Sample records for intravenous challenge model

  1. Intravenous hemostats: challenges in translation to patients (United States)

    Lashof-Sullivan, Margaret; Shoffstall, Andrew; Lavik, Erin


    Excessive bleeding and the resulting complications are a leading killer of young people globally. There are many successful methods to halt bleeding in the extremities, including compression, tourniquets, and dressings. However, current treatments for internal hemorrhage (including from head or truncal injuries), termed non-compressible bleeding, are inadequate. For these non-compressible injuries, blood transfusions are the current treatment standard. However, they must be refrigerated, may potentially transfer disease, and are of limited supply. In addition, time is of the essence for halting hemorrhage, since more than a third of civilian deaths due to hemorrhage from trauma occur before the patient even reaches the hospital. As a result, particles that can cross-link activated platelets through the glycoprotein IIb/IIIa receptor expressed on activated platelets are being investigated as an alternative treatment for non-compressible bleeding. Ideally, these particles would interact specifically with platelets to stabilize the platelet plug. Initial designs used biologically derived microparticles with red blood cell fragment or albumin cores decorated with RGD or fibrinogen, which bind to GPIIb/IIIa. More recently there has been research into the use of fully synthetic nanoparticles with liposomal or polymer cores that crosslink platelets through a targeting peptide bound to the surface. Some of the challenges for the development of these particles include appropriate sizing to prevent blocking the capillaries of the lungs, immune system evasion to prevent strong reactions and increase circulation time, and storage and resuspension so that first responders can easily use the particles. In addition, the effectiveness of the variety of animal bleeding models in predicting outcomes must be examined before test results can be fully understood. Progress has been made in the development of particles to combat hemorrhage, but issues of immune sensitivity and storage

  2. Modelling Framework and Assistive Device for Peripheral Intravenous Injections (United States)

    Kam, Kin F.; Robinson, Martin P.; Gilbert, Mathew A.; Pelah, Adar


    Intravenous access for blood sampling or drug administration that requires peripheral venepuncture is perhaps the most common invasive procedure practiced in hospitals, clinics and general practice surgeries.We describe an idealised mathematical framework for modelling the dynamics of the peripheral venepuncture process. Basic assumptions of the model are confirmed through motion analysis of needle trajectories during venepuncture, taken from video recordings of a skilled practitioner injecting into a practice kit. The framework is also applied to the design and construction of a proposed device for accurate needle guidance during venepuncture administration, assessed as consistent and repeatable in application and does not lead to over puncture. The study provides insights into the ubiquitous peripheral venepuncture process and may contribute to applications in training and in the design of new devices, including for use in robotic automation.

  3. Mathematical modelling of the intravenous glucose tolerance test. (United States)

    De Gaetano, A; Arino, O


    Several attempts at building a satisfactory model of the glucose-insulin system are recorded in the literature. The minimal model, which is the model currently mostly used in physiological research on the metabolism of glucose, was proposed in the early eighties for the interpretation of the glucose and insulin plasma concentrations following the intravenous glucose tolerance test. It is composed of two parts: the first consists of two differential equations and describes the glucose plasma concentration time-course treating insulin plasma concentration as a known forcing function; the second consists of a single equation and describes the time course of plasma insulin concentration treating glucose plasma concentration as a known forcing function. The two parts are to be separately estimated on the available data. In order to study glucose-insulin homeostasis as a single dynamical system, a unified model would be desirable. To this end, the simple coupling of the original two parts of the minimal model is not appropriate, since it can be shown that, for commonly observed combinations of parameter values, the coupled model would not admit an equilibrium and the concentration of active insulin in the "distant" compartment would be predicted to increase without bounds. For comparison, a simple delay-differential model is introduced, is demonstrated to be globally asymptotically stable around a unique equilibrium point corresponding to the pre-bolus conditions, and is shown to have positive and bounded solutions for all times. The results of fitting the delay-differential model to experimental data from ten healthy volunteers are also shown. It is concluded that a global unified model is both theoretically desirable and practically usable, and that any such model ought to undergo formal analysis to establish its appropriateness and to exclude conflicts with accepted physiological notions.

  4. Overcoming the Challenges of Low Drug Solubility in the Intravenous Formulation of Solithromycin. (United States)

    Evans, Daniel; Yalkowsky, Samuel; Wu, Sara; Pereira, David; Fernandes, Prabha


    Solithromycin is a fluoro-ketolide (a fourth-generation macrolide) antibiotic that has been undergoing clinical trials for the treatment of community-acquired bacterial pneumonia. In this study, development of the tri-amino acid-buffered solithromycin intravenous (IV) formulation was performed to minimize the occurrence of infusion-associated local adverse events (infusion-site pain or phlebitis) observed in patients who received the tartaric acid-buffered IV formulation with a lower buffered capacity during phase I clinical trials. Development of the tri-amino acids-buffered solithromycin IV formulation was achieved using a dynamic in vitro precipitation model. Computational modeling also supports the superiority of the amino acid-buffered formulation over the tartaric aid-buffered formulation. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Stable-label intravenous glucose tolerance test minimal model

    International Nuclear Information System (INIS)

    Avogaro, A.; Bristow, J.D.; Bier, D.M.; Cobelli, C.; Toffolo, G.


    The minimal model approach to estimating insulin sensitivity (Sl) and glucose effectiveness in promoting its own disposition at basal insulin (SG) is a powerful tool that has been underutilized given its potential applications. In part, this has been due to its inability to separate insulin and glucose effects on peripheral uptake from their effects on hepatic glucose inflow. Prior enhancements, with radiotracer labeling of the dosage, permit this separation but are unsuitable for use in pregnancy and childhood. In this study, we labeled the intravenous glucose tolerance test (IVGTT) dosage with [6,6- 2 H 2 ]glucose, [2- 2 H]glucose, or both stable isotopically labeled glucose tracers and modeled glucose kinetics in six postabsorptive, nonobese adults. As previously found with the radiotracer model, the tracer-estimated S*l derived from the stable-label IVGTT was greater than Sl in each case except one, and the tracer-estimated SG* was less than SG in each instance. More importantly, however, the stable-label IVGTT estimated each parameter with an average precision of +/- 5% (range 3-9%) compared to average precisions of +/- 74% (range 7-309%) for SG and +/- 22% (range 3-72%) for Sl. In addition, because of the different metabolic fates of the two deuterated tracers, there were minor differences in basal insulin-derived measures of glucose effectiveness, but these differences were negligible for parameters describing insulin-stimulated processes. In conclusion, the stable-label IVGTT is a simple, highly precise means of assessing insulin sensitivity and glucose effectiveness at basal insulin that can be used to measure these parameters in individuals of all ages, including children and pregnant women

  6. Towards system-level modeling and characterization of components for intravenous therapy

    NARCIS (Netherlands)

    Alveringh, Dennis; Wiegerink, Remco J.; Lötters, Joost Conrad


    Problems occur regularly with intravenous therapy, especially with the flow behavior. A mechanical model can predict which components of intravenous therapy systems introduce non-ideal effects in the flow. This study concentrates on gaining quantitative information of each separate component for

  7. Hydropower Modeling Challenges

    Energy Technology Data Exchange (ETDEWEB)

    Stoll, Brady [National Renewable Energy Lab. (NREL), Golden, CO (United States); Andrade, Juan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Cohen, Stuart [National Renewable Energy Lab. (NREL), Golden, CO (United States); Brinkman, Greg [National Renewable Energy Lab. (NREL), Golden, CO (United States); Brancucci Martinez-Anido, Carlo [National Renewable Energy Lab. (NREL), Golden, CO (United States)


    Hydropower facilities are important assets for the electric power sector and represent a key source of flexibility for electric grids with large amounts of variable generation. As variable renewable generation sources expand, understanding the capabilities and limitations of the flexibility from hydropower resources is important for grid planning. Appropriately modeling these resources, however, is difficult because of the wide variety of constraints these plants face that other generators do not. These constraints can be broadly categorized as environmental, operational, and regulatory. This report highlights several key issues involving incorporating these constraints when modeling hydropower operations in terms of production cost and capacity expansion. Many of these challenges involve a lack of data to adequately represent the constraints or issues of model complexity and run time. We present several potential methods for improving the accuracy of hydropower representation in these models to allow for a better understanding of hydropower's capabilities.

  8. Pretreatment with intravenous lipid emulsion reduces mortality from cocaine toxicity in a rat model. (United States)

    Carreiro, Stephanie; Blum, Jared; Hack, Jason B


    We compare the effects of intravenous lipid emulsion and normal saline solution pretreatment on mortality and hemodynamic changes in a rat model of cocaine toxicity. We hypothesize that intravenous lipid emulsion will decrease mortality and hemodynamic changes caused by cocaine administration compared with saline solution. Twenty male Sprague-Dawley rats were sedated and randomized to receive intravenous lipid emulsion or normal saline solution, followed by a 10 mg/kg bolus of intravenous cocaine. Continuous monitoring included intra-arterial blood pressure, pulse rate and ECG tracing. Endpoints included a sustained undetectable mean arterial pressure (MAP) or return to baseline MAP for 5 minutes. The log-rank test was used to compare mortality. A mixed-effect repeated-measures ANOVA was used to estimate the effects of group (intravenous lipid emulsion versus saline solution), time, and survival on change in MAP, pulse rate, or pulse pressure. In the normal saline solution group, 7 of 10 animals died compared with 2 of 10 in the intravenous lipid emulsion group. The survival rate of 80% (95% confidence interval 55% to 100%) for the intravenous lipid emulsion rats and 30% (95% confidence interval 0.2% to 58%) for the normal saline solution group was statistically significant (P=.045). Intravenous lipid emulsion pretreatment decreased cocaine-induced cardiovascular collapse and blunted hypotensive effects compared with normal saline solution in this rat model of acute lethal cocaine intoxication. Intravenous lipid emulsion should be investigated further as a potential adjunct in the treatment of severe cocaine toxicity. Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

  9. A metabolomic analysis of two intravenous lipid emulsions in a murine model.

    Directory of Open Access Journals (Sweden)

    Brian T Kalish

    Full Text Available Parenteral nutrition (PN, including intravenous lipid administration, is a life-saving therapy but can be complicated by cholestasis and liver disease. The administration of intravenous soy bean oil (SO has been associated with the development of liver disease, while the administration of intravenous fish oil (FO has been associated with the resolution of liver disease. The biochemical mechanism of this differential effect is unclear. This study compares SO and FO lipid emulsions in a murine model of hepatic steatosis, one of the first hits in PN-associated liver disease.We established a murine model of hepatic steatosis in which liver injury is induced by orally feeding mice a PN solution. C57BL/6J mice were randomized to receive PN alone (a high carbohydrate diet (HCD, PN plus intravenous FO (Omegaven®; Fresenius Kabi AG, Bad Homburg VDH, Germany, PN plus intravenous SO (Intralipid®; Fresenius Kabi AG, Bad Homburg v.d.H., Germany, for Baxter Healthcare, Deerfield, IL, or a chow diet. After 19 days, liver tissue was harvested from all animals and subjected to metabolomic profiling.The administration of an oral HCD without lipid induced profound hepatic steatosis. SO was associated with macro- and microvesicular hepatic steatosis, while FO largely prevented the development of steatosis. 321 detectable compounds were identified in the metabolomic analysis. HCD induced de novo fatty acid synthesis and oxidative stress. Both FO and SO relieved some of the metabolic shift towards de novo lipogenesis, but FO offered additional advantages in terms of lipid peroxidation and the generation of inflammatory precursors.Improved lipid metabolism combined with reduced oxidative stress may explain the protective effect offered by intravenous FO in vivo.

  10. Synchrotron-based intravenous cerebral angiography in a small animal model

    International Nuclear Information System (INIS)

    Kelly, Michael E; Schueltke, Elisabeth; Fiedler, Stephan; Nemoz, Christian; Guzman, Raphael; Corde, Stephanie; Esteve, Francois; LeDuc, Geraldine; Juurlink, Bernhard H J; Meguro, Kotoo


    K-edge digital subtraction angiography (KEDSA), a recently developed synchrotron-based technique, utilizes monochromatic radiation and allows acquisition of high-quality angiography images after intravenous administration of contrast agent. We tested KEDSA for its suitability for intravenous cerebral angiography in an animal model. Adult male New Zealand rabbits were subjected to either angiography with conventional x-ray equipment or synchrotron-based intravenous KEDSA, using an iodine-based contrast agent. Angiography with conventional x-ray equipment after intra-arterial administration of contrast agent demonstrated the major intracranial vessels but no smaller branches. KEDSA was able to visualize the major intracranial vessels as well as smaller branches in both radiography mode (planar images) and tomography mode. Visualization was achieved with as little as 0.5 ml kg -1 of iodinated contrast material. We were able to obtain excellent visualization of the cerebral vasculature in an animal model using intravenous injection of contrast material, using synchrotron-based KEDSA

  11. Intravenous lipid emulsion in the resuscitation of cocaine-induced cardiovascular arrest in a rat model. (United States)

    Chai, Peter R; Hack, Jason B


    Intravenous lipid emulsion (ILE) is a potential antidote for severe overdose of certain lipophilic drugs. Cocaine overdose is often fatal and has no antidote. The use of ILE after cocaine-induced cardiac arrest has been suggested but is not well characterized. The objective of the study is to determine if ILE would reverse cocaine-induced cardiac arrest in a rat model. Twelve Sprague-Dawley rats with intra-arterial and intravenous access were sedated with isoflurane and split into 2 cocaine dose groups, then given either ILE or normal saline (NS) intravenously (IV)-group A, 7 animals received cocaine (10 mg/kg IV) with 6 of 7 given ILE (15 mg/kg IV) and 1 of 7 given NS (equal volume); group B, 5 animals received cocaine (5 mg/kg IV) with 3 of 5 given ILE (15 mg/kg IV) and 2 of 5 given NS (equal volume). Closed chest compressions were initiated for asystole and continued for 15 minutes with rhythm checks every minute. All 12 rats experienced cardiac arrest after cocaine bolus. Resuscitation was successful in 1 of 7 rats in group A and 0 of 5 in group B. Intravenous lipid emulsion administration did not affect outcome of cocaine-induced cardiac arrest compared with control in this model. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Pharmacokinetic-pharmacodynamic modelling of intravenous buprenorphine in conscious horses. (United States)

    Love, Emma J; Pelligand, Ludovic; Taylor, Polly M; Murrell, Joanna C; Sear, John W


    Describe the pharmacokinetics of buprenorphine and norbuprenorphine in horses and to relate the plasma buprenorphine concentration to the pharmacodynamic effects. Single phase non-blinded study. Six dedicated research horses, aged 3-10 years and weighing 480-515 kg. Thermal and mechanical nociceptive thresholds, heart and respiratory rates and locomotor activity were measured before and 15, 30, 45 & 60 minutes and 2, 4, 6, 8, 12 & 24 hours post-administration of 10 μg kg(-1) buprenorphine IV. Intestinal motility was measured 1, 6, 12 & 24 hours after buprenorphine administration. Venous blood samples were obtained before administration of buprenorphine 10 μg kg(-1) IV and 1, 2, 4, 6, 10, 15, 30, 45 & 60 minutes, and 2, 4, 6, 8, 12 & 24 hours afterwards. Plasma buprenorphine and norbuprenorphine concentrations were measured using a liquid chromatography-tandem mass spectroscopy (LC-MS/MS) assay with solid-phase extraction. A non-compartmental method was used for analysis of the plasma concentration-time data and plasma buprenorphine concentrations were modelled against two dynamic effects (change in thermal threshold and mechanical threshold) using a simple Emax model. Plasma buprenorphine concentrations were detectable to 480 minutes in all horses and to 720 minutes in two out of six horses. Norbuprenorphine was not detected. Thermal thresholds increased from 15 minutes post-buprenorphine administration until the 8-12 hour time points. The increase in mechanical threshold ranged from 3.5 to 6.0 Newtons (median: 4.4 N); and was associated with plasma buprenorphine concentrations in the range 0.34-2.45 ng mL(-1) . The suitability of the use of buprenorphine for peri-operative analgesia in the horse is supported by the present study. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  13. A Neospora caninum vaccine using recombinant proteins fails to prevent foetal infection in pregnant cattle after experimental intravenous challenge. (United States)

    Hecker, Yanina P; Cóceres, Verónica; Wilkowsky, Silvina E; Jaramillo Ortiz, José M; Morrell, Eleonora L; Verna, Andrea E; Ganuza, Agustina; Cano, Dora B; Lischinsky, Lilian; Angel, Sergio O; Zamorano, Patricia; Odeón, Anselmo C; Leunda, María R; Campero, Carlos M; Morein, Bror; Moore, Dadín P


    The aim of the present study was to evaluate the immunogenicity and protective efficacy of rNcSAG1, rNcHSP20 and rNcGRA7 recombinant proteins formulated with immune stimulating complexes (ISCOMs) in pregnant heifers against vertical transmission of Neospora caninum. Twelve pregnant heifers were divided into 3 groups of 4 heifers each, receiving different formulations before mating. Immunogens were administered twice subcutaneously: group A animals were inoculated with three recombinant proteins (rNcSAG1, rNcHSP20, rNcGRA7) formulated with ISCOMs; group B animals received ISCOM-MATRIX (without antigen) and group C received sterile phosphate-buffered saline (PBS) only. The recombinant proteins were expressed in Escherichia coli and purified nickel resin. All groups were intravenously challenged with the NC-1 strain of N. caninum at Day 70 of gestation and dams slaughtered at week 17 of the experiment. Heifers from group A developed specific antibodies against rNcSAG1, rNcHSP20 and rNcGRA7 prior to the challenge. Following immunization, an statistically significant increase of antibodies against rNcSAG1 and rNcHSP20 in all animals of group A was detected compared to animals in groups B and C at weeks 5, 13 and 16 (P0.001). There were no differences in IFN-γ production among the experimental groups at any time point (P>0.05). Transplacental transmission was determined in all foetuses of groups A, B and C by Western blot, immunohistochemistry and nested PCR. This work showed that rNcSAG1, rNcHSP20 and rNcGRA7 proteins while immunogenic in cattle failed to prevent the foetal infection in pregnant cattle challenged at Day 70 of gestation. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Neuroprotective and behavioral efficacy of intravenous transplanted adipose stem cells in experimental Parkinsonian rat models

    Directory of Open Access Journals (Sweden)

    Malihe Nakhaeifard


    Full Text Available Background: Parkinson's disease is a deficiency of dopamine in the striatum, characterized by bradykinesis, rigidity and resting tremor. Adipose tissue-Derived Stem Cells (ADSCs have many advantages for cell therapy because of the easy availability and pluripotency without ethical problems. In this research, the effects of ADSCs transplantation on motor impairment of rat Parkinsonian models were evaluated. Materials and Methods: Parkinson model was constructed by the unilateral lesion of striatum of male Wistar rats using 20µg of 6-hydroxydopamine (6-OHDA as lesion group. Cell and α-MEM (α-minimal essential medium groups were lesioned animals that received intravenous injection of 3×106 cells suspended in medium and medium repectively. All rats were evaluated behaviorally with rotarod and apomorphine-induced rotation tests, at 4 and 8 weeks after cell transplantation. Results: Lesion and α-MEM groups showed increased contralateral turns while cell group significantly ameliorated both in rotarod and apomorphine-induced rotation tests. There was a significant difference of contralateral turns between cell and lesioned groups at 8 weeks after transplantation. Lesioned rats showed significant decrease of staying on the rod as compared to control, but in cell group there was a significant increase in comparision with the lesioned animals. Conclusion: ADSCs injected intravenously promote functional recovery in Parkinsonian rats.

  15. Comparison of the Effectiveness of a Virtual Simulator With a Plastic Arm Model in Teaching Intravenous Catheter Insertion Skills. (United States)

    Günay İsmailoğlu, Elif; Zaybak, Ayten


    The objective of this study was to compare the effectiveness of a virtual intravenous simulator with a plastic arm model in teaching intravenous catheter insertion skills to nursing students. We used a randomized controlled quasi-experimental trial design and recruited 65 students who were assigned to the experimental (n = 33) and control (n = 32) groups using the simple random sampling method. The experimental group received intravenous catheterization skills training on the virtual intravenous simulator, and the control group received the same training on a plastic model of a human arm. Data were collected using the personal information form, intravenous catheterization knowledge assessment form, Intravenous Catheterization Skill Test, Self-Confidence and Satisfaction Scale, and Fear Symptoms Scale. In the study, the mean scores in the control group were 20.44 for psychomotor skills, 15.62 for clinical psychomotor skills, 31.78 for self-confidence, and 21.77 for satisfaction. The mean scores in the experimental group were 45.18 for psychomotor skills, 16.28 for clinical psychomotor skills, 34.18 for self-confidence, and 43.89 for satisfaction. The results indicated that psychomotor skills and satisfaction scores were higher in the experimental group, while the clinical psychomotor skills and self-confidence scores were similar in both groups. More students in the control group reported experiencing symptoms such as cold and sweaty hands, significant restlessness, and tense muscles than those in the experimental group.

  16. Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics. (United States)

    Heuberger, Jules A A C; Guan, Zheng; Oyetayo, Olubukayo-Opeyemi; Klumpers, Linda; Morrison, Paul D; Beumer, Tim L; van Gerven, Joop M A; Cohen, Adam F; Freijer, Jan


    Δ(9)-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized through more accurate predictions of the dosing sequence and the wash-out between occasions in a crossover setting, which is mainly determined by the terminal half-life of the compound. The purpose of this study is to better quantify the long-term pharmacokinetics of THC. A population-based PK model for THC was developed describing the profile up to 48 h after an oral, intravenous, and pulmonary dose of THC in humans. In contrast to earlier models, the current model integrates all three major administration routes and covers the long terminal phase of THC. Results show that THC has a fast initial and intermediate half-life, while the apparent terminal half-life is long (21.5 h), with a clearance of 38.8 L/h. Because the current model characterizes the long-term pharmacokinetics, it can be used to assess the accumulation of THC in a multiple-dose setting and to forecast concentration profiles of the drug under many different dosing regimens or administration routes. Additionally, this model could provide helpful insights into the THC challenge test used for the development of (novel) compounds targeting the cannabinoid system for different therapeutic applications and could improve decision making in future clinical trials.

  17. Oscillatory dynamics of an intravenous glucose tolerance test model with delay interval (United States)

    Shi, Xiangyun; Kuang, Yang; Makroglou, Athena; Mokshagundam, Sriprakash; Li, Jiaxu


    Type 2 diabetes mellitus (T2DM) has become prevalent pandemic disease in view of the modern life style. Both diabetic population and health expenses grow rapidly according to American Diabetes Association. Detecting the potential onset of T2DM is an essential focal point in the research of diabetes mellitus. The intravenous glucose tolerance test (IVGTT) is an effective protocol to determine the insulin sensitivity, glucose effectiveness, and pancreatic β-cell functionality, through the analysis and parameter estimation of a proper differential equation model. Delay differential equations have been used to study the complex physiological phenomena including the glucose and insulin regulations. In this paper, we propose a novel approach to model the time delay in IVGTT modeling. This novel approach uses two parameters to simulate not only both discrete time delay and distributed time delay in the past interval, but also the time delay distributed in a past sub-interval. Normally, larger time delay, either a discrete or a distributed delay, will destabilize the system. However, we find that time delay over a sub-interval might not. We present analytically some basic model properties, which are desirable biologically and mathematically. We show that this relatively simple model provides good fit to fluctuating patient data sets and reveals some intriguing dynamics. Moreover, our numerical simulation results indicate that our model may remove the defect in well known Minimal Model, which often overestimates the glucose effectiveness index.

  18. Photoacoustic imaging of intravenously injected photosensitizer in rat burn models for efficient antibacterial photodynamic therapy (United States)

    Tsunoi, Yasuyuki; Sato, Shunichi; Ashida, Hiroshi; Terakawa, Mitsuhiro


    For efficient photodynamic treatment of wound infection, a photosensitizer must be distributed in the whole infected tissue region. To ensure this, depth profiling of a photosensitizer is necessary in vivo. In this study, we applied photoacoustic (PA) imaging to visualize the depth profile of an intravenously injected photosensitizer in rat burn models. In burned tissue, pharmacokinetics is complicated; vascular occlusion takes place in the injured tissue, while vascular permeability increases due to thermal invasion. In this study, we first used Evans Blue (EB) as a test drug to examine the feasibility of photosensitizer dosimetry based on PA imaging. On the basis of the results, an actual photosensitizer, talaporfin sodium was used. An EB solution was intravenously injected into a rat deep dermal burn model. PA imaging was performed on the wound with 532 nm and 610 nm nanosecond light pulses for visualizing vasculatures (blood) and EB, respectively. Two hours after injection, the distribution of EB-originated signal spatially coincided well with that of blood-originated signal measured after injury, indicating that EB molecules leaked out from the blood vessels due to increased permeability. Afterwards, the distribution of EB signal was broadened in the depth direction due to diffusion. At 12 hours after injection, clear EB signals were observed even in the zone of stasis, demonstrating that the leaked EB molecules were delivered to the injured tissue layer. The level and time course of talaporfin sodium-originated signals were different compared with those of EB-originated signals, showing animal-dependent and/or drug-dependent permeabilization and diffusion in the tissue. Thus, photosensitizer dosimetry should be needed before every treatment to achieve desirable outcome of photodynamic treatment, for which PA imaging can be concluded to be valid and useful.

  19. Computer Aided Modelling – Opportunities and Challenges

    DEFF Research Database (Denmark)

    Cameron, Ian; Gani, Rafiqul


    to easily generate new models from underlying phenomena continues to be a challenge, especially in the face of time and cost constraints.Integrated frameworks that allow flexibility of model development and access to a range of embedded tools are central to future model developments. The challenges...

  20. The 24-Hour Mathematical Modeling Challenge (United States)

    Galluzzo, Benjamin J.; Wendt, Theodore J.


    Across the mathematics curriculum there is a renewed emphasis on applications of mathematics and on mathematical modeling. Providing students with modeling experiences beyond the ordinary classroom setting remains a challenge, however. In this article, we describe the 24-hour Mathematical Modeling Challenge, an extracurricular event that exposes…

  1. Pharmacokinetic and Pharmacodynamic Modeling Analysis of Intravenous Esomeprazole in Healthy Volunteers. (United States)

    Liu, Dongyang; Yang, Hong; Jiang, Ji; Nagy, Péter; Shen, Kai; Qian, Jiaming; Hu, Pei


    Esomeprazole is one of the most commonly used drugs to treat gastroesophageal reflux disease and peptic ulcers, but the quantitative relationships among the pharmacokinetics (PK), pharmacodynamics (PD), and pharmacogenomics (PG) of the drug are not fully understood in special patient populations. A clinical PK/PD/PG study of intravenous (IV) esomeprazole in 5 dosing regimens was conducted in 20 healthy Chinese volunteers, who were categorized into Helicobacter pylori (HP)-negative and HP-positive subgroups. Plasma esomeprazole concentration and intragastric H(+) concentration were monitored for 24 hours postdosing. Population PK (PopPK) models were tested based on elimination characteristics and other data. For a single-dose IV esomeprazole regimen, a 2-compartment model with nonlinear elimination characteristics fitted the PK data well. The elimination of esomeprazole was found to be significantly linked to CYP2C19 genotype by 11% to 29%. A mechanism-based PD model was first tested to mimic the irreversible inhibition of H(+) /K(+) -ATPase by esomeprazole using a cell-killing mechanism and models of gastric H(+) secretion that included the effects of an asymmetric circadian rhythm and food effects. Results from this PD model showed that the turnover rate of H(+) /K(+) -ATPase was significantly different between HP-negative and HP-positive subgroups. In conclusion, the PopPK model quantitatively identified the effects of the CYP2C19 genotype on esomeprazole elimination in healthy subjects for the first time. In addition, the effects of HP status on drug effect, H(+) /K(+) -ATPase turnover, and circadian rhythm amplitude were preliminarily explored using a mechanism-based PD model. © 2016, The American College of Clinical Pharmacology.

  2. A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration. (United States)

    Kalluri, Hari V; Zhang, Hongfei; Caritis, Steve N; Venkataramanan, Raman


    Opioid dependence is associated with high morbidity and mortality. Buprenorphine (BUP) is approved by the Food and Drug Administration to treat opioid dependence. There is a lack of clear consensus on the appropriate dosing of BUP due to interpatient physiological differences in absorption/disposition, subjective response assessment and other patient comorbidities. The objective of the present study was to build and validate robust physiologically based pharmacokinetic (PBPK) models for intravenous (IV) and sublingual (SL) BUP as a first step to optimizing BUP pharmacotherapy. BUP-PBPK modelling and simulations were performed using SimCyp® by incorporating the physiochemical properties of BUP, establishing intersystem extrapolation factors-based in vitro-in-vivo extrapolation (IVIVE) methods to extrapolate in vitro enzyme activity data, and using tissue-specific plasma partition coefficient estimations. Published data on IV and SL-BUP in opioid-dependent and non-opioid-dependent patients were used to build the models. Fourteen model-naïve BUP-PK datasets were used for inter- and intrastudy validations. The IV and SL-BUP-PBPK models developed were robust in predicting the multicompartment disposition of BUP over a dosing range of 0.3-32 mg. Predicted plasma concentration-time profiles in virtual patients were consistent with reported data across five single-dose IV, five single-dose SL and four multiple dose SL studies. All PK parameter predictions were within 75-137% of the corresponding observed data. The model developed predicted the brain exposure of BUP to be about four times higher than that of BUP in plasma. The validated PBPK models will be used in future studies to predict BUP plasma and brain concentrations based on the varying demographic, physiological and pathological characteristics of patients. © 2017 The British Pharmacological Society.

  3. A discrete Single Delay Model for the Intra-Venous Glucose Tolerance Test

    Directory of Open Access Journals (Sweden)

    Panunzi Simona


    Full Text Available Abstract Background Due to the increasing importance of identifying insulin resistance, a need exists to have a reliable mathematical model representing the glucose/insulin control system. Such a model should be simple enough to allow precise estimation of insulin sensitivity on a single patient, yet exhibit stable dynamics and reproduce accepted physiological behavior. Results A new, discrete Single Delay Model (SDM of the glucose/insulin system is proposed, applicable to Intra-Venous Glucose Tolerance Tests (IVGTTs as well as to multiple injection and infusion schemes, which is fitted to both glucose and insulin observations simultaneously. The SDM is stable around baseline equilibrium values and has positive bounded solutions at all times. Applying a similar definition as for the Minimal Model (MM SI index, insulin sensitivity is directly represented by the free parameter KxgI of the SDM. In order to assess the reliability of Insulin Sensitivity determinations, both SDM and MM have been fitted to 40 IVGTTs from healthy volunteers. Precision of all parameter estimates is better with the SDM: 40 out of 40 subjects showed identifiable (CV xgI from the SDM, 20 out of 40 having identifiable SI from the MM. KxgI correlates well with the inverse of the HOMA-IR index, while SI correlates only when excluding five subjects with extreme SI values. With the exception of these five subjects, the SDM and MM derived indices correlate very well (r = 0.93. Conclusion The SDM is theoretically sound and practically robust, and can routinely be considered for the determination of insulin sensitivity from the IVGTT. Free software for estimating the SDM parameters is available.

  4. Pharmacokinetic and pharmacodynamic modelling of intravenous, intramuscular and subcutaneous buprenorphine in conscious cats. (United States)

    Steagall, Paulo V M; Pelligand, Ludovic; Giordano, Tatiana; Auberger, Christophe; Sear, John W; Luna, Stelio P L; Taylor, Polly M


    To describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (SC) buprenorphine in cats. Randomized, prospective, blinded, three period crossover experiment. Six healthy adult cats weighing 4.1±0.5 kg. Buprenorphine (0.02 mg kg(-1)) was administered i.v., i.m. or s.c.. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (pbuprenorphine concentration-time data decreased curvilinearly. S.c. PK could not be modeled due to erratic absorption and disposition. I.v. buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t(1/2) k(e0)=47.4 minutes) and receptor binding (k(on)=0.011 mL ng(-1) minute(-1)). Persistence of thermal antinociception was due to slow receptor dissociation (t(1/2) k(off)=18.2 minutes). I.v. and i.m. data followed classical disposition and elimination in most cats. Plasma concentrations after i.v. administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the i.v. route should be preferred over the i.m. and s.c. routes when buprenorphine is administered to cats. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  5. Challenges for Modeling and Simulation

    National Research Council Canada - National Science Library

    Johnson, James


    This document deals with modeling and stimulation. The strengths are study processes that rarely or never occur, evaluate a wide range of alternatives, generate new ideas, new concepts and innovative solutions...

  6. New primate model for the study of intravenous thrombotic potential and its modification

    International Nuclear Information System (INIS)

    Shoenfeld, N.A.; Yeager, A.; Connolly, R.; Ramberg, K.; Forgione, L.; Giorgio, A.; Valeri, C.R.; Callow, A.D.


    Advances in venous reconstruction have been limited by inherent venous thrombogenicity and the absence of a suitable prosthetic material for use in the venous system. We have designed an in vivo experimental model to evaluate early blood-material interactions within the venous system and to quantitate drug efficacy in the alteration of platelet function and fibrin deposition in the baboon. An 8F catheter was placed percutaneously in the femoral vein of an adult male baboon. Indium 111-labeled autogenous platelets or iodine 125-labeled human fibrinogen was infused before the introduction, into the inferior vena cava, of a linear array of 5 x 15 mm alternating Dacron and polytetrafluoroethylene samples attached to a benzalkonium-heparin-treated guide wire. At 60 or 120 minutes the samples were removed and a 1 ml aliquot of blood was drawn. The materials and blood samples were counted in a gamma well counter, and the material counts were normalized to the circulating label present in the 1 ml blood sample. The experiment was repeated after pretreatment with heparin, aspirin, or dextran. Whole blood clotting times and bleeding times were monitored. The results showed decreased platelet and fibrin deposition on polytetrafluoroethylene when compared with Dacron in the venous system. Aspirin, heparin, and dextran were all found to decrease platelet and fibrin deposition onto intravenously placed graft material samples (p less than 0.05, Student's t test). The data confirm the ability of the model to evaluate quantitatively anticoagulants, antiplatelet agents, and prospective graft materials for use in venous reconstructions

  7. A new mouse model for renal lesions produced by intravenous injection of diphtheria toxin A-chain expression plasmid

    Directory of Open Access Journals (Sweden)

    Nakamura Shingo


    Full Text Available Abstract Background Various animal models of renal failure have been produced and used to investigate mechanisms underlying renal disease and develop therapeutic drugs. Most methods available to produce such models appear to involve subtotal nephrectomy or intravenous administration of antibodies raised against basement membrane of glomeruli. In this study, we developed a novel method to produce mouse models of renal failure by intravenous injection of a plasmid carrying a toxic gene such as diphtheria toxin A-chain (DT-A gene. DT-A is known to kill cells by inhibiting protein synthesis. Methods An expression plasmid carrying the cytomegalovirus enhancer/chicken β-actin promoter linked to a DT-A gene was mixed with lipid (FuGENE™6 and the resulting complexes were intravenously injected into adult male B6C3F1 mice every day for up to 6 days. After final injection, the kidneys of these mice were sampled on day 4 and weeks 3 and 5. Results H-E staining of the kidney specimens sampled on day 4 revealed remarkable alterations in glomerular compartments, as exemplified by mesangial cell proliferation and formation of extensive deposits in glomerular basement membrane. At weeks 3 and 5, gradual recovery of these tissues was observed. These mice exhibited proteinuria and disease resembling sub-acute glomerulonephritis. Conclusions Repeated intravenous injections of DT-A expression plasmid DNA/lipid complex caused temporary abnormalities mainly in glomeruli of mouse kidney. The disease in these mice resembles sub-acute glomerulonephritis. These DT-A gene-incorporated mice will be useful as animal models in the fields of nephrology and regenerative medicine.

  8. Comparative kinetics of serum and vitreous humor digoxin concentrations in a guinea pig model. Part I: Intravenous administration of digoxin

    International Nuclear Information System (INIS)

    Donnelly, B.; Balkon, J.; Bidanset, J.H.; Belmonte, A.; Barletta, M.; Manning, T.


    The pharmacokinetics of a single intravenous dose of digoxin in the guinea pig was investigated with emphasis on the penetration of digoxin into the vitreous humor. A controlled study was undertaken and data was collected which indicated that digoxin follows an open, two-compartment pharmacokinetic model with a terminal half-life of 318 minutes. The data indicated that the ratio of vitreous concentrations to serum concentrations were determined to be equal following an initial tissue distribution phase

  9. Five challenges in modelling interacting strain dynamics

    Directory of Open Access Journals (Sweden)

    Paul S. Wikramaratna


    Full Text Available Population epidemiological models where hosts can be infected sequentially by different strains have the potential to help us understand many important diseases. Researchers have in recent years started to develop and use such models, but the extra layer of complexity from multiple strains brings with it many technical challenges. It is therefore hard to build models which have realistic assumptions yet are tractable. Here we outline some of the main challenges in this area. First we begin with the fundamental question of how to translate from complex small-scale dynamics within a host to useful population models. Next we consider the nature of so-called “strain space”. We describe two key types of host heterogeneities, and explain how models could help generate a better understanding of their effects. Finally, for diseases with many strains, we consider the challenge of modelling how immunity accumulates over multiple exposures.

  10. Nine challenges for deterministic epidemic models

    DEFF Research Database (Denmark)

    Roberts, Mick G; Andreasen, Viggo; Lloyd, Alun


    Deterministic models have a long history of being applied to the study of infectious disease epidemiology. We highlight and discuss nine challenges in this area. The first two concern the endemic equilibrium and its stability. We indicate the need for models that describe multi-strain infections......, infections with time-varying infectivity, and those where superinfection is possible. We then consider the need for advances in spatial epidemic models, and draw attention to the lack of models that explore the relationship between communicable and non-communicable diseases. The final two challenges concern...

  11. Synchrotron-based intra-venous K-edge digital subtraction angiography in a pig model: A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Schueltke, Elisabeth [Departments of Surgery, University of Saskatchewan, Saskatoon, SK (Canada); Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK (Canada); Department of Neurological Sciences, Walton Medical Centre, University of Liverpool, Liverpool L97 LJ (United Kingdom)], E-mail:; Fiedler, Stefan [European Molecular Biology Laboratory (EMBL), Nottkestrasse 85, 22603 Hamburg (Germany); Nemoz, Christian [European Synchrotron Radiation Facility (ESRF), 6 rue Horowitz, 38043 Grenoble (France); Ogieglo, Lissa [Departments of Surgery, University of Saskatchewan, Saskatoon, SK (Canada); Kelly, Michael E. [Departments of Surgery, University of Saskatchewan, Saskatoon, SK (Canada); Department of Neurosurgery, Section of Cerebrovascular and Endovascular Neurosurgery, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH (United States); Crawford, Paul [Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herfordshire AL9 7TA (United Kingdom); Esteve, Francois [INSERM U836-ESRF, 6 rue Horowitz, 38043 Grenoble (France); Brochard, Thierry; Renier, Michel; Requardt, Herwig; Le Duc, Geraldine [European Synchrotron Radiation Facility (ESRF), 6 rue Horowitz, 38043 Grenoble (France); Juurlink, Bernhard [Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK (Canada); Meguro, Kotoo [Departments of Surgery, University of Saskatchewan, Saskatoon, SK (Canada)


    Background: K-edge digital subtraction angiography (KEDSA) combined with the tunability of synchrotron beam yields an imaging technique that is highly sensitive to low concentrations of contrast agents. Thus, contrast agent can be administered intravenously, obviating the need for insertion of a guided catheter to deliver a bolus of contrast agent close to the target tissue. With the high-resolution detectors used at synchrotron facilities, images can be acquired at high spatial resolution. Thus, the KEDSA appears particularly suited for studies of neurovascular pathology in animal models, where the vascular diameters are significantly smaller than in human patients. Materials and methods: This feasibility study was designed to test the suitability of KEDSA after intravenous injection of iodine-based contrast agent for use in a pig model. Four adult male pigs were used for our experiments. Neurovascular angiographic images were acquired using KEDSA with a solid state Germanium (Ge) detector at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Results: After intravenous injection of 0.9 ml/kg iodinated contrast agent (Xenetix), the peak iodine concentrations in the internal carotid and middle cerebral arteries reached 35 mg/ml. KEDSA images in radiography mode allowed the visualization of intracranial arteries of less than 1.5 mm diameter.

  12. Intravenous Leiomyomatosis

    African Journals Online (AJOL)

    Hemostasis was well achieved. The tumor weighed 6.7 kg. The postoperative course. Intravenous Leiomyomatosis. Narayanaswamy Mariyappa, Uday Kumar Manikyam1, Dinesh Krishnamurthy2, Preeti K,. Yamini Agarwal, Prakar U. Departments of Obstetrics and Gynaecology, 1Pathology and 2Anaesthesia, Sri Devaraj ...

  13. Acute Metabolic Effects of Exenatide in Patients With Type 1 Diabetes With and Without Residual Insulin to Oral and Intravenous Glucose Challenges (United States)

    Ghazi, Tara; Rink, Linda; Sherr, Jennifer L.; Herold, Kevan C.


    OBJECTIVE Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the gastrointestinal tract. Treatment with GLP-1 analogs has proven to be of clinical use for patients with type 2 diabetes. Patients with type 1 diabetes, particularly those with residual β-cell function, may also respond to treatment, but the acute metabolic effects of GLP-1 analogs on these patients in reaction to both oral and intravenous glucose challenges are not well understood. RESEARCH DESIGN AND METHODS Seventeen patients with type 1 diabetes, half of whom had residual insulin production, underwent two mixed-meal tolerance tests (MMTTs) and two intravenous glucose tolerance tests (IVGTTs), with and without pretreatment with exenatide. No exogenous bolus insulin was administered for the studies. Glucose excursions, insulin secretion rates (ISRs), and levels of glucagon, endogenous GLP-1, and gastric inhibitory polypeptide were measured after the meal or glucose loads. RESULTS During the MMTT, glucose levels were suppressed with exenatide in patients with or without residual insulin production (P = 0.0003). Exenatide treatment did not change the absolute ISR, but the ISR to glucose levels were increased (P = 0.0078). Gastric emptying was delayed (P = 0.0017), and glucagon was suppressed (P = 0.0015). None of these hormonal or glucose changes were detected during the IVGTT with exenatide administration. CONCLUSIONS Exenatide showed a significant antidiabetogenic effect prior to an oral meal in patients with type 1 diabetes involving glucagon suppression and gastric emptying, while preserving increased insulin secretion. GLP-1 analogs may be useful as an adjunctive treatment in type 1 diabetes. PMID:23939544

  14. Effects of Intraosseous Tibial vs. Intravenous Vasopressin in a Hypovolemic Cardiac Arrest Model

    Directory of Open Access Journals (Sweden)

    Justin Fulkerson, MSN


    Full Text Available Introduction: This study compared the effects of vasopressin via tibial intraosseous (IO and intravenous (IV routes on maximum plasma concentration (Cmax, the time to maximum concentration (Tmax, return of spontaneous circulation (ROSC, and time to ROSC in a hypovolemic cardiac arrest model. Methods: This study was a randomized prospective, between-subjects experimental design. A computer program randomly assigned 28 Yorkshire swine to one of four groups: IV (n=7, IO tibia (n=7, cardiopulmonary resuscitation (CPR + defibrillation (n=7, and a control group that received just CPR (n=7. Ventricular fibrillation was induced, and subjects remained in arrest for two minutes. CPR was initiated and 40 units of vasopressin were administered via IO or IV routes. Blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, and 4 minutes. CPR and defibrillation were initiated for 20 minutes or until ROSC was achieved. We measured vasopressin concentrations using highperformance liquid chromatography. Results: There was no significant difference between the IO and IV groups relative to achieving ROSC (p=1.0 but a significant difference between the IV compared to the CPR+ defibrillation group (p=0.031 and IV compared to the CPR-only group (p=0.001. There was a significant difference between the IO group compared to the CPR+ defibrillation group (p=0.031 and IO compared to the CPR-only group (p=0.001. There was no significant difference between the CPR + defibrillation group and the CPR group (p=0.127. There was no significant difference in Cmax between the IO and IV groups (p=0.079. The mean ± standard deviation of Cmax of the IO group was 58,709±25,463pg/mL compared to the IV group, which was 106,198±62,135pg/mL. There was no significant difference in mean Tmax between the groups (p=0.084. There were no significant differences in odds of ROSC between the tibial IO and IV groups. Conclusion: Prompt access to the vascular system using the IO route can circumvent

  15. Eight challenges for network epidemic models

    Directory of Open Access Journals (Sweden)

    Lorenzo Pellis


    Full Text Available Networks offer a fertile framework for studying the spread of infection in human and animal populations. However, owing to the inherent high-dimensionality of networks themselves, modelling transmission through networks is mathematically and computationally challenging. Even the simplest network epidemic models present unanswered questions. Attempts to improve the practical usefulness of network models by including realistic features of contact networks and of host–pathogen biology (e.g. waning immunity have made some progress, but robust analytical results remain scarce. A more general theory is needed to understand the impact of network structure on the dynamics and control of infection. Here we identify a set of challenges that provide scope for active research in the field of network epidemic models.

  16. Intravenous lipid emulsion alters the hemodynamic response to epinephrine in a rat model. (United States)

    Carreiro, Stephanie; Blum, Jared; Jay, Gregory; Hack, Jason B


    Intravenous lipid emulsion (ILE) is an adjunctive antidote used in selected critically ill poisoned patients. These patients may also require administration of advanced cardiac life support (ACLS) drugs. Limited data is available to describe interactions of ILE with standard ACLS drugs, specifically epinephrine. Twenty rats with intra-arterial and intravenous access were sedated with isoflurane and split into ILE or normal saline (NS) pretreatment groups. All received epinephrine 15 μm/kg intravenously (IV). Continuous mean arterial pressure (MAP) and heart rate (HR) were monitored until both indices returned to baseline. Standardized t tests were used to compare peak MAP, time to peak MAP, maximum change in HR, time to maximum change in HR, and time to return to baseline MAP/HR. There was a significant difference (p = 0.023) in time to peak MAP in the ILE group (54 s, 95 % CI 44-64) versus the NS group (40 s, 95 % CI 32-48) and a significant difference (p = 0.004) in time to return to baseline MAP in ILE group (171 s, 95 % CI 148-194) versus NS group (130 s, 95 % CI 113-147). There were no significant differences in the peak change in MAP, peak change in HR, time to minimum HR, or time to return to baseline HR between groups. ILE-pretreated rats had a significant difference in MAP response to epinephrine; ILE delayed the peak effect and prolonged the duration of effect of epinephrine on MAP, but did not alter the peak increase in MAP or the HR response.

  17. Challenges in modelling nanoparticles for drug delivery

    International Nuclear Information System (INIS)

    Barnard, Amanda S


    Although there have been significant advances in the fields of theoretical condensed matter and computational physics, when confronted with the complexity and diversity of nanoparticles available in conventional laboratories a number of modeling challenges remain. These challenges are generally shared among application domains, but the impacts of the limitations and approximations we make to overcome them (or circumvent them) can be more significant one area than another. In the case of nanoparticles for drug delivery applications some immediate challenges include the incompatibility of length-scales, our ability to model weak interactions and solvation, the complexity of the thermochemical environment surrounding the nanoparticles, and the role of polydispersivity in determining properties and performance. Some of these challenges can be met with existing technologies, others with emerging technologies including the data-driven sciences; some others require new methods to be developed. In this article we will briefly review some simple methods and techniques that can be applied to these (and other) challenges, and demonstrate some results using nanodiamond-based drug delivery platforms as an exemplar. (topical review)

  18. A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience

    Directory of Open Access Journals (Sweden)

    Andrew Robert Gallimore


    Full Text Available The state of consciousness induced by N,N-dimethyltryptamine (DMT is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel alternate universe, often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient beings. The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects—less than 20 minutes—militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modelling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anaesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent.

  19. Intravenous lipid emulsion does not reverse dabigatran-induced anticoagulation in a rat model. (United States)

    Blum, Jared; Carreiro, Stephanie; Hack, Jason B


    The anticoagulant dabigatran has no reversal agent and may cause life-threatening bleeding in patients with trauma or closed-space hemorrhage. Intravenous lipid emulsion (ILE) is thought to create a lipid compartment in serum that sequesters lipophilic drugs. Dabigatran is lipophilic, and its anticoagulant effects are concentration dependent. The study objective was to determine if ILE therapy reverses dabigatran's anticoagulant effects. Twenty rats were selected at random, 10 in the ILE group and 10 in a normal saline (NS) control group. Animals had a baseline tail bleeding time (T0), followed by oral dabigatran administration (15 mg/kg). At 45 minutes (T45), a second tail bleed time measurement was performed, followed by a 7-minute infusion of 15 mL/kg ILE or NS. A final 60-minute (T60) bleed time measurement was obtained. An ILE-only group of five animals had bleeding times assessed prior to (T0) and 15 minutes after (T15) ILE therapy. A mixed-effect repeated-measures analysis of variance modeling the effect of time, group, and the interaction of group and time on bleed times was conducted. There was a significant within-subject change in bleeding time across the assessment points (F(2,36) = 33; p < 0.001), but there were no effect of group (F(1,18) = 1.42, p = 0.25) or an interaction between group and assessment point on mean bleeding time (F(2,36) = 0.59, p = 56). Between T0 and T45, average bleeding times increased from 109.5 seconds (95% confidence interval [CI] = 94 to 125 seconds) to 231.8 seconds (95% CI = 193 to 271 seconds; p < 0.0001) for both the ILE group and the NS control group. Between T45 and T60, bleeding times in the ILE group decreased by 31.5 seconds (95% CI = -77 to 14 seconds) and by 6 seconds (95% CI = -67 to 55 seconds) in the NS group (p = 0.46). In the five ILE-only animals, the average bleeding time at T0 was 114 seconds (95% CI = 62 to 166 seconds), which increased significantly at T15 to 237

  20. MRI Based Localisation and Quantification of Abscesses following Experimental S. aureus Intravenous Challenge: Application to Vaccine Evaluation.

    Directory of Open Access Journals (Sweden)

    Elizabeth R Allen

    Full Text Available To develop and validate a sensitive and specific method of abscess enumeration and quantification in a preclinical model of Staphylococcus aureus infection.S. aureus infected murine kidneys were fixed in paraformaldehyde, impregnated with gadolinium, and embedded in agar blocks, which were subjected to 3D magnetic resonance microscopy on a 9.4T MRI scanner. Image analysis techniques were developed, which could identify and quantify abscesses. The result of this imaging was compared with histological examination. The impact of a S. aureus Sortase A vaccination regime was assessed using the technique.Up to 32 murine kidneys could be imaged in a single MRI run, yielding images with voxels of about 25 μm3. S. aureus abscesses could be readily identified in blinded analyses of the kidneys after 3 days of infection, with low inter-observer variability. Comparison with histological sections shows a striking correlation between the two techniques: all presumptive abscesses identified by MRI were confirmed histologically, and histology identified no abscesses not evident on MRI. In view of this, simulations were performed assuming that both MRI reconstruction, and histology examining all sections of the tissue, were fully sensitive and specific at abscess detection. This simulation showed that MRI provided more sensitive and precise estimates of abscess numbers and volume than histology, unless at least 5 histological sections are taken through the long axis of the kidney. We used the MRI technique described to investigate the impact of a S. aureus Sortase A vaccine.Post mortem MRI scanning of large batches of fixed organs has application in the preclinical assessment of S. aureus vaccines.

  1. Seven challenges in modeling vaccine preventable diseases

    Directory of Open Access Journals (Sweden)

    C.J.E. Metcalf


    Full Text Available Vaccination has been one of the most successful public health measures since the introduction of basic sanitation. Substantial mortality and morbidity reductions have been achieved via vaccination against many infections, and the list of diseases that are potentially controllable by vaccines is growing steadily. We introduce key challenges for modeling in shaping our understanding and guiding policy decisions related to vaccine preventable diseases.

  2. Intravenous cobinamide versus hydroxocobalamin for acute treatment of severe cyanide poisoning in a swine (Sus scrofa) model. (United States)

    Bebarta, Vikhyat S; Tanen, David A; Boudreau, Susan; Castaneda, Maria; Zarzabal, Lee A; Vargas, Toni; Boss, Gerry R


    Hydroxocobalamin is a Food and Drug Administration-approved antidote for cyanide poisoning. Cobinamide is a potential antidote that contains 2 cyanide-binding sites. To our knowledge, no study has directly compared hydroxocobalamin with cobinamide in a severe, cyanide-toxic large-animal model. Our objective is to compare the time to return of spontaneous breathing in swine with acute cyanide-induced apnea treated with intravenous hydroxocobalamin, intravenous cobinamide, or saline solution (control). Thirty-three swine (45 to 55 kg) were intubated, anesthetized, and instrumented (continuous mean arterial pressure and cardiac output monitoring). Anesthesia was adjusted to allow spontaneous breathing with FiO2 of 21% during the experiment. Cyanide was continuously infused intravenously until apnea occurred and lasted for 1 minute (time zero). Animals were then randomly assigned to receive intravenous hydroxocobalamin (65 mg/kg), cobinamide (12.5 mg/kg), or saline solution and monitored for 60 minutes. A sample size of 11 animals per group was selected according to obtaining a power of 80%, an α of .05, and an SD of 0.17 in mean time to detect a 20% difference in time to spontaneous breathing. We assessed differences in time to death among groups, using Kaplan-Meier estimation methods, and compared serum lactate, blood pH, cardiac output, mean arterial pressure, respiratory rate, and minute ventilation time curves with repeated-measures ANOVA. Baseline weights and vital signs were similar among groups. The time to apnea and cyanide dose required to achieve apnea were similar. At time zero, mean cyanide blood and lactate concentrations and reduction in mean arterial pressure from baseline were similar. In the saline solution group, 2 of 11 animals survived compared with 10 of 11 in the hydroxocobalamin and cobinamide groups (Pcyanide concentrations became undetectable at the end of the study in both antidote-treated groups, and no statistically significant differences

  3. Aeronautical telecommunications network advances, challenges, and modeling

    CERN Document Server

    Musa, Sarhan M


    Addresses the Challenges of Modern-Day Air Traffic Air traffic control (ATC) directs aircraft in the sky and on the ground to safety, while the Aeronautical Telecommunications Network (ATN) comprises all systems and phases that assist in aircraft departure and landing. The Aeronautical Telecommunications Network: Advances, Challenges, and Modeling focuses on the development of ATN and examines the role of the various systems that link aircraft with the ground. The book places special emphasis on ATC-introducing the modern ATC system from the perspective of the user and the developer-and provides a thorough understanding of the operating mechanism of the ATC system. It discusses the evolution of ATC, explaining its structure and how it works; includes design examples; and describes all subsystems of the ATC system. In addition, the book covers relevant tools, techniques, protocols, and architectures in ATN, including MIPv6, air traffic control (ATC), security of air traffic management (ATM), very-high-frequenc...


    Directory of Open Access Journals (Sweden)

    Ginne Ussi Guadalupe Apodaca-Orozco


    Full Text Available The actual society is undergoing major changes in all its fields; the globalization and liberation of the economy, competitiveness but also international collaboration in capital, goods and services, has led to the need to modify the traditionalist model towards a modern model, where the teacher has to make a synthesis of different theories and new pedagogical approaches that guide the construction of quality study programs that allow to improve the teaching- learning process. Regarding the educational model for the development of human resources in health, it should consider the scientific, technological and humanistic competences, instilling a strong social commitment, whose paradigm is the formation of professionals prepared for the social demand in an integral, competent way, with scientific preparation to accept the challenges of modern society and with a humanistic broad development to live in the society of this time and to serve it with simplicity and modesty, with values as a fundamental pillar of its development.

  5. [An experiment control study on the ovarian reserve function after cisplatin intraperitoneal or intravenous chemotherapy in rats model]. (United States)

    Fan, B Z; Xia, H; Chu, L; Tong, X W


    Objective: To compare the impact on the ovarian reserve function after cisplatin intraperitoneal or intravenous chemotherapy in rats model. Methods: Thirty 8-weeks old female Sprague Dawley rats were randomly assigned to control group (group A, n= 10), intraperitoneal chemotherapy group (group B, n= 10) and intravenous chemotherapy group (group C, n= 10). Cisplatin was diluted by normal saline (NS) into 4 mg/ml. On the first day of chemotherapy, 0.2 ml cisplatin dilution was injected into the abdomen of rats in group B, isodose cisplatin was injected into vein and 1.8 ml NS was injected into abdomen of rats in group C, 2.0 ml NS was injected into abdomen of rats in group A for control. Feed the three groups rats and test the anti-Mullerian hormone (AMH) in serum on day 0 (just before injection), day 10 and day 20 by ELISA, count the numble of follicle in bilateral ovaries on day 20. Results: (1) The levels of serum AMH in the three groups before and after chemotherapy were compared: ① comparison between groups: On day 10 and day 20, the AMH level in group B [(64.5±2.9), (68.6±3.4) ng/L] and group C [(76.1±4.9), (91.3±3.9) ng/L] was significantly lower than that in group A [(120.1±5.3), (121.7±4.6) ng/L; P< 0.01], AMH level in group B was significantly also lower than that in group C ( P= 0.000). ② Comparison within groups: the AMH level on day 0 was significantly lower than that on day 10 and day 20 in group A ( P< 0.01), but there was no significant difference between day 10 and day 20 ( P= 0.427). The AMH level on day 0 was significantly higher than those on day 10 and day 20 in group B ( P< 0.01) and group C ( P< 0.01). There was no difference in AMH level between day 10 and day 20 ( P= 0.124) in group B, but the level was significant lower on day 10 than that on day 20 in group C ( P= 0.011). (2)Comparison of the number of follicles in ovaries of three groups 20 days after chemotherapy: the follicles number in group A (35±13) was greater than that in

  6. Efficacy of Intravenous Mannitol in the Management of Orbital Compartment Syndrome: A Nonhuman Primate Model. (United States)

    Johnson, Davin; Winterborn, Andrew; Kratky, Vladimir


    To report the efficacy of intravenous mannitol in the treatment of orbital compartment syndrome. An experimental study was conducted on 4 nonhuman primates (8 orbits). Orbital compartment syndrome was simulated by injecting autologous blood into both orbits of each nonhuman primate until a pressure of 80 mm Hg was reached (time 0). After 10 minutes, nonhuman primates were randomized to receive an infusion of either mannitol or saline, given over 15 minutes. Five minutes after the infusion was complete, lateral canthotomy and cantholysis was performed on both orbits in isolated steps every 5 minutes. During the study protocol, orbital and intraocular pressures were recorded every 5 minutes, with a final set of measurements at 60 minutes. The primary outcome measures were the mean change in pressure from time 0 to 60 minutes, as well as the mean change in pressure during the infusion period. There was no statistically significant difference in the mean changes in orbital or intraocular pressure from time 0 to 60 minutes of the protocol. However, during the infusion period there was significantly greater decrease in both orbital and intraocular pressure in the mannitol compared with saline group (-34.0 vs. -9.3 mm Hg for orbital pressure [p = 0.03]; -34.8 vs. -9.7 mm Hg for intraocular pressure [p = 0.04]). While the definitive treatment of orbital compartment syndrome is lateral canthotomy and cantholysis, mannitol results in a rapid and clinically meaningful drop in orbital and intraocular pressure. The authors believe that their data support the routine use of mannitol in orbital compartment syndrome, especially when there is a delay in timely surgical management.

  7. Intravenous S-Ketamine Does Not Inhibit Alveolar Fluid Clearance in a Septic Rat Model (United States)

    Weber, Nina C.; van der Sluijs, Koen; Hackl, Florian; Hotz, Lorenz; Dahan, Albert; Hollmann, Markus W.; Berger, Marc M.


    We previously demonstrated that intratracheally administered S-ketamine inhibits alveolar fluid clearance (AFC), whereas an intravenous (IV) bolus injection had no effect. The aim of the present study was to characterize whether continuous IV infusion of S-ketamine, yielding clinically relevant plasma concentrations, inhibits AFC and whether its effect is enhanced in acute lung injury (ALI) which might favor the appearance of IV S-ketamine at the alveolar surface. AFC was measured in fluid-instilled rat lungs. S-ketamine was administered IV over 6 h (loading dose: 20 mg/kg, followed by 20 mg/kg/h), or intratracheally by addition to the instillate (75 µg/ml). ALI was induced by IV lipopolysaccharide (LPS; 7 mg/kg). Interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC)-3 were measured by ELISA in plasma and bronchoalveolar lavage fluid. Isolated rat alveolar type-II cells were exposed to S-ketamine (75 µg/ml) and/or LPS (1 mg/ml) for 6 h, and transepithelial ion transport was measured as short circuit current (ISC). AFC was 27±5% (mean±SD) over 60 min in control rats and was unaffected by IV S-ketamine. Tracheal S-ketamine reduced AFC to 18±9%. In LPS-treated rats, AFC decreased to 16±6%. This effect was not enhanced by IV S-ketamine. LPS increased IL-6 and CINC-3 in plasma and bronchoalveolar lavage fluid. In alveolar type-II cells, S-ketamine reduced ISC by 37% via a decrease in amiloride-inhibitable sodium transport. Continuous administration of IV S-ketamine does not affect rat AFC even in endotoxin-induced ALI. Tracheal application with direct exposure of alveolar epithelial cells to S-ketamine decreases AFC by inhibition of amiloride-inhibitable sodium transport. PMID:25386677

  8. Eight challenges in modelling infectious livestock diseases

    Directory of Open Access Journals (Sweden)

    E. Brooks-Pollock


    Full Text Available The transmission of infectious diseases of livestock does not differ in principle from disease transmission in any other animals, apart from that the aim of control is ultimately economic, with the influence of social, political and welfare constraints often poorly defined. Modelling of livestock diseases suffers simultaneously from a wealth and a lack of data. On the one hand, the ability to conduct transmission experiments, detailed within-host studies and track individual animals between geocoded locations make livestock diseases a particularly rich potential source of realistic data for illuminating biological mechanisms of transmission and conducting explicit analyses of contact networks. On the other hand, scarcity of funding, as compared to human diseases, often results in incomplete and partial data for many livestock diseases and regions of the world. In this overview of challenges in livestock disease modelling, we highlight eight areas unique to livestock that, if addressed, would mark major progress in the area.

  9. A Live Attenuated Equine Infectious Anemia Virus Proviral Vaccine with a Modified S2 Gene Provides Protection from Detectable Infection by Intravenous Virulent Virus Challenge of Experimentally Inoculated Horses (United States)

    Li, Feng; Craigo, Jodi K.; Howe, Laryssa; Steckbeck, Jonathan D.; Cook, Sheila; Issel, Charles; Montelaro, Ronald C.


    Previous evaluations of inactivated whole-virus and envelope subunit vaccines to equine infectious anemia virus (EIAV) have revealed a broad spectrum of efficacy ranging from highly type-specific protection to severe enhancement of viral replication and disease in experimentally immunized equids. Among experimental animal lentivirus vaccines, immunizations with live attenuated viral strains have proven most effective, but the vaccine efficacy has been shown to be highly dependent on the nature and severity of the vaccine virus attenuation. We describe here for the first time the characterization of an experimental attenuated proviral vaccine, EIAVUKΔS2, based on inactivation of the S2 accessory gene to down regulate in vivo replication without affecting in vitro growth properties. The results of these studies demonstrated that immunization with EIAVUKΔS2 elicited mature virus-specific immune responses by 6 months and that this vaccine immunity provided protection from disease and detectable infection by intravenous challenge with a reference virulent biological clone, EIAVPV. This level of protection was observed in each of the six experimental horses challenged with the reference virulent EIAVPV by using a low-dose multiple-exposure protocol (three administrations of 10 median horse infectious doses [HID50], intravenous) designed to mimic field exposures and in all three experimentally immunized ponies challenged intravenously with a single inoculation of 3,000 HID50. In contrast, naïve equids subjected to the low- or high-dose challenge develop a detectable infection of challenge virus and acute disease within several weeks. Thus, these data demonstrate that the EIAV S2 gene provides an optimal site for modification to achieve the necessary balance between attenuation to suppress virulence and replication potential to sufficiently drive host immune responses to produce vaccine immunity to viral exposure. PMID:12805423

  10. A live attenuated equine infectious anemia virus proviral vaccine with a modified S2 gene provides protection from detectable infection by intravenous virulent virus challenge of experimentally inoculated horses. (United States)

    Li, Feng; Craigo, Jodi K; Howe, Laryssa; Steckbeck, Jonathan D; Cook, Sheila; Issel, Charles; Montelaro, Ronald C


    Previous evaluations of inactivated whole-virus and envelope subunit vaccines to equine infectious anemia virus (EIAV) have revealed a broad spectrum of efficacy ranging from highly type-specific protection to severe enhancement of viral replication and disease in experimentally immunized equids. Among experimental animal lentivirus vaccines, immunizations with live attenuated viral strains have proven most effective, but the vaccine efficacy has been shown to be highly dependent on the nature and severity of the vaccine virus attenuation. We describe here for the first time the characterization of an experimental attenuated proviral vaccine, EIAV(UK)deltaS2, based on inactivation of the S2 accessory gene to down regulate in vivo replication without affecting in vitro growth properties. The results of these studies demonstrated that immunization with EIAV(UK)deltaS2 elicited mature virus-specific immune responses by 6 months and that this vaccine immunity provided protection from disease and detectable infection by intravenous challenge with a reference virulent biological clone, EIAV(PV). This level of protection was observed in each of the six experimental horses challenged with the reference virulent EIAV(PV) by using a low-dose multiple-exposure protocol (three administrations of 10 median horse infectious doses [HID(50)], intravenous) designed to mimic field exposures and in all three experimentally immunized ponies challenged intravenously with a single inoculation of 3,000 HID(50). In contrast, naïve equids subjected to the low- or high-dose challenge develop a detectable infection of challenge virus and acute disease within several weeks. Thus, these data demonstrate that the EIAV S2 gene provides an optimal site for modification to achieve the necessary balance between attenuation to suppress virulence and replication potential to sufficiently drive host immune responses to produce vaccine immunity to viral exposure.

  11. Collaborative Inquiry Learning: Models, tools, and challenges (United States)

    Bell, Thorsten; Urhahne, Detlef; Schanze, Sascha; Ploetzner, Rolf


    Collaborative inquiry learning is one of the most challenging and exciting ventures for today's schools. It aims at bringing a new and promising culture of teaching and learning into the classroom where students in groups engage in self-regulated learning activities supported by the teacher. It is expected that this way of learning fosters students' motivation and interest in science, that they learn to perform steps of inquiry similar to scientists and that they gain knowledge on scientific processes. Starting from general pedagogical reflections and science standards, the article reviews some prominent models of inquiry learning. This comparison results in a set of inquiry processes being the basis for cooperation in the scientific network NetCoIL. Inquiry learning is conceived in several ways with emphasis on different processes. For an illustration of the spectrum, some main conceptions of inquiry and their focuses are described. In the next step, the article describes exemplary computer tools and environments from within and outside the NetCoIL network that were designed to support processes of collaborative inquiry learning. These tools are analysed by describing their functionalities as well as effects on student learning known from the literature. The article closes with challenges for further developments elaborated by the NetCoIL network.

