CRPCa. By deletion-spanning PCR, we discovered a 8579-bp deletion of AR exons 5, 6 and 7 in the LuCaP 86.2 xenograft, which provides a rational explanation for synthesis of the truncated AR v567es AR variant in this model. Similarly, targeted resequencing of the AR gene in CWR-R1 cells led to the discovery of a 48-kb deletion in AR intron 1. This intragenic deletion marked a specific CWR-R1 cell population with enhanced expression of the truncated AR-V7/AR3 variant, a high level of androgen-independent AR transcriptional activity and rapid androgen independent growth. Together, these data demonstrate that structural alterations in the AR gene are linked to stable gain-of-function splicing alterations in CRPCa.

  6. 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

  7. 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.

  8. 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.

  9. 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.

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

    PubMed Central

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

    2015-01-01

    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

  11. Link between statistical equilibrium fidelity and forecasting skill for complex systems with model error.

    PubMed

    Majda, Andrew J; Gershgorin, Boris

    2011-08-02

    Understanding and improving the predictive skill of imperfect models for complex systems in their response to external forcing is a crucial issue in diverse applications such as for example climate change science. Equilibrium statistical fidelity of the imperfect model on suitable coarse-grained variables is a necessary but not sufficient condition for this predictive skill, and elementary examples are given here demonstrating this. Here, with equilibrium statistical fidelity of the imperfect model, a direct link is developed between the predictive fidelity of specific test problems in the training phase where the perfect natural system is observed and the predictive skill for the forced response of the imperfect model by combining appropriate concepts from information theory with other concepts based on the fluctuation dissipation theorem. Here a suite of mathematically tractable models with nontrivial eddy diffusivity, variance, and intermittent non-Gaussian statistics mimicking crucial features of atmospheric tracers together with stochastically forced standard eddy diffusivity approximation with model error are utilized to illustrate this link.

  12. 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.

  13. 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

  14. 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.

  15. A simple pharmacokinetic model linking plasma progesterone concentrations with the hormone released from bovine intravaginal inserts.

    PubMed

    Mariano, R N; Turino, L N; Cabrera, M I; Scándolo, D E; Maciel, M G; Grau, R J A

    2010-10-01

    On the basis of pharmacokinetic modeling, this study provides some insights into predicting in vivo plasma progesterone concentrations when using bovine intravaginal inserts for systemic progesterone delivery. More significantly, this contribution is the first attempt to build a simple pharmacokinetic model that links plasma progesterone concentrations with the hormone released from bovine intravaginal inserts. After evaluating three rival pharmacokinetic models and considering some phenomena involved in the intravaginal administration of progesterone, a primary pharmacokinetic model having a good data fitting capability with only two adjustable parameters is proposed to the above mentioned task. Kinetic parameters are given for lactating Holstein dairy cows with two levels of daily milk yields; and non-pregnant, non-lactating Holstein-Friesian cattle. Model predictions indicate the occurrence of a preferential distribution of the intravaginally administered progesterone dose through a first uterine pass effect.

  16. Clinical pharmacology of analgesics assessed with human experimental pain models: bridging basic and clinical research

    PubMed Central

    Oertel, Bruno Georg; Lötsch, Jörn

    2013-01-01

    The medical impact of pain is such that much effort is being applied to develop novel analgesic drugs directed towards new targets and to investigate the analgesic efficacy of known drugs. Ongoing research requires cost-saving tools to translate basic science knowledge into clinically effective analgesic compounds. In this review we have re-examined the prediction of clinical analgesia by human experimental pain models as a basis for model selection in phase I studies. The overall prediction of analgesic efficacy or failure of a drug correlated well between experimental and clinical settings. However, correct model selection requires more detailed information about which model predicts a particular clinical pain condition. We hypothesized that if an analgesic drug was effective in an experimental pain model and also a specific clinical pain condition, then that model might be predictive for that particular condition and should be selected for development as an analgesic for that condition. The validity of the prediction increases with an increase in the numbers of analgesic drug classes for which this agreement was shown. From available evidence, only five clinical pain conditions were correctly predicted by seven different pain models for at least three different drugs. Most of these models combine a sensitization method. The analysis also identified several models with low impact with respect to their clinical translation. Thus, the presently identified agreements and non-agreements between analgesic effects on experimental and on clinical pain may serve as a solid basis to identify complex sets of human pain models that bridge basic science with clinical pain research. PMID:23082949

  17. A data model that captures clinical reasoning about patient problems.

    PubMed Central

    Barrows, R. C.; Johnson, S. B.

    1995-01-01

    We describe a data model that has been implemented for the CPMC Ambulatory Care System, and exemplify its function for patient problems. The model captures some nuances of clinical thinking about patients that are not accommodated in most other models, such as an evolution of clinical understanding about patient problems. A record of this understanding has clinical utility, and serves research interests as well as medical audit concerns. The model is described with an example, and advantages and limitations in the current implementation are discussed. PMID:8563311

  18. Linking models of land use, resources, and economy to simulate the development of mountain regions (ALPSCAPE).

    PubMed

    Lundström, Corinne; Kytzia, Susanne; Walz, Ariane; Gret-Regamey, Adrienne; Bebi, Peter

    2007-09-01

    We present a framework of a scenario-based model that simulates the development of the municipality of Davos (Swiss Alps). We illustrate our method with the calculation of the scenario for 2050 "Decrease in subsidies for mountain agriculture and liberalization of markets." The main objective was to link submodels of land-use allocation (regression-based approach), material and energy flows submodels (Material and Energy Flux Analysis), and economic submodels (Input-Output Analysis). Letting qualitative and quantitative information flow from one submodel to the next, following the storyline describing a scenario, has proven to be suitable for linking submodels. The succession of the submodels is then strongly dependent on the scenario. Qualitative information flows are simulated with microsimulations of actor choices. Links between the submodels show different degrees of robustness: although the links involving microsimulations are the weakest, the uncertainty introduced by the land-use allocation model is actually advantageous because it allows one possible change in the landscape in the future to be simulated. The modeling results for the scenario here presented show that the disappearance of agriculture only marginally affects the region's factor income, but that the consequences for the self-sufficiency rate, for various landscape-related indicators and ecosystem services, and for the economy in the long term may be considerable. These benefits compensate for agriculture's modest direct economic value. The framework presented can potentially be applied to any region and scenario. This framework provides a basis for a learning package that allows potential detrimental consequences of regional development to be anticipated at an early stage.

  19. Conformational analysis of a covalently cross-linked Watson-Crick base pair model.

    PubMed

    Jensen, Erik A; Allen, Benjamin D; Kishi, Yoshito; O'Leary, Daniel J

    2008-11-15

    Low-temperature NMR experiments and molecular modeling have been used to characterize the conformational behavior of a covalently cross-linked DNA base pair model. The data suggest that Watson-Crick or reverse Watson-Crick hydrogen bonding geometries have similar energies and can interconvert at low temperatures. This low-temperature process involves rotation about the crosslink CH(2)C(5') (psi) carbon-carbon bond, which is energetically preferred over the alternate CH(2)N(3) (phi) carbon-nitrogen bond rotation.

  20. Viscoelastic Model of Cross-Linked Polyethylene Including Effects of Temperature and Crystallinity

    NASA Astrophysics Data System (ADS)

    Olasz, L.; Gudmundson, P.

    2005-12-01

    Characterization of the mechanical behavior of cross-linked polyethylene (XLPE) commonly used in high voltage cable insulation was performed by an extensive set of isothermal uniaxial tensile relaxation tests. Tensile relaxation experiments were complemented by pressure-volume-temperature experiments as well as density and crystallinity measurements. Based on the experimental results, a viscoelastic power law model with four parameters was formulated, incorporating temperature and crystallinity dependence. It was found that a master curve can be developed by both horizontal and vertical shifting of the relaxation curves. The model was evaluated by making comparisons of the predicted stress responses with the measured responses in relaxation tests with transient temperature histories.

  1. A clinical internship model for the nurse practitioner programme.

    PubMed

    Lee, Geraldine A; Fitzgerald, Les

    2008-11-01

    Nurse practitioners in Victoria, Australia must be prepared to Masters level before seeking nurse practitioner (NP) endorsement. The challenge from a university curriculum development perspective was to develop a programme that prepares the NP theoretically and clinically for their advanced practice role. The aim of this discussion paper is to outline how the internship model was developed and report the students' opinions on the model. The NP students complete the internship with a suitably qualified mentor which requires them to work together to develop and maintain a clinical learning plan, keep a log of the weekly meetings that shows how the objectives have been achieved. The internship includes advanced clinical assessment, prescribing, diagnostic and treatment skills and knowledge related to the nurse's specialty. The clinical assessment tool incorporates the National Competency Standards for the Nurse Practitioner and allows students and mentors to identify the level of practice and set clinical objectives. Students were asked to give feedback on the clinical internship and overall their comments were favourable, reporting benefits of a clinical mentor in their work and the clinical case presentations. The clinical internship allows the acquisition of knowledge and clinical skills in the clinical specialty with an expert clinical mentor in this innovative programme.

  2. 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.

  3. Molecular and clinical implementations of ovarian cancer mouse avatar models

    PubMed Central

    Zayed, Amira A.; Mandrekar, Sumithra J.; Haluska, Paul

    2016-01-01

    Innovation in oncology drug development has been hindered by lack of preclinical models that reliably predict clinical activity of novel therapies in cancer patients. Increasing desire for individualize treatment of patients with cancer has led to an increase in the use of patient-derived xenografts (PDX) engrafted into immune-compromised mice for preclinical modeling. Large numbers of tumor-specific PDX models have been established and proved to be powerful tools in pre-clinical testing. A subset of PDXs, referred to as Avatars, establish tumors in an orthotopic and treatment naïve fashion that may represent the most clinical relevant model of individual human cancers. This review will discuss ovarian cancer (OC) PDX models demonstrating the opportunities and limitations of these models in cancer drug development, and describe concepts of clinical trials design in Avatar guided therapy. PMID:26408297

  4. Determination of urban groundwater pollution in alluvial aquifer using linked process models considering urban water cycle

    NASA Astrophysics Data System (ADS)

    Vizintin, Goran; Souvent, Petra; Veselič, Miran; Cencur Curk, Barbara

    2009-10-01

    SummaryThis paper presents the results of the 5th FP project AISUWRS (Assessing and Improving the Sustainability of Urban Water Resources and Systems) which aimed to assess the impact of the urban water infrastructure to underlying or nearby aquifers with the urban water balance modelling approach - a chain of different models that handle with contaminant fluxes and the movement of contaminants from the urban infrastructure into the underlying aquifer. An existing urban water management model UVQ was linked to a model for sewer infiltration and exfiltration (NEIMO), as well as unsaturated zone models (SLeakI/POSI, UL_FLOW) with existing numerical groundwater models. The linked process models offer the prospect of better quantification of urban water balance and contaminant loads, including improved estimates of total recharge and its components in urban areas. Once the model framework has been set up for a selected city, it can easily be updated in the future and it can be used for other purposes like planning of local remediation measures in the vicinity of individual contaminant spillages. This paper describes the application and results of the urban water model chain for the city of Ljubljana, which is the capital of Slovenia. The results from this study suggest that residential land-uses in urban areas with thick unsaturated zone may have significantly smaller impact on the groundwater than agriculture or industry. This can be seen as a speculative understanding of the groundwater pollutions problems. In this respect, use of sustainable urban development systems like on-site infiltration of roof runoff and improved sewer control and standards could result in better groundwater quality.

  5. 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

    2014-09-12

    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.

  6. 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.

  7. Juvenile retinoschisis: a model for molecular diagnostic testing of X-linked ophthalmic disease.

    PubMed Central

    Sieving, P A; Yashar, B M; Ayyagari, R

    1999-01-01

    BACKGROUND AND PURPOSE: X-linked juvenile retinoschisis (RS) provides a starting point to define clinical paradigms and understand the limitations of diagnostic molecular testing. The RS phenotype is specific, but the broad severity range is clinically confusing. Molecular diagnostic testing obviates unnecessary examinations for boys at-risk and identifies carrier females who otherwise show no clinical signs. METHODS: The XLRS1 gene has 6 exons of 26-196 base-pair size. Each exon is amplified by a single polymerase chain reaction and then sequenced, starting with exons 4 through 6, which contain mutation "hot spots." RESULTS: The 6 XLRS1 exons are sequenced serially. If alterations are found, they are compared with mutations in our > 120 XLRS families and with the > 300 mutations reported worldwide. Point mutations, small deletions, or rearrangements are identified in nearly 90% of males with a clinical diagnosis of RS. XLRS1 has very few sequence polymorphisms. Carrier-state testing produces 1 of 3 results: (1) positive, in which the woman has the same mutation as an affected male relative or known in other RS families; (2) negative, in which she lacks the mutation of her affected male relative; and (3) uninformative, in which no known mutation is identified or no information exists about the familial mutation. CONCLUSIONS: Molecular RS screening is an effective diagnostic tool that complements the clinician's skills for early detection of at-risk males. Useful outcomes of carrier testing depend on several factors: (1) a male relative with a clear clinical diagnosis; (2) a well-defined inheritance pattern; (3) high disease penetrance; (4) size and organization of the gene; and (5) the types of disease-associated mutations. Ethical questions include molecular diagnostic testing of young at-risk females before the age of consent, the impact of this information on the emotional health of the patient and family, and issues of employability and insurance coverage

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

    DOE PAGES

    Safta, C.; Ricciuto, Daniel M.; Sargsyan, Khachik; ...

    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 employedmore » in the second part of the paper to assess the predictive skill of the model via posterior predictive checks.« less

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

    SciTech Connect

    Safta, C.; Ricciuto, Daniel M.; Sargsyan, Khachik; Debusschere, B.; Najm, H. N.; Williams, M.; Thornton, Peter 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.

  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. 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.

  12. 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.

  13. Tumour targeting of humanised cross-linked divalent-fab′ antibody fragments: a clinical phase I/II study

    PubMed Central

    Casey, J L; Napier, M P; King, D J; Pedley, R B; Chaplin, L C; Weir, N; Skelton, L; Green, A J; Hope-Stone, L D; Yarranton, G T; Begent, R H J

    2002-01-01

    Antibody engineering has made it possible to design antibodies with optimal characteristics for delivery of radionuclides for tumour imaging and therapy. A humanised divalent-Fab′ cross-linked with a bis-maleimide linker referred to as humanised divalent-Fab′ maleimide was produced as a result of this design process. It is a humanised divalent antibody with no Fc, which can be produced in bacteria and has enhanced stability compared with F(ab′)2. Here we describe a clinical study in patients with colorectal cancer using humanised divalent-Fab′ maleimide generated from the anti-carcinoembryonic antigen antibody A5B7 radiolabelled with iodine-131. Ten patients received an i.v. injection of iodine-131-labelled A5B7 humanised divalent-Fab′ maleimide, and positive tumour images were obtained by gamma camera imaging in eight patients with known lesions, and one previously undetected lesion was identified. True negative results were obtained in two patients without tumour. Area under the curve analysis of serial blood gamma counting and gamma camera images showed a higher tumour to blood ratio compared to A5B7 mF(ab′)2 used previously in the clinic, implying this new molecule may be superior for radioimmunotherapy. MIRD dose calculations showed a relatively high radiation dose to the kidney, which may limit the amount of activity that could be administered in radioimmunotherapy. However the reduction in immunogenicity was also a major advantage for A5B7 humanised divalent-Fab′ maleimide over murine versions of this antibody suggesting that humanised divalent-Fab′ maleimide should be a useful vehicle for repeated therapies. British Journal of Cancer (2002) 86, 1401–1410. DOI: 10.1038/sj/bjc/6600198 www.bjcancer.com © 2002 Cancer Research UK PMID:11986771

  14. Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.

    PubMed

    Naves, Luciana A; Daly, Adrian F; Dias, Luiz Augusto; Yuan, Bo; Zakir, Juliano Coelho Oliveira; Barra, Gustavo Barcellos; Palmeira, Leonor; Villa, Chiara; Trivellin, Giampaolo; Júnior, Armindo Jreige; Neto, Florêncio Figueiredo Cavalcante; Liu, Pengfei; Pellegata, Natalia S; Stratakis, Constantine A; Lupski, James R; Beckers, Albert

    2016-02-01

    X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome.

  15. Structural equation modeling in the context of clinical research

    PubMed Central

    2017-01-01

    Structural equation modeling (SEM) has been widely used in economics, sociology and behavioral science. However, its use in clinical medicine is quite limited, probably due to technical difficulties. Because SEM is particularly suitable for analysis of complex relationships among observed variables, it must have potential applications to clinical medicine. The article introduces basic ideas of SEM in the context of clinical medicine. A simulated dataset is employed to show how to do model specification, model fit, visualization and assessment of goodness-of-fit. The first example fits a SEM with continuous outcome variable using sem() function, and the second explores the binary outcome variable using lavaan() function. PMID:28361067

  16. 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

    2016-08-23

    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.

  17. 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

  18. 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.

  19. Group-based trajectory modeling in clinical research.

    PubMed

    Nagin, Daniel S; Odgers, Candice L

    2010-01-01

    Group-based trajectory models are increasingly being applied in clinical research to map the developmental course of symptoms and assess heterogeneity in response to clinical interventions. In this review, we provide a nontechnical overview of group-based trajectory and growth mixture modeling alongside a sampling of how these models have been applied in clinical research. We discuss the challenges associated with the application of both types of group-based models and propose a set of preliminary guidelines for applied researchers to follow when reporting model results. Future directions in group-based modeling applications are discussed, including the use of trajectory models to facilitate causal inference when random assignment to treatment condition is not possible.

  20. Human models of pain for the prediction of clinical analgesia.

    PubMed

    Lötsch, Jörn; Oertel, Bruno G; Ultsch, Alfred

    2014-10-01

    Human experimental pain models are widely used to study drug effects under controlled conditions. However, efforts to improve both animal and human experimental model selection, on the basis of increased understanding of the underlying pathophysiological pain mechanisms, have been disappointing, with poor translation of results to clinical analgesia. We have developed an alternative approach to the selection of suitable pain models that can correctly predict drug efficacy in particular clinical settings. This is based on the analysis of successful or unsuccessful empirical prediction of clinical analgesia using experimental pain models. We analyzed statistically the distribution of published mutual agreements or disagreements between drug efficacy in experimental and clinical pain settings. Significance limits were derived by random permutations of agreements. We found that a limited subset of pain models predicts a large number of clinically relevant pain settings, including efficacy against neuropathic pain for which novel analgesics are particularly needed. Thus, based on empirical evidence of agreement between drugs for their efficacy in experimental and clinical pain settings, it is possible to identify pain models that reliably predict clinical analgesic drug efficacy in cost-effective experimental settings.

  1. Clinical results of the wear performance of cross-linked polyethylene in total hip arthroplasty: prospective randomized trial.

