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Sample records for model system acute

  1. Acute Pancreatitis as a Model to Predict Transition of Systemic Inflammation to Organ Failure in Trauma and Critical Illness

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-14-1-0376 TITLE: Acute Pancreatitis as a Model to Predict Transition of Systemic Inflammation to Organ Failgure in Trauma...COVERED 22 Sep 2016 - 21 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Acute Pancreatitis as a Model to Predict Transition of Systemic...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Trauma, extensive burns, bacterial infections, and acute pancreatitis (AP) are common

  2. Application of mobile blood purification system in the treatment of acute renal failure dog model in the field environment

    Directory of Open Access Journals (Sweden)

    Zhi-min ZHANG

    2014-01-01

    Full Text Available Objective To evaluate the stability, safety and efficacy of mobile blood purification system in the treatment of acute renal failure dog model in the field environment. Methods The acute renal failure model was established in 4 dogs by bilateral nephrectomy, which was thereafter treated with the mobile blood purification system. The evaluation of functional index of the mobile blood purification system was performed after a short-time (2 hours and conventional (4 hours dialysis treatment. Results The mobile blood purification system ran stably in the field environment at a blood flow of 150-180ml/min, a dialysate velocity of 2000ml/h, a replacement fluid velocity of 2000ml/h, and ultrafiltration rate of 100-200ml/h. All the functions of alarming system worked well, including static upper limit alarm of ultrafiltration pressure (>100 mmHg, upper limit alarm of ambulatory arterial pressure (>400mmHg, upper limit alarm of ambulatory venous pressure (>400mmHg, bubble alarm of vascular access, bubble alarm during the infusion of solutions, pressure alarm at the substitution pump segment and blood leaking alarm. The vital signs of the 4 dogs with acute renal failure kept stable during the treatment. After the treatment, a remarkable decrease was seen in the levels of serum urea nitrogen, creatinine and serum potassium (P0.05. Conclusions The mobile blood purification system runs normally even in a field environment. It is a flexible and portable device with a great performance in safety and stability in the treatment of acute renal failure. DOI: 10.11855/j.issn.0577-7402.2013.12.15

  3. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Francis Richard W

    2010-04-01

    Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

  4. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

    International Nuclear Information System (INIS)

    Mullenix, P.J.; Kernan, W.J.; Tassinari, M.S.; Schunior, A.; Waber, D.P.; Howes, A.; Tarbell, N.J.

    1990-01-01

    Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy

  5. Natural Variation in Responses to Acute Heat and Cold Stress in a Sea Anemone Model System for Coral Bleaching.

    Science.gov (United States)

    Bellis, Emily S; Denver, Dee R

    2017-10-01

    Rising ocean temperatures disrupt the symbiosis between corals and their microalgae, accelerating global decline of coral reef ecosystems. Because of the difficulty of performing laboratory experiments with corals, the sea anemone Aiptasia has emerged as an important model system for molecular studies of coral bleaching and symbiosis. Here, we investigate natural variation in bleaching responses among different genetic lineages of Aiptasia. Both heat- and cold-induced paths to symbiosis breakdown were analyzed. Significant genetic variation in response to acute heat stress was observed, with severe bleaching of two Aiptasia strains from Hawaii but minimal bleaching of strains from the U.S. South Atlantic, including the strain used to generate the Aiptasia reference genome. Both strains from Hawaii hosted Symbiodinium type B1, whereas strains from the U.S. South Atlantic hosted type A4 or B2. In contrast to the results from exposures to acute heat stress, negligible variation was observed in response to a pulsed cold shock despite moderate bleaching across all strains. These results support our hypothesis that bleaching responses to distinct stressors are independent. Our findings emphasize the role of stress regime when predicting adaptive responses of symbiotic cnidarians to changing climates, because genetic variation may exist for some forms of stress-induced bleaching but not others.

  6. Acute toxicities of pharmaceuticals toward green algae. mode of action, biopharmaceutical drug disposition classification system and quantile regression models.

    Science.gov (United States)

    Villain, Jonathan; Minguez, Laetitia; Halm-Lemeille, Marie-Pierre; Durrieu, Gilles; Bureau, Ronan

    2016-02-01

    The acute toxicities of 36 pharmaceuticals towards green algae were estimated from a set of quantile regression models representing the first global quantitative structure-activity relationships. The selection of these pharmaceuticals was based on their predicted environmental concentrations. An agreement between the estimated values and the observed acute toxicity values was found for several families of pharmaceuticals, in particular, for antidepressants. A recent classification (BDDCS) of drugs based on ADME properties (Absorption, Distribution, Metabolism and Excretion) was clearly correlated with the acute ecotoxicities towards algae. Over-estimation of toxicity from our QSAR models was observed for classes 2, 3 and 4 whereas our model results were in agreement for the class 1 pharmaceuticals. Clarithromycin, a class 3 antibiotic characterized by weak metabolism and high solubility, was the most toxic to algae (molecular stability and presence in surface water). Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Effects of Acute Systemic Hypoxia and Hypercapnia on Brain Damage in a Rat Model of Hypoxia-Ischemia.

    Directory of Open Access Journals (Sweden)

    Wanchao Yang

    Full Text Available Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O2,13%O2,15%O2 and 18%O2 (targeted to PaO2 30-39 mmHg, 40-49 mmHg, 50-59 mmHg, and 60-69 mmHg, respectively or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO2 60-80 mmHg for 180 min. The mean artery pressure (MAP, blood gas, and cerebral blood flow (CBF were evaluated. The cortical vascular permeability and brain edema were examined. The ipsilateral cortex damage and the percentage of hippocampal apoptotic neurons were evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL assay as well as flow cytometry, respectively. Immunofluorescence and western blotting were performed to determine aquaporin-4 (AQP4 expression. In rats treated with severe hypoxia (PaO2 50 mmHg, hypercapnia protected against these pathophysiological changes. Moreover, hypercapnia treatment significantly reduced brain damage in the ischemic ipsilateral cortex and decreased the percentage of apoptotic neurons in the hippocampus after the CCA ligated rats were exposed to mild or moderate hypoxemia (PaO2 > 50 mmHg; especially under mild hypoxemia (PaO2 > 60 mmHg, hypercapnia significantly attenuated the expression of AQP4 protein with brain edema (p < 0.05. Hypercapnia exerts beneficial effects under mild to moderate hypoxemia and augments detrimental effects under severe hypoxemia on brain damage in a rat model of hypoxia-ischemia.

  8. Comparison of acute effect of systemic versus intravitreal infliximab treatment in an experimental model of endotoxin-induced uveitis.

    Science.gov (United States)

    Yuksel, Erdem; Hasanreisoglu, Berati; Yuksel, Nilay; Yilmaz, Guldal; Ercin, Ugur; Bilgihan, Ayse

    2014-02-01

    In this study, we investigated the efficacy of systemic and intravitreal (IV) infliximab treatments and compared these 2 different treatment modalities in an experimental model of endotoxin-induced uveitis (EIU). Twenty-four white New Zealand rabbits were equally divided into 4 groups. Group 1 received IV injection of lipopolysaccharide (LPS), group 2 received IV injections of LPS and saline, group 3 received IV LPS and IV 2 mg/0.1 cc infliximab, and group 4 received IV LPS and 5 mg/kg intravenous infliximab. Inflammation was determined with objective and subjective tests. The subjective test was clinical determination of uveitis, the objective tests were determination of protein concentrations and tumor necrosis factor alpha (TNF-α) levels and histopathology. Clinical examination score was lower in group 3 and group 4 (4±0.6 and 3.5±1.6, respectively) when compared with group 1 (P=0.02; P=0.04, respectively) and group 2. In group 3 and 4, the aqueous and vitreous protein and TNF-α concentration measured significantly lower than group 1 and 2. In histopathologic examination, there was no statistically significant difference between group 1, 2, and 3 (3.5±0.5, 3.6±0.5, 3.6±0.5, respectively). However, the lowest histopathologic inflammation was determined in group 4 (2.5±0.5) (compared with group 1 and group 3, respectively; P=0.03; P=0.014). In a rabbit model of experimental EIU, intravenous administration of infliximab was more effective than IV route in an acute period.

  9. Gerbil model of acute neosporosis.

    Science.gov (United States)

    Ramamoorthy, Sheela; Sriranganathan, N; Lindsay, David S

    2005-01-20

    Experimental infections with the NC-1 strain of Neospora caninum were conducted in gerbils (Meriones unguiculatus) to determine their acute responses to experimental intraperitoneal infection. Five groups of five female gerbils were used and they were intraperitoneally infected with 1x10(6), 2x10(6), 3x10(6), 4x10(6) or 5x10(6) tachyzoites. Gerbils in all groups developed clinical signs of neosporosis which consisted of inactivity 4-5 days post-inoculation. Morbidity and mortality were observed in all groups. Grossly there was a clear fibrinous exudate in the abdominal cavity and adhesions of the spleen and pancreas to the stomach in gerbils suffering from acute neosporosis. The LD50 was calculated as 9.3x10(5) tachyzoites per gerbil. The results indicate that gerbils can be used as a suitable model of acute neosporosis. This model can be used to screen candidate treatments and to test the efficacy of vaccines for neosporosis without the need to use histology or PCR to demonstrate treatment efficacy.

  10. Comparison of the effect of topical versus systemic L-arginine on wound healing in acute incisional diabetic rat model

    Directory of Open Access Journals (Sweden)

    Alireza Zandifar

    2015-01-01

    Full Text Available Background: Diabetes is associated with endothelial dysfunction and impaired wound healing. The amino acid L-arginine is the only substrate for nitric oxide (NO synthesis. The purpose of this study was to compare the topical versus systemic L-arginine treatment on total nitrite (NO x and vascular endothelial growth factor (VEGF concentrations in wound fluid and rate of wound healing in an acute incisional diabetic wound model. Materials and Methods: A total of 56 Sprague-Dawley rats were used of which 32 were rendered diabetic. Animals underwent a dorsal skin incision. Dm-sys-arg group (N = 8, diabetic and Norm-sys-arg group (N = 8, normoglycemic were gavaged with L-arginine. Dm-sys-control group (N = 8, diabetic and Norm-sys-control group (N = 8, normoglycemic were gavaged with water. Dm-top-arg group (N = 8, diabetic and norm-top-arg group (N = 8, normoglycemic received topical L-arginine gel. Dm-top-control group (N = 8, diabetic received gel vehicle. On the day 5 the amount of NO x in wound fluid was measured by Griess reaction. VEGF/total protein in wound fluids was also measured on day 5 using enzyme-linked immunosorbent assay. All wound tissue specimens were fixed and stained to be evaluated for rate of healing. Data were analyzed using SPSS software (version 18.0, Chicago, IL, USA through One-way analysis of variance test and Tukey′s post-hoc. Results: In dm-sys-arg group, the level of NO x on day 5 was significantly more than dm-top-arg group (P < 0.05. VEGF content in L-arginine treated groups were significantly more than controls (P < 0.05. Rate of diabetic wound healing in dm-sys-arg group was significantly more than dm-top-arg group. Conclusion: Systemic L-arginine is more efficient than topical L-arginine in wound healing. This process is mediated at least in part, by increasing VEGF and NO in the wound fluid.

  11. Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

    2015-10-01

    The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Prognostic modeling in pediatric acute liver failure.

    Science.gov (United States)

    Jain, Vandana; Dhawan, Anil

    2016-10-01

    Liver transplantation (LT) is the only proven treatment for pediatric acute liver failure (PALF). However, over a period of time, spontaneous native liver survival is increasingly reported, making us wonder if we are overtransplanting children with acute liver failure (ALF). An effective prognostic model for PALF would help direct appropriate organ allocation. Only patients who would die would undergo LT, and those who would spontaneously recover would avoid unnecessary LT. Deriving and validating such a model for PALF, however, encompasses numerous challenges. In particular, the heterogeneity of age and etiology in PALF, as well as a lack of understanding of the natural history of the disease, contributed by the availability of LT has led to difficulties in prognostic model development. Several prognostic laboratory variables have been identified, and the incorporation of these variables into scoring systems has been attempted. A reliable targeted prognostic model for ALF in Wilson's disease has been established and externally validated. The roles of physiological, immunological, and metabolomic parameters in prognosis are being investigated. This review discusses the challenges with prognostic modeling in PALF and describes predictive methods that are currently available and in development for the future. Liver Transplantation 22 1418-1430 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

  13. Modelling Systemic Iron Regulation during Dietary Iron Overload and Acute Inflammation: Role of Hepcidin-Independent Mechanisms.

    Science.gov (United States)

    Enculescu, Mihaela; Metzendorf, Christoph; Sparla, Richard; Hahnel, Maximilian; Bode, Johannes; Muckenthaler, Martina U; Legewie, Stefan

    2017-01-01

    Systemic iron levels must be maintained in physiological concentrations to prevent diseases associated with iron deficiency or iron overload. A key role in this process plays ferroportin, the only known mammalian transmembrane iron exporter, which releases iron from duodenal enterocytes, hepatocytes, or iron-recycling macrophages into the blood stream. Ferroportin expression is tightly controlled by transcriptional and post-transcriptional mechanisms in response to hypoxia, iron deficiency, heme iron and inflammatory cues by cell-autonomous and systemic mechanisms. At the systemic level, the iron-regulatory hormone hepcidin is released from the liver in response to these cues, binds to ferroportin and triggers its degradation. The relative importance of individual ferroportin control mechanisms and their interplay at the systemic level is incompletely understood. Here, we built a mathematical model of systemic iron regulation. It incorporates the dynamics of organ iron pools as well as regulation by the hepcidin/ferroportin system. We calibrated and validated the model with time-resolved measurements of iron responses in mice challenged with dietary iron overload and/or inflammation. The model demonstrates that inflammation mainly reduces the amount of iron in the blood stream by reducing intracellular ferroportin transcription, and not by hepcidin-dependent ferroportin protein destabilization. In contrast, ferroportin regulation by hepcidin is the predominant mechanism of iron homeostasis in response to changing iron diets for a big range of dietary iron contents. The model further reveals that additional homeostasis mechanisms must be taken into account at very high dietary iron levels, including the saturation of intestinal uptake of nutritional iron and the uptake of circulating, non-transferrin-bound iron, into liver. Taken together, our model quantitatively describes systemic iron metabolism and generated experimentally testable predictions for additional

  14. Systemic Lupus Erythematosus Presenting as Acute Adrenal ...

    African Journals Online (AJOL)

    hanumantp

    hereby report such a case of SLE presenting as acute adrenal insufficiency. ... Kidney function tests, Liver function tests, serum calcium, and ... renal involvement. Patient was successfully managed with steroids and improved clinically. Keywords: Addison's disease, Autoimmune diseases, Systemic lupus erythematosus.

  15. Fault-diagnosis applications. Model-based condition monitoring. Acutators, drives, machinery, plants, sensors, and fault-tolerant systems

    Energy Technology Data Exchange (ETDEWEB)

    Isermann, Rolf [Technische Univ. Darmstadt (DE). Inst. fuer Automatisierungstechnik (IAT)

    2011-07-01

    Supervision, condition-monitoring, fault detection, fault diagnosis and fault management play an increasing role for technical processes and vehicles in order to improve reliability, availability, maintenance and lifetime. For safety-related processes fault-tolerant systems with redundancy are required in order to reach comprehensive system integrity. This book is a sequel of the book ''Fault-Diagnosis Systems'' published in 2006, where the basic methods were described. After a short introduction into fault-detection and fault-diagnosis methods the book shows how these methods can be applied for a selection of 20 real technical components and processes as examples, such as: Electrical drives (DC, AC) Electrical actuators Fluidic actuators (hydraulic, pneumatic) Centrifugal and reciprocating pumps Pipelines (leak detection) Industrial robots Machine tools (main and feed drive, drilling, milling, grinding) Heat exchangers Also realized fault-tolerant systems for electrical drives, actuators and sensors are presented. The book describes why and how the various signal-model-based and process-model-based methods were applied and which experimental results could be achieved. In several cases a combination of different methods was most successful. The book is dedicated to graduate students of electrical, mechanical, chemical engineering and computer science and for engineers. (orig.)

  16. Zebrafish Models for Human Acute Organophosphorus Poisoning.

    Science.gov (United States)

    Faria, Melissa; Garcia-Reyero, Natàlia; Padrós, Francesc; Babin, Patrick J; Sebastián, David; Cachot, Jérôme; Prats, Eva; Arick Ii, Mark; Rial, Eduardo; Knoll-Gellida, Anja; Mathieu, Guilaine; Le Bihanic, Florane; Escalon, B Lynn; Zorzano, Antonio; Soares, Amadeu M V M; Raldúa, Demetrio

    2015-10-22

    Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning.

  17. Ossicular bone modeling in acute otitis media

    DEFF Research Database (Denmark)

    Salomonsen, Rasmus Lysholdt; Hermansson, Ann; Cayé-Thomasen, Per

    2010-01-01

    A number of middle ear diseases are associated with pathologic bone modeling, either formative or resorptive. As such, the pathogenesis of a sclerotic mastoid has been controversial for decades. Experimental studies on acute middle ear infection have shown progressive osteoneogenesis in the bone ...... structures surrounding the middle ear cavity, and a few studies have reported acute changes of the ossicular chain. However, detailed qualitative and quantitative information on ossicular bone modeling dynamics has not been accounted for and is thus the purpose of this study....

  18. A Mathematical Model of the Honeybee-Varroa destructor-Acute Bee Paralysis Virus System with Seasonal Effects.

    Science.gov (United States)

    Ratti, Vardayani; Kevan, Peter G; Eberl, Hermann J

    2015-08-01

    A mathematical model for the honeybee-varroa mite-ABPV system is proposed in terms of four differential equations for the: infected and uninfected bees in the colony, number of mites overall, and of mites carrying the virus. To account for seasonal variability, all parameters are time periodic. We obtain linearized stability conditions for the disease-free periodic solutions. Numerically, we illustrate that, for appropriate parameters, mites can establish themselves in colonies that are not treated with varroacides, leading to colonies with slightly reduced number of bees. If some of these mites carry the virus, however, the colony might fail suddenly after several years without a noticeable sign of stress leading up to the failure. The immediate cause of failure is that at the end of fall, colonies are not strong enough to survive the winter in viable numbers. We investigate the effect of the initial disease infestation on collapse time, and how varroacide treatment affects long-term behavior. We find that to control the virus epidemic, the mites as disease vector should be controlled.

  19. Ossicular bone modeling in acute otitis media

    DEFF Research Database (Denmark)

    Salomonsen, Rasmus Lysholdt; Hermansson, Ann; Cayé-Thomasen, Per

    2010-01-01

    A number of middle ear diseases are associated with pathologic bone modeling, either formative or resorptive. As such, the pathogenesis of a sclerotic mastoid has been controversial for decades. Experimental studies on acute middle ear infection have shown progressive osteoneogenesis in the bone ...

  20. 20180311 - Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development (SOT)

    Science.gov (United States)

    Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

  1. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on growth and craniofacial proportion

    International Nuclear Information System (INIS)

    Schunior, A.; Zengel, A.E.; Mullenix, P.J.; Tarbell, N.J.; Howes, A.; Tassinari, M.S.

    1990-01-01

    Many long term survivors of childhood acute lymphoblastic leukemia have short stature, as well as craniofacial and dental abnormalities, as side effects of central nervous system prophylactic therapy. An animal model is presented to assess these adverse effects on growth. Cranial irradiation (1000 cGy) with and without prednisolone (18 mg/kg i.p.) and methotrexate (2 mg/kg i.p.) was administered to 17- and 18-day-old Sprague-Dawley male and female rats. Animals were weighed 3 times/week. Final body weight and body length were measured at 150 days of age. Femur length and craniofacial dimensions were measured directly from the bones, using calipers. For all exposed groups there was a permanent suppression of weight gain with no catch-up growth or normal adolescent growth spurt. Body length was reduced for all treated groups, as were the ratios of body weight to body length and cranial length to body length. Animals subjected to cranial irradiation exhibited microcephaly, whereas those who received a combination of radiation and chemotherapy demonstrated altered craniofacial proportions in addition to microcephaly. Changes in growth patterns and skeletal proportions exhibited sexually dimorphic characteristics. The results indicate that cranial irradiation is a major factor in the growth failure in exposed rats, but chemotherapeutic agents contribute significantly to the outcome of growth and craniofacial dimensions

  2. Modeling acute respiratory illness during the 2007 San Diego wildland fires using a coupled emissions-transport system and generalized additive modeling.

    Science.gov (United States)

    Thelen, Brian; French, Nancy H F; Koziol, Benjamin W; Billmire, Michael; Owen, Robert Chris; Johnson, Jeffrey; Ginsberg, Michele; Loboda, Tatiana; Wu, Shiliang

    2013-11-05

    A study of the impacts on respiratory health of the 2007 wildland fires in and around San Diego County, California is presented. This study helps to address the impact of fire emissions on human health by modeling the exposure potential of proximate populations to atmospheric particulate matter (PM) from vegetation fires. Currently, there is no standard methodology to model and forecast the potential respiratory health effects of PM plumes from wildland fires, and in part this is due to a lack of methodology for rigorously relating the two. The contribution in this research specifically targets that absence by modeling explicitly the emission, transmission, and distribution of PM following a wildland fire in both space and time. Coupled empirical and deterministic models describing particulate matter (PM) emissions and atmospheric dispersion were linked to spatially explicit syndromic surveillance health data records collected through the San Diego Aberration Detection and Incident Characterization (SDADIC) system using a Generalized Additive Modeling (GAM) statistical approach. Two levels of geographic aggregation were modeled, a county-wide regional level and division of the county into six sub regions. Selected health syndromes within SDADIC from 16 emergency departments within San Diego County relevant for respiratory health were identified for inclusion in the model. The model captured the variability in emergency department visits due to several factors by including nine ancillary variables in addition to wildfire PM concentration. The model coefficients and nonlinear function plots indicate that at peak fire PM concentrations the odds of a person seeking emergency care is increased by approximately 50% compared to non-fire conditions (40% for the regional case, 70% for a geographically specific case). The sub-regional analyses show that demographic variables also influence respiratory health outcomes from smoke. The model developed in this study allows a

  3. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

  4. Comparison of blood biochemics between acute myocardial infarction models with blood stasis and simple acute myocardial infarction models in rats

    International Nuclear Information System (INIS)

    Qu Shaochun; Yu Xiaofeng; Wang Jia; Zhou Jinying; Xie Haolin; Sui Dayun

    2010-01-01

    Objective: To construct the acute myocardial infarction models in rats with blood stasis and study the difference on blood biochemics between the acute myocardial infarction models with blood stasis and the simple acute myocardial infarction models. Methods: Wistar rats were randomly divided into control group, acute blood stasis model group, acute myocardial infarction sham operation group, acute myocardial infarction model group and of acute myocardial infarction model with blood stasis group. The acute myocardial infarction models under the status of the acute blood stasis in rats were set up. The serum malondialdehyde (MDA), nitric oxide (NO), free fatty acid (FFA), tumor necrosis factor-α (TNF-α) levels were detected, the activities of serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the levels of prostacycline (PGI2), thromboxane A 2 (TXA 2 ) and endothelin (ET) in plasma were determined. Results: There were not obvious differences in MDA, SOD, GSH-Px and FFA between the acute myocardial infarction models with blood stasis in rats and the simple acute myocardial infarction models (P 2 and NO, and the increase extents of TXA 2 , ET and TNF-α in the acute myocardial infarction models in rats with blood stasis were higher than those in the simple acute myocardial infarction models (P 2 and NO, are significant when the acute myocardial infarction models in rats with blood stasis and the simple acute myocardial infarction models are compared. The results show that it is defective to evaluate pharmacodynamics of traditional Chinese drug with only simple acute myocardial infarction models. (authors)

  5. Experimental models of transfusion-related acute lung injury.

    Science.gov (United States)

    Gilliss, Brian M; Looney, Mark R

    2011-01-01

    Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approaches. Experimental models suggest that TRALI occurs when a host, with a primed immune system, is exposed to an activating agent such as anti-leukocyte antibody or a biologic response modifier such as lysophosphatidylcholines. Recent work has suggested a critical role for platelets in antibody-based experimental models and identified potential therapeutic strategies for TRALI. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Experimental Models of Transfusion-Related Acute Lung Injury (TRALI)

    Science.gov (United States)

    Gilliss, Brian M.; Looney, Mark R.

    2010-01-01

    Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we will discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approaches. Experimental models suggest that TRALI occurs when a host, with a primed immune system, is exposed to an activating agent such as anti-leukocyte antibody or a biologic response modifier such as lysophosphatidylcholines. Recent work has suggested a critical role for platelets in antibody-based experimental models and identified potential therapeutic strategies for TRALI. PMID:21134622

  7. Interaction between the immune system and acute myeloid leukemia: A model incorporating promotion of regulatory T cell expansion by leukemic cells.

    Science.gov (United States)

    Nishiyama, Yoshiaki; Saikawa, Yutaka; Nishiyama, Nobuaki

    2018-03-01

    Population dynamics of regulatory T cells (Treg) are crucial for the underlying interplay between leukemic and immune cells in progression of acute myeloid leukemia (AML). The goal of this work is to elucidate the dynamics of a model that includes Treg, which can be qualitatively assessed by accumulating clinical findings on the impact of activated immune cell infusion after selective Treg depletion. We constructed an ordinary differential equation model to describe the dynamics of three components in AML: leukemic blast cells, mature regulatory T cells (Treg), and mature effective T cells (Teff), including cytotoxic T lymphocytes. The model includes promotion of Treg expansion by leukemic blast cells, leukemic stem cell and progenitor cell targeting by Teff, and Treg-mediated Teff suppression, and exhibits two coexisting, stable steady states, corresponding to high leukemic cell load at diagnosis or relapse, and to long-term complete remission. Our model is capable of explaining the clinical findings that the survival of patients with AML after allogeneic stem cell transplantation is influenced by the duration of complete remission, and that cut-off minimal residual disease thresholds associated with a 100% relapse rate are identified in AML. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. ACUTE RESPIRATORY DISEASE AS THE DEBUT OF SYSTEMIC LUPUS ERYTHEMATOSUS

    Directory of Open Access Journals (Sweden)

    A. Yu. Ischenko

    2015-01-01

    Full Text Available Systemic lupus erythematosus — a chronic autoimmune disease that is often associated with infectious processes. The paper presents two clinical cases of systemic lupus erythematosus , debuted with acute respiratory infection.

  9. A novel two-hit rodent model of postoperative acute lung injury: priming the immune system leads to an exaggerated injury after pneumonectomy.

    Science.gov (United States)

    Evans, Robert G; Ndunge, Oscar B A; Naidu, Babu

    2013-06-01

    Postoperative acute lung injury (PALI) is a rare, poorly understood, usually fatal condition, accounting for the majority of deaths following lung resection. Its low frequency and unpredictable development make the identification of the mechanisms of injury from clinical studies alone almost impossible. Multiple validated 'two-hit models' exist for ALI secondary to other causes. We describe a novel rodent 'two-hit' model of PALI: a low-grade immune stimulus, such as sepsis, greatly aggravates the injury in the remaining lung observed following pneumonectomy. Under general anaesthesia, rats received either low-dose intratracheal lipopolysaccharide (IT-LPS) challenge (10 μg for 1 h) followed by left posterolateral thoracotomy, one-lung ventilation (OLV), pneumonectomy and 3 h of ventilation; 500 μl IT 0.9% saline followed by the same surgery or IT-LPS followed by sham surgery and ventilation. All other conditions were constant. Lung injury is heralded by neutrophil accumulation, which was determined by right lung bronchoalveolar lavage cell count. Data are presented as mean ± standard error of the mean. The T-test was used to compare normally distributed groups with correction for multiple comparisons. A dose-response curve identified the clinically relevant 'low dose' of LPS to be used in further studies. Ventilatory parameters were standardized to reflect clinical practice (volume-control, tidal volume of 6 ml/kg, positive end-expiratory pressure of 2 cmH2O, maximum airway pressure of model with retest validity. OLV and pneumonectomy alone produced a small lung injury (65.1 ± 5), as did 10 µg intratracheal LPS alone (50.7 ± 6.9). However, when OLV, pneumonectomy and 10 µg LPS were combined, an exaggerated injury occurred (161.4 ± 10.3), P = 0.007. Early results show that a two-hit model of PALI is viable and that sepsis aggravates the response to pneumonectomy. The model is now being further characterized. Once established, this model will offer the chance

  10. Systemic corticosteroid therapy for acute sinusitis

    NARCIS (Netherlands)

    Venekamp, Roderick P.; Thompson, Matthew J.; Rovers, Maroeska M.

    2015-01-01

    CLINICAL QUESTION: Are oral or parenteral corticosteroids associated with improved clinical outcomes in patients with acute sinusitis compared with placebo or nonsteroidal anti-inflammatory drugs (NSAIDs)? BOTTOM LINE: Oral corticosteroids combined with antibioticsmay be associated with modest

  11. Systemic corticosteroid therapy for acute sinusitis

    NARCIS (Netherlands)

    Venekamp, R.P.; Thompson, M.J.; Rovers, M.M.

    2015-01-01

    CLINICAL QUESTION: Are oral or parenteral corticosteroids associated with improved clinical outcomes in patients with acute sinusitis compared with placebo or nonsteroidal anti-inflammatory drugs (NSAIDs)? BOTTOM LINE: Oral corticosteroids combined with antibiotics may be associated with modest

  12. Systemic sarcoidosis complicated of acute renal failure: about 12 ...

    African Journals Online (AJOL)

    The sarcoidosis is a systemic granulomatosis affecting most frequently the lungs and the mediastinum. An acute renal failure reveals exceptionally this disease. It's a retrospective study implicating 12 cases of sarcoidosis complicated of acute renal failure. The aim of this study is to determine epidemiological, clinical, ...

  13. Developing a consensus classification system for acute renal failure

    NARCIS (Netherlands)

    Kellum, John A.; Levin, Nathan; Bouman, Catherine; Lameire, Norbert

    2002-01-01

    A biochemical definition and classification system for acute renal dysfunction is long overdue. Its absence has impeded progress in clinical and even basic research concerning a syndrome associated with mortality rates of 30 to 80%. No definition of acute renal dysfunction will be perfect, but the

  14. Quantum chemistry based quantitative structure-activity relationships for modeling the (sub)acute toxicity of substituted mononitrobenzenes in aquatic systems

    NARCIS (Netherlands)

    Zvinavashe, E.; Murk, A.J.; Vervoort, J.; Soffers, A.E.M.F.; Freidig, A.; Rietjens, I.M.C.M.

    2006-01-01

    Fifteen experimental literature data sets on the acute toxicity of substituted nitrobenzenes to algae (Scenedesmus obliquus, Chlorella pyrenoidosa, C. vulgaris), daphnids (Daphnia magna, D. carinata), fish (Cyprinus carpio, Poecilia reticulata), protozoa (Tetrahymena pyriformis), bacteria

  15. Rat Models of Ventricular Fibrillation Following Acute Myocardial Infarction

    DEFF Research Database (Denmark)

    Hundahl, Laura A.; Tfelt-Hansen, Jacob; Jespersen, Thomas

    2017-01-01

    A number of animal models have been designed in order to unravel the underlying mechanisms of acute ischemia-induced arrhythmias and to test compounds and interventions for antiarrhythmic therapy. This is important as acute myocardial infarction (AMI) continues to be the major cause of sudden car...... for ventricular arrhythmias occurring during the acute phase of AMI. It provides a description of models developed, advantages and disadvantages of rats, as well as an overview of the most important interventions investigated and the relevance for human pathophysiology....

  16. Animal Model of Acute Deep Vein Thrombosis

    International Nuclear Information System (INIS)

    Roy, Sumit; Laerum, Frode; Brosstad, Frank; Kvernebo, Knut; Sakariassen, Kjell S.

    1998-01-01

    Purpose: To develop an animal model of acute deep vein thrombosis (DVT). Methods: In part I of the study nine juvenile domestic pigs were used. Each external iliac vein was transluminally occluded with a balloon catheter. Thrombin was infused through a microcatheter in one leg according to one of the following protocols: (1) intraarterial (IA): 1250 U at 25 U/min in the common femoral artery (n= 3); (2) intravenous (IV): 5000 U in the popliteal vein at 500 U/min (n= 3), or at 100 U/min (n= 3). Saline was administered in the opposite leg. After the animals were killed, the mass of thrombus in the iliofemoral veins was measured. The pudendoepiploic (PEV), profunda femoris (PF), and popliteal veins (PV) were examined. Thrombosis in the tributaries of the superficial femoral vein (SFVt) was graded according to a three-point scale (0, +, ++). In part II of the study IV administration was further investigated in nine pigs using the following three regimens with 1000 U at 25 U/min serving as the control: (1) 1000 U at 100 U/min, (2) 250 U at 25 U/min, (3) 250 U at 6.25 U/min. Results: All animals survived. In part I median thrombus mass in the test limbs was 1.40 g as compared with 0.25 g in the controls (p= 0.01). PEV, PFV and PV were thrombosed in all limbs infused with thrombin. IV infusion was more effective in inducing thrombosis in both the parent veins (mass 1.32-1.78 g) and SVFt (++ in 4 of 6 legs), as compared with IA infusion (mass 0.0-1.16 g; SFVt ++ in 1 of 3 legs). In part II thrombus mass in axial veins ranged from 1.23 to 2.86 g, and showed no relationship with the dose of thrombin or the rate of infusion. Tributary thrombosis was less extensive with 250 U at 25 U/min than with the other regimens. Conclusion: Slow distal intravenous thrombin infusion in the hind legs of pigs combined with proximal venous occlusion induces thrombosis in the leg veins that closely resembles clinical DVT in distribution

  17. [Intelligent systems tools in the diagnosis of acute coronary syndromes: A systemic review].

    Science.gov (United States)

    Sprockel, John; Tejeda, Miguel; Yate, José; Diaztagle, Juan; González, Enrique

    2017-03-27

    Acute myocardial infarction is the leading cause of non-communicable deaths worldwide. Its diagnosis is a highly complex task, for which modelling through automated methods has been attempted. A systematic review of the literature was performed on diagnostic tests that applied intelligent systems tools in the diagnosis of acute coronary syndromes. A systematic review of the literature is presented using Medline, Embase, Scopus, IEEE/IET Electronic Library, ISI Web of Science, Latindex and LILACS databases for articles that include the diagnostic evaluation of acute coronary syndromes using intelligent systems. The review process was conducted independently by 2 reviewers, and discrepancies were resolved through the participation of a third person. The operational characteristics of the studied tools were extracted. A total of 35 references met the inclusion criteria. In 22 (62.8%) cases, neural networks were used. In five studies, the performances of several intelligent systems tools were compared. Thirteen studies sought to perform diagnoses of all acute coronary syndromes, and in 22, only infarctions were studied. In 21 cases, clinical and electrocardiographic aspects were used as input data, and in 10, only electrocardiographic data were used. Most intelligent systems use the clinical context as a reference standard. High rates of diagnostic accuracy were found with better performance using neural networks and support vector machines, compared with statistical tools of pattern recognition and decision trees. Extensive evidence was found that shows that using intelligent systems tools achieves a greater degree of accuracy than some clinical algorithms or scales and, thus, should be considered appropriate tools for supporting diagnostic decisions of acute coronary syndromes. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  18. Acute and chronic exposure to Tyrophagus putrescentiae induces allergic pulmonary response in a murine model

    OpenAIRE

    Nu?ez, Nail? Karine; da Cunha, Aline Andrea; dos Santos Dutra, Mois?s; Barbosa, Gustavo Leivas; Morassutti, Alessandra Loureiro; de Souza, Rodrigo Godinho; Vargas, Mauro Henrique Moraes; Antunes, G?ssica Luana; Silveira, Josiane Silva; da Silva, Guilherme Liberato; Pitrez, Paulo M?rcio

    2016-01-01

    Background Tyrophagus putrescentiae (Tp) is a source of aeroallergen that causes allergic diseases. Objective To describe an acute and chronic murine model of allergic asthma with Tp extract with no systemic sensitization and no use of adjuvant. Methods Mites from dust sample were cultured and a raw extract was produced. Female BALB/c mice (6-8 weeks) were challenged intranasally with Tp extract or Dulbecco's phosphate-buffered saline, for 10 consecutive days (acute protocol) or for 6 weeks (...

  19. Experimental Models of Transfusion-Related Acute Lung Injury (TRALI)

    OpenAIRE

    Gilliss, Brian M.; Looney, Mark R.

    2011-01-01

    Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we will discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approache...

  20. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

    2017-02-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central

  1. Acute irradiation injury and autonomic nervous system. 2

    International Nuclear Information System (INIS)

    Matsuu, Mutsumi; Sekine, Ichiro; Shichijo, Kazuko; Ito, Masahiro; Ikeda, Yuzi; Matsuzaki, Sumihiro; Zea-Iriate, W.-L.; Kondo, Takahito

    1996-01-01

    In order to elucidate the mechanism of occurrence of radiation sickness, whole body irradiation of various doses of X-ray was done on male spontaneously hypertensive rats (SHR) whose sympathetic nervous system is functionally activated and on their original male Wistar Kyoto rats (WKY) and the change of their body weights was examined. Further, changes of blood pressure in rats irradiated at 7.5 Gy, of norepinephrine contents in their gut as a parameter of sympathetic nervous function and of acetylcholine contents as that of parasympathetic nervous function were measured. Histopathological examinations were also performed. SHR died at smaller dose than WKY. The blood pressure as a parameter of systemic sympathetic nervous system varied greatly in SHR. Norepinephrine contents elevated rapidly and greatly in SHR after irradiation and acetylcholine contents rapidly elevated in WKY. Apoptosis was more frequently observed in the intestinal crypt of SHR. Participation of autonomic nervous system was thus shown in the appearance of acute radiation injury and sickness in SHR, which was thought to be a useful model for the investigation. (K.H.)

  2. A mathematical model of phosphorylation AKT in Acute Myeloid Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Adi, Y. A., E-mail: yudi.adi@math.uad.ac.id [Department of Mathematic Faculty of MIPA Universitas Ahmad Dahlan (Indonesia); Department of Mathematic Faculty of MIPA Universitas Gadjah Mada (Indonesia); Kusumo, F. A.; Aryati, L. [Department of Mathematic Faculty of MIPA Universitas Gadjah Mada (Indonesia); Hardianti, M. S. [Department of Internal Medicine, Faculty of Medicine, Universitas Gadjah Mada (Indonesia)

    2016-04-06

    In this paper we consider a mathematical model of PI3K/AKT signaling pathways in phosphorylation AKT. PI3K/AKT pathway is an important mediator of cytokine signaling implicated in regulation of hematopoiesis. Constitutive activation of PI3K/AKT signaling pathway has been observed in Acute Meyloid Leukemia (AML) it caused by the mutation of Fms-like Tyrosine Kinase 3 in internal tandem duplication (FLT3-ITD), the most common molecular abnormality associated with AML. Depending upon its phosphorylation status, protein interaction, substrate availability, and localization, AKT can phosphorylate or inhibite numerous substrates in its downstream pathways that promote protein synthesis, survival, proliferation, and metabolism. Firstly, we present a mass action ordinary differential equation model describing AKT double phosphorylation (AKTpp) in a system with 11 equations. Finally, under the asumtion enzyme catalyst constant and steady state equilibrium, we reduce the system in 4 equation included Michaelis Menten constant. Simulation result suggested that a high concentration of PI3K and/or a low concentration of phospatase increased AKTpp activation. This result also indicates that PI3K is a potential target theraphy in AML.

  3. A mathematical model of phosphorylation AKT in Acute Myeloid Leukemia

    Science.gov (United States)

    Adi, Y. A.; Kusumo, F. A.; Aryati, L.; Hardianti, M. S.

    2016-04-01

    In this paper we consider a mathematical model of PI3K/AKT signaling pathways in phosphorylation AKT. PI3K/AKT pathway is an important mediator of cytokine signaling implicated in regulation of hematopoiesis. Constitutive activation of PI3K/AKT signaling pathway has been observed in Acute Meyloid Leukemia (AML) it caused by the mutation of Fms-like Tyrosine Kinase 3 in internal tandem duplication (FLT3-ITD), the most common molecular abnormality associated with AML. Depending upon its phosphorylation status, protein interaction, substrate availability, and localization, AKT can phosphorylate or inhibite numerous substrates in its downstream pathways that promote protein synthesis, survival, proliferation, and metabolism. Firstly, we present a mass action ordinary differential equation model describing AKT double phosphorylation (AKTpp) in a system with 11 equations. Finally, under the asumtion enzyme catalyst constant and steady state equilibrium, we reduce the system in 4 equation included Michaelis Menten constant. Simulation result suggested that a high concentration of PI3K and/or a low concentration of phospatase increased AKTpp activation. This result also indicates that PI3K is a potential target theraphy in AML.

  4. Alvarado vs Lintula Scoring Systems in Acute Appendicitis

    African Journals Online (AJOL)

    relocation of pain, location of pain, vomiting, elevated temperature, guarding, bowel sounds and rebound tenderness).The aim of this study was therefore, to compare the accuracy of two commonly applied scoring systems in the diagnosis of acute appendicitis, namely the Alvarado scoring system and the Lintula scoring ...

  5. Acute ingestion dosimetry using the ICRP 30 gastrointestinal tract model

    International Nuclear Information System (INIS)

    Cassels, B.M.

    1987-01-01

    This paper examines the gastrointestinal (GI) tract model used for dosimetry as outlined in ICRP30, to allow quick calculations of effective dose equivalents for acute radionuclide ingestion. A computer program has been developed to emulate the GI tract model. The program and associated data files are structured so that the GI tract model parameters can be varied, while the file structure and algorithm for the GI tract model should require minimal modification to allow the same theories that apply in this model to be used for other dosimetric models

  6. Systemic inflammatory response following acute traumatic brain injury.

    Science.gov (United States)

    Lu, Jia; Goh, Samantha Jianli; Tng, Priscilla Ying Lei; Deng, Yi Yu; Ling, Eng-Ang; Moochhala, Shabbir

    2009-01-01

    The early, delayed, and systemic effects of acute traumatic brain injury (TBI) are the result of inflammatory mediators which initiate systemic inflammatory response syndrome (SIRS), subsequent complement deficits and coagulopathy. Once SIRS is triggered by acute inflammation, it can detrimentally self-propagate. Systemic inflammation causes tissue damage leading to further inflammation and damage, leaving the body in a vicious cycle of hyperinflammation. Therefore, important inflammatory mediators like interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF) alpha, are targeted in compensatory anti-inflammatory response syndrome (CARS) in an attempt to control the development of SIRS. The hypothalamus-pituitary (HPA)-axis and sympathetic nervous system (SNS) efferent limbs in CARS provide negative feedback for the production of inflammatory mediators. However, in the case of acute TBI, the activation of CARS often leads to the complication of immunosuppression which may result in multi-organ dysfunction syndrome (MODS) and mortality. In light of this, the activation of the SIRS following acute TBI does not bode well. If left uncontrolled, multiple systems will be implicated making it difficult to remedy.

  7. An integrative scoring system for survival prediction following umbilical cord blood transplantation in acute leukemia

    NARCIS (Netherlands)

    Shouval, Roni; Ruggeri, Annalisa; Labopin, Myriam; Mohty, Mohamad; Sanz, Guillermo; Michel, Gerard; Kuball, Jürgen; Chevallier, Patrice; Al-Seraihy, Amal; Milpied, Noel Jean; De Heredia, Cristina Diaz; Arcese, William; Blaise, Didier; Rocha, Vanderson; Fein, Joshua; Unger, Ron; Baron, Frederic; Bader, Peter; Gluckman, Eliane; Nagler, Arnon

    2017-01-01

    Purpose: Survival of acute leukemia (AL) patients following umbilical cord blood transplantation (UCBT) is dependent on an array of individual features. Integrative models for risk assessment are lacking. We sought to develop a scoring system for prediction of overall survival (OS) and leukemia-free

  8. A restrospective study of acute systemic poisoning of ...

    African Journals Online (AJOL)

    Paraphenylenediamine (PPD) is commonly used in several industries (dyeing furs, photochemical processes, tyre vulcanisation industries, oxidisable hair dye, etc.). Its allergic effect is well established and many studies are devoted to the subject, but PPD systemic poisoning is not understood. Several acute PPD poisoning ...

  9. R1 autonomic nervous system in acute kidney injury.

    Science.gov (United States)

    Hering, Dagmara; Winklewski, Pawel J

    2017-02-01

    Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin-angiotensin-aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti-inflammatory effects and modulation of centrally-mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti-inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre-clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented. © 2016 John Wiley & Sons Australia, Ltd.

  10. Utilization and cost of a new model of care for managing acute knee injuries: the Calgary acute knee injury clinic

    Directory of Open Access Journals (Sweden)

    Lau Breda HF

    2012-12-01

    Full Text Available Abstract Background Musculoskeletal disorders (MSDs affect a large proportion of the Canadian population and present a huge problem that continues to strain primary healthcare resources. Currently, the Canadian healthcare system depicts a clinical care pathway for MSDs that is inefficient and ineffective. Therefore, a new inter-disciplinary team-based model of care for managing acute knee injuries was developed in Calgary, Alberta, Canada: the Calgary Acute Knee Injury Clinic (C-AKIC. The goal of this paper is to evaluate and report on the appropriateness, efficiency, and effectiveness of the C-AKIC through healthcare utilization and costs associated with acute knee injuries. Methods This quasi-experimental study measured and evaluated cost and utilization associated with specific healthcare services for patients presenting with acute knee injuries. The goal was to compare patients receiving care from two clinical care pathways: the existing pathway (i.e. comparison group and a new model, the C-AKIC (i.e. experimental group. This was accomplished through the use of a Healthcare Access and Patient Satisfaction Questionnaire (HAPSQ. Results Data from 138 questionnaires were analyzed in the experimental group and 136 in the comparison group. A post-hoc analysis determined that both groups were statistically similar in socio-demographic characteristics. With respect to utilization, patients receiving care through the C-AKIC used significantly less resources. Overall, patients receiving care through the C-AKIC incurred 37% of the cost of patients with knee injuries in the comparison group and significantly incurred less costs when compared to the comparison group. The total aggregate average cost for the C-AKIC group was $2,549.59 compared to $6,954.33 for the comparison group (p Conclusions The Calgary Acute Knee Injury Clinic was able to manage and treat knee injured patients for less cost than the existing state of healthcare delivery. The

  11. Mortality Probability Model III and Simplified Acute Physiology Score II

    Science.gov (United States)

    Vasilevskis, Eduard E.; Kuzniewicz, Michael W.; Cason, Brian A.; Lane, Rondall K.; Dean, Mitzi L.; Clay, Ted; Rennie, Deborah J.; Vittinghoff, Eric; Dudley, R. Adams

    2009-01-01

    Background: To develop and compare ICU length-of-stay (LOS) risk-adjustment models using three commonly used mortality or LOS prediction models. Methods: Between 2001 and 2004, we performed a retrospective, observational study of 11,295 ICU patients from 35 hospitals in the California Intensive Care Outcomes Project. We compared the accuracy of the following three LOS models: a recalibrated acute physiology and chronic health evaluation (APACHE) IV-LOS model; and models developed using risk factors in the mortality probability model III at zero hours (MPM0) and the simplified acute physiology score (SAPS) II mortality prediction model. We evaluated models by calculating the following: (1) grouped coefficients of determination; (2) differences between observed and predicted LOS across subgroups; and (3) intraclass correlations of observed/expected LOS ratios between models. Results: The grouped coefficients of determination were APACHE IV with coefficients recalibrated to the LOS values of the study cohort (APACHE IVrecal) [R2 = 0.422], mortality probability model III at zero hours (MPM0 III) [R2 = 0.279], and simplified acute physiology score (SAPS II) [R2 = 0.008]. For each decile of predicted ICU LOS, the mean predicted LOS vs the observed LOS was significantly different (p ≤ 0.05) for three, two, and six deciles using APACHE IVrecal, MPM0 III, and SAPS II, respectively. Plots of the predicted vs the observed LOS ratios of the hospitals revealed a threefold variation in LOS among hospitals with high model correlations. Conclusions: APACHE IV and MPM0 III were more accurate than SAPS II for the prediction of ICU LOS. APACHE IV is the most accurate and best calibrated model. Although it is less accurate, MPM0 III may be a reasonable option if the data collection burden or the treatment effect bias is a consideration. PMID:19363210

  12. Computational modeling of acute myocardial infarction.

    Science.gov (United States)

    Sáez, P; Kuhl, E

    2016-01-01

    Myocardial infarction, commonly known as heart attack, is caused by reduced blood supply and damages the heart muscle because of a lack of oxygen. Myocardial infarction initiates a cascade of biochemical and mechanical events. In the early stages, cardiomyocytes death, wall thinning, collagen degradation, and ventricular dilation are the immediate consequences of myocardial infarction. In the later stages, collagenous scar formation in the infarcted zone and hypertrophy of the non-infarcted zone are auto-regulatory mechanisms to partly correct for these events. Here we propose a computational model for the short-term adaptation after myocardial infarction using the continuum theory of multiplicative growth. Our model captures the effects of cell death initiating wall thinning, and collagen degradation initiating ventricular dilation. Our simulations agree well with clinical observations in early myocardial infarction. They represent a first step toward simulating the progression of myocardial infarction with the ultimate goal to predict the propensity toward heart failure as a function of infarct intensity, location, and size.

  13. Cryo-Induced Thermal Wounds: A Human Acute Wound Model.

    Science.gov (United States)

    Vivas, Alejandra; Fox, Joshua D; Baquerizo Nole, Katherine L; Maderal, Andrea D; Badiavas, Evangelos; Cargill, D Innes; Slade, Herbert B; Feldman, Steven R; Kirsner, Robert S

    2015-07-01

    Clinical models are invaluable in studying wound healing. Challenges in studying human wounds include heterogeneity of patients and wounds, as well as prolonged study time, resulting in high costs. Animal models are an efficient method to study wound healing, but often lack correlation with human acute wound healing. Human wound models can be created using sharp instruments, suction, acids, heat and cold. In this observational study, we propose a practical human acute wound model where partial thickness wounds are induced by cryosurgery to create wounds that could facilitate wound healing research and development. On forearms of 8 healthy adult volunteers, freeze injuries were induced using liquid nitrogen spray delivered onto a target area of a 1 cm circular opening at a distance from the cryo-device to the skin of 0.5-1 cm. Several freeze-thaw time cycles were implemented by administering pulses ranging from 3 to 12 seconds. Clinical evaluation was performed at a 24-hour follow-up period. Blister roofs were histologically analyzed by a blinded dermatophathologist. Clinical assessment of time to heal was determined. Freeze-times greater than 5 seconds caused a majority of subjects to develop blisters, and freeze-times greater than 8 seconds resulted in uniform blister formation. Consistent histology of full thickness necrotic epidermis with intact detached basement membrane with minimal acute neutrophilic inflammatory infiltrate was observed in all blister specimens examined. The 8-second freeze-time group had a time to heal of 13-14 days, while the 12-second freeze-time group required 3 weeks to heal. After healing, an area of hypopigmented skin and slightly hypertrophic scarring remained. This novel cryo-induced wound model is a potential simple, efficient and reliable model for studying the dynamic processes involved in acute wound healing and to aid in the development of new wound healing therapies. Clinicaltrials.gov identifier: NCT01253135.

  14. Non-thrombogenic hemofiltration system for acute renal failure treatment.

    Science.gov (United States)

    Tong, S D; Hsu, L C

    1992-01-01

    Continuous arteriovenous hemofiltration (CAVH) has become an accepted therapy for patients with acute renal failure. A major technical concern with CAVH is clotting of the hemofilter, resulting from blood-material interactions. This study compares the thromboresistance and performance characteristics of a Duraflo II heparin treated CAVH circuit with those of an untreated control circuit. The circuit consisted of a polysulfone hemofilter, tubing sets, and catheters. The heparin treatment did not change the mass transfer properties of the hemofilter. The thromboresistance of the heparin treated circuit was compared directly with that of an untreated circuit in a heparinless sheep model using bilateral circuits. The heparin treatment significantly enhanced the blood compatibility of the circuit, as indicated by the reduction in thrombus formation, prolonged work life, and superior performance in heparinless sheep. There was minimal heparin leaching from the hemo-filter. A heparin treated circuit may improve the safety and effectiveness of the CAVH procedure, and offers potential for a systemic heparin protocol to be modified for patients with bleeding disorders.

  15. Modeling of System Families

    National Research Council Canada - National Science Library

    Feiler, Peter

    2007-01-01

    .... The Society of Automotive Engineers (SAE) Architecture Analysis & Design Language (AADL) is an industry-standard, architecture-modeling notation specifically designed to support a component- based approach to modeling embedded systems...

  16. Modelling Railway Interlocking Systems

    DEFF Research Database (Denmark)

    Lindegaard, Morten Peter; Viuf, P.; Haxthausen, Anne Elisabeth

    2000-01-01

    In this report we present a model of interlocking systems, and describe how the model may be validated by simulation. Station topologies are modelled by graphs in which the nodes denote track segments, and the edges denote connectivity for train traÆc. Points and signals are modelled by annotatio...

  17. 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

    2012-10-01

    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 

  18. Modeling the Dynamics of Acute Phase Protein Expression in Human Hepatoma Cells Stimulated by IL-6

    Directory of Open Access Journals (Sweden)

    Zhaobin Xu

    2015-01-01

    Full Text Available Interleukin-6 (IL-6 is a systemic inflammatory mediator that triggers the human body’s acute phase response to trauma or inflammation. Although mathematical models for IL-6 signaling pathways have previously been developed, reactions that describe the expression of acute phase proteins were not included. To address this deficiency, a recent model of IL-6 signaling was extended to predict the dynamics of acute phase protein expression in IL-6-stimulated HepG2 cells (a human hepatoma cell line. This included reactions that describe the regulation of haptoglobin, fibrinogen, and albumin secretion by nuclear transcription factors STAT3 dimer and C/EBPβ. This new extended model was validated against two different sets of experimental data. Using the validated model, a sensitivity analysis was performed to identify seven potential drug targets to regulate the secretion of haptoglobin, fibrinogen, and albumin. The drug-target binding kinetics for these seven targets was then integrated with the IL-6 kinetic model to rank them based upon the influence of their pairing with drugs on acute phase protein dynamics. It was found that gp80, JAK, and gp130 were the three most promising drug targets and that it was possible to reduce the therapeutic dosage by combining drugs aimed at the top three targets in a cocktail. These findings suggest hypotheses for further experimental investigation.

  19. The establishment of animal model of acute massive pulmonary embolism

    International Nuclear Information System (INIS)

    Lu Junliang; Yang Ning; Yang Jianping; Ma Junshan; Zhao Shijun

    2008-01-01

    Objective: To find a way of establishing the model of acute massive pulmonary embolism in dog. Methods: Seven dogs were selected with self-clots made outside the body transferring through a 10 F guiding catheter into the central branch of pulmonary artery via the femoral vein approach on one side and then under pressure monitor of pulmonary artery until the very branch of pulmonary artery was occluded. Blood gas and pulmonary arterial pressure were tested before and after the embolization, Pulmonary artery pressure was continuously monitored together with the examinations of angiography. The bilateral lung specimens were resected for histological examination 12 hours in average after the embolization for comparative study. Results: One animal died of cardiogenic shock after clots injection; the other one presented with tachycardia and premature ventricular beat causing partial recanalization 12 h later. The others were occluded successfully in central branch of pulmonary artery and the pulmonary arterial pressure reached above 50 mmHg after occlusion. Pathologic examination showed the formation of red and mix thrombi within the vascular lumens. Conclusions: This method for making acute massive pulmonary embolism animal model was reliable, feasible and reproducible, and could provide an animal model of acute massive pulmonary embolism for other correlative experiments. (authors)

  20. Electroacupuncture Alleviates Pain Responses and Inflammation in a Rat Model of Acute Gout Arthritis

    Directory of Open Access Journals (Sweden)

    Wenxin Chai

    2018-01-01

    Full Text Available Acute gout arthritis is one of the most painful inflammatory conditions. Treatments for gout pain are limited to colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids, which oftentimes result in severe adverse effects. Electroacupuncture (EA has been proved to be effective in relieving many inflammatory pain conditions with few side effects. Here, we aim to investigate the therapeutic potentials of EA on pain and inflammation of a rat model of acute gout arthritis and underlying mechanisms. We found that 2/100 Hz EA produced the most robust analgesic effect on mechanical hyperalgesia of acute gout arthritis rat model compared with 2 and 100 Hz. EA produced similar analgesic effect compared with indomethacin. 2/100 Hz EA also significantly alleviates the ongoing pain behavior, thermal hyperalgesia, and ankle edema. Locally applied μ and κ-opioid receptor antagonists but not adenosine A1 receptor antagonist significantly abolished the analgesic effect of EA. Locally applied μ and κ-opioid receptor agonists produced significant antiallodynia on acute gout arthritis rats, mimicking EA. Furthermore, 2/100 Hz EA upregulated β-endorphin expression in inflamed ankle skin tissue. Our results demonstrated, for the first time, that EA can be used for relieving acute gout arthritis with effect dependent on peripheral opioid system and comparable with the one obtained with indomethacin.

  1. An experimental model of hemolysis-induced acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Saruc M.

    2003-01-01

    Full Text Available The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH in 20% (v/v ethanol on the first experimental day (day 0. One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha and platelet-activating factor (PAF contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70% of 50 rats, moderate hemolysis in seven (14%, and no hemolysis in eight (16%. Thirty-three of 35 (94.2% rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8% had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.

  2. Acute metabolic decompensation due to influenza in a mouse model of ornithine transcarbamylase deficiency

    Directory of Open Access Journals (Sweden)

    Peter J. McGuire

    2014-02-01

    Full Text Available The urea cycle functions to incorporate ammonia, generated by normal metabolism, into urea. Urea cycle disorders (UCDs are caused by loss of function in any of the enzymes responsible for ureagenesis, and are characterized by life-threatening episodes of acute metabolic decompensation with hyperammonemia (HA. A prospective analysis of interim HA events in a cohort of individuals with ornithine transcarbamylase (OTC deficiency, the most common UCD, revealed that intercurrent infection was the most common precipitant of acute HA and was associated with markers of increased morbidity when compared with other precipitants. To further understand these clinical observations, we developed a model system of metabolic decompensation with HA triggered by viral infection (PR8 influenza using spf-ash mice, a model of OTC deficiency. Both wild-type (WT and spf-ash mice displayed similar cytokine profiles and lung viral titers in response to PR8 influenza infection. During infection, spf-ash mice displayed an increase in liver transaminases, suggesting a hepatic sensitivity to the inflammatory response and an altered hepatic immune response. Despite having no visible pathological changes by histology, WT and spf-ash mice had reduced CPS1 and OTC enzyme activities, and, unlike WT, spf-ash mice failed to increase ureagenesis. Depression of urea cycle function was seen in liver amino acid analysis, with reductions seen in aspartate, ornithine and arginine during infection. In conclusion, we developed a model system of acute metabolic decompensation due to infection in a mouse model of a UCD. In addition, we have identified metabolic perturbations during infection in the spf-ash mice, including a reduction of urea cycle intermediates. This model of acute metabolic decompensation with HA due to infection in UCD serves as a platform for exploring biochemical perturbations and the efficacy of treatments, and could be adapted to explore acute decompensation in other

  3. [Predictive value of pediatrics end-stage liver disease or model for end-stage liver disease score in the prognosis of pediatric acute liver failure treated with artificial liver support system].

    Science.gov (United States)

    Jinhao, Tao; Weiming, Chen; Jing, Hu; Jun, He; Jian, Ma; Peng, Shi; Zhujin, Lu; Guoping, Lu; Yimin, Zhu

    2015-04-01

    To investigate the predictive value of pediatrics end-stage liver disease (PELD) or the model for end-stage liver disease (MELD) in the prognosis of pediatric acute liver failure (PALF) treated with artificial liver support system (ALSS). The clinical data of 47 children with acute liver failure seen from August 2008 to July 2013 treated in Children's Hospital, Fudan University were analyzed. Thirty children were treated with ALSS in addition to conventional comprehensive medical treatment (ALSS group). Seventeen children were treated with only conventional comprehensive medical treatment (control group). The main biochemical parameters and coagulation function parameters before and after treatment were compared in the ALSS group and the mortality rates were compared between the two groups. The patients were graded by PELD or MELD when they were hospitalized and the relationship of PELD or MELD scores and mortalities of child patients with the receiver operating characteristic curve (ROC) were analyzed. There were significant differences in total bilirubin (TB) ((302 ± 208) vs. (161 ± 129) µmol/L); alanine aminotransferase (ALT) ((161 ± 225) vs. (761 ± 834) U/L); aspartate aminotransferase ( AST) (66 (35, 123 ) vs. 447 (184, 1,129 ) U/L) ; international normalized ratio (INR) ((2.6 ± 1.6) vs. (5.1 ± 4.0)); prothrombin time activity percentage (PTA) ((42 ± 25)% vs. (22 ± 13)%); albumin( ALB) ((35 ± 5) vs. (33 ± 6) g/L) in the ALSS group after treatment. Through the ROC curve analysis, the best PELD/MELD threshold was 25 to predict the patients survival after ALSS therapy, with a sensitivity of 92. 3% , and a specificity of 94.1% at the cutoff point. The area under the ROC curve was 0. 912. The mortality of patients with PELD or MELD score below 25 in the ALSS group (1/13) was lower than the control group (3/4) (P = 0.022), and the mortality of patients with PELD or MELD score over 25 (16/17) was higher than that of the control group (10/13) (P = 0

  4. Acute inflammatory responses of nanoparticles in an intra-tracheal instillation rat model.

    Science.gov (United States)

    Armstead, Andrea L; Minarchick, Valerie C; Porter, Dale W; Nurkiewicz, Timothy R; Li, Bingyun

    2015-01-01

    Exposure to hard metal tungsten carbide cobalt (WC-Co) "dusts" in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP) exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT) model and compared to those of CeO2 (another occupational hazard) NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat) of WC-Co or CeO2 NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation) in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO2 NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivo study illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO2; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs.