  12. Product Development and Cost Analysis of Fabricating the Prototype of Roller Clamp in Intravenous (I.V) Tubing Medical Devices using Fused Deposition Modeling (FDM) Technology (United States)

    Way, Yusoff


    The main aim of this research is to develop a new prototype and to conduct cost analysis of the existing roller clamp which is one of parts attached to Intravenous (I.V) Tubing used in Intravenous therapy medical device. Before proceed with the process to manufacture the final product using Fused Deposition Modeling (FDM) Technology, the data collected from survey were analyzed using Product Design Specifications approach. Selected concept has been proven to have better quality, functions and criteria compared to the existing roller clamp and the cost analysis of fabricating the roller clamp prototype was calculated.

  13. Screening and confirmatory analyses of flunixin in tissues and bodily fluids after intravenous or intramuscular administration to cull dairy cows with or without lipopolysaccharide challenge (United States)

    Twenty cull dairy cows (645 ± 83 kg) were treated with 2.2 mg/kg bw flunixin by intravenous (IV) or intramuscular (IM) administration with, or without, exposure to lipopolysaccharide in a two factor balanced design. The usefulness of screening assays to identify violative flunixin levels in a varie...

  14. Modeling Heliospheric Interface: Observational and Theoretical Challenges (United States)

    Pogorelov, N.; Heerikhuisen, J.; Borovikov, S.; Zank, G.


    Observational data provided by Voyager 1 and Voyager 2 spacecraft ahead of the heliospheric termination shock (TS) and in the heliosheath require considerate reassessment of theoretical models of the solar wind (SW) interaction with the magnetized interstellar medium (LISM). Contemporary models, although sophisticated enough to take into account kinetic processes accompanying charge exchange between ions and atoms and address the coupling of the interstellar and interplanetary magnetic fields (ISMF and IMF) at the heliospheric interface, are still unable to analyze the effect of non-thermal pick-up ions (PUI's) in the heliosheath. The presence of PUI's undermines the assumption of a Maxwellian distribution of the SW ions. We discuss the ways to improve physical models in this respect. The TS asymmetry observed by Voyagers can be attributed to the combination of 3D, time- dependent behavior of the SW and by the action of the ISMF. It is clear, however, that the ISMF alone can account for the TS asymmetry of about 10 AU only if it is unexpectedly strong (greater than 4 microgauss). We analyze the consequences of such magnetic fields for the neutral hydrogen deflection in the inner heliosphere from its original direction in the unperturbed LISM. We also discuss the conditions for the 2-3 kHz radio emission, which is believed to be generated in the outer heliosheath beyond the heliopause, and analyze possible location of radio emission sources under the assumption of strong magnetic field. The quality of the physical model becomes crucial when we need to address modern observational and theoretical challenges. We compare the plasma, neutral particle, and magnetic field distributions obtained with our MHD-kinetic and 5-fluid models. The transport of neutral particles is treated kinetically in the former and by a multiple neutral-fluid approach in the latter. We also investigate the distribution of magnetic field in the inner heliosheath for large angles between the Sun

  15. Vasoactive side effects of intravenous immunoglobulin preparations in a rat model and their treatment with recombinant platelet-activating factor acetylhydrolase

    NARCIS (Netherlands)

    Bleeker, W. K.; Teeling, J. L.; Verhoeven, A. J.; Rigter, G. M.; Agterberg, J.; Tool, A. T.; Koenderman, A. H.; Kuijpers, T. W.; Hack, C. E.


    Previously, we observed in a rat model that intravenous administration of intramuscular immunoglobulin preparations induced a long-lasting hypotension, which appeared to be associated with the presence of IgG polymers and dimers in the preparations, but unrelated to complement activation. We found

  16. Statistical Challenges in Modeling Big Brain Signals

    KAUST Repository

    Yu, Zhaoxia


    Brain signal data are inherently big: massive in amount, complex in structure, and high in dimensions. These characteristics impose great challenges for statistical inference and learning. Here we review several key challenges, discuss possible solutions, and highlight future research directions.

  17. Dosimetry of intravenously administered oxygen-15 labelled water in man: a model based on experimental human data from 21 subjects

    International Nuclear Information System (INIS)

    Smith, T.; Tong, C.; Lammertsma, A.A.; Butler, K.R.; Schnorr, L.; Watson, J.D.G.; Ramsay, S.; Clark, J.C.; Jones, T.


    Models based on uniform distribution of tracer in total body water underestimate the absorbed dose from H 2 15 O because of the short half-life (2.04 min) of 15 O, which leads to non-uniform distribution of absorbed dose and also complicates the direct measurement of organ retention curves. However, organ absorbed doses can be predicted by the present kinetic model based on the convolution technique. The measured time course of arterial H 2 15 O concentration following intravenous administration represents the input function to organs. The impulse response of a given organ is its transit time function determined by blood flow and the partition of water between tissue and blood. Values of these two parameters were taken from the literature. Integrals of the arterial input function and organ transit time functions were used to derive integrals of organ retention functions (organ residence times). The latter were used with absorbed dose calculation software (MIRDOSE-2) to obtain estimates for 24 organs. From the mean values of organ absorbed doses, the effective dose equivalent (EDE) and effective dose (ED) were calculated. From measurements on 21 subjects, the average value for both EDE and ED was calculated to be 1.2 μSv.MBq -1 compared with a value of about 0.5 μSv.MBq -1 predicted by uniform water distribution models. Based on the human data, a method of approximating H 2 15 O absorbed dose values from body surface area is described. (orig.)

  18. Integrated Environmental Modelling: Human decisions, human challenges (United States)

    Glynn, Pierre D.


    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  19. Integrated Environmental Modelling: human decisions, human challenges (United States)

    Glynn, Pierre D.


    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  20. Development and application of an oral challenge mouse model for studying Clostridium perfringens type D infection. (United States)

    Fernandez-Miyakawa, Mariano E; Sayeed, Sameera; Fisher, Derek J; Poon, Rachael; Adams, Vicki; Rood, Julian I; McClane, Bruce A; Saputo, Julian; Uzal, Francisco A


    Clostridium perfringens type D isolates cause enterotoxemia in sheep, goats, and probably cattle. While the major disease signs and lesions of type D animal disease are usually attributed to epsilon toxin, a class B select agent, these bacteria typically produce several lethal toxins. Understanding of disease pathogenesis and development of improved vaccines are hindered by the lack of a small-animal model mimicking natural disease caused by type D isolates. Addressing this need, we developed an oral challenge mouse model of C. perfringens type D enterotoxemia. When BALB/c mice with a sealed anus were inoculated by intragastric gavage with type D isolates, 7 of 10 type D isolates were lethal, as defined by spontaneous death or severe clinical signs necessitating euthanasia. The lethalities of the seven type D isolates varied between 14 and 100%. Clinical signs in the lethally challenged mice included seizures, convulsions, hyperexcitability, and/or depression. Mild intestinal gas distention and brain edema were observed at necropsy in a few mice, while histology showed multifocal acute tubular necrosis of the kidney and edema in the lungs of most challenged mice that developed a clinical response. When the lethality of type D isolates in this model was compared with in vitro toxin production, only a limited correlation was observed. However, mice could be protected against lethality by intravenous passive immunization with an epsilon toxin antibody prior to oral challenge. This study provides an economical new model for studying the pathogenesis of C. perfringens type D infections.

  1. The effect of methylprednisolone intravenous infusion on the expression of ciliary neurotrophic factor in a rat spinal cord injury model. (United States)

    Del Gaizo, Daniel J; Regan, Conor M; Graff, Ronald D; Mathur, Sameer


    Methylprednisolone (MP) infusion after acute spinal cord injury (SCI) remains controversial despite large randomized studies, including the National Acute Spinal Cord Injury Studies (NASCIS). To determine the effect of NASCIS protocol MP infusion on the expression of ciliary neurotrophic factor (CNTF), a neuroprotective cytokine, in a rat model after SCI. Animal laboratory study. Thirty rats were randomized into an MP infusion group (intravenous [IV]-MP) versus normal saline (NS) control group (IV-NS) after a standardized SCI. Ciliary neurotrophic factor expression was measured by reverse transcription-polymerase chain reaction at 6, 12, 24, 48, and 72 hours post-SCI. Mean CNTF expression was diminished in the MP group at 12 (p=.006) and 24 (p=.008) hours postinjury compared with the control group. Expression of CNTF was not significantly different between the groups at 6, 48, and 72 hours post-SCI. Standardized MP infusion post-SCI reduces CNTF activation in a rat SCI model. Further study is needed to determine if this effect is seen in human SCIs. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

    Directory of Open Access Journals (Sweden)

    Noriaki Nagai


    Full Text Available It was reported that cilostazol (CLZ suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D., and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice. The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage.

  3. Challenges in Modeling of the Global Atmosphere (United States)

    Janjic, Zavisa; Djurdjevic, Vladimir; Vasic, Ratko; Black, Tom


    ") with significant amplitudes can develop. Due to their large scales, that are comparable to the scales of the dominant Rossby waves, such fictitious solutions are hard to identify and remove. Another new challenge on the global scale is that the limit of validity of the hydrostatic approximation is rapidly being approached. Having in mind the sensitivity of extended deterministic forecasts to small disturbances, we may need global non-hydrostatic models sooner than we think. The unified Non-hydrostatic Multi-scale Model (NMMB) that is being developed at the National Centers for Environmental Prediction (NCEP) as a part of the new NOAA Environmental Modeling System (NEMS) will be discussed as an example. The non-hydrostatic dynamics were designed in such a way as to avoid over-specification. The global version is run on the latitude-longitude grid, and the polar filter selectively slows down the waves that would otherwise be unstable. The model formulation has been successfully tested on various scales. A global forecasting system based on the NMMB has been run in order to test and tune the model. The skill of the medium range forecasts produced by the NMMB is comparable to that of other major medium range models. The computational efficiency of the global NMMB on parallel computers is good.

  4. Pharmacokinetic-pharmacodynamic modelling of intravenous and oral topiramate and its effect on phonemic fluency in adult healthy volunteers. (United States)

    Ahmed, Ghada F; Marino, Susan E; Brundage, Richard C; Pakhomov, Serguei V S; Leppik, Ilo E; Cloyd, James C; Clark, Annie; Birnbaum, Angela K


    The aim was to develop a quantitative approach that characterizes the magnitude of and variability in phonemic generative fluency scores as measured by the Controlled Oral Word Association (COWA) test in healthy volunteers after administration of an oral and a novel intravenous (IV) formulation of topiramate (TPM). Nonlinear mixed-effects modelling was used to describe the plasma TPM concentrations resulting from oral or IV administration. A pharmacokinetic-pharmacodynamic (PK-PD) model was developed sequentially to characterize the effect of TPM concentrations on COWA with different distributional assumptions. Topiramate was rapidly absorbed, with a median time to maximal concentration of 1 h and an oral bioavailability of ~100%. Baseline COWA score increased by an average of 12% after the third administration on drug-free sessions. An exponential model described the decline of COWA scores, which decreased by 14.5% for each 1 mg l(-1) increase in TPM concentration. The COWA scores were described equally well by both continuous normal and Poisson distributions. This analysis quantified the effect of TPM exposure on generative verbal fluency as measured by COWA. Repetitive administration of COWA resulted in a better performance, possibly due to a learning effect. The model predicts a 27% reduction in the COWA score at the average observed maximal plasma concentration after a 100 mg dose of TPM. The single-dose administration of relatively low TPM doses and narrow range of resultant concentrations in our study were limitations to investigating the PK-PD relationship at higher TPM exposures. Hence, the findings may not be readily generalized to the broader patient population. © 2014 The British Pharmacological Society.

  5. Pharmacokinetic–pharmacodynamic modelling of intravenous and oral topiramate and its effect on phonemic fluency in adult healthy volunteers (United States)

    Ahmed, Ghada F; Marino, Susan E; Brundage, Richard C; Pakhomov, Serguei V S; Leppik, Ilo E; Cloyd, James C; Clark, Annie; Birnbaum, Angela K


    Aims The aim was to develop a quantitative approach that characterizes the magnitude of and variability in phonemic generative fluency scores as measured by the Controlled Oral Word Association (COWA) test in healthy volunteers after administration of an oral and a novel intravenous (IV) formulation of topiramate (TPM). Methods Nonlinear mixed-effects modelling was used to describe the plasma TPM concentrations resulting from oral or IV administration. A pharmacokinetic–pharmacodynamic (PK-PD) model was developed sequentially to characterize the effect of TPM concentrations on COWA with different distributional assumptions. Results Topiramate was rapidly absorbed, with a median time to maximal concentration of 1 h and an oral bioavailability of ∼100%. Baseline COWA score increased by an average of 12% after the third administration on drug-free sessions. An exponential model described the decline of COWA scores, which decreased by 14.5% for each 1 mg l−1 increase in TPM concentration. The COWA scores were described equally well by both continuous normal and Poisson distributions. Conclusions This analysis quantified the effect of TPM exposure on generative verbal fluency as measured by COWA. Repetitive administration of COWA resulted in a better performance, possibly due to a learning effect. The model predicts a 27% reduction in the COWA score at the average observed maximal plasma concentration after a 100 mg dose of TPM. The single-dose administration of relatively low TPM doses and narrow range of resultant concentrations in our study were limitations to investigating the PK-PD relationship at higher TPM exposures. Hence, the findings may not be readily generalized to the broader patient population. PMID:25403343

  6. Sustained virological response with intravenous silibinin: individualized IFN-free therapy via real-time modeling of HCV kinetics (United States)

    Dahari, Harel; Shteingart, Shimon; Gafanovich, Inna; Cotler, Scott J.; D'Amato, Massimo; Pohl, Ralf T.; Weiss, Gali; Ashkenazi, Yaakov Jack; Tichler, Thomas; Goldin, Eran; Lurie, Yoav


    Background & Aims Intravenous silibinin (SIL) is a potent antiviral agent against hepatitis C virus (HCV) genotype-1. In this proof of concept case-study we tested: (i) whether interferon-alfa (IFN)-free treatment with SIL plus ribavirin (RBV) can achieve sustained virological response (SVR), (ii) whether SIL is safe and feasible for prolonged duration of treatment, and (iii) whether mathematical modeling of early on-treatment HCV kinetics can guide duration of therapy to achieve SVR. Methods A 44 year-old female HCV-(genotype-1)-infected patient who developed severe psychiatric adverse events to a previous course of pegIFN+RBV, initiated combination treatment with 1200 mg/day of SIL, 1200 mg/day of RBV and 6000 u/day vitamin D. Blood samples were collected frequently till week 4, thereafter every 1 to 12 weeks until the end of therapy. The standard-biphasic-mathematical model was used to predict the duration of therapy to achieve SVR. Results Based on modeling the observed viral kinetics during the first 3 weeks of treatment, SVR was predicted to be achieved within 34 weeks of therapy. Provided with this information, the patient agreed to complete 34 weeks of treatment. IFN-free treatment with SIL+RBV was feasible, safe, and achieved SVR (week-33). Conclusions We report, for the first time, the use of real-time mathematical modeling of HCV kinetics to individualize duration of IFN-free therapy and to empower a patient to participate in shared decision making regarding length of treatment. SIL-based individualized therapy provides a treatment option for patients who do not respond to or cannot receive other HCV agents and should be further validated. PMID:25251042

  7. Sustained virological response with intravenous silibinin: individualized IFN-free therapy via real-time modelling of HCV kinetics. (United States)

    Dahari, Harel; Shteingart, Shimon; Gafanovich, Inna; Cotler, Scott J; D'Amato, Massimo; Pohl, Ralf T; Weiss, Gali; Ashkenazi, Yaakov J; Tichler, Thomas; Goldin, Eran; Lurie, Yoav


    Intravenous silibinin (SIL) is a potent antiviral agent against hepatitis C virus (HCV) genotype-1. In this proof of concept case-study we tested: (i) whether interferon-alfa (IFN)-free treatment with SIL plus ribavirin (RBV) can achieve sustained virological response (SVR); (ii) whether SIL is safe and feasible for prolonged duration of treatment and (iii) whether mathematical modelling of early on-treatment HCV kinetics can guide duration of therapy to achieve SVR. A 44 year-old female HCV-(genotype-1)-infected patient who developed severe psychiatric adverse events to a previous course of pegIFN+RBV, initiated combination treatment with 1200 mg/day of SIL, 1200 mg/day of RBV and 6000 u/day vitamin D. Blood samples were collected frequently till week 4, thereafter every 1-12 weeks until the end of therapy. The standard biphasic mathematical model with time-varying SIL effectiveness was used to predict the duration of therapy to achieve SVR. Based on modelling the observed viral kinetics during the first 3 weeks of treatment, SVR was predicted to be achieved within 34 weeks of therapy. Provided with this information, the patient agreed to complete 34 weeks of treatment. IFN-free treatment with SIL+RBV was feasible, safe and achieved SVR (week-33). We report, for the first time, the use of real-time mathematical modelling of HCV kinetics to individualize duration of IFN-free therapy and to empower a patient to participate in shared decision making regarding length of treatment. SIL-based individualized therapy provides a treatment option for patients who do not respond to or cannot receive other HCV agents and should be further validated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Intravenous Cobinamide, a Novel Cyanide Antidote, versus Hydroxocobalamin in the Treatment of Acute Cyanide Toxicity and Apnea in a Swine (Sus scrofa) Model (United States)


    and severe toxicity. Cobinamide was 5 times as potent as hydroxocobalamin. hydroxocobalamin, cobinamide, cyanide , poisoning , Vitamin B12a, Vit B12...treatment of acute, severe cyanide induced cardiotoxicity of severe hypotension and of cardiac arrest in a swine (Sus Scrofa) model Intravenous...cobinamide, a novel cyanide antidote, versus hydroxocobalamin in the treatment of acute cyanide toxicity and apnea in a swine (Sus Scrofa) model

  9. Eliminating the use of intravenous glass bottles using a FOCUS-PDCA model and providing a practical stability reference guide. (United States)

    Maraiki, Fatma; Farooq, Faiyaz; Ahmed, Mohamed


    To identify the intravenous (IV) medications that are prepared in glass bottles at the institution and establish which of these medications can be prepared in flexible IV bags such as polyvinyl chloride (PVC) or non-PVC instead of glass bottles. The cost implication of switching from glass bottles to flexible IV bags was calculated. A study using FOCUS-PDCA model to identify IV medications prepared in glass bottles and establish which of these medications could be prepared in IV bags (PVC or non-PVC). The cost impact of switching from glass bottles to IV plastic bags (including PVC or non-PVC) was calculated. The stability data obtained were used as a reference for updating pharmacy internal IV preparation charts. A total of 17 IV medications were found to be prepared in IV glass bottles. Of these 17 medications, only 8 (47%) were prepared in IV glass bottles due to incompatibility with PVC bags. For 7 (41%) of the medications, of which 6 were monoclonal antibodies (MABs), the reason for preparation in glass bottles was unclear as these medications are compatible with either PVC or non-PVC or both. The potential cost savings associated with switching all of the identified medications to IV plastic bags (either non-PVC or PVC) exceeded $200 000. The elimination of glass bottles within the institution resulted in a significant cost saving. The use of FOCUS-PDCA model can help healthcare institution achieve significant improvements in process and realize significant cost savings. © 2016 Royal Pharmaceutical Society.

  10. Randomized comparison of intra-arterial and intravenous thrombolysis in a canine model of acute basilar artery thrombosis

    International Nuclear Information System (INIS)

    Qureshi, A.I.; Yahia, A.M.; Boulos, A.S.; Hanel, R.A.; Suri, M.F.K.; Hopkins, L.N.; Alberico, R.A.


    We compared the rates of recanalization cerebral infarct and hemorrhage between intra-arterial (IA) reteplase and intravenous (IV) alteplase thrombolysis in a canine model of basilar artery thrombosis. Thrombosis was induced by injecting a clot in the basilar artery of 13 anesthetized dogs via superselective catheterization. The animals were randomized in a blinded fashion, 2 h after clot injection and verification of arterial occlusion, to receive IV alteplase 0.9 mg/kg over 60 min and IA placebo, or IA reteplase 0.09 units/kg over 20 min, equivalent to one-half the alteplase dose, and IV placebo. Recanalization was studied for 6 h after treatment with serial angiography; the images were later graded in a blinded fashion. Blinded interpretation of postmortem MRI was performed to assess the presence of brain infarcts and/or hemorrhage. At 3 h after initiation of treatment, partial or complete recanalization was observed in one of six dogs in the IV alteplase group and in five of seven in the IA reteplase group (P = 0.08). At 6 h, no significant difference in partial or complete recanalization was observed between the groups (two of six vs. five of seven; P = 0.20). Postmortem MRI revealed infarcts in four of six animals treated with IV alteplase and three of seven treated with IA reteplase (P = 0.4). Intracerebral hemorrhage was more common in the IV alteplase group (four of six vs. none of seven; P = 0.02). This study thus suggests that IA thrombolysis affords a recanalization rate similar to that of IV thrombolysis, but with a lower rate of intracerebral hemorrhage. (orig.)

  11. Collaborative Inquiry Learning: Models, Tools, and Challenges (United States)

    Bell, Thorsten; Urhahne, Detlef; Schanze, Sascha; Ploetzner, Rolf


    Collaborative inquiry learning is one of the most challenging and exciting ventures for today's schools. It aims at bringing a new and promising culture of teaching and learning into the classroom where students in groups engage in self-regulated learning activities supported by the teacher. It is expected that this way of learning fosters…

  12. Investigation of Intravenous Hydroxocobalamin Compared to Hextend for Resuscitation in a Swine Model of Uncontrolled Hemorrhagic Shock: A Preliminary Report (United States)


    Castaneda4 , K Canellis 4 \\,J ... .r: ...,,,,..... 1Dept of Emergency Medicine, San Antonio Military Medical Center, San Antonio, TX, 2University...of Colorado-Denver, 3Geneva Foundation, San Antonio, TX ’""" •• 4Clinical Resuscitation, Emergency Sciences, and Toxicology Research Program...Program, Wilford Hall Ambulatory Surgical Center, Lackland AFB, TX, Background Previously we reported that intravenous (IV) hydroxocobalamin is as

  13. Toxicokinetic modeling challenges for aquatic nanotoxicology

    Directory of Open Access Journals (Sweden)

    Wei-Yu eChen


    Full Text Available Nanotoxicity has become of increasing concern since the rapid development of metal nanoparticles (NPs. Aquatic nanotoxicity depends on crucial qualitative and quantitative properties of nanomaterials that induce adverse effects on subcellular, tissue, and organ level. The dose-response effects of size-dependent metal NPs, however, are not well investigated in aquatic organisms. In order to determine the uptake and elimination rate constants for metal NPs in the metabolically active/ detoxified pool of tissues, a one-compartmental toxicokinetic model can be applied when subcellular partitioning of metal NPs data would be available. The present review is an attempt to describe the nano-characteristics of toxicokinetics and subcellular partitioning on aquatic organisms with the help of the mechanistic modeling for NP size-dependent physiochemical properties and parameters. Physiologically-based pharmacokinetic (PBPK models can provide an effective tool to estimate the time course of NP accumulation in target organs and is useful in quantitative risk assessments. NP accumulation in fish should take into account different effects of different NP sizes to better understand tissue accumulative capacities and dynamics. The size-dependent NP partition coefficient is a crucial parameter that influences tissue accumulation levels in PBPK modeling. Further research is needed to construct the effective systems-level oriented toxicokinetic model that can provide a useful tool to develop quantitatively the robustly approximate relations that convey a better insight into the impacts of environmental metal NPs on subcellular and tissue/organ responses in aquatic organisms.

  14. Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy. (United States)

    Leitner, Wolfgang W; Bergmann-Leitner, Elke S; Angov, Evelina


    The immunological mechanisms responsible for protection against malaria infection vary among Plasmodium species, host species and the developmental stage of parasite, and are poorly understood. A challenge with live parasites is the most relevant approach to testing the efficacy of experimental malaria vaccines. Nevertheless, in the mouse models of Plasmodium berghei and Plasmodium yoelii, parasites are usually delivered by intravenous injection. This route is highly artificial and particularly in the P. berghei model produces inconsistent challenge results. The initial objective of this study was to compare an optimized intravenous (IV) delivery challenge model with an optimized single infectious mosquito bite challenge model. Finding shortcomings of both approaches, an alternative approach was explored, i.e., the subcutaneous challenge. Mice were infected with P. berghei sporozoites by intravenous (tail vein) injection, single mosquito bite, or subcutaneous injection of isolated parasites into the subcutaneous pouch at the base of the hind leg. Infection was determined in blood smears 7 and 14 days later. To determine the usefulness of challenge models for vaccine testing, mice were immunized with circumsporozoite-based DNA vaccines by gene gun. Despite modifications that allowed infection with a much smaller than reported number of parasites, the IV challenge remained insufficiently reliable and reproducible. Variations in the virulence of the inoculum, if not properly monitored by the rigorous inclusion of sporozoite titration curves in each experiment, can lead to unacceptable variations in reported vaccine efficacies. In contrast, mice with different genetic backgrounds were consistently infected by a single mosquito bite, without overwhelming vaccine-induced protective immune responses. Because of the logistical challenges associated with the mosquito bite model, the subcutaneous challenge route was optimized. This approach, too, yields reliable challenge

  15. Eight challenges in modelling infectious livestock diseases

    NARCIS (Netherlands)

    Brooks-Pollock, E.; Jong, de M.; Keeling, M.J.; Klinkenberg, D.; Wood, J.L.N.


    The transmission of infectious diseases of livestock does not differ in principle from disease transmission in any other animals, apart from that the aim of control is ultimately economic, with the influence of social, political and welfare constraints often poorly defined. Modelling of livestock

  16. Grand Challenges in Protoplanetary Disc Modelling

    NARCIS (Netherlands)

    Haworth, Thomas J.; Ilee, John D.; Forgan, Duncan H.; Facchini, Stefano; Price, Daniel J.; Boneberg, Dominika M.; Booth, Richard A.; Clarke, Cathie J.; Gonzalez, Jean-François; Hutchison, Mark A.; Kamp, Inga; Laibe, Guillaume; Lyra, Wladimir; Meru, Farzana; Mohanty, Subhanjoy; Panić, Olja; Rice, Ken; Suzuki, Takeru; Teague, Richard; Walsh, Catherine; Woitke, Peter; authors, Community


    The Protoplanetary Discussions conference-held in Edinburgh, UK, from 2016 March 7th-11th-included several open sessions led by participants. This paper reports on the discussions collectively concerned with the multi-physics modelling of protoplanetary discs, including the self-consistent

  17. Kinetics of intravenous radiographic contrast medium injections as used on CT: simulation with time delay differential equations in a basic human cardiovascular multicompartment model. (United States)

    Violon, D


    To develop a multicompartment model of only essential human body components that predicts the contrast medium concentration vs time curve in a chosen compartment after an intravenous injection. Also to show that the model can be used to time adequately contrast-enhanced CT series. A system of linked time delay instead of ordinary differential equations described the model and was solved with a Matlab program (Matlab v. 6.5; The Mathworks, Inc., Natick, MA). All the injection and physiological parameters were modified to cope with normal or pathological situations. In vivo time-concentration curves from the literature were recalculated to validate the model. The recalculated contrast medium time-concentration curves and parameters are given. The results of the statistical analysis of the study findings are expressed as the median prediction error and the median absolute prediction error values for both the time delay and ordinary differential equation systems; these are situated well below the generally accepted maximum 20% limit. The presented program correctly predicts the time-concentration curve of an intravenous contrast medium injection and, consequently, allows an individually tailored approach of CT examinations with optimised use of the injected contrast medium volume, as long as time delay instead of ordinary differential equations are used. The presented program offers good preliminary knowledge of the time-contrast medium concentration curve after any intravenous injection, allowing adequate timing of a CT examination, required by the short scan time of present-day scanners. The injected volume of contrast medium can be tailored to the individual patient with no more contrast medium than is strictly needed.

  18. Modeling solutions to Tanzania's physician workforce challenge

    Directory of Open Access Journals (Sweden)

    Alex J. Goodell


    Full Text Available Background: There is a great need for physicians in Tanzania. In 2012, there were approximately 0.31 physicians per 10,000 individuals nationwide, with a lower ratio in the rural areas, where the majority of the population resides. In response, universities across Tanzania have greatly increased the enrollment of medical students. Yet evidence suggests high attrition of medical graduates to other professions and emigration from rural areas where they are most needed. Objective: To estimate the future number of physicians practicing in Tanzania and the potential impact of interventions to improve retention, we built a model that tracks medical students from enrollment through clinical practice, from 1990 to 2025. Design: We designed a Markov process with 92 potential states capturing the movement of 25,000 medical students and physicians from medical training through employment. Work possibilities included clinical practice (divided into rural or urban, public or private, non-clinical work, and emigration. We populated and calibrated the model using a national 2005/2006 physician mapping survey, as well as graduation records, graduate tracking surveys, and other available data. Results: The model projects massive losses to clinical practice between 2016 and 2025, especially in rural areas. Approximately 56% of all medical school students enrolled between 2011 and 2020 will not be practicing medicine in Tanzania in 2025. Even with these losses, the model forecasts an increase in the physician-to-population ratio to 1.4 per 10,000 by 2025. Increasing the absorption of recent graduates into the public sector and/or developing a rural training track would ameliorate physician attrition in the most underserved areas. Conclusions: Tanzania is making significant investments in the training of physicians. Without linking these doctors to employment and ensuring their retention, the majority of this investment in medical education will be jeopardized.

  19. GEOS Atmospheric Model: Challenges at Exascale (United States)

    Putman, William M.; Suarez, Max J.


    The Goddard Earth Observing System (GEOS) model at NASA's Global Modeling and Assimilation Office (GMAO) is used to simulate the multi-scale variability of the Earth's weather and climate, and is used primarily to assimilate conventional and satellite-based observations for weather forecasting and reanalysis. In addition, assimilations coupled to an ocean model are used for longer-term forecasting (e.g., El Nino) on seasonal to interannual times-scales. The GMAO's research activities, including system development, focus on numerous time and space scales, as detailed on the GMAO website, where they are tabbed under five major themes: Weather Analysis and Prediction; Seasonal-Decadal Analysis and Prediction; Reanalysis; Global Mesoscale Modeling, and Observing System Science. A brief description of the GEOS systems can also be found at the GMAO website. GEOS executes as a collection of earth system components connected through the Earth System Modeling Framework (ESMF). The ESMF layer is supplemented with the MAPL (Modeling, Analysis, and Prediction Layer) software toolkit developed at the GMAO, which facilitates the organization of the computational components into a hierarchical architecture. GEOS systems run in parallel using a horizontal decomposition of the Earth's sphere into processing elements (PEs). Communication between PEs is primarily through a message passing framework, using the message passing interface (MPI), and through explicit use of node-level shared memory access via the SHMEM (Symmetric Hierarchical Memory access) protocol. Production GEOS weather prediction systems currently run at 12.5-kilometer horizontal resolution with 72 vertical levels decomposed into PEs associated with 5,400 MPI processes. Research GEOS systems run at resolutions as fine as 1.5 kilometers globally using as many as 30,000 MPI processes. Looking forward, these systems can be expected to see a 2 times increase in horizontal resolution every two to three years, as well as

  20. Intentional intravenous mercury injection

    African Journals Online (AJOL)

    In this case report, intravenous complications, treatment strategies and possible ... Mercury toxicity is commonly associated with vapour inhalation or oral ingestion, for which there exist definite treatment options. Intravenous mercury ... personality, anxiousness, irritability, insomnia, depression and drowsi- ness.[1] However ...

  1. Transnational nursing programs: models, advantages and challenges. (United States)

    Wilson, Michael


    Conducting transnational programs can be a very rewarding activity for a School, Faculty or University. Apart from increasing the profile of the university, the conduct of transnational programs can also provide the university with openings for business opportunities, consultative activities, and collaborative research. It can also be a costly exercise placing an enormous strain on limited resources with little reward for the provider. Transnational ventures can become nonviable entities in a very short period of time due to unanticipated global economic trends. Transnational courses offered by Faculties of Business and Computing are commonplace, however, there is a growing number of health science programs, particularly nursing that are being offered transnational. This paper plans an overview of several models employed for the delivery of transnational nursing courses and discusses several key issues pertaining to conducting courses outside the host university's country.

  2. Modelling challenges in context: Lessons from malaria, HIV, and tuberculosis

    Directory of Open Access Journals (Sweden)

    Lauren M. Childs


    Full Text Available Malaria, HIV, and tuberculosis (TB collectively account for several million deaths each year, with all three ranking among the top ten killers in low-income countries. Despite being caused by very different organisms, malaria, HIV, and TB present a suite of challenges for mathematical modellers that are particularly pronounced in these infections, but represent general problems in infectious disease modelling, and highlight many of the challenges described throughout this issue. Here, we describe some of the unifying challenges that arise in modelling malaria, HIV, and TB, including variation in dynamics within the host, diversity in the pathogen, and heterogeneity in human contact networks and behaviour. Through the lens of these three pathogens, we provide specific examples of the other challenges in this issue and discuss their implications for informing public health efforts.

  3. Value Creation Challenges in Multichannel Retail Business Models

    Directory of Open Access Journals (Sweden)

    Mika Yrjölä


    Full Text Available Purpose: The purpose of the paper is to identify and analyze the challenges of value creation in multichannel retail business models. Design/methodology/approach: With the help of semi-structured interviews with top executives from different retailing environments, this study introduces a model of value creation challenges in the context of multichannel retailing. The challenges are analyzed in terms of three retail business model elements, i.e., format, activities, and governance. Findings: Adopting a multichannel retail business model requires critical rethinking of the basic building blocks of value creation. First of all, as customers effortlessly move between multiple channels, multichannel formats can lead to a mismatch between customer and firm value. Secondly, retailers face pressures to use their activities to form integrated total offerings to customers. Thirdly, multiple channels might lead to organizational silos with conflicting goals. A careful orchestration of value creation is needed to determine the roles and incentives of the channel parties involved. Research limitations/implications: In contrast to previous business model literature, this study did not adopt a network-centric view. By embracing the boundary-spanning nature of the business model, other challenges and elements might have been discovered (e.g., challenges in managing relationships with suppliers. Practical implications: As a practical contribution, this paper has analyzed the challenges retailers face in adopting multichannel business models. Customer tendencies for showrooming behavior highlight the need for generating efficient lock-in strategies. Customized, personal offers and information are ways to increase customer value, differentiate from competition, and achieve lock-in. Originality/value: As a theoretical contribution, this paper empirically investigates value creation challenges in a specific context, lowering the level of abstraction in the mostly

  4. Comparison of the Intravenous and Epidural Administration of Tumor Necrosis Factor-alpha Antagonists in an Experimental Rat Pain Model (United States)

    Beyaz, Serbülent Gökhan; İnanmaz, Mustafa Erkan; Ergönenç, Tolga; Palabıyık, Onur; Tomak, Yakup; Tuna, Ayça Taş


    Introduction: Inflammatory cytokines secreted from the nucleus pulposus are thought to lead to lumbar nerve root compression-like symptoms. Tumor necrosis factor-alpha (TNF-α), an inflammatory cytokine, likely plays an important role in lumbar disc hernia-related leg pain. In this experimental study, we compared the effectiveness of TNF-α antagonists administered through the intravenous or epidural route in lumbar spine pathologies. Materials and Methods: After ethics committee approval had been obtained, 24 Sprague Dawley male rats aged 70–90 days and weighing 250–300 g each were allocated to four groups. In Group I, only the surgical procedure was performed; in Group II, 1 ml of saline solution was administered into the epidural field; in Group III, 10 mg/kg of infliximab was administered into the coccygeal vein; and in Group IV (epidural group), 25 mg of etanercept was administered into the epidural region. Results: When the left leg pull values were analyzed on day 14, whereas there was not a significant difference among the three groups, a decreasing difference was observed in Group IV (P discopathy, TNF-α antagonists administered epidurally led to earlier recovery from radiculopathy-related allodynia compared to intravenous administration. PMID:29284846

  5. Challenges in LCA modelling of multiple loops for aluminium cans

    DEFF Research Database (Denmark)

    Niero, Monia; Olsen, Stig Irving

    one of the main features of circular product systems, i.e. the need to model multiple life cycles. There are some key methodological challenges that LCA has to face in order to exploit its potential in a circular economy framework, e.g. how to model the recycling of materials in multiple loops. We...

  6. Maternal intravenous fluids and postpartum breast changes: a pilot observational study. (United States)

    Kujawa-Myles, Sonya; Noel-Weiss, Joy; Dunn, Sandra; Peterson, Wendy E; Cotterman, Kermaline Jean


    The current breastfeeding initiation rate in Canada is approximately 87%. By one month, about 21% of women have stopped breastfeeding. Engorgement and edema in breast tissue can lead to breastfeeding challenges which may contribute to early weaning. The aims of this pilot research study were to explore the relationship between intrapartum intravenous fluids given to mothers and postpartum breast swelling in the first 10 days postpartum and to determine if a larger study was warranted and feasible. A prospective, longitudinal, observational cohort pilot study with repeated measures and a within-subjects design was completed. Participants were first time mothers who have a single, healthy newborn and had a spontaneous vaginal birth. Daily data collection from admission into the study until postpartum day 10 took place. Descriptive statistics are reported and linear regression analysis was used to model the relationship between IV therapy and postpartum breast edema. Women who received intravenous fluids during labour had higher levels of breast edema postpartum and rated their breasts as firmer and more tender than women who did not receive intravenous fluids. Participants who had intravenous fluids described patterns of fullness that appeared to be related to edema as opposed to fullness associated with engorgement and lactogenesis II. The findings demonstrate that mothers in this pilot study who received intravenous fluids in labour and postpartum had higher levels of breast edema. These results suggest a larger study is warranted to more fully examine the effects of intravenous fluids on postpartum breast swelling.

  7. Using phenomenological models for forecasting the 2015 Ebola challenge

    Directory of Open Access Journals (Sweden)

    Bruce Pell


    Full Text Available Background: The rising number of novel pathogens threatening the human population has motivated the application of mathematical modeling for forecasting the trajectory and size of epidemics. Materials and methods: We summarize the real-time forecasting results of the logistic equation during the 2015 Ebola challenge focused on predicting synthetic data derived from a detailed individual-based model of Ebola transmission dynamics and control. We also carry out a post-challenge comparison of two simple phenomenological models. In particular, we systematically compare the logistic growth model and a recently introduced generalized Richards model (GRM that captures a range of early epidemic growth profiles ranging from sub-exponential to exponential growth. Specifically, we assess the performance of each model for estimating the reproduction number, generate short-term forecasts of the epidemic trajectory, and predict the final epidemic size. Results: During the challenge the logistic equation consistently underestimated the final epidemic size, peak timing and the number of cases at peak timing with an average mean absolute percentage error (MAPE of 0.49, 0.36 and 0.40, respectively. Post-challenge, the GRM which has the flexibility to reproduce a range of epidemic growth profiles ranging from early sub-exponential to exponential growth dynamics outperformed the logistic growth model in ascertaining the final epidemic size as more incidence data was made available, while the logistic model underestimated the final epidemic even with an increasing amount of data of the evolving epidemic. Incidence forecasts provided by the generalized Richards model performed better across all scenarios and time points than the logistic growth model with mean RMS decreasing from 78.00 (logistic to 60.80 (GRM. Both models provided reasonable predictions of the effective reproduction number, but the GRM slightly outperformed the logistic growth model with a MAPE of 0

  8. Combination therapy with antibiotics and anthrax immune globulin intravenous (AIGIV is potentially more effective than antibiotics alone in rabbit model of inhalational anthrax.

    Directory of Open Access Journals (Sweden)

    Srinivas Kammanadiminti

    Full Text Available BACKGROUND: We have evaluated the therapeutic efficacy of AIGIV when given in combination with levofloxacin and the effective window of treatment to assess the added benefit provided by AIGIV over standard antibiotic treatment alone in a New Zealand white rabbit model of inhalational anthrax. METHODS: Rabbits were exposed to lethal dose of aerosolized spores of Bacillus anthracis (Ames strain and treated intravenously with either placebo, (normal immune globulin intravenous, IGIV or 15 U/kg of AIGIV, along with oral levofloxacin treatment at various time points (30-96 hours after anthrax exposure. RESULTS: The majority of treated animals (>88% survived in both treatment groups when treatment was initiated within 60 hours of post-exposure. However, reduced survival of 55%, 33% and 25% was observed for placebo + levofloxacin group when the treatment was initiated at 72, 84 and 96 hours post-exposure, respectively. Conversely, a survival rate of 65%, 40% and 71% was observed in the AIGIV + levofloxacin treated groups at these time points. CONCLUSIONS: The combination of AIGIV with antibiotics provided an improvement in survival compared to levofloxacin treatment alone when treatment was delayed up to 96 hours post-anthrax exposure. Additionally, AIGIV treatment when given as an adjunct therapy at any of the time points tested did not interfere with the efficacy of levofloxacin.

  9. Challenges and opportunities for integrating lake ecosystem modelling approaches (United States)

    Mooij, Wolf M.; Trolle, Dennis; Jeppesen, Erik; Arhonditsis, George; Belolipetsky, Pavel V.; Chitamwebwa, Deonatus B.R.; Degermendzhy, Andrey G.; DeAngelis, Donald L.; Domis, Lisette N. De Senerpont; Downing, Andrea S.; Elliott, J. Alex; Ruberto, Carlos Ruberto; Gaedke, Ursula; Genova, Svetlana N.; Gulati, Ramesh D.; Hakanson, Lars; Hamilton, David P.; Hipsey, Matthew R.; Hoen, Jochem 't; Hulsmann, Stephan; Los, F. Hans; Makler-Pick, Vardit; Petzoldt, Thomas; Prokopkin, Igor G.; Rinke, Karsten; Schep, Sebastiaan A.; Tominaga, Koji; Van Dam, Anne A.; Van Nes, Egbert H.; Wells, Scott A.; Janse, Jan H.


    A large number and wide variety of lake ecosystem models have been developed and published during the past four decades. We identify two challenges for making further progress in this field. One such challenge is to avoid developing more models largely following the concept of others ('reinventing the wheel'). The other challenge is to avoid focusing on only one type of model, while ignoring new and diverse approaches that have become available ('having tunnel vision'). In this paper, we aim at improving the awareness of existing models and knowledge of concurrent approaches in lake ecosystem modelling, without covering all possible model tools and avenues. First, we present a broad variety of modelling approaches. To illustrate these approaches, we give brief descriptions of rather arbitrarily selected sets of specific models. We deal with static models (steady state and regression models), complex dynamic models (CAEDYM, CE-QUAL-W2, Delft 3D-ECO, LakeMab, LakeWeb, MyLake, PCLake, PROTECH, SALMO), structurally dynamic models and minimal dynamic models. We also discuss a group of approaches that could all be classified as individual based: super-individual models (Piscator, Charisma), physiologically structured models, stage-structured models and trait-based models. We briefly mention genetic algorithms, neural networks, Kalman filters and fuzzy logic. Thereafter, we zoom in, as an in-depth example, on the multi-decadal development and application of the lake ecosystem model PCLake and related models (PCLake Metamodel, Lake Shira Model, IPH-TRIM3D-PCLake). In the discussion, we argue that while the historical development of each approach and model is understandable given its 'leading principle', there are many opportunities for combining approaches. We take the point of view that a single 'right' approach does not exist and should not be strived for. Instead, multiple modelling approaches, applied concurrently to a given problem, can help develop an integrative

  10. Intravenous Administration of Adipose-Derived Stem Cell Protein Extracts Improves Neurological Deficits in a Rat Model of Stroke

    Directory of Open Access Journals (Sweden)

    Kai Zhao


    Full Text Available Treatment of adipose-derived stem cell (ADSC substantially improves the neurological deficits during stroke by reducing neuronal injury, limiting proinflammatory immune responses, and promoting neuronal repair, which makes ADSC-based therapy an attractive approach for treating stroke. However, the potential risk of tumorigenicity and low survival rate of the implanted cells limit the clinical use of ADSC. Cell-free extracts from ADSC (ADSC-E may be a feasible approach that could overcome these limitations. Here, we aim to explore the potential usage of ADSC-E in treating rat transient middle cerebral artery occlusion (tMCAO. We demonstrated that intravenous (IV injection of ADSC-E remarkably reduces the ischemic lesion and number of apoptotic neurons as compared to other control groups. Although ADSC and ADSC-E treatment results in a similar degree of a long-term clinical beneficial outcome, the dynamics between two ADSC-based therapies are different. While the injection of ADSC leads to a relatively mild but prolonged therapeutic effect, the administration of ADSC-E results in a fast and pronounced clinical improvement which was associated with a unique change in the molecular signature suggesting that potential mechanisms underlying different therapeutic approach may be different. Together these data provide translational evidence for using protein extracts from ADSC for treating stroke.


    Directory of Open Access Journals (Sweden)

    Achmad Asrori


    Full Text Available This paper discusses the issue of religious education in relation to the challenge of religious multiculturalism in Indonesia. The focus of this paper is to find out the kind of religious education that is compatible with the challenge of religious multiculturalism. By employing the concept of religious multiculturalism and theory of religious education, this paper argues that to face the challenge of religious multiculturalism it is necessary to change the model of religious education from within, at and beyond the wall. Religious education “in” the wall contributes to shape an exclusive model of religiosity; while religious education “at” and “beyond” the wall contributes to shape an inclusive multiculturalistic model of religiosity. The last two models are applicable in Indonesia in order to face the challenge of multiculturalism, because both of them help students to accept, respect, and value religious differences. Religious education should show that the common enemy of religion is not people of different faiths, but poverty, corruption, violence, ignorance, and the like, and they have to stand together to fight against these true enemies.

  12. Building challenge : international education model for construction education

    NARCIS (Netherlands)

    Stern, G.P. (Glenn); Bazen, J.C. (Jacques); Gavrikov, D.S. (Dennis)

    2016-01-01 In 2015 and 2016, Saxion University of Applied Sciences organized the 2nd and 3rd edition of the Regional Innovation and Entrepreneurship Conference (RIEC).   The Building challenge is a new education model in which

  13. Editorial: Modelling and computational challenges in granular materials

    NARCIS (Netherlands)

    Weinhart, Thomas; Thornton, Anthony Richard; Einav, Itai


    This is the editorial for the special issue on “Modelling and computational challenges in granular materials” in the journal on Computational Particle Mechanics (CPM). The issue aims to provide an opportunity for physicists, engineers, applied mathematicians and computational scientists to discuss

  14. Visualizing Decimal Multiplication with Area Models: Opportunities and Challenges (United States)

    Rathouz, Margaret


    This article describes a pilot study in which pre-service elementary teachers (PSTs) used rectangular area models on base-10 grid paper to begin making sense of multiplication of decimal fractions. Although connections were made to multi-digit whole number multiplication and to the distributive property, the PSTs were challenged by interpreting…

  15. International Students Take Up the Model Solar Car Challenge. (United States)

    Wellington, Paul


    Introduces an event in which two school teams from Argentina and Vietnam joined those from each Australian state in a race of model cars powered by the sun that provides a challenging and exciting approach for students to apply their scientific and technological knowledge to design and build the most efficient vehicles possible to gain hands-on…

  16. Business Model Innovation in Incumbent Organizations: : Challenges and Success Routes


    Salama, Ahmad; Parvez, Khawar


    In this thesis major challenges of creating business models at incumbents within mature industries are identified along with a mitigation plan. Pressure is upon incumbent organizations in order to keep up with the latest rapid technological advancements, the launching of startups that almost cover every field of business and the continuous change in customers’ tastes and needs. That along with various factors either forced organizations to continually reevaluate their current business models ...

  17. Editorial: Modelling and computational challenges in granular materials


    Weinhart, Thomas; Thornton, Anthony Richard; Einav, Itai


    This is the editorial for the special issue on “Modelling and computational challenges in granular materials” in the journal on Computational Particle Mechanics (CPM). The issue aims to provide an opportunity for physicists, engineers, applied mathematicians and computational scientists to discuss the current progress and latest advancements in the field of advanced numerical methods and modelling of granular materials. The focus will be on computational methods, improved algorithms and the m...

  18. Challenges and perspectives for species distribution modelling in the neotropics


    Kamino, Luciana H. Y.; Stehmann, João Renato; Amaral, Silvana; De Marco, Paulo; Rangel, Thiago F.; de Siqueira, Marinez F.; De Giovanni, Renato; Hortal, Joaquín


    The workshop ‘Species distribution models: applications, challenges and perspectives’ held at Belo Horizonte (Brazil), 29–30 August 2011, aimed to review the state-of-the-art in species distribution modelling (SDM) in the neotropical realm. It brought together researchers in ecology, evolution, biogeography and conservation, with different backgrounds and research interests. The application of SDM in the megadiverse neotropics—where data on species occurrences are scarce—presents several chal...

  19. Crowd Sourcing for Challenging Technical Problems and Business Model (United States)

    Davis, Jeffrey R.; Richard, Elizabeth


    imaging, microbial detection and even the use of pharmaceuticals for radiation protection. The internal challenges through NASA@Work drew over 6000 participants across all NASA centers. Challenges conducted by each NASA center elicited ideas and solutions from several other NASA centers and demonstrated rapid and efficient participation from employees at multiple centers to contribute to problem solving. Finally, on January 19, 2011, the SLSD conducted a workshop on open collaboration and innovation strategies and best practices through the newly established NASA Human Health and Performance Center (NHHPC). Initial projects will be described leading to a new business model for SLSD.

  20. Research Challenges in Financial Data Modeling and Analysis. (United States)

    Alexander, Lewis; Das, Sanjiv R; Ives, Zachary; Jagadish, H V; Monteleoni, Claire


    Significant research challenges must be addressed in the cleaning, transformation, integration, modeling, and analytics of Big Data sources for finance. This article surveys the progress made so far in this direction and obstacles yet to be overcome. These are issues that are of interest to data-driven financial institutions in both corporate finance and consumer finance. These challenges are also of interest to the legal profession as well as to regulators. The discussion is relevant to technology firms that support the growing field of FinTech.

  1. Impact of intravenous immunoglobulin on the dopaminergic system and immune response in the acute MPTP mouse model of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    St-Amour Isabelle


    Full Text Available Abstract Intravenous immunoglobulin (IVIg is a blood-derived product, used for the treatment of immunodeficiency and autoimmune diseases. Since a range of immunotherapies have recently been proposed as a therapeutic strategy for Parkinson’s disease (PD, we investigated the effects of an IVIg treatment in a neurotoxin-induced animal model of PD. Mice received four injections of MPTP (15 mg/kg at 2-hour intervals followed by a 14-day IVIg treatment, which induced key immune-related changes such as increased regulatory T-cell population and decreased CD4+/CD8+ ratio. The MPTP treatment induced significant 80% and 84% decreases of striatal dopamine concentrations (P P P 

  2. Patency of heart blood vessels under photosensitization reaction shortly after intravenous injection of talaporfin sodium in canine model (United States)

    Hamada, Risa; Matsuzaki, Ryota; Ogawa, Emiyu; Arai, Tsunenori


    In order to investigate patency of heart blood vessels by photosensitization reaction shortly after intravenous injection of talaporfin sodium, we performed in vitro endothelial cell lethality study and in vivo study of heart blood vessel patency in canine one week after photosensitization reaction. Cell lethality of human umbilical vein endothelial cells under different albumin concentrations corresponding with blood and interstice concentrations were employed and their lethality 2 hours after the reaction was measured by WST assay in vitro. Almost all cells survived by 40 J/cm2 photosensitization reaction with blood albumin concentration. Laser diffuser made of plastic optical fiber with 70 mm in length was used in vivo. Red diode laser of 664nm wavelength was emitted from this diffuser with 17.1-42.9 mW/cm in 10 minutes. We estimated the fluence rate distribution by a ray-trace simulator using pre-measured optical coefficients of myocardium tissue, μa 0.12 mm-1 and μs' 0.36 mm-1. Almost all blood vessels were patent in every irradiation conditions in canine heart. Coronary artery and vein up to 1 mm diameter were patent in typical myocardium sample with 25.7 mW/cm. We estimated fluence rate distribution of this sample and found that blood vessels were patent even fluence rate over 40 J/cm2. This in vivo study could be explained by the result of in vitro study. We suggest that this blood vessel patency after our particular photosensitization reaction might be because of few photosensitizer uptake in the blood endothelial cells and/or reduced oxidation damage by thick albumin concentration in blood.

  3. Intravenous Treatment with a Long-Chain Omega-3 Lipid Emulsion Provides Neuroprotection in a Murine Model of Ischemic Stroke - A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Dirk Berressem

    Full Text Available Single long-chain omega-3 fatty acids (e.g. docosahexaenoic acid (DHA or eicosapentaenoic acid (EPA are known for their neuroprotective properties associated with ischemic stroke. This pilot study aimed to test the effectiveness of an acute treatment with a long-chain omega-3 lipid emulsion (Omegaven 10%®, OGV that contains fish oil (DHA 18 mg/ml; EPA 21 mg/ml and α-tocopherol (0.2 mg/ml in a transient middle cerebral artery occlusion (MCAO model of ischemic stroke in mice. For this purpose, female CD-1 mice were anesthetized and subjected to 90 minutes of MCAO. To reflect a clinically relevant situation for an acute treatment, either after induction of stroke or after reperfusion, a single dose of OGV was injected intravenously into the tail vein (5 ml/kg b.w.. A neurological severity score was used to assess motor function and neurological outcome. Stroke-related parameters were determined 24 hours after MCAO. Microdialysis was used to collect samples from extracellular space of the striatum. Mitochondrial function was determined in isolated mitochondria or dissociated brain cells. Inflammation markers were measured in brain homogenate. According to control experiments, neuroprotective effects could be attributed to the long-chain omega-3 content of the emulsion. Intravenous injection of OGV reduced size and severity of stroke, restored mitochondrial function, and prevented excitotoxic glutamate release. Increases of pro-inflammatory markers (COX-2 and IL-6 were attenuated. Neurological severity scoring and neurochemical data demonstrated that acute OGV treatment shortly after induction of stroke was most efficient and able to improve short-term neurological outcome, reflecting the importance of an acute treatment to improve the outcome. Summarising, acute treatment of stroke with a single intravenous dose of OGV provided strong neuroprotective effects and was most effective when given immediately after onset of ischemia. As OGV is an

  4. Studying cancer metastasis: Existing models, challenges and future perspectives. (United States)

    van Marion, Denise M S; Domanska, Urszula M; Timmer-Bosscha, Hetty; Walenkamp, Annemiek M E


    Cancer metastasis causes most cancer-related deaths. Several model systems to study the complex and multi step process of metastasis exist, including in vitro systems, ex-vivo organ slices, Drosophila Melanogaster and zebrafish models and the use of the chorio allantoic membrane (CAM) of fertilized chicken eggs. These models are relatively easy and cheap but often lack the opportunity to study the complete metastasis cascade. More complex but also more expensive is the use of animal models including the more recently developed patient derived tumor xenografts (PDTX). In this review, we give an overview of the existing metastatic models, discuss the challenges of improving current models to enhance translation from the preclinical to the clinical setting and consider future perspectives. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Five (or so) challenges for species distribution modelling

    DEFF Research Database (Denmark)

    Bastos Araujo, Miguel; Guisan, Antoine


    Species distribution modelling is central to both fundamental and applied research in biogeography. Despite widespread use of models, there are still important conceptual ambiguities as well as biotic and algorithmic uncertainties that need to be investigated in order to increase confidence in mo...... contribution; and (5) improved model evaluation. The challenges discussed in this essay do not preclude the need for developments of other areas of research in this field. However, they are critical for allowing the science of species distribution modelling to move forward.......Species distribution modelling is central to both fundamental and applied research in biogeography. Despite widespread use of models, there are still important conceptual ambiguities as well as biotic and algorithmic uncertainties that need to be investigated in order to increase confidence...

  6. Pain management in emergency department: intravenous morphine vs. intravenous acetaminophen

    Directory of Open Access Journals (Sweden)

    Morteza Talebi Doluee


    Full Text Available Pain is the most common complaint in emergency department and there are several methods for its control. Among them, pharmaceutical methods are the most effective. Although intravenous morphine has been the most common choice for several years, it has some adverse effects. There are many researches about intravenous acetaminophen as an analgesic agent and it appears that it has good analgesic effects for various types of pain. We searched some electronic resources for clinical trials comparing analgesic effects of intravenous acetaminophen vs. intravenous morphine for acute pain treatment in emergency setting.In two clinical trials, the analgesic effect of intravenous acetaminophen has been compared with intravenous morphine for renal colic. The results revealed no significant difference between analgesic effects of two medications. Another clinical trial revealed that intravenous acetaminophen has acceptable analgesic effects on the post-cesarean section pain when combined with other analgesic medications. One study revealed that administration of intravenous acetaminophen compared to placebo before hysterectomy decreased consumption of morphine via patient-controlled analgesia pump and decreased the side effects. Similarly, another study revealed that the infusion of intravenous acetaminophen vs. placebo after orthopedic surgery decreased the consumption of morphine after the surgery. A clinical trial revealed intravenous acetaminophen provided a level of analgesia comparable to intravenous morphine in isolated limb trauma, while causing less side effects than morphine.It appears that intravenous acetaminophen has good analgesic effects for visceral, traumatic and postoperative pains compare with intravenous morphine.

  7. Challenges and perspectives for species distribution modelling in the neotropics (United States)

    Kamino, Luciana H. Y.; Stehmann, João Renato; Amaral, Silvana; De Marco, Paulo; Rangel, Thiago F.; de Siqueira, Marinez F.; De Giovanni, Renato; Hortal, Joaquín


    The workshop ‘Species distribution models: applications, challenges and perspectives’ held at Belo Horizonte (Brazil), 29–30 August 2011, aimed to review the state-of-the-art in species distribution modelling (SDM) in the neotropical realm. It brought together researchers in ecology, evolution, biogeography and conservation, with different backgrounds and research interests. The application of SDM in the megadiverse neotropics—where data on species occurrences are scarce—presents several challenges, involving acknowledging the limitations imposed by data quality, including surveys as an integral part of SDM studies, and designing the analyses in accordance with the question investigated. Specific solutions were discussed, and a code of good practice in SDM studies and related field surveys was drafted. PMID:22031720

  8. The status and challenge of global fire modelling (United States)

    Hantson, Stijn; Arneth, Almut; Harrison, Sandy P.; Kelley, Douglas I.; Prentice, I. Colin; Rabin, Sam S.; Archibald, Sally; Mouillot, Florent; Arnold, Steve R.; Artaxo, Paulo; Bachelet, Dominique; Ciais, Philippe; Forrest, Matthew; Friedlingstein, Pierre; Hickler, Thomas; Kaplan, Jed O.; Kloster, Silvia; Knorr, Wolfgang; Lasslop, Gitta; Li, Fang; Mangeon, Stephane; Melton, Joe R.; Meyn, Andrea; Sitch, Stephen; Spessa, Allan; van der Werf, Guido R.; Voulgarakis, Apostolos; Yue, Chao


    Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, using either well-founded empirical relationships or process-based models with good predictive skill. While a large variety of models exist today, it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project (FireMIP), an international initiative to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we review how fires have been represented in fire-enabled dynamic global vegetation models (DGVMs) and give an overview of the current state of the art in fire-regime modelling. We indicate which challenges still remain in global fire modelling and stress the need for a comprehensive model evaluation and outline what lessons may be learned from FireMIP.

  9. Modeling Biology Spanning Different Scales: An Open Challenge

    Directory of Open Access Journals (Sweden)

    Filippo Castiglione


    Full Text Available It is coming nowadays more clear that in order to obtain a unified description of the different mechanisms governing the behavior and causality relations among the various parts of a living system, the development of comprehensive computational and mathematical models at different space and time scales is required. This is one of the most formidable challenges of modern biology characterized by the availability of huge amount of high throughput measurements. In this paper we draw attention to the importance of multiscale modeling in the framework of studies of biological systems in general and of the immune system in particular.

  10. Preclinical Mouse Cancer Models: A Maze of Opportunities and Challenges (United States)

    Day, Chi-Ping; Merlino, Glenn; Van Dyke, Terry


    Significant advances have been made in developing novel therapeutics for cancer treatment, and targeted therapies have revolutionized the treatment of some cancers. Despite the promise, only about five percent of new cancer drugs are approved, and most fail due to lack of efficacy. The indication is that current preclinical methods are limited in predicting successful outcomes. Such failure exacts enormous cost, both financial and in the quality of human life. This primer explores the current status, promise and challenges of preclinical evaluation in advanced mouse cancer models and briefly addresses emerging models for early-stage preclinical development. PMID:26406370

  11. Biodistribution and Clearance of Human Mesenchymal Stem Cells by Quantitative Three-Dimensional Cryo-Imaging After Intravenous Infusion in a Rat Lung Injury Model. (United States)

    Schmuck, Eric G; Koch, Jill M; Centanni, John M; Hacker, Timothy A; Braun, Rudolf K; Eldridge, Marlowe; Hei, Derek J; Hematti, Peiman; Raval, Amish N


    : Cell tracking is a critical component of the safety and efficacy evaluation of therapeutic cell products. To date, cell-tracking modalities have been hampered by poor resolution, low sensitivity, and inability to track cells beyond the shortterm. Three-dimensional (3D) cryo-imaging coregisters fluorescent and bright-field microcopy images and allows for single-cell quantification within a 3D organ volume. We hypothesized that 3D cryo-imaging could be used to measure cell biodistribution and clearance after intravenous infusion in a rat lung injury model compared with normal rats. A bleomycin lung injury model was established in Sprague-Dawley rats (n = 12). Human mesenchymal stem cells (hMSCs) labeled with QTracker655 were infused via jugular vein. After 2, 4, or 8 days, a second dose of hMSCs labeled with QTracker605 was infused, and animals were euthanized after 60, 120, or 240 minutes. Lungs, liver, spleen, heart, kidney, testis, and intestine were cryopreserved, followed by 3D cryo-imaging of each organ. At 60 minutes, 82% ± 9.7% of cells were detected; detection decreased to 60% ± 17% and 66% ± 22% at 120 and 240 minutes, respectively. At day 2, 0.06% of cells were detected, and this level remained constant at days 4 and 8 postinfusion. At 60, 120, and 240 minutes, 99.7% of detected cells were found in the liver, lungs, and spleen, with cells primarily retained in the liver. This is the first study using 3D cryo-imaging to track hMSCs in a rat lung injury model. hMSCs were retained primarily in the liver, with fewer detected in lungs and spleen. Effective bench-to-bedside clinical translation of cellular therapies requires careful understanding of cell fate through tracking. Tracking cells is important to measure cell retention so that delivery methods and cell dose can be optimized and so that biodistribution and clearance can be defined to better understand potential off-target toxicity and redosing strategies. This article demonstrates, for the first

  12. Current advancements and challenges in soil-root interactions modelling (United States)

    Schnepf, Andrea; Huber, Katrin; Abesha, Betiglu; Meunier, Felicien; Leitner, Daniel; Roose, Tiina; Javaux, Mathieu; Vanderborght, Jan; Vereecken, Harry


    Roots change their surrounding soil chemically, physically and biologically. This includes changes in soil moisture and solute concentration, the exudation of organic substances into the rhizosphere, increased growth of soil microorganisms, or changes in soil structure. The fate of water and solutes in the root zone is highly determined by these root-soil interactions. Mathematical models of soil-root systems in combination with non-invasive techniques able to characterize root systems are a promising tool to understand and predict the behaviour of water and solutes in the root zone. With respect to different fields of applications, predictive mathematical models can contribute to the solution of optimal control problems in plant recourse efficiency. This may result in significant gains in productivity, efficiency and environmental sustainability in various land use activities. Major challenges include the coupling of model parameters of the relevant processes with the surrounding environment such as temperature, nutrient concentration or soil water content. A further challenge is the mathematical description of the different spatial and temporal scales involved. This includes in particular the branched structures formed by root systems or the external mycelium of mycorrhizal fungi. Here, reducing complexity as well as bridging between spatial scales is required. Furthermore, the combination of experimental and mathematical techniques may advance the field enormously. Here, the use of root system, soil and rhizosphere models is presented through a number of modelling case studies, including image based modelling of phosphate uptake by a root with hairs, model-based optimization of root architecture for phosphate uptake from soil, upscaling of rhizosphere models, modelling root growth in structured soil, and the effect of root hydraulic architecture on plant water uptake efficiency and drought resistance.

  13. Contributions and challenges for network models in cognitive neuroscience. (United States)

    Sporns, Olaf


    The confluence of new approaches in recording patterns of brain connectivity and quantitative analytic tools from network science has opened new avenues toward understanding the organization and function of brain networks. Descriptive network models of brain structural and functional connectivity have made several important contributions; for example, in the mapping of putative network hubs and network communities. Building on the importance of anatomical and functional interactions, network models have provided insight into the basic structures and mechanisms that enable integrative neural processes. Network models have also been instrumental in understanding the role of structural brain networks in generating spatially and temporally organized brain activity. Despite these contributions, network models are subject to limitations in methodology and interpretation, and they face many challenges as brain connectivity data sets continue to increase in detail and complexity.

  14. Navigating disciplinary challenges to global sustainability science: an archaeological model

    Directory of Open Access Journals (Sweden)

    Mark J Hudson


    Full Text Available Current threats posed by anthropogenic climate change, biodiversity loss, the degradation of ecosystem services, and other related impacts of human activity require a concerted res- ponse through a global science of sustainability. The threats faced by humanity are so extensive that all academic disciplines are affected in some way and all have a role to play in developing potential responses. Given that few academic disciplines have traditionally focused on issues of ecology or sustainability, however, major challenges remain with respect to how we might build a global science of sustainability that can support concrete policy and interventions. This paper proposes a developmental model with five levels of research and practice required for an effective global sustainability science and examines some of the challenges faced by archaeology in moving up these levels.

  15. Six challenges in modelling for public health policy

    Directory of Open Access Journals (Sweden)

    C.J.E. Metcalf


    Full Text Available The World Health Organisation's definition of public health refers to all organized measures to prevent disease, promote health, and prolong life among the population as a whole (World Health Organization, 2014. Mathematical modelling plays an increasingly important role in helping to guide the most high impact and cost-effective means of achieving these goals. Public health programmes are usually implemented over a long period of time with broad benefits to many in the community. Clinical trials are seldom large enough to capture these effects. Observational data may be used to evaluate a programme after it is underway, but have limited value in helping to predict the future impact of a proposed policy. Furthermore, public health practitioners are often required to respond to new threats, for which there is little or no previous data on which to assess the threat. Computational and mathematical models can help to assess potential threats and impacts early in the process, and later aid in interpreting data from complex and multifactorial systems. As such, these models can be critical tools in guiding public health action. However, there are a number of challenges in achieving a successful interface between modelling and public health. Here, we discuss some of these challenges.