    PubMed

    Ise, Kentaro; Kawanabe, Keiichi; Tamura, Jiro; Akiyama, Haruhiko; Goto, Koji; Nakamura, Takashi

    2009-12-01

    To investigate the clinical results of cross-linked polyethylene (CLPE) and to compare the CLPE wear against zirconia and stainless steel heads, we studied the radiographic wear after a minimum 3-year follow-up in total hip arthroplasty (THA). Ninety-four hips were randomly implanted with a 22.225-mm head cemented THA-the group of non-CLPE against zirconia and CLPE against 2 different zirconias and stainless steel. The linear wear rate was significantly lower in the group of CLPE against zirconia (0.067, 0.059 mm/y) and against stainless steel (0.068 mm/y) compared with non-CLPE against zirconia (0.170 mm/y). In the short-term results, the wear performance of CLPE against zirconia was superior to that of non-CLPE; however, it did not show a better wear rate than CLPE against stainless steel. Furthermore, long-term investigations will be necessary for understanding CLPE wear in vivo.

  2. A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.

    PubMed

    Patel, R M; Nagamani, S C S; Cuthbertson, D; Campeau, P M; Krischer, J P; Shapiro, J R; Steiner, R D; Smith, P A; Bober, M B; Byers, P H; Pepin, M; Durigova, M; Glorieux, F H; Rauch, F; Lee, B H; Hart, T; Sutton, V R

    2015-02-01

    Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing.

  3. 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.

  4. Synthesis, cholinesterase inhibition and molecular modelling studies of coumarin linked thiourea derivatives.

    PubMed

    Saeed, Aamer; Zaib, Sumera; Ashraf, Saba; Iftikhar, Javeria; Muddassar, Muhammad; Zhang, Kam Y J; Iqbal, Jamshed

    2015-12-01

    Alzheimer's disease is among the most widespread neurodegenerative disorder. Cholinesterases (ChEs) play an indispensable role in the control of cholinergic transmission and thus the acetylcholine level in the brain is enhanced by inhibition of ChEs. Coumarin linked thiourea derivatives were designed, synthesized and evaluated biologically in order to determine their inhibitory activity against acetylcholinesterases (AChE) and butyrylcholinesterases (BChE). The synthesized derivatives of coumarin linked thiourea compounds showed potential inhibitory activity against AChE and BChE. Among all the synthesized compounds, 1-(2-Oxo-2H-chromene-3-carbonyl)-3-(3-chlorophenyl)thiourea (2e) was the most potent inhibitor against AChE with an IC50 value of 0.04±0.01μM, while 1-(2-Oxo-2H-chromene-3-carbonyl)-3-(2-methoxyphenyl)thiourea (2b) showed the most potent inhibitory activity with an IC50 value of 0.06±0.02μM against BChE. Molecular docking simulations were performed using the homology models of both cholinesterases in order to explore the probable binding modes of inhibitors. Results showed that the novel synthesized coumarin linked thiourea derivatives are potential candidates to develop for potent and efficacious acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors.

  5. 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.

  6. 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.

  7. Neoproterozoic paleogeography of the Tarim Block: An extended or alternative "missing-link" model for Rodinia?

    NASA Astrophysics Data System (ADS)

    Wen, Bin; Evans, David A. D.; Li, Yong-Xiang

    2017-01-01

    Recent reconstructions of the Rodinia supercontinent and its breakup incorporate South China as a ;missing link; between Australia and Laurentia, and place the Tarim craton adjacent to northwestern Australia on the supercontinent's periphery. However, subsequent kinematic evolution toward Gondwana amalgamation requires complex geometric shuffling between South China and Tarim, which cannot be easily resolved with the stratigraphic records of those blocks. Here we present new paleomagnetic data from early Ediacaran strata of northwest Tarim, and document large-scale rotation at near-constant paleolatitudes during Cryogenian time. The rotation is coeval with Rodinia breakup, and Tarim's paleolatitudes are compatible with its placement between Australia and Laurentia, either by itself as an alternative ;missing link; or joined with South China in that role. At the same time, indications of subduction-related magmatism in Tarim's Neoproterozoic record suggest that Rodinia breakup was dynamically linked to subduction retreat along its northern margin. Such a model is akin to early stages of Jurassic fragmentation within southern Gondwana, and implies more complicated subduction-related dynamics of supercontinent breakup than superplume impingement alone.

  8. 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....

  9. 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…

  10. Four Factors of Clinical Decision Making: A Teaching Model.

    ERIC Educational Resources Information Center

    Leist, James C.; Konen, Joseph C.

    1996-01-01

    Four factors of clinical decision making identified by medical students include quality of care, cost, ethics, and legal concerns. This paper argues that physicians have two responsibilities in the clinical decision-making model: to be the primary advocate for quality health care and to ensure balance among the four factors, working in partnership…

  11. Organizational Models of Medical School Relationships to the Clinical Enterprise.

    ERIC Educational Resources Information Center

    Culbertson, Richard A.; And Others

    1996-01-01

    Analyzed existing relationships between medical schools and clinical enterprises to develop models of these relationships. Four conceptual models were identified: (1) "single ownership, owned integrated system"; (2) "general partner"; (3) "limited partner"; and (4) "wholly owned, subsidiary." The advantages and disadvantages of each model are…

  12. A Model for Evaluating Student Clinical Psychomotor Skills.

    ERIC Educational Resources Information Center

    And Others; Fiel, Nicholas J.

    1979-01-01

    A long-range plan to evaluate medical students' physical examination skills was undertaken at the Ingham Family Medical Clinic at Michigan State University. The development of the psychomotor skills evaluation model to evaluate the skill of blood pressure measurement, tests of the model's reliability, and the use of the model are described. (JMD)

  13. 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

  14. 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

  15. Link between hopping models and percolation scaling laws for charge transport in mixtures of small molecules

    SciTech Connect

    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) 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.

  16. 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.

  17. Exploring the link between emotional and behavioral dysregulation: a test of the emotional cascade model.

    PubMed

    Tuna, Ezgi; Bozo, Özlem

    2014-01-01

    The emotional cascade model (Selby, Anestis, & Joiner, 2008) posits that the link between emotional and behavioral dysregulation may be through emotional cascades, which are repetitive cycles of rumination and negative affect that result in an intensification of emotional distress. Dysregulated behaviors, such as non-suicidal self-injury, are used to reduce aversive emotions and distract the person from ruminative processes. The aim of the present study was to investigate the emotional cascade model in a non-Western sample of Turkish university students. Accordingly, a structural equation model was tested, and the results demonstrated that the emotional cascades were indeed associated to dysregulated behaviors, even when the effect of current symptoms of depression and anxiety on behavioral dysregulation was statistically controlled. Furthermore, thought suppression had a stronger relationship with all symptom patterns as compared to rumination, which may point to a cultural difference. Possible implications of the findings are discussed.

  18. Bayesian analysis of an admixture model with mutations and arbitrarily linked markers.

    PubMed

    Excoffier, Laurent; Estoup, Arnaud; Cornuet, Jean-Marie

    2005-03-01

    We introduce here a Bayesian analysis of a classical admixture model in which all parameters are simultaneously estimated. Our approach follows the approximate Bayesian computation (ABC) framework, relying on massive simulations and a rejection-regression algorithm. Although computationally intensive, this approach can easily deal with complex mutation models and partially linked loci, and it can be thoroughly validated without much additional computation cost. Compared to a recent maximum-likelihood (ML) method, the ABC approach leads to similarly accurate estimates of admixture proportions in the case of recent admixture events, but it is found superior when the admixture is more ancient. All other parameters of the admixture model such as the divergence time between parental populations, the admixture time, and the population sizes are also well estimated, unlike the ML method. The use of partially linked markers does not introduce any particular bias in the estimation of admixture, but ML confidence intervals are found too narrow if linkage is not specifically accounted for. The application of our method to an artificially admixed domestic bee population from northwest Italy suggests that the admixture occurred in the last 10-40 generations and that the parental Apis mellifera and A. ligustica populations were completely separated since the last glacial maximum.

  19. 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.

  20. Bridging the HL7 template - 13606 archetype gap with detailed clinical models.

    PubMed

    Goossen, William T F; Goossen-Baremans, Anneke

    2010-01-01

    The idea of two level modeling has been taken up in healthcare information systems development. There is ongoing debate which approach should be taken. From the premise that there is a lack of clinician's time available, and the need for semantic interoperability, harmonization efforts are important. The question this paper addresses is whether Detailed Clinical Models (DCM) can bridge the gap between existing approaches. As methodology, a bottom up approach in multilevel comparison of existing content and modeling is used. Results indicate that it is feasible to compare and reuse DCM with clinical content from one approach to the other, when specific limitations are taken into account and precise analysis of each data-item is carried out. In particular the HL7 templates, the ISO/CEN 13606 and OpenEHR archetypes reveal more commonalties than differences. The linkage of DCM to terminologies suggests that data-items can be linked to concepts present in multiple terminologies. This work concludes that it is feasible to model a multitude of precise items of clinical information in the format of DCM and that transformations between different approaches are possible without loss of meaning. However, a set of single or combined clinical items and assessment scales have been tested. Larger groupings of clinical information might bring up more challenges.

  1. 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.

  2. Ensuring congruency in multiscale modeling: towards linking agent based and continuum biomechanical models of arterial adaptation.

    PubMed

    Hayenga, Heather N; Thorne, Bryan C; Peirce, Shayn M; Humphrey, Jay D

    2011-11-01

    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.

  3. 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.

  4. Linking market interaction intensity of 3D Ising type financial model with market volatility

    NASA Astrophysics Data System (ADS)

    Fang, Wen; Ke, Jinchuan; Wang, Jun; Feng, Ling

    2016-11-01

    Microscopic interaction models in physics have been used to investigate the complex phenomena of economic systems. The simple interactions involved can lead to complex behaviors and help the understanding of mechanisms in the financial market at a systemic level. This article aims to develop a financial time series model through 3D (three-dimensional) Ising dynamic system which is widely used as an interacting spins model to explain the ferromagnetism in physics. Through Monte Carlo simulations of the financial model and numerical analysis for both the simulation return time series and historical return data of Hushen 300 (HS300) index in Chinese stock market, we show that despite its simplicity, this model displays stylized facts similar to that seen in real financial market. We demonstrate a possible underlying link between volatility fluctuations of real stock market and the change in interaction strengths of market participants in the financial model. In particular, our stochastic interaction strength in our model demonstrates that the real market may be consistently operating near the critical point of the system.

  5. Pre-clinical drug tests in the mdx mouse as a model of dystrophinopathies: an overview.

    PubMed

    De Luca, Annamaria

    2012-05-01

    Duchenne muscular dystrophy is a lethal X-linked muscle disease affecting 1/3500 live male birth. It results from defects in the subsarcolemmal protein dystrophin, a component of the dystrophin-glycoprotein complex (DGC) which links the intracellular cytoskeleton to the extracellular matrix. The absence of dystrophin leads to muscle membrane fragility, muscle necrosis and gradual replacement of skeletal muscle by fat and connective tissue, through a complex and still unclear cascade of interconnecting events. No cure is currently available, with glucocorticoids being the sole drugs in clinical use in spite of their remarkable side effects. A great effort is devoted at performing pre-clinical tests on the mdx mouse, the mostly used homologous animal model for DMD, with the final aim to identify drugs safer than steroids and able to target the pathogenic mechanisms so to delay pathology progression. This review updates the efforts on this topic, focusing on the open issues about the animal model and highlighting the classes of pharmaceuticals that are more promising as disease-modifiers, while awaiting for more corrective therapies. Although caution is necessary in data transfer from mdx model to DMD patients, the implementation of standard operating procedures and the growing understanding of the pathology may allow a more accurate evaluation of therapeutics, alone or in combination, in pre-clinical settings. A continuous cross-talk with clinicians and patients associations are also crucial points for proper translation of data from mouse to bedside.

  6. New links between SOD1 and metabolic dysfunction from a yeast model of amyotrophic lateral sclerosis

    PubMed Central

    Bastow, Emma L.; Peswani, Amber R.; Tarrant, Daniel S. J.; Pentland, Daniel R.; Chen, Xi; Staniforth, Gemma L.; Rowe, Michelle L.; Howard, Mark J.

    2016-01-01

    ABSTRACT A number of genes have been linked to familial forms of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS). Over 150 mutations within the gene encoding superoxide dismutase 1 (SOD1) have been implicated in ALS, but why such mutations lead to ALS-associated cellular dysfunction is unclear. In this study, we identify how ALS-linked SOD1 mutations lead to changes in the cellular health of the yeast Saccharomyces cerevisiae. We find that it is not the accumulation of aggregates but the loss of Sod1 protein stability that drives cellular dysfunction. The toxic effect of Sod1 instability does not correlate with a loss of mitochondrial function or increased production of reactive oxygen species, but instead prevents acidification of the vacuole, perturbs metabolic regulation and promotes senescence. Central to the toxic gain-of-function seen with the SOD1 mutants examined was an inability to regulate amino acid biosynthesis. We also report that leucine supplementation results in an improvement in motor function in a Caenorhabditis elegans model of ALS. Our data suggest that metabolic dysfunction plays an important role in Sod1-mediated toxicity in both the yeast and worm models of ALS. PMID:27656112

  7. Links between deterministic and stochastic approaches for invasion in growth-fragmentation-death models.

    PubMed

    Campillo, Fabien; Champagnat, Nicolas; Fritsch, Coralie

    2016-12-01

    We present two approaches to study invasion in growth-fragmentation-death models. The first one is based on a stochastic individual based model, which is a piecewise deterministic branching process with a continuum of types, and the second one is based on an integro-differential model. The invasion of the population is described by the survival probability for the former model and by an eigenproblem for the latter one. We study these two notions of invasion fitness, giving different characterizations of the growth of the population, and we make links between these two complementary points of view. In particular we prove that the two approaches lead to the same criterion of possible invasion. Based on Krein-Rutman theory, we also give a proof of the existence of a solution to the eigenproblem, which satisfies the conditions needed for our study of the stochastic model, hence providing a set of assumptions under which both approaches can be carried out. Finally, we motivate our work in the context of adaptive dynamics in a chemostat model.

  8. Dynamically linking economic models to ecological condition for coastal zone management: Application to sustainable tourism planning.

    PubMed

    Dvarskas, Anthony

    2017-03-01

    While the development of the tourism industry can bring economic benefits to an area, it is important to consider the long-run impact of the industry on a given location. Particularly when the tourism industry relies upon a certain ecological state, those weighing different development options need to consider the long-run impacts of increased tourist numbers upon measures of ecological condition. This paper presents one approach for linking a model of recreational visitor behavior with an ecological model that estimates the impact of the increased visitors upon the environment. Two simulations were run for the model using initial parameters available from survey data and water quality data for beach locations in Croatia. Results suggest that the resilience of a given tourist location to the changes brought by increasing tourism numbers is important in determining its long-run sustainability. Further work should investigate additional model components, including the tourism industry, refinement of the relationships assumed by the model, and application of the proposed model in additional areas.

  9. Dynamic hysteresis modelling of entangled cross-linked fibres in shear

    NASA Astrophysics Data System (ADS)

    Piollet, Elsa; Poquillon, Dominique; Michon, Guilhem

    2016-11-01

    The objective of this paper is to characterize and model the vibration behaviour of entangled carbon fibres cross-linked with epoxy resin. The material is tested in shear, in a double lap configuration. Experimental testing is carried out for frequencies varying from 1 Hz to 80 Hz and for shear strain amplitudes ranging from 5 ·10-4 to 1 ·10-2. Measured shear stress-strain hysteresis loops show a nonlinear behaviour with a low frequency dependency. The hysteresis loops are decomposed in a linear part and three nonlinear parts: a dry friction hysteresis, a stiffening term and a stiction-like overshoot term. The Generalized Dahl Model is used in conjunction with other hysteresis models to develop an appropriate description of the measured hysteresis loops, based on the three nonlinear parts. In particular, a new one-state formulation of the Bliman-Sorine model is developed. A new identification procedure is also introduced for the Dahl model, based on the so-called backbone curve. The model is shown to capture well the complex shapes of the measured hysteresis loops at all amplitudes.

  10. 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.

  11. 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

  12. The Long-term Clinical Outcome after Corneal Collagen Cross-linking in Korean Patients with Progressive Keratoconus

    PubMed Central

    Kim, Tae Gi; Kim, Ki Young; Han, Jung Bin

    2016-01-01

    Purpose To evaluate the long-term clinical effectiveness and safety of corneal collagen cross-linking (CXL) in progressive keratoconus compared with untreated contralateral eyes. Methods In this retrospective study, nine eyes of nine patients with progressive keratoconus who received CXL (treatment group) and nine untreated contralateral eyes with keratoconus (control group) were included. All patients were followed for at least 5 years and assessed with best-corrected visual acuity, maximum keratometry, mean keratometry, corneal astigmatism, and corneal thickness. Clinical data were collected preoperatively and at 1, 3, 6, 12, 24, 36, 48, and 60 months, postoperatively. Results Mean best-corrected visual acuity improved significantly from 0.58 ± 0.37 logarithm of minimum angle of resolution preoperatively to 0.39 ± 0.29 logarithm of minimum angle of resolution at 5 years after corneal CXL (p = 0.012). There was significant flattening of the maximum keratometry and mean keratometry from preoperative values of 63.39 ± 10.89 and 50.87 ± 6.27 diopter (D) to postoperative values of 60.89 ± 11.29 and 49.54 ± 7.23 D, respectively (p = 0.038, 0.021). Corneal astigmatism decreased significantly from 7.20 ± 1.83 D preoperatively to 5.41 ± 1.79 D postoperatively (p = 0.021). The thinnest corneal thickness decreased from 434.00 ± 54.13 to 365.78 ± 71.58 µm during 1 month after treatment, then increased to 402.67 ± 52.55 µm at 5 years, which showed a statistically significant decrease compared to the baseline (p = 0.020). In the untreated contralateral eyes, mean keratometry increased significantly at 2 years compared with the baseline (p = 0.043). Conclusions CXL seems to be an effective and safe treatment for halting the progression of keratoconus over a long-term follow-up period of up to 5 years in progressive keratoconus. PMID:27729752

  13. Developing and testing a theoretical model linking work-family conflict to employee safety.

    PubMed

    Cullen, Jennifer C; Hammer, Leslie B

    2007-07-01

    Despite work-family conflict being recognized as a source of stress, no published research to our knowledge has considered how it negatively affects workplace safety. A theoretical model linking strain-based work-family conflict and employee safety was tested with 243 health care workers. Within this model, work-family conflict is conceptualized as a workplace hazard. As expected, strong work performance norms and high work overload were associated with higher work-family conflict; increased family-to-work conflict was associated with decreased compliance with safety rules and less willingness to participate in discretionary safety meetings. Work-to-family conflict, however, was not associated with safety. These findings underscore the importance of work redesign strategies that consider work performance norms and work-family conflict for expecting a return on investment in terms of a safer workplace.