  5. Acute Inflammatory Responses of Nanoparticles in an Intra-Tracheal Instillation Rat Model

    Science.gov (United States)

    Armstead, Andrea L.; Minarchick, Valerie C.; Porter, Dale W.; Nurkiewicz, Timothy R.; Li, Bingyun

    2015-01-01

    Exposure to hard metal tungsten carbide cobalt (WC-Co) “dusts” in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP) exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT) model and compared to those of CeO2 (another occupational hazard) NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat) of WC-Co or CeO2 NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation) in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO2 NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivo study illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO2; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs. PMID:25738830

  6. Development of Toxicological Risk Assessment Models for Acute and Chronic Exposure to Pollutants

    Directory of Open Access Journals (Sweden)

    Elke S. Reichwaldt

    2016-08-01

    Full Text Available Alert level frameworks advise agencies on a sequence of monitoring and management actions, and are implemented so as to reduce the risk of the public coming into contact with hazardous substances. Their effectiveness relies on the detection of the hazard, but with many systems not receiving any regular monitoring, pollution events often go undetected. We developed toxicological risk assessment models for acute and chronic exposure to pollutants that incorporate the probabilities that the public will come into contact with undetected pollution events, to identify the level of risk a system poses in regards to the pollutant. As a proof of concept, we successfully demonstrated that the models could be applied to determine probabilities of acute and chronic illness types related to recreational activities in waterbodies containing cyanotoxins. Using the acute model, we identified lakes that present a ‘high’ risk to develop Day Away From Work illness, and lakes that present a ‘low’ or ‘medium’ risk to develop First Aid Cases when used for swimming. The developed risk models succeeded in categorising lakes according to their risk level to the public in an objective way. Modelling by how much the probability of public exposure has to decrease to lower the risks to acceptable levels will enable authorities to identify suitable control measures and monitoring strategies. We suggest broadening the application of these models to other contaminants.

  7. Effects of Erdosteine on Experimental Acute Pancreatitis Model.

    Science.gov (United States)

    Karapolat, Banu; Karapolat, Sami; Gurleyik, Emin; Yasar, Mehmet

    2017-10-01

    To create acute pancreatitis condition experimentally in rats using cerulein, and to reveal histopathological effects in pancreatic tissue with erdosteine. An experimental study. Department of General Surgery, Duzce University, Turkey, from June to October 2014. Thirty male Wistar albino rats were divided into three groups. No procedures were applied to Group 1. The rats in Group 2 and Group 3 were injected cerulein, to establish an experimental pancreatitis model and the blood amylase and lipase values were examined. The rats in Group 3 were given 10 mg/kg erdosteine. This treatment was continued for another 2 days and the rats were sacrificed. The pancreatic tissues were examined histopathologically for edema, inflammation, acinar necrosis, fat necrosis, and vacuolization. The lipase and amylase values and the histopathological examination of pancreatic tissues evidenced that the experimental acute pancreatitis model was established and edema, inflammation, acinar necrosis, fat necrosis, and vacuolization were observed in the pancreatic tissues. The statistical results suggest that erdosteine can decrease the edema, inflammation, acinar necrosis, fat necrosis and vacuolization scores in the tissues. The severity of acute pancreatitis, induced by cerulein in rats, is reduced with the use of erdosteine.

  8. RSMASS system model development

    International Nuclear Information System (INIS)

    Marshall, A.C.; Gallup, D.R.

    1998-01-01

    RSMASS system mass models have been used for more than a decade to make rapid estimates of space reactor power system masses. This paper reviews the evolution of the RSMASS models and summarizes present capabilities. RSMASS has evolved from a simple model used to make rough estimates of space reactor and shield masses to a versatile space reactor power system model. RSMASS uses unique reactor and shield models that permit rapid mass optimization calculations for a variety of space reactor power and propulsion systems. The RSMASS-D upgrade of the original model includes algorithms for the balance of the power system, a number of reactor and shield modeling improvements, and an automatic mass optimization scheme. The RSMASS-D suite of codes cover a very broad range of reactor and power conversion system options as well as propulsion and bimodal reactor systems. Reactor choices include in-core and ex-core thermionic reactors, liquid metal cooled reactors, particle bed reactors, and prismatic configuration reactors. Power conversion options include thermoelectric, thermionic, Stirling, Brayton, and Rankine approaches. Program output includes all major component masses and dimensions, efficiencies, and a description of the design parameters for a mass optimized system. In the past, RSMASS has been used as an aid to identify and select promising concepts for space power applications. The RSMASS modeling approach has been demonstrated to be a valuable tool for guiding optimization of the power system design; consequently, the model is useful during system design and development as well as during the selection process. An improved in-core thermionic reactor system model RSMASS-T is now under development. The current development of the RSMASS-T code represents the next evolutionary stage of the RSMASS models. RSMASS-T includes many modeling improvements and is planned to be more user-friendly. RSMASS-T will be released as a fully documented, certified code at the end of

  9. Acute liver failure: a critical appraisal of available animal models.

    Science.gov (United States)

    Bélanger, Mireille; Butterworth, Roger F

    2005-12-01

    The availability of adequate experimental models of acute liver failure (ALF) is of prime importance to provide a better understanding of this condition and allow the development and testing of new therapeutic approaches for patients with ALF. However, the numerous etiologies and complications of ALF contribute to the complexity of this condition and render the development of an ideal experimental model of ALF more difficult than expected. Instead, a number of different models that may be used for the study of specific aspects of ALF have been developed. The most common approaches used to induce ALFin experimental animals are surgical procedures, toxic liver injury,or a combination of both. Despite the high prevalence of viral hepatitis worldwide, very few satisfactory viral models of ALF are available. Established and newly developed models of ALF are reviewed.

  10. Systemic resilience model

    International Nuclear Information System (INIS)

    Lundberg, Jonas; Johansson, Björn JE

    2015-01-01

    It has been realized that resilience as a concept involves several contradictory definitions, both for instance resilience as agile adjustment and as robust resistance to situations. Our analysis of resilience concepts and models suggest that beyond simplistic definitions, it is possible to draw up a systemic resilience model (SyRes) that maintains these opposing characteristics without contradiction. We outline six functions in a systemic model, drawing primarily on resilience engineering, and disaster response: anticipation, monitoring, response, recovery, learning, and self-monitoring. The model consists of four areas: Event-based constraints, Functional Dependencies, Adaptive Capacity and Strategy. The paper describes dependencies between constraints, functions and strategies. We argue that models such as SyRes should be useful both for envisioning new resilience methods and metrics, as well as for engineering and evaluating resilient systems. - Highlights: • The SyRes model resolves contradictions between previous resilience definitions. • SyRes is a core model for envisioning and evaluating resilience metrics and models. • SyRes describes six functions in a systemic model. • They are anticipation, monitoring, response, recovery, learning, self-monitoring. • The model describes dependencies between constraints, functions and strategies

  11. Selected System Models

    Science.gov (United States)

    Schmidt-Eisenlohr, F.; Puñal, O.; Klagges, K.; Kirsche, M.

    Apart from the general issue of modeling the channel, the PHY and the MAC of wireless networks, there are specific modeling assumptions that are considered for different systems. In this chapter we consider three specific wireless standards and highlight modeling options for them. These are IEEE 802.11 (as example for wireless local area networks), IEEE 802.16 (as example for wireless metropolitan networks) and IEEE 802.15 (as example for body area networks). Each section on these three systems discusses also at the end a set of model implementations that are available today.

  12. Experimental model of intracranial arteriovenous shunting in the acute stage.

    Science.gov (United States)

    Numazawa, Shinichi; Sasaki, Tatsuya; Sato, Sonomi; Watanabe, Yoichi; Watanabe, Zenichiro; Kodama, Namio

    2005-06-01

    A model of intracranial arteriovenous (AV) shunting must incorporate local hypoperfusion and simulate the hemodynamics of arteriovenous malformations. In this study, the hemodynamics of an intracranial AV shunt model in the acute stage were clarified. End-to-side anastomoses with a femoral vein graft were performed between a cortical branch of the middle cerebral artery (MCA) and the superior sagittal sinus in anesthetized dogs. Local cerebral blood flow (l-CBF) was measured by laser Doppler blood flowmetry. l-CBF decreased suddenly by 34.2% when the shunt was opened in the ipsilateral MCA territory. Upon re-occlusion, l-CBF immediately equaled or exceeded the pre-opening value and returned to the pre-opening value within the next 15 minutes. Opening the shunt produced little change in l-CBF in the territory of the ipsilateral or contralateral anterior cerebral artery. The decrease in l-CBF was correlated with shunt volume only in the MCA territory. l-CBF manifested a PaCO(2)-dependent increase before shunt opening, but CO(2) reactivity was impaired after opening the shunt only in the MCA territory. This dog model features local hypoperfusion due to intracranial AV shunting and disturbance of CO(2) reactivity in the acute stage. The hemodynamics of this model will be confirmed in the chronic stage.

  13. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  14. Systemic sarcoidosis complicated of acute renal failure: about 12 cases.

    Science.gov (United States)

    Mahfoudhi, Madiha; Mamlouk, Habiba; Turki, Sami; Kheder, Adel

    2015-01-01

    The sarcoidosis is a systemic granulomatosis affecting most frequently the lungs and the mediastinum. An acute renal failure reveals exceptionally this disease. It's a retrospective study implicating 12 cases of sarcoidosis complicated of acute renal failure. The aim of this study is to determine epidemiological, clinical, biological and histological profile in these cases and then to indicate the interest to consider the diagnosis of sarcoidosis in cases of unexplained renal failure. Extra-renal complications, therapeutic modalities and the outcome were determined in all patients. Our series involved 12 women with an average age of 40 years. Biological investigations showed an abnormal normocalcemia in 7 cases, a hypercalcemia in 5 cases, a hypercalciuria in 10 cases and polyclonal hypergammaglobulinemia in 7 cases. An acute renal failure was found in all patients with a median creatinin of 520 umol/L. For all patients, the renal echography was normal however, the kidney biopsy showed tubulo-interstitial nephritis. The extra-renal signs highlighting pulmonary interstitial syndrome in 5 cases, a sicca syndrome in 4 cases, mediastinal lymph nodes in 2 cases, a lymphocytic alveolitis in 3 cases, an anterior granulomatous uveitis in 2 cases and a polyarthritis in 5 cases. Five patients benefited of hemodialysis. The treatment consisted of corticosteroid in all cases. The follow up was marked by complete resolution of clinical and biological signs. The diagnosis of renal sarcoidosis must be done quickly to prevent renal failure.

  15. Central nervous system effects in acute thallium poisoning.

    Science.gov (United States)

    Tsai, Yu-Tai; Huang, Chin-Chang; Kuo, Hung-Chou; Wang, Hsuan-Min; Shen, Wu-Shiun; Shih, Tung-Sheng; Chu, Nai-Shin

    2006-03-01

    We report the central nervous system manifestations, neuropsychological studies and brain magnetic resonance image (MRI) findings of two patients with acute thallium intoxication. Neurologically the patients suffered from confusion, disorientation, and hallucination in the acute stage, followed by anxiety, depression, lack of attention, and memory impairment, in addition to peripheral neuropathy. Neuropsychological tests revealed an impairment of memory function, including reversed digital span, memory registration, memory recall, memory recognition, similarity, proverb reasoning, and verbal fluency. High concentrations of thallium were found in the urine, blood, and drinking water of these two patients. Brain MRI showed lesions in the corpus striatum in one patient. During the follow-up periods, the clinical manifestations and neuropsychological studies showed a slowly progressive improvement, and a follow-up brain MRI 1.5 months later demonstrated a resolution of the lesions. We conclude that thallium intoxication might induce encephalopathy, and brain MRI studies demonstrated the acute-stage brain lesions in a severe intoxicated patient. In addition, neuropsychological tests also confirmed memory deficits, although the brain lesions in the corpus striatum might resolve.

  16. Paediatric community home nursing: a model of acute care.

    Science.gov (United States)

    Ng, Sze May; Mariguddi, Shyam; Coward, Shirley; Middleton, Holly

    The aim of this pilot service development was to determine if the community children's nursing outreach team(CCNOT) service, as a model of care, was effective and efficient in its delivery of reducing unscheduled care and admissions to hospital, and improving patient satisfaction. CCNOT was developed to manage acutely ill children at home and to reduce the demand for unscheduled care. This is a pilot prospective study within a dual-site integrated care organisation. The CCNOT service was developed with the aim of determining the effectiveness of the CCNOT model of care and service delivery inthe following outcomes: 1) reducing length of hospital stay (LOS)2) reducing A&E admissions 3) reducing non-elective admissions 4) reducing readmissions and 5) improving patient satisfaction. Data were obtained from hospital episode statistics (HES) and patient satisfaction questionnaires. The data indicate that, after the implementation of the CCNOT service, A&E attendances fell by 5%per month, non-elective admissions by 15.8% and readmissions by 17.3%. Overall, LOS rose by 2.3%-0.88 days compared with 0.9 days-but the difference was not significant. The results of the patient satisfaction survey show high overall satisfaction with the service. A paediatric CCNOT as a model of service delivery in acute paediatric care is effective in reducing hospital admissions. It also increases patient and carer satisfaction with care provision for sick children in the home environment.

  17. Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury.

    Science.gov (United States)

    Ritter, Anne C; Wagner, Amy K; Szaflarski, Jerzy P; Brooks, Maria M; Zafonte, Ross D; Pugh, Mary Jo V; Fabio, Anthony; Hammond, Flora M; Dreer, Laura E; Bushnik, Tamara; Walker, William C; Brown, Allen W; Johnson-Greene, Doug; Shea, Timothy; Krellman, Jason W; Rosenthal, Joseph A

    2016-09-01

    Posttraumatic seizures (PTS) are well-recognized acute and chronic complications of traumatic brain injury (TBI). Risk factors have been identified, but considerable variability in who develops PTS remains. Existing PTS prognostic models are not widely adopted for clinical use and do not reflect current trends in injury, diagnosis, or care. We aimed to develop and internally validate preliminary prognostic regression models to predict PTS during acute care hospitalization, and at year 1 and year 2 postinjury. Prognostic models predicting PTS during acute care hospitalization and year 1 and year 2 post-injury were developed using a recent (2011-2014) cohort from the TBI Model Systems National Database. Potential PTS predictors were selected based on previous literature and biologic plausibility. Bivariable logistic regression identified variables with a p-value load, and pre-injury limitation in learning/remembering/concentrating as significant PTS predictors during acute hospitalization. Significant predictors of PTS at year 1 were subdural hematoma (SDH), contusion load, craniotomy, craniectomy, seizure during acute hospitalization, duration of posttraumatic amnesia, preinjury mental health treatment/psychiatric hospitalization, and preinjury incarceration. Year 2 significant predictors were similar to those of year 1: SDH, intraparenchymal fragment, craniotomy, craniectomy, seizure during acute hospitalization, and preinjury incarceration. Corrected concordance (C) statistics were 0.599, 0.747, and 0.716 for acute hospitalization, year 1, and year 2 models, respectively. The prognostic model for PTS during acute hospitalization did not discriminate well. Year 1 and year 2 models showed fair to good predictive validity for PTS. Cranial surgery, although medically necessary, requires ongoing research regarding potential benefits of increased monitoring for signs of epileptogenesis, PTS prophylaxis, and/or rehabilitation/social support. Future studies should

  18. Modelling of wastewater systems

    DEFF Research Database (Denmark)

    Bechmann, Henrik

    Oxygen Demand) flux and SS flux in the inlet to the WWTP. COD is measured by means of a UV absorption sensor while SS is measured by a turbidity sensor. These models include a description of the deposit of COD and SS amounts, respectively, in the sewer system, and the models can thus be used to quantify......In this thesis, models of pollution fluxes in the inlet to 2 Danish wastewater treatment plants (WWTPs) as well as of suspended solids (SS) concentrations in the aeration tanks of an alternating WWTP and in the effluent from the aeration tanks are developed. The latter model is furthermore used...... to analyze and quantify the effect of the Aeration Tank Settling (ATS) operating mode, which is used during rain events. Furthermore, the model is used to propose a control algorithm for the phase lengths during ATS operation. The models are mainly formulated as state space model in continuous time...

  19. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

    DEFF Research Database (Denmark)

    Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.

    2015-01-01

    Background: In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS...... expressions in blood leukocytes during equine acute LPS-induced systemic inflammation thoroughly characterized a highly regulated and dynamic innate immune response. These results provide new insights into the molecular mechanisms of equine systemic inflammation.......) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...

  20. Manipulation of nitric oxide in an animal model of acute liver injury ...

    African Journals Online (AJOL)

    We evaluated the impact of altering nitric oxide release on acute liver injury, the associated gut injury and bacterial translocation, at different time intervals. Methods: An acute rat liver injury model induced by D-galactosamine was used. Sprague Dawley rats were divided into four main groups: normal control, acute liver ...

  1. Predictive models for acute kidney injury following cardiac surgery.

    Science.gov (United States)

    Demirjian, Sevag; Schold, Jesse D; Navia, Jose; Mastracci, Tara M; Paganini, Emil P; Yared, Jean-Pierre; Bashour, Charles A

    2012-03-01

    Accurate prediction of cardiac surgery-associated acute kidney injury (AKI) would improve clinical decision making and facilitate timely diagnosis and treatment. The aim of the study was to develop predictive models for cardiac surgery-associated AKI using presurgical and combined pre- and intrasurgical variables. Prospective observational cohort. 25,898 patients who underwent cardiac surgery at Cleveland Clinic in 2000-2008. Presurgical and combined pre- and intrasurgical variables were used to develop predictive models. Dialysis therapy and a composite of doubling of serum creatinine level or dialysis therapy within 2 weeks (or discharge if sooner) after cardiac surgery. Incidences of dialysis therapy and the composite of doubling of serum creatinine level or dialysis therapy were 1.7% and 4.3%, respectively. Kidney function parameters were strong independent predictors in all 4 models. Surgical complexity reflected by type and history of previous cardiac surgery were robust predictors in models based on presurgical variables. However, the inclusion of intrasurgical variables accounted for all explained variance by procedure-related information. Models predictive of dialysis therapy showed good calibration and superb discrimination; a combined (pre- and intrasurgical) model performed better than the presurgical model alone (C statistics, 0.910 and 0.875, respectively). Models predictive of the composite end point also had excellent discrimination with both presurgical and combined (pre- and intrasurgical) variables (C statistics, 0.797 and 0.825, respectively). However, the presurgical model predictive of the composite end point showed suboptimal calibration (P predictive models in other cohorts is required before wide-scale application. We developed and internally validated 4 new models that accurately predict cardiac surgery-associated AKI. These models are based on readily available clinical information and can be used for patient counseling, clinical

  2. [Discussion of Chinese syndrome typing in acute hepatic failure model].

    Science.gov (United States)

    Zhang, Jin-liang; Zeng, Hui; Wang, Xian-bo

    2011-05-01

    To study Chinese syndrome typing of acute hepatic failure (AHF) mice model by screening effective formulae. Lipoplysaccharides (LPS)/D-galactosamine (D-GaIN) was intraperitoneally injected to mice to establish the AHF mice model. Yinchenhao Decoction, Huanglian Jiedu Decoction, Buzhong Yiqi Decoction, and Xijiao Dihuang Decoction were administered to model mice respectively by gastrogavage. The behavior and the survival rate were monitored. The liver function and pathological changes of liver tissues were detected. In all the tested classic recipes, the survival rate was elevated from 10% to 60% by administration of Xijiao Dihuang Decoction. Five h after modeling, the serum alanine aminotransferase (ALT) level was (183.95 +/- 52.00) U/L, and aspartate aminotransferase (AST) (235.70 +/- 34.03) U/L in Xijiao Di-huang Decoction Group, lower than those of the model control group, but with insignificant difference (ALT: 213.32 +/- 71.93 U/L; AST: 299.48 +/- 70.56 U/L, both P > 0.05). Xijiao Dihuang Decoction could obviously alleviate the liver injury. Xijiao Dihuang Decoction was an effective formula for LPS/D-GaIN induced AHF model. According to syndrome typing through formula effect, heat toxin and blood stasis syndrome dominated in the LPS/D-GalN induced AHF mice model.

  3. Modeling Complex Systems

    CERN Document Server

    Boccara, Nino

    2010-01-01

    Modeling Complex Systems, 2nd Edition, explores the process of modeling complex systems, providing examples from such diverse fields as ecology, epidemiology, sociology, seismology, and economics. It illustrates how models of complex systems are built and provides indispensable mathematical tools for studying their dynamics. This vital introductory text is useful for advanced undergraduate students in various scientific disciplines, and serves as an important reference book for graduate students and young researchers. This enhanced second edition includes: . -recent research results and bibliographic references -extra footnotes which provide biographical information on cited scientists who have made significant contributions to the field -new and improved worked-out examples to aid a student’s comprehension of the content -exercises to challenge the reader and complement the material Nino Boccara is also the author of Essentials of Mathematica: With Applications to Mathematics and Physics (Springer, 2007).

  4. Modeling Complex Systems

    International Nuclear Information System (INIS)

    Schreckenberg, M

    2004-01-01

    This book by Nino Boccara presents a compilation of model systems commonly termed as 'complex'. It starts with a definition of the systems under consideration and how to build up a model to describe the complex dynamics. The subsequent chapters are devoted to various categories of mean-field type models (differential and recurrence equations, chaos) and of agent-based models (cellular automata, networks and power-law distributions). Each chapter is supplemented by a number of exercises and their solutions. The table of contents looks a little arbitrary but the author took the most prominent model systems investigated over the years (and up until now there has been no unified theory covering the various aspects of complex dynamics). The model systems are explained by looking at a number of applications in various fields. The book is written as a textbook for interested students as well as serving as a comprehensive reference for experts. It is an ideal source for topics to be presented in a lecture on dynamics of complex systems. This is the first book on this 'wide' topic and I have long awaited such a book (in fact I planned to write it myself but this is much better than I could ever have written it!). Only section 6 on cellular automata is a little too limited to the author's point of view and one would have expected more about the famous Domany-Kinzel model (and more accurate citation!). In my opinion this is one of the best textbooks published during the last decade and even experts can learn a lot from it. Hopefully there will be an actualization after, say, five years since this field is growing so quickly. The price is too high for students but this, unfortunately, is the normal case today. Nevertheless I think it will be a great success! (book review)

  5. Pharmacological characterisation of anti-inflammatory compounds in acute and chronic mouse models of cigarette smoke-induced inflammation

    Directory of Open Access Journals (Sweden)

    Mok Joanie

    2010-09-01

    Full Text Available Abstract Background Candidate compounds being developed to treat chronic obstructive pulmonary disease are typically assessed using either acute or chronic mouse smoking models; however, in both systems compounds have almost always been administered prophylactically. Our aim was to determine whether the prophylactic effects of reference anti-inflammatory compounds in acute mouse smoking models reflected their therapeutic effects in (more clinically relevant chronic systems. Methods To do this, we started by examining the type of inflammatory cell infiltrate which occurred after acute (3 days or chronic (12 weeks cigarette smoke exposure (CSE using female, C57BL/6 mice (n = 7-10. To compare the effects of anti-inflammatory compounds in these models, mice were exposed to either 3 days of CSE concomitant with compound dosing or 14 weeks of CSE with dosing beginning after week 12. Budesonide (1 mg kg-1; i.n., q.d., roflumilast (3 mg kg-1; p.o., q.d. and fluvastatin (2 mg kg-1; p.o., b.i.d. were dosed 1 h before (and 5 h after for fluvastatin CSE. These dose levels were selected because they have previously been shown to be efficacious in mouse models of lung inflammation. Bronchoalveolar lavage fluid (BALF leukocyte number was the primary endpoint in both models as this is also a primary endpoint in early clinical studies. Results To start, we confirmed that the inflammatory phenotypes were different after acute (3 days versus chronic (12 weeks CSE. The inflammation in the acute systems was predominantly neutrophilic, while in the more chronic CSE systems BALF neutrophils (PMNs, macrophage and lymphocyte numbers were all increased (p Conclusions These results demonstrate that the acute, prophylactic systems can be used to identify compounds with therapeutic potential, but may not predict a compound's efficacy in chronic smoke exposure models.

  6. Modeling the earth system

    Energy Technology Data Exchange (ETDEWEB)

    Ojima, D. [ed.

    1992-12-31

    The 1990 Global Change Institute (GCI) on Earth System Modeling is the third of a series organized by the Office for Interdisciplinary Earth Studies to look in depth at particular issues critical to developing a better understanding of the earth system. The 1990 GCI on Earth System Modeling was organized around three themes: defining critical gaps in the knowledge of the earth system, developing simplified working models, and validating comprehensive system models. This book is divided into three sections that reflect these themes. Each section begins with a set of background papers offering a brief tutorial on the subject, followed by working group reports developed during the institute. These reports summarize the joint ideas and recommendations of the participants and bring to bear the interdisciplinary perspective that imbued the institute. Since the conclusion of the 1990 Global Change Institute, research programs, nationally and internationally, have moved forward to implement a number of the recommendations made at the institute, and many of the participants have maintained collegial interactions to develop research projects addressing the needs identified during the two weeks in Snowmass.

  7. Topical vs. systemic treatments for acute otitis media.

    Science.gov (United States)

    Thornton, Kathy; Parrish, Francie; Swords, Christine

    2011-01-01

    Acute otitis media (AOM) is a common condition in children that is often treated with systemic antibiotic therapy; however, research suggests that non-complicated AOM will resolve spontaneously using only eardrops. To determine best practice for the use of systematic antibiotics compared to topical treatment of AOM, a systematic review of evidence was conducted. Cochrane, Medline, CINAHL, and other databases were searched. Inclusion criteria were studies published from 1995-2010 that included children with AOM and were randomized controlled trials (RCTs). Five systematic reviews and five RCTs were included in the review. Current evidence recommends using topical and other alternative approaches for treating non-complicated AOM in children 2 years of age or older; however, many practitioners are not currently following these recommendations for various reasons. Additional research to address these reasons may help determine how to improve practitioner adherence to best practice evidence and guidelines to help reduce the unnecessary use of systemic antibiotics.

  8. Novel assessment of haemodynamic kinetics with acute exercise in a rat model of pulmonary arterial hypertension.

    Science.gov (United States)

    Brown, Mary Beth; Chingombe, Tsungai J; Zinn, Abigail B; Reddy, Jagadeshwar G; Novack, Rachel A; Cooney, Sean A; Fisher, Amanda J; Presson, Robert G; Lahm, Tim; Petrache, Irina

    2015-06-01

    What is the central question of this study? The acute effect of exercise at moderately high intensity on already-elevated pulmonary arterial pressures and right ventricular wall stress in a rat model of pulmonary arterial hypertension (PAH) is unknown. What is the main finding and its importance? We show, for the first time, that in a rat model of PAH, exercise induces an acute reduction in pulmonary artery pressure associated with lung endothelial nitric oxide synthase activation, without evidence of acute right ventricular inflammation or myocyte apoptosis. Haemodynamic measures obtained with traditional invasive methodology as well as novel implantable telemetry reveal an exercise-induced 'window' of pulmonary hypertension alleviation, supporting future investigations of individualized exercise as therapy in PAH. Exercise improves outcomes of multiple chronic conditions, but controversial results, including increased pulmonary artery (PA) pressure, have prevented its routine implementation in pulmonary arterial hypertension (PAH), an incurable disease that drastically reduces exercise tolerance. Individualized, optimized exercise prescription for PAH requires a better understanding of disease-specific exercise responses. We investigated the acute impact of exercise on already-elevated PA pressure and right ventricular (RV) wall stress and inflammation in a rat model of PAH (PAH group, n = 12) induced once by monocrotaline (50 mg kg(-1) , i.p.; 2 weeks), compared with healthy control animals (n = 8). Single bouts of exercise consisted of a 45 min treadmill run at 75% of individually determined aerobic capacity (V̇O2max). Immediately after exercise, measurements of RV systolic pressure and systemic pressure were made via jugular and carotid cannulation, and were followed by tissue collection. Monocrotaline induced moderate PAH, evidenced by RV hypertrophy, decreased V̇O2max, PA muscularization, and RV and skeletal muscle cytoplasmic glycolysis detected by

  9. Information Systems Efficiency Model

    Directory of Open Access Journals (Sweden)

    Milos Koch

    2017-07-01

    Full Text Available This contribution discusses the basic concept of creating a new model for the efficiency and effectiveness assessment of company information systems. The present trends in this field are taken into account, and the attributes are retained of measuring the optimal solutions for a company’s ICT (the implementation, functionality, service, innovations, safety, relationships, costs, etc.. The proposal of a new model of assessment comes from our experience with formerly implemented and employed methods, methods which we have modified in time and adapted to companies’ needs but also to the necessaries of our research that has been done through the ZEFIS portal. The most noteworthy of them is the HOS method that we have discussed in a number of forums. Its main feature is the fact that it respects the complexity of an information system in correlation with the balanced state of its individual parts.

  10. Hepatic perfusion changes in an experimental model of acute pancreatitis: Evaluation by perfusion CT

    Energy Technology Data Exchange (ETDEWEB)

    Tutcu, Semra [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey); Serter, Selim, E-mail: serterselim@gmail.co [Department of Radiology, Celal Bayar University, School of Medicine, Manisa (Turkey); Kaya, Yavuz; Kara, Eray [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey); Nese, Nalan [Department of Pathology, Celal Bayar University, School of Medicine, Manisa (Turkey); Pekindil, Goekhan [Department of Radiology, Celal Bayar University, School of Medicine, Manisa (Turkey); Coskun, Teoman [Department of Surgery, Celal Bayar University, School of Medicine, Manisa (Turkey)

    2010-08-15

    Purpose: It is known that acute pancreatitis may cause secondary changes in several organs. Liver is one of these involved organs. In different experimental studies hepatic damages were shown histopathologically in acute pancreatitis but there are a few studies about perfusion disorders that accompany these histopathologic changes. Perfusion CT (pCT) provides the ability to detect regional and global alterations in organ blood flow. The purpose of the study was to describe hepatic perfusion changes in experimental acute pancreatitis model with pCT. Materials and methods: Forty Sprague-Dawley rats of both genders with average weights of 250 g were used. Rats were randomized into two groups. Twenty rats were in control group and 20 in acute pancreatitis group. pCT was performed. Perfusion maps were formed by processing the obtained images with perfusion CT software. Blood flow (BF) and blood volume (BV) values were obtained from these maps. All pancreatic and liver tissues were taken off with laparotomy and histopathologic investigation was performed. Student's t test was used for statistical analyses. Results: In pCT we found statistically significant increase in blood volume in both lobes of liver and in blood flow in right lobe of the liver (p < 0.01). Although blood flow in left lobe of the liver increased, it did not reach statistical significance. Conclusion: The quantitative analysis of liver parenchyma with pCT showed that acute pancreatitis causes a significant perfusion changes in the hepatic tissue. Systemic mediators seem to be effective as well as local inflammatory changes in perfusion changes.

  11. Acute injury in the peripheral nervous system triggers an alternative macrophage response

    Directory of Open Access Journals (Sweden)

    Ydens Elke

    2012-07-01

    Full Text Available Abstract Background The activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective. Methods To determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative using real-time quantitative polymerase chain reaction (RT-qPCR, western blot, and immunohistochemistry. Results Our results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFNγ, and IL12p40, and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2. The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response. Conclusions We here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the

  12. Effect of peripheral morphine in a human model of acute inflammatory pain

    DEFF Research Database (Denmark)

    Lillesø, J; Hammer, N A; Pedersen, J L

    2000-01-01

    Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

  13. Novel swine model of transfusion-related acute lung injury.

    Science.gov (United States)

    Okazaki, Hitoshi; Ishikawa, Osamu; Iijima, Takehiko; Kohira, Takahiro; Teranishi, Mai; Kawasaki, Shin; Saito, Akira; Mikami, Yu; Sugiura, Asuka; Hashimoto, Shiho; Shimada, Eiko; Uchikawa, Makoto; Matsuhashi, Mika; Tsuno, Nelson H; Tanaka, Minoru; Kiyokawa, Nobutaka; Fujimoto, Junichiro; Nagase, Takahide; Tadokoro, Kenji; Takahashi, Koki

    2014-12-01

    Transfusion-related acute lung injury (TRALI) is a life-threatening complication of blood transfusion. Antibodies against human leukocyte antigens in donors' plasma are the major causes of TRALI. Several animal models of TRALI have been developed, and the mechanism underlying TRALI development has been extensively investigated using rodent models. Although sheep models of nonimmune TRALI have been developed, large-animal models of antibody-mediated TRALI are not yet available. To develop a swine model of TRALI, male Clawn strain miniature pigs were used. A monoclonal antibody (MoAb) against swine leukocyte antigens (SLAs) Class I (4G8, 0.3 or 1.0 mg/kg body weight [BW]) and a control antibody (1.0 mg/kg BW) were injected into the peripheral vein after priming with or without 1 μg/kg BW lipopolysaccharide (LPS; n = 3 each). Lung injury was assessed using PaO2 /FiO2 (P/F) ratio and by chest X-ray imaging. Histopathologic analysis was also conducted. Lung injury could be induced by injecting 4G8 at an amount of 1.0 mg/kg BW, after LPS. The P/F ratio 90 minutes after the administration of 4G8 significantly decreased (p Lung injury was confirmed by histopathologic analysis. Lung injury in pigs was successfully induced by anti-SLA MoAb. Priming with LPS is a prerequisite for inducing lung injury and the amount of the antibody is a critical condition. © 2014 AABB.

  14. Bilateral acute iris transillumination following systemic administration of antibiotics.

    Science.gov (United States)

    Tranos, Paris; Lokovitis, Evangelos; Masselos, Stelios; Kozeis, Nikolaos; Triantafylla, Magda; Markomichelakis, Nikolaos

    2018-03-02

    To describe the demographic characteristics, clinical features, and potential prognostic factors of bilateral acute iris transillumination (BAIT) following oral antibiotic uptake. A retrospective study of 16 consecutive patients who developed BAIT following treatment with systemic antibiotics. Detailed past medical and ocular history was obtained, presenting signs and symptoms were documented and demographic characteristics were analyzed. All patients underwent a complete ocular examination and laboratory investigation. The course of best corrected visual acuity (BCVA), anterior chamber activity, and intraocular pressure (IOP) during the follow-up period were recorded and possible correlations with potential prognosticators were investigated. Fourteen females and two males were included in the present study. The mean age (SD) of the patients was 43 (14) years. All individuals presented conjunctival injection and photophobia and developed bilateral transillumination defects, fixed mid-dilated pupils and pigment dispersion in the anterior chamber. Systemic antibiotics were previously prescribed in all cases (13 patients with moxifloxacin and three patients with clarithromycin) and the mean (SD) interval between onset of symptoms and antibiotic administration was 17 (4) days. Ocular hypertension complicated all eyes and required antiglaucoma medication in 25 eyes. Severe anterior chamber pigment dispersion and higher IOP during the first week after presentation was significantly associated with longer duration of ocular hypertension (OHT) (p = 0.019). BAIT represents a rare clinical entity with characteristic features. Although etiopathogenesis of this condition remains unclear, a series of cases that indicate a strong correlation between systemic antibiotic administration and BAIT is herein presented.

  15. Enhancing systems to improve the management of acute, unscheduled care.

    Science.gov (United States)

    Braithwaite, Sabina A; Pines, Jesse M; Asplin, Brent R; Epstein, Stephen K

    2011-06-01

    For acutely ill patients, health care services are available in many different settings, including hospital-based emergency departments (EDs), retail clinics, federally qualified health centers, and outpatient clinics. Certain conditions are the sole domain of particular settings: stabilization of critically ill patients can typically only be provided in EDs. By contrast, many conditions that do not require hospital resources, such as advanced radiography, admission, and same-day consultation can often be managed in clinic settings. Because clinics are generally not open nights, and often not on weekends or holidays, the ED remains the only option for face-to-face medical care during these times. For patients who can be managed in either setting, there are many open research questions about which is the best setting, because these venues differ in terms of access, costs of care, and potentially, quality. Consideration of these patients must be risk-adjusted, as patients may self-select a venue for care based upon perceived acuity. We present a research agenda for acute, unscheduled care in the United States developed in conjunction with an Agency for Healthcare Research and Quality-funded conference hosted by the American College of Emergency Physicians in October 2009, titled "Improving the Quality and Efficiency of Emergency Care Across the Continuum: A Systems Approach." Given the possible increase in ED utilization over the next several years as more people become insured, understanding differences in cost, quality, and access for conditions that may be treated in EDs or clinic settings will be vital in guiding national health policy. © 2011 by the Society for Academic Emergency Medicine.

  16. Azithromycin reduces inflammation in a rat model of acute conjunctivitis

    Science.gov (United States)

    Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduña, Maite; García-García, Laura; Zarranz-Ventura, Javier; García-Layana, Alfredo

    2013-01-01

    Purpose Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Methods Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Results Azithromycin-treated animals showed a significant reduction in all clinical signs (pazithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (pazithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis. PMID:23378729

  17. Increased risk of acute myocardial infarction in systemic sclerosis: a nationwide population-based study.

    Science.gov (United States)

    Chu, Szu-Ying; Chen, Yi-Ju; Liu, Chia-Jen; Tseng, Wei-Cheng; Lin, Ming-Wei; Hwang, Chian-Yaw; Chen, Chih-Chiang; Lee, Ding-Dar; Chen, Tzeng-Ji; Chang, Yun-Ting; Wang, Wen-Jen; Liu, Han-Nan

    2013-11-01

    Systemic sclerosis is a life-threatening autoimmune disease characterized by vasculopathy, which results in myocardial involvement in an extremely high percentage of patients. Nevertheless, there have been no large-scale epidemiological studies about the risk of acute myocardial infarction in patients with systemic sclerosis. The aims of this study were to evaluate the hazard ratio (HR) and risk factors of acute myocardial infarction in patients with systemic sclerosis, as well as to compare the risks of acute myocardial infarction among systemic sclerosis patients taking different immunosuppressors. The study cohort included 1344 patients with systemic sclerosis and 13,440 (1:10) age-, sex-, and comorbidity-matched controls during the period between 1997 and 2006, from the National Health Insurance Research Database. We compared the risk of acute myocardial infarction between patients with systemic sclerosis and controls and calculated the adjusted HRs for acute myocardial infarction in systemic sclerosis patients taking immunosuppressors and not taking immunosuppressors. The incidence rates of acute myocardial infarction were 535 and 313 cases per 100,000 person-years for systemic sclerosis cohort and reference cohort, respectively (P systemic sclerosis was found to be an independent risk factor for acute myocardial infarction (HR 2.45). Other risk factors included hypertension (HR 2.08) and diabetes (HR 2.14). The multivariate adjusted HR for acute myocardial infarction did not decrease among the systemic sclerosis patients taking systemic steroids, penicillamine, cyclophosphamide, azathioprine, methotrexate, or cyclosporine. Systemic sclerosis is independently associated with an increased risk of acute myocardial infarction. Immunosuppressors do not lower the risk of acute myocardial infarction in our study. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Alternative approaches for identifying acute systemic toxicity : Moving from research to regulatory testing

    NARCIS (Netherlands)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, B; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for

  19. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Bañares, Rafael; Nevens, Frederik; Larsen, Fin Stolze

    2013-01-01

    Acute-on-chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189...... sessions were scheduled. The main endpoint was 28-day ITT and PP survival. There were no significant differences at inclusion, although the proportion of patients with Model for Endstage Liver Disease (MELD) score over 20 points and with spontaneous bacterial peritonitis (SBP) as a precipitating event...

  20. The role of the immune system in central nervous system plasticity after acute injury.

    Science.gov (United States)

    Peruzzotti-Jametti, Luca; Donegá, Matteo; Giusto, Elena; Mallucci, Giulia; Marchetti, Bianca; Pluchino, Stefano

    2014-12-26

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Risk of viral acute gastrointestinal illness from non-disinfected drinking water distribution systems

    Science.gov (United States)

    Acute gastrointestinal illness (AGI) resulting from pathogens directly entering the piping of drinking water distribution systems is insufficiently understood. Here, we estimate AGI incidence attributable to virus intrusions into non-disinfecting municipal distribution systems. Viruses were enumerat...

  2. Systemic corticosteroids for acute otitis media in children.

    Science.gov (United States)

    Ranakusuma, Respati W; Pitoyo, Yupitri; Safitri, Eka D; Thorning, Sarah; Beller, Elaine M; Sastroasmoro, Sudigdo; Del Mar, Chris B

    2018-03-15

    Acute otitis media (AOM) is a common acute infection in children. Pain is its most prominent and distressing symptom. Antibiotics are commonly prescribed for AOM, although they have only a modest effect in reducing pain at two to three days. There is insufficient evidence for benefits of other treatment options, including systemic corticosteroids. However, systemic corticosteroids are potent anti-inflammatory drugs, and so theoretically could be effective, either alone or as an addition to antibiotics. To assess the effects of systemic corticosteroids (oral or parenteral), with or without antibiotics, for AOM in children. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane ARI Group's Specialised Register, MEDLINE (Ovid), Embase (Elsevier), CINAHL (EBSCO), Web of Science (Thomson Reuters), and LILACS (BIREME) for published studies, and ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for completed and ongoing studies, to 20 February 2018. We checked the reference lists of all primary studies and review articles for additional references and contacted experts in the field to identify additional unpublished materials. We included randomised controlled trials of children with AOM that compared any systemic corticosteroid (oral or parenteral) with placebo, either with antibiotics (corticosteroid plus antibiotic versus placebo plus antibiotic) or without antibiotics (corticosteroid versus placebo). Three review authors (EDS, RR, YP) independently screened the titles and abstracts and retrieved the full texts of potentially relevant studies. We independently extracted study characteristics and outcome data from the included studies, and assessed the risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed study quality using the GRADE method. We included two studies involving 252

  3. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Seong Ho, E-mail: yoosh@snu.ac.kr [Seoul National University Hospital, Biomedical Research Institute and Institute of Forensic Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Abdelmegeed, Mohamed A. [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States); Song, Byoung-Joon, E-mail: bj.song@nih.gov [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)

    2013-07-05

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI.

  4. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    International Nuclear Information System (INIS)

    Yoo, Seong Ho; Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2013-01-01

    Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI

  5. Defining nervous system susceptibility during acute and latent herpes simplex virus-1 infection.

    Science.gov (United States)

    Menendez, Chandra M; Carr, Daniel J J

    2017-07-15

    Herpes simplex viruses are neurotropic human pathogens that infect and establish latency in peripheral sensory neurons of the host. Herpes Simplex Virus-1 (HSV-1) readily infects the facial mucosa that can result in the establishment of a latent infection in the sensory neurons of the trigeminal ganglia (TG). From latency, HSV-1 can reactivate and cause peripheral pathology following anterograde trafficking from sensory neurons. Under rare circumstances, HSV-1 can migrate into the central nervous system (CNS) and cause Herpes Simplex Encephalitis (HSE), a devastating disease of the CNS. It is unclear whether HSE is the result of viral reactivation within the TG, from direct primary infection of the olfactory mucosa, or from other infected CNS neurons. Areas of the brain that are susceptible to HSV-1 during acute infection are ill-defined. Furthermore, whether the CNS is a true reservoir of viral latency following clearance of virus during acute infection is unknown. In this context, this review will identify sites within the brain that are susceptible to acute infection and harbor latent virus. In addition, we will also address findings of HSV-1 lytic gene expression during latency and comment on the pathophysiological consequences HSV-1 infection may have on long-term neurologic performance in animal models and humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    OpenAIRE

    Li, Minmin; Lu, Chengwen; Zhang, Leiming; Zhang, Jianqiao; Du, Yuan; Duan, Sijin; Wang, Tian; Fu, Fenghua

    2015-01-01

    The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2) and cyclo...

  7. Development of an Animal Model of Thoracolumbar Burst Fracture-Induced Acute Spinal Cord Injury

    Science.gov (United States)

    2016-07-01

    spinal cord impactor and sustained balloon compression. 2. Keywords Spinal cord injury, spine trauma , burst fracture, large animal model 3...AWARD NUMBER: W81XWH-14-2-0013 TITLE: DEVELOPMENT OF AN ANIMAL MODEL OF THORACOLUMBAR BURST FRACTURE-INDUCED ACUTE SPINAL CORD INJURY...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER DEVELOPMENT OF AN ANIMAL MODEL OF THORACOLUMBAR BURST FRACTURE-INDUCED ACUTE SPINAL CORD INJURY 5b. GRANT

  8. Linear and nonlinear heart-rate analysis in a rat model of acute anoxia

    International Nuclear Information System (INIS)

    Gonçalves, Hernâni; Rocha, Ana Paula; Henriques-Coelho, Tiago; Nogueira, Ana; Leite-Moreira, Adelino; Bernardes, João

    2008-01-01

    The objective of this study was the assessment of heart-rate (HR) dynamics with linear and nonlinear methods during episodes of mechanical ventilation and acute anoxia in rats. Namely, to assess whether linear and nonlinear HR analysis was able to discriminate acute anoxia from baseline in rats and if this was consistent with human foetal and adult studies. Five HR segments of 1 min duration, during baseline recording, mechanical ventilation and first, second and third minutes of induced acute anoxia, were analysed in ten adult Wistar rats. Linear time and frequency domain and nonlinear methods were used, namely mean HR (mHR), long-term irregularity (LTI), interval index (II), low frequency (LF) and high frequency (HF), approximate entropy (ApEn) and sample entropy (SampEn). New parameters for the entropy indices are proposed for the analysis of rats' HR. Bootstrap percentile confidence intervals and nonparametric statistical tests were used in the evaluation of the differences between segments. During mechanical ventilation a clear spectral band was detectable at the ventilation rate, but mHR, II and the 'new' entropy indices were the only significantly changed indices. In the transition from baseline–mechanical-ventilation to mechanical-ventilation–induced anoxia, a statistically significant decrease of mHR, II and entropy indices was observed, clearly discriminating these two instances, whereas most linear indices increased. With continued anoxia, most linear indices decreased significantly, whereas entropy remained stably low. These results are consistent with other foetal human and non-human studies and evidence that the rat model may be used for further research on linear and nonlinear analysis of heart-rate dynamics. The transition from baseline to acute anoxia was encompassed by signs of increased activation of the autonomic nervous system sympathetic branch, and decreased or blunted activity of the HR complexity regulatory centres

  9. Intracoronary and systemic melatonin to patients with acute myocardial infarction

    DEFF Research Database (Denmark)

    Løvland Halladin, Natalie; Busch, Sarah Ekeløf; Jensen, Svend Eggert

    2014-01-01

    Ischaemia-reperfusion injury following acute myocardial infarctions (AMI) is an unavoidable consequence of the primary percutaneous coronary intervention (pPCI) procedure. A pivotal mechanism in ischaemia-reperfusion injury is the production of reactive oxygen species following reperfusion...

  10. Validation of risk stratification models in acute myeloid leukemia using sequencing-based molecular profiling.

    Science.gov (United States)

    Wang, M; Lindberg, J; Klevebring, D; Nilsson, C; Mer, A S; Rantalainen, M; Lehmann, S; Grönberg, H

    2017-10-01

    Risk stratification of acute myeloid leukemia (AML) patients needs improvement. Several AML risk classification models based on somatic mutations or gene-expression profiling have been proposed. However, systematic and independent validation of these models is required for future clinical implementation. We performed whole-transcriptome RNA-sequencing and panel-based deep DNA sequencing of 23 genes in 274 intensively treated AML patients (Clinseq-AML). We also utilized the The Cancer Genome Atlas (TCGA)-AML study (N=142) as a second validation cohort. We evaluated six previously proposed molecular-based models for AML risk stratification and two revised risk classification systems combining molecular- and clinical data. Risk groups stratified by five out of six models showed different overall survival in cytogenetic normal-AML patients in the Clinseq-AML cohort (P-value0.5). Risk classification systems integrating mutational or gene-expression data were found to add prognostic value to the current European Leukemia Net (ELN) risk classification. The prognostic value varied between models and across cohorts, highlighting the importance of independent validation to establish evidence of efficacy and general applicability. All but one model replicated in the Clinseq-AML cohort, indicating the potential for molecular-based AML risk models. Risk classification based on a combination of molecular and clinical data holds promise for improved AML patient stratification in the future.

  11. Barthel Index-Enhanced Feedback for Effective Cardiac Treatment (BI-EFFECT) Study: contribution of the Barthel Index to the Heart Failure Risk Scoring System model in elderly adults with acute heart failure in the emergency department.

    Science.gov (United States)

    Martín-Sánchez, F Javier; Gil, Víctor; Llorens, Pere; Herrero, Pablo; Jacob, Javier; Fernández, Cristina; Miró, Òscar

    2012-03-01

    To evaluate whether the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) scale for 30-day prediction of mortality is applicable to elderly adults with acute heart failure (AHF) in emergency departments (EDs) and whether discriminatory power is added with the inclusion of the Barthel Index (BI) to this scale (BI-EFFECT scale). BI-EFFECT is a multipurpose, nonintervention, multicenter cohort study. Twenty EDs. Individuals aged 65 and older with AHF. Information on baseline and episode characteristics and 30-day mortality was collected, and participants were categorized according to the EFFECT scale. Baseline degree of functional dependence was measured using the BI. Receiver operating characteristic (ROC) curves were made of the EFFECT and BI-EFFECT scales to predict mortality. One thousand sixty-eight participants were included. Thirty-day mortality was 5.1% and was directly and independently associated with high and very high risk categories of the EFFECT scale and with severe dependence. These two variables remained significant after adjustment of the model for both (OR = 4.5, 95% CI = 1.8-11.1 and OR = 2.9, 95% CI = 1.6-5.4, respectively). The EFFECT and the BI-EFFECT scales had significant ROC curves (area under the ROC curve (AUC) = 0.69, 95% CI = from 0.62 to 0.76; and AUC = 0.75, 95% CI = 0.69-0.81, respectively), and the difference in discriminatory power between the second and the first was also statistically significant (P = .02). The EFFECT scale may be applied in the elderly population, and inclusion of functional status according to the BI in the new BI-EFFECT scale significantly improves the model for the prediction of 30-day mortality. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

  12. Pathological differences in acute inflammatory demyelinating diseases of the central nervous system.

    Science.gov (United States)

    Wegner, C

    2005-04-01

    This article reviews the different pathological and immunological features of MS, acute variants of MS and acute disseminated encephalomyelitis (ADEM). T-cell-mediated inflammatory reactions are involved in all acute inflammatory diseases of the central nervous system, but the diseases discussed also exhibit distinct immunopathological features. The perivascular infiltrate of T-cells and macrophages seen in ADEM resembles the pathological pattern found in experimental autoimmune encephalomyelitis. In addition, there is evidence that humoral mechanisms play a crucial role in some acute MS lesions, Devics syndrome and Marburgs syndrome. Analysis of acute MS lesions shows many different structural and immunological features, indicating that different mechanisms may be involved in lesion formation. Distinct subtypes of acute lesions exhibit either similarities with T-cell-mediated autoimmune encephalomyelitis or signs of primary oligodendrocyte damage.

  13. Mouse model for acute Epstein-Barr virus infection.

    Science.gov (United States)

    Wirtz, Tristan; Weber, Timm; Kracker, Sven; Sommermann, Thomas; Rajewsky, Klaus; Yasuda, Tomoharu

    2016-11-29

    Epstein-Barr Virus (EBV) infects human B cells and drives them into continuous proliferation. Two key viral factors in this process are the latent membrane proteins LMP1 and LMP2A, which mimic constitutively activated CD40 receptor and B-cell receptor signaling, respectively. EBV-infected B cells elicit a powerful T-cell response that clears the infected B cells and leads to life-long immunity. Insufficient immune surveillance of EBV-infected B cells causes life-threatening lymphoproliferative disorders, including mostly germinal center (GC)-derived B-cell lymphomas. We have modeled acute EBV infection of naive and GC B cells in mice through timed expression of LMP1 and LMP2A. Although lethal when induced in all B cells, induction of LMP1 and LMP2A in just a small fraction of naive B cells initiated a phase of rapid B-cell expansion followed by a proliferative T-cell response, clearing the LMP-expressing B cells. Interfering with T-cell activity prevented clearance of LMP-expressing B cells. This was also true for perforin deficiency, which in the human causes a life-threatening EBV-related immunoproliferative syndrome. LMP expression in GC B cells impeded the GC reaction but, upon loss of T-cell surveillance, led to fatal B-cell expansion. Thus, timed expression of LMP1 together with LMP2A in subsets of mouse B cells allows one to study major clinically relevant features of human EBV infection in vivo, opening the way to new therapeutic approaches.

  14. Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults.

    Science.gov (United States)

    Cope, Anwen; Francis, Nick; Wood, Fiona; Mann, Mala K; Chestnutt, Ivor G

    2014-06-26

    publication when searching the electronic databases. Randomised controlled trials of systemic antibiotics in adults with a clinical diagnosis of symptomatic apical periodontitis or acute apical abscess, with or without surgical intervention (considered in this situation to be extraction, incision and drainage or endodontic treatment) and with or without analgesics. Two review authors screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias independently and in duplicate. We calculated mean differences (MD) (standardised mean difference (SMD) when different scales were reported) and 95% confidence intervals (CI) for continuous data and, where results were meta-analysed, we used a fixed-effect model as there were fewer than four studies. We contacted study authors to obtain missing information. We included two trials in this review, with 62 participants included in the analyses. Both trials were conducted in university dental schools in the USA and compared the effects of oral penicillin V potassium (penicillin VK) versus a matched placebo given in conjunction with a surgical intervention (total or partial pulpectomy) and analgesics to adults with acute apical abscess or symptomatic necrotic tooth (no signs of spreading infection or systemic involvement (fever, malaise)). We assessed one study as having a high risk of bias and the other study as having unclear risk of bias.The primary outcome variables presented were participant-reported pain and swelling (one trial also reported participant-reported percussion pain). One study reported the type and number of analgesics taken by participants. One study recorded the incidence of postoperative endodontic flare-ups (people who returned with symptoms that necessitated further treatment). Adverse effects as reported in one study were diarrhoea (one participant, placebo group) and fatigue and reduced energy postoperatively (one participant, antibiotic group). No studies reporting

  15. The Acute Toxicity of Major Ion Salts to Ceriodaphnia dubia. III. Mathematical models for mixture toxicity

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset concerns the development of models for describing the acute toxicity of major ions to Ceriodaphnia dubia using data from single salt tests and binary...

  16. Modeling and estimating system availability

    International Nuclear Information System (INIS)

    Gaver, D.P.; Chu, B.B.

    1976-11-01

    Mathematical models to infer the availability of various types of more or less complicated systems are described. The analyses presented are probabilistic in nature and consist of three parts: a presentation of various analytic models for availability; a means of deriving approximate probability limits on system availability; and a means of statistical inference of system availability from sparse data, using a jackknife procedure. Various low-order redundant systems are used as examples, but extension to more complex systems is not difficult

  17. Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

    Science.gov (United States)

    Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

    2016-01-01

    Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

  18. Respiratory Effects and Systemic Stress Response Following Acute Acrolein Inhalation in Rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data set is an Excel file pertaining to the study that examined nasal, pulmonary, and systemic effects of acrolein in rats acutely exposed to a range of...

  19. Acute central nervous system infection by Trypanosoma cruzi and AIDS

    Directory of Open Access Journals (Sweden)

    Pasquale Gallo

    1992-09-01

    Full Text Available The acute infection of the CNS by Trypanosoma cruzi acquired by blood transfusion is uncommon. The concomitance of AIDS in the patient reported shows the importance of cellular immunity in restriction of this parasite, and reinforces the problem of blood transfusion in endemic zones.

  20. GABAergic modulation of human social interaction in a prisoner’s dilemma model via acute administration of alprazolam

    OpenAIRE

    Lane, Scott D.; Gowin, Joshua L.

    2009-01-01

    Recent work in neuroeconomics has utilized game theory paradigms to examine neural systems that subserve human social interaction and decision making. Attempts to modify social interaction through pharmacological manipulation have been less common. Here we show dose-dependent modification of human social behavior in a prisoner’s dilemma (PD) model following acute administration of the GABA-A modulating benzodiazepine alprazolam. Nine healthy adults received doses of placebo, 0.5, 1.0, and 2.0...

  1. Modelling of reverberation enhancement systems

    OpenAIRE

    ROUCH , Jeremy; Schmich , Isabelle; Galland , Marie-Annick

    2012-01-01

    International audience; Electroacoustic enhancement systems are increasingly specified by acoustic consultants to address the requests for a multi-purpose use of performance halls. However, there is still a lack of simple models to predict the effect induced by these systems on the acoustic field. Two models are introduced to establish the impulse responses of a room equipped with a reverberation enhancement system. These models are based on passive impulse responses according to the modified...

  2. MODELLING OF MATERIAL FLOW SYSTEMS

    OpenAIRE

    PÉTER TELEK

    2012-01-01

    Material flow systems are in generally very complex processes. During design, building and operation of complex systems there are many different problems. If these complex processes can be described in a simple model, the tasks will be clearer, better adaptable and easier solvable. As the material flow systems are very different, so using models is a very important aid to create uniform methods and solutions. This paper shows the details of the application possibilities of modelling in the ma...

  3. Dynamic Modeling of ALS Systems

    Science.gov (United States)

    Jones, Harry

    2002-01-01

    The purpose of dynamic modeling and simulation of Advanced Life Support (ALS) systems is to help design them. Static steady state systems analysis provides basic information and is necessary to guide dynamic modeling, but static analysis is not sufficient to design and compare systems. ALS systems must respond to external input variations and internal off-nominal behavior. Buffer sizing, resupply scheduling, failure response, and control system design are aspects of dynamic system design. We develop two dynamic mass flow models and use them in simulations to evaluate systems issues, optimize designs, and make system design trades. One model is of nitrogen leakage in the space station, the other is of a waste processor failure in a regenerative life support system. Most systems analyses are concerned with optimizing the cost/benefit of a system at its nominal steady-state operating point. ALS analysis must go beyond the static steady state to include dynamic system design. All life support systems exhibit behavior that varies over time. ALS systems must respond to equipment operating cycles, repair schedules, and occasional off-nominal behavior or malfunctions. Biological components, such as bioreactors, composters, and food plant growth chambers, usually have operating cycles or other complex time behavior. Buffer sizes, material stocks, and resupply rates determine dynamic system behavior and directly affect system mass and cost. Dynamic simulation is needed to avoid the extremes of costly over-design of buffers and material reserves or system failure due to insufficient buffers and lack of stored material.

  4. Modeling soft interface dominated systems

    NARCIS (Netherlands)

    Lamorgese, A.; Mauri, R.; Sagis, L.M.C.

    2017-01-01

    The two main continuum frameworks used for modeling the dynamics of soft multiphase systems are the Gibbs dividing surface model, and the diffuse interface model. In the former the interface is modeled as a two dimensional surface, and excess properties such as a surface density, or surface energy

  5. Validation of systems biology models

    NARCIS (Netherlands)

    Hasdemir, D.

    2015-01-01

    The paradigm shift from qualitative to quantitative analysis of biological systems brought a substantial number of modeling approaches to the stage of molecular biology research. These include but certainly are not limited to nonlinear kinetic models, static network models and models obtained by the

  6. From Numeric Models to Granular System Modeling

    Directory of Open Access Journals (Sweden)

    Witold Pedrycz

    2015-03-01

    To make this study self-contained, we briefly recall the key concepts of granular computing and demonstrate how this conceptual framework and its algorithmic fundamentals give rise to granular models. We discuss several representative formal setups used in describing and processing information granules including fuzzy sets, rough sets, and interval calculus. Key architectures of models dwell upon relationships among information granules. We demonstrate how information granularity and its optimization can be regarded as an important design asset to be exploited in system modeling and giving rise to granular models. With this regard, an important category of rule-based models along with their granular enrichments is studied in detail.

  7. EVALUATION OF PRE-OPERATIVE DIAGNOSTIC EFFICACY OF MODIFIED ALVARADO SCORING SYSTEM IN ACUTE APPENDICITIS

    Directory of Open Access Journals (Sweden)

    Anand Kumar Jaiswal

    2017-05-01

    Full Text Available BACKGROUND Acute Appendicitis is the one of the most common acute surgical condition of abdomen. Acute Appendicitis may occur but is most commonly seen in the second and third decade of life. Acute Appendicitis if not diagnosed early and treated properly, may lead to fatal outcome. MATERIALS AND METHODS A prospective study of 100 patients, with a clinical diagnosis of acute appendicitis, admitted in the department of general surgery, B.R.D. Medical College Gorakhpur during a period of one year. RESULTS The age group in which acute appendicitis occurred commonly was between 18 to 30 years. It is clear that incidence is less in younger and older is group with peak incidence in second and third decade. Female to male ratio was 1.8:1. Pain was the commonest presenting symptom and has been observed in all the cases (100% in present series followed by nausea/vomiting in 87% cases and anorexia in 49% cases. CONCLUSION In the diagnosis of acute appendicitis the modified Alvarado Scoring System has a diagnostic value of 88.66%. This system is simple, reliable, cheap, non-invasive and safe diagnostic modality. The application of this scoring system improved diagnostic accuracy and consequently reduced negative appendectomy rate.

  8. Challenges and rewards on the road to translational systems biology in acute illness: four case reports from interdisciplinary teams.

    Science.gov (United States)

    An, Gary; Hunt, C Anthony; Clermont, Gilles; Neugebauer, Edmund; Vodovotz, Yoram

    2007-06-01

    Translational systems biology approaches can be distinguished from mainstream systems biology in that their goal is to drive novel therapies and streamline clinical trials in critical illness. One systems biology approach, dynamic mathematical modeling (DMM), is increasingly used in dealing with the complexity of the inflammatory response and organ dysfunction. The use of DMM often requires a broadening of research methods and a multidisciplinary team approach that includes bioscientists, mathematicians, engineers, and computer scientists. However, the development of these groups must overcome domain-specific barriers to communication and understanding. We present 4 case studies of successful translational, interdisciplinary systems biology efforts, which differ by organizational level from an individual to an entire research community. Case 1 is a single investigator involved in DMM of the acute inflammatory response at Cook County Hospital, in which extensive translational progress was made using agent-based models of inflammation and organ damage. Case 2 is a community-level effort from the University of Witten-Herdecke in Cologne, whose efforts have led to the formation of the Society for Complexity in Acute Illness. Case 3 is an institution-based group, the Biosystems Group at the University of California, San Francisco, whose work has included a focus on a common lexicon for DMM. Case 4 is an institution-based, transdisciplinary research group (the Center for Inflammation and Regenerative Modeling at the University of Pittsburgh), whose modeling work has led to internal education efforts, grant support, and commercialization. A transdisciplinary approach, which involves team interaction in an iterative fashion to address ambiguity and is supported by educational initiatives, is likely to be necessary for DMM in acute illness. Communitywide organizations such as the Society of Complexity in Acute Illness must strive to facilitate the implementation of DMM in

  9. Coastal Modeling System Advanced Topics

    Science.gov (United States)

    2012-06-18

    22 June 2012 - Day 5  Debugging and Problem solving  Model Calibration  Post-processing Coastal and Hydraulics Laboratory Focus of...Efficiently: • The setup process is fast and without wasted time or effort 3 Coastal and Hydraulics Laboratory 4 Coastal Modeling System (CMS) What...is the CMS? Integrated wave, current, and morphology change model in the Surface- water Modeling System (SMS). Why CMS? Operational at 10

  10. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

    Bennett, H.A.; Boozer, D.D.; Chapman, L.D.; Daniel, S.L.; Engi, D.; Hulme, B.L.; Varnado, G.B.

    1976-01-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. The overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  11. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

    Bennett, H.A.; Boozer, D.D.; Chapman, L.D.; Daniel, S.L.; Engi, D.; Hulme, B.L.; Varnado, G.B.

    1976-01-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. In this paper, the overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  12. A Novel Large Animal Model of Acute Respiratory Distress Syndrome Induced by Mitochondrial Products.