  16. Six challenges in modelling for public health policy. (United States)

    Metcalf, C J E; Edmunds, W J; Lessler, J


    The World Health Organisation's definition of public health refers to all organized measures to prevent disease, promote health, and prolong life among the population as a whole (World Health Organization, 2014). Mathematical modelling plays an increasingly important role in helping to guide the most high impact and cost-effective means of achieving these goals. Public health programmes are usually implemented over a long period of time with broad benefits to many in the community. Clinical trials are seldom large enough to capture these effects. Observational data may be used to evaluate a programme after it is underway, but have limited value in helping to predict the future impact of a proposed policy. Furthermore, public health practitioners are often required to respond to new threats, for which there is little or no previous data on which to assess the threat. Computational and mathematical models can help to assess potential threats and impacts early in the process, and later aid in interpreting data from complex and multifactorial systems. As such, these models can be critical tools in guiding public health action. However, there are a number of challenges in achieving a successful interface between modelling and public health. Here, we discuss some of these challenges. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Benchmark dose (BMD) modeling: current practice, issues, and challenges. (United States)

    Haber, Lynne T; Dourson, Michael L; Allen, Bruce C; Hertzberg, Richard C; Parker, Ann; Vincent, Melissa J; Maier, Andrew; Boobis, Alan R


    Benchmark dose (BMD) modeling is now the state of the science for determining the point of departure for risk assessment. Key advantages include the fact that the modeling takes account of all of the data for a particular effect from a particular experiment, increased consistency, and better accounting for statistical uncertainties. Despite these strong advantages, disagreements remain as to several specific aspects of the modeling, including differences in the recommendations of the US Environmental Protection Agency (US EPA) and the European Food Safety Authority (EFSA). Differences exist in the choice of the benchmark response (BMR) for continuous data, the use of unrestricted models, and the mathematical models used; these can lead to differences in the final BMDL. It is important to take confidence in the model into account in choosing the BMDL, rather than simply choosing the lowest value. The field is moving in the direction of model averaging, which will avoid many of the challenges of choosing a single best model when the underlying biology does not suggest one, but additional research would be useful into methods of incorporating biological considerations into the weights used in the averaging. Additional research is also needed regarding the interplay between the BMR and the UF to ensure appropriate use for studies supporting a lower BMR than default values, such as for epidemiology data. Addressing these issues will aid in harmonizing methods and moving the field of risk assessment forward.

  18. Citizen observations contributing to flood modelling: opportunities and challenges (United States)

    Assumpção, Thaine H.; Popescu, Ioana; Jonoski, Andreja; Solomatine, Dimitri P.


    Citizen contributions to science have been successfully implemented in many fields, and water resources is one of them. Through citizens, it is possible to collect data and obtain a more integrated decision-making process. Specifically, data scarcity has always been an issue in flood modelling, which has been addressed in the last decades by remote sensing and is already being discussed in the citizen science context. With this in mind, this article aims to review the literature on the topic and analyse the opportunities and challenges that lie ahead. The literature on monitoring, mapping and modelling, was evaluated according to the flood-related variable citizens contributed to. Pros and cons of the collection/analysis methods were summarised. Then, pertinent publications were mapped into the flood modelling cycle, considering how citizen data properties (spatial and temporal coverage, uncertainty and volume) are related to its integration into modelling. It was clear that the number of studies in the area is rising. There are positive experiences reported in collection and analysis methods, for instance with velocity and land cover, and also when modelling is concerned, for example by using social media mining. However, matching the data properties necessary for each part of the modelling cycle with citizen-generated data is still challenging. Nevertheless, the concept that citizen contributions can be used for simulation and forecasting is proved and further work lies in continuing to develop and improve not only methods for collection and analysis, but certainly for integration into models as well. Finally, in view of recent automated sensors and satellite technologies, it is through studies as the ones analysed in this article that the value of citizen contributions, complementing such technologies, is demonstrated.

  19. Citizen observations contributing to flood modelling: opportunities and challenges

    Directory of Open Access Journals (Sweden)

    T. H. Assumpção


    Full Text Available Citizen contributions to science have been successfully implemented in many fields, and water resources is one of them. Through citizens, it is possible to collect data and obtain a more integrated decision-making process. Specifically, data scarcity has always been an issue in flood modelling, which has been addressed in the last decades by remote sensing and is already being discussed in the citizen science context. With this in mind, this article aims to review the literature on the topic and analyse the opportunities and challenges that lie ahead. The literature on monitoring, mapping and modelling, was evaluated according to the flood-related variable citizens contributed to. Pros and cons of the collection/analysis methods were summarised. Then, pertinent publications were mapped into the flood modelling cycle, considering how citizen data properties (spatial and temporal coverage, uncertainty and volume are related to its integration into modelling. It was clear that the number of studies in the area is rising. There are positive experiences reported in collection and analysis methods, for instance with velocity and land cover, and also when modelling is concerned, for example by using social media mining. However, matching the data properties necessary for each part of the modelling cycle with citizen-generated data is still challenging. Nevertheless, the concept that citizen contributions can be used for simulation and forecasting is proved and further work lies in continuing to develop and improve not only methods for collection and analysis, but certainly for integration into models as well. Finally, in view of recent automated sensors and satellite technologies, it is through studies as the ones analysed in this article that the value of citizen contributions, complementing such technologies, is demonstrated.

  20. Addressing Energy System Modelling Challenges: The Contribution of the Open Energy Modelling Framework (oemof)

    DEFF Research Database (Denmark)

    Hilpert, Simon; Günther, Stephan; Kaldemeyer, Cord


    complexity of energy systems and high uncertainties on different levels. In addition, interdisciplinary modelling is necessary for getting insight in mechanisms of an integrated world. At the same time models need to meet scientific standards as public acceptance becomes increasingly important......The process of modelling energy systems is accompanied by challenges inherently connected with mathematical modelling. However, due to modern realities in the 21st century, existing challenges are gaining in magnitude and are supplemented with new ones. Modellers are confronted with a rising....... In this intricate environment model application as well as result communication and interpretation is also getting more difficult. In this paper we present the open energy modelling framework (oemof) as a novel approach for energy system modelling and derive its contribution to existing challenges. Therefore, based...


    Directory of Open Access Journals (Sweden)

    Rostyslav Baran


    Full Text Available The article investigates the development of E-commerce business models and highlights its current problems. The aim of the article is to research the application features of E-commerce models, forms and instruments, as well as to define its basic challenges at the present stage of world economic development. The article explores the current state of E-commerce market development both worldwide and in Ukraine. This allows determining the mainstream of E-commerce market - growth of M-commerce and transnational online trade. The article analyzes the activities of leading global marketplaces and offers their performance comparison. It defines the basic modifications in E-commerce models and singles out the key problems in this field thus enabling domestic enterprises to improve the efficiency of their Internet business activities. Key words: E-commerce, Internet, marketplace, M-commerce

  2. Models of marine molluscan diseases: Trends and challenges. (United States)

    Powell, Eric N; Hofmann, Eileen E


    Disease effects on host population dynamics and the transmission of pathogens between hosts are two important challenges for understanding how epizootics wax and wane and how disease influences host population dynamics. For the management of marine shellfish resources, marine diseases pose additional challenges in early intervention after the appearance of disease, management of the diseased population to limit a decline in host abundance, and application of measures to restrain that decline once it occurs. Mathematical models provide one approach for quantifying these effects and addressing the competing goals of managing the diseased population versus managing the disease. The majority of models for molluscan diseases fall into three categories distinguished by these competing goals. (1) Models that consider disease effects on the host population tend to focus on pathogen proliferation within the host. Many of the well-known molluscan diseases are pandemic, in that they routinely reach high prevalence rapidly over large geographic expanses, are characterized by transmission that does not depend upon a local source, and exert a significant influence on host population dynamics. Models focused on disease proliferation examine the influence of environmental change on host population metrics and provide a basis to better manage diseased stocks. Such models are readily adapted to questions of fishery management and habitat restoration. (2) Transmission models are designed to understand the mechanisms triggering epizootics, identify factors impeding epizootic development, and evaluate controls on the rate of disease spread over the host's range. Transmission models have been used extensively to study terrestrial diseases, yet little attention has been given to their potential for understanding the epidemiology of marine molluscan diseases. For management of diseases of wild stocks, transmission models open up a range of options, including the application of area

  3. Computed tomography intravenous cholangiography

    International Nuclear Information System (INIS)

    Nascimento, S.; Murray, W.; Wilson, P.


    Indications for direct visualization of the bile ducts include bile duct dilatation demonstrated by ultrasound or computed tomography (CT) scanning, where the cause of the bile duct dilatation is uncertain or where the anatomy of bile duct obstruction needs further clarification. Another indication is right upper quadrant pain, particularly in a post-cholecystectomy patient, where choledocholithiasis is suspected. A possible new indication is pre-operative evaluation prior to laparoscopic cholecystectomy. The bile ducts are usually studied by endoscopic retrograde cholangiopancreatography (ERCP), or, less commonly, trans-hepatic cholangiography. The old technique of intravenous cholangiography has fallen into disrepute because of inconsistent bile-duct opacification. The advent of spiral CT scanning has renewed interest in intravenous cholangiography. The CT technique is very sensitive to the contrast agent in the bile ducts, and angiographic and three-dimensional reconstructions of the biliary tree can readily be obtained using the CT intravenous cholangiogram technique (CT IVC). Seven patients have been studied using this CT IVC technique, between February 1995 and June 1996, and are the subject of the present report. Eight further studies have since been performed. The results suggest that CT IVC could replace ERCP as the primary means of direct cholangiography, where pancreatic duct visualization is not required. (authors)

  4. Computed tomography intravenous cholangiography

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, S.; Murray, W.; Wilson, P. [Pittwater Radiology, Dee Why, NSW, (Australia)


    Indications for direct visualization of the bile ducts include bile duct dilatation demonstrated by ultrasound or computed tomography (CT) scanning, where the cause of the bile duct dilatation is uncertain or where the anatomy of bile duct obstruction needs further clarification. Another indication is right upper quadrant pain, particularly in a post-cholecystectomy patient, where choledocholithiasis is suspected. A possible new indication is pre-operative evaluation prior to laparoscopic cholecystectomy. The bile ducts are usually studied by endoscopic retrograde cholangiopancreatography (ERCP), or, less commonly, trans-hepatic cholangiography. The old technique of intravenous cholangiography has fallen into disrepute because of inconsistent bile-duct opacification. The advent of spiral CT scanning has renewed interest in intravenous cholangiography. The CT technique is very sensitive to the contrast agent in the bile ducts, and angiographic and three-dimensional reconstructions of the biliary tree can readily be obtained using the CT intravenous cholangiogram technique (CT IVC). Seven patients have been studied using this CT IVC technique, between February 1995 and June 1996, and are the subject of the present report. Eight further studies have since been performed. The results suggest that CT IVC could replace ERCP as the primary means of direct cholangiography, where pancreatic duct visualization is not required. (authors). 11 refs., 6 figs.

  5. Challenges in LCA modelling of multiple loops for aluminium cans


    Niero, Monia; Olsen, Stig Irving


    Life Cycle Assessment (LCA) has traditionally played a key role in identifying the most efficient envi- ronmental design strategies and the best option for the end-of-life of products from an environmental point of view, within “one life cycle” approach. However, such an approach fails to capture one of themain features of circular product systems, i.e. the need to model multiple life cycles. There are some key methodological challenges that LCA has to face in order to exploit its potential i...

  6. European Continental Scale Hydrological Model, Limitations and Challenges (United States)

    Rouholahnejad, E.; Abbaspour, K.


    The pressures on water resources due to increasing levels of societal demand, increasing conflict of interest and uncertainties with regard to freshwater availability create challenges for water managers and policymakers in many parts of Europe. At the same time, climate change adds a new level of pressure and uncertainty with regard to freshwater supplies. On the other hand, the small-scale sectoral structure of water management is now reaching its limits. The integrated management of water in basins requires a new level of consideration where water bodies are to be viewed in the context of the whole river system and managed as a unit within their basins. In this research we present the limitations and challenges of modelling the hydrology of the continent Europe. The challenges include: data availability at continental scale and the use of globally available data, streamgauge data quality and their misleading impacts on model calibration, calibration of large-scale distributed model, uncertainty quantification, and computation time. We describe how to avoid over parameterization in calibration process and introduce a parallel processing scheme to overcome high computation time. We used Soil and Water Assessment Tool (SWAT) program as an integrated hydrology and crop growth simulator to model water resources of the Europe continent. Different components of water resources are simulated and crop yield and water quality are considered at the Hydrological Response Unit (HRU) level. The water resources are quantified at subbasin level with monthly time intervals for the period of 1970-2006. The use of a large-scale, high-resolution water resources models enables consistent and comprehensive examination of integrated system behavior through physically-based, data-driven simulation and provides the overall picture of water resources temporal and spatial distribution across the continent. The calibrated model and results provide information support to the European Water

  7. Challenges of model transferability to data-scarce regions (Invited) (United States)

    Samaniego, L. E.


    Developing the ability to globally predict the movement of water on the land surface at spatial scales from 1 to 5 km constitute one of grand challenges in land surface modelling. Copying with this grand challenge implies that land surface models (LSM) should be able to make reliable predictions across locations and/or scales other than those used for parameter estimation. In addition to that, data scarcity and quality impose further difficulties in attaining reliable predictions of water and energy fluxes at the scales of interest. Current computational limitations impose also seriously limitations to exhaustively investigate the parameter space of LSM over large domains (e.g. greater than half a million square kilometers). Addressing these challenges require holistic approaches that integrate the best techniques available for parameter estimation, field measurements and remotely sensed data at their native resolutions. An attempt to systematically address these issues is the multiscale parameterisation technique (MPR) that links high resolution land surface characteristics with effective model parameters. This technique requires a number of pedo-transfer functions and a much fewer global parameters (i.e. coefficients) to be inferred by calibration in gauged basins. The key advantage of this technique is the quasi-scale independence of the global parameters which enables to estimate global parameters at coarser spatial resolutions and then to transfer them to (ungauged) areas and scales of interest. In this study we show the ability of this technique to reproduce the observed water fluxes and states over a wide range of climate and land surface conditions ranging from humid to semiarid and from sparse to dense forested regions. Results of transferability of global model parameters in space (from humid to semi-arid basins) and across scales (from coarser to finer) clearly indicate the robustness of this technique. Simulations with coarse data sets (e.g. EOBS

  8. Overcoming challenges of catastrophe modelling in data poor regions (United States)

    Grassby, L.; Millinship, I.; Breinl, K.


    There is an increasing demand for loss accumulation tools in expanding international insurance markets such as India, China and Thailand. This reflects the combination of an increase in exposures in these territories as industry intensifies and urban development expands, as well as several notable natural catastrophes affecting these areas over the past few years (e.g. extreme floods in Mumbai in 2006 and in Thailand in 2011). Large, global insurers and reinsurers are embracing the opportunity to underwrite these exposures but only where adequate tools are available to provide understanding of the hazards, exposures and potential losses. Unlike more developed countries, data availability in these regions is typically limited and of poor resolution, but model development is still required in order to analyse the risk. Some of the modelling challenges associated with data limitations include: (1) dealing with a lack of hydrological data which results in greater uncertainty of the flow rate and event frequency; (2) lower DTM resolution than that available across much of Europe, which underlies the hazard component of the catastrophe model; (3) limited accessibility to data that characterises the Built Environment including information on different building types and their susceptibility to damage; and (4) a lack of claims data from previous events or engineering research into the vulnerability of different building types. This is used to generate of country and structure specific vulnerability curves that explain the relationship between hazard intensity and damages. By presenting an industry specific flood model for data-poor India in collaboration with Allianz Re, we illustrate how we have overcome many of these challenges to allow loss accumulations to be made. The resulting model was successfully validated against the floods in Mumbai and Surat in 2006 and is being developed further with the availability of new data.

  9. Intraarterial reteplase and intravenous abciximab for treatment of acute ischemic stroke. A preliminary feasibility and safety study in a non-human primate model

    International Nuclear Information System (INIS)

    Qureshi, Adnan I.; Suri, M. Fareed K.; Ali, Zulfiqar; Ringer, Andrew J.; Boulos, Alan S.; Guterman, Lee R.; Hopkins, L. Nelson; Nakada, Marian T.; Alberico, Ronald A.; Martin, Lisa B.E.


    We performed a preliminary feasibility and safety study using intravenous (IV) administration of a platelet glycoprotein IIb/IIIa inhibitor (abciximab) in conjunction with intraarterial (IA) administration of a thrombolytic agent (reteplase) in a primate model of intracranial thrombosis. We introduced thrombus through superselective catheterization of the intracranial segment of the internal carotid artery in 16 primates. The animals were randomly assigned to receive IA reteplase and IV abciximab (n =4), IA reteplase and IV placebo (n =4), IA placebo and IV abciximab (n =4) or IA and IV placebo (n =4). Recanalization was assessed by serial angiography during the 6-h period after initiation of treatment. Postmortem magnetic resonance (MR) imaging was performed to determine the presence of cerebral infarction or intracranial hemorrhage. Partial or complete recanalization at 6 h after initiation of treatment (decrease of two or more points in pre-treatment angiographic occlusion grade) was observed in two animals treated with IA reteplase and IV abciximab, three animals treated with IA reteplase alone and one animal treated with IV abciximab alone. No improvement in perfusion was observed in animals that received IV and IA placebo. Cerebral infarction was demonstrated on postmortem MR imaging in three animals that received IA and IV placebo and in one animal each from the groups that received IA reteplase and IV abciximab or IV abciximab alone. One animal that received IV abciximab alone had a small intracerebral hemorrhage on MR imaging. (orig.)

  10. MATLAB-implemented estimation procedure for model-based assessment of hepatic insulin degradation from standard intravenous glucose tolerance test data. (United States)

    Di Nardo, Francesco; Mengoni, Michele; Morettini, Micaela


    Present study provides a novel MATLAB-based parameter estimation procedure for individual assessment of hepatic insulin degradation (HID) process from standard frequently-sampled intravenous glucose tolerance test (FSIGTT) data. Direct access to the source code, offered by MATLAB, enabled us to design an optimization procedure based on the alternating use of Gauss-Newton's and Levenberg-Marquardt's algorithms, which assures the full convergence of the process and the containment of computational time. Reliability was tested by direct comparison with the application, in eighteen non-diabetic subjects, of well-known kinetic analysis software package SAAM II, and by application on different data. Agreement between MATLAB and SAAM II was warranted by intraclass correlation coefficients ≥0.73; no significant differences between corresponding mean parameter estimates and prediction of HID rate; and consistent residual analysis. Moreover, MATLAB optimization procedure resulted in a significant 51% reduction of CV% for the worst-estimated parameter by SAAM II and in maintaining all model-parameter CV% MATLAB-based procedure was suggested as a suitable tool for the individual assessment of HID process. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Challenges to the standard model of Big Bang nucleosynthesis

    International Nuclear Information System (INIS)

    Steigman, G.


    Big Bang nucleosynthesis provides a unique probe of the early evolution of the Universe and a crucial test of the consistency of the standard hot Big Bang cosmological model. Although the primordial abundances of 2 H, 3 He, 4 He, and 7 Li inferred from current observational data are in agreement with those predicted by Big Bang nucleosynthesis, recent analysis has severely restricted the consistent range for the nucleon-to-photon ratio: 3.7 ≤ η 10 ≤ 4.0. Increased accuracy in the estimate of primordial 4 he and observations of Be and B in Pop II stars are offering new challenges to the standard model and suggest that no new light particles may be allowed (N ν BBN ≤ 3.0, where N ν is the number of equivalent light neutrinos). 23 refs

  12. Challenge models for RTFS in rainbow trout fry (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Henriksen, Maya Maria Mihályi; Madsen, Lone; Dalsgaard, Inger


    forms of stress have shown to be reproducible. Bath challenge is more appropriate for vaccine testing, since natural transmission of infection is imitated and is also more suitable due to the small size of the fry. A bath-model using H2O2 as a stressor is currently being tested on 1.4g rainbow trout fry...... in four experimental groups: 1) no H2O2/no bath infection, 2) H2O2/no bath infection, 3) no H2O2/ bath infection and 4) H2O2/ bath infection. Mortality will be evaluated over approximately 25 days. The project is currently in its preliminary phase and presently focused on development of a model...


    Directory of Open Access Journals (Sweden)

    Antonio COMI


    Full Text Available This paper explores the new research challenges for forecasting urban goods demand by rail. In fact, the growing interest to find urban logistics solutions for improving city sustainability and liveability, mainly due to the reduction of urban road accessibility and environmental constraints, has pushed to explore solutions alternative to the road. Multimodal urban logistics, based on the use of railway, seem an interesting alternative solution, but it remained mainly at conceptual level. Few studies have explored the factors, that push actors to find competitive such a system with respect to the road, and modelling framework for forecasting the relative demand. Therefore, paper reviews the current literature, investigates the factors involved in choosing such a mode, and finally, recalls a recent modelling framework and hence proposes some advancements that allow to point out the rail transport alternative.

  14. Modeling and Analysis in Marine Big Data: Advances and Challenges

    Directory of Open Access Journals (Sweden)

    Dongmei Huang


    Full Text Available It is aware that big data has gathered tremendous attentions from academic research institutes, governments, and enterprises in all aspects of information sciences. With the development of diversity of marine data acquisition techniques, marine data grow exponentially in last decade, which forms marine big data. As an innovation, marine big data is a double-edged sword. On the one hand, there are many potential and highly useful values hidden in the huge volume of marine data, which is widely used in marine-related fields, such as tsunami and red-tide warning, prevention, and forecasting, disaster inversion, and visualization modeling after disasters. There is no doubt that the future competitions in marine sciences and technologies will surely converge into the marine data explorations. On the other hand, marine big data also brings about many new challenges in data management, such as the difficulties in data capture, storage, analysis, and applications, as well as data quality control and data security. To highlight theoretical methodologies and practical applications of marine big data, this paper illustrates a broad view about marine big data and its management, makes a survey on key methods and models, introduces an engineering instance that demonstrates the management architecture, and discusses the existing challenges.

  15. Pharmacokinetic-Pharmacodynamic Modelling of the Analgesic and Antihyperalgesic Effects of Morphine after Intravenous Infusion in Human Volunteers

    DEFF Research Database (Denmark)

    Ravn, Pernille; Foster, David J. R.; Kreilgaard, Mads


    Using a modelling approach, this study aimed to (i) examine whether the pharmacodynamics of the analgesic and antihyperalgesic effects of morphine differ; (ii) investigate the influence of demographic, pain sensitivity and genetic (OPRM1) variables on between-subject variability of morphine...... evidence for adding between-occasion variability (BOV) on baseline and the placebo slope for EPTo and 2HA, respectively. The sensitivity covariate was significant on baseline EPTo values and genetics as a covariate on the placebo slope for 2HA. The analgesic and antihyperalgesic effects of morphine were...

  16. Some Challenges Posed by Coal Bed Methane Regional Assessment Modeling. (United States)

    Moore, Catherine R; Doherty, John; Howell, Stephen; Erriah, Leon


    Coal measures (coal bearing rock strata) can contain large reserves of methane. These reserves are being exploited at a rapidly increasing rate in many parts of the world. To extract coal seam gas, thousands of wells are drilled at relatively small spacing to depressurize coal seams to induce desorption and allow subsequent capture of the gas. To manage this process effectively, the effect of coal bed methane (CBM) extraction on regional aquifer systems must be properly understood and managed. Groundwater modeling is an integral part of this management process. However, modeling of CBM impacts presents some unique challenges, as processes that are operative at two very different scales must be adequately represented in the models. The impacts of large-scale gas extraction may be felt over a large area, yet despite the significant upscaling that accompanies construction of a regional model, near-well conditions and processes cannot be ignored. These include the highly heterogeneous nature of many coal measures, and the dual-phase flow of water and gas that is induced by coal seam depressurization. To understand these challenges, a fine-scale model was constructed incorporating a detailed representation of lithological heterogeneity to ensure that near-well processes and conditions could be examined. The detail of this heterogeneity was at a level not previously employed in models built to assess groundwater impacts arising from CBM extraction. A dual-phase reservoir simulator was used to examine depressurization and water desaturation processes in the vicinity of an extractive wellfield within this fine-scale model. A single-phase simulator was then employed so that depressurization errors incurred by neglecting near-well, dual-phase flow could be explored. Two models with fewer lithological details were then constructed in order to examine the nature of depressurization errors incurred by upscaling and to assess the interaction of the upscaling process with the


    Energy Technology Data Exchange (ETDEWEB)

    Heinze, Jonas; Boncioli, Denise; Winter, Walter [Deutsches Elektronen-Synchrotron (DESY), Platanenallee 6, D-15738 Zeuthen (Germany); Bustamante, Mauricio, E-mail:, E-mail:, E-mail:, E-mail: [Center for Cosmology and AstroParticle Physics (CCAPP), The Ohio State University, Columbus, OH 43210 (United States)


    The origin and composition of ultra-high-energy cosmic rays (UHECRs) remain a mystery. The proton dip model describes their spectral shape in the energy range above 10{sup 9} GeV by pair production and photohadronic interactions with the cosmic microwave background. The photohadronic interactions also produce cosmogenic neutrinos peaking around 10{sup 9} GeV. We test whether this model is still viable in light of recent UHECR spectrum measurements from the Telescope Array experiment and upper limits on the cosmogenic neutrino flux from IceCube. While two-parameter fits have been already presented, we perform a full scan of the three main physical model parameters: source redshift evolution, injected proton maximal energy, and spectral index. We find qualitatively different conclusions compared to earlier two-parameter fits in the literature: a mild preference for a maximal energy cutoff at the sources instead of the Greisen–Zatsepin–Kuzmin cutoff, hard injection spectra, and strong source evolution. The predicted cosmogenic neutrino flux exceeds the IceCube limit for any parameter combination. As a result, the proton dip model is challenged at more than 95% C.L. This is strong evidence against this model independent of mass composition measurements.

  18. Cosmogenic Neutrinos Challenge the Cosmic-ray Proton Dip Model (United States)

    Heinze, Jonas; Boncioli, Denise; Bustamante, Mauricio; Winter, Walter


    The origin and composition of ultra-high-energy cosmic rays (UHECRs) remain a mystery. The proton dip model describes their spectral shape in the energy range above 109 GeV by pair production and photohadronic interactions with the cosmic microwave background. The photohadronic interactions also produce cosmogenic neutrinos peaking around 109 GeV. We test whether this model is still viable in light of recent UHECR spectrum measurements from the Telescope Array experiment and upper limits on the cosmogenic neutrino flux from IceCube. While two-parameter fits have been already presented, we perform a full scan of the three main physical model parameters: source redshift evolution, injected proton maximal energy, and spectral index. We find qualitatively different conclusions compared to earlier two-parameter fits in the literature: a mild preference for a maximal energy cutoff at the sources instead of the Greisen-Zatsepin-Kuzmin cutoff, hard injection spectra, and strong source evolution. The predicted cosmogenic neutrino flux exceeds the IceCube limit for any parameter combination. As a result, the proton dip model is challenged at more than 95% C.L. This is strong evidence against this model independent of mass composition measurements.

  19. PP024. Effects of intravenous magnesium sulfate on the characteristics of eclamptic seizures induced by electrical stimuli in a rat preeclampsia/eclampsia model. (United States)

    Liu, Lei; Liu, Huishu; Huang, Qian; Brennecke, Shaun; Hu, Bihui


    Eclampsia is a serious complication of pregnancy and remains a leading cause of maternal mortality worldwide. Magnesium sulfate is commonly used in the prophylaxis and treatment of eclampsia. However, uncertainty remain regarding its anticonvulsant mechanism(s) of action. This study examined the effects of intravenous magnesium sulfate on the characteristics of eclamptic seizures in a rat preeclampsia/eclampsia model. All rats were implanted with stainless nickel-cadmium alloy bipolar electrodes one week before fertilization. Next, an experimental rat preeclampsia (PE) model was induced on gestational day 14 by anaesthetising rats and infusing over 1 hour into their tail veins lipopolysaccharide (LPS) (1.0μg/kg body weight) (with control rats receiving normal saline). The rats were then divided into three groups: a normal pregnancy (NP) group (n=6) which received a continuous infusion of saline; a control PE model group (n=7) (which had previously received the LPS treatment) which also received a continuous infusion of saline; and a treated PE model group (n=8) (which had previously received the LPS treatment) which received a continuous infusion of magnesium sulfate (60mg/kg/day). The continuous infusions in all three groups were delivered by implanted osmotic minipumps . Measurements were made of blood pressure, albuminuria, serum ALT, AST, and creatinine, BUN and serum magnesium concentrations. On gestational day 18, all experimental rats received a standardized electrical stimulus. Seizure activity was assessed using electroencephalogram (EEG) recordings. Terminations of pregnancy were performed on gestational day 21. Resorptions and pup birth weights were recorded. The pregnant LPS treated rats developed many features of human PE (e.g. hypertension, proteinuria, liver and kidney dysfunctions). The mean concentration of Mg(2+) in the magnesium sulfate therapy group (0.86±0.24mmol/L) was significantly higher (p0.05) between the latency periods of the NP group

  20. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. (United States)

    Woodcock, T E; Woodcock, T M


    I.V. fluid therapy does not result in the extracellular volume distribution expected from Starling's original model of semi-permeable capillaries subject to hydrostatic and oncotic pressure gradients within the extracellular fluid. Fluid therapy to support the circulation relies on applying a physiological paradigm that better explains clinical and research observations. The revised Starling equation based on recent research considers the contributions of the endothelial glycocalyx layer (EGL), the endothelial basement membrane, and the extracellular matrix. The characteristics of capillaries in various tissues are reviewed and some clinical corollaries considered. The oncotic pressure difference across the EGL opposes, but does not reverse, the filtration rate (the 'no absorption' rule) and is an important feature of the revised paradigm and highlights the limitations of attempting to prevent or treat oedema by transfusing colloids. Filtered fluid returns to the circulation as lymph. The EGL excludes larger molecules and occupies a substantial volume of the intravascular space and therefore requires a new interpretation of dilution studies of blood volume and the speculation that protection or restoration of the EGL might be an important therapeutic goal. An explanation for the phenomenon of context sensitivity of fluid volume kinetics is offered, and the proposal that crystalloid resuscitation from low capillary pressures is rational. Any potential advantage of plasma or plasma substitutes over crystalloids for volume expansion only manifests itself at higher capillary pressures.

  1. Challenges in Species Tree Estimation Under the Multispecies Coalescent Model. (United States)

    Xu, Bo; Yang, Ziheng


    The multispecies coalescent (MSC) model has emerged as a powerful framework for inferring species phylogenies while accounting for ancestral polymorphism and gene tree-species tree conflict. A number of methods have been developed in the past few years to estimate the species tree under the MSC. The full likelihood methods (including maximum likelihood and Bayesian inference) average over the unknown gene trees and accommodate their uncertainties properly but involve intensive computation. The approximate or summary coalescent methods are computationally fast and are applicable to genomic datasets with thousands of loci, but do not make an efficient use of information in the multilocus data. Most of them take the two-step approach of reconstructing the gene trees for multiple loci by phylogenetic methods and then treating the estimated gene trees as observed data, without accounting for their uncertainties appropriately. In this article we review the statistical nature of the species tree estimation problem under the MSC, and explore the conceptual issues and challenges of species tree estimation by focusing mainly on simple cases of three or four closely related species. We use mathematical analysis and computer simulation to demonstrate that large differences in statistical performance may exist between the two classes of methods. We illustrate that several counterintuitive behaviors may occur with the summary methods but they are due to inefficient use of information in the data by summary methods and vanish when the data are analyzed using full-likelihood methods. These include (i) unidentifiability of parameters in the model, (ii) inconsistency in the so-called anomaly zone, (iii) singularity on the likelihood surface, and (iv) deterioration of performance upon addition of more data. We discuss the challenges and strategies of species tree inference for distantly related species when the molecular clock is violated, and highlight the need for improving the

  2. Intravenous injection of artificial red cells and subsequent dye laser irradiation causes deep vessel impairment in an animal model of port-wine stain. (United States)

    Rikihisa, Naoaki; Tominaga, Mai; Watanabe, Shoji; Mitsukawa, Nobuyuki; Saito, Yoshiaki; Sakai, Hiromi


    Our previous study proposed using artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment for port-wine stains (PWSs). Dye laser photons are absorbed by red blood cells (RBCs) and hemoglobin (Hb) mixture, which potentially produce more heat and photocoagulation and effectively destroy endothelial cells. Hb-Vs combination therapy will improve clinical outcomes of dye laser treatment for PWSs because very small vessels do not contain sufficient RBCs and they are poor absorbers/heaters of lasers. In the present study, we analyzed the relationship between vessel depth from the skin surface and vessel distraction through dye laser irradiation following intravenous Hb-Vs injection using a chicken wattle model. Hb-Vs were administered and chicken wattles underwent high-energy irradiation at energy higher than in the previous experiments. Hb-Vs location in the vessel lumen was identified to explain its photosensitizer effect using human Hb immunostaining of the irradiated wattles. Laser irradiation with Hb-Vs can effectively destroy deep vessels in animal models. Hb-Vs tend to flow in the marginal zone of both small and large vessels. Increasing laser power combined with Hb-Vs injection contributed for deep vessel impairment because of the synergetic effect of both methods. Newly added Hb tended to flow near the target endothelial cells of the laser treatment. In Hb-Vs and RBC mixture, heat transfer to endothelial cells from absorbers/heater may increase. Hb-Vs function as photosensitizers to destroy deep vessels within a restricted distance that the photon can reach.

  3. Elucidation of arctigenin pharmacokinetics after intravenous and oral administrations in rats: integration of in vitro and in vivo findings via semi-mechanistic pharmacokinetic modeling. (United States)

    Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong


    Although arctigenin (AR) has attracted substantial research interests due to its promising and diverse therapeutic effects, studies regarding its biotransformation were limited. The current study aims to provide information regarding the pharmacokinetic properties of AR via various in vitro and in vivo experiments as well as semi-mechanistic pharmacokinetic modeling. Our in vitro rat microsome incubation studies revealed that glucuronidation was the main intestinal and liver metabolic pathway of AR, which occurred with V max, K m, and Clint of 47.5 ± 3.4 nmol/min/mg, 204 ± 22 μM, and 233 ± 9 μl/min/mg with intestinal microsomes and 2.92 ± 0.07 nmol/min/mg, 22.7 ± 1.2 μM, and 129 ± 4 μl/min/mg with liver microsomes, respectively. In addition, demethylation and hydrolysis of AR occurred with liver microsomes but not with intestinal microsomes. In vitro incubation of AR and its metabolites in intestinal content demonstrated that glucuronides of AR excreted in bile could be further hydrolyzed back to the parent compound, suggesting its potential enterohepatic circulation. Furthermore, rapid formation followed by fast elimination of arctigenic acid (AA) and arctigenin-4'-O-glucuronide (AG) was observed after both intravenous (IV) and oral administrations of AR in rats. Linear pharmacokinetics was observed at three different doses for AR, AA, and AG after IV administration of AR (0.48-2.4 mg/kg, r (2) > 0.99). Finally, an integrated semi-mechanistic pharmacokinetic model using in vitro enzyme kinetic and in vivo pharmacokinetic parameters was successfully developed to describe plasma concentrations of AR, AA, and AG after both IV and oral administration of AR at all tested doses.

  4. Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and buccal administration of a high-concentration formulation of buprenorphine in conscious cats (United States)

    Doodnaught, Graeme M.; Monteiro, Beatriz P.; Benito, Javier; Edge, Daniel; Beaudry, Francis; Pelligand, Ludovic


    Background The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats. Methods Six healthy cats (4.9 ± 0.7 kg) were included in a prospective, randomized, blinded, crossover study. Simbadol™ (1.8 mg mL-1) was administered by the subcutaneous (SC; 0.24 mg kg-1), intravenous (IV; 0.12 mg kg-1) or buccal (OTM; 0.12 mg kg-1) route of administration and thermal thresholds (TT) were compared with a saline group (SAL). Thermal threshold testing and blood sampling were performed at predetermined time points up to 72 hours including a placebo group. Plasma buprenorphine and norbuprenorphine concentrations were measured using liquid chromatography mass spectrometry. A bespoke bicompartmental pharmacokinetic model simultaneously fitted data from two analytes/three routes of administration. Temporal changes in TT were analyzed using one-way ANOVA followed by Dunnett’s test and treatment comparisons using two-way ANOVA with Bonferroni’s correction (P buprenorphine-treated cats. The absolute buprenorphine clearance was 0.98 L kg-1 hour-1, volume of distribution at steady state was 7.9 L kg-1 and the elimination-half-life was 12.3 hours. Bioavailability for SC and OTM was 94% and 24%, respectively. Subcutaneous absorption was biphasic. An initial peak (0.08 hours) was followed by a slow (half-life 11.2 hours) and progressive (peak acceleration at 2.8 hours) uptake. Conclusion The SC administration of Simbadol™ was characterized by prolonged absorption half-life and sustained plasma concentrations yielding long-lasting antinociception (≥ 24 hours) when compared with the IV and OTM routes. PMID:28445495


    Energy Technology Data Exchange (ETDEWEB)



    Development of real-time predictive modeling to identify the dispersion and/or source(s) of airborne weapons of mass destruction including chemical, biological, radiological, and nuclear material in urban environments is needed to improve response to potential releases of these materials via either terrorist or accidental means. These models will also prove useful in defining airborne pollution dispersion in urban environments for pollution management/abatement programs. Predicting gas flow in an urban setting on a scale of less than a few kilometers is a complicated and challenging task due to the irregular flow paths that occur along streets and alleys and around buildings of different sizes and shapes, i.e., ''urban canyons''. In addition, air exchange between the outside and buildings and subway areas further complicate the situation. Transport models that are used to predict dispersion of WMD/CBRN materials or to back track the source of the release require high-density data and need defensible parameterizations of urban processes. Errors in the data or any of the parameter inputs or assumptions will lead to misidentification of the airborne spread or source release location(s). The need for these models to provide output in a real-time fashion if they are to be useful for emergency response provides another challenge. To improve the ability of New York City's (NYC's) emergency management teams and first response personnel to protect the public during releases of hazardous materials, the New York City Urban Dispersion Program (UDP) has been initiated. This is a four year research program being conducted from 2004 through 2007. This paper will discuss ground level and subway Perfluorocarbon tracer (PFT) release studies conducted in New York City. The studies released multiple tracers to study ground level and vertical transport of contaminants. This paper will discuss the results from these tests and how these results can be used

  6. Intravenous lidocaine infusion. (United States)

    Soto, G; Naranjo González, M; Calero, F


    Systemic lidocaine used in continuous infusion during the peri-operative period has analgesic, anti-hyperalgesic, as well as anti-inflammatory properties. This makes it capable of reducing the use of opioids and inhalational anaesthetics, and the early return of bowel function, and patient hospital stay. The aim of this narrative review was to highlight the pharmacology and indications for clinical application, along with new and interesting research areas. The clinical applications of peri-operative lidocaine infusion have been reviewed in several recent systematic reviews and meta-analyses in patients undergoing open and laparoscopic abdominal procedures, ambulatory procedures, and other types of surgery. Peri-operative lidocaine infusion may be a useful analgesic adjunct in enhanced recovery protocols. Potential benefits of intravenous lidocaine in chronic post-surgical pain, post-operative cognitive dysfunction, and cancer recurrence are under investigation. Due to its immunomodulation properties over surgical stress, current evidence suggests that intravenous lidocaine could be used in the context of multimodal analgesia. Copyright © 2018 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Challenges of Microgrids in Remote Communities: A STEEP Model Application

    Directory of Open Access Journals (Sweden)

    Daniel Akinyele


    Full Text Available There is a growing interest in the application of microgrids around the world because of their potential for achieving a flexible, reliable, efficient and smart electrical grid system and supplying energy to off-grid communities, including their economic benefits. Several research studies have examined the application issues of microgrids. However, a lack of in-depth considerations for the enabling planning conditions has been identified as a major reason why microgrids fail in several off-grid communities. This development requires research efforts that consider better strategies and framework for sustainable microgrids in remote communities. This paper first presents a comprehensive review of microgrid technologies and their applications. It then proposes the STEEP model to examine critically the failure factors based on the social, technical, economic, environmental and policy (STEEP perspectives. The model details the key dimensions and actions necessary for addressing the challenge of microgrid failure in remote communities. The study uses remote communities within Nigeria, West Africa, as case studies and demonstrates the need for the STEEP approach for better understanding of microgrid planning and development. Better insights into microgrid systems are expected to address the drawbacks and improve the situation that can lead to widespread and sustainable applications in off-grid communities around the world in the future. The paper introduces the sustainable planning framework (SPF based on the STEEP model, which can form a general basis for planning microgrids in any remote location.

  8. Ensemble models on palaeoclimate to predict India's groundwater challenge

    Directory of Open Access Journals (Sweden)

    Partha Sarathi Datta


    Full Text Available In many parts of the world, freshwater crisis is largely due to increasing water consumption and pollution by rapidly growing population and aspirations for economic development, but, ascribed usually to the climate. However, limited understanding and knowledge gaps in the factors controlling climate and uncertainties in the climate models are unable to assess the probable impacts on water availability in tropical regions. In this context, review of ensemble models on δ18O and δD in rainfall and groundwater, 3H- and 14C- ages of groundwater and 14C- age of lakes sediments helped to reconstruct palaeoclimate and long-term recharge in the North-west India; and predict future groundwater challenge. The annual mean temperature trend indicates both warming/cooling in different parts of India in the past and during 1901–2010. Neither the GCMs (Global Climate Models nor the observational record indicates any significant change/increase in temperature and rainfall over the last century, and climate change during the last 1200 yrs BP. In much of the North-West region, deep groundwater renewal occurred from past humid climate, and shallow groundwater renewal from limited modern recharge over the past decades. To make water management to be more responsive to climate change, the gaps in the science of climate change need to be bridged.

  9. Challenges in modelling the reaction chemistry of interstellar dust. (United States)

    Bromley, S T; Goumans, T P M; Herbst, E; Jones, A P; Slater, B


    Studies aiming to understand the physicochemical properties of interstellar dust and the chemical reactions that occur on and in it have traditionally been the preserve of astronomical observation and experimental attempts to mimic astronomically relevant conditions in the laboratory. Increasingly, computational modelling in its various guises is establishing a complementary third pillar of support to this endeavour by providing detailed insights into the complexities of interstellar dust chemistry. Inherently, the basis of computational modelling is to be found in the details (e.g. atomic structure/composition, reaction barriers) that are difficult to probe accurately from observation and experiment. This bottom-up atom-based theoretical approach, often itself based on deeper quantum mechanical principles, although extremely powerful, also has limitations when systems become too large or complex. In this Perspective, after first providing a general background to the current state of observational-based knowledge, we introduce a number of computational modelling methods with reference to recent state-of-the-art studies, in order to highlight the capabilities of such approaches in this field. Specifically, we first outline the use of computational chemistry methods for dust nucleation, structure, and individual reactions on bare and icy dust surfaces. Later, we review kinetic modelling of networks of reactions relevant to dust chemistry and how to take into account quantum tunnelling effects in the low temperature reactions in the interstellar medium. Finally, we point to the future challenges that need to be overcome for computational modelling to provide even more detailed and encompassing perspectives on the nature and reaction chemistry of interstellar dust.

  10. Challenges of citizen science contributions to modelling hydrodynamics of floods (United States)

    Assumpção, Thaine Herman; Popescu, Ioana; Jonoski, Andreja; Solomatine, Dimitri P.


    Citizen science is an established mechanism in many fields of science, including ecology, biology and astronomy. Citizen participation ranges from collecting and interpreting data towards designing experiments with scientists and cooperating with water management authorities. In the environmental sciences, its potential has begun to be explored in the past decades and many studies on the applicability to water resources have emerged. Citizen Observatories are at the core of several EU-funded projects such as WeSenseIt, GroundTruth, GroundTruth 2.0 and SCENT (Smart Toolbox for Engaging Citizens into a People-Centric Observation Web) that already resulted in valuable contributions to the field. Buytaert et al. (2014) has already reviewed the role of citizen science in hydrology. The work presented here aims to complement it, reporting and discussing the use of citizen science for modelling the hydrodynamics of floods in a variety of studies. Additionally, it highlights the challenges that lie ahead to utilize more fully the citizen science potential contribution. In this work, focus is given to each component of hydrodynamic models: water level, velocity, flood extent, roughness and topography. It is addressed how citizens have been contributing to each aspect, mainly considering citizens as sensors and citizens as data interpreters. We consider to which kind of model (1D or 2D) the discussed approaches contribute and what their limitations and potential uses are. We found that although certain mechanisms are well established (e.g. the use of Volunteer Geographic Information for soft validation of land-cover and land-use maps), the applications in a modelling context are rather modest. Also, most studies involving models are limited to replacing traditional data with citizen data. We recommend that citizen science continue to be explored in modelling frameworks, in different case studies, taking advantage of the discussed mechanisms and of new sensor technologies

  11. Pelagic functional group modeling: Progress, challenges and prospects (United States)

    Hood, Raleigh R.; Laws, Edward A.; Armstrong, Robert A.; Bates, Nicholas R.; Brown, Christopher W.; Carlson, Craig A.; Chai, Fei; Doney, Scott C.; Falkowski, Paul G.; Feely, Richard A.; Friedrichs, Marjorie A. M.; Landry, Michael R.; Keith Moore, J.; Nelson, David M.; Richardson, Tammi L.; Salihoglu, Baris; Schartau, Markus; Toole, Dierdre A.; Wiggert, Jerry D.


    In this paper, we review the state of the art and major challenges in current efforts to incorporate biogeochemical functional groups into models that can be applied on basin-wide and global scales, with an emphasis on models that might ultimately be used to predict how biogeochemical cycles in the ocean will respond to global warming. We define the term "biogeochemical functional group" to refer to groups of organisms that mediate specific chemical reactions in the ocean. Thus, according to this definition, "functional groups" have no phylogenetic meaning—these are composed of many different species with common biogeochemical functions. Substantial progress has been made in the last decade toward quantifying the rates of these various functions and understanding the factors that control them. For some of these groups, we have developed fairly sophisticated models that incorporate this understanding, e.g. for diazotrophs (e.g. Trichodesmium), silica producers (diatoms) and calcifiers (e.g. coccolithophorids and specifically Emiliania huxleyi). However, current representations of nitrogen fixation and calcification are incomplete, i.e., based primarily upon models of Trichodesmium and E. huxleyi, respectively, and many important functional groups have not yet been considered in open-ocean biogeochemical models. Progress has been made over the last decade in efforts to simulate dimethylsulfide (DMS) production and cycling (i.e., by dinoflagellates and prymnesiophytes) and denitrification, but these efforts are still in their infancy, and many significant problems remain. One obvious gap is that virtually all functional group modeling efforts have focused on autotrophic microbes, while higher trophic levels have been completely ignored. It appears that in some cases (e.g., calcification), incorporating higher trophic levels may be essential not only for representing a particular biogeochemical reaction, but also for modeling export. Another serious problem is our

  12. Challenges and potential solutions for European coastal ocean modelling (United States)

    She, Jun; Stanev, Emil


    Coastal operational oceanography is a science and technological platform to integrate and transform the outcomes in marine monitoring, new knowledge generation and innovative technologies into operational information products and services in the coastal ocean. It has been identified as one of the four research priorities by EuroGOOS (She et al. 2016). Coastal modelling plays a central role in such an integration and transformation. A next generation coastal ocean forecasting system should have following features: i) being able to fully exploit benefits from future observations, ii) generate meaningful products in finer scales e.g., sub-mesoscale and in estuary-coast-sea continuum, iii) efficient parallel computing and model grid structure, iv) provide high quality forecasts as forcing to NWP and coastal climate models, v) resolving correctly inter-basin and inter-sub-basin water exchange, vi) resolving synoptic variability and predictability in marine ecosystems, e.g., for algae bloom, vi) being able to address critical and relevant issues in coastal applications, e.g., marine spatial planning, maritime safety, marine pollution protection, disaster prevention, offshore wind energy, climate change adaptation and mitigation, ICZM (integrated coastal zone management), the WFD (Water Framework Directive), and the MSFD (Marine Strategy Framework Directive), especially on habitat, eutrophication, and hydrographic condition descriptors. This presentation will address above challenges, identify limits of current models and propose correspondent research needed. The proposed roadmap will address an integrated monitoring-modelling approach and developing Unified European Coastal Ocean Models. In the coming years, a few new developments in European Sea observations can expected, e.g., more near real time delivering on profile observations made by research vessels, more shallow water Argo floats and bio-Argo floats deployed, much more high resolution sea level data from SWOT

  13. The Biochemical, Histopathological and Clinical Comparison of the Neuroprotective Effects of Subcutaneous Adalimumab and Intravenous Methylprednisolone in an Experimental Compressive Spinal Cord Trauma Model. (United States)

    Celik, Haydar; Karatay, Mete; Erdem, Yavuz; Yildirim, Ali Erdem; Sertbas, Idris; Karatay, Eylem; Kul, Halil; Guvenc, Yahya; Koksal, Ismet; Menekse, Guner; Alagoz, Fatih; Kertmen, Huseyin Hayri; Caydere, Muzaffer

    To evaluate the neuroprotective effects of adalimumab in an experimental spinal cord injury model and compare them with those of the widely-used methylprednisolone. Forty male Wistar rats were divided into 5 as the sham, trauma, adalimumab, methylprednisolone, and adalimumab+methylprednisolone groups. Only laminectomy was performed in the sham group. Laminectomy and trauma was performed to the trauma group but no treatment was given. A single dose of 40 mg/kg subcutaneous adalimumab was administered after the laminectomy and trauma to group 3. A single dose of intravenous 30 mg/kg methylprednisolone was administered right after laminectomy and trauma to group 4. Single doses of 40 mg/kg adalimumab and 30 mg/kg methylprednisolone were administered together after laminectomy and trauma to group 5. Serum malondialdehyde (MDA), TNF-α, IL-1β and IL-6 levels were measured and sections were obtained for histopathological study at the end of the 7 th day. MDA, TNF-α, IL-1β and IL-6 levels in serum were significantly decreased in the adalimumab group with clinical and histopathological improvement not less than the methylprednisolone group. The serum MDA levels were similar when the two drugs were given together or separately but there was a statistically quite significant decrease in TNF-α, IL-1β and IL-6 levels with concurrent use. Statistically significantly better results were obtained on histopathological evaluation with the use of both drugs together. This study revealed that adalimumab is as effective as methylprednisolone in compressive spinal cord injury in rats.

  14. Challenge

    International Nuclear Information System (INIS)

    Schwitters, R.F.


    The design of new and upgrades of existing high energy particle accelerators is reviewed in light of the current knowledge of the standard model determined from existing and past machines and funding factors. Current financing of science will delay determining unknowns, such as CP violation, proton decay, neutrino properties, and dark matter. Three options are given: (1) obtain more funding, (2) downsize scientific personnel as are private enterprises or (3) develop new technology which will reduce the high cost of building current designs of high energy accelerators. (AIP) copyright 1996 American Institute of Physics

  15. Smart services – characteristics, challenges, opportunities and business models

    Directory of Open Access Journals (Sweden)

    Marquardt Katrin


    Full Text Available “Industry 4.0”, “Digitalization”, “Internet of Things” and “Smart Services” are the today’s buzzwords when tracking economic news. It is to ask about the meaning of those phrases. The world has changed over the last decade from a mainly physical to software controlled economy and the information technology has become an integral part of our industry and society in its entirety. Nowadays it is no longer the product that matters it is the data that are generated by using the product or service. Those usage data collected and analyzed commence new business models and services. The economic future of a company will much more rely on the ability to collect and use the data to generate Smart Services for their customers and to transform from a simple product supplier to an entertainment provider. However there are not only opportunities there are also challenges on the way to that new services which needs to be known and considered. For instance the development cycles need to be faster, the business models need to be adjusted and the positive financial results will not come into the picture on the first day. Based on those thoughts and while there only a handful of researches about that new services exists, the main purpose of the present study is at first, to gain a common understanding about the meaning and the characteristics of Smart Services and their adjacencies. Secondly, the study summarizes the identified challenges and opportunities in relation to them. Thirdly, the author introduce and explain the main business models usable for those Smart Services and the requirements for starting the transformation towards those services. The aim of this paper is to set a basis for this exciting and relatively unsought topic and to produce an interest in further empirical and practical researches in this area. The methodologies used for this research are a systematic literature review and an evaluation of existing studies with the

  16. Developing natural resource models using the object modeling system: feasibility and challenges

    Directory of Open Access Journals (Sweden)

    L. R. Ahuja


    Full Text Available Current challenges in natural resource management have created demand for integrated, flexible, and easily parameterized hydrologic models. Most of these monolithic models are not modular, thus modifications (e.g., changes in process representation require considerable time, effort, and expense. In this paper, the feasibility and challenges of using the Object Modeling System (OMS for natural resource model development will be explored. The OMS is a Java-based modeling framework that facilitates simulation model development, evaluation, and deployment. In general, the OMS consists of a library of science, control, and database modules and a means to assemble the selected modules into an application-specific modeling package. The framework is supported by data dictionary, data retrieval, GIS, graphical visualization, and statistical analysis utility modules. Specific features of the OMS that will be discussed include: 1 how to reduce duplication of effort in natural resource modeling; 2 how to make natural resource models easier to build, apply, and evaluate; 3 how to facilitate long-term maintainability of existing and new natural resource models; and 4 how to improve the quality of natural resource model code and ensure credibility of model implementations. Examples of integrating a simple water balance model and a large monolithic model into the OMS will be presented.

  17. Challenges of 4D(ata Model for Electronic Government

    Directory of Open Access Journals (Sweden)

    Bogdan GHILIC-MICU


    Full Text Available Social evolution pyramid, built on the foundation of the ‘90s capitalist society, lead to the emergence of the informational society – years 1990 to 2005 – and knowledge society – years 2005 to 2020. The literature starts using a new concept, a new form of association – artificial intelligence society – foreseen to be established in the next time frame. All these developments of human society and translations or leaps (most of the times apparently timeless were, are and will be possible only due to the advancing information and communications technologies. The leap to Democracy 3.0, based on information and communication technologies prompts to a radical change in the majority of the classical concepts targeting society structure and the way it is guided and controlled. Thus, concepts become electronic concepts (or e-concepts through the use of new technologies. E-concepts keep the essence of the classical principles of liberty and democracy, adding a major aspect of the new way of communication and spreading ideas between people. The main problem is to quantify, analyze and foresee the way technological changes will influence not only the economic system, but also the daily life of the individual and the society. Unfortunately (or maybe fortunately, depending on the point of view, all these evolutions and technological and social developments are as many challenges for the governments of the world. In this paper we will highlight only four of the challenges facing the governments, grouped in a structured model with the following specific concepts: Big Data, Social Data, Linked Data and Mobile Data. This is an emerging paradigm of the information and communication technology supporting national and global eGovernment projects.

  18. Intravenous fluids: balancing solutions. (United States)

    Hoorn, Ewout J


    The topic of intravenous (IV) fluids may be regarded as "reverse nephrology", because nephrologists usually treat to remove fluids rather than to infuse them. However, because nephrology is deeply rooted in fluid, electrolyte, and acid-base balance, IV fluids belong in the realm of our specialty. The field of IV fluid therapy is in motion due to the increasing use of balanced crystalloids, partly fueled by the advent of new solutions. This review aims to capture these recent developments by critically evaluating the current evidence base. It will review both indications and complications of IV fluid therapy, including the characteristics of the currently available solutions. It will also cover the use of IV fluids in specific settings such as kidney transplantation and pediatrics. Finally, this review will address the pathogenesis of saline-induced hyperchloremic acidosis, its potential effect on outcomes, and the question if this should lead to a definitive switch to balanced solutions.

  19. Intravenous versus oral etoposide

    DEFF Research Database (Denmark)

    Ali, Abir Salwa; Grönberg, Malin; Langer, Seppo W.


    High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently...... administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter- and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS......) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (≤ 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS...

  20. Continuous total intravenous anesthesia, using propofol and fentanyl in an open-thorax rabbit model: evaluation of cardiac contractile function and biochemical assessment

    NARCIS (Netherlands)

    de Mulder, P. A.; van Kerckhoven, R. J.; Adriaensen, H. F.; Gillebert, T. C.; de Hert, S. G.


    Effects are reported of an anesthetic protocol involving use of predetermined intravenous (i.v.)-administered drug doses during acute experimental procedures in vagotomized, New Zealand White rabbits with open thorax (n = 20) in a nonsurvival study. After induction of anesthesia by intramuscular

  1. A comparison in therapeutic efficacy of several time points of intravenous StemBell administration in a rat model of acute myocardial infarction

    NARCIS (Netherlands)

    Emmens, Reindert W.; Oedayrajsingh-Varma, Maikel; Woudstra, Linde; Kamp, Otto; Meinster, Elisa; van Dijk, Annemieke; Helder, Marco N.; Wouters, Diana; Zeerleder, Sacha; van Ham, S. Marieke; de Jong, Nico; Niessen, Hans W. M.; Juffermans, Lynda J. M.; Krijnen, Paul A. J.


    Adipose-derived stromal cells (ASCs) are a promising new therapeutic option for patients with acute myocardial infarction (AMI). Previously, we found that ASCs coupled to antibody-targeted microbubbles (StemBells [StBs]) improved cardiac function when administered intravenously 7 days post-AMI in

  2. Intravenous infusion of docosahexaenoic acid increases serum concentrations in a dose-dependent manner and increases seizure latency in the maximal PTZ model. (United States)

    Trépanier, Marc-Olivier; Kwong, Kei-Man; Domenichiello, Anthony F; Chen, Chuck T; Bazinet, Richard P; Burnham, W M


    Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) that has been shown to raise seizure thresholds in the maximal pentylenetetrazole model following acute subcutaneous (s.c.) administration in rats. Following s.c. administration, however, the dose-response relationship for DHA has shown an inverted U-pattern. The purposes of the present experiment were as follows: (1) to determine the pattern of serum unesterified concentrations resulting from the intravenous (i.v.) infusions of various doses of DHA, (2) to determine the time course of these concentrations following the discontinuation of the infusions, and (3) to determine whether seizure protection in the maximal PTZ model would correlate with serum unesterified DHA levels. Animals received 5-minute i.v. infusions of saline or 25, 50, 100, or 200mg/kg of DHA via a cannula inserted into one of the tail veins. Blood was collected during and after the infusions by means of a second cannula inserted into the other tail vein (Experiment 1). A separate group of animals received saline or 12.5-, 25-, 50-, 100-, or 200 mg/kg DHA i.v. via a cannula inserted into one of the tail veins and were then seizure-tested in the maximal PTZ model either during infusion or after the discontinuation of the infusions. Slow infusions of DHA increased serum unesterified DHA concentrations in a dose-dependent manner, with the 200-mg/kg dose increasing the concentration approximately 260-fold compared with saline-infused animals. Following discontinuation of the infusions, serum concentrations rapidly dropped toward baseline, with half-lives of approximately 40 and 11s for the 25-mg/kg dose and 100-mg/kg dose, respectively. In the seizure-tested animals, DHA significantly increased latency to seizure onset in a dose-dependent manner. Following the discontinuation of infusion, seizure latency rapidly decreased toward baseline. Overall, our study suggests that i.v. infusion of unesterified DHA results in

  3. Experiences in applying Bayesian integrative models in interdisciplinary modeling: the computational and human challenges

    DEFF Research Database (Denmark)

    Kuikka, Sakari; Haapasaari, Päivi Elisabet; Helle, Inari


    networks are flexible tools that can take into account the different research traditions and the various types of information sources. We present two types of cases. With the Baltic salmon stocks modeled with Bayesian techniques, the existing data sets are rich and the estimation of the parameters...... components, which favors the use of quantitative risk analysis. However, the traditions and quality criteria of these scientific fields are in many respects different. This creates both technical and human challenges to the modeling tasks....

  4. Challenges and opportunities in land surface modelling of savanna ecosystems (United States)

    Whitley, Rhys; Beringer, Jason; Hutley, Lindsay B.; Abramowitz, Gabriel; De Kauwe, Martin G.; Evans, Bradley; Haverd, Vanessa; Li, Longhui; Moore, Caitlin; Ryu, Youngryel; Scheiter, Simon; Schymanski, Stanislaus J.; Smith, Benjamin; Wang, Ying-Ping; Williams, Mathew; Yu, Qiang


    The savanna complex is a highly diverse global biome that occurs within the seasonally dry tropical to sub-tropical equatorial latitudes and are structurally and functionally distinct from grasslands and forests. Savannas are open-canopy environments that encompass a broad demographic continuum, often characterised by a changing dominance between C3-tree and C4-grass vegetation, where frequent environmental disturbances such as fire modulates the balance between ephemeral and perennial life forms. Climate change is projected to result in significant changes to the savanna floristic structure, with increases to woody biomass expected through CO2 fertilisation in mesic savannas and increased tree mortality expected through increased rainfall interannual variability in xeric savannas. The complex interaction between vegetation and climate that occurs in savannas has traditionally challenged terrestrial biosphere models (TBMs), which aim to simulate the interaction between the atmosphere and the land surface to predict responses of vegetation to changing in environmental forcing. In this review, we examine whether TBMs are able to adequately represent savanna fluxes and what implications potential deficiencies may have for climate change projection scenarios that rely on these models. We start by highlighting the defining characteristic traits and behaviours of savannas, how these differ across continents and how this information is (or is not) represented in the structural framework of many TBMs. We highlight three dynamic processes that we believe directly affect the water use and productivity of the savanna system: phenology, root-water access and fire dynamics. Following this, we discuss how these processes are represented in many current-generation TBMs and whether they are suitable for simulating savanna fluxes.Finally, we give an overview of how eddy-covariance observations in combination with other data sources can be used in model benchmarking and

  5. Challenges and opportunities in land surface modelling of savanna ecosystems

    Directory of Open Access Journals (Sweden)

    R. Whitley


    Full Text Available The savanna complex is a highly diverse global biome that occurs within the seasonally dry tropical to sub-tropical equatorial latitudes and are structurally and functionally distinct from grasslands and forests. Savannas are open-canopy environments that encompass a broad demographic continuum, often characterised by a changing dominance between C3-tree and C4-grass vegetation, where frequent environmental disturbances such as fire modulates the balance between ephemeral and perennial life forms. Climate change is projected to result in significant changes to the savanna floristic structure, with increases to woody biomass expected through CO2 fertilisation in mesic savannas and increased tree mortality expected through increased rainfall interannual variability in xeric savannas. The complex interaction between vegetation and climate that occurs in savannas has traditionally challenged terrestrial biosphere models (TBMs, which aim to simulate the interaction between the atmosphere and the land surface to predict responses of vegetation to changing in environmental forcing. In this review, we examine whether TBMs are able to adequately represent savanna fluxes and what implications potential deficiencies may have for climate change projection scenarios that rely on these models. We start by highlighting the defining characteristic traits and behaviours of savannas, how these differ across continents and how this information is (or is not represented in the structural framework of many TBMs. We highlight three dynamic processes that we believe directly affect the water use and productivity of the savanna system: phenology, root-water access and fire dynamics. Following this, we discuss how these processes are represented in many current-generation TBMs and whether they are suitable for simulating savanna fluxes.Finally, we give an overview of how eddy-covariance observations in combination with other data sources can be used in model

  6. Maternal intravenous treatment with either azithromycin or solithromycin clears Ureaplasma parvum from the amniotic fluid in an ovine model of intrauterine infection. (United States)

    Miura, Yuichiro; Payne, Matthew S; Keelan, Jeffrey A; Noe, Andres; Carter, Sean; Watts, Rory; Spiller, Owen B; Jobe, Alan H; Kallapur, Suhas G; Saito, Masatoshi; Stock, Sarah J; Newnham, John P; Kemp, Matthew W


    Intrauterine infection with Ureaplasma spp. is strongly associated with preterm birth and adverse neonatal outcomes. We assessed whether combined intraamniotic (IA) and maternal intravenous (IV) treatment with one of two candidate antibiotics, azithromycin (AZ) or solithromycin (SOLI), would eradicate intrauterine Ureaplasma parvum infection in a sheep model of pregnancy. Sheep with singleton pregnancies received an IA injection of U. parvum serovar 3 at 85 days of gestational age (GA). At 120 days of GA, animals (n=5 to 8/group) received one of the following treatments: (i) maternal IV SOLI with a single IA injection of vehicle (IV SOLI only); (ii) maternal IV SOLI with a single IA injection of SOLI (IV+IA SOLI); (iii) maternal IV AZ and a single IA injection of vehicle (IV AZ only); (iv) maternal IV AZ and a single IA injection of AZ (IV+IA AZ); or (v) maternal IV and single IA injection of vehicle (control). Lambs were surgically delivered at 125 days of GA. Treatment efficacies were assessed by U. parvum culture, quantitative PCR, enzyme-linked immunosorbent assay, and histopathology. Amniotic fluid (AF) from all control animals contained culturable U. parvum. AF, lung, and chorioamnion from all AZ- or SOLI-treated animals (IV only or IV plus IA) were negative for culturable U. parvum. Relative to the results for the control, the levels of expression of interleukin 1β (IL-1β), IL-6, IL-8, and monocyte chemoattractant protein 2 (MCP-2) in fetal skin were significantly decreased in the IV SOLI-only group, the MCP-1 protein concentration in the amniotic fluid was significantly increased in the IV+IA SOLI group, and there was no significant difference in the histological inflammation scoring of lung or chorioamnion among the five groups. In the present study, treatment with either AZ or SOLI (IV only or IV+IA) effectively eradicated macrolide-sensitive U. parvum from the AF. There was no discernible difference in antibiotic therapy efficacy between IV-only and IV

  7. Evaluation of the biological activities of the IL-15 superagonist complex, ALT-803, following intravenous versus subcutaneous administration in murine models. (United States)

    Liu, Bai; Jones, Monica; Kong, Lin; Noel, Terra; Jeng, Emily K; Shi, Sixiang; England, Christopher G; Alter, Sarah; Miller, Jeffrey S; Cai, Weibo; Rhode, Peter R; Wong, Hing C


    ALT-803 is a fusion protein complex consisting of an interleukin (IL)-15 superagonist and a dimeric IL-15 receptor alpha sushi domain IgG1 Fc fusion protein. When administered to mice, ALT-803 is capable of inducing natural killer (NK) and CD8 + T cell proliferation and activation, and effectively promoting potent anti-tumor responses. Currently, ALT-803 is in clinical trials for treatment of various solid tumors and hematological malignancies. In the initial phase of these clinical studies, intravenous (iv) injection was used according to the route used in pre-clinical efficacy studies. In order to evaluate the possible advantage of subcutaneous (sc) injection versus iv injection, this study compared the biological activity of the two treatment regimens of ALT-803 in pre-clinical in vivo models. The pharmacokinetics, immune stimulation, and anti-tumor efficacy of iv and sc injection routes of ALT-803 in C57BL/6 mice were compared. The half-life of ALT-803 was 7.5 h for iv versus 7.7 h for sc with the maximal detected serum concentration of ALT-803 to be 3926 ng/ml at 0.5 h time-point following iv injection versus 495 ng/ml at 16 h post sc injection. Biodistribution studies indicated that sc ALT-803, similarly to iv ALT-803 as previously reported, has a greater tissue distribution and longer residence time in lymphoid tissues compared to recombinant IL-15. Notably, ALT-803 when administered either iv or sc induced comparable proliferation and activation of CD8 + T and NK cells and resulted in similar reductions of tumor burden. A toxicity study of mice receiving multiple injections of ALT-803 for 4 weeks by iv or sc routes revealed equivalent immune-related changes. The gradual absorbance into the blood stream and lower maximal blood levels of ALT-803 in sc-injected mice, along with similar anti-tumor efficacy support the administration of ALT-803 by sc injection in patients with various malignancies and infectious diseases. Copyright © 2017 Elsevier

  8. Ultrasonography versus intravenous urography

    International Nuclear Information System (INIS)

    Aslaksen, A.