  14. Disease dynamics in a coupled cholera model linking within-host and between-host interactions.

    PubMed

    Wang, Xueying; Wang, Jin

    2016-09-19

    A new modelling framework is proposed to study the within-host and between-host dynamics of cholera, a severe intestinal infection caused by the bacterium Vibrio cholerae. The within-host dynamics are characterized by the growth of highly infectious vibrios inside the human body. These vibrios shed from humans contribute to the environmental bacterial growth and the transmission of the disease among humans, providing a link from the within-host dynamics at the individual level to the between-host dynamics at the population and environmental level. A fast-slow analysis is conducted based on the two different time scales in our model. In particular, a bifurcation study is performed, and sufficient and necessary conditions are derived that lead to a backward bifurcation in cholera epidemics. Our result regarding the backward bifurcation highlights the challenges in the prevention and control of cholera.

  15. Atmospheric turbulence-induced fading channel model for space-to-ground laser communications links

    NASA Astrophysics Data System (ADS)

    Toyoshima, Morio; Takenaka, Hideki; Takayama, Yoshihisa

    2011-08-01

    The fading channel model for generating a random time-varying signal based on the atmospheric turbulence spectrum for space-to-ground laser links is discussed. The temporal frequency characteristics of the downlink are theoretically derived based on the von Karman spectrum. The rms wind speed based on the Bufton wind model is used as the transverse wind velocity, which makes the simulation simple. The time-varying signal is generated as functions of the receiver aperture diameter and the rms wind speed. The simulated result of the time-varying signal is presented and compared with the gamma-gamma distribution based on the scintillation theory in a moderate-to-strong-turbulence regime.

  16. Using mathematical modeling as a resource in clinical trials.

    PubMed

    Afenya, Evans K

    2005-07-01

    In light of recent clinical developments, the importance of mathematical modeling in cancer prevention and treatment is discussed. An exist- ing model of cancer chemotherapy is reintroduced and placed within current investigative frameworks regarding approaches to treatment optimization. Areas of commonality between the model predictions and the clinical findings are investigated as a way of further validating the model predictions and also establishing mathematical foundations for the clinical studies. The model predictions are used to propose additional ways that treatment optimization could enhance the clinical processes. Arising out of these, an expanded model of cancer is proposed and a treatment model is subsequently obtained. These models predict that malignant cells in the marrow and peripheral blood exhibit the tendency to evolve toward population levels that enable them to replace normal cells in these compartments in the untreated case. In the case of dose-dense treatment along with recombinant hematopoietic growth factors, the models predict a situation in which normal and abnormal cells in the marrow and peripheral blood are obliterated by drug action, while the normal cells regain their growth capabilities through growth-factor stimulation.

  17. Linking sediment fingerprinting and modeling outputs for a Spanish Pyrenean river catchment.

    NASA Astrophysics Data System (ADS)

    Palazón, Leticia; Latorre, Borja; Gaspar, Leticia; Blake, Williams H.; Smith, Hugh G.; Navas, Ana

    2015-04-01

    Indirect techniques to study fine sediment redistribution in river catchments could provide unique and diverse information, which, when combined become a powerful tool to address catchment management problems. Such combinations could solve limitations of individual techniques and provide different lines of information to address a particular problem. The Barasona reservoir has suffered from siltation since its construction, with the loss of over one third of its storage volume in around 30 study years (period 1972-1996). Information on sediment production from tributary catchments for the reservoir is required to develop management plans for maintaining reservoir sustainability. Large spatial variability in sediment delivery was found in previous studies in the Barasona catchment and the major sediment sources identified included badlands developed in the middle part of the catchment and the agricultural fields in its lower part. From the diverse range of indirect techniques, fingerprinting sediment sources and computer models could be linked to obtain a more holistic view of the processes related to sediment redistribution in the Barasona river catchment (1509 km2, Central Spanish Pyrenees), which comprises agricultural and forest land uses. In the present study, the results from a fingerprinting procedure and the SWAT model were compared and combined to improve the knowledge of land use sediment source contributions to the reservoir. Samples from the study catchment were used to define soil parameters for the model and for fingerprinting the land use sources. The fingerprinting approach provided information about relative contributions from land use sources to the superficial sediment samples taken from the reservoir infill. The calibration and validation of the model provided valuable information, for example on the timescale of sediment production from the different land uses within the catchment. Linking results from both techniques enabled us to achieve a

  18. 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.

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

    DTIC Science & Technology

    2015-03-01

    patient’s clinical history . This information is usually not rich enough to develop predictive models. To construct a useful patient profile requires...in AP and CP. This served as useful validation of our data set before entering the Bayesian Network phase which began in the summer of 2013 Data...case of AP . Thus using the index hospitalization, which presumably is an easily searchable event in any EMR one could better characterize the cohort

  20. Assessing intervention efficacy on high-risk drinkers using generalized linear mixed models with a new class of link functions.

    PubMed

    Prates, Marcos O; Aseltine, Robert H; Dey, Dipak K; Yan, Jun

    2013-11-01

    Unhealthy alcohol use is one of the leading causes of morbidity and mortality in the United States. Brief interventions with high-risk drinkers during an emergency department (ED) visit are of great interest due to their possible efficacy and low cost. In a collaborative study with patients recruited at 14 academic ED across the United States, we examined the self-reported number of drinks per week by each patient following the exposure to a brief intervention. Count data with overdispersion have been mostly analyzed with generalized linear mixed models (GLMMs), of which only a limited number of link functions are available. Different choices of link function provide different fit and predictive power for a particular dataset. We propose a class of link functions from an alternative way to incorporate random effects in a GLMM, which encompasses many existing link functions as special cases. The methodology is naturally implemented in a Bayesian framework, with competing links selected with Bayesian model selection criteria such as the conditional predictive ordinate (CPO). In application to the ED intervention study, all models suggest that the intervention was effective in reducing the number of drinks, but some new models are found to significantly outperform the traditional model as measured by CPO. The validity of CPO in link selection is confirmed in a simulation study that shared the same characteristics as the count data from high-risk drinkers. The dataset and the source code for the best fitting model are available in Supporting Information.

  1. 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.

  2. A dynamical systems analysis of the data assimilation linked ecosystem carbon (DALEC) models.

    PubMed

    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. 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.

  4. 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.

  5. 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.

  6. 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.

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

    PubMed

    Liu, Zitao; Hauskrecht, Milos

    2016-02-01

    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.

  8. 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

  9. Role modelling practice with students on clinical placements.

    PubMed

    Price, Adrienne; Price, Bob

    This article explores practical ways of role modelling practice with students on clinical placements. Students are frequently assigned to a senior practitioner for periods of observation, which involves shadowing the practitioner in practice. Learning opportunities are not necessarily seized because a strategy is not in place to enhance learning. The article provides guidance on how to proceed effectively with role modelling.

  10. 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.

  11. Innovative model of interprofessional geriatric consultation: specialized seniors clinics.

    PubMed

    Kadowaki, Laura; Chow, Helen; Metcalfe, Sarah; Friesen, Kathleen

    2014-01-01

    As the Canadian population ages, healthcare systems have become increasingly interested in exploring new ways to deliver services to frail older adults, and in particular older adults with dementia. The Specialized Seniors Clinics (SSCs) are an innovative integrated network of six outpatient clinics in BC's Fraser Health Authority that utilize interprofessional teams to provide comprehensive geriatric assessments and care planning for frail older adults. The SSCs provided approximately 19,000 appointments in the past fiscal year, and clients and primary care physicians are highly satisfied with the model. This article describes the SSC model and provides reflection on the model development, implementation and standardization processes.

  12. Linking leaf and tree water use with an individual-tree model.

    PubMed

    Medlyn, Belinda E; Pepper, David A; O'Grady, Anthony P; Keith, Heather

    2007-12-01

    We tested the ability of a model to scale gas exchange from leaf level to whole-tree level by: (1) measuring leaf gas exchange in the canopy of 10 trees in a tall Eucalyptus delegatensis RT Baker forest in NSW, Australia; (2) monitoring sap flow of the same 10 trees during the measurement week; and (3) using an individual-tree-based model (MAESTRA) to link the two sets of measurements. Photosynthesis and stomatal conductance components of the model were parameterized with the leaf gas exchange data, and canopy structure was parameterized with crown heights, dimensions and leaf areas of each of the measurement trees and up to 45 neighboring trees. Transpiration of the measurement trees was predicted by the model and compared with sap flow data. Leaf gas exchange parameters were similar for all 10 trees, with the exception of two smaller trees that had relatively low stomatal conductances. We hypothesize that these trees may have experienced water stress as a result of competition from large neighboring trees. The model performed well, and in most cases, was able to replicate the time course of tree transpiration. Maximum rates of transpiration were higher than measured rates for some trees and lower than measured rates for others, which may have been a result of inaccuracy in estimating tree leaf area. There was a small lag (about 15-30 minutes) between sap flow and modeled transpiration for some trees in the morning, likely associated with use of water stored in stems. The model also captured patterns of variation in sap flow among trees. Overall, the study confirms the ability of models to estimate forest canopy transpiration from leaf-level measurements.

  13. 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.

  14. A novel method to link and validate routinely collected emergency department clinical data to measure quality of care.

    PubMed

    Yip, Amelia; Leduc, Matthew; Teo, Vincent; Timmons, Matthew; Schull, Michael J

    2009-01-01

    The objective was to develop and validate a method to link routinely captured electronic data for the measurement of emergency department (ED) quality indicators. Electronic ED data were linked to calculate time to antibiotics and time to electrocardiogram (ECG) for pneumonia and chest pain patients, respectively; validation was by comparison with chart data. Linked electronic data correctly identified 40/40 pneumonia and 65/65 chest pain patients. The median difference in time to antibiotics calculated from linked electronic data versus chart data was 6 minutes (standard deviation [SD] = 14.0); for time to ECG it was 0 minutes (SD = 70). The percentage of ED patients meeting target time to antibiotics was 47% with electronic data versus 44% with charts; for time to ECG, 8% met target time with electronic data versus 11% with charts. A simple computer algorithm for linking routine ED electronic data for quality-of-care measurement was validated.

  15. Clinical Data Models at University Hospitals of Geneva.

    PubMed

    Vishnyakova, Dina; Gaudet-Blavignac, Christophe; Baumann, Philippe; Lovis, Christian

    2016-01-01

    In order to reuse data for clinical research it is then necessary to overcome two main challenges - to formalize data sources and to increase the portability. Once the challenge is resolved, it then will allow research applications to reuse clinical data. In this paper, three data models such as entity-attribute-value, ontological and data-driven are described. Their further implementation at University Hospitals of Geneva (HUG) in the data integration methodologies for operational healthcare data sources of the European projects such as DebugIT and EHR4CR and national project the Swiss Transplant Cohort Study are explained. In these methodologies the clinical data are either aligned according to standardised terminologies using different processing techniques or transformed and loaded directly to data models. Then these models are compared and discussed based on the quality criteria. The comparison shows that the described data models are strongly dependent on the objectives of the projects.

  16. 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 ...

  17. Connecting the Dots: Linking Environmental Justice Indicators to Daily Dose Model Estimates

    PubMed Central

    Huang, Hongtai; Barzyk, Timothy M.

    2016-01-01

    Many different quantitative techniques have been developed to either assess Environmental Justice (EJ) issues or estimate exposure and dose for risk assessment. However, very few approaches have been applied to link EJ factors to exposure dose estimate and identify potential impacts of EJ factors on dose-related variables. The purpose of this study is to identify quantitative approaches that incorporate conventional risk assessment (RA) dose modeling and cumulative risk assessment (CRA) considerations of disproportionate environmental exposure. We apply the Average Daily Dose (ADD) model, which has been commonly used in RA, to better understand impacts of EJ indicators upon exposure dose estimates and dose-related variables, termed the Environmental-Justice-Average-Daily-Dose (EJ-ADD) approach. On the U.S. nationwide census tract-level, we defined and quantified two EJ indicators (poverty and race/ethnicity) using an EJ scoring method to examine their relation to census tract-level multi-chemical exposure dose estimates. Pollutant doses for each tract were calculated using the ADD model, and EJ scores were assigned to each tract based on poverty- or race-related population percentages. Single- and multiple-chemical ADD values were matched to the tract-level EJ scores to analyze disproportionate dose relationships and contributing EJ factors. We found that when both EJ indicators were examined simultaneously, ADD for all pollutants generally increased with larger EJ scores. To demonstrate the utility of using EJ-ADD on the local scale, we approximated ADD levels of lead via soil/dust ingestion for simulated communities with different EJ-related scenarios. The local-level simulation indicates a substantial difference in exposure-dose levels between wealthy and EJ communities. The application of the EJ-ADD approach can link EJ factors to exposure dose estimate and identify potential EJ impacts on dose-related variables. PMID:28036053

  18. A neural network model of semantic memory linking feature-based object representation and words.

    PubMed

    Cuppini, C; Magosso, E; Ursino, M

    2009-06-01

    Recent theories in cognitive neuroscience suggest that semantic memory is a distributed process, which involves many cortical areas and is based on a multimodal representation of objects. The aim of this work is to extend a previous model of object representation to realize a semantic memory, in which sensory-motor representations of objects are linked with words. The model assumes that each object is described as a collection of features, coded in different cortical areas via a topological organization. Features in different objects are segmented via gamma-band synchronization of neural oscillators. The feature areas are further connected with a lexical area, devoted to the representation of words. Synapses among the feature areas, and among the lexical area and the feature areas are trained via a time-dependent Hebbian rule, during a period in which individual objects are presented together with the corresponding words. Simulation results demonstrate that, during the retrieval phase, the network can deal with the simultaneous presence of objects (from sensory-motor inputs) and words (from acoustic inputs), can correctly associate objects with words and segment objects even in the presence of incomplete information. Moreover, the network can realize some semantic links among words representing objects with shared features. These results support the idea that semantic memory can be described as an integrated process, whose content is retrieved by the co-activation of different multimodal regions. In perspective, extended versions of this model may be used to test conceptual theories, and to provide a quantitative assessment of existing data (for instance concerning patients with neural deficits).

  19. Pattern formation in a model for mountain pine beetle dispersal: linking model predictions to data.

    PubMed

    Strohm, S; Tyson, R C; Powell, J A

    2013-10-01

    Pattern formation occurs in a wide range of biological systems. This pattern formation can occur in mathematical models because of diffusion-driven instability or due to the interaction between reaction, diffusion, and chemotaxis. In this paper, we investigate the spatial pattern formation of attack clusters in a system for Mountain Pine Beetle. The pattern formation (aggregation) of the Mountain Pine Beetle in order to attack susceptible trees is crucial for their survival and reproduction. We use a reaction-diffusion equation with chemotaxis to model the interaction between Mountain Pine Beetle, Mountain Pine Beetle pheromones, and susceptible trees. Mathematical analysis is utilized to discover the spacing in-between beetle attacks on the susceptible landscape. The model predictions are verified by analysing aerial detection survey data of Mountain Pine Beetle Attack from the Sawtooth National Recreation Area. We find that the distance between Mountain Pine Beetle attack clusters predicted by our model closely corresponds to the observed attack data in the Sawtooth National Recreation Area. These results clarify the spatial mechanisms controlling the transition from incipient to epidemic populations and may lead to control measures which protect forests from Mountain Pine Beetle outbreak.

  20. Particle Tracking Model (PTM) in the SMS 10: IV. Link to Coastal Modeling System

    DTIC Science & Technology

    2008-07-01

    CMS- M2D : Version 3.0; Report 2: Sediment transport and morphology change. ERDC/CHL TR-06-7. Vicksburg, MS: U.S. Army Engineer Research and...W. Reed, A. K. Zundel, and N. C. Kraus. 2004. Two-dimensional depth-averaged circulation model CMS- M2D : Version 2.0; Report 1: Technical

  1. 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

  2. Putting the five-factor model into context: evidence linking big five traits to narrative identity.

    PubMed

    Raggatt, Peter

    2006-10-01

    The study examined relationships between the Big Five personality traits and thematic content extracted from self-reports of life history data. One hundred and five "mature age" university students (M=30.1 years) completed the NEO PI-R trait measure, and the Personality Web Protocol. The protocol examines constituents of identity by asking participants to describe 24 key "attachments" from their life histories (significant events, people, places, objects, and possessions). Participants sorted these attachments into clusters and provided a self-descriptive label for each cluster (e.g., "adventurous self"). It was predicted that the thematic content of these cluster labels would be systematically related to Big Five trait scores (e.g., that labels referring to strength or positive emotions would be linked to Extraversion). The hypothesized links were obtained for each of the Big Five trait domains except Conscientiousness. Results are discussed with a view to broadening our understanding of the Five-Factor Model in relation to units of personality other than traits.

  3. A review of the evidence linking adult attachment theory and chronic pain: presenting a conceptual model.

    PubMed

    Meredith, Pamela; Ownsworth, Tamara; Strong, Jenny

    2008-03-01

    It is now well established that pain is a multidimensional phenomenon, affected by a gamut of psychosocial and biological variables. According to diathesis-stress models of chronic pain, some individuals are more vulnerable to developing disability following acute pain because they possess particular psychosocial vulnerabilities which interact with physical pathology to impact negatively upon outcome. Attachment theory, a theory of social and personality development, has been proposed as a comprehensive developmental model of pain, implicating individual adult attachment pattern in the ontogenesis and maintenance of chronic pain. The present paper reviews and critically appraises studies which link adult attachment theory with chronic pain. Together, these papers offer support for the role of insecure attachment as a diathesis (or vulnerability) for problematic adjustment to pain. The Attachment-Diathesis Model of Chronic Pain developed from this body of literature, combines adult attachment theory with the diathesis-stress approach to chronic pain. The evidence presented in this review, and the associated model, advances our understanding of the developmental origins of chronic pain conditions, with potential application in guiding early pain intervention and prevention efforts, as well as tailoring interventions to suit specific patient needs.

  4. A Linked Simulation-Optimization (LSO) Model for Conjunctive Irrigation Management using Clonal Selection Algorithm

    NASA Astrophysics Data System (ADS)

    Islam, Sirajul; Talukdar, Bipul

    2016-09-01

    A Linked Simulation-Optimization (LSO) model based on a Clonal Selection Algorithm (CSA) was formulated for application in conjunctive irrigation management. A series of measures were considered for reducing the computational burden associated with the LSO approach. Certain modifications were incurred to the formulated CSA, so as to decrease the number of function evaluations. In addition, a simple problem specific code for a two dimensional groundwater flow simulation model was developed. The flow model was further simplified by a novel approach of area reduction, in order to save computational time in simulation. The LSO model was applied in the irrigation command of the Pagladiya Dam Project in Assam, India. With a view to evaluate the performance of the CSA, a Genetic Algorithm (GA) was used as a comparison base. The results from the CSA compared well with those from the GA. In fact, the CSA was found to consume less computational time than the GA while converging to the optimal solution, due to the modifications incurred in it.

