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  1. Blockade of the renin-angiotensin system prevents acute and immunologically relevant colitis in murine models.

    Science.gov (United States)

    Okawada, Manabu; Wilson, Michael W; Larsen, Scott D; Lipka, Elke; Hillfinger, John; Teitelbaum, Daniel H

    2016-12-01

    Blockade of the renin-angiotensin system (RAS) has been shown to alleviate inflammatory processes in the gastrointestinal tract. The aim of this study was to determine if blockade of the RAS would be effective in an immunologically relevant colitis model, and to compare outcome with an acute colitis model. A losartan analog, CCG-203025 (C23H26ClN3O5S) containing a highly polar sulfonic acid moiety that we expected would allow localized mucosal antagonism with minimal systemic absorption was selected as an angiotensin II type 1a receptor antagonist (AT1aR-A). Two colitis models were studied: (1) Acute colitis was induced in 8- to 10-week-old C57BL/6J mice by 2.5 % dextran sodium sulfate (DSS, in drinking water) for 7 days. (2) IL10-/-colitis Piroxicam (200 ppm) was administered orally in feed to 5-week-old IL-10-/-mice (C57BL/6J background) for 14 days followed by enalaprilat (ACE-I), CCG-203025 or PBS administered transanally for 14 days. In the DSS model, weight loss and histologic score for CCG-203025 were better than with placebo. In the IL10-/-model, ACE-I suppressed histologic damage better than CCG-203025. Both ACE-I and CCG-203025 reduced pro-inflammatory cytokines and chemokines. This study demonstrated the therapeutic efficacy of both ACE-I and AT1aR-A for preventing the development of both acute and immunologically relevant colitis.

  2. Effects of kadsurenone on the systemic inflammatory response in rat model of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jun Yao; Qingyong; Lin Wang

    2006-01-01

    Objective: To study the effects of kadsurenone on inflammatory mediators Platelet-activating factor (PAF),tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in rat model of acute pancreatitis(AP). Methods: SD male rats (104)were randomly divided into sham group (n = 24), AP group (n = 40) and kadsurenone group (n = 40). The rats were killed 3,6, 12 and 24 hours after operation. The serum level of PAF, TNF-α and IL-6 was measured. Results: The serum level of PAF,TNF-α and IL-6 of AP group was significantly increased(P < 0.01)compared with control group. The serum level of TNF-α got to a peak 6 hours after operation, and the serum IL-6 getting to a peak 12 hours after operation in AP group. After kadsurenone was administered to AP rats, pancreas and lung myeloperoxidase (MPO), serum amylase activity was reduced. Histology showed a trend toward improvement. The serum level of PAF, TNF-α and IL-6 was significantly decreased (P < 0.05). Conclusion:Kadsurenone can reduce the severity of systemic inflammation in rats with AP and relieve the damage of the pancreas and lung in AP rats. These results suggested that kadsurenone may be useful in the treatment of acute pancreatitis.

  3. 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

  4. 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.

  5. Effects of systemic domestic recombinant human erythropoietin on HIF-1α expression in the retina in a rabbit model of acute high intraocular pressure

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To observe the expression of hypoxia inducible factor-1α (HIF-1α) in the retina of rabbits with acute high intraocular pressure and to investigate the mechanism of systemic domestic recombinant human erythropoietin (rhEPO) protecting the retina from ischemia-reperfusion injury. Methods First,control group and model group were established in rabbit eyes. The acute high intraocular pressure model was established by saline perfusion into anterior chamber,and then hypodermic injection of domestic rhEP...

  6. TRAIL administration down-modulated the acute systemic inflammatory response induced in a mouse model by muramyldipeptide or lipopolysaccharide.

    Science.gov (United States)

    Marcuzzi, Annalisa; Secchiero, Paola; Crovella, Sergio; Zauli, Giorgio

    2012-10-01

    The potent inducer of apoptosis TRAIL/Apo2 ligand is now under considerations in clinical trials for the treatment of different types of cancer. Since the natural history of cancer is often characterized by microbial infections, we have investigated the effect of recombinant human TRAIL in a mouse model of systemic acute inflammation of microbial origin represented by BALB/c mice treated with either bacterial muramyldipeptide (MDP) or lipopolysaccharide (LPS). When administered intraperitoneally (i.p.), these inflammatory bacterial compounds triggered a severe systemic inflammatory response within 2h, represented by body temperature elevation, increase of circulating serum amyloid-A (SAA) and of the number of leukocytes in the peritoneal cavity. Moreover, both MDP and LPS induced a significant elevation of the circulating levels of several inflammatory cytokines and chemokines. Noteworthy, pre-treatment with recombinant human TRAIL 48 and 72 h before administration of either MDP or LPS, significantly counteracted all acute inflammatory responses, including the elevation of key pro-inflammatory cytokines/chemokines such as IL-1α, IL-6, G-CSF, MCP-1. These data demonstrate for the first time that TRAIL has a potent anti-inflammatory activity, which might be beneficial for the anti-tumoral activity of TRAIL.

  7. Mathematical Modeling of the Expert System Predicting the Severity of Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Maria A. Ivanchuk

    2014-01-01

    Full Text Available The method of building the hyperplane which separates the convex hulls in the Euclidean space Rn is proposed. The algorithm of prediction of the presence of severity in patients based on this method is developed and applied in practice to predict the presence of severity in patients with acute pancreatitis.

  8. 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).

  9. Modeling and Hemofiltration Treatment of Acute Inflammation

    Directory of Open Access Journals (Sweden)

    Robert S. Parker

    2016-10-01

    Full Text Available The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL-6, tumor necrosis factor (TNF, and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC algorithm was synthesized to control a hemoadsorption (HA device, a blood purification treatment for acute inflammation. A particle filter (PF algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i the apparent primary mechanism of HA efficacy is white blood cell (WBC capture, with cytokine capture a secondary benefit; and (ii differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.

  10. Systemic corticosteroids for acute sinusitis.

    Science.gov (United States)

    Venekamp, Roderick P; Thompson, Matthew J; Hayward, Gail; Heneghan, Carl J; Del Mar, Chris B; Perera, Rafael; Glasziou, Paul P; Rovers, Maroeska M

    2014-03-25

    Acute sinusitis is the inflammation and swelling of the nasal and paranasal mucous membranes and is a common reason for patients to seek primary care consultations. The related impairment of daily functioning and quality of life is attributable to symptoms such as facial pain and nasal congestion. To assess the effects of systemic corticosteroids on clinical response rates and to determine adverse effects and relapse rates of systemic corticosteroids compared to placebo or standard clinical care in children and adults with acute sinusitis. We searched CENTRAL (2014, Issue 1), MEDLINE (1966 to February week 1, 2014) and EMBASE (January 2009 to February 2014). Randomised controlled trials (RCTs) comparing systemic corticosteroids to placebo or standard clinical care for patients with acute sinusitis. Two review authors independently assessed the methodological quality of the trials and extracted data. Five RCTs with a total of 1193 adult participants met our inclusion criteria. We judged methodological quality to be moderate in four trials and high in one trial. Acute sinusitis was defined clinically in all trials. However, the three trials performed in ear, nose and throat (ENT) outpatient clinics also used radiological assessment as part of their inclusion criteria. All participants were assigned to either oral corticosteroids (prednisone 24 mg to 80 mg daily or betamethasone 1 mg daily) or the control treatment (placebo in four trials and non-steroidal anti-inflammatory drugs (NSAIDs) in one trial). In four trials antibiotics were prescribed in addition to oral corticosteroids or control treatment, while one trial investigated the effects of oral corticosteroids as a monotherapy.When combining data from the five trials, participants treated with oral corticosteroids were more likely to have short-term resolution or improvement of symptoms than those receiving the control treatment: at days three to seven (risk ratio (RR) 1.3, 95% confidence interval (CI) 1.1 to 1

  11. 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.

  12. Effects of systemic domestic recombinant human erythropoietin on HIF-1α expression in the retina in a rabbit model of acute high intraocular pressure

    Institute of Scientific and Technical Information of China (English)

    Yan-ping Song; Jian-ming Wang; Mei Zhang; Na Hui; Shi-ping Zhao; Kai Hu

    2009-01-01

    Objective To observe the expression of hypoxia inducible faetor-1α (HIF-1α) in the retina of rabbits with acute high intraocular pressure and to investigate the mechanism of systemic domestic recombinant human erythropoietin (rhEPO) protecting the retina from ischemia-reperfusion injury. Methods First, control group and model group were established in rabbit eyes. The acute high intraocular pressure model was established by saline perfusion into anterior chamber, and then hypodermic injection of domestic rhEPO was made. HIF-1α protein in the retina was observed by immunohistochemical staining method on days 1, 3, 7 and 14 after retinal ischemla-reperfusion, respectively. Results No cells with HIF-la positive expression were observed in the retina of the control group. Ceils with HIF-1α positive expression in the model group outnumbered those in the control group (P < 0. 01). The resemblance pattern occurred in EPO group but its degree was slightly greater than that in the model group from day 3 after ischemia-reperfusion (P<0.05). Conclusion Domestic rhEPO can down-regulate the expression of HIF-1α in the retina with acute high intraocular pressure, which may be one of the mechanisms that rhEPO protects the retina from ischemia-reperfusion injury.

  13. A Conceptual Model for Episodes of Acute, Unscheduled Care.

    Science.gov (United States)

    Pines, Jesse M; Lotrecchiano, Gaetano R; Zocchi, Mark S; Lazar, Danielle; Leedekerken, Jacob B; Margolis, Gregg S; Carr, Brendan G

    2016-10-01

    We engaged in a 1-year process to develop a conceptual model representing an episode of acute, unscheduled care. Acute, unscheduled care includes acute illnesses (eg, nausea and vomiting), injuries, or exacerbations of chronic conditions (eg, worsening dyspnea in congestive heart failure) and is delivered in emergency departments, urgent care centers, and physicians' offices, as well as through telemedicine. We began with a literature search to define an acute episode of care and to identify existing conceptual models used in health care. In accordance with this information, we then drafted a preliminary conceptual model and collected stakeholder feedback, using online focus groups and concept mapping. Two technical expert panels reviewed the draft model, examined the stakeholder feedback, and discussed ways the model could be improved. After integrating the experts' comments, we solicited public comment on the model and made final revisions. The final conceptual model includes social and individual determinants of health that influence the incidence of acute illness and injury, factors that affect care-seeking decisions, specific delivery settings where acute care is provided, and outcomes and costs associated with the acute care system. We end with recommendations for how researchers, policymakers, payers, patients, and providers can use the model to identify and prioritize ways to improve acute care delivery.