    The present study was performed to compare the clinical value of urography and ultrasonography in a non-selected group of patients referred for urography to a university hospital. The conslusions and clinical implications of the study are as follows: Intravenous urography remains the cornerstone imaging examination in the evaluation of ureteral calculi. Ultrasonography is a valuable adjunct in cases of non- visualization of the kidneys, in distal obstruction and known contrast media allergy. When women with recurrent urinary tract infection are referred for imaging of the urinary tract, ultrasonography should be used. Ultrasonography should replace urography for screening of non-acute hydronephrosis like in female genital cancer and benign prostate hyperplasia. There is good correlation between urography and ultrasonography in assessing the degree of hydronephrosis. However, more researh on the relationship between hydronephrosis and obstruction is necessary. Ultrasonography should be used as the only imaging method of the upper urinary tract in patients with microscopic hematuria. In patients less than 50 years with macroscopic hematuria, ultrasonography should be used as the only imaging of the upper urinary tract, and an examination of the urinary bladder should be included. In patients over 50 years, urography supplied with ultrasonography should be used, but more research is necessary on the subject of imaging method and age. 158 refs

  9. Intravenous Lipids for Preterm Infants: A Review

    Directory of Open Access Journals (Sweden)

    Ghassan S. A. Salama


    Full Text Available Extremely low birth weight infants (ELBW are born at a time when the fetus is undergoing rapid intrauterine brain and body growth. Continuation of this growth in the first several weeks postnatally during the time these infants are on ventilator support and receiving critical care is often a challenge. These infants are usually highly stressed and at risk for catabolism. Parenteral nutrition is needed in these infants because most cannot meet the majority of their nutritional needs using the enteral route. Despite adoption of a more aggressive approach with amino acid infusions, there still appears to be a reluctance to use early intravenous lipids. This is based on several dogmas that suggest that lipid infusions may be associated with the development or exacerbation of lung disease, displace bilirubin from albumin, exacerbate sepsis, and cause CNS injury and thrombocytopena. Several recent reviews have focused on intravenous nutrition for premature neonate, but very little exists that provides a comprehensive review of intravenous lipid for very low birth and other critically ill neonates. Here, we would like to provide a brief basic overview, of lipid biochemistry and metabolism of lipids, especially as they pertain to the preterm infant, discuss the origin of some of the current clinical practices, and provide a review of the literature, that can be used as a basis for revising clinical care, and provide some clarity in this controversial area, where clinical care is often based more on tradition and dogma than science.

  10. Modeling of HABs and eutrophication: Status, advances, challenges

    NARCIS (Netherlands)

    Glibert, P.M.; Allen, J.I.; Bouwman, A.F.; Brown, C.W.; Flynn, K.J.; Lewitus, A.J.; Madden, C.J.


    Harmful algal blooms (HABs) are often associated with eutrophication of coastal waters and estuaries. However, identifying quantitative relationships between nutrient input and proliferation of specific algal species is very challenging and complex. The complexity arises from the diversity of

  11. Why Is Improvement of Earth System Models so Elusive? Challenges and Strategies from Dust Aerosol Modeling (United States)

    Miller, Ronald L.; Garcia-Pando, Carlos Perez; Perlwitz, Jan; Ginoux, Paul


    Past decades have seen an accelerating increase in computing efficiency, while climate models are representing a rapidly widening set of physical processes. Yet simulations of some fundamental aspects of climate like precipitation or aerosol forcing remain highly uncertain and resistant to progress. Dust aerosol modeling of soil particles lofted by wind erosion has seen a similar conflict between increasing model sophistication and remaining uncertainty. Dust aerosols perturb the energy and water cycles by scattering radiation and acting as ice nuclei, while mediating atmospheric chemistry and marine photosynthesis (and thus the carbon cycle). These effects take place across scales from the dimensions of an ice crystal to the planetary-scale circulation that disperses dust far downwind of its parent soil. Representing this range leads to several modeling challenges. Should we limit complexity in our model, which consumes computer resources and inhibits interpretation? How do we decide if a process involving dust is worthy of inclusion within our model? Can we identify a minimal representation of a complex process that is efficient yet retains the physics relevant to climate? Answering these questions about the appropriate degree of representation is guided by model evaluation, which presents several more challenges. How do we proceed if the available observations do not directly constrain our process of interest? (This could result from competing processes that influence the observed variable and obscure the signature of our process of interest.) Examples will be presented from dust modeling, with lessons that might be more broadly applicable. The end result will either be clinical depression or there assuring promise of continued gainful employment as the community confronts these challenges.

  12. Dst Index in the 2008 GEM Modeling Challenge - Model Performance for Moderate and Strong Magnetic Storms (United States)

    Rastaetter, Lutz; Kuznetsova, Maria; Hesse, Michael; Chulaki, Anna; Pulkkinen, Antti; Ridley, Aaron J.; Gombosi, Tamas; Vapirev, Alexander; Raeder, Joachim; Wiltberger, Michael James; hide


    The GEM 2008 modeling challenge efforts are expanding beyond comparing in-situ measurements in the magnetosphere and ionosphere to include the computation of indices to be compared. The Dst index measures the largest deviations of the horizontal magnetic field at 4 equatorial magnetometers from the quiet-time background field and is commonly used to track the strength of the magnetic disturbance of the magnetosphere during storms. Models can calculate a proxy Dst index in various ways, including using the Dessler-Parker Sckopke relation and the energy of the ring current and Biot-Savart integration of electric currents in the magnetosphere. The GEM modeling challenge investigates 4 space weather events and we compare models available at CCMC against each other and the observed values of Ost. Models used include SWMF/BATSRUS, OpenGGCM, LFM, GUMICS (3D magnetosphere MHD models), Fok-RC, CRCM, RAM-SCB (kinetic drift models of the ring current), WINDMI (magnetosphere-ionosphere electric circuit model), and predictions based on an impulse response function (IRF) model and analytic coupling functions with inputs of solar wind data. In addition to the analysis of model-observation comparisons we look at the way Dst is computed in global magnetosphere models. The default value of Dst computed by the SWMF model is for Bz the Earth's center. In addition to this, we present results obtained at different locations on the Earth's surface. We choose equatorial locations at local noon, dusk (18:00 hours), midnight and dawn (6:00 hours). The different virtual observatory locations reveal the variation around the earth-centered Dst value resulting from the distribution of electric currents in the magnetosphere during different phases of a storm.

  13. Recent European Challenges and the Danish Collective Agreement Model

    DEFF Research Database (Denmark)

    Larsen, Trine Pernille; Navrbjerg, Steen Erik

    are related to the new forms of cross-border collaboration and negotiations taking place within multi-national corporations (MNC's). This research paper examines a series of challenges facing the collective bargaining systems in Denmark, Estonia, Northern Ireland and Sweden. These countries represent four...

  14. Feeding Challenges in Young Children: Toward a Best Practices Model (United States)

    Bruns, Deborah A.; Thompson, Stacy D.


    Young children often encounter feeding challenges, such as food refusal, an inability to meet nutritional needs, and limited skills to self-feed. Further, overall development can be adversely affected when an infant or a toddler has difficulties with intake of fluid and solid foods. A variety of strategies are available to address these challenges…

  15. Modelling water use in global hydrological models: review, challenges and directions (United States)

    Bierkens, M. F.; de Graaf, I.; Wada, Y.; Wanders, N.; Van Beek, L. P.


    During the late 1980s and early 1990s, awareness of the shortage of global water resources lead to the first detailed global water resources assessments using regional statistics of water use and observations of meteorological and hydrological variables. Shortly thereafter, the first macroscale hydrological models (MHM) appeared. In these models, blue water (i.e., surface water and renewable groundwater) availability was calculated by accumulating runoff over a stream network and comparing it with population densities or with estimated water demand for agriculture, industry and households. In this talk we review the evolution of human impact modelling in global land models with a focus on global water resources, touching upon developments of the last 15 years: i.e. calculating human water scarcity; estimating groundwater depletion; adding dams and reservoirs; fully integrating water use (demand, withdrawal, consumption, return flow) in the hydrology; simulating the effects of land use change. We show example studies for each of these steps. We identify We identify major challenges that hamper the further development of integrated water resources modelling. Examples of these are: 1) simulating reservoir operations; 2) including local infrastructure and redistribution; 3) using the correct allocations rules; 4) projecting future water demand and water use. For each of these challenges we signify promising directions for further research.

  16. Analysis of Challenges for Management Education in India Using Total Interpretive Structural Modelling (United States)

    Mahajan, Ritika; Agrawal, Rajat; Sharma, Vinay; Nangia, Vinay


    Purpose: The purpose of this paper is to identify challenges for management education in India and explain their nature, significance and interrelations using total interpretive structural modelling (TISM), an innovative version of Warfield's interpretive structural modelling (ISM). Design/methodology/approach: The challenges have been drawn from…

  17. Challenges and needs in fire management: A landscape simulation modeling perspective [chapter 4 (United States)

    Robert E. Keane; Geoffrey J. Cary; Mike D. Flannigan


    Fire management will face many challenges in the future from global climate change to protecting people, communities, and values at risk. Simulation modeling will be a vital tool for addressing these challenges but the next generation of simulation models must be spatially explicit to address critical landscape ecology relationships and they must use mechanistic...

  18. Challenges in Educational Modelling: Expressiveness of IMS Learning Design (United States)

    Caeiro-Rodriguez, Manuel; Anido-Rifon, Luis; Llamas-Nistal, Martin


    Educational Modelling Languages (EMLs) have been proposed to enable the authoring of models of "learning units" (e.g., courses, lessons, lab practices, seminars) covering the broad variety of pedagogical approaches. In addition, some EMLs have been proposed as computational languages that support the processing of learning unit models by…

  19. Implementing new business models : What challenges lie ahead?

    NARCIS (Netherlands)

    Broekhuizen, Thijs; Bakker, T.; Postma, Theodorus


    What strategic choices do business leaders make when implementing new business models? This study tries to answer this question by analyzing the development of several business model innovations that were new to the industry. We find that business model innovators face four strategic tradeoffs

  20. Intravenous pyogenic granuloma or intravenous lobular capillary hemangioma

    Energy Technology Data Exchange (ETDEWEB)

    Ghekiere, Olivier; Galant, Christine; Berg, Bruno Vande [Cliniques Universitaires St. Luc, Department of Radiology, Brussels (Belgium)


    Lobular capillary hemangioma is a vascular neoplasm that commonly occurs as a cutaneous tumor. When it involves the skin and mucosal surfaces, ulceration and suppuration may occur, hence the classic term of pyogenic granuloma. Intravenous pyogenic granuloma is a rare solitary form of lobular capillary hemangioma that usually occurs in the veins of the neck and upper extremities. We report the ultrasonographic and magnetic resonance imaging findings of a pyogenic intravenous granuloma localized in the right cephalic vein. The imaging and pathological findings and the differential diagnoses are discussed. (orig.)

  1. Modeling radiation belt electron dynamics during GEM challenge intervals with the DREAM3D diffusion model (United States)

    Tu, Weichao; Cunningham, G. S.; Chen, Y.; Henderson, M. G.; Camporeale, E.; Reeves, G. D.


    a response to the Geospace Environment Modeling (GEM) "Global Radiation Belt Modeling Challenge," a 3D diffusion model is used to simulate the radiation belt electron dynamics during two intervals of the Combined Release and Radiation Effects Satellite (CRRES) mission, 15 August to 15 October 1990 and 1 February to 31 July 1991. The 3D diffusion model, developed as part of the Dynamic Radiation Environment Assimilation Model (DREAM) project, includes radial, pitch angle, and momentum diffusion and mixed pitch angle-momentum diffusion, which are driven by dynamic wave databases from the statistical CRRES wave data, including plasmaspheric hiss, lower-band, and upper-band chorus. By comparing the DREAM3D model outputs to the CRRES electron phase space density (PSD) data, we find that, with a data-driven boundary condition at Lmax = 5.5, the electron enhancements can generally be explained by radial diffusion, though additional local heating from chorus waves is required. Because the PSD reductions are included in the boundary condition at Lmax = 5.5, our model captures the fast electron dropouts over a large L range, producing better model performance compared to previous published results. Plasmaspheric hiss produces electron losses inside the plasmasphere, but the model still sometimes overestimates the PSD there. Test simulations using reduced radial diffusion coefficients or increased pitch angle diffusion coefficients inside the plasmasphere suggest that better wave models and more realistic radial diffusion coefficients, both inside and outside the plasmasphere, are needed to improve the model performance. Statistically, the results show that, with the data-driven outer boundary condition, including radial diffusion and plasmaspheric hiss is sufficient to model the electrons during geomagnetically quiet times, but to best capture the radiation belt variations during active times, pitch angle and momentum diffusion from chorus waves are required.

  2. Modeling urban landscape: New paradigms and challenges in territorial representation

    Directory of Open Access Journals (Sweden)

    Sheyla Aguilar de Santana


    Full Text Available This paper aims to give a brief background on the production of urban space considering the social functions of the city, the needs of contemporary urban reforms and the need for tools that assist in decision making. This state of the art about the production space justifies the current studies on the development of geoprocessing tools, techniques and methodologies that attempt the needs of creating interpretive portraits of urban landscapes to facilitate dialogue between urban technical, administrators and community. In this sense, it is presented how GIS has been working within the context of urban planning and appointed the new challenges and paradigms of territorial representation.

  3. Progress and challenges in coupled hydrodynamic-ecological estuarine modeling. (United States)

    Ganju, Neil K; Brush, Mark J; Rashleigh, Brenda; Aretxabaleta, Alfredo L; Del Barrio, Pilar; Grear, Jason S; Harris, Lora A; Lake, Samuel J; McCardell, Grant; O'Donnell, James; Ralston, David K; Signell, Richard P; Testa, Jeremy M; Vaudrey, Jamie M P


    Numerical modeling has emerged over the last several decades as a widely accepted tool for investigations in environmental sciences. In estuarine research, hydrodynamic and ecological models have moved along parallel tracks with regard to complexity, refinement, computational power, and incorporation of uncertainty. Coupled hydrodynamic-ecological models have been used to assess ecosystem processes and interactions, simulate future scenarios, and evaluate remedial actions in response to eutrophication, habitat loss, and freshwater diversion. The need to couple hydrodynamic and ecological models to address research and management questions is clear, because dynamic feedbacks between biotic and physical processes are critical interactions within ecosystems. In this review we present historical and modern perspectives on estuarine hydrodynamic and ecological modeling, consider model limitations, and address aspects of model linkage, skill assessment, and complexity. We discuss the balance between spatial and temporal resolution and present examples using different spatiotemporal scales. Finally, we recommend future lines of inquiry, approaches to balance complexity and uncertainty, and model transparency and utility. It is idealistic to think we can pursue a "theory of everything" for estuarine models, but recent advances suggest that models for both scientific investigations and management applications will continue to improve in terms of realism, precision, and accuracy.

  4. Bioenergy crop models: Descriptions, data requirements and future challenges

    Energy Technology Data Exchange (ETDEWEB)

    Nair, S. Surendran [University of Tennessee, Knoxville (UTK); Kang, Shujiang [ORNL; Zhang, Xuesong [Pacific Northwest National Laboratory (PNNL); Miguez, Fernando [Iowa State University; Izaurralde, Dr. R. Cesar [Pacific Northwest National Laboratory (PNNL); Post, Wilfred M [ORNL; Dietze, Michael [University of Illinois, Urbana-Champaign; Lynd, L. [Dartmouth College; Wullschleger, Stan D [ORNL


    Field studies that address the production of lignocellulosic biomass as a source of renewable energy provide critical data for the development of bioenergy crop models. A literature survey revealed that 14 models have been used for simulating bioenergy crops including herbaceous and woody bioenergy crops, and for crassulacean acid metabolism (CAM) crops. These models simulate field-scale production of biomass for switchgrass (ALMANAC, EPIC, and Agro-BGC), miscanthus (MISCANFOR, MISCANMOD, and WIMOVAC), sugarcane (APSIM, AUSCANE, and CANEGRO), and poplar and willow (SECRETS and 3PG). Two models are adaptations of dynamic global vegetation models and simulate biomass yields of miscanthus and sugarcane at regional scales (Agro-IBIS and LPJmL). Although it lacks the complexity of other bioenergy crop models, the environmental productivity index (EPI) is the only model used to estimate biomass production of CAM (Agave and Opuntia) plants. Except for the EPI model, all models include representations of leaf area dynamics, phenology, radiation interception and utilization, biomass production, and partitioning of biomass to roots and shoots. A few models simulate soil water, nutrient, and carbon cycle dynamics, making them especially useful for assessing the environmental consequences (e.g., erosion and nutrient losses) associated with the large-scale deployment of bioenergy crops. The rapid increase in use of models for energy crop simulation is encouraging; however, detailed information on the influence of climate, soils, and crop management practices on biomass production is scarce. Thus considerable work remains regarding the parameterization and validation of process-based models for bioenergy crops; generation and distribution of high-quality field data for model development and validation; and implementation of an integrated framework for efficient, high-resolution simulations of biomass production for use in planning sustainable bioenergy systems.

  5. Establishment of an animal challenge model as a potency assay for an inactivated Enterovirus Type 71 vaccine. (United States)

    Wang, Kun-Teng; Lin, Shih-Jie; Wang, Hsiu-Chi; Chen, Pin-Chun; Lin, Jiao-Jung; Chiang, Jen-Ron; Chang, Chao-Liang; Shih, Daniel Yang-Chih; Lo, Chi-Fang; Wang, Der-Yuan


    Enterovirus 71 (EV71) belongs to the Enterovirus genus of the Picornaviridae family, and its occurrence in Asia is associated with hand-foot-and-mouth disease (HFMD), leading to death in some cases, in young children. An effective EV71 vaccine is therefore urgently needed. In this study, we established a two-step EV71 vaccine potency model. Intraperitoneal injections in 2-day-old suckling mice were used to establish the LD50 of EV71 B4, B5, C2, C4, and C5 subgenotypes. Only C4 caused hind limb paralysis in mice (LD50: 2.62 ± 0.45). EV71 VP1 protein was identified in the brain tissues at histology. In the second phase of the model, 3-week-old female ICR mice received one primary and two boosting i.p. injections of formalin-inactivated EV71 B4 and C4 vaccine. Immunized serum was neutralized in vitro with EV71 C4 and applied to the murine challenge model. The C4 vaccine-immunized serum exhibited the highest protective titre (ED50 = 114.6), while the B4 immunized serum had the weakest protective titre (ED50 = 34.3). Additionally, human plasma and intravenous immunoglobulin displayed significant protection in the neutralization assay. Our results could facilitate candidate EV71 vaccine immunogenicity and efficacy evaluations, and may help establish reference EV71 antisera in the future. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  6. Challenges of transferring models of fish abundance between coral reefs. (United States)

    Sequeira, Ana M M; Mellin, Camille; Lozano-Montes, Hector M; Meeuwig, Jessica J; Vanderklift, Mathew A; Haywood, Michael D E; Babcock, Russell C; Caley, M Julian


    Reliable abundance estimates for species are fundamental in ecology, fisheries, and conservation. Consequently, predictive models able to provide reliable estimates for un- or poorly-surveyed locations would prove a valuable tool for management. Based on commonly used environmental and physical predictors, we developed predictive models of total fish abundance and of abundance by fish family for ten representative taxonomic families for the Great Barrier Reef (GBR) using multiple temporal scenarios. We then tested if models developed for the GBR (reference system) could predict fish abundances at Ningaloo Reef (NR; target system), i.e., if these GBR models could be successfully transferred to NR. Models of abundance by fish family resulted in improved performance (e.g., 44.1% fish abundance (9% fish species richness from the GBR to NR, transferability for these fish abundance models was poor. When compared with observations of fish abundance collected in NR, our transferability results had low validation scores ( R 2   0.05). High spatio-temporal variability of patterns in fish abundance at the family and population levels in both reef systems likely affected the transferability of these models. Inclusion of additional predictors with potential direct effects on abundance, such as local fishing effort or topographic complexity, may improve transferability of fish abundance models. However, observations of these local-scale predictors are often not available, and might thereby hinder studies on model transferability and its usefulness for conservation planning and management.

  7. Orthostatic stability with intravenous levodopa

    Directory of Open Access Journals (Sweden)

    Shan H. Siddiqi


    Full Text Available Intravenous levodopa has been used in a multitude of research studies due to its more predictable pharmacokinetics compared to the oral form, which is used frequently as a treatment for Parkinson’s disease (PD. Levodopa is the precursor for dopamine, and intravenous dopamine would strongly affect vascular tone, but peripheral decarboxylase inhibitors are intended to block such effects. Pulse and blood pressure, with orthostatic changes, were recorded before and after intravenous levodopa or placebo—after oral carbidopa—in 13 adults with a chronic tic disorder and 16 tic-free adult control subjects. Levodopa caused no statistically or clinically significant changes in blood pressure or pulse. These data add to previous data that support the safety of i.v. levodopa when given with adequate peripheral inhibition of DOPA decarboxylase.

  8. Prediction Models and Decision Support: Chances and Challenges

    NARCIS (Netherlands)

    Kappen, T.H.


    A clinical prediction model can assist doctors in arriving at the most likely diagnosis or estimating the prognosis. By utilizing various patient- and disease-related properties, such models can yield objective estimations of the risk of a disease or the probability of a certain disease course for

  9. Key Challenges and Potential Urban Modelling Opportunities in ...

    African Journals Online (AJOL)

    Urban growth and land use change models, supported by Geographic Information Systems (GIS) software and increased digital data availability, have the ... and opportunities for modelling urban spatial change, with specific reference to the Gauteng City-Region – the heartland of the South African economy and the ...

  10. The Job Demands–Resources model: Challenges for future research

    Directory of Open Access Journals (Sweden)

    Evangelia Demerouti


    Research purpose: To provide an overview of the JD–R model, which incorporates many possible working conditions and focuses on both negative and positive indicators of employee well-being. Moreover, the studies of the special issue were introduced. Research design: Qualitative and quantitative studies on the JD–R model were reviewed to enlighten the health and motivational processes suggested by the model. Main findings: Next to the confirmation of the two suggested processes of the JD–R model, the studies of the special issue showed that the model can be used to predict work-place bullying, incidences of upper respiratory track infection, work-based identity, and early retirement intentions. Moreover, whilst psychological safety climate could be considered as a hypothetical precursor of job demands and resources, compassion satisfaction moderated the health process of the model. Contribution/value-add: The findings of previous studies and the studies of the special issue were integrated in the JD–R model that can be used to predict well-being and performance at work. New avenues for future research were suggested. Practical/managerial implications: The JD–R model is a framework that can be used for organisations to improve employee health and motivation, whilst simultaneously improving various organisational outcomes.

  11. Studying cancer metastasis : Existing models, challenges and future perspectives

    NARCIS (Netherlands)

    van Marion, Denise M. S.; Domanska, Urszula M.; Timmer-Bosscha, Hetty; Walenkamp, Annemiek M. E.

    Cancer metastasis causes most cancer-related deaths. Several model systems to study the complex and multi step process of metastasis exist, including in vitro systems, ex-vivo organ slices, Drosophila Melanogaster and zebrafish models and the use of the chorio allantoic membrane (CAM) of fertilized

  12. The Job Demands?Resources model: Challenges for future research

    NARCIS (Netherlands)

    E. Demerouti (Eva); A.B. Bakke (Arnold B.)


    textabstractMotivation: The motivation of this overview is to present the state of the art of Job Demands-Resources (JD-R) model whilst integrating the various contributions to the special issue. Research purpose: To provide an overview of the JD-R model, which incorporates many possible working

  13. Six challenges in measuring contact networks for use in modelling

    Directory of Open Access Journals (Sweden)

    K. Eames


    Full Text Available Contact networks are playing an increasingly important role in epidemiology. A contact network represents individuals in a host population as nodes and the interactions among them that may lead to the transmission of infection as edges. New avenues for data collection in recent years have afforded us the opportunity to collect individual- and population-scale information to empirically describe the patterns of contact within host populations. Here, we present some of the current challenges in measuring empirical contact networks. We address fundamental questions such as defining contact; measurement of non-trivial contact properties; practical issues of bounding measurement of contact networks in space, time and scope; exploiting proxy information about contacts; dealing with missing data. Finally, we consider the privacy and ethical issues surrounding the collection of contact network data.

  14. Modeling bladder cancer in mice: opportunities and challenges (United States)

    Kobayashi, Takashi; Owczarek, Tomasz B.; McKiernan, James M.; Abate-Shen, Cory


    The prognosis and treatment of bladder cancer have hardly improved in the last 20 years. Bladder cancer remains a debilitating and often fatal disease, and among the most costly cancers to treat. The generation of informative mouse models has the potential to improve our understanding of bladder cancer progression, as well as impact its diagnosis and treatment. However, relatively few mouse models of bladder cancer have been described and particularly few that develop invasive cancer phenotypes. This review focuses on opportunities for improving the landscape of mouse models of bladder cancer. PMID:25533675

  15. [New models in the model (Managerial challenges in the Hungarian managed care model)]. (United States)

    Csedö, Zoltán; Nagy, Balázs; Dobák, Miklós; Dózsa, Csaba; Gulácsi, László


    The Hungarian managed care model integrates the different levels of health care services. Its goal is a more efficient resource allocation within the health care system, quality improvement of services, developing incentives and financing methods. The basic concept of the model is to introduce the benefits of the American managed care and the British fundholding system. The managed care model brought a new approach in the Hungarian health care system and meets a lot of expectation in both professional and political context. The model has certain problems, but these are handled at macro level. Without an integrated approach of macro, meso and micro levels is hardly believable the efficient and effective functioning of the model. Such macro level problems are the cost-efficiency versus high quality health services, financing incentives, and risk taking. At meso and micro level we are facing with questionable efficiency and effectiveness of the MCOs other health care organisations, which are based on strong bureaucratic paradigms and are convicted to a long lasting crisis in their changing environment. The integrated use of Mintzberg's management models (machine model, network model, performance-control model, virtual government model and normative-control model) adapted by us for the Hungarian managed care model could resolve certain problems or make them at least more solvable. In the changing environment of the health cares organisations the top management has to frame the change-scenario, to initiate, realise and sustain organisational changes. Achieving this, the proposed management models are a useful support. Their practical application could contribute to the efficient and effective functioning of the Hungarian managed care model at macro, meso and micro levels, as well.

  16. Major challenges in Mark-I containment modelling with ASTEC

    Energy Technology Data Exchange (ETDEWEB)

    Iglesias, R.; Fontanet, J.; Herranz, L.E.


    The proper modelling of the NPP systems using engineering codes is an important task for the studies of the plant behavior during Severe Accident (SA) scenarios. At present, the Accident Source Term Evaluation Code (ASTEC) is being improved for the application to the main European reactor types in the frame of the EU-R&D CESAM project. This paper presents the ASTEC generic Mark-I containment model developed by CIEMAT in the context of this project. The model includes the nodalisation of the PCV, RB and the safety related systems. The in-vessel phase of a LOOP sequence scenario has been simulated and results compared with MELCOR ones with the objective of proving the model robustness. The comparison extends to the main thermal-hydraulics variables and, although ASTEC results show satisfactory agreement with MELCOR, there are differences of about 7% in drywell pressure. (Author)

  17. A new challenge: Model of positive health and clinical psychology


    Miloseva, Lence; Milosev, Vladimir


    The main aim of this paper is to present a new model and approach in Health and Clinical practice – Applied Positive Psychology. Through discussion about the roots of Positive Psychology and interest in what is good about humans and their lives and in optimal human functioning we will try to introduce a new model of Positive Health and Clinical Psychology. From Aristotle’s treatises on eudemonia, through Aquinas’ writings about virtue during the Renaissance, to the inquires of modern psycholo...

  18. Empirical agent-based modelling challenges and solutions

    CERN Document Server

    Barreteau, Olivier


    This instructional book showcases techniques to parameterise human agents in empirical agent-based models (ABM). In doing so, it provides a timely overview of key ABM methodologies and the most innovative approaches through a variety of empirical applications.  It features cutting-edge research from leading academics and practitioners, and will provide a guide for characterising and parameterising human agents in empirical ABM.  In order to facilitate learning, this text shares the valuable experiences of other modellers in particular modelling situations. Very little has been published in the area of empirical ABM, and this contributed volume will appeal to graduate-level students and researchers studying simulation modeling in economics, sociology, ecology, and trans-disciplinary studies, such as topics related to sustainability. In a similar vein to the instruction found in a cookbook, this text provides the empirical modeller with a set of 'recipes'  ready to be implemented. Agent-based modeling (AB...

  19. Computational brain models: Advances from system biology and future challenges

    Directory of Open Access Journals (Sweden)

    George E. Barreto


    Full Text Available Computational brain models focused on the interactions between neurons and astrocytes, modeled via metabolic reconstructions, are reviewed. The large source of experimental data provided by the -omics techniques and the advance/application of computational and data-management tools are being fundamental. For instance, in the understanding of the crosstalk between these cells, the key neuroprotective mechanisms mediated by astrocytes in specific metabolic scenarios (1 and the identification of biomarkers for neurodegenerative diseases (2,3. However, the modeling of these interactions demands a clear view of the metabolic and signaling pathways implicated, but most of them are controversial and are still under evaluation (4. Hence, to gain insight into the complexity of these interactions a current view of the main pathways implicated in the neuron-astrocyte communication processes have been made from recent experimental reports and reviews. Furthermore, target problems, limitations and main conclusions have been identified from metabolic models of the brain reported from 2010. Finally, key aspects to take into account into the development of a computational model of the brain and topics that could be approached from a systems biology perspective in future research are highlighted.

  20. Challenges in the development of analytical soil compaction models

    DEFF Research Database (Denmark)

    Keller, Thomas; Lamandé, Mathieu


    Soil compaction can cause a number of environmental and agronomic problems (e.g. flooding, erosion, leaching of agrochemicals to recipient waters, emission of greenhouse gases to the atmosphere, crop yield losses), resulting in significant economic damage to society and agriculture. Strategies...... and recommendations for the prevention of soil compaction often rely on simulation models. This paper highlights some issues that need further consideration in order to improve soil compaction modelling, with the focus on analytical models. We discuss the different issues based on comparisons between experimental...... to stress propagation, an anomaly that needs further attention. We found large differences between soil stress-strain behaviour obtained from in situ measurements during wheeling experiments and those measured on cylindrical soil samples in standard laboratory tests. We concluded that the main reason...

  1. Unfolding Challenges of Business Model Innovation towards Circular Economy

    DEFF Research Database (Denmark)

    Hvass, Kerli Kant


    in industry, academia and policy, however, there is limited research that studies this concept from a business model perspective supported with empirical evidence. Traditional fashion companies’ business models mainly focus on creating and capturing value from the sale of new products, while aspects related...... of a product take-back system and closed loop recycling into an existing business model. The study shows that closed loop fashion is a complex matter with several uncertainties and difficulties that span across the entire value chain. Moving towards a circular textile system implies wider systemic change...... extensive attention (EMF 2012; 2013), even though the concept is not a new and traces back several decades to Stahel & Reday’s (1976) work on the ecology behind product life extensions and their sketched vision for “an economy of loops” or “circular economy.“ Addressing circular economy is an emerging field...

  2. Extending the Challenge-Hindrance Model of Occupational Stress: The Role of Appraisal (United States)

    Webster, Jennica R.; Beehr, Terry A.; Love, Kevin


    Interest regarding the challenge-hindrance occupational stress model has increased in recent years, however its theoretical foundation has not been tested. Drawing from the transactional theory of stress, this study tests the assumptions made in past research (1) that workload and responsibility are appraised as challenges and role ambiguity and…

  3. Intravenous urography and childhood trauma


    Okorie, N. M.; MacKinnon, A. E.


    Results of intravenous urography (IVU) in 33 patients suspected of suffering from renal trauma were reviewed. It was concluded that when haematuria is only detected microscopically and clears within 24 hr then an IVU is not necessary, in the absence of other evidence of significant urinary tract injury.

  4. Challenges in soil erosion research and prediction model development (United States)

    Quantification of soil erosion has been traditionally considered as a surface hydrologic process with equations for soil detachment and sediment transport derived from the mechanics and hydraulics of the rainfall and surface flow. Under the current erosion modeling framework, the soil has a constant...

  5. Key Challenges and Potential Urban Modelling Opportunities in ...

    African Journals Online (AJOL)

    Chris Wray

    thus, used to explain and predict land use and transport relationships in urban systems treated earlier as static, but now considered dynamic (Batty, .... People's Republic of China using logistic regression. 3. South Africa Urban Growth Modelling ..... delivery (GDED, 2008; Kekana, 2010). However, after six years and despite ...

  6. Challenging the Standard Model with the muon g− 2

    Indian Academy of Sciences (India)

    Abstract. The discrepancy between experiment and the Standard Model prediction of the muon −2 is reviewed. The possibility to bridge it by hypothetical increases in the hadronic cross-section used to determine the leading hadronic contribution to the latter is analysed.

  7. Challenging the Standard Model with the muon g − 2

    Indian Academy of Sciences (India)

    the muon g−2 is reviewed. The possibility to bridge it by hypothetical increases in the hadronic cross-section used to determine the leading hadronic contribution to the latter is analysed. Keywords. Muon anomalous magnetic moment; Standard Model Higgs boson. PACS Nos 13.40.Em; 14.60.Ef; 12.15.Lk; 14.80.Bn. 1.

  8. Informing agricultural management - The challenge of modelling grassland phenology (United States)

    Calanca, Pierluigi


    Grasslands represent roughly 70% of the agricultural land worldwide, are the backbone of animal husbandry and contribute substantially to agricultural income. At the farm scale a proper management of meadows and pastures is necessary to attain a balance between forage production and consumption. A good hold on grassland phenology is of paramount importance in this context, because forage quantity and quality critically depend on the developmental stage of the sward. Traditionally, empirical rules have been used to advise farmers in this respect. Yet the provision of supporting information for decision making would clearly benefit from dedicated tools that integrate reliable models of grassland phenology. As with annual crops, in process-based models grassland phenology is usually described as a linear function of so-called growing degree days, whereby data from field trials and monitoring networks are used to calibrate the relevant parameters. It is shown in this contribution that while the approach can provide reasonable estimates of key developmental stages in an average sense, it fails to account for the variability observed in managed grasslands across sites and years, in particular concerning the start of the growing season. The analysis rests on recent data from western Switzerland, which serve as a benchmark for simulations carried out with grassland models of increasing complexity. Reasons for an unsatisfactory model performance and possibilities to improve current models are discussed, including the necessity to better account for species composition, late season management decisions, as well as plant physiological processes taking place during the winter season. The need to compile existing, and collect new data doe managed grasslands is also stressed.

  9. Challenges in validating model results for first year ice (United States)

    Melsom, Arne; Eastwood, Steinar; Xie, Jiping; Aaboe, Signe; Bertino, Laurent


    In order to assess the quality of model results for the distribution of first year ice, a comparison with a product based on observations from satellite-borne instruments has been performed. Such a comparison is not straightforward due to the contrasting algorithms that are used in the model product and the remote sensing product. The implementation of the validation is discussed in light of the differences between this set of products, and validation results are presented. The model product is the daily updated 10-day forecast from the Arctic Monitoring and Forecasting Centre in CMEMS. The forecasts are produced with the assimilative ocean prediction system TOPAZ. Presently, observations of sea ice concentration and sea ice drift are introduced in the assimilation step, but data for sea ice thickness and ice age (or roughness) are not included. The model computes the age of the ice by recording and updating the time passed after ice formation as sea ice grows and deteriorates as it is advected inside the model domain. Ice that is younger than 365 days is classified as first year ice. The fraction of first-year ice is recorded as a tracer in each grid cell. The Ocean and Sea Ice Thematic Assembly Centre in CMEMS redistributes a daily product from the EUMETSAT OSI SAF of gridded sea ice conditions which include "ice type", a representation of the separation of regions between those infested by first year ice, and those infested by multi-year ice. The ice type is parameterized based on data for the gradient ratio GR(19,37) from SSMIS observations, and from the ASCAT backscatter parameter. This product also includes information on ambiguity in the processing of the remote sensing data, and the product's confidence level, which have a strong seasonal dependency.

  10. Detection of early changes in autoimmune T cell phenotype and function following intravenous administration of type II collagen in a TCR-transgenic model. (United States)

    Brand, David D; Myers, Linda K; Whittington, Karen B; Latham, Kary A; Stuart, John M; Kang, Andrew H; Rosloniec, Edward F


    To study the phenotypic and functional changes in naive type II collagen (CII)-specific autoimmune T cells following a tolerogenic signal, a TCR-transgenic (Tg) mouse model of collagen-induced arthritis was developed. These Tg mice express an I-A(q)-restricted CII (260-267)-specific TCR that confers severe accelerated autoimmune arthritis following immunization with CII. Despite the fact that >90% of the alphabeta T cells express the Tg, these mice can be rendered completely tolerant to the induction of arthritis by i.v. administration of 200 microg of CII. As early as 24 h after CII administration, CII-specific T cells demonstrated a decreased ability to proliferate in response to the CII immunodominant peptide and phenotypically altered the expression of L-selectin to CD62L(low) and of phagocytic glycoprotein-1 to CD44(high), expression levels consistent with the phenotype of memory T cells. In addition, they up-regulated the expression of the activation markers CD71 and CD69. Functionally, following tolerogenic stimulation, the CII-specific T cells produced similar levels of IL-2 in comparison to controls when challenged with CII peptide, however, by 48 h after exposure to tolerogen, IL-2 production dropped and was replaced by high levels of IL-10 and IL-4. Based on their production of Th2 cytokines, these data suggest that T regulatory cells expressing activation and memory markers are induced by the tolerogen and may exert their influence via cytokines to protect the animals from the induction of arthritis.

  11. Challenges in Modeling the Degradation of Ceramic Waste Forms

    Energy Technology Data Exchange (ETDEWEB)

    Devanathan, Ramaswami; Gao, Fei; Sun, Xin


    We identify the state of the art, gaps in current understanding, and key research needs in the area of modeling the long-term degradation of ceramic waste forms for nuclear waste disposition. The directed purpose of this report is to define a roadmap for Waste IPSC needs to extend capabilities of waste degradation to ceramic waste forms, which overlaps with the needs of the subconsinuum scale of FMM interests. The key knowledge gaps are in the areas of (i) methodology for developing reliable interatomic potentials to model the complex atomic-level interactions in waste forms; (ii) characterization of water interactions at ceramic surfaces and interfaces; and (iii) extension of atomic-level insights to the long time and distance scales relevant to the problem of actinide and fission product immobilization.

  12. Atmospheric dispersion modeling: Challenges of the Fukushima Daiichi response

    Energy Technology Data Exchange (ETDEWEB)

    Sugiyama, Gayle [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Nasstrom, John [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Pobanz, Brenda [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Foster, Kevin [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Simpson, Matthew [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Vogt, Phil [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Aluzzi, Fernando [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Homann, Steve [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)


    In this research, the U.S. Department of Energy’s (DOE) National Atmospheric Release Advisory Center (NARAC) provided a wide range of predictions and analyses as part of the response to the Fukushima Daiichi Nuclear Power Plant accident including: daily Japanese weather forecasts and atmospheric transport predictions to inform planning for field monitoring operations and to provide U.S. government agencies with ongoing situational awareness of meteorological conditions; estimates of possible dose in Japan based on hypothetical U.S. Nuclear Regulatory Commission scenarios of potential radionuclide releases to support protective action planning for U.S. citizens; predictions of possible plume arrival times and dose levels at U.S. locations; and source estimation and plume model refinement based on atmospheric dispersion modeling and available monitoring data.

  13. Interest rate modeling post-crisis challenges and approaches

    CERN Document Server

    Grbac, Zorana


    Filling a gap in the literature caused by the recent financial crisis, this book provides a treatment of the techniques needed to model and evaluate interest rate derivatives according to the new paradigm for fixed income markets. Concerning this new development, there presently exist only research articles and two books, one of them an edited volume, both being written by researchers working mainly in practice. The aim of this book is to concentrate primarily on the methodological side, thereby providing an overview of the state-of-the-art and also clarifying the link between the new models and the classical literature. The book is intended to serve as a guide for graduate students and researchers as well as practitioners interested in the paradigm change for fixed income markets. A basic knowledge of fixed income markets and related stochastic methodology is assumed as a prerequisite.


    Directory of Open Access Journals (Sweden)

    Vladimir I. Kuznetsov


    Full Text Available In recent years a special attention is given to various aspects and problems of development of business and steady social and economic growth of modern Russia. In this context, a big scientific and practical interest is the all-round analysis of various barriers arising on a way of this process. A significant role belongs to specific threats of formation and modeling movement of the personnel in enterprises.

  15. Understanding rare disease pathogenesis: a grand challenge for model organisms. (United States)

    Hieter, Philip; Boycott, Kym M


    In this commentary, Philip Hieter and Kym Boycott discuss the importance of model organisms for understanding pathogenesis of rare human genetic diseases, and highlight the work of Brooks et al., "Dysfunction of 60S ribosomal protein L10 (RPL10) disrupts neurodevelopment and causes X-linked microcephaly in humans," published in this issue of GENETICS. Copyright © 2014 by the Genetics Society of America.

  16. Educational Modelling Language and Learning Design: new challenges for instructional re-usability and personalized learning

    NARCIS (Netherlands)

    Hummel, Hans; Manderveld, Jocelyn; Tattersall, Colin; Koper, Rob


    Published: Hummel, H. G. K., Manderveld, J. M., Tattersall, C.,& Koper, E. J. R. (2004). Educational Modelling Language: new challenges for instructional re-usability and personalized learning. International Journal of Learning Technology, 1, 1, 110-111.

  17. Lesson Study Model: The Challenge of Transforming a Global Idea into Local Practice (United States)

    Grimsaeth, Gerd; Hallås, Bjørg Oddrun


    The lesson study (LS) model, which originated in Japan, has become popular all over the world. This article will highlight some of the challenges encountered when the LS model was picked up and introduced in a local school context in a Norwegian municipality. The article views this process in the light of research on LS-model transfer into local…

  18. Assessing dengue vaccination impact: Model challenges and future directions. (United States)

    Recker, Mario; Vannice, Kirsten; Hombach, Joachim; Jit, Mark; Simmons, Cameron P


    In response to the sharp rise in the global burden caused by dengue virus (DENV) over the last few decades, the WHO has set out three specific key objectives in its disease control strategy: (i) to estimate the true burden of dengue by 2015; (ii) a reduction in dengue mortality by at least 50% by 2020 (used as a baseline); and (iii) a reduction in dengue morbidity by at least 25% by 2020. Although various elements will all play crucial parts in achieving this goal, from diagnosis and case management to integrated surveillance and outbreak response, sustainable vector control, vaccine implementation and finally operational and implementation research, it seems clear that new tools (e.g. a safe and effective vaccine and/or effective vector control) are key to success. The first dengue vaccine was licensed in December 2015, Dengvaxia® (CYD-TDV) developed by Sanofi Pasteur. The WHO has provided guidance on the use of CYD-TDV in endemic countries, for which there are a variety of considerations beyond the risk-benefit evaluation done by regulatory authorities, including public health impact and cost-effectiveness. Population-level vaccine impact and economic and financial aspects are two issues that can potentially be considered by means of mathematical modelling, especially for new products for which empirical data are still lacking. In December 2014 a meeting was convened by the WHO in order to revisit the current status of dengue transmission models and their utility for public health decision-making. Here, we report on the main points of discussion and the conclusions of this meeting, as well as next steps for maximising the use of mathematical models for vaccine decision-making. Copyright © 2016.

  19. Status and challenges in risk assessment - the DREAM model

    Energy Technology Data Exchange (ETDEWEB)

    Johnsen, Staale


    This publication relates to the Norwegian DREAM project. The objective of the project is to develop a general environmental risk analysis methodology which allows for time-varying sub-lethal exposures of marine biota to discharge plumes which may be composed of mixtures of chemicals. The DREAM project is based on research in this area over the past five years, and a pre-runner of the DREAM model, PROVANN, is presently available, and has been applied for regional risk assessment studies in the Norwegian seas. 7 figs., 2 tabs.

  20. Challenges for the kinetic unified dark matter model

    International Nuclear Information System (INIS)

    Giannakis, Dimitrios; Hu, Wayne


    Given that the dark matter and dark energy in the Universe affect cosmological observables only gravitationally, their phenomenology may be described by a single stress-energy tensor. True unification however requires a theory that reproduces the successful phenomenology of ΛCDM and that requirement places specific constraints on the stress structure of the matter. We show that a recently proposed unification through an offset quadratic kinetic term for a scalar field is exactly equivalent to a fluid with a closed-form barotropic equation of state plus cosmological constant. The finite pressure at high densities introduces a cutoff in the linear power spectrum, which may alleviate the dark matter substructure problem; we provide a convenient fitting function for such studies. Given that sufficient power must remain to reionize the Universe, the equation of state today is nonrelativistic with p∝ρ 2 and a Jeans scale in the parsec regime for all relevant densities. Structure may then be evolved into the nonlinear regime with standard hydrodynamic techniques. In fact, the model is equivalent to the well-studied collisional dark matter with negligible mean free path. If recent observations of the triaxiality of dark matter halos and ram pressure stripping in galaxy clusters are confirmed, this model will be ruled out

  1. Retrocaval ureter: the importance of intravenous urography. (United States)

    Hassan, Radhiana; Aziz, Azian Abd; Mohamed, Siti Kamariah Che


    Retrocaval ureter is a rare cause of hydronephrosis. Its rarity and non-specific presentation pose a challenge to surgeons and radiologists in making the correct diagnosis. Differentiation from other causes of urinary tract obstruction, especially the more common urolithiasis, is important for successful surgical management. Current practice has seen multislice computed tomography (MSCT) rapidly replaces intravenous urography (IVU) in the assessment of patients with hydronephrosis due to suspected urolithiasis, especially ureterolithiasis. However, MSCT, without adequate opacification of the entire ureter, may allow the physician to overlook a retrocaval ureter as the cause of hydronephrosis. High-resolution IVU images can demonstrate the typical appearance that leads to the accurate diagnosis of a retrocaval ureter. We reported a case that illustrates this scenario and highlights the importance of IVU in the assessment of a complex congenital disorder involving the urinary tract.

  2. Opportunities and challenges of pluripotent stem cell neurodegenerative disease models. (United States)

    Sandoe, Jackson; Eggan, Kevin


    Human neurodegenerative disorders are among the most difficult to study. In particular, the inability to readily obtain the faulty cell types most relevant to these diseases has impeded progress for decades. Recent advances in pluripotent stem cell technology now grant access to substantial quantities of disease-pertinent neurons both with and without predisposing mutations. While this suite of technologies has revolutionized the field of 'in vitro disease modeling', great care must be taken in their deployment if robust, durable discoveries are to be made. Here we review what we perceive to be several of the stumbling blocks in the use of stem cells for the study of neurological disease and offer strategies to overcome them.

  3. Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans (United States)

    Lile, Joshua A.; Stoops, William W.; Rush, Craig R.; Negus, S. Stevens; Glaser, Paul E. A.; Hatton, Kevin W.; Hays, Lon R.


    Background A medication for treating cocaine use disorder has yet to be approved. Laboratory-based evaluation of candidate medications in animals and humans is a valuable means to demonstrate safety, tolerability and initial efficacy of potential medications. However, animal-to-human translation has been hampered by a lack of coordination. Therefore, we designed homologous cocaine self-administration studies in rhesus monkeys (see companion article) and human subjects in an attempt to develop linked, functionally equivalent procedures for research on candidate medications for cocaine use disorder. Methods Eight (N=8) subjects with cocaine use disorder completed 12 experimental sessions in which they responded to receive money ($0.01, $1.00 and $3.00) or intravenous cocaine (0, 3, 10 and 30 mg/70 kg) under independent, concurrent progressive-ratio schedules. Prior to the completion of 9 choice trials, subjects sampled the cocaine dose available during that session and were informed of the monetary alternative value. Results The allocation of behavior varied systematically as a function of cocaine dose and money value. Moreover, a similar pattern of cocaine choice was demonstrated in rhesus monkeys and humans across different cocaine doses and magnitudes of the species-specific alternative reinforcers. The subjective and cardiovascular responses to IV cocaine were an orderly function of dose, although heart rate and blood pressure remained within safe limits. Conclusions These coordinated studies successfully established drug vs. non-drug choice procedures in humans and rhesus monkeys that yielded similar cocaine choice behavior across species. This translational research platform will be used in future research to enhance the efficiency of developing interventions to reduce cocaine use. PMID:27269368

  4. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

    Directory of Open Access Journals (Sweden)

    Tayra Judith


    Full Text Available Abstract Background Mesenchymal stem cells (MSCs are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL staining. Results Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups. Conclusions Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

  5. Effect of External Pressure and Catheter Gauge on Flow Rate, Kinetic Energy, and Endothelial Injury During Intravenous Fluid Administration in a Rabbit Model. (United States)

    Hu, Mei-Hua; Chan, Wei-Hung; Chen, Yao-Chang; Cherng, Chen-Hwan; Lin, Chih-Kung; Tsai, Chien-Sung; Chou, Yu-Ching; Huang, Go-Shine


    The effects of intravenous (IV) catheter gauge and pressurization of IV fluid (IVF) bags on fluid flow rate have been studied. However, the pressure needed to achieve a flow rate equivalent to that of a 16 gauge (G) catheter through smaller G catheters and the potential for endothelial damage from the increased kinetic energy produced by higher pressurization are unclear. Constant pressure on an IVF bag was maintained by an automatic adjustable pneumatic pressure regulator of our own design. Fluids running through 16 G, 18 G, 20 G, and 22 G catheters were assessed while using IV bag pressurization to achieve the flow rate equivalent to that of a 16 G catheter. We assessed flow rates, kinetic energy, and flow injury to rabbit inferior vena cava endothelium. By applying sufficient external constant pressure to an IVF bag, all fluids could be run through smaller (G) catheters at the flow rate in a 16 G catheter. However, the kinetic energy increased significantly as the catheter G increased. Damage to the venous endothelium was negligible or minimal/patchy cell loss. We designed a new rapid infusion system, which provides a constant pressure that compresses the fluid volume until it is free from visible residual fluid. When large-bore venous access cannot be obtained, multiple smaller catheters, external pressure, or both should be considered. However, caution should be exercised when fluid pressurized to reach a flow rate equivalent to that in a 16 G catheter is run through a smaller G catheter because of the profound increase in kinetic energy that can lead to venous endothelium injury.

  6. Intravenous Antiepileptic Drugs in Russia

    Directory of Open Access Journals (Sweden)

    P. N. Vlasov


    Full Text Available Launching four intravenous antiepileptic drugs: valproate (Depakene and Convulex, lacosamide (Vimpat, and levetiracetam (Keppra – into the Russian market has significantly broadened the possibilities of rendering care to patients in seizure emergency situations. The chemi- cal structure, mechanisms of action, indications/contraindications, clinical effectiveness and tolerability, advantages/disadvantages, and adverse events of using these drugs in urgent and elective neurology are discussed. 

  7. Stratified flows with variable density: mathematical modelling and numerical challenges. (United States)

    Murillo, Javier; Navas-Montilla, Adrian


    Stratified flows appear in a wide variety of fundamental problems in hydrological and geophysical sciences. They may involve from hyperconcentrated floods carrying sediment causing collapse, landslides and debris flows, to suspended material in turbidity currents where turbulence is a key process. Also, in stratified flows variable horizontal density is present. Depending on the case, density varies according to the volumetric concentration of different components or species that can represent transported or suspended materials or soluble substances. Multilayer approaches based on the shallow water equations provide suitable models but are not free from difficulties when moving to the numerical resolution of the governing equations. Considering the variety of temporal and spatial scales, transfer of mass and energy among layers may strongly differ from one case to another. As a consequence, in order to provide accurate solutions, very high order methods of proved quality are demanded. Under these complex scenarios it is necessary to observe that the numerical solution provides the expected order of accuracy but also converges to the physically based solution, which is not an easy task. To this purpose, this work will focus in the use of Energy balanced augmented solvers, in particular, the Augmented Roe Flux ADER scheme. References: J. Murillo , P. García-Navarro, Wave Riemann description of friction terms in unsteady shallow flows: Application to water and mud/debris floods. J. Comput. Phys. 231 (2012) 1963-2001. J. Murillo B. Latorre, P. García-Navarro. A Riemann solver for unsteady computation of 2D shallow flows with variable density. J. Comput. Phys.231 (2012) 4775-4807. A. Navas-Montilla, J. Murillo, Energy balanced numerical schemes with very high order. The Augmented Roe Flux ADER scheme. Application to the shallow water equations, J. Comput. Phys. 290 (2015) 188-218. A. Navas-Montilla, J. Murillo, Asymptotically and exactly energy balanced augmented flux

  8. Muscle power during intravenous sedation

    Directory of Open Access Journals (Sweden)

    Nobuyuki Matsuura


    Full Text Available Intravenous sedation is effective to reduce fear and anxiety in dental treatment. It also has been used for behavior modification technique in dental patients with special needs. Midazolam and propofol are commonly used for intravenous sedation. Although there have been many researches on the effects of midazolam and propofol on vital function and the recovery profile, little is known about muscle power. This review discusses the effects of intravenous sedation using midazolam and propofol on both grip strength and bite force. During light propofol sedation, grip strength increases slightly and bite force increases in a dose-dependent manner. Grip strength decreases while bite force increases during light midazolam sedation, and also during light sedation using a combination of midazolam and propofol. Flumazenil did not antagonise the increase in bite force by midazolam. These results may suggest following possibilities; (1 Activation of peripheral benzodiazepine receptors located within the temporomandibular joint region and masticatory muscles may be the cause of increasing bite force. (2 Propofol limited the long-latency exteroceptive suppression (ES2 period during jaw-opening reflex. Thus, control of masticatory muscle contraction, which is thought to have a negative feedback effect on excessive bite force, may be depressed by propofol.

  9. Modelling a full scale membrane bioreactor using Activated Sludge Model No.1: challenges and solutions. (United States)

    Delrue, F; Choubert, J M; Stricker, A E; Spérandio, M; Mietton-Peuchot, M; Racault, Y


    A full-scale membrane bioreactor (1,600 m(3) d(-1)) was monitored for modelling purposes during the summer of 2006. A complete calibration of the ASM1 model is presented, in which the key points were the wastewater characterisation, the oxygen transfer and the biomass kinetics. Total BOD tests were not able to correctly estimate the biodegradable fraction of the wastewater. Therefore the wastewater fractionation was identified by adjusting the simulated sludge production rate to the measured value. MLVSS and MLSS were accurately predicted during both calibration and validation periods (20 and 30 days). Because the membranes were immerged in the aeration tank, the coarse bubble and fine bubble diffusion systems coexisted in the same tank. This allowed five different aeration combinations, depending whether the 2 systems were operating separately or simultaneously, and at low speed or high speed. The aeration control maintained low DO concentrations, allowing simultaneous nitrification and denitrification. This made it difficult to calibrate the oxygen transfer. The nitrogen removal kinetics were determined using maximum nitrification rate tests and an 8-hour intensive sampling campaign. Despite the challenges encountered, a calibrated set of parameters was identified for ASM1 that gave very satisfactory results for the calibration period. Matching simulated and measured data became more difficult during the validation period, mainly because the dominant aeration configuration had changed. However, the merit of this study is to be the first effort to simulate a full-scale MBR plant.

  10. Facing up to 'challenging behaviour': a model for training in staff-client interaction. (United States)

    Farrell, Gerald A; Shafiei, Touran; Salmon, Peter


    This paper draws on theory and evidence to develop a conceptual staff training model for the management of 'challenging behaviour'. Staff working with clients who are experienced as challenging commonly report negative feelings such as anxiety, anger, guilt, fear, self-blame and powerlessness, as well as dissatisfaction with their jobs. Current training programmes in challenging behaviour offer a 'smorgasbord' of content, without a clearly defined conceptual framework. Medline and PsychInfo were searched for papers in English from 1998 to 2008, linking 'nurs*' to 'challenging behavio*' and its related terms. Additional hand-searching identified informative papers from disciplines outside nursing older than the search period. We developed an applied model for training educators in respect of challenging behaviours. The model directs educators to consider: the influence of the nurse, including their values, emotional processes and behavioural skills; features of the client; and features of the situation in which the behaviour occurs, including its culture and working practices and physical environment. The most striking implication of the model is that it explicitly recognizes the importance of domains of learning other than skill. This enables educators to find educationally appropriate responses to resource limitations that inevitably constrain training. Challenging behaviour should be considered as a product of several intertwined factors: the actors involved - nurses, clients and others - and the situation in which the behaviour occurs, including its culture and working practices and physical environment.

  11. Preclinical Development of an In Vivo BCG Challenge Model for Testing Candidate TB Vaccine Efficacy (United States)

    Minassian, Angela M.; Ronan, Edward O.; Poyntz, Hazel; Hill, Adrian V. S.; McShane, Helen


    There is an urgent need for an immunological correlate of protection against tuberculosis (TB) with which to evaluate candidate TB vaccines in clinical trials. Development of a human challenge model of Mycobacterium tuberculosis (M.tb) could facilitate the detection of such correlate(s). Here we propose a novel in vivo Bacille Calmette-Guérin (BCG) challenge model using BCG immunization as a surrogate for M.tb infection. Culture and quantitative PCR methods have been developed to quantify BCG in the skin, using the mouse ear as a surrogate for human skin. Candidate TB vaccines have been evaluated for their ability to protect against a BCG skin challenge, using this model, and the results indicate that protection against a BCG skin challenge is predictive of BCG vaccine efficacy against aerosol M.tb challenge. Translation of these findings to a human BCG challenge model could enable more rapid assessment and down selection of candidate TB vaccines and ultimately the identification of an immune correlate of protection. PMID:21629699

  12. Key challenges and priorities for modelling European grasslands under climate change. (United States)

    Kipling, Richard P; Virkajärvi, Perttu; Breitsameter, Laura; Curnel, Yannick; De Swaef, Tom; Gustavsson, Anne-Maj; Hennart, Sylvain; Höglind, Mats; Järvenranta, Kirsi; Minet, Julien; Nendel, Claas; Persson, Tomas; Picon-Cochard, Catherine; Rolinski, Susanne; Sandars, Daniel L; Scollan, Nigel D; Sebek, Leon; Seddaiu, Giovanna; Topp, Cairistiona F E; Twardy, Stanislaw; Van Middelkoop, Jantine; Wu, Lianhai; Bellocchi, Gianni


    Grassland-based ruminant production systems are integral to sustainable food production in Europe, converting plant materials indigestible to humans into nutritious food, while providing a range of environmental and cultural benefits. Climate change poses significant challenges for such systems, their productivity and the wider benefits they supply. In this context, grassland models have an important role in predicting and understanding the impacts of climate change on grassland systems, and assessing the efficacy of potential adaptation and mitigation strategies. In order to identify the key challenges for European grassland modelling under climate change, modellers and researchers from across Europe were consulted via workshop and questionnaire. Participants identified fifteen challenges and considered the current state of modelling and priorities for future research in relation to each. A review of literature was undertaken to corroborate and enrich the information provided during the horizon scanning activities. Challenges were in four categories relating to: 1) the direct and indirect effects of climate change on the sward 2) climate change effects on grassland systems outputs 3) mediation of climate change impacts by site, system and management and 4) cross-cutting methodological issues. While research priorities differed between challenges, an underlying theme was the need for accessible, shared inventories of models, approaches and data, as a resource for stakeholders and to stimulate new research. Developing grassland models to effectively support efforts to tackle climate change impacts, while increasing productivity and enhancing ecosystem services, will require engagement with stakeholders and policy-makers, as well as modellers and experimental researchers across many disciplines. The challenges and priorities identified are intended to be a resource 1) for grassland modellers and experimental researchers, to stimulate the development of new research

  13. BIG DATA-Related Challenges and Opportunities in Earth System Modeling (United States)

    Bamzai, A. S.


    Knowledge of the Earth's climate has increased immensely in recent decades, both through observational analysis and modeling. BIG DATA-related challenges emerge in our quest for understanding the variability and predictability of the climate and earth system on a range of time scales, as well as in our endeavor to improve predictive capability using state-of-the-science models. To enable further scientific discovery, bottlenecks in current paradigms need to be addressed. An overview of current NSF activities in Earth System Modeling with a focus on associated data-related challenges and opportunities, will be presented.

  14. Application and Development of Energy System Optimisation Models to Meet Challenges of the Future

    DEFF Research Database (Denmark)

    Balyk, Olexandr

    Climate change, security of supply and local air pollution are among the challenges that are shaping the future of energy systems worldwide. In response to these challenges, various goals are set nationally and internationally that energy systems are supposed to fulfil. These include e.g. EU 20...... them. The challenges of climate change, security of supply, and local air pollution are addressed in the papers by focusing on renewable energy systems, demand side management options, climate change mitigation and resource potentials. In the process of the study the energy system optimisation models...... upon in the Copenhagen Accord and the importance of large emerging economies in this context, and the role of district heating in the future Danish renewable energy system.The outcomes of this work illustrate the potential of energy system optimisation models to address challenges of the future...

  15. Grand challenge problems in environmental modeling and remediation: groundwater contaminant transport

    Energy Technology Data Exchange (ETDEWEB)

    Todd Arbogast; Steve Bryant; Clint N. Dawson; Mary F. Wheeler


    This report describes briefly the work of the Center for Subsurface Modeling (CSM) of the University of Texas at Austin (and Rice University prior to September 1995) on the Partnership in Computational Sciences Consortium (PICS) project entitled Grand Challenge Problems in Environmental Modeling and Remediation: Groundwater Contaminant Transport.

  16. The Challenge of Grounding Planning in Simulation with an Interactive Model Development Environment (United States)

    Clement, Bradley J.; Frank, Jeremy D.; Chachere, John M.; Smith, Tristan B.; Swanson, Keith J.


    A principal obstacle to fielding automated planning systems is the difficulty of modeling. Physical systems are modeled conventionally based on specification documents and the modeler's understanding of the system. Thus, the model is developed in a way that is disconnected from the system's actual behavior and is vulnerable to manual error. Another obstacle to fielding planners is testing and validation. For a space mission, generated plans must be validated often by translating them into command sequences that are run in a simulation testbed. Testing in this way is complex and onerous because of the large number of possible plans and states of the spacecraft. Though, if used as a source of domain knowledge, the simulator can ease validation. This paper poses a challenge: to ground planning models in the system physics represented by simulation. A proposed, interactive model development environment illustrates the integration of planning and simulation to meet the challenge. This integration reveals research paths for automated model construction and validation.

  17. [Stump pain relieved by continuous intravenous ketamine infusion therapy]. (United States)

    Mizuno, J; Sugimoto, S; Ohmori, T; Itadera, E; Ichikawa, N; Machida, K


    We experienced a case of stump pain relieved by continuous intravenous ketamine infusion therapy. A 59-year-old male had his left first through fourth toes amputated because a giant iron plate at work fell on his left foot fifteen years ago. Thereafter he had refractory spontaneous burning pain and night pain on his stump. On examination, we found his left foot skin hard, lustrous, and with sweating disturbance, allodynia and hyperpathia. As intravenous administrations of ketamine 10 mg and thiamylal 50 mg were positive as a drug challenge test, we performed intravenous ketamine infusion at 1 for 1 hour and a half. After this treatment, his visual analogue scale (VAS) improved dramatically to 0 mm, and night pain, allodynia and hyperpathia disappeared for three days. Thereafter stump pain was relieved to the level of VAS 20 mm. Therefore we diagnosed his stump pain as central pain of neuropathic origin. We suspect that continuous intravenous infusion of ketamine, a noncompetitive blocker of N-methyl-D-aspartic acid receptor, might be an effective and useful alternative treatment in a patient with refractory stump pain.

  18. Area under the curve predictions of dalbavancin, a new lipoglycopeptide agent, using the end of intravenous infusion concentration data point by regression analyses such as linear, log-linear and power models. (United States)

    Bhamidipati, Ravi Kanth; Syed, Muzeeb; Mullangi, Ramesh; Srinivas, Nuggehally


    1. Dalbavancin, a lipoglycopeptide, is approved for treating gram-positive bacterial infections. Area under plasma concentration versus time curve (AUC inf ) of dalbavancin is a key parameter and AUC inf /MIC ratio is a critical pharmacodynamic marker. 2. Using end of intravenous infusion concentration (i.e. C max ) C max versus AUC inf relationship for dalbavancin was established by regression analyses (i.e. linear, log-log, log-linear and power models) using 21 pairs of subject data. 3. The predictions of the AUC inf were performed using published C max data by application of regression equations. The quotient of observed/predicted values rendered fold difference. The mean absolute error (MAE)/root mean square error (RMSE) and correlation coefficient (r) were used in the assessment. 4. MAE and RMSE values for the various models were comparable. The C max versus AUC inf exhibited excellent correlation (r > 0.9488). The internal data evaluation showed narrow confinement (0.84-1.14-fold difference) with a RMSE regression models, a single time point strategy of using C max (i.e. end of 30-min infusion) is amenable as a prospective tool for predicting AUC inf of dalbavancin in patients.

  19. The Electric Vehicles Ecosystem Model: Construct, Analysis and Identification of Key Challenges

    Directory of Open Access Journals (Sweden)



    Full Text Available This paper builds a conceptual model of electric vehicles’ (EV ecosystem and value chain build-up. Based on the literature, the research distinguishes the most critical challenges that are on the way of mobility systems’ electrification. Consumers still have some questions that call for answers before they are ready to adopt evs.With regard to technical aspects, some challenges are coming from vehicles, charging infrastructure, battery technology, and standardization. The use of battery in EVs will bring in additional environmental challenges, coming from the battery life cycle for used battery, the manufacturing, and from some materials used and treated in the manufacturing process. The policy aspects include mostly taxation strategies. For most part, established market conditions are still lacking and there are a number of unresolved challenges on both supply and demand side of the EV market.

  20. Summary of the DREAM8 Parameter Estimation Challenge: Toward Parameter Identification for Whole-Cell Models.

    Directory of Open Access Journals (Sweden)

    Jonathan R Karr


    Full Text Available Whole-cell models that explicitly represent all cellular components at the molecular level have the potential to predict phenotype from genotype. However, even for simple bacteria, whole-cell models will contain thousands of parameters, many of which are poorly characterized or unknown. New algorithms are needed to estimate these parameters and enable researchers to build increasingly comprehensive models. We organized the Dialogue for Reverse Engineering Assessments and Methods (DREAM 8 Whole-Cell Parameter Estimation Challenge to develop new parameter estimation algorithms for whole-cell models. We asked participants to identify a subset of parameters of a whole-cell model given the model's structure and in silico "experimental" data. Here we describe the challenge, the best performing methods, and new insights into the identifiability of whole-cell models. We also describe several valuable lessons we learned toward improving future challenges. Going forward, we believe that collaborative efforts supported by inexpensive cloud computing have the potential to solve whole-cell model parameter estimation.