    Science.gov (United States)

    Sanchez, Pablo G; Pasrija, Chetan; Mulligan, Matthew J; Wadhwa, Mandheer; Pratt, Diana L; Li, Tieluo; Gammie, James S; Kon, Zachary N; Pham, Si M; Griffith, Bartley P

    2017-12-01

    We aimed to create a reproducible lung injury model utilizing injection of mitochondrial damage-associated molecular products. Our goal was to characterize the pathophysiologic response to damage-associated molecular pattern mediated organ injury. There remain significant gaps in our understanding of acute respiratory distress syndrome, in part due to the lack of clinically applicable animal models of this disease. Animal models of noninfectious, tissue damage-induced lung injury are needed to understand the signals and responses associated with this injury. Ten pigs (35-45 kg) received an intravenous dose of disrupted mitochondrial products and were followed for 6 hours under general anesthesia. These animals were compared to a control group (n = 5) and a model of lung injury induced by bacterial products (lipopolysaccharide n = 5). Heart rate and temperature were significantly elevated in the mitochondrial product (204 ± 12 and 41 ± 1) and lipopolysaccharide groups (178 ± 18 and 42 ± 0.5) compared with controls (100 ± 13 and 38 ± 0.5) (P products and lipopolysaccharide groups compared with controls (170 ± 39, 196 ± 27, and 564 ± 75 mm Hg respectively, P = 0.001). Lung injury scoring of histological sections was significantly worse in mitochondrial and lipopolysaccharide groups compared with controls (mitochondrial-64 ± 6, lipopolysaccharide-54 ± 8, control-14 ± 1.5, P= 0.002). Our data demonstrated that the presence of mitochondrial products in the circulation leads to systemic inflammatory response and lung injury. In its acute phase lung injury induced by tissue or bacterial products is clinically indistinguishable.

  13. A new approach to scoring systems to improve identification of acute medical admissions that will require critical care.

    Science.gov (United States)

    Carmichael, H A; Robertson, E; Austin, J; McCruden, D; Messow, C M; Belcher, P R

    2011-11-01

    Removal of the intensive care unit (ICU) at the Vale of Leven Hospital mandated the identification and transfer out of those acute medical admissions with a high risk of requiring ICU. The aim of the study was to develop triaging tools that identified such patients and compare them with other scoring systems. The methodology included a retrospective analysis of physiological and arterial gas measurements from 1976 acute medical admissions produced PREEMPT-1 (PRE-critical Emergency Medical Patient Triage). A simpler one for ambulance use (PREAMBLE-1 [PRE-Admission Medical Blue-Light Emergency]) was produced by the addition of peripheral oxygen saturation to a modification of MEWS (Modified Early Warning Score). Prospective application of these tools produced a larger database of 4447 acute admissions from which logistic regression models produced PREEMPT-2 and PREAMBLE-2, which were then compared with the original systems and seven other early warning scoring systems. Results showed that in patients with arterial gases, the area under the receiver operator characteristic curve was significantly higher in PREEMPT-2 (89·1%) and PREAMBLE-2 (84.4%) than all other scoring systems. Similarly, in all patients, it was higher in PREAMBLE-2 (92·4%) than PREAMBLE-1 (88·1%) and the other scoring systems. In conclusion, risk of requiring ICU can be more accurately predicted using PREEMPT-2 and PREAMBLE-2, as described here, than by other early warning scoring systems developed over recent years.

  14. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    Directory of Open Access Journals (Sweden)

    Minmin Li

    2015-01-01

    Full Text Available The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2 and cyclooxygenase- (COX- 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models.

  15. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models.

    Science.gov (United States)

    Li, Minmin; Lu, Chengwen; Zhang, Leiming; Zhang, Jianqiao; Du, Yuan; Duan, Sijin; Wang, Tian; Fu, Fenghua

    2015-01-01

    The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2) and cyclooxygenase- (COX-) 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models.

  16. Kynurenine-3-monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis.

    Science.gov (United States)

    Mole, Damian J; Webster, Scott P; Uings, Iain; Zheng, Xiaozhong; Binnie, Margaret; Wilson, Kris; Hutchinson, Jonathan P; Mirguet, Olivier; Walker, Ann; Beaufils, Benjamin; Ancellin, Nicolas; Trottet, Lionel; Bénéton, Véronique; Mowat, Christopher G; Wilkinson, Martin; Rowland, Paul; Haslam, Carl; McBride, Andrew; Homer, Natalie Z M; Baily, James E; Sharp, Matthew G F; Garden, O James; Hughes, Jeremy; Howie, Sarah E M; Holmes, Duncan S; Liddle, John; Iredale, John P

    2016-02-01

    Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death. Acute mortality from AP-MODS exceeds 20% (ref. 3), and the lifespans of those who survive the initial episode are typically shorter than those of the general population. There are no specific therapies available to protect individuals from AP-MODS. Here we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism, is central to the pathogenesis of AP-MODS. We created a mouse strain that is deficient for Kmo (encoding KMO) and that has a robust biochemical phenotype that protects against extrapancreatic tissue injury to the lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of the oxazolidinone GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Å resolution. Treatment with GSK180 resulted in rapid changes in the levels of kynurenine pathway metabolites in vivo, and it afforded therapeutic protection against MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS, and they open up a new area for drug discovery in critical illness.

  17. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-02-22

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  18. Approach to building knowledge bases in information-measuring systems diagnostics of acute leukemias

    Science.gov (United States)

    Nikitaev, V. G.; Pronichev, A. N.; Polyakov, E. V.; Dmitrieva, V. V.

    2018-01-01

    The paper describes an approach for the formation of the reference base of peripheral blood cells and bone marrow in information-measuring systems of acute leukemia diagnostics. The proposed approach has allowed to create a system, that is enable peer evaluation of blood cells needed for the training of recognition systems when carrying out microscopic studies.

  19. Artificial and bioartificial support systems for acute and acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Kjaergard, Lise L; Liu, Jianping; Als-Nielsen, Bodil

    2003-01-01

    Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation.......Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation....

  20. Intestinal bacterial overgrowth includes potential pathogens in the carbohydrate overload models of equine acute laminitis.

    Science.gov (United States)

    Onishi, Janet C; Park, Joong-Wook; Prado, Julio; Eades, Susan C; Mirza, Mustajab H; Fugaro, Michael N; Häggblom, Max M; Reinemeyer, Craig R

    2012-10-12

    Carbohydrate overload models of equine acute laminitis are used to study the development of lameness. It is hypothesized that a diet-induced shift in cecal bacterial communities contributes to the development of the pro-inflammatory state that progresses to laminar failure. It is proposed that vasoactive amines, protease activators and endotoxin, all bacterial derived bioactive metabolites, play a role in disease development. Questions regarding the oral bioavailability of many of the bacterial derived bioactive metabolites remain. This study evaluates the possibility that a carbohydrate-induced overgrowth of potentially pathogenic cecal bacteria occurs and that bacterial translocation contributes toward the development of the pro-inflammatory state. Two groups of mixed-breed horses were used, those with laminitis induced by cornstarch (n=6) or oligofructan (n=6) and non-laminitic controls (n=8). Cecal fluid and tissue homogenates of extra-intestinal sites including the laminae were used to enumerate Gram-negative and -positive bacteria. Horses that developed Obel grade2 lameness, revealed a significant overgrowth of potentially pathogenic Gram-positive and Gram-negative intestinal bacteria within the cecal fluid. Although colonization of extra-intestinal sites with potentially pathogenic bacteria was not detected, results of this study indicate that cecal/colonic lymphadenopathy and eosinophilia develop in horses progressing to lameness. It is hypothesized that the pro-inflammatory state in carbohydrate overload models of equine acute laminitis is driven by an immune response to the rapid overgrowth of Gram-positive and Gram-negative cecal bacterial communities in the gut. Further equine research is indicated to study the immunological response, involving the lymphatic system that develops in the model. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Host immune response and acute disease in a zebrafish model of francisella pathogenesis

    Science.gov (United States)

    Vojtech, L.N.; Sanders, G.E.; Conway, C.; Ostland, V.; Hansen, J.D.

    2009-01-01

    Members of the bacterial genus Francisella are highly virulent and infectious pathogens. New models to study Francisella pathogenesis in evolutionarily distinct species are needed to provide comparative insight, as the mechanisms of host resistance and pathogen virulence are not well understood. We took advantage of the recent discovery of a novel species of Francisella to establish a zebrafish/Francisella comparative model of pathogenesis and host immune response. Adult zebraflsh were susceptible to acute Francisella-induced disease and suffered mortality in a dose-dependent manner. Using immunohistochemical analysis, we localized bacterial antigens primarily to lymphoid tissues and livers of zebraflsh following infection by intraperitoneal injection, which corresponded to regions of local cellular necrosis. Francisella sp. bacteria replicated rapidly in these tissues beginning 12 h postinfection, and bacterial titers rose steadily, leveled off, and then decreased by 7 days postinfection. Zebraflsh mounted a significant tissue-specific proinflammatory response to infection as measured by the upregulation of interleukin-l?? (IL-1??), gamma interferon, and tumor necrosis factor alpha mRNA beginning by 6 h postinfection and persisting for up to 7 days postinfection. In addition, exposure of zebraflsh to heat-killed bacteria demonstrated that the significant induction of IL-?? was highly specific to live bacteria. Taken together, the pathology and immune response to acute Francisella infection in zebraflsh share many features with those in mammals, highlighting the usefulness of this new model system for addressing both general and specific questions about Francisella host-pathogen interactions via an evolutionary approach. Copyright ?? 2009, American Society for Microbiology. All Rights Reserved.

  2. Mechanical Systems, Classical Models

    CERN Document Server

    Teodorescu, Petre P

    2007-01-01

    All phenomena in nature are characterized by motion; this is an essential property of matter, having infinitely many aspects. Motion can be mechanical, physical, chemical or biological, leading to various sciences of nature, mechanics being one of them. Mechanics deals with the objective laws of mechanical motion of bodies, the simplest form of motion. In the study of a science of nature mathematics plays an important role. Mechanics is the first science of nature which was expressed in terms of mathematics by considering various mathematical models, associated to phenomena of the surrounding nature. Thus, its development was influenced by the use of a strong mathematical tool; on the other hand, we must observe that mechanics also influenced the introduction and the development of many mathematical notions. In this respect, the guideline of the present book is precisely the mathematical model of mechanics. A special accent is put on the solving methodology as well as on the mathematical tools used; vectors, ...

  3. Stochastic Modelling of Energy Systems

    DEFF Research Database (Denmark)

    Andersen, Klaus Kaae

    2001-01-01

    In this thesis dynamic models of typical components in Danish heating systems are considered. Emphasis is made on describing and evaluating mathematical methods for identification of such models, and on presentation of component models for practical applications. The thesis consists of seven...... of component models, such as e.g. heat exchanger and valve models, adequate for system simulations. Furthermore, the thesis demonstrates and discusses the advantages and disadvantages of using statistical methods in conjunction with physical knowledge in establishing adequate component models of heating...... research papers (case studies) together with a summary report. Each case study takes it's starting point in typical heating system components and both, the applied mathematical modelling methods and the application aspects, are considered. The summary report gives an introduction to the scope...

  4. Construction of protein profile classification model and screening of proteomic signature of acute leukemia.

    Science.gov (United States)

    Xu, Yun; Zhuo, Jiacai; Duan, Yonggang; Shi, Benhang; Chen, Xuhong; Zhang, Xiaoli; Xiao, Liang; Lou, Jin; Huang, Ruihong; Zhang, Qiongli; Du, Xin; Li, Ming; Wang, Daping; Shi, Dunyun

    2014-01-01

    The French-American-British (FAB) and WHO classifications provide important guidelines for the diagnosis, treatment, and prognostic prediction of acute leukemia, but are incapable of accurately differentiating all subtypes, and not well correlated with the clinical outcomes. In this study, we performed the protein profiling of the bone marrow mononuclear cells from the patients with acute leukemia and the health volunteers (control) by surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI_TOF_MS). The patients with acute leukemia were analyzed as unitary by the profiling that were grouped into acute promyelocytic leukemia (APL), acute myeloid leukemia-granulocytic (AML-Gran), acute myeloid leukemia-monocytic (AML-Mon) acute lymphocytic leukemia (ALL), and control. Based on 109 proteomic signatures, the classification models of acute leukemia were constructed to screen the predictors by the improvement of the proteomic signatures and to detect their expression characteristics. According to the improvement and the expression characteristics of the predictors, the proteomic signatures (M3829, M1593, M2121, M2536, M1016) characterized successively each group (CON, APL, AML-Gra, AML-Mon, ALL) were screened as target molecules for identification. Meanwhile, the proteomic-based class of determinant samples could be made by the classification models. The credibility of the proteomic-based classification passed the evaluation of Biomarker Patterns Software 5.0 (BPS 5.0) scoring and validated application in clinical practice. The results suggested that the proteomic signatures characterized by different blasts were potential for developing new treatment and monitoring approaches of leukemia blasts. Moreover, the classification model was potential in serving as new diagnose approach of leukemia.

  5. Persistent socio-economic differences in revascularization after acute myocardial infarction despite a universal health care system-a Danish study

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Nørgaard; Rasmussen, Søren; Gislason, Gunnar H

    2007-01-01

    , but not for acute PCI, for which no gradient was seen. No educational gradient was found for CABG, and that for non-acute and acute PCI decreased during the period; by the end of the period, more patients with low than high education received acute PCI. CONCLUSION: In the universal health care system of Denmark...... AND METHODS: All patients aged 30-74 years in hospital for a first AMI in Denmark between 1996 and 2004 were included. Cox proportional hazard models were used to estimate the association between individual income (tertiles) and education (>12, 10-12 and ... months. Revascularization was stratified into CABG, acute PCI (within 2 days of admission) and non-acute PCI (after the third day). RESULTS: A total of 38,803 patients were included. In 1996-1998, 6.8% received CABG, 9.3% non-acute PCI and 2.4% acute PCI; in 2002-2004, these numbers were 11.8, 36...

  6. Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Chen, Daphne Wei-Chen; Krstic-Demonacos, Marija; Schwartz, Jean-Marc

    2012-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs) are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adopting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data by building a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Ets-related gene (Erg) as potential biomarker of GC resistance. The results revealed an alternative possible mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  7. Model Reduction of Hybrid Systems

    DEFF Research Database (Denmark)

    Shaker, Hamid Reza

    for model reduction of switched systems is based on the switching generalized gramians. The reduced order switched system is guaranteed to be stable for all switching signal in this method. This framework uses stability conditions which are based on switching quadratic Lyapunov functions which are less...... conservative than the stability conditions based on common quadratic Lyapunov functions. The stability conditions which are used for this method are very useful in model reduction and design problems because they have slack variables in the conditions. Similar conditions for a class of switched nonlinear......High-Technological solutions of today are characterized by complex dynamical models. A lot of these models have inherent hybrid/switching structure. Hybrid/switched systems are powerful models for distributed embedded systems design where discrete controls are applied to continuous processes...

  8. Hemorheology index changes in a rat acute blood stasis model: a ...

    African Journals Online (AJOL)

    Hemorheology index changes in a rat acute blood stasis model: a systematic review and meta-analysis. ... Chinese National Knowledge Infrastructure database (CNKI), Chinese Medical Journal Database (CMJD), Chinese Biology Medicine disc (CBM), Wanfang database, and PubMed for studies of rat blood stasis models; ...

  9. Development of Hamster Models for Acute and Chronic Infections with Leptospira borgpetersenii serovar Hardjo

    Science.gov (United States)

    The Golden Syrian hamster is frequently used as a small animal model to study acute leptospirosis. However, use of this small animal model to study Leptospira borgpetersenii serovar Hardjo infections has not been well documented. Cattle are the normal maintenance hosts of L. borgpetersenii serovar...

  10. Internal gallbladder drainage prevents development of acute cholecystitis in a pig model

    DEFF Research Database (Denmark)

    Kjaer, Daniel W; Mortensen, Frank V; Møller, Jens K

    2010-01-01

    BACKGROUND: Acute cholecystitis can be the result of retention of bile in the gallbladder with possible secondary infection and ischaemia. The aim of the present study was to investigate whether internal drainage of the gallbladder could protect against the development of acute cholecystitis...... in a pig model. MATERIALS AND METHODS: Twenty pigs were randomized to either internal drainage (drained) or not (undrained). Day 0 acute cholecystitis was induced by ligation of the cystic artery and duct together with inoculation of bacteria. Four days later the pigs were killed and the gallbladders were...... removed and histologically scored for the presence of cholecystitis. Bile and blood samples were collected for bacterial culturing and biochemical analyses. RESULTS: The histological examination demonstrated statistical significant differences in acute cholecystitis development between groups, the degree...

  11. Distribution system modeling and analysis

    CERN Document Server

    Kersting, William H

    2001-01-01

    For decades, distribution engineers did not have the sophisticated tools developed for analyzing transmission systems-often they had only their instincts. Things have changed, and we now have computer programs that allow engineers to simulate, analyze, and optimize distribution systems. Powerful as these programs are, however, without a real understanding of the operating characteristics of a distribution system, engineers using the programs can easily make serious errors in their designs and operating procedures. Distribution System Modeling and Analysis helps prevent those errors. It gives readers a basic understanding of the modeling and operating characteristics of the major components of a distribution system. One by one, the author develops and analyzes each component as a stand-alone element, then puts them all together to analyze a distribution system comprising the various shunt and series devices for power-flow and short-circuit studies. He includes the derivation of all models and includes many num...

  12. Hydronic distribution system computer model

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, J.W.; Strasser, J.J.

    1994-10-01

    A computer model of a hot-water boiler and its associated hydronic thermal distribution loop has been developed at Brookhaven National Laboratory (BNL). It is intended to be incorporated as a submodel in a comprehensive model of residential-scale thermal distribution systems developed at Lawrence Berkeley. This will give the combined model the capability of modeling forced-air and hydronic distribution systems in the same house using the same supporting software. This report describes the development of the BNL hydronics model, initial results and internal consistency checks, and its intended relationship to the LBL model. A method of interacting with the LBL model that does not require physical integration of the two codes is described. This will provide capability now, with reduced up-front cost, as long as the number of runs required is not large.

  13. [System evaluation on Ginkgo Biloba extract in the treatment of acute cerebral infarction].

    Science.gov (United States)

    Wang, Lin; Zhang, Tao; Bai, Kezhen

    2015-10-01

    To evaluate the effect and safety of Ginkgo Biloba extract on the treatment of acute cerebral infarction.
 The Database of Wanfang, China National Knowledge Infrastructure (CNKI) and VIPU were screened for literatures regarding Ginkgo Biloba extract in the treatment of acute cerebral infarction, including the clinical randomized controlled trials. Meta-analysis based on the Revman 4.2 system was performed.
 Compared with the control group, treatment with Ginkgo Biloba extract enhanced efficacy in the treatment of acute cerebral infarction (OR: 1.60-5.53), which displayed an improved neural function defect score [WMD -3.12 (95%CI: -3.96- -2.28)].
 Ginkgo Biloba extract is beneficial to the improvement of neurological function in patients with acute cerebral infarction and it is safe for patients.

  14. Cross-Sector Review of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing

    Science.gov (United States)

    Seidle, Troy; Robinson, Sally; Holmes, Tom; Creton, Stuart; Prieto, Pilar; Scheel, Julia; Chlebus, Magda

    2010-01-01

    Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or refining the use of animals, and (3) recommendations for future work in this area. PMID:20484382

  15. Venous System in Acute Brain Injury: Mechanisms of Pathophysiological Change and Function

    Science.gov (United States)

    Xu, Liang; Matei, Nathanael; Tang, Jiping; Feng, Hua; Zhang, JohnH

    2015-01-01

    Cerebral vascular injury is a major component of acute brain injury. Currently, neuroprotective strategies primarily focus on the recanalization of cerebral arteries and capillaries, and the protection of insulted neurons. Hitherto, the role of vein drainage in the pathophysiology of acute brain injury has been overlooked, due to an under appreciation of the magnitude of the impact of veins in circulation. In this review, we summarize the changes in the vein morphology and functions that are known, or likely to occur related to acute brain injury, and aim to advance the therapeutic management of acute brain injury by shifting the focus from reperfusion to another term: recirculation. Recent progress in the neurobiological understanding of the vascular neural network has demonstrated that cerebral venous systems are able to respond to acute brain injury by regulating the blood flow disharmony following brain edema, blood brain barrier disruption, ischemia, and hemorrhage. With the evidence presented in this review, future clinical management of acutely brain injured patients will expand to include the recirculation concept, establishing a harmony between arterial and venous systems, in addition to the established recanalization and reperfusion strategies. PMID:25783658

  16. Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy

    Directory of Open Access Journals (Sweden)

    Julia M. Post

    2018-03-01

    Full Text Available Research on the antiepileptic effects of (endo-cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]. Concomitant research has uncovered the contribution of neuroinflammatory processes and peripheral immunity to the onset and progression of epilepsy. Accordingly, modulation of inflammatory pathways such as cyclooxygenase-2 (COX-2 was pursued as alternative therapeutic strategy for epilepsy. Palmitoylethanolamide (PEA is an endogenous fatty acid amide related to the centrally and peripherally present eCB AEA, and is a naturally occurring nutrient that has long been recognized for its analgesic and anti-inflammatory properties. Neuroprotective and anti-hyperalgesic properties of PEA were evidenced in neurodegenerative diseases, and antiepileptic effects in pentylenetetrazol (PTZ, maximal electroshock (MES and amygdaloid kindling models of epileptic seizures. Moreover, numerous clinical trials in chronic pain revealed that PEA treatment is devoid of addiction potential, dose limiting side effects and psychoactive effects, rendering PEA an appealing candidate as antiepileptic compound or adjuvant. In the present study, we aimed at assessing antiepileptic properties of PEA in a mouse model of acute epileptic seizures induced by systemic administration of kainic acid (KA. KA-induced epilepsy in rodents is assumed to resemble to different extents human temporal lobe epilepsy (TLE depending on the route of KA administration; intracerebral (i

  17. External validation of severity scoring systems for acute renal failure using a multinational database

    NARCIS (Netherlands)

    Uchino, Shigehiko; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Doig, Gordon S.; Oudemans van Straaten, Heleen; Ronco, Claudio; Kellum, John A.

    2005-01-01

    Several different severity scoring systems specific to acute renal failure have been proposed. However, most validation studies of these scoring systems were conducted in a single center or in a small number of centers, often the same ones used for their development. Therefore, it is not known

  18. Thrombocytopenia Is Associated With Multi-organ System Failure in Patients With Acute Liver Failure

    NARCIS (Netherlands)

    Stravitz, R. Todd; Ellerbe, Caitlyn; Durkalski, Valerie; Reuben, Adrian; Lisman, Ton; Lee, William M.

    BACKGROUND & AIMS: Acute liver failure (ALF) is a syndrome characterized by an intense systemic inflammatory response (SIRS) and multi-organ system failure (MOSF). Platelet-derived microparticles increase in proportion to the severity of the SIRS and MOSF, and are associated with poor outcome. We

  19. Intrusion detection: systems and models

    Science.gov (United States)

    Sherif, J. S.; Dearmond, T. G.

    2002-01-01

    This paper puts forward a review of state of the art and state of the applicability of intrusion detection systems, and models. The paper also presents a classfication of literature pertaining to intrusion detection.

  20. Plant and safety system model

    International Nuclear Information System (INIS)

    Beltracchi, Leo

    1999-01-01

    The design and development of a digital computer-based safety system for a nuclear power plant is a complex process. The process of design and product development must result in a final product free of critical errors; operational safety of nuclear power plants must not be compromised. This paper focuses on the development of a safety system model to assist designers, developers, and regulators in establishing and evaluating requirements for a digital computer-based safety system. The model addresses hardware, software, and human elements for use in the requirements definition process. The purpose of the safety system model is to assist and serve as a guide to humans in the cognitive reasoning process of establishing requirements. The goals in the use of the model are to: (1) enhance the completeness of the requirements and (2) reduce the number of errors associated with the requirements definition phase of a project

  1. Human endotoxemia as a model of systemic inflammation

    DEFF Research Database (Denmark)

    Krabbe, K.S.; Krogh-Madsen, R.; Taudorf, S.

    2008-01-01

    Systemic inflammation is a pathogenetic component in a vast number of acute and chronic diseases such as sepsis, trauma, type 2 diabetes, atherosclerosis, and Alzheimer's disease, all of which are associated with a substantial morbidity and mortality. However, the molecular mechanisms...... and physiological significance of the systemic inflammatory response are still not fully understood. The human endotoxin model, an in vivo model of systemic inflammation in which lipopolysaccharide is injected or infused intravenously in healthy volunteers, may be helpful in unravelling these issues. The present...

  2. Outcomes of an innovative model of acute delirium care: the Geriatric Monitoring Unit (GMU

    Directory of Open Access Journals (Sweden)

    Chong MS

    2014-04-01

    s recovery from the delirium episode. Conclusion: This study shows the benefits of a specialized delirium management unit for older persons. The GMU model is thus a relevant system of care for rapidly “graying” nations with high rates of frail elderly hospital admissions, which can be easily transposed across acute care settings. Keywords: delirium, function, elderly

  3. Blocking neurogenic inflammation for the treatment of acute disorders of the central nervous system.

    Science.gov (United States)

    Lewis, Kate Marie; Turner, Renée Jade; Vink, Robert

    2013-01-01

    Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis.

  4. Blocking Neurogenic Inflammation for the Treatment of Acute Disorders of the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Kate Marie Lewis

    2013-01-01

    Full Text Available Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis.

  5. Radioprotective effect of cimitidine on acutely irradiated mice survival and hematopoietic system

    Directory of Open Access Journals (Sweden)

    Qing-rong WANG

    2017-02-01

    Full Text Available Objective To investigate the radioprotective effect of cimetidine on survival rate and hematopoietic system in acutely irradiated mice. Methods The total body irradiation doses were 6.0Gy and 8.0Gy respectively at 1.01Gy/min rate. Sixty healthy male C57BL/6 mice were randomly divided into control group, model group, positive-drug (523 group and cimetidine groups (33.3mg/kg, 100mg/kg and 300mg/kg. Each group had ten mice. The mice were given intragastric administration of cimetidine for 6d before the irradiation in cimetidine groups, and 523 was administered before irradiation once a day for one day in 523 group, and at 5h after irradiation, was given again. The 30d survival rate after 8.0Gy irradiation was recorded. The peripheral blood cells, bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fMNPCE were determined 30d after 6.0Gy irradiation. Results After 8.0Gy irradiation, all the mice died on 21th day in model control group. The survival rates in cimetidine groups were 50%, 20% and 30%, respectively. After 6.0Gy irradiation on 30th day, compared with control group, the peripheral white blood cells (WBC and bone marrow DNA content were decreased significantly (P<0.01, P<0.05 in model group, and fMNPCE was increased significantly (P<0.05. Compared with model group, WBC was significantly increased in 300mg/kg cimetidine group (P<0.01. In cimetidine groups, the bone marrow DNA content was increased significantly after irradiation (P<0.01 or P<0.05, and the fMNPCE was decreased significantly (P<0.01 or P<0.05and tended towards normal. Conclusion Cimetidine could improve 30d survival rate of acutely irradiated mice and has good protective effect on hematopoietic system. DOI: 10.11855/j.issn.0577-7402.2017.01.12

  6. Mathematical modeling of aeroelastic systems

    Science.gov (United States)

    Velmisov, Petr A.; Ankilov, Andrey V.; Semenova, Elizaveta P.

    2017-12-01

    In the paper, the stability of elastic elements of a class of designs that are in interaction with a gas or liquid flow is investigated. The definition of the stability of an elastic body corresponds to the concept of stability of dynamical systems by Lyapunov. As examples the mathematical models of flowing channels (models of vibration devices) at a subsonic flow and the mathematical models of protective surface at a supersonic flow are considered. Models are described by the related systems of the partial differential equations. An analytic investigation of stability is carried out on the basis of the construction of Lyapunov-type functionals, a numerical investigation is carried out on the basis of the Galerkin method. The various models of the gas-liquid environment (compressed, incompressible) and the various models of a deformable body (elastic linear and elastic nonlinear) are considered.

  7. ABSTRACT MODELS FOR SYSTEM VIRTUALIZATION

    Directory of Open Access Journals (Sweden)

    M. G. Koveshnikov

    2015-05-01

    Full Text Available The paper is dedicated to issues of system objects securing (system files and user system or application configuration files against unauthorized access including denial of service attacks. We have suggested the method and developed abstract system virtualization models, which are used toresearch attack scenarios for different virtualization modes. Estimation for system tools virtualization technology effectiveness is given. Suggested technology is based on redirection of access requests to system objects shared among access subjects. Whole and partial system virtualization modes have been modeled. The difference between them is the following: in the whole virtualization mode all copies of access system objects are created whereon subjects’ requests are redirected including corresponding application objects;in the partial virtualization mode corresponding copies are created only for part of a system, for example, only system objects for applications. Alternative solutions effectiveness is valued relating to different attack scenarios. We consider proprietary and approved technical solution which implements system virtualization method for Microsoft Windows OS family. Administrative simplicity and capabilities of correspondingly designed system objects security tools are illustrated on this example. Practical significance of the suggested security method has been confirmed.

  8. Aerodynamic and Mechanical System Modelling

    DEFF Research Database (Denmark)

    Jørgensen, Martin Felix

    This thesis deals with mechanical multibody-systems applied to the drivetrain of a 500 kW wind turbine. Particular focus has been on gearbox modelling of wind turbines. The main part of the present project involved programming multibody systems to investigate the connection between forces, moments...

  9. Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

    Science.gov (United States)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    2017-06-01

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Preface: the hydra model system.

    Science.gov (United States)

    Galliot, Brigitte

    2012-01-01

    The freshwater Hydra polyp emerged as a model system in 1741 when Abraham Trembley not only discovered its amazing regenerative potential, but also demonstrated that experimental manipulations pave the way to research in biology. Since then, Hydra flourished as a potent and fruitful model system to help answer questions linked to cell and developmental biology, as such as the setting up of an organizer to regenerate a complex missing structure, the establishment and maintainance of polarity in a multicellular organism, the development of mathematical models to explain the robust developmental rules observed in this animal, the maintainance of stemness and multipotency in a highly dynamic environment, the plasticity of differentiated cells, to name but a few. However the Hydra model system is not restricted to cell and developmental biology; during the past 270 years it has also been heavily used to investigate the relationships between Hydra and its environment, opening new horizons concerning neurophysiology, innate immunity, ecosystems, ecotoxicology, symbiosis...

  11. Modeling Multi-Level Systems

    CERN Document Server

    Iordache, Octavian

    2011-01-01

    This book is devoted to modeling of multi-level complex systems, a challenging domain for engineers, researchers and entrepreneurs, confronted with the transition from learning and adaptability to evolvability and autonomy for technologies, devices and problem solving methods. Chapter 1 introduces the multi-scale and multi-level systems and highlights their presence in different domains of science and technology. Methodologies as, random systems, non-Archimedean analysis, category theory and specific techniques as model categorification and integrative closure, are presented in chapter 2. Chapters 3 and 4 describe polystochastic models, PSM, and their developments. Categorical formulation of integrative closure offers the general PSM framework which serves as a flexible guideline for a large variety of multi-level modeling problems. Focusing on chemical engineering, pharmaceutical and environmental case studies, the chapters 5 to 8 analyze mixing, turbulent dispersion and entropy production for multi-scale sy...

  12. System Convergence in Transport Modelling

    DEFF Research Database (Denmark)

    Rich, Jeppe; Nielsen, Otto Anker; Cantarella, Guilio E.

    2010-01-01

    A fundamental premise of most applied transport models is the existence and uniqueness of an equilibrium solution that balances demand x(t) and supply t(x). The demand consists of the people that travel in the transport system and on the defined network, whereas the supply consists of the resulting...... level-of-service attributes (e.g., travel time and cost) offered to travellers. An important source of complexity is the congestion, which causes increasing demand to affect travel time in a non-linear way. Transport models most often involve separate models for traffic assignment and demand modelling...

  13. Management outcome of acute urinary retention: model of prediction.

    LENUS (Irish Health Repository)

    Daly, Padraig

    2012-01-31

    OBJECTIVES: To assess for predictors of outcome in patients presenting with acute urinary retention (AUR). METHODS: A study was performed in our unit to evaluate trial without catheter (TWOC) and successive management. We assessed for predictors of surgical or medical management, which included: age, volume drained at time of catheterisation, cause of retention, serum creatinine, success of trial of voiding, co-morbidities, prostate-specific antigen (PSA) and prostate size on digital rectal examination (DRE). RESULTS: 72 men were entered into the study over an 18-month period: 27 had a successful first TWOC, 20 patients had a second TWOC, and 6 were successful. In total, 31 of the 33 patients with a successful TWOC remained on alpha-blockers without a further episode of AUR within a minimum of 6 months\\' follow-up. Patients failing TWOC were managed by transurethral resection of the prostate (n = 22), long-term catheterisation (n = 15) or prostatic stents (n = 3), and 1 patient died prior to intervention. Three predictors were significant on multivariate analysis: PSA (>2.9 ng\\/ml), prostate size on DRE (large) and volume drained at time of catheterisation (>or=1,000 ml). CONCLUSION: Patients with elevated PSA (>2.9 ng\\/ml), a large prostate size on DRE and a volume drained at time of catheterisation >1,000 ml are best managed by surgical intervention, while those with volumes drained at time of catheterisation of <1,000 ml, a PSA

  14. Expression and clinical significance of rhubarb on serum amylase and TNF-alpha of rat model of acute pancreatitis.

    Science.gov (United States)

    Zhang, W F; Li, Z T; Fang, J J; Wang, G B; Yu, Y; Liu, Z Q; Wu, Y N; Zheng, S S; Cai, L

    2017-01-01

    The aim of this study was to evaluate the therapeutic effect of rhubarb extract on acute pancreatitis. Ninety-six healthy Sprague Dawley rats, weighing 301±5.12 g were randomly divided into 4 groups: sham surgery (group A), acute pancreatitis model (group B), acute pancreatitis with normal saline (group C), and acute pancreatitis model with rhubarb (group D). The levels of serum amylase (AMY) and TNF-α were measured at 1st, 6th, 12th and 24th hour after modeling, and the pancreatic tissue were used to observe the pathologic changes. Compared to the sham group, the serum AMY and serum tumor necrosis factor (TNF-α) levels were significantly increased in the other groups (p acute pancreatitis. The rhubarb reduced the serum AMY and TNF-α level in rats with acute pancreatitis and reduced the pathological changes of pancreas and other tissues.

  15. Hemodynamic support with the pulsatile catheter pump in a sheep model of acute heart failure

    NARCIS (Netherlands)

    Li, Zhicheng; Gu, Y. John; Ye, Qing; Cheng, Shaofei; Wang, Weijun; Tang, Min; Zhao, Xiaogang; Rakhorst, Gerhard; Chen, Changzhi

    2006-01-01

    This study was aimed to mimic clinical heart failure (HF) conditions and to assess the effect of pulsatilecatheter (PUCA) pump support on hemodynamics and tissue perfusion in a sheep model of acute HF. In 14 sheep, HF was induced by partial occluding the middle left circumflex coronary artery

  16. Large Dataset of Acute Oral Toxicity Data Created for Testing in Silico Models (ASCCT meeting)

    Science.gov (United States)

    Acute toxicity data is a common requirement for substance registration in the US. Currently only data derived from animal tests are accepted by regulatory agencies, and the standard in vivo tests use lethality as the endpoint. Non-animal alternatives such as in silico models are ...

  17. A porcine model of acute, haematogenous, localized osteomyelitis due to Staphylococcus aureus

    DEFF Research Database (Denmark)

    Johansen, Louise Kruse; Frees, Dorte; Aalbæk, Bent

    2011-01-01

    A porcine model of acute, haematogenous, localized osteomyelitis was established. Serial dilutions of Staphylococcus aureus [5–50–500–5000–50 000 CFU/kg body weight (BW) suspended in saline or saline alone] were inoculated into the right brachial artery of pigs (BW 15 kg) separated into six groups...

  18. A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures

    Science.gov (United States)

    2016-08-01

    intestinal lumen Cell Migration Radiation damages proliferating crypt cells, causing mitotic arrest and delaying regeneration Burns can...04-08-2016 Technical Report A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures HDTRA1...the small intestine , reducing the density of the gut barrier. A reduced epithelial lining can result in suppressed nutrient absorption, bacterial

  19. Development of Chronic and Acute Golden Syrian Hamster Infection Models with Leptospira borgpetersenii serovar Hardjo

    Science.gov (United States)

    The golden Syrian hamster (Mesocricetus auratus) is frequently used as a model to study virulence for several species of Leptospira. Onset of an acute, lethal infection following infection with several pathogenic Leptospira species has been widely adopted for vaccine testing. An important exceptio...

  20. Preliminary early evaluation of radiation acute syndrome severity in an animal model

    International Nuclear Information System (INIS)

    Gimenez, J.C.; Nasazzi, N.B.; Taja, M.R.; Nagle, C.; Dubner, D.; Di Rizzio, C.

    1992-01-01

    To improve the knowledge of Radiation Acute Syndrome radiopathological picture, whole body x-rays irradiation at 2Gy of a primate (Cebus apella paraguayanus) used as model has been performed. Early evaluations of clinical symptoms and dose and damage biological indicators have shown that this primate has given out similar responses to those of man. (author)

  1. Feedback mechanisms control coexistence in a stem cell model of acute myeloid leukaemia.

    Science.gov (United States)

    Crowell, Helena L; MacLean, Adam L; Stumpf, Michael P H

    2016-07-21

    Haematopoietic stem cell dynamics regulate healthy blood cell production and are disrupted during leukaemia. Competition models of cellular species help to elucidate stem cell dynamics in the bone marrow microenvironment (or niche), and to determine how these dynamics impact leukaemia progression. Here we develop two models that target acute myeloid leukaemia with particular focus on the mechanisms that control proliferation via feedback signalling. It is within regions of parameter space permissive of coexistence that the effects of competition are most subtle and the clinical outcome least certain. Steady state and linear stability analyses identify parameter regions that allow for coexistence to occur, and allow us to characterise behaviour near critical points. Where analytical expressions are no longer informative, we proceed statistically and sample parameter space over a coexistence region. We find that the rates of proliferation and differentiation of healthy progenitors exert key control over coexistence. We also show that inclusion of a regulatory feedback onto progenitor cells promotes healthy haematopoiesis at the expense of leukaemia, and that - somewhat paradoxically - within the coexistence region feedback increases the sensitivity of the system to dominance by one lineage over another. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Case Report: Systemic Lupus Erythematosus Presenting as Acute ...

    African Journals Online (AJOL)

    Systemic lupus erythematosus is a complex autoimmune disease with multisystem involvement with varied presentation. Autoimmune adrenal disease, on the other hand, can be associated with other autoimmune diseases. Adrenal insufficiency as a presenting feature of Systemic lupus erythematosus is a rare occurrence.

  3. Acute Stroke as the first manifestation of Systemic Lupus ...

    African Journals Online (AJOL)

    Systemic lupus erythematosus (SLE) is an autoimmune, multisystem disease that is characterized by a bewildering array of antibodies. Central nervous system manifestations of SLE are highly diverse and often have major prognostic consequences, accounting for 15% of cases. It is a known cause of 'stroke in the young' ...

  4. Acute resistance exercise induces antinociception by activation of the endocannabinoid system in rats.

    Science.gov (United States)

    Galdino, Giovane; Romero, Thiago; Silva, José Felippe Pinho da; Aguiar, Daniele; Paula, Ana Maria de; Cruz, Jader; Parrella, Cosimo; Piscitelli, Fabiana; Duarte, Igor; Di Marzo, Vincenzo; Perez, Andrea

    2014-09-01

    Resistance exercise (RE) is also known as strength training, and it is performed to increase the strength and mass of muscles, bone strength, and metabolism. RE has been increasingly prescribed for pain relief. However, the endogenous mechanisms underlying this antinociceptive effect are still largely unexplored. Thus, we investigated the involvement of the endocannabinoid system in RE-induced antinociception. Male Wistar rats were submitted to acute RE in a weight-lifting model. The nociceptive threshold was measured by a mechanical nociceptive test (paw pressure) before and after exercise. To investigate the involvement of cannabinoid receptors and endocannabinoids in RE-induced antinociception, cannabinoid receptor inverse agonists, endocannabinoid metabolizing enzyme inhibitors, and an anandamide reuptake inhibitor were injected before RE. After RE, CB1 cannabinoid receptors were quantified in rat brain tissue by Western blot and immunofluorescence. In addition, endocannabinoid plasma levels were measured by isotope dilution-liquid chromatography mass spectrometry. RE-induced antinociception was prevented by preinjection with CB1 and CB2 cannabinoid receptor inverse agonists. By contrast, preadministration of metabolizing enzyme inhibitors and the anandamide reuptake inhibitor prolonged and enhanced this effect. RE also produced an increase in the expression and activation of CB1 cannabinoid receptors in rat brain tissue and in the dorsolateral and ventrolateral periaqueductal regions and an increase in endocannabinoid plasma levels. The present study suggests that a single session of RE activates the endocannabinoid system to induce antinociception.

  5. Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota.

    Directory of Open Access Journals (Sweden)

    Eliane von Klitzing

    Full Text Available Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction.Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based methods. At day 7 post infection (p.i. with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney and systemic compartments including spleen and serum.With respect to the intestinal microbiota composition "humanized" mice display

  6. [Characteristics of antiischemic and nootropic properties of ademol in a rat model of acute brain ischemia].

    Science.gov (United States)

    Khodakivs'kyĭ, O A

    2013-01-01

    In experiments with the rat model of acute disorder of encephalic circulation (bilateral carotid occlusion) it was found that introduction of derivate of adamantan 1-adamantiloxy-3-morfolino-2 propanol (under conventional name ademol) in the dose 2 mg/kg intraabdominal in treatment regimen (in an hour after reconstruction of insult and further 1 time every 24 hours during 21 days) was accompanied by a recovery of mnemotropic properties and is more effective than cytikolin, resulting in a decreased lethality and neurological deficiency in acute and recovery periods of insults. The data received proved the usefulness of development of ademol based cerebroprotective remedy.

  7. Executive Information Systems' Multidimensional Models

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available Executive Information Systems are design to improve the quality of strategic level of management in organization through a new type of technology and several techniques for extracting, transforming, processing, integrating and presenting data in such a way that the organizational knowledge filters can easily associate with this data and turn it into information for the organization. These technologies are known as Business Intelligence Tools. But in order to build analytic reports for Executive Information Systems (EIS in an organization we need to design a multidimensional model based on the business model from the organization. This paper presents some multidimensional models that can be used in EIS development and propose a new model that is suitable for strategic business requests.

  8. The Development of a Machine Learning Inpatient Acute Kidney Injury Prediction Model.

    Science.gov (United States)

    Koyner, Jay L; Carey, Kyle A; Edelson, Dana P; Churpek, Matthew M

    2018-03-28

    To develop an acute kidney injury risk prediction model using electronic health record data for longitudinal use in hospitalized patients. Observational cohort study. Tertiary, urban, academic medical center from November 2008 to January 2016. All adult inpatients without pre-existing renal failure at admission, defined as first serum creatinine greater than or equal to 3.0 mg/dL, International Classification of Diseases, 9th Edition, code for chronic kidney disease stage 4 or higher or having received renal replacement therapy within 48 hours of first serum creatinine measurement. None. Demographics, vital signs, diagnostics, and interventions were used in a Gradient Boosting Machine algorithm to predict serum creatinine-based Kidney Disease Improving Global Outcomes stage 2 acute kidney injury, with 60% of the data used for derivation and 40% for validation. Area under the receiver operator characteristic curve (AUC) was calculated in the validation cohort, and subgroup analyses were conducted across admission serum creatinine, acute kidney injury severity, and hospital location. Among the 121,158 included patients, 17,482 (14.4%) developed any Kidney Disease Improving Global Outcomes acute kidney injury, with 4,251 (3.5%) developing stage 2. The AUC (95% CI) was 0.90 (0.90-0.90) for predicting stage 2 acute kidney injury within 24 hours and 0.87 (0.87-0.87) within 48 hours. The AUC was 0.96 (0.96-0.96) for receipt of renal replacement therapy (n = 821) in the next 48 hours. Accuracy was similar across hospital settings (ICU, wards, and emergency department) and admitting serum creatinine groupings. At a probability threshold of greater than or equal to 0.022, the algorithm had a sensitivity of 84% and a specificity of 85% for stage 2 acute kidney injury and predicted the development of stage 2 a median of 41 hours (interquartile range, 12-141 hr) prior to the development of stage 2 acute kidney injury. Readily available electronic health record data can be used

  9. Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions.

    Science.gov (United States)

    Dutta, Sara; Mincholé, Ana; Quinn, T Alexander; Rodriguez, Blanca

    2017-10-01

    Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models (ten Tusscher and Panfilov, 2006; Grandi et al., 2010; Carro et al., 2011; O'Hara et al., 2011) to simulate key electrophysiological consequences of acute myocardial ischemia in single cell and tissue simulations. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia. However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. ”Missing clot” during mechanical thrombectomy in acute stroke using Solitaire stent retrieval system

    Directory of Open Access Journals (Sweden)

    Vikram Huded

    2016-01-01

    Full Text Available Stent retrieval system is an established treatment modality in acute ischemic stroke with large vessel occlusion. Here, we describe a complication which occurred during mechanical thrombectomy in three cases where the clot dislodged during retrieval. There was a possibility of the clot getting reinjected into the artery with possible dire consequences.

  11. 77 FR 53257 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Science.gov (United States)

    2012-08-31

    ..., Hospital Inpatient Quality Reporting and Hospital Value-Based Purchasing--Program Administration... for Medicare & Medicaid Services 42 CFR Parts 412, 413, 424, et al. Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective...

  12. The effect of central nervous system involvement and irradiation in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Taskinen, Mervi; Oskarsson, Trausti; Levinsen, Mette

    2017-01-01

    BACKGROUND: Central nervous system irradiation (CNS-RT) has played a central role in the cure of acute lymphoblastic leukemia (ALL), but due to the risk of long-term toxicity, it is now considered a less-favorable method of CNS-directed therapy. PROCEDURES: Retrospectively, we estimated the effect...

  13. Excacerbation of systemic lupus erythematodes, aseptic meningitis and acute mental symptoms, following metrizamide lumbar myelography

    Energy Technology Data Exchange (ETDEWEB)

    Gelmers, H.J.

    1984-01-01

    A clinical constellation of excacerbation of systemic lupus erythematodes (SLE), together with aseptic meningitis, and acutre mental symptoms occurred following lumbar myelography with metrizamide. Excacerbation of SLE has not been previously described following myelography with any contrast agent. Meningeal reactions and acute mental symptoms have been reported earlier, but this clinical constellation is new.

  14. Excacerbation of systemic lupus erythematodes, aseptic meningitis and acute mental symptoms, following metrizamide lumbar myelography

    International Nuclear Information System (INIS)

    Gelmers, H.J.

    1984-01-01

    A clinical constellation of excacerbation of systemic lupus erythematodes (SLE), together with aseptic meningitis, and acutre mental symptoms occurred following lumbar myelography with metrizamide. Excacerbation of SLE has not been previously described following myelography with any contrast agent. Meningeal reactions and acute mental symptoms have been reported earlier, but this clinical constellation is new. (orig.)

  15. Numerical Modeling of Microelectrochemical Systems

    DEFF Research Database (Denmark)

    Adesokan, Bolaji James

    for the reactants in the bulk electrolyte that are traveling waves. The first paper presents the mathematical model which describes an electrochemical system and simulates an electroanalytical technique called cyclic voltammetry. The model is governed by a system of advection–diffusion equations with a nonlinear...... reaction term at the boundary. We investigate the effect of flow rates, scan rates, and concentration on the cyclic voltammetry. We establish that high flow rates lead to the reduced hysteresis in the cyclic voltammetry curves and increasing scan rates lead to more pronounced current peaks. The final part...... of the paper shows that the response current in a cyclic voltammetry increases proportionally to the electrolyte concentration. In the second paper we present an experiment of an electrochemical system in a microfluidc system and compare the result to the numerical solutions. We investigate how the position...

  16. System Code Models and Capabilities

    International Nuclear Information System (INIS)

    Bestion, D.

    2008-01-01

    System thermalhydraulic codes such as RELAP, TRACE, CATHARE or ATHLET are now commonly used for reactor transient simulations. The whole methodology of code development is described including the derivation of the system of equations, the analysis of experimental data to obtain closure relation and the validation process. The characteristics of the models are briefly presented starting with the basic assumptions, the system of equations and the derivation of closure relationships. An extensive work was devoted during the last three decades to the improvement and validation of these models, which resulted in some homogenisation of the different codes although separately developed. The so called two-fluid model is the common basis of these codes and it is shown how it can describe both thermal and mechanical nonequilibrium. A review of some important physical models allows to illustrate the main capabilities and limitations of system codes. Attention is drawn on the role of flow regime maps, on the various methods for developing closure laws, on the role of interfacial area and turbulence on interfacial and wall transfers. More details are given for interfacial friction laws and their relation with drift flux models. Prediction of chocked flow and CFFL is also addressed. Based on some limitations of the present generation of codes, perspectives for future are drawn.

  17. Experimental Modeling of Dynamic Systems

    DEFF Research Database (Denmark)

    Knudsen, Morten Haack

    2006-01-01

    An engineering course, Simulation and Experimental Modeling, has been developed that is based on a method for direct estimation of physical parameters in dynamic systems. Compared with classical system identification, the method appears to be easier to understand, apply, and combine with physical...... insight. It is based on a sensitivity approach that is useful for choice of model structure, for experiment design, and for accuracy verification. The method is implemented in the Matlab toolkit Senstools. The method and the presentation have been developed with generally preferred learning styles in mind...

  18. Building and verifying a severity prediction model of acute pancreatitis (AP) based on BISAP, MEWS and routine test indexes.

    Science.gov (United States)

    Ye, Jiang-Feng; Zhao, Yu-Xin; Ju, Jian; Wang, Wei

    2017-10-01

    To discuss the value of the Bedside Index for Severity in Acute Pancreatitis (BISAP), Modified Early Warning Score (MEWS), serum Ca2+, similarly hereinafter, and red cell distribution width (RDW) for predicting the severity grade of acute pancreatitis and to develop and verify a more accurate scoring system to predict the severity of AP. In 302 patients with AP, we calculated BISAP and MEWS scores and conducted regression analyses on the relationships of BISAP scoring, RDW, MEWS, and serum Ca2+ with the severity of AP using single-factor logistics. The variables with statistical significance in the single-factor logistic regression were used in a multi-factor logistic regression model; forward stepwise regression was used to screen variables and build a multi-factor prediction model. A receiver operating characteristic curve (ROC curve) was constructed, and the significance of multi- and single-factor prediction models in predicting the severity of AP using the area under the ROC curve (AUC) was evaluated. The internal validity of the model was verified through bootstrapping. Among 302 patients with AP, 209 had mild acute pancreatitis (MAP) and 93 had severe acute pancreatitis (SAP). According to single-factor logistic regression analysis, we found that BISAP, MEWS and serum Ca2+ are prediction indexes of the severity of AP (P-valueprediction index of AP severity (P-value>0.05). The multi-factor logistic regression analysis showed that BISAP and serum Ca2+ are independent prediction indexes of AP severity (P-valueprediction index of AP severity (P-value>0.05); BISAP is negatively related to serum Ca2+ (r=-0.330, P-valuemodel is as follows: ln()=7.306+1.151*BISAP-4.516*serum Ca2+. The predictive ability of each model for SAP follows the order of the combined BISAP and serum Ca2+ prediction model>Ca2+>BISAP. There is no statistical significance for the predictive ability of BISAP and serum Ca2+ (P-value>0.05); however, there is remarkable statistical significance for

  19. Mouse models of acute and chronic hepacivirus infection

    DEFF Research Database (Denmark)

    Billerbeck, Eva; Wolfisberg, Raphael; Fahnøe, Ulrik

    2017-01-01

    An estimated 71 million people worldwide are infected with hepatitis C virus (HCV). The lack of small-animal models has impeded studies of antiviral immune mechanisms. Here we show that an HCV-related hepacivirus discovered in Norway rats can establish high-titer hepatotropic infections in labora......An estimated 71 million people worldwide are infected with hepatitis C virus (HCV). The lack of small-animal models has impeded studies of antiviral immune mechanisms. Here we show that an HCV-related hepacivirus discovered in Norway rats can establish high-titer hepatotropic infections...... provide mechanistic insights into hepatic antiviral immunity, a prerequisite for the development of HCV vaccines....

  20. Compositional Modeling of Biological Systems

    OpenAIRE

    Zámborszky, Judit

    2010-01-01

    Molecular interactions are wired in a fascinating way resulting in complex behavior of bio-logical systems. Theoretical modeling provides us a useful framework for understanding the dynamics and the function of such networks. The complexity of the biological systems calls for conceptual tools that manage the combinatorial explosion of the set of possible interac-tions. A suitable conceptual tool to attack complexity is compositionality, already success-fully used in the process algebra field ...

  1. Scintigraphic and Endoscopic Evaluation of Radiation-induced Acute Gastrointestinal Syndrome in Micro-pig Model

    International Nuclear Information System (INIS)

    Lee, Seung-Sook; Kim, Kyung-Min; Kim, Jin; Jang, Won-Suk; Lee, Jung-Eun; Kim, Noo-Ri; Lee, Sun-Joo; Kim, Mi-Sook; Ji, Young-Hoon; Cheon, Gi-Jeong; Lim, Sang-Moo

    2007-01-01

    Micro-pig model can be served as a proper substitute for humans in studying acute radiation syndrome following radiation-exposure accidents, especially showing similar clinico-pathologic response of hematopoietic and gastrointestinal (GI) syndrome to human. Among acute GI syndrome induced by radiation, GI motility disturbance has not been studied, however, it would be important in a viewpoint of affecting infectious progression from GI tract. Here, we employed scintigraphy of GI transit time and sequential endoscopic examination and tissue sampling in micropigs followed by abdominal radiation exposure. The specific aims of this study are to evaluate objective evidence of GI motility disturbance by scintigraphic evaluation and to find corresponding clinicoapthologic changes in radiation-induced acute GI syndrome

  2. A Model of Acute Antibody-Mediated Renal Allograft Rejection in the Sensitized Rata.

    Science.gov (United States)

    Chandran, Sharmila Ramessur; Mulley, William R; Kanellis, John; Nikolic-Paterson, David J; Ma, Frank Y

    2017-07-31

    Antibody-mediated rejection in transplant recipients with preexisting donor-specific antibodies is a challenging clinical situation. However, we lack suitable animal models to study this scenario. The aim of this study was to develop an animal model of acute antibody-mediated rejection of renal allografts in sensitized recipients. We used major histocompatibility complex class I and II incompatible rat strains (Dark Agouti RT1av1 and Lewis RT1l), which develop aggressive rejection. Recipient Lewis rats were immunized with donor strain spleen cells 5 days before surgery to induce donor-specific antibodies. Rats underwent bilateral nephrectomy and orthotopic transplant of the donor kidney. To minimize T-cell-mediated rejection while allowing the development of donor-specific antibodies, recipient animals were given tacrolimus starting the day before surgery. Hyperacute rejection was not seen, but acute graft dysfunction was evident on day 1 with a rapid deterioration of graft function by day 3. Histologic damage featured glomerulopathy, capillaritis, capillary thrombosis, and acute tubular injury. Recipients exhibited high serum levels of donor-specific antibodies and deposition of immunoglobulin G and C4d on graft endothelium. Immunostaining showed substantial endothelial damage, fibrin deposition in glomerular and peritubular capillaries, and infiltrates of macrophages, neutrophils, and natural killer cells. T-cell activation was efficiently suppressed by tacrolimus. We have developed a clinically relevant model of acute antibody-mediated rejection in recipients with preexisting donor-specific antibodies, which is suitable for testing novel therapies.

  3. Do diabetes mellitus and systemic hypertension predispose to left ventricular free wall rupture in acute myocardial infarction?

    DEFF Research Database (Denmark)

    Melchior, T; Hildebrant, P; Køber, L

    1997-01-01

    Diabetes and systemic hypertension had no influence on left ventricular free wall rupture complicating acute myocardial infarction. Age <65 years and a history of coronary artery disease offers some protection from protection.......Diabetes and systemic hypertension had no influence on left ventricular free wall rupture complicating acute myocardial infarction. Age artery disease offers some protection from protection....

  4. Systemic acute-phase reactants, C-reactive protein and haptoglobin, in adult periodontitis

    Science.gov (United States)

    EBERSOLE, J L; MACHEN, R L; STEFFEN, M J; WILLMANN, D E

    1997-01-01

    Capture ELISAs with biotinylated monospecific antibodies were developed to detect both C-reactive protein (CRP) and haptoglobin (Hp) in serum of adult periodontitis (AP) patients and normal subjects. Each acute-phase reactant was significantly increased in serum from AP patients with CRP at 9.12 ±1.61 mg/l versus 2.17 ± 0.41 mg/l (P acute-phase reactants. The conclusions are that either these molecules are formed locally and distributed to the serum, or these presumably localized infections impact upon the systemic components of the host protective responses. PMID:9030874

  5. Parametric Modeling for Fluid Systems

    Science.gov (United States)

    Pizarro, Yaritzmar Rosario; Martinez, Jonathan

    2013-01-01

    Fluid Systems involves different projects that require parametric modeling, which is a model that maintains consistent relationships between elements as is manipulated. One of these projects is the Neo Liquid Propellant Testbed, which is part of Rocket U. As part of Rocket U (Rocket University), engineers at NASA's Kennedy Space Center in Florida have the opportunity to develop critical flight skills as they design, build and launch high-powered rockets. To build the Neo testbed; hardware from the Space Shuttle Program was repurposed. Modeling for Neo, included: fittings, valves, frames and tubing, between others. These models help in the review process, to make sure regulations are being followed. Another fluid systems project that required modeling is Plant Habitat's TCUI test project. Plant Habitat is a plan to develop a large growth chamber to learn the effects of long-duration microgravity exposure to plants in space. Work for this project included the design and modeling of a duct vent for flow test. Parametric Modeling for these projects was done using Creo Parametric 2.0.

  6. Acute viral infections of the central nervous system, 2014-2016, Greece.

    Science.gov (United States)

    Papa, Anna; Papadopoulou, Elpida

    2018-04-01

    In order to investigate the viral etiology of acute infections of central nervous system (CNS), multiplex and single PCRs combined with serology for arboviruses were applied on samples from 132 hospitalized patients in Greece during May 2014-December 2016. A viral pathogen was detected in 52 of 132 (39.4%) cases with acute CNS infection. Enteroviruses predominated (15/52, 28.8%), followed by West Nile virus (9/52, 17.3%). Phleboviruses, varicella-zoster virus, and Epstein-Barr virus accounted for 15.4%, 13.5%, and 11.5% of the cases, respectively. The study gives an insight into the etiology of viral CNS infections in a Mediterranean country, where arboviruses should be included in the differential diagnosis of acute CNS infections. © 2017 Wiley Periodicals, Inc.

  7. Mathematical Models of Human Hematopoiesis Following Acute Radiation Exposure

    Science.gov (United States)

    2014-05-01

    mediator to the action of known hematopoietic stimulators such as thrombopoietin ( TPO ) and granulocyte colony-stimulating factor (G-CSF). Thus, in our...significant stimulatory role of TPO in thrombopoiesis (Kaushansky 2005), it is assumed to represent a large portion of the generic mediator. Thus, known...biological mechanisms involving TPO are used to justify the effects of the generic mediator in our model. TPO concentration is regulated by platelets

  8. Acute asthma severity identification of expert system flow in emergency department

    Science.gov (United States)

    Sharif, Nurul Atikah Mohd; Ahmad, Norazura; Ahmad, Nazihah; Desa, Wan Laailatul Hanim Mat

    2017-11-01

    Integration of computerized system in healthcare management help in smoothening the documentation of patient records, highly accesses of knowledge and clinical practices guideline, and advice on decision making. Exploit the advancement of artificial intelligent such as fuzzy logic and rule-based reasoning may improve the management of emergency department in terms of uncertainty condition and medical practices adherence towards clinical guideline. This paper presenting details of the emergency department flow for acute asthma severity identification with the embedding of acute asthma severity identification expert system (AASIES). Currently, AASIES is still in preliminary stage of system validation. However, the implementation of AASIES in asthma bay management is hope can reduce the usage of paper for manual documentation and be a pioneer for the development of a more complex decision support system to smoothen the ED management and more systematic.

  9. Model checking embedded system designs

    NARCIS (Netherlands)

    Brinksma, Hendrik; Mader, Angelika H.

    2002-01-01

    Model checking has established itself as a successful tool supported technique for the verification and debugging of various hardware and software systems [16]. Not only in academia, but also by industry this technique is increasingly being regarded as a promising and practical proposition,

  10. GENERIC model for multiphase systems

    NARCIS (Netherlands)

    Sagis, L.M.C.

    2010-01-01

    GENERIC is a nonequilibrium thermodynamic formalism in which the dynamic behavior of a system is described by a single compact equation involving two types of brackets: a Poisson bracket and a dissipative bracket. This formalism has proved to be a very powerful instrument to model the dynamic

  11. An extensible analysable system model

    DEFF Research Database (Denmark)

    Probst, Christian W.; Hansen, Rene Rydhof

    2008-01-01

    Analysing real-world systems for vulnerabilities with respect to security and safety threats is a difficult undertaking, not least due to a lack of availability of formalisations for those systems. While both formalisations and analyses can be found for artificial systems such as software......, this does not hold for real physical systems. Approaches such as threat modelling try to target the formalisation of the real-world domain, but still are far from the rigid techniques available in security research. Many currently available approaches to assurance of critical infrastructure security...... are based on (quite successful) ad-hoc techniques. We believe they can be significantly improved beyond the state-of-the-art by pairing them with static analyses techniques. In this paper we present an approach to both formalising those real-world systems, as well as providing an underlying semantics, which...

  12. Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

    Science.gov (United States)

    Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

    2013-05-01

    Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

  13. Acute systemic inflammatory response after cardiac surgery in ...

    African Journals Online (AJOL)

    2017-09-03

    Sep 3, 2017 ... pandemic, there have been various concerns about the operative risks, infections and benefits of cardiac surgery in patients infected with HIV, as they are known to al- ready have a compromised immune system, chronic in- flammation and reduced survival.1,2 This led to cardiac surgery departments setting ...