  5. MARKAL-MACRO: A linked model for energy-economy analysis

    SciTech Connect

    Manne, A.S. ); Wene, C.O. Chalmers Univ. of Tech., Goeteborg )

    1992-02-01

    MARKAL-MACRO is an experiment in model linkage for energy and economy analysis. This new tool is intended as an improvement over existing methods for energy strategy assessment. It is designed specifically for estimating the costs and analyzing the technologies proposed for reducing environmental risks such as global climate change or regional air pollution. The greenhouse gas debate illustrates the usefulness of linked energy-economy models. A central issue is the coupling between economic growth, the level of energy demands, and the development of an energy system to supply these demands. The debate is often connected with alternative modeling approaches. The competing philosophies may be labeled top-down macroeconomic'' and bottom-up engineering'' perspectives. MARKAL is a systems engineering (physical process) analysis built on the concept of a Reference Energy System (RES). MARKAL is solved by means of dynamic linear programming. In most applications, the end use demands are fixed, and an economically efficient solution is obtained by minimizing the present value of energy system's costs throughout the planning horizon. MACRO is a macroeconomic model with an aggregated view of long-term economic growth. The basis input factors of production are capital, labor and individual forms of energy. MACRO is solved by nonlinear optimization.

  6. MARKAL-MACRO: A linked model for energy-economy analysis

    SciTech Connect

    Manne, A.S.; Wene, C.O. |

    1992-02-01

    MARKAL-MACRO is an experiment in model linkage for energy and economy analysis. This new tool is intended as an improvement over existing methods for energy strategy assessment. It is designed specifically for estimating the costs and analyzing the technologies proposed for reducing environmental risks such as global climate change or regional air pollution. The greenhouse gas debate illustrates the usefulness of linked energy-economy models. A central issue is the coupling between economic growth, the level of energy demands, and the development of an energy system to supply these demands. The debate is often connected with alternative modeling approaches. The competing philosophies may be labeled ``top-down macroeconomic`` and ``bottom-up engineering`` perspectives. MARKAL is a systems engineering (physical process) analysis built on the concept of a Reference Energy System (RES). MARKAL is solved by means of dynamic linear programming. In most applications, the end use demands are fixed, and an economically efficient solution is obtained by minimizing the present value of energy system`s costs throughout the planning horizon. MACRO is a macroeconomic model with an aggregated view of long-term economic growth. The basis input factors of production are capital, labor and individual forms of energy. MACRO is solved by nonlinear optimization.

  7. Linking linear programming and spatial simulation models to predict landscape effects of forest management alternatives.

    PubMed

    Gustafson, Eric J; Roberts, L Jay; Leefers, Larry A

    2006-12-01

    Forest management planners require analytical tools to assess the effects of alternative strategies on the sometimes disparate benefits from forests such as timber production and wildlife habitat. We assessed the spatial patterns of alternative management strategies by linking two models that were developed for different purposes. We used a linear programming model (Spectrum) to optimize timber harvest schedules, then a simulation model (HARVEST) to project those schedules in a spatially explicit way and produce maps from which the spatial pattern of habitat could be calculated. We demonstrated the power of this approach by evaluating alternative plans developed for a national forest plan revision in Wisconsin, USA. The amount of forest interior habitat was inversely related to the amount of timber cut, and increased under the alternatives compared to the current plan. The amount of edge habitat was positively related to the amount of timber cut, and increased under all alternatives. The amount of mature northern hardwood interior and edge habitat increased for all alternatives, but mature pine habitat area varied. Mature age classes of all forest types increased, and young classes decreased under all alternatives. The average size of patches (defined by age class) generally decreased. These results are consistent with the design goals of each of the alternatives, but reveal that the spatial differences among the alternatives are modest. These complementary models are valuable for quantifying and comparing the spatial effects of alternative management strategies.

  8. 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.

  9. Link or sink: a modelling interpretation of the open Baltic biogeochemistry

    NASA Astrophysics Data System (ADS)

    Vichi, M.; Ruardij, P.; Baretta, J. W.

    2004-08-01

    A 1-D model system, consisting of the 1-D version of the Princeton Ocean Model (POM) coupled with the European Regional Seas Ecosystem Model (ERSEM) has been applied to a sub-basin of the Baltic Proper, the Bornholm basin. The model has been forced with 3h meteorological data for the period 1979-1990, producing a 12-year hindcast validated with datasets from the Baltic Environmental Database for the same period. The model results demonstrate the model to hindcast the time-evolution of the physical structure very well, confirming the view of the open Baltic water column as a three layer system of surface, intermediate and bottom waters. Comparative analyses of modelled hydrochemical components with respect to the independent data have shown that the long-term system behaviour of the model is within the observed ranges. Also primary production processes, deduced from oxygen (over)saturation are hindcast correctly over the entire period and the annual net primary production is within the observed range. The largest mismatch with observations is found in simulating the biogeochemistry of the Baltic intermediate waters. Modifications in the structure of the model (addition of fast-sinking detritus and polysaccharide dynamics) have shown that the nutrient dynamics is linked to the quality and dimensions of the organic matter produced in the euphotic zone, highlighting the importance of the residence time of the organic matter within the microbial foodweb in the intermediate waters. Experiments with different scenarios of riverine nutrient loads, assessed in the limits of a 1-D setup, have shown that the external input of organic matter makes the open Baltic model more heterotrophic. The characteristics of the inputs also drive the dynamics of nitrogen in the bottom layers leading either to nitrate accumulation (when the external sources are inorganic), or to coupled nitrification-denitrification (under strong organic inputs). The model indicates the permanent

  10. Link or sink: a modelling interpretation of the open Baltic biogeochemistry

    NASA Astrophysics Data System (ADS)

    Vichi, M.; Ruardij, P.; Baretta, J. W.

    A 1-D model system, consisting of the 1-D version of the Princeton Ocean Model (POM) coupled with the European Regional Seas Ecosystem Model (ERSEM) has been applied to a sub-basin of the Baltic Proper, the Bornholm basin. The model has been forced with 3h meteorological data for the period 1979-1990, producing a 12-year hindcast validated with datasets from the Baltic Environmental Database for the same period. The model results demonstrate the model to hindcast the time-evolution of the physical structure very well, confirming the view of the open Baltic water column as a three layer system of surface, intermediate and bottom waters. Comparative analyses of modelled hydrochemical components with respect to the independent data have shown that the long-term system behaviour of the model is within the observed ranges. Also primary production processes, deduced from oxygen (over)saturation are hindcast correctly over the entire period and the annual net primary production is within the observed range. The largest mismatch with observations is found in simulating the biogeochemistry of the Baltic intermediate waters. Modifications in the structure of the model (addition of fast-sinking detritus and polysaccharide dynamics) have shown that the nutrient dynamics are linked to the quality and dimensions of the organic matter produced in the euphotic zone, highlighting the importance of the residence time of the organic matter within the microbial foodweb in the intermediate waters. Experiments with different scenarios of riverine nutrient loads, assessed in the limits of a 1-D setup, have shown that the external input of organic matter makes the open Baltic model more heterotrophic. The characteristics of the inputs also drive the dynamics of nitrogen in the bottom layers leading either to nitrate accumulation (when the external sources are inorganic), or to coupled nitrification-denitrification (under strong organic inputs). The model indicates the permanent

  11. A model for ethical practices in clinical phonetics and linguistics.

    PubMed

    Powell, Thomas W

    2007-01-01

    The emergence of clinical phonetics and linguistics as an area of scientific inquiry gives rise to the need for guidelines that define ethical and responsible conduct. The diverse membership of the International Clinical Phonetics and Linguistics Association (ICPLA) and the readership of this journal are uniquely suited to consider ethical issues from diverse perspectives. Accordingly, this paper introduces a multi-tiered six-factor model for ethical practices to stimulate discussion of ethical issues.

  12. 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

  13. Exposure-response modeling of clinical end points using latent variable indirect response models.

    PubMed

    Hu, C

    2014-06-04

    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.

  14. 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

  15. 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.

  16. Preparedness for clinical: evaluation of the core elements of the Clinical Immersion curriculum model.

    PubMed

    Diefenbeck, Cynthia; Herrman, Judith; Wade, Gail; Hayes, Evelyn; Voelmeck, Wayne; Cowperthwait, Amy; Norris, Susan

    2015-01-01

    The Clinical Immersion Model is an innovative baccalaureate nursing curriculum that has demonstrated successful outcomes over the past 10 years. For those intending to adopt the model, individual components in isolation may prove ineffective. This article describes three core components of the curriculum that form the foundation of preparation for the senior-year clinical immersion. Detailed student-centered outcomes evaluation of these critical components is shared. Results of a mixed-methods evaluation, including surveys and focus groups, are presented. Implications of this curricular evaluation and future directions are explored.

  17. a Six-Link Kinematic Chain Model of Human Body Using Kane's Method

    NASA Astrophysics Data System (ADS)

    Rambely, A. S.; Fazrolrozi

    A biomechanics model of six-link kinematic chain of human body is developed by using Kane's method. The kinematic data comprise of six segments; foot, calf, thigh, trunk, upper arm and forearm, are obtained through data collection of walking, running and jumping using the Vicon Nexus system. The motion capture system uses 12 Vicon MX-3+ cameras and 12 Vicon MX-F40 cameras, two DV (50 Hz) cameras and a force plate (100 Hz). Inverse dynamics approach is used to obtain the unknown value of torques produced by joint segments during walking, running and jumping activities. The results show that the largest value of torques produced occurs at the foot segment.

  18. Assessing the potential of using telecommunication microwave links in urban drainage modelling.

    PubMed

    Fencl, M; Rieckermann, J; Schleiss, M; Stránský, D; Bareš, V

    2013-01-01

    The ability to predict the runoff response of an urban catchment to rainfall is crucial for managing drainage systems effectively and controlling discharges from urban areas. In this paper we assess the potential of commercial microwave links (MWL) to capture the spatio-temporal rainfall dynamics and thus improve urban rainfall-runoff modelling. Specifically, we perform numerical experiments with virtual rainfall fields and compare the results of MWL rainfall reconstructions to those of rain gauge (RG) observations. In a case study, we are able to show that MWL networks in urban areas are sufficiently dense to provide good information on spatio-temporal rainfall variability and can thus considerably improve pipe flow prediction, even in small subcatchments. In addition, the better spatial coverage also improves the control of discharges from urban areas. This is especially beneficial for heavy rainfall, which usually has a high spatial variability that cannot be accurately captured by RG point measurements.

  19. 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.

  20. Three Papers in International Health Policy: Modeling the Links between Economics and Epidemiology

    DTIC Science & Technology

    2008-04-01

    The base infectivity of  influenza A  viruses  depends  12 on the rate at which the average  infected person  ‘sheds’  the  virus ,  the  timing of  the...under  several  scenarios  of  infectiousness  and  virulence  of  a  pandemic  influenza  virus  (11, 12). These studies do not conduct  epidemiological ...International Health Policy. Modeling the Links Between Economics and Epidemiology 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER

  1. 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.

  2. 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

  3. 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

  4. Effect of Clinical Teaching Associate Model on Nursing Students' Clinical Skills and Nurses' Satisfaction.

    PubMed

    Rahnavard, Zahra; Eybpoosh, Sana; Alianmoghaddam, Narges

    2013-10-02

    Abstract Background and Objectives: The credit of the practice nurses in developing countries, due to gap between theory and practice in nursing education and health care delivery has been questioned by nursing professionals. Therefore, the aims of this study were to investigate the effectiveness of the application of the CTA model in nursing students' clinical skills and to assess the participants' (faculty members, staff nurses, and nursing students) level of satisfaction with the CTA model and with achieving the educational goals in Iran, as a developing country. Methods and Materials: In this experimental study, random sampling was used to assess 104 nursing students' clinical skills, and assess 6 faculty members and 6 staff nurses. After obtaining informed consent, the level of satisfaction was evaluated by a questionnaire and clinical skills were evaluated by standard checklists. Data were assessed and analyzed with SPSS version 15. Results: The results showed that the mean scores of all clinical skills of the students were significantly higher after intervention (p<0.01). Moreover, the mean scores of instructors' satisfaction with applying the CTA model was significantly higher (p = 0.004), but their satisfaction with achieving clinical education outcomes did not show a significant difference (p = 0.109). Similarly, students' satisfaction with achieving educational outcomes did not show any significant differences between the two groups (P = 0.058). Conclusion: According to this study, the CTA model is an effective method for developing clinical skills in nursing students in Iran as a developing country. Therefore, application of the method is recommended in clinical nursing education systems of such counties.

  5. Coupled dynamics of node and link states in complex networks: a model for language competition

    NASA Astrophysics Data System (ADS)

    Carro, Adrián; Toral, Raúl; San Miguel, Maxi

    2016-11-01

    Inspired by language competition processes, we present a model of coupled evolution of node and link states. In particular, we focus on the interplay between the use of a language and the preference or attitude of the speakers towards it, which we model, respectively, as a property of the interactions between speakers (a link state) and as a property of the speakers themselves (a node state). Furthermore, we restrict our attention to the case of two socially equivalent languages and to socially inspired network topologies based on a mechanism of triadic closure. As opposed to most of the previous literature, where language extinction is an inevitable outcome of the dynamics, we find a broad range of possible asymptotic configurations, which we classify as: frozen extinction states, frozen coexistence states, and dynamically trapped coexistence states. Moreover, metastable coexistence states with very long survival times and displaying a non-trivial dynamics are found to be abundant. Interestingly, a system size scaling analysis shows, on the one hand, that the probability of language extinction vanishes exponentially for increasing system sizes and, on the other hand, that the time scale of survival of the non-trivial dynamical metastable states increases linearly with the size of the system. Thus, non-trivial dynamical coexistence is the only possible outcome for large enough systems. Finally, we show how this coexistence is characterized by one of the languages becoming clearly predominant while the other one becomes increasingly confined to ‘ghetto-like’ structures: small groups of bilingual speakers arranged in triangles, with a strong preference for the minority language, and using it for their intra-group interactions while they switch to the predominant language for communications with the rest of the population.

  6. Dependence of Invadopodia Function on Collagen Fiber Spacing and Cross-Linking: Computational Modeling and Experimental Evidence

    PubMed Central

    Enderling, Heiko; Alexander, Nelson R.; Clark, Emily S.; Branch, Kevin M.; Estrada, Lourdes; Crooke, Cornelia; Jourquin, Jérôme; Lobdell, Nichole; Zaman, Muhammad H.; Guelcher, Scott A.; Anderson, Alexander R. A.; Weaver, Alissa M.

    2008-01-01

    Invadopodia are subcellular organelles thought to be critical for extracellular matrix (ECM) degradation and the movement of cells through tissues. Here we examine invadopodia generation, turnover, and function in relation to two structural aspects of the ECM substrates they degrade: cross-linking and fiber density. We set up a cellular automaton computational model that simulates ECM penetration and degradation by invadopodia. Experiments with denatured collagen (gelatin) were used to calibrate the model and demonstrate the inhibitory effect of ECM cross-linking on invadopodia degradation and penetration. Incorporation of dynamic invadopodia behavior into the model amplified the effect of cross-linking on ECM degradation, and was used to model feedback from the ECM. When the model was parameterized with spatial fibrillar dimensions that closely matched the organization, in real life, of native ECM collagen into triple-helical monomers, microfibrils, and macrofibrils, little or no inhibition of invadopodia penetration was observed in simulations of sparse collagen gels, no matter how high the degree of cross-linking. Experimental validation, using live-cell imaging of invadopodia in cells plated on cross-linked gelatin, was consistent with simulations in which ECM cross-linking led to higher rates of both invadopodia retraction and formation. Analyses of invadopodia function from cells plated on cross-linked gelatin and collagen gels under standard concentrations were consistent with simulation results in which sparse collagen gels provided a weak barrier to invadopodia. These results suggest that the organization of collagen, as it may occur in stroma or in vitro collagen gels, forms gaps large enough so as to have little impact on invadopodia penetration/degradation. By contrast, dense ECM, such as gelatin or possibly basement membranes, is an effective obstacle to invadopodia penetration and degradation, particularly when cross-linked. These results provide a

  7. 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.

  8. An X-linked three allele model of hand preference and hand posture for writing.

    PubMed

    McKeever, Walter F

    2004-04-01

    This paper describes a genetic model of hand preferences for writing and for handwriting posture (HWP). The challenge of devising an X-linked model for these aspects of human handedness was posed by the results of a large family handedness study (McKeever, 2000) that showed evidence of such linkage. Because X-linkage for handedness has been widely regarded as untenable, the prospects for developing such a model were not initially encouraging, but ultimately a viable model did suggest itself. Family studies of handedness and leading theories of handedness are briefly described, as is some of the research on HWP motivated by the theory of Levy and Nagylaki (1972). It is argued that there is evidence that HWP reflects a biological dictate and not just individual "choices" or "adaptations" to writing in a left-to-right direction with the left hand. The model proposes that inverted handwriting posture is not necessarily highly related to speech and language lateralities of sinistrals, but that it reveals an interhemispheric mediation of writing. It is hypothesised that it reflects a specialisation of the left angular gyrus (with some possible extension into the supramarginal gyrus) for the storage of movement and timing sequences of cursive writing, and right hemisphere motor programming of the motor output of writing. It is also argued that no family handedness study conducted to date is adequate for testing the predictions of extant handedness theories, and the often wide variations between the results of family handedness studies are noted. It is suggested that fMRI studies could definitively test the HWP hypotheses of the model and that the hypothesis of X-linkage could be tested definitively should studies of the human genome identify a gene for handedness.

  9. Linking state-and-transition simulation and timber supply models for forest biomass production scenarios

    USGS Publications Warehouse

    Costanza, Jennifer; Abt, Robert C.; McKerrow, Alexa; Collazo, Jaime

    2015-01-01

    We linked state-and-transition simulation models (STSMs) with an economics-based timber supply model to examine landscape dynamics in North Carolina through 2050 for three scenarios of forest biomass production. Forest biomass could be an important source of renewable energy in the future, but there is currently much uncertainty about how biomass production would impact landscapes. In the southeastern US, if forests become important sources of biomass for bioenergy, we expect increased land-use change and forest management. STSMs are ideal for simulating these landscape changes, but the amounts of change will depend on drivers such as timber prices and demand for forest land, which are best captured with forest economic models. We first developed state-and-transition model pathways in the ST-Sim software platform for 49 vegetation and land-use types that incorporated each expected type of landscape change. Next, for the three biomass production scenarios, the SubRegional Timber Supply Model (SRTS) was used to determine the annual areas of thinning and harvest in five broad forest types, as well as annual areas converted among those forest types, agricultural, and urban lands. The SRTS output was used to define area targets for STSMs in ST-Sim under two scenarios of biomass production and one baseline, business-as-usual scenario. We show that ST-Sim output matched SRTS targets in most cases. Landscape dynamics results indicate that, compared with the baseline scenario, forest biomass production leads to more forest and, specifically, more intensively managed forest on the landscape by 2050. Thus, the STSMs, informed by forest economics models, provide important information about potential landscape effects of bioenergy production.