  1. Seven challenges for modelling indirect transmission: Vector-borne diseases, macroparasites and neglected tropical diseases

    Directory of Open Access Journals (Sweden)

    T. Déirdre Hollingsworth


    Full Text Available Many of the challenges which face modellers of directly transmitted pathogens also arise when modelling the epidemiology of pathogens with indirect transmission – whether through environmental stages, vectors, intermediate hosts or multiple hosts. In particular, understanding the roles of different hosts, how to measure contact and infection patterns, heterogeneities in contact rates, and the dynamics close to elimination are all relevant challenges, regardless of the mode of transmission. However, there remain a number of challenges that are specific and unique to modelling vector-borne diseases and macroparasites. Moreover, many of the neglected tropical diseases which are currently targeted for control and elimination are vector-borne, macroparasitic, or both, and so this article includes challenges which will assist in accelerating the control of these high-burden diseases. Here, we discuss the challenges of indirect measures of infection in humans, whether through vectors or transmission life stages and in estimating the contribution of different host groups to transmission. We also discuss the issues of “evolution-proof” interventions against vector-borne disease.

  2. Industrial Adoption of Model-Based Systems Engineering: Challenges and Strategies (United States)

    Maheshwari, Apoorv

    As design teams are becoming more globally integrated, one of the biggest challenges is to efficiently communicate across the team. The increasing complexity and multi-disciplinary nature of the products are also making it difficult to keep track of all the information generated during the design process by these global team members. System engineers have identified Model-based Systems Engineering (MBSE) as a possible solution where the emphasis is placed on the application of visual modeling methods and best practices to systems engineering (SE) activities right from the beginning of the conceptual design phases through to the end of the product lifecycle. Despite several advantages, there are multiple challenges restricting the adoption of MBSE by industry. We mainly consider the following two challenges: a) Industry perceives MBSE just as a diagramming tool and does not see too much value in MBSE; b) Industrial adopters are skeptical if the products developed using MBSE approach will be accepted by the regulatory bodies. To provide counter evidence to the former challenge, we developed a generic framework for translation from an MBSE tool (Systems Modeling Language, SysML) to an analysis tool (Agent-Based Modeling, ABM). The translation is demonstrated using a simplified air traffic management problem and provides an example of a potential quite significant value: the ability to use MBSE representations directly in an analysis setting. For the latter challenge, we are developing a reference model that uses SysML to represent a generic infusion pump and SE process for planning, developing, and obtaining regulatory approval of a medical device. This reference model demonstrates how regulatory requirements can be captured effectively through model-based representations. We will present another case study at the end where we will apply the knowledge gained from both case studies to a UAV design problem.

  3. Time Course Study of Delayed Wound Healing in a Biofilm-Challenged Diabetic Mouse Model (United States)

    Zhao, Ge; Usui, Marcia L.; Underwood, Robert A.; Singh, Pradeep K.; James, Garth A.; Stewart, Philip S.; Fleckman, Philip; Olerud, John E.


    Bacterial biofilm has been shown to play a role in delaying wound healing of chronic wounds, a major medical problem that results in significant healthcare burden. A reproducible animal model could be very valuable for studying the mechanism and management of chronic wounds. Our previous work demonstrated that Pseudomonas aeruginosa (PAO1) biofilmchallenge on wounds in diabetic (db/db) mice significantly delayed wound healing. In this wound time course study, we further characterize the bacterial burden, delayed wound healing and certain aspects of the host inflammatory response in the PAO1 biofilm-challenged db/db mouse model. PAO1 biofilms were transferred onto 2 day old wounds created on the dorsal surface of db/db mice. Control wounds without biofilm-challenge healed by 4 weeks, consistent with previous studies; none of the biofilm-challenged wounds healed by 4 weeks; 64% of the biofilm-challenged wounds healed by 6 weeks; and all of the biofilm-challenged wounds healed by 8 weeks. During the wound healing process, P. aeruginosa were gradually cleared from the wounds while the presence of S. aureus (part of the normal mouse skin flora) increased. Scabs from all unhealed wounds contained 107 P. aeruginosa, which was 100 fold higher than the counts isolated from wound beds (i.e. 99% of the P. aeruginosa was in the scab). Histology and genetic analysis showed proliferative epidermis, deficient vascularization and increased inflammatory cytokines. Hypoxia inducible factor (HIF) expression increased 3 fold in 4 week wounds. In summary, our study demonstrates that biofilm-challenged wounds typically heal in approximately 6 weeks, at least 2 weeks longer than non biofilm-challenged normal wounds. These data suggest that this delayed wound healing model enables the in vivo study of bacterial biofilm responses to host defenses and the effects of biofilms on host wound healing pathways. It may also be used to test anti-biofilm strategies the treatment of chronic wounds

  4. Participation and occupation in occupational therapy models of practice: A discussion of possibilities and challenges. (United States)

    Larsson-Lund, Maria; Nyman, Anneli


    Occupation has been the focus in occupational therapy practice to greater or lesser degrees from a historical viewpoint. This evokes a need to discuss whether concepts that are added to our field will enhance or blur our focus on occupation. To explore how the concept of participation in the International Classification of Functioning, Disability and Health (ICF) is related to the concept of occupation by reviewing and comparing its use in three models of practice within occupational therapy. The aim was also to generate discussion on possibilities and challenges concerning the relationship of participation and occupation. The models reviewed were The Model of Human Occupation (MOHO), the Canadian Model of Occupational Performance and Engagement (CMOP-E) and the Occupational Therapy Intervention Process Model (OTIPM). The concept of participation was related to occupation in different ways in these models. Based on the review some challenges and considerations for occupational therapy were generated. Relating the concept of participation from the ICF to the concept of occupation in models of practice can be challenging. At the same time, relating the concepts can be a resource to develop occupational therapy and the understanding of occupational issues in society.

  5. Decision-Making in Agent-Based Models of Migration: State of the Art and Challenges. (United States)

    Klabunde, Anna; Willekens, Frans

    We review agent-based models (ABM) of human migration with respect to their decision-making rules. The most prominent behavioural theories used as decision rules are the random utility theory, as implemented in the discrete choice model, and the theory of planned behaviour. We identify the critical choices that must be made in developing an ABM, namely the modelling of decision processes and social networks. We also discuss two challenges that hamper the widespread use of ABM in the study of migration and, more broadly, demography and the social sciences: (a) the choice and the operationalisation of a behavioural theory (decision-making and social interaction) and (b) the selection of empirical evidence to validate the model. We offer advice on how these challenges might be overcome.

  6. The Challenge of Forecasting the Onset and Development of Radiation Fog Using Mesoscale Atmospheric Models

    NARCIS (Netherlands)

    Steeneveld, G.J.; Ronda, R.J.; Holtslag, A.A.M.


    The numerical weather prediction of radiation fog is challenging, as many models typically show large biases for the timing of the onset and dispersal of the fog, as well as for its depth and liquid water content. To understand the role of physical processes, i.e. turbulence, radiation, land-surface

  7. Challenges of assessing fire and burn severity using field measures, remote sensing and modelling (United States)

    Penelope Morgan; Robert E. Keane; Gregory K. Dillon; Theresa B. Jain; Andrew T. Hudak; Eva C. Karau; Pamela G. Sikkink; Zachery A. Holden; Eva K. Strand


    Comprehensive assessment of ecological change after fires have burned forests and rangelands is important if we are to understand, predict and measure fire effects. We highlight the challenges in effective assessment of fire and burn severity in the field and using both remote sensing and simulation models. We draw on diverse recent research for guidance on assessing...

  8. From the Building to the Grid: An Energy Revolution and Modeling Challenge; Workshop Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Kroposki, B.; Komomua, C.; O' Malley, M.


    This report summarizes the workshop entitled: From the Building to the Grid: An Energy Revolution and Modeling Challenge. The first workshop was held May 1-2, 2012 on NREL's campus in Golden, Colorado. The second was held June 6-7, 2012 at the University College Dublin, in Dublin, Ireland.

  9. Toward an Integrated Competence-based System Supporting Lifelong Learning and Employability: Concepts, Model, and Challenges

    NARCIS (Netherlands)

    Miao, Yongwu; Van der Klink, Marcel; Boon, Jo; Sloep, Peter; Koper, Rob


    Miao, Y., Van der Klink, M., Boon, J., Sloep, P. B., & Koper, R. (2009). Toward an Integrated Competence-based System Supporting Lifelong Learning and Employability: Concepts, Model, and Challenges. In M. Spaniol, Q. Li, R. Klamma & R. W. H. Lau (Eds.), Proceedings of the 8th International

  10. Verslag van de 'Sanitation Challenge: An international conference on new sanitation concepts and models of governance'.

    NARCIS (Netherlands)

    Vliet, van B.J.M.; Eekert, van M.H.A.; Zeeman, G.; Mels, A.R.


    Van 19 tot en met 21 mei vond in Wageningen de `Sanitation Challenge: an international conference on new sanitation concepts and models of governance¿ plaats. Het voornaamste doel was om de verschillende groepen die betrokken zijn bij onderzoek, ontwikkeling en implementatie van (nieuwe) sanitatie

  11. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats

    NARCIS (Netherlands)

    Cornelissen, J.B.W.J.; Giessen, van der J.W.B.; Takumi, K.; Teunis, P.F.M.; Wisselink, H.J.


    High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment.

  12. Toward an Integrated Competence-based System Supporting Lifelong Learning and Employability: Concepts, Model, and Challenges

    NARCIS (Netherlands)

    Miao, Yongwu; Van der Klink, Marcel; Boon, Jo; Sloep, Peter; Koper, Rob


    Miao, Y., Van der Klink, M., Boon, J., Sloep, P. B., & Koper, R. (2009). Toward an Integrated Competence-based System Supporting Lifelong Learning and Employability: Concepts, Model, and Challenges. Presentation at the 8th International Conference Advances in Web Based Learning - ICWL 2009. August,

  13. Challenges of forest landscape modeling - simulating large landscapes and validating results (United States)

    Hong S. He; Jian Yang; Stephen R. Shifley; Frank R. Thompson


    Over the last 20 years, we have seen a rapid development in the field of forest landscape modeling, fueled by both technological and theoretical advances. Two fundamental challenges have persisted since the inception of FLMs: (1) balancing realistic simulation of ecological processes at broad spatial and temporal scales with computing capacity, and (2) validating...

  14. Modelling of vector hysteresis at macromagnetic scale: Open questions and challenges

    International Nuclear Information System (INIS)

    Cardelli, E.; Faba, A.


    After a short review of some experimental evidences the motivations that lead to the practical need of phenomenological modelling for the analysis of magnetic materials at macro-scale, and some challenging formulations are presented and discussed. Examples of practical applications are reported.

  15. Challenges and priorities for modelling livestock health and pathogens in the context of climate change. (United States)

    Özkan, Şeyda; Vitali, Andrea; Lacetera, Nicola; Amon, Barbara; Bannink, André; Bartley, Dave J; Blanco-Penedo, Isabel; de Haas, Yvette; Dufrasne, Isabelle; Elliott, John; Eory, Vera; Fox, Naomi J; Garnsworthy, Phil C; Gengler, Nicolas; Hammami, Hedi; Kyriazakis, Ilias; Leclère, David; Lessire, Françoise; Macleod, Michael; Robinson, Timothy P; Ruete, Alejandro; Sandars, Daniel L; Shrestha, Shailesh; Stott, Alistair W; Twardy, Stanislaw; Vanrobays, Marie-Laure; Ahmadi, Bouda Vosough; Weindl, Isabelle; Wheelhouse, Nick; Williams, Adrian G; Williams, Hefin W; Wilson, Anthony J; Østergaard, Søren; Kipling, Richard P


    Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire based exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can

  16. The trainable trajectory formation model TD-HMM parameterized for the LIPS 2008 challenge


    Bailly , Gérard; Govokhina , Oxana; Breton , Gaspard; Elisei , Frédéric; Savariaux , Christophe


    International audience; We describe here the trainable trajectory formation model that will be used for the LIPS'2008 challenge organized at InterSpeech'2008. It predicts articulatory trajectories of a talking face from phonetic input. It basically uses HMM-based synthesis but asynchrony between acoustic and gestural boundaries - taking for example into account non audible anticipatory gestures - is handled by a phasing model that predicts the delays between the acoustic boundaries of allopho...

  17. Asset transformation and the challenges to servitize a utility business model

    International Nuclear Information System (INIS)

    Helms, Thorsten


    The traditional energy utility business model is under pressure, and energy services are expected to play an important role for the energy transition. Experts and scholars argue that utilities need to innovate their business models, and transform from commodity suppliers to service providers. The transition from a product-oriented, capital-intensive business model based on tangible assets, towards a service-oriented, expense-intensive business model based on intangible assets may present great managerial and organizational challenges. Little research exists about such transitions for capital-intensive commodity providers, and particularly energy utilities, where the challenges to servitize are expected to be greatest. This qualitative paper explores the barriers to servitization within selected Swiss and German utility companies through a series of interviews with utility managers. One of them is ‘asset transformation’, the shift from tangible to intangible assets as major input factor for the value proposition, which is proposed as a driver for the complexity of business model transitions. Managers need to carefully manage those challenges, and find ways to operate both new service and established utility business models aside. Policy makers can support the transition of utilities through more favorable regulatory frameworks for energy services, and by supporting the exchange of knowledge in the industry. - Highlights: •The paper analyses the expected transformation of utilities into service-providers. •Service and utility business models possess very different attributes. •The former is based on intangible, the latter on tangible assets. •The transformation into a service-provider is related with great challenges. •Asset transformation is proposed as a barrier for business model innovation.

  18. Understanding, modeling and predicting weather and climate extremes: Challenges and opportunities

    Directory of Open Access Journals (Sweden)

    Jana Sillmann


    Full Text Available Weather and climate extremes are identified as major areas necessitating further progress in climate research and have thus been selected as one of the World Climate Research Programme (WCRP Grand Challenges. Here, we provide an overview of current challenges and opportunities for scientific progress and cross-community collaboration on the topic of understanding, modeling and predicting extreme events based on an expert workshop organized as part of the implementation of the WCRP Grand Challenge on Weather and Climate Extremes. In general, the development of an extreme event depends on a favorable initial state, the presence of large-scale drivers, and positive local feedbacks, as well as stochastic processes. We, therefore, elaborate on the scientific challenges related to large-scale drivers and local-to-regional feedback processes leading to extreme events. A better understanding of the drivers and processes will improve the prediction of extremes and will support process-based evaluation of the representation of weather and climate extremes in climate model simulations. Further, we discuss how to address these challenges by focusing on short-duration (less than three days and long-duration (weeks to months extreme events, their underlying mechanisms and approaches for their evaluation and prediction.

  19. Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment. (United States)

    DeYoung, Dustin Z; Heinzerling, Keith G; Swanson, Aimee-Noelle; Tsuang, John; Furst, Benjamin A; Yi, Yi; Wu, Ying Nian; Moody, David E; Andrenyak, David M; Shoptaw, Steven J


    Methamphetamine dependence is a significant public health concern without any approved medications for treatment. We evaluated ibudilast, a nonselective phosphodiesterase inhibitor, to assess the safety and tolerability during intravenous methamphetamine administration. We conducted a randomized, double-blind, placebo-controlled, within-subjects crossover clinical trial. Participants received ibudilast (20 mg twice daily followed by 50 mg twice daily) and placebo, with order determined by randomization, and then underwent intravenous methamphetamine challenges (15 and 30 mg). We monitored cardiovascular effects, methamphetamine pharmacokinetics, and reported adverse events. Ibudilast treatment had similar rates of adverse events compared with placebo, and there was no significant augmentation of cardiovascular effects of methamphetamine. Pharmacokinetic analysis revealed no clinically significant change in maximum concentration or half-life of methamphetamine with ibudilast. Methamphetamine administration during ibudilast treatment was well tolerated without additive cardiovascular effects or serious adverse events, providing initial safety data to pursue ibudilast's effectiveness for the treatment of methamphetamine dependence.

  20. Measurement of cerebral blood flow by intravenous xenon-133 technique and a mobile system. Reproducibility using the Obrist model compared to total curve analysis

    DEFF Research Database (Denmark)

    Schroeder, T; Holstein, P; Lassen, N A


    was considerably more reproducible than CBF level. Using a single detector instead of five regional values averaged as the hemispheric flow increased standard deviation of CBF level by 10-20%, while the variation in asymmetry was doubled. In optimal measuring conditions the two models revealed no significant...... differences, but in low flow situations the artifact model yielded significantly more stable results. The present apparatus, equipped with 3-5 detectors covering each hemisphere, offers the opportunity of performing serial CBF measurements in situations not otherwise feasible.......The recent development of a mobile 10 detector unit, using i.v. Xenon-133 technique, has made it possible to perform repeated bedside measurements of cerebral blood flow (CBF). Test-retest studies were carried out in 38 atherosclerotic subjects, in order to evaluate the reproducibility of CBF level...

  1. Influence of intravenously administered lidocaine on cerebral blood flow in a baboon model standardized under controlled general anaesthesia using single-photon emission tomography and technetium-99m hexamethylpropylene amine oxime

    Energy Technology Data Exchange (ETDEWEB)

    Dormehl, I.C. (AEC Inst. for Life Sciences, Pretoria Univ. (South Africa)); Lipp, M.D.W. (Klinik fuer Anaesthesiologie, Johannes Gutenberg Univ., Mainz (Germany)); Hugo, N. (AEC Inst. for Life Sciences, Pretoria Univ. (South Africa)); Daublaender, M. (Stadtkrankenhaus Landau, Abt. fuer Mund-, Kiefer- und Gesichtschirurgie (Germany)); Picard, J.A. (H.A. Grove Research Centre, Pretoria (South Africa))


    The baboon under general anaesthesia as a model to assess druginduced cerebral blood flow changes ([Delta] CBF) using single-photon emission tomography (SPET) offers great in vivo possibilities but has to comply with demands on control of anaestesia-related influencing factors, such as P[sub a]CO[sub 2] changes. The model sought in this study and described here allows control of P[sub a]CO[sub 2], in the baboon under thiopentone anaesthesia by ventilation, and was evaluated for the functioal dependence of [Delta] CBF vs [Delta] P[sub a]CO[sub 2], using SPET technetium-99m hexamethylpropylene amine oxime (HMPAO) and the split-dose method together with controlled ventilation. During the experiment the model was validated for normal reactivity to P[sub a]CO[sub 2] changes, and subsequently applied to investigate the mechanisms (still uncertain) of CBF increase known to follow administration of the local anaesthetic lidocaine. Six baboons received 6 mg/kg lidocaine intravenously. CBF was measured between two consecutive SPET acquisitions (split-dose method) respectively relating to HMPAO distributions in the brain before and after the injection of lidocaine. Meanwhile the animals were maintained at constant respiratory rate and volume. The results indicate that the correlation between D CBF and the ensuing fall in P[sub a]CO[sub 2] deviated from the baseline pattern from the model and confirmed a cerebrovascular contribution to the lidocaine-induced CBF increase. This agreed well with mean and systolic blood pressure changes and heart rate. (orig.)

  2. Capacity of the manufacturing process of Flebogamma(®) DIF, a new human high purity intravenous immunoglobulin, to remove a TSE model-agent. (United States)

    Diez, José M; Caballero, Santiago; Belda, Francisco; Otegui, Magdalena; Gajardo, Rodrigo; Jorquera, Juan I


    The variant Creutfeldt-Jakob disease (vCJD) is a transmissible spongiform encephalopathy (TSE) associated with the ingestion of cattle derived products affected with bovine spongiform encephalopathy. vCJD emerged in the UK, where most of the cases occurred (170 of 217 cases worldwide). Manufacturers of biological products must investigate the ability of their production processes to remove TSE agents. Two manufacturing steps (polyethylene glycol-PEG precipitation and nanofiltration down to 20 nm) of Flebogamma(®) DIF, were evaluated by western blot and bioassay to measure the prion protein (PrP(Sc)) and infectivity clearance capacity, respectively. A laboratory scale model representative of the industrial process and a (experimentally) spiked TSE model-agent (hamster scrapie strain 263 K) were employed. Both steps showed a significant capacity to clear the TSE model-agent used since no PrP(Sc) signal or infectivity was detected in the resulting product of each step. PEG precipitation and nanofiltration provided reduction factors of ≥6.19 log(10)ID(50) and ≥5.45 log(10)ID(50) respectively. Both steps showed consistency between western blot and bioassay results. These results demonstrate the ability of the Flebogamma(®) DIF manufacturing process to clear TSE agents beyond the limit of detection of the assays, by several orders of magnitude. Copyright © 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

  3. Comparison of the Intraperitoneal, Retroorbital and per Oral Routes for F 18 FDG Administration as Effective Alternatives to Intravenous Administration in Mouse Tumor Models Using Small Animal PET/CT Studies

    International Nuclear Information System (INIS)

    Kim, Chulhan; Kim, In Hye; Kim, Seo il; Kim, Young Sang; Kang, Se Hun; Moon, Seung Hwan; Kim, Tae Sung; Kim, Seok ki


    We compared alternative routes for 18F fluorodeoxyglucose (FDG) administration, such as the retroorbital (RO), intraperitoneal (IP) and per oral (PO) routes, with the intravenous (IV) route in normal tissues and tumors of mice. CRL 1642 (ATCC, Lewis lung carcinoma) cells were inoculated in female BALB/c nu/nu mice 6 to 10 weeks old. When the tumor grew to about 9mm in diameter, positron emission tomography (PET) scans were performed after FDG administration via the RO, IP, PO or IV route. Additional serial PET scans were performed using the RO, IV or IP route alternatively from 5 to 29 days after the tumor cell injection. There was no significant difference in the FDG uptake in normal tissues at 60 min after FDG administration via RO, IP and IV routes. PO administration, however, showed delayed distribution and unwanted high gastrointestinal uptake. Tumoral uptake of FDG showed a similar temporal pattern and increased until 60 min after FDG administration in the RO, IP and IV injection groups. In the PO administration group, tumoral uptake was delayed and reduced. There was no statistical difference among the RO, IP and IV administration groups for additional serial PET scans. RO administration is an effective alternative route to IV administration for mouse FDG PET scans using normal mice and tumor models. In addition, IP administration can be a practical alternative in the late phase, although the initial uptake is lower than those in the IV and RO groups.

  4. Challenges in land model representation of heat transfer in snow and frozen soils (United States)

    Musselman, K. N.; Clark, M. P.; Nijssen, B.; Arnold, J.


    Accurate model simulations of soil thermal and moisture states are critical for realistic estimates of exchanges of energy, water, and biogeochemical fluxes at the land-atmosphere interface. In cold regions, seasonal snow-cover and organic soils form insulating barriers, modifying the heat and moisture exchange that would otherwise occur between mineral soils and the atmosphere. The thermal properties of these media are highly dynamic functions of mass, water and ice content. Land surface models vary in their representation of snow and soil processes, and thus in the treatment of insulation and heat exchange. For some models, recent development efforts have improved representation of heat transfer in cold regions, such as with multi-layer snow treatment, inclusion of soil freezing and organic soil properties, yet model deficiencies remain prevalent. We evaluate models that participated in the Protocol for the Analysis of Land Surface Models (PALS) Land Surface Model Benchmarking Evaluation Project (PLUMBER) experiment for proficiency in simulating heat transfer between the soil through the snowpack to the atmosphere. Using soil observations from cold region sites and a controlled experiment with Structure for Unifying Multiple Modeling Alternatives (SUMMA), we explore the impact of snow and soil model decisions and parameter values on heat transfer model skill. Specifically, we use SUMMA to mimic the spread of behaviors exhibited by the models that participated in PLUMBER. The experiment allows us to isolate relationships between model skill and process representation. The results are aimed to better understand existing model challenges and identify potential advances for cold region models.

  5. Next-Generation Climate Modeling Science Challenges for Simulation, Workflow and Analysis Systems (United States)

    Koch, D. M.; Anantharaj, V. G.; Bader, D. C.; Krishnan, H.; Leung, L. R.; Ringler, T.; Taylor, M.; Wehner, M. F.; Williams, D. N.


    We will present two examples of current and future high-resolution climate-modeling research that are challenging existing simulation run-time I/O, model-data movement, storage and publishing, and analysis. In each case, we will consider lessons learned as current workflow systems are broken by these large-data science challenges, as well as strategies to repair or rebuild the systems. First we consider the science and workflow challenges to be posed by the CMIP6 multi-model HighResMIP, involving around a dozen modeling groups performing quarter-degree simulations, in 3-member ensembles for 100 years, with high-frequency (1-6 hourly) diagnostics, which is expected to generate over 4PB of data. An example of science derived from these experiments will be to study how resolution affects the ability of models to capture extreme-events such as hurricanes or atmospheric rivers. Expected methods to transfer (using parallel Globus) and analyze (using parallel "TECA" software tools) HighResMIP data for such feature-tracking by the DOE CASCADE project will be presented. A second example will be from the Accelerated Climate Modeling for Energy (ACME) project, which is currently addressing challenges involving multiple century-scale coupled high resolution (quarter-degree) climate simulations on DOE Leadership Class computers. ACME is anticipating production of over 5PB of data during the next 2 years of simulations, in order to investigate the drivers of water cycle changes, sea-level-rise, and carbon cycle evolution. The ACME workflow, from simulation to data transfer, storage, analysis and publication will be presented. Current and planned methods to accelerate the workflow, including implementing run-time diagnostics, and implementing server-side analysis to avoid moving large datasets will be presented.

  6. Addressing current challenges in cancer immunotherapy with mathematical and computational modelling. (United States)

    Konstorum, Anna; Vella, Anthony T; Adler, Adam J; Laubenbacher, Reinhard C


    The goal of cancer immunotherapy is to boost a patient's immune response to a tumour. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumour microenvironment, immune-modulating effects of conventional treatments and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modelling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumour classification, optimal treatment scheduling and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modellers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumour-immune biology. We conclude the review with recommendations for modellers both with respect to methodology and biological direction that might help keep modellers at the forefront of cancer immunotherapy development. © 2017 The Author(s).

  7. Intravenous Therapy: Hazards, Complications and Their Prevention ...

    African Journals Online (AJOL)

    In this review article, the local and systemic complications of intravenous therapy are highlighted and their preventive measures are discussed. Intravenous therapy exposes the patient to numerous hazards and many of them are avoidable, if the health care provider understands the risks involved and acts appropriately and ...

  8. Intentional intravenous mercury injection | Yudelowitz | South African ...

    African Journals Online (AJOL)

    Intravenous mercury injection is rarely seen, with few documented cases. Treatment strategies are not clearly defined for such cases, although a few options do show benefit. This case report describes a 29-year-old man suffering from bipolar disorder, who presented following self-inflicted intravenous injection of mercury.

  9. Intravenous immunoglobulin prophylaxis in neonates on artificial ...

    African Journals Online (AJOL)

    The efficacy of the prophylactic use of intravenous immunoglobulin (Ig) was evaluated in a double-blind placebo-controlled trial of 21 pairs of ventilated neonates weighing more than 1 500 g, Each infant received 0.4 g/kglday of intravenous Ig or a similar volume of placebo daily for 5 days. Criteria used to assess the ...

  10. Probabilistic risk assessment of gold nanoparticles after intravenous administration by integrating in vitro and in vivo toxicity with physiologically based pharmacokinetic modeling. (United States)

    Cheng, Yi-Hsien; Riviere, Jim E; Monteiro-Riviere, Nancy A; Lin, Zhoumeng


    This study aimed to conduct an integrated and probabilistic risk assessment of gold nanoparticles (AuNPs) based on recently published in vitro and in vivo toxicity studies coupled to a physiologically based pharmacokinetic (PBPK) model. Dose-response relationships were characterized based on cell viability assays in various human cell types. A previously well-validated human PBPK model for AuNPs was applied to quantify internal concentrations in liver, kidney, skin, and venous plasma. By applying a Bayesian-based probabilistic risk assessment approach incorporating Monte Carlo simulation, probable human cell death fractions were characterized. Additionally, we implemented in vitro to in vivo and animal-to-human extrapolation approaches to independently estimate external exposure levels of AuNPs that cause minimal toxicity. Our results suggest that under the highest dosing level employed in existing animal studies (worst-case scenario), AuNPs coated with branched polyethylenimine (BPEI) would likely induce ∼90-100% cellular death, implying high cytotoxicity compared to risk prediction, and point of departure estimation of AuNP exposure for humans and illustrate an approach that could be applied to other NPs when sufficient data are available.

  11. Addressing challenges in single species assessments via a simple state-space assessment model

    DEFF Research Database (Denmark)

    Nielsen, Anders

    Single-species and age-structured fish stock assessments still remains the main tool for managing fish stocks. A simple state-space assessment model is presented as an alternative to (semi) deterministic procedures and the full parametric statistical catch at age models. It offers a solution...... to some of the key challenges of these models. Compared to the deterministic procedures it solves a list of problems originating from falsely assuming that age classified catches are known without errors and allows quantification of uncertainties of estimated quantities of interest. Compared to full...

  12. Development of patient specific cardiovascular models predicting dynamics in response to orthostatic stress challenges

    DEFF Research Database (Denmark)

    Ottesen, Johnny T.


    Physiological realistic models of the controlled cardiovascular system are constructed and validated against clinical data. Special attention is paid to the control of blood pressure, cerebral blood flow velocity, and heart rate during postural challenges, including sit-to-stand and head-up tilt....... This study describes development of patient specific models, and how sensitivity analysis and nonlinear optimization methods can be used to predict patient specific characteristics when analyzed using experimental data. Finally, we discuss how a given model can be used to understand physiological changes...

  13. Fate of challenge schistosomula in the murine anti-schistosome vaccine model

    International Nuclear Information System (INIS)

    Von Lichtenberg, F.; Correa-Oliveira, R.; Sher, A.


    Mice exposed to irradiated cercariae of Schistosoma mansoni develop a partial resistance to subsequent parasite challenge. In this study the authors utilized histopathologic methods to investigate the fate of both the immunizing and challenge cercariae in C57BL/6J mice. After immunization by percutaneous infection, a large number of the 50 Kr irradiated organisms could be detected in tissue sections of lung. However, as early as 2 weeks after immunization, the majority of these schistosomula apparently had died, leaving residual inflammatory foci. The numbers of these foci then gradually declined during the next 4 weeks of examination. Cercarial challenge of mice vaccinated 4 weeks previously provoked an intense eosinophil-enriched inflammatory response in percutaneously exposed ear pinnae. Despite these pronounced tissue reactions, no evidence of significant parasite damage or attrition was detected in this migration site. In contrast, schistosomula arriving in the lungs of vaccinated mice produced a greater number of residual inflammatory foci than did larvae appearing in the lungs of normal mice. In addition, challenge schistosomula were cleared from the lungs of vaccinated mice at a slower rate than they were from the lungs of control mice. These observations suggest that the lung is a major site of parasite attrition for both immunizing and challenge infections in the mouse irradiated vaccine model

  14. Combining Genetic Circuit and Microbial Growth Kinetic Models: A Challenge for Biological Modelling

    NARCIS (Netherlands)

    Koutinas, M.; Kiparissides, A.; Lam, M.C.; Silva-Rocha, R.; Lorenzo, de V.; Martins Dos Santos, V.A.P.; Pistikopoulos, E.N.; Mantalaris, A.


    A modelling framework that consists of model building, validation and analysis, leading to model-based design of experiments and to the application of optimisation-based model-predictive control strategies for the development of optimised bioprocesses is presented. An example of this framework is

  15. Challenges and Advances for Genetic Engineering of Non-model Bacteria and Uses in Consolidated Bioprocessing

    Directory of Open Access Journals (Sweden)

    Qiang Yan


    Full Text Available Metabolic diversity in microorganisms can provide the basis for creating novel biochemical products. However, most metabolic engineering projects utilize a handful of established model organisms and thus, a challenge for harnessing the potential of novel microbial functions is the ability to either heterologously express novel genes or directly utilize non-model organisms. Genetic manipulation of non-model microorganisms is still challenging due to organism-specific nuances that hinder universal molecular genetic tools and translatable knowledge of intracellular biochemical pathways and regulatory mechanisms. However, in the past several years, unprecedented progress has been made in synthetic biology, molecular genetics tools development, applications of omics data techniques, and computational tools that can aid in developing non-model hosts in a systematic manner. In this review, we focus on concerns and approaches related to working with non-model microorganisms including developing molecular genetics tools such as shuttle vectors, selectable markers, and expression systems. In addition, we will discuss: (1 current techniques in controlling gene expression (transcriptional/translational level, (2 advances in site-specific genome engineering tools [homologous recombination (HR and clustered regularly interspaced short palindromic repeats (CRISPR], and (3 advances in genome-scale metabolic models (GSMMs in guiding design of non-model species. Application of these principles to metabolic engineering strategies for consolidated bioprocessing (CBP will be discussed along with some brief comments on foreseeable future prospects.

  16. Challenges and Advances for Genetic Engineering of Non-model Bacteria and Uses in Consolidated Bioprocessing (United States)

    Yan, Qiang; Fong, Stephen S.


    Metabolic diversity in microorganisms can provide the basis for creating novel biochemical products. However, most metabolic engineering projects utilize a handful of established model organisms and thus, a challenge for harnessing the potential of novel microbial functions is the ability to either heterologously express novel genes or directly utilize non-model organisms. Genetic manipulation of non-model microorganisms is still challenging due to organism-specific nuances that hinder universal molecular genetic tools and translatable knowledge of intracellular biochemical pathways and regulatory mechanisms. However, in the past several years, unprecedented progress has been made in synthetic biology, molecular genetics tools development, applications of omics data techniques, and computational tools that can aid in developing non-model hosts in a systematic manner. In this review, we focus on concerns and approaches related to working with non-model microorganisms including developing molecular genetics tools such as shuttle vectors, selectable markers, and expression systems. In addition, we will discuss: (1) current techniques in controlling gene expression (transcriptional/translational level), (2) advances in site-specific genome engineering tools [homologous recombination (HR) and clustered regularly interspaced short palindromic repeats (CRISPR)], and (3) advances in genome-scale metabolic models (GSMMs) in guiding design of non-model species. Application of these principles to metabolic engineering strategies for consolidated bioprocessing (CBP) will be discussed along with some brief comments on foreseeable future prospects. PMID:29123506

  17. Challenges of the expansive use of Building Information Modeling (BIM in construction projects

    Directory of Open Access Journals (Sweden)

    Hannele Kerosuo


    Full Text Available Building information modeling (BIM is an emerging modeling technology which challenges existing work procedures and practices in the construction industry. In this article we study the challenges, problems and potential expansions of BIM as a tool in the design, construction and operation of buildings. For this purpose the interfaces between different parties are examined in Finnish construction projects. The methodological approach of the study is cultural-historical activity theory, according to which a new artifact becomes a mediating instrument when the participatory subjects reconfigure the entire activity. The implementation of BIM is now spreading from the design activity to other phases of the construction projects, but its use is still limited in the projects' other three interfaces. BIM is an evolving set of software developed for various purposes which is locally 'combined' to fit the circumstances and capabilities of the stakeholders of the construction process.

  18. Development of Rainfall-runoff Model Using Tank Model: Problems and Challenges in Province of Aceh, Indonesia

    Directory of Open Access Journals (Sweden)

    Hairul Basri


    Full Text Available Rainfall-runoff model using tank model founded by Sugawara has been widely used in Asia. Many researchers use the tank model to predict water availability and flooding in a watershed. This paper describes the concept of rainfall-runoff model using tank model, discuss the problems and challenges in using of the model, especially in Province of Aceh, Indonesia and how to improve the outcome of simulation of tank model. Many factors affect the rainfall-runoff phenomena of a wide range of watershed include: soil types, land use types, rainfall, morphometry, geology and geomorphology, caused the tank model usefull only for concerning watershed. It is necessary to adjust some parameters of tank model for other watershed by recalibrating the parameters of the model. Rainfall runoff model using the tank model for a watershed scale is more reasonable focused on each sub-watershed by considering soil types, land use types and rainfall of the concerning watershed. Land use data can be enhanced by using landsat imagery or aerial photographs to support the validation the existing of land use type. Long term of observed discharges and rainfall data should be increased by set up the AWLR (Automatic Water Level Recorder and rainfall stations for each of sub-watersheds. The reasonable tank model can be resulted not only by calibrating the parameters, but also by considering the observed and simulated infiltration for each soil and land use types of the concerning watershed

  19. Evaluation of blood-brain barrier transport and CNS drug metabolism in diseased and control brain after intravenous L-DOPA in a unilateral rat model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Ravenstijn Paulien GM


    Full Text Available Abstract Background Changes in blood-brain barrier (BBB functionality have been implicated in Parkinson's disease. This study aimed to investigate BBB transport of L-DOPA transport in conjunction with its intra-brain conversion, in both control and diseased cerebral hemispheres in the unilateral rat rotenone model of Parkinson's disease. Methods In Lewis rats, at 14 days after unilateral infusion of rotenone into the medial forebrain bundle, L-DOPA was administered intravenously (10, 25 or 50 mg/kg. Serial blood samples and brain striatal microdialysates were analysed for L-DOPA, and the dopamine metabolites DOPAC and HVA. Ex-vivo brain tissue was analyzed for changes in tyrosine hydroxylase staining as a biomarker for Parkinson's disease severity. Data were analysed by population pharmacokinetic analysis (NONMEM to compare BBB transport of L-DOPA in conjunction with the conversion of L-DOPA into DOPAC and HVA, in control and diseased cerebral hemisphere. Results Plasma pharmacokinetics of L-DOPA could be described by a 3-compartmental model. In rotenone responders (71%, no difference in L-DOPA BBB transport was found between diseased and control cerebral hemisphere. However, in the diseased compared with the control side, basal microdialysate levels of DOPAC and HVA were substantially lower, whereas following L-DOPA administration their elimination rates were higher. Conclusions Parkinson's disease-like pathology, indicated by a huge reduction of tyrosine hydroxylase as well as by substantially reduced levels and higher elimination rates of DOPAC and HVA, does not result in changes in BBB transport of L-DOPA. Taking the results of this study and that of previous ones, it can be concluded that changes in BBB functionality are not a specific characteristic of Parkinson's disease, and cannot account for the decreased benefit of L-DOPA at later stages of Parkinson's disease.



    Mohammed A.KA. AL-Btoush*, Ahmad Tarmizi Haron


    Construction companies are faced with the need to innovatively integrate the construction process and address project development challenges. One way of doing that is the integration of building information modelling (BIM) in the building design and development cycles. However, due to the lack of clear understanding and the absence of a holistic implementation guideline, many companies are unable to fully achieve BIM potentials or implement BIM in their project and building lifecycle. BIM imp...

  1. Usage, Potentials and Challenges of Building Information Modelling (BIM) in Slovenia, Austria, Germany and Switzerland


    Jus, Amanda


    In the master’s thesis, the main potentials, challenges and usage of Information Building Modelling (BIM) in Slovenia, Austria, Germany and Switzerland are presented, including its, because BIM is currently the most widely discussed topic in civil engineering. The study was based on a questionnaire that was carefully created at the HSLU (Hochschule Luzern) in Switzerland. We participated in the last phases of its development. With the help of the results of the questionnaire, we evaluated ...

  2. Challenges in Computational Social Modeling and Simulation for National Security Decision Making (United States)


    may literally be dealing with life-and- death challenges. Finally, no model or simulation is inherently a “decision support tool;” instead, tool... semiotics . In her paper, Resnyansky argues that the rapid rise of information and communications technologies has raised significant ethical 20...Dynamics in Human and Primate Societies, T. Koehler and G. Gumerman, Eds. New York: Oxford University Press, 2000. [20] P. Ormerod, The Death of

  3. An Anti-Nicotinic Cognitive Challenge Model using Mecamylamine in Comparison with the Anti-Muscarinic Cognitive Challenge using Scopolamine

    NARCIS (Netherlands)

    Baakman, A. C.; Alvarez-jimenez, R.; Rissmann, R.; Klaassen, E. S.; Stevens, J.; Goulooze, S. C.; Burger, J.; Swart, E. L.; Van Gerven, J. M. A.; Groeneveld, G. J.

    Aims The muscarinic acetylcholine receptor antagonist scopolamine is often used for proof-of-pharmacology studies with pro-cognitive compounds. From a pharmacological point of view, it would seem more rational to use a nicotinic rather than a muscarinic anticholinergic challenge to prove

  4. The evolution of process-based hydrologic models: historical challenges and the collective quest for physical realism

    Directory of Open Access Journals (Sweden)

    M. P. Clark


    Full Text Available The diversity in hydrologic models has historically led to great controversy on the correct approach to process-based hydrologic modeling, with debates centered on the adequacy of process parameterizations, data limitations and uncertainty, and computational constraints on model analysis. In this paper, we revisit key modeling challenges on requirements to (1 define suitable model equations, (2 define adequate model parameters, and (3 cope with limitations in computing power. We outline the historical modeling challenges, provide examples of modeling advances that address these challenges, and define outstanding research needs. We illustrate how modeling advances have been made by groups using models of different type and complexity, and we argue for the need to more effectively use our diversity of modeling approaches in order to advance our collective quest for physically realistic hydrologic models.

  5. Numerical Modeling of Climate-Chemistry Connections: Recent Developments and Future Challenges

    Directory of Open Access Journals (Sweden)

    Patrick Jöckel


    Full Text Available This paper reviews the current state and development of different numerical model classes that are used to simulate the global atmospheric system, particularly Earth’s climate and climate-chemistry connections. The focus is on Chemistry-Climate Models. In general, these serve to examine dynamical and chemical processes in the Earth atmosphere, their feedback, and interaction with climate. Such models have been established as helpful tools in addition to analyses of observational data. Definitions of the global model classes are given and their capabilities as well as weaknesses are discussed. Examples of scientific studies indicate how numerical exercises contribute to an improved understanding of atmospheric behavior. There, the focus is on synergistic investigations combining observations and model results. The possible future developments and challenges are presented, not only from the scientific point of view but also regarding the computer technology and respective consequences for numerical modeling of atmospheric processes. In the future, a stronger cross-linkage of subject-specific scientists is necessary, to tackle the looming challenges. It should link the specialist discipline and applied computer science.

  6. Challenges in Soft Computing: Case Study with Louisville MSD CSO Modeling (United States)

    Ormsbee, L.; Tufail, M.


    The principal constituents of soft computing include fuzzy logic, neural computing, evolutionary computation, machine learning, and probabilistic reasoning. There are numerous applications of these constituents (both individually and combination of two or more) in the area of water resources and environmental systems. These range from development of data driven models to optimal control strategies to assist in more informed and intelligent decision making process. Availability of data is critical to such applications and having scarce data may lead to models that do not represent the response function over the entire domain. At the same time, too much data has a tendency to lead to over-constraining of the problem. This paper will describe the application of a subset of these soft computing techniques (neural computing and genetic algorithms) to the Beargrass Creek watershed in Louisville, Kentucky. The application include development of inductive models as substitutes for more complex process-based models to predict water quality of key constituents (such as dissolved oxygen) and use them in an optimization framework for optimal load reductions. Such a process will facilitate the development of total maximum daily loads for the impaired water bodies in the watershed. Some of the challenges faced in this application include 1) uncertainty in data sets, 2) model application, and 3) development of cause-and-effect relationships between water quality constituents and watershed parameters through use of inductive models. The paper will discuss these challenges and how they affect the desired goals of the project.

  7. Model-based nonlinear control of hydraulic servo systems: Challenges, developments and perspectives (United States)

    Yao, Jianyong


    Hydraulic servo system plays a significant role in industries, and usually acts as a core point in control and power transmission. Although linear theory-based control methods have been well established, advanced controller design methods for hydraulic servo system to achieve high performance is still an unending pursuit along with the development of modern industry. Essential nonlinearity is a unique feature and makes model-based nonlinear control more attractive, due to benefit from prior knowledge of the servo valve controlled hydraulic system. In this paper, a discussion for challenges in model-based nonlinear control, latest developments and brief perspectives of hydraulic servo systems are presented: Modelling uncertainty in hydraulic system is a major challenge, which includes parametric uncertainty and time-varying disturbance; some specific requirements also arise ad hoc difficulties such as nonlinear friction during low velocity tracking, severe disturbance, periodic disturbance, etc.; to handle various challenges, nonlinear solutions including parameter adaptation, nonlinear robust control, state and disturbance observation, backstepping design and so on, are proposed and integrated, theoretical analysis and lots of applications reveal their powerful capability to solve pertinent problems; and at the end, some perspectives and associated research topics (measurement noise, constraints, inner valve dynamics, input nonlinearity, etc.) in nonlinear hydraulic servo control are briefly explored and discussed.

  8. Intravenous adenosine SPECT thallium imaging

    International Nuclear Information System (INIS)

    Joyce, J.M.; Grossman, S.J.; Garrett, J.S.; Sharma, B.; Geller, M.; Sweeney, P.J.


    This paper determines the safety and efficacy of intravenous (IV) adenosine in females for the evaluation of coronary artery disease, since only limited data are available. Eighty consecutive studies of 78 female subjects (aged 43-83 years) using IV adenosine (0.14 mg/kg per minute) with T1-201 SPECT imaging were reviewed. Fifty-eight (73%) had mild symptoms; mild dyspnea (24%), flushing (23%), chest pain (23%), headache (11%), dizziness (11%), weakness (9%), nausea (8%), abdominal pain (8%), arm pain (6%), chest tightness (4%), neck tightness (4%), dry mouth (4%), and dropped P waves (4%). Four had moderate symptoms: dyspnea requiring Proventil or aminophylline (2%), significant hypotension (1%), and third-degree atrioventicular heart block (1%). Two had severe symptoms (ventricular tachycardia requiring cardioversion (1%) and severe dyspnea requiring epinephrine (1%). Twenty-two (28%) underwent cardiac catheterization that demonstrated coronary artery disease or postangioplasty results. The thallium SPECT images were 94% sensitive and 100% specific in detecting significant disease. The one false-negative result was in a subject who experienced no symptoms for ECG changes during adenosine infusion. Ischemic ECG changes were 35% sensitive and 100% specific. Chest pain was 53% sensitive and 60% specific

  9. A novel porcine model of ventilator-associated pneumonia caused by oropharyngeal challenge with Pseudomonas aeruginosa. (United States)

    Li Bassi, Gianluigi; Rigol, Montserrat; Marti, Joan-Daniel; Saucedo, Lina; Ranzani, Otavio T; Roca, Ignasi; Cabanas, Maria; Muñoz, Laura; Giunta, Valeria; Luque, Nestor; Rinaudo, Mariano; Esperatti, Mariano; Fernandez-Barat, Laia; Ferrer, Miquel; Vila, Jordi; Ramirez, Jose; Torres, Antoni


    Animal models of ventilator-associated pneumonia (VAP) in primates, sheep, and pigs differ in the underlying pulmonary injury, etiology, bacterial inoculation methods, and time to onset. The most common ovine and porcine models do not reproduce the primary pathogenic mechanism of the disease, through the aspiration of oropharyngeal pathogens, or the most prevalent human etiology. Herein the authors characterize a novel porcine model of VAP due to aspiration of oropharyngeal secretions colonized by Pseudomonas aeruginosa. Ten healthy pigs were intubated, positioned in anti-Trendelenburg, and mechanically ventilated for 72 h. Three animals did not receive bacterial challenge, whereas in seven animals, a P. aeruginosa suspension was instilled into the oropharynx. Tracheal aspirates were cultured and respiratory mechanics were recorded. On autopsy, lobar samples were obtained to corroborate VAP through microbiological and histological studies. In animals not challenged, diverse bacterial colonization of the airways was found and monolobar VAP rarely developed. In animals with P. aeruginosa challenge, colonization of tracheal secretion increased up to 6.39 ± 0.34 log colony-forming unit (cfu)/ml (P VAP was confirmed in six of seven pigs, in 78% of the cases developed in the dependent lung segments (right medium and lower lobes, P = 0.032). The static respiratory system elastance worsened to 41.5 ± 5.8 cm H2O/l (P = 0.001). The authors devised a VAP model caused by aspiration of oropharyngeal P. aeruginosa, a frequent causative pathogen of human VAP. The model also overcomes the practical and legislative limitations associated with the use of primates. The authors' model could be employed to study pathophysiologic mechanisms, as well as novel diagnostic/preventive strategies.

  10. The big challenges in modeling human and environmental well-being. (United States)

    Tuljapurkar, Shripad


    This article is a selective review of quantitative research, historical and prospective, that is needed to inform sustainable development policy. I start with a simple framework to highlight how demography and productivity shape human well-being. I use that to discuss three sets of issues and corresponding challenges to modeling: first, population prehistory and early human development and their implications for the future; second, the multiple distinct dimensions of human and environmental well-being and the meaning of sustainability; and, third, inequality as a phenomenon triggered by development and models to examine changing inequality and its consequences. I conclude with a few words about other important factors: political, institutional, and cultural.

  11. Challenges in Slug Modeling and Control for Offshore Oil and Gas Productions

    DEFF Research Database (Denmark)

    Pedersen, Simon; Løhndorf, Petar Durdevic; Yang, Zhenyu


    The upstream offshore multi-phase well-pipeline-riser installations are facing huge challenges related to slugging flow: An unstable flow regime where the flow rates, pressures and temperatures oscillate in the multi-phase pipelines. One typical severe slug is induced by vertical wells or risers...... the state-of-the-art related to analysis, detection, dynamical modeling and elimination of the slug within the offshore oil & gas Exploration and Production (E&P) processes. Modeling of slugging flow has been used to investigate the slug characteristics and for design of anti-slug control as well, however...

  12. In vivo models in breast cancer research: progress, challenges and future directions

    Directory of Open Access Journals (Sweden)

    Ingunn Holen


    Full Text Available Research using animal model systems has been instrumental in delivering improved therapies for breast cancer, as well as in generating new insights into the mechanisms that underpin development of the disease. A large number of different models are now available, reflecting different types and stages of the disease; choosing which one to use depends on the specific research question(s to be investigated. Based on presentations and discussions from leading experts who attended a recent workshop focused on in vivo models of breast cancer, this article provides a perspective on the many varied uses of these models in breast cancer research, their strengths, associated challenges and future directions. Among the questions discussed were: how well do models represent the different stages of human disease; how can we model the involvement of the human immune system and microenvironment in breast cancer; what are the appropriate models of metastatic disease; can we use models to carry out preclinical drug trials and identify pathways responsible for drug resistance; and what are the limitations of patient-derived xenograft models? We briefly outline the areas where the existing breast cancer models require improvement in light of the increased understanding of the disease process, reflecting the drive towards more personalised therapies and identification of mechanisms of drug resistance.

  13. A History of Intravenous Anesthesia in War (1656-1988). (United States)

    Roberts, Matthew; Jagdish, S


    The practice of anesthesia in war places significant restraints on the choice of anesthetic technique used; these include, but are not limited to, safety, simplicity, and portability. Ever since intravenous anesthesia became a practical alternative, there have been military doctors who felt that this technique was particularly suited to this environment. The challenge, as in civilian practice, has been to find the appropriate drugs as well as simple and safe delivery systems. The urgency of war has always stimulated innovation in medicine to counteract the ongoing development of weapons of war and their effects on the human body and to achieve improved survival as public expectations rise. This article traces the development of and the use of intravenous anesthesia by military physicians for battle casualties. The story starts long before the era of modern anesthesia, and the discussion concludes in the dog days of the cold war. The rapidly increasing interest in intravenous anesthesia in both civilian and military practice since the early 1990s is left for other authors to examine. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Efficacy and Tolerability of Intravenous Levetiracetam in Children

    Directory of Open Access Journals (Sweden)

    Jose eAceves


    Full Text Available Intractable epilepsy in children poses a serious medical challenge. Acute repetitive seizures and status epilepticus leads to frequent emergency room visits and hospital admissions. Permanent neurological damage can occur if there is delay in treatment. It has been shown that these children continue to remain intractable even after acute seizure management with approved FDA agents. Intravenous levetiracetam, a second-generation anticonvulsant was approved by the FDA in 2006 in patients 16 years and older as an alternative when oral treatment is not an option. It has been shown that oral levetiracetam can be used in the treatment of status epilepticus and acute repetitive seizures. Data have been published showing that intravenous levetiracetam is safe and efficacious, and can be used in an acute inpatient setting. This current review will discuss the recent data about the safety and tolerability of intravenous levetiracetam in children and neonates, and emphasize the need for a larger prospective multicenter trial to prove the efficacy of this agent in acute seizure management.

  15. Entering new fields of simulation application - challenges faced in simulation modelling of stroke systems

    NARCIS (Netherlands)

    van der Zee, D.J.; Monks, T.; Lahr, Maarten; Luijckx, Gert Jan; Buskens, Erik; Anagnostou, Anastasia; Hoad, Katy; Kunc, Martin


    Stroke is a major cause of death and long-term disability world-wide. To improve functional outcome treatment with intravenous tissue plasminogen activator (tPA) is the most effective medical treatment for acute brain infarction within 4.5 hours after the onset of stroke symptoms. Unfortunately, tPA

  16. Using natural selection and optimization for smarter vegetation models - challenges and opportunities (United States)

    Franklin, Oskar; Han, Wang; Dieckmann, Ulf; Cramer, Wolfgang; Brännström, Åke; Pietsch, Stephan; Rovenskaya, Elena; Prentice, Iain Colin


    Dynamic global vegetation models (DGVMs) are now indispensable for understanding the biosphere and for estimating the capacity of ecosystems to provide services. The models are continuously developed to include an increasing number of processes and to utilize the growing amounts of observed data becoming available. However, while the versatility of the models is increasing as new processes and variables are added, their accuracy suffers from the accumulation of uncertainty, especially in the absence of overarching principles controlling their concerted behaviour. We have initiated a collaborative working group to address this problem based on a 'missing law' - adaptation and optimization principles rooted in natural selection. Even though this 'missing law' constrains relationships between traits, and therefore can vastly reduce the number of uncertain parameters in ecosystem models, it has rarely been applied to DGVMs. Our recent research have shown that optimization- and trait-based models of gross primary production can be both much simpler and more accurate than current models based on fixed functional types, and that observed plant carbon allocations and distributions of plant functional traits are predictable with eco-evolutionary models. While there are also many other examples of the usefulness of these and other theoretical principles, it is not always straight-forward to make them operational in predictive models. In particular on longer time scales, the representation of functional diversity and the dynamical interactions among individuals and species presents a formidable challenge. Here we will present recent ideas on the use of adaptation and optimization principles in vegetation models, including examples of promising developments, but also limitations of the principles and some key challenges.

  17. Scale effect challenges in urban hydrology highlighted with a distributed hydrological model

    Directory of Open Access Journals (Sweden)

    A. Ichiba


    Full Text Available Hydrological models are extensively used in urban water management, development and evaluation of future scenarios and research activities. There is a growing interest in the development of fully distributed and grid-based models. However, some complex questions related to scale effects are not yet fully understood and still remain open issues in urban hydrology. In this paper we propose a two-step investigation framework to illustrate the extent of scale effects in urban hydrology. First, fractal tools are used to highlight the scale dependence observed within distributed data input into urban hydrological models. Then an intensive multi-scale modelling work is carried out to understand scale effects on hydrological model performance. Investigations are conducted using a fully distributed and physically based model, Multi-Hydro, developed at Ecole des Ponts ParisTech. The model is implemented at 17 spatial resolutions ranging from 100 to 5 m. Results clearly exhibit scale effect challenges in urban hydrology modelling. The applicability of fractal concepts highlights the scale dependence observed within distributed data. Patterns of geophysical data change when the size of the observation pixel changes. The multi-scale modelling investigation confirms scale effects on hydrological model performance. Results are analysed over three ranges of scales identified in the fractal analysis and confirmed through modelling. This work also discusses some remaining issues in urban hydrology modelling related to the availability of high-quality data at high resolutions, and model numerical instabilities as well as the computation time requirements. The main findings of this paper enable a replacement of traditional methods of model calibration by innovative methods of model resolution alteration based on the spatial data variability and scaling of flows in urban hydrology.

  18. Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience (United States)

    Huffman, Derek M.; Justice, Jamie N.; Stout, Michael B.; Kirkland, James L.; Barzilai, Nir


    Life extension is no longer considered sufficient evidence of delayed aging in research animals. It must also be demonstrated that a broad swathe of health indicators have been extended. During a retreat of the Geroscience Network, a consortium of basic and clinical aging researchers, potential measures of mouse health were considered for their potential as easily standardized, highly informative metrics. Major health domains considered were neuromuscular, cognitive, cardiovascular, metabolic, and inflammatory functions as well as body composition and energetics and a multitude of assays interrogating these domains. A particularly sensitive metric of health is the ability to respond to, and recover, from stress. Therefore, the Network also considered stresses of human relevance that could be implemented in mouse models to assess frailty and resilience. Mouse models already exist for responses to forced immobility, cancer chemotherapy, infectious diseases, dietary challenges, and surgical stress, and it was felt that these could be employed to determine whether putative senescence-retarding interventions increased and extended organismal robustness. The Network discussed challenges in modeling age-related human chronic diseases and concluded that more attention needs to be paid to developing disease models with later age of onset, models of co- and multimorbidity, diversifying the strains and sexes commonly used in aging research, and considering additional species. PMID:27535967

  19. Modelling of Multi-Agent Systems: Experiences with Membrane Computing and Future Challenges

    Directory of Open Access Journals (Sweden)

    Petros Kefalas


    Full Text Available Formal modelling of Multi-Agent Systems (MAS is a challenging task due to high complexity, interaction, parallelism and continuous change of roles and organisation between agents. In this paper we record our research experience on formal modelling of MAS. We review our research throughout the last decade, by describing the problems we have encountered and the decisions we have made towards resolving them and providing solutions. Much of this work involved membrane computing and classes of P Systems, such as Tissue and Population P Systems, targeted to the modelling of MAS whose dynamic structure is a prominent characteristic. More particularly, social insects (such as colonies of ants, bees, etc., biology inspired swarms and systems with emergent behaviour are indicative examples for which we developed formal MAS models. Here, we aim to review our work and disseminate our findings to fellow researchers who might face similar challenges and, furthermore, to discuss important issues for advancing research on the application of membrane computing in MAS modelling.

  20. GEM-CEDAR Challenge: Poynting Flux at DMSP and Modeled Joule Heat (United States)

    Rastaetter, Lutz; Shim, Ja Soon; Kuznetsova, Maria M.; Kilcommons, Liam M.; Knipp, Delores J.; Codrescu, Mihail; Fuller-Rowell, Tim; Emery, Barbara; Weimer, Daniel R.; Cosgrove, Russell; hide


    Poynting flux into the ionosphere measures the electromagnetic energy coming from the magnetosphere. This energy flux can vary greatly between quiet times and geomagnetic active times. As part of the Geospace Environment Modeling-coupling energetics and dynamics of atmospheric regions modeling challenge, physics-based models of the 3-D ionosphere and ionospheric electrodynamics solvers of magnetosphere models that specify Joule heat and empirical models specifying Poynting flux were run for six geomagnetic storm events of varying intensity. We compared model results with Poynting flux values along the DMSP-15 satellite track computed from ion drift meter and magnetic field observations. Although being a different quantity, Joule heat can in practice be correlated to incoming Poynting flux because the energy is dissipated primarily in high latitudes where Poynting flux is being deposited. Within the physics-based model group, we find mixed results with some models overestimating Joule heat and some models agreeing better with observed Poynting flux rates as integrated over auroral passes. In contrast, empirical models tend to underestimate integrated Poynting flux values. Modeled Joule heat or Poynting flux patterns often resemble the observed Poynting flux patterns on a large scale, but amplitudes can differ by a factor of 2 or larger due to the highly localized nature of observed Poynting flux deposition that is not captured by the models. In addition, the positioning of modeled patterns appear to be randomly shifted against the observed Poynting flux energy input. This study is the first to compare Poynting flux and Joule heat in a large variety of models of the ionosphere.

  1. GEM-CEDAR challenge: Poynting flux at DMSP and modeled Joule heat (United States)

    Rastätter, Lutz; Shim, Ja Soon; Kuznetsova, Maria M.; Kilcommons, Liam M.; Knipp, Delores J.; Codrescu, Mihail; Fuller-Rowell, Tim; Emery, Barbara; Weimer, Daniel R.; Cosgrove, Russell; Wiltberger, Michael; Raeder, Joachim; Li, Wenhui; Tóth, Gábor; Welling, Daniel


    Poynting flux into the ionosphere measures the electromagnetic energy coming from the magnetosphere. This energy flux can vary greatly between quiet times and geomagnetic active times. As part of the Geospace Environment Modeling-coupling energetics and dynamics of atmospheric regions modeling challenge, physics-based models of the 3-D ionosphere and ionospheric electrodynamics solvers of magnetosphere models that specify Joule heat and empirical models specifying Poynting flux were run for six geomagnetic storm events of varying intensity. We compared model results with Poynting flux values along the DMSP-15 satellite track computed from ion drift meter and magnetic field observations. Although being a different quantity, Joule heat can in practice be correlated to incoming Poynting flux because the energy is dissipated primarily in high latitudes where Poynting flux is being deposited. Within the physics-based model group, we find mixed results with some models overestimating Joule heat and some models agreeing better with observed Poynting flux rates as integrated over auroral passes. In contrast, empirical models tend to underestimate integrated Poynting flux values. Modeled Joule heat or Poynting flux patterns often resemble the observed Poynting flux patterns on a large scale, but amplitudes can differ by a factor of 2 or larger due to the highly localized nature of observed Poynting flux deposition that is not captured by the models. In addition, the positioning of modeled patterns appear to be randomly shifted against the observed Poynting flux energy input. This study is the first to compare Poynting flux and Joule heat in a large variety of models of the ionosphere.

  2. Comparison of functional and histological outcomes after intralesional, intracisternal, and intravenous transplantation of human bone marrow-derived mesenchymal stromal cells in a rat model of spinal cord injury. (United States)

    Shin, Dong Ah; Kim, Jin-Myung; Kim, Hyoung-Ihl; Yi, Seong; Ha, Yoon; Yoon, Do Heum; Kim, Keung Nyun


    Few studies have compared methods of stem cell transplantation. The aim of the present study was to determine the optimal method of delivery of therapeutic stem cells in spinal cord injury (SCI). We compared functional and histologic outcomes after administration of human bone marrow stromal cells (BMSCs) by intralesional (ILT), intracisternal (ICT), and intravenous transplantation (IVT). A rat model of spinal cord injury was produced by dropping a 10-g weight, 2 mm in diameter, onto the exposed spinal cords of animals from a height of 25 mm. In each treatment group, 24 animals were randomly assigned for functional assessment and 24 for histologic examination. BMSCs (3 × 10(5), ILT; 1 × 10(6), ICT; 2 × 10(6), IVT) were transplanted 1 week after SCI in numbers determined in previous studies. Basso-Beattie-Bresnahan scoring was performed in all animals weekly for 6 weeks. Spinal cord specimens were obtained from eight animals in each group 2, 4, and 6 weeks after SCI. Viable BMSCs were counted in six sagittal sections from each spinal cord. All three treatment groups showed improved functional recovery compared to controls beginning 2 weeks after stem cell injection (P < 0.01). The ICT group showed the best functional recovery, followed by the ILT and IVT groups, respectively (P < 0.01). Histological analysis showed the largest number of viable BMSCs in the ILT group, followed by the ICT and IVT groups, respectively (P < 0.01). ICT may be the safest and most effective method for delivering stem cells and improving functional outcome in SCI when no limits are placed on the number of cells transplanted. As research on enhancing engraftment rates advances, further improvement of functional outcome can be expected.

  3. Linking Murine and Human Plasmodium falciparum Challenge Models in a Translational Path for Antimalarial Drug Development (United States)

    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


    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 [] under registration number ACTRN12612000323820.) PMID:27044554

  4. Cloud service performance evaluation: status, challenges, and opportunities – a survey from the system modeling perspective

    Directory of Open Access Journals (Sweden)

    Qiang Duan


    Full Text Available With rapid advancement of Cloud computing and networking technologies, a wide spectrum of Cloud services have been developed by various providers and utilized by numerous organizations as indispensable ingredients of their information systems. Cloud service performance has a significant impact on performance of the future information infrastructure. Thorough evaluation on Cloud service performance is crucial and beneficial to both service providers and consumers; thus forming an active research area. Some key technologies for Cloud computing, such as virtualization and the Service-Oriented Architecture (SOA, bring in special challenges to service performance evaluation. A tremendous amount of effort has been put by the research community to address these challenges and exciting progress has been made. Among the work on Cloud performance analysis, evaluation approaches developed with a system modeling perspective play an important role. However, related works have been reported in different sections of the literature; thus lacking a big picture that shows the latest status of this area. The objectives of this article is to present a survey that reflects the state of the art of Cloud service performance evaluation from the system modeling perspective. This articles also examines open issues and challenges to the surveyed evaluation approaches and identifies possible opportunities for future research in this important field.

  5. Advantages and challenges of using physics curricula as a model for reforming an undergraduate biology course. (United States)

    Donovan, D A; Atkins, L J; Salter, I Y; Gallagher, D J; Kratz, R F; Rousseau, J V; Nelson, G D


    We report on the development of a life sciences curriculum, targeted to undergraduate students, which was modeled after a commercially available physics curriculum and based on aspects of how people learn. Our paper describes the collaborative development process and necessary modifications required to apply a physics pedagogical model in a life sciences context. While some approaches were easily adapted, others provided significant challenges. Among these challenges were: representations of energy, introducing definitions, the placement of Scientists' Ideas, and the replicability of data. In modifying the curriculum to address these challenges, we have come to see them as speaking to deeper differences between the disciplines, namely that introductory physics--for example, Newton's laws, magnetism, light--is a science of pairwise interaction, while introductory biology--for example, photosynthesis, evolution, cycling of matter in ecosystems--is a science of linked processes, and we suggest that this is how the two disciplines are presented in introductory classes. We illustrate this tension through an analysis of our adaptations of the physics curriculum for instruction on the cycling of matter and energy; we show that modifications of the physics curriculum to address the biological framework promotes strong gains in student understanding of these topics, as evidenced by analysis of student work.