  14. A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with Acute Myeloid Leukemia.

    Science.gov (United States)

    Sloan, Caroline E; Luskin, Marlise R; Boccuti, Anne M; Sehgal, Alison R; Zhao, Jianhua; Daber, Robert D; Morrissette, Jennifer J D; Luger, Selina M; Bagg, Adam; Gimotty, Phyllis A; Carroll, Martin

    2016-01-01

    Although cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML), overall survival (OS) remains highly variable within risk groups. An integrated genetic prognostic (IGP) model using cytogenetics plus mutations in nine genes was recently proposed for patients ≤60 years to improve classification. This model has not been validated in clinical practice. We retrospectively studied 197 patients with newly diagnosed de novo AML. We compared OS curves among the mutational profiles defined by the IGP model. The IGP model assigned patients with intermediate cytogenetics as having favorable, intermediate or unfavorable mutational profiles. The IGP model reassigned 50 of 137 patients with intermediate cytogenetics to favorable or unfavorable mutational profiles. Median OS was 2.8 years among 14 patients with intermediate cytogenetics and favorable mutational profiles (mutant NPM1 and mutant IDH1 or IDH2) and 1.3 years among patients with intermediate mutational profiles. Among patients with intermediate cytogenetics labeled as having unfavorable mutational profiles, median OS was 0.8 years among 24 patients with FLT3-ITD positive AML and high-risk genetic changes (trisomy 8, TET2 and/or DNMT3A) and 1.7 years among 12 patients with FLT3-ITD negative AML and high-risk mutations (TET2, ASXL1 and/or PHF6). OS for patients with intermediate cytogenetics and favorable mutational profiles was similar to OS for patients with favorable cytogenetics (p = 0.697) and different from patients with intermediate cytogenetics and intermediate mutational profiles (p = 0.028). OS among patients with FLT3-ITD positive AML and high-risk genetic changes was similar to patients with unfavorable cytogenetics (p = 0.793) and different from patients with intermediate IGP profile (p = 0.022). Patients with FLT3-ITD negative AML and high-risk mutations, defined as 'unfavorable' in the IGP model, had OS similar to patients with intermediate IGP profile (p = 0

  15. A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with Acute Myeloid Leukemia.

    Directory of Open Access Journals (Sweden)

    Caroline E Sloan

    Full Text Available Although cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML, overall survival (OS remains highly variable within risk groups. An integrated genetic prognostic (IGP model using cytogenetics plus mutations in nine genes was recently proposed for patients ≤60 years to improve classification. This model has not been validated in clinical practice.We retrospectively studied 197 patients with newly diagnosed de novo AML. We compared OS curves among the mutational profiles defined by the IGP model. The IGP model assigned patients with intermediate cytogenetics as having favorable, intermediate or unfavorable mutational profiles. The IGP model reassigned 50 of 137 patients with intermediate cytogenetics to favorable or unfavorable mutational profiles. Median OS was 2.8 years among 14 patients with intermediate cytogenetics and favorable mutational profiles (mutant NPM1 and mutant IDH1 or IDH2 and 1.3 years among patients with intermediate mutational profiles. Among patients with intermediate cytogenetics labeled as having unfavorable mutational profiles, median OS was 0.8 years among 24 patients with FLT3-ITD positive AML and high-risk genetic changes (trisomy 8, TET2 and/or DNMT3A and 1.7 years among 12 patients with FLT3-ITD negative AML and high-risk mutations (TET2, ASXL1 and/or PHF6. OS for patients with intermediate cytogenetics and favorable mutational profiles was similar to OS for patients with favorable cytogenetics (p = 0.697 and different from patients with intermediate cytogenetics and intermediate mutational profiles (p = 0.028. OS among patients with FLT3-ITD positive AML and high-risk genetic changes was similar to patients with unfavorable cytogenetics (p = 0.793 and different from patients with intermediate IGP profile (p = 0.022. Patients with FLT3-ITD negative AML and high-risk mutations, defined as 'unfavorable' in the IGP model, had OS similar to patients with intermediate IGP profile (p

  16. Systems modeling for laser IFE

    Science.gov (United States)

    Meier, W. R.; Raffray, A. R.; Sviatoslavsky, I. N.

    2006-06-01

    A systems model of a laser-driven IFE power plant is being developed to assist in design trade-offs and optimization. The focus to date has been on modeling the fusion chamber, blanket and power conversion system. A self-consistent model has been developed to determine key chamber and thermal cycle parameters (e.g., chamber radius, structure and coolant temperatures, cycle efficiency, etc.) as a function of the target yield and pulse repetition rate. Temperature constraints on the tungsten armor, ferritic steel wall, and structure/coolant interface are included in evaluating the potential design space. Results are presented for a lithium cooled first wall coupled with a Brayton power cycle. LLNL work performed under the auspices of the US Department of Energy by the University of California LLNL under Contract W-7405-Eng-48.

  17. Cotangent Models for Integrable Systems

    Science.gov (United States)

    Kiesenhofer, Anna; Miranda, Eva

    2017-03-01

    We associate cotangent models to a neighbourhood of a Liouville torus in symplectic and Poisson manifolds focusing on b-Poisson/ b-symplectic manifolds. The semilocal equivalence with such models uses the corresponding action-angle theorems in these settings: the theorem of Liouville-Mineur-Arnold for symplectic manifolds and an action-angle theorem for regular Liouville tori in Poisson manifolds (Laurent- Gengoux et al., IntMath Res Notices IMRN 8: 1839-1869, 2011). Our models comprise regular Liouville tori of Poisson manifolds but also consider the Liouville tori on the singular locus of a b-Poisson manifold. For this latter class of Poisson structures we define a twisted cotangent model. The equivalence with this twisted cotangent model is given by an action-angle theorem recently proved by the authors and Scott (Math. Pures Appl. (9) 105(1):66-85, 2016). This viewpoint of cotangent models provides a new machinery to construct examples of integrable systems, which are especially valuable in the b-symplectic case where not many sources of examples are known. At the end of the paper we introduce non-degenerate singularities as lifted cotangent models on b-symplectic manifolds and discuss some generalizations of these models to general Poisson manifolds.

  18. Development and validation of a dynamic outcome prediction model for paracetamol-induced acute liver failure

    DEFF Research Database (Denmark)

    Bernal, William; Wang, Yanzhong; Maggs, James

    2016-01-01

    BACKGROUND: Early, accurate prediction of survival is central to management of patients with paracetamol-induced acute liver failure to identify those needing emergency liver transplantation. Current prognostic tools are confounded by recent improvements in outcome independent of emergency liver...... transplantation, and constrained by static binary outcome prediction. We aimed to develop a simple prognostic tool to reflect current outcomes and generate a dynamic updated estimation of risk of death. METHODS: Patients with paracetamol-induced acute liver failure managed at intensive care units in the UK...... normalised ratio (INR), and cardiovascular failure were used to derive an initial predictive model, with a second (day 2) model including additional changes in INR and lactate. FINDINGS: We developed and validated new high-performance statistical models to support decision making in patients with paracetamol...

  19. Characterization of inflammation in a rat model of acute lung injury after repeated pulmonary lavage.

    Science.gov (United States)

    Menk, Mario; Graw, Jan Adriaan; Steinkraus, Henrik; Haefen, Clarissa von; Sifringer, Marco; Spies, Claudia D; Lachmann, Burkhard; Schwaiberger, David

    2015-01-01

    Repeated pulmonary lavage allows to reliably reproduce failure of gas exchange and major histological findings of acute lung injury (ALI). However, because the capacity of pulmonary lavage to induce pulmonary inflammation is not well established in rodents, this study aims to characterize the induction of pulmonary inflammation in a rat model of ALI. Male adult rats were divided into a treatment group (n = 9) that received pulmonary lavage with consecutive mechanical ventilation, and a control group that received mechanical ventilation only (n = 9). Arterial blood gas analyses were performed every 30 min throughout the study. Pressure-volume curves, and lung tissue and plasma samples, were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid was assessed. Transcriptional and translational regulation of pro- and anti-inflammatory cytokines IL-1β, TNF-α, IL-6, and IL-10 was determined in lungs and plasma. Markers of cellular stress were measured in lung tissue. Pulmonary lavage significantly decreased lung compliance, induced hypoxia and hypercapnia, and mediated respiratory acidosis. Protein content of lavage fluid was significantly increased and contained washed out surfactant. Expression of IL-1β, TNF-α, and IL-6 mRNA and protein expression of IL-1β and TNF-α was significantly induced in lavaged lungs, without spillover into the systemic circulation. Markers of cellular stress were significantly upregulated in lavaged lungs. This model of ALI applied in rats can induce pulmonary inflammation. The model might be used to develop therapeutic strategies that target pulmonary inflammation in ALI.

  20. Early immunopathological events in acute model of mycobacterial hypersensitivity pneumonitis in mice.

    Science.gov (United States)

    Johansson, Elisabet; Boivin, Gregory P; Yadav, Jagjit S

    2017-12-01

    Prolonged exposure to antigens of non-tuberculous mycobacteria species colonizing industrial metalworking fluid (MWF), particularly Mycobacterium immunogenum (MI), has been implicated in chronic forms of hypersensitivity pneumonitis (HP) in machinists based on epidemiology studies and long-term exposure of mouse models. However, a role of short-term acute exposure to these antigens has not been described in the context of acute forms of HP. This study investigated short-term acute exposure of mice to MI cell lysate (or live cell suspension) via oropharyngeal aspiration. The results showed there was a dose- and time-dependent increase (peaking at 2 h post-instillation) in lung immunological responses in terms of the pro- (TNFα, IL-6, IL-1β) and anti-inflammatory (IL-10) cytokines. Bronchoalveolar lavage and histology showed neutrophils as the predominant infiltrating cell type, with lymphocytes mice led to a transient early immunopathologic response, with little adaptive immunity, which is consistent with events associated with human acute forms of HP. Screening of MWF-originated mycobacterial genotypes/variants (six of MI, four of M. chelonae, two of M. abscessus) showed both inter- and intra-species differences, with MI genotype MJY10 being the most immunogenic. In conclusion, this study characterized the first short-term mycobacterial exposure mouse model that mimics acute HP in machinists; this could serve as a potentially useful model for rapid screening of field MWF-associated mycobacteria for routine and timely occupational risk assessment and for investigating early biomarkers and mechanisms of this understudied immune lung disease.

  1. Paraquat poisoning: an experimental model of dose-dependent acute lung injury due to surfactant dysfunction

    Directory of Open Access Journals (Sweden)

    M.F.R. Silva

    1998-03-01

    Full Text Available Since the most characteristic feature of paraquat poisoning is lung damage, a prospective controlled study was performed on excised rat lungs in order to estimate the intensity of lesion after different doses. Twenty-five male, 2-3-month-old non-SPF Wistar rats, divided into 5 groups, received paraquat dichloride in a single intraperitoneal injection (0, 1, 5, 25, or 50 mg/kg body weight 24 h before the experiment. Static pressure-volume (PV curves were performed in air- and saline-filled lungs; an estimator of surface tension and tissue works was computed by integrating the area of both curves and reported as work/ml of volume displacement. Paraquat induced a dose-dependent increase of inspiratory surface tension work that reached a significant two-fold order of magnitude for 25 and 50 mg/kg body weight (P<0.05, ANOVA, sparing lung tissue. This kind of lesion was probably due to functional abnormalities of the surfactant system, as was shown by the increase in the hysteresis of the paraquat groups at the highest doses. Hence, paraquat poisoning provides a suitable model of acute lung injury with alveolar instability that can be easily used in experimental protocols of mechanical ventilation

  2. Graph modeling systems and methods

    Science.gov (United States)

    Neergaard, Mike

    2015-10-13

    An apparatus and a method for vulnerability and reliability modeling are provided. The method generally includes constructing a graph model of a physical network using a computer, the graph model including a plurality of terminating vertices to represent nodes in the physical network, a plurality of edges to represent transmission paths in the physical network, and a non-terminating vertex to represent a non-nodal vulnerability along a transmission path in the physical network. The method additionally includes evaluating the vulnerability and reliability of the physical network using the constructed graph model, wherein the vulnerability and reliability evaluation includes a determination of whether each terminating and non-terminating vertex represents a critical point of failure. The method can be utilized to evaluate wide variety of networks, including power grid infrastructures, communication network topologies, and fluid distribution systems.

  3. Prophylactic radiotherapy for central nervous system in acute leukemias

    International Nuclear Information System (INIS)

    Faria, S.L.; Ferrigno, R.

    1994-01-01

    Prophylaxis of the central nervous system in leukemias is a complex problem and there is no optimal solution that is universal for all patients. Radiation therapy, because of its CNS toxicity and potential carcinogenicity, is reserved for those in the highest risk groups. The cranial radiation dose is 18 Gy, while the spinal cord is treated with intrathecal methotrexate or multidrug therapy. The authors describe the basic aspects of radiation therapy treatment planning, as the main areas that should be included in treatment field, in order to guarantee favourable results. (author)

  4. An open source 3-d printed modular micro-drive system for acute neurophysiology.

    Directory of Open Access Journals (Sweden)

    Shaun R Patel

    Full Text Available Current, commercial, electrode micro-drives that allow independent positioning of multiple electrodes are expensive. Custom designed solutions developed by individual laboratories require fabrication by experienced machinists working in well equipped machine shops and are therefore difficult to disseminate into widespread use. Here, we present an easy to assemble modular micro-drive system for acute primate neurophysiology (PriED that utilizes rapid prototyping (3-d printing and readily available off the shelf-parts. The use of 3-d printed parts drastically reduces the cost of the device, making it available to labs without the resources of sophisticated machine shops. The direct transfer of designs from electronic files to physical parts also gives researchers opportunities to easily modify and implement custom solutions to specific recording needs. We also demonstrate a novel model of data sharing for the scientific community: a publicly available repository of drive designs. Researchers can download the drive part designs from the repository, print, assemble and then use the drives. Importantly, users can upload their modified designs with annotations making them easily available for others to use.

  5. Probabilistic models for feedback systems.

    Energy Technology Data Exchange (ETDEWEB)

    Grace, Matthew D.; Boggs, Paul T.

    2011-02-01

    In previous work, we developed a Bayesian-based methodology to analyze the reliability of hierarchical systems. The output of the procedure is a statistical distribution of the reliability, thus allowing many questions to be answered. The principal advantage of the approach is that along with an estimate of the reliability, we also can provide statements of confidence in the results. The model is quite general in that it allows general representations of all of the distributions involved, it incorporates prior knowledge into the models, it allows errors in the 'engineered' nodes of a system to be determined by the data, and leads to the ability to determine optimal testing strategies. In this report, we provide the preliminary steps necessary to extend this approach to systems with feedback. Feedback is an essential component of 'complexity' and provides interesting challenges in modeling the time-dependent action of a feedback loop. We provide a mechanism for doing this and analyze a simple case. We then consider some extensions to more interesting examples with local control affecting the entire system. Finally, a discussion of the status of the research is also included.

  6. Stochastic Modelling of Hydrologic Systems

    DEFF Research Database (Denmark)

    Jonsdottir, Harpa

    2007-01-01

    In this PhD project several stochastic modelling methods are studied and applied on various subjects in hydrology. The research was prepared at Informatics and Mathematical Modelling at the Technical University of Denmark. The thesis is divided into two parts. The first part contains an introduct......In this PhD project several stochastic modelling methods are studied and applied on various subjects in hydrology. The research was prepared at Informatics and Mathematical Modelling at the Technical University of Denmark. The thesis is divided into two parts. The first part contains...... an introduction and an overview of the papers published. Then an introduction to basic concepts in hydrology along with a description of hydrological data is given. Finally an introduction to stochastic modelling is given. The second part contains the research papers. In the research papers the stochastic methods...... are described, as at the time of publication these methods represent new contribution to hydrology. The second part also contains additional description of software used and a brief introduction to stiff systems. The system in one of the papers is stiff....

  7. Dynamic Measurement of Disease Activity in Acute Pancreatitis: The Pancreatitis Activity Scoring System.

    Science.gov (United States)

    Wu, Bechien U; Batech, Michael; Quezada, Michael; Lew, Daniel; Fujikawa, Kelly; Kung, Jonathan; Jamil, Laith H; Chen, Wansu; Afghani, Elham; Reicher, Sonya; Buxbaum, James; Pandol, Stephen J

    2017-07-01

    Acute pancreatitis has a highly variable course. Currently there is no widely accepted method to measure disease activity in patients hospitalized for acute pancreatitis. We aimed to develop a clinical activity index that incorporates routine clinical parameters to assist in the measurement, study, and management of acute pancreatitis. We used the UCLA/RAND appropriateness method to identify items for inclusion in the disease activity instrument. We conducted a systematic literature review followed by two sets of iterative modified Delphi meetings including a panel of international experts between November 2014 and November 2015. The final instrument was then applied to patient data obtained from five separate study cohorts across Southern California to assess profiles of disease activity. From a list of 35 items comprising 6 domains, we identified 5 parameters for inclusion in the final weighted clinical activity scoring system: organ failure, systemic inflammatory response syndrome, abdominal pain, requirement for opiates and ability to tolerate oral intake. We applied the weighted scoring system across the 5 study cohorts comprising 3,123 patients. We identified several distinct patterns of disease activity: (i) overall there was an elevated score at baseline relative to discharge across all study cohorts, (ii) there were distinct patterns of disease activity related to duration of illness as well as (iii) early and persistent elevation of disease activity among patients with severe acute pancreatitis defined as persistent organ failure. We present the development and initial validation of a clinical activity score for real-time assessment of disease activity in patients with acute pancreatitis.

  8. Discrete modelling of drapery systems

    Science.gov (United States)

    Thoeni, Klaus; Giacomini, Anna

    2016-04-01

    Drapery systems are an efficient and cost-effective measure in preventing and controlling rockfall hazards on rock slopes. The simplest form consists of a row of ground anchors along the top of the slope connected to a horizontal support cable from which a wire mesh is suspended down the face of the slope. Such systems are generally referred to as simple or unsecured draperies (Badger and Duffy 2012). Variations such as secured draperies, where a pattern of ground anchors is incorporated within the field of the mesh, and hybrid systems, where the upper part of an unsecured drapery is elevated to intercept rockfalls originating upslope of the installation, are becoming more and more popular. This work presents a discrete element framework for simulation of unsecured drapery systems and its variations. The numerical model is based on the classical discrete element method (DEM) and implemented into the open-source framework YADE (Šmilauer et al., 2010). The model takes all relevant interactions between block, drapery and slope into account (Thoeni et al., 2014) and was calibrated and validated based on full-scale experiments (Giacomini et al., 2012).The block is modelled as a rigid clump made of spherical particles which allows any shape to be approximated. The drapery is represented by a set of spherical particle with remote interactions. The behaviour of the remote interactions is governed by the constitutive behaviour of the wire and generally corresponds to a piecewise linear stress-strain relation (Thoeni et al., 2013). The same concept is used to model wire ropes. The rock slope is represented by rigid triangular elements where material properties (e.g., normal coefficient of restitution, friction angle) are assigned to each triangle. The capabilities of the developed model to simulate drapery systems and estimate the residual hazard involved with such systems is shown. References Badger, T.C., Duffy, J.D. (2012) Drapery systems. In: Turner, A.K., Schuster R

  9. Importance of brood maintenance terms in simple models of the honeybee - Varroa destructor - acute bee paralysis virus complex

    Directory of Open Access Journals (Sweden)

    Hermann J. Eberl

    2010-09-01

    Full Text Available We present a simple mathematical model of the infestation of a honeybee colony by the Acute Paralysis Virus, which is carried by parasitic varroa mites (Varroa destructor. This is a system of nonlinear ordinary differential equations for the dependent variables: number of mites that carry the virus, number of healthy bees and number of sick bees. We study this model with a mix of analytical and computational techniques. Our results indicate that, depending on model parameters and initial data, bee colonies in which the virus is present can, over years, function seemingly like healthy colonies before they decline and disappear rapidly (e.g. Colony Collapse Disorder, wintering losses. This is a consequence of the fact that a certain number of worker bees is required in a colony to maintain and care for the brood, in order to ensure continued production of new bees.

  10. Intra- and interrater reliability of three different MRI grading and classification systems after acute hamstring injuries

    International Nuclear Information System (INIS)

    Wangensteen, Arnlaug; Tol, Johannes L.; Roemer, Frank W.; Bahr, Roald; Dijkstra, H. Paul; Crema, Michel D.; Farooq, Abdulaziz; Guermazi, Ali

    2017-01-01

    Highlights: • Three different MRI grading and classification systems for acute hamstring injuries are overall reliable. • Reliability for the subcategories within these MRI grading and classification systems remains, however, unclear. - Abstract: Objective: To assess and compare the intra- and interrater reliability of three different MRI grading and classification systems after acute hamstring injury. Methods: Male athletes (n = 40) with clinical diagnosis of acute hamstring injury and MRI ≤5 days were selected from a prospective cohort. Two radiologists independently evaluated the MRIs using standardised scoring form including the modified Peetrons grading system, the Chan acute muscle strain injury classification and the British Athletics Muscle Injury Classification. Intra-and interrater reliability was assessed with linear weighted kappa (κ) or unweighted Cohen's κ and percentage agreement was calculated. Results: We observed ‘substantial’ to ‘almost perfect’ intra- (κ range 0.65–1.00) and interrater reliability (κ range 0.77–1.00) with percentage agreement 83–100% and 88–100%, respectively, for severity gradings, overall anatomical sites and overall classifications for the three MRI systems. We observed substantial variability (κ range −0.05 to 1.00) for subcategories within the Chan classification and the British Athletics Muscle Injury Classification, however, the prevalence of positive scorings was low for some subcategories. Conclusions: The modified Peetrons grading system, overall Chan classification and overall British Athletics Muscle Injury Classification demonstrated ‘substantial' to ‘almost perfect' intra- and interrater reliability when scored by experienced radiologists. The intra- and interrater reliability for the anatomical subcategories within the classifications remains unclear.

  11. Intra- and interrater reliability of three different MRI grading and classification systems after acute hamstring injuries

    Energy Technology Data Exchange (ETDEWEB)

    Wangensteen, Arnlaug, E-mail: arnlaug.wangensteen@nih.no [Aspetar, Orthopaedic and Sports Medicine Hospital, Doha (Qatar); Oslo Sports Trauma Research Center, Department of Sports Medicine, Norwegian School of Sport Sciences, Oslo (Norway); Tol, Johannes L., E-mail: johannes.tol@aspetar.com [Aspetar, Orthopaedic and Sports Medicine Hospital, Doha (Qatar); Amsterdam Center for Evidence Sports Medicine, Academic Medical Center (Netherlands); The Sports Physician Group, OLVG, Amsterdam (Netherlands); Roemer, Frank W. [Quantitative Imaging Center, Department of Radiology, Boston University School of Medicine, Boston, MA (United States); Department of Radiology, University of Erlangen-Nuremberg, Erlangen (Germany); Bahr, Roald [Aspetar, Orthopaedic and Sports Medicine Hospital, Doha (Qatar); Oslo Sports Trauma Research Center, Department of Sports Medicine, Norwegian School of Sport Sciences, Oslo (Norway); Dijkstra, H. Paul [Aspetar, Orthopaedic and Sports Medicine Hospital, Doha (Qatar); Crema, Michel D. [Quantitative Imaging Center, Department of Radiology, Boston University School of Medicine, Boston, MA (United States); Department of Radiology, Saint-Antoine Hospital, University Paris VI, Paris (France); Farooq, Abdulaziz [Aspetar, Orthopaedic and Sports Medicine Hospital, Doha (Qatar); Guermazi, Ali [Quantitative Imaging Center, Department of Radiology, Boston University School of Medicine, Boston, MA (United States)

    2017-04-15

    Highlights: • Three different MRI grading and classification systems for acute hamstring injuries are overall reliable. • Reliability for the subcategories within these MRI grading and classification systems remains, however, unclear. - Abstract: Objective: To assess and compare the intra- and interrater reliability of three different MRI grading and classification systems after acute hamstring injury. Methods: Male athletes (n = 40) with clinical diagnosis of acute hamstring injury and MRI ≤5 days were selected from a prospective cohort. Two radiologists independently evaluated the MRIs using standardised scoring form including the modified Peetrons grading system, the Chan acute muscle strain injury classification and the British Athletics Muscle Injury Classification. Intra-and interrater reliability was assessed with linear weighted kappa (κ) or unweighted Cohen's κ and percentage agreement was calculated. Results: We observed ‘substantial’ to ‘almost perfect’ intra- (κ range 0.65–1.00) and interrater reliability (κ range 0.77–1.00) with percentage agreement 83–100% and 88–100%, respectively, for severity gradings, overall anatomical sites and overall classifications for the three MRI systems. We observed substantial variability (κ range −0.05 to 1.00) for subcategories within the Chan classification and the British Athletics Muscle Injury Classification, however, the prevalence of positive scorings was low for some subcategories. Conclusions: The modified Peetrons grading system, overall Chan classification and overall British Athletics Muscle Injury Classification demonstrated ‘substantial' to ‘almost perfect' intra- and interrater reliability when scored by experienced radiologists. The intra- and interrater reliability for the anatomical subcategories within the classifications remains unclear.

  12. Dynamic computed tomography (CT) in the rat kidney and application to acute renal failure models

    International Nuclear Information System (INIS)

    Ishikawa, Isao; Saito, Tadashi; Ishii, Hirofumi; Bansho, Junichi; Koyama, Yukinori; Tobita, Akira

    1995-01-01

    Renal dynamic CT scanning is suitable for determining the excretion of contrast medium in the cortex and medulla of the kidney, which is valuable for understanding the pathogenesis of disease processes in various conditions. This form of scanning would be convenient for use, if a method of application to the rat kidney were available. Therefore, we developed a method of applying renal dynamic CT to rats and evaluated the cortical and medullary curves, e.g., the corticomedullary junction time which is correlated to creatinine clearance, in various rat models of acute renal failure. The rat was placed in a 10deg oblique position and a bilateral hilar slice was obtained before and 5, 10, 15, 20, 25, 30, 40, 50, 60, 80, 100, 120, 140, 160 and 180 sec after administering 0.5 ml of contrast medium using Somatom DR. The width of the slice was 4 mm and the scan time was 3 sec. The corticomedullary junction time in normal rats was 23.0±10.5 sec, the peak value of the cortical curve was 286.3±76.7 Hounsfield Unit (HU) and the peak value of the medullary curve was 390.1±66.2 HU. Corticomedullary junction time after exposure of the kidney was prolonged compared to that of the unexposed kidney. In rats with acute renal failure, the excretion pattern of contrast medium was similar in both the glycerol- and HgCl2-induced acute renal failure models. The peak values of the cortical curve were maintained three hours after a clamp was placed at the hilar region of the kidney for one hour, and the peak values of the medullary curve were maintained during the administration of 10μg/kg/min of angiotensin II. Dynamic CT curves in the acute renal failure models examined were slightly different from those in human acute renal failure. These results suggest that rats do not provide an ideal model for human acute renal failure. However, the application of dynamic CT to the rat kidney models was valuable for estimating the pathogenesis of various human kidney diseases. (author)

  13. Anticonvulsant activity of Aloe vera leaf extract in acute and chronic models of epilepsy in mice.

    Science.gov (United States)

    Rathor, Naveen; Arora, Tarun; Manocha, Sachin; Patil, Amol N; Mediratta, Pramod K; Sharma, Krishna K

    2014-03-01

    The effect of Aloe vera in epilepsy has not yet been explored. This study was done to explore the effect of aqueous extract of Aloe vera leaf powder on three acute and one chronic model of epilepsy. In acute study, aqueous extract of Aloe vera leaf (extract) powder was administered in doses 100, 200 and 400 mg/kg p.o. Dose of 400 mg/kg of Aloe vera leaf extract was chosen for chronic administration. Oxidative stress parameters viz. malondialdehyde (MDA) and reduced glutathione (GSH) were also estimated in brain of kindled animals. In acute study, Aloe vera leaf (extract) powder in a dose-dependent manner significantly decreased duration of tonic hind limb extension in maximal electroshock seizure model, increased seizure threshold current in increasing current electroshock seizure model, and increased latency to onset and decreased duration of clonic convulsion in pentylenetetrazole (PTZ) model as compared with control group. In chronic study, Aloe vera leaf (extract) powder prevented progression of kindling in PTZ-kindled mice. Aloe vera leaf (extract) powder 400 mg/kg p.o. also reduced brain levels of MDA and increased GSH levels as compared to the PTZ-kindled non-treated group. The results of study showed that Aloe vera leaf (extract) powder possessed significant anticonvulsant and anti-oxidant activity. © 2013 Royal Pharmaceutical Society.

  14. The Acute Physiology and Chronic Health Evaluation IV, a New Scoring System for Predicting Mortality and Complications of Severe Acute Pancreatitis.

    Science.gov (United States)

    Mok, Shaffer R S; Mohan, Sachin; Elfant, Adam B; Judge, Thomas A

    2015-11-01

    Severe acute pancreatitis is associated with significant morbidity/mortality; thus, the ability to predict hospital course is imperative. An updated version of the Acute Physiology and Chronic Health Evaluation II (APACHE), APACHE IV, has recently been validated. Unlike other versions, APACHE IV uses hepatobiliary parameters and accounts for multiple comorbid conditions and sedation. The intention of this study was to examine APACHE IV for predicting mortality and secondary outcomes for pancreatitis in a prospective cohort. In addition, we compared APACHE IV to APACHE II, Bedside Index for Severity in Acute Pancreatitis, and Ranson criterion. We prospectively collected physiologic parameters for each scoring system in 266 patients with severe acute pancreatitis from August 2011 to April 2014. Prognostic value of each score was determined using the area under the receiver operating characteristic curve. Among 266 patients, 59% were men, 52% were white, and 36.5% had alcohol-induced pancreatitis. Mortality occurred in 15 (5.6%), and an APACHE IV of 44 or greater predicted mortality in 100% of cases. The receiver operating characteristic curve for APACHE IV was 0.93 (confidence interval [CI], 0.88-0.97); APACHE II, 0.87 (CI, 0.80-0.94); Bedside Index for Severity in Acute Pancreatitis, 0.86 (CI, 0.78-0.94); and Ranson criterion, 0.90 (CI, 0.94-0.96). The APACHE IV is a valid means for predicting mortality and disease-related complications in acute pancreatitis.

  15. Public Health Response Systems In-Action: Learning from Local Health Departments’ Experiences with Acute and Emergency Incidents

    Science.gov (United States)

    Hunter, Jennifer C.; Yang, Jane E.; Crawley, Adam W.; Biesiadecki, Laura; Aragón, Tomás J.

    2013-01-01

    As part of their core mission, public health agencies attend to a wide range of disease and health threats, including those that require routine, acute, and emergency responses. While each incident is unique, the number and type of response activities are finite; therefore, through comparative analysis, we can learn about commonalities in the response patterns that could improve predictions and expectations regarding the resources and capabilities required to respond to future acute events. In this study, we interviewed representatives from more than 120 local health departments regarding their recent experiences with real-world acute public health incidents, such as infectious disease outbreaks, severe weather events, chemical spills, and bioterrorism threats. We collected highly structured data on key aspects of the incident and the public health response, particularly focusing on the public health activities initiated and community partners engaged in the response efforts. As a result, we are able to make comparisons across event types, create response profiles, and identify functional and structural response patterns that have import for future public health preparedness and response. Our study contributes to clarifying the complexity of public health response systems and our analysis reveals the ways in which these systems are adaptive to the character of the threat, resulting in differential activation of functions and partners based on the type of incident. Continued and rigorous examination of the experiences of health departments throughout the nation will refine our very understanding of what the public health response system is, will enable the identification of organizational and event inputs to performance, and will allow for the construction of rich, relevant, and practical models of response operations that can be employed to strengthen public health systems. PMID:24236137

  16. Hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in a rat model of acute hyperammonemia

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Eefsen, Martin; Larsen, Fin Stolze

    2011-01-01

    . These factors are also thought to be involved in the development of brain edema in acute liver failure. We wanted to study whether hypermagnesemia prevented development of intracranial hypertension and hyperperfusion in a rat model of portacaval anastomosis (PCA) and acute hyperammonemia. We also studied...

  17. Computational modeling to predict nitrogen balance during acute metabolic decompensation in patients with urea cycle disorders.

    Science.gov (United States)

    MacLeod, Erin L; Hall, Kevin D; McGuire, Peter J

    2016-01-01

    Nutritional management of acute metabolic decompensation in amino acid inborn errors of metabolism (AA IEM) aims to restore nitrogen balance. While nutritional recommendations have been published, they have never been rigorously evaluated. Furthermore, despite these recommendations, there is a wide variation in the nutritional strategies employed amongst providers, particularly regarding the inclusion of parenteral lipids for protein-free caloric support. Since randomized clinical trials during acute metabolic decompensation are difficult and potentially dangerous, mathematical modeling of metabolism can serve as a surrogate for the preclinical evaluation of nutritional interventions aimed at restoring nitrogen balance during acute decompensation in AA IEM. A validated computational model of human macronutrient metabolism was adapted to predict nitrogen balance in response to various nutritional interventions in a simulated patient with a urea cycle disorder (UCD) during acute metabolic decompensation due to dietary non-adherence or infection. The nutritional interventions were constructed from published recommendations as well as clinical anecdotes. Overall, dextrose alone (DEX) was predicted to be better at restoring nitrogen balance and limiting nitrogen excretion during dietary non-adherence and infection scenarios, suggesting that the published recommended nutritional strategy involving dextrose and parenteral lipids (ISO) may be suboptimal. The implications for patients with AA IEM are that the medical course during acute metabolic decompensation may be influenced by the choice of protein-free caloric support. These results are also applicable to intensive care patients undergoing catabolism (postoperative phase or sepsis), where parenteral nutritional support aimed at restoring nitrogen balance may be more tailored regarding metabolic fuel selection.

  18. Predicting acute copper toxicity to valve closure behavior in the freshwater clam Corbicula fluminea supports the biotic ligand model.

    Science.gov (United States)

    Liao, Chung-Min; Jou, Li-John; Lin, Chieh-Ming; Chiang, Kuo-Chin; Yeh, Ching-Hung; Chou, Berry Yun-Hua

    2007-06-01

    The objective of this paper is to employ biotic ligand model (BLM) to link between acute copper (Cu) toxicity and its effect on valve closure behavior of freshwater clam Corbicula fluminea in order to further support for the BLM that potentially offers a rapid and cost-effective method to conduct the acute toxicity tests for freshwater clam exposed to waterborne Cu. Reanalysis of published experimental data of C. fluminea closure daily rhythm and dose-response profiles based on the laboratory-acclimated clams showed that a BLM-based Hill model best described the free Cu(2+)-activity-valve closure response relationships. Our proposed Cu-BLM-Corbicula model shows that free ionic form of waterborne Cu binds specifically to a biotic ligand (i.e., clam gills) and impairs normal valve closure behavior, indicating that a fixed-level of metal accumulation at a biotic ligand is required to elicit specific biological effects. With derived mechanistic-based Cu-BLM-Corbicula model, we show that the site-specific EC50(t) and valve closure behavior at any integrated time can be well predicted, indicating that our model has the potential to develop a biomonitoring system as a bioassay tool to on-line measure waterborne Cu levels in aquatic systems. Our results confirm that BLM can be improved to analytically and rigorously describe the bioavailable fraction of metal causing toxicity to valve closure behavior in freshwater C. fluminea. We suggest that the Cu-BLM-Corbicula model can be used to assist in developing technically defensible site-specific water quality criteria and performing ecological risk assessment and to promote more focused and efficient uses of resources in the regulation and control of metals and the protection of the aquatic ecosystems.

  19. Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass.

    Directory of Open Access Journals (Sweden)

    Xiaocou Wang

    Full Text Available Infants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF. This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass.Eighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6, the control group (Group C, n = 6, and the sham operation group (Group S, n = 6, and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected.The expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation

  20. Anticonvulsant effects of mefloquine on generalized tonic-clonic seizures induced by two acute models in rats.

    Science.gov (United States)

    Franco-Pérez, Javier; Ballesteros-Zebadúa, Paola; Manjarrez-Marmolejo, Joaquín

    2015-03-01

    Mefloquine can cross the blood-brain barrier and block the gap junction intercellular communication in the brain. Enhanced electrical coupling mediated by gap junctions is an underlying mechanism involved in the generation and maintenance of seizures. For this reason, the aim of this study was to analyze the effects of the systemic administration of mefloquine on tonic-clonic seizures induced by two acute models such as pentylenetetrazole and maximal electroshock. All the control rats presented generalized tonic-clonic seizures after the administration of pentylenetetrazole. However, the incidence of seizures induced by pentylenetetrazole significantly decreased in the groups administered systematically with 40 and 80 mg/kg of mefloquine. In the control group, none of the rats survived after the generalized tonic-clonic seizures induced by pentylenetetrazole, but survival was improved by mefloquine. Besides, mefloquine significantly modified the total spectral power as well as the duration, amplitude and frequency of the epileptiform activity induced by pentylenetetrazole. For the maximal electroshock model, mefloquine did not change the occurrence of tonic hindlimb extension. However, this gap junction blocker significantly decreased the duration of the tonic hindlimb extension induced by the acute electroshock. These data suggest that mefloquine at low doses might be eliciting some anticonvulsant effects when is systemically administered to rats.

  1. Hyperalgesia in a human model of acute inflammatory pain: a methodological study

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    sensitive to heat pain on their left side (P ... measurements themselves evoked hyperalgesia to heat and mechanical stimuli on the arm, but only to mechanical stimuli on the legs. including secondary hyperalgesia. Hyperalgesia evoked by the measurements was significantly less intense than that induced by injury. Habituation to the painful stimuli...... was demonstrated by significantly higher pain thresholds and lower pain responses on the second and third day of the study. The burn model is a sensitive psychophysical model of acute inflammatory pain, when cross-over designs and within-day comparisons are used, and the model is suitable for double-blind, placebo...

  2. Acute effects of Surya Namaskar on the cardiovascular & metabolic system.

    Science.gov (United States)

    Mody, Bhavesh Surendra

    2011-07-01

    With the recent rise in obesity awareness and the increased understanding of the importance of physical activity in promoting overall health, greater emphasis has been placed on improving physical fitness to enhance quality of life. Surya Namaskar, a component of Hatha Yoga, has been practiced by Asian Indians for hundreds of years and is often used in place of a typical fitness program. It consists of a series of postures (asanas) that are repeated 12 times per round. Only one published study has looked specifically at Surya Namaskar, measuring the energy cost of individual asanas (Sinha et al., 2004). However, practitioners typically perform several rounds of the asanas during a session. To assess the cardiorespiratory and metabolic responses of four rounds of Surya Namaskar, a typical amount performed by practitioners, to determine its potential as a training and weight loss tool. Six healthy Asian Indian men and women (18-22 years) who had trained in Surya Namaskar for over two years participated in the study. Testing was completed in a single session lasting about 30 min. To measure heart rate and oxygen consumption while performing the four rounds, participants were connected to a heart rate monitor and the Oxycon Mobile Metabolic System. Participants exercised at 80% of age-predicted maximal heart rate (HRmax) during Round 2, 84% during Round 3, and 90% during Round 4. Average intensity during the four rounds was 80% HRmax, sufficient to elicit a cardiorespiratory training effect. Oxygen consumption averaged 26 ml/kg/min during each round, resulting in an energy expenditure of 230 kcals during a 30 min session for a 60 kg individual. Regular practice of Surya Namaskar may maintain or improve cardiorespiratory fitness, as well as promote weight management. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Computational models of complex systems

    CERN Document Server

    Dabbaghian, Vahid

    2014-01-01

    Computational and mathematical models provide us with the opportunities to investigate the complexities of real world problems. They allow us to apply our best analytical methods to define problems in a clearly mathematical manner and exhaustively test our solutions before committing expensive resources. This is made possible by assuming parameter(s) in a bounded environment, allowing for controllable experimentation, not always possible in live scenarios. For example, simulation of computational models allows the testing of theories in a manner that is both fundamentally deductive and experimental in nature. The main ingredients for such research ideas come from multiple disciplines and the importance of interdisciplinary research is well recognized by the scientific community. This book provides a window to the novel endeavours of the research communities to present their works by highlighting the value of computational modelling as a research tool when investigating complex systems. We hope that the reader...

  4. Model reduction of parametrized systems

    CERN Document Server

    Ohlberger, Mario; Patera, Anthony; Rozza, Gianluigi; Urban, Karsten

    2017-01-01

    The special volume offers a global guide to new concepts and approaches concerning the following topics: reduced basis methods, proper orthogonal decomposition, proper generalized decomposition, approximation theory related to model reduction, learning theory and compressed sensing, stochastic and high-dimensional problems, system-theoretic methods, nonlinear model reduction, reduction of coupled problems/multiphysics, optimization and optimal control, state estimation and control, reduced order models and domain decomposition methods, Krylov-subspace and interpolatory methods, and applications to real industrial and complex problems. The book represents the state of the art in the development of reduced order methods. It contains contributions from internationally respected experts, guaranteeing a wide range of expertise and topics. Further, it reflects an important effor t, carried out over the last 12 years, to build a growing research community in this field. Though not a textbook, some of the chapters ca...

  5. Radionuclides in fruit systems: Model-model intercomparison study

    Energy Technology Data Exchange (ETDEWEB)

    Linkov, I. [Cambridge Environmental, 58 Charles Street, Cambridge, MA 02141 (United States)]. E-mail: linkov@cambridgeenvironmental.com; Carini, F. [Universita Cattolica del Sacro Cuore, Faculty of Agricultural Sciences, Institute of Agricultural and Environmental Chemistry, Via Emilia Parmense, 84, I-29100 Piacenza (Italy); Collins, C. [T.H. Huxley School of Environment, Earth Sciences and Engineering (United Kingdom); Eged, K. [Department of Radiochemistry, University of Veszprem, P.O. Box 158 H-8201, H-8200 Veszprem (Hungary); Mitchell, N.G. [Mouchel Consulting Ltd., West Hall, Parvis Road, West Byfleet, Surrey, KT14 6EZ (United Kingdom); Mourlon, C. [Institute of Protection and Nuclear Safety (IPSN)/Division of Environmental Protection (DPRE), Laboratory of Environmental Modelling - LMODE, CE/Cadarache, 13 108 St Paul-lez-Durance Cedex (France); Ould-Dada, Z. [Food Standards Agency, Radiological Protection and Research Management Division, Aviation House, 125 Kingsway, Room 715B, London WC2B 6NH (United Kingdom); Robles, B. [CIEMAT, Dept. de Impacto Ambiental (DIAE), Edif. 3A, Avenida Complutense 22, E-28040 Madrid (Spain); Sweeck, L. [SCK.CEN, Boeretang 200, 2400 Mol (Belgium); Venter, A. [Enviros Consulting Ltd., Telegraphic House, Waterfront Quay, Salford Quays, Greater Manchester, M50 3XW (United Kingdom)

    2006-07-01

    Modeling is widely used to predict radionuclide distribution following accidental radionuclide releases. Modeling is crucial in emergency response planning and risk communication, and understanding model uncertainty is important not only in conducting analysis consistent with current regulatory guidance, but also in gaining stakeholder and decision-maker trust in the process and confidence in the results. However, while methods for dealing with parameter uncertainty are fairly well developed, an adequate representation of uncertainties associated with models remains rare. This paper addresses uncertainty about a model's structure (i.e., the relevance of simplifying assumptions and mathematical equations) that is seldom addressed in practical applications of environmental modeling. The use of several alternative models to derive a range of model outputs or risks is probably the only available technique to assess consistency in model prediction. Since each independent model requires significant resources for development and calibration, multiple models are not generally applied to the same problem. This study uses results from one such model intercomparison conducted by the Fruits Working Group, which was created under the International Atomic Energy Agency (IAEA) BIOMASS (BIOsphere Modelling and ASSessment) Program. Model-model intercomparisons presented in this study were conducted by the working group for two different scenarios (acute or continuous deposition), one radionuclide ({sup 137}Cs), and three fruit-bearing crops (strawberries, apples, and blackcurrants). The differences between models were as great as five orders of magnitude for short-term predictions following acute radionuclide deposition. For long-term predictions and for the continuous deposition scenario, the differences between models were about two orders of magnitude. The difference between strawberry, apple, and blackcurrant contamination predicted by one model is far less than the

  6. Radionuclides in fruit systems. Model-model intercomparison study

    Energy Technology Data Exchange (ETDEWEB)

    Linkov, I. [Cambridge Environmental, 58 Charles Street, Cambridge, MA 02141 (United States); Carini, F. [Universita Cattolica del Sacro Cuore, Faculty of Agricultural Sciences, Institute of Agricultural and Environmental Chemistry, Via Emilia Parmense, 84, I-29100 Piacenza (Italy); Collins, C. [T.H. Huxley School of Environment, Earth Sciences and Engineering (United Kingdom); Eged, K. [Department of Radiochemistry, University of Veszprem, P.O. Box 158 H-8201, H-8200 Veszprem (Hungary); Mitchell, N.G. [Mouchel Consulting Ltd., West Hall, Parvis Road, West Byfleet, Surrey, KT14 6EZ (United Kingdom); Mourlon, C. [Institute of Protection and Nuclear Safety IPSN, Division of Environmental Protection (DPRE), Laboratory of Environmental Modelling LMODE, CE/Cadarache, 13 108 St Paul-lez-Durance (France); Ould-Dada, Z. [Food Standards Agency, Radiological Protection and Research Management Division, Aviation House, 125 Kingsway, Room 715B, London WC2B 6NH (United Kingdom); Robles, B. [CIEMAT, Dept. de Impacto Ambiental (DIAE), Edif. 3A, Avenida Complutense 22, E-28040 Madrid (Spain); Sweeck, L. [SCK-CEN, Boeretang 200, 2400 Mol (Belgium); Venter, A. [Enviros Consulting Ltd., Telegraphic House, Waterfront Quay, Salford Quays, Greater Manchester, M50 3XW (United Kingdom)

    2006-07-01

    Modeling is widely used to predict radionuclide distribution following accidental radionuclide releases. Modeling is crucial in emergency response planning and risk communication, and understanding model uncertainty is important not only in conducting analysis consistent with current regulatory guidance, but also in gaining stakeholder and decision-maker trust in the process and confidence in the results. However, while methods for dealing with parameter uncertainty are fairly well developed, an adequate representation of uncertainties associated with models remains rare. This paper addresses uncertainty about a model's structure (i.e., the relevance of simplifying assumptions and mathematical equations) that is seldom addressed in practical applications of environmental modeling. The use of several alternative models to derive a range of model outputs or risks is probably the only available technique to assess consistency in model prediction. Since each independent model requires significant resources for development and calibration, multiple models are not generally applied to the same problem. This study uses results from one such model intercomparison conducted by the Fruits Working Group, which was created under the International Atomic Energy Agency (IAEA) BIOMASS (BIOsphere Modelling and ASSessment) Program. Model-model intercomparisons presented in this study were conducted by the working group for two different scenarios (acute or continuous deposition), one radionuclide ({sup 137}Cs), and three fruit-bearing crops (strawberries, apples, and blackcurrants). The differences between models were as great as five orders of magnitude for short-term predictions following acute radionuclide deposition. For long-term predictions and for the continuous deposition scenario, the differences between models were about two orders of magnitude. The difference between strawberry, apple, and blackcurrant contamination predicted by one model is far less than the

  7. Effects of Tempol on Experimental Acute Necrotizing Pancreatitis Model in Rats.

    Science.gov (United States)

    Erbıs, Halil; Aykota, Muhammed Rasid; Ozturk, Bunyamin; Kabay, Burhan; Sungurtekin, Ugur; Ozden, Akın; Yenisey, Cigdem; Turk, Nilay Sen; Erdem, Ergun

    2015-01-01

    We aimed to investigate the effects of Tempol on local organ damage in an experimental acute pancreatitis model. This experimental study was conducted on 40 male Wistar- albino rats. The animals were randomly allocated into four groups: (i) Sham-operated group, laparotomies and cannulations of the pancreatic duct without acute necrotizing pancreatitis (ANP) (n=10); (ii) Sham + Tempol group, identical to group 1 except for intravenous tempol treatment for 4 hours (n = 10); (iii) ANP group, glycodeoxycholic acid was infused into the pancreatic duct and cerulein was infused intravenously for 6 hours for development of ANP (n=10); and (iv) ANP + Tempol treated group, in addition to the procedure in group 3, rats were administered tempol intravenously for 4 hours (n = 10). Injury of the pancreas was evaluated histopathologically. Malondialdehyde and myeloperoxidase levels of the pancreatic tissue, blood gas analysis, leukocyte and hematocrit levels were measured. Wet/dry weight of pancreatic tissue was also measured. Serum amylase levels, pancreatic tissue malondialdehyde and myeloperoxidase levels, wet/dry weight ratio, pancreatic edema, acinar necrosis, fat necrosis and hemorrhage, inflammation and perivascular infiltration were significantly lower in the ANP + Tempol group compared with the ANP group. Tempol infusion reduced local organ damage due to acute necrotizing pancreatitis in this experimental study. These findings demonstrate that tempol has protective effects on local organ damage due to acute necrotizing pancreatitis in rats.

  8. Intra- and interrater reliability of three different MRI grading and classification systems after acute hamstring injuries.

    Science.gov (United States)

    Wangensteen, Arnlaug; Tol, Johannes L; Roemer, Frank W; Bahr, Roald; Dijkstra, H Paul; Crema, Michel D; Farooq, Abdulaziz; Guermazi, Ali

    2017-04-01

    To assess and compare the intra- and interrater reliability of three different MRI grading and classification systems after acute hamstring injury. Male athletes (n=40) with clinical diagnosis of acute hamstring injury and MRI ≤5days were selected from a prospective cohort. Two radiologists independently evaluated the MRIs using standardised scoring form including the modified Peetrons grading system, the Chan acute muscle strain injury classification and the British Athletics Muscle Injury Classification. Intra-and interrater reliability was assessed with linear weighted kappa (κ) or unweighted Cohen's κ and percentage agreement was calculated. We observed 'substantial' to 'almost perfect' intra- (κ range 0.65-1.00) and interrater reliability (κ range 0.77-1.00) with percentage agreement 83-100% and 88-100%, respectively, for severity gradings, overall anatomical sites and overall classifications for the three MRI systems. We observed substantial variability (κ range -0.05 to 1.00) for subcategories within the Chan classification and the British Athletics Muscle Injury Classification, however, the prevalence of positive scorings was low for some subcategories. The modified Peetrons grading system, overall Chan classification and overall British Athletics Muscle Injury Classification demonstrated 'substantial' to 'almost perfect' intra- and interrater reliability when scored by experienced radiologists. The intra- and interrater reliability for the anatomical subcategories within the classifications remains unclear. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Modeling software systems by domains

    Science.gov (United States)

    Dippolito, Richard; Lee, Kenneth

    1992-01-01

    The Software Architectures Engineering (SAE) Project at the Software Engineering Institute (SEI) has developed engineering modeling techniques that both reduce the complexity of software for domain-specific computer systems and result in systems that are easier to build and maintain. These techniques allow maximum freedom for system developers to apply their domain expertise to software. We have applied these techniques to several types of applications, including training simulators operating in real time, engineering simulators operating in non-real time, and real-time embedded computer systems. Our modeling techniques result in software that mirrors both the complexity of the application and the domain knowledge requirements. We submit that the proper measure of software complexity reflects neither the number of software component units nor the code count, but the locus of and amount of domain knowledge. As a result of using these techniques, domain knowledge is isolated by fields of engineering expertise and removed from the concern of the software engineer. In this paper, we will describe kinds of domain expertise, describe engineering by domains, and provide relevant examples of software developed for simulator applications using the techniques.

  10. Characterisation of Leukocytes in a Human Skin Blister Model of Acute Inflammation and Resolution

    OpenAIRE

    Jenner, William; Motwani, Madhur; Veighey, Kristin; Newson, Justine; Audzevich, Tatsiana; Nicolaou, Anna; Murphy, Sharon; MacAllister, Raymond; Gilroy, Derek W.

    2014-01-01

    There is an increasing need to understand the leukocytes and soluble mediators that drive acute inflammation and bring about its resolution in humans. We therefore carried out an extensive characterisation of the cantharidin skin blister model in healthy male volunteers. A novel fluorescence staining protocol was designed and implemented, which facilitated the identification of cell populations by flow cytometry. We observed that at the onset phase, 24 h after blister formation, the predomina...

  11. A New Model of Delirium Care in the Acute Geriatric Setting: Geriatric Monitoring Unit

    Directory of Open Access Journals (Sweden)

    Chong Mei

    2011-08-01

    Full Text Available Abstract Background Delirium is a common and serious condition, which affects many of our older hospitalised patients. It is an indicator of severe underlying illness and requires early diagnosis and prompt treatment, associated with poor survival, functional outcomes with increased risk of institutionalisation following the delirium episode in the acute care setting. We describe a new model of delirium care in the acute care setting, titled Geriatric Monitoring Unit (GMU where the important concepts of delirium prevention and management are integrated. We hypothesize that patients with delirium admitted to the GMU would have better clinical outcomes with less need for physical and psychotropic restraints compared to usual care. Methods/Design GMU models after the Delirium Room with adoption of core interventions from Hospital Elder Life Program and use of evening bright light therapy to consolidate circadian rhythm and improve sleep in the elderly patients. The novelty of this approach lies in the amalgamation of these interventions in a multi-faceted approach in acute delirium management. GMU development thus consists of key considerations for room design and resource planning, program specific interventions and daily core interventions. Assessments undertaken include baseline demographics, comorbidity scoring, duration and severity of delirium, cognitive, functional measures at baseline, 6 months and 12 months later. Additionally we also analysed the pre and post-GMU implementation knowledge and attitude on delirium care among staff members in the geriatric wards (nurses, doctors and undertook satisfaction surveys for caregivers of patients treated in GMU. Discussion This study protocol describes the conceptualization and implementation of a specialized unit for delirium management. We hypothesize that such a model of care will not only result in better clinical outcomes for the elderly patient with delirium compared to usual geriatric care

  12. New Grading System and Treatment Guidelines for the Acute Ocular Manifestations of Stevens-Johnson Syndrome.

    Science.gov (United States)

    Gregory, Darren G

    2016-08-01

    To describe a new grading system and associated treatment guidelines for the acute ocular manifestations of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Prospective case series. Seventy-nine consecutive patients (158 eyes) evaluated and treated for acute ocular involvement in SJS or TEN during hospitalization. Photographic and chart review of acute ocular findings, interventions received, and outcomes with regard to visual acuity, dry eye symptoms, and scarring sequelae at least 3 months after the acute illness. Visual acuity, dry eye severity, and scarring of the ocular surface and eyelids were assessed after follow-up of at least 3 months. Cases graded as mild or moderate were managed medically. All had best-corrected visual acuity (BCVA) of 20/20, no dry eye symptoms, and no scarring sequelae. Cases graded as severe or extremely severe were treated with urgent amniotic membrane transplantation (AMT) in addition to medical management. Severe cases all had BCVA of 20/20 and mild or no dry eye problems. Five of 28 patients had mild tarsal conjunctival scarring. No other scarring sequelae occurred. Nine of the 10 extremely severe cases had BCVA of 20/20 (1 was 20/30). Three of 10 had moderate scarring of the tarsal conjunctiva and lid margins and also moderate dry eyes with severe photophobia. Seven of 10 had only mild or no dry eye symptoms and scarring sequelae. This grading system facilitates decision making in the evaluation and management of the acute ocular manifestations of SJS and TEN. Mild and moderate cases have a low risk of significant scarring or visual sequelae and may be monitored and treated medically if not worsening. Severe and extremely severe cases should receive urgent AMT to decrease the risk of scarring and visual sequelae. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  13. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae

    International Nuclear Information System (INIS)

    Laningham, Fred H.; Kun, Larry E.; Reddick, Wilburn E.; Ogg, Robert J.; Morris, E.B.; Pui, Ching-Hon

    2007-01-01

    During the past three decades, improvements in the treatment of childhood leukemia have resulted in high cure rates, particularly for acute lymphoblastic leukemia (ALL). Unfortunately, successful therapy has come with a price, as significant morbidity can result from neurological affects which harm the brain and spinal cord. The expectation and hope is that chemotherapy, as a primary means of CNS therapy, will result in acceptable disease control with less CNS morbidity than has been observed with combinations of chemotherapy and radiotherapy over the past several decades. In this review we discuss the poignant, historical aspects of CNS leukemia therapy, outline current methods of systemic and CNS leukemia therapy, and present imaging findings we have encountered in childhood leukemia patients with a variety of acute neurological conditions. A major objective of our research is to understand the neuroimaging correlates of acute and chronic effects of cancer and therapy. Specific features related to CNS leukemia and associated short-term toxicities, both disease- and therapy-related, are emphasized in this review with the specific neuroimaging findings. Specific CNS findings are similarly important when treating acute myelogenous leukemia (AML), and details of leukemic involvement and toxicities are also presented in this entity. Despite contemporary treatment approaches which favor the use of chemotherapy (including intrathecal therapy) over radiotherapy in the treatment of CNS leukemia, children still occasionally experience morbid neurotoxicity. Standard neuroimaging is sufficient to identify a variety of neurotoxic sequelae in children, and often suggest specific etiologies. Specific neuroimaging findings frequently indicate a need to alter antileukemia therapy. It is important to appreciate that intrathecal and high doses of systemic chemotherapy are not innocuous and are associated with acute, specific, recognizable, and often serious neurological

  14. Reproducibility of the acute rejection diagnosis in human cardiac allografts. The Stanford Classification and the International Grading System

    DEFF Research Database (Denmark)

    Nielsen, H; Sørensen, Flemming Brandt; Nielsen, B

    1993-01-01

    Transplantation has become an accepted treatment of many cardiac end-stage diseases. Acute cellular rejection accounts for 15% to 20% of all graft failures. The first grading system of acute cellular rejection, the Stanford Classification, was introduced in 1979, and since then many other grading...

  15. Regional Validation and Recalibration of Clinical Predictive Models for Patients With Acute Heart Failure.

    Science.gov (United States)

    Wessler, Benjamin S; Ruthazer, Robin; Udelson, James E; Gheorghiade, Mihai; Zannad, Faiez; Maggioni, Aldo; Konstam, Marvin A; Kent, David M

    2017-11-18

    Heart failure clinical practice guidelines recommend applying validated clinical predictive models (CPMs) to support decision making. While CPMs are now widely available, the generalizability of heart failure CPMs is largely unknown. We identified CPMs derived in North America that predict mortality for patients with acute heart failure and validated these models in different world regions to assess performance in a contemporary international clinical trial (N=4133) of patients with acute heart failure treated with guideline-directed medical therapy. We performed independent external validations of 3 CPMs predicting in-hospital mortality, 60-day mortality, and 1-year mortality, respectively. CPM discrimination decreased in all regional validation cohorts. The median change in area under the receiver operating curve was -0.09 (range -0.05 to -0.23). Regional calibration was highly variable (90th percentile of absolute difference between smoothed observed and predicted values range 50%). Calibration remained poor after global recalibrations; however, region-specific recalibration procedures significantly improved regional performance (recalibrated 90th percentile of absolute difference range models). Acute heart failure CPM discrimination and calibration vary substantially across different world regions; region-specific (as opposed to global) recalibration techniques are needed to improve CPM calibration. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  16. Prolonged Survival of Acute Lymphoblastic Leukemia with Intrathecal Treatments for Isolated Central Nervous System Relapse

    Directory of Open Access Journals (Sweden)

    Elan Gorshein

    2018-01-01

    Full Text Available Acute lymphoblastic leukemia is commonly cured when diagnosed in the pediatric population. It portends a poorer prognosis if present in adult patients. Although adults frequently achieve complete remission, relapse rates are substantial, particularly among the elderly and high-risk populations. In the absence of prophylactic intrathecal chemotherapy, more than half of patients may develop CNS involvement or relapse, which is associated with significant risk for systemic illness. This report describes a patient with acute lymphoblastic leukemia with repeated isolated CNS relapses. This case should remind clinicians that isolated CNS disease in the absence of systemic recurrence could successfully respond to intrathecal therapy and offer patients a favorable quality of life.

  17. [An autopsy case of untreated systemic lupus erythematosus with death from acute pulmonary hemorrhage].

    Science.gov (United States)

    Fujinami, M; Sato, K; Tateishi, M; Okuda, M; Akashi, T; Okeda, R; Miyasaka, N

    1992-04-01

    An autopsy case of SLE died from acute and diffuse pulmonary hemorrhage is presented. A 50 year-old woman with SLE was admitted to our hospital because of high fever, butterfly rash, discoid skin lesions and renal dysfunction. She died from acute respiratory failure before initiation of the therapy with corticosteroid. Autopsy findings revealed a massive acute intrapulmonary hemorrhage. Histological study demonstrated a pulmonary arterial vasculitis with prominent fibrinoid necrosis at muscular pulmonary artery. No remarkable deposit of immunoglobulins and complements was found within the alveolar walls and pulmonary vessels by immunofluorescence and electron microscopy. Renal histology revealed diffuse proliferative glomerulonephritis with fibrinoid necrosis, crescent formation and wireloop lesions compatible with type IVb according to the WHO classification. The granular deposit of IgM, C3 and Clq, and electron dense deposit was found by immunofluorescence and by electron microscopy, respectively, in the kidney. The small arteries and veins in other organs, such as liver, spleen, bladder, ovary and rectum also revealed fibrinoid vasculitis. Acute infectious lesion was not observed in any tissue examined. The diffuse pulmonary hemorrhage in SLE could be one of the manifestations of active and severe systemic vasculitis.

  18. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

  19. Elevation of intact and proteolytic fragments of acute phase proteins constitutes the earliest systemic antiviral response in HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Holger B Kramer

    2010-05-01

    Full Text Available The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, beta-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA occurred as early as 5-7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha-1-antitrypsin (AAT, termed virus inhibitory peptide (VIRIP, was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.

  20. Development of a biotic ligand model and a regression model predicting acute copper toxicity to the earthworm Aporrectodea caliginosa.

    Science.gov (United States)

    Steenbergen, Nathanaël T T M; Iaccino, Federica; de Winkel, Maaike; Reijnders, Lucas; Peijnenburg, Willie J G M

    2005-08-01

    The purpose of this study was to develop a terrestrial biotic ligand model (BLM) for predicting acute copper toxicity to the earthworm Aporrectodea caliginosa. To overcome the basic problems hampering development of BLMs for terrestrial organisms, an artificial flow-through exposure system was developed consisting of an inert quartz sand matrix and a nutrient solution, of which the composition was univariately modified. A. caliginosa was exposed for 7 days under varying concentrations of copper and the major cations modifying toxicity: H+, Ca2+, Mg2+, and Na+. In addition copper speciation was modulated by means of EDTA or dissolved organic carbon (DOC). An increase in pH or pNa resulted in a linear decrease of 7-days median lethal concentrations. Increasing Ca2+ and Mg2+ activities had inconsistent effects. EDTA addition decreased toxicity when the total copper concentration in the pore water was kept the same. This is attributed to the strong complexation capacity of EDTA and shows that total copper is not the toxic species. DOC was more protective than could be explained by its metal complexing properties. The BLM developed incorporates the effects of H+ and Na+. This BLM was validated with the results of a set of bioassays with artificial pore water in quartz sand and by a set of bioassays in spiked field soils. Prediction error was within a factor of 2, but some predictions were not within the 95% confidence interval. Therefore a more widely applicable regression type model was developed that was able to explain >95% of the (lack of) toxicity observed. To our knowledge this is the first report of the successful development of a terrestrial BLM.