  10. A New Model of Clinical Education to Increase Student Placement Availability: The Capacity Development Facilitator Model

    ERIC Educational Resources Information Center

    Fairbrother, Michele; Nicole, Madelyn; Blackford, Julia; Nagarajan, Srivalli Vilapakkam; McAllister, Lindy

    2016-01-01

    This paper reports on a trial of a new model of clinical education designed to increase student clinical placement availability and address workforce constraints on supervision. The University of Sydney deployed the Capacity Development Facilitators (CDF) in selected Sydney hospitals to work with staff to expand student clinical placement…

  11. 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

    2016-02-09

    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.

  12. 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

  13. Pre-clinical Orthotopic Murine Model of Human Prostate Cancer.

    PubMed

    Shahryari, Varahram; Nip, Hannah; Saini, Sharanjot; Dar, Altaf A; Yamamura, Soichiro; Mitsui, Yozo; Colden, Melissa; Bucay, Nathan; Tabatabai, Laura Z; Greene, Kirsten; Deng, Guoren; Tanaka, Yuichiro; Dahiya, Rajvir; Majid, Shahana

    2016-08-29

    To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information about this disease. The human orthotopic prostate cancer xenograft mouse model provides a useful alternative approach for understanding the specific interactions between genetically and molecularly altered tumor cells, their organ microenvironment, and for evaluation of efficacy of therapeutic regimens. This is a well characterized model designed to study the molecular events of primary tumor development and it recapitulates the early events in the metastatic cascade prior to embolism and entry of tumor cells into the circulation. Thus it allows elucidation of molecular mechanisms underlying the initial phase of metastatic disease. In addition, this model can annotate drug targets of clinical relevance and is a valuable tool to study prostate cancer progression. In this manuscript we describe a detailed procedure to establish a human orthotopic prostate cancer xenograft mouse model.

  14. Simplifying complex clinical element models to encourage adoption.

    PubMed

    Freimuth, Robert R; Zhu, Qian; Pathak, Jyotishman; Chute, Christopher G

    2014-01-01

    Clinical Element Models (CEMs) were developed to provide a normalized form for the exchange of clinical data. The CEM specification is quite complex and specialized knowledge is required to understand and implement the models, which presents a significant barrier to investigators and study designers. To encourage the adoption of CEMs at the time of data collection and reduce the need for retrospective normalization efforts, we developed an approach that provides a simplified view of CEMs for non-experts while retaining the full semantic detail of the underlying logical models. This allows investigators to approach CEMs through generalized representations that are intended to be more intuitive than the native models, and it permits them to think conceptually about their data elements without worrying about details related to the CEM logical models and syntax. We demonstrate our approach using data elements from the Pharmacogenomics Research Network (PGRN).

  15. Modelling clinical systemic lupus erythematosus: similarities, differences and success stories.

    PubMed

    Celhar, Teja; Fairhurst, Anna-Marie

    2016-12-24

    Mouse models of SLE have been indispensable tools to study disease pathogenesis, to identify genetic susceptibility loci and targets for drug development, and for preclinical testing of novel therapeutics. Recent insights into immunological mechanisms of disease progression have boosted a revival in SLE drug development. Despite promising results in mouse studies, many novel drugs have failed to meet clinical end points. This is probably because of the complexity of the disease, which is driven by polygenic predisposition and diverse environmental factors, resulting in a heterogeneous clinical presentation. Each mouse model recapitulates limited aspects of lupus, especially in terms of the mechanism underlying disease progression. The main mouse models have been fairly successful for the evaluation of broad-acting immunosuppressants. However, the advent of targeted therapeutics calls for a selection of the most appropriate model(s) for testing and, ultimately, identification of patients who will be most likely to respond.

  16. 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

  17. 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

  18. Link between hopping models and percolation scaling laws for charge transport in mixtures of small molecules

    DOE PAGES

    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

  19. 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.

  20. Linking river management to species conservation using dynamic landscape scale models

    USGS Publications Warehouse

    Freeman, Mary C.; Buell, Gary R.; Hay, Lauren E.; Hughes, W. Brian; Jacobson, Robert B.; Jones, John W.; Jones, S.A.; LaFontaine, Jacob H.; Odom, Kenneth R.; Peterson, James T.; Riley, Jeffrey W.; Schindler, J. Stephen; Shea, C.; Weaver, J.D.

    2013-01-01

    Efforts to conserve stream and river biota could benefit from tools that allow managers to evaluate landscape-scale changes in species distributions in response to water management decisions. We present a framework and methods for integrating hydrology, geographic context and metapopulation processes to simulate effects of changes in streamflow on fish occupancy dynamics across a landscape of interconnected stream segments. We illustrate this approach using a 482 km2 catchment in the southeastern US supporting 50 or more stream fish species. A spatially distributed, deterministic and physically based hydrologic model is used to simulate daily streamflow for sub-basins composing the catchment. We use geographic data to characterize stream segments with respect to channel size, confinement, position and connectedness within the stream network. Simulated streamflow dynamics are then applied to model fish metapopulation dynamics in stream segments, using hypothesized effects of streamflow magnitude and variability on population processes, conditioned by channel characteristics. The resulting time series simulate spatially explicit, annual changes in species occurrences or assemblage metrics (e.g. species richness) across the catchment as outcomes of management scenarios. Sensitivity analyses using alternative, plausible links between streamflow components and metapopulation processes, or allowing for alternative modes of fish dispersal, demonstrate large effects of ecological uncertainty on model outcomes and highlight needed research and monitoring. Nonetheless, with uncertainties explicitly acknowledged, dynamic, landscape-scale simulations may prove useful for quantitatively comparing river management alternatives with respect to species conservation.

  1. Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis.

    PubMed

    Rajan, Thangavelu Soundara; Scionti, Domenico; Diomede, Francesca; Grassi, Gianpaolo; Pollastro, Federica; Piattelli, Adriano; Cocco, Lucio; Bramanti, Placido; Mazzon, Emanuela; Trubiani, Oriana

    2017-04-01

    Research in recent years has extensively investigated the therapeutic efficacy of mesenchymal stromal cells in regenerative medicine for many neurodegenerative diseases at preclinical and clinical stages. However, the success rate of stem cell therapy remains less at translational phase. Lack of relevant animal models that potentially simulate the molecular etiology of human pathological symptoms might be a reason behind such poor clinical outcomes associated with stem cell therapy. Apparently, self-renewal and differentiation ability of mesenchymal stem cells may help to study the early developmental signaling pathways connected with the diseases, such as Alzheimer's disease, Amyotrophic lateral sclerosis (ALS), etc., at in vitro level. Cannabidiol, a non-psychotrophic cannabinoid, has been demonstrated as a potent anti-inflammatory and neuroprotective agent in neurological preclinical models. In the present study, we investigated the modulatory role of cannabidiol on genes associated with ALS using human gingiva-derived mesenchymal stromal cells (hGMSCs) as an in vitro model system. Next generation transcriptomic sequencing analysis demonstrated considerable modifications in the expression of genes connected with ALS pathology, oxidative stress, mitochondrial dysfunction, and excitotoxicity in hGMSCs treated with cannabidiol. Our results suggest the efficacy of cannabidiol to delineate the unknown molecular pathways, which may underlie ALS pathology at an early stage using hGMSCs as a compelling in vitro system. J. Cell. Biochem. 118: 819-828, 2017. © 2016 Wiley Periodicals, Inc.

  2. 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.

  3. ACE--Alliance for Clinical Enhancement: a collaborative model.

    PubMed

    Poirrier, G P; Granger, M; Todaro, M

    1993-01-01

    This paper introduces an innovative collaborative model developed by nursing educators and practitioners, the Alliance for Clinical Enhancement Program (ACE), that combines components of traditional internship and extender programs. The goals of ACE are opportunities for role socialization, role transition, and role modeling for nursing students; enhancing clinical competence and provision of financial assistance to the students; increased recruitment of RN graduates by the involved hospital; and decreased RN time spent on non-nursing tasks by hospital RNs. The total development, implementation, and analysis of ACE Program is discussed.

  4. Dynamic root growth and architecture responses to limiting nutrient availability: linking physiological models and experimentation.

    PubMed

    Postma, Johannes A; Schurr, Ulrich; Fiorani, Fabio

    2014-01-01

    In recent years the study of root phenotypic plasticity in response to sub-optimal environmental factors and the genetic control of these responses have received renewed attention. As a path to increased productivity, in particular for low fertility soils, several applied research projects worldwide target the improvement of crop root traits both in plant breeding and biotechnology contexts. To assist these tasks and address the challenge of optimizing root growth and architecture for enhanced mineral resource use, the development of realistic simulation models is of great importance. We review this research field from a modeling perspective focusing particularly on nutrient acquisition strategies for crop production on low nitrogen and low phosphorous soils. Soil heterogeneity and the dynamics of nutrient availability in the soil pose a challenging environment in which plants have to forage efficiently for nutrients in order to maintain their internal nutrient homeostasis throughout their life cycle. Mathematical models assist in understanding plant growth strategies and associated root phenes that have potential to be tested and introduced in physiological breeding programs. At the same time, we stress that it is necessary to carefully consider model assumptions and development from a whole plant-resource allocation perspective and to introduce or refine modules simulating explicitly root growth and architecture dynamics through ontogeny with reference to key factors that constrain root growth. In this view it is important to understand negative feedbacks such as plant-plant competition. We conclude by briefly touching on available and developing technologies for quantitative root phenotyping from lab to field, from quantification of partial root profiles in the field to 3D reconstruction of whole root systems. Finally, we discuss how these approaches can and should be tightly linked to modeling to explore the root phenome.

  5. Looking beyond historical patient outcomes to improve clinical models.

    PubMed

    Chia, Chih-Chun; Rubinfeld, Ilan; Scirica, Benjamin M; McMillan, Sean; Gurm, Hitinder S; Syed, Zeeshan

    2012-04-25

    Conventional algorithms for modeling clinical events focus on characterizing the differences between patients with varying outcomes in historical data sets used for the model derivation. For many clinical conditions with low prevalence and where small data sets are available, this approach to developing models is challenging due to the limited number of positive (that is, event) examples available for model training. Here, we investigate how the approach of developing clinical models might be improved across three distinct patient populations (patients with acute coronary syndrome enrolled in the DISPERSE2-TIMI33 and MERLIN-TIMI36 trials, patients undergoing inpatient surgery in the National Surgical Quality Improvement Program registry, and patients undergoing percutaneous coronary intervention in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium registry). For each of these cases, we supplement an incomplete characterization of patient outcomes in the derivation data set (uncensored view of the data) with an additional characterization of the extent to which patients differ from the statistical support of their clinical characteristics (censored view of the data). Our approach exploits the same training data within the derivation cohort in multiple ways to improve the accuracy of prediction. We position this approach within the context of traditional supervised (2-class) and unsupervised (1-class) learning methods and present a 1.5-class approach for clinical decision-making. We describe a 1.5-class support vector machine (SVM) classification algorithm that implements this approach, and report on its performance relative to logistic regression and 2-class SVM classification with cost-sensitive weighting and oversampling. The 1.5-class SVM algorithm improved prediction accuracy relative to other approaches and may have value in predicting clinical events both at the bedside and for risk-adjusted quality of care assessment.

  6. [Application of three compartment model and response surface model to clinical anesthesia using Microsoft Excel].

    PubMed

    Abe, Eiji; Abe, Mari

    2011-08-01

    With the spread of total intravenous anesthesia, clinical pharmacology has become more important. We report Microsoft Excel file applying three compartment model and response surface model to clinical anesthesia. On the Microsoft Excel sheet, propofol, remifentanil and fentanyl effect-site concentrations are predicted (three compartment model), and probabilities of no response to prodding, shaking, surrogates of painful stimuli and laryngoscopy are calculated using predicted effect-site drug concentration. Time-dependent changes in these calculated values are shown graphically. Recent development in anesthetic drug interaction studies are remarkable, and its application to clinical anesthesia with this Excel file is simple and helpful for clinical anesthesia.

  7. Sports medicine training room clinic model for the military.

    PubMed

    Brawley, Stephen; Fairbanks, Keith; Nguyen, William; Blivin, Steve; Frantz, Earl

    2012-02-01

    A transition from traditional problem-based clinics to the Sports Medicine and Reconditioning Team (SMART) clinic model was completed by January 2009 at Marine Corps Base Camp Lejeune. The SMART clinic model allows for more patients to be seen and enhances coordinated care between providers. The objective of this research is to show the advantages of implementing a training room team approach for the care of musculoskeletal injuries in active duty members by comparing the number of patients seen, the number of limited duty (LIMDU) periods, the number of physical evaluation boards (PEBs), and the percentage of orthopedic referrals. Electronic medical records for patients seen at sports medicine clinics between January 1, 2007 and December 31, 2010 were reviewed. Naval Hospital Camp Lejeune provided a database of patients placed on LIMDU and PEB from 2007 through 2010. Fifty-eight and twenty-four percent more encounters occurred in 2009 and 2010, respectively, than that in 2007. The percentage of LIMDU referred for PEB in 2010 was reduced to 9% compared to that in 2007. In conclusion, the SMART clinic model allows for more patients to be seen and a reduction in the percentage of patients recommended for PEB from LIMDU.

  8. 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.

  9. 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.

  10. Cross-linked xenogenic collagen implantation in the sheep model for vaginal surgery.

    PubMed

    Endo, Masayuki; Urbankova, Iva; Vlacil, Jaromir; Sengupta, Siddarth; Deprest, Thomas; Klosterhalfen, Bernd; Feola, Andrew; Deprest, Jan

    The properties of meshes used in reconstructive surgery affect the host response and biomechanical characteristics of the grafted tissue. Whereas durable synthetics induce a chronic inflammation, biological grafts are usually considered as more biocompatible. The location of implantation is another determinant of the host response: the vagina is a different environment with specific function and anatomy. Herein, we evaluated a cross-linked acellular collagen matrix (ACM), pretreated by the anti-calcification procedure ADAPT® in a sheep model for vaginal surgery. Ten sheep were implanted with a cross-linked ACM, and six controls were implanted with a polypropylene (PP; 56 g/m(2)) control. One implant was inserted in the lower rectovaginal septum, and one was used for abdominal wall defect reconstruction. Grafts were removed after 180 days; all graft-related complications were recorded, and explants underwent bi-axial tensiometry and contractility testing. Half of ACM-implanted animals had palpable induration in the vaginal implantation area, two of these also on the abdominal implant. One animal had a vaginal exposure. Vaginal ACMs were 63 % less stiff compared to abdominal ACM explants (p = 0.01) but comparable to vaginal PP explants. Seven anterior vaginal ACM explants showed areas of graft degradation on histology. There was no overall difference in vaginal contractility. Considering histologic degradation in the anterior vaginal implant as representative for the host, posterior ACM explants of animals with degradation had a 60 % reduced contractility as compared to PP (p = 0.048). Three abdominal implants showed histologic degradation; those were more compliant than non-degraded implants. Vaginal implantation with ACM was associated with graft-related complications (GRCs) and biomechanical properties comparable to PP. Partially degraded ACM had a decreased vaginal contractility.

  11. Animal models of frailty: current applications in clinical research.

    PubMed

    Kane, Alice E; Hilmer, Sarah N; Mach, John; Mitchell, Sarah J; de Cabo, Rafael; Howlett, Susan E

    2016-01-01

    The ethical, logistical, and biological complications of working with an older population of people inherently limits clinical studies of frailty. The recent development of animal models of frailty, and tools for assessing frailty in animal models provides an invaluable opportunity for frailty research. This review summarizes currently published animal models of frailty including the interleukin-10 knock-out mouse, the mouse frailty phenotype assessment tool, and the mouse clinical frailty index. It discusses both current and potential roles of these models in research into mechanisms of frailty, interventions to prevent/delay frailty, and the effect of frailty on outcomes. Finally, this review discusses some of the challenges and opportunities of translating research findings from animals to humans.

  12. Animal models of frailty: current applications in clinical research

    PubMed Central

    Kane, Alice E; Hilmer, Sarah N; Mach, John; Mitchell, Sarah J; de Cabo, Rafael; Howlett, Susan E

    2016-01-01

    The ethical, logistical, and biological complications of working with an older population of people inherently limits clinical studies of frailty. The recent development of animal models of frailty, and tools for assessing frailty in animal models provides an invaluable opportunity for frailty research. This review summarizes currently published animal models of frailty including the interleukin-10 knock-out mouse, the mouse frailty phenotype assessment tool, and the mouse clinical frailty index. It discusses both current and potential roles of these models in research into mechanisms of frailty, interventions to prevent/delay frailty, and the effect of frailty on outcomes. Finally, this review discusses some of the challenges and opportunities of translating research findings from animals to humans. PMID:27822024

  13. Ecological-network models link diversity, structure and function in the plankton food-web

    NASA Astrophysics Data System (ADS)

    D’Alelio, Domenico; Libralato, Simone; Wyatt, Timothy; Ribera D’Alcalà, Maurizio

    2016-02-01

    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.

  14. 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

  15. Novel approximation of misalignment fading modeled by Beckmann distribution on free-space optical links.

    PubMed

    Boluda-Ruiz, Rubén; García-Zambrana, Antonio; Castillo-Vázquez, Carmen; Castillo-Vázquez, Beatriz

    2016-10-03

    A novel accurate and useful approximation of the well-known Beckmann distribution is presented here, which is used to model generalized pointing errors in the context of free-space optical (FSO) communication systems. We derive an approximate closed-form probability density function (PDF) for the composite gamma-gamma (GG) atmospheric turbulence with the pointing error model using the proposed approximation of the Beckmann distribution, which is valid for most practical terrestrial FSO links. This approximation takes into account the effect of the beam width, different jitters for the elevation and the horizontal displacement and the simultaneous effect of nonzero boresight errors for each axis at the receiver plane. Additionally, the proposed approximation allows us to delimit two different FSO scenarios. The first of them is when atmospheric turbulence is the dominant effect in relation to generalized pointing errors, and the second one when generalized pointing error is the dominant effect in relation to atmospheric turbulence. The second FSO scenario has not been studied in-depth by the research community. Moreover, the accuracy of the method is measured both visually and quantitatively using curve-fitting metrics. Simulation results are further included to confirm the analytical results.