  6. Ganoderma tsugae supplementation alleviates bronchoalveolar inflammation in an airway sensitization and challenge mouse model. (United States)

    Lin, Jin-Yuarn; Chen, Miaw-Ling; Chiang, Bor-Luen; Lin, Bi-Fong


    Ganoderma tsugae (a Chinese mushroom Songshan lingzhi) cultivated in Taiwan is extensively used in Chinese traditional medicine to treat different diseases. To determine whether G. tsugae has anti-inflammatory effects on bronchoalveolar inflammation in vivo, we investigated the anti-inflammatory effects of G. tsugae products, YK01 and YK07, on bronchoalveolar inflammation using an airway sensitization and challenge mouse model. Female BALB/c mice were weekly sensitized by intraperitoneal injection of ovalbumin (OVA) three times and challenged with aerosolized OVA twice. Differential cell counts of infiltrating leukocytes, inflammatory mediators, cytokines in bronchoalvelor lavage fluid (BALF) of OVA-challenged mice were examined after continuously consuming G. tsugae diets for 5 weeks. We found that supplementation of G. tsugae significantly decreased total infiltrating leukocytes and lymphocyte percentage in BALF in the experimental groups. Supplementation of G. tsugae also significantly reduced inflammatory mediators in BALF including histamine, prostaglandin E2, eotaxin, and protein levels, however the levels of pro-inflammatory cytokines, interleukin (IL)-1beta and IL-6, in BALF did not significantly change. These results suggest that both G. tsugae supplementation diets YK01 and YK07 might alleviate bronchoalveolar inflammation via decreasing the infiltration of inflammatory cells and the secretion of inflammatory mediators into the local tissues of lungs and airways. Further, these results indicate that the relief of bronchoalveolar inflammation in an airway sensitization murine model provides a possible therapeutic application for G. tsugae in allergic asthma.

  7. Intravenous thrombolysis and platelet count. (United States)

    Gensicke, Henrik; Al Sultan, Abdulaziz S; Strbian, Daniel; Hametner, Christian; Zinkstok, Sanne M; Moulin, Solène; Bill, Olivier; Zini, Andrea; Padjen, Visnja; Kägi, Georg; Pezzini, Alessandro; Seiffge, David J; Traenka, Christopher; Räty, Silja; Amiri, Hemasse; Zonneveld, Thomas P; Lachenmeier, Romina; Polymeris, Alexandros; Roos, Yvo B; Gumbinger, Christoph; Jovanovic, Dejana R; Curtze, Sami; Sibolt, Gerli; Vandelli, Laura; Ringleb, Peter A; Leys, Didier; Cordonnier, Charlotte; Michel, Patrik; Lyrer, Philippe A; Peters, Nils; Tatlisumak, Turgut; Nederkoorn, Paul J; Engelter, Stefan T


    To study the effect of platelet count (PC) on bleeding risk and outcome in stroke patients treated with IV thrombolysis (IVT) and to explore whether withholding IVT in PC 450 × 10 9 /L), and normal PC (150-450 × 10 9 /L [reference group]). Moreover, PC < 100 × 10 9 /L was compared to PC ≥ 100 × 10 9 /L. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) from the logistic regression models were calculated. Among 7,533 IVT-treated stroke patients, 6,830 (90.7%) had normal PC, 595 (7.9%) had thrombocytopenia, and 108 (1.4%) had thrombocytosis. Decreasing PC (every 10 × 10 9 /L) was associated with increasing risk of sICH (OR adjusted 1.03, 95% CI 1.02-1.05) but decreasing risk of poor outcome (OR adjusted 0.99, 95% CI 0.98-0.99) and mortality (OR adjusted 0.98, 95% CI 0.98-0.99). The risk of sICH was higher in patients with thrombocytopenic than in patients with normal PC (OR adjusted 1.73, 95% CI 1.24-2.43). However, the risk of poor outcome (OR adjusted 0.89, 95% CI 0.39-1.97) and mortality (OR adjusted 1.09, 95% CI 0.83-1.44) did not differ significantly. Thrombocytosis was associated with mortality (OR adjusted 2.02, 95% CI 1.21-3.37). Forty-four (0.3%) patients had PC < 100 × 10 9 /L. Their risks of sICH (OR unadjusted 1.56, 95% CI 0.48-5.07), poor outcome (OR adjusted 1.63, 95% CI 0.82-3.24), and mortality (OR adjusted 1.38, 95% CI 0.64-2.98) did not differ significantly from those of patients with PC ≥ 100 × 10 9 /L. Lower PC was associated with increased risk of sICH, while higher PC indicated increased mortality. Our data suggest that PC modifies outcome and complications in individual patients, while withholding IVT in all patients with PC < 100 × 10 9 /L is challenged. © 2018 American Academy of Neurology.

  8. Total Intravenous Anesthesia (TIVA) in pediatric cardiac anesthesia


    Wong , Grace Lai Sze


    Abstract Inhalational anesthesia with moderate to high-dose opioid analgesia has been the mainstay of pediatric cardiac anesthesia but the advances in understanding of pharmacology and availability of new fast-acting drugs coupled with the advanced concepts in pharmacokinetic modeling and computer technology have made total intravenous anesthesia (TIVA) an attractive option. In this article, we review some of the TIVA techniques used in pediatric cardiac anesthesia. gracewong531...

  9. Microglia Transcriptome Changes in a Model of Depressive Behavior after Immune Challenge.

    Directory of Open Access Journals (Sweden)

    Dianelys Gonzalez-Pena

    Full Text Available Depression symptoms following immune response to a challenge have been reported after the recovery from sickness. A RNA-Seq study of the dysregulation of the microglia transcriptome in a model of inflammation-associated depressive behavior was undertaken. The transcriptome of microglia from mice at day 7 after Bacille Calmette Guérin (BCG challenge was compared to that from unchallenged Control mice and to the transcriptome from peripheral macrophages from the same mice. Among the 562 and 3,851 genes differentially expressed between BCG-challenged and Control mice in microglia and macrophages respectively, 353 genes overlapped between these cells types. Among the most differentially expressed genes in the microglia, serum amyloid A3 (Saa3 and cell adhesion molecule 3 (Cadm3 were over-expressed and coiled-coil domain containing 162 (Ccdc162 and titin-cap (Tcap were under-expressed in BCG-challenged relative to Control. Many of the differentially expressed genes between BCG-challenged and Control mice were associated with neurological disorders encompassing depression symptoms. Across cell types, S100 calcium binding protein A9 (S100A9, interleukin 1 beta (Il1b and kynurenine 3-monooxygenase (Kmo were differentially expressed between challenged and control mice. Immune response, chemotaxis, and chemokine activity were among the functional categories enriched by the differentially expressed genes. Functional categories enriched among the 9,117 genes differentially expressed between cell types included leukocyte regulation and activation, chemokine and cytokine activities, MAP kinase activity, and apoptosis. More than 200 genes exhibited alternative splicing events between cell types including WNK lysine deficient protein kinase 1 (Wnk1 and microtubule-actin crosslinking factor 1(Macf1. Network visualization revealed the capability of microglia to exhibit transcriptome dysregulation in response to immune challenge still after resolution of sickness


    Directory of Open Access Journals (Sweden)

    E. Y. Ponomareva


    Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

  11. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy

    NARCIS (Netherlands)

    Eftimov, Filip; Winer, John B.; Vermeulen, Marinus; de Haan, Rob; van Schaik, Ivo N.


    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled studies suggest that intravenous immunoglobulin (IVIg) helps. This review was first published in 2002 and has since

  12. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy

    NARCIS (Netherlands)

    Eftimov, Filip; Winer, John B.; Vermeulen, Marinus; de Haan, Rob; van Schaik, Ivo N.


    Background Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled studies suggest that intravenous immunoglobulin (IVIg) helps. Objectives To review systematically the

  13. The Challenge of Forecasting Metropolitan Growth: Urban Characteristics Based Models versus Regional Dummy Based Models




    This paper presents a study of errors in forecasting the population of Metropolitan Statistical Areas and the Primary MSAs of Consolidated Metropolitan Statistical Areas and New England MAs. The forecasts are for the year 2000 and are based on a semi-structural model estimated by Mills and Lubelle using 1970 to 1990 census data on population, employment and relative real wages. This model allows the testing of regional effects on population and employment growth. The year 2000 forecasts are f...

  14. Development of a prediction model of severe reaction in boiled egg challenges. (United States)

    Sugiura, Shiro; Matsui, Teruaki; Nakagawa, Tomoko; Sasaki, Kemal; Nakata, Joon; Kando, Naoyuki; Ito, Komei


    We have proposed a new scoring system (Anaphylaxis SCoring Aichi: ASCA) for a quantitative evaluation of the anaphylactic reaction that is observed in an oral food challenge (OFC). Furthermore, the TS/Pro (Total Score of ASCA/cumulative protein dose) can be a marker to represent the overall severity of a food allergy. We aimed to develop a prediction model for a severe allergic reaction that is provoked in a boiled egg white challenge. We used two separate datasets to develop and validate the prediction model, respectively. The development dataset included 198 OFCs, that tested positive. The validation dataset prospectively included 140 consecutive OFCs, irrespective of the result. A 'severe reaction' was defined as a TS/Pro higher than 31 (the median score of the development dataset). A multivariate logistic regression analysis was performed to identify the factors associated with a severe reaction and develop the prediction model. The following four factors were independently associated with a severe reaction: ovomucoid specific IgE class (OM-sIgE: 0-6), aged 5 years or over, a complete avoidance of egg, and a total IgE prediction model. The model showed good discrimination in a receiver operating characteristic analysis; area under the curve (AUC) = 0.84 in development dataset, AUC = 0.85 in validation dataset. The prediction model significantly improved the AUC in both datasets compared to OM-sIgE alone. This simple scoring prediction model was useful for avoiding risky OFC. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  15. Modelling noninvasively measured cerebral signals during a hypoxemia challenge: steps towards individualised modelling.

    Directory of Open Access Journals (Sweden)

    Beth Jelfs

    Full Text Available Noninvasive approaches to measuring cerebral circulation and metabolism are crucial to furthering our understanding of brain function. These approaches also have considerable potential for clinical use "at the bedside". However, a highly nontrivial task and precondition if such methods are to be used routinely is the robust physiological interpretation of the data. In this paper, we explore the ability of a previously developed model of brain circulation and metabolism to explain and predict quantitatively the responses of physiological signals. The five signals all noninvasively-measured during hypoxemia in healthy volunteers include four signals measured using near-infrared spectroscopy along with middle cerebral artery blood flow measured using transcranial Doppler flowmetry. We show that optimising the model using partial data from an individual can increase its predictive power thus aiding the interpretation of NIRS signals in individuals. At the same time such optimisation can also help refine model parametrisation and provide confidence intervals on model parameters. Discrepancies between model and data which persist despite model optimisation are used to flag up important questions concerning the underlying physiology, and the reliability and physiological meaning of the signals.

  16. Intravenous iron-containing products: EMA procrastination. (United States)


    A European reassessment has led to identical changes in the summaries of product characteristics (SPCs) for all intravenous iron-containing products: the risk of serious adverse effects is now highlighted, underlining the fact that intravenous iron-containing products should only be used when the benefits clearly outweigh the harms. Unfortunately, iron dextran still remains on the market despite a higher risk of hypersensitivity reactions than with iron sucrose.

  17. Contrast medium extravasation in intravenous urography

    International Nuclear Information System (INIS)

    Tosch, U.; Becker-Gaab, C.; Hahn, D.


    Aetiology and diagnostic procedure of calyceal fornix rupture during intravenous urography are discussed. In the literature the fornix rupture is discribed as a spontaneous event - not so in the four cases presented. In two cases a sudden increase in intrapelvic pressure was due to an ureteric calculus, in the other cases an obstruction of the ureter was secondary to neoplasm. It is recommended to perform a CT as soon as a contrastmedium extravasation in intravenous urography is diagnosed. (orig.) [de

  18. Contrast medium extravasation in intravenous urography

    Energy Technology Data Exchange (ETDEWEB)

    Tosch, U.; Becker-Gaab, C.; Hahn, D.


    Aetiology and diagnostic procedure of calyceal fornix rupture during intravenous urography are discussed. In the literature the fornix rupture is discribed as a spontaneous event - not so in the four cases presented. In two cases a sudden increase in intrapelvic pressure was due to an ureteric calculus, in the other cases an obstruction of the ureter was secondary to neoplasm. It is recommended to perform a CT as soon as a contrast medium extravasation in intravenous urography is diagnosed.

  19. Challenges and opportunities of modeling plasma-surface interactions in tungsten using high-performance computing (United States)

    Wirth, Brian D.; Hammond, K. D.; Krasheninnikov, S. I.; Maroudas, D.


    The performance of plasma facing components (PFCs) is critical for ITER and future magnetic fusion reactors. The ITER divertor will be tungsten, which is the primary candidate material for future reactors. Recent experiments involving tungsten exposure to low-energy helium plasmas reveal significant surface modification, including the growth of nanometer-scale tendrils of "fuzz" and formation of nanometer-sized bubbles in the near-surface region. The large span of spatial and temporal scales governing plasma surface interactions are among the challenges to modeling divertor performance. Fortunately, recent innovations in computational modeling, increasingly powerful high-performance computers, and improved experimental characterization tools provide a path toward self-consistent, experimentally validated models of PFC and divertor performance. Recent advances in understanding tungsten-helium interactions are reviewed, including such processes as helium clustering, which serve as nuclei for gas bubbles; and trap mutation, dislocation loop punching and bubble bursting; which together initiate surface morphological modification.

  20. Challenges and opportunities of modeling plasma–surface interactions in tungsten using high-performance computing

    International Nuclear Information System (INIS)

    Wirth, Brian D.; Hammond, K.D.; Krasheninnikov, S.I.; Maroudas, D.


    The performance of plasma facing components (PFCs) is critical for ITER and future magnetic fusion reactors. The ITER divertor will be tungsten, which is the primary candidate material for future reactors. Recent experiments involving tungsten exposure to low-energy helium plasmas reveal significant surface modification, including the growth of nanometer-scale tendrils of “fuzz” and formation of nanometer-sized bubbles in the near-surface region. The large span of spatial and temporal scales governing plasma surface interactions are among the challenges to modeling divertor performance. Fortunately, recent innovations in computational modeling, increasingly powerful high-performance computers, and improved experimental characterization tools provide a path toward self-consistent, experimentally validated models of PFC and divertor performance. Recent advances in understanding tungsten–helium interactions are reviewed, including such processes as helium clustering, which serve as nuclei for gas bubbles; and trap mutation, dislocation loop punching and bubble bursting; which together initiate surface morphological modification

  1. Geant4 Hadronic Cascade Models and CMS Data Analysis : Computational Challenges in the LHC era

    CERN Document Server

    Heikkinen, Aatos

    This work belongs to the field of computational high-energy physics (HEP). The key methods used in this thesis work to meet the challenges raised by the Large Hadron Collider (LHC) era experiments are object-orientation with software engineering, Monte Carlo simulation, the computer technology of clusters, and artificial neural networks. The first aspect discussed is the development of hadronic cascade models, used for the accurate simulation of medium-energy hadron-nucleus reactions, up to 10 GeV. These models are typically needed in hadronic calorimeter studies and in the estimation of radiation backgrounds. Various applications outside HEP include the medical field (such as hadron treatment simulations), space science (satellite shielding), and nuclear physics (spallation studies). Validation results are presented for several significant improvements released in Geant4 simulation tool, and the significance of the new models for computing in the Large Hadron Collider era is estimated. In particular, we es...

  2. Some considerations concerning the challenge of incorporating social variables into epidemiological models of infectious disease transmission. (United States)

    Barnett, Tony; Fournié, Guillaume; Gupta, Sunetra; Seeley, Janet


    Incorporation of 'social' variables into epidemiological models remains a challenge. Too much detail and models cease to be useful; too little and the very notion of infection - a highly social process in human populations - may be considered with little reference to the social. The French sociologist Émile Durkheim proposed that the scientific study of society required identification and study of 'social currents'. Such 'currents' are what we might today describe as 'emergent properties', specifiable variables appertaining to individuals and groups, which represent the perspectives of social actors as they experience the environment in which they live their lives. Here we review the ways in which one particular emergent property, hope, relevant to a range of epidemiological situations, might be used in epidemiological modelling of infectious diseases in human populations. We also indicate how such an approach might be extended to include a range of other potential emergent properties to represent complex social and economic processes bearing on infectious disease transmission.

  3. Recent progress and modern challenges in applied mathematics, modeling and computational science

    CERN Document Server

    Makarov, Roman; Belair, Jacques


    This volume is an excellent resource for professionals in various areas of applications of mathematics, modeling, and computational science. It focuses on recent progress and modern challenges in these areas. The volume provides a balance between fundamental theoretical and applied developments, emphasizing the interdisciplinary nature of modern trends and detailing state-of-the-art achievements in Applied Mathematics, Modeling, and Computational Science.  The chapters have been authored by international experts in their respective fields, making this book ideal for researchers in academia, practitioners, and graduate students. It can also serve as a reference in the diverse selected areas of applied mathematics, modelling, and computational sciences, and is ideal for interdisciplinary collaborations.

  4. The Nordic Model in a Global Company Situated in Norway. Challenging Institutional Orders?

    Directory of Open Access Journals (Sweden)

    Elin Kvande


    Full Text Available In this article, we explore the impact of internationalization as organizational processes where institutional actors meet in local contexts and negotiate the institutional order. The internationalization of working life implies that different traditions and practices meet and challenge each other. The focus is on how important elements of the Nordic micro model like cooperation between employees and employers and regulation of working hours are implemented in a global company situated in Norway. In general, it seems that employees and employers cooperate in line with this tradition in the Nordic micro model. Norwegian manager’s practices are described to be in accordance with Scandinavian management traditions, while managers from the United States appear to practice management consistent with the liberal working life model. The findings show a tension-filled clash between two different management practices, which indicates that the Nordic micro model in this field might be under pressure. Manager’s recommendation to the employees was not to become members of the trade union. The absence of trade unions in the organization implies that employees and employers are not cooperating on a collective level. This means that only parts of the regulatory arrangement related to participation and cooperation are implemented. Findings concerning working time and the relation to the institutional order represented by the Norwegian Work Environment Act indicate a clear tension between different institutional traditions in the organization. The company does not respect the Norwegian in working time regulations. These regulations are seen as counterproductive for a company that competes in the international market. This devaluation of the regulations in the Nordic model implies that the institutional order represented in the Nordic micro model is challenged.

  5. Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challenges. (United States)

    Kufareva, Irina; Katritch, Vsevolod; Stevens, Raymond C; Abagyan, Ruben


    Despite tremendous successes of GPCR crystallography, the receptors with available structures represent only a small fraction of human GPCRs. An important role of the modeling community is to maximize structural insights for the remaining receptors and complexes. The community-wide GPCR Dock assessment was established to stimulate and monitor the progress in molecular modeling and ligand docking for GPCRs. The four targets in the present third assessment round presented new and diverse challenges for modelers, including prediction of allosteric ligand interaction and activation states in 5-hydroxytryptamine receptors 1B and 2B, and modeling by extremely distant homology for smoothened receptor. Forty-four modeling groups participated in the assessment. State-of-the-art modeling approaches achieved close-to-experimental accuracy for small rigid orthosteric ligands and models built by close homology, and they correctly predicted protein fold for distant homology targets. Predictions of long loops and GPCR activation states remain unsolved problems. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Challenges in animal modelling of mesenchymal stromal cell therapy for inflammatory bowel disease. (United States)

    Chinnadurai, Raghavan; Ng, Spencer; Velu, Vijayakumar; Galipeau, Jacques


    Utilization of mesenchymal stromal cells (MSCs) for the treatment of Crohn's disease and ulcerative colitis is of translational interest. Safety of MSC therapy has been well demonstrated in early phase clinical trials but efficacy in randomized clinical trials needs to be demonstrated. Understanding MSC mechanisms of action to reduce gut injury and inflammation is necessary to improve current ongoing and future clinical trials. However, two major hurdles impede the direct translation of data derived from animal experiments to the clinical situation: (1) limitations of the currently available animal models of colitis that reflect human inflammatory bowel diseases (IBD). The etiology and progression of human IBD are multifactorial and hence a challenge to mimic in animal models; and (2) Species specific differences in the functionality of MSCs derived from mice versus humans. MSCs derived from mice and humans are not identical in their mechanisms of action in suppressing inflammation. Thus, preclinical animal studies with murine derived MSCs cannot be considered as an exact replica of human MSC based clinical trials. In the present review, we discuss the therapeutic properties of MSCs in preclinical and clinical studies of IBD. We also discuss the challenges and approaches of using appropriate animal models of colitis, not only to study putative MSC therapeutic efficacy and their mechanisms of action, but also the suitability of translating findings derived from such studies to the clinic.

  7. Seamless Meteorology-Composition Models: Challenges, Gaps, Needs and Future Directions (United States)

    Vogel, Bernhard; Baklanov, Alexander; Bouchet, Véronique; Marécal, Virginie; Benedetti, Angela; Heinke Schlünzen, K.


    Seamless meteorology - composition - chemistry models (SMCM) have several advantages: They allow the consideration of two - way interactions (i.e. feedbacks), ensure synergies in research, development, maintenance and application. "Seamless" is introduced here in relation to two aspects. Firstly, at the process - scale where it refers to the coupling within a model of meteorology and composition processes to represent for example the two - way interactions between composition and radiative processes or microphysics, or the consistent treatment of water vapor. Secondly, in terms time and space where it refers to the absence of discontinuities in model behavior when used at multiple temporal or spatial resolutions to have for example consistent treatment of black carbon for air quality and climate applications. SMCMs describe the relevant processes to investigate long - standing scientific questions on the interactions between atmospheric constituents and atmospheric processes and support the creation of new environmental prediction services. This paper presents a review of the current research status of SMCMs and recommendations to address limitations in weather, climate and atmospheric composition fields whose interests, applications and challenges are now overlapping. The contribution highlights the challenges towards seamlessness and presents priority areas for research to further this path. It will present examples where SMCMs are already in or close to operational use.

  8. Circular Business Model Challenges and Lessons Learned—An Industrial Perspective

    Directory of Open Access Journals (Sweden)

    Pejvak Oghazi


    Full Text Available Both practitioners and researchers are concerned about resource deficiencies on the planet earth and agree that circular business models (CBMs represent solutions to move towards zero waste, improving environmental impacts and increasing economic profit. Despite all of the benefits of CBMs, the implications are not widely available, and failure rates are high. Thus, there is a need to identify the obstacles that stand in the way of CBM transition. This paper aims to identify the primary challenges of CBMs. Multiple case studies are employed, incorporating six companies and data gleaned from 17 in-depth interviews. Theoretical and managerial implications are described at the end of the study.

  9. Challenges of using model predictive control for active demand side management

    DEFF Research Database (Denmark)

    Zong, Yi; You, Shi; Hu, Junjie


    architecture design for Model Predictive Controller (MPC), and discusses the challenges encountered during the implementation of MPC for active demand side management. The two different pilot case studies show that energy savings and load shifting can be achieved by applying MPC with weather forecast......When there is a high penetration of renewables in the power system, it requires coordinated management of large numbers of distributed and demand response resources, intermittent resources to maintain the grid reliability and improve operational economics. This paper presents a hierarchical...

  10. Superficial spreading and nodular melanoma are distinct biological entities: a challenge to the linear progression model. (United States)

    Greenwald, Holly S; Friedman, Erica B; Osman, Iman


    The classification of melanoma subtypes into prognostically relevant and therapeutically insightful categories has been a challenge since the first description of melanoma in the 1800s. One limitation has been the assumption that the two most common histological subtypes of melanoma, superficial spreading and nodular, evolve according to a linear model of progression, as malignant melanocytes spread radially and then invade vertically. However, recent clinical, pathological, and molecular data indicate that these two histological subtypes might evolve as distinct entities. Here, we review the published data that support distinct molecular characterization of superficial spreading and nodular melanoma, the clinical significance of this distinction including prognostic relevance and the therapeutic implications.

  11. Advances and Challenges in Space-time Modelling of Natural Events

    CERN Document Server

    Porcu, Emilio; Schlather, Martin


    This book arises as the natural continuation of the International Spring School "Advances and Challenges in Space-Time modelling of Natural Events," which took place in Toledo (Spain) in March 2010. This Spring School above all focused on young researchers (Master students, PhD students and post-doctoral researchers) in academics, extra-university research and the industry who are interested in learning about recent developments, new methods and applications in spatial statistics and related areas, and in exchanging ideas and findings with colleagues.

  12. Development of a BCG challenge model for the testing of vaccine candidates against tuberculosis in cattle. (United States)

    Villarreal-Ramos, Bernardo; Berg, Stefan; Chamberlain, Laura; McShane, Helen; Hewinson, R Glyn; Clifford, Derek; Vordermeier, Martin


    Vaccination is being considered as part of a sustainable strategy for the control of bovine tuberculosis (BTB) in the UK. The live attenuated Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used experimentally to vaccinate cattle against BTB. However, BCG confers partial protection against BTB and therefore, there is a need to develop improved vaccines. BTB vaccine efficacy experiments require the use of biosafety level 3 facilities which are expensive to maintain, generally oversubscribed and represent a bottle neck for the testing of vaccine candidates. One indicator of the induction of protective responses would be the ability of the host's immune response to control/kill mycobacteria. In this work we have evaluated an intranodal BCG challenge for the selection of vaccine candidates at biosafety level 2 which are capable of inducing mycobactericidal responses. To our knowledge, this is the first such report. Whilst BCG only confers partial protection, it is still the standard against which other vaccines are judged. Therefore we tested the BCG intranodal challenge in BCG (Danish strain) vaccinated cattle and showed that vaccinated cattle had lower BCG cfu counts than naïve cattle at 14 and 21 days after intranodal challenge with BCG (Tokyo strain). This model could help prioritize competing TB vaccine candidates and exploration of primary and secondary immune responses to mycobacteria. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  13. Intravenous injection of ioxilan, iohexol and diatrizoate

    Energy Technology Data Exchange (ETDEWEB)

    Thomsen, H.S.; Dorph, S.; Mygind, T.; Sovak, M.; Nielsen, H.; Rygaard, H.; Larsen, S.; Skaarup, P.; Hemmingsen, L.; Holm, J.

    Effects of intravenous ioxilan, a new third generation non-ionic contrast medium, diatrizoate, iohexol and saline on urine profiles were compared. Albumin, glucose, sodium, phosphate, and the enzymes NAG, LDH and GGT were followed in 24 normal rats over 7 days. Diatrizoate significantly affected all profile components during the first two hours. Albuminuria was significantly greater after diatrizoate than after iohexol or ioxilan, and excretion of glucose, LDH and GGT was significantly higher than after ioxilan. Both iohexol and ioxilan increased the excretion of albumin, LDH and GGT, while iohexol also significantly increased excretion of glucose and sodium. There was a greater excretion of glucose and GGT after iohexol than after ioxilan. Saline did not induce any changes. At day 7, serum sodium, urea, creatinine, and albumin were normal for all test substances, and kidney histology revealed no difference between the groups of animals. It is thus concluded that both high osmolar ionic and low osmolar non-ionic contrast media may cause temporary glomerular and tubular dysfunction in rats. In this model, the kidney is affected most by diatrizoate, less by iohexol, and least by ioxilan.

  14. Intravenous Iron Carboxymaltose as a Potential Therapeutic in Anemia of Inflammation.

    Directory of Open Access Journals (Sweden)

    Niklas Lofruthe

    Full Text Available Intravenous iron supplementation is an effective therapy in iron deficiency anemia (IDA, but controversial in anemia of inflammation (AI. Unbound iron can be used by bacteria and viruses for their replication and enhance the inflammatory response. Nowadays available high molecular weight iron complexes for intravenous iron substitution, such as ferric carboxymaltose, might be useful in AI, as these pharmaceuticals deliver low doses of free iron over a prolonged period of time. We tested the effects of intravenous iron carboxymaltose in murine AI: Wild-type mice were exposed to the heat-killed Brucella abortus (BA model and treated with or without high molecular weight intravenous iron. 4h after BA injection followed by 2h after intravenous iron treatment, inflammatory cytokines were upregulated by BA, but not enhanced by iron treatment. In long term experiments, mice were fed a regular or an iron deficient diet and then treated with intravenous iron or saline 14 days after BA injection. Iron treatment in mice with BA-induced AI was effective 24h after iron administration. In contrast, mice with IDA (on iron deficiency diet prior to BA-IA required 7d to recover from AI. In these experiments, inflammatory markers were not further induced in iron-treated compared to vehicle-treated BA-injected mice. These results demonstrate that intravenous iron supplementation effectively treated the murine BA-induced AI without further enhancement of the inflammatory response. Studies in humans have to reveal treatment options for AI in patients.

  15. Challenges in modeling unstable two-phase flow experiments in porous micromodels (United States)

    Meheust, Y.; Ferrari, A.; Jimenez-Martinez, J.; Le Borgne, T.; Lunati, I.


    The simulation of unstable invasion patterns in porous media flow is challenging since small perturbations tend to grow in time, so that slight differences in geometry or initial conditions potentially give rise to significantly different solutions. Here we present a detailed comparison of pore scale simulations and experiments of unstable primary drainage in porous micromodels. The porous medium consists of a Hele-Shaw cell containing cylindrical obstacles. Two experimental flow cells have been constructed by soft lithography, with different degrees of heterogeneity in the grain size distribution. To model two-phase flow at the pore scale, we solve Navier-Stokes equations for mass and momentum conservation in the discretized pore space and employ the Volume of Fluid (VOF) method to track the evolution of the interface. During drainage, if the defending fluid is the most viscous, viscous forces destabilize the interface, giving rise to the formation of preferential flow paths, in the form of a branched fingering structure. We test different numerical models (a 2D vertical integrated model and a full 3D model) and different initial conditions, studying their impact on the simulated spatial distributions of the fluid phases. Although due to the unstable nature of the invasion, small discrepancies between the experimental setup and the numerical model can result in different fluids patterns (see figure), simulations show a satisfactory agreement with the structures observed experimentally. To estimate the ability of the numerical approach to reproduce unstable displacement, we compare several quantities in both the statistical and deterministic sense. We demonstrate the impact of three main sources of uncertainty : i) the uncertainty on the pore space geometry, ii) the interface initialization and ii) three dimensional effects [1]. Simulations in weakly heterogeneous geometries are found to be more challenging because uncertainties on pore neck widths are on the same

  16. Adapting a regularized canopy reflectance model (REGFLEC) for the retrieval challenges of dryland agricultural systems

    KAUST Repository

    Houborg, Rasmus


    A regularized canopy reflectance model (REGFLEC) is applied over a dryland irrigated agricultural system in Saudi Arabia for the purpose of retrieving leaf area index (LAI) and leaf chlorophyll content (Chll). To improve the robustness of the retrieved properties, REGFLEC was modified to 1) correct for aerosol and adjacency effects, 2) consider foliar dust effects on modeled canopy reflectances, 3) include spectral information in the red-edge wavelength region, and 4) exploit empirical LAI estimates in the model inversion. Using multi-spectral RapidEye imagery allowed Chll to be retrieved with a Mean Absolute Deviation (MAD) of 7.9 μg cm− 2 (16%), based upon in-situ measurements conducted in fields of alfalfa, Rhodes grass and maize over the course of a growing season. LAI and Chll compensation effects on canopy reflectance were largely avoided by informing the inversion process with ancillary LAI inputs established empirically on the basis of a statistical machine learning technique. As a result, LAI was reproduced with good accuracy, with an overall MAD of 0.42 m2 m− 2 (12.5%). Results highlighted the considerable challenges associated with the translation of at-sensor radiance observations to surface bidirectional reflectances in dryland environments, where issues such as high aerosol loadings and large spatial gradients in surface reflectance from bright desert soils to dark vegetated fields are often present. Indeed, surface reflectances in the visible bands were reduced by up to 60% after correction for such adjacency effects. In addition, dust deposition on leaves required explicit modification of the reflectance sub-model to account for its influence. By implementing these model refinements, REGFLEC demonstrated its utility for within-field characterization of vegetation conditions over the challenging landscapes typical of dryland agricultural regions, offering a means through which improvements can be made in the management of these globally

  17. Sixth Grade Students' Content-Specific Competencies and Challenges in Learning the Seasons Through Modeling (United States)

    Sung, Ji Young; Oh, Phil Seok


    Recent science education reform initiatives suggest that learning in science should be organized on the basis of scientists' actual practices including the development and use of models. In line with this, the current study adapted three types of modeling practices to teach two Korean 6th grade science classes the causes of the Earth's seasons. Specifically, the study aimed to identify the students' content-specific competencies and challenges based on fine-grained descriptions and analyses of two target groups' cases. Data included digital recordings of modeling-based science lessons in the two classes, the teacher's and students' artifacts, and interviews with the students. These multiple types of data were analyzed complementarily and qualitatively. It was revealed that the students had a competency in constructing models to generate the desired phenomenon (i.e., seasons). They had difficulty, however, in considering the tilt of the Earth's rotation axis as a cause of the seasons and in finding a proper way of representing the Sun's meridian altitude on a globe. But, when the students were helped and guided by the teacher and peers' interventions, they were able to revise their models in alignment with the scientific understanding of the seasons. Based on these findings, the teacher's pedagogical roles, which include using student competencies as resources, asking physical questions, and explicit guidance on experimentation skills, were recommended to support successful incorporations of modeling practices in the science classroom.

  18. Environmental fate and exposure models: advances and challenges in 21st century chemical risk assessment. (United States)

    Di Guardo, Antonio; Gouin, Todd; MacLeod, Matthew; Scheringer, Martin


    Environmental fate and exposure models are a powerful means to integrate information on chemicals, their partitioning and degradation behaviour, the environmental scenario and the emissions in order to compile a picture of chemical distribution and fluxes in the multimedia environment. A 1995 pioneering book, resulting from a series of workshops among model developers and users, reported the main advantages and identified needs for research in the field of multimedia fate models. Considerable efforts were devoted to their improvement in the past 25 years and many aspects were refined; notably the inclusion of nanomaterials among the modelled substances, the development of models at different spatial and temporal scales, the estimation of chemical properties and emission data, the incorporation of additional environmental media and processes, the integration of sensitivity and uncertainty analysis in the simulations. However, some challenging issues remain and require research efforts and attention: the need of methods to estimate partition coefficients for polar and ionizable chemical in the environment, a better description of bioavailability in different environments as well as the requirement of injecting more ecological realism in exposure predictions to account for the diversity of ecosystem structures and functions in risk assessment. Finally, to transfer new scientific developments into the realm of regulatory risk assessment, we propose the formation of expert groups that compare, discuss and recommend model modifications and updates and help develop practical tools for risk assessment.

  19. Crises and Collective Socio-Economic Phenomena: Simple Models and Challenges (United States)

    Bouchaud, Jean-Philippe


    Financial and economic history is strewn with bubbles and crashes, booms and busts, crises and upheavals of all sorts. Understanding the origin of these events is arguably one of the most important problems in economic theory. In this paper, we review recent efforts to include heterogeneities and interactions in models of decision. We argue that the so-called Random Field Ising model ( rfim) provides a unifying framework to account for many collective socio-economic phenomena that lead to sudden ruptures and crises. We discuss different models that can capture potentially destabilizing self-referential feedback loops, induced either by herding, i.e. reference to peers, or trending, i.e. reference to the past, and that account for some of the phenomenology missing in the standard models. We discuss some empirically testable predictions of these models, for example robust signatures of rfim-like herding effects, or the logarithmic decay of spatial correlations of voting patterns. One of the most striking result, inspired by statistical physics methods, is that Adam Smith's invisible hand can fail badly at solving simple coordination problems. We also insist on the issue of time-scales, that can be extremely long in some cases, and prevent socially optimal equilibria from being reached. As a theoretical challenge, the study of so-called "detailed-balance" violating decision rules is needed to decide whether conclusions based on current models (that all assume detailed-balance) are indeed robust and generic.

  20. Optimization of a Human Bacille Calmette-Guérin Challenge Model: A Tool to Evaluate Antimycobacterial Immunity. (United States)

    Minhinnick, Alice; Harris, Stephanie; Wilkie, Morven; Peter, Jonathan; Stockdale, Lisa; Manjaly-Thomas, Zita-Rose; Vermaak, Samantha; Satti, Iman; Moss, Paul; McShane, Helen


    There is an urgent need for an improved tuberculosis vaccine. The lack of a validated correlate of protection slows progress in achieving this goal. A human mycobacterial challenge model, using bacille Calmette-Guérin (BCG) as a surrogate for a Mycobacterium tuberculosis challenge, would facilitate vaccine selection for field efficacy testing. Optimization of this model is required. Healthy BCG-naive adults were assigned to receive intradermal standard-dose BCG SSI (group A), standard-dose BCG TICE (group B), high-dose BCG SSI (group C), and high-dose BCG TICE (group D). Two weeks after BCG challenge, skin biopsy of the challenge site was performed. BCG mycobacterial load was quantified by solid culture and quantitative polymerase chain reaction. BCG was well tolerated, and reactogenicity was similar between groups, regardless of strain and dose. There was significantly greater recovery of BCG from the high-dose challenge groups, compared with standard-dose challenge. BCG strain did not significantly affect BCG recovery. BCG challenge dose affects sensitivity of this model. We have selected high-dose BCG SSI to take forward in future challenge studies. Assessment of candidate tuberculosis vaccine effectiveness with this optimized model could contribute to vaccine selection for efficacy trials. NCT02088892. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  1. Findings and Challenges in Fine-Resolution Large-Scale Hydrological Modeling (United States)

    Her, Y. G.


    Fine-resolution large-scale (FL) modeling can provide the overall picture of the hydrological cycle and transport while taking into account unique local conditions in the simulation. It can also help develop water resources management plans consistent across spatial scales by describing the spatial consequences of decisions and hydrological events extensively. FL modeling is expected to be common in the near future as global-scale remotely sensed data are emerging, and computing resources have been advanced rapidly. There are several spatially distributed models available for hydrological analyses. Some of them rely on numerical methods such as finite difference/element methods (FDM/FEM), which require excessive computing resources (implicit scheme) to manipulate large matrices or small simulation time intervals (explicit scheme) to maintain the stability of the solution, to describe two-dimensional overland processes. Others make unrealistic assumptions such as constant overland flow velocity to reduce the computational loads of the simulation. Thus, simulation efficiency often comes at the expense of precision and reliability in FL modeling. Here, we introduce a new FL continuous hydrological model and its application to four watersheds in different landscapes and sizes from 3.5 km2 to 2,800 km2 at the spatial resolution of 30 m on an hourly basis. The model provided acceptable accuracy statistics in reproducing hydrological observations made in the watersheds. The modeling outputs including the maps of simulated travel time, runoff depth, soil water content, and groundwater recharge, were animated, visualizing the dynamics of hydrological processes occurring in the watersheds during and between storm events. Findings and challenges were discussed in the context of modeling efficiency, accuracy, and reproducibility, which we found can be improved by employing advanced computing techniques and hydrological understandings, by using remotely sensed hydrological

  2. Intravenous fluids in acute decompensated heart failure. (United States)

    Bikdeli, Behnood; Strait, Kelly M; Dharmarajan, Kumar; Li, Shu-Xia; Mody, Purav; Partovian, Chohreh; Coca, Steven G; Kim, Nancy; Horwitz, Leora I; Testani, Jeffrey M; Krumholz, Harlan M


    This study sought to determine the use of intravenous fluids in the early care of patients with acute decompensated heart failure (HF) who are treated with loop diuretics. Intravenous fluids are routinely provided to many hospitalized patients. We conducted a retrospective cohort study of patients admitted with HF to 346 hospitals from 2009 to 2010. We assessed the use of intravenous fluids during the first 2 days of hospitalization. We determined the frequency of adverse in-hospital outcomes. We assessed variation in the use of intravenous fluids across hospitals and patient groups. Among 131,430 hospitalizations for HF, 13,806 (11%) were in patients treated with intravenous fluids during the first 2 days. The median volume of administered fluid was 1,000 ml (interquartile range: 1,000 to 2,000 ml), and the most commonly used fluids were normal saline (80%) and half-normal saline (12%). Demographic characteristics and comorbidities were similar in hospitalizations in which patients did and did not receive fluids. Patients who were treated with intravenous fluids had higher rates of subsequent critical care admission (5.7% vs. 3.8%; p fluid treatment varied widely across hospitals (range: 0% to 71%; median: 12.5%). Many patients who are hospitalized with HF and receive diuretics also receive intravenous fluids during their early inpatient care, and the proportion varies among hospitals. Such practice is associated with worse outcomes and warrants further investigation. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  3. Addressing the urban pipeline challenge for the physician workforce: the Sophie Davis model. (United States)

    Roman, Stanford A


    The convergence of numerous trends indicates that a physician shortage by 2020 is likely. There is a 25% growth in the overall population, but that of the college-age sector is increasing by only 5%. The numbers of African Americans and Latinos in that sector will increase more than will members of other population groups; these two groups are most affected by the uneven quality of science education in urban high schools. Challenges to create a pipeline of a large, diverse, and qualified pool of medical school applicants are great, and are influenced by the actual and perceived cost of medical school tuition and the competition from other professions. Since 1973, the Sophie Davis School of Biomedical Education, a seven-year joint BS/MD program, has expanded access to medical school education for talented inner-city youths, including minorities and those with limited financial resources. Students receive a BS degree and their first two years of medical school education and, upon successful completion of the United States Medical Licensing Examination Step 1, transfer to one of five cooperating medical schools in New York State that confer the terminal MD degree. Sophie Davis integrates medical studies in the baccalaureate program, using actual performance in medical studies as a predictor of success. Of the more than 1,400 of its graduates, 25% are African American, 8% are Latino, 28% are Asian American, and 39% are white. Over 25% of its current student body comes from federally defined low-income families, and almost three-quarters qualify for New York State financial aid. The Sophie Davis School of Biomedical Education is a model that offers a partial response to those factors that will challenge the achievement of an adequate supply of physicians for our urban communities. The author describes the model in detail and explains how it helps talented but unevenly educated students rise to the challenge of a medical education.

  4. Practice models and challenges in teledermatology: a study of collective experiences from teledermatologists.

    Directory of Open Access Journals (Sweden)

    April W Armstrong

    Full Text Available BACKGROUND: Despite increasing practice of teledermatology in the U.S., teledermatology practice models and real-world challenges are rarely studied. METHODS: The primary objective was to examine teledermatology practice models and shared challenges among teledermatologists in California, focusing on practice operations, reimbursement considerations, barriers to sustainability, and incentives. We conducted in-depth interviews with teledermatologists that practiced store-and-forward or live-interactive teledermatology from January 1, 2007 through March 30, 2011 in California. RESULTS: Seventeen teledermatologists from academia, private practice, health maintenance organizations, and county settings participated in the study. Among them, 76% practiced store-and-forward only, 6% practiced live-interactive only, and 18% practiced both modalities. Only 29% received structured training in teledermatology. The average number of years practicing teledermatology was 4.29 years (SD±2.81. Approximately 47% of teledermatologists served at least one Federally Qualified Health Center. Over 75% of patients seen via teledermatology were at or below 200% federal poverty level and usually lived in rural regions without dermatologist access. Practice challenges were identified in the following areas. Teledermatologists faced delays in reimbursements and non-reimbursement of teledermatology services. The primary reason for operational inefficiency was poor image quality and/or inadequate history. Costly and inefficient software platforms and lack of communication with referring providers also presented barriers. CONCLUSION: Teledermatology enables underserved populations to access specialty care. Improvements in reimbursement mechanisms, efficient technology platforms, communication with referring providers, and teledermatology training are necessary to support sustainable practices.

  5. Intravenous cidofovir for resistant cutaneous warts in a patient with psoriasis treated with monoclonal antibodies.

    LENUS (Irish Health Repository)

    McAleer, M A


    Human papilloma virus is a common and often distressing cutaneous disease. It can be therapeutically challenging, especially in immunocompromised patients. We report a case of recalcitrant cutaneous warts that resolved with intravenous cidofovir treatment. The patient was immunocompromised secondary to monoclonal antibody therapy for psoriasis.

  6. Iris abscess a rare presentation of intravenous drug abuse associated Candida endophthalmitis

    Directory of Open Access Journals (Sweden)

    Jonathan Pierce


    Conclusions and importance: An iris abscess is a rare clinical presentation of intravenous drug use-associated endogenous endophthalmitis and as a result may present a diagnostic challenge as it requires a high level of clinical suspicion and a detailed social history to elicit the drug abuse. Early diagnosis and aggressive therapy is the key to better visual outcomes in these patients.

  7. Toward an Integrated Competence-Based System Supporting Lifelong Learning and Employability: Concepts, Model, and Challenges (United States)

    Miao, Yongwu; van der Klink, Marcel; Boon, Jo; Sloep, Peter; Koper, Rob

    Efficient and effective lifelong learning requires that people can make informed decisions about their continuous personal development in the different stages of their life. In this paper we state that lifelong learners need to be characterized as decision-makers. In order to improve the quality of their decisions, we propose the development of an integrated lifelong learning and employment support system, which traces learners’ competence development and provides a decision support environment. An abstract conceptual model has been developed and the main design ideas have been documented using Z notation. Moreover, we analyzed the main technical challenges for the realization of the target system: competence information fusion, decision analysis models, spatial indexing structures and browsing structures and visualization of competence-related information objects.

  8. From the Rodent Spinal Cord Injury Model to Human Application: Promises and Challenges. (United States)

    Dietz, Volker; Schwab, Martin E


    Repair of the spinal cord and improvement of mobility after injury has been a matter of basic and clinical research for several decades. A number of repair approaches were performed in animals, mainly rodent models of spinal cord injury (SCI). Some of these experimental therapies resulted in significant regeneration of tract fibers, formation of new connections and circuits, and associated improvement of mobility. Some clinical trials aiming at translating these approaches to the human condition of an SCI are currently on-going. The present therapy, however, remains rehabiliation: Mobility of patients with an SCI can be improved to a limited extent by the exploition of neuroplasticity. In this article the present state of the art in the field of SCI research will be discussed. Studies dealing with the promotion of spinal cord repair and those directed to improve mobility by exploition of neuroplasticity will be summarized. The promises and challenges of translational basic research in rodent SCI models will be presented.

  9. Energy efficiency and renewable energy modeling with ETSAP TIAM - challenges, opportunities, and solutions

    DEFF Research Database (Denmark)

    Gregg, Jay Sterling; Balyk, Olexandr; Pérez, Cristian Hernán Cabrera

    The objectives of the Sustainable Energy for All (SE4ALL), a United Nations (UN) global initiative, are to achieve, by 2030: 1) universal access to modern energy services; 2) a doubling of the global rate of improvement in energy efficiency; and 3) a doubling of the share of renewable energy...... in the global energy mix (United Nations, 2011; SE4ALL, 2013a). The purpose of this study is to determine to what extent the energy efficiency objective supports the other two objectives, and to what extent the SE4ALL objectives support the climate target of limiting the global mean temperature increase to 2° C...... over pre-industrial times. To accomplish this, pathways are constructed for each objective, which then form the basis for a scenario analysis using the Energy Technology System Analysis Program TIMES Integrated Assessment Model (ETSAP-TIAM). This presentation focuses on the modeling challenges...

  10. Unique Challenges for Modeling Defect Dynamics in Concentrated Solid-Solution Alloys (United States)

    Zhao, Shijun; Weber, William J.; Zhang, Yanwen


    Recently developed concentrated solid solution alloys (CSAs) are shown to have improved performance under irradiation that depends strongly on the number of alloying elements, alloying species, and their concentrations. In contrast to conventional dilute alloys, CSAs are composed of multiple principal elements situated randomly in a simple crystalline lattice. As a result, the intrinsic disorder has a profound influence on energy dissipation pathways and defect evolution when these CSAs are subjected to energetic particle irradiation. Extraordinary irradiation resistance, including suppression of void formation by two orders of magnitude at an elevated temperature, has been achieved with increasing compositional complexity in CSAs. Unfortunately, the loss of translational invariance associated with the intrinsic chemical disorder poses great challenges to theoretical modeling at the electronic and atomic levels. Based on recent computer simulation results for a set of novel Ni-containing, face-centered cubic CSAs, we review theoretical modeling progress in handling disorder in CSAs and underscore the impact of disorder on defect dynamics. We emphasize in particular the unique challenges associated with the description of defect dynamics in CSAs.

  11. Outreach training model for accredited colorectal specialists in laparoscopic colorectal surgery: feasibility and evaluation of challenges. (United States)

    Hamdan, M F; Day, A; Millar, J; Carter, F J C; Coleman, M G; Francis, N K


    The aim of this study was to explore the feasibility and safety of an outreach model of laparoscopic colorectal training of accredited specialists in advanced laparoscopic techniques and to explore the challenges of this model from the perspective of a National Training Programme (NTP) trainer. Prospective data were collected for unselected laparoscopic colorectal training procedures performed by five laparoscopic colorectal NTP trainees supervised by a single NTP trainer with an outreach model between 2009 and 2012. The operative and postoperative outcomes were compared with standard laparoscopic colorectal training procedures performed by six senior colorectal trainees under the supervision of the same NTP trainer within the same study period. The primary outcome was 30-day mortality. The Mann-Whitney test was used to compare continuous variables and the Chi squared or Fisher's exact tests were applied for the analysis of categorical variables. The level of statistical significance was set at P groups. Seventy-eight per cent of the patients operated on by the NTP trainees had had no previous abdominal surgery, compared with 50% in the supervised trainees' group (P = 0.0005). There were no significant differences in 30-day mortality or the operative and postoperative outcome between both groups. There were, however, difficulties in training an already established consultant in his or her own hospital and these were overcome by certain adjustments to the programme. Outreach laparoscopic training of colorectal surgeons is a feasible and safe model of training accredited specialists and does not compromise patient care. The challenges encountered can be overcome with optimum training and preparation. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

  12. Intravenous and Intramuscular Formulations of Antiseizure Drugs in the Treatment of Epilepsy. (United States)

    Patel, Sima I; Birnbaum, Angela K; Cloyd, James C; Leppik, Ilo E


    Intravenous and intramuscular antiseizure drugs (ASDs) are essential in the treatment of clinical seizure emergencies as well as in replacement therapy when oral administration is not possible. The parenteral formulations provide rapid delivery and complete (intravenous) or nearly complete (intramuscular) bioavailability. Controlled administration of the ASD is feasible with intravenous but not intramuscular formulations. This article reviews the literature and discusses the chemistry, pharmacology, pharmacokinetics, and clinical use of currently available intravenous and intramuscular ASD formulations as well as the development of new formulations and agents. Intravenous or intramuscular formulations of lorazepam, diazepam, midazolam, and clonazepam are typically used as the initial treatment agents in seizure emergencies. Recent studies also support the use of intramuscular midazolam as easier than the intravenous delivery of lorazepam in the pre-hospital setting. However, benzodiazepines may be associated with hypotension and respiratory depression. Although loading with intravenous phenytoin was an early approach to treatment, it is associated with cardiac arrhythmias, hypotension, and tissue injury at the injection site. This has made it less favored than fosphenytoin, a water-soluble, phosphorylated phenytoin molecule. Other drugs being used for acute seizure emergencies are intravenous formulations of valproic acid, levetiracetam, and lacosamide. However, the comparative effectiveness of these for status epilepticus (SE) has not been evaluated adequately. Consequently, guidelines for the medical management of SE continue to recommend lorazepam followed by fosphenytoin, or phenytoin if fosphenytoin is not available. Intravenous solutions for carbamazepine, lamotrigine, and topiramate have been developed but remain investigational. The current ASDs were not developed for use in emergency situations, but were adapted from ASDs approved for chronic oral use. New

  13. Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation. (United States)

    Renukaradhya, Gourapura J; Narasimhan, Balaji; Mallapragada, Surya K


    Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers - 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, is discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity

    Directory of Open Access Journals (Sweden)

    Robert Nunan


    Full Text Available The efficient healing of a skin wound is something that most of us take for granted but is essential for surviving day-to-day knocks and cuts, and is absolutely relied on clinically whenever a patient receives surgical intervention. However, the management of a chronic wound – defined as a barrier defect that has not healed in 3 months – has become a major therapeutic challenge throughout the Western world, and it is a problem that will only escalate with the increasing incidence of conditions that impede wound healing, such as diabetes, obesity and vascular disorders. Despite being clinically and molecularly heterogeneous, all chronic wounds are generally assigned to one of three major clinical categories: leg ulcers, diabetic foot ulcers or pressure ulcers. Although we have gleaned much knowledge about the fundamental cellular and molecular mechanisms that underpin healthy, acute wound healing from various animal models, we have learned much less about chronic wound repair pathology from these models. This might largely be because the animal models being used in this field of research have failed to recapitulate the clinical features of chronic wounds. In this Clinical Puzzle article, we discuss the clinical complexity of chronic wounds and describe the best currently available models for investigating chronic wound pathology. We also assess how such models could be optimised to become more useful tools for uncovering pathological mechanisms and potential therapeutic treatments.

  15. Modeling of biomass-to-energy supply chain operations: Applications, challenges and research directions

    International Nuclear Information System (INIS)

    Mafakheri, Fereshteh; Nasiri, Fuzhan


    Reducing dependency on fossil fuels and mitigating their environmental impacts are among the most promising aspects of utilizing renewable energy sources. The availability of various biomass resources has made it an appealing source of renewable energy. Given the variability of supply and sources of biomass, supply chains play an important role in the efficient provisioning of biomass resources for energy production. This paper provides a comprehensive review and classification of the excising literature in modeling of biomass supply chain operations while linking them to the wider strategic challenges and issues with the design, planning and management of biomass supply chains. On that basis, we will present an analysis of the existing gaps and the potential future directions for research in modeling of biomass supply chain operations. - Highlights: • An extensive review of biomass supply chain operations management models presented in the literature is provided. • The models are classified in line with biomass supply chain activities from harvesting to conversion. • The issues surrounding biomass supply chains are investigated manifesting the need to novel modeling approaches. • Our gap analysis has identified a number of existing shortcomings and opportunities for future research

  16. Business model generation a handbook for visionaries, game changers, and challengers

    CERN Document Server

    Osterwalder, Alexander


    Business Model Generation is a handbook for visionaries, game changers, and challengers striving to defy outmoded business models and design tomorrow′s enterprises. If your organization needs to adapt to harsh new realities, but you don′t yet have a strategy that will get you out in front of your competitors, you need Business Model Generation. Co–created by 470 "Business Model Canvas" practitioners from 45 countries, the book features a beautiful, highly visual, 4–color design that takes powerful strategic ideas and tools, and makes them easy to implement in your organization. It explains the most common Business Model patterns, based on concepts from leading business thinkers, and helps you reinterpret them for your own context. You will learn how to systematically understand, design, and implement a game–changing business model––or analyze and renovate an old one. Along the way, you′ll understand at a much deeper level your customers, distribution channels, partners, revenue streams, costs...

  17. State and transition models: Theory, applications, and challenges. In: Briske, D.D. Rangeland Systems: Processes, Management and Challenges (United States)

    State and transition models (STMs) are used for communicating about ecosystem change in rangelands and other ecosystems, especially the implications for management. The fundamental premise that rangelands can exhibit multiple states is now widely accepted. The current application of STMs for managem...

  18. Models of disability: their influence in nursing and potential role in challenging discrimination. (United States)

    Scullion, Philip Andrew


    This paper presents a discussion of medical and social models of disability associated with experiences of disabled people as citizens and patients. Disability is fairly universally a negative concept. Disabled people have frequent contact with health services, however much of this experience is viewed as discriminatory. Literature was obtained using the Psych-INFO, Medline and CINAHL databases for the years 1989-2009, using derivatives of the concept 'disability' and associated 'models', and then these terms combined with 'nursing'. Nursing as a profession embraces the need to avoid discrimination, yet disability as an equal opportunity issue is relatively neglected in nursing. Nursing has a moral, professional and, in some countries, a legal responsibility to promote disability equality in the provision of nursing services. Insights offered by the social model of disability may be instrumental in empowering nurses to respond to this obligation. While some groups may not be well-represented in this model and there is risk in embracing the social model of exposing a policy-practice divide, it nevertheless represents a powerful tool for strengthening nurses' advocacy role. In particular, 'social advocacy' may be enhanced by a paradigm shift away from the medical model of disability. Nurses have an obligation to promote disability equality in relation to the provision of health care. Adoption of the social model of disability in nursing practice, education and research as a strategy to challenge discrimination should be seriously considered. The utility value of the social model of disability in strengthening the social advocacy role of nurses should be investigated.

  19. Prediction of lake surface temperature using the air2water model: guidelines, challenges, and future perspectives

    Directory of Open Access Journals (Sweden)

    Sebastiano Piccolroaz


    leading to the risk of overfitting. The final aim of the work is to facilitate the use of the model also by scientists that do not necessarily have a solid background on modelling or physics. However, this work should not be considered simply as a collection of best practices, but also as the attempt to foster the communication and interaction among colleagues of a branch of science, limnology, that suffer of significant fragmentation. This is summarized in the future perspectives and challenges concerning potential improvements of the air2water, with a particular emphasis on possible cross-sectoral applications.

  20. Evaluation of a cohabitation challenge model in immunization trials for channel catfish Ictalurus punctatus against Ichthyophthirius multifiliis. (United States)

    Xu, De-Hai; Klesius, Phillip H; Shoemaker, Craig A


    Calcein marking and cohabitation challenges have not been investigated in fish parasite research. This study evaluated a cohabitation challenge method in immunization trials against Ichthyophthirius multifiliis (Ich) using calcein, a fluorescent dye, to mark channel catfish Ictalurus punctatus (Rafinesque). Fish were marked by calcein immersion at 0, 500, and 1500 mg l(-1), and then challenged with 15 000 theronts fish(-1). No difference was noted in fish infection levels, mortality, and mean days to death (MDD) caused by Ich between unmarked and marked fish or between fish marked with high (1500 mg l(-1)) and low (500 mg l(-1)) concentrations of calcein. After ensuring that calcein marking had no effect on the susceptibility of fish to Ich theronts, 2 immunization trials were conducted to evaluate the cohabitation challenge model using calcein-marked catfish. Fish mortality, relative percent survival (RPS), and MDD were compared between cohabitation-challenged fish and fish challenged by non-cohabitation. No significant difference was observed in RPS for cohabitation-challenged fish and fish challenged by non-cohabitation. A cohabitation challenge can be used as an alternative challenge method in parasite studies, since it closely mimics natural exposure.

  1. What´s cheapest, intravenous iron sucrose- or intravenous iron carboxymaltose treatment in IBD patients?

    DEFF Research Database (Denmark)

    Bager, Palle; Dahlerup, Jens Frederik

      What´s cheapest, intravenous iron sucrose- or intravenous iron carboxymaltose treatment in IBD patients? It dependent on the economic evaluation perspective!   Aim: To evaluate the health care cost for intravenous iron sucrose (Venofer®, Vifor) and intravenous iron carboxymaltose (Ferinject......-cost per mg iron is for iron carboxymaltose approximately double the cost of iron sucrose.   Patients and Methods: Data related to 111 IBD-patients treated with intravenous iron at Aarhus University Hospital from August 2005 until October 2009 was used for the economic evaluation. Analysis included......, utensils and ½ hour spend by a nurse per visit; showed approximately 150€ extra cost per 1000 mg Fe++ administrated, if iron carboxymaltose was chosen. In contrast the CEA including both BIA-values and patient-related costs (transportation and lost income) showed iron carboxymaltose to be more cost...

  2. The Grand Challenge of Basin-Scale Groundwater Quality Management Modelling (United States)

    Fogg, G. E.


    The last 50+ years of agricultural, urban and industrial land and water use practices have accelerated the degradation of groundwater quality in the upper portions of many major aquifer systems upon which much of the world relies for water supply. In the deepest and most extensive systems (e.g., sedimentary basins) that typically have the largest groundwater production rates and hold fresh groundwaters on decadal to millennial time scales, most of the groundwater is not yet contaminated. Predicting the long-term future groundwater quality in such basins is a grand scientific challenge. Moreover, determining what changes in land and water use practices would avert future, irreversible degradation of these massive freshwater stores is a grand challenge both scientifically and societally. It is naïve to think that the problem can be solved by eliminating or reducing enough of the contaminant sources, for human exploitation of land and water resources will likely always result in some contamination. The key lies in both reducing the contaminant sources and more proactively managing recharge in terms of both quantity and quality, such that the net influx of contaminants is sufficiently moderate and appropriately distributed in space and time to reverse ongoing groundwater quality degradation. Just as sustainable groundwater quantity management is greatly facilitated with groundwater flow management models, sustainable groundwater quality management will require the use of groundwater quality management models. This is a new genre of hydrologic models do not yet exist, partly because of the lack of modeling tools and the supporting research to model non-reactive as well as reactive transport on large space and time scales. It is essential that the contaminant hydrogeology community, which has heretofore focused almost entirely on point-source plume-scale problems, direct it's efforts toward the development of process-based transport modeling tools and analyses capable

  3. Assessment and challenges of ligand docking into comparative models of G-protein coupled receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth Dong Nguyen

    Full Text Available The rapidly increasing number of high-resolution X-ray structures of G-protein coupled receptors (GPCRs creates a unique opportunity to employ comparative modeling and docking to provide valuable insight into the function and ligand binding determinants of novel receptors, to assist in virtual screening and to design and optimize drug candidates. However, low sequence identity between receptors, conformational flexibility, and chemical diversity of ligands present an enormous challenge to molecular modeling approaches. It is our hypothesis that rapid Monte-Carlo sampling of protein backbone and side-chain conformational space with Rosetta can be leveraged to meet this challenge. This study performs unbiased comparative modeling and docking methodologies using 14 distinct high-resolution GPCRs and proposes knowledge-based filtering methods for improvement of sampling performance and identification of correct ligand-receptor interactions. On average, top ranked receptor models built on template structures over 50% sequence identity are within 2.9 Å of the experimental structure, with an average root mean square deviation (RMSD of 2.2 Å for the transmembrane region and 5 Å for the second extracellular loop. Furthermore, these models are consistently correlated with low Rosetta energy score. To predict their binding modes, ligand conformers of the 14 ligands co-crystalized with the GPCRs were docked against the top ranked comparative models. In contrast to the comparative models themselves, however, it remains difficult to unambiguously identify correct binding modes by score alone. On average, sampling performance was improved by 10(3 fold over random using knowledge-based and energy-based filters. In assessing the applicability of experimental constraints, we found that sampling performance is increased by one order of magnitude for every 10 residues known to contact the ligand. Additionally, in the case of DOR, knowledge of a single specific

  4. Statistical challenges in modelling the health consequences of social mobility: the need for diagonal reference models. (United States)

    van der Waal, Jeroen; Daenekindt, Stijn; de Koster, Willem


    Various studies on the health consequences of socio-economic position address social mobility. They aim to uncover whether health outcomes are affected by: (1) social mobility, besides, (2) social origin, and (3) social destination. Conventional methods do not, however, estimate these three effects separately, which may produce invalid conclusions. We highlight that diagonal reference models (DRMs) overcome this problem, which we illustrate by focusing on overweight/obesity (OWOB). Using conventional methods (logistic-regression analyses with dummy variables) and DRMs, we examine the effects of intergenerational educational mobility on OWOB (BMI ≥ 25 kg/m 2 ) using survey data representative of the Dutch population aged 18-45 (1569 males, 1771 females). Conventional methods suggest that mobility effects on OWOB are present. Analyses with DRMs, however, indicate that no such effects exist. Conventional analyses of the health consequences of social mobility may produce invalid results. We, therefore, recommend the use of DRMs. DRMs also validly estimate the health consequences of other types of social mobility (e.g. intra- and intergenerational occupational and income mobility) and status inconsistency (e.g. in educational or occupational attainment between partners).

  5. Modeling-challenge paradigm using design of experiments for spacecraft immersed in nonstationary, between-regimes, flowing plasma (United States)

    Koepke, Me; Marchand, R.


    A conducting sphere and cylinder under the conditions of nonstationary, between-regimes, flowing plasma is adopted as a test case for a modeling-challenge paradigm based on design of experiments (DOE) methodology that merges numerical simulation and testing. This model/simulation development platform facilitates a red-team/blue-team style challenge aimed at a tailored set of standard experimental conditions and measurements addressing specific questions in spacecraft-environment interactions and assessing the capability of models to describe those conditions. The goal is streamlining the Model/Simulation development process. A byproduct is an enhancement of the interrelationship between experiments in the laboratory and in space. Here, we conceptualize the advantage of the model-challenge over conventional validation in advancing whole-device modeling objectives in basic and applied plasma science.

  6. Mathematical models for lymphatic filariasis transmission and control: Challenges and prospects

    Directory of Open Access Journals (Sweden)

    Kaliannagounder Krishnamoorthy


    Full Text Available Abstract Background Mathematical models developed for describing the dynamics of transmission, infection, disease and control of lymphatic filariasis (LF gained momentum following the 1997 World Health Assembly resolution and the launching of the Global Programme to Eliminate Lymphatic Filariasis (GPELF in 2000. Model applications could provide valuable inputs for making decisions while implementing large scale programmes. However these models need to be evaluated at different epidemiological settings for optimization and fine-tuning with new knowledge and understanding on infection/disease dynamics. Discussion EPIFIL and LYMFASIM are the two mathematical simulation models currently available for lymphatic filariasis transmission and control. Both models have been used for prediction and evaluation of control programmes under research settings. Their widespread application in evaluating large-scale elimination programmes warrants validation of assumptions governing the dynamics of infection and disease in different epidemiological settings. Furthermore, the predictive power of the models for decision support can be enhanced by generating knowledge on some important issues that pose challenges and incorporating such knowledge into the models. We highlight factors related to the efficacy of the drugs of choice, their mode of action, and the possibility that drug resistance may develop; the role of vector-parasite combinations; the magnitude of transmission thresholds; host-parasite interactions and their effects on the dynamics of infection and immunity; parasite biology, and progression to LF-associated disease. Summary The two mathematical models developed offer potential decision making tools for transmission and control of LF. In view of the goals of the GPELF, the predictive power of these models needs to be enhanced for their wide-spread application in large scale programmes. Assimilation and translation of new information into the models is

  7. Dynamics of dissolved organic carbon in hillslope discharge: Modeling and challenges (United States)

    Dusek, Jaromir; Vogel, Tomas; Dohnal, Michal; Barth, Johannes A. C.; Sanda, Martin; Marx, Anne; Jankovec, Jakub


    Reliable quantitative prediction of water movement and fluxes of dissolved substances - specifically organic carbon - at both the hillslope and the catchment scales remains a challenge due to complex boundary conditions and soil spatial heterogeneity. In addition, microbially mediated transformations of dissolved organic carbon (DOC) are recognized to determine the balance of DOC in soils. So far, only few studies utilized stable water isotope information in modeling and even fewer linked dissolved carbon fluxes to mixing and/or transport models. In this study, stormflow dynamics of 18O/16O ratios in the water molecules (expressed as δ18O) and DOC were analyzed using a physically-based modeling approach. A one-dimensional dual-continuum vertical flow and transport model was used to simulate the subsurface transport processes in a forest hillslope soil over a period of 2.5 years. The model was applied to describe the transformation of input signals of δ18O and DOC into output signals observed in the hillslope stormflow. To quantify uncertainty associated with the model parameterization, Monte Carlo analysis in conjunction with Latin hypercube sampling was applied. δ18O variations in hillslope discharge and in soil pore water were predicted reasonably well. Despite the complex nature of microbial transformations that caused uncertainty in model parameters and subsequent prediction of DOC transport, the simulated temporal patterns of DOC concentration in stormflow showed similar behavior to that reflected in the observed DOC fluxes. Due to preferential flow, the contribution of the hillslope DOC export was higher than the amounts that are usually found in the available literature.

  8. Modeling and simulation challenges pursued by the Consortium for Advanced Simulation of Light Water Reactors (CASL) (United States)

    Turinsky, Paul J.; Kothe, Douglas B.