  1. Understanding factors that influence the integration of acute malnutrition interventions into the national health system in Niger.

    Science.gov (United States)

    Deconinck, Hedwig; Hallarou, Mahaman Elh; Pesonen, Anais; Gérard, Jean Christophe; Criel, Bart; Donnen, Philippe; Macq, Jean

    2016-12-01

    Since 2007 to address a high burden, integration of acute malnutrition has been promoted in Niger. This paper studies factors that influenced the integration process of acute malnutrition into the Niger national health system.We used qualitative methods of observation, key informant interviews and focus group discussions at national level, two districts and nine communities selected through convenience sampling, as well as document review. A framework approach constructed around the problem, intervention, adoption system, health system characteristics and broad context guided the analysis. Data were recorded on paper, transcribed in a descriptive record, coded by themes deduced by building on the framework and triangulated for comprehensiveness.Key facilitating factors identified were knowledge and recognition of the problem helped by accurate information; effectiveness of decentralized continuity of care; compatibility with goals, support and involvement of health actors; and leadership for aligning policies and partnerships and mobilizing resources within a favourable political context driven by multisectoral development goals. Key hindering factors identified were not fully understanding severity, causes and consequences of the problem; limited utilization and trust in health interventions; high workload, and health worker turnover and attrition; and high dependence on financial and technical support based on short-term emergency funding within a context of high demographic pressure.The study uncovered influencing factors of integrating acute malnutrition into the national health system and their complex dynamics and relationships. It elicited the need for goal-oriented strategies and alignment of health actors to achieve sustainability, and systems thinking to understand pathways that foster integration. We recommend that context-specific learning of integrating acute malnutrition may expand to include causal modelling and scenario testing to inform strategy

  2. The effect of intra-abdominal hypertension incorporating severe acute pancreatitis in a porcine model.

    Directory of Open Access Journals (Sweden)

    Lu Ke

    Full Text Available INTRODUCTION: Abdominal compartment syndrome (ACS and intra abdominal hypertension(IAH are common clinical findings in patients with severe acute pancreatitis(SAP. It is thought that an increased intra abdominal pressure(IAP is associated with poor prognosis in SAP patients. But the detailed effect of IAH/ACS on different organ system is not clear. The aim of this study was to assess the effect of SAP combined with IAH on hemodynamics, systemic oxygenation, and organ damage in a 12 h lasting porcine model. MEASUREMENTS AND METHODS: Following baseline registrations, a total of 30 animals were divided into 5 groups (6 animals in each group: SAP+IAP30 group, SAP+IAP20 group, SAP group, IAP30 group(sham-operated but without SAP and sham-operated group. We used a N(2 pneumoperitoneum to induce different levels of IAH and retrograde intra-ductal infusion of sodium taurocholate to induce SAP. The investigation period was 12 h. Hemodynamic parameters (CO, HR, MAP, CVP, urine output, oxygenation parameters(e.g., S(vO(2, PO(2, PaCO(2, peak inspiratory pressure, as well as serum parameters (e.g., ALT, amylase, lactate, creatinine were recorded. Histological examination of liver, intestine, pancreas, and lung was performed. MAIN RESULTS: Cardiac output significantly decreased in the SAP+IAH animals compared with other groups. Furthermore, AST, creatinine, SUN and lactate showed similar increasing tendency paralleled with profoundly decrease in S(vO(2. The histopathological analyses also revealed higher grade injury of liver, intestine, pancreas and lung in the SAP+IAH groups. However, few differences were found between the two SAP+IAH groups with different levels of IAP. CONCLUSIONS: Our newly developed porcine SAP+IAH model demonstrated that there were remarkable effects on global hemodynamics, oxygenation and organ function in response to sustained IAH of 12 h combined with SAP. Moreover, our model should be helpful to study the mechanisms of IAH

  3. Acute pain management efficiency improves with point-of-care handheld electronic billing system.

    Science.gov (United States)

    Fahy, Brenda G

    2009-02-01

    Technology advances continue to impact patient care and physician workflow. To enable more efficient performance of billing activities, a point-of-care (POC) handheld computer technology replaced a paper-based system on an acute pain management service. Using a handheld personal digital assistant (PDA) and software from MDeverywhere (MDe, MDeverywhere, Long Island, NY), we performed a 1-yr prospective observational study of an anesthesiology acute pain management service billings and collections. Seventeen anesthesiologists providing billable acute pain services were trained and entered their charges on a PDA. Twelve months of data, just before electronic implementation (pre-elec), were compared to a 12-m period after implementation (post-elec). The total charges were 4883 for 890 patients pre-elec and 5368 for 1128 patients post-elec. With adoption of handheld billing, the charge lag days decreased from 29.3 to 7.0 (P billing using PDAs to replace a paper-based billing system improved the collection rate and decreased the number of charge lag days with a positive return on investment. The handheld PDA billing system provided POC support for physicians during their daily clinical (e.g., patient locations, rounding lists) and billing activities, improving workflow.

  4. The effect of acute exposure to hyperbaric oxygen on respiratory system mechanics in the rat.

    Science.gov (United States)

    Rubini, Alessandro; Porzionato, Andrea; Zara, Susi; Cataldi, Amelia; Garetto, Giacomo; Bosco, Gerardo

    2013-10-01

    This study was designed to investigate the possible effects of acute hyperbaric hyperoxia on respiratory mechanics of anaesthetised, positive-pressure ventilated rats. We measured respiratory mechanics by the end-inflation occlusion method in nine rats previously acutely exposed to hyperbaric hyperoxia in a standard fashion. The method allows the measurements of respiratory system elastance and of both the "ohmic" and of the viscoelastic components of airway resistance, which respectively depend on the newtonian pressure dissipation due to the ohmic airway resistance to air flow, and on the viscoelastic pressure dissipation caused by respiratory system tissues stress-relaxation. The activities of inducible and endothelial NO-synthase in the lung's tissues (iNOS and eNOS respectively) also were investigated. Data were compared with those obtained in control animals. We found that the exposure to hyperbaric hyperoxia increased respiratory system elastance and both the "ohmic" and viscoelastic components of inspiratory resistances. These changes were accompanied by increased iNOS but not eNOS activities. Hyperbaric hyperoxia was shown to acutely induce detrimental effects on respiratory mechanics. A possible causative role was suggested for increased nitrogen reactive species production because of increased iNOS activity.

  5. Acute and chronic pathological effects of sulfur mustard on genitourinary system and male fertility.

    Science.gov (United States)

    Panahi, Yunes; Ghanei, Mostafa; Ghabili, Kamyar; Ansarin, Khalil; Aslanabadi, Saeid; Poursaleh, Zohreh; Golzari, Samad Eslam Jamal; Etemadi, Jalal; Khalili, Majid; Shoja, Mohammadali Mohajel

    2013-01-01

    To review the acute and chronic pathological effects of sulfur mustard on the genitourinary system and male fertility. We searched PubMed and Google Scholar to find studies related to the sulfur mustard-induced genitourinary effects and male infertility. Information in the abstracts of non-English related papers as well as those in the proceedings of congresses on sulfur mustard were reviewed as well. In acute phase after sulfur mustard exposure, evidences are in favor of microscopic and macroscopic renal lesions, very low androgen levels, and impaired spermatogenesis. Several years following sulfur mustard exposure, the long-term pathological effects vary from the renal function impairment to the gonadal damage, in particular the spermatogenesis. Nevertheless, carcinogenic effect of sulfur mustard on the genitourinary system as well as the prevalence of male infertility among sulfur mustard-exposed veterans in the chronic post-exposure phase is still unclear. Sulfur mustard causes both acute and chronic injuries to different parts of the genitourinary system.

  6. A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

    International Nuclear Information System (INIS)

    Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro; Uehara, Takeki; Kato, Yuki; Kono, Hiroshi; Bataller, Ramon; Rusyn, Ivan

    2016-01-01

    Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl 4 )-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl 4 (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl 4 . We observed that combined treatment with CCl 4 and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis

  7. Models of partnership within family-centred care in the acute paediatric setting: a discussion paper.

    Science.gov (United States)

    Dennis, Christine; Baxter, Pamela; Ploeg, Jenny; Blatz, Susan

    2017-02-01

    A discussion of partnership in the context of family-centred care in the acute paediatric setting, through a critical analysis of partnership models. Paediatric healthcare practitioners understand the importance of family-centred care, but struggle with how to translate the core tenets into action and are confused by several rival terms. Partnering relationships are included in definitions of family-centred care, yet less is known about strategies to fully engage or support parents in these partnerships. A rigorous examination of concepts embedded in family-centred care such as partnership may provide a better understanding of how to implement the broader concept and support exemplary care in today's clinical practice environment. Discussion paper. Electronic search (January 2000 - December 2014) performed on CINAHL, Medline, EMBASE, Sociological Abstracts and PsychINFO using keywords partnership, family-centred care and conceptual framework. Eligible references were drawn from the databases, reference lists and expert sources. Eight models met inclusion criteria and had currency and relevance to the acute paediatric setting. Nurses should continue exploring partnership in various paediatric contexts given the wide-ranging definitions, lack of operational indicators and need for stronger relational statements in current models. An examination of key strategies, barriers and facilitators of partnership is recommended. One partnership model had both high overall maturity and best fit with family-centred care principles. All models originate from Western and developed countries, indicating that future partnership models should be more geographically, culturally and economically diverse. © 2016 John Wiley & Sons Ltd.

  8. Cognitive models embedded in system simulation models

    International Nuclear Information System (INIS)

    Siegel, A.I.; Wolf, J.J.

    1982-01-01

    If we are to discuss and consider cognitive models, we must first come to grips with two questions: (1) What is cognition; (2) What is a model. Presumably, the answers to these questions can provide a basis for defining a cognitive model. Accordingly, this paper first places these two questions into perspective. Then, cognitive models are set within the context of computer simulation models and a number of computer simulations of cognitive processes are described. Finally, pervasive issues are discussed vis-a-vis cognitive modeling in the computer simulation context

  9. [Implementation of a regional system for the emergency care of acute ischemic stroke: Initial results].

    Science.gov (United States)

    Soares-Oliveira, Miguel; Araújo, Fernando

    2014-06-01

    Implementing integrated systems for emergency care of patients with acute ischemic stroke helps reduce morbidity and mortality. We describe the process of organizing and implementing a regional system to cover around 3.7 million people and its main initial results. We performed a descriptive analysis of the implementation process and a retrospective analysis of the following parameters: number of patients prenotified by the pre-hospital system; number of times thrombolysis was performed; door-to-needle time; and functional assessment three months after stroke. The implementation process started in November 2005 and ended in December 2009, and included 11 health centers. There were 3574 prenotifications from the prehospital system. Thrombolysis was performed in 1142 patients. The percentage of patients receiving thrombolysis rose during the study period, with a maximum of 16%. Median door-to-needle time was 62 min in 2009. Functional recovery three months after stroke was total or near total in 50% of patients. The regional system implemented for emergency care of patients with acute ischemic stroke has led to health gains, with progressive improvements in patients' access to thrombolysis, and to greater equity in the health care system, thus helping to reduce mortality from cerebrovascular disease in Portugal. Our results, which are comparable with those of international studies, support the strategy adopted for implementation of this system. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  10. Thermodynamic modeling of complex systems

    DEFF Research Database (Denmark)

    Liang, Xiaodong

    . Contrary to earlier theories, the oil is not only present on the surface, but also in great volumes both in the water column and on the seafloor, which indicates that we do not know enough about how oil behaves in water and interacts with it. Sonar detection is one of the most important and necessary...... after an oil spill. Engineering thermodynamics could be applied in the state-of-the-art sonar products through advanced artificial technology, if the speed of sound, solubility and density of oil-seawater systems could be satisfactorily modelled. The addition of methanol or glycols into unprocessed well...... streams during subsea pipelines is necessary to inhibit gas hydrate formation, and the offshore reservoirs often mean complicated temperature and pressure conditions. Accurate description of the phase behavior and thermalphysical properties of complex systems containing petroleum fluids and polar...

  11. Studies of Catalytic Model Systems

    DEFF Research Database (Denmark)

    Holse, Christian

    of the Cu/ZnO nanoparticles is highly relevant to industrial methanol synthesis for which the direct interaction of Cu and ZnO nanocrystals synergistically boost the catalytic activity. The dynamical behavior of the nanoparticles under reducing and oxidizing environments were studied by means of ex situ X...... as the nanoparticles are reduced. The Cu/ZnO nanoparticles are tested on a  µ-reactor platform and prove to be active towards methanol synthesis, making it an excellent model system for further investigations into activity depended morphology changes....

  12. Power Doppler Imaging in Acute Renal Vein Occlusion and Recanalization: a Canine Model

    International Nuclear Information System (INIS)

    Yoo, So-Young; Kim, In-One; Kim, Young-Il; Lee, Kyoung Ho; Lee, Min Woo; Youn, Byung Jae; Kim, Woo Sun; Yeon, Kyung Mo

    2008-01-01

    Objective : To evaluate the dynamic changes of the power Doppler (PD) in acute renal vein occlusion and recanalization in a canine model. Materials and Methods : We performed a PD of the kidney during graded renal vein occlusion and recanalization induced by balloon inflation and deflation in nine dogs. The PD images were transferred to a personal computer, and the PD signals were quantified. Result : We observed the temporal change of the PD signal during renal vein occlusion and recanalization, with a decrease in the PD signal during occlusion and an increase during recanalization. The mean PD signal decreased gradually as the renal vein was occluded, and conversely increased gradually with sequential relief of occlusion. The sequential change of the mean value of the PD signal was statistically significant. Conclusion : The PD can detect a change in renal blood flow during acute renal vein occlusion and recanalization in a canine model. The PD may be used as a helpful tool for the early detection of acute renal vein thrombosis and the monitoring of renal perfusion

  13. EFFECTS OF LUDARTIN AND LEUKOMISIN ON THE ACUTE HYPERLIPIDEMIA MODEL INDUCED BY ETHANOL

    Directory of Open Access Journals (Sweden)

    A. V. Ratkin

    2015-01-01

    Full Text Available Objective: study sesquiterpene lactones ludartin and leukomisin lipid-lowering properties on the model of acute hyperlipidemia induced by ethanol in rats.Material and methods. Rats during 7 days injected into the stomach ludartin and leukomisin in a dose 10 mg/kg or reference drug nicotinic acid in a dose 25 mg/kg. Hyperlipidemia caused by single introduc-tion of ethanol into the stomach in a dose 5 g/kg. In blood serum of tail vein measured the triacylgly-cerols, total cholesterol, high density and low density lipoproteins cholesterol, also the level of free fatty acids. Calculated the ratio of high density lipoproteins cholesterol to the amount of low density lipopro-teins cholesterol and the index of atherogenicity.Results. A single dose of ethanol increased serum level of triacylglycerols in 1.9 times, free fatty acids – in 3.2 times, low density lipoproteins – on 44% in comparison with the intact animals indices. It shows the development of acute hyperlipidemia. Serum total cholesterol, high density lipoproteins cholesterol and the index of atherogenicity were not changed. Course introduction of sesquiterpene lactones ludartin and leukomisin against the background of acute hyperlipidemia was accompanied by a decrease in the serum of triacylglycerols levels respectively by 37.5% and 49.5%. Nicotinic acid lowered the content of triacylglycerols by 42.4%. Ludartin, leukomisin and nicotinic acid reduced the increased level of free fatty acids in the blood serum by 63.4%, 41.6% and 67.9%. Ludartin, leukomisin and nicotinic acid de-creased by 15.8%, 20.3% and 17.2% of total cholesterol in the blood serum. In acute hyperlipidemia ludartin and leukomisin reduced low density lipoproteins cholesterol by 23.8% and 14.8%, respectively, nicotinic acid – by 15.7%. Both of sesquiterpene lactone and nicotinic acid did not modify the content of high density lipoproteins cholesterol. When introduction ludartin and nicotinic acid ratio of high density

  14. EFFECTS OF GROSSHEMIN AND GROSSMISIN ON THE ACUTE HYPERLIPIDEMIA MODEL INDUCED BY ETHANOL

    Directory of Open Access Journals (Sweden)

    A. V. Ratkin

    2014-01-01

    Full Text Available Objective: study sesquiterpene lactones grosshemin and grossmisin lipid-lowering properties on the model of acute hyperlipidemia induced by ethanol in rats.Materials and methods. Rats during 7 days injected into the stomach grosshemin and grossmisin in a dose 10 mg/kg or reference drug nicotinic acid in a dose 25 mg/kg. Hyperlipidemia caused by single introduction of ethanol into the stomach in a dose 5 g/kg. In blood serum of tail vein measured the triacylglycerols, total cholesterol, high density and low density lipoproteins cholesterol, also the level of free fatty acids. Calculated the ratio of high density lipoproteins cholesterol to the amount of low density lipoproteins cholesterol and the index of atherogenicity.Results. A single dose of ethanol increased serum level of triacylglycerols in 1.9 times, free fatty acids – in 3.2 times, low density lipoproteins – on 44% in comparison with the intact animals indices. It shows the development of acute hyperlipidemia. Serum total cholesterol, high density lipoproteins cholesterol and the index of atherogenicity were not changed. Course sesquiterpene lactones grosshemin and grossmisin introduction against the background of acute hyperlipidemia was accompanied by a decrease in the serum of triacylglycerols levels respectively by 19.8% and 34.1%. Nicotinic acid lowered the content of triacylglycerols by 42.4%. Grosshemin and nicotinic acid reduced the increased level of free fatty acids in the blood serum by 60.7–67.9%. Grossmisin and nicotinic acid decreased by 14.6–17.2% of total cholesterol in the blood serum. In acute hyperlipidemia grosshemin and grossmisin reduced low density lipoproteins cholesterol by 17.6% and 20%, respectively, nicotinic acid – by 15.7%. Both of sesquiterpene lactone and nicotinic acid did not modify the content of high density lipoproteins cholesterol. When introduction grosshemin, grossmisin and nicotinic acid ratio of high density lipoproteins cholesterol to

  15. The influence of a fentanyl and dexmedetomidine combination on external respiratory functions in acute hemorrhage model

    Directory of Open Access Journals (Sweden)

    Nikolay G. Vengerovich

    2017-01-01

    Full Text Available Background. The synthetic opioid analgesic fentanyl is widely used for prophylaxis and therapy of traumatic shock associated with massive bleeding. Its side effects – skeletal muscle rigidity and respiratory center depression – are especially pronounced with repeated administration. It is rational to apply fentanyl in diminished doses in combination with non-opioid analgesics in order to reduce respiratory disturbances risk.Aim. The aim of the work is to justify the influence of opioid analgesic fentanyl and α2 -adrenomimetic dexmedetomidine combination on external respiratory functions in acute hemorrhage model.Materials and methods. Acute loss of 35–40% of circulating blood volume was modeled in experiments on 75 white mongrel male rats. The external respiratory functions (respiratory rate, respiratory volume, breath volume per minute were estimated in animals of 5 groups: 1 – rats without analgesic help (controls; 2–3 – rats receiving a single fentanyl intramuscular injection (ED99 98,96 mcg/kg or fentanyl together with dexme detomidine (ED99 of combination 67,94 mcg/kg 15 min after acute blood loss; 4–5 – rats receiving the same drugs 15 min, 30, 45 and 60 min later.Results. In experimental acute loss of 35–40% of circulating blood volume, 15 min later a secondary acute respiratory failure developed with a drop of respiratory rate, respiratory volume and volume of breath per minute by 30%, 21 and 47% (p < 0,05. The external respiratory functions recoverеd after 4 h mainly due to the increase of respiratory volume. A single intramuscular injection of fentanyl caused respiratory depression 15 min after experimental blood loss which resulted in the decrease of breath volume per minute to 30–61% (p < 0,05 for 90 min. Four intramuscular injections of fentanyl 15 min, 30, 45 and 60 min after hemorrhage caused a severe respiratory dysfunction, accompanied by apnea periods and Biot’s respiration. Respiratory rate was reduced

  16. Experimentally derived acute and chronic copper Biotic Ligand Models for rainbow trout.

    Science.gov (United States)

    Crémazy, Anne; Wood, Chris M; Ng, Tania Y-T; Smith, D Scott; Chowdhury, M Jasim

    2017-11-01

    We evaluated the effects of varying water chemistry ([Ca 2+ ]=0.2-3mM, [Mg 2+ ]=0.05-3mM, dissolved organic matter (DOM, natural, from maple leaves)=0.3-10mg of CL -1 , pH=5.0-8.5) on the acute (96-h, unfed fish) and chronic (30-d, fed fish) toxicity of waterborne Cu to juvenile rainbow trout (Oncorhynchus mykiss) exposed in flow-through conditions. Acute and chronic Biotic Ligand Models (BLMs) were developed from the obtained toxicity data-sets, using the Visual MINTEQ software. Our results indicate that Cu is predominantly an acute toxicant to rainbow trout, as there were no observable growth effects and the 96-h and 30-d LC50 values were similar, with mortality mostly occurring within the first few days of exposure. Calcium and DOM were greatly protective against both acute and chronic Cu toxicity, but Mg seemed to only protect against chronic toxicity. Additional protection by pH 5.0 in acute exposure and by pH 8.5 in chronic exposure occurred. In the range of conditions tested, the observed 96-h LC50 and 30-d LC20 values varied by a factor of 39 and 27 respectively. The newly developed acute and chronic BLMs explained these variations reasonably well (i.e. within a 2-fold error), except at pH≥8 where the high observed acute toxicity could not be explained, even by considering an equal contribution of CuOH + and Cu 2+ to the overall Cu toxicity. The 96-h LC50 values of 59% of 90 toxicity tests from 19 independent studies in the literature were reasonably well predicted by the new acute BLM. The LC20 predictions from the new chronic BLM were reasonable for 7 out of 14 toxicity tests from 6 independent chronic studies (with variable exposure durations). The observed deviations from BLM predictions may be due to uncertainties in the water chemistry in these literature studies and/or to differences in fish sensitivity. A residual pH effect was also observed for both the acute and the chronic data-sets, as the ratio of predicted vs. observed LC values generally

  17. Dopamine-independent locomotor actions of amphetamines in a novel acute mouse model of Parkinson disease.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available Brain dopamine is critically involved in movement control, and its deficiency is the primary cause of motor symptoms in Parkinson disease. Here we report development of an animal model of acute severe dopamine deficiency by using mice lacking the dopamine transporter. In the absence of transporter-mediated recycling mechanisms, dopamine levels become entirely dependent on de novo synthesis. Acute pharmacological inhibition of dopamine synthesis in these mice induces transient elimination of striatal dopamine accompanied by the development of a striking behavioral phenotype manifested as severe akinesia, rigidity, tremor, and ptosis. This phenotype can be reversed by administration of the dopamine precursor, L-DOPA, or by nonselective dopamine agonists. Surprisingly, several amphetamine derivatives were also effective in reversing these behavioral abnormalities in a dopamine-independent manner. Identification of dopamine transporter- and dopamine-independent locomotor actions of amphetamines suggests a novel paradigm in the search for prospective anti-Parkinsonian drugs.

  18. Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias.

    Science.gov (United States)

    Stubenhaus, Bradford M; Dustin, John P; Neverett, Emily R; Beaudry, Megan S; Nadeau, Leanna E; Burk-McCoy, Ethan; He, Xinwen; Pearson, Bret J; Pellettieri, Jason

    2016-05-31

    Porphyrias are disorders of heme metabolism frequently characterized by extreme photosensitivity. This symptom results from accumulation of porphyrins, tetrapyrrole intermediates in heme biosynthesis that generate reactive oxygen species when exposed to light, in the skin of affected individuals. Here we report that in addition to producing an ommochrome body pigment, the planarian flatworm Schmidtea mediterranea generates porphyrins in its subepithelial pigment cells under physiological conditions, and that this leads to pigment cell loss when animals are exposed to intense visible light. Remarkably, porphyrin biosynthesis and light-induced depigmentation are enhanced by starvation, recapitulating a common feature of some porphyrias - decreased nutrient intake precipitates an acute manifestation of the disease. Our results establish planarians as an experimentally tractable animal model for research into the pathophysiology of acute porphyrias, and potentially for the identification of novel pharmacological interventions capable of alleviating porphyrin-mediated photosensitivity or decoupling dieting and fasting from disease pathogenesis.

  19. Efficacy of voriconazole in a murine model of acute Trypanosoma cruzi infection.

    Science.gov (United States)

    Gulin, J E N; Eagleson, M A; Postan, M; Cutrullis, R A; Freilij, H; Bournissen, F Garcia; Petray, P B; Altcheh, J

    2013-04-01

    Antifungal triazole derivatives have been studied as possible alternatives for the treatment of Chagas' disease. Voriconazole has demonstrated in vitro activity against Trypanosoma cruzi, but its efficacy in vivo has not yet been tested. We aimed to determine the effect of voriconazole in a murine model of acute T. cruzi infection. Treatment efficacy was evaluated by comparing parasitaemia, mortality and organ involvement (by histological examination) of infected mice. Treatment with voriconazole significantly lowered parasitaemia and mortality compared with controls, reduced the percentage of mice with amastigote nests in heart and skeletal muscle and moderately decreased myocardial inflammation. Our findings support the potential of voriconazole for the treatment of acute Chagas' disease and motivate future animal studies using varying doses and treatment schemes. Further evaluation of voriconazole for clinical use in human Chagas' patients is warranted.

  20. Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience

    Science.gov (United States)

    2015-10-01

    prevention programs, including pressure relief regimes and selection of support surfaces , to optimize tissue heath during initial rehabilitation. Study...AWARD NUMBER: W81XWH-14-1-0618 TITLE: Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury...Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience 5a. CONTRACT NUMBER

  1. Polysaccharides from Arnebia euchroma Ameliorated Endotoxic Fever and Acute Lung Injury in Rats Through Inhibiting Complement System.

    Science.gov (United States)

    Ou, Ying-Ye; Jiang, Yun; Li, Hong; Zhang, Yun-Yi; Lu, Yan; Chen, Dao-Feng

    2017-02-01

    Arnebiaeuchroma (Royle) Johnst (Ruanzicao) is a traditional Chinese herbal medicine (TCM). It is extensively used in China and other countries for treatment of inflammatory diseases. It is known that hyper-activated complement system involves in the fever and acute lung injury (ALI) in rats. In our preliminary studies, anti-complementary activity of crude Arnebiaeuchroma polysaccharides (CAEP) had been demonstrated in vitro. This study aimed to investigate the role and mechanism of crude Arnebiaeuchroma polysaccharides (CAEP) using two animal models, which relate with inappropriate activation of complement system. In lipopolysaccharide (LPS)-induced fever model, the body temperature and leukocytes of peripheral blood in rats were significantly increased, while the complement levels of serum were remarkably decreased. CAEP administration alleviated the LPS-induced fever, reduced the number of leukocytes, and improved the levels of complement. Histological assay showed that there were severe damages and complement depositions in lung of the ALI rats. Further detection displayed that the oxidant stress was enhanced, and total hemolytic activity and C3/C4 levels in serum were decreased significantly in the ALI model group. Remarkably, CAEP not only attenuated the morphological injury, edema, and permeability in the lung but also significantly weakened the oxidant stress in bronchoalveolar lavage fluid (BALF) in the ALI rats. The levels of complement and complement depositions were improved by the CAEP treatment. In conclusion, the CAEP treatment ameliorated febrile response induced by LPS and acute lung injury induced by LPS plus ischemia-reperfusion. CAEP exerted beneficial effects on inflammatory disease potentially via inhibiting the inappropriate activation of complement system.

  2. ApoSense: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Damianovich, Maya; Ziv, Ilan; Aloya, Tali; Grimberg, Hagit; Levin, Galit; Reshef, Ayelet; Bentolila, Alfonso; Cohen, Avi; Shirvan, Anat [NeuroSurvival Technologies (NST) Ltd., Petah Tikva (Israel); Heyman, Samuel N.; Shina, Ahuva [Mt.Scopus and the Hebrew University Medical School, Department of Medicine, Hadassah Hospital, Jerusalem (Israel); Rosen, Seymour [Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Pathology, Boston, MA (United States); Kidron, Dvora [Meir Hospital, Department of Pathology, Kfar-Saba (Israel)

    2006-03-15

    Acute renal tubular necrosis (ATN), a common cause of acute renal failure, is a dynamic, rapidly evolving clinical condition associated with apoptotic and necrotic tubular cell death. Its early identification is critical, but current detection methods relying upon clinical assessment, such as kidney biopsy and functional assays, are insufficient. We have developed a family of small molecule compounds, ApoSense, that is capable, upon systemic administration, of selectively targeting and accumulating within apoptotic/necrotic cells and is suitable for attachment of different markers for clinical imaging. The purpose of this study was to test the applicability of these molecules as a diagnostic imaging agent for the detection of renal tubular cell injury following renal ischemia. Using both fluorescent and radiolabeled derivatives of one of the ApoSense compounds, didansyl cystine, we evaluated cell death in three experimental, clinically relevant animal models of ATN: renal ischemia/reperfusion, radiocontrast-induced distal tubular necrosis, and cecal ligature and perforation-induced sepsis. ApoSense showed high sensitivity and specificity in targeting injured renal tubular epithelial cells in vivo in all three models used. Uptake of ApoSense in the ischemic kidney was higher than in the non-ischemic one, and the specificity of ApoSense targeting was demonstrated by its localization to regions of apoptotic/necrotic cell death, detected morphologically and by TUNEL staining. (orig.)

  3. Systems modeling and simulation applications for critical care medicine.

    Science.gov (United States)

    Dong, Yue; Chbat, Nicolas W; Gupta, Ashish; Hadzikadic, Mirsad; Gajic, Ognjen

    2012-06-15

    Critical care delivery is a complex, expensive, error prone, medical specialty and remains the focal point of major improvement efforts in healthcare delivery. Various modeling and simulation techniques offer unique opportunities to better understand the interactions between clinical physiology and care delivery. The novel insights gained from the systems perspective can then be used to develop and test new treatment strategies and make critical care delivery more efficient and effective. However, modeling and simulation applications in critical care remain underutilized. This article provides an overview of major computer-based simulation techniques as applied to critical care medicine. We provide three application examples of different simulation techniques, including a) pathophysiological model of acute lung injury, b) process modeling of critical care delivery, and c) an agent-based model to study interaction between pathophysiology and healthcare delivery. Finally, we identify certain challenges to, and opportunities for, future research in the area.

  4. Reservoir Model Information System: REMIS

    Science.gov (United States)

    Lee, Sang Yun; Lee, Kwang-Wu; Rhee, Taehyun; Neumann, Ulrich

    2009-01-01

    We describe a novel data visualization framework named Reservoir Model Information System (REMIS) for the display of complex and multi-dimensional data sets in oil reservoirs. It is aimed at facilitating visual exploration and analysis of data sets as well as user collaboration in an easier way. Our framework consists of two main modules: the data access point module and the data visualization module. For the data access point module, the Phrase-Driven Grammar System (PDGS) is adopted for helping users facilitate the visualization of data. It integrates data source applications and external visualization tools and allows users to formulate data query and visualization descriptions by selecting graphical icons in a menu or on a map with step-by-step visual guidance. For the data visualization module, we implemented our first prototype of an interactive volume viewer named REMVR to classify and to visualize geo-spatial specific data sets. By combining PDGS and REMVR, REMIS assists users better in describing visualizations and exploring data so that they can easily find desired data and explore interesting or meaningful relationships including trends and exceptions in oil reservoir model data.

  5. Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study

    NARCIS (Netherlands)

    Attia, Suzanna; Versloot, Christian J.; Voskuijl, Wieger; van Vliet, Sara J.; Di Giovanni, Valeria; Zhang, Ling; Richardson, Susan; Bourdon, Céline; Netea, Mihai G.; Berkley, James A.; van Rheenen, Patrick F.; Bandsma, Robert Hj

    2016-01-01

    Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear. We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their associations with mortality in

  6. Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation : an observational cohort study

    NARCIS (Netherlands)

    Attia, Suzanna; Versloot, Christian J.; Voskuijl, Wieger; van Vliet, Sara J.; Di Giovanni, Valeria; Zhang, Ling; Richardson, Susan; Bourdon, Celine; Netea, Mihai G.; Berkley, James A.; van Rheenen, Patrick F.; Bandsma, Robert H. J.

    2016-01-01

    Background: Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear. Objective: We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their

  7. Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study

    NARCIS (Netherlands)

    Attia, S.; Versloot, C.J.; Voskuijl, W.; Vliet, S.J. van; Giovanni, V. Di; Zhang, L.; Richardson, S.; Bourdon, C.; Netea, M.G.; Berkley, J.A.; Rheenen, P.F. van; Bandsma, R.H.

    2016-01-01

    BACKGROUND: Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear. OBJECTIVE: We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their

  8. Acute Care Referral Systems in Liberia: Transfer and Referral Capabilities in a Low-Income Country.

    Science.gov (United States)

    Kim, Jimin; Barreix, Maria; Babcock, Christine; Bills, Corey B

    2017-12-01

    Introduction Following two decades of armed conflict in Liberia, over 95% of health care facilities were partially or completely destroyed. Although the Liberian health system has undergone significant rehabilitation, one particular weakness is the lack of organized systems for referral and prehospital care. Acute care referral systems are a critical component of effective health care delivery and have led to improved quality of care and patient outcomes. Problem This study aimed to characterize the referral and transfer systems in the largest county of Liberia. A cross-sectional, health referral survey of a representative sample of health facilities in Montserrado County, Liberia was performed. A systematic random sample of all primary health care (PHC) clinics, fraction proportional to district population size, and all secondary and tertiary health facilities were included in the study sample. Collected data included baseline information about the health facility, patient flow, and qualitative and quantitative data regarding referral practices. A total of 62 health facilities-41 PHC clinics, 11 health centers (HCs), and 10 referral hospitals (RHs)-were surveyed during the 6-week study period. In sum, three percent of patients were referred to a higher-level of care. Communication between health facilities was largely unsystematic, with lack of specific protocols (n=3; 5.0%) and standardized documentation (n=26; 44.0%) for referral. While most health facilities reported walking as the primary means by which patients presented to initial health facilities (n=50; 81.0%), private vehicles, including commercial taxis (n=37; 60.0%), were the primary transport mechanism for referral of patients between health facilities. This study identified several weaknesses in acute care referral systems in Liberia, including lack of systematic care protocols for transfer, documentation, communication, and transport. However, several informal, well-functioning mechanisms for

  9. Modeling learning technology systems as business systems

    NARCIS (Netherlands)

    Avgeriou, Paris; Retalis, Symeon; Papaspyrou, Nikolaos

    2003-01-01

    The design of Learning Technology Systems, and the Software Systems that support them, is largely conducted on an intuitive, ad hoc basis, thus resulting in inefficient systems that defectively support the learning process. There is now justifiable, increasing effort in formalizing the engineering

  10. Bond graph modeling of centrifugal compression systems

    OpenAIRE

    Uddin, Nur; Gravdahl, Jan Tommy

    2015-01-01

    A novel approach to model unsteady fluid dynamics in a compressor network by using a bond graph is presented. The model is intended in particular for compressor control system development. First, we develop a bond graph model of a single compression system. Bond graph modeling offers a different perspective to previous work by modeling the compression system based on energy flow instead of fluid dynamics. Analyzing the bond graph model explains the energy flow during compressor surge. Two pri...

  11. Structuring Problem Analysis for Embedded Systems Modelling

    NARCIS (Netherlands)

    Marincic, J.; Mader, Angelika H.; Wieringa, Roelf J.; Lucas, Yan

    Our interest is embedded systems validation as part of the model-driven approach. To design a model, the modeller needs to obtain knowledge about the system and decide what is relevant to model and how. A part of the modelling activities is inherently informal - it cannot be formalised in such a way

  12. Blockade of Rennin-Angiotensin system blunts the fibrotic response in experimental acute pyelonephritis

    Directory of Open Access Journals (Sweden)

    Singal A

    2005-01-01

    Full Text Available Aim: To study the impact of Renin-Angiotensin system blockade in experimental acute pyelonephritis, induced by a novel surgical approach via dorsal lumbotomy incision. Materials and Methods : 45 Adult female WISTAR rats aged 8-12 weeks, underwent direct inoculation of 0.1 ml of E.coli suspension into the parenchyma of the surgically exposed kidney. 3 groups of rats were studied: Group A - treated with antibiotics only; Group B- Captopril and antibiotics and Group C- Losartan and antibiotics. Changes of acute inflammation, parenchymal destruction and scarring were compared between the groups on histopathological sections. Kruskal-Wallis test was used for statistical analysis. Results : Changes consistent with acute pyelonephritis were seen in all the kidneys. Mean% scar area in Group A, Group B and Group C was 37.08±1.79, 24.40±1.88 and 24.68±1.32% respectively at end of six weeks. Mean tubular density in Group A, B and C was 17.26±1.92, 47.18±3.00 and 47.00±5.08-tubules/lac mm2 respectively. The differences between the control and the treated animals were significant, though the results did not differ between the losartan and captopril treated rats. Conclusions : Dorsal lumbotomy approach to the kidney provides a good exposure of the kidney. Induction of acute pyelonephritis by direct inoculation of bacteria into renal cortex produced a consistent scar at 6 weeks. Blockade of renin angiotensin system by either captopril or losartan decreased the renal scar area by almost 1/3 at 6 weeks.

  13. The mathematical pathogenetic factors analysis of acute inflammatory diseases development of bronchopulmonary system among infants

    Directory of Open Access Journals (Sweden)

    G. O. Lezhenko

    2017-10-01

    Full Text Available The purpose. To study the factor structure and to establish the associative interaction of pathogenetic links of acute diseases development of the bronchopulmonary system in infants.Materials and methods. The examination group consisted of 59 infants (average age 13.8 ± 1.4 months sick with acute inflammatory bronchopulmonary diseases. Also we tested the level of 25-hydroxyvitamin D (25(ОНD, vitamin D-binding protein, hBPI, cathelicidin LL-37, ß1-defensins, lactoferrin in blood serum with the help of immunoenzymometric analysis. Selection of prognostically important pathogenetic factors of acute bronchopulmonary disease among infants was conducted using ROC-analysis. The procedure for classifying objects was carried out using Hierarchical Cluster Analysis by the method of Centroid-based clustering. Results. Based on the results of the ROC-analysis were selected 15 potential predictors of the development of acute inflammatory diseases of the bronchopulmonary system among infants. The factor analysis made it possible to determine the 6 main components . The biggest influence in the development of the disease was made by "the anemia factor", "the factor of inflammation", "the maternal factor", "the vitamin D supply factor", "the immune factor" and "the phosphorus-calcium exchange factor” with a factor load of more than 0.6. The performed procedure of hierarchical cluster analysis confirmed the initial role of immuno-inflammatory components. The conclusions. The highlighted factors allowed to define a group of parameters, that must be influenced to achieve a maximum effect in carrying out preventive and therapeutic measures. First of all, it is necessary to influence the "the anemia factor" and "the calcium exchange factor", as well as the "the vitamin D supply factor". In other words, to correct vitamin D deficiency and carry out measures aimed at preventing the development of anemia. The prevention and treatment of the pathological course of

  14. A Novel Scoring System for Diagnosing Acute Mesenteric Ischemia in the Emergency Ward.

    Science.gov (United States)

    Wang, Zhen; Chen, Jun-Qiang; Liu, Jin-Lu; Tian, Lei

    2017-08-01

    Early diagnosis of acute mesenteric ischemia (AMI) based on clinical judgment has been proved to be too difficult. Therefore, it is important for identifying clinical parameters that can differentiate AMI from other acute abdomen upon presentation. We analyzed a database of 106 consecutive patients admitted to the emergency ward for suspected AMI in whom diagnosis of AMI was confirmed by laparotomy, CT angiography or mesenteric angiography. The patients' demographics, previous history, clinical signs, results of laboratory investigations and ultrasonography were collected. Diagnostic cutoff value of quantitative indexes was derived from the receiver operating curve. Multivariate logistic regression was used to identify risk factors for AMI and formulated these risk factors into a scoring system. A total of 45 patients (42.5%) were confirmed to have AMI. Compared with other acute abdomen, AMI had significantly increased level of white blood cell (Odds ratio (OR) 16.11, 95% confidence interval (CI) 1.10-235.34), red cell distribution width (OR 27.65, 95% CI 1.53-501.02), mean platelet volume (OR 16.06, 95% CI 1.48-174.50) and D-dimer (OR 42.91, 95% CI 2.56-718.09). A diagnostic score was calculated by adding points assigned to the four parameters, and a cutoff score of four best identified patients with AMI, with sensitivity, specificity, positive and negative predictive values of 97.8, 91.8, 89.8 and 98.2%, respectively. This scoring system based on easily available parameters could be used as a useful tool for differentiating AMI from other acute abdomen in the emergency ward. Prospective studies with large sample remain needed for validating the results.

  15. Changes in Heart Rhythm and Breathing in Acute Systemic Injury Due to Cold

    Directory of Open Access Journals (Sweden)

    D. Yu. Konnov

    2015-01-01

    Full Text Available Objective: to reveal the patterns of a change in heart rhythm and breathing in patients with acute systemic injury due to cold in hypothermic and early posthypothermic periods.Subjects and methods. Thirty patients aged 18 to 60 years (3 groups of 10 patients with mild, moderate, and severe cold injury were examined in hypothermic and posthypothermic periods. The patient groups did not differ in gender, age, and weight. Within the first 24 hours after admission, all the patients underwent high-resolution Holter electrocardiographic monitoring that recorded cardiac arrhythmias and breathing disorders.Results. During the therapy performed, as the degree of acute systemic cold injury increased, the patients were found to have a heart rate reduction (from 102 [90; 122] beats/min in Group 1 to 49 [38; 58] beats/min in Group 3 and a circadian index increase (from 105 [88; 125]% in Group 1 to 210 [185; 223]% in Group 3. With increased hypothermia, the victims were detected to have progressive cardiac rhythm and cardiac electrical conduction disturbances, such as supraventricular pacemaker migration, single and paired supraventricular premature beats, paroxysmal atrial tachycardia, atrial fibrillations, and ventricular premature beats. There was decreased heart rhythm variability in all the study groups, to the greatest extent in the patents with severe systemic cold injury. Late ventricular potentials were found in 2 and 7 patients with moderate and severe cold injury, respectively. Breathing disorders were recorded in all the study groups, the greatest increase in the frequency and duration of apnea/hypopnea episodes was noted in the patients with severe hypothermia. A fatal outcome occurred in 4 of the 10 patients with critical hypothermia due to the occurrence of idioventricular rhythm with transition to asystole.Conclusion. Systemic hypothermia is accompanied by cardiac rhythm and cardiac electrical conduction disturbances and respiratory depression

  16. Establishment and evaluation of acute pulmonary embolism model in rabbit monitored with echocardiography

    International Nuclear Information System (INIS)

    Cong Dengli; Yu Xiaofeng; Qu Shaochun; Cong Zhibin

    2010-01-01

    Objective: To establish acute pulmonary embolism (APE) model in rabbit under echocardiography, and compare with the pathological results, and explore the feasibility of establishment of APE model monitored with echocardiography. Methods: APE models were established in 25 healthy Japanese white rabbits. The rabbit models of APE were created by right external jugular vena catheter using gelatin sponge monitored with echocardiography. Gelatin sponge emboli, 2 mm x 2 mm x 10 mm each, following with 5 mL physiologic saline were injected separately to right atrium via the right external jugular vein, which could make these emboli embolize pulmonary artery following blood stream. And the pulmonary artery systolic pressure was detected. Then the lung tissues slices near embolism place were detected by pathology after the model rabbits were dissected. Results: Twenty-three rabbit models with APE were successfully established from twenty-five healthy rabbits. However, one rabbit was unexpectedly dead because of anesthesia, another rabbit was dead owing to acute congestive heart failure of cor dextrum by emboli stagnation in cor dextrum. The echocardiogram of rabbits before and after model establishment showed that the pulmonary artery systolic pressure was significantly increased after APE, the main pulmonary artery, the left pulmonary artery and the right pulmonary artery were passively expanded. The right ventricle was increased and left ventricle was decreased oppositely, interventricular septum expanded toward left ventricle. there was significant difference compared with pre-embolism (P< 0.01). Gelatin sponge emboli in the pulmonary artery were detected by pathological detection. Conclusion: The method to establish APE model monitored with echocardiography is simple and feasible. It could be used as one of methods to establish APE model, animal. (authors)

  17. Systemic administration of a novel human umbilical cord mesenchymal stem cells population accelerates the resolution of acute liver injury

    Directory of Open Access Journals (Sweden)

    Burra Patrizia

    2012-07-01

    Full Text Available Abstract Background Hepatocytes and stem cells transplantation may be an alternative to liver transplantation in acute or chronic liver disease. We aimed to evaluate the therapeutic potential of mesenchymal stem cells from human umbilical cord (UCMSCs, a readily available source of mesenchymal stem cells, in the CCl4-induced acute liver injury model. Methods Mesenchymal stem cells profile was analyzed by flow cytometry. In order to evaluate the capability of our UCMSCs to differentiate in hepatocytes, cells were seeded on three different supports, untreated plastic support, MatrigelTM and human liver acellular matrix. Cells were analyzed by immunocitochemistry for alpha-fetoprotein and albumin expression, qPCR for hepatocyte markers gene expression, Periodic Acid-Schiff staining for glycogen storage, ELISA for albumin detection and colorimetric assay for urea secretion. To assess the effects of undifferentiated UCMSCs in hepatic regeneration after an acute liver injury, we transplanted them via tail vein in mice injected intraperitoneally with a single dose of CCl4. Livers were analyzed by histological evaluation for damage quantification, immunostaining for Kupffer and stellate cells/liver myofibroblasts activation and for UCMSCs homing. Pro- and anti-inflammatory cytokines gene expression was evaluated by qPCR analysis and antioxidant enzyme activity was measured by catalase quantification. Data were analyzed by Mann–Whitney U-test, Kruskal-Wallis test and Cuzick’s test followed by Bonferroni correction for multiple comparisons. Results We have standardized the isolation procedure to obtain a cell population with hepatogenic properties prior to in vivo transplantation. When subjected to hepatogenic differentiation on untreated plastic support, UCMSCs differentiated in hepatocyte-like cells as demonstrated by their morphology, progressive up-regulation of mature hepatocyte markers, glycogen storage, albumin and urea secretion. However

  18. Effect of nitric oxide pathway regulation on water/sodium balance and renal function in a rodent model of acute liver and renal failure.

    Science.gov (United States)

    Saracyn, Marek; Ząbkowski, Tomasz; Zdanowski, Robert; Brytan, Marek; Patera, Janusz; Nowak, Zbigniew; Kade, Grzegorz; Wańkowicz, Zofia

    2014-09-27

    The pathomechanism of acute hepatorenal syndrome (HRS), a particular form of acute renal failure that occurs in the course of acute liver injury, is still poorly understood. The aim of our study was to estimate the influence of the activation and inhibition of the nitric oxide pathway on the water/sodium balance and development of acute renal failure in the course of HRS. We used male Sprague-Dawley rats in the acute galactosamine (Ga1N) model of HRS. The nitric oxide synthase (NOS) inhibitors L-NAME and L-arginine were administered intraperitoneally before and after liver damage. HRS developed in all tested groups. L-NAME increased osmotic clearance and urine volume more effectively before liver injury. Furthermore, administration of L-NAME increased creatinine clearance both before and after Ga1N injection. A double dose of L-NAME did not yield further improvement before Ga1N injection, but improved creatinine clearance after Ga1N intoxication. Injection of L-arginine increased sodium excretion and urine volume, but only after liver injury. Moreover, L-arginine injected after Ga1N caused significant improvement of the creatinine clearance in a dose-dependent manner. Our study shows that inhibition of the nitric oxide pathway improves parameters of water and sodium balance and prevents development of acute renal failure in the course of acute liver injury and liver failure. Activation of the nitric oxide system also has a favorable influence on water/sodium balance and renal failure, but only after liver injury.

  19. Comparison of the Mortality Probability Admission Model III, National Quality Forum, and Acute Physiology and Chronic Health Evaluation IV hospital mortality models: implications for national benchmarking*.

    Science.gov (United States)

    Kramer, Andrew A; Higgins, Thomas L; Zimmerman, Jack E

    2014-03-01

    To examine the accuracy of the original Mortality Probability Admission Model III, ICU Outcomes Model/National Quality Forum modification of Mortality Probability Admission Model III, and Acute Physiology and Chronic Health Evaluation IVa models for comparing observed and risk-adjusted hospital mortality predictions. Retrospective paired analyses of day 1 hospital mortality predictions using three prognostic models. Fifty-five ICUs at 38 U.S. hospitals from January 2008 to December 2012. Among 174,001 intensive care admissions, 109,926 met model inclusion criteria and 55,304 had data for mortality prediction using all three models. None. We compared patient exclusions and the discrimination, calibration, and accuracy for each model. Acute Physiology and Chronic Health Evaluation IVa excluded 10.7% of all patients, ICU Outcomes Model/National Quality Forum 20.1%, and Mortality Probability Admission Model III 24.1%. Discrimination of Acute Physiology and Chronic Health Evaluation IVa was superior with area under receiver operating curve (0.88) compared with Mortality Probability Admission Model III (0.81) and ICU Outcomes Model/National Quality Forum (0.80). Acute Physiology and Chronic Health Evaluation IVa was better calibrated (lowest Hosmer-Lemeshow statistic). The accuracy of Acute Physiology and Chronic Health Evaluation IVa was superior (adjusted Brier score = 31.0%) to that for Mortality Probability Admission Model III (16.1%) and ICU Outcomes Model/National Quality Forum (17.8%). Compared with observed mortality, Acute Physiology and Chronic Health Evaluation IVa overpredicted mortality by 1.5% and Mortality Probability Admission Model III by 3.1%; ICU Outcomes Model/National Quality Forum underpredicted mortality by 1.2%. Calibration curves showed that Acute Physiology and Chronic Health Evaluation performed well over the entire risk range, unlike the Mortality Probability Admission Model and ICU Outcomes Model/National Quality Forum models. Acute

  20. Endoglin: a novel target for therapeutic intervention in acute leukemias revealed in xenograft mouse models.

    Science.gov (United States)

    Dourado, Keina M C; Baik, June; Oliveira, Vanessa K P; Beltrame, Miriam; Yamamoto, Ami; Theuer, Charles P; Figueiredo, Camila A V; Verneris, Michael R; Perlingeiro, Rita C R

    2017-05-04

    Endoglin (CD105), a receptor of the transforming growth factor-β superfamily, has been reported to identify functional long-term repopulating hematopoietic stem cells, and has been detected in certain subtypes of acute leukemias. Whether this receptor plays a functional role in leukemogenesis remains unknown. We identified endoglin expression on the majority of blasts from patients with acute myeloid leukemia (AML) and acute B-lymphoblastic leukemia (B-ALL). Using a xenograft model, we find that CD105 + blasts are endowed with superior leukemogenic activity compared with the CD105 - population. We test the effect of targeting this receptor using the monoclonal antibody TRC105, and find that in AML, TRC105 prevented the engraftment of primary AML blasts and inhibited leukemia progression following disease establishment, but in B-ALL, TRC105 alone was ineffective due to the shedding of soluble CD105. However, in both B-ALL and AML, TRC105 synergized with reduced intensity myeloablation to inhibit leukemogenesis, indicating that TRC105 may represent a novel therapeutic option for B-ALL and AML. © 2017 by The American Society of Hematology.

  1. [Validation of a diagnostic scoring system (Ohmann score) in acute appendicitis].

    Science.gov (United States)

    Zielke, A; Sitter, H; Rampp, T A; Schäfer, E; Hasse, C; Lorenz, W; Rothmund, M

    1999-07-01

    A diagnostic scoring system, recently published by Ohmann et al. in this journal, was validated by analyzing the clinicopathological data of a consecutive series of 2,359 patients, admitted for suspicion of acute appendicitis. The results of the scoring system were compared to the results of clinical evaluation by junior (provisional) and senior surgeons (final clinical diagnosis). To assess the diagnostic ability of the score, the accuracy and positive predictive value were defined as the major diagnostic performance parameters; the rate of theoretical negative laparotomies and that of diagnostic errors served as the major procedural performance parameters. Of 2,359 patients admitted for suspected acute appendicitis, 662 were proven to have acute appendicitis by histology, for a prevalence of 28%. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the provisional clinical diagnosis were 0.50, 0.94, 0.77, 0.83, and 0.82; 0.93, for the score 0.63, 0.93, 0.77, 0.86 and 0.84, and for the final clinical diagnosis 0.90, 0.94, 0.85, 0.96, and 0.93, respectively. Of the main diagnostic performance parameter, the accuracy of the score was significantly better than that of provisional clinical diagnosis (P apendicitis, the score demonstrated a superior performance, with only 6 cases missed (0.9%). However, the number of patients with acute appendicitis, including those with perforated disease, who were not identified by the score, was almost four times that of the final clinical diagnosis (245 vs 63). With regard to the main procedural performance parameter, the score resulted in a significantly smaller number of diagnostic errors than the provisional clinical investigator (P < 0.05, chi 2 test). The results of this study indicate that the diagnostic scoring system might be helpful when experienced investigators or additional diagnostic modalities such as ultrasonography are not available. It may therefore be of value

  2. A comparison of leak compensation in acute care ventilators during noninvasive and invasive ventilation: a lung model study.

    Science.gov (United States)

    Oto, Jun; Chenelle, Christopher T; Marchese, Andrew D; Kacmarek, Robert M

    2013-12-01

    Although leak compensation has been widely introduced to acute care ventilators to improve patient-ventilator synchronization in the presence of system leaks, there are no data on these ventilators' ability to prevent triggering and cycling asynchrony. The goal of this study was to evaluate the ability of leak compensation in acute care ventilators during invasive and noninvasive ventilation (NIV). Using a lung simulator, the impact of system leaks was compared on 7 ICU ventilators and 1 dedicated NIV ventilator during triggering and cycling at 2 respiratory mechanics (COPD and ARDS models) settings, various modes of ventilation (NIV mode [pressure support ventilation], and invasive mode [pressure support and continuous mandatory ventilation]), and 2 PEEP levels (5 and 10 cm H(2)O). Leak levels used were up to 35-36 L/min in NIV mode and 26-27 L/min in invasive mode. Although all of the ventilators were able to synchronize with the simulator at baseline, only 4 of the 8 ventilators synchronized to all leaks in NIV mode, and 2 of the 8 ventilators in invasive mode. The number of breaths to synchronization was higher during increasing than during decreasing leak. In the COPD model, miss-triggering occurred more frequently and required a longer time to stabilize tidal volume than in the ARDS model. The PB840 required fewer breaths to synchronize in both invasive and noninvasive modes, compared with the other ventilators (P ventilators. The PB840 and the V60 were the only ventilators to acclimate to all leaks, but there were differences in performance between these 2 ventilators. It is not clear if these differences have clinical importance.

  3. Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash

    Energy Technology Data Exchange (ETDEWEB)

    Marchini, T.; Magnani, N.D. [Cátedra de Química General e Inorgánica, Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Paz, M.L. [Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Vanasco, V. [Cátedra de Química General e Inorgánica, Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Tasat, D. [CESyMA, Facultad de Ciencia Tecnología, Universidad Nacional de General San Martín, Martín de Irigoyen 3100, 1650 San Martín, Buenos Aires (Argentina); González Maglio, D.H. [Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); and others

    2014-01-15

    It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5 h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1 h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3 h. The onset of an adaptive response was observed at 5 h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation. - Highlights: • An acute exposure to ROFA triggers the occurrence of systemic oxidative stress. • Changes in plasmatic oxidative stress markers appear as early as 1 h after exposure. • ROFA induces proinflammatory cytokines release and intravascular leukocyte activation. • PMN

  4. Hypothalamic pituitary dysfunction in acute nonmycobacterial infections of central nervous system

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    Dinesh K Dhanwal

    2011-01-01

    Full Text Available Background and Objective: Acute and chronic central nervous system (CNS infections are not uncommon in tropical countries and are associated with high morbidity and mortality if specific targeted therapy is not instituted in time. Effects of tubercular meningitis, a form of chronic meningitis on hypothalamic pituitary axis, are well known both at the time of diagnosis and after few months to years of illness. However, there are few reports of pituitary dysfunction in subjects with acute CNS infections. Therefore, this study was aimed at evaluating the pituitary hormonal profile in patients with nonmycobacterial acute meningitis at the time of presentation. Materials and Methods: This prospective case series study included 30 untreated adult patients with acute meningitis, meningoencephalitis, or encephalitis, due to various nonmycobacterial agents, admitted and registered with Lok Nayak Hospital, Maulana Aazd Medical College, New Delhi, between September 2007 and March 2009. Patients with preexisting endocrine diseases, tubercular meningitis and patients on steroids were carefully excluded from the study. The basal pituitary hormonal profile was measured by the electrochemilumniscence technique for serum cortisol, luetinizing hormone (LH, follicular stimulating hormone (FSH, prolactin (PRL, thyrotropin (TSH, free tri-iodothyronine (fT3, and free thyroxine (fT4. Results: The cases (n = 30 comprised of patients with acute pyogenic meningitis (n = 23, viral meningoencephalitis (n = 4, brain abscess (n = 2, and cryptococcal meningitis (n = 1. The mean age of patients was 28.97 ± 11.306 years. Out of 30 patients, 14 (46.7% were males and 16 (58.1% were females. Adrenal insufficiency both absolute and relative was seen in seven (23.3% and hyperprolactinemia was seen in nine (30.0% of the patients. One study subject had central hypothyroidism and seven (23.3 showed low levels of LH and/or FSH. None of patients showed clinical features suggestive of

  5. Performance of in-hospital mortality prediction models for acute hospitalization: Hospital Standardized Mortality Ratio in Japan

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    Motomura Noboru

    2008-11-01

    Full Text Available Abstract Objective In-hospital mortality is an important performance measure for quality improvement, although it requires proper risk adjustment. We set out to develop in-hospital mortality prediction models for acute hospitalization using a nation-wide electronic administrative record system in Japan. Methods Administrative records of 224,207 patients (patients discharged from 82 hospitals in Japan between July 1, 2002 and October 31, 2002 were randomly split into preliminary (179,156 records and test (45,051 records groups. Study variables included Major Diagnostic Category, age, gender, ambulance use, admission status, length of hospital stay, comorbidity, and in-hospital mortality. ICD-10 codes were converted to calculate comorbidity scores based on Quan's methodology. Multivariate logistic regression analysis was then performed using in-hospital mortality as a dependent variable. C-indexes were calculated across risk groups in order to evaluate model performances. Results In-hospital mortality rates were 2.68% and 2.76% for the preliminary and test datasets, respectively. C-index values were 0.869 for the model that excluded length of stay and 0.841 for the model that included length of stay. Conclusion Risk models developed in this study included a set of variables easily accessible from administrative data, and still successfully exhibited a high degree of prediction accuracy. These models can be used to estimate in-hospital mortality rates of various diagnoses and procedures.

  6. Reduced Genetic Diversity in Lymphoid and Central Nervous System Tissues and Selection-Induced Tissue-Specific Compartmentalization of Neuropathogenic SIVsmmFGb during Acute Infection

    OpenAIRE

    Reeve, Aaron B.; Patel, Kalpana; Pearce, Nicholas C.; Augustus, Katherine V.; Domingues, Heber G.; O'Neil, Shawn P.; Novembre, Francis J.

    2009-01-01

    The simian lentivirus strain SIVsmmFGb is a viral swarm population inducing neuropathology in over 90% of infected pigtailed macaques and serves as a reliable model for HIV neuropathogenesis. However, little is understood about the genetic diversity of this virus, how said diversity influences the initial seeding of the central nervous system and lymph nodes, or whether the virus forms distinct genetic compartments between tissues during acute infection. In this study, we establish that our S...

  7. Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model.

    Science.gov (United States)

    Korpela, Elina; Yohan, Darren; Chin, Lee Cl; Kim, Anthony; Huang, Xiaoyong; Sade, Shachar; Van Slyke, Paul; Dumont, Daniel J; Liu, Stanley K

    2014-08-26

    Most cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Acute skin damage from cancer radiotherapy diminishes patients' quality of life, yet effective biological interventions for this damage are lacking. Protecting microvascular endothelial cells from irradiation-induced perturbations is emerging as a targeted damage-reduction strategy. Since Angiopoetin-1 signaling through the Tie2 receptor on endothelial cells opposes microvascular perturbations in other disease contexts, we used a preclinical Angiopoietin-1 mimic called Vasculotide to investigate its effect on skin radiation toxicity using a preclinical model. Athymic mice were treated intraperitoneally with saline or Vasculotide and their flank skin was irradiated with a single large dose of ionizing radiation. Acute cutaneous damage and wound healing were evaluated by clinical skin grading, histology and immunostaining. Diffuse reflectance optical spectroscopy, myeloperoxidase-dependent bioluminescence imaging of neutrophils and a serum cytokine array were used to assess inflammation. Microvascular endothelial cell response to radiation was tested with in vitro clonogenic and Matrigel tubule formation assays. Tumour xenograft growth delay experiments were also performed. Appreciable differences between treatment groups were assessed mainly using parametric and non-parametric statistical tests comparing areas under curves, followed by post-hoc comparisons. In vivo, different schedules of Vasculotide treatment reduced the size of the irradiation-induced wound. Although skin damage scores remained similar on individual days, Vasculotide administered post irradiation resulted in less skin damage overall. Vasculotide alleviated irradiation-induced inflammation in the form of reduced levels of oxygenated hemoglobin, myeloperoxidase bioluminescence and chemokine MIP-2. Surprisingly, Vasculotide-treated animals also had higher microvascular endothelial cell

  8. Acute impact of drinking coffee on the cerebral and systemic vasculature.

    Science.gov (United States)

    Washio, Takuro; Sasaki, Hiroyuki; Ogoh, Shigehiko

    2017-05-01

    Previous studies have suggested that the risk of ischemic stroke increases immediately after drinking coffee. Indeed, drinking coffee, that is, caffeine, acutely increases arterial stiffness as well as blood pressure and peripheral vascular resistance. On the other hand, it has been reported that arterial stiffening is associated with elevation in the pulsatility index (PI) of cerebral blood flow (CBF), which increases the risk of brain disease. However, the effect of drinking coffee on the PI of the CBF and its interaction with arterial stiffness remain unknown. Against this background, we hypothesized that an acute increase in arterial stiffness induced by drinking coffee augments cerebral pulsatile stress. To test this hypothesis, in 10 healthy young men we examined the effects of drinking coffee on the PI of middle cerebral artery blood velocity (MCAv) and brachial-ankle pulse wave velocity (baPWV) as indices of cerebral pulsatile stress and arterial stiffness, respectively. Mean arterial blood pressure and baPWV were higher ( P  coffee ( P  = 0.02 and P  coffee). However, there was no difference in the PI of MCAv between drinking coffee and the placebo condition. These findings suggest that drinking coffee does not increase cerebral pulsatile stress acutely despite an elevation in arterial stiffness in the systemic circulation. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  9. Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system.