  14. 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.

  15. In vitro and in vivo models of acute alcohol exposure

    Institute of Scientific and Technical Information of China (English)

    Angela Dolganiuc; Gyongyi Szabo

    2009-01-01

    Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute alcohol consumption also affects human wellbeing. Thus, there is a need for research models in order to fully understand the effect of acute alcohol abuse on different body systems and organs. The present manuscript summarizes the interdisciplinary advantages and disadvantages of currently available human and non-human models of acute alcohol abuse,and identifies their suitability for biomedical research.

  16. Comparison of a New Miniaturized Extracorporeal Membrane Oxygenation System With Integrated Rotary Blood Pump to a Standard System in a Porcine Model of Acute Lung Injury.

    Science.gov (United States)

    Pilarczyk, Kevin; Heckmann, Jens; Lyskawa, Kathrin; Strauß, Andreas; Haake, Nils; Wiese, Ingo; Jakob, Heinz; Kamler, Markus; Pizanis, Nikolaus

    2016-07-01

    Extracorporeal membrane oxygenation (ECMO) is used for severe acute respiratory distress syndrome. However, available ECMO systems are large and not well designed for fast delivery, emergency implantation, and interhospital transfer. Therefore, a new miniaturized oxygenator with integrated rotary blood pump (ILIAS) was developed and compared with a standard ECMO system in a large animal model. Acute lung injury was induced with repeated pulmonary saline lavage in 14 pigs until PaO2 /FiO2 -ratio was ECMO; group 3 (n = 5): vv-ILIAS. Gas exchange, hemodynamics, hemolysis, and coagulation activation were examined over a period of 8 h. No device failed during the observation period. PaCO2 decreased from 59.40 ± 4.14 mm Hg to 48.62 ± 4.50 mm Hg after 1 h in the ILIAS group compared with an improvement of PaCO2 from 48.86 ± 7.45 to 40.10 ± 6.02 in the conventional ECMO group (P = not significant [n.s.]). ARDS-induced respiratory acidosis was controlled promptly with a pH of 7.2 ± 0.1 at baseline increasing to 7.4 ± 0.1 in both study groups after 60 min of ECMO support. Mean carbon dioxide transfer was comparable between the conventional ECMO and ILIAS (211.36 ± 78.39 mL/min vs. 219.99 ± 76.72 mL/min, P = n.s.). PaO2 /FiO2 increased from 118.4 ± 15.5 mm Hg to 179.1 ± 72.4 mm Hg in the ILIAS group compared with an improvement of oxygenation from 107.1 ± 24.9 mm Hg to 179.0 ± 45.7 mm Hg in the standard ECMO group (P = n.s.). Mean oxygen transfer was calculated with 136.09 ± 30.25 mL/min for the ILIAS and 129.05 ± 36.28 mL/min for the standard ECMO. Hemodynamic instability or significant activation of the plasmatic coagulation was not observed. However, hemolysis was significantly higher in the ILIAS group compared with the conventional ECMO. As the ILIAS prototype provided excellent gas exchange with hemodynamic stability comparable with a standard ECMO

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

    African Journals Online (AJOL)

    hanumantp

    Systemic lupus erythematosus (SLE) is the prototypic autoimmune disease ... association with diverse clinical manifestations encompassing almost all organ .... acute adrenal insufficiency. The diagnosis of Addison's disease in our patient was.

  18. Systemic corticosteroids for acute sinusitis

    NARCIS (Netherlands)

    Venekamp, R.P.; Thompson, M.J.; Hayward, G.; Heneghan, C.J.; Mar, C.B. Del; Perera, R.; Glasziou, P.P.; Rovers, M.M.

    2014-01-01

    BACKGROUND: Acute sinusitis is the inflammation and swelling of the nasal and paranasal mucous membranes and is a common reason for patients to seek primary care consultations. The related impairment of daily functioning and quality of life is attributable to symptoms such as facial pain and nasal

  19. Systemic corticosteroids for acute sinusitis

    NARCIS (Netherlands)

    Venekamp, R.P.; Thompson, M.J.; Hayward, G.; Heneghan, C.J.; Mar, C.B. Del; Perera, R.; Glasziou, P.P.; Rovers, M.M.

    2014-01-01

    BACKGROUND: Acute sinusitis is the inflammation and swelling of the nasal and paranasal mucous membranes and is a common reason for patients to seek primary care consultations. The related impairment of daily functioning and quality of life is attributable to symptoms such as facial pain and nasal c

  20. 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.)

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

    Science.gov (United States)

    2016-10-01

    The problem being addressed is the unknown mechanism(s) in patients with acute pancreatitis, multiple trauma, severe burn, or sepsis responsible...technology. MSD technology enables measurement of biomarker levels using electrochemiluminescense detection . This process is initiated at carbon electrodes...enhance detection and improve sensitivity. Cytokines well-known to be involved in the SIRS early in AP were measured including interleukin-1β (IL-1β

  2. 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.

  3. Acute cerebral vasculopathy in systemic sclerosis.

    Science.gov (United States)

    Faucher, Benoit; Granel, Brigitte; Nicoli, Francois

    2013-12-01

    Systemic sclerosis is an autoimmune disease characterized by skin and deep organ fibrosis and obliterative microvasculopathy. Cerebral involvement is currently not recognized as a manifestation of the disease, although several morphologic and functional studies suggested a frequent cerebral involvement in systemic sclerosis. We report a new case of acute cerebral vasculopathy in a patient suffering from systemic sclerosis together with five historical cases identified through a literature review. Cerebral acute vasculopathy most often revealed the disease. Affected patients suffered often from limited or diffuse cutaneous systemic sclerosis. Reversibility of arterial lesions, absence of specific histologic findings, and association with severe peripheral vascular involvement plead for a major role of vasospasm. However, the apparent efficacy of immunosuppressive treatments suggests an association with inflammatory or immune mechanisms. Awareness should be raised because of the severity of the disease, the risk of relapse, and the possible occurrence early in the course of systemic sclerosis.

  4. Systemic corticosteroids for acute gout (Review)

    NARCIS (Netherlands)

    Janssens, H.J.; Lucassen, P.L.B.J.; Laar, F.A. van de; Janssen, M.; Lisdonk, E.H. van de

    2008-01-01

    BACKGROUND: Gout is one of the most frequently occurring rheumatic diseases, worldwide. Given the well-known drawbacks of the regular treatments for acute gout (non-steroidal anti-inflammatory drugs (NSAIDs), colchicine), systemic corticosteroids might be safe alternatives. OBJECTIVES: To assess the

  5. Systemic corticosteroids for acute gout (Review)

    NARCIS (Netherlands)

    Janssens, H.J.; Lucassen, P.L.B.J.; Laar, F.A. van de; Janssen, M.; Lisdonk, E.H. van de

    2008-01-01

    BACKGROUND: Gout is one of the most frequently occurring rheumatic diseases, worldwide. Given the well-known drawbacks of the regular treatments for acute gout (non-steroidal anti-inflammatory drugs (NSAIDs), colchicine), systemic corticosteroids might be safe alternatives. OBJECTIVES: To assess the

  6. 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 ...

  7. 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 ...

  8. 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.

  9. Models of acute and chronic pancreatitis.

    Science.gov (United States)

    Lerch, Markus M; Gorelick, Fred S

    2013-06-01

    Animal models of acute and chronic pancreatitis have been created to examine mechanisms of pathogenesis, test therapeutic interventions, and study the influence of inflammation on the development of pancreatic cancer. In vitro models can be used to study early stage, short-term processes that involve acinar cell responses. Rodent models reproducibly develop mild or severe disease. One of the most commonly used pancreatitis models is created by administration of supraphysiologic concentrations of caerulein, an ortholog of cholecystokinin. Induction of chronic pancreatitis with factors thought to have a role in human disease, such as combinations of lipopolysaccharide and chronic ethanol feeding, might be relevant to human disease. Models of autoimmune chronic pancreatitis have also been developed. Most models, particularly of chronic pancreatitis, require further characterization to determine which features of human disease they include.

  10. Systemic inflammatory response following acute myocardial infarction.

    Science.gov (United States)

    Fang, Lu; Moore, Xiao-Lei; Dart, Anthony M; Wang, Le-Min

    2015-05-01

    Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Inflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction (AMI). Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes (such as death, recurrent myocardial infarction, and heart failure) in patients with AMI.

  11. Systemic inflammatory response following acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Lu FANG; Xiao-Lei Moore; Anthony M Dart; Le-Min WANG

    2015-01-01

    Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Inflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction (AMI). Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes (such as death, recurrent myocardial in-farction, and heart failure) in patients with AMI.

  12. A canine model of normovolaemic acute anaemia

    Directory of Open Access Journals (Sweden)

    T.C. Spotswood

    2005-09-01

    Full Text Available The objective was to develop a non-terminal, acute normovolaemic anaemia model in dogs that has minimal effects on patient well-being. Eleven normal Beagle dogs were used. About 20 % of the circulating blood volume was removed from the jugular vein 1-3 times per day over a 3-4 day period until a haematocrit (Ht of 13-17 % was obtained. Normovolaemia was maintained by replacing the volume deficit of the red blood cells with Ringer's lactate and re-infusing the plasma. Full blood count and Ht were monitored twice daily. The 13-17 % Ht was reached within 3-4 days with the number of phlebotomies ranging from four to seven. The model was primarily developed to determine echocardiographic values as well as Doppler abdominal splanchnic blood flow parameters in anaemic dogs as part of a study that will compare these results to similar studies in babesiosis-induced anaemia. The model may also be useful in the evaluation of the pathophysiology of anaemia in dogs or as a model for anaemia in humans.