    The Consortium for the Advanced Simulation of Light Water Reactors (CASL), the first Energy Innovation Hub of the Department of Energy, was established in 2010 with the goal of providing modeling and simulation (M&S) capabilities that support and accelerate the improvement of nuclear energy's economic competitiveness and the reduction of spent nuclear fuel volume per unit energy, and all while assuring nuclear safety. To accomplish this requires advances in M&S capabilities in radiation transport, thermal-hydraulics, fuel performance and corrosion chemistry. To focus CASL's R&D, industry challenge problems have been defined, which equate with long standing issues of the nuclear power industry that M&S can assist in addressing. To date CASL has developed a multi-physics ;core simulator; based upon pin-resolved radiation transport and subchannel (within fuel assembly) thermal-hydraulics, capitalizing on the capabilities of high performance computing. CASL's fuel performance M&S capability can also be optionally integrated into the core simulator, yielding a coupled multi-physics capability with untapped predictive potential. Material models have been developed to enhance predictive capabilities of fuel clad creep and growth, along with deeper understanding of zirconium alloy clad oxidation and hydrogen pickup. Understanding of corrosion chemistry (e.g., CRUD formation) has evolved at all scales: micro, meso and macro. CFD R&D has focused on improvement in closure models for subcooled boiling and bubbly flow, and the formulation of robust numerical solution algorithms. For multiphysics integration, several iterative acceleration methods have been assessed, illuminating areas where further research is needed. Finally, uncertainty quantification and data assimilation techniques, based upon sampling approaches, have been made more feasible for practicing nuclear engineers via R&D on dimensional reduction and biased sampling. Industry adoption of CASL's evolving M

  9. Hyperresolution Global Land Surface Modeling: Meeting a Grand Challenge for Monitoring Earth's Terrestrial Water (United States)

    Wood, Eric F.; Roundy, Joshua K.; Troy, Tara J.; van Beek, L. P. H.; Bierkens, Marc F. P.; 4 Blyth, Eleanor; de Roo, Ad; Doell. Petra; Ek, Mike; Famiglietti, James; hide


    Monitoring Earth's terrestrial water conditions is critically important to many hydrological applications such as global food production; assessing water resources sustainability; and flood, drought, and climate change prediction. These needs have motivated the development of pilot monitoring and prediction systems for terrestrial hydrologic and vegetative states, but to date only at the rather coarse spatial resolutions (approx.10-100 km) over continental to global domains. Adequately addressing critical water cycle science questions and applications requires systems that are implemented globally at much higher resolutions, on the order of 1 km, resolutions referred to as hyperresolution in the context of global land surface models. This opinion paper sets forth the needs and benefits for a system that would monitor and predict the Earth's terrestrial water, energy, and biogeochemical cycles. We discuss six major challenges in developing a system: improved representation of surface-subsurface interactions due to fine-scale topography and vegetation; improved representation of land-atmospheric interactions and resulting spatial information on soil moisture and evapotranspiration; inclusion of water quality as part of the biogeochemical cycle; representation of human impacts from water management; utilizing massively parallel computer systems and recent computational advances in solving hyperresolution models that will have up to 10(exp 9) unknowns; and developing the required in situ and remote sensing global data sets. We deem the development of a global hyperresolution model for monitoring the terrestrial water, energy, and biogeochemical cycles a grand challenge to the community, and we call upon the international hydrologic community and the hydrological science support infrastructure to endorse the effort.

  10. GIS-Based Planning and Modeling for Renewable Energy: Challenges and Future Research Avenues

    Directory of Open Access Journals (Sweden)

    Bernd Resch


    Full Text Available In the face of the broad political call for an “energy turnaround”, we are currently witnessing three essential trends with regard to energy infrastructure planning, energy generation and storage: from planned production towards fluctuating production on the basis of renewable energy sources, from centralized generation towards decentralized generation and from expensive energy carriers towards cost-free energy carriers. These changes necessitate considerable modifications of the energy infrastructure. Even though most of these modifications are inherently motivated by geospatial questions and challenges, the integration of energy system models and Geographic Information Systems (GIS is still in its infancy. This paper analyzes the shortcomings of previous approaches in using GIS in renewable energy-related projects, extracts distinct challenges from these previous efforts and, finally, defines a set of core future research avenues for GIS-based energy infrastructure planning with a focus on the use of renewable energy. These future research avenues comprise the availability base data and their “geospatial awareness”, the development of a generic and unified data model, the usage of volunteered geographic information (VGI and crowdsourced data in analysis processes, the integration of 3D building models and 3D data analysis, the incorporation of network topologies into GIS, the harmonization of the heterogeneous views on aggregation issues in the fields of energy and GIS, fine-grained energy demand estimation from freely-available data sources, decentralized storage facility planning, the investigation of GIS-based public participation mechanisms, the transition from purely structural to operational planning, data privacy aspects and, finally, the development of a new dynamic power market design.

  11. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

    Directory of Open Access Journals (Sweden)

    Jan B W J Cornelissen

    Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

  12. Molecular genetic models related to schizophrenia and psychotic illness: heuristics and challenges. (United States)

    O'Tuathaigh, Colm M P; Desbonnet, Lieve; Moran, Paula M; Kirby, Brian P; Waddington, John L


    Schizophrenia is a heritable disorder that may involve several common genes of small effect and/or rare copy number variation, with phenotypic heterogeneity across patients. Furthermore, any boundaries vis-à-vis other psychotic disorders are far from clear. Consequently, identification of informative animal models for this disorder, which typically relate to pharmacological and putative pathophysiological processes of uncertain validity, faces considerable challenges. In juxtaposition, the majority of mutant models for schizophrenia relate to the functional roles of a diverse set of genes associated with risk for the disorder or with such putative pathophysiological processes. This chapter seeks to outline the evidence from phenotypic studies in mutant models related to schizophrenia. These have commonly assessed the degree to which mutation of a schizophrenia-related gene is associated with the expression of several aspects of the schizophrenia phenotype or more circumscribed, schizophrenia-related endophenotypes; typically, they place specific emphasis on positive and negative symptoms and cognitive deficits, and extend to structural and other pathological features. We first consider the primary technological approaches to the generation of such mutants, to include their relative merits and demerits, and then highlight the diverse phenotypic approaches that have been developed for their assessment. The chapter then considers the application of mutant phenotypes to study pathobiological and pharmacological mechanisms thought to be relevant for schizophrenia, particularly in terms of dopaminergic and glutamatergic dysfunction, and to an increasing range of candidate susceptibility genes and copy number variants. Finally, we discuss several pertinent issues and challenges within the field which relate to both phenotypic evaluation and a growing appreciation of the functional genomics of schizophrenia and the involvement of gene × environment interactions.

  13. Challenges to achieving sustainable community health development within a donor aid business model. (United States)

    Ashwell, Helen; Barclay, Lesley


    This paper explores the paradox of donor aid being delivered through a business model through a case study in Papua New Guinea. A retrospective review of project implementation and an outcome evaluation provided an opportunity to examine the long-term results and sustainability of a large project. Analysis was informed by data collected from 175 interviews (national, provincial, district and village), 93 community discussions and observations across 10 provinces. Problems with the business model of delivering aid were evident from implementation data and in an evaluation conducted two years after project completion (2006). Compounding the business model effect were challenges of over-ambitious project goals with limited flexibility to adapt to changing circumstances, a donor payment system requiring short-term productivity and excessive reporting requirements. An overly ambitious project design, donor dominance within the business model and limited local counterpart capacity created problems in the community initiatives component of the project. Contractual pressures can negatively influence long-term outcomes that require development of local leadership and capacity. Future planning for donor project designs needs to be flexible, smaller in scope and have a longer timeframe of seven to 10 years. Donor-funded projects need to be sufficiently flexible to apply proven principles of community development, build local ownership and allow adequate time to build counterpart knowledge and skills.

  14. Laboratory cohabitation challenge model for shrimp hepatopancreatic microsporidiosis (HPM) caused by Enterocytozoon hepatopenaei (EHP). (United States)

    Salachan, Paul Vinu; Jaroenlak, Pattana; Thitamadee, Siripong; Itsathitphaisarn, Ornchuma; Sritunyalucksana, Kallaya


    Enterocytozoon hepatopenaei (EHP) causes hepatopancreatic microsporidiosis (HPM) in shrimp. It is probably endemic in Australasia and was first characterized and named from the giant or black tiger shrimp Penaeus monodon from Thailand in 2009. Later, it was also found to infect exotic Penaeus vannamei imported for cultivation in Asia. HPM is not normally associated with shrimp mortality, but information from shrimp farmers indicates that it is associated with significant growth retardation that is not clearly noticeable until 2-3 months of cultivation. In order to study modes of HPM transmission and to test possible control measures, a laboratory challenge model was needed that would mimic the mode of infection in shrimp ponds. We describe successful transmission in a cohabitation model with natural E. hepatopenaei (EHP)-infected shrimp in closed, perforated plastic containers placed in aquaria together with free-swimming, uninfected shrimp. After a period of 14 days all the free-swimming shrimp tested positive by PCR (approximately 60% with heavy infections evident by 1-step PCR positive test results) and gave positive histological and in situ hybridization results for E. hepatopenaei (EHP) in the hepatopancreas. A laboratory cohabitation model for studying E. hepatopenaei (EHP) has been developed and used to confirm that E. hepatopenaei (EHP) can be directly transmitted horizontally among shrimp via water. The model will facilitate studies on methods to prevent the E. hepatopenaei (EHP) transmission.

  15. Review article: Hydrological modeling in glacierized catchments of central Asia - status and challenges (United States)

    Chen, Yaning; Li, Weihong; Fang, Gonghuan; Li, Zhi


    Meltwater from glacierized catchments is one of the most important water supplies in central Asia. Therefore, the effects of climate change on glaciers and snow cover will have increasingly significant consequences for runoff. Hydrological modeling has become an indispensable research approach to water resources management in large glacierized river basins, but there is a lack of focus in the modeling of glacial discharge. This paper reviews the status of hydrological modeling in glacierized catchments of central Asia, discussing the limitations of the available models and extrapolating these to future challenges and directions. After reviewing recent efforts, we conclude that the main sources of uncertainty in assessing the regional hydrological impacts of climate change are the unreliable and incomplete data sets and the lack of understanding of the hydrological regimes of glacierized catchments of central Asia. Runoff trends indicate a complex response to changes in climate. For future variation of water resources, it is essential to quantify the responses of hydrologic processes to both climate change and shrinking glaciers in glacierized catchments, and scientific focus should be on reducing uncertainties linked to these processes.

  16. Challenges of Representing Sub-Grid Physics in an Adaptive Mesh Refinement Atmospheric Model (United States)

    O'Brien, T. A.; Johansen, H.; Johnson, J. N.; Rosa, D.; Benedict, J. J.; Keen, N. D.; Collins, W.; Goodfriend, E.


    Some of the greatest potential impacts from future climate change are tied to extreme atmospheric phenomena that are inherently multiscale, including tropical cyclones and atmospheric rivers. Extremes are challenging to simulate in conventional climate models due to existing models' coarse resolutions relative to the native length-scales of these phenomena. Studying the weather systems of interest requires an atmospheric model with sufficient local resolution, and sufficient performance for long-duration climate-change simulations. To this end, we have developed a new global climate code with adaptive spatial and temporal resolution. The dynamics are formulated using a block-structured conservative finite volume approach suitable for moist non-hydrostatic atmospheric dynamics. By using both space- and time-adaptive mesh refinement, the solver focuses computational resources only where greater accuracy is needed to resolve critical phenomena. We explore different methods for parameterizing sub-grid physics, such as microphysics, macrophysics, turbulence, and radiative transfer. In particular, we contrast the simplified physics representation of Reed and Jablonowski (2012) with the more complex physics representation used in the System for Atmospheric Modeling of Khairoutdinov and Randall (2003). We also explore the use of a novel macrophysics parameterization that is designed to be explicitly scale-aware.

  17. Multiscale Mechanics of Articular Cartilage: Potentials and Challenges of Coupling Musculoskeletal, Joint, and Microscale Computational Models (United States)

    Halloran, J. P.; Sibole, S.; van Donkelaar, C. C.; van Turnhout, M. C.; Oomens, C. W. J.; Weiss, J. A.; Guilak, F.; Erdemir, A.


    Articular cartilage experiences significant mechanical loads during daily activities. Healthy cartilage provides the capacity for load bearing and regulates the mechanobiological processes for tissue development, maintenance, and repair. Experimental studies at multiple scales have provided a fundamental understanding of macroscopic mechanical function, evaluation of the micromechanical environment of chondrocytes, and the foundations for mechanobiological response. In addition, computational models of cartilage have offered a concise description of experimental data at many spatial levels under healthy and diseased conditions, and have served to generate hypotheses for the mechanical and biological function. Further, modeling and simulation provides a platform for predictive risk assessment, management of dysfunction, as well as a means to relate multiple spatial scales. Simulation-based investigation of cartilage comes with many challenges including both the computational burden and often insufficient availability of data for model development and validation. This review outlines recent modeling and simulation approaches to understand cartilage function from a mechanical systems perspective, and illustrates pathways to associate mechanics with biological function. Computational representations at single scales are provided from the body down to the microstructure, along with attempts to explore multiscale mechanisms of load sharing that dictate the mechanical environment of the cartilage and chondrocytes. PMID:22648577

  18. High resolution weather data for urban hydrological modelling and impact assessment, ICT requirements and future challenges (United States)

    ten Veldhuis, Marie-claire; van Riemsdijk, Birna


    presentation will highlight ICT-related requirements and limitations in high resolution urban hydrological modelling and analysis. Further ICT challenges arise in provision of high resolution radar data for diverging information needs as well as in combination with other data sources in the urban environment. Different types of information are required for such diverse activities as operational flood protection, traffic management, large event organisation, business planning in shopping districts and restaurants, timing of family activities. These different information needs may require different configurations and data processing for radars and other data sources. An ICT challenge is to develop techniques for deciding how to automatically respond to these diverging information needs (e.g., through (semi-)automated negotiation). Diverse activities also provide a wide variety of information resources that can supplement traditional networks of weather sensors, such as rain sensors on cars and social media. Another ICT challenge is how to combine data from these different sources for answering a particular information need. Examples will be presented of solutions are currently being explored.

  19. Coupled Atmosphere-Wave-Ocean Modeling of Tropical Cyclones: Progress, Challenges, and Ways Forward (United States)

    Chen, Shuyi


    /s. It is found that the air-sea fluxes are quite asymmetric around a storm with complex features representing various air-sea interaction processes in TCs. A unique observation in Typhoon Fanapi is the development of a stable boundary layer in the near-storm cold wake region, which has a direct impact on TC inner core structure and intensity. Despite of the progress, challenges remain. Air-sea momentum exchange in wind speed greater than 30-40 m/s is largely unresolved. Directional wind-wave stress and wave-current stress are difficult to determine from observations. Effects of sea spray on the air-sea fluxes are still not well understood. This talk will provide an overview on progress made in recent years, challenges we are facing, and ways forward. An integrated coupled observational and atmosphere-wave-ocean modeling system is urgently needed, in which coupled model development and targeted observations from field campaign and lab measurements together form the core of the research and prediction system. Another important aspect is that fully coupled models provide explicit, integrated impact forecasts of wind, rain, waves, ocean currents and surges in TCs and winter storms, which are missing in most current NWP models. It requires a new strategy for model development, evaluation, and verification. Ensemble forecasts using high-resolution coupled atmosphere-wave-ocean models can provide probabilistic forecasts and quantitative uncertainty estimates, which also allow us to explore new methodologies to verify probabilistic impact forecasts and evaluate model physics using a stochastic approach. Examples of such approach in TCs including Superstorm Sandy will be presented.

  20. Multi -omics and metabolic modelling pipelines: challenges and tools for systems microbiology. (United States)

    Fondi, Marco; Liò, Pietro


    Integrated -omics approaches are quickly spreading across microbiology research labs, leading to (i) the possibility of detecting previously hidden features of microbial cells like multi-scale spatial organization and (ii) tracing molecular components across multiple cellular functional states. This promises to reduce the knowledge gap between genotype and phenotype and poses new challenges for computational microbiologists. We underline how the capability to unravel the complexity of microbial life will strongly depend on the integration of the huge and diverse amount of information that can be derived today from -omics experiments. In this work, we present opportunities and challenges of multi -omics data integration in current systems biology pipelines. We here discuss which layers of biological information are important for biotechnological and clinical purposes, with a special focus on bacterial metabolism and modelling procedures. A general review of the most recent computational tools for performing large-scale datasets integration is also presented, together with a possible framework to guide the design of systems biology experiments by microbiologists. Copyright © 2015. Published by Elsevier GmbH.

  1. A Comprehensive Study on the Internet of Underwater Things: Applications, Challenges, and Channel Models. (United States)

    Kao, Chien-Chi; Lin, Yi-Shan; Wu, Geng-De; Huang, Chun-Ju


    The Internet of Underwater Things (IoUT) is a novel class of Internet of Things (IoT), and is defined as the network of smart interconnected underwater objects. IoUT is expected to enable various practical applications, such as environmental monitoring, underwater exploration, and disaster prevention. With these applications, IoUT is regarded as one of the potential technologies toward developing smart cities. To support the concept of IoUT, Underwater Wireless Sensor Networks (UWSNs) have emerged as a promising network system. UWSNs are different from the traditional Territorial Wireless Sensor Networks (TWSNs), and have several unique properties, such as long propagation delay, narrow bandwidth, and low reliability. These unique properties would be great challenges for IoUT. In this paper, we provide a comprehensive study of IoUT, and the main contributions of this paper are threefold: (1) we introduce and classify the practical underwater applications that can highlight the importance of IoUT; (2) we point out the differences between UWSNs and traditional TWSNs, and these differences are the main challenges for IoUT; and (3) we investigate and evaluate the channel models, which are the technical core for designing reliable communication protocols on IoUT.

  2. University of Wisconsin IAIMS planning: organizational challenges within a faculty governance model. (United States)

    Kwiatkowski, K; Brennan, P F; DeMets, D; Dahlen, K; Buchanan, J


    The University of Wisconsin-Madison Health Sciences Schools are currently in the planning stage of developing an Integrated Advanced Information Management System (IAIMS). The planning phase of this project attends to the unique opportunities that are found at the flagship campus of a large state university system. Statewide teaching and research initiatives and accelerated campus-level capital development challenge the planners to create an IAIMS plan that anticipates an emerging health science environment. Additionally, UW-Madison has an organizational culture with a strong tradition of faculty governance, which provides a very desirable and flexible decision-making environment for a cross-discipline collaborative information management initiative. Development of a shared IAIMS vision conflicts with a governance model that most directly supports intradepartmental decision-making. The challenge presented here for an IAIMS initiative has less to do with hard wiring a technical infrastructure and more to do with increased stakeholder cooperation in a highly decentralized organization with autonomous information systems.

  3. Methodological challenges and analytic opportunities for modeling and interpreting Big Healthcare Data. (United States)

    Dinov, Ivo D


    Managing, processing and understanding big healthcare data is challenging, costly and demanding. Without a robust fundamental theory for representation, analysis and inference, a roadmap for uniform handling and analyzing of such complex data remains elusive. In this article, we outline various big data challenges, opportunities, modeling methods and software techniques for blending complex healthcare data, advanced analytic tools, and distributed scientific computing. Using imaging, genetic and healthcare data we provide examples of processing heterogeneous datasets using distributed cloud services, automated and semi-automated classification techniques, and open-science protocols. Despite substantial advances, new innovative technologies need to be developed that enhance, scale and optimize the management and processing of large, complex and heterogeneous data. Stakeholder investments in data acquisition, research and development, computational infrastructure and education will be critical to realize the huge potential of big data, to reap the expected information benefits and to build lasting knowledge assets. Multi-faceted proprietary, open-source, and community developments will be essential to enable broad, reliable, sustainable and efficient data-driven discovery and analytics. Big data will affect every sector of the economy and their hallmark will be 'team science'.

  4. Building Information Modelling: Challenges and Barriers in Implement of BIM for Interior Design Industry in Malaysia (United States)

    Hamid, A. B. Abd; Taib, M. Z. Mohd; Razak, A. H. N. Abdul; Embi, M. R.


    Building Information Modelling (BIM) is an innovative approach that has developed crossways the global in architecture, engineering and construction (AEC) industry. The construction industry of Malaysia has undergone a rapid development and dynamic technology adoption in advance and methods between the players industry and stakeholders. Consequently, limited technologies and devices have not been successful as it should have been. This study will be emphasizing scenarios of challenges and barriers in adopting BIM in interior design industry in Malaysia. The study was emphasizing the challenges and barriers in BIM usage from the designer’s perspective. The data are collected through the questionnaires as to identifying the barriers, knowledge, readiness and awareness and distributed to interior design firms were selected randomly. The finding of this research is to examine the barriers and causes of variables BIM usage for interior design industry in Malaysia. The outcome of this study is to identify the constraint of adoption BIM in interior design industry compare to others players in same industry.

  5. The Regional Nature of Global Challenges. A Need and Strategy for Integrated Regional Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Hibbard, Kathleen A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Janetos, Anthony C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)


    In this paper, we explore the regional nature of global environmental challenges. We take a broad approach by examining the scientific foundation that is needed to support policy and decision making and identifying some of the most important barriers to progress that are truly scale-dependent. In so doing, we hope to show that understanding global environmental changes requires understanding a number of intrinsically regional phenomena, and that successful decision making likewise requires an integrated approach that accounts for a variety of regional Earth system processes—which we define to include both human activities and environmental systems that operate or interact primarily at sub-continental scales. Understanding regional processes and phenomena, including regional decision-making processes and information needs, should thus be an integral part of the global change research agenda. To address some of the key issues and challenges, we propose an integrated regional modeling approach that accounts for the dynamic interactions among physical, ecological, biogeochemical, and human processes and provides relevant information to regional decision makers and stakeholders.

  6. A Comprehensive Study on the Internet of Underwater Things: Applications, Challenges, and Channel Models

    Directory of Open Access Journals (Sweden)

    Chien-Chi Kao


    Full Text Available The Internet of Underwater Things (IoUT is a novel class of Internet of Things (IoT, and is defined as the network of smart interconnected underwater objects. IoUT is expected to enable various practical applications, such as environmental monitoring, underwater exploration, and disaster prevention. With these applications, IoUT is regarded as one of the potential technologies toward developing smart cities. To support the concept of IoUT, Underwater Wireless Sensor Networks (UWSNs have emerged as a promising network system. UWSNs are different from the traditional Territorial Wireless Sensor Networks (TWSNs, and have several unique properties, such as long propagation delay, narrow bandwidth, and low reliability. These unique properties would be great challenges for IoUT. In this paper, we provide a comprehensive study of IoUT, and the main contributions of this paper are threefold: (1 we introduce and classify the practical underwater applications that can highlight the importance of IoUT; (2 we point out the differences between UWSNs and traditional TWSNs, and these differences are the main challenges for IoUT; and (3 we investigate and evaluate the channel models, which are the technical core for designing reliable communication protocols on IoUT.

  7. A phase I trial of intravenous catumaxomab

    DEFF Research Database (Denmark)

    Mau-Sørensen, Morten; Dittrich, Christian; Dienstmann, Rodrigo


    design in epithelial cancers with known EpCAM expression. The dose-limiting toxicity (DLT) period consisted of 4 weeks, with weekly intravenous administration of catumaxomab. Key DLTs were ≥grade 3 optimally treated non-hematological toxicity; ≥grade 3 infusion-related reactions refractory to supportive....... A reversible decrease in liver function test (prothrombin time) at the 7-µg dose level was considered a DLT. The first patient at 10 µg experienced a fatal hepatic failure related to catumaxomab that led to the termination of the study. CONCLUSIONS: The MTD of weekly intravenous catumaxomab was 7 µg. Major...

  8. Intravenous polyclonal human immunoglobulins in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Per Soelberg


    Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta-analysis ......Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta...

  9. Dynamic, spatial models of parasite transmission in wildlife: Their structure, applications and remaining challenges. (United States)

    White, Lauren A; Forester, James D; Craft, Meggan E


    Individual differences in contact rate can arise from host, group and landscape heterogeneity and can result in different patterns of spatial spread for diseases in wildlife populations with concomitant implications for disease control in wildlife of conservation concern, livestock and humans. While dynamic disease models can provide a better understanding of the drivers of spatial spread, the effects of landscape heterogeneity have only been modelled in a few well-studied wildlife systems such as rabies and bovine tuberculosis. Such spatial models tend to be either purely theoretical with intrinsic limiting assumptions or individual-based models that are often highly species- and system-specific, limiting the breadth of their utility. Our goal was to review studies that have utilized dynamic, spatial models to answer questions about pathogen transmission in wildlife and identify key gaps in the literature. We begin by providing an overview of the main types of dynamic, spatial models (e.g., metapopulation, network, lattice, cellular automata, individual-based and continuous-space) and their relation to each other. We investigate different types of ecological questions that these models have been used to explore: pathogen invasion dynamics and range expansion, spatial heterogeneity and pathogen persistence, the implications of management and intervention strategies and the role of evolution in host-pathogen dynamics. We reviewed 168 studies that consider pathogen transmission in free-ranging wildlife and classify them by the model type employed, the focal host-pathogen system, and their overall research themes and motivation. We observed a significant focus on mammalian hosts, a few well-studied or purely theoretical pathogen systems, and a lack of studies occurring at the wildlife-public health or wildlife-livestock interfaces. Finally, we discuss challenges and future directions in the context of unprecedented human-mediated environmental change. Spatial models

  10. Optimising The Available Scarce Water Resources At European Scale In A Modelling Environment: Results And Challenges (United States)

    de Roo, Ad; Burek, Peter; Gentile, Alessandro; Udias, Angel; Bouraoui, Faycal


    sector, the manufacturing-industry sector, the energy-production sector and the domestic sector. Also, potential flood damage of a 100-year return period flood has been used as an indicator. The study has shown that technically this modelling software environment can deliver optimum scenario combinations of packages of measures that improve various water quantity and water quality indicators, but that additional work is needed before final conclusions can be made using the tool. Further work is necessary, especially in the economic loss estimations, the water prices and price-elasticity, as well as the implementation and maintenance costs of individual scenarios. First results and challenges will be presented and discussed.

  11. Evaluation of Orally Delivered ST-246 as Postexposure Prophylactic and Antiviral Therapeutic in an Aerosolized Rabbitpox Rabbit Model (United States)


    the ketamine–xylazinemixture and then euthanized with an overdose of intravenous pentobarbital solution. 2.6. Plaque assay Viral contents of starting...anesthetized and then euthanized with an overdose of intravenous pentobarbital solution as described above. Although a complete gross necropsy was...challenge meth- ods. In: Swearengen, J.L. (Ed.), Biodefense: Research Methodology and Animal Models. CRC Press, Boca Raton , FL, pp. 61–76. Sbrana, E

  12. A Systematic Approach towards Optimizing a Cohabitation Challenge Model for Infectious Pancreatic Necrosis Virus in Atlantic Salmon (Salmo salar L.). (United States)

    Munang'andu, Hetron Mweemba; Santi, Nina; Fredriksen, Børge Nilsen; Løkling, Knut-Egil; Evensen, Øystein


    A cohabitation challenge model was developed for use in evaluating the efficacy of vaccines developed against infectious pancreatic necrosis virus (IPNV) in Atlantic salmon (Salmo salar L) using a stepwise approach. The study involved identifying a set of input variables that were optimized before inclusion in the model. Input variables identified included the highly virulent Norwegian Sp strain NVI015-TA encoding the T217A221 motif having the ability to cause >90% mortality and a hazard risk ratio of 490.18 (p75% in the unvaccinated fish in order to attain a high discriminatory capacity (DC) between the vaccinated and control fish as a measure of vaccine efficacy. The model shows the importance of using highly susceptible fish to IPNV in the optimization of challenge models by showing that highly susceptible fish had a better DC of differentiating vaccine protected fish from the unvaccinated control fish than the less susceptible fish. Once all input variables were optimized, the model was tested for its reproducibility by generating similar results from three independent cohabitation challenge trials using the same input variables. Overall, data presented here show that the cohabitation challenge model developed in this study is reproducible and that it can reliably be used to evaluate the efficacy of vaccines developed against IPNV in Atlantic salmon. We envision that the approach used here will open new avenues for developing optimal challenge models for use in evaluating the efficacy of different vaccines used in aquaculture.

  13. ACADEMIC DISHONESTY IN DISTANCE HIGHER EDUCATION: Challenges and Models for Moral Education in the Digital Era

    Directory of Open Access Journals (Sweden)

    Mohammad Imam FARISI


    Full Text Available Today, in the era of open access to digital-based information and communication, one of the biggest challenges in higher education to realize moral education and to build academic culture and integrity is the emergence of academic dishonesty behaviors among academic members. The paper describes academic dishonesty behaviors in Distance Higher Education (DHE institutions within the context of moral education in the digital era. The paper reviews the results of the research on academic dishonesty behaviors and practices in DHE institutions worldwide; factors which have a very significant role for the emergence of academic dishonesty behaviors and practices. It is also discusses an integrated model of moral education as interdisciplinary strategy in combating academic dishonesty and in promoting academic culture and integrity in DHE.

  14. Challenges of electricity production scenarios modelling for life cycle assessment of environmental impacts

    International Nuclear Information System (INIS)

    Blanc, Isabelle; Beloin-Saint-Pierre, Didier


    This communication presents a first attempt at making a life cycle assessment of prospective electricity production scenarios which were designed in the EnerGEO project. We start by a basic review of system (in this case, scenario) modelling expectations in today's LCA study. We then review some of the challenges of implementation due to the lack of detailed description of present and future electricity production systems. The importance of a detailed description is then shown with an evaluation of uncertainty of life cycle impact assessment results for three scenarios of German electricity production in 2030. The significant uncertainties we found, prevent us from detecting a relevant trend or making any comparison between the three chosen scenarios. We finally come to the conclusion that the LCA methodology will become relevant for the environmental assessment of electricity production scenarios when many more detailed information are accounted to describe future technologies, structures and sources of energy. (orig.)

  15. Challenging passivity in venous leg ulcer care - the ABC model of management. (United States)

    Harding, Keith


    The under-utilisation of compression for venous leg ulcer (VLU) management translates into lost opportunities to heal wounds, improve patients' quality of life and maximise health care system efficiency. Although compression therapy is considered gold standard according to clinical guidelines, lack of clinician knowledge, unclear referral pathways, local unavailability of compression and patient unwillingness to receive compression, amongst other reasons, mean many candidates for compression do not receive appropriate treatment. This article presents a solution in the form of the 'ABC model of VLU management, a simplified approach that challenges passivity in the current approach to VLU treatment and supports wider adoption of appropriate compression therapy systems. © 2016 Inc and John Wiley & Sons Ltd.

  16. Industrial-Strength Model-Based Testing - State of the Art and Current Challenges

    Directory of Open Access Journals (Sweden)

    Jan Peleska


    Full Text Available As of today, model-based testing (MBT is considered as leading-edge technology in industry. We sketch the different MBT variants that - according to our experience - are currently applied in practice, with special emphasis on the avionic, railway and automotive domains. The key factors for successful industrial-scale application of MBT are described, both from a scientific and a managerial point of view. With respect to the former view, we describe the techniques for automated test case, test data and test procedure generation for concurrent reactive real-time systems which are considered as the most important enablers for MBT in practice. With respect to the latter view, our experience with introducing MBT approaches in testing teams are sketched. Finally, the most challenging open scientific problems whose solutions are bound to improve the acceptance and effectiveness of MBT in industry are discussed.

  17. The Challenge of Teaching Blind Students Atomic Models and the Process of Teacher Education

    Directory of Open Access Journals (Sweden)

    Renata Cardoso de Sá Ribeiro Razuck


    Full Text Available Based on the National Special Education in the Perspective of Inclusive Education (2008, students with special educational needs have to be included in the regular schools. Specifically blind students, because of their specific characteristics, they need necessary resources and suitable materials that can provide overcoming the lack of visualization. In this context, chemistry has a great visual appeal and provides a huge challenge for the acquisition of its concepts by the blinds. In order to try to fill some gaps in Chemistry contents with great visual appeal, this paper proposes a discussion on the importance of applying alternative pedagogical resources that enable visually impaired to understand and construct this imaginary science, working to this with prototypes of atomic models. This work is intended not only to contribute to the teaching-learning process, but also for the training of undergraduate courses to work towards inclusion.

  18. Current Challenges in the First Principle Quantitative Modelling of the Lower Hybrid Current Drive in Tokamaks (United States)

    Peysson, Y.; Bonoli, P. T.; Chen, J.; Garofalo, A.; Hillairet, J.; Li, M.; Qian, J.; Shiraiwa, S.; Decker, J.; Ding, B. J.; Ekedahl, A.; Goniche, M.; Zhai, X.


    The Lower Hybrid (LH) wave is widely used in existing tokamaks for tailoring current density profile or extending pulse duration to steady-state regimes. Its high efficiency makes it particularly attractive for a fusion reactor, leading to consider it for this purpose in ITER tokamak. Nevertheless, if basics of the LH wave in tokamak plasma are well known, quantitative modeling of experimental observations based on first principles remains a highly challenging exercise, despite considerable numerical efforts achieved so far. In this context, a rigorous methodology must be carried out in the simulations to identify the minimum number of physical mechanisms that must be considered to reproduce experimental shot to shot observations and also scalings (density, power spectrum). Based on recent simulations carried out for EAST, Alcator C-Mod and Tore Supra tokamaks, the state of the art in LH modeling is reviewed. The capability of fast electron bremsstrahlung, internal inductance li and LH driven current at zero loop voltage to constrain all together LH simulations is discussed, as well as the needs of further improvements (diagnostics, codes, LH model), for robust interpretative and predictive simulations.

  19. Challenges and models in supporting logistics system design for dedicated-biomass-based bioenergy industry. (United States)

    Zhu, Xiaoyan; Li, Xueping; Yao, Qingzhu; Chen, Yuerong


    This paper analyzed the uniqueness and challenges in designing the logistics system for dedicated biomass-to-bioenergy industry, which differs from the other industries, due to the unique features of dedicated biomass (e.g., switchgrass) including its low bulk density, restrictions on harvesting season and frequency, content variation with time and circumambient conditions, weather effects, scattered distribution over a wide geographical area, and so on. To design it, this paper proposed a mixed integer linear programming model. It covered from planting and harvesting switchgrass to delivering to a biorefinery and included the residue handling, concentrating on integrating strategic decisions on the supply chain design and tactical decisions on the annual operation schedules. The present numerical examples verified the model and demonstrated its use in practice. This paper showed that the operations of the logistics system were significantly different for harvesting and non-harvesting seasons, and that under the well-designed biomass logistics system, the mass production with a steady and sufficient supply of biomass can increase the unit profit of bioenergy. The analytical model and practical methodology proposed in this paper will help realize the commercial production in biomass-to-bioenergy industry. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Induced Pluripotency and Gene Editing in Disease Modelling: Perspectives and Challenges

    Directory of Open Access Journals (Sweden)

    Yu Fen Samantha Seah


    Full Text Available Embryonic stem cells (ESCs are chiefly characterized by their ability to self-renew and to differentiate into any cell type derived from the three main germ layers. It was demonstrated that somatic cells could be reprogrammed to form induced pluripotent stem cells (iPSCs via various strategies. Gene editing is a technique that can be used to make targeted changes in the genome, and the efficiency of this process has been significantly enhanced by recent advancements. The use of engineered endonucleases, such as homing endonucleases, zinc finger nucleases (ZFNs, transcription activator-like effector nucleases (TALENs and Cas9 of the CRISPR system, has significantly enhanced the efficiency of gene editing. The combination of somatic cell reprogramming with gene editing enables us to model human diseases in vitro, in a manner considered superior to animal disease models. In this review, we discuss the various strategies of reprogramming and gene targeting with an emphasis on the current advancements and challenges of using these techniques to model human diseases.

  1. Current challenges using models to forecast seawater intrusion: lessons from the Eastern Shore of Virginia, USA (United States)

    Sanford, Ward E.; Pope, Jason P.


    A three-dimensional model of the aquifer system of the Eastern Shore of Virginia, USA was calibrated to reproduce historical water levels and forecast the potential for saltwater intrusion. Future scenarios were simulated with two pumping schemes to predict potential areas of saltwater intrusion. Simulations suggest that only a few wells would be threatened with detectable salinity increases before 2050. The objective was to examine whether salinity increases can be accurately forecast for individual wells with such a model, and to address what the challenges are in making such model forecasts given current (2009) simulation capabilities. The analysis suggests that even with current computer capabilities, accurate simulations of concentrations within a regional-scale (many km) transition zone are computationally prohibitive. The relative paucity of data that is typical for such regions relative to what is needed for accurate transport simulations suggests that even with an infinitely powerful computer, accurate forecasting for a single well would still be elusive. Useful approaches may include local-grid refinement near wells and geophysical surveys, but it is important to keep expectations for simulated forecasts at wells in line with chloride concentration and other data that can be obtained at that local scale.

  2. Longitudinal Omics Modelling and Integration in Clinical Metabonomics Research: challenges in childhood metabolic health research

    Directory of Open Access Journals (Sweden)

    Peter eSperisen


    Full Text Available Systems biology is an important approach for deciphering the complex processes in health maintenance and the etiology of metabolic diseases. Such integrative methodologies will help better understand the molecular mechanisms involved in growth and development throughout childhood, and consequently will result in new insights about metabolic and nutritional requirements of infants, children and adults. To achieve this, a better understanding of the physiological processes at anthropometric, cellular and molecular level for any given individual is needed. In this respect, novel omics technologies in combination with sophisticated data modelling techniques are key. Due to the highly complex network of influential factors determining individual trajectories, it becomes imperative to develop proper tools and solutions that will comprehensively model biological information related to growth and maturation of our body functions. The aim of this review and perspective is to evaluate, succinctly, promising data analysis approaches to enable data integration for clinical research, with an emphasis on the longitudinal component. Approaches based on empirical and mechanistic modelling of omics data are essential to leverage findings from high dimensional omics datasets and enable biological interpretation and clinical translation. On the one hand, empirical methods, which provide quantitative descriptions of patterns in the data, are mostly used for exploring and mining datasets. On the other hand, mechanistic models are based on an understanding of the behavior of a system’s components and condense information about the known functions, allowing robust and reliable analyses to be performed by bioinformatics pipelines and similar tools. Herein, we will illustrate current examples, challenges and perspectives in the applications of empirical and mechanistic modelling in the context of childhood metabolic health research.

  3. Longitudinal omics modeling and integration in clinical metabonomics research: challenges in childhood metabolic health research (United States)

    Sperisen, Peter; Cominetti, Ornella; Martin, François-Pierre J.


    Systems biology is an important approach for deciphering the complex processes in health maintenance and the etiology of metabolic diseases. Such integrative methodologies will help better understand the molecular mechanisms involved in growth and development throughout childhood, and consequently will result in new insights about metabolic and nutritional requirements of infants, children and adults. To achieve this, a better understanding of the physiological processes at anthropometric, cellular and molecular level for any given individual is needed. In this respect, novel omics technologies in combination with sophisticated data modeling techniques are key. Due to the highly complex network of influential factors determining individual trajectories, it becomes imperative to develop proper tools and solutions that will comprehensively model biological information related to growth and maturation of our body functions. The aim of this review and perspective is to evaluate, succinctly, promising data analysis approaches to enable data integration for clinical research, with an emphasis on the longitudinal component. Approaches based on empirical and mechanistic modeling of omics data are essential to leverage findings from high dimensional omics datasets and enable biological interpretation and clinical translation. On the one hand, empirical methods, which provide quantitative descriptions of patterns in the data, are mostly used for exploring and mining datasets. On the other hand, mechanistic models are based on an understanding of the behavior of a system's components and condense information about the known functions, allowing robust and reliable analyses to be performed by bioinformatics pipelines and similar tools. Herein, we will illustrate current examples, challenges and perspectives in the applications of empirical and mechanistic modeling in the context of childhood metabolic health research. PMID:26301225

  4. Design Challenges of an Episode-Based Payment Model in Oncology: The Centers for Medicare & Medicaid Services Oncology Care Model. (United States)

    Kline, Ronald M; Muldoon, L Daniel; Schumacher, Heidi K; Strawbridge, Larisa M; York, Andrew W; Mortimer, Laura K; Falb, Alison F; Cox, Katherine J; Bazell, Carol; Lukens, Ellen W; Kapp, Mary C; Rajkumar, Rahul; Bassano, Amy; Conway, Patrick H


    The Centers for Medicare & Medicaid Services developed the Oncology Care Model as an episode-based payment model to encourage participating practitioners to provide higher-quality, better-coordinated care at a lower cost to the nearly three-quarter million fee-for-service Medicare beneficiaries with cancer who receive chemotherapy each year. Episode payment models can be complex. They combine into a single benchmark price all payments for services during an episode of illness, many of which may be delivered at different times by different providers in different locations. Policy and technical decisions include the definition of the episode, including its initiation, duration, and included services; the identification of beneficiaries included in the model; and beneficiary attribution to practitioners with overall responsibility for managing their care. In addition, the calculation and risk adjustment of benchmark episode prices for the bundle of services must reflect geographic cost variations and diverse patient populations, including varying disease subtypes, medical comorbidities, changes in standards of care over time, the adoption of expensive new drugs (especially in oncology), as well as diverse practice patterns. Other steps include timely monitoring and intervention as needed to avoid shifting the attribution of beneficiaries on the basis of their expected episode expenditures as well as to ensure the provision of necessary medical services and the development of a meaningful link to quality measurement and improvement through the episode-based payment methodology. The complex and diverse nature of oncology business relationships and the specific rules and requirements of Medicare payment systems for different types of providers intensify these issues. The Centers for Medicare & Medicaid Services believes that by sharing its approach to addressing these decisions and challenges, it may facilitate greater understanding of the model within the oncology

  5. Challenges for modelling spatio-temporal variations of malaria risk in Malawi (United States)

    Lowe, R.; Chirombo, J.; Tompkins, A. M.


    Malaria is the leading cause of morbidity and mortality in Malawi with more than 6 million episodes reported each year. Malaria poses a huge economic burden to Malawi in terms of the direct cost of treating malaria patients and also indirect costs resulting from workdays lost in agriculture and industry and absenteeism from school. Malawi implements malaria control activities within the Roll Back Malaria framework, with the objective to provide those most at risk (i.e. children under five years, pregnant woman and individuals with suppressed immune systems) access to personal and community protective measures. However, at present there is no mechanism by which to target the most 'at risk' populations ahead of an impending epidemic. Malaria transmission is influenced by variations in meteorological conditions, which impact the biology of the mosquito and the availability of breeding sites, but also socio-economic conditions such as levels of urbanisation, poverty and education, which influence human vulnerability and vector habitat. The many potential drivers of malaria, both extrinsic, such as climate, and intrinsic, such as population immunity are often difficult to disentangle. This presents a challenge for modelling of malaria risk in space and time. Using an age-stratified spatio-temporal dataset of malaria cases at the district level from July 2004 - June 2011, we use a spatio-temporal modelling framework to model variations in malaria risk in Malawi. Climatic and topographic variations are accounted for using an interpolation method to relate gridded products to administrative districts. District level data is tested in the model to account for confounding factors, including the proportion of the population living in urban areas; residing in traditional housing; with no toilet facilities; who do not attend school, etc, the number of health facilities per population and yearly estimates of insecticide-treated mosquito net distribution. In order to account for

  6. Administration and monitoring of intravenous anesthetics

    NARCIS (Netherlands)

    Sahinovic, Marko M.; Absalom, Anthony R.; Struys, Michel M. R. F.


    Purpose of review The importance of accuracy in controlling the dose-response relation for intravenous anesthetics is directly related to the importance of optimizing the efficacy and quality of anesthesia while minimizing adverse drug effects. Therefore, it is important to measure and control all

  7. Intravenous immunoglobulin treatment for secondary recurrent miscarriage

    DEFF Research Database (Denmark)

    Christiansen, O B; Larsen, E C; Egerup, P


    OBJECTIVE: To determine whether infusions with intravenous immunoglobulin (IVIg) during early pregnancy increase live birth rate in women with secondary recurrent miscarriage compared with placebo. DESIGN: A single-centre, randomised, double-blind, placebo-controlled trial. SETTING: A tertiary...

  8. Intravenous iron supplementation in children on hemodialysis.

    NARCIS (Netherlands)

    Leijn, E.; Monnens, L.A.H.; Cornelissen, E.A.M.


    BACKGROUND: Children with end-stage renal disease (ESRD) on hemodialysis (HD) are often absolute or functional iron deficient. There is little experience in treating these children with intravenous (i.v.) iron-sucrose. In this prospective study, different i.v. iron-sucrose doses were tested in

  9. Intravenous and intramuscular magnesium sulphate regimens in ...

    African Journals Online (AJOL)


    Sep 3, 1993 ... parenterally, usually according to one of two popular regimens: the intramuscular (IM) regimen introduced by. Pritchard' and a continuous intravenous (IV) infusion described by Zuspan! Sibai et a/.3 have reported that lower serum magnesium values are achieved with Zuspan's regimen (maintenance dose ...

  10. Clinical Evaluation of Ciprofloxacin Intravenous Preparation ...

    African Journals Online (AJOL)

    The most common site of bacteria infection in humans is the urinary tract. For nosocomial infections it is the catheterized urinary tract. Compromised immune responses in hospitalized patients contribute to the difficulties encountered in treating their infections. In these patients, administration of intravenous antibiotic is ...

  11. A Comparison of Prophylactic Intravenous Glycopyrrolate and ...

    African Journals Online (AJOL)

    Ephedrine is gradually falling out of favour because of the associated tachyarrhythmia and foetal acidosis. This study compared the effect of preoperative administration of intravenous glycopyrrolate and ephedrine on spinal induced maternal hypotension. Patients and Methods: Fifty patients scheduled for elective C/S were ...

  12. Comparative Evaluation of Ultrasonography and Intravenous ...

    African Journals Online (AJOL)

    Background: Renal ultrasonography an easily available procedure was compared to intravenous urogram (IVU) to determine its suitability as an alternative to the latter, which is a relatively invasive test for demonstrating hydronephrosis/ or ureteric obstruction in cervical cancer staging. Study design: Thirty five histologically ...

  13. Intravenous voriconazole after toxic oral administration

    NARCIS (Netherlands)

    Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

    In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

  14. Intravenous paracetamol overdose in a paediatric patient

    NARCIS (Netherlands)

    Broeks, Ilse J.; Van Roon, Eric N.; Van Pinxteren-Nagler, Evelyn; De Vries, Tjalling W.


    BACKGROUND: Paracetamol is a widely used drug in children. In therapeutic doses, paracetamol has an excellent safety profile. Since the introduction of the intravenous form in 2004, only three reports of accidental overdose in children have been published. The low number probably is due to

  15. Intramuscular compared to intravenous midazolam for paediatric ...

    African Journals Online (AJOL)

    Background: Sedation in children remains a controversial issue in emergency departments (ED). Midazolam, as a benzodiazepine is widely used for procedural sedation among paediatrics. We compared the effectiveness and safety of two forms of midazolam prescription; intramuscular (IM) and intravenous (IV). Patients ...

  16. Intravenous platelet blockade with cangrelor during PCI

    NARCIS (Netherlands)

    Bhatt, Deepak L.; Lincoff, A. Michael; Gibson, C. Michael; Stone, Gregg W.; McNulty, Steven; Montalescot, Gilles; Kleiman, Neal S.; Goodman, Shaun G.; White, Harvey D.; Mahaffey, Kenneth W.; Pollack, Charles V.; Manoukian, Steven V.; Widimsky, Petr; Chew, Derek P.; Cura, Fernando; Manukov, Ivan; Tousek, Frantisek; Jafar, M. Zubair; Arneja, Jaspal; Skerjanec, Simona; Harrington, Robert A.; Bhatt, D. L.; Harrington, R. A.; Lincoff, A. M.; Pollack, C. V.; Gibson, C. M.; Stone, G. W.; Mahaffey, K. W.; Kleiman, N. S.; Montalescot, G.; White, H. D.; Goodman, S. G.; Greenbaum, A.; Simon, D.; Lee, D.; Feit, F.; Dauerman, H.; Gurbel, P.; Berger, P.; Makkar, R.; Becker, R. C.; Manoukian, S.; Jorgova, J.; Chew, D. P.; Storey, R.; Desmet, W.; Cura, F.; Herrmann, H.; Rizik, D.; DeServi, S.; Huber, K.; Jukema, W. J.; Knopf, W.; Steg, P. G.; Schunkert, H.; Widimsky, P.; Betriu, A.; Aylward, P.; Polonestsky, L.; Lima, V.; Kobulia, B.; Navickas, R.; Gasior, Z.; Vasilieva, E.; Bennett, J. M.; Kraiz, I.; Van de Werf, F.; Faxon, D.; Ohman, E. M.; Tijssen, J. G. P.; Verheugt, F.; Weaver, W. D.; Califf, R. M.; Mehta, C.; Hamm, C. W.; Pepine, C. J.; Ware, J.; Wilson, M.; Gorham, C.; Maran, A.; McNulty, S.; Fasteson, D.; Ryan, G.; Bradsher, J.; Connolly, P.; Mehta, R.; Leonardi, S.; Brennan, M.; Patel, M.; Petersen, J.; Bushnel, C.; Jolicoeur, M.; Chan, M.; Dowd, L.; Skinner, P.; Lawrence, G.; Jordon, M.; Dickerson, S.; Meyer, M.; Hartford, S.; Garcia Escudero, Alejandro; Poy, Carlos; Miceli, Miguel; Pocovi, Antonio; Londero, Hugo; Baccaro, Jorge; Polonetsky, Leonid; Karotkin, Aliaksey; Shubau, Leanid; Maffini, Eduardo; Machado, Bruno; Airton, José; Lima, Valter; Martinez Filho, Eulogio; Herdy, Arthur; Tumelero, Rogerio; Precoma, Dalton; Botelho, Roberto; Saad, Jamil; Jatene, Jose; Vilas-Boas, Fabio; Godinho, Antonio; Perin, Marco; Caramori, Paulo; Castro, Iran; Grigorov, Mladen; Milkov, Plamen; Jorgova, Julia; Georgiev, Svetoslav; Rifai, Nizar; Doganov, Alexander; Petrov, Ivo; Hui, William; Lazzam, Charles; Reeves, Francois; Tanguay, Jean-Francois; Richter, Marek; Klimsa, Zdenek; Padour, Michal; Mrozek, Jan; Branny, Marian; Coufal, Zdenek; Simek, Stanislav; Rozsival, Vladimir; Pleva, Leos; Stasek, Josef; Kala, Petr; Groch, Ladislav; Kocka, Viktor; Shaburishvili, Tamaz; Khintibidze, Irakli; Chapidze, Gulnara; Mamatsashvili, Merab; Mohanan, Padinhare; Jain, Rajesh; Parikh, Keyur; Patel, Tejas; Kumar, Sampath; Mehta, Ashwani; Banker, Darshan; Krishna, Lanka; Gadkari, Milind; Joshi, Hasit; Hiremath, Shirish; Grinius, Virgilijus; Norkiene, Sigute; Petrauskiene, Birute; Michels, Rolf; Tjon, Melvin; de Swart, Hans; de Winter, Robbert; White, Harvey; Devlin, Gerard; Abernethey, Malcolm; Osiev, Alexander; Linev, Kirill; Kalinina, Svetlana; Baum, Svetlana; Kosmachova, Elena; Shogenov, Zaur; Markov, Valentin; Boldueva, Svetlana; Barbarash, Olga; Kostenko, Victor; Vasilieva, Elena; Gruzdev, Aleksey; Lusov, Victor; Dovgalevsky, Pavel; Azarin, Oleg; Chernov, Sergey; Smolenskaya, Olga; Duda, Alexey; Fridrich, Viliam; Hranai, Marian; Studencan, Martin; Kurray, Peter; Bennett, John; Blomerus, Pieter; Disler, Laurence; Engelbrecht, Johannes; Klug, Eric; Routier, Robert; Venter, Tjaart; van der Merwe, Nico; Becker, Anthony; Cha, Kwang-Soo; Lee, Seung-Hwan; Han, Sang-Jin; Youn, Tae Jin; Hur, Seung-Ho; Seo, Hong Seog; Park, Hun-Sik; Rhim, Chong-Yun; Pyun, Wook-Bum; Choe, Hyunmin; Jeong, Myung-Ho; Park, Jong-Seon; Shin, Eak-Kyun; Hernández, Felipe; Figueras, Jaume; Hernández, Rosana; López-Minguez, José Ramón; González Juanatey, José Ramón; Palop, Ramón López; Galeote, Guillermo; Chamnarnphol, Noppadol; Buddhari, Wacin; Sansanayudh, Nakarin; Kuanprasert, Srun; Penny, William; Lui, Charles; Grimmett, Garfield; Srinivasan, Venkatraman; Ariani, Kevin; Khan, Waqor; Blankenship, James; Cannon, Louis; Eisenberg, Steven; McLaurin, Brent; Mahoney, Paul; Greenberg, Jerry; Breall, Jeffrey; Chandna, Harish; Hockstad, Eric; Tolerico, Paul; Kao, John; Shroff, Adhir; Nseir, Georges; Greenbaum, Adam; Cohn, Joel; Gogia, Harinder; Nahhas, Ahed; Istfan, Pierre; Orlow, Steve; Spriggs, Douglas; Sklar, Joel; Paulus, Richard; Cochran, David; Smith, Robert; Ferrier, L. Norman; Scott, J. Christopher; Xenopoulos, Nicholaos; Mulumudi, Mahesh; Hoback, James; Ginete, Wilson; Ballard, William; Stella, Joseph; Voeltz, Michele; Staniloae, Cezar; Eaton, Gregory; Griffin, John; Kumar, Krishna; Ebrahimi, Ramin; O'Shaughnessy, Charles; Lundstrom, Lundstrom; Temizer, Dogan; Tam, Kenneth; Suarez, Jose; Raval, Amish; Kaufman, Jay; Brilakis, Emmanouil; Stillabower, Michael; Quealy, Kathleen; Nunez, Boris; Pow, Thomas; Samuels, Bruce; Argenal, Agustin; Srinivas, Vankeepuram; Rosenthal, Andrew; Tummala, Pradyumna; Myers, Paul; LaMarche, Nelson; Chan, Michael; Bach, Richard; Simon, Daniel; Kettelkamp, Richard; Helmy, Tarek; Schaer, Gary; Kosinski, Edward; Buchbinder, Maurice; Sharma, Mukesh; Goodwin, Mark; Horwitz, Phillip; Mann, J. Tift; Holmes, David; Angiolillo, Dominick; Rao, Sunil; Azrin, Michael; Gammon, Roger; Mavromatis, Kreton; Ahmed, Abdel; Kent, Kenneth; Zughaib, Marcel; Westcott, R. Jeffrey; Jain, Ash; Gruberg, Luis; LeGalley, Thomas


    BACKGROUND: Intravenous cangrelor, a rapid-acting, reversible adenosine diphosphate (ADP) receptor antagonist, might reduce ischemic events during percutaneous coronary intervention (PCI). METHODS: In this double-blind, placebo-controlled study, we randomly assigned 5362 patients who had not been

  17. Effect of intravenous dexmedetomidine infusion on some ...

    African Journals Online (AJOL)

    Background: This study was designed to evaluate the effect of intravenous dexmedetomidine infusion in patients undergoing major abdominal surgery on stress response markers as plasma interleukin-6, cortisol and blood glucose level. It also assessed its effect on recovery profile and postoperative pain. Methods: Thirty ...

  18. A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.

    Directory of Open Access Journals (Sweden)

    Joel Bozue

    Full Text Available Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

  19. Islands in the stream? Challenges and resilience of the Danish industrial relations model in a liberalising world

    DEFF Research Database (Denmark)

    Refslund, Bjarke; Sørensen, Ole H.


    Nordic IR models have often been highlighted as being successful “highroads” in advanced capitalism. However, the economic crisis has increased pressures to liberalise and deregulate labour markets. Although this challenges the Danish IR model, there are several countermeasures in particular strong...

  20. Challenges in modelling the random structure correctly in growth mixture models and the impact this has on model mixtures. (United States)

    Gilthorpe, M S; Dahly, D L; Tu, Y K; Kubzansky, L D; Goodman, E


    Lifecourse trajectories of clinical or anthropological attributes are useful for identifying how our early-life experiences influence later-life morbidity and mortality. Researchers often use growth mixture models (GMMs) to estimate such phenomena. It is common to place constrains on the random part of the GMM to improve parsimony or to aid convergence, but this can lead to an autoregressive structure that distorts the nature of the mixtures and subsequent model interpretation. This is especially true if changes in the outcome within individuals are gradual compared with the magnitude of differences between individuals. This is not widely appreciated, nor is its impact well understood. Using repeat measures of body mass index (BMI) for 1528 US adolescents, we estimated GMMs that required variance-covariance constraints to attain convergence. We contrasted constrained models with and without an autocorrelation structure to assess the impact this had on the ideal number of latent classes, their size and composition. We also contrasted model options using simulations. When the GMM variance-covariance structure was constrained, a within-class autocorrelation structure emerged. When not modelled explicitly, this led to poorer model fit and models that differed substantially in the ideal number of latent classes, as well as class size and composition. Failure to carefully consider the random structure of data within a GMM framework may lead to erroneous model inferences, especially for outcomes with greater within-person than between-person homogeneity, such as BMI. It is crucial to reflect on the underlying data generation processes when building such models.

  1. W(h)ither the Oracle? Cognitive biases and other human challenges of integrated environmental modeling (United States)

    Glynn, Pierre D.; Ames, D.P.; Quinn, N. W. T.; Rizzoli, A.E.


    Integrated environmental modeling (IEM) can organize and increase our knowledge of the complex, dynamic ecosystems that house our natural resources and control the quality of our environments. Human behavior, however, must be taken into account. Human biases/heuristics reflect adaptation over our evolutionary past to frequently experienced situations that affected our survival and that provided sharply distinguished feedbacks at the level of the individual. Unfortunately, human behavior is not adapted to the more diffusely experienced, less frequently encountered, problems and issues that IEM typically seeks to address in the simulation of natural resources and environments. While seeking inspiration from the prophetic traditions of the Oracle of Delphi, several human biases are identified that may affect how the science base of IEM is assembled, and how IEM results are interpreted and used. These biases are supported by personal observations, and by the findings of behavioral scientists. A process for critical analysis is proposed that solicits explicit accounting and cognizance of potential human biases. A number of suggestions are made to address the human challenges of IEM, in addition to maintaining attitudes of watchful humility, open-mindedness, honesty, and transparent accountability. These include creating a new area of study in the behavioral biogeosciences, using structured processes for engaging the modeling and stakeholder community in IEM, and using “red teams” to increase resilience of IEM constructs and use.

  2. Overcoming challenges to initiating cell therapy clinical trials in rapidly developing countries: India as a model. (United States)

    Viswanathan, Sowmya; Rao, Mahendra; Keating, Armand; Srivastava, Alok


    Increasingly, a number of rapidly developing countries, including India, China, Brazil, and others, are becoming global hot spots for the development of regenerative medicine applications, including stem cell-based therapies. Identifying and overcoming regulatory and translational research challenges and promoting scientific and ethical clinical trials with cells will help curb the growth of stem cell tourism for unproven therapies. It will also enable academic investigators, local regulators, and national and international biotechnology and biopharmaceutical companies to accelerate stem cell-based clinical research that could lead to effective innovative treatments in these regions. Using India as a model system and obtaining input from regulators, clinicians, academics, and industry representatives across the stem cell field in India, we reviewed the role of key agencies and processes involved in this field. We have identified areas that need attention and here provide solutions from other established and functioning models in the world to streamline and unify the regulatory and ethics approval processes for cell-based therapies. We also make recommendations to check the growth and functioning of clinics offering unproven treatments. Addressing these issues will remove considerable hurdles to both local and international investigators, accelerate the pace of research and development, and create a quality environment for reliable products to emerge. By doing so, these countries would have taken one important step to move to the forefront of stem cell-based therapeutics.

  3. Challenges and gaps for energy planning models in the developing-world context (United States)

    Debnath, Kumar Biswajit; Mourshed, Monjur


    Energy planning models (EPMs) support multi-criteria assessments of the impact of energy policies on the economy and environment. Most EPMs originated in developed countries and are primarily aimed at reducing greenhouse gas emissions while enhancing energy security. In contrast, most, if not all, developing countries are predominantly concerned with increasing energy access. Here, we review thirty-four widely used EPMs to investigate their applicability to developing countries and find an absence of consideration of the objectives, challenges, and nuances of the developing context. Key deficiencies arise from the lack of deliberation of the low energy demand resulting from lack of access and availability of supply. Other inadequacies include the lack of consideration of socio-economic nuances such as the prevalence of corruption and resulting cost inflation, the methods for adequately addressing the shortcomings in data quality, availability and adequacy, and the effects of climate change. We argue for further research on characterization and modelling of suppressed demand, climate change impacts, and socio-political feedback in developing countries, and the development of contextual EPMs.

  4. Meeting the challenges of bringing a new base facility operation model to Gemini Observatory (United States)

    Nitta, Atsuko; Arriagada, Gustavo; Adamson, A. J.; Cordova, Martin; Nunez, Arturo; Serio, Andrew; Kleinman, Scot


    The aim of the Gemini Observatory's Base Facilities Project is to provide the capabilities to perform routine night time operations with both telescopes and their instruments from their respective base facilities without anyone present at the summit. Tightening budget constraints prompted this project as both a means to save money and an opportunity to move toward increasing remote operations in the future. We successfully moved Gemini North nighttime operation to our base facility in Hawaii in Nov., 2015. This is the first 8mclass telescope to completely move night time operations to base facility. We are currently working on implementing BFO to Gemini South. Key challenges for this project include: (1) This is a schedule driven project. We have to implement the new capabilities by the end of 2015 for Gemini North and end of 2016 for Gemini South. (2) The resources are limited and shared with operations which has the higher priority than our project. (3) Managing parallel work within the project. (4) Testing, commissioning and introducing new tools to operational systems without adding significant disruptions to nightly operations. (5) Staff buying to the new operational model. (6) The staff involved in the project are spread on two locations separated by 10,000km, seven time zones away from each other. To overcome these challenges, we applied two principles: "Bare Minimum" and "Gradual Descent". As a result, we successfully completed the project ahead of schedule at Gemini North Telescope. I will discuss how we managed the cultural and human aspects of the project through these concepts. The other management aspects will be presented by Gustavo Arriagada [2], the Project Manager of this project. For technical details, please see presentations from Andrew Serio [3] and Martin Cordova [4].

  5. Cost-effectiveness of oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin in the emergency department. (United States)

    Rudis, Maria I; Touchette, Daniel R; Swadron, Stuart P; Chiu, Amy P; Orlinsky, Michael


    Oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin are all commonly used for loading phenytoin in the emergency department (ED). The cost-effectiveness of each was compared for patients presenting with seizures and subtherapeutic phenytoin concentrations. A simple decision tree was developed to determine the treatment costs associated with each of 3 loading techniques. We determined effectiveness by comparing adverse event rates and by calculating the time to safe ED discharge. Time to safe ED discharge was defined as the time at which therapeutic concentrations of phenytoin (>or=10 mg/L) were achieved with an absence of any adverse events that precluded discharge. The comparative cost-effectiveness of alternatives to oral phenytoin was determined by combining net costs and number of adverse events, expressed as cost per adverse events avoided. Cost-effectiveness was also determined by comparing the net costs of each loading technique required to achieve the time to safe ED discharge, expressed as cost per hour of ED time saved. The outcomes and costs were primarily derived from a prospective, randomized controlled trial, augmented by time-motion studies and alternate-cost sources. Costs included the cost of drugs, supplies, and personnel. Analyses were also performed in scenarios incorporating labor costs and savings from using a lower-urgency area of the ED. The mean number of adverse events per patient for oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin was 1.06, 1.93, and 2.13, respectively. Mean time to safe ED discharge in the 3 groups was 6.4 hours, 1.7 hours, and 1.3 hours. Cost per patient was 2.83 dollars, 21.16 dollars, and 175.19 dollars, respectively, and did not differ substantially in the Labor and Triage (lower-urgency area of ED) scenarios. When the measure of effectiveness was adverse events, oral phenytoin dominated intravenous phenytoin and intravenous fosphenytoin, with a lower cost and number of adverse

  6. Inversion-based propofol dosing for intravenous induction of hypnosis (United States)

    Padula, F.; Ionescu, C.; Latronico, N.; Paltenghi, M.; Visioli, A.; Vivacqua, G.


    In this paper we propose an inversion-based methodology for the computation of a feedforward action for the propofol intravenous administration during the induction of hypnosis in general anesthesia. In particular, the typical initial bolus is substituted with a command signal that is obtained by predefining a desired output and by applying an input-output inversion procedure. The robustness of the method has been tested by considering a set of patients with different model parameters, which is representative of a large population.

  7. Intravenous/oral ciprofloxacin therapy versus intravenous ceftazidime therapy for selected bacterial infections. (United States)

    Gaut, P L; Carron, W C; Ching, W T; Meyer, R D


    The efficacy and toxicity of sequential intravenous and oral ciprofloxacin therapy was compared with intravenously administered ceftazidime in a prospective, randomized, controlled, non-blinded trial. Thirty-two patients (16 patients receiving ciprofloxacin and 16 patients receiving ceftazidime) with 38 infections caused by susceptible Pseudomonas aeruginosa, enteric gram-negative rods, Salmonella group B, Serratia marcescens, Pseudomonas cepacia, and Xanthomonas maltophilia at various sites were evaluable for determination of efficacy. Length of therapy varied from seven to 25 days. Concomitant antimicrobials included intravenously administered beta-lactams for gram-positive organisms, intravenous/oral metronidazole and clindamycin for anaerobes, and intravenous/local amphotericin B for Candida albicans. Intravenous administration of 200 mg ciprofloxacin every 12 hours to 11 patients produced peak serum levels between 1.15 and 3.12 micrograms/ml; trough levels ranged between 0.08 and 0.86 micrograms/ml. Overall response rates were similar for patients receiving ciprofloxacin and ceftazidime. Emergence of resistance was similar in both groups--one Enterobacter cloacae and two P. aeruginosa became resistant after ciprofloxacin therapy and two P. aeruginosa became resistant after ceftazidime therapy. The frequency of superinfection with a variety of organisms was also similar in both groups. Adverse events related to ciprofloxacin included transient pruritus at the infusion site and generalized rash leading to drug discontinuation (one patient each), and with ceftazidime adverse effects included pain at the site of infusion and the development of allergic interstitial nephritis (one patient each). Overall, intravenous/oral ciprofloxin therapy appears to be as safe and effective as intravenous ceftazidime therapy in the treatment of a variety of infections due to susceptible aerobic gram-negative organisms.