    Science.gov (United States)

    Owaidah, T M; Al Beihany, A; Iqbal, M A; Elkum, N; Roberts, G T

    2006-04-01

    Biphenotypic acute leukemia (BAL) is a rare, difficult to diagnose entity. Its identification is important for risk stratification in acute leukemia (AL). The scoring proposal of the European Group for the Classification of Acute Leukemia (EGIL) is useful for this purpose, but its performance against objective benchmarks is unclear. Using the EGIL system, we identified 23 (3.4%) BAL from among 676 newly diagnosed AL patients. Mixed, small and large blast cells predominated, with FAB M2 and L1 constituting the majority. All patients were positive for myeloid (M) markers and either B cell (B) (17 or 74%) or T cell (T) (8 or 34%) markers with two exceptional patients demonstrating trilineage phenotype. Six (50%) of studied M-B cases were positive for both IGH and TCR. In six (26%) patients myeloid lineage commitment was also demonstrable by electron cytochemistry. Abnormal findings were present in 19 (83%) patients by cytogenetics/FISH/molecular analysis as follows: t(9;22) (17%); MLL gene rearrangement (26%); deletion(6q) (13%); 12p11.2 (9%); numerical abnormalities (13%), and three (13%) new, previously unreported translocations t(X;6)(p22.3;q21); t(2;6)(q37;p21.3); and t(8;14)(p21;q32). In conclusion, the EGIL criteria for BAL appear robust when compared against molecular techniques that, if applied routinely, could aid in detecting BAL and help in risk stratification.

  10. A Case of Systemic Lupus Erythematosus Presenting with an Acute Abdomen: Successful Treatment with Steroid

    Directory of Open Access Journals (Sweden)

    Haruka Fukatsu

    2014-01-01

    Full Text Available Abdominal pain continues to pose diagnostic challenges for emergency clinicians. A 56-year-old Japanese woman was referred to our hospital due to severe abdominal pain which presented as occasional epigastric pain five months before and intermittent abdominal pain. She had a past history of ileus twice, for both of which laparotomy was performed without an alimentary tract resection. The wall thickening with marked three-wall structure from terminal ileum to sigmoid colon was seen and bladder wall was irregularly thick and enhanced irregularly. Among the differential diagnosis of the acute abdomen, autoimmune diseases were suspected, especially lupus erythematosus and Henoch-Schönlein purpura. On the second day of admission, abdominal pain worsened. The results of examinations of antinuclear antibody, anti-double-stranded DNA antibody, ANCA, and the complements were not obtained at that time; however, we started 1-g steroid pulse treatment for three days with success. With the results obtained later, the patient was given a diagnosis of probable systemic lupus erythematosus (SLE. The present case shows that SLE can present with acute abdomen and should be included in the wide range of the differential diagnosis of acute abdomen.

  11. The delayed pulmonary syndrome following acute high-dose irradiation: a rhesus macaque model.

    Science.gov (United States)

    Garofalo, Michael; Bennett, Alexander; Farese, Ann M; Harper, Jamie; Ward, Amanda; Taylor-Howell, Cheryl; Cui, Wanchang; Gibbs, Allison; Lasio, Giovanni; Jackson, William; MacVittie, Thomas J

    2014-01-01

    Several radiation dose- and time-dependent tissue sequelae develop following acute high-dose radiation exposure. One of the recognized delayed effects of such exposures is lung injury, characterized by respiratory failure as a result of pneumonitis that may subsequently develop into lung fibrosis. Since this pulmonary subsyndrome may be associated with high morbidity and mortality, comprehensive treatment following high-dose irradiation will ideally include treatments that mitigate both the acute hematologic and gastrointestinal subsyndromes as well as the delayed pulmonary syndrome. Currently, there are no drugs approved by the Food and Drug Administration to counteract the effects of acute radiation exposure. Moreover, there are no relevant large animal models of radiation-induced lung injury that permit efficacy testing of new generation medical countermeasures in combination with medical management protocols under the FDA animal rule criteria. Herein is described a nonhuman primate model of delayed lung injury resulting from whole thorax lung irradiation. Rhesus macaques were exposed to 6 MV photon radiation over a dose range of 9.0-12.0 Gy and medical management administered according to a standardized treatment protocol. The primary endpoint was all-cause mortality at 180 d. A comparative multiparameter analysis is provided, focusing on the lethal dose response relationship characterized by a lethal dose50/180 of 10.27 Gy [9.88, 10.66] and slope of 1.112 probits per linear dose. Latency, incidence, and severity of lung injury were evaluated through clinical and radiographic parameters including respiratory rate, saturation of peripheral oxygen, corticosteroid requirements, and serial computed tomography. Gross anatomical and histological analyses were performed to assess radiation-induced injury. The model defines the dose response relationship and time course of the delayed pulmonary sequelae and consequent morbidity and mortality. Therefore, it may provide

  12. Evaluating Systemic Toxicity in Rabbits after Acute Ocular Exposure to Irritant Chemicals

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    Reshma Sebastian Cherian

    2014-01-01

    Full Text Available Acute systemic toxicity via ocular exposure route is not a well understood aspect. Any material/drug/chemical that comes in contact with the eye can evade the first pass metabolism and enter the systemic circulation through the conjunctival blood vessels or via the nasolacrimal route. In this study, the effect of ocular irritant chemicals on the systemic toxicity was assessed in rabbit. Eyes of rabbits were exposed to known ocular irritant (cetyl pyridinium chloride, sodium salicylate, imidazole, acetaminophen, and nicotinamide for 24 h and scored. After a period of 72 h, blood was collected from the animals for examining the hematological and biochemical parameters. The animals were then sacrificed and the eyes were collected for histopathology and cytokine analysis by ELISA. Splenocyte proliferation was assessed by tritiated thymidine incorporation assay. The liver and brain of the treated animals were retrieved for evaluating oxidative damage. The chemicals showed moderate to severe eye irritation. Inflammation was not evident in the histopathology but proinflammatory markers were significantly high. The splenocyte proliferation capacity was undeterred. And there was minimal oxidative stress in the brain and liver. In conclusion, acute exposure of ocular irritants was incapable of producing a prominent systemic side effect in the current scenario.

  13. Modeling Power Systems as Complex Adaptive Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Malard, Joel M.; Posse, Christian; Gangopadhyaya, Asim; Lu, Ning; Katipamula, Srinivas; Mallow, J V.

    2004-12-30

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today's most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This report explores the state-of-the-art physical analogs for understanding the behavior of some econophysical systems and deriving stable and robust control strategies for using them. We review and discuss applications of some analytic methods based on a thermodynamic metaphor, according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood. We apply these methods to the question of how power markets can be expected to behave under a variety of conditions.

  14. Evaluating the Siebens Model in Geriatric-Stroke Inpatient Rehabilitation to Reduce Institutionalization and Acute-Care Readmissions.

    Science.gov (United States)

    Kushner, David S; Peters, Kenneth M; Johnson-Greene, Doug

    2016-02-01

    The objective of the study is to evaluate the use of Siebens Domain Management Model (SDMM) in geriatric-stroke patients during inpatient rehabilitation (IR) to increase functional independence, and to reduce institutionalization and acute-care readmissions, which are quality indicators under the U.S. Affordable Care Act. In 2010 (preintervention), 66 stroke patients aged more than 75 years were admitted to an IR facility, on average, 8.8 days postacute care. In 2012 (postintervention), 58 patients aged more than 75 years were admitted to the same IR facility, on average, 5.0 days postacute care. SDMM intervention involved weekly adjustments of clinical care focused on potential barriers to discharge home. Functional Independence Measure (FIM) efficiency, length of stay (LOS), and disposition rates to community or home, acute care, and long-term care were compared pre- and postintervention within facility, and facility data were compared to national case-mix-group-adjusted data from the Uniform Data System for Medical Rehabilitation for both years (2010/2012). Pre- and postintervention demographics and prestroke living support/setting were similar, but preintervention had on average 4 more days LOS in IR and 3.8 more days to IR onset. There were significantly more discharges to community in postintervention (79.3%) compared to preintervention (56.9%) (chi-square = 6.02, P < .013). The preintervention group did not significantly differ from 2010 national data whereas the postintervention/2012 group significantly differed from 2012 national data for higher FIM efficiency (t = -3.1, P < .002) and more discharges to community (chi-square = 19.7; P < .0001). From 2010 to 2012, there were 3.8 times more discharges to community (chi-square = 8535; P < .0001) and 6 times fewer acute-care dispositions postintervention than nationally (chi-square = 58.7; P < .0001). Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  15. Towards Global QSAR Model Building for Acute Toxicity: Munro Database Case Study

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    Swapnil Chavan

    2014-10-01

    Full Text Available A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.

  16. Acute high fat diet consumption activates the mesolimbic circuit and requires orexin signaling in a mouse model.

    Directory of Open Access Journals (Sweden)

    Spring Valdivia

    Full Text Available Overconsumption of palatable energy-dense foods has negative health implications and it is associated with obesity and several eating disorders. Currently, little is known about the neuronal circuitries activated by the acute ingestion of a rewarding stimulus. Here, we used a combination of immunohistochemistry, pharmacology and neuronal tracing analyses to examine the role of the mesolimbic system in general, and the orexin neurons in particular, in a simple experimental test in which naïve mice are allowed to spontaneously eat a pellet of a high fat diet (HFD for 2 h. We found that acute HFD activates c-Fos expression in several reward-related brain areas, including the ventral tegmental area (VTA, nucleus accumbens, central amygdala and lateral hypothalamic area. We also found that: i- HFD-mediated orosensory stimulation was required for the mesolimbic pathway activation, ii- acute HFD differentially activates dopamine neurons of the paranigral, parabrachial pigmented and interfascicular sub-regions of the VTA, and iii- orexin neurons of the lateral hypothalamic area are responsive to acute HFD. Moreover, orexin signaling blockade, with the orexin 1 receptor antagonist SB-334867, reduces acute HFD consumption and c-Fos induction in the VTA but not in the other mesolimbic nuclei under study. Finally, we found that most orexin neurons responsive to acute HFD innervate the VTA. Our results show that acute HFD consumption recruits the mesolimbic system and that the full manifestation of this eating behavior requires the activation of orexin signaling.

  17. Visual computing model for immune system and medical system.

    Science.gov (United States)

    Gong, Tao; Cao, Xinxue; Xiong, Qin

    2015-01-01

    Natural immune system is an intelligent self-organizing and adaptive system, which has a variety of immune cells with different types of immune mechanisms. The mutual cooperation between the immune cells shows the intelligence of this immune system, and modeling this immune system has an important significance in medical science and engineering. In order to build a comprehensible model of this immune system for better understanding with the visualization method than the traditional mathematic model, a visual computing model of this immune system was proposed and also used to design a medical system with the immune system, in this paper. Some visual simulations of the immune system were made to test the visual effect. The experimental results of the simulations show that the visual modeling approach can provide a more effective way for analyzing this immune system than only the traditional mathematic equations.

  18. [Efficacy of systemic glucocorticoids combined with inhaled steroid on children with acute laryngitis].

    Science.gov (United States)

    Chen, Q P; Zhou, R F; Zhang, Y M; Yang, L

    2018-01-07

    Objective: To evaluate the efficacy of systemic glucocorticoid (steroid) combined with high dose inhaled steroid in the treatment of children with acute laryngitis. Methods: A total of 78 children with acute laryngitis were randomly divided into study group( n =40) and control group( n =38) between November 2016 and April 2017. In addition to routine treatment of anti infection and symptomatic treatment, Dexamethasone injection(0.3-0.5 mg/kg, 1-3 d, according to the patient's condition) was provided to each group. In addition to the treatment mentioned above, the study group were assigned to receive 1.0 mg Budesonide suspension for inhalation, oxygen-driven atomizing inhalation, every/30 minutes, 2 times in a row, after that every 12 hours. The improvement of inspiratory dyspnea, hoarseness, barking cough and wheezing of both groups was evaluated at 30 min, 1 h, 2 h, 6 h, 12 h, 24 h and 72 h after treatment.Sigmaplot 11.5 software was used to analyze the data. Results: No significant difference was detected in terms of inspiratory dyspnea, hoarseness, barking cough or stridor score before treatment between the two groups( P >0.05). Compared with those before treatment, symptoms of inspiratory dyspnea, hoarseness, barking cough and stridor score of both groups improved markedly at 12 h and 24 h after treatment( P dyspnea, hoarseness, barking cough or stridor score at each time point after treatment between the two groups( P >0.05). The effective rate was 92.50% and 92.11% in study group and control group, respectively, and no significant difference was noted ( P >0.05). Conclusion: Compared with single systemic glucocorticoid, systemic glucocorticoids combined with inhaled steroid possessed similar efficacy in treating acute laryngitis and relieving laryngeal obstruction of children.

  19. Acute intraperitoneal lipopolysaccharide influences the immune system in the absence of gut dysbiosis.

    Science.gov (United States)

    Sylvia, Kristyn E; Demas, Gregory E

    2018-03-01

    There is bidirectional communication between the immune system and the gut microbiome, however the precise mechanisms regulating this crosstalk are not well understood. Microbial-associated molecular patterns (MAMPs) within the gut, including lipopolysaccharide (LPS) that produces a quick and robust activation of the immune system, may be one way by which these interactions occur. Endogenous levels of LPS in the gut are low enough that they do not usually cause disease, although, in times of increased LPS loads, they may be capable of increasing vulnerability of the gut to pathogenic bacteria. Furthermore, chronic, low-grade inflammation can have lasting effects on the gut, but the effects of acute inflammation on gut communities have not been thoroughly assessed. In this study, we first investigated whether a single modest dose of LPS administered to adult male and female Siberian hamsters (Phodopus sungorus) activated the immune system by measuring levels of circulating cortisol and the proinflammatory cytokine TNF-α in the liver compared with saline-treated animals. We then investigated whether this same acute dose of LPS altered the microbiome 48 h after treatment. We found that, although LPS increased cortisol and liver cytokine levels, and produced changes in food intake and body mass in both sexes, immunological changes were independent of gut dysbiosis 48 h after LPS injection. These data suggest that an acute immune activation may not be capable of altering the gut microbiome in healthy individuals. It is likely, however, that this type of immune challenge may have other physiological impacts on the gut's vulnerability, and future studies will investigate these relationships further. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  20. [Study on predicting model for acute hypotensive episodes in ICU based on support vector machine].

    Science.gov (United States)

    Lai, Lijuan; Wang, Zhigang; Wu, Xiaoming; Xiong, Dongsheng

    2011-06-01

    The occurrence of acute hypotensive episodes (AHE) in intensive care units (ICU) seriously endangers the lives of patients, and the treatment is mainly depended on the expert experience of doctors. In this paper, a model for predicting the occurrence of AHE in ICU has been developed using the theory of medical Informatics. We analyzed the trend and characteristics of the mean arterial blood pressure (MAP) between the patients who were suffering AHE and those who were not, and extracted the median, mean and other statistical parameters for learning and training based on support vector machine (SVM), then developed a predicting model. On this basis, we also compared different models consisted of different kernel functions. Experiments demonstrated that this approach performed well on classification and prediction, which would contribute to forecast the occurrence of AHE.

  1. Histone Deacetylase Inhibitors Are Protective in Acute but Not in Chronic Models of Ototoxicity

    Directory of Open Access Journals (Sweden)

    Chao-Hui Yang

    2017-10-01

    Full Text Available Previous studies have reported that modification of histones alters aminoglycoside-induced hair cell death and hearing loss. In this study, we investigated three FDA-approved histone deacetylase (HDAC inhibitors (vorinostat/SAHA, belinostat, and panobinostat as protectants against aminoglycoside-induced ototoxicity in murine cochlear explants and in vivo in both guinea pigs and CBA/J mice. Individually, all three HDAC inhibitors reduced gentamicin (GM-induced hair cell loss in a dose-dependent fashion in explants. In vivo, however, treatment with SAHA attenuated neither GM-induced hearing loss and hair cell loss in guinea pigs nor kanamycin (KM-induced hearing loss and hair cell loss in mice under chronic models of ototoxicity. These findings suggest that treatment with the HDAC inhibitor SAHA attenuates aminoglycoside-induced ototoxicity in an acute model, but not in chronic models, cautioning that one cannot rely solely on in vitro experiments to test the efficacy of otoprotectant compounds.

  2. Manganese-enhanced magnetic resonance imaging in the acute phase of the pilocarpine-induced model of epilepsy

    Directory of Open Access Journals (Sweden)

    Jackeline Moraes Malheiros

    2012-06-01

    Full Text Available Magnetic resonance images are useful in the study of experimentalmodels of temporal lobe epilepsy. The manganese-enhanced MRI(MEMRI technique is of interest since it combines the effects causedby manganese on the increased contrast in activated cell populations,when competing with calcium in synaptic transmission. Thus, thepurpose of this study was to investigate the temporal evolution ofthe contrast related to manganese in the acute phase of temporallobe epilepsy induced by systemic pilocarpine and compare it to theexpression of the c-Fos protein. During this phase, the intensity ofthe MEMRI signal was analyzed at three different time points (5, 15or 30 minutes after the onset of status epilepticus (SE. The groupthat was maintained in status epilepticus for 30 minutes showed adecrease in intensity of the signal in CA1 and the dentate gyrus (DG.There were no differences between the control group and the othergroups treated with pilocarpine. The expression of the protein, c-Fos,in the same animals showed that even in the short-duration statusepilepticus (5 minutes, there was already maximal cellular activationin subregions of the hippocampus (DG, CA1 and CA3. Under theexperimental conditions tested, our data suggest that the MEMRIsignal was not sensitive for the identification of detectable variationsof cell activation in the acute phase of the pilocarpine model. Ourfindings are not consistent with the idea that manganese contrastreflects primarily alterations in cellular activity during SE when othersignal-modifying elements can act.

  3. Model Information Exchange System (MIXS).

    Science.gov (United States)

    2013-08-01

    Many travel demand forecast models operate at state, regional, and local levels. While they share the same physical network in overlapping geographic areas, they use different and uncoordinated modeling networks. This creates difficulties for models ...

  4. Systemic vascular function, measured with forearm flow mediated dilatation, in acute and stable cerebrovascular disease: a case-control study

    Directory of Open Access Journals (Sweden)

    Blacker David

    2010-10-01

    Full Text Available Abstract Background Acute ischaemic stroke is associated with alteration in systemic markers of vascular function. We measured forearm vascular function (using forearm flow mediated dilatation to clarify whether recent acute ischaemic stroke/TIA is associated with impaired systemic vascular function. Methods Prospective case control study enrolling 17 patients with recent acute ischaemic stroke/TIA and 17 sex matched controls with stroke more than two years previously. Forearm vascular function was measured using flow medicated dilatation (FMD. Results Flow mediated dilatation was 6.0 ± 1.1% in acute stroke/TIA patients and 4.7 ± 1.0% among control subjects (p = 0.18. The mean paired difference in FMD between subjects with recent acute stroke and controls was 1.25% (95% CI -0.65, 3.14; p = 0.18. Endothelium independent dilatation was measured in six pairs of participants and was similar in acute stroke/TIA patients (22.6 ± 4.3% and control subjects (19.1 ± 2.6%; p = 0.43. Conclusions Despite the small size of this study, these data indicate that recent acute stroke is not necessarily associated with a clinically important reduction in FMD.

  5. Two sustainable energy system analysis models

    DEFF Research Database (Denmark)

    Lund, Henrik; Goran Krajacic, Neven Duic; da Graca Carvalho, Maria

    2005-01-01

    This paper presents a comparative study of two energy system analysis models both designed with the purpose of analysing electricity systems with a substantial share of fluctuating renewable energy.......This paper presents a comparative study of two energy system analysis models both designed with the purpose of analysing electricity systems with a substantial share of fluctuating renewable energy....

  6. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke

    2012-01-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic...... and cerebrovascular variables following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk; n=8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 ± 3...

  7. Role of neuroimaging in children with acute lymphoblastic leukemia and central nervous system involvement at diagnosis

    DEFF Research Database (Denmark)

    Ranta, Susanna; Palomäki, Maarit; Levinsen, Mette

    2017-01-01

    BACKGROUND: Each year approximately 200 children and adolescents are diagnosed with acute lymphoblastic leukemia (ALL) in the five Nordic countries, and 3% of these have central nervous system (CNS) involvement confirmed by leukemic cells in the cerebrospinal fluid (CSF) or neurological symptoms....... We sought to determine the significance of neuraxis imaging in such patients. PROCEDURE: Magnetic resonance images of children aged 1-17.9 with CNS leukemia at diagnosis of ALL were centrally reviewed and clinical data were retrieved from the medical records and the Nordic leukemia registry. Patients...

  8. Models for multimegawatt space power systems

    Energy Technology Data Exchange (ETDEWEB)

    Edenburn, M.W.

    1990-06-01

    This report describes models for multimegawatt, space power systems which Sandia's Advanced Power Systems Division has constructed to help evaluate space power systems for SDI's Space Power Office. Five system models and models for associated components are presented for both open (power system waste products are exhausted into space) and closed (no waste products) systems: open, burst mode, hydrogen cooled nuclear reactor -- turboalternator system; open, hydrogen-oxygen combustion turboalternator system; closed, nuclear reactor powered Brayton cycle system; closed, liquid metal Rankine cycle system; and closed, in-core, reactor therminonic system. The models estimate performance and mass for the components in each of these systems. 17 refs., 8 figs., 15 tabs.

  9. Psychobiology of PTSD in the acute aftermath of trauma: Integrating research on coping, HPA function and sympathetic nervous system activity.

    Science.gov (United States)

    Morris, Matthew C; Rao, Uma

    2013-02-01

    Research on the psychobiological sequelae of trauma has typically focused on long-term alterations in individuals with chronic posttraumatic stress disorder (PTSD). Far less is known about the nature and course of psychobiological risk factors for PTSD during the acute aftermath of trauma. In this review, we summarize data from prospective studies focusing on the relationships among sympathetic nervous system activity, hypothalamic-pituitary-adrenal function, coping strategies and PTSD symptoms during the early recovery (or non-recovery) phase. Findings from pertinent studies are integrated to inform psychobiological profiles of PTSD-risk in children and adults in the context of existing models of PTSD-onset and maintenance. Data regarding bidirectional relations between coping strategies and stress hormones is reviewed. Limitations of existing literature and recommendations for future research are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. The effects of pregnancy on the cardiovascular response to acute systemic isocapnic hypoxia in conscious sheep.

    Science.gov (United States)

    Jellyman, J K; Gardner, D S; Edwards, C M B; Fowden, A L; Giussani, D A

    2005-07-01

    This study tested the hypothesis that pregnancy affects the cardiovascular responses to hypoxia by altering the outputs of the peripheral components of the stress system and independent of changes in P(a)CO(2). Comparison of cardiovascular and endocrine responses to acute isocapnic hypoxia between pregnant and non-pregnant ewes. Experimental laboratory. Fifteen pregnant (118 days of gestation; term is ca. 145 days) and 8 non-pregnant sheep. Chronically instrumented pregnant and non-pregnant ewes were subjected to 1 hour normoxia, 1 hour of acute systemic isocapnic hypoxia and 1 hour recovery. Arterial blood pressure, heart rate, femoral blood flow and femoral vascular conductance were recorded continuously throughout and arterial blood samples were taken during normoxia, hypoxia and recovery for the measurement of blood gas, metabolic and endocrine status. Basal blood pressure and blood glucose and lactate concentrations were lower in pregnant animals (P pressure and sustained tachycardia without significant changes in femoral haemodynamics. Pregnancy attenuated the cardiovascular response, significantly diminishing the magnitude of the increment in heart rate throughout the hypoxic challenge (P blood metabolites or in plasma concentrations of any stress hormone measured in either pregnant or non-pregnant animals. Pregnancy not only affects basal but also stimulated cardiovascular function in the mother. The diminished chronotropic response to hypoxia in pregnancy is mediated via mechanisms independent of changes in P(a)CO(2) or in plasma concentrations of hormones or metabolites associated with activation of the stress system.

  11. The use Prometheus FPSA system in the treatment of acute liver failure: preliminary results.

    Science.gov (United States)

    Skwarek, A; Grodzicki, M; Nyckowski, P; Kotulski, M; Zieniewicz, K; Michalowicz, B; Patkowski, W; Grzelak, I; Paczkowska, A; Giercuszkiewicz, D; Sańko-Resmer, J; Paczek, L; Krawczyk, M

    2006-01-01

    The preliminary outcomes of patients with acute liver failure treated with the Prometheus Fractionated Plasma Separation and Absorption (FPSA) system are presented herein. The procedures were performed in 13 patients (4, intoxication by Amanita phalloides; 4, unknown reason; 3, acetaminophen intoxication; 1, Wilson disease, and 1, liver insufficiency after hemihepatectomy owing to metastases of colon adenocarcinoma). The patients were qualified for the procedure according to the King's College Hospital criteria. The patients' general status was assessed on basic of GCS, UNOS, and the 4-grade encephalopathy classifications. The procedures were performed with the Prometheus 4008H Fresenius Medical Care unit. The 29 procedures were of mean duration 6.5 hours. There were statistically significant reductions in total bilirubin, ammonia, and aminotransferase levels. In addition, the procedures corrected water, mineral, and carbohydrate disorders. One patient did not require liver transplantation. Seven patients received liver transplants: three patients with positive outcomes; two died due to septicemia within 30 days perioperatively, one died at 6 months after OLT owing to respiratory failure; and one, owing to hemorrhagic diathesis. Four patients did not receive a liver transplant because of lack of a organ, no consent for the surgery, or neoplastic disease with metastases. The Prometheus FPSA-System was an effective detoxication method for patients with acute liver failure. The system was useful as a symptomatic treatment before liver transplantation allowing a longer wait for a graft.

  12. A severe case of acute exogenous lipoid pneumonia treated with systemic corticosteroid

    Directory of Open Access Journals (Sweden)

    Hideki Yasui

    2016-01-01

    Full Text Available Acute exogenous lipoid pneumonia is a rare disorder in adults. A treatment of choice for lipoid pneumonia has not been established, and systemic corticosteroid use remains controversial. We report the case of a 32-year-old man with schizophrenia who presented with kerosene-induced acute exogenous lipoid pneumonia that was treated with a systemic corticosteroid. In this case, supportive therapy did not improve the patient's condition, so systemic corticosteroid therapy was commenced four days after he ingested the kerosene. After corticosteroid commencement, the patient's symptoms and hypoxia improved within a few days. Although some radiological characteristics of this disorder have been reported previously, the process of radiological improvement of exogenous lipoid pneumonia is not well known. In this case, computed tomography findings changed dramatically after corticosteroid therapy was initiated. Extensive bilateral consolidations that were observed on admission improved. Although pneumatoceles developed two weeks after corticosteroid commencement, they were nearly gone after two months of the treatment. While corticosteroid therapy is not suitable for all cases, it should be considered for severe or refractory cases.

  13. Acute kidney injury following liver transplantation: a systematic review of published predictive models.

    Science.gov (United States)

    Caragata, R; Wyssusek, K H; Kruger, P

    2016-03-01

    Acute kidney injury is a frequent postoperative complication amongst liver transplant recipients and is associated with increased morbidity and mortality. This systematic review analysed the existing predictive models, in order to solidify current understanding. Articles were selected for inclusion if they described the primary development of a clinical prediction model (either an algorithm or risk score) to predict AKI post liver transplantation. The database search yielded a total of seven studies describing the primary development of a prediction model or risk score for the development of AKI following liver transplantation. The models span thirteen years of clinical research and highlight a gradual change in the definitions of AKI, emphasising the need to employ standardised definitions for subsequent studies. Collectively, the models identify a diverse range of predictive factors with several common trends. They emphasise the impact of preoperative renal dysfunction, liver disease severity and aetiology, metabolic risk factors as well as intraoperative variables including measures of haemodynamic instability and graft quality. Although several of the models address postoperative parameters, their utility in predictive modelling seems to be of questionable relevance. The common risk factors identified within this systematic review provide a minimum list of variables, which future studies should address. Research in this area would benefit from prospective, multi-site studies with larger cohorts as well as the subsequent internal and external validation of predictive models. Ultimately, the ability to identify patients at high risk of post-transplant AKI may enable early intervention and perhaps prevention.

  14. Modeling traceability in system of systems

    NARCIS (Netherlands)

    Tekinerdogan, Bedir; Erata, Ferhat

    2017-01-01

    An important aspect in SoS is the realization of the concerns in different systems that work together. Identifying and locating these concerns is important to orchestrate the overall activities and hereby to achieve the overall goal of the SoS. Moreover, concerns in SoS are rarely stable and need

  15. Modeling of Nonlinear Systems using Genetic Algorithm

    Science.gov (United States)

    Hayashi, Kayoko; Yamamoto, Toru; Kawada, Kazuo

    In this paper, a newly modeling system by using Genetic Algorithm (GA) is proposed. The GA is an evolutionary computational method that simulates the mechanisms of heredity or evolution of living things, and it is utilized in optimization and in searching for optimized solutions. Most process systems have nonlinearities, so it is necessary to anticipate exactly such systems. However, it is difficult to make a suitable model for nonlinear systems, because most nonlinear systems have a complex structure. Therefore the newly proposed method of modeling for nonlinear systems uses GA. Then, according to the newly proposed scheme, the optimal structure and parameters of the nonlinear model are automatically generated.

  16. A review of sufentanil and the sufentanil sublingual tablet system for acute moderate to severe pain.

    Science.gov (United States)

    Minkowitz, Harold S

    2015-01-01

    The sufentanil sublingual tablet system (SSTS) is a novel patient-controlled analgesia (PCA) system that is pending approval from the US FDA for the management of moderate to severe acute pain in hospitalized patients. SSTS offers a noninvasive alternative to intravenous (iv.) PCA and optimized on-demand analgesia with the rapid onset and titratibility of sublingual sufentanil. Phase III clinical trials have demonstrated that SSTS has greater efficacy for the treatment of pain during the 72-h postoperative period after open abdominal and major orthopedic (total knee or total hip arthroplasty) surgery compared with iv. PCA with morphine sulfate (MS) or a placebo system. Safety assessments indicate that adverse events are typical for postoperative patients taking opioid analgesics. While the frequency of adverse events is comparable between patients using SSTS and iv. PCA MS, the incidence of oxygen desaturation is lower in those using SSTS.

  17. KRAS (G12D Cooperates with AML1/ETO to Initiate a Mouse Model Mimicking Human Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao

    2014-01-01

    Full Text Available Background/Aims: It has been demonstrated that KRAS mutations represent about 90% of cancer-associated mutations, and that KRAS mutations play an essential role in neoplastic transformation. Cancer-associated RAS mutations occur frequently in acute myeloid leukemia (AML, suggesting a functional role for Ras in leukemogenesis. Methods: We successfully established a mouse model of human leukemia by transplanting bone marrow cells co-transfected with the K-ras (G12D mutation and AML1/ETO fusion protein. Results: Mice transplanted with AML/ETO+KRAS co-transduced cells had the highest mortality rate than mice transplanted with AML/ETO- or KRAS-transduced cells (115d vs. 150d. Upon reaching a terminal disease stage, EGFP-positive cells dominated their spleen, lymph nodes, peripheral blood and central nervous system tissue. Immunophenotyping, cytologic analyses revealed that AML/ETO+KRAS leukemias predominantly contained immature myeloid precursors (EGFP+/c-Kit+/Mac-1-/Gr-1-. Histologic analyses revealed that massive leukemic infiltrations were closely packed in dense sheets that effaced the normal architecture of spleen and thymus in mice transplanted with AML1/ETO + KRAS co-transduced cells. K-ras mRNA and protein expression were upregulated in bone marrow cells of the K-ras group and AML1/ETO + Kras group. The phosphorylation of MEK/ERK was significantly enhanced in the AML1/ETO + Kras group. The similar results of the AML1/ETO + Nras group were consistent with those reported previously. Conclusion: Co-transduction of KrasG12D and AML1/ETO induces acute monoblastic leukemia. Since expression of mutant K-ras alone was insufficient to induce leukemia, this model may be useful for investigating the multi-step leukemogenesis model of human leukemia.

  18. Acute inflammatory and anabolic systemic responses to peak and constant-work-rate exercise bout in hospitalized patients with COPD

    OpenAIRE

    Spruit, Martijn A; Troosters, Thierry; Gosselink, Rik; Kasran, Ahmad; Decramer, Marc

    2007-01-01

    Study objectives: To explore the acute systemic inflammatory and anabolic effects of cycling in hospital admitted patients with chronic obstructive pulmonary disease (COPD) and in patients with clinically stable disease. Design: Cross-sectional comparative study. Setting: University Hospital Gasthuisberg, a tertiary care setting. Patients: 16 patients with clinically stable COPD (no acute exacerbation in the past 12 weeks; median age: 73 years (IQR: 60 to 75); median forced expiratory volume ...

  19. Probenecid prevents acute tubular necrosis in a mouse model of aristolochic acid nephropathy.

    Science.gov (United States)

    Baudoux, Thomas E R; Pozdzik, Agnieszka A; Arlt, Volker M; De Prez, Eric G; Antoine, Marie-Hélène; Quellard, Nathalie; Goujon, Jean-Michel; Nortier, Joëlle L

    2012-11-01

    Experimental aristolochic acid nephropathy is characterized by early tubulointerstitial injury followed by fibrosis, reproducing chronic lesions seen in humans. In vitro, probenecid inhibits aristolochic acid entry through organic anion transporters, reduces specific aristolochic acid-DNA adduct formation, and preserves cellular viability. To test this in vivo, we used a mouse model of aristolochic acid nephropathy displaying severe tubulointerstitial injuries consisting of proximal tubular epithelial cell necrosis associated to transient acute kidney injury followed by mononuclear cell infiltration, tubular atrophy, and interstitial fibrosis. Treatment with probenecid prevented increased plasma creatinine and tubulointerstitial injuries, and reduced both the extent and the severity of ultrastructural lesions induced by aristolochic acid, such as the loss of brush border, mitochondrial edema, and the disappearance of mitochondrial crests. Further, the number of proliferating cell nuclear antigen-positive cells and total aristolochic acid-DNA adducts were significantly reduced in mice receiving aristolochic acid plus probenecid compared with mice treated with aristolochic acid alone. Thus, we establish the nephroprotective effect of probenecid, an inhibitor of organic acid transporters, in vivo toward acute proximal tubular epithelial cell toxicity in a mouse model of aristolochic acid nephropathy.

  20. Application of Biotic Ligand Model in Predicting Copper Acute Toxicity to Carp (Cyprinidae).

    Science.gov (United States)

    Wang, Wanbin; Liang, Qibin; Zhao, Jing; Chen, Rui

    2017-01-01

    Three representative species of Cyprinidae fishes (Aristichthys nobilis, Ctenopharyngodon idellus, and Cyprinus carpio), which are abundant in Chinese surface waters, were studied to determine their sensitivity to copper (Cu) in acute exposures. We first performed acute toxicity tests to determine the Cu LC 50 value for each species in water with varying characteristics. The biotic ligand model (BLM) was then calibrated using the toxicity data for these species together with binding properties specific to Cu. The BLM calibration involved the calculation of the level of Cu accumulation in the gills that resulted in 50% lethality (i.e., LA 50 ). The LA 50 values for A. nobilis, C. idellus and C. carpio were 5.16, 11.60 and 9.00 nmol g -1 . The model calibrated to these data was improved by adjusting the Cu-proton exchange constant (pK CuHA-A ) and dissolved organic carbon (DOC) to values of 1.84 and 4.67E-3 mol g -1 , respectively. The calibrated Cu-BLM was validated for these three common fish species by comparing predicted and observed LC 50 values, which were in agreement to within a factor of 2. The results of this study provide an important contribution to ecological risk assessment and establishment of water quality criteria for Cu in China.

  1. Liver function during extracorporeal whole liver perfusion in a pig model of acute ischemic liver failure.

    Science.gov (United States)

    Méchet, Isabelle; Lhuillier, Franck; Blanchet, Marie Cécile; Pouyet, Michel; Viale, Jean-Paul; Goudable, Joelle; Annat, Guy; Scoazec, Jean Yves; Boillot, Olivier; Liotard, Dominique; Merle, Eric; Delafosse, Bertrand

    2004-01-01

    The shortage of livers for transplant has renewed interest in the potential of temporary liver support such as extra corporeal whole liver perfusion. In an ischemic induced liver failure model we perfused an extra corporeal liver through only a portal vein and assessed the function of this ex vivo liver by using hepatic tests to estimate elimination as well as synthesis capacities. Acute liver failure was performed in five control pigs by a hepatic devascularization associated to an end to side portocaval shunt. In a treated group, 5 to 6 h after this hepatic devascularization, animals were connected to an extra corporeal liver perfused via the portal vein with blood withdrawn from the ischemic liver animal from its portal vein. Devascularization of the liver induced an increase in liver enzymes and ammonia, a drop in the ratio of branched chain amino acids to aromatic amino acids, and a decrease in blood urea and indocyanine green and galactose clearances. In treated animals, urea, amino acid ratio, and clearances increased after the ex vivo liver perfusion. In this group, mean bile production and mean liver oxygen consumption were 13.7 +/- 3.6 ml/h and 16.1 +/- 7.7 ml/min, respectively. In an acute ischemic liver failure pig model, an extra corporeal whole liver perfusion demonstrated detoxification properties as well as synthesis capacities.

  2. Model Driven Development of Data Sensitive Systems

    DEFF Research Database (Denmark)

    Olsen, Petur

    2014-01-01

    to the values of variables. This theses strives to improve model-driven development of such data-sensitive systems. This is done by addressing three research questions. In the first we combine state-based modeling and abstract interpretation, in order to ease modeling of data-sensitive systems, while allowing...... efficient model-checking and model-based testing. In the second we develop automatic abstraction learning used together with model learning, in order to allow fully automatic learning of data-sensitive systems to allow learning of larger systems. In the third we develop an approach for modeling and model-based...... detection and pushing error detection to earlier stages of development. The complexity of modeling and the size of systems which can be analyzed is severely limited when introducing data variables. The state space grows exponentially in the number of variable and the domain size of the variables...

  3. A mathematical model for leukemogenesis of radiation-induced acute myeloid leukemia in C3H/He mice

    International Nuclear Information System (INIS)

    Kai, M.; Ban, N.

    2002-01-01

    We developed a mathematical model in leukemogenesis of acute myeloid leukemia(AML) in C3H/He mice irradiated. Our previous study indicated that the leukemogenesis of AML was associated with a deletion of chromosome 2 directly induced by acute radiation. We hypothesized that radiation-induced AML needs both inactivation of one allele of a causative gene directly induced by acute radiation and another mutational event at the other allele. We analyzed data using a two-stage stochastic model for carcinogenesis. Model fitting was based on the maximum likelihood method. Our model analysis suggested that a single exposure might induce the long-lasting delayed cell death of radiation-induced initiated cells, and that the incidence of AML may be determined through both radiation-induced initiation and persistent increase of delayed cell death of the initiated cell induced by radiation

  4. Modeling of a Hydraulic Braking System

    OpenAIRE

    Lundin, Christopher

    2015-01-01

    The objective of this thesis is to derive an analytical model representing a reduced form of a mine hoist hydraulic braking system. Based primarily on fluid mechanical and mechanical physical modeling, along with a number of simplifying assumptions, the analytical model will be derived and expressed in the form of a system of differential equations including a set of static functions. The obtained model will be suitable for basic simulation and analysis of system dynamics, with the aim to cap...

  5. Standardizing acute toxicity data for use in ecotoxicology models: influence of test type, life stage, and concentration reporting.

    Science.gov (United States)

    Raimondo, Sandy; Vivian, Deborah N; Barron, Mace G

    2009-10-01

    Ecotoxicological models generally have large data requirements and are frequently based on existing information from diverse sources. Standardizing data for toxicological models may be necessary to reduce extraneous variation and to ensure models reflect intrinsic relationships. However, the extent to which data standardization is necessary remains unclear, particularly when data transformations are used in model development. An extensive acute toxicity database was compiled for aquatic species to comprehensively assess the variation associated with acute toxicity test type (e.g., flow-through, static), reporting concentrations as nominal or measured, and organism life stage. Three approaches were used to assess the influence of these factors on log-transformed acute toxicity: toxicity ratios, log-linear models of factor groups, and comparison of interspecies correlation estimation (ICE) models developed using either standardized test types or reported concentration type. In general, median ratios were generally less than 2.0, the slopes of log-linear models were approximately one for well-represented comparisons, and ICE models developed using data from standardized test types or reported concentrations did not differ substantially. These results indicate that standardizing test data by acute test type, reported concentration type, or life stage may not be critical for developing ecotoxicological models using large datasets of log-transformed values.

  6. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Science.gov (United States)

    Cancela, Camila Silva Peres; Murao, Mitiko; Viana, Marcos Borato; de Oliveira, Benigna Maria

    2012-01-01

    Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia. PMID:23323068

  7. Graphical Model Debugger Framework for Embedded Systems

    DEFF Research Database (Denmark)

    Zeng, Kebin

    2010-01-01

    Model Driven Software Development has offered a faster way to design and implement embedded real-time software by moving the design to a model level, and by transforming models to code. However, the testing of embedded systems has remained at the code level. This paper presents a Graphical Model...... Debugger Framework, providing an auxiliary avenue of analysis of system models at runtime by executing generated code and updating models synchronously, which allows embedded developers to focus on the model level. With the model debugger, embedded developers can graphically test their design model...... and check the running status of the system, which offers a debugging capability on a higher level of abstraction. The framework intends to contribute a tool to the Eclipse society, especially suitable for model-driven development of embedded systems....

  8. An accurate two-phase approximate solution to the acute viral infection model

    Energy Technology Data Exchange (ETDEWEB)

    Perelson, Alan S [Los Alamos National Laboratory

    2009-01-01

    During an acute viral infection, virus levels rise, reach a peak and then decline. Data and numerical solutions suggest the growth and decay phases are linear on a log scale. While viral dynamic models are typically nonlinear with analytical solutions difficult to obtain, the exponential nature of the solutions suggests approximations can be found. We derive a two-phase approximate solution to the target cell limited influenza model and illustrate the accuracy using data and previously established parameter values of six patients infected with influenza A. For one patient, the subsequent fall in virus concentration was not consistent with our predictions during the decay phase and an alternate approximation is derived. We find expressions for the rate and length of initial viral growth in terms of the parameters, the extent each parameter is involved in viral peaks, and the single parameter responsible for virus decay. We discuss applications of this analysis in antiviral treatments and investigating host and virus heterogeneities.

  9. Effects of acute systemic administration of cannabidiol on sleep-wake cycle in rats.

    Science.gov (United States)

    Chagas, Marcos Hortes N; Crippa, José Alexandre S; Zuardi, Antonio Waldo; Hallak, Jaime E C; Machado-de-Sousa, João Paulo; Hirotsu, Camila; Maia, Lucas; Tufik, Sergio; Andersen, Monica Levy

    2013-03-01

    Cannabidiol (CBD) is one of the main components of Cannabis sativa and has a wide spectrum of action, including effects in the sleep-wake cycle. The objective of this paper is to assess the effects on sleep of acute systemic administration of CBD. Adult male Wistar rats were randomly distributed into four groups that received intraperitoneal injections of CBD 2.5 mg/kg, CBD 10 mg/kg, CBD 40 mg/kg or vehicle (n=seven animals/group). Sleep recordings were made during light and dark periods for four days: two days of baseline recording, one day of drug administration (test), and one day after drug (post-test). During the light period of the test day, the total percentage of sleep significantly increased in the groups treated with 10 and 40 mg/kg of CBD compared to placebo. REM sleep latency increased in the group injected with CBD 40 mg/kg and was significantly decreased with the dose of 10 mg/kg on the post-test day. There was an increase in the time of SWS in the group treated with CBD 40 mg/kg, although this result did not reach statistical significance. The systemic acute administration of CBD appears to increase total sleep time, in addition to increasing sleep latency in the light period of the day of administration.

  10. Hydrological modelling in forested systems

    Science.gov (United States)

    This chapter provides a brief overview of forest hydrology modelling approaches for answering important global research and management questions. Many hundreds of hydrological models have been applied globally across multiple decades to represent and predict forest hydrological p...

  11. Towards Modelling of Hybrid Systems

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2006-01-01

    The article is an attempt to use methods of category theory and topology for analysis of hybrid systems. We use the notion of a directed topological space; it is a topological space together with a set of privileged paths. Dynamical systems are examples of directed topological spaces. A hybrid...... system consists of a number of dynamical systems that are glued together according to information encoded in the discrete part of the system. We develop a definition of a hybrid system as a functor from the category generated by a transition system to the category of directed topological spaces. Its...... directed homotopy colimit (geometric realization) is a single directed topological space. The behavior of hybrid systems can be then understood in terms of the behavior of dynamical systems through the directed homotopy colimit....

  12. Association between prepayment systems and emergency medical services use among patients with acute chest discomfort syndrome.

    Science.gov (United States)

    Siepmann, David B; Mann, N Clay; Hedges, Jerris R; Daya, Mohamud R

    2000-06-01

    Cost concerns may inhibit emergency medical services (EMS) use. Novel tax-based and subscription prepayment programs indemnify patients against the cost of EMS treatment and transport. We determine whether the presence of (or enrollment in) prepayment plans increase EMS use among patients with acute chest discomfort, particularly those residing in low-income areas, those lacking private insurance, or both. This study uses a subset of baseline data from the REACT trial, a multicenter, randomized controlled community trial designed, in part, to increase EMS use. The sample includes 860 consecutive noninstitutionalized patients (>30 years old) presenting with nontraumatic chest discomfort to hospital emergency departments in 4 Oregon/Washington communities. The association between prepayment systems and EMS use was analyzed using multivariable logistic regression. Overall EMS use was 52% (n=445). Among EMS users, 338 (75%) were subsequently admitted to the hospital and 110 (25%) were released from the ED. Prepayment was not associated with increased EMS use in the overall patient sample. However, patients residing in low-income census block groups (median annual income higher-income block group residents. Among low-income block group residents lacking private insurance, prepayment systems were associated with 3.8 times (95% CI 1.2 to 13.4) greater EMS usage. Economic considerations may affect EMS system utilization among underinsured and low-income patients experiencing a cardiac event. Prepayment systems may increase EMS utilization among these groups. [Seipmann DB, Mann NC, Hedges JR, Daya MR, for the Rapid Early Action for Coronary Treatment (REACT) Study. Association between prepayment systems and emergency medical services use among patients with acute chest discomfort syndrome. Ann Emerg Med. June 2000;35:573-578.]. Copyright © 2000 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  13. Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Buehler, Paul W.; Butt, Omer I. [Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); D' Agnillo, Felice, E-mail: felice.dagnillo@fda.hhs.gov [Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

    2011-06-10

    Highlights: {yields} Toxicological implications associated with the use of NaNO{sub 2} therapy to treat systemic cell-free Hb exposure are not well-defined. {yields} Systemic Hb exposure followed by NaNO{sub 2} infusion induces acute CNS toxicities in guinea pigs. {yields} These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO{sub 2} alone. {yields} NaNO{sub 2}-mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO{sub 2}) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO{sub 2} with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO{sub 2} on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO{sub 2}, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO{sub 2} alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

  14. Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

    International Nuclear Information System (INIS)

    Buehler, Paul W.; Butt, Omer I.; D'Agnillo, Felice

    2011-01-01

    Highlights: → Toxicological implications associated with the use of NaNO 2 therapy to treat systemic cell-free Hb exposure are not well-defined. → Systemic Hb exposure followed by NaNO 2 infusion induces acute CNS toxicities in guinea pigs. → These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO 2 alone. → NaNO 2 -mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO 2 ) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO 2 with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO 2 on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO 2 , at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO 2 alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

  15. Extramuscular myofascial force transmission alters substantially the acute effects of surgical aponeurotomy: assessment by finite element modeling

    NARCIS (Netherlands)

    Yucesoy, Can; Koopman, Bart; Grootenboer, Henk; Huijing, Peter

    2007-01-01

    Effects of extramuscular myofascial force transmission on the acute effects of aponeurotomy were studied using finite element modeling and implications of such effects on surgery were discussed. Aponeurotomized EDL muscle of the rat was modeled in two conditions: (1) fully isolated (2) with intact

  16. Acute kidney injuries induced by various irrigation pressures in rat models of mild and severe hydronephrosis.

    Science.gov (United States)

    Cao, Zhixiu; Yu, Weimin; Li, Wei; Cheng, Fan; Xia, Yue; Rao, Ting; Yao, Xiaobing; Zhang, Xiaobin; Larré, Stéphane

    2013-12-01

    To clarify whether tolerance to irrigation pressure could be modified over varying degrees of kidney obstruction during the endoscopic treatment of kidney stones in a rat model. A total of 126 rats were randomly allocated into 2 experimental groups and a control group. The experimental groups underwent a surgical procedure to induce mild (group M, n = 60) or severe (group S, n = 60) hydronephrosis. In each group, the rats were then randomly allocated into 4 subgroups (M0 to M3 and S0 to S3) of respectively 6, 18, 18, and 18 rats. Groups 0 to 3 were respectively perfused with 0 (no irrigation), 20, 60, and 100 mm Hg pressure fluid. The control group underwent no surgical procedures and was only perfused with 100 mm Hg pressure fluid. Acute kidney injuries were assessed by analyzing the kidney microstructure, tubular cell apoptosis, kidney injury molecule-1, and cysteine-rich 61 (Cyr61/CCN1) expression using immunohistochemistry. No abnormalities were observed for the control group, groups 0, or 1. In group 2, abnormalities were observed only in the S group, whereas all kidneys in group 3 suffered acute kidneys injuries, along with occurrence of tubular cells necrosis, increased apoptosis, and increased expression of kidney injury molecule-1 and Cyr61. Rats with severely obstructed kidneys were more likely to suffer acute kidney injuries than those with less obstructed kidneys when exposed to higher kidney irrigation pressures. This suggests that the pressure should be controlled and reduced when performing endourologic procedures in the context of kidney obstruction. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  17. Service systems concepts, modeling, and programming

    CERN Document Server

    Cardoso, Jorge; Poels, Geert

    2014-01-01

    This SpringerBrief explores the internal workings of service systems. The authors propose a lightweight semantic model for an effective representation to capture the essence of service systems. Key topics include modeling frameworks, service descriptions and linked data, creating service instances, tool support, and applications in enterprises.Previous books on service system modeling and various streams of scientific developments used an external perspective to describe how systems can be integrated. This brief introduces the concept of white-box service system modeling as an approach to mo

  18. A Biomathematical Model of Lymphopoiesis and Its Application to Acute and Chronic Irradiation Assessment

    Science.gov (United States)

    Hu, Shaowen; Cucinotta, Francis A.

    2010-01-01

    After the events of September 11, 2001, there is an increasing concern of the occurrence of radiological terrorism that may result in significant casualties in densely populated areas. Much effort has been made to establish various biomarkers to rapidly assess radiation dose in mass-casualty and population-monitoring scenarios, which are demanded for effective medical management and treatment of the exposed victims. Among these the count of lymphocytes in peripheral blood and their depletion kinetics are the most important early indicators of the severity of the radiation injury. In this study, we examine a biomathematical model of lymphopoiesis which has been successfully utilized to simulate and interpret experimental data of acute and chronic irradiations on rodents [1]. With revised parameters for humans, we find this model can reproduce several sets of clinical lymphocyte data of accident victims over a wide range of absorbed doses. In addition, the absolute lymphocyte counts and the depletion rate constants calculated by this model also show good correlation with the Guskova formula and the Goans model, the two empirical tools which have been widely recognized for early estimation of the exposed dose after radiation accidents [2]. We also use the model to analyze the hematological data of the Techa River residents which were exposed to chronic low-dose irradiation during 1950-1956 [3]. This model can serve as a computational tool in radiation accident management, military operations involving nuclear warfare, radiation therapy, and space radiation risk assessment.

  19. Anticonvulsant profile of a balanced ketogenic diet in acute mouse seizure models.

    Science.gov (United States)

    Samala, Ramakrishna; Willis, Sarah; Borges, Karin

    2008-10-01

    Anticonvulsant effects of the ketogenic diet (KD) have been reported in the mouse, although previous studies did not control for intake of vitamins, minerals and antioxidants. The aim of this study was to examine the effects of balanced ketogenic and control diets in acute mouse seizure models. The behavior in four mouse seizure models, plasma d-beta-hydroxybutyrate (d-BHB) and glucose levels were determined after feeding control diet, 4:1 and 6:1 KDs with matched vitamins, minerals and antioxidants. Feeding 4:1 and 6:1 KDs ad lib to 3-week-old (adolescent) mice resulted in 1.2-2.2mM d-BHB in plasma, but did not consistently change glucose levels. The 6:1 KD reproducibly elevated the CC50 (current that initiates seizures in 50% mice tested) in the 6-Hz model after 14 days of feeding to adolescent CD1 mice. Higher plasma d-BHB levels correlated with anticonvulsant effects. Despite ketosis, no consistent anticonvulsant effects of KDs were found in the fluorothyl or pentylenetetrazole CD1 mouse models. The 4:1 KD was neither anticonvulsant nor neuroprotective in hippocampus in the C3H mouse kainate model. Taken together, the KD's anticonvulsant effect was limited to the 6-Hz model, required chronic feeding with 6:1 fat content, and was independent from lowering plasma glucose.

  20. On Verification Modelling of Embedded Systems

    NARCIS (Netherlands)

    Brinksma, Hendrik; Mader, Angelika H.

    Computer-aided verification of embedded systems hinges on the availability of good verification models of the systems at hand. Such models must be much simpler than full design models or specifications to be of practical value, because of the unavoidable combinatorial complexities in the

  1. Balmorel open source energy system model

    DEFF Research Database (Denmark)

    Wiese, Frauke; Bramstoft, Rasmus; Koduvere, Hardi

    2018-01-01

    As the world progresses towards a cleaner energy future with more variable renewable energy sources, energy system models are required to deal with new challenges. This article describes design, development and applications of the open source energy system model Balmorel, which is a result of a l...... transport of local biomass as part of the optimisation and speeding up the model....

  2. Systemic not just mesenteric lymph causes acute lung injury following hemorrhagic shock.

    Science.gov (United States)

    Diebel, Lawrence N; Liberati, David M; Ledgerwood, Anna M; Lucas, Charles E

    2008-10-01

    Recent studies have demonstrated a significant role for factor(s) present in mesenteric lymph following hemorrhagic shock in the etiology of post-hemorrhagic shock acute lung injury (ALI). Earlier studies have shown that ischemia-reperfusion insults to systemic tissue beds can also result in ALI. We therefore hypothesized that factors in systemic lymph may cause lung injury after hemorrhagic shock; this was studied in vitro. Confluent human pulmonary microvascular endothelial cells (HMVEC) maintained in a 2-chamber cell culture system were exposed to systemic lymph obtained from dogs exposed to sham operation or hemorrhagic shock and resuscitation. HMVEC injury was indexed by apoptosis (% Apo, Hoechst staining) and permeability to albumin (microL/min). HMVEC activation was indexed by surface expression of intracellular adhesion molecule-1 (ICAM-1) expressed as mean fluorescence intensity using flow cytometry. There was a 2-fold increase in HMVEC permeability and apoptotic rate after incubation with postshock systemic lymph. A similar effect was noted with ICAM expression, which was 2.5 fold higher after incubation with postshock lymph. These biologic effects were first noted with the 120-minute postresuscitation lymph. Lymph obtained during shock or from sham animals had no effect. Pulmonary microvascular endothelial dysfunction is evident after exposure to lymph obtained from systemic sites after hemorrhagic shock. The "unique" properties ascribed to post-hemorrhagic shock mesenteric lymph in causing ALI seem to be shared by lymph from systemic sites as well.

  3. Modeling, Control and Coordination of Helicopter Systems

    CERN Document Server

    Ren, Beibei; Chen, Chang; Fua, Cheng-Heng; Lee, Tong Heng

    2012-01-01

    Modeling, Control and Coordination of Helicopter Systems provides a comprehensive treatment of helicopter systems, ranging from related nonlinear flight dynamic modeling and stability analysis to advanced control design for single helicopter systems, and also covers issues related to the coordination and formation control of multiple helicopter systems to achieve high performance tasks. Ensuring stability in helicopter flight is a challenging problem for nonlinear control design and development. This book is a valuable reference on modeling, control and coordination of helicopter systems,providing readers with practical solutions for the problems that still plague helicopter system design and implementation. Readers will gain a complete picture of helicopters at the systems level, as well as a better understanding of the technical intricacies involved. This book also: Presents a complete picture of modeling, control and coordination for helicopter systems Provides a modeling platform for a general class of ro...

  4. Systems Biology—Biomedical Modeling

    OpenAIRE

    Sobie, Eric A.; Lee, Young-Seon; Jenkins, Sherry L.; Iyengar, Ravi

    2011-01-01

    Because of the complexity inherent in biological systems, many researchers frequently rely on a combination of global analysis and computational approaches to gain insight into both (i) how interacting components can produce complex system behaviors, and (ii) how changes in conditions may alter these behaviors. Because the biological details of a particular system are generally not taught along with the quantitative approaches that enable hypothesis generation and analysis of the system, we d...

  5. Henoch-Schönlein purpura without systemic involvement beginning with acute scrotum and mimicking torsion of testis

    Directory of Open Access Journals (Sweden)

    Levent Verim

    2013-04-01

    Full Text Available Henoch-Schönlein purpura (HSP is the most common systemic vasculitis in children. Typical presentations of HSP are palpable purpura of the small vessels in the hips and lower limbs, abdominal pain, arthritis, and hematuria. Scrotal involvement manifested by the presence of scrotal pain and swelling during the course of the disease is rarely seen. HSP without systemic involvement with acute scrotum mimicking testicular torsion is even rare in the medical literature. In most cases, patients with this disease achieve complete recovery. Herein, we report an interesting HSP case with skin symptoms but without systemic involvement and then progression to acute scrotum resembling torsion of testis.

  6. Systemic thrombolytic therapy alone and in combination with mechanical revascularization in acute ischemic stroke in two children

    DEFF Research Database (Denmark)

    Modrau, B; Sørensen, L; Bartholdy, N J

    2011-01-01

    Thrombolytic therapy is not recommended for acute ischemic stroke (AIS) in patients under the age of 18 and published experience is limited. In this case report, we describe two children treated with systemic thrombolytic therapy. One child received additional mechanical revascularization...... and achieved a good clinical outcome. The differences in the fibrinolytic system and the different etiology of AIS in childhood may limit a simple extrapolation of the adult guidelines for systemic thrombolytic therapy. Acute multimodal imaging to clarify the etiology of AIS might help to select the most...... appropriate treatment modality....

  7. Modeling and simulation of systems using Matlab and Simulink

    CERN Document Server

    Chaturvedi, Devendra K

    2009-01-01

    Introduction to SystemsSystemClassification of SystemsLinear SystemsTime-Varying vs. Time-Invariant Systems Lumped vs. Distributed Parameter SystemsContinuous- and Discrete-Time Systems Deterministic vs. Stochastic Systems Hard and Soft Systems Analysis of Systems Synthesis of Systems Introduction to System Philosophy System Thinking Large and Complex Applied System Engineering: A Generic ModelingSystems ModelingIntroduction Need of System Modeling Modeling Methods for Complex Systems Classification of ModelsCharacteristics of Models ModelingMathematical Modeling of Physical SystemsFormulation of State Space Model of SystemsPhysical Systems Theory System Components and Interconnections Computation of Parameters of a Component Single Port and Multiport Systems Techniques of System Analysis Basics of Linear Graph Theoretic ApproachFormulation of System Model for Conceptual SystemFormulation System Model for Physical SystemsTopological RestrictionsDevelopment of State Model of Degenerative SystemSolution of Stat...

  8. Modelling and Verification of Relay Interlocking Systems

    DEFF Research Database (Denmark)

    Haxthausen, Anne Elisabeth; Bliguet, Marie Le; Kjær, Andreas

    2010-01-01

    This paper describes how relay interlocking systems as used by the Danish railways can be formally modelled and verified. Such systems are documented by circuit diagrams describing their static layout. It is explained how to derive a state transition system model for the dynamic behaviour of a re...

  9. Compositional Modelling of Stochastic Hybrid Systems

    NARCIS (Netherlands)

    Strubbe, S.N.

    2005-01-01

    In this thesis we present a modelling framework for compositional modelling of stochastic hybrid systems. Hybrid systems consist of a combination of continuous and discrete dynamics. The state space of a hybrid system is hybrid in the sense that it consists of a continuous component and a discrete

  10. Logical Analysis of Data (LAD model for the early diagnosis of acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Hoehn Gerard

    2008-07-01

    Full Text Available Abstract Background Strokes are a leading cause of morbidity and the first cause of adult disability in the United States. Currently, no biomarkers are being used clinically to diagnose acute ischemic stroke. A diagnostic test using a blood sample from a patient would potentially be beneficial in treating the disease. Results A classification approach is described for differentiating between proteomic samples of stroke patients and controls, and a second novel predictive model is developed for predicting the severity of stroke as measured by the National Institutes of Health Stroke Scale (NIHSS. The models were constructed by applying the Logical Analysis of Data (LAD methodology to the mass peak profiles of 48 stroke patients and 32 controls. The classification model was shown to have an accuracy of 75% when tested on an independent validation set of 35 stroke patients and 25 controls, while the predictive model exhibited superior performance when compared to alternative algorithms. In spite of their high accuracy, both models are extremely simple and were developed using a common set consisting of only 3 peaks. Conclusion We have successfully identified 3 biomarkers that can detect ischemic stroke with an accuracy of 75%. The performance of the classification model on the validation set and on cross-validation does not deteriorate significantly when compared to that on the training set, indicating the robustness of the model. As in the case of the LAD classification model, the results of the predictive model validate the function constructed on our support-set for approximating the severity scores of stroke patients. The correlation and root mean absolute error of the LAD predictive model are consistently superior to those of the other algorithms used (Support vector machines, C4.5 decision trees, Logistic regression and Multilayer perceptron.