  13. 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.

  14. 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 bene

  15. 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 benef

  16. 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

  17. 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

  18. 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 bene

  19. 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 benef

  20. Experimental models of hepatotoxicity related to acute liver failure

    Science.gov (United States)

    Maes, Michaël; Vinken, Mathieu; Jaeschke, Hartmut

    2015-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. PMID:26631581

  1. Model Systems

    Directory of Open Access Journals (Sweden)

    Francisco Rodríguez-Trelles

    1998-12-01

    Full Text Available Current efforts to study the biological effects of global change have focused on ecological responses, particularly shifts in species ranges. Mostly ignored are microevolutionary changes. Genetic changes may be at least as important as ecological ones in determining species' responses. In addition, such changes may be a sensitive indicator of global changes that will provide different information than that provided by range shifts. We discuss potential candidate systems to use in such monitoring programs. Studies of Drosophila subobscura suggest that its chromosomal inversion polymorphisms are responding to global warming. Drosophila inversion polymorphisms can be useful indicators of the effects of climate change on populations and ecosystems. Other species also hold the potential to become important indicators of global change. Such studies might significantly influence ecosystem conservation policies and research priorities.

  2. 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 (Phosphoba

  3. 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

  4. [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 modeling through automated methods has been attempted. A systematic review of the literature of diagnostic tests that applied intelligent systems tools in the diagnosis of acute coronary syndromes. This manuscript presents a systematic review of the literature from the Medline, Embase, Scopus, IEEE/IET Electronic Library, ISI Web Of Science, Latindex and LILACS databases that includes the diagnostic evaluation of acute coronary syndromes through 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. In total, 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; 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. We found extensive evidence that approaches using intelligent systems tools achieve 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.

  5. [The glutathione system in the blood of rats and morphological changes of the pancreas under experimental acute and chronic pancreatitis].

    Science.gov (United States)

    Makarchuk, V A; Ushakova, H O; Krylova, O O

    2013-01-01

    In experiment on laboratory rats the models of acute and chronic pancreatitis were developed to study the changes of lipoperoxidation-antioxidant protection system depending on morphological changes of the pancreas. The acute and chronic pancreatitis is accompanied with intensification of lipoperoxidation and gradual inhibition of antioxidant system due to development of subsequent chronization of the pathological process.

  6. Severity assessment of acute pancreatitis: applying Marshall scoring system

    Directory of Open Access Journals (Sweden)

    André Lanza Carioca

    2015-10-01

    Full Text Available Objective: To analyze the effectiveness of the Marshall scoring system to evaluate the severity of acute pancreatitis (AP. Methods : We performed a prospective, observational study in 39 patients with AP evaluated by the Marshall scoring system and the Ranson criteria (admission and 48 hours. We assessed the progression of the disease for seven days and compared the data of the two criteria. Results : Seven patients died during the observation period and one died afterwards. All deaths had shown failure of at least one system by the Marshall method. Conclusion : The Marshall scoring system may be used as an effective and simplified application method to assess the severity of acute pancreatitis.

  7. Non lineal respiratory systems mechanics simulation of acute respiratory distress syndrome during mechanical ventilation.

    Science.gov (United States)

    Madorno, Matias; Rodriguez, Pablo O

    2010-01-01

    Model and simulation of biological systems help to better understand these systems. In ICUs patients often reach a complex situation where supportive maneuvers require special expertise. Among them, mechanical ventilation in patients suffering from acuter respiratory distress syndrome (ARDS) is specially challenging. This work presents a model which can be simulated and use to help in training of physicians and respiratory therapists to analyze the respiratory mechanics in this kind of patients. We validated the model in 2 ARDS patients.

  8. COMIDA: a radionuclide food chain model for acute fallout deposition.

    Science.gov (United States)

    Abbott, M L; Rood, A S

    1994-01-01

    A dynamic food chain model and computer code, named "COMIDA," has been developed to estimate radionuclide concentrations in agricultural food products following an acute fallout event. COMIDA estimates yearly harvest concentrations for five human crop types (Bq kg-1 crop per Bq m-2 deposited) and integrated concentrations for four animal products (Bq d kg-1 animal product per Bq m-2) for a unit deposition that occurs on any user-specified day of the year. COMIDA is structurally very similar to the PATHWAY model and includes the same seasonal transport processes and discrete events for soil and vegetation compartments. Animal product assimilation is modeled using simpler equilibrium models. Differential transport and ingrowth of up to three radioactive progeny are also evaluated. Benchmark results between COMIDA and PATHWAY for monthly fallout events show very similar seasonal agreement for integrated concentrations in milk and beef. Benchmark results between COMIDA and four international steady-state models show good agreement for deposition events that occur during the middle of the growing season. COMIDA will be implemented in the new Department of Energy version of the MELCOR Accident Consequence Code System for evaluation of accidental releases from nuclear power plants.

  9. EFFECTS OF ACUTE HYPOGLYCEMIA ON THE OREXIN SYSTEM IN RAT

    Institute of Scientific and Technical Information of China (English)

    Yu-yan Zhao; Lei Guo; Jian Du; Guo-liang Liu

    2005-01-01

    Objective To evaluate the effects of acute glucose level changes on expression of prepro-orexin, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) mRNA in rat hypothalamus tissue and pancreatic islets cells.Methods Thirty adult male Wistar rats were randomly divided into three equal groups (n= 10). The acute hypoglycemia rat model was induced by a single subcutaneous injection of insulin. Twenty acute hypoglycemia rats were divided into group B and group C. Group B was allowed to eat freely, while group C was food-deprived. Control rats were injected the same volume of saline. The effect of glucose levels (2.8 mmol/L and 8.3 mmol/L) on pancreatic islet cell orexin system was detected in pancreas islet cell cultured in vitro. The expression of prepro-orexin and OXR mRNA was examined in rat hypothalamus tissue and pancreatic islets cell cultured in vitro using reverse transcription-polymerase chain reaction (RTPCR).Results Expression of orexin mRNA increased about 150% for the food-deprived hypoglycemia rats in comparison with control group (P < 0.01), whereas expression of OX1R mRNA decreased up to 30% (P < 0.01). However, expression of OX2R mRNA was unchanged in comparison with control group. In vitro, after incubation with 2.8 mmol/L glucose for 6hours, the expression of prepro-orexin mRNA increased 2 times in rat pancreas islet cells in comparison with 8.3 mmol/Lglucose group (P < 0.01). But the expression of OX1R mRNA was not sensitive to acute glucose fluctuation.Conclusions Orexin in rat hypothalamus is stimulated by decline in blood glucose and inhibited by signals related to feeding. Moreover, glucose plays a role in modulating the gene expression of prepro-orexin in rat pancreatic islet cells.

  10. 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.

    2017-01-01

    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

  11. 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

  12. Mouse models of acute exacerbations of allergic asthma.

    Science.gov (United States)

    Kumar, Rakesh K; Herbert, Cristan; Foster, Paul S

    2016-07-01

    Most of the healthcare costs associated with asthma relate to emergency department visits and hospitalizations because of acute exacerbations of underlying chronic disease. Development of appropriate animal models of acute exacerbations of asthma is a necessary prerequisite for understanding pathophysiological mechanisms and assessing potential novel therapeutic approaches. Most such models have been developed using mice. Relatively few mouse models attempt to simulate the acute-on-chronic disease that characterizes human asthma exacerbations. Instead, many reported models involve relatively short-term challenge with an antigen to which animals are sensitized, followed closely by an unrelated triggering agent, so are better described as models of potentiation of acute allergic inflammation. Triggers for experimental models of asthma exacerbations include (i) challenge with high levels of the sensitizing allergen (ii) infection by viruses or fungi, or challenge with components of these microorganisms (iii) exposure to environmental pollutants. In this review, we examine the strengths and weaknesses of published mouse models, their application for investigation of novel treatments and potential future developments.

  13. 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.

  14. 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.

  15. Nursing practice models for acute and critical care: overview of care delivery models.

    Science.gov (United States)

    Shirey, Maria R

    2008-12-01

    This article provides a historical overview of nursing models of care for acute and critical care based on currently available literature. Models of care are defined and their advantages and disadvantages presented. The distinctive differences between care delivery models and professional practice models are explained. The historical overview of care delivery models provides a foundation for the introduction of best practice models that will shape the environment for acute and critical care in the future.

  16. Continuous system modeling

    Science.gov (United States)

    Cellier, Francois E.

    1991-01-01

    A comprehensive and systematic introduction is presented for the concepts associated with 'modeling', involving the transition from a physical system down to an abstract description of that system in the form of a set of differential and/or difference equations, and basing its treatment of modeling on the mathematics of dynamical systems. Attention is given to the principles of passive electrical circuit modeling, planar mechanical systems modeling, hierarchical modular modeling of continuous systems, and bond-graph modeling. Also discussed are modeling in equilibrium thermodynamics, population dynamics, and system dynamics, inductive reasoning, artificial neural networks, and automated model synthesis.

  17. Towards a Multiscale Model of Acute HIV Infection

    Directory of Open Access Journals (Sweden)

    Anass Bouchnita

    2017-01-01

    Full Text Available Human Immunodeficiency Virus (HIV infection of humans represents a complex biological system and a great challenge to public health. Novel approaches for the analysis and prediction of the infection dynamics based on a multi-scale integration of virus ontogeny and immune reactions are needed to deal with the systems’ complexity. The aim of our study is: (1 to formulate a multi-scale mathematical model of HIV infection; (2 to implement the model computationally following a hybrid approach; and (3 to calibrate the model by estimating the parameter values enabling one to reproduce the “standard” observed dynamics of HIV infection in blood during the acute phase of primary infection. The modeling approach integrates the processes of infection spread and immune responses in Lymph Nodes (LN to that observed in blood. The spatio-temporal population dynamics of T lymphocytes in LN in response to HIV infection is governed by equations linking an intracellular regulation of the lymphocyte fate by intercellular cytokine fields. We describe the balance of proliferation, differentiation and death at a single cell level as a consequence of gene activation via multiple signaling pathways activated by IL-2, IFNa and FasL. Distinct activation thresholds are used in the model to relate different modes of cellular responses to the hierarchy of the relative levels of the cytokines. We specify a reference set of model parameter values for the fundamental processes in lymph nodes that ensures a reasonable agreement with viral load and CD4+ T cell dynamics in blood.