  8. Intravenous HOE-642 reduces brain edema and Na uptake in the rat permanent middle cerebral artery occlusion model of stroke: evidence for participation of the blood-brain barrier Na/H exchanger. (United States)

    O'Donnell, Martha E; Chen, Yi-Je; Lam, Tina I; Taylor, Kelleen C; Walton, Jeffrey H; Anderson, Steven E


    Cerebral edema forms in the early hours of ischemic stroke by processes involving increased transport of Na and Cl from blood into brain across an intact blood-brain barrier (BBB). Our previous studies provided evidence that the BBB Na-K-Cl cotransporter is stimulated by the ischemic factors hypoxia, aglycemia, and arginine vasopressin (AVP), and that inhibition of the cotransporter by intravenous bumetanide greatly reduces edema and infarct in rats subjected to permanent middle cerebral artery occlusion (pMCAO). More recently, we showed that BBB Na/H exchanger activity is also stimulated by hypoxia, aglycemia, and AVP. The present study was conducted to further investigate the possibility that a BBB Na/H exchanger also participates in edema formation during ischemic stroke. Sprague-Dawley rats were subjected to pMCAO and then brain edema and Na content assessed by magnetic resonance imaging diffusion-weighed imaging and magnetic resonance spectroscopy Na spectroscopy, respectively, for up to 210 minutes. We found that intravenous administration of the specific Na/H exchange inhibitor HOE-642 significantly decreased brain Na uptake and reduced cerebral edema, brain swelling, and infarct volume. These findings support the hypothesis that edema formation and brain Na uptake during the early hours of cerebral ischemia involve BBB Na/H exchanger activity as well as Na-K-Cl cotransporter activity.

  9. 2008 GEM Modeling Challenge: Metrics Study of the Dst Index in Physics-Based Magnetosphere and Ring Current Models and in Statistical and Analytic Specifications (United States)

    Rastaetter, L.; Kuznetsova, M.; Hesse, M.; Pulkkinen, A.; Glocer, A.; Yu, Y.; Meng, X.; Raeder, J.; Wiltberger, M.; Welling, D.; hide


    In this paper the metrics-based results of the Dst part of the 2008-2009 GEM Metrics Challenge are reported. The Metrics Challenge asked modelers to submit results for 4 geomagnetic storm events and 5 different types of observations that can be modeled by statistical or climatological or physics-based (e.g. MHD) models of the magnetosphere-ionosphere system. We present the results of over 25 model settings that were run at the Community Coordinated Modeling Center (CCMC) and at the institutions of various modelers for these events. To measure the performance of each of the models against the observations we use comparisons of one-hour averaged model data with the Dst index issued by the World Data Center for Geomagnetism, Kyoto, Japan, and direct comparison of one-minute model data with the one-minute Dst index calculated by the United States Geologic Survey (USGS).

  10. Evaluation of the effects of intravenous anaesthesia using a ...

    African Journals Online (AJOL)

    medetomidine for total intravenous anaesthesia were evaluated in six sahel goats. The goats were administered a combination of ketamine (5mg/kg) and medetomidine (0.01mg/kg) intravenously. Baseline measurements of heart rate, respiratory ...

  11. Optimal timing for intravenous administration set replacement. (United States)

    Gillies, D; O'Riordan, L; Wallen, M; Morrison, A; Rankin, K; Nagy, S


    Administration of intravenous therapy is a common occurrence within the hospital setting. Routine replacement of administration sets has been advocated to reduce intravenous infusion contamination. If decreasing the frequency of changing intravenous administration sets does not increase infection rates, a change in practice could result in considerable cost savings. The objective of this review was to identify the optimal interval for the routine replacement of intravenous administration sets when infusate or parenteral nutrition (lipid and non-lipid) solutions are administered to people in hospital via central or peripheral venous catheters. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL, EMBASE: all from inception to February 2004; reference lists of identified trials, and bibliographies of published reviews. We also contacted researchers in the field. We did not have a language restriction. We included all randomized or quasi-randomized controlled trials addressing the frequency of replacing intravenous administration sets when parenteral nutrition (lipid and non-lipid containing solutions) or infusions (excluding blood) were administered to people in hospital via a central or peripheral catheter. Two authors assessed all potentially relevant studies. We resolved disagreements between the two authors by discussion with a third author. We collected data for the outcomes; infusate contamination; infusate-related bloodstream infection; catheter contamination; catheter-related bloodstream infection; all-cause bloodstream infection and all-cause mortality. We identified 23 references for review. We excluded eight of these studies; five because they did not fit the inclusion criteria and three because of inadequate data. We extracted data from the remaining 15 references (13 studies) with 4783 participants. We conclude that there is no evidence that changing intravenous administration sets more often than every 96 hours

  12. Fast and accurate computational modeling of adsorption on graphene: a dispersion interaction challenge. (United States)

    Gordeev, Evgeniy G; Polynski, Mikhail V; Ananikov, Valentine P


    Understanding molecular interactions of graphene is a question of key importance to design new materials and catalytic systems for practical usage. Although for small models good accuracy was demonstrated in theoretical analysis with ab initio and density functional methods, the application to real-size systems with thousands of atoms is currently hardly possible on routine bases due to the high computational cost. In the present study we report that incorporation of dispersion correction led to the principal improvement in the description of graphene systems at a semi-empirical level. The accuracy and the scope of the calculations were explored for a wide range of molecules adsorbed on graphene surfaces (H2, N2, CO, CO2, NH3, CH4, H2O, benzene, naphthalene, coronene, ovalene and cyclohexane). As a challenging parameter, the calculated adsorption energy of aromatic hydrocarbons on graphene Eads = -1.8 ± 0.1 kcal mol(-1) (per one carbon atom) at the PM6-DH2 level was in excellent agreement with the experimentally determined value of Eads = -1.7 ± 0.3 kcal mol(-1). The dispersion corrected semi-empirical method was found to be a remarkable computational tool suitable for everyday laboratory studies of real-size graphene systems. Significant performance improvement (ca. 10(3) times faster) and excellent accuracy were found as compared to the ωB97X-D density functional calculations.

  13. Discovery of optimal zeolites for challenging separations and chemical conversions through predictive materials modeling (United States)

    Siepmann, J. Ilja; Bai, Peng; Tsapatsis, Michael; Knight, Chris; Deem, Michael W.


    Zeolites play numerous important roles in modern petroleum refineries and have the potential to advance the production of fuels and chemical feedstocks from renewable resources. The performance of a zeolite as separation medium and catalyst depends on its framework structure and the type or location of active sites. To date, 213 framework types have been synthesized and >330000 thermodynamically accessible zeolite structures have been predicted. Hence, identification of optimal zeolites for a given application from the large pool of candidate structures is attractive for accelerating the pace of materials discovery. Here we identify, through a large-scale, multi-step computational screening process, promising zeolite structures for two energy-related applications: the purification of ethanol beyond the ethanol/water azeotropic concentration in a single separation step from fermentation broths and the hydroisomerization of alkanes with 18-30 carbon atoms encountered in petroleum refining. These results demonstrate that predictive modeling and data-driven science can now be applied to solve some of the most challenging separation problems involving highly non-ideal mixtures and highly articulated compounds. Financial support from the Department of Energy Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences under Award DE-FG02-12ER16362 is gratefully acknowledged.

  14. Modeling of Materials for Energy Storage: A Challenge for Density Functional Theory (United States)

    Kaltak, Merzuk; Fernandez-Serra, Marivi; Hybertsen, Mark S.

    Hollandite α-MnO2 is a promising material for rechargeable batteries and is studied extensively in the community because of its interesting tunnel structure and the corresponding large capacity for lithium as well as sodium ions. However, the presence of partially reduced Mn ions due to doping with Ag or during lithiation makes hollandite a challenging system for density functional theory and the conventionally employed PBE+U method. A naive attempt to model the ternary system LixAgyMnO2 with density functionals, similar to those employed for the case y = 0 , fails and predicts a strong monoclinic distortion of the experimentally observed tetragonal unit cell for Ag2Mn8O16. Structure and binding energies are compared with experimental data and show the importance of van der Waals interactions as well as the necessity for an accurate description of the cooperative Jan-Teller effects for silver hollandite AgyMnO2. Based on these observations a ternary phase diagram is calculated allowing to predict the physical and chemical properties of LixAgyMnO2, such as stable stoichiometries, open circuit voltages, the formation of Ag metal and the structural change during lithiation. Department of Energy (DOE) under award #DE-SC0012673.

  15. Challenging the Uppsala Internationalization Model: a Contingent Approach to the Internationalization of Services

    Directory of Open Access Journals (Sweden)

    Jorge Carneiro


    Full Text Available Some authors have questioned whether the well-known Uppsala internationalization model would be generalizable to services. We take one of the model’s assumptions – that firms will follow a gradually increasing resource commitment path in each country – and challenge whether it would hold up under specific service characteristics or particular combinations of environmental variables and service characteristics. We review the literature in search of more appropriate dimensions for the classification of services that would allow for the test of the Uppsala model’s assumption. Based on purely conceptual reasoning, supported by previous empirical studies, we propose some hypotheses about how service firms would be expected to behave – in terms of their choice of foreign entry mode - under certain circumstances and what the performance implications would be expected to be. These hypotheses are contrary to the Uppsala model’s predictions. This paper is solelyconceptual, so the key constructs (environment and service-specific variables would still require operationalization before the hypotheses can be empirically tested.

  16. Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression (United States)

    Rose, Amy E.; Poliseno, Laura; Wang, Jinhua; Clark, Michael; Pearlman, Alexander; Wang, Guimin; Vega y Saenz de Miera, Eleazar C.; Medicherla, Ratna; Christos, Paul J.; Shapiro, Richard; Pavlick, Anna; Darvishian, Farbod; Zavadil, Jiri; Polsky, David; Hernando, Eva; Ostrer, Harry; Osman, Iman


    Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathological and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (SNP 6.0, Affymetrix) with gene expression array (U133A 2.0, Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N=114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (Pmelanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM. PMID:21343389

  17. Integration of treatment innovation planning and implementation: strategic process models and organizational challenges. (United States)

    Lehman, Wayne E K; Simpson, D Dwayne; Knight, Danica K; Flynn, Patrick M


    Sustained and effective use of evidence-based practices in substance abuse treatment services faces both clinical and contextual challenges. Implementation approaches are reviewed that rely on variations of plan-do-study-act (PDSA) cycles, but most emphasize conceptual identification of core components for system change strategies. A two-phase procedural approach is therefore presented based on the integration of Texas Christian University (TCU) models and related resources for improving treatment process and program change. Phase 1 focuses on the dynamics of clinical services, including stages of client recovery (cross-linked with targeted assessments and interventions), as the foundations for identifying and planning appropriate innovations to improve efficiency and effectiveness. Phase 2 shifts to the operational and organizational dynamics involved in implementing and sustaining innovations (including the stages of training, adoption, implementation, and practice). A comprehensive system of TCU assessments and interventions for client and program-level needs and functioning are summarized as well, with descriptions and guidelines for applications in practical settings. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  18. From California dreaming to California data: Challenging historic models for landfill CH4 emissions

    Directory of Open Access Journals (Sweden)

    Kurt Spokas


    Full Text Available Abstract Improved quantification of diverse CH4 sources at the urban scale is needed to guide local GHG mitigation strategies in the Anthropocene. Herein, we focus on landfill CH4 emissions in California, challenging the current IPCC methodology which focuses on a climate dependency for landfill CH4 generation (methanogenesis, but does not explicitly consider climate or soil dependencies for emissions. Relying on a comprehensive California landfill database, a field-validated process-based model for landfill CH4 emissions (CALMIM, and select field measurements at 10 California sites with a variety of methods, we support the contrary position: Limited climate dependency for methanogenesis, but strong climate dependency for landfill CH4 emissions. Contrary to the historic IPCC empirical model for methanogenesis with kinetic constants related to climate, we demonstrate a simpler and more robust linear empirical relationship (r2 = 0.85; n=128 between waste mass and landfill biogas recovery [126 × 10-6 Nm3 CH4 hr-1 Mgwaste-1]. More interestingly, there are no statistically significant relationships with climate, site age, or status (open/closed for landfill biogas recovery. The current IPCC methodology does not consider soil or climate drivers for gaseous transport or seasonal methanotrophy in different cover soils. On the other hand, we illustrate strong climate and soil dependencies for landfill emissions—e.g., average intermediate cover emissions below 20 g CH4 m-2 d-1 when the site’s mean annual precipitation is >500 mm y-1. Thereby, for the California landfill CH4 inventory, the highest-emitting sites shift from landfills containing the largest mass of waste to sites dominated by intermediate cover types having a reduced rate of soil CH4 oxidation during the annual cycle. These differences have profound implications for developing more realistic, science-based urban and regional scale GHG inventories for landfill CH4 while reducing

  19. Satellites and Steep Slopes - the challenge of topography in the Himalaya - Karakorum for cryosphere models (United States)

    Steiner, J. F.; Buri, P.; Miles, E. S.; Immerzeel, W.


    The topography in glaciated catchments in the Himalaya - Karakoram range are extreme in a number of aspects that proof to be a challenge for distributed modelling. High altitude regions, where accumulation areas of glaciers are generally located, can at times be very steep, covered in hanging ice and seasonal snow. On the other hand, lower areas, where ablation zones on glacier tongues are located, tend to be very shallow. This has consequences for obtaining glacier areas from satellite derived glacier inventories (e.g. RGI, ICIMOD). As they are taken perpendicular to the center of the earth, these inventories will underestimate the area of steep regions, sometimes quite considerably (Figure 1). This can have consequences for a number of statistics in glaciological modeling, especially when it comes to the relative comparison of accumulation and ablation and hence overall melt from a glacier. Additionally, these steep head walls cause topographic shading. Depending on the exposition of the valley this can result in very divergent amounts of direct solar radiation reaching the glacier surface from valley to valley. Comparisons of melt between different regions and even glaciers have to be taken with considerable caution. Finally, these shallow glacier tongues are increasingly covered in debris. Such glacier surfaces with a debris cover ranging in grain size from sand to boulders several meters in diameter are very hummocky rather than flat bare ice glacier surfaces. This in turn increases local shading but also increases the overall glacier surface. Using high resolution satellite imagery and DEMs ( 5m) from our field site we investigate the effects of areal misrepresentations on the local scale. Decreasing resolution we then take this analysis to the mountain range scale and can identify to what degree these factors are significant and considering literature values determine the quantitative impact for energy and mass balance studies. Figure 1: A schematic

  20. Multiscale cartilage biomechanics: technical challenges in realizing a high-throughput modelling and simulation workflow. (United States)

    Erdemir, Ahmet; Bennetts, Craig; Davis, Sean; Reddy, Akhil; Sibole, Scott


    interpretation of the results. This study aims to summarize various strategies to address the technical challenges of post-processing-based simulations of cartilage and chondrocyte mechanics with the ultimate goal of establishing the foundations of a high-throughput multiscale analysis framework. At the joint-tissue scale, rapid development of regional models of articular contact is possible by automating the process of generating parametric representations of cartilage boundaries and depth-dependent zonal delineation with associated constitutive relationships. At the tissue-cell scale, models descriptive of multicellular and fibrillar architecture of cartilage zones can also be generated in an automated fashion. Through post-processing, scripts can extract biphasic mechanical metrics at a desired point in the cartilage to assign loading and boundary conditions to models at the lower spatial scale of cells. Cell deformation metrics can be extracted from simulation results to provide a simplified description of individual chondrocyte responses. Simulations at the tissue-cell scale can be parallelized owing to the loosely coupled nature of the feed-forward approach. Verification studies illustrated the necessity of a second-order data passing scheme between scales and evaluated the role that the microscale representative volume size plays in appropriately predicting the mechanical response of the chondrocytes. The tools summarized in this study collectively provide a framework for high-throughput exploration of cartilage biomechanics, which includes minimally supervised model generation, and prediction of multiscale biomechanical metrics across a range of spatial scales, from joint regions and cartilage zones, down to that of the chondrocytes.

  1. r.avaflow, the GIS simulation model for avalanche and debris flows: new developments and challenges (United States)

    Mergili, Martin; Queiroz de Oliveira, Gustavo; Fischer, Jan-Thomas; Krenn, Julia; Kulisch, Helmut; Malcherek, Andreas; Pudasaini, Shiva P.


    We present the latest developments and discuss some of the key challenges with regard to the novel and unified computational tool r.avaflow, representing an advanced, comprehensive, GIS-based open source simulation environment for two-phase geophysical mass flows such as avalanches of snow or rock, flows of debris or mud, and related process chains. r.avaflow is freely available and adoptable as a raster module of the GRASS GIS software ( We focus on the following issues: (1) We back-calculate a laboratory-scale debris flow experiment with r.avaflow and thereby show that different types of drag may govern the evolving flow dynamics, depending on the initial flow configuratiuon. In particular, it appears necessary to consider viscous ambient drag in order to achieve simulation results in line with experimentally measurements. (2) We employ a set of well-documented rock avalanche events to illustrate the use of a built-in functionality for parameter sensitivity analysis and optimization. To do so, we demonstrate possible strategies going beyond the deficient one-at-a-time simulation approach. They allow us to test three or more parameters at once with a limited number of model runs. Computational times are kept at an acceptable level by multi-core processing strategies and use of the Vienna Scientific Cluster. We further discuss a number of key issues with regard to (i) arbitrary mountain topography; and (ii) entrainment and deposition of material. Most tests indicate a good model performance when the affected areas predicted for a late stage of the flow simulation are compared with observed affected areas. However, we note that such a validation is not fully justified without the implementation of a physically correct model for the deposition process. Acknowledgement: The work was conducted as part of the international cooperation project "A GIS simulation model for avalanche and debris flows (avaflow)" supported by the Austrian Science Fund

  2. Photons, photosynthesis, and high-performance computing: challenges, progress, and promise of modeling metabolism in green algae

    International Nuclear Information System (INIS)

    Chang, C H; Graf, P; Alber, D M; Kim, K; Murray, G; Posewitz, M; Seibert, M


    The complexity associated with biological metabolism considered at a kinetic level presents a challenge to quantitative modeling. In particular, the relatively sparse knowledge of parameters for enzymes with known kinetic responses is problematic. The possible space of these parameters is of high-dimension, and sampling of such a space typifies a combinatorial explosion of possible dynamic states. However, with sufficient quantitative transcriptomics, proteomics, and metabolomics data at hand, these challenges could be met by high-performance software with sampling, fitting, and optimization capabilities. With this in mind, we present the High-Performance Systems Biology Toolkit HiPer SBTK, an evolving software package to simulate, fit, and optimize metabolite concentrations and fluxes within the space of rate and binding parameters associated with detailed enzyme kinetic models. We present our chosen modeling paradigm for the formulation of metabolic pathway models, the means to address the challenge of representing such models in a precise and persistent fashion using the standardized Systems Biology Markup Language, and our second-generation model of H2-associated Chlamydomonas metabolism. Processing of such models for hierarchically parallelized simulation and optimization, job specification by the user through a GUI interface, software capabilities and initial scaling data, and the mapping of the computation to biological questions is also discussed. Moreover, we present near-term future software and model development goals

  3. Intravenous immunoglobulin therapy for refractory recurrent pericarditis. (United States)

    del Fresno, M Rosa; Peralta, Julio E; Granados, Miguel Ángel; Enríquez, Eugenia; Domínguez-Pinilla, Nerea; de Inocencio, Jaime


    Recurrent pericarditis is a troublesome complication of idiopathic acute pericarditis and occurs more frequently in pediatric patients after cardiac surgery (postpericardiotomy syndrome). Conventional treatment with nonsteroidal antiinflammatory drugs, corticosteroids, and colchicine is not always effective or may cause serious adverse effects. There is no consensus, however, on how to proceed in those patients whose disease is refractory to conventional therapy. In such cases, human intravenous immunoglobulin, immunosuppressive drugs, and biological agents have been used. In this report we describe 2 patients with refractory recurrent pericarditis after cardiac surgery who were successfully treated with 3 and 5 monthly high-dose (2 g/kg) intravenous immunoglobulin until resolution of the effusion. Our experience supports the effectiveness and safety of this therapy. Copyright © 2014 by the American Academy of Pediatrics.

  4. Opportunity by Design: New High School Models for Student Success. Carnegie Challenge (United States)

    Hamilton, Leah; Mackinnon, Anne


    The goal of Carnegie "Challenge" papers is to lift up ideas and issues in a way that elevates them to the nation's agenda. This paper is a "Challenge" paper, and serves as a call to realize the full power of the Common Core by redesigning and reshaping schools to support teachers and maximize key resources, rather than…

  5. Retroperitoneal fibrosis with normal intravenous urogram.


    Creagh, F. M.; Stone, T.; Stephenson, T. P.; Lazarus, J. H.


    A 58 year old male presented with a two week history of low back pain and malaise. The intravenous urogram (IVU) at presentation was normal but within three months he had developed renal failure with bilateral ureteric obstruction on repeat IVU. Primary retroperitoneal fibrosis was confirmed at operation. This case demonstrates that retroperitoneal fibrosis may progress rapidly to renal failure within a few months of the first symptoms. In addition, the IVU may be normal in the early stages o...

  6. Total intravenous anesthesia for major burn surgery


    Cancio, Leopoldo C; Cuenca, Phillip B; Walker, Stephen C; Shepherd, John M


    Total intravenous anesthesia (TIVA) is frequently used for major operations requiring general anesthesia in critically ill burn patients. We reviewed our experience with this approach. Methods: During a 22-month period, 547 major burn surgeries were performed in this center’s operating room and were staffed by full-time burn anesthesiologists. The records of all 123 TIVA cases were reviewed; 112 records were complete and were included. For comparison, 75 cases were selected at random from a t...

  7. Methodological challenges to bridge the gap between regional climate and hydrology models (United States)

    Bozhinova, Denica; José Gómez-Navarro, Juan; Raible, Christoph; Felder, Guido


    The frequency and severity of floods worldwide, together with their impacts, are expected to increase under climate change scenarios. It is therefore very important to gain insight into the physical mechanisms responsible for such events in order to constrain the associated uncertainties. Model simulations of the climate and hydrological processes are important tools that can provide insight in the underlying physical processes and thus enable an accurate assessment of the risks. Coupled together, they can provide a physically consistent picture that allows to assess the phenomenon in a comprehensive way. However, climate and hydrological models work at different temporal and spatial scales, so there are a number of methodological challenges that need to be carefully addressed. An important issue pertains the presence of biases in the simulation of precipitation. Climate models in general, and Regional Climate models (RCMs) in particular, are affected by a number of systematic biases that limit their reliability. In many studies, prominently the assessment of changes due to climate change, such biases are minimised by applying the so-called delta approach, which focuses on changes disregarding absolute values that are more affected by biases. However, this approach is not suitable in this scenario, as the absolute value of precipitation, rather than the change, is fed into the hydrological model. Therefore, bias has to be previously removed, being this a complex matter where various methodologies have been proposed. In this study, we apply and discuss the advantages and caveats of two different methodologies that correct the simulated precipitation to minimise differences with respect an observational dataset: a linear fit (FIT) of the accumulated distributions and Quantile Mapping (QM). The target region is Switzerland, and therefore the observational dataset is provided by MeteoSwiss. The RCM is the Weather Research and Forecasting model (WRF), driven at the

  8. Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and intramuscular administration to sheep.


    Escudero, E; Espuny, A; Vicente, S; Cárceles, C M


    The pharmacokinetics of a 2:1 ampicillin-sulbactam combination were studied in 6 sheep, after intravenous and intramuscular injection at a single dose rate of 20 mg/kg body weight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open 2-compartment model after intravenous administration and a one-compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by th...

  9. Contrast agent choice for intravenous coronary angiography

    International Nuclear Information System (INIS)

    Zeman, H.D.; Siddons, D.P.


    The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation x-rays and an iodine containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic x-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the x-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation x-rays is visualizing a coronary artery through the left ventricle or aorta which also contains a contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth


    Bagheri-Nesami, Masoumeh; Esmaeili, Ravanbakhsh; Tajari, Mojdeh


    The dangerous events caused by medication errors are one of the main challenges faced in critical care units. The present study was conducted to determine the frequency of intravenous medication administration errors and their causes in cardiac critical care units in Iran. The present descriptive study was conducted in the critical care units (CCUs and cardiac surgery intensive care units) of 12 teaching hospitals. Of the total of 240 nurses working in these departments, 190 participated in the present study. The data collection tools used in this study included the "nurses' demographic data questionnaire", the "patients' medical and demographic data questionnaire" and the "nurses' self-reporting questionnaire about the frequency of intravenous medication administration errors and their causes". The data obtained were analyzed in SPSS-20 using descriptive statistics such as the absolute and relative frequency. During the 2 months in which this study was being conducted, 2542 patients were admitted to these departments and 20240 doses of intravenous medications were administered to these patients. The nurses reported 262 intravenous medication administration errors. The most common intravenous medication error pertained to administering the wrong medication (n=71 and 27.1%). As for the causes of intravenous medication administration errors, 51.5% of the errors were associated with work conditions, 24% with packaging, 13.4% with communication, 9.9% with transcription and 1.2% with pharmacies. According to the results, strategies are recommended to be adopted for reducing or limiting medication errors, such as building a stronger pharmacology knowledge base in nurses and nursing students, improving work conditions and improving communication between the nurses and physicians.

  11. Challenges in Mentoring Software Development Projects in the High School: Analysis According to Shulman's Teacher Knowledge Base Model (United States)

    Meerbaum-Salant, Orni; Hazzan, Orit


    This paper focuses on challenges in mentoring software development projects in the high school and analyzes difficulties encountered by Computer Science teachers in the mentoring process according to Shulman's Teacher Knowledge Base Model. The main difficulties that emerged from the data analysis belong to the following knowledge sources of…

  12. Simulating the impacts of disturbances on forest carbon cycling in North America: processes, data, models, and challenges (United States)

    Shuguang Liu; Ben Bond-Lamberty; Jeffrey A. Hicke; Rodrigo Vargas; Shuqing Zhao; Jing Chen; Steven L. Edburg; Yueming Hu; Jinxun Liu; A. David McGuire; Jingfeng Xiao; Robert Keane; Wenping Yuan; Jianwu Tang; Yiqi Luo; Christopher Potter; Jennifer Oeding


    Forest disturbances greatly alter the carbon cycle at various spatial and temporal scales. It is critical to understand disturbance regimes and their impacts to better quantify regional and global carbon dynamics. This review of the status and major challenges in representing the impacts of disturbances in modeling the carbon dynamics across North America revealed some...

  13. Challenges in understanding, modelling, and mitigating Lake Outburst Flood Hazard: experiences from Central Asia (United States)

    Mergili, Martin; Schneider, Demian; Andres, Norina; Worni, Raphael; Gruber, Fabian; Schneider, Jean F.


    Lake Outburst Floods can evolve from complex process chains like avalanches of rock or ice that produce flood waves in a lake which may overtop and eventually breach glacial, morainic, landslide, or artificial dams. Rising lake levels can lead to progressive incision and destabilization of a dam, to enhanced ground water flow (piping), or even to hydrostatic failure of ice dams which can cause sudden outflow of accumulated water. These events often have a highly destructive potential because a large amount of water is released in a short time, with a high capacity to erode loose debris, leading to a powerful debris flow with a long travel distance. The best-known example of a lake outburst flood is the Vajont event (Northern Italy, 1963), where a landslide rushed into an artificial lake which spilled over and caused a flood leading to almost 2000 fatalities. Hazards from the failure of landslide dams are often (not always) fairly manageable: most breaches occur in the first few days or weeks after the landslide event and the rapid construction of a spillway - though problematic - has solved some hazardous situations (e.g. in the case of Hattian landslide in 2005 in Pakistan). Older dams, like Usoi dam (Lake Sarez) in Tajikistan, are usually fairly stable, though landsildes into the lakes may create floodwaves overtopping and eventually weakening the dams. The analysis and the mitigation of glacial lake outburst flood (GLOF) hazard remains a challenge. A number of GLOFs resulting in fatalities and severe damage have occurred during the previous decades, particularly in the Himalayas and in the mountains of Central Asia (Pamir, Tien Shan). The source area is usually far away from the area of impact and events occur at very long intervals or as singularities, so that the population at risk is usually not prepared. Even though potentially hazardous lakes can be identified relatively easily with remote sensing and field work, modeling and predicting of GLOFs (and also

  14. Grand challenge problems in environmental modeling and remediation: Groundwater contaminant transport. Final project report 1998

    International Nuclear Information System (INIS)


    The over-reaching goal of the Groundwater Grand Challenge component of the Partnership in Computational Science (PICS) was to develop and establish the massively parallel approach for the description of groundwater flow and transport and to address the problem of uncertainties in the data and its interpretation. This necessitated the development of innovative algorithms and the implementation of massively parallel computational tools to provide a suite of simulators for groundwater flow and transport in heterogeneous media. This report summarizes the activities and deliverables of the Groundwater Grand Challenge project funded through the High Performance Computing grand challenge program of the Department of Energy from 1995 through 1997

  15. Modelling Land Use and Transport Policies to Measure Their Contribution to Urban Challenges: The Case of Madrid

    Directory of Open Access Journals (Sweden)

    Andrea Alonso


    Full Text Available Urban areas play a key role in the development of European territories, and it is essential for them to be sustainable and efficient. However, the European cities are facing some challenges related to certain trends that are threatening their sustainable development and operational efficiency. In this paper, we compare the contribution of three policy measures—cordon toll accompanied by public transport improvements, teleworking and re-densification—to address different city challenges. The policy assessment requires a long term simulation tool, i.e., the MARS (Metropolitan Activity Relocation Simulator model, which is able to consider interactions between land use and transport systems. The simulations of the different policy scenarios were carried out for the case of Madrid in the period 2012–2031. The contribution of the policy measures to address the city challenges was measured through different indicators. The results indicated that the three policy measures contributed to the time efficiency challenge, by saving time for the commute, reducing congestion and improving the traffic flows at peak hours. The most effective policy in this regard is the teleworking measure. Another challenge addressed by the three policies was the accessibility to PT. The three policy scenarios, when simulated, showed higher PT use, especially the cordon toll scenario. However, the only policy that really contributed to the energy, emissions and pollution city challenges was the re-densification measure, which reduced travel distances and encouraged a mobility that relies more on PT and slow modes.

  16. A novel segmental challenge model for bleomycin-induced pulmonary fibrosis in sheep. (United States)

    Organ, Louise; Bacci, Barbara; Koumoundouros, Emmanuel; Barcham, Garry; Kimpton, Wayne; Nowell, Cameron J; Samuel, Chrishan; Snibson, Ken


    Idiopathic Pulmonary fibrosis (IPF) is a fatal respiratory disease, characterized by a progressive fibrosis and worsening lung function. While the outcomes of recent clinical trials have resulted in therapies to slow the progression of the disease, there is still a need to develop alternative therapies, which are able to prevent fibrosis. This study uses a segmental lung infusion of bleomycin (BLM) to investigate pulmonary fibrosis in a physiologically relevant large animal species. Two separate lung segments in eight sheep received two fortnightly challenges of either 3U or 30U BLM per segment, and a third segment received saline (control). Lung function was assessed using a wedged-bronchoscope procedure. Bronchoalveolar lavage fluid and lung tissue were assessed for inflammation, fibrosis and collagen content two weeks after the final dose of BLM. Instillation of both BLM doses resulted in prominent fibrosis in the treated lobes. More diffuse fibrosis and loss of alveolar airspace was observed in high-dose BLM-treated segments, while multifocal fibrosis was seen in low-dose BLM-treated segments. Extensive and disorganised collagen deposition occurred in the BLM-treated lobes, compared to controls. Significant loss of lung compliance was also observed in the BLM-treated lobes, which did not occur in controls. Fibrosis comparable to IPF was induced into isolated lung segments, without compromising the respiratory functioning of the animal. This model may have potential for investigating novel therapies for IPF by allowing direct comparison of multiple treatments with internal controls, and sampling and drug delivery that are clinically relevant.

  17. List context effects in languages with opaque and transparent orthographies: A challenge for models of reading

    Directory of Open Access Journals (Sweden)

    Daniela eTraficante


    Full Text Available This paper offers a review of data which show that reading is a flexible and dynamic process and that readers can exert strategic control over it. Two main hypotheses on the control of reading processes have been suggested: the route de-emphasis hypothesis and the time-criterion hypothesis. According to the former, the presence of irregular words in the list might lead to an attenuation of the non-lexical process, while the presence of non-words could trigger a de-emphasis of the lexical route. An alternative account is proposed by the time-criterion hypothesis whereby the reader sets a flexible deadline to initiate the response. According to the latter view, it is the average pronunciation difficulty of the items in the block that modulates the time-criterion for response. However, it is worth noting that the list composition has been shown to exert different effects in transparent compared to opaque orthographies, as the consistency of spelling-sound correspondences can influence the processing costs of the non-lexical pathway. In transparent orthographies, the non-lexical route is not resource demanding and can successfully contribute to the pronunciation of regular words, thus its de-emphasis could not be as useful/necessary as in opaque orthographies. The complex patterns of results from the literature on list context effects are a challenge for computational models of reading which face the problem of simulating strategic control over reading processes. Different proposals suggest a modification of parameter setting in the non-lexical route or the implementation of a new module aimed at focusing attention on the output of the more convenient pathway. Simulation data and an assessment of the models’ fit to the behavioral results are presented and discussed to shed light on the role of the cognitive system when reading aloud.

  18. The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model. (United States)

    Kirkpatrick, Beth D; Whitehead, Stephen S; Pierce, Kristen K; Tibery, Cecilia M; Grier, Palmtama L; Hynes, Noreen A; Larsson, Catherine J; Sabundayo, Beulah P; Talaat, Kawsar R; Janiak, Anna; Carmolli, Marya P; Luke, Catherine J; Diehl, Sean A; Durbin, Anna P


    A dengue human challenge model can be an important tool to identify candidate dengue vaccines that should be further evaluated in large efficacy trials in endemic areas. Dengue is responsible for about 390 million infections annually. Protective efficacy results for the most advanced dengue vaccine candidate (CYD) were disappointing despite its ability to induce neutralizing antibodies against all four dengue virus (DENV) serotypes. TV003 is a live attenuated tetravalent DENV vaccine currently in phase 2 evaluation. To better assess the protective efficacy of TV003, a randomized double-blind, placebo-controlled trial in which recipients of TV003 or placebo were challenged 6 months later with a DENV-2 strain, rDEN2Δ30, was conducted. The primary endpoint of the trial was protection against dengue infection, defined as rDEN2Δ30 viremia. Secondary endpoints were protection against rash and neutropenia. All 21 recipients of TV003 who were challenged with rDEN2Δ30 were protected from infection with rDEN2Δ30. None developed viremia, rash, or neutropenia after challenge. In contrast, 100% of the 20 placebo recipients who were challenged with rDEN2Δ30 developed viremia, 80% developed rash, and 20% developed neutropenia. TV003 induced complete protection against challenge with rDEN2Δ30 administered 6 months after vaccination. TV003 will be further evaluated in dengue-endemic areas. The controlled dengue human challenge model can accelerate vaccine development by evaluating the protection afforded by the vaccine, thereby eliminating poor candidates from further consideration before the initiation of large efficacy trials. Copyright © 2016, American Association for the Advancement of Science.

  19. Wind vs Water in Hurricanes: The Challenge of Multi-peril Hazard Modeling (United States)

    Powell, M. D.


    operational solution to collect wind and water level measurements, and to conduct observation based modeling of wind and water impacts. My presentation will discuss some of the challenges to wind and water hazard monitoring and modeling.

  20. Transferring Knowledge from Observations and Models to Decision Makers: An Overview and Challenges (United States)

    Habib, Shahid; Nokra, Nada Abu


    Over the last 25 years, a tremendous progress has been made in the Earth science space-based remote sensing observations, technologies and algorithms. Such advancements have improved the predictability by providing lead-time and accuracy of forecast in weather, climate, natural hazards, and natural resources. It has further reduced or bounded the overall uncertainties by partially improving our understanding of planet Earth as an integrated system that is governed by non-linear and chaotic behavior. Many countries such US, European Community, Japan, China and others have invested billions of dollars in developing and launching space-based assets in the low earth (LEO) and geostationary (GEO) orbits. However, the wealth of this scientific knowledge that has potential of extracting monumental socio-economic benefits from such large investments have been slow in reaching to public and decision makers. For instance, there are a number of areas such as energy forecasting, aviation safety, agricultural competitiveness, disaster management, security, air quality and public health can directly take advantage. Nevertheless, we all live in a global economy that depends on access to the best available Earth Science information for all inhabitants of this planet. This paper surveys and examines a number such applications in terms of their architecture, maturity and economic applicability as they apply to the societal needs. A detailed analysis is also presented of various challenges and issues that pertain to a number of areas such as: (1) difficulties in making a speedy transition of data and information from observations and models to relevant Decision Support Systems (DSS) or tools, (2) data and models inter-operability issues, (3) limitations of spatial, spectral and temporal resolution, (4) communication limitations as dictated by the availability of image processing and data compression techniques. Additionally, the most critical element amongst all is the organizational

  1. Transferring knowledge from observations and models to decision makers: an overview and challenges (United States)

    Habib, Shahid; Nokra, Nada A.


    Over the last 25 years, a tremendous progress has been made in the Earth science space-based remote sensing observations, technologies and algorithms. Such advancements have improved the predictability by providing lead-time and accuracy of forecast in weather, climate, natural hazards, and natural resources. It has further reduced or bounded the overall uncertainties by partially improving our understanding of planet Earth as an integrated system that is governed by non-linear and chaotic behavior. Many countries such US, European Community, Japan, China and others have invested billions of dollars in developing and launching space-based assets in the low earth (LEO) and geostationary (GEO) orbits. However, the wealth of this scientific knowledge that has potential of extracting monumental socio-economic benefits from such large investments have been slow in reaching the public and decision makers. For instance, there are a number of areas such as energy forecasting, aviation safety, agricultural competitiveness, disaster management, homeland security, air quality and public health, which can directly take advantage. Nevertheless, we all live in a global economy that depends on access to the best available Earth Science information for all inhabitants of this planet. This paper surveys and examines a number such applications in terms of their architecture, maturity and economic applicability as they apply to the societal needs. A detailed analysis is also presented of various challenges and issues that pertain to a number of areas such as: (1) difficulties in making a speedy transition of data and information from observations and models to relevant Decision Support Systems (DSS) or tools, (2) data and models inter-operability issues, (3) limitations of spatial, spectral and temporal resolution,(4) communication limitations as dictated by the availability of image processing and data compression techniques. Additionally, the most critical element amongst all is

  2. Quantum control and the challenge of non-Hermitian model-building (United States)

    Znojil, Miloslav


    In a way inspired by the brief 2002 note “The challenge of nonhermitian structures in physics” by Ramirez and Mielnik (with the text most easily available via arXiv:quant- ph/0211048) the situation in the theory is briefly summarized here as it looks twelve years later. Our text has three parts. In the first one we briefly mention the pre-history (dating back to the Freeman Dyson's proposal of the non-Hermitian-Hamiltonian method in 1956 and to its subsequent successful “interacting boson model” applications in nuclear physics) and, first of all, the amazing recent progress reached, in the stationary case, using, in essence, an inversion of the Dyson's approach. The impact on the latter idea upon abstract quantum physics is sampled, first of all, by the reference to papers by Bender et al. (who made the non-Hermitian model-building popular under the nickname of parity-times-time-reflection- symmetric alias PT-symmetric quantum mechanics) and by Mostafazadeh (who reinterpreted PT-symmetry as P-pseudo-Hermiticity). In the second part of our review the emphasis is shifted to the newest, non-stationary upgrade of the formalism which we proposed in the year 2009 and which is characterized by the simultaneous participation of a triplet of Hilbert spaces H in the representation of a single quantum system. In the third part of the review we finally emphasize that the majority of applications of our three-Hilbert-space (THS) recipe is still ahead of us because the enhancement of the flexibility is necessarily accompanied by an enhancement of the technical difficulties. An escape out of the technical trap is proposed to be sought in a restriction of attention to quantum models living in finite-dimensional Hilbert spaces H. As long as the use of such spaces is so typical for the quantum-control considerations, we conclude with conjecture that the THS formalism should start searching for implementations in the field of quantum control.

  3. Seroprevalence of hepatitis B markers among incarcerated intravenous drug users. (United States)

    Nokhodian, Zary; Yaran, Majid; Adibi, Peyman; Kassaian, Nazila; Meshkati, Marjan; Ataei, Behrooz


    Drug injection is one of the most prominent risk factors for transmission of viral hepatitis. Prevalence of hepatitis B virus (HBV) is generally higher in prisoners compared with the general population. The object of this study was to assess the markers of HBV and related risk factors among intravenous drug users (IVDU) in prisoners. Through a cross-sectional study in 2012 HBV infection and its risk factors were assessed in prisoners with a history of intravenous drug use in Isfahan, Iran. A checklist was fulfilled for each participant and 5 ml blood was taken from each subject. Sera were analyzed for markers of the hepatitis B: Hepatitis B virus surface antigen (HBsAg), antibody to hepatitis B virus surface antigen (HBsAb) and hepatitis B virus core antibody (HBcAb) by ELISA. We used Chi-square test and logistic regression model to analyze data and P HBcAb+. 120 (12.37%) were found positive for isolated HBsAb, 45 (4.64%) for isolated HBcAb and 67 (6.9%) for both HBsAb and HBcAb. History of sharing needle (odds ratio: 2.25, 95% confidence interval: 1.09-4.65) had a significant association with HBsAg positivity. The results suggest that history of sharing needle had a significant association with HBsAg positivity. It seems that educational programs for injecting drug related behaviors, especially syringe sharing, are needed for IVDU.

  4. Mycotic aneurysms in intravenous drug abusers: the utility of intravenous digital subtraction angiography

    International Nuclear Information System (INIS)

    Shetty, P.C.; Krasicky, G.A.; Sharma, R.P.; Vemuri, B.R.; Burke, M.M.


    Two-hundred thirteen intravenous digital subtraction angiographic (DSA) examinations were performed on 195 intravenous drug abusers to rule out the possibility of a mycotic aneurysm in a groin, neck, or upper extremity infection. Twenty-three surgically proved cases of mycotic aneurysm were correctly identified with no false positive results. In addition, six cases of major venous occlusion were documented. The authors present the results of their experience and conclude that DSA is an effective and cost-efficient method of examining this high risk patient population

  5. Protective immunization with homologous and heterologous antigens against Helicobacter suis challenge in a mouse model. (United States)

    Flahou, Bram; Hellemans, Ann; Meyns, Tom; Duchateau, Luc; Chiers, Koen; Baele, Margo; Pasmans, Frank; Haesebrouck, Freddy; Ducatelle, Richard


    Helicobacter (H.) suis colonizes the stomach of more than 60% of slaughter pigs and is also of zoonotic importance. Recently, this bacterium was isolated in vitro, enabling the use of pure cultures for research purposes. In this study, mice were immunized intranasally or subcutaneously with whole bacterial cell lysate of H. suis or the closely related species H. bizzozeronii and H. cynogastricus, and subsequently challenged with H. suis. Control groups consisted of non-immunized and non-challenged mice (negative control group), as well as of sham-immunized mice that were inoculated with H. suis (positive control group). Urease tests on stomach tissue samples at 7 weeks after challenge infection were negative in all negative control mice, all intranasally immunized mice except one, and in all and 3 out of 5 animals of the H. cynogastricus and H. suis subcutaneously immunized groups, respectively. H. suis DNA was detected by PCR in the stomach of all positive control animals and all subcutaneously immunized/challenged animals. All negative control animals and some intranasally immunized/challenged mice were PCR-negative. In conclusion, immunization using antigens derived from the same or closely related bacterial species suppressed gastric colonization with H. suis, but complete protection was only achieved in a minority of animals following intranasal immunization.

  6. Intravenous drugs infusion safety through smart pumps

    Directory of Open Access Journals (Sweden)

    C. Gómez-Baraza


    Full Text Available Objective: To analyze the role of smart infusion pumps in reducing errors related with the administration of intravenous medications. Method: Retrospective, observational study analyzing the implementation of a system with smart intravenous infusion pumps (Hospira MedNetTM and the role of the safety system for the detection of errors during the administration of drugs, sera, and blood. We included infusions administered at the day-care hospitals of hematology, oncology, rheumatology, and oncopediatrics. We analyzed adherence to the safety system, the number of programming errors detected, the commonly implicated drugs in these errors, and improvement actions. Results: During the study period, 120 smart pumps were implemented and data on 70,028 infusions were gathered. The rate of adherence to the safety program was 62.30% in hematology (6,887 infusions, 60,30% in oncology (28,127 infusions, 46,50% in rheumatology (1,950 infusions and 1.8% in oncopediatrics (139 infusions. 3,481 out of the established limits programming alerts were generated by the pumps: 2,716 of relative limit and 765 of absolute limit. En 807 infusions (2.17%, errors that could have had consequences for the patients could be prevented. These findings allowed implementing a series of strategies aimed at minimizing these errors in the future. Conclusions: The Hospira MedNetTM system detects deviations from the established protocols of intravenous infusion, preventing in this way potential adverse events for the patients. It also allows establishing correction measures and implementing the improvement strategies.

  7. Effect of intravenous lipid on human pancreatic secretion. (United States)

    Edelman, K; Valenzuela, J E


    Parenteral alimentation, including intravenous fat, is sometimes used in the treatment of patients with pancreatitis, although the effect of intravenous fat on human pancreatic secretion has not been systematically studied. Intravenous fat, however, has been shown to stimulate pancreatic protein secretion in the dog. The purpose of these studies was to clarify the effect of intravenous fat on human pancreatic secretion. Pancreatic secretion was assessed by measurement of enzymes and bicarbonate in duodenal aspirate collected via a double-lumen tube from 6 healthy volunteers. Four studies were randomly conducted on different days. On day 1, graded concentrations of Intralipid (5%, 10%, and 20%) were given intravenously for 1 h each, while secretin (8.2 pmol . kg-1 . h-1) was given as a background. On day 2, the same doses of Intralipid were infused intravenously without secretin. On day 3, the same doses of Intralipid were perfused into the intestine, and, finally, on day 4, 20% Intralipid was given by intestinal infusion for 2 h while 10% Intralipid was infused intravenously during the second hour. Significant stimulation of enzyme secretion was observed only during the infusion of fat into the intestine, not after intravenous infusion at any concentration. Pancreatic enzyme secretion, stimulated by intraintestinal fat, was not significantly modified by simultaneous intravenous lipid infusion. We conclude that since intravenous fat does not stimulate pancreatic secretion, its use in conditions where pancreatic stimulation is undesirable appears safe.

  8. Retroperitoneal fibrosis with normal intravenous urogram. (United States)

    Creagh, F. M.; Stone, T.; Stephenson, T. P.; Lazarus, J. H.


    A 58 year old male presented with a two week history of low back pain and malaise. The intravenous urogram (IVU) at presentation was normal but within three months he had developed renal failure with bilateral ureteric obstruction on repeat IVU. Primary retroperitoneal fibrosis was confirmed at operation. This case demonstrates that retroperitoneal fibrosis may progress rapidly to renal failure within a few months of the first symptoms. In addition, the IVU may be normal in the early stages of the illness. Images Figure 1 Figure 2 PMID:3983053

  9. Pyeloureteral visualization using glucagon during intravenous urography

    International Nuclear Information System (INIS)

    Nepper-Rasmussen, J.; Nielsen, P.H.; Kruse, V.


    194 adult patients were subjected to intravenous urography. In order to study the effect of glucagon on the visualization of the pyeloureteral system, IVU's were performed in four different ways: I. with abdominal compression, II. with glucagon 1 mg.i.v., III. without abdominal compression and without glucagon, and IV. with abdominal compression and glucagon 1 mg.i.v. Coded objective and subjective analyses showed significant worsened visualization of the pyelocalyceal systems, when IVU was performed with glucagon alone. Ureteral visualization was equal in all four groups. Glucagon fails as a pharmacological alternative to abdominal compression in adult human subjects. (orig.) [de

  10. Switching between intravenous and subcutaneous trastuzumab

    DEFF Research Database (Denmark)

    Gligorov, Joseph; Curigliano, Giuseppe; Müller, Volkmar


    AIM: To assess the safety and tolerability of switching between subcutaneous (SC) and intravenous (IV) trastuzumab in the PrefHer study (NCT01401166). PATIENTS AND METHODS: Patients with HER2-positive early breast cancer completed (neo)adjuvant chemotherapy and were randomised to receive four....... Rates of clinically important events, including grade ≥3 AEs, serious AEs, AEs leading to study drug discontinuation and cardiac AEs, were low and similar between treatment arms (safety signals for trastuzumab were observed. CONCLUSIONS: PrefHer revealed...... that switching from IV to SC trastuzumab (hand-held syringe or SID) or vice versa did not impact the known safety profile of trastuzumab....

  11. Mercury poisoning through intravenous administration: Two case reports with literature review. (United States)

    Lu, Qiuying; Liu, Zilong; Chen, Xiaorui


    Metallic mercury poisoning through intravenous injection is rare, especially for a homicide attempt. Diagnosis and treatment of the disease are challenging. A 34-year-old male presented with pyrexia, chill, fatigue, body aches, and pain of the dorsal aspect of right foot. Another case is that of a 29-year-old male who committed suicide by injecting himself metallic mercury 15 g intravenously and presented with dizzy, dyspnea, fatigue, sweatiness, and waist soreness. The patient's condition in case 1 was deteriorated after initial treatment. Imaging studies revealed multiple high-density spots throughout the body especially in the lungs. On further questioning, the patient's girlfriend acknowledged that she injected him about 40 g mercury intravenously 11 days ago. The diagnosis was then confirmed with a urinary mercury concentration of 4828 mg/L. Surgical excision, continuous blood purification, plasma exchange, alveolar lavage, and chelation were performed successively in case 1. Blood irrigation and chelation therapy were performed in case 2. The laboratory test results and organ function of the patient in case 1 gradually returned to normal. However, in case 2, the patient's dyspnea was getting worse and he finally died due to toxic encephalopathy and respiratory failure. Early diagnosis and appropriate treatment are critical for intravenous mercury poisoning. It should be concerned about the combined use of chelation agents and other treatments, such as surgical excision, hemodialysis and plasma exchange in clinical settings.

  12. Pulmonary edema following high intravenous doses of diatrizoate in the rat

    International Nuclear Information System (INIS)

    Maare, K.; Violante, M.; Zack, A.


    Serious adverse reactions to intravenous contrast media are rare but of major concern. Corticosteroids are the most commonly used drugs for prophylaxis but there is little documentation of their effectiveness. Controversy also exists about the optimum regime for these drugs. A rat model was used to evaluate the effect of methylprednisolone pretreatment for contrast media-induced pulmonary edema. Rats were given 40 mg methylprednisolone/kg intravenously at various time intervals before the intravenous injection of a high dose of diatrizoate (6 g I/kg). The combination of one dose of methylprednisolone at 24 hours plus another dose at 0.5 hours was the only regimen that caused a significant reduction in the degree of pulmonary edema induced by contrast media. This result provides support for the clinical regimen utilizing iterated doses of corticosteroids over a prolonged period of time. (orig.)

  13. Pelvic Organ Distribution of Mesenchymal Stem Cells Injected Intravenously after Simulated Childbirth Injury in Female Rats

    Directory of Open Access Journals (Sweden)

    Michelle Cruz


    Full Text Available The local route of stem cell administration utilized presently in clinical trials for stress incontinence may not take full advantage of the capabilities of these cells. The goal of this study was to evaluate if intravenously injected mesenchymal stem cells (MSCs home to pelvic organs after simulated childbirth injury in a rat model. Female rats underwent either vaginal distension (VD or sham VD. All rats received 2 million GFP-labeled MSCs intravenously 1 hour after injury. Four or 10 days later pelvic organs and muscles were imaged for visualization of GFP-positive cells. Significantly more MSCs home to the urethra, vagina, rectum, and levator ani muscle 4 days after VD than after sham VD. MSCs were present 10 days after injection but GFP intensity had decreased. This study provides basic science evidence that intravenous administration of MSCs could provide an effective route for cell-based therapy to facilitate repair after injury and treat stress incontinence.

  14. Challenge problem and milestones for : Nuclear Energy Advanced Modeling and Simulation (NEAMS) waste Integrated Performance and Safety Codes (IPSC).

    Energy Technology Data Exchange (ETDEWEB)

    Freeze, Geoffrey A.; Wang, Yifeng; Howard, Robert; McNeish, Jerry A.; Schultz, Peter Andrew; Arguello, Jose Guadalupe, Jr.


    This report describes the specification of a challenge problem and associated challenge milestones for the Waste Integrated Performance and Safety Codes (IPSC) supporting the U.S. Department of Energy (DOE) Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) Campaign. The NEAMS challenge problems are designed to demonstrate proof of concept and progress towards IPSC goals. The goal of the Waste IPSC is to develop an integrated suite of modeling and simulation capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive waste storage or disposal system. The Waste IPSC will provide this simulation capability (1) for a range of disposal concepts, waste form types, engineered repository designs, and geologic settings, (2) for a range of time scales and distances, (3) with appropriate consideration of the inherent uncertainties, and (4) in accordance with robust verification, validation, and software quality requirements. To demonstrate proof of concept and progress towards these goals and requirements, a Waste IPSC challenge problem is specified that includes coupled thermal-hydrologic-chemical-mechanical (THCM) processes that describe (1) the degradation of a borosilicate glass waste form and the corresponding mobilization of radionuclides (i.e., the processes that produce the radionuclide source term), (2) the associated near-field physical and chemical environment for waste emplacement within a salt formation, and (3) radionuclide transport in the near field (i.e., through the engineered components - waste form, waste package, and backfill - and the immediately adjacent salt). The initial details of a set of challenge milestones that collectively comprise the full challenge problem are also specified.

  15. Challenge problem and milestones for: Nuclear Energy Advanced Modeling and Simulation (NEAMS) waste Integrated Performance and Safety Codes (IPSC)

    International Nuclear Information System (INIS)

    Freeze, Geoffrey A.; Wang, Yifeng; Howard, Robert; McNeish, Jerry A.; Schultz, Peter Andrew; Arguello, Jose Guadalupe Jr.


    This report describes the specification of a challenge problem and associated challenge milestones for the Waste Integrated Performance and Safety Codes (IPSC) supporting the U.S. Department of Energy (DOE) Office of Nuclear Energy Advanced Modeling and Simulation (NEAMS) Campaign. The NEAMS challenge problems are designed to demonstrate proof of concept and progress towards IPSC goals. The goal of the Waste IPSC is to develop an integrated suite of modeling and simulation capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive waste storage or disposal system. The Waste IPSC will provide this simulation capability (1) for a range of disposal concepts, waste form types, engineered repository designs, and geologic settings, (2) for a range of time scales and distances, (3) with appropriate consideration of the inherent uncertainties, and (4) in accordance with robust verification, validation, and software quality requirements. To demonstrate proof of concept and progress towards these goals and requirements, a Waste IPSC challenge problem is specified that includes coupled thermal-hydrologic-chemical-mechanical (THCM) processes that describe (1) the degradation of a borosilicate glass waste form and the corresponding mobilization of radionuclides (i.e., the processes that produce the radionuclide source term), (2) the associated near-field physical and chemical environment for waste emplacement within a salt formation, and (3) radionuclide transport in the near field (i.e., through the engineered components - waste form, waste package, and backfill - and the immediately adjacent salt). The initial details of a set of challenge milestones that collectively comprise the full challenge problem are also specified.

  16. Intravenous Infusion of Bone Marrow–Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats


    Yohei Matsuda, MD; Masanori Sasaki, MD, PhD; Yuko Kataoka-Sasaki, MD, PhD; Akio Takayanagi, MD, PhD; Ko Kobayashi, MD, PhD; Shinichi Oka, MD, PhD; Masahito Nakazaki, MD, PhD; Naoya Masumori, MD, PhD; Jeffery D. Kocsis, PhD; Osamu Honmou, MD, PhD


    Introduction: Intravenous preload (delivered before cavernous nerve [CN] injury) of bone marrow–derived mesenchymal stem cells (MSCs) can prevent or decrease postoperative erectile dysfunction (J Sex Med 2015;12:1713–1721). In the present study, the potential therapeutic effects of intravenously administered MSCs on postoperative erectile dysfunction were evaluated in a rat model of CN injury. Methods: Male Sprague-Dawley rats were randomized into 2 groups after electric CN injury. Intrave...

  17. Safety and pharmacokinetics of intravenous levetiracetam infusion as add-on in status epilepticus

    NARCIS (Netherlands)

    Uges, Joris W F; van Huizen, Marc D; Engelsman, Jeroen; Wilms, Erik B; Touw, Daniel J; Peeters, Els; Vecht, Charles J

    PURPOSE: To evaluate the feasibility and safety of intravenous (iv) levetiracetam (LEV) added to the standard therapeutic regimen in adults with status epilepticus (SE), and as secondary objective to assess a population pharmacokinetic (PK) model for ivLEV in patients with SE. METHODS: In 12 adults

  18. Protective vaccination with hepatitis C virus NS3 but not core antigen in a novel mouse challenge model. (United States)

    El-Gogo, Susanne; Staib, Caroline; Lasarte, Juan José; Sutter, Gerd; Adler, Heiko


    Efficient vaccines against hepatitis C virus (HCV) infection are urgently needed. Vaccine development has been hampered by the lack of suitable small animal models to reliably test the protective capacity of immmunization. We used recombinant murine gammaherpesvirus 68 (MHV-68) as a novel challenge virus in mice and tested the efficacy of heterologous candidate human vaccines based on modified vaccinia virus Ankara or adenovirus, both delivering HCV non-structural NS3 or core proteins. Recombinant MHV-68 expressing NS3 (MHV-68-NS3) or core (MHV-68-core) were constructed and characterized in vitro and in vivo. Mice immunized with NS3-specific vector vaccines and challenged with MHV-68-NS3 were infected but showed significantly reduced viral loads in the acute and latent phase of infection. NS3-specific CD8+ T cells were amplified in immunized mice after challenge with MHV-68-NS3. By contrast, we did neither detect a reduction of viral load nor an induction of core-specific CD8+ T cells after core-specific immunization. Our data suggest that the challenge system using recombinant MHV-68 is a highly suitable model to test the immunogenicity and protective capacity of HCV candidate vaccine antigens. Using this system, we demonstrated the usefulness of NS3-specific immunization. By contrast, our analysis rather discarded core as a vaccine antigen.

  19. From California dreaming to California data: Challenging historic models for landfill CH4 emissions (United States)

    Improved quantification of diverse CH4 sources at the urban scale is needed to guide local greenhouse gas (GHG) mitigation strategies in the Anthropocene. Herein, we focus on landfill CH4 emissions in California, challenging the current IPCC methodology which focuses on a climate dependency for land...

  20. Academic Dishonesty in Distance Higher Education: Challenges and Models for Moral Education in the Digital Era (United States)

    Farisi, Mohammad Imam


    Today, in the era of open access to digital-based information and communication, one of the biggest challenges in higher education to realize moral education and to build academic culture and integrity is the emergence of academic dishonesty behaviors among academic members. The paper describes academic dishonesty behaviors in Distance Higher…

  1. Exploring challenges and solutions for container transportation using rail: A modelling and simulation gaming study

    NARCIS (Netherlands)

    Kurapati, S.; Kourounioti, I.; Lukosch, H.; Tavaszzy, L.; Verbraeck, A.; Veen, L. van; Nuland, B. van; Smit, T.


    Rail is a cost-effective and environment friendly freight transport modality when used efficiently. Stakeholders around Dutch ports are discouraged to choose rail due to uncertain train schedules and the dispersed nature of freight flows across terminals in the port. To understand the challenges and

  2. Challenge models to study the effect of immune system activation on amino acid metabolism in pigs

    NARCIS (Netherlands)

    Hoek, van de E.; Gerrits, W.J.J.; Borne, van den J.J.G.C.; Peet-Schwering, van der C.M.C.; Beers, van H.; Jansman, A.J.M.


    In response to (non-)pathogenic challenges, the immune system of pigs can be activated. During immune system activation, there is a competition for amino acids (AA) between body protein deposition (growth) and immune function (Sandberg et al., 2007). As a consequence, feed intake and growth are

  3. Motivation, Challenges, Support (MCS) Cycle Model for the Development of PBL Tutors (United States)

    Constantinou, Costas S.; Nicolaou, Stella A.


    Problem-Based Learning (PBL) is well known for enhancing students' problem solving skills and teamwork, while the role of PBL tutors is to facilitate discussion rather than teach. This study used four focus groups to explore PBL tutors' motivation, challenges and support mechanisms, and the relationship between these. The study found that there…

  4. Confronting the STEM Challenge: A New Modeling Tool for U.S. Education Policymakers (United States)

    Business-Higher Education Forum (NJ1), 2010


    The Business-Higher Education Forum (BHEF) is an organization of Fortune 500 chief executive officers (CEOs,) prominent college and university presidents, and foundation leaders working to advance innovative solutions to the nation's education challenges in order to enhance U.S. competitiveness. This paper presents questions and answers about the…

  5. Classroom ICT Integration in Tanzania: Opportunities and Challenges from the Perspectives of TPACK and SAMR Models (United States)

    Kihoza, Patrick; Zlotnikova, Irina; Bada, Joseph; Kalegele, Khamisi


    With the education systems demand of contemporary technologies, teacher trainees should be imparted with competencies and skills to integrate information and communication technology (ICT) into their future teaching and learning practices. This study assessed classroom ICTs integration opportunities and the challenges in relation to Technological…

  6. Ultrasonography-guided peripheral intravenous access versus traditional approaches in patients with difficult intravenous access. (United States)

    Costantino, Thomas G; Parikh, Aman K; Satz, Wayne A; Fojtik, John P


    We assess the success rate of emergency physicians in placing peripheral intravenous catheters in difficult-access patients who were unsuccessfully cannulated by emergency nurses. A technique using real-time ultrasonographic guidance by 2 physicians was compared with traditional approaches using palpation and landmark guidance. This was a prospective, systematically allocated study of all patients requiring intravenous access who presented to 2 university hospitals between October 2003 and March 2004. Inclusion criterion was the inability of any available nurse to obtain intravenous access after at least 3 attempts on a subgroup of patients who had a history of difficult intravenous access because of obesity, history of intravenous drug abuse, or chronic medical problems. Exclusion criterion was the need for central venous access. Patients presenting on odd days were allocated to the ultrasonographic-guided group, and those presenting on even days were allocated to the traditional-approach group. Endpoints were successful cannulation, number of sticks, time, and patient satisfaction. Sixty patients were enrolled, 39 on odd days and 21 on even days. Success rate was greater for the ultrasonographic group (97%) versus control (33%), difference in proportions of 64% (95% confidence interval [CI] 39% to 71%). The ultrasonographic group required less overall time (13 minutes versus 30 minutes, for a difference of 17 [95% CI 0.8 to 25.6]), less time to successful cannulation from first percutaneous puncture (4 minutes versus 15 minutes, for a difference of 11 [95% CI 8.2 to 19.4]), and fewer percutaneous punctures (1.7 versus 3.7, for a difference of 2.0 [95% CI 1.27 to 2.82]) and had greater patient satisfaction (8.7 versus 5.7, for a difference of 3.0 [95% CI 1.82 to 4.29]) than the traditional landmark approach. Ultrasonographic-guided peripheral intravenous access is more successful than traditional "blind" techniques, requires less time, decreases the number of

  7. Intravenous Carbamazepine for Adults With Seizures. (United States)

    Vickery, P Brittany; Tillery, Erika E; DeFalco, Alicia Potter


    To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions, and place in therapy of the intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of seizures in adult patients. A comprehensive PubMed and EBSCOhost search (1945 to August 2017) was performed utilizing the keywords carbamazepine, Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and seizure disorder. Additional data were obtained from literature review citations, manufacturer's product labeling, and Lundbeck website as well as and governmental sources. All English-language trials evaluating IV carbamazepine were analyzed for this review. IV carbamazepine is FDA approved as temporary replacement therapy for treatment of adult seizures. Based on a phase I trial and pooled data from 2 open-label bioavailability studies comparing oral with IV dosing, there was no noted indication of loss of seizure control in patients switched to short-term replacement antiepileptic drug therapy with IV carbamazepine. The recommended dose of IV carbamazepine is 70% of the patient's oral dose, given every 6 hours via 30-minute infusions. The adverse effect profile of IV carbamazepine is similar to that of the oral formulation, with the exception of added infusion-site reactions. IV carbamazepine is a reasonable option for adults with generalized tonic-clonic or focal seizures, previously stabilized on oral carbamazepine, who are unable to tolerate oral medications for up to 7 days. Unknown acquisition cost and lack of availability in the United States limit its use currently.

  8. The human experience with intravenous levodopa

    Directory of Open Access Journals (Sweden)

    Shan H Siddiqi


    Full Text Available Objective: To compile a comprehensive summary of published human experience with levodopa given intravenously, with a focus on information required by regulatory agencies.Background: While safe intravenous (IV use of levodopa has been documented for over 50 years, regulatory supervision for pharmaceuticals given by a route other than that approved by the U.S. Food and Drug Administration (FDA has become increasingly cautious. If delivering a drug by an alternate route raises the risk of adverse events, an investigational new drug (IND application is required, including a comprehensive review of toxicity data.Methods: Over 200 articles referring to IV levodopa were examined for details of administration, pharmacokinetics, benefit and side effects.Results: We identified 142 original reports describing IVLD use in humans, beginning with psychiatric research in 1959-1960 before the development of peripheral decarboxylase inhibitors. Over 2750 subjects have received IV levodopa, and reported outcomes include parkinsonian signs, sleep variables, hormone levels, hemodynamics, CSF amino acid composition, regional cerebral blood flow, cognition, perception and complex behavior. Mean pharmacokinetic variables were summarized for 49 healthy subjects and 190 with Parkinson’s disease. Side effects were those expected from clinical experience with oral levodopa and dopamine agonists. No articles reported deaths or induction of psychosis.Conclusion: Over 2750 patients have received IV levodopa with a safety profile comparable to that seen with oral administration.

  9. Flank pain: is Intravenous Urogram necessary? (United States)

    Teh, H S; Lin, M B; Khoo, T K


    To determine the diagnostic yield of Intravenous Urogram (IVU) and the values of plain radiograph of kidney, ureter and bladder (KUB) and urinalysis as screening tests, with the objective to improve the cost effectiveness, in the management of patients presenting with flank pain due to urinary lithiasis. All Intravenous Urogram (IVU) request forms and reports for the month of February 1998 were audited. The case notes, urinalysis, KUB and IVU films were traced and reviewed. There were 110 patients investigated, 61.8% (68) had normal IVU, 38.2% (42) had abnormal IVU. The sensitivity and specificity of KUB alone was 79.4% and 90%. The sensitivity using urinalysis alone was 90.9% and its specificity 33.8%. The sensitivity of combined KUB and urinalysis was 100% and its specificity 26%, with a negative predictive value of 100%. All the patients with both negative KUB and urinalysis in our study were found to have negative IVU. Our study shows that in patients with both negative KUB and urinalysis, the yield of IVU is very low and may not be necessary. This is important, as an IVU examination is not without risk. A combination of KUB with urinary analysis and careful evaluation of clinical symptoms will improve the cost-effectiveness of patient management.

  10. Intravenous<