  11. Red cell distribution width and neurological scoring systems in acute stroke patients

    Directory of Open Access Journals (Sweden)

    Kara H

    2015-03-01

    Full Text Available Hasan Kara,1 Selim Degirmenci,1 Aysegul Bayir,1 Ahmet Ak,1 Murat Akinci,1 Ali Dogru,1 Fikret Akyurek,2 Seyit Ali Kayis3 1Department of Emergency Medicine, Faculty of Medicine, Selcuk University, Konya, Turkey; 2Department of Biochemistry, Faculty of Medicine, Selcuk University, Konya, Turkey; 3Department of Biostatistics, Faculty of Medicine, Karabuk University, Karabuk, Turkey Objectives: The purpose of the present study was to evaluate the association between the red blood cell distribution width (RDW and the Glasgow Coma Scale (GCS, Canadian Neurological Scale (CNS, and National Institutes of Health Stroke Scale (NIHSS scores in patients who had acute ischemic stroke. Methods: This prospective observational cohort study included 88 patients who have had acute ischemic stroke and a control group of 40 patients who were evaluated in the Emergency Department for disorders other than acute ischemic stroke. All subjects had RDW determined, and stroke patients had scoring with the GCS, CNS, and NIHSS scores. The GCS, CNS, and NIHSS scores of the patients were rated as mild, moderate, or severe and compared with RDW. Results: Stroke patients had significantly higher median RDW than control subjects. The median RDW values were significantly elevated in patients who had more severe rather than milder strokes rated with all three scoring systems (GCS, CNS, and NIHSS. The median RDW values were significantly elevated for patients who had moderate rather than mild strokes rated by GCS and CNS and for patients who had severe rather than mild strokes rated by NIHSS. The area under the receiver operating characteristic curve was 0.760 (95% confidence interval, 0.676–0.844. Separation of stroke patients and control groups was optimal with RDW 14% (sensitivity, 71.6%; specificity, 67.5%; accuracy, 70.3%. Conclusion: In stroke patients who have symptoms <24 hours, the RDW may be useful in predicting the severity and functional outcomes of the stroke

  12. Models of complex attitude systems

    DEFF Research Database (Denmark)

    Sørensen, Bjarne Taulo

    Existing research on public attitudes towards agricultural production systems is largely descriptive, abstracting from the processes through which members of the general public generate their evaluations of such systems. The present paper adopts a systems perspective on such evaluations, understa......Existing research on public attitudes towards agricultural production systems is largely descriptive, abstracting from the processes through which members of the general public generate their evaluations of such systems. The present paper adopts a systems perspective on such evaluations......, understanding them as embedded into a wider attitude system that consists of attitudes towards objects of different abstraction levels, ranging from personal value orientations over general socio-political attitudes to evaluations of specific characteristics of agricultural production systems. It is assumed...... that evaluative affect propagates through the system in such a way that the system becomes evaluatively consistent and operates as a schema for the generation of evaluative judgments. In the empirical part of the paper, the causal structure of an attitude system from which people derive their evaluations of pork...

  13. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.

    Science.gov (United States)

    Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

    2016-09-01

    Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. Copyright © 2016 the American Physiological Society.

  14. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

    Science.gov (United States)

    Zhan, Xianbao; Wang, Fan; Bi, Yan

    2016-01-01

    Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. PMID:27418683

  15. The urgent need for a harmonized severity scoring system for acute allergic reactions.

    Science.gov (United States)

    Muraro, Antonella; Fernandez-Rivas, Montserrat; Beyer, Kirsten; Cardona, Victòria; Clark, Andrew; Eller, Esben; Hourihane, Jonathan O'B; Jutel, Marek; Sheikh, Aziz; Agache, Ioana; Allen, Katrina J; Angier, Liz; Ballmer-Weber, Barbara; Bilò, Maria Beatrice; Bindslev-Jensen, Carsten; Camargo, Carlos A; Cianferoni, Antonella; DunnGalvin, Audrey; Eigenmann, Philippe A; Halken, Susanne; Hoffmann-Sommergruber, Karin; Lau, Susanne; Nilsson, Caroline; Poulsen, Lars K; Rueff, Franziska; Spergel, Jonathan; Sturm, Gunter; Timmermans, Frans; Torres, Maria J; Turner, Paul; van Ree, Ronald; Wickman, Magnus; Worm, Margitta; Clare Mills, E N; Roberts, Graham

    2018-01-13

    The accurate assessment and communication of the severity of acute allergic reactions is important to patients, clinicians, researchers, the food industry, public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that works across the range of allergenic triggers and addresses the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that is clinically meaningful and is useful for allergy healthcare professionals and researchers; and (ii) a three grade based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Overnight responses of the circulating IGF-I system after acute, heavy-resistance exercise.

    Science.gov (United States)

    Nindl, B C; Kraemer, W J; Marx, J O; Arciero, P J; Dohi, K; Kellogg, M D; Loomis, G A

    2001-04-01

    This study evaluated the individual components of the insulin-like growth factor I (IGF-I) system [i.e., total and free IGF-I, insulin-like growth factor binding protein (IGFBP)-2 and -3, and the acid-labile subunit (ALS)] in 10 young, healthy men (age: 22 +/- 1 yr, height: 177 +/- 2 cm, weight: 79 +/- 3 kg, body fat: 11 +/- 1%) overnight for 13 h after two conditions: a resting control (Con) and an acute, heavy-resistance exercise protocol (Ex). The Ex was a high-volume, multiset exercise protocol that alternated between 10- and 5-repetition maximum sets with 90-s rest periods between sets. The Ex was performed from 1500 to 1700; blood was obtained immediately postexercise and sampled throughout the night (every 10 min for the first hour and every hour thereafter) until 0600 the next morning. For the first hour, significant differences (P Con: 3,531 ng/ml). For the overnight responses, no differences were observed for total or free IGF-I or IGFBP-3, whereas IGFBP-2 increased (Ex: 561 > Con: 500 ng/ml) and ALS decreased (Ex: 35 < Con: 39 microg/ml) after exercise. The results from this study suggest that the impact that resistance exercise exerts on the circulating IGF-I system is not in the alteration of the amount of IGF-I but rather of the manner in which IGF-I is partitioned among its family of binding proteins. Thus acute, heavy-resistance exercise can lead to alterations in the IGF-I system that can be detected in the systemic circulation.

  17. Topical ROR Inverse Agonists Suppress Inflammation in Mouse Models of Atopic Dermatitis and Acute Irritant Dermatitis.

    Science.gov (United States)

    Dai, Jun; Choo, Min-Kyung; Park, Jin Mo; Fisher, David E

    2017-12-01

    The retinoic acid receptor-related orphan receptors RORα and RORγ are critical for the functions of specific subsets of T cells and innate lymphoid cells, which are key drivers of inflammatory disease in barrier tissues. Here, we investigate the anti-inflammatory potential of SR1001, a synthetic RORα/γ inverse agonist, in mouse models of atopic dermatitis and acute irritant dermatitis. Topical treatment with SR1001 reduces epidermal and dermal features of MC903-induced atopic dermatitis-like disease and suppresses the production of type 2 cytokines and other inflammatory mediators in lesional skin. In the epidermis, SR1001 treatment blocks MC903-induced expression of TSLP and reverses impaired keratinocyte differentiation. SR1001 is also effective in alleviating acute dermatitis triggered by 12-O-tetradecanoylphorbol-13-acetate. Overall, our results suggest that RORα/γ are important therapeutic targets for cutaneous inflammation and suggest topical usage of inhibitory ligands as an approach to treating skin diseases of inflammatory etiology. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. A New Acute Attack of Angle Closure Glaucoma Animal Model with Healon 5

    Directory of Open Access Journals (Sweden)

    Silvania Y. F. Lau

    2011-05-01

    Full Text Available Acute angle closure glaucoma (AACG is an ocular emergency and sight -threatening disease in which the intraocular ocular pressure (IOP rises suddenly due to blockage of aqueous humor outflow. It can cause permanent loss in visual acuity and visual field. In animal study, the well-established model to study AACG is by fluid infusion and by adjusting the bottle level, a high IOP can be induced in a few seconds. However, there is no blockage of aqueous outflow and the pressure rise is unrealistically fast. To mimic human AACG, we suggest to use Healon 5, an ophthalmic viscosurgical device, which is injected intracamerally to block the aqueous outflow. The IOP is allowed to build up naturally. We found that, with this technique, the IOP elevated at a rate of 0.57 mmHg/min before it hit 40 mmHg, which is considered as AACG in human. The maximum IOP registered was above 70 mmHg. Thinning of retinal nerve fiber layer (RNFL and neural cells lost were seen. Visual function evaluated by ERG showed reduction in a-wave, b-wave, photopic negative response (PhNR and oscillatory potentials (OPs activities. In conclusion, Healon 5 is effective in inducing acute transient rise in IOP which mimics human AACG.

  19. Mechanism and prevention of acute kidney injury from cast nephropathy in a rodent model

    Science.gov (United States)

    Ying, Wei-Zhong; Allen, Christopher E.; Curtis, Lisa M.; Aaron, Kristal J.; Sanders, Paul W.

    2012-01-01

    A common renal complication of multiple myeloma is “myeloma kidney,” a condition also known as cast nephropathy. The renal lesions (casts) are directly related to the production of monoclonal immunoglobulin free light chains (FLCs), which coprecipitate with Tamm-Horsfall glycoprotein (THP) in the lumen of the distal nephron, obstructing tubular fluid flow. Here, we report that analysis of the binding interaction between FLCs and THP demonstrates that the secondary structure and key amino acid residues on the complementarity-determining region 3 (CDR3) of FLCs are critically important determinants of the molecular interaction with THP. The findings permitted development of a cyclized competitor peptide that demonstrated strong inhibitory capability in the binding of FLCs to THP in vitro. When used in a rodent model of cast nephropathy, this cyclized peptide construct served as an effective inhibitor of intraluminal cast formation and prevented the functional manifestations of acute kidney injury in vivo. These experiments provide proof of concept that intraluminal cast formation is integrally involved in the pathogenesis of acute kidney injury from cast nephropathy. Further, the data support a clinically relevant approach to the management of renal failure in the setting of multiple myeloma. PMID:22484815

  20. Risk model for suspected acute coronary syndrome is of limited value in an emergency department

    DEFF Research Database (Denmark)

    Mogensen, Christian Backer; Christiansen, Maja; Jørgensen, Jess Bjerre

    2015-01-01

    if assigned to the high-risk group was 3.0. Allocation to the high-risk group, male gender and age above 60 years was associated with a higher risk of ACS. For patients fulfilling the high-risk definition, sensitivity was 71%, specificity 55%, negative predictive value 90% and positive predictive value 24......INTRODUCTION: Among patients with acute chest pain, acute coronary syndrome (ACS) is seen only in a minority of the patients, which raises the question, whether it is possible to separate a group with a high risk of ACS for admission to a cardiac care unit (CCU) from those with a low risk who would...... be treated at an emergency department (ED). The aim of this study was to describe a risk stratification model for a Danish context. METHODS: This was a historic prospective cohort study of patients with suspicion of ACS. The patient was defined as a low-risk patient and admitted to the ED if: 1...

  1. The therapeutic efficacy of azithromycin and nitazoxanide in the acute pig model of Cryptosporidium hominis.

    Science.gov (United States)

    Lee, Sangun; Harwood, Melanie; Girouard, Don; Meyers, Marvin J; Campbell, Mary A; Beamer, Gillian; Tzipori, Saul

    2017-01-01

    Recent reports highlighting the global significance of cryptosporidiosis among children, have renewed efforts to develop control measures. We have optimized the gnotobiotic piglet model of acute diarrhea to evaluate azithromycin (AZR), nitazoxanide (NTZ), or treatment with both against Cryptosporidium hominis, the species responsible for most human cases. Piglets, animals reproducibly clinically susceptible to C. hominis, when inoculated with 106 oocysts, developed acute diarrhea with oocyst excretion in feces within 3 days. Ten day-treatment with recommended doses for children, commencing at onset of diarrhea, showed that treatment with AZR or NTZ relieved symptoms early in the treatment compared with untreated animals. Piglets treated with AZR exhibited no reduction of oocyst excretion whereas treatment with NTZ significantly reduced oocyst shedding early, increasing however after 5 days. While treatment with AZR+NTZ led to considerable symptomatic improvement, it had a modest effect on reducing mucosal injury, and did not completely eliminate oocyst excretion. Doubling the dose of AZR and/or NTZ did not improve the clinical outcome, confirming clinical observations that NTZ is only partially effective in reducing duration of diarrhea in children. This investigation confirms the gnotobiotic piglet as a useful tool for drug evaluation for the treatment of cryptosporidiosis in children.

  2. 76 FR 39883 - Design of Clinical Trials for Systemic Antibacterial Drugs for the Treatment of Acute Otitis...

    Science.gov (United States)

    2011-07-07

    ... HUMAN SERVICES Food and Drug Administration Design of Clinical Trials for Systemic Antibacterial Drugs for the Treatment of Acute Otitis Media; Public Workshop AGENCY: Food and Drug Administration, HHS... workshop regarding the design of Clinical Trials for Systemic Antibacterial Agents for the Treatment of...

  3. Modeling Control Situations in Power System Operations

    DEFF Research Database (Denmark)

    Saleem, Arshad; Lind, Morten; Singh, Sri Niwas

    2010-01-01

    Increased interconnection and loading of the power system along with deregulation has brought new challenges for electric power system operation, control and automation. Traditional power system models used in intelligent operation and control are highly dependent on the task purpose. Thus, a model...... of explicit principles for model construction. This paper presents a work on using explicit means-ends model based reasoning about complex control situations which results in maintaining consistent perspectives and selecting appropriate control action for goal driven agents. An example of power system...... for intelligent operation and control must represent system features, so that information from measurements can be related to possible system states and to control actions. These general modeling requirements are well understood, but it is, in general, difficult to translate them into a model because of the lack...

  4. Combination systemic and intravitreal antiviral therapy in the management of acute retinal necrosis syndrome.

    Science.gov (United States)

    Yeh, Steven; Suhler, Eric B; Smith, Justine R; Bruce, Beau; Fahle, Gary; Bailey, Steven T; Hwang, Thomas S; Stout, J Timothy; Lauer, Andreas K; Wilson, David J; Rosenbaum, James T; Flaxel, Christina J

    2014-01-01

    Acute retinal necrosis (ARN) may lead to severe visual loss because of its rapid progression and high likelihood of retinal detachment (RD). This study investigates whether combination systemic and intravitreal antiviral therapy is superior to systemic antiviral therapy alone. Single-center, interventional, comparative case series of patients with ARN treated with combination systemic antiviral and intravitreal foscarnet injection therapy or systemic antiviral therapy alone. Survival analysis and incidence rates of visual acuity (VA) gain of two lines or greater, severe visual loss of 20/200 or worse, and RD were assessed. Twelve patients received combination therapy and 12 received systemic therapy alone. Patients receiving combination therapy were more likely to gain two or more lines of VA and showed decreased incidences of severe visual loss and RD. Combination oral and intravitreal antiviral therapy may improve the likelihood for VA gain and decrease the risk of RD in patients with ARN. Clinicians should consider administering combination systemic and intravitreal antiviral therapy for patients with the ARN syndrome.

  5. A Microfluidic Device for Continuous Sensing of Systemic Acute Toxicants in Drinking Water

    Directory of Open Access Journals (Sweden)

    Xinyan Zhao

    2013-12-01

    Full Text Available A bioluminescent-cell-based microfluidic device for sensing toxicants in drinking water was designed and fabricated. The system employed Vibrio fischeri cells as broad-spectrum sensors to monitor potential systemic cell toxicants in water, such as heavy metal ions and phenol. Specifically, the chip was designed for continuous detection. The chip design included two counter-flow micromixers, a T-junction droplet generator and six spiral microchannels. The cell suspension and water sample were introduced into the micromixers and dispersed into droplets in the air flow. This guaranteed sufficient oxygen supply for the cell sensors. Copper (Cu2+, zinc (Zn2+, potassium dichromate and 3,5-dichlorophenol were selected as typical toxicants to validate the sensing system. Preliminary tests verified that the system was an effective screening tool for acute toxicants although it could not recognize or quantify specific toxicants. A distinct non-linear relationship was observed between the zinc ion concentration and the Relative Luminescence Units (RLU obtained during testing. Thus, the concentration of simple toxic chemicals in water can be roughly estimated by this system. The proposed device shows great promise for an early warning system for water safety.

  6. Holonic Models for Traffic Control Systems

    Science.gov (United States)

    Ciufudean, Calin; Filote, Constantin

    This paper proposes a new time-placed net model for traffic control systems, respectively railway control traffic systems. This model can be interpreted as a holonic one, and contains three modules: Transport Planning Module, Transport Control Module and Priority Control Module. For railway traffic systems we introduce a strategy in a timed-place Petri net model to solve collision and traffic jam problems.

  7. Hydrological modeling in forested systems

    Science.gov (United States)

    H.E. Golden; G.R. Evenson; S. Tian; Devendra Amatya; Ge Sun

    2015-01-01

    Characterizing and quantifying interactions among components of the forest hydrological cycle is complex and usually requires a combination of field monitoring and modelling approaches (Weiler and McDonnell, 2004; National Research Council, 2008). Models are important tools for testing hypotheses, understanding hydrological processes and synthesizing experimental data...

  8. A smartphone client-server teleradiology system for primary diagnosis of acute stroke.

    Science.gov (United States)

    Mitchell, J Ross; Sharma, Pranshu; Modi, Jayesh; Simpson, Mark; Thomas, Monroe; Hill, Michael D; Goyal, Mayank

    2011-05-06

    Recent advances in the treatment of acute ischemic stroke have made rapid acquisition, visualization, and interpretation of images a key factor for positive patient outcomes. We have developed a new teleradiology system based on a client-server architecture that enables rapid access to interactive advanced 2-D and 3-D visualization on a current generation smartphone device (Apple iPhone or iPod Touch, or an Android phone) without requiring patient image data to be stored on the device. Instead, a server loads and renders the patient images, then transmits a rendered frame to the remote device. Our objective was to determine if a new smartphone client-server teleradiology system is capable of providing accuracies and interpretation times sufficient for diagnosis of acute stroke. This was a retrospective study. We obtained 120 recent consecutive noncontrast computed tomography (NCCT) brain scans and 70 computed tomography angiogram (CTA) head scans from the Calgary Stroke Program database. Scans were read by two neuroradiologists, one on a medical diagnostic workstation and an iPod or iPhone (hereafter referred to as an iOS device) and the other only on an iOS device. NCCT brain scans were evaluated for early signs of infarction, which includes early parenchymal ischemic changes and dense vessel sign, and to exclude acute intraparenchymal hemorrhage and stroke mimics. CTA brain scans were evaluated for any intracranial vessel occlusion. The interpretations made on an iOS device were compared with those made at a workstation. The total interpretation times were recorded for both platforms. Interrater agreement was assessed. True positives, true negatives, false positives, and false negatives were obtained, and sensitivity, specificity, and accuracy of detecting the abnormalities on the iOS device were computed. The sensitivity, specificity, and accuracy of detecting intraparenchymal hemorrhage were 100% using the iOS device with a perfect interrater agreement (kappa=1

  9. Acute respiratory distress syndrome in a pregnant woman with systemic lupus erythematosus: a case report.

    Science.gov (United States)

    Chen, Y-J A; Tseng, J-J; Yang, M-J; Tsao, Y-P; Lin, H-Y

    2014-12-01

    When the disease activity of systemic lupus erythematosus (SLE) is controlled appropriately, a pregnant woman who has lupus is able to carry safely to term and deliver a healthy infant. While the physiology of a healthy pregnancy itself influences ventilatory function, acute pulmonary distress may decrease oxygenation and influence both mother and fetus. Though respiratory failure in pregnancy is relatively rare, it remains one of the leading conditions requiring intensive care unit admission in pregnancy and carries a high risk of maternal and fetal morbidity and mortality, not to mention the complexity caused by lupus flare. We report a case of SLE complicated with lupus pneumonitis and followed by acute respiratory distress during pregnancy. Though there is a high risk of maternal and fetal morbidity and mortality, maternal respiratory function improved after cesarean section and treatment of the underlying causes. The newborn had an extremely low birth weight but was well at discharge. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  10. Acute effects of dokha smoking on the cardiovascular and respiratory systems among UAE male university students.

    Science.gov (United States)

    Shaikh, Rizwana B; Abdul Haque, Noor Mohammad; Abdul Hadi Khalil Al Mohsen, Hassan; Abdul Hadi Khalil Al Mohsen, Ali; Haitham Khalaf Humadi, Marwa; Zaki Al Mubarak, Zainab; Mathew, Elsheba; Al Sharbatti, Shatha

    2012-01-01

    In the United Arab Emirates (UAE) tobacco use is rampant. A less reported, yet widely used form of smoking native to UAE is midwakh or dhokha. The aim of the study is to assess the acute effects of smoking dokha (Arabian pipe) on the cardiovascular and respiratory systems among male university students in the UAE. A quasi-experimental study was conducted among 97 male volunteers aged more than 17 years. Blood pressure, heart rate and respiratory rate of each participant, were measured before and immediately after smoking. A self administered questionnaire was used to collect personal details and data about smoking pattern. Mean increases in systolic blood pressures (12±1 mmHg), heart rates (20±2 bpm) and respiratory rates (4±1 breaths/min) were observed (pSmoking dokha has a significant acute effect on systolic blood pressure, heart rate and respiratory rate. Anti smoking campaigns must address the ill effects of this form of smoking. Results from the study warrant further research into this method of smoking which is becoming more popular.

  11. Life-Cycle Models for Survivable Systems

    National Research Council Canada - National Science Library

    Linger, Richard

    2002-01-01

    .... Current software development life-cycle models are not focused on creating survivable systems, and exhibit shortcomings when the goal is to develop systems with a high degree of assurance of survivability...

  12. Model Updating Nonlinear System Identification Toolbox Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ZONA Technology (ZONA) proposes to develop an enhanced model updating nonlinear system identification (MUNSID) methodology that utilizes flight data with...

  13. An expert system for dispersion model interpretation

    International Nuclear Information System (INIS)

    Skyllingstad, E.D.; Ramsdell, J.V.

    1988-10-01

    A prototype expert system designed to diagnose dispersion model uncertainty is described in this paper with application to a puff transport model. The system obtains qualitative information from the model user and through an expert-derived knowledge base, performs a rating of the current simulation. These results can then be used in combination with dispersion model output for deciding appropriate evacuation measures. Ultimately, the goal of this work is to develop an expert system that may be operated accurately by an individual uneducated in meteorology or dispersion modeling. 5 refs., 3 figs

  14. Semantic models for adaptive interactive systems

    CERN Document Server

    Hussein, Tim; Lukosch, Stephan; Ziegler, Jürgen; Calvary, Gaëlle

    2013-01-01

    Providing insights into methodologies for designing adaptive systems based on semantic data, and introducing semantic models that can be used for building interactive systems, this book showcases many of the applications made possible by the use of semantic models.Ontologies may enhance the functional coverage of an interactive system as well as its visualization and interaction capabilities in various ways. Semantic models can also contribute to bridging gaps; for example, between user models, context-aware interfaces, and model-driven UI generation. There is considerable potential for using

  15. Models of the venous system

    DEFF Research Database (Denmark)

    Mehlsen, J

    2000-01-01

    of the venous system require at least three elements: a resistor, a capacitor and an inductor, with the latter being of more importance in the venous than in the arterial system. Non-linearities must be considered in pressure/flow relations in the small venules, during venous collapse, or low flow conditions...

  16. Stochastic Models of Polymer Systems

    Science.gov (United States)

    2016-01-01

    published in non-peer-reviewed journals (N/A for none) The dynamics of stochastic gradient algorithms (submitted); Noisy Hegselmann- Krause Systems...algorithms for big data applications. (2) We studied stochastic dynamics of polymer systems in the mean field limit. (3) We studied noisy Hegselmann- Krause

  17. Monitoring the impact of the DRG payment system on nursing service context factors in Swiss acute care hospitals: Study protocol.

    Science.gov (United States)

    Spirig, Rebecca; Spichiger, Elisabeth; Martin, Jacqueline S; Frei, Irena Anna; Müller, Marianne; Kleinknecht, Michael

    2014-01-01

    With this study protocol, a research program is introduced. Its overall aim is to prepare the instruments and to conduct the first monitoring of nursing service context factors at three university and two cantonal hospitals in Switzerland prior to the introduction of the reimbursement system based on Diagnosis Related Groups (DRG) and to further develop a theoretical model as well as a methodology for future monitoring following the introduction of DRGs. DRG was introduced to all acute care hospitals in Switzerland in 2012. In other countries, DRG introduction led to rationing and subsequently to a reduction in nursing care. As result, nursing-sensitive patient outcomes were seriously jeopardised. Switzerland has the opportunity to learn from the consequences experienced by other countries when they introduced DRGs. Their experiences highlight that DRGs influence nursing service context factors such as complexity of nursing care or leadership, which in turn influence nursing-sensitive patient outcomes. For this reason, the monitoring of nursing service context factors needs to be an integral part of the introduction of DRGs. However, most acute care hospitals in Switzerland do not monitor nursing service context data. Nursing managers and hospital executive boards will be in need of this data in the future, in order to distribute resources effectively. A mixed methods design in the form of a sequential explanatory strategy was chosen. During the preparation phase, starting in spring 2011, instruments were selected and prepared, and the access to patient and nursing data in the hospitals was organized. Following this, online collection of quantitative data was conducted in fall 2011. In summer 2012, qualitative data was gathered using focus group interviews, which helped to describe the processes in more detail. During 2013 and 2014, an integration process is being conducted involving complementing, comparing and contrasting quantitative and qualitative findings

  18. Monitoring the impact of the DRG payment system on nursing service context factors in Swiss acute care hospitals: Study protocol

    Science.gov (United States)

    Spirig, Rebecca; Spichiger, Elisabeth; Martin, Jacqueline S.; Frei, Irena Anna; Müller, Marianne; Kleinknecht, Michael

    2014-01-01

    Aims: With this study protocol, a research program is introduced. Its overall aim is to prepare the instruments and to conduct the first monitoring of nursing service context factors at three university and two cantonal hospitals in Switzerland prior to the introduction of the reimbursement system based on Diagnosis Related Groups (DRG) and to further develop a theoretical model as well as a methodology for future monitoring following the introduction of DRGs. Background: DRG was introduced to all acute care hospitals in Switzerland in 2012. In other countries, DRG introduction led to rationing and subsequently to a reduction in nursing care. As result, nursing-sensitive patient outcomes were seriously jeopardised. Switzerland has the opportunity to learn from the consequences experienced by other countries when they introduced DRGs. Their experiences highlight that DRGs influence nursing service context factors such as complexity of nursing care or leadership, which in turn influence nursing-sensitive patient outcomes. For this reason, the monitoring of nursing service context factors needs to be an integral part of the introduction of DRGs. However, most acute care hospitals in Switzerland do not monitor nursing service context data. Nursing managers and hospital executive boards will be in need of this data in the future, in order to distribute resources effectively. Methods/Design: A mixed methods design in the form of a sequential explanatory strategy was chosen. During the preparation phase, starting in spring 2011, instruments were selected and prepared, and the access to patient and nursing data in the hospitals was organized. Following this, online collection of quantitative data was conducted in fall 2011. In summer 2012, qualitative data was gathered using focus group interviews, which helped to describe the processes in more detail. During 2013 and 2014, an integration process is being conducted involving complementing, comparing and contrasting

  19. Successful treatment using corticosteroid combined antibiotic for acute acalculous cholecystitis patients with systemic lupus erythematosus.

    Science.gov (United States)

    Liu, Wei; Chen, Weijie; He, Xiaodong; Qu, Qiang; Hong, Tao; Li, Binglu

    2017-07-01

    There is no consensus of treatments for acute acalculous cholecystitis with systemic lupus erythematosus (SLE). The study was aimed to investigate the effect of the corticosteroid for these patients.A series of patients who were diagnosed as acute acalculous cholecystitis with SLE in the period from January 2012 to December 2016 at our hospital were included. They accepted 2 different conservative treatment strategies initially: the treatment using moxifloxacin (the antibiotic group), and the treatment using corticosteroid combined moxifloxacin (the corticosteroid group). Then clinical manifestations, laboratory features, and outcomes were analyzed.The study identified 22 women Han Chinese patients with the SLE history of 2.8 ± 1.4 year. There was no significant difference in SLE history, Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000), Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SLICC/ACR), hematologic examination results, and corticosteroid dosage between 2 groups. And there was no significant difference in the symptom of acute cholecystitis, duration of the symptoms, white blood level, and the thickness of gallbladder wall between 2 groups either. However, the SLEDAI-2000 of the corticosteroid group was lower than that of the antibiotic group (7.3 ± 1.4 vs 10.7 ± 3.0, P = .03), so was the SLICC/ACR (0.1 ± 0.3 vs 0.3 ± 0.5, P = .01). Moreover, total 11 of 12 patients were successfully treated in the corticosteroid group, only 1 patient got cholecystectomy because no improvement after conservative treatment. While 4 of 10 patients were successfully treated by moxifloxacin alone, 6 patients had to accept cholecystectomy in the antibiotic group. The rate of successful conservative treatment in the corticosteroid group was higher than that of the antibiotic group (P = .02). All patients were followed up at least 6 months, there was no statistical

  20. Early Development of Right Ventricular Ischemic Lesions in a Novel Large Animal Model of Acute Right Heart Failure in Chronic Thromboembolic Pulmonary Hypertension.

    Science.gov (United States)

    Boulate, David; Arthur Ataam, Jennifer; Connolly, Andrew J; Giraldeau, Genevieve; Amsallem, Myriam; Decante, Benoit; Lamrani, Lilia; Fadel, Elie; Dorfmuller, Peter; Perros, Frederic; Haddad, Francois; Mercier, Olaf

    2017-12-01

    Our aim was to develop a model of acute right heart failure (ARHF) in the setting of pulmonary hypertension and to characterize acute right ventricular lesions that develop early after hemodynamic restoration. We used a described piglet model of chronic pulmonary hypertension (cPH) induced by pulmonary artery occlusions. We induced ARHF in animals with cPH (ARHF-cPH group, n = 9) by volume loading and iterative acute pulmonary embolism until hemodynamic compromise followed by dobutamine infusion for hemodynamic restoration before sacrifice for right ventricular tissue evaluation. The median duration of ARHF before sacrifice was 162 (135-189) minutes. Although ventriculoarterial coupling (measured with multibeat pressure-volume loops) and stroke volume decreased after iterative pulmonary embolism and improved with dobutamine, relative pulmonary to systemic pressure increased by 2-fold and remained similarly increased with dobutamine. Circulating high-sensitivity troponin I increased after hemodynamic restoration. We found an increase in right ventricular subendocardial and subepicardial focal ischemic lesions and in expression of autophagy-related protein LC3-II (Western blot) in the ARHF-cPH group compared with the cPH (n = 5) and control (n = 5) groups. We developed and phenotyped a novel large animal model of ARHF on cPH in which right ventricular ischemic lesions were observed early after hemodynamic restoration. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Switching model photovoltaic pumping system

    Science.gov (United States)

    Anis, Wagdy R.; Abdul-Sadek Nour, M.

    Photovoltaic (PV) pumping systems are widely used due to their simplicity, high reliability and low cost. A directly-coupled PV pumping system is the most reliable and least-cost PV system. The d.c. motor-pump group is not, however, working at its optimum operating point. A battery buffered PV pumping system introduces a battery between the PV array and the d.c. motor-pump group to ensure that the motor-pump group is operating at its optimum point. The size of the battery storage depends on system economics. If the battery is fully charged while solar radiation is available, the battery will discharge through the load while the PV array is disconnected. Hence, a power loss takes place. To overcome the above mentioned difficulty, a switched mode PV pumping is proposed. When solar radiation is available and the battery is fully charged, the battery is disconnected and the d.c. motor-pump group is directly coupled to the PV array. To avoid excessive operating voltage for the motor, a part of the PV array is switched off to reduce the voltage. As a result, the energy loss is significantly eliminated. Detailed analysis of the proposed system shows that the discharged water increases by about 10% when compared with a conventional battery-buffered system. The system transient performance just after the switching moment shows that the system returns to a steady state in short period. The variations in the system parameters lie within 1% of the rated values.

  2. Multiple system modelling of waste management

    International Nuclear Information System (INIS)

    Eriksson, Ola; Bisaillon, Mattias

    2011-01-01

    Highlights: → Linking of models will provide a more complete, correct and credible picture of the systems. → The linking procedure is easy to perform and also leads to activation of project partners. → The simulation procedure is a bit more complicated and calls for the ability to run both models. - Abstract: Due to increased environmental awareness, planning and performance of waste management has become more and more complex. Therefore waste management has early been subject to different types of modelling. Another field with long experience of modelling and systems perspective is energy systems. The two modelling traditions have developed side by side, but so far there are very few attempts to combine them. Waste management systems can be linked together with energy systems through incineration plants. The models for waste management can be modelled on a quite detailed level whereas surrounding systems are modelled in a more simplistic way. This is a problem, as previous studies have shown that assumptions on the surrounding system often tend to be important for the conclusions. In this paper it is shown how two models, one for the district heating system (MARTES) and another one for the waste management system (ORWARE), can be linked together. The strengths and weaknesses with model linking are discussed when compared to simplistic assumptions on effects in the energy and waste management systems. It is concluded that the linking of models will provide a more complete, correct and credible picture of the consequences of different simultaneous changes in the systems. The linking procedure is easy to perform and also leads to activation of project partners. However, the simulation procedure is a bit more complicated and calls for the ability to run both models.

  3. Modeling of power electronic systems with EMTP

    Science.gov (United States)

    Tam, Kwa-Sur; Dravid, Narayan V.

    1989-01-01

    In view of the potential impact of power electronics on power systems, there is need for a computer modeling/analysis tool to perform simulation studies on power systems with power electronic components as well as to educate engineering students about such systems. The modeling of the major power electronic components of the NASA Space Station Freedom Electric Power System is described along with ElectroMagnetic Transients Program (EMTP) and it is demonstrated that EMTP can serve as a very useful tool for teaching, design, analysis, and research in the area of power systems with power electronic components. EMTP modeling of power electronic circuits is described and simulation results are presented.

  4. System Level Modelling and Performance Estimation of Embedded Systems

    DEFF Research Database (Denmark)

    Tranberg-Hansen, Anders Sejer

    The advances seen in the semiconductor industry within the last decade have brought the possibility of integrating evermore functionality onto a single chip forming functionally highly advanced embedded systems. These integration possibilities also imply that as the design complexity increases, so...... an efficient system level design methodology, a modelling framework for performance estimation and design space exploration at the system level is required. This thesis presents a novel component based modelling framework for system level modelling and performance estimation of embedded systems. The framework...... is performed by having the framework produce detailed quantitative information about the system model under investigation. The project is part of the national Danish research project, Danish Network of Embedded Systems (DaNES), which is funded by the Danish National Advanced Technology Foundation. The project...

  5. The hairless guinea-pig as a model for treatment of acute irritation in humans

    DEFF Research Database (Denmark)

    Andersen, F; Hedegaard, K; Fullerton, A

    2006-01-01

    BACKGROUND: The effect of six skin care formulations on experimentally induced acute irritation was studied in hairless guinea-pigs (HLGP) and in human volunteers (HV). The formulations were a basic cream, a carbomer cream and four modifications of the carbomer cream, containing either 10......-propanol (NON) 20%. The irritant reactions were treated twice daily with the formulations from the time of removal of the patches. Evaluation of skin irritation and efficacy of treatments was performed daily for 4 days using clinical scoring, evaporimetry (transepidermal water loss), hydration measurement...... and colorimetry. RESULTS: The glycerol cream was the only product showing effects potentially better than no treatment in HV. CONCLUSION: The HLGP was too sensitive an animal model as a predictor for effect in humans. There was no difference in efficacy of the formulations against the two different irritants...

  6. Examination of Gelatinase Isoforms in Rodent Models of Acute Neurodegenerative Diseases Using Two-Dimensional Zymography.

    Science.gov (United States)

    Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Qu, Zhe; Cui, Jiankun; Gu, Zezong

    2017-01-01

    Pathological activation of gelatinases (matrix metalloproteinase-2 and -9; MMP-2/-9) has been shown to cause a number of detrimental outcomes in neurodegenerative diseases. In gel gelatin zymography is a highly sensitive methodology commonly used in revealing levels of gelatinase activity and in separating the proform and active form of gelatinases, based on their different molecular weights. However, this methodology is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity can be regulated at transcriptional and/or post-translational levels under in vivo conditions resulting in alternation of their isoelectric focusing (IEF) points. In this chapter, we describe an advanced methodology, termed two-dimensional zymography, combining IEF with zymographic electrophoresis under non-reducing conditions to achieve significant improvement in separation of the gelatinase isoforms in both cell-based and in vivo models for acute brain injuries and neuroinflammation.

  7. Effect of decellularized tissue powders on a rat model of acute myocardial infarction.

    Science.gov (United States)

    Tabuchi, Masaki; Negishi, Jun; Yamashita, Akitatsu; Higami, Tetsuya; Kishida, Akio; Funamoto, Seiichi

    2015-11-01

    Many research groups are currently investigating new treatment modalities for myocardial infarction. Numerous aspects need to be considered for the clinical application of these therapies, such as low cell integration and engraftment rates of cell injection techniques. Decellularized tissues are considered good materials for promoting regeneration of traumatic tissues. The properties of the decellularized tissues are sustained after processing to powder form. In this study, we examined the use of decellularized tissue powder in a rat model of acute myocardial infarction. The decellularized tissue powders, especially liver powder, promoted cell integration and neovascularization both in vitro and in vivo. Decellularized liver powder induced neovascularization in the infarct area, resulting in the suppression of myocardial necrosis. The results of this study suggest that decellularized liver powder has good potential for application as a blood supply material for the treatment of myocardial infarction. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Network model of security system

    Directory of Open Access Journals (Sweden)

    Adamczyk Piotr

    2016-01-01

    Full Text Available The article presents the concept of building a network security model and its application in the process of risk analysis. It indicates the possibility of a new definition of the role of the network models in the safety analysis. Special attention was paid to the development of the use of an algorithm describing the process of identifying the assets, vulnerability and threats in a given context. The aim of the article is to present how this algorithm reduced the complexity of the problem by eliminating from the base model these components that have no links with others component and as a result and it was possible to build a real network model corresponding to reality.

  9. Sesamol treatment reduces plasma cholesterol and triacylglycerol levels in mouse models of acute and chronic hyperlipidemia.

    Science.gov (United States)

    Kumar, Nitesh; Mudgal, Jayesh; Parihar, Vipan K; Nayak, Pawan G; Kutty, N Gopalan; Rao, C Mallikarjuna

    2013-06-01

    The active constituents of Sesamum indicum, sesamin and sesamolin, have already been explored for hypolipidemic action. In this study we have explored the anti-dyslipidemic activity of another active component and metabolite of sesamolin (sesamol), by using acute models of hyperlipidemia viz., a fat tolerance test, a tyloxapol-induced hyperlipidemia model and a chronic model of hyperlipidemia viz., a high-fat diet-induced hyperlipidemia model in Swiss albino mice. Sesamol (100 and 200 mg/kg) significantly (P cholesterol and triacylglycerol compared with the tyloxapol group at 12 and 24 h, which indicates its probable effect on cholesterol synthesis. Chronic hyperlipidemia in mice was produced by feeding a high-diet, a mixture of cholesterol (2 % w/w), cholic acid (1 % w/w) and coconut oil 30 % (v/w) with standard powdered standard animal chow (up to 100 g). Niacin (100 mg/kg) and sesamol (100 mg/kg) significantly (P cholesterol and triacylglycerol were significantly (P cholesterol as well.

  10. Characterization of rat model of acute anterior uveitis using optical coherence tomography angiography

    Science.gov (United States)

    Choi, Woo June; Pepple, Kathryn L.; Zhi, Zhongwei; Wang, Ruikang K.

    2015-03-01

    Uveitis, or ocular inflammation, is a cause of severe visual impairment. Rodent models of uveitis are powerful tools used to investigate the pathological mechanisms of ocular inflammation and to study the efficacy of new therapies prior to human testing. In this paper, we report the utility of spectral-domain optical coherence tomography (SD-OCT) angiography in characterizing the inflammatory changes induced in the anterior segment of a rat model of uveitis. Acute anterior uveitis (AAU) was induced in two rats by intravitreal injection of a killed mycobacterial extract. One of them received a concurrent periocular injection of steroids to model a treatment effect. OCT imaging was performed prior to inflammation induction on day 0 (baseline), and 2 days post-injection (peak inflammation). Baseline and inflamed images were compared. OCT angiography identified swelling of the cornea, inflammatory cells in the anterior and posterior chambers, a fibrinous papillary membrane, and dilation of iris vessels in the inflamed eyes when compared to baseline images. Steroid treatment was shown to prevent the changes associated with inflammation. This is a novel application of anterior OCT imaging in animal models of uveitis, and provides a high resolution, in vivo assay for detecting and quantifying ocular inflammation and the response to new therapies.

  11. Intravesical Dimethyl Sulfoxide Inhibits Acute and Chronic Bladder Inflammation in Transgenic Experimental Autoimmune Cystitis Models

    Directory of Open Access Journals (Sweden)

    Ronald Kim

    2011-01-01

    Full Text Available New animal models are greatly needed in interstitial cystitis/painful bladder syndrome (IC/PBS research. We recently developed a novel transgenic cystitis model (URO-OVA mice that mimics certain key aspects of IC/PBS pathophysiology. This paper aimed to determine whether URO-OVA cystitis model was responsive to intravesical dimethyl sulfoxide (DMSO and if so identify the mechanisms of DMSO action. URO-OVA mice developed acute cystitis upon adoptive transfer of OVA-specific OT-I splenocytes. Compared to PBS-treated bladders, the bladders treated with 50% DMSO exhibited markedly reduced bladder histopathology and expression of various inflammatory factor mRNAs. Intravesical DMSO treatment also effectively inhibited bladder inflammation in a spontaneous chronic cystitis model (URO-OVA/OT-I mice. Studies further revealed that DMSO could impair effector T cells in a dose-dependent manner in vitro. Taken together, our results suggest that intravesical DMSO improves the bladder histopathology of IC/PBS patients because of its ability to interfere with multiple inflammatory and bladder cell types.

  12. An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Zhisheng Her

    2017-10-01

    Full Text Available Abstract Background Xenotransplantation of patient-derived AML (acute myeloid leukemia cells in NOD-scid Il2rγ null (NSG mice is the method of choice for evaluating this human hematologic malignancy. However, existing models constructed using intravenous injection in adult or newborn NSG mice have inferior engraftment efficiency, poor peripheral blood engraftment, or are difficult to construct. Methods Here, we describe an improved AML xenograft model where primary human AML cells were injected into NSG newborn pups intrahepatically. Results Introduction of primary cells from AML patients resulted in high levels of engraftment in peripheral blood, spleen, and bone marrow (BM of recipient mice. The phenotype of engrafted AML cells remained unaltered during serial transplantation. The mice developed features that are consistent with human AML including spleen enlargement and infiltration of AML cells into multiple organs. Importantly, we demonstrated that although leukemic stem cell activity is enriched and mediated by CD34+CD117+ subpopulation, CD34+CD117− subpopulation can acquire CD34+CD117+ phenotype through de-differentiation. Lastly, we evaluated the therapeutic potential of Sorafenib and Regorafenib in this AML model and found that periphery and spleen AML cells are sensitive to these treatments, whereas BM provides a protective environment to AML. Conclusions Collectively, our improved model is robust, easy-to-construct, and reliable for pre-clinical AML studies.

  13. Mouse models of NPM1-mutated acute myeloid leukemia: biological and clinical implications.

    Science.gov (United States)

    Sportoletti, P; Varasano, E; Rossi, R; Mupo, A; Tiacci, E; Vassiliou, G; Martelli, M P; Falini, B

    2015-02-01

    Acute myeloid leukemia (AML) carrying nucleophosmin (NPM1) mutations displays distinct biological and clinical features that led to its inclusion as a provisional disease entity in the 2008 World Health Organization (WHO) classification of myeloid neoplasms. Studies of the molecular mechanisms underlying the pathogenesis of NPM1-mutated AML have benefited greatly from several mouse models of this leukemia developed over the past few years. Immunocompromised mice xenografted with NPM1-mutated AML served as the first valuable tool for defining the biology of the disease in vivo. Subsequently, genetically engineered mouse models of the NPM1 mutation, including transgenic and knock-in alleles, allowed the generation of mice with a constant genotype and a reproducible phenotype. These models have been critical for investigating the nature of the molecular effects of these mutations, defining the function of leukemic stem cells in NPM1-mutated AML, identifying chemoresistant preleukemic hemopoietic stem cells and unraveling the key molecular events that cooperate with NPM1 mutations to induce AML in vivo. Moreover, they can serve as a platform for the discovery and validation of new antileukemic drugs in vivo. Advances derived from the analysis of these mouse models promise to greatly accelerate the development of new molecularly targeted therapies for patients with NPM1-mutated AML.

  14. Using adaptive model predictive control to customize maintenance therapy chemotherapeutic dosing for childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Noble, Sarah L; Sherer, Eric; Hannemann, Robert E; Ramkrishna, Doraiswami; Vik, Terry; Rundell, Ann E

    2010-06-07

    Acute lymphoblastic leukemia (ALL) is a common childhood cancer in which nearly one-quarter of patients experience a disease relapse. However, it has been shown that individualizing therapy for childhood ALL patients by adjusting doses based on the blood concentration of active drug metabolite could significantly improve treatment outcome. An adaptive model predictive control (MPC) strategy is presented in which maintenance therapy for childhood ALL is personalized using routine patient measurements of red blood cell mean corpuscular volume as a surrogate for the active drug metabolite concentration. A clinically relevant mathematical model is developed and used to describe the patient response to the chemotherapeutic drug 6-mercaptopurine, with some model parameters being patient-specific. During the course of treatment, the patient-specific parameters are adaptively identified using recurrent complete blood count measurements, which sufficiently constrain the patient parameter uncertainty to support customized adjustments of the drug dose. While this work represents only a first step toward a quantitative tool for clinical use, the simulated treatment results indicate that the proposed mathematical model and adaptive MPC approach could serve as valuable resources to the oncologist toward creating a personalized treatment strategy that is both safe and effective. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  15. Modeling Adaptive Behavior for Systems Design

    DEFF Research Database (Denmark)

    Rasmussen, Jens

    1994-01-01

    Field studies in modern work systems and analysis of recent major accidents have pointed to a need for better models of the adaptive behavior of individuals and organizations operating in a dynamic and highly competitive environment. The paper presents a discussion of some key characteristics...... of the predictive models required for the design of work supports systems, that is,information systems serving as the human-work interface. Three basic issues are in focus: 1.) Some fundamental problems in analysis and modeling modern dynamic work systems caused by the adaptive nature of human behavior; 2.......) The basic difference between the models of system functions used in engineering and design and those evolving from basic research within the various academic disciplines and finally 3.) The models and methods required for closed-loop, feedback system design....

  16. Model-based version management system framework

    International Nuclear Information System (INIS)

    Mehmood, W.

    2016-01-01

    In this paper we present a model-based version management system. Version Management System (VMS) a branch of software configuration management (SCM) aims to provide a controlling mechanism for evolution of software artifacts created during software development process. Controlling the evolution requires many activities to perform, such as, construction and creation of versions, identification of differences between versions, conflict detection and merging. Traditional VMS systems are file-based and consider software systems as a set of text files. File based VMS systems are not adequate for performing software configuration management activities such as, version control on software artifacts produced in earlier phases of the software life cycle. New challenges of model differencing, merge, and evolution control arise while using models as central artifact. The goal of this work is to present a generic framework model-based VMS which can be used to overcome the problem of tradition file-based VMS systems and provide model versioning services. (author)

  17. A Model for Predicting Persistent Elevation of Factor VIII among Patients with Acute Ischemic Stroke

    Science.gov (United States)

    Samai, Alyana A.; Boehme, Amelia K.; Shaban, Amir; George, Alexander J.; Dowell, Lauren; Monlezun, Dominique J.; Leissinger, Cindy; Schluter, Laurie; El Khoury, Ramy; Martin-Schild, Sheryl

    2016-01-01

    Background and Purpose Elevated levels of coagulation factor VIII (FVIII) may persist independent of the acute-phase response; however, this relationship has not been investigated relative to acute ischemic stroke (AIS). We examined the frequency and predictors of persistently elevated FVIII in AIS patients. Methods AIS patients admitted between July 2008 and May 2014 with elevated baseline FVIII levels and repeat FVIII levels drawn for more than 7 days postdischarge were included. The patients were dichotomized by repeat FVIII level for univariate analysis at 150% and 200% activity thresholds. An adjusted model was developed to predict the likelihood of persistently elevated FVIII levels. Results Among 1616 AIS cases, 98 patients with elevated baseline FVIII had repeat FVIII levels. Persistent FVIII elevation was found in more than 75% of patients. At the 150% threshold, the prediction score ranged from 0 to 7 and included black race, female sex, prior stroke, hyperlipidemia, smoking, baseline FVIII > 200%, and baseline von Willebrand factor (vWF) level greater than 200%. At the 200% threshold, the prediction score ranged from 0–5 and included female sex, prior stroke, diabetes mellitus, baseline FVIII level greater 200%, and baseline vWF level greater than 200%. For each 1-point increase in score, the odds of persistent FVIII at both the 150% threshold (odds ratio [OR] = 10.4, 95% confidence interval [CI] 1.63–66.9, P = .0134) and 200% threshold (OR = 10.2, 95% CI 1.82–57.5, P = .0083) increased 10 times. Conclusion Because an elevated FVIII level confers increased stroke risk, our model for anticipating a persistently elevated FVIII level may identify patients at high risk for recurrent stroke. FVIII may be a target for secondary stroke prevention. PMID:26777556

  18. Characterisation of leukocytes in a human skin blister model of acute inflammation and resolution.

    Directory of Open Access Journals (Sweden)

    William Jenner

    Full Text Available There is an increasing need to understand the leukocytes and soluble mediators that drive acute inflammation and bring about its resolution in humans. We therefore carried out an extensive characterisation of the cantharidin skin blister model in healthy male volunteers. A novel fluorescence staining protocol was designed and implemented, which facilitated the identification of cell populations by flow cytometry. We observed that at the onset phase, 24 h after blister formation, the predominant cells were CD16hi/CD66b+ PMNs followed by HLA-DR+/CD14+ monocytes/macrophages, CD11c+ and CD141+ dendritic cells as well as Siglec-8+ eosinophils. CD3+ T cells, CD19+ B cells and CD56+ NK cells were also present, but in comparatively fewer numbers. During resolution, 72 h following blister induction, numbers of PMNs declined whilst the numbers of monocyte/macrophages remain unchanged, though they upregulated expression of CD16 and CD163. In contrast, the overall numbers of dendritic cells and Siglec-8+ eosinophils increased. Post hoc analysis of these data revealed that of the inflammatory cytokines measured, TNF-α but not IL-1β or IL-8 correlated with increased PMN numbers at the onset. Volunteers with the greatest PMN infiltration at onset displayed the fastest clearance rates for these cells at resolution. Collectively, these data provide insight into the cells that occupy acute resolving blister in humans, the soluble mediators that may control their influx as well as the phenotype of mononuclear phagocytes that predominate the resolution phase. Further use of this model will improve our understanding of the evolution and resolution of inflammation in humans, how defects in these over-lapping pathways may contribute to the variability in disease longevity/chronicity, and lends itself to the screen of putative anti-inflammatory or pro-resolution therapies.

  19. Characterisation of leukocytes in a human skin blister model of acute inflammation and resolution.

    Science.gov (United States)

    Jenner, William; Motwani, Madhur; Veighey, Kristin; Newson, Justine; Audzevich, Tatsiana; Nicolaou, Anna; Murphy, Sharon; Macallister, Raymond; Gilroy, Derek W

    2014-01-01

    There is an increasing need to understand the leukocytes and soluble mediators that drive acute inflammation and bring about its resolution in humans. We therefore carried out an extensive characterisation of the cantharidin skin blister model in healthy male volunteers. A novel fluorescence staining protocol was designed and implemented, which facilitated the identification of cell populations by flow cytometry. We observed that at the onset phase, 24 h after blister formation, the predominant cells were CD16hi/CD66b+ PMNs followed by HLA-DR+/CD14+ monocytes/macrophages, CD11c+ and CD141+ dendritic cells as well as Siglec-8+ eosinophils. CD3+ T cells, CD19+ B cells and CD56+ NK cells were also present, but in comparatively fewer numbers. During resolution, 72 h following blister induction, numbers of PMNs declined whilst the numbers of monocyte/macrophages remain unchanged, though they upregulated expression of CD16 and CD163. In contrast, the overall numbers of dendritic cells and Siglec-8+ eosinophils increased. Post hoc analysis of these data revealed that of the inflammatory cytokines measured, TNF-α but not IL-1β or IL-8 correlated with increased PMN numbers at the onset. Volunteers with the greatest PMN infiltration at onset displayed the fastest clearance rates for these cells at resolution. Collectively, these data provide insight into the cells that occupy acute resolving blister in humans, the soluble mediators that may control their influx as well as the phenotype of mononuclear phagocytes that predominate the resolution phase. Further use of this model will improve our understanding of the evolution and resolution of inflammation in humans, how defects in these over-lapping pathways may contribute to the variability in disease longevity/chronicity, and lends itself to the screen of putative anti-inflammatory or pro-resolution therapies.

  20. Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury.

    Science.gov (United States)

    Boyce, M K; Trumble, T N; Carlson, C S; Groschen, D M; Merritt, K A; Brown, M P

    2013-05-01

    Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) were graded. At week 16, synovium and cartilage biopsies were taken arthroscopically from OC injured and sham joints for histologic evaluation and the OC fragment was removed. OC fragments were successfully created and horses were free of clinical lameness after fragment removal. Forelimb gait asymmetry was observed at week 2 (P = 0.0012), while joint circumference (P < 0.0001) and effusion scores (P < 0.0001) were increased in injured limbs compared to baseline from weeks 2 to 16. Positive flexion response of injured limbs was noted at multiple time points. Capsular enthesophytes were seen radiographically in injured limbs. Articular cartilage damage was demonstrated arthroscopically as mild wear-lines and histologically as superficial zone chondrocyte death accompanied by mild proliferation. Synovial hyperemia and fibrosis were present at the site of OC injury. Acute OC injury to the MCP joint resulted in clinical, imaging, and histologic changes in cartilage and synovium characteristic of early PTOA. This model will be useful for defining biomarkers of early osteoarthritis and for monitoring response to therapy and surgery. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  1. A model of acute renal allograft rejection in outbred Yorkshire piglets.

    Science.gov (United States)

    Lassiter, Randi; Wang, Youli; Fang, Xuexiu; Winn, Matt; Ghaffari, Arina; Ho, Chak-Sum; Helman, Sandra; Jajosky, Ryan; Kleven, Daniel; Stanley Nahman, N; Merchen, Todd D

    2017-06-01

    Pigs represent a desirable animal model for the study of rejection in kidney transplantation with inbred Yucatan miniature swine (YMS) the most commonly studied strain due to well defined swine leukocyte antigen (SLA) genotypes. However, limitations to YMS may include cost and availability. Outbred Yorkshire pigs are widely available and significantly cheaper than YMS. Recent advances in SLA genotyping have allowed its application to outbred strains. On this basis, we theorized that Yorkshire pigs would be a viable alternative to YMS for the study of rejection in kidney transplantation. To address this question, we performed auto (Auto) and allotransplants (Allo) in 24 Yorkshire pigs, and assessed SLA genotypes and acute rejection after 72h. At sacrifice, and when compared to autotransplants, allotransplants had significant elevations in serum creatinine (8.4±1.3 vs 2.8±2.0mg/dL for Allo vs autotransplants, respectively) and BUN (61±9 vs 19.2±15mg/dL for Allo vs autotransplants, respectively). Warm ischemia times between the two groups did not differ (24±2.3 vs 26.4±1.4min for Auto vs Allo, respectively). There were 16 distinct SLA haplotypes identified from pigs undergoing allotransplantion, no matched donor-recipient pairs, and all allografts demonstrated rejection. Type IIA cellular rejection (Banff) was the most common. One allograft demonstrated hyperacute rejection due a blood group incompatibility. Histologically, the expression of regulatory Tcells and dendritic cells was increased in allografts. These data suggest that Yorkshire pigs may be a useful model for the study of acute rejection in experimental kidney transplantation. Copyright © 2017. Published by Elsevier B.V.

  2. Risk model for suspected acute coronary syndrome is of limited value in an emergency department.

    Science.gov (United States)

    Mogensen, Christian Backer; Christiansen, Maja; Jørgensen, Jess Bjerre; Staehr, Peter Bisgaard

    2015-10-01

    Among patients with acute chest pain, acute coronary syndrome (ACS) is seen only in a minority of the patients, which raises the question, whether it is possible to separate a group with a high risk of ACS for admission to a cardiac care unit (CCU) from those with a low risk who would be treated at an emergency department (ED). The aim of this study was to describe a risk stratification model for a Danish context. This was a historic prospective cohort study of patients with suspicion of ACS. The patient was defined as a low-risk patient and admitted to the ED if: 1) electrocardiogram (ECG) was normal, 2) the patient did not have persisting chest pain and 3) there was no history of ischaemic heart disease, heart failure or cardioverter defibrillator. Otherwise, patients were admitted to the CCU. The primary outcome was whether the ACS diagnosis was confirmed or rejected. We included a total of 488 patients with suspicion of ACS, 50% of whom were low-risk patients. 17% had a verified ACS; 10% of those in the low-risk group and 24% of those in the high-risk group (p = 0.0001). Among the verified ACS cases, 71% went primarily to the CCU. The odds ratio for an ACS if assigned to the high-risk group was 3.0. Allocation to the high-risk group, male gender and age above 60 years was associated with a higher risk of ACS. For patients fulfilling the high-risk definition, sensitivity was 71%, specificity 55%, negative predictive value 90% and positive predictive value 24% for an ACS. The model for stratification separated patients into two equal groups, allocated 71% of all ACS directly to the CCU and could not be improved by any of the additional factors examined. Further development of referral strategies for chest pain patients is required. none. not relevant.

  3. Carisbamate acutely suppresses spasms in a rat model of symptomatic infantile spasms.

    Science.gov (United States)

    Ono, Tomonori; Moshé, Solomon L; Galanopoulou, Aristea S

    2011-09-01

    Infantile spasms are the signature seizures of West syndrome. The conventional treatments for infantile spasms, such as adrenocorticotropic hormone (ACTH) and vigabatrin, are not always effective, especially in symptomatic infantile spasms (SIS). We tested the efficacy of carisbamate, a novel neurotherapeutic drug, to suppress spasms in the multiple-hit rat model of SIS, and compared it with phenytoin to determine if its effect is via sodium-channel blockade. Sprague-Dawley rats received right intracerebral infusions of doxorubicin and lipopolysaccharide at postnatal day 3 (PN3) and intraperitoneal p-chlorophenylalanine at PN5. A single intraperitoneal injection of carisbamate was administered at PN4, after the onset of spasms, at the following doses: 10 mg/kg (CRS-10), 30 mg/kg (CRS-30), and 60 mg/kg (CRS-60), and was compared to vehicle-injected group (VEH). Video-monitoring of PN6-7 CRS-60 or VEH-injected pups was also done. Carisbamate acutely reduced both behavioral spasms (CRS-30 and CRS-60 groups only) and electroclinical spasms during the first 2-3 postinjection hours, without detectable toxicity or mortality. In contrast, phenytoin (20 or 50 mg/kg) failed to suppress spasms. Our findings provide preclinical evidence that carisbamate displays acute anticonvulsive effect on spasms through a sodium channel-independent mechanism. Because spasms in the multiple-hit rat model are refractory to ACTH and transiently sensitive to vigabatrin, carisbamate may constitute a candidate new therapy for SIS, including the ACTH-refractory spasms. Further confirmation with clinical studies is needed. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  4. Very Large System Dynamics Models - Lessons Learned

    Energy Technology Data Exchange (ETDEWEB)

    Jacob J. Jacobson; Leonard Malczynski

    2008-10-01

    This paper provides lessons learned from developing several large system dynamics (SD) models. System dynamics modeling practice emphasize the need to keep models small so that they are manageable and understandable. This practice is generally reasonable and prudent; however, there are times that large SD models are necessary. This paper outlines two large SD projects that were done at two Department of Energy National Laboratories, the Idaho National Laboratory and Sandia National Laboratories. This paper summarizes the models and then discusses some of the valuable lessons learned during these two modeling efforts.

  5. Test-driven modeling of embedded systems

    DEFF Research Database (Denmark)

    Munck, Allan; Madsen, Jan

    2015-01-01

    To benefit maximally from model-based systems engineering (MBSE) trustworthy high quality models are required. From the software disciplines it is known that test-driven development (TDD) can significantly increase the quality of the products. Using a test-driven approach with MBSE may have...... a similar positive effect on the quality of the system models and the resulting products and may therefore be desirable. To define a test-driven model-based systems engineering (TD-MBSE) approach, we must define this approach for numerous sub disciplines such as modeling of requirements, use cases......, scenarios, behavior, architecture, etc. In this paper we present a method that utilizes the formalism of timed automatons with formal and statistical model checking techniques to apply TD-MBSE to the modeling of system architecture and behavior. The results obtained from applying it to an industrial case...

  6. Precipitation-runoff modeling system; user's manual

    Science.gov (United States)

    Leavesley, G.H.; Lichty, R.W.; Troutman, B.M.; Saindon, L.G.

    1983-01-01

    The concepts, structure, theoretical development, and data requirements of the precipitation-runoff modeling system (PRMS) are described. The precipitation-runoff modeling system is a modular-design, deterministic, distributed-parameter modeling system developed to evaluate the impacts of various combinations of precipitation, climate, and land use on streamflow, sediment yields, and general basin hydrology. Basin response to normal and extreme rainfall and snowmelt can be simulated to evaluate changes in water balance relationships, flow regimes, flood peaks and volumes, soil-water relationships, sediment yields, and groundwater recharge. Parameter-optimization and sensitivity analysis capabilites are provided to fit selected model parameters and evaluate their individual and joint effects on model output. The modular design provides a flexible framework for continued model system enhancement and hydrologic modeling research and development. (Author 's abstract)

  7. An Empirical Model for Energy Storage Systems

    Energy Technology Data Exchange (ETDEWEB)

    Rosewater, David Martin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Scott, Paul [TransPower, Poway, CA (United States)

    2016-03-17

    Improved models of energy storage systems are needed to enable the electric grid’s adaptation to increasing penetration of renewables. This paper develops a generic empirical model of energy storage system performance agnostic of type, chemistry, design or scale. Parameters for this model are calculated using test procedures adapted from the US DOE Protocol for Uniformly Measuring and Expressing the Performance of Energy Storage. We then assess the accuracy of this model for predicting the performance of the TransPower GridSaver – a 1 MW rated lithium-ion battery system that underwent laboratory experimentation and analysis. The developed model predicts a range of energy storage system performance based on the uncertainty of estimated model parameters. Finally, this model can be used to better understand the integration and coordination of energy storage on the electric grid.

  8. Rapid pulmonary expression of acute-phase reactants after local lipopolysaccharide exposure in mice is followed by an interleukin-6 mediated systemic acute-phase response.