  18. Ligustrazine alleviates acute lung injury in a rat model of acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jian-Xin Zhang; Sheng-Chun Dang

    2006-01-01

    BACKGROUND:Acute necrotizing pancreatitis leads to a systemic inlfammatory response characterized by widespread leukocyte activation and, as a consequence, distant lung injury. The aim of this study was to evaluate the effect of ligustrazine, extracted from Ligusticum wallichii a traditional Chinese medicine, on lung injury in a rat model of acute necrotizing pancreatitis (ANP). METHODS:A total of 192 rats were randomly divided into three groups: control (C group); ANP without treatment (P group); and ANP treated with ligustrazine (T group). Each group was further divided into 0.5, 2, 6 and 12 hours subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. For the T group, sodium taurocholate was infused as above, then 0.6%ligustrazine was administered via the femoral vein. The effects of ligustrazine on the severity of lung injury were assessed by lung wet/dry weight ratio, myeloperoxidase (MPO) activity and histopathological changes. Pulmonary blood lfow was determined by the radioactive microsphere technique (RMT). RESULTS:The blood lfow in the P group was signiifcantly lower than that of the C group, while the blood lfow in the T group was signiifcantly higher than that of the P group but showed no signiifcant difference from the C group. Compared with C group, the lung wet/dry ratios in both the P and T groups were signiifcantly increased, but there was no signiifcant difference between them. The MPO activity in the P group was greatly increased over that of the C group. In the T group, although the MPO activity was also higher than in the C group, it much less increased than in the P group. Moreover, the difference between P and T groups was signiifcant after 0.5 to 12 hours. After induction of the ANP model, the pancreas showed mild edema and congestion;the longer the time, the more severe this became. The pulmonary pathological changes were

  19. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    Science.gov (United States)

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-06-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

  20. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    Science.gov (United States)

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-01-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries. PMID:27351915

  1. 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

  2. Preliminary Model of Acute Mountain Sickness Severity

    Science.gov (United States)

    2010-10-01

    variance, the Akaike information criterion (AIC) and Bayesian information criterion (BIC) were utilized in selecting the final model using the... information and completed an Environmental Symptoms Questionnaire (ESQ). The ESQ assessed AMS severity using the validated AMS-Cerebral (AMS-C) factor...reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching

  3. Adequacy indices for dialysis in acute renal failure: kinetic modeling.

    Science.gov (United States)

    Debowska, Malgorzata; Lindholm, Bengt; Waniewski, Jacek

    2010-05-01

    Many aspects of the management of renal replacement therapy in acute renal failure (ARF), including the appropriate assessment of dialysis adequacy, remain unresolved, because ARF patients often are not in a metabolic steady state. The aim of this study was to evaluate a system of adequacy indices for dialysis in ARF patients using urea and creatinine kinetic modeling. Kinetic modeling was performed for two different fictitious patients (A and B) with characteristics described by the average parameters for two patient groups and for two blood purification treatments: sustained low efficiency daily dialysis (SLEDD) in Patient A and continuous venovenous hemofiltration (CVVH) in Patient B, based on data from a clinical report. Urea and creatinine generation rates were estimated according to the clinical data on the solute concentrations in blood. Then, using estimated generation rates, two hypothetical treatments were simulated, CVVH in Patient A and SLEDD in Patient B. KT/V, fractional solute removal (FSR) and equivalent renal clearance (EKR) were calculated according to the definitions developed for metabolically unstable patients. CVVH appeared as being more effective than SLEDD because KT/V, FSR, and EKR were higher for CVVH than SLEDD in Patients A and B. Creatinine KT/V, FSR, and EKR were lower and well correlated to the respective indices for urea. Urea and creatinine generation rates were overestimated more than twice in Patient A and by 30-40% in Patient B if calculated assuming the metabolically stable state than if estimated by kinetic modeling. Adequacy indices and solute generation rates for ARF patients should be estimated using the definition for unsteady metabolic state. EKR and FSR were higher for urea and creatinine with CVVH than with SLEDD, because of higher K.T and minimized compartmental effects for CVVH.

  4. 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.

  5. Systemic inflammation as a therapeutic target in acute ischemic stroke.

    Science.gov (United States)

    Dziedzic, Tomasz

    2015-05-01

    Acute systemic inflammatory reaction superimposed on chronic low-grade inflammation accompanies acute ischemic stroke. Elevated blood levels of systemic inflammatory markers such as IL-6 or C-reactive protein are associated with an unfavorable functional outcome and increased mortality after stroke. Animal studies have demonstrated a causal relationship between systemic inflammation and ischemic brain damage. The mechanisms linking systemic inflammation with poor outcome include increased neutrophil infiltration of cerebral cortex, disruption of the blood-brain barrier, impaired tissue reperfusion, increased platelet activation and microvascular coagulation and complement-dependent brain injury. Non-selective (e.g., by statins) or selective (e.g., by inhibition of IL-6) attenuation of systemic inflammation, enhancement of systemic anti-inflammatory response (e.g., by infusion of IL-1 receptor antagonist), prevention of infections that exacerbate systemic inflammation or inhibition of neuronal pathways triggering inflammatory reaction are potential therapeutic targets in stroke patients. This review discusses the relationship between systemic inflammation, cerebral ischemia and prognosis in the context of therapeutic strategies.

  6. 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 

  7. Enhanced muscle shortening and impaired Ca2+ channel function in an acute septic myopathy model.

    Science.gov (United States)

    Friedrich, Oliver; Hund, Ernst; von Wegner, Frederic

    2010-04-01

    Myopathies in critically ill patients are increasingly documented. Various animal models of chronic sepsis have been employed to investigate reduced membrane excitability or altered isometric contractility of skeletal muscle. In contrast, immediate changes occurring during acute sepsis are significantly under-characterised; L-type Ca(2+) channel function or isotonic shortening are examples. We recorded slowly activating L-type Ca(2+) currents (I (Ca)) in voltage-clamped single intact mouse skeletal muscle fibres and tested the effects of acute challenge with serum fractions from critical illness myopathy patients (CIM). Using a high-speed camera system, we simultaneously recorded unloaded fibre shortening during isotonic contractions with unprecedented temporal resolution (approximately 1,600 frames/s). Time courses of fibre lengths and shortening velocity were determined from automated imaging algorithms. CIM fractions acutely induced depression of I (Ca) amplitudes with no shifts in I (Ca)-V-relations. Voltage-dependent inactivation was unaltered and I (Ca) activation and inactivation kinetics were prolonged compared to controls. Unexpectedly, maximum unloaded speed of shortening was slightly faster following CIM serum applications, suggesting a direct action of CIM serum on weak-binding-state cross-bridges. Our results are compatible with a model where CIM serum might acutely reduce a fraction of functional L-type Ca(2+) channels and could account for reduced SR Ca(2+) release and force production in CIM patients. Acute increase in isotonic shortening velocity might be an early diagnostic feature suitable for testing in clinical studies. The acute challenge model is also robust against atrophy or fibre type changes that ordinarily would have to be considered in chronic sepsis models.

  8. Breast cancer acute radiotherapy morbidity evaluated by different scoring systems.

    Science.gov (United States)

    López, Escarlata; Núñez, M Isabel; Guerrero, M Rosario; del Moral, Rosario; de Dios Luna, Juan; del Mar Rodríguez, M; Valenzuela, M Teresa; Villalobos, Mercedes; Ruiz de Almodóvar, José Mariano

    2002-05-01

    Reporting of the outcome of radiotherapy is not satisfactory without a description of the treatment-related side effects. The purposes of this paper were: (1) to evaluate the frequency and the severity of collateral skin reactions in a group of breast cancer patients; (2) to report the acute reactions using some current scoring systems and to compare the application of them, and (3) to investigate the variation between intra- and interobservers using these different scales. We studied 108 breast cancer patients who, after surgical treatment, received adjuvant radiotherapy. Clinical skin evaluation was always performed by the same radiotherapist the last day of treatment, and the collateral radiation effects were photographed at that moment to facilitate later evaluations by another two expert doctors. Normal tissue damage was scored according to the Radiation Therapy Oncology Group/The European Organisation for Research, and Treatment of Cancer/ (RTOG/EORTC), the Danish, the European, and the Biomed2 side-effect scales. The most frequent acute complications found were erythema (91.7%), dry desquamation (29.6%) and moist desquamation (35.2%). The reactions were classified as severe in 13.9, 23, 18.5 and 13% of the patients with each of the different systems used, respectively. The concordance between the scoring of radiation-induced side effects on the skin assessed by direct observation of the patients or by examination of the photographic document was sufficient. This is a warrant of accuracy in the evaluation of acute normal tissue lesions. Our results allow us to state the advantage of the RTOG system over the others in terms of evaluating the acute effects produced by radiotherapy of women with breast cancer.

  9. 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

  10. 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.

  11. Prediction of Severe Acute Pancreatitis Using a Decision Tree Model Based on the Revised Atlanta Classification of Acute Pancreatitis.

    Directory of Open Access Journals (Sweden)

    Zhiyong Yang

    Full Text Available To develop a model for the early prediction of severe acute pancreatitis based on the revised Atlanta classification of acute pancreatitis.Clinical data of 1308 patients with acute pancreatitis (AP were included in the retrospective study. A total of 603 patients who were admitted to the hospital within 36 hours of the onset of the disease were included at last according to the inclusion criteria. The clinical data were collected within 12 hours after admission. All the patients were classified as having mild acute pancreatitis (MAP, moderately severe acute pancreatitis (MSAP and severe acute pancreatitis (SAP based on the revised Atlanta classification of acute pancreatitis. All the 603 patients were randomly divided into training group (402 cases and test group (201 cases. Univariate and multiple regression analyses were used to identify the independent risk factors for the development of SAP in the training group. Then the prediction model was constructed using the decision tree method, and this model was applied to the test group to evaluate its validity.The decision tree model was developed using creatinine, lactate dehydrogenase, and oxygenation index to predict SAP. The diagnostic sensitivity and specificity of SAP in the training group were 80.9% and 90.0%, respectively, and the sensitivity and specificity in the test group were 88.6% and 90.4%, respectively.The decision tree model based on creatinine, lactate dehydrogenase, and oxygenation index is more likely to predict the occurrence of SAP.