  16. 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

    2016-02-17

    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.

  17. 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.

  18. 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.

  19. 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

  20. Assessing biocomputational modelling in transforming clinical guidelines for osteoporosis management.

    PubMed

    Thiel, Rainer; Viceconti, Marco; Stroetmann, Karl

    2011-01-01

    Biocomputational modelling as developed by the European Virtual Physiological Human (VPH) Initiative is the area of ICT most likely to revolutionise in the longer term the practice of medicine. Using the example of osteoporosis management, a socio-economic assessment framework is presented that captures how the transformation of clinical guidelines through VPH models can be evaluated. Applied to the Osteoporotic Virtual Physiological Human Project, a consequent benefit-cost analysis delivers promising results, both methodologically and substantially.

  1. 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…

  2. 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.

  3. Playing the role of weak clique property in link prediction: A friend recommendation model.

    PubMed

    Ma, Chuang; Zhou, Tao; Zhang, Hai-Feng

    2016-07-21

    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.

  4. Numerical modelling of the shoulder for clinical applications.

    PubMed

    Favre, Philippe; Snedeker, Jess G; Gerber, Christian

    2009-05-28

    Research activity involving numerical models of the shoulder is dramatically increasing, driven by growing rates of injury and the need to better understand shoulder joint pathologies to develop therapeutic strategies. Based on the type of clinical question they can address, existing models can be broadly categorized into three groups: (i) rigid body models that can simulate kinematics, collisions between entities or wrapping of the muscles over the bones, and which have been used to investigate joint kinematics and ergonomics, and are often coupled with (ii) muscle force estimation techniques, consisting mainly of optimization methods and electromyography-driven models, to simulate muscular action and joint reaction forces to address issues in joint stability, muscular rehabilitation or muscle transfer, and (iii) deformable models that account for stress-strain distributions in the component structures to study articular degeneration, implant failure or muscle/tendon/bone integrity. The state of the art in numerical modelling of the shoulder is reviewed, and the advantages, limitations and potential clinical applications of these modelling approaches are critically discussed. This review concentrates primarily on muscle force estimation modelling, with emphasis on a novel muscle recruitment paradigm, compared with traditionally applied optimization methods. Finally, the necessary benchmarks for validating shoulder models, the emerging technologies that will enable further advances and the future challenges in the field are described.

  5. Implementation of a new model of clinical education for regional occupational therapy student clinical placements.

    PubMed

    Furness, Linda; Pighills, Alison C; Ducat, Wendy; Tynan, Anna

    2016-09-16

    Expansion of occupational therapy education programs has resulted in increased student numbers and demand on clinicians to host clinical placements while also maintaining the delivery of high-quality, safe clinical services to patients. Much of the research about innovative placement models, including student contributions to service delivery, has been conducted in metropolitan areas. Therefore, there is a need to develop models that are suited to regional settings that face diversity of caseload, more generalised occupational therapy roles and variations in patient flow. The aim of the present study was to describe the initial application of the Calderdale Framework in student education in a regional context and look at lessons learnt. The Calderdale Framework provided a structured, clinically governed process whereby occupational therapists were able to determine which tasks could be allocated to students and provided a framework to support student training and competency development. The Calderdale Framework has been used successfully to implement allied health models involving professional skill sharing and delegation of tasks to allied health assistants, but it has not been used in clinical education. Pilot implementation of the Calderdale Framework showed that the model supports quality and safety of student-provided occupational therapy services and that the teaching method provides a platform for student skill development. These results warrant further investigation and are potentially transferrable to student education in other health professions.What is known about the topic? The Calderdale Framework provides a systematic method for reviewing skill mix, developing new roles, identifying new ways of working and facilitating service redesign in healthcare environments. It provides a structure for service and task analysis with a focus on developing clinical competencies, but has not been used in clinical education.What does this paper add? This paper

  6. 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...

  7. 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.

  8. 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.

  9. A model of placebo response in antidepressant clinical trials.

    PubMed

    Rutherford, Bret R; Roose, Steven P

    2013-07-01

    Placebo response in clinical trials of antidepressant medications is substantial and has been increasing. High placebo response rates hamper efforts to detect signals of efficacy for new antidepressant medications, contributing to trial failures 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. In this review, the authors examine contributors to placebo response in antidepressant clinical trials and propose 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 designed to enhance treatment response.

  10. Model-based query language for analyzing clinical processes.

    PubMed

    Barzdins, Janis; Barzdins, Juris; Rencis, Edgars; Sostaks, Agris

    2013-01-01

    Nowadays large databases of clinical process data exist in hospitals. However, these data are rarely used in full scope. In order to perform queries on hospital processes, one must either choose from the predefined queries or develop queries using MS Excel-type software system, which is not always a trivial task. In this paper we propose a new query language for analyzing clinical processes that is easily perceptible also by non-IT professionals. We develop this language based on a process modeling language which is also described in this paper. Prototypes of both languages have already been verified using real examples from hospitals.

  11. Linking optimization and ecological models in a decision support tool for oyster restoration and management.

    PubMed

    North, E W; King, D M; Xu, J; Hood, R R; Newell, R I E; Paynter, K; Kellogg, M L; Liddel, M K; Boesch, D F

    2010-04-01

    Restoration of ecologically important marine species and habitats is restricted by funding constraints and hindered by lack of information about trade-offs among restoration goals and the effectiveness of alternative restoration strategies. Because ecosystems provide diverse human and ecological benefits, achieving one restoration benefit may take place at the expense of other benefits. This poses challenges when attempting to allocate limited resources to optimally achieve multiple benefits, and when defining measures of restoration success. We present a restoration decision-support tool that links ecosystem prediction and human use in a flexible "optimization" framework that clarifies important restoration trade-offs, makes location-specific recommendations, predicts benefits, and quantifies the associated costs (in the form of lost opportunities). The tool is illustrated by examining restoration options related to the eastern oyster, Crassostrea virginica, which supported an historically important fishery in Chesapeake Bay and provides a range of ecosystem services such as removing seston, enhancing water clarity, and creating benthic habitat. We use an optimization approach to identify the locations where oyster restoration efforts are most likely to maximize one or more benefits such as reduction in seston, increase in light penetration, spawning stock enhancement, and harvest, subject to funding constraints and other limitations. This proof-of-concept Oyster Restoration Optimization model (ORO) incorporates predictions from three-dimensional water quality (nutrients-phytoplankton zooplankton-detritus [NPZD] with oyster filtration) and larval transport models; calculates size- and salinity-dependent growth, mortality, and fecundity of oysters; and includes economic costs of restoration efforts. Model results indicate that restoration of oysters in different regions of the Chesapeake Bay would maximize different suites of benefits due to interactions between

  12. 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

  13. Linking rates of folding in lattice models of proteins with underlying thermodynamic characteristics

    NASA Astrophysics Data System (ADS)

    Klimov, D. K.; Thirumalai, D.

    1998-09-01

    We investigate the sequence-dependent properties of proteins that determine the dual requirements of stability of the native state and its kinetic accessibility using simple cubic lattice models. Three interaction schemes are used to describe the potentials between nearest neighbor nonbonded beads. We show that, under the simulation conditions when the native basin of attraction (NBA) is the most stable, there is an excellent correlation between folding times τF and the dimensionless parameter σT=(Tθ-TF)/Tθ, where Tθ is the collapse temperature and TF is the folding transition temperature. There is also a significant correlation between τF and another dimensionless quantity Z=(EN-Ems)/δ, where EN is the energy of the native state, Ems is the average energy of the ensemble of misfolded structures, and δ is the dispersion in the contact energies. In contrast, there is no significant correlation between τF and the Z-score gap ΔZ=EN-Ems. An approximate relationship between σT and the Z-score is derived, which explains the superior correlation seen between τF and σT. For two state folders τF is linked to the free energy difference (not simply energy gap, however it is defined) between the unfolded states and the NBA.

  14. 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

  15. 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

  16. Three-Dimensional Characterization and Modeling of Microstructural Weak Links for Spall Damage in FCC Metals

    SciTech Connect

    Krishnan, Kapil; Brown, Andrew; Wayne, Leda; Vo, Johnathan; Opie, Saul; Lim, Harn; Peralta, Pedro; Luo, Sheng-Nian; Byler, Darrin; McClellan, Kenneth J.; Koskelo, Aaron; Dickerson, Robert

    2014-11-25

    Local microstructural weak links for spall damage were investigated using three-dimensional (3-D) characterization in multicrystalline copper samples (grain size ≈ 450 µm) shocked with laser-driven plates at low pressures (2 to 4 GPa). The thickness of samples and flyer plates, approximately 1000 and 500 µm respectively, led to short pressure pulses that allowed isolating microstructure effects on local damage characteristics. Electron Backscattering Diffraction and optical microscopy were used to relate the presence, size, and shape of porosity to local microstructure. The experiments were complemented with 3-D finite element simulations of individual grain boundaries (GBs) that resulted in large damage volumes using crystal plasticity coupled with a void nucleation and growth model. Results from analysis of these damage sites show that the presence of a GB-affected zone, where strain concentration occurs next to a GB, correlates strongly with damage localization at these sites, most likely due to the inability of maintaining strain compatibility across these interfaces, with additional effects due to the inclination of the GB with respect to the shock. Results indicate that strain compatibility plays an important role on intergranular spall damage in metallic materials.

  17. Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.

    PubMed

    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.

  18. Genetic and Environmental Models of Circadian Disruption Link SRC-2 Function to Hepatic Pathology.

    PubMed

    Fleet, Tiffany; Stashi, Erin; Zhu, Bokai; Rajapakshe, Kimal; Marcelo, Kathrina L; Kettner, Nicole M; Gorman, Blythe K; Coarfa, Cristian; Fu, Loning; O'Malley, Bert W; York, Brian

    2016-10-01

    Circadian rhythmicity is a fundamental process that synchronizes behavioral cues with metabolic homeostasis. Disruption of daily cycles due to jet lag or shift work results in severe physiological consequences including advanced aging, metabolic syndrome, and even cancer. Our understanding of the molecular clock, which is regulated by intricate positive feedforward and negative feedback loops, has expanded to include an important metabolic transcriptional coregulator, Steroid Receptor Coactivator-2 (SRC-2), that regulates both the central clock of the suprachiasmatic nucleus (SCN) and peripheral clocks including the liver. We hypothesized that an environmental uncoupling of the light-dark phases, termed chronic circadian disruption (CCD), would lead to pathology similar to the genetic circadian disruption observed with loss of SRC-2 We found that CCD and ablation of SRC-2 in mice led to a common comorbidity of metabolic syndrome also found in humans with circadian disruption, non-alcoholic fatty liver disease (NAFLD). The combination of SRC-2(-/-) and CCD results in a more robust phenotype that correlates with human non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) gene signatures. Either CCD or SRC-2 ablation produces an advanced aging phenotype leading to increased mortality consistent with other circadian mutant mouse models. Collectively, our studies demonstrate that SRC-2 provides an essential link between the behavioral activities influenced by light cues and the metabolic homeostasis maintained by the liver.

  19. Three-Dimensional Characterization and Modeling of Microstructural Weak Links for Spall Damage in FCC Metals

    DOE PAGES

    Krishnan, Kapil; Brown, Andrew; Wayne, Leda; ...

    2014-11-25

    Local microstructural weak links for spall damage were investigated using three-dimensional (3-D) characterization in multicrystalline copper samples (grain size ≈ 450 µm) shocked with laser-driven plates at low pressures (2 to 4 GPa). The thickness of samples and flyer plates, approximately 1000 and 500 µm respectively, led to short pressure pulses that allowed isolating microstructure effects on local damage characteristics. Electron Backscattering Diffraction and optical microscopy were used to relate the presence, size, and shape of porosity to local microstructure. The experiments were complemented with 3-D finite element simulations of individual grain boundaries (GBs) that resulted in large damage volumesmore » using crystal plasticity coupled with a void nucleation and growth model. Results from analysis of these damage sites show that the presence of a GB-affected zone, where strain concentration occurs next to a GB, correlates strongly with damage localization at these sites, most likely due to the inability of maintaining strain compatibility across these interfaces, with additional effects due to the inclination of the GB with respect to the shock. Results indicate that strain compatibility plays an important role on intergranular spall damage in metallic materials.« less

  20. Linked-cluster expansion for the Green's function of the infinite-U Hubbard model.

    PubMed

    Khatami, Ehsan; Perepelitsky, Edward; Rigol, Marcos; Shastry, B Sriram

    2014-06-01

    We implement a highly efficient strong-coupling expansion for the Green's function of the Hubbard model. In the limit of extreme correlations, where the onsite interaction is infinite, the evaluation of diagrams simplifies dramatically enabling us to carry out the expansion to the eighth order in powers of the hopping amplitude. We compute the finite-temperature Green's function analytically in the momentum and Matsubara frequency space as a function of the electron density. Employing Padé approximations, we study the equation of state, Kelvin thermopower, momentum distribution function, quasiparticle fraction, and quasiparticle lifetime of the system at temperatures lower than, or of the order of, the hopping amplitude. We also discuss several different approaches for obtaining the spectral functions through analytic continuation of the imaginary frequency Green's function, and show results for the system near half filling. We benchmark our results for the equation of state against those obtained from a numerical linked-cluster expansion carried out to the eleventh order.

  1. Development and Validation of Detailed Clinical Models for Nursing Problems in Perinatal care

    PubMed Central

    Kim, Y.; Park, H.-A.

    2011-01-01

    Objectives The aims of this study were to develop detailed clinical models (DCMs) for nursing problems related to perinatal care and to test the applicability of these detailed clinical models. Methods First, we extracted entities of nursing problems by analyzing nursing-problem statements from nursing records, reviewing the literature, and interviewing nurse experts. Second, we extracted attributes and possible values needed to describe the entities in more detail by again analyzing nursing statements, reviewing the literature, and consulting nurse experts. Third, DCMs were modeled by linking each entity with possible attributes with value sets and optionalities. Fourth, entities, attributes and value sets in the DCMs were mapped to the International Classification for Nursing Practice (ICNP) version 2. Finally, DCMs were validated by consulting a group of experts and by applying them to real clinical data and nursing care scenarios published in the literature. The adequacy of the entities, attributes, value sets, and optionalities of the attributes were validated. Results Fifty-eight entities were identified, 41 entities from nursing records, 12 entities from literature review and 5 entities from nurse experts. Sixty-five attributes with values were identified, 25 attributes from nursing records, 34 attributes from literature review, and 6 attributes from nurse experts. In total 58 DCMs were developed and validated. Conclusions The DCMs developed in this study can ensure that electronic health records contain meaningful and valid information, and support the semantic interoperability of nursing information. PMID:23616872

  2. Multiscale Modeling in the Clinic: Drug Design and Development

    SciTech Connect

    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.

    2016-02-17

    A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multi-scale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multi-scale 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 multi-scale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical techniques employed for multi-scale modeling approaches used in pharmacology and present several examples illustrating the current state-of-the-art regarding drug development for: Excitable Systems (Heart); Cancer (Metastasis and Differentiation); Cancer (Angiogenesis and Drug Targeting); Metabolic Disorders; and Inflammation and Sepsis. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multi-scale models.

  3. 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.

  4. Modeling decision support rule interactions in a clinical setting.

    PubMed

    Sordo, Margarita; Rocha, Beatriz H; Morales, Alfredo A; Maviglia, Saverio M; Oglio, Elisa Dell'Oglio; Fairbanks, Amanda; Aroy, Teal; Dubois, David; Bouyer-Ferullo, Sharon; Rocha, Roberto A

    2013-01-01

    Traditionally, rule interactions are handled at implementation time through rule task properties that control the order in which rules are executed. By doing so, knowledge about the behavior and interactions of decision rules is not captured at modeling time. We argue that this is important knowledge that should be integrated in the modeling phase. In this project, we build upon current work on a conceptual schema to represent clinical knowledge for decision support in the form of if then rules. This schema currently captures provenance of the clinical content, context where such content is actionable (i.e. constraints) and the logic of the rule itself. For this project, we borrowed concepts from both the Semantic Web (i.e., Ontologies) and Complex Adaptive Systems (CAS), to explore a conceptual approach for modeling rule interactions in an enterprise-wide clinical setting. We expect that a more comprehensive modeling will facilitate knowledge authoring, editing and update; foster consistency in rules implementation and maintenance; and develop authoritative knowledge repositories to promote quality, safety and efficacy of healthcare.

  5. Model-Driven Paediatric Cardiomyopathy Pathways - A Clinical Impact Assessment.

    PubMed

    Stroetmann, Karl A; Thiel, Rainer

    2017-01-01

    Intermediate results from an ongoing health technology assessment exercise of a simulation model of paediatric cardiomyopathy are reported. Comprehensive data on paediatric cardiomyopathy/heart failure, treatment options, incidence and prevalence, prognoses for different outcomes to be expected were collected. Based on this knowledge, a detailed clinical pathway model was developed and validated against the clinical workflow in a tertiary paediatric care hospital. It combines three disease stages and various treatment options with estimates of the probabilities of a child moving from one stage to another. To reflect the complexity of initial decision taking by clinicians, a three-stage Markov model was combined with a decision tree approach - a Markov decision process. A Markov Chain simulation tool was applied to compare estimates of transition probabilities and cost data of present standard of care treatment options for a cohort of children over ten years with expected improvements from using a clinical decision support tool based on the disease model under development. Early results indicate a slight increase of overall costs resulting from the extra cost of using such a tool in spite of some savings to be expected from improved care. However, the intangible benefits in life years saved of severely ill children and the improvement in QoL to be expected for moderately ill ones should more than compensate for this.

  6. Model Linking Plasma and Intracellular Tenofovir/Emtricitabine with Deoxynucleoside Triphosphates

    PubMed Central

    Castillo-Mancilla, Jose R.; Bushman, Lane R.; Zheng, Jia-Hua; Kiser, Jennifer J.; MaWhinney, Samantha; Anderson, Peter L.