    Science.gov (United States)

    Vernooy, Juanita H J; Reynaert, Niki; Wolfs, Tim G A M; Cloots, Roy H E; Haegens, Astrid; de Vries, Bart; Dentener, Mieke A; Buurman, Wim A; Wouters, Emiel M

    2005-01-01

    This study investigated local and systemic innate immune responses in lipopolysaccharide (LPS)-induced lung inflammation in mice. Intratracheal LPS exposure resulted in increased pulmonary mRNA expression for acute-phase reactants (APRs) alpha(1)-antitrypsin (alpha(1)-AT), alpha(1)-acid glycoprotein (AGP), and LPS-binding protein (LBP) from 4 hours post exposure. Although pulmonary serum amyloid P component (SAP) mRNA was not increased, systemic levels of SAP, AGP, and LBP were elevated from 24 hours post exposure. Systemic APRs increase was associated with hepatic mRNA expression. As in vivo neutralization of interleukin (IL)-6, but not tumor necrosis factor (TNF)-alpha, fully ablated hepatic APR mRNA expression, IL-6 may act as signaling molecule between lung and liver. In conclusion, pulmonary LPS exposure induced rapid APR expression in lung, which precedes IL-6-mediated systemic elevation of APRs associated with hepatic APRs expression.

  9. Neuroprotection neurotrophic cerebroprotector Сerebroсurin in terms of modeling acute stroke

    Directory of Open Access Journals (Sweden)

    S. A. Morguntsova

    2014-10-01

    Full Text Available Aim. The high frequency of cerebral blood flow causes the relevance of further study pathogenic mechanisms of cerebral ischemia and the search and study of highly cerebroprotector. In order to obtain comparative evaluation of the safety and neuroprotective effect of the drug Сerebroсurin the dependence of the effect on the ways of administration. Methods and results. Results of the study revealed the advantage of intrathecal route of administration before the intraperitoneal. The effect is manifested in increased survival of animals, decrease the manifestations of mitochondrial dysfunction, oxidative stress inhibition, activation of the antioxidant system in rat brain. Conclusion. The obtained results show the effectiveness of the intrathecal route of administration Сerebroсurin in the context of an acute cerebrovascular accident.

  10. Intervention of Peiyuan Huayu Decoction on the neuron damage in model rats with acute subdural hematoma

    Directory of Open Access Journals (Sweden)

    Xiao-Xuan Fan

    2017-07-01

    Full Text Available Objective: To study the intervention effect of Peiyuan Huayu Decoction on the neuron damage in model rats with acute subdural hematoma (ASDH. Methods: 160 SD rats were randomly divided into four groups, and the ASDH model rats were made by stereotactic autoblood injection, and sham operation group received craniotomy without blood injection. Sham operation group and model group were normally bred after model establishment, and 6 h after model establishment, the treatment group received intragastric administration of Peiyuan Huayu Decoction, and control group received intragastric administration of Piracetam Tablets, 1 time a day. On the 1d, 3d, 5d and 7d after model establishment, the general conditions of rats (activity, food intake and mental state were observed, blood was collected via auricula dextra, ELISA method was used to determine peripheral plasma NSE and S100毬 protein contents, routine HE staining was conducted after perfusion fixation, the neurons in blood injection side of brain tissue were counted, and the neuron damage was observed. Results: 26 rats were dead in the experiment. The general conditions of sham operation group were significantly better than those of other groups, treatment group was significantly better than model group and control group on the 5d group (P0.05; neuron count of sham operation group was basically stable, treatment group was not different from model group and control group on the 1d (P>0.05, treatment group was better than model group (P0.05 on the 3d, and treatment group was better than model group and control group on the 5d and 7d (P0.05, S100毬 protein and NSE contents decreased significantly on the 3d, and treatment group was significantly different from model group and control group (P<0.05, S100毬 protein and NSE contents increased on the 5d and 7d, the increase in treatment group was slower than that in model group and control group, and there was significant difference (P<0.05. Conclusion

  11. Brief History of Agricultural Systems Modeling

    Science.gov (United States)

    Jones, James W.; Antle, John M.; Basso, Bruno O.; Boote, Kenneth J.; Conant, Richard T.; Foster, Ian; Godfray, H. Charles J.; Herrrero, Mario; Howitt, Richard E.; Janssen, Sandor; hide

    2016-01-01

    Agricultural systems science generates knowledge that allows researchers to consider complex problems or take informed agricultural decisions. The rich history of this science exemplifies the diversity of systems and scales over which they operate and have been studied. Modeling, an essential tool in agricultural systems science, has been accomplished by scientists from a wide range of disciplines, who have contributed concepts and tools over more than six decades. As agricultural scientists now consider the next generation models, data, and knowledge products needed to meet the increasingly complex systems problems faced by society, it is important to take stock of this history and its lessons to ensure that we avoid re-invention and strive to consider all dimensions of associated challenges. To this end, we summarize here the history of agricultural systems modeling and identify lessons learned that can help guide the design and development of next generation of agricultural system tools and methods. A number of past events combined with overall technological progress in other fields have strongly contributed to the evolution of agricultural system modeling, including development of process-based bio-physical models of crops and livestock, statistical models based on historical observations, and economic optimization and simulation models at household and regional to global scales. Characteristics of agricultural systems models have varied widely depending on the systems involved, their scales, and the wide range of purposes that motivated their development and use by researchers in different disciplines. Recent trends in broader collaboration across institutions, across disciplines, and between the public and private sectors suggest that the stage is set for the major advances in agricultural systems science that are needed for the next generation of models, databases, knowledge products and decision support systems. The lessons from history should be considered

  12. Formal Modeling and Analysis of Timed Systems

    DEFF Research Database (Denmark)

    Larsen, Kim Guldstrand; Niebert, Peter

    This book constitutes the thoroughly refereed post-proceedings of the First International Workshop on Formal Modeling and Analysis of Timed Systems, FORMATS 2003, held in Marseille, France in September 2003. The 19 revised full papers presented together with an invited paper and the abstracts...... of two invited talks were carefully selected from 36 submissions during two rounds of reviewing and improvement. All current aspects of formal method for modeling and analyzing timed systems are addressed; among the timed systems dealt with are timed automata, timed Petri nets, max-plus algebras, real......-time systems, discrete time systems, timed languages, and real-time operating systems....

  13. Improving patient outcomes from acute cardiovascular events through regionalized systems of care.

    Science.gov (United States)

    Edwards, J Matthew; Carr, Brendan G

    2010-11-01

    ST-segment elevation myocardial infarction (STEMI), cardiac arrest, and ischemic stroke are a diverse group of cardiovascular illnesses linked by the necessity for timely intervention in order to maximize patient outcomes. Despite the known efficacies of therapies, such as emergent percutaneous coronary intervention (PCI), rapid administration of tissue plasminogen activator, and induction of therapeutic hypothermia after cardiac arrest, translating these discoveries into standard practice nationwide has proven difficult to achieve. Significant regional variations in practice are commonplace, and facilities with higher patient volumes of STEMI, cardiac arrest, and ischemic stroke consistently have better outcomes compared with lower-volume facilities. Such disparities in emergency care led the Institute of Medicine in 2006 to describe the existing emergency care system as "at the breaking point," and to call for "coordinated, regionalized, and accountable" systems of care. An effective and equitable regionalized emergency care system would resemble the existing US trauma system in some respects, with transparent and standard triage guidelines, cooperation between local and regional emergency medical service systems, and an integrated network of referring and receiving facilities. Emerging technologies, such as telemedicine, will likely play a significant role. Regionalized referral systems, such as designated PCI centers and designated stroke centers, are in existence, but have largely been reactive and local, and no mechanism is in place to ensure equitable distribution of such facilities across all geographic regions. As scientific advances in the treatment of these conditions continue to evolve, so too must the system of care that provides these therapies. Evidence suggests that regionalized systems of care for acute cardiovascular events may increase compliance with existing life-saving guidelines and improve patient outcomes.

  14. Systemic inflammation in acute intermittent porphyria: a case-control study.

    Science.gov (United States)

    Storjord, E; Dahl, J A; Landsem, A; Fure, H; Ludviksen, J K; Goldbeck-Wood, S; Karlsen, B O; Berg, K S; Mollnes, T E; W Nielsen, E; Brekke, O-L

    2017-03-01

    This study aimed to examine whether acute intermittent porphyria (AIP) is associated with systemic inflammation and whether the inflammation correlates with disease activity. A case-control study with 50 AIP cases and age-, sex- and place of residence-matched controls was performed. Plasma cytokines, insulin and C-peptide were analysed after an overnight fast using multiplex assay. Long pentraxin-3 (PTX3) and complement activation products (C3bc and TCC) were analysed using enzyme-linked immunosorbent assay (ELISA). Urine porphobilinogen ratio (U-PBG, µmol/mmol creatinine), haematological and biochemical tests were performed using routine methods. Questionnaires were used to register AIP symptoms, medication and other diseases. All 27 cytokines, chemokines and growth factors investigated were increased significantly in symptomatic AIP cases compared with controls (P inflammation. Decreased C-peptide levels in symptomatic AIP cases indicate that reduced insulin release is associated with enhanced disease activity and reduced kidney function. © 2016 British Society for Immunology.

  15. Grey Box Modelling of Hydrological Systems

    DEFF Research Database (Denmark)

    Thordarson, Fannar Ørn

    The main topic of the thesis is grey box modelling of hydrologic systems, as well as formulation and assessment of their embedded uncertainties. Grey box model is a combination of a white box model, a physically-based model that is traditionally formulated using deterministic ordinary differential...... the lack of fit in state space formulation, and further support decisions for a model expansion. By using stochastic differential equations to formulate the dynamics of the hydrological system, either the complexity of the model can be increased by including the necessary hydrological processes...... in the model, or formulation of process noise can be considered so that it meets the physical limits of the hydrological system and give an adequate description of the embedded uncertainty in model structure. The thesis consists of two parts: a summary report and a part which contains six scientific papers...

  16. The Guided System Development Framework: Modeling and Verifying Communication Systems

    DEFF Research Database (Denmark)

    Carvalho Quaresma, Jose Nuno; Probst, Christian W.; Nielson, Flemming

    2014-01-01

    . The Guided System Development framework contributes to more secure communication systems by aiding the development of such systems. The framework features a simple modelling language, step-wise refinement from models to implementation, interfaces to security verification tools, and code generation from...... the verified specification. The refinement process carries thus security properties from the model to the implementation. Our approach also supports verification of systems previously developed and deployed. Internally, the reasoning in our framework is based on the Beliefs and Knowledge tool, a verification...

  17. System Advisor Model: Flat Plate Photovoltaic Performance Modeling Validation Report

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, Janine [National Renewable Energy Lab. (NREL), Golden, CO (United States); Whitmore, Jonathan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kaffine, Leah [National Renewable Energy Lab. (NREL), Golden, CO (United States); Blair, Nate [National Renewable Energy Lab. (NREL), Golden, CO (United States); Dobos, Aron P. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2013-12-01

    The System Advisor Model (SAM) is a free software tool that performs detailed analysis of both system performance and system financing for a variety of renewable energy technologies. This report provides detailed validation of the SAM flat plate photovoltaic performance model by comparing SAM-modeled PV system generation data to actual measured production data for nine PV systems ranging from 75 kW to greater than 25 MW in size. The results show strong agreement between SAM predictions and field data, with annualized prediction error below 3% for all fixed tilt cases and below 8% for all one axis tracked cases. The analysis concludes that snow cover and system outages are the primary sources of disagreement, and other deviations resulting from seasonal biases in the irradiation models and one axis tracking issues are discussed in detail.

  18. Noninvasive ventilation for acute respiratory distress in children with central nervous system disorders.

    Science.gov (United States)

    Falsaperla, Raffaele; Elli, Marco; Pavone, Piero; Isotta, Gentile; Lubrano, Riccardo

    2013-09-01

    Acute respiratory distress (ARD) is a relatively frequent occurrence in patients suffering from central nervous system disorders (CNSD) and moderate to severe mental retardation. Whenever conventional therapy is little effective, noninvasive mechanical ventilation (NIV) is the additional treatment in patients with diseases of the peripheral nervous system. However, NIV is traditionally little employed in the acute phase in patients suffering from CNSD. In the latter, either conventional therapy is maintained or invasive mechanical ventilation is instituted if the patient's condition worsens severely. To challenge the traditional view, we conducted the study to prove that NIV is both applicable and effective in the treatment of ARD also in children with moderate to severe mental retardation. We studied 44 children with ARD secondary to pneumonia and CNSD causing moderate to severe mental retardation. The children were divided in two groups. One group received conventional therapy and NIV, the other conventional therapy only, before being advanced to invasive ventilator support when nonresponding. On admission to hospital and one hour following admission we registered pH, PaCO(2), PaO2, A - a DO2 and the PaO2/FiO2 ratio. The mean hospital stay was also recorded. After one hour on NIV PaO2 and pH increased, PaCO(2) decreased, A - a DO2 and PaO2/FiO2 ratio improved. No changes in the above parameters were observed in children on conventional therapy only. Hospital stay was shorter when NIV was instituted. NIV is both applicable and beneficial in stabilizing blood gases, respiratory and cardiovascular parameters also in children with CNSD. Moreover its use shortens the hospital stay. © 2013 Elsevier Ltd. All rights reserved.

  19. Coupling population dynamics with earth system models: the POPEM model.

    Science.gov (United States)

    Navarro, Andrés; Moreno, Raúl; Jiménez-Alcázar, Alfonso; Tapiador, Francisco J

    2017-09-16

    Precise modeling of CO 2 emissions is important for environmental research. This paper presents a new model of human population dynamics that can be embedded into ESMs (Earth System Models) to improve climate modeling. Through a system dynamics approach, we develop a cohort-component model that successfully simulates historical population dynamics with fine spatial resolution (about 1°×1°). The population projections are used to improve the estimates of CO 2 emissions, thus transcending the bulk approach of existing models and allowing more realistic non-linear effects to feature in the simulations. The module, dubbed POPEM (from Population Parameterization for Earth Models), is compared with current emission inventories and validated against UN aggregated data. Finally, it is shown that the module can be used to advance toward fully coupling the social and natural components of the Earth system, an emerging research path for environmental science and pollution research.

  20. Acute pollution of recipients in urban areas

    DEFF Research Database (Denmark)

    Rauch, W.; Harremoës, P.

    1997-01-01

    Oxygen and ammonia concentration are key parameters of acute water pollution in urban rivers. These two abiotic parameters are statistically assessed for a historical rain series by means of a simplified deterministic model of the integrated drainage system. Continuous simulation of the system...... performance indicates that acute water pollution is caused by intermittent discharges from both sewer system and wastewater treatment plant. Neglecting one of them in the evaluation of the environmental impact gives a wrong impression of total system behavior. Detention basins and alternative operational...... modes in the treatment plant under wet weather loading have a limited positive effect for minimizing acute water pollution. (C) 1997 IAWQ. Published by Elsevier Science Ltd....

  1. The Systemic Inflammatory Response Syndrome (SIRS) in acutely hospitalised medical patients: a cohort study

    DEFF Research Database (Denmark)

    Comstedt, Pal; Storgaard, Merete; Lassen, Annmarie T

    2009-01-01

    ABSTRACT: BACKGROUND: Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS) is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count. The rel......ABSTRACT: BACKGROUND: Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS) is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count....... The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown. METHODS: We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status......, blood pressure, infection and comorbidity on admission was registered together with 28-day mortality. RESULTS: A hundred and fifty-four patients (35%) had SIRS on admission, 211 patients (48%) had no SIRS, and 72 patients (16%) had insufficient data to evaluate their SIRS status. SIRS patients were 2...

  2. Model study of radiation effects on the gastrointestinal cell system

    International Nuclear Information System (INIS)

    Kicherer, G.

    1983-03-01

    Since it is now possible to calculate the radiation fields used for medicinal purposes by means of radiation transport programs it was started to determine with mathematical models of radioeffects not only the physical effects or irradiation, but also the resulting biological radioresponses. This supplementary biologic information is not only of large general importance, but particularly valuable for the medicinal application of the biologically highly effective neutron radiation. With support by the Institute for Medicinal Radiophysics and Radiobiology of Essen University Hospital, and of two biomathematical working groups of Ulm University and Cologne University Hospital, who are experienced in the field of establishing mathematical models of the hematogenic cellular system, we developed out of experimental fundamental findings a cellkinetic, kybernetic model of the intestinal mucosa, which is highly sensitive to radiation. With this newly established model we succeeded for the first time in simulating comprehensively and quantitatively the time-dependent acute radioresponse of such a radiosensitive cellular system. For the first time we successfully used the computer simulation languages DARE-P and GASP, which are principally employed for solving problems in automatic control technology, and set up a radioresponse model. (orig.) [de

  3. Accumulation dynamics and acute toxicity of silver nanoparticles to Daphnia magna and Lumbriculus variegatus: implications for metal modeling approaches.

    Science.gov (United States)

    Khan, Farhan R; Paul, Kai B; Dybowska, Agnieszka D; Valsami-Jones, Eugenia; Lead, Jamie R; Stone, Vicki; Fernandes, Teresa F

    2015-04-07

    Frameworks commonly used in trace metal ecotoxicology (e.g., biotic ligand model (BLM) and tissue residue approach (TRA)) are based on the established link between uptake, accumulation and toxicity, but similar relationships remain unverified for metal-containing nanoparticles (NPs). The present study aimed to (i) characterize the bioaccumulation dynamics of PVP-, PEG-, and citrate-AgNPs, in comparison to dissolved Ag, in Daphnia magna and Lumbriculus variegatus; and (ii) investigate whether parameters of bioavailability and accumulation predict acute toxicity. In both species, uptake rate constants for AgNPs were ∼ 2-10 times less than for dissolved Ag and showed significant rank order concordance with acute toxicity. Ag elimination by L. variegatus fitted a 1-compartment loss model, whereas elimination in D. magna was biphasic. The latter showed consistency with studies that reported daphnids ingesting NPs, whereas L. variegatus biodynamic parameters indicated that uptake and efflux were primarily determined by the bioavailability of dissolved Ag released by the AgNPs. Thus, principles of BLM and TRA frameworks are confounded by the feeding behavior of D. magna where the ingestion of AgNPs perturbs the relationship between tissue concentrations and acute toxicity, but such approaches are applicable when accumulation and acute toxicity are linked to dissolved concentrations. The uptake rate constant, as a parameter of bioavailability inclusive of all available pathways, could be a successful predictor of acute toxicity.

  4. The 5-HT3Receptor Antagonist Ondansetron Attenuates Pancreatic Injury in Cerulein-Induced Acute Pancreatitis Model.

    Science.gov (United States)

    Tsukamoto, Atsushi; Sugimoto, Takuto; Onuki, Yuta; Shinoda, Hajime; Mihara, Taiki; Hori, Masatoshi; Inomata, Tomo

    2017-08-01

    The 5-hydroxytryptamine-3 receptor (5-HT 3 R) antagonist ondansetron has been clinically approved as an anti-emetic agent. Recent findings indicate that ondansetron has anti-inflammatory properties. The aim of the present study was to assess the therapeutic action of ondansetron in cerulein-induced acute pancreatitis model. Male-BALB/c mice were used in the present study. Acute pancreatitis was induced by an hourly injection of cerulein. Ondansetron was administered subcutaneously at a dose of 3 mg/kg. The messenger RNA (mRNA) expression of 5-HT 3 R in pancreatic tissue was assessed with RT-PCR. Plasma amylase, lipase, and interleukin (IL)-6 levels were evaluated. Pancreatic injury was histopathologically graded, and myeloperoxidase (MPO)-positive cells were counted. 5-HT 3 R mRNA was expressed in the pancreas. In acute pancreatitis model mice, amylase, lipase, and IL-6 levels were significantly increased in the blood. With ondansetron treatment, these levels were significantly decreased. Histopathological evaluation revealed that ondansetron attenuated the inflammatory damage in acute pancreatitis. The number of infiltrated neutrophils stained by MPO was decreased by ondansetron treatment. In summary, the 5-HT 3 R antagonist ondansetron attenuated pancreatic injury through its anti-inflammatory action. These findings suggest that ondansetron may potentially be of use for therapy of acute pancreatitis.

  5. Spinal Cord Injury Model System Information Network

    Science.gov (United States)

    ... the UAB-SCIMS Contact the UAB-SCIMS UAB Spinal Cord Injury Model System Newly Injured Health Daily Living Consumer ... Information Network The University of Alabama at Birmingham Spinal Cord Injury Model System (UAB-SCIMS) maintains this Information Network ...

  6. Statistical Model Checking for Stochastic Hybrid Systems

    DEFF Research Database (Denmark)

    David, Alexandre; Du, Dehui; Larsen, Kim Guldstrand

    2012-01-01

    This paper presents novel extensions and applications of the UPPAAL-SMC model checker. The extensions allow for statistical model checking of stochastic hybrid systems. We show how our race-based stochastic semantics extends to networks of hybrid systems, and indicate the integration technique ap...

  7. Systemic, Ecological Model for Rehabilitation Counseling.

    Science.gov (United States)

    Hershenson, David B.

    1998-01-01

    Presents a reformulation of Hershenson's theoretical model for rehabilitation counseling in systemic and ecological terms. This macrosystem is organized by precipitating event of disability and is composed of four systems: consumer, functional, provider, and contextual. Discusses the use of the model for selecting rehabilitation interventions…

  8. Modeling complex work systems - method meets reality

    NARCIS (Netherlands)

    van der Veer, Gerrit C.; Hoeve, Machteld; Lenting, Bert

    1996-01-01

    Modeling an existing task situation is often a first phase in the (re)design of information systems. For complex systems design, this model should consider both the people and the organization involved, the work, and situational aspects. Groupware Task Analysis (GTA) as part of a method for the

  9. System dynamics modelling of situation awareness

    CSIR Research Space (South Africa)

    Oosthuizen, R

    2015-11-01

    Full Text Available . The feedback loops and delays in the Command and Control system also contribute to the complex dynamic behavior. This paper will build on existing situation awareness models to develop a System Dynamics model to support a qualitative investigation through...

  10. Dynamic modeling of the INAPRO aquaponic system

    NARCIS (Netherlands)

    Karimanzira, Divas; Keesman, Karel J.; Kloas, Werner; Baganz, Daniela; Rauschenbach, Thomas

    2016-01-01

    The use of modeling techniques to analyze aquaponics systems is demonstrated with an example of dynamic modeling for the production of Nile tilapia (Oreochromis niloticus) and tomatoes (Solanum lycopersicon) using the innovative double recirculating aquaponic system ASTAF-PRO. For the management

  11. Catchment & sewer network simulation model to benchmark control strategies within urban wastewater systems

    DEFF Research Database (Denmark)

    Saagi, Ramesh; Flores Alsina, Xavier; Fu, Guangtao

    2016-01-01

    This paper aims at developing a benchmark simulation model to evaluate control strategies for the urban catchment and sewer network. Various modules describing wastewater generation in the catchment, its subsequent transport and storage in the sewer system are presented. Global/local overflow based....../standard wastewater treatment models (Activated Sludge Models) to finally promote integrated assessment of urban wastewater systems....... evaluation criteria describing the cumulative and acute effects are presented. Simulation results show that the proposed set of models is capable of generating daily, weekly and seasonal variations as well as describing the effect of rain events on wastewater characteristics. Two sets of case studies...

  12. Formal heterogeneous system modeling with SystemC

    DEFF Research Database (Denmark)

    Niaki, Seyed Hosein Attarzadeh; Jakobsen, Mikkel Koefoed; Sulonen, Tero

    2012-01-01

    Electronic System Level (ESL) design of embedded systems proposes raising the abstraction level of the design entry to cope with the increasing complexity of such systems. To exploit the benefits of ESL, design languages should allow specification of models which are a) heterogeneous, to describe...... to focus on specifying the pure functional aspects. A key advantage is that the formalism is used to export the structure and behavior of the models via introspection as an abstract representation for further analysis and synthesis....

  13. Regression Models for Repairable Systems

    Czech Academy of Sciences Publication Activity Database

    Novák, Petr

    2015-01-01

    Roč. 17, č. 4 (2015), s. 963-972 ISSN 1387-5841 Institutional support: RVO:67985556 Keywords : Reliability analysis * Repair models * Regression Subject RIV: BB - Applied Statistics , Operational Research Impact factor: 0.782, year: 2015 http://library.utia.cas.cz/separaty/2015/SI/novak-0450902.pdf

  14. The acute toxicity of major ion salts to Ceriodaphnia dubia. III. Mathematical models for mixture toxicity.

    Science.gov (United States)

    Erickson, Russell J; Mount, David R; Highland, Terry L; Hockett, J Russell; Hoff, Dale J; Jenson, Correne T; Norberg-King, Teresa J; Peterson, Kira N

    2018-01-01

    Based on previous research on the acute toxicity of major ions (Na + , K + , Ca 2+ , Mg 2+ , Cl - , SO 4 2- , and HCO 3 - /CO 3 2- ) to Ceriodaphnia dubia, a mathematical model was developed for predicting the median lethal concentration (LC50) for any ion mixture, excepting those dominated by K-specific toxicity. One component of the model describes a mechanism of general ion toxicity to which all ions contribute and predicts LC50s as a function of osmolarity and Ca activity. The other component describes Mg/Ca-specific toxicity to apply when such toxicity exceeds the general ion toxicity and predicts LC50s as a function of Mg and Ca activities. This model not only tracks well the observed LC50s from past research used for model development but also successfully predicts LC50s from new toxicity tests on synthetic mixtures of ions emulating chemistries of various ion-enriched effluents and receiving waters. It also performs better than a previously published model for major ion toxicity. Because of the complexities of estimating chemical activities and osmolarity, a simplified model based directly on ion concentrations was also developed and found to provide useful predictions. Environ Toxicol Chem 2018;37:247-259. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

  15. Mitochondrial Alterations and Oxidative Stress in an Acute Transient Mouse Model of Muscle Degeneration

    Science.gov (United States)

    Ramadasan-Nair, Renjini; Gayathri, Narayanappa; Mishra, Sudha; Sunitha, Balaraju; Mythri, Rajeswara Babu; Nalini, Atchayaram; Subbannayya, Yashwanth; Harsha, Hindalahalli Chandregowda; Kolthur-Seetharam, Ullas; Bharath, Muchukunte Mukunda Srinivas

    2014-01-01

    Muscular dystrophies (MDs) and inflammatory myopathies (IMs) are debilitating skeletal muscle disorders characterized by common pathological events including myodegeneration and inflammation. However, an experimental model representing both muscle pathologies and displaying most of the distinctive markers has not been characterized. We investigated the cardiotoxin (CTX)-mediated transient acute mouse model of muscle degeneration and compared the cardinal features with human MDs and IMs. The CTX model displayed degeneration, apoptosis, inflammation, loss of sarcolemmal complexes, sarcolemmal disruption, and ultrastructural changes characteristic of human MDs and IMs. Cell death caused by CTX involved calcium influx and mitochondrial damage both in murine C2C12 muscle cells and in mice. Mitochondrial proteomic analysis at the initial phase of degeneration in the model detected lowered expression of 80 mitochondrial proteins including subunits of respiratory complexes, ATP machinery, fatty acid metabolism, and Krebs cycle, which further decreased in expression during the peak degenerative phase. The mass spectrometry (MS) data were supported by enzyme assays, Western blot, and histochemistry. The CTX model also displayed markers of oxidative stress and a lowered glutathione reduced/oxidized ratio (GSH/GSSG) similar to MDs, human myopathies, and neurogenic atrophies. MS analysis identified 6 unique oxidized proteins from Duchenne muscular dystrophy samples (n = 6) (versus controls; n = 6), including two mitochondrial proteins. Interestingly, these mitochondrial proteins were down-regulated in the CTX model thereby linking oxidative stress and mitochondrial dysfunction. We conclude that mitochondrial alterations and oxidative damage significantly contribute to CTX-mediated muscle pathology with implications for human muscle diseases. PMID:24220031

  16. Cardiovascular system and physical working capacity in patients who had acute radiation syndrome as the result of Chernobyl accident

    International Nuclear Information System (INIS)

    Belyi, D.; Gergel, O.; Kovalenko, A.

    1996-01-01

    The functional state of cardiovascular system has been studied since 1986 in 168 patients who had acute radiation syndrome as the result of Chernobyl accident. There was revealed a progressive increase of cardiovascular system pathology. The number of patients with pathological signs at ECG increased from 4.8 % in 1987 to 11.3 % in 1994 and with myocardial hypertrophy from 1.2 % to 22.6 %. The number of patients with coronary heart disease increased on 17.2% and with essential hypertension on 15.5%. The physical working capacity reduced to 50-60 % of a due level for healthy persons. Two patients suffered from acute myocardial infarction during this period of observation. Thirteenth patients died from 1987 to 1995. Among them 4 patient died in a result of acute cardiac failure. The development of cardiovascular pathology has no any correlation with a dose of exposure. Three factors of cardiovascular pathology growth are supposed

  17. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis.

    Science.gov (United States)

    Jin, Yuepeng; Bai, Yongyu; Li, Qiang; Bhugul, Pravin Avinash; Huang, Xince; Liu, Lewei; Pan, Liangliang; Ni, Haizhen; Chen, Bicheng; Sun, Hongwei; Zhang, Qiyu; Hehir, Michael; Zhou, Mengtao

    2016-01-01

    The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP). AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg) into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF). The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER) were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP.

  18. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis.

    Directory of Open Access Journals (Sweden)

    Yuepeng Jin

    Full Text Available The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP. AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF. The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP.

  19. Transplantation of human stem cell-derived hepatocytes in an animal model of acute liver failure.

    Science.gov (United States)

    Ramanathan, Rajesh; Pettinato, Giuseppe; Beeston, John T; Lee, David D; Wen, Xuejun; Mangino, Martin J; Fisher, Robert A

    2015-08-01

    Hepatocyte cell transplantation can be life-saving in patients with acute liver failure (ALF); however, primary human hepatocyte transplantation is limited by the scarcity of donor hepatocytes. We investigated the effect of stem cell-derived, hepatocyte-like cells in an animal xenotransplant model of ALF. Intraperitoneal d-galactosamine was used to develop a lethal model of ALF in the rat. Human induced pluripotent stem cells (iPSC), human mesenchymal stem cells, and human iPSC combined with human endothelial cells (iPSC + EC) were differentiated into hepatocyte-like cells and transplanted into the spleens of athymic nude rats with ALF. A reproducible lethal model of ALF was achieved with nearly 90% death within 3 days. Compared with negative controls, rats transplanted with stem cell-derived, hepatocyte-like cells were associated with increased survival. Human albumin was detected in the rat serum 3 days after transplantation in more than one-half the animals transplanted with hepatocyte-like cells. Only animals transplanted with iPSC + EC-derived hepatocytes had serum human albumin at 14 days posttransplant. Transplanted hepatocyte-like cells homed to the injured rat liver, whereas the ECs were only detected in the spleen. Transplantation of stem cell-derived, hepatocyte-like cells improved survival with evidence of in vivo human albumin production. Combining ECs may prolong cell function after transplantation. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. A Multiscale Computational Model of the Response of Swine Epidermis After Acute Irradiation

    Science.gov (United States)

    Hu, Shaowen; Cucinotta, Francis A.

    2012-01-01

    Radiation exposure from Solar Particle Events can lead to very high skin dose for astronauts on exploration missions outside the protection of the Earth s magnetic field [1]. Assessing the detrimental effects to human skin under such adverse conditions could be predicted by conducting territorial experiments on animal models. In this study we apply a computational approach to simulate the experimental data of the radiation response of swine epidermis, which is closely similar to human epidermis [2]. Incorporating experimentally measured histological and cell kinetic parameters into a multiscale tissue modeling framework, we obtain results of population kinetics and proliferation index comparable to unirradiated and acutely irradiated swine experiments [3]. It is noted the basal cell doubling time is 10 to 16 days in the intact population, but drops to 13.6 hr in the regenerating populations surviving irradiation. This complex 30-fold variation is proposed to be attributed to the shortening of the G1 phase duration. We investigate this radiation induced effect by considering at the sub-cellular level the expression and signaling of TGF-beta, as it is recognized as a key regulatory factor of tissue formation and wound healing [4]. This integrated model will allow us to test the validity of various basic biological rules at the cellular level and sub-cellular mechanisms by qualitatively comparing simulation results with published research, and should lead to a fuller understanding of the pathophysiological effects of ionizing radiation on the skin.

  1. Insights from computational modeling in inflammation and acute rejection in limb transplantation.

    Directory of Open Access Journals (Sweden)

    Dolores Wolfram

    Full Text Available Acute skin rejection in vascularized composite allotransplantation (VCA is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplexed analysis technology. Hierarchical Clustering Analysis, Principal Component Analysis, Random Forest Classification and Multinomial Logistic Regression models were used to segregate experimental groups. Based on Random Forest Classification, Multinomial Logistic Regression and Hierarchical Clustering Analysis models, IL-4, TNF-α and IL-12p70 were the best predictors of skin rejection and identified rejection well in advance of histopathological alterations. TNF-α and IL-12p70 were the best predictors of muscle rejection and also preceded histopathological alterations. Principal Component Analysis identified IL-1α, IL-18, IL-1β, and IL-4 as principal drivers of transplant rejection. Thus, inflammatory patterns associated with rejection are specific for the individual tissue and may be superior for early detection and targeted treatment of rejection.

  2. Characterization of a murine model of monocrotaline pyrrole-induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Pullamsetti Soni S

    2008-12-01

    Full Text Available Abstract Background New animal models of chronic pulmonary hypertension in mice are needed. The injection of monocrotaline is an established model of pulmonary hypertension in rats. The aim of this study was to establish a murine model of pulmonary hypertension by injection of the active metabolite, monocrotaline pyrrole. Methods Survival studies, computed tomographic scanning, histology, bronchoalveolar lavage were performed, and arterial blood gases and hemodynamics were measured in animals which received an intravenous injection of different doses of monocrotaline pyrrole. Results Monocrotaline pyrrole induced pulmonary hypertension in Sprague Dawley rats. When injected into mice, monocrotaline pyrrole induced dose-dependant mortality in C57Bl6/N and BALB/c mice (dose range 6–15 mg/kg bodyweight. At a dose of 10 mg/kg bodyweight, mice developed a typical early-phase acute lung injury, characterized by lung edema, neutrophil influx, hypoxemia and reduced lung compliance. In the late phase, monocrotaline pyrrole injection resulted in limited lung fibrosis and no obvious pulmonary hypertension. Conclusion Monocrotaline and monocrotaline pyrrole pneumotoxicity substantially differs between the animal species.

  3. Mathematical Modeling Of Life-Support Systems

    Science.gov (United States)

    Seshan, Panchalam K.; Ganapathi, Balasubramanian; Jan, Darrell L.; Ferrall, Joseph F.; Rohatgi, Naresh K.

    1994-01-01

    Generic hierarchical model of life-support system developed to facilitate comparisons of options in design of system. Model represents combinations of interdependent subsystems supporting microbes, plants, fish, and land animals (including humans). Generic model enables rapid configuration of variety of specific life support component models for tradeoff studies culminating in single system design. Enables rapid evaluation of effects of substituting alternate technologies and even entire groups of technologies and subsystems. Used to synthesize and analyze life-support systems ranging from relatively simple, nonregenerative units like aquariums to complex closed-loop systems aboard submarines or spacecraft. Model, called Generic Modular Flow Schematic (GMFS), coded in such chemical-process-simulation languages as Aspen Plus and expressed as three-dimensional spreadsheet.

  4. Systematic modelling and simulation of refrigeration systems

    DEFF Research Database (Denmark)

    Rasmussen, Bjarne D.; Jakobsen, Arne

    1998-01-01

    The task of developing a simulation model of a refrigeration system can be very difficult and time consuming. In order for this process to be effective, a systematic method for developing the system model is required. This method should aim at guiding the developer to clarify the purpose of the s......The task of developing a simulation model of a refrigeration system can be very difficult and time consuming. In order for this process to be effective, a systematic method for developing the system model is required. This method should aim at guiding the developer to clarify the purpose...... of the simulation, to select appropriate component models and to set up the equations in a well-arranged way. In this paper the outline of such a method is proposed and examples showing the use of this method for simulation of refrigeration systems are given....

  5. Modeling and analysis of stochastic systems

    CERN Document Server

    Kulkarni, Vidyadhar G

    2011-01-01

    Based on the author's more than 25 years of teaching experience, Modeling and Analysis of Stochastic Systems, Second Edition covers the most important classes of stochastic processes used in the modeling of diverse systems, from supply chains and inventory systems to genetics and biological systems. For each class of stochastic process, the text includes its definition, characterization, applications, transient and limiting behavior, first passage times, and cost/reward models. Along with reorganizing the material, this edition revises and adds new exercises and examples. New to the second edi

  6. Respiratory Effects and Systemic Stress Response Following Acute Acrolein Inhalation in Rats#

    Science.gov (United States)

    Previous studies have demonstrated that exposure to the pulmonary irritant ozone causes myriad systemic metabolic and pulmonary effects attributed to sympathetic and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically impaired models. We...

  7. Respiratory Effects and Systemic Stress Response Following Acute Acrolein Inhalation in Rats

    Science.gov (United States)

    Previous studies have demonstrated that exposure to ozone, a pulmonary irritant, causes myriad systemic metabolic and pulmonary effects that are attributed to neuronal and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically-impaired models...

  8. Respiratory Effects and Systemic Stress Response Following Acute Acrolein Inhalation in Rats.

    Science.gov (United States)

    Previous studies have demonstrated that exposure to the pulmonary irritant ozone causes myriad systemic metabolic and pulmonary effects attributed to sympathetic and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically impaired models. We...

  9. Formal heterogeneous system modeling with SystemC

    DEFF Research Database (Denmark)

    Niaki, Seyed Hosein Attarzadeh; Jakobsen, Mikkel Koefoed; Sulonen, Tero

    2012-01-01

    Electronic System Level (ESL) design of embedded systems proposes raising the abstraction level of the design entry to cope with the increasing complexity of such systems. To exploit the benefits of ESL, design languages should allow specification of models which are a) heterogeneous, to describe...

  10. A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking

    Science.gov (United States)

    Gilbert, David

    2016-01-01

    , the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems. PMID:27187178

  11. System barriers to the evidence-based care of acute coronary syndrome patients in China: qualitative analysis.

    Science.gov (United States)

    Ranasinghe, Isuru; Rong, Ye; Du, Xin; Wang, Yangfang; Gao, Runlin; Patel, Anushka; Wu, Yangfeng; Iedema, Rick; Hao, Zhixin; Hu, Dayi; Turnbull, Fiona

    2014-03-01

    Organizational and wider health system factors influence the implementation and success of interventions. Clinical Pathways in Acute Coronary Syndromes 2 is a cluster randomized trial of a clinical pathway-based intervention to improve acute coronary syndrome care in hospitals in China. We performed a qualitative evaluation to examine the system-level barriers to implementing clinical pathways in the dynamic healthcare environment of China. A qualitative descriptive analysis of 40 in-depth interviews with health professionals conducted in a sample of 10 hospitals purposively selected to explore barriers to implementation of the intervention. Qualitative data were analyzed using the Framework method. In-depth interviews identified 5 key system-level barriers to effective implementation: (1) leadership support for implementing quality improvement, (2) variation in the capacity of clinical services and quality improvement resources, (3) fears of patient disputes and litigation, (4) healthcare funding constraints and high out-of-pocket expenses, and (5) patient-related factors. System-level barriers affect the ability of acute coronary syndrome clinical pathways to change practice. Addressing these barriers in the context of current and planned national health system reform will be critical for future improvements in the management of acute coronary syndromes, and potentially other hospitalized conditions, in China. Clinical Trial Registration- URL: http://www.anzctr.org.au/default.aspx. Register. Unique identifier: ACTRN12609000491268.

  12. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    Science.gov (United States)

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (Ppreeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. © 2015 American Heart Association, Inc.

  13. Systems Engineering Model for ART Energy Conversion

    Energy Technology Data Exchange (ETDEWEB)

    Mendez Cruz, Carmen Margarita [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rochau, Gary E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wilson, Mollye C. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-02-01

    The near-term objective of the EC team is to establish an operating, commercially scalable Recompression Closed Brayton Cycle (RCBC) to be constructed for the NE - STEP demonstration system (demo) with the lowest risk possible. A systems engineering approach is recommended to ensure adequate requirements gathering, documentation, and mode ling that supports technology development relevant to advanced reactors while supporting crosscut interests in potential applications. A holistic systems engineering model was designed for the ART Energy Conversion program by leveraging Concurrent Engineering, Balance Model, Simplified V Model, and Project Management principles. The resulting model supports the identification and validation of lifecycle Brayton systems requirements, and allows designers to detail system-specific components relevant to the current stage in the lifecycle, while maintaining a holistic view of all system elements.

  14. Modeling aluminum-air battery systems

    Science.gov (United States)

    Savinell, R. F.; Willis, M. S.

    The performance of a complete aluminum-air battery system was studied with a flowsheet model built from unit models of each battery system component. A plug flow model for heat transfer was used to estimate the amount of heat transferred from the electrolyte to the air stream. The effect of shunt currents on battery performance was found to be insignificant. Using the flowsheet simulator to analyze a 100 cell battery system now under development demonstrated that load current, aluminate concentration, and electrolyte temperature are dominant variables controlling system performance. System efficiency was found to decrease as both load current and aluminate concentration increases. The flowsheet model illustrates the interdependence of separate units on overall system performance.

  15. Acute systemic accumulation of acrolein in mice by inhalation at a concentration similar to that in cigarette smoke

    OpenAIRE

    Tully, Melissa; Zheng, Lingxing; Acosta, Glen; Tian, Ran; Shi, Riyi

    2014-01-01

    Cigarette smoke is an important environmental factor associated with a wide array of public health concerns. Acrolein, a component of tobacco smoke and a known toxin to various cell types, may be a key pathological factor mediating the adverse effects linked with tobacco smoke. Although acrolein is known to accumulate in the respiratory system after acute nasal exposure, it is not clear if it accumulates systemically, and less is known in the nervous system. The aim of this study was to asses...

  16. Antinociceptive effect of Zanthoxylum rhoifolium Lam. (Rutaceae) in models of acute pain in rodents.

    Science.gov (United States)

    Pereira, S S; Lopes, L S; Marques, R B; Figueiredo, K A; Costa, D A; Chaves, M H; Almeida, F R C

    2010-05-27

    Zanthoxylum rhoifolium Lam. (Rutaceae) is locally known as "mamica de cadela", and its bark is popularly used for toothache and earache. The objective of this study was to investigate the antinociceptive effect of the ethanolic extract from this species' stem bark (EtOH), its fractions of partition (hexane-HEX, ethyl acetate-AcOEt, aqueous-AQ) and lupeol (a triterpene obtained from HEX) in models of acute pain. Male and female Swiss mice (25-35 g, n=6-12 animals/group) were used to assess acute toxicity and nociception (Animal Ethics Committee/UFPI, No. 09/2008). Acute toxicity was studied up to 2 g/kg p.o. of EtOH. In the formalin test (2%, 20 microL/paw), the licking time of the stimulated paw was quantified during the first 5 min (first phase) and at 15-30 min (second phase), 1h after oral treatment with EtOH, HEX, AcOEt or saline, and 30 min after use of morphine-MOR (5 mg/kg i.p.). The same response evoked by capsaicin (2 microg/20 microL/paw) was quantified during 5 min, after administration of EtOH, HEX, AcOEt, AQ, saline and MOR. The licking time of the paw that was stimulated with glutamate (10 micromol/20 microL) was measured (15 min) after treatment with EtOH, HEX, AcOEt, AQ, lupeol, saline or MK801 (0.03 mg/kg, i.p.). Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of EtOH (250 mg/kg p.o.) and HEX (500 mg/kg p.o.). The animals did not exhibit any acute toxicity to EtOH (up to 2 g/kg p.o.), so it was not possible to calculate the LD50. EtOH, HEX and AcOEt (62.5-250 mg/kg) produced a significant antinociceptive effect in the formalin and capsaicin tests. However, AQ was ineffective. EtOH, HEX, AcOEt and lupeol reduced the glutamate-evoked nociceptive response, but AQ had no effect. EtOH and HEX did not alter the locomotion of animals in the open-field or rota-rod tests, which suggest a lack of a central depressant effect. The results confirm the popular use of Zanthoxylum

  17. Prediction of acute toxicity of cadmium and lead to zebrafish larvae by using a refined toxicokinetic-toxicodynamic model

    International Nuclear Information System (INIS)

    Gao, Yongfei; Feng, Jianfeng; Zhu, Lin

    2015-01-01

    Highlights: • We developed a BLM-aided TK-TD model that considers the effects of H + . • The time-course metal concentration in larvae was well described by the TK model. • The time-course survival of zebrafish larvae was well simulated by the TD model. - Abstract: The biotic ligand model (BLM) and the toxicokinetic-toxicodynamic (TK-TD) model are essential in predicting the acute toxicity of metals in various species and exposure conditions; however, these models are usually separately utilized. In this study, a mechanistic TK-TD model was developed to predict the acute toxicity of 10 −6 M Cd and 10 −6 M Pb to zebrafish (Danio rerio) larvae. The novel approach links the BLM with relevant TK processes to simulate the bioaccumulation processes of Cd or Pb as a function of the maximum uptake rate of each metal, the affinity constants, and the concentrations of free metal ions and H + in test solutions. Results showed that the refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb to zebrafish larvae at pH 5.5, 6.5, and 7.0.

  18. Prediction of acute toxicity of cadmium and lead to zebrafish larvae by using a refined toxicokinetic-toxicodynamic model

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yongfei; Feng, Jianfeng, E-mail: fengjf@nankai.edu.cn; Zhu, Lin, E-mail: zhulin@nankai.edu.cn

    2015-12-15

    Highlights: • We developed a BLM-aided TK-TD model that considers the effects of H{sup +}. • The time-course metal concentration in larvae was well described by the TK model. • The time-course survival of zebrafish larvae was well simulated by the TD model. - Abstract: The biotic ligand model (BLM) and the toxicokinetic-toxicodynamic (TK-TD) model are essential in predicting the acute toxicity of metals in various species and exposure conditions; however, these models are usually separately utilized. In this study, a mechanistic TK-TD model was developed to predict the acute toxicity of 10{sup −6} M Cd and 10{sup −6} M Pb to zebrafish (Danio rerio) larvae. The novel approach links the BLM with relevant TK processes to simulate the bioaccumulation processes of Cd or Pb as a function of the maximum uptake rate of each metal, the affinity constants, and the concentrations of free metal ions and H{sup +} in test solutions. Results showed that the refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb to zebrafish larvae at pH 5.5, 6.5, and 7.0.

  19. The chain of care enabling tPA treatment in acute ischemic stroke : a comprehensive review of organisational models

    NARCIS (Netherlands)

    Lahr, Maarten M. H.; Luijckx, Gert-Jan; Vroomen, Patrick; van der Zee, D.J.; Buskens, Erik

    Protracted and partial implementation of treatment with intravenous tissue plasminogen activator (tPA) within 4.5 h after acute stroke onset results in potentially eligible patients not receiving optimal treatment. The goal of this study was to review the performance of various organisational models

  20. Finite element modeling of aponeurotomy: altered intramuscular myofascial force transmission yields complex sarcomere length distributions determining acute effects

    NARCIS (Netherlands)

    Yucesoy, C.A.; Koopman, B.H.; Grootenboer, H.J.; Huijing, P.A.J.B.M.

    2007-01-01

    Finite element modeling of aponeurotomized rat extensor digitorium longus muscle was performed to investigate the acute effects of proximal aponeurotomy. The specific goal was to assess the changes in lengths of sarcomeres within aponeurotomized muscle and to explain how the intervention leads to

  1. Primary Screening for Proteins Differentially Expressed in the Myocardium of a Rat Model of Acute Methamphetamine Intoxication

    Directory of Open Access Journals (Sweden)

    Guoqiang Qu

    2016-01-01

    Full Text Available The mechanism of myocardial injury induced by the cardiovascular toxicity of methamphetamine (MA has been shown to depend on alterations in myocardial proteins caused by MA. Primary screening of the expression of myocardial proteins in a rat model of MA intoxication was achieved by combining two-dimensional electrophoresis and mass spectrometry analyses, which revealed a total of 100 differentially expressed proteins. Of these, 13 displayed significantly altered expression. Moreover, Western blotting and real-time reverse transcription quantitative polymerase chain reaction analyses of several relative proteins demonstrated that acute MA intoxication lowers protein expression and mRNA transcription of aldehyde dehydrogenase-2 and NADH dehydrogenase (ubiquinone 1 alpha subcomplex subunit 10. In contrast, MA intoxication elevated the protein expression and mRNA transcription of heat shock protein family B (small member 1. By combining behavioral assessments of experimental rat models with the histological and pathological changes evident in cardiomyocytes, a mechanism accounting for MA myocardial toxicity was suggested. MA alters the regulation of gene transcription and the subsequent expression of certain proteins that participate in myocardial respiration and in responding to oxidative stress, resulting in myocardial dysfunction and structural changes that affect the functioning of the cardiovascular system.

  2. Model-Based Design for Embedded Systems

    CERN Document Server

    Nicolescu, Gabriela

    2009-01-01

    Model-based design allows teams to start the design process from a high-level model that is gradually refined through abstraction levels to ultimately yield a prototype. This book describes the main facets of heterogeneous system design. It focuses on multi-core methodological issues, real-time analysis, and modeling and validation

  3. Modeling the patient journey from injury to community reintegration for persons with acute traumatic spinal cord injury in a Canadian centre.

    Directory of Open Access Journals (Sweden)

    Argelio Santos

    Full Text Available BACKGROUND: A patient's journey through the health care system is influenced by clinical and system processes across the continuum of care. METHODS: To inform optimized access to care and patient flow for individuals with traumatic spinal cord injury (tSCI, we developed a simulation model that can examine the full impact of therapeutic or systems interventions across the care continuum for patients with traumatic spinal cord injuries. The objective of this paper is to describe the detailed development of this simulation model for a major trauma and a rehabilitation centre in British Columbia (BC, Canada, as part of the Access to Care and Timing (ACT project and is referred to as the BC ACT Model V1.0. FINDINGS: To demonstrate the utility of the simulation model in clinical and administrative decision-making we present three typical scenarios that illustrate how an investigator can track the indirect impact(s of medical and administrative interventions, both upstream and downstream along the continuum of care. For example, the model was used to estimate the theoretical impact of a practice that reduced the incidence of pressure ulcers by 70%. This led to a decrease in acute and rehabilitation length of stay of 4 and 2 days, respectively and a decrease in bed utilization of 9% and 3% in acute and rehabilitation. CONCLUSION: The scenario analysis using the BC ACT Model V1.0 demonstrates the flexibility and value of the simulation model as a decision-making tool by providing estimates of the effects of different interventions and allowing them to be objectively compared. Future work will involve developing a generalizable national Canadian ACT Model to examine differences in care delivery and identify the ideal attributes of SCI care delivery.

  4. Critically Important Object Security System Element Model

    Directory of Open Access Journals (Sweden)

    I. V. Khomyackov

    2012-03-01

    Full Text Available A stochastic model of critically important object security system element has been developed. The model includes mathematical description of the security system element properties and external influences. The state evolution of the security system element is described by the semi-Markov process with finite states number, the semi-Markov matrix and the initial semi-Markov process states probabilities distribution. External influences are set with the intensity of the Poisson thread.

  5. A model for international border management systems.

    Energy Technology Data Exchange (ETDEWEB)

    Duggan, Ruth Ann

    2008-09-01

    To effectively manage the security or control of its borders, a country must understand its border management activities as a system. Using its systems engineering and security foundations as a Department of Energy National Security Laboratory, Sandia National Laboratories has developed such an approach to modeling and analyzing border management systems. This paper describes the basic model and its elements developed under Laboratory Directed Research and Development project 08-684.

  6. Catchment & sewer network simulation model to benchmark control strategies within urban wastewater systems

    OpenAIRE

    Saagi, Ramesh; Flores Alsina, Xavier; Fu, Guangtao; Butler, David; Gernaey, Krist V.; Jeppsson, Ulf

    2016-01-01

    This paper aims at developing a benchmark simulation model to evaluate control strategies for the urban catchment and sewer network. Various modules describing wastewater generation in the catchment, its subsequent transport and storage in the sewer system are presented. Global/local overflow based evaluation criteria describing the cumulative and acute effects are presented. Simulation results show that the proposed set of models is capable of generating daily, weekly and seasonal variations...

  7. A strategic review of electricity systems models

    International Nuclear Information System (INIS)

    Foley, A.M.; O Gallachoir, B.P.; McKeogh, E.J.; Hur, J.; Baldick, R.

    2010-01-01

    Electricity systems models are software tools used to manage electricity demand and the electricity systems, to trade electricity and for generation expansion planning purposes. Various portfolios and scenarios are modelled in order to compare the effects of decision making in policy and on business development plans in electricity systems so as to best advise governments and industry on the least cost economic and environmental approach to electricity supply, while maintaining a secure supply of sufficient quality electricity. The modelling techniques developed to study vertically integrated state monopolies are now applied in liberalised markets where the issues and constraints are more complex. This paper reviews the changing role of electricity systems modelling in a strategic manner, focussing on the modelling response to key developments, the move away from monopoly towards liberalised market regimes and the increasing complexity brought about by policy targets for renewable energy and emissions. The paper provides an overview of electricity systems modelling techniques, discusses a number of key proprietary electricity systems models used in the USA and Europe and provides an information resource to the electricity analyst not currently readily available in the literature on the choice of model to investigate different aspects of the electricity system. (author)

  8. Beneficial hemodynamic effects of nicorandil in a canine model of acute congestive heart failure: comparison with nitroglycerin and cromakalim.

    Science.gov (United States)

    Noguchi, K; Matsuzaki, T; Ojiri, Y; Koyama, T; Nakasone, J; Sakanashi, M

    1998-01-01

    Comparative hemodynamic effects of nicorandil (NCR), nitroglycerin (NTG) and cromakalim (CRM) were examined in a canine model of acute congestive heart failure (CHF). CHF was produced by injections of saponin into coronary arteries of anesthetized dogs followed by volume loading and continuous i.v. infusion of methoxamine. After the treatment, aortic blood flow (AoF), left ventricular dP/dt and myocardial segment shortening (SS) markedly decreased, while the left ventricular end-diastolic pressure (LVEDP), the right atrial pressure (RAP) and the systemic vascular resistance (SVR) increased. NCR (n = 6), NTG (n = 6) and CRM (n = 8), which were administered i.v. after production of CHF, caused a comparable reduction in LVEDP. NCR and CRM profoundly increased AoF and SS but NTG did only slightly. On the other hand, NTG and NCR but not CRM significantly reduced RAP. Intracoronary NCR (n = 8) exerted no or similar effects on SS as well as systemic hemodynamic indices to those observed with i.v. NCR despite distinct coronary vasodilation. These results indicate that NCR may exert beneficial hemodynamic effects in an experimental CHF mainly due to lessening both afterload and preload rather than the coronary vasodilating effect.

  9. MEK1/2 inhibitors reverse acute vascular occlusion in mouse models of sickle cell disease.

    Science.gov (United States)

    Zhao, Yulin; Schwartz, Evan A; Palmer, Gregory M; Zennadi, Rahima

    2016-03-01

    In sickle cell disease (SCD), treatment of recurrent vasoocclusive episodes, leading to pain crises and organ damage, is still a therapeutic challenge. Vasoocclusion is caused primarily by adherence of homozygous for hemoglobin S (SS) red blood cells (SSRBCs) and leukocytes to the endothelium. We tested the therapeutic benefits of MEK1/2 inhibitors in reversing vasoocclusion in nude and humanized SCD mouse models of acute vasoocclusive episodes using intravital microscopy. Administration of 0.2, 0.3, 1, or 2 mg/kg MEK1/2 inhibitor to TNF-α-pretreated nude mice before human SSRBC infusion inhibited SSRBC adhesion in inflamed vessels, prevented the progression of vasoocclusion, and reduced SSRBC organ sequestration. By use of a more clinically relevant protocol, 0.3 or 1 mg/kg MEK1/2 inhibitor given to TNF-α-pretreated nude mice after human SSRBC infusion and onset of vasoocclusion reversed SSRBC adhesion and vasoocclusion and restored blood flow. In SCD mice, 0.025, 0.05, or 0.1 mg/kg MEK1/2 inhibitor also reversed leukocyte and erythrocyte adhesion after the inflammatory trigger of vasoocclusion and improved microcirculatory blood flow. Cell adhesion was reversed by shedding of endothelial E-selectin, P-selectin, and αvβ3 integrin, and leukocyte CD44 and β2 integrin. Thus, MEK1/2 inhibitors, by targeting the adhesive function of SSRBCs and leukocytes, could represent a valuable therapeutic intervention for acute sickle cell vasoocclusive crises. © FASEB.

  10. Neuregulin-1 protects against acute optic nerve injury in rat model.

    Science.gov (United States)

    Yang, Wei; Liu, Tao-Tao; Song, Xiao-Bin; Zhang, Yan; Li, Zhao-Hui; Hao, Qian; Cui, Zhi-Hua; Liu, Hong Lei; Lei, Chun Ling; Liu, Jun

    2015-10-15

    In this study, we employed a rat model and examined the expression pattern of neuregulin-1 (NRG-1) in optic nerve and retinal ganglion cells (RGCs) in response to optic nerve injury to understand the role of NRG-1 in conferring protection against acute optic nerve injury. Forty-eight male rats were randomly divided into two groups, the sham-operation group (n=24) and optic nerve injury group (n=24). Flash visual evoked potentials (FVEP) and fundography images were acquired at different time points following optic nerve injury (2h, 1d, 2d, 7d, 14d and 28d). Semi-quantitative analysis of NGR-1 expression pattern was performed by immunohistochemistry (IHC) staining. In a related experiment, 100 male rats were randomly divided into NGR-1 treatment group (n=60) (treated with increasing dose of NGR-1 at 0.5μg, 1μg and 3μg), normal saline (NS) group (n=20) and negative control group (n=20). Optic nerve injury was induced in all the animals and in situ cell death was measured by detecting the apoptosis rates using TUNEL assay. Fundus photography results revealed no detectable differences between the sham-operation group and optic nerve injury group at 2h, 1d, 2d and 7d. However at 2weeks, the optic discs turned pale in all animals in the optic nerve injury group. NRG-1 expression increased significantly at all time points in the optic nerve injury group (Pnerve injury and sham-operation group (Ptime points and the reduction was statistically significant in 3μg NRG-1 treatment group at 7d, 14d and 28d (all Pnerve function and is essential for tissue repair following optic nerve injury. Thus, NRG-1 expression confers protection against acute optic nerve injury in a dose-dependent manner. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent.

    Science.gov (United States)

    Maddens, Bert; Vandendriessche, Benjamin; Demon, Dieter; Vanholder, Raymond; Chiers, Koen; Cauwels, Anje; Meyer, Evelyne

    2012-09-01

    Despite extensive research, the mortality rate of patients with sepsis-induced acute kidney injury (AKI) is unacceptably high, especially in the elderly. Current sepsis models have difficulties in reproducing AKI. This study aimed to develop a novel, clinically relevant mouse model for sepsis-induced AKI by uterine ligation and inoculation of bacteria. In addition, the age dependency of the severity of sepsis and sepsis-induced AKI was studied by validating this model in three different age categories. Experimental animal investigation. University research laboratory. Young (12-14 wks), aged (46-48 wks), and old (70-72 wks) C57BL/6 female mice were used as models for adolescent, adult premenopausal, and elderly postmenopausal women, respectively. Uterine ligation and inoculation with 10 colony forming unit Escherichia coli or saline (sham) was performed; in vivo imaging with a luminescent Escherichia coli strain documented the course of infection. All mice had established Escherichia coli sepsis at 48 hrs postinfection, with higher mortality rate in old (43%) compared to aged (23%) or young (9%) mice. Infected mice had elevated serum or plasma cytokine, chemokine (tumor necrosis factor, interleukin-6, keratinocyte-derived chemokine, monocyte chemoattractant protein 1, and interleukin-10), and NOx concentrations compared to sham mice. AKI was confirmed by renal histology. Serum creatinine concentrations at 48 hrs increased with age (mean ± SEM; controls 0.18 ± 0.03 mg/dL, young 0.28 ± 0.03 mg/dL, aged 0.38 ± 0.05 mg/dL, and old 0.44 ± 0.06 mg/dL). The uterine ligation and inoculation model for sepsis-induced AKI starts from a real infectious focus and shows an age-dependent severity of septic AKI that resembles AKI in humans.

  12. Human performance modeling for system of systems analytics.

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Kevin R.; Lawton, Craig R.; Basilico, Justin Derrick; Longsine, Dennis E. (INTERA, Inc., Austin, TX); Forsythe, James Chris; Gauthier, John Henry; Le, Hai D.

    2008-10-01

    A Laboratory-Directed Research and Development project was initiated in 2005 to investigate Human Performance Modeling in a System of Systems analytic environment. SAND2006-6569 and SAND2006-7911 document interim results from this effort; this report documents the final results. The problem is difficult because of the number of humans involved in a System of Systems environment and the generally poorly defined nature of the tasks that each human must perform. A two-pronged strategy was followed: one prong was to develop human models using a probability-based method similar to that first developed for relatively well-understood probability based performance modeling; another prong was to investigate more state-of-art human cognition models. The probability-based modeling resulted in a comprehensive addition of human-modeling capability to the existing SoSAT computer program. The cognitive modeling resulted in an increased understanding of what is necessary to incorporate cognition-based models to a System of Systems analytic environment.

  13. Systemic Corticosteroids Therapy in the Management of Acute Zonal Occult Outer Retinopathy

    Directory of Open Access Journals (Sweden)

    San-Ni Chen

    2015-01-01

    Full Text Available Purpose. To report the efficacy of systemic steroid in treating acute zonal occult outer retinopathy (AZOOR. Methods. Retrospective study of 9 consecutive patients of AZOOR, who received systemic steroid therapy in Changhua Christian Hospital from 2005 to 2013, is presented. The duration of therapy was at least 3 months. Patients were evaluated with best corrected visual acuity (BCVA, optical coherence tomography (OCT, fluorescein angiography (FA, indocyanine green angiography (ICG, visual field test, and electroretinography (ERG. Results. At the initial visit, visual field defect was noted in all patients and impaired visual acuity was noted in 4 eyes. OCT examination revealed disrupted ellipsoid zone at the macular area in 8 eyes and outer nuclear layer (ONL loss in 1 eye. At the end of follow-up, all patients had improvement of visual field. The 4 eyes with initial impaired visual acuity had BCVA recovering to 20/20. Follow-up OCT showed partial or complete recovery of the ellipsoid zone at the macular area in the 8 eyes with initial disrupted ellipsoid zone and stable condition in the eye with ONL loss. The mean follow-up duration was 47.11±26.65 months. Conclusion. Visual improvement was achieved in most cases of recent onset AZOOR after systemic steroid treatment.

  14. CENTRAL NERVOUS SYSTEM INVOLVEMENT IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA: DIAGNOSTIC TOOLS, PROPHYLAXIS AND THERAPY

    Directory of Open Access Journals (Sweden)

    Maria Ilaria Del Principe

    2014-11-01

    Full Text Available In adult patients with acute lymphoblastic leukemia (ALL, Central Nervous System (CNS involvement is associated with a very poor prognosis. The diagnostic assessment of this condition relie