  12. 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.

  13. 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...

  14. Is leptin related to systemic inflammatory response in acute pancreatitis?

    Institute of Scientific and Technical Information of China (English)

    Andrés Duarte-Rojo; Ana Lezama-Barreda; Mar(i)a Teresa Ram(i)rez-lglesias; Mario Peláez Luna; Guillermo Robles-Diaz

    2006-01-01

    AIM: To evaluate the relationship between leptin and systemic inflammation in acute pancreatitis.METHODS: Consecutive patients with acute pancreatitis were included. Body mass index and serum samples were obtained at admission. Leptin, TNF-α, IL-6, -8and -10 levels were determined by ELISA. Severity was defined according to Atlanta criteria.RESULTS: Fifty-two (29 females) patients were studied.Overall body mass index was similar between mild and severe cases, although women with severe pancreatitis had lower body mass index (P = 0.04) and men showed higher body mass index (P = 0.05). No difference was found in leptin levels regarding the severity of pancreatitis, but higher levels tended to appear in male patients with increased body mass index and severe pancreatitis (P = 0.1). A multivariate analysis showed no association between leptin levels and severity. The strongest cytokine associated with severity was IL-6.Correlations of leptin with another cytokines only showed a trend for IL-8 (P = 0.058).CONCLUSION: High body mass index was associated with severity only in males, which may be related to android fat distribution. Serum leptin seems not to play a role on the systemic inflammatory response in acute pancreatitis and its association with severe outcome in males might represent a marker of increased adiposity.

  15. Digestive system manifestations in patients with severe acute respiratory syndrome

    Institute of Scientific and Technical Information of China (English)

    詹俊; 陈为宪; 李楚强; 伍卫; 李建军; 江山平; 王景峰; 曾志勇; 黄子通; 黄洪章

    2003-01-01

    Objective To explore digestive system manifestations in patients with severe acute respiratory syndrome (SARS).Method The clinical data of 96 cases with SARS admitted into our hospital from February 6, 2003 to March 28, 2003 were retrospectively analyzed.Results Among the 96 cases, 26 cases (27%) had diarrhea, 17 (18%) had nausea, 6 (6%) had vomiting, 16 (17%) had bellyache, and 8 (8%) had ALT elevation.Conclusions Patients with SARS may have digestive system manifestations; diarrhea is the most common symptom.

  16. Decision support systems for robotic surgery and acute care

    Science.gov (United States)

    Kazanzides, Peter

    2012-06-01

    Doctors must frequently make decisions during medical treatment, whether in an acute care facility, such as an Intensive Care Unit (ICU), or in an operating room. These decisions rely on a various information sources, such as the patient's medical history, preoperative images, and general medical knowledge. Decision support systems can assist by facilitating access to this information when and where it is needed. This paper presents some research eorts that address the integration of information with clinical practice. The example systems include a clinical decision support system (CDSS) for pediatric traumatic brain injury, an augmented reality head- mounted display for neurosurgery, and an augmented reality telerobotic system for minimally-invasive surgery. While these are dierent systems and applications, they share the common theme of providing information to support clinical decisions and actions, whether the actions are performed with the surgeon's own hands or with robotic assistance.

  17. 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.

  18. Calpains promote neutrophil recruitment and bacterial clearance in an acute bacterial peritonitis model.

    Science.gov (United States)

    Kumar, Vijay; Everingham, Stephanie; Hall, Christine; Greer, Peter A; Craig, Andrew W B

    2014-03-01

    Activation of the innate immune system is critical for clearance of bacterial pathogens to limit systemic infections and host tissue damage. Here, we report a key role for calpain proteases in bacterial clearance in mice with acute peritonitis. Using transgenic mice expressing Cre recombinase primarily in innate immune cells (fes-Cre), we generated conditional capns1 knockout mice. Consistent with capns1 being essential for stability and function of the ubiquitous calpains (calpain-1, calpain-2), peritoneal cells from these mice had reduced levels of calpain-2/capns1, and reduced proteolysis of their substrate selenoprotein K. Using an acute bacterial peritonitis model, we observed impaired bacterial killing within the peritoneum and development of bacteremia in calpain knockout mice. These defects correlated with significant reductions in IL-1α release, neutrophil recruitment, and generation of reactive oxygen species in calpain knockout mice with acute bacterial peritonitis. Peritoneal macrophages from calpain knockout mice infected with enterobacteria ex vivo, were competent in phagocytosis of bacteria, but showed impaired clearance of intracellular bacteria compared with control macrophages. Together, these results implicate calpains as key mediators of effective innate immune responses to acute bacterial infections, to prevent systemic dissemination of bacteria that can lead to sepsis.

  19. 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.

  20. Fentanyl Iontophoretic Transdermal System: A Review in Acute Postoperative Pain.

    Science.gov (United States)

    Scott, Lesley J

    2016-04-01

    Fentanyl iontophoretic transdermal system (ITS) [Ionsys(®)] is indicated for the management of acute postoperative pain in adults requiring opioid analgesia in the hospital setting. This article reviews the clinical use of fentanyl ITS for postoperative pain management, and summarizes the pharmacology of fentanyl and the characteristics of the two-component fentanyl ITS (Ionsys(®)) device. In well-designed, multicentre clinical trials, fentanyl ITS was an effective and generally well tolerated method for managing acute postoperative pain in inpatients who had undergone major abdominal, thoracic or orthopaedic surgery. Overall, fentanyl ITS provided equivalent analgesic efficacy to that with morphine patient-controlled intravenous analgesia (PCIA), but was perceived to be more convenient/easier to use than morphine PCIA by patients, nurses and physical therapists. Patients receiving fentanyl ITS also had a greater ability to mobilize after surgery than patients receiving morphine PCIA. In addition, relative to morphine PCIA, fentanyl ITS offers advantages in terms of the noninvasive administrative route (i.e. transdermal needle-free administration), pre-programmed delivery (no risk of programming errors/incorrect dosing) and improved tolerability with regard to the overall incidence of opioid-related adverse events (ORAEs) and some individual ORAEs. Hence, fentanyl ITS is a useful option for the management of acute postoperative pain in adults requiring opioid analgesia in the hospital setting.

  1. Acute systemic rapamycin induces neurobehavioral alterations in rats.

    Science.gov (United States)

    Hadamitzky, Martin; Herring, Arne; Keyvani, Kathy; Doenlen, Raphael; Krügel, Ute; Bösche, Katharina; Orlowski, Kathrin; Engler, Harald; Schedlowski, Manfred

    2014-10-15

    Rapamycin is a drug with antiproliferative and immunosuppressive properties, widely used for prevention of acute graft rejection and cancer therapy. It specifically inhibits the activity of the mammalian target of rapamycin (mTOR), a protein kinase known to play an important role in cell growth, proliferation and antibody production. Clinical observations show that patients undergoing therapy with immunosuppressive drugs frequently suffer from affective disorders such as anxiety or depression. However, whether these symptoms are attributed to the action of the distinct compounds remains rather elusive. The present study investigated in rats neurobehavioral consequences of acute rapamycin treatment. Systemic administration of a single low dose rapamycin (3mg/kg) led to enhanced neuronal activity in the amygdala analyzed by intracerebral electroencephalography and FOS protein expression 90min after drug injection. Moreover, behavioral investigations revealed a rapamycin-induced increase in anxiety-related behaviors in the elevated plus-maze and in the open-field. The behavioral alterations correlated to enhanced amygdaloid expression of KLK8 and FKBP51, proteins that have been implicated in the development of anxiety and depression. Together, these results demonstrate that acute blockade of mTOR signaling by acute rapamycin administration not only causes changes in neuronal activity, but also leads to elevated protein expression in protein kinase pathways others than mTOR, contributing to the development of anxiety-like behavior. Given the pivotal role of the amygdala in mood regulation, associative learning, and modulation of cognitive functions, our findings raise the question whether therapy with rapamycin may induce alterations in patients neuropsychological functioning.

  2. 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

    ) 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...

  3. 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......) 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...... 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....

  4. 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.

  5. 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.

  6. Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis.

    Science.gov (United States)

    Wang, Yunan; Kayoumu, Abudurexiti; Lu, Guotao; Xu, Pengfei; Qiu, Xu; Chen, Liye; Qi, Rong; Huang, Shouxiong; Li, Weiqin; Wang, Yuhui; Liu, George

    2016-06-15

    The hamster has been shown to share a variety of metabolic similarities with humans. To replicate human acute pancreatitis with hamsters, we comparatively studied the efficacy of common methods, such as the peritoneal injections of caerulein, L-arginine, the retrograde infusion of sodium taurocholate, and another novel model with concomitant administration of ethanol and fatty acid. The severity of pancreatitis was evaluated by serum amylase activity, pathological scores, myeloperoxidase activity, and the expression of inflammation factors in pancreas. The results support that the severity of pathological injury is consistent with the pancreatitis induced in mice and rat using the same methods. Specifically, caerulein induced mild edematous pancreatitis accompanied by minimal lung injury, while L-arginine induced extremely severe pancreatic injury including necrosis and neutrophil infiltration. Infusion of Na-taurocholate into the pancreatic duct induced necrotizing pancreatitis in the head of pancreas and lighter inflammation in the distal region. The severity of acute pancreatitis induced by combination of ethanol and fatty acids was between the extent of caerulein and L-arginine induction, with obvious inflammatory cells infiltration. In view of the advantages in lipid metabolism features, hamster models are ideally suited for the studies of pancreatitis associated with altered metabolism in humans.

  7. Multiscale Cloud System Modeling

    Science.gov (United States)

    Tao, Wei-Kuo; Moncrieff, Mitchell W.