    2016-01-01

    The coformulation of the nucleos(t)ide analogs (NA) tenofovir (TFV) disoproxil fumarate (TDF) and emtricitabine (FTC) is approved for HIV-infection treatment and prevention. Plasma TFV and FTC undergo complicated hybrid processes to form, accumulate, and retain as their active intracellular anabolites: TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP). Such complexities manifest in nonlinear intracellular pharmacokinetics (PK). In target cells, TFV-DP/FTC-TP compete with endogenous deoxynucleoside triphosphates (dNTP) at the active site of HIV reverse transcriptase, underscoring the importance of analog:dNTP ratios for antiviral efficacy. However, NA such as TFV and FTC have the potential to disturb the dNTP pool, which could augment or reduce their efficacies. We conducted a pharmacokinetics-pharmacodynamics (PKPD) study among forty subjects receiving daily TDF/FTC (300 mg/200 mg) from the first-dose to pharmacological intracellular steady-state (30 days). TFV/FTC in plasma, TFV-DP/FTC-TP and dNTPs in peripheral blood mononuclear cells (PBMC) were quantified using validated LC/MS/MS methodologies. Concentration-time data were analyzed using nonlinear mixed effects modeling (NONMEM). Formations and the accumulation of intracellular TFV-DP/FTC-TP was driven by plasma TFV/FTC, which was described by a hybrid of first-order formation and saturation. An indirect response link model described the interplay between TFV-DP/FTC-TP and the dNTP pool change. The EC50 (interindividual variability, (%CV)) of TFV-DP and FTC-TP on the inhibition of deoxyadenosine triphosphate (dATP) and deoxycytidine triphosphate (dCTP) production were 1020 fmol/106 cells (130%) and 44.4 pmol/106 cells (82.5%), resulting in (90% prediction interval) 11% (0.45%, 53%) and 14% (2.6%, 35%) reductions. Model simulations of analog:dNTP molar ratios using IPERGAY dosing suggested that FTC significantly contributes to the protective effect of preexposure prophylaxis (PrEP). Simulation

  7. 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.

  8. Clinically applied models of bone regeneration in tissue engineering research.

    PubMed

    Einhorn, T A

    1999-10-01

    The development of new strategies for the engineering of bone regeneration requires appropriate model systems. Selection of the best model for testing a new technology depends on a host of factors. In general, the best model system is the one which most closely mimics the clinical situation for which this technology is being developed, will not heal spontaneously unless the technology is used, and will not heal when another technology is used if that technology is less advanced than the one being tested. For the purposes of developing new strategies for bone regeneration, systems which can be considered include those which model normal fracture healing, the segmental loss of bone or critical size defects, and various forms of nonunions in which fracture healing is perturbed either by mechanical, metabolic, or neurologic means. Careful experimental design and selection of the appropriate model system will enhance scientific efforts in bone regeneration research.

  9. [Clinical research XX. From clinical judgment to multiple logistic regression model].

    PubMed

    Berea-Baltierra, Ricardo; Rivas-Ruiz, Rodolfo; Pérez-Rodríguez, Marcela; Palacios-Cruz, Lino; Moreno, Jorge; Talavera, Juan O

    2014-01-01

    The complexity of the causality phenomenon in clinical practice implies that the result of a maneuver is not solely caused by the maneuver, but by the interaction among the maneuver and other baseline factors or variables occurring during the maneuver. This requires methodological designs that allow the evaluation of these variables. When the outcome is a binary variable, we use the multiple logistic regression model (MLRM). This multivariate model is useful when we want to predict or explain, adjusting due to the effect of several risk factors, the effect of a maneuver or exposition over the outcome. In order to perform an MLRM, the outcome or dependent variable must be a binary variable and both categories must mutually exclude each other (i.e. live/death, healthy/ill); on the other hand, independent variables or risk factors may be either qualitative or quantitative. The effect measure obtained from this model is the odds ratio (OR) with 95 % confidence intervals (CI), from which we can estimate the proportion of the outcome's variability explained through the risk factors. For these reasons, the MLRM is used in clinical research, since one of the main objectives in clinical practice comprises the ability to predict or explain an event where different risk or prognostic factors are taken into account.

  10. 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.

  11. 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.

  12. A comparison of low back kinetic estimates obtained through posture matching, rigid link modeling and an EMG-assisted model.

    PubMed

    Parkinson, R J; Bezaire, M; Callaghan, J P

    2011-07-01

    This study examined errors introduced by a posture matching approach (3DMatch) relative to dynamic three-dimensional rigid link and EMG-assisted models. Eighty-eight lifting trials of various combinations of heights (floor, 0.67, 1.2 m), asymmetry (left, right and center) and mass (7.6 and 9.7 kg) were videotaped while spine postures, ground reaction forces, segment orientations and muscle activations were documented and used to estimate joint moments and forces (L5/S1). Posture matching over predicted peak and cumulative extension moment (p < 0.0001 for all variables). There was no difference between peak compression estimates obtained with posture matching or EMG-assisted approaches (p = 0.7987). Posture matching over predicted cumulative (p < 0.0001) compressive loading due to a bias in standing, however, individualized bias correction eliminated the differences. Therefore, posture matching provides a method to analyze industrial lifting exposures that will predict kinetic values similar to those of more sophisticated models, provided necessary corrections are applied.

  13. A regulatory model for clinical laboratories: an empirical evaluation.

    PubMed

    Peddecord, K M

    1989-04-01

    Clinical laboratories in the United States are subject to various regulatory and accreditation programs, which mandate a broad range of requirements regarding personnel, quality-control systems, and analytical proficiency standards. Reported here, for a cross-section of U.S. laboratories, is the degree of compliance with these regulatory requirements, some other laboratory characteristics, and their relation to analytical proficiency. The results suggest that those laboratory characteristics that predict highest proficiency-test performance differ for each laboratory specialty. Regression models are presented that explain from 12% to 35% of the variation in analytical performance and suggest that factors outside of those specified in the regulatory model and other characteristics measured in this research are important. Indeed, the current regulatory approach may not ensure highest performance. Also discussed are the current status, limitations, and prospects for change of the clinical laboratory regulatory system.

  14. 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

  15. 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.

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

    DTIC Science & Technology

    2013-06-01

    AD_________________ Award Number: W81XWH-11-2-0133 TITLE: Framework for Smart Electronic Health...NUMBER Framework for Smart Electronic Health Record-Linked Predictive Models to Optimize Care for Complex Digestive Diseases 5b. GRANT NUMBER...an intelligent workspace , by displaying annotation forms and de-identified reports with the same view, automatic report queuing and providing easy

  17. 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.…

  18. 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...

  19. "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...

  20. 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...

  1. Bringing computational models of bone regeneration to the clinic.

    PubMed

    Carlier, Aurélie; Geris, Liesbet; Lammens, Johan; Van Oosterwyck, Hans

    2015-01-01

    Although the field of bone regeneration has experienced great advancements in the last decades, integrating all the relevant, patient-specific information into a personalized diagnosis and optimal treatment remains a challenging task due to the large number of variables that affect bone regeneration. Computational models have the potential to cope with this complexity and to improve the fundamental understanding of the bone regeneration processes as well as to predict and optimize the patient-specific treatment strategies. However, the current use of computational models in daily orthopedic practice is very limited or inexistent. We have identified three key hurdles that limit the translation of computational models of bone regeneration from bench to bed side. First, there exists a clear mismatch between the scope of the existing and the clinically required models. Second, most computational models are confronted with limited quantitative information of insufficient quality thereby hampering the determination of patient-specific parameter values. Third, current computational models are only corroborated with animal models, whereas a thorough (retrospective and prospective) assessment of the computational model will be crucial to convince the health care providers of the capabilities thereof. These challenges must be addressed so that computational models of bone regeneration can reach their true potential, resulting in the advancement of individualized care and reduction of the associated health care costs.

  2. 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

  3. 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.

  4. 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).

  5. Linking the Weather Generator with Regional Climate Model: Effect of Higher Resolution

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

    This contribution builds on our last year EGU contribution, which followed two aims: (i) validation of the simulations of the present climate made by the ALADIN-Climate Regional Climate Model (RCM) at 25 km resolution, and (ii) presenting a methodology for linking the parametric weather generator (WG) with RCM output (aiming to calibrate a gridded WG capable of producing realistic synthetic multivariate weather series for weather-ungauged locations). Now we have available new higher-resolution (6.25 km) simulations with the same RCM. The main topic of this contribution is an anser to a following question: What is an effect of using a higher spatial resolution on a quality of simulating the surface weather characteristics? In the first part, the high resolution RCM simulation of the present climate will be validated in terms of selected WG parameters, which 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. When comparing the WG parameters from the two sources (RCM vs observations), we interpolate the RCM-based parameters into the station locations while accounting for the effect of altitude. In the second part, we will discuss an effect of using the higher resolution: the results of the validation tests will be compared with those obtained with the lower-resolution RCM. 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 action).

  6. Spontaneous shaker rat mutant – a new model for X-linked tremor/ataxia

    PubMed Central

    Figueroa, Karla P.; Paul, Sharan; Calì, Tito; Lopreiato, Raffaele; Karan, Sukanya; Frizzarin, Martina; Ames, Darren; Zanni, Ginevra; Brini, Marisa; Dansithong, Warunee; Milash, Brett; Scoles, Daniel R.; Carafoli, Ernesto; Pulst, Stefan M.

    2016-01-01

    ABSTRACT The shaker rat is an X-linked recessive spontaneous model of progressive Purkinje cell (PC) degeneration exhibiting a shaking ataxia and wide stance. Generation of Wistar Furth (WF)/Brown Norwegian (BN) F1 hybrids and genetic mapping of F2 sib-sib offspring using polymorphic markers narrowed the candidate gene region to 26 Mbp denoted by the last recombinant genetic marker DXRat21 at 133 Mbp to qter (the end of the long arm). In the WF background, the shaker mutation has complete penetrance, results in a stereotypic phenotype and there is a narrow window for age of disease onset; by contrast, the F2 hybrid phenotype was more varied, with a later age of onset and likely non-penetrance of the mutation. By deep RNA-sequencing, five variants were found in the candidate region; four were novel without known annotation. One of the variants caused an arginine (R) to cysteine (C) change at codon 35 of the ATPase, Ca2+ transporting, plasma membrane 3 (Atp2b3) gene encoding PMCA3 that has high expression in the cerebellum. The variant was well supported by hundreds of overlapping reads, and was found in 100% of all affected replicas and 0% of the wild-type (WT) replicas. The mutation segregated with disease in all affected animals and the amino acid change was found in an evolutionarily conserved region of PMCA3. Despite strong genetic evidence for pathogenicity, in vitro analyses of PMCA3R35C function did not show any differences to WT PMCA3. Because Atp2b3 mutation leads to congenital ataxia in humans, the identified Atp2b3 missense change in the shaker rat presents a good candidate for the shaker rat phenotype based on genetic criteria, but cannot yet be considered a definite pathogenic variant owing to lack of functional changes. PMID:27013529

  7. Linking flickering to waves and whole-cell oscillations in a mitochondrial network model.

    PubMed

    Nivala, Melissa; Korge, Paavo; Nivala, Michael; Weiss, James N; Qu, Zhilin

    2011-11-02

    It has been shown that transient single mitochondrial depolarizations, known as flickers, tend to occur randomly in space and time. On the other hand, many studies have shown that mitochondrial depolarization waves and whole-cell oscillations occur under oxidative stress. How single mitochondrial flickering events and whole-cell oscillations are mechanistically linked remains unclear. In this study, we developed a Markov model of the inner membrane anion channel in which reactive-oxidative-species (ROS)-induced opening of the inner membrane anion channel causes transient mitochondrial depolarizations in a single mitochondrion that occur in a nonperiodic manner, simulating flickering. We then coupled the individual mitochondria into a network, in which flickers occur randomly and sparsely when a small number of mitochondria are in the state of high superoxide production. As the number of mitochondria in the high-superoxide-production state increases, short-lived or abortive waves due to ROS-induced ROS release coexist with flickers. When the number of mitochondria in the high-superoxide-production state reaches a critical number, recurring propagating waves are observed. The origins of the waves occur randomly in space and are self-organized as a consequence of random flickering and local synchronization. We show that at this critical state, the depolarization clusters exhibit a power-law distribution, a signature of self-organized criticality. In addition, the whole-cell mitochondrial membrane potential changes from exhibiting small random fluctuations to more periodic oscillations as the superoxide production rate increases. These simulation results may provide mechanistic insight into the transition from random mitochondrial flickering to the waves and whole-cell oscillations observed in many experimental studies.

  8. 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.

  9. 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

  10. Pyrolysis of simple coal model compounds containing aromatic carboxylic acids: Does decarboxylation lead to cross-linking?

    SciTech Connect

    Eskay, T.P.; Britt, P.F.; Buchanan, A.C. III

    1996-02-01

    The thermolysis of two aromatic carboxylic acids 1,2-(3,3`-dicarboxyphenyl)ethane (2) have been investigated at 400{degree} C as models of carboxylic acids in low rank coals. The major decomposition pathway observed is decarboxylation, which mainly occurs by an ionic pathway. This decarboxylation route does not lead to any significant amount of coupling or high molecular weight products that would be indicative of cross-linking products in coal. The pyrolysis of 1 and 2 will be investigated under a variety of conditions that better mimic the enviromment found in coal to further delineate the role that decarboxylation plays in coal cross-linking chemistry.

  11. [Clinical research XIV. From the clinical judgment to the statistical model].

    PubMed

    Talavera, Juan O; Rivas-Ruiz, Rodolfo

    2013-01-01

    A statistical test is incomprehensible when it is out of context, so it is necessary to identify the details of the phenomenon of causality in the clinical course of the disease and to integrate the statistical model. Thus, the statistical tests used will try to characterize baseline, maneuver and the outcome, and will show the relationship between them. When we read the results in clinical research, the first thing that the author describes are general characteristics of the population, starting with number of patients evaluated and selected, average age, gender, and number of subjects meeting the outcome. This is extremely important because with the same criteria two studies may contain populations completely opposite. Posterior description usually continues through tables that follow a logical sequence, which allow us to integrate the statistical model to clinical judgment: baseline characteristics of the population and its distribution in each of the maneuvers, characteristics of the main and peripheral maneuvers, main effect of the maneuver on the outcome, and the impact of principal maneuver in the outcome, but adjusted for any variable that can alter this impact.

  12. 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

  13. On the Links between Attachment Style, Parental Rearing Behaviors, and Internalizing and Externalizing Problems in Non-Clinical Children

    ERIC Educational Resources Information Center

    Roelofs, Jeffrey; Meesters, Cor; ter Huurne, Mijke; Bamelis, Lotte; Muris, Peter

    2006-01-01

    We sought to investigate the relationships between negative family factors such as insecure attachment and adverse parental rearing, and internalizing and externalizing symptoms in a large sample of non-clinical children (N = 237) aged 9 to 12 years. All children completed a set of self-report questionnaires including a single-item measure of…

  14. 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 and tested using advanced human exposure models linked to electronic health records. Methods and analysis This study has 5 stages: (1) development and deployment of personal air monitors; (2) recruitment and monitoring of a cohort of 160 patients with COPD for up to 6 months with recruitment of participants through the Clinical Practice Research Datalink (CPRD); (3) statistical associations between personal exposure with COPD-related health outcomes; (4) validation of a time-activity exposure model and (5) development of a COPD prediction model for London. Ethics and dissemination The Research Ethics Committee for Camden and Islington has provided ethical approval for the conduct of the study. Approval has also been granted by National Health Service (NHS) Research and Development and the Independent Scientific Advisory Committee. The results of the study will be disseminated through appropriate conference presentations and peer-reviewed journals. PMID:27412104

  15. Keratoconus, cross-link-induction, comparison between fitting exponential function and a fitting equation obtained by a mathematical model.

    PubMed

    Albanese, A; Urso, R; Bianciardi, L; Rigato, M; Battisti, E

    2009-11-01

    With reference to experimental data in the literature, we present a model consisting of two elastic elements, conceived to simulate resistance to stretching, at constant velocity of elongation, of corneal tissue affected by keratoconus, treated with riboflavin and ultraviolet irradiation to induce cross-linking. The function describing model behaviour adapted to stress and strain values. It was found that the Young's moduli of the two elastic elements increased in cross-linked tissues and that cross-linking treatment therefore increased corneal rigidity. It is recognized that this observation is substantially in line with the conclusion reported in the literature, obtained using an exponential fitting function. It is observed, however, that the latter function implies a condition of non-zero stresses without strain, and does not provide interpretative insights for lack of any biomechanical basis. Above all, the function fits a singular trend, inexplicably claimed to be viscoelastic, with surprising perfection. In any case, using the reported data, the study demonstrates that a fitting equation obtained by a modelling approach not only shows the evident efficacy of the treatment, but also provides orientations for studying modifications induced in cross-linked fibres.

  16. 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

  17. Linking HIV-positive adolescents to care in 15 different clinics across the United States: creating solutions to address structural barriers for linkage to care.

    PubMed

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

    2014-01-01

    Linkage to care is a critical corollary to expanded HIV testing, but many adolescents are not successfully linked to care, in part due to fragmented care systems. Through a collaboration of the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC) and the Adolescent Trials Network (ATN), a linkage to care outreach worker was provided to ATN clinics. Factors related to linkage were explored to better understand how to improve retention rates and health outcomes for HIV-positive adolescents. We conducted 124 interviews with staff at 15 Adolescent Trials Network clinics to better understand linkage to care processes, barriers, and facilitators. Content analysis was conducted focusing on structural barriers to care and potential solutions, specifically at the macro-, meso-, and micro-levels. Macro-level barriers included navigating health insurance policies, transportation to appointments, and ease of collecting and sharing client-level contact information between testing agencies, local health departments and clinics; meso-level barriers included lack of youth friendliness within clinic space and staff, and duplication of linkage services; micro-level barriers included adolescents' readiness for care and adolescent developmental capacity. Staff initiated solutions included providing transportation for appointments and funding clinic visits and tests with a range of grants and clinic funds while waiting for insurance approval. However, such solutions were often ad hoc and partial, using micro-level solutions to address macro-level barriers. Comprehensive initiatives to improve linkage to care are needed to address barriers to HIV-care for adolescents, whose unique developmental needs make accessing care particularly challenging. Matching the level of structural solution to the level of structural barriers (i.e., macro-level with macro-level), such as creating policy to address needed youth healthcare entitlements versus covering

  18. The animal models of dementia and Alzheimer's disease for pre-clinical testing and clinical translation.

    PubMed

    Anand, Akshay; Banik, Avijit; Thakur, Keshav; Masters, Colin L

    2012-11-01

    Dementia is a clinical syndrome with abnormal degree of memory loss and impaired ability to recall events from the past often characterized by Alzheimer's disease. The various strategies to treat dementia need validation of novel compounds in suitable animal models for testing their safety and efficacy. These may include novel anti-amnesic drugs derived from synthetic chemistry or those derived from traditional herbal sources. Multiple approaches have been adopted to create reliable animal models ranging from rodents to non-human primates, where the animals are exposed to a predetermined injury or causing genetic ablation across specific regions of brain suspected to affect learning functions. In this review various animal models for Alzheimer's disease and treatment strategies in development of anti dementia drugs are discussed and an attempt has been made to provide a comprehensive report of the latest developments in the field.

  19. Linking Predictive Models to Generic Planning Methods for Water Resource System Adaptation: Initial Application to The Thames Basin

    NASA Astrophysics Data System (ADS)

    Harou, J. J.; Matrosov, E.; Wade, S.; New, M. G.; Pinte, D.