    2009-01-01

    The central theme of this paper is to describe how cloud system resolving models (CRMs) of grid spacing approximately 1 km have been applied to various important problems in atmospheric science across a wide range of spatial and temporal scales and how these applications relate to other modeling approaches. A long-standing problem concerns the representation of organized precipitating convective cloud systems in weather and climate models. Since CRMs resolve the mesoscale to large scales of motion (i.e., 10 km to global) they explicitly address the cloud system problem. By explicitly representing organized convection, CRMs bypass restrictive assumptions associated with convective parameterization such as the scale gap between cumulus and large-scale motion. Dynamical models provide insight into the physical mechanisms involved with scale interaction and convective organization. Multiscale CRMs simulate convective cloud systems in computational domains up to global and have been applied in place of contemporary convective parameterizations in global models. Multiscale CRMs pose a new challenge for model validation, which is met in an integrated approach involving CRMs, operational prediction systems, observational measurements, and dynamical models in a new international project: the Year of Tropical Convection, which has an emphasis on organized tropical convection and its global effects.

  8. 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.

  9. Acute carbon monoxide poisoning: animal models: a review.

    Science.gov (United States)

    Penney, D G

    1990-05-31

    Animals have been used for well over a century in an attempt to understand the toxicology, physiology, and pathology of acute carbon monoxide poisoning. Whether the toxic effects of this gas result from primary hypoxia, as in hypoxic hypoxia to which it is frequently compared, or from direct tissue effects since it enters cells and binds to certain vital components, remains a point of controversy. Acute severe poisoning in man and animals affects primarily the cardiovascular and nervous systems, and frequently produces neurologic dysfunction. Morphologically, tissue damage is usually confined to the white matter. The root cause is at best poorly understood and major investigative efforts have been made toward its elucidation. Many studies with rats, cats and primates indicate a major role for CO-induced hypotension, which serves to compromise blood flow and exacerbate acidosis. The likely cellular mechanisms in this process are only now becoming apparent. This review critically examines the recent as well as a few older CO-animal studies. In scope, they fall into several broad categories: general cardiopulmonary effects, metabolic and tissue effects, general resistance (i.e. tolerance), effects on the central nervous system including blood flow, neurochemistry, morphology and behavior, and finally, experimental therapeutic approaches.

  10. Dynamic Systems Modeling

    Directory of Open Access Journals (Sweden)

    Sorin Dan ŞANDOR

    2003-01-01

    Full Text Available System Dynamics was introduced by Jay W. Forrester in the 1960s. Since then the methodology was adopted in many areas of natural or social sciences. This article tries to present briefly how this methodology works, both as Systems Thinking and as Modelling with Vensim computer software.

  11. Modeling Sustainable Food Systems

    Science.gov (United States)

    Allen, Thomas; Prosperi, Paolo

    2016-05-01

    The processes underlying environmental, economic, and social unsustainability derive in part from the food system. Building sustainable food systems has become a predominating endeavor aiming to redirect our food systems and policies towards better-adjusted goals and improved societal welfare. Food systems are complex social-ecological systems involving multiple interactions between human and natural components. Policy needs to encourage public perception of humanity and nature as interdependent and interacting. The systemic nature of these interdependencies and interactions calls for systems approaches and integrated assessment tools. Identifying and modeling the intrinsic properties of the food system that will ensure its essential outcomes are maintained or enhanced over time and across generations, will help organizations and governmental institutions to track progress towards sustainability, and set policies that encourage positive transformations. This paper proposes a conceptual model that articulates crucial vulnerability and resilience factors to global environmental and socio-economic changes, postulating specific food and nutrition security issues as priority outcomes of food systems. By acknowledging the systemic nature of sustainability, this approach allows consideration of causal factor dynamics. In a stepwise approach, a logical application is schematized for three Mediterranean countries, namely Spain, France, and Italy.

  12. Resveratrol lacks protective activity against acute seizures in mouse models.

    Science.gov (United States)

    Tomaciello, Francesca; Leclercq, Karine; Kaminski, Rafal M

    2016-10-06

    Resveratrol (3,4',5-stilbenetriol) is a natural product having diverse anti-inflammatory and antioxidant properties. The compound has a wide spectrum of pharmacological and metabolic activity, including cardioprotective, neuroprotective, anticarcinogenic and anti-aging effects reported in numerous studies. Some reports also suggest potential anticonvulsant properties of resveratrol. In the present study, we used in mice three different seizure models which are routinely applied in preclinical drug discovery. The protective effects of resveratrol were evaluated in the pentylenetetrazole (PTZ), maximal electroshock (MES) and 6-Hz electrical seizure models. Resveratrol (up to 300mg/kg) administered ip (5-60min pre-treatment time) remained without any protective activity against seizures induced in these models. There was only a trend towards a delay in seizure latency, which reached statistical significance after treatment with resveratrol (100mg/kg; 15min) in case of tonic convulsions induced by PTZ. Phenobarbital (PHB, ip, 45min), used as a reference compound, displayed a clear-cut and dose-dependent protection against seizures in all the models. The ED50 values obtained with PHB were as follows: 7.3mg/kg (PTZ model), 13.3mg/kg (MES model) and 29.7mg/kg (6-Hz model). The present data demonstrate that an acute treatment with resveratrol does not provide any significant protection in three seizure models which collectively are able to detect anticonvulsants with diverse mechanisms of action. However, it cannot be excluded that chronic treatment with resveratrol may offer some protection in these or other seizure models. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. 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).

  14. System of acute medical support to emergency during dental treatment.

    Science.gov (United States)

    Kawahara, M; Takeshita, T; Akita, S

    1986-01-01

    The Resuscitation Committee of Hiroshima City Dental Association was established in 1983 in order to provide acute medical support in case of emergency during dental treatment at private dental clinics. This Committee is composed of representatives from the Hiroshima City Dental Association, Hiroshima University School of Dentistry, Hiroshima University School of Medicine, Hiroshima City Health Bureau, and Hiroshima City Fire and Ambulance Department. A portable ECG monitor with defibrillator and a resuscitation kit are held in readiness at the Hiroshima University Hospital. In case of emergency during dental treatment at a private dental clinic, we hurry to the clinic with the resuscitation set and give emergency treatment. We have been involved in two cases of emergency since this system started. Both of them recovered without any sequelae. Besides these activities, we give lectures annually to dentists and dental hygienists on the treatment of medical emergencies.

  15. Acute macular neuroretinopathy associated with systemic lupus erythematosus.

    Science.gov (United States)

    Lee, D H; Lee, S C; Kim, M

    2016-04-01

    Acute macular neuroretinopathy (AMN) is a rare disorder that presents with abrupt visual change with wedge-shaped or flower-like lesions pointing towards the fovea. Ischemic insults to the retinal capillary plexus may be important for development of this disease. While many case reports have been published on AMN, none have described AMN in association with systemic lupus erythematosus (SLE). Here, we report a case of AMN associated with newly-diagnosed SLE. We speculate that in patients with lupus flares, immune complex-mediated vascular injury and microvascular thrombosis may disrupt the deep retinal capillary network, causing ischemic damages to the outer retina and leading to the development of AMN. AMN can develop in patients with lupus flares, and must be considered as an SLE-associated ophthalmologic complication. To the best of our knowledge, this is the first case report of AMN associated with SLE. © The Author(s) 2015.

  16. Distributed generation systems model

    Energy Technology Data Exchange (ETDEWEB)

    Barklund, C.R.

    1994-12-31

    A slide presentation is given on a distributed generation systems model developed at the Idaho National Engineering Laboratory, and its application to a situation within the Idaho Power Company`s service territory. The objectives of the work were to develop a screening model for distributed generation alternatives, to develop a better understanding of distributed generation as a utility resource, and to further INEL`s understanding of utility concerns in implementing technological change.

  17. 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.

  18. Acute pancreatitis

    Science.gov (United States)

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... pancreatitis; Pancreas - inflammation Images Digestive system Endocrine glands Pancreatitis, acute - CT scan Pancreatitis - series References Forsmark CE. Pancreatitis. ...

  19. Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effect of exogenous erythropoietin (EPO) administration on acute lung injury (ALI) in an experimental model of sodium taurodeoxycholateinduced acute necrotizing pancreatitis (ANP).METHODS: Forty-seven male Wistar albino rats were randomly divided into 7 groups: sham group (n = 5),3 ANP groups (n = 7 each) and 3 EPO groups (n = 7each). ANP was induced by retrograde infusion of 5% sodium taurodeoxycholate into the common bile duct.Rats in EPO groups received 1000 U/kg intramuscular EPO immediately after induction of ANP. Rats in ANP groups were given 1 mL normal saline instead. All animals were sacrificed at postoperative 24 h, 48 h and 72 h. Serum amilase, IL-2, IL-6 and lung tissue malondialdehyde (MDA) were measured. Pleural effusion volume and lung/body weight (LW/BW) ratios were calculated. Tissue levels of TNF-α, IL-2 and IL-6 were screened immunohistochemically. Additionally, ox-LDL accumulation was assessed with immune-fluorescent staining. Histopathological alterations in the lungs were also scored.RESULTS: The mean pleural effusion volume, calculated LW/BW ratio, serum IL-6 and lung tissue MDA levels were significantly lower in EPO groups than in ANP groups. No statistically significant difference was observed in either serum or tissue values of IL-2 among the groups. The level of tumor necrosis factor-α (TNF-α)and IL-6 and accumulation of ox-LDL were evident in the lung tissues of ANP groups when compared to EPO groups, particularly at 72 h. Histopathological evaluation confirmed the improvement in lung injury parameters after exogenous EPO administration, particularly at 48 h and 72 h.CONCLUSION: EPO administration leads to a significant decrease in ALI parameters by inhibiting polymorphonuclear leukocyte (PMNL) accumulation,decreasing the levels of proinflammatory cytokines in circulation, preserving microvascular endothelial cell integrity and reducing oxidative stress-associated lipid peroxidation and therefore, can be

  20. 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.

  1. Dynamics of acutely irradiated skin epidermal epithelium in swine: modeling studies.

    Science.gov (United States)

    Smirnova, Olga A; Hu, Shaowen; Cucinotta, Francis A

    2014-07-01

    A mathematical model, which describes the dynamics of acutely irradiated skin epidermal epithelium in swine, is developed. This model embodies the key mechanisms of regulation of skin epidermal epithelium and the principal stages of development of its cells (basal, prickle, and corneal). The model is implemented as a system of nonlinear ordinary differential equations, whose variables and parameters have clear biological meaning. The modeling results for the dose- and time-dependent changes in basal and prickle cell populations are in a good agreement with relevant experimental data. The correlation between the experimental data on the dynamics of moist reaction in acutely irradiated swine skin epidermal epithelium and the corresponding modeling results on the dynamics of corneal cells is revealed. Proceeding from this, the threshold level of corneal cells, which indicates the appearance of the moist reaction, is found. All this bears witness to the validity of employment of the developed model, after appropriate identification, in the investigation and prediction of radiation effects on skin epidermal epithelium in humans.

  2. Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach

    Science.gov (United States)

    Ross, Clare L; Galloway-Phillipps, Neil; Armstrong, Paul C; Mitchell, Jane A; Warner, Timothy D; Brearley, Christopher; Ito, Mari; Tunstall, Tanushree; Elkin, Sarah; Kon, Onn Min; Hansel, Trevor T; Paul-Clark, Mark J

    2015-01-01

    Introduction Cigarette smoke contributes to a diverse range of diseases including chronic obstructive pulmonary disease (COPD), cardiovascular disorders and many cancers. There currently is a need for human challenge models, to assess the acute effects of a controlled cigarette smoke stimulus, followed by serial sampling of blood and respiratory tissue for advanced molecular profiling. We employ precision sampling of nasal mucosal lining fluid by absorption to permit soluble mediators measurement in eluates. Serial nasal curettage was used for transcriptomic analysis of mucosal tissue. Methods and analysis Three groups of strictly defined patients will be studied: 12 smokers with COPD (GOLD Stage 2) with emphysema, 12 matched smokers with normal lung function and no evidence of emphysema, and 12 matched never smokers with normal spirometry. Patients in the smoking groups are current smokers, and will be given full support to stop smoking immediately after this study. In giving a controlled cigarette smoke stimulus, all patients will have abstained from smoking for 12 h, and will smoke two cigarettes with expiration through the nose in a ventilated chamber. Before and after inhalation of cigarette smoke, a series of samples will be taken from the blood, nasal mucosal lining fluid and nasal tissue by curettage. Analysis of plasma nicotine and metabolites in relation to levels of soluble inflammatory mediators in nasal lining fluid and blood, as well as assessing nasal transcriptomics, ex vivo blood platelet aggregation and leucocyte responses to toll-like receptor agonists will be undertaken. Implications Development of acute cigarette smoke challenge models has promise for the study of molecular effects of smoking in a range of pathological processes. Ethics and dissemination This study was approved by the West London National Research Ethics Committee (12/LO/1101). The study findings will be presented at conferences and will be reported in peer-reviewed journals

  3. Relationship between autonomic nervous system function and acute mountain sickness

    Institute of Scientific and Technical Information of China (English)

    Long Min; Huang Lan; Tian Kaixin; Yu Shiyong; Yu Yang; Qin Jun

    2008-01-01

    Objective: To elucidate the role of the autonomic nervous system (ANS) in acute mountain sickness (AMS) during the initial phase at acute high-altitude exposure. Methods: Ninety-nine healthy sea-level residents rapidly ascended to Tibet plateau (3 675 m altitude) by airplane from Chengdu plain (560 m altitude). ANS function was tested in plain and day 2-4 in Tibet by heart rate variability (HRV), cold pressor test (CPT). AMS was evaluated by clinic symptomatic scores. All subjects were divided into non-AMS group (57, scores(4). Results: Compared with non-AMS group, AMS group had higher standard deviation of normal to normal intervals (SDNN), root mean square of delta RR (rMSSD), low-frequency (LF) power, and normalized low-frequency (Lfnu) power in plain (P50 ms(PNN50), rMSSD (P<0.01) and SDNN, LF, total power (TP) (P<0.05). Although no significant differences in the increase of SP and DP during CPT were found between 2 groups in plain, the SP increase during CPT of AMS group was less than non-AMS group (P<0.05) at 3 675 m altitude. AMS symptomatic scores was not only positively correlated with SDNN,rMSSD, LF/HF in plain (P<0.05), but also negatively correlated with Hfnu in plain (P<0.05). Conclusion: During the initial high altitude exposure, ANS modulation is generally blunted, but the relatively predominant sympathetic control is enhanced, and this characteristic change of ANS function is positively correlated with the development of AMS.

  4. Mechanical Systems, Classical Models

    CERN Document Server

    Teodorescu, Petre P

    2009-01-01

    This third volume completes the Work Mechanical Systems, Classical Models. The first two volumes dealt with particle dynamics and with discrete and continuous mechanical systems. The present volume studies analytical mechanics. Topics like Lagrangian and Hamiltonian mechanics, the Hamilton-Jacobi method, and a study of systems with separate variables are thoroughly discussed. Also included are variational principles and canonical transformations, integral invariants and exterior differential calculus, and particular attention is given to non-holonomic mechanical systems. The author explains in detail all important aspects of the science of mechanics, regarded as a natural science, and shows how they are useful in understanding important natural phenomena and solving problems of interest in applied and engineering sciences. Professor Teodorescu has spent more than fifty years as a Professor of Mechanics at the University of Bucharest and this book relies on the extensive literature on the subject as well as th...

  5. Mathematical Models of Human Hematopoiesis Following Acute Radiation Exposure

    Science.gov (United States)

    2014-05-01

    the model predicts. Radiation dose from skin contamination can result in cutaneous injury leading to systemic responses and may im- pact the observed...medical and performance consequences from radiation and combined injuries , thereby enhancing our understanding of the potential impact of a nuclear...subsequently. In addition to the insight gained from combined injury modeling, the models of hematopoiesis and radiation alone provide clini- cally

  6. NEP systems model

    Science.gov (United States)

    George, Jeffrey A.

    A new nuclear electric propulsion (NEP) systems analysis code is discussed. The new code is modular and consists of a driver code and various subsystem models. The code models five different subsystems: (1) reactor/shield; (2) power conversion; (3) heat rejection; (4) power management and distribution (PMAD); and (5) thrusters. The code optimizes for the following design criteria: minimum mass; minimum radiator area; and low mass/low area. The code also optimizes the following parameters: separation distance; temperature ratio; pressure ratio; and transmission frequency. The discussion is presented in vugraph form.

  7. Damage of the auditory system associated with acute blast trauma.

    Science.gov (United States)

    Roberto, M; Hamernik, R P; Turrentine, G A

    1989-05-01

    This paper reviews the results of several studies on the effects of blast wave exposure on the auditory system of the chinchilla, the pig, and the sheep. The chinchillas were exposed at peak sound pressure levels of approximately 160 dB under well-controlled laboratory conditions. A modified shock tube was used to generate the blast waves. The pigs and sheep were exposed under field conditions in an instrumented hard-walled enclosure. Blast trauma was induced by the impact of a single explosive projectile. The peak sound pressure levels varied between 178 and 209 dB. All animals were killed immediately following exposure, and their temporal bones were removed for fixation and histologic analysis using light microscopy and scanning electron microscopy. Middle ears were examined visually for damage to the conductive system. There were well-defined differences in susceptibility to acoustic trauma among species. However, common findings in each species were the acute mechanical fracture and separation of the organ of Corti from the basilar membrane, and tympanic membrane and ossicular failure.

  8. Physiologically based toxicokinetic modeling of secondary acute myelolytic leukemia.

    Science.gov (United States)

    Mukhopadhyay, Manas Kumar; Nath, Debjani

    2014-01-01

    Benzene, designated as environmental and occupational carcinogen and hematotoxin, has been associated with secondary leukemia. To develop a toxicokinetic model of AML, benzene can be used as leukemogenic agent. The aim of the present study was to optimize the dose, period and time of cumulative benzene exposure of Swiss Albino mice and to analyze survival rate; alteration in cell cycle regulation and other clinical manifestations in mice exposed to benzene vapour at a dose 300 ppm × 6 h/day × 5 days/week for 2 weeks, i.e., 9000(a)ppm cumulative dose. Analyzing physiological parameters like plasma enzyme profile, complete hematology (Hb %, RBC indices and WBC differentials), hematopoietic cells morphology, expression of cell cycle regulatory proteins, tissue histology and analysis of DNA fragmentation, optimum conditions were established. Down regulation of p53 and p21 and up regulation of CDK2, CDK4, CDK6, cyclin D1 and E in this exposed group were marked as the optimum conditions of cellular deregulation for the development of secondary AML. Elevated level of Plasma AST/ALT with corresponding changes in liver histology showing extended sinusoids within the hepatocytic cell cords in optimally exposed animals also confirmed the toxicokinetic relation of benzene with leukemia. It can be concluded from the above observations that the 9000(a)ppm exposed animals can serve as the induced laboratory model of secondary acute myeloid leukemia.

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

    Science.gov (United States)

    Peruzzotti-Jametti, L; Donegá, M; Giusto, E; Mallucci, G; Marchetti, B; Pluchino, S

    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.

  10. National Energy Modeling System

    Energy Technology Data Exchange (ETDEWEB)

    Skinner, C.W. (Energy Information Administration, Washington, DC (United States))

    1993-01-01

    The Energy Information Administration is developing a new National Energy Modeling System to provide annual forecasts of energy supply, demand, and prices on a regional basis in the United States and, to a limited extent, in the rest of the world. The design for the system was based on a requirements analysis, a comparison of requirements with existing modeling capabilities, and a series of widely circulated issue papers defining the choices and tradeoffs for 13 key design decisions. An initial prototpye of the new NEMS was implemented in late 1992, with a more complete, operational version in 1993. NEMS is expected to provide EIA and other users with a greatly enhanced ability to illustrate quickly and effectively the effects of a wide range of energy policy proposals.