    2009-12-01

    Adapting water resource systems to unknown future conditions will involve using trusted predictive models within planning methods. Planning methods include stochastic simulation and optimization, shared vision planning, robust-decision making, and others. The methods embed existing predictive models into the core of a planning process aiming to improve system design and/or operation. Planning methods that connect in a generic and modular way to predictive models will enable flexible and efficient deployment. This talk describes a generic open-source model platform that helps link models to planning methods. The link is made through standardized import/export functions or customized add-ins. The program allows to edit, organize, store, visualize and transfer model inputs and outputs. A computationally efficient water resource simulation model, IRAS, was connected to the platform using an add-in. A simple IRAS model of the Thames basin system was built with a weekly time step and 80 year time horizon and compared to a more detailed daily predictive model used by the UK’s Environment Agency. The Thames model is being connected to a scenario generator based on robust decision making. The scenarios will help identify robust system designs given multiple uncertain inputs (inflows, demands, energy prices).

  20. Linking observations at active volcanoes to physical processes through conduit flow modelling

    NASA Astrophysics Data System (ADS)

    Thomas, Mark; Neuberg, Jurgen

    2010-05-01

    of the Low frequency events observed on Montserrat is their tightly confined source region. The high degree of similarity of the waveforms from such events indicates a stationary common source within a finite volume of 150m x 150m x 150m (Neuberg et al., 2006). By modelling the physical processes that occur at depth within the volcano it has been possible to identify a potential source region of these events caused by the shape of the conduit, that has a fixed position and will have the potential cause repeatable events whenever magma is moving within the system. Making links of this type is essential to form a better understanding of what the observations made by monitoring systems actually relate to in terms of the volcanoes activity. Tuffen, H., Dingwell, D.B., and Pinkerton, H. 2003. Repeated fracture and healing of silicic magma generate flow banding and earthquakes? Geology, 31(12), 1089-1092. Collier, L. and Neuberg, J. 2006. Incorporating seismic observations into 2D conduit flow modelling. Journal of volcanology and geothermal research, 152, 331-346. Neuberg, J., Tuffen, H., Collier, L., Green, D., Powell, T., and Dingwell, P. 2006. The trigger mechanisms of low-frequency swarms on Montserrat. Journal of volcanology and geothermal research, 153, 37-50.

  1. Preparing clinically expert faculty educators: an academic partnership model.

    PubMed

    Guttman, Minerva S; Parietti, Elizabeth S; Reineke, Patricia R; Mahoney, Janet

    2011-01-01

    To increase nursing education capacity in New Jersey, the Robert Wood Johnson Foundation (RWJF) New Jersey Nursing Initiative (NJNI) awarded grants to prepare graduate nursing students to become clinically expert faculty. The purpose of this article was to describe the experiences of a collaborative partnership in preparing 14 scholars for the faculty role. The partnership developed two innovative models of preparing faculty with clinical expertise. The curriculum of the Fairleigh Dickinson University Adult Nurse Practitioner program was enhanced with education courses and intensive teaching practicum. The curriculum of the Monmouth University Nursing Education program was enhanced with more intensive clinical immersion in a selected concentration. Both models were based on the National League for Nursing nurse educator competencies (J. A. Halstead, 2007). The RWJF scholars were socialized into the faculty role from the start of the program through curricular and extracurricular activities. To date, all components of the enhanced curriculum were implemented with plans for sustaining the programs and partnership. Of 14 scholars, 4 graduated, and 10 are on track to graduate as projected. The curriculum enhancements improved two successful master's programs preparing graduates for not one, but two advanced practice roles.

  2. On the contribution of moment-bearing links to bending and twisting in a three-dimensional sliding filament model.

    PubMed Central

    Hines, M; Blum, J J

    1984-01-01

    Previously (Hines, M., and J.J. Blum 1983, Biophys. J., 41:67-79), a method was developed that allowed one to compute curvature and twist for a three-dimensional sliding filament model. In that formalism it was difficult to specify the shear and bending moments arising from moment-bearing interfilament links such as fixed 5-6 bridges or dyneins. Euler's equation offers a straightforward method for computing these bending and shear moments when the potential energy stored in the links as a function of axonemal shape is specified. We used this approach to examine the effect of 5-6 bridges on curvature and twist for several distributions of internal shear moments. Twist changes the angle that a link makes with a doublet and thus in some circumstances may reduce the potential energy stored in those links. Twist is a second-order effect proportional to the square of the distance between an outer doublet and the neutral axis. Fixed links will not generate twist if they are symmetrically located around the axoneme. PMID:6548650

  3. Non-parametric estimation of the odds ratios for continuous exposures using generalized additive models with an unknown link function.

    PubMed

    Cadarso-Suárez, Carmen; Roca-Pardiñas, Javier; Figueiras, Adolfo; González-Manteiga, Wenceslao

    2005-04-30

    The generalized additive, model (GAM) is a powerful and widely used tool that allows researchers to fit, non-parametrically, the effect of continuous predictors on a transformation of the mean response variable. Such a transformation is given by a so-called link function, and in GAMs this link function is assumed to be known. Nevertheless, if an incorrect choice is made for the link, the resulting GAM is misspecified and the results obtained may be misleading. In this paper, we propose a modified version of the local scoring algorithm that allows for the non-parametric estimation of the link function, by using local linear kernel smoothers. To better understand the effect that each covariate produces on the outcome, results are expressed in terms of the non-parametric odds ratio (OR) curves. Bootstrap techniques were used to correct the bias in the OR estimation and to construct point-wise confidence intervals. A simulation study was carried out to assess the behaviour of the resulting estimates. The proposed methodology was illustrated using data from the AIDS Register of Galicia (NW Spain), with a view to assessing the effect of the CD4 lymphocyte count on the probability of being AIDS-diagnosed via Tuberculosis (TB). This application shows how the link's flexibility makes it possible to obtain OR curve estimates that are less sensitive to the presence of outliers and unusual values that are often present in the extremes of the covariate distributions.

  4. RPGR-Associated Retinal Degeneration in Human X-Linked RP and a Murine Model

    PubMed Central

    Huang, Wei Chieh; Wright, Alan F.; Roman, Alejandro J.; Cideciyan, Artur V.; Manson, Forbes D.; Gewaily, Dina Y.; Schwartz, Sharon B.; Sadigh, Sam; Limberis, Maria P.; Bell, Peter; Wilson, James M.; Swaroop, Anand; Jacobson, Samuel G.

    2012-01-01

    Purpose. We investigated the retinal disease due to mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in human patients and in an Rpgr conditional knockout (cko) mouse model. Methods. XLRP patients with RPGR-ORF15 mutations (n = 35, ages at first visit 5–72 years) had clinical examinations, and rod and cone perimetry. Rpgr-cko mice, in which the proximal promoter and first exon were deleted ubiquitously, were back-crossed onto a BALB/c background, and studied with optical coherence tomography and electroretinography (ERG). Retinal histopathology was performed on a subset. Results. Different patterns of rod and cone dysfunction were present in patients. Frequently, there were midperipheral losses with residual rod and cone function in central and peripheral retina. Longitudinal data indicated that central rod loss preceded peripheral rod losses. Central cone-only vision with no peripheral function was a late stage. Less commonly, patients had central rod and cone dysfunction, but preserved, albeit abnormal, midperipheral rod and cone vision. Rpgr-cko mice had progressive retinal degeneration detectable in the first months of life. ERGs indicated relatively equal rod and cone disease. At late stages, there was greater inferior versus superior retinal degeneration. Conclusions. RPGR mutations lead to progressive loss of rod and cone vision, but show different patterns of residual photoreceptor disease expression. Knowledge of the patterns should guide treatment strategies. Rpgr-cko mice had onset of degeneration at relatively young ages and progressive photoreceptor disease. The natural history in this model will permit preclinical proof-of-concept studies to be designed and such studies should advance progress toward human therapy. PMID:22807293

  5. A model linking video gaming, sleep quality, sweet drinks consumption and obesity among children and youth.

    PubMed

    Turel, O; Romashkin, A; Morrison, K M

    2017-03-20

    There is a growing need to curb paediatric obesity. The aim of this study is to untangle associations between video-game-use attributes and obesity as a first step towards identifying and examining possible interventions. Cross-sectional time-lagged cohort study was employed using parent-child surveys (t1) and objective physical activity and physiological measures (t2) from 125 children/adolescents (mean age = 13.06, 9-17-year-olds) who play video games, recruited from two clinics at a Canadian academic children's hospital. Structural equation modelling and analysis of covariance were employed for inference. The results of the study are as follows: (i) self-reported video-game play duration in the 4-h window before bedtime is related to greater abdominal adiposity (waist-to-height ratio) and this association may be mediated through reduced sleep quality (measured with the Pittsburgh Sleep Quality Index); and (ii) self-reported average video-game session duration is associated with greater abdominal adiposity and this association may be mediated through higher self-reported sweet drinks consumption while playing video games and reduced sleep quality. Video-game play duration in the 4-h window before bedtime, typical video-game session duration, sweet drinks consumption while playing video games and poor sleep quality have aversive associations with abdominal adiposity. Paediatricians and researchers should further explore how these factors can be altered through behavioural or pharmacological interventions as a means to reduce paediatric obesity.

  6. Functional Characterization of IPSC-Derived Brain Cells as a Model for X-Linked Adrenoleukodystrophy.

    PubMed

    Baarine, Mauhamad; Khan, Mushfiquddin; Singh, Avtar; Singh, Inderjit

    2015-01-01

    X-ALD is an inherited neurodegenerative disorder where mutations in the ABCD1 gene result in clinically diverse phenotypes: the fatal disorder of cerebral childhood ALD (cALD) or a milder disorder of adrenomyeloneuropathy (AMN). The various models used to study the pathobiology of X-ALD disease lack the appropriate presentation for different phenotypes of cALD vs AMN. This study demonstrates that induced pluripotent stem cells (IPSC) derived brain cells astrocytes (Ast), neurons and oligodendrocytes (OLs) express morphological and functional activities of the respective brain cell types. The excessive accumulation of saturated VLCFA, a "hallmark" of X-ALD, was observed in both AMN OLs and cALD OLs with higher levels observed in cALD OLs than AMN OLs. The levels of ELOVL1 (ELOVL Fatty Acid Elongase 1) mRNA parallel the VLCFA load in AMN and cALD OLs. Furthermore, cALD Ast expressed higher levels of proinflammatory cytokines than AMN Ast and control Ast with or without stimulation with lipopolysaccharide. These results document that IPSC-derived Ast and OLs from cALD and AMN fibroblasts mimic the respective biochemical disease phenotypes and thus provide an ideal platform to investigate the mechanism of VLCFA load in cALD OLs and VLCFA-induced inflammatory disease mechanisms of cALD Ast and thus for testing of new therapeutics for AMN and cALD disease of X-ALD.

  7. A model to facilitate reflective thinking in clinical nursing education.

    PubMed

    Chabeli, M; Muller, M

    2004-11-01

    A qualitative, contextual, exploratory and descriptive design for theory generation was used to develop a model to facilitate reflective thinking in clinical nursing education (Mouton & Marais, 1990:43; Mouton, 1996: 103-109; Chinn & Kramer 1991:79-120). A model was developed within the existing frameworks of theory generation. Wilson (1963:23-39) and Gift (1997:75,76) provided a theoretical framework for a concept analysis of reflective thinking in phase one of the study. Further conceptual meaning was attained through a perceptual survey where twelve nurse educators participated in a focus group interview with regard to how reflective thinking can be facilitated in clinical nursing education. Classification of the main concepts and sub-concepts was made through a conceptualisation process within Dickoff, James and Wiedenbach's (1968:415-435) theoretical framework using the six elements of practice theory. Concluding relation statements were inferred through deductive analysis and synthesis after conceptualisation of each main concept. The relation statements provided the basis for model description (Chinn & Kramer, 1991:107-125). Definitions of the main concepts and sub-concepts were described using the basic rules by (Rossouw, 2001:10-11; Cohen & Copi, 1994:192-195). The adapted educational process from five learning theories provided a framework through which the procedure to facilitate reflective thinking in clinical nursing education was described. Lastly, the model was evaluated using the pre-determined criteria by Chinn and Kramer (1991:128-137) and refined by experts in qualitative research and theory generation. Guidelines were developed which do not form part of this article. Theoretical validity was ensured. Recommendations, limitations, challenging hypothesis and a conclusion were made.

  8. 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

  9. Implementation of the Clinical Facilitation Model within an Australian rural setting: the role of the Clinical Facilitator.

    PubMed

    Sanderson, Helena; Lea, Jacqueline

    2012-11-01

    Education providers globally use various models for undergraduate nurse clinical education. This paper presents the major findings of a research project conducted by a rural university in Australia that aimed to explore the Clinical Facilitation Model of undergraduate nursing education from a rural perspective. In particular how the Clinical Facilitators enacted their role within the rural environment and to identify any barriers to the provision of effective clinical learning during facilitated clinical experience within this context. This qualitative study used a phenomenological approach to explore the experiences of Clinical Facilitators. Individual in-depth interviews were conducted with eight Clinical Facilitators. Data was analysed using thematic analysis and several themes emerged from the study. This paper will report two of the major findings which are based on how Clinical Facilitators enacted their role within the rural environment. Whilst this study has a rural focus the findings will add to the limited body of knowledge internationally regarding the Clinical Facilitation model used as a result of balancing educational needs of the student with the care needs of the patients in the current health policy climate. The findings will be useful for informing undergraduate curricula, and will assist faculty and health services in planning and implementation of models of clinical education that meet the needs of the student and that are specific to the rural environment. In addition, the findings will provide insight into strategies that the rural Clinical Facilitator can utilise to assist in fulfilling their teaching role.

  10. Accurate Modelling of a Flexible-Link Planar Mechanism by Means of a Linearized Model in the State-Space Form for Design of a Vibration Controller

    NASA Astrophysics Data System (ADS)

    GASPARETTO, A.

    2001-02-01

    Vibration control of flexible link mechanisms with more than two flexible links is still an open question, mainly because defining a model that is adequate for the designing of a controller is a rather difficult task. In this work, an accurate dynamic non-linear model of a flexible-link planar mechanism is presented. In order to bring the system into a form that is suitable for the design of a vibration controller, the model is then linearized about an operating point, so as to achieve a linear model of the system in the standard state-space form of system theory. The linear model obtained, which is valid for whatever planar mechanism with any number of flexible link, is then applied to a four-bar planar linkage. Extensive simulation is carried out, aimed at comparing the system dynamic evolution, both in the open- and in the closed-loop case, using the non-linear model and the linearized one. The results prove that the error made by using the linearized system instead of the non-linear one is small. Therefore, it can be concluded that the model proposed in this work can constitute an effective basis for designing and testing many types of vibration controllers for flexible planar mechanisms.

  11. An 'integrative neuroscience' perspective on ADHD: linking cognition, emotion, brain and genetic measures with implications for clinical support.

    PubMed

    Williams, Leanne M; Tsang, Tracey W; Clarke, Simon; Kohn, Michael

    2010-10-01

    There remains a translational gap between research findings and their implementation in clinical practice that applies to attention-deficit/hyperactivity disorder (ADHD), as well as to other major disorders of brain health in childhood, adolescence and adulthood. Research studies have identified potential 'markers' to support diagnostic, functional assessment and treatment decisions, but there is little consensus about these markers. Of these potential markers, cognitive measures of thinking functions, such as sustaining attention and associated electrical brain activity, show promise in complementing the clinical management process. Emerging evidence highlights the relevance of emotional, as well as thinking, functions to ADHD. Here, we outline an integrative neuroscience framework for ADHD that offers one means to bring together cognitive measures of thinking functions with measures of emotion, and their brain and genetic correlates. Understanding these measures and the relationships between them is a first step towards the development of tools that will help to assess the heterogeneity of ADHD, and aid in tailoring treatment choices.

  12. 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.

  13. 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.

  14. A temporal model for Clinical Data Analytics language.

    PubMed

    Safari, Leila; Patrick, Jon D

    2013-01-01

    The proposal of a special purpose language for Clinical Data Analytics (CliniDAL) is presented along with a general model for expressing temporal events in the language. The temporal dimension of clinical data needs to be addressed from at least five different points of view. Firstly, how to attach the knowledge of time based constraints to queries; secondly, how to mine temporal data in different CISs with various data models; thirdly, how to deal with both relative time and absolute time in the query language; fourthly, how to tackle internal time-event dependencies in queries, and finally, how to manage historical time events preserved in the patient's narrative. The temporal elements of the language are defined in Bachus Naur Form (BNF) along with a UML schema. Its use in a designed taxonomy of a five class hierarchy of data analytics tasks shows the solution to problems of time event dependencies in a highly complex cascade of queries needed to evaluate scientific experiments. The issues in using the model in a practical way are discussed as well.

  15. Clinical Trials

    MedlinePlus

    ... Sponsors Why Are They Important How Do They Work Who Can Participate What To Expect During Benefits and Risks How They Protect Participants Finding Clinical Trials Links Children & Clinical Studies NHLBI Trials Clinical Trial Websites What Are Clinical ...

  16. Testing a Dual Cascade Model Linking Competence and Symptoms over 20 Years from Childhood to Adulthood

    ERIC Educational Resources Information Center

    Obradovic, Jelena; Burt, Keith B.; Masten, Ann S.

    2010-01-01

    This study examined the unique longitudinal effects linking academic competence, social competence, and internalizing symptoms from childhood to adulthood. A multimethod and multi-informant approach was used to assess psychopathology and competence in 205 participants during four developmental periods. Social competence in childhood had a…

  17. Common Ground: Exploring Compatibilities between the Linked Data Models of the Library of Congress and OCLC

    ERIC Educational Resources Information Center

    Godby, Carol Jean; Denenberg, Ray

    2015-01-01

    Jointly released by OCLC and the Library of Congress, this white paper compares and contrasts the compatible linked data initiatives at both institutions. It is an executive summary of a more detailed technical analysis that will be released later this year. The white paper summarizes the recent activity of the Bibliographic Framework Initiative…

  18. Markers, Models, and Measurement Error: Exploring the Links between Attention Deficits and Language Impairments

    ERIC Educational Resources Information Center

    Redmond, Sean M.

    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…

  19. ParentLink: A Model of Integration and Support for Parents.

    ERIC Educational Resources Information Center

    Mertensmeyer, Carol; Fine, Mark

    2000-01-01

    Discusses ParentLink, a collective of Missouri organizations and agencies striving to simplify parents' access to research-based information, services, and problem-solving support pertaining to parenting. It is based on systems theory, specifically the ecology of human development. A comprehensive array of technologies augments ParentLink…

  20. Patient safety's missing link: using clinical expertise to recognize, respond to and reduce risks at a population level

    PubMed Central</