  11. Ligustrazine alleviates acute renal injury in a rat model of acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jian-Xin Zhang; Sheng-Chun Dang; Jian-Guo Qu; Xue-Qing Wang

    2006-01-01

    AIM: To evaluate the effect of ligustrazine, a traditional Chinese medicine, on renal injury in a rat model of acute necrotizing pancreatitis (ANP).METHODS: A total of 192 rats were randomly divided into three groups: control (C group), ANP without treatment (P group), and ANP treated with ligustrazine (T group). Each group was further divided into 0.5,2, 6, 12 h subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital.Sodium taurocholate was infused through the pancreatic membrane to induce ANP. T group was infused sodium taurocholate as above, and 0.6% ligustrazine was then administered via the femoral vein. Serum urea nitrogen (BUN) and creatinine (Cr) concentrations were measured for the evaluation of renal function. The effects of ligustrazine on the severity of renal injury were assessed by renal function, TXA2/PGI2 and histopathological changes. Renal blood flow was determined by the radioactive microsphere technique (RMT).RESULTS: Compared with control group, the renal blood flow in P group was decreased significantly. Serious renal and pancreatic damages were found in P group, the BUN and Cr levels were elevated significantly, and the ratio of TXA2 to PGI2 was increased at 2, 6 and 12 h. Compared with P group, the blood flow of kidney was elevated significantly at 6 and 12 h after induction of ANP, the renal and pancreatic damages were attenuated, and the BUN and Cr levels were decreased significantly, and the ratio of TXA2 to PGI2 was decreased at 6 and 12 h in T group.CONCLUSION: Microcirculatory disorder (MCD) is an important factor for renal injury in ANP. Ligustrazine can ameliorate the condition of MCD and the damage of pancreas and kidney.

  12. Using acute kidney injury severity and scoring systems to predict outcome in patients with burn injury.

    Science.gov (United States)

    Kuo, George; Yang, Shih-Yi; Chuang, Shiow-Shuh; Fan, Pei-Chun; Chang, Chih-Hsiang; Hsiao, Yen-Chang; Chen, Yung-Chang

    2016-12-01

    Acute kidney injury (AKI) is a frequent complication of severe burn injury and is associated with mortality. The definition of AKI was modified by the Kidney Disease Improving Global Outcomes Group in 2012. So far, no study has compared the outcome accuracy of the new AKI staging guidelines with that of the complex score system. Hence, we compared the accuracy of these approaches in predicting mortality. This was a post hoc analysis of prospectively collected data from an intensive care burn unit in a tertiary care university hospital. Patients admitted to this unit from July 2004 to December 2006 were enrolled. Demographic, clinical, and laboratory data and prognostic risk scores were used as predictors of mortality. A total of 145 adult patients with a mean age of 41.9 years were studied. Thirty-five patients (24.1%) died during the hospital course. Among the prognostic risk models, the Acute Physiology and Chronic Health Evaluation III system exhibited the strongest discriminative power and the AKI staging system also predicted mortality well (areas under the receiver operating characteristic curve: 0.889 vs. 0.835). Multivariate logistic regression analysis identified total burn surface area, ventilator use, AKI, and toxic epidermal necrolysis as independent risk factors for mortality. Our results revealed that AKI stage has considerable discriminative power for predicting mortality. Compared with other prognostic models, AKI stage is easier to use to assess outcome in patients with severe burn injury. Copyright © 2016. Published by Elsevier B.V.

  13. Changes of High Mobility Group box 1 in Serum of Pig Acute Hepatic Failure Model and Significance

    Institute of Scientific and Technical Information of China (English)

    Fan ZHANG; Yongwen HE; Zhongping DUAN

    2008-01-01

    The role of the high mobility group box 1 (HMGB-1) in acute hepatic failure and the ef- fect of artificial liver support system treatment on HMGB-1 level were investigated. Pig models of acute hepatic failure were induced by D-galactosamine and randomly divided into two groups with or without artificial liver support system treatment. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were detected by the enzyme linked immunosorbent assay (ELISA), the expression of HMGB-1 by Western blot, and serum levels of HMGB-1, liver function and hepatic pathology were observed after artificial liver support system treatment. The levels of TNF-α and IL-1β were increased and reached the peak at 24th h in the acute hepatic failure group, then quickly decreased. The serum level of HMGB-1 was increased at 24th h in the acute hepatic failure group and reached the peak at 48th h, then kept a stable high level. Significant liver injury appeared at 24th h and was continuously getting worse in the pig models of acute hepatic failure. In contrast, the liver injury was significantly alleviated and serum level of HMGB-1 was significantly decreased in the group treated with artificial liver support system (P<0.05). It was suggested that HMGB-1 may participate in the inflammatory response and liver injury in the late stage of the acute liver failure. Artificial liver support system treatment can reduce serum HMGB-1 level and relieve liver pathological damage.

  14. Modeling Novo Nordisk Production Systems

    DEFF Research Database (Denmark)

    Miller, Thomas Dedenroth

    1997-01-01

    This report describes attributes of models and systems, and how models can be used for description of production systems. There are special attention on the 'Theory of Domains'.......This report describes attributes of models and systems, and how models can be used for description of production systems. There are special attention on the 'Theory of Domains'....

  15. Local Renin-Angiotensin System in the Pancreas: The Significance in Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Lai PBS

    2001-01-01

    Full Text Available Acute pancreatitis is a complex disease entity of which the pathogenesis is still not completely known. Research into the initiation and propagation of the diseases would hopefully help to design new treatment strategies for patients, especially those with severe acute pancreatitis. The novel observation of the activation of the local pancreatic renin-angiotensin system in experimental pancreatitis opens up new horizons for research regarding the pathogenesis of acute pancreatitis.

  16. Effect of neurotoxin DSP4 on EEG power spectra in the rat acute model of epilepsy.

    Science.gov (United States)

    Culić, M; Saponjić, J; Janković, B; Udović, S; Popović, S; Rakić, L

    1995-08-18

    The effect of the adrenergic neurotoxin N-(chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on electroencephalographic (EEG) activity was studied in the model of epilepsy induced by systemic application of penicillin (1,000,000 IU/kg, i.p). DSP4 (50 mg/kg, i.p.) was administrated to male Wistar rats, while the control animals were rats from the same litters. EEG activity was recorded in acute and chronic experiments 3 or 4 weeks after DSP4 treatment, before and after penicillin administration. Occasional locus coeruleus (LC) stimulation served as an electrophysiological test of DSP4 toxic effect. EEG power spectra in DSP4 treated animals showed a tendency to be greater in lower frequency bands than in controls before penicillin administration; there was almost no effect of electrical LC stimulation, regardless on penicillin treatment. In the model of epilepsy, the mean total EEG power spectra were greater in the period of 135-330 min after penicillin administration, as well as during 345-540 min, in DSP4 treated animals as compared to the controls. It seems that neurotoxin DSP4 is an optimal tool for studying the removal of LC influence in the acute model of epilepsy. It is also suggested that norepinephrine (NE) may have a modulatory role in the systemic penicillin epilepsy.

  17. 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.

  18. COAP BASED ACUTE PARKING LOT MONITORING SYSTEM USING SENSOR NETWORKS

    Directory of Open Access Journals (Sweden)

    R. Aarthi

    2014-06-01

    Full Text Available Vehicle parking is the act of temporarily maneuvering a vehicle in to a certain location. To deal with parking monitoring system issue such as traffic, this paper proposes a vision of improvements in monitoring the vehicles in parking lots based on sensor networks. Most of the existing paper deals with that of the automated parking which is of cluster based and each has its own overheads like high power, less energy efficiency, incompatible size of lots, space. The novel idea in this work is usage of CoAP (Constrained Application Protocol which is recently created by IETF (draft-ietf-core-coap-18, June 28, 2013, CoRE group to develop RESTful application layer protocol for communications within embedded wireless networks. This paper deals with the enhanced CoAP protocol using multi hop flat topology, which makes the acuters feel soothe towards parking vehicles. We aim to minimize the time consumed for finding free parking lot as well as increase the energy efficiency

  19. System of systems modeling and analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, James E.; Anderson, Dennis James; Longsine, Dennis E. (Intera, Inc., Austin, TX); Shirah, Donald N.

    2005-01-01

    This report documents the results of an LDRD program entitled 'System of Systems Modeling and Analysis' that was conducted during FY 2003 and FY 2004. Systems that themselves consist of multiple systems (referred to here as System of Systems or SoS) introduce a level of complexity to systems performance analysis and optimization that is not readily addressable by existing capabilities. The objective of the 'System of Systems Modeling and Analysis' project was to develop an integrated modeling and simulation environment that addresses the complex SoS modeling and analysis needs. The approach to meeting this objective involved two key efforts. First, a static analysis approach, called state modeling, has been developed that is useful for analyzing the average performance of systems over defined use conditions. The state modeling capability supports analysis and optimization of multiple systems and multiple performance measures or measures of effectiveness. The second effort involves time simulation which represents every system in the simulation using an encapsulated state model (State Model Object or SMO). The time simulation can analyze any number of systems including cross-platform dependencies and a detailed treatment of the logistics required to support the systems in a defined mission.

  20. Central nervous system events in children with sickle cell disease presenting acutely with headache.

    Science.gov (United States)

    Hines, Patrick C; McKnight, Therese P; Seto, Wendy; Kwiatkowski, Janet L

    2011-09-01

    To determine the frequency of acute care visits and risk factors for central nervous system (CNS) events in children with homozygous sickle cell disease (SCD-SS) with an acute headache. This is a retrospective cohort study of acute care visits for headache in children with SCD-SS. The prevalence of headache visits, neuroimaging evaluation, and acute CNS events were calculated and clinical and laboratory variables assessed. Headache was the chief complaint in 102 of 2685 acute care visits (3.8%) by children with SCD-SS. Acute CNS events were detected in 6.9% of these visits. Neuroimaging was performed in 42.2% of visits, and acute CNS events were identified in 16.3% of studies. Factors associated with acute CNS events included older age, history of stroke, transient ischemic attack, or seizure, neurologic symptoms, focal neurologic exam findings, and elevated platelets. Acute headache is common in pediatric SCD-SS and more frequently associated with acute CNS events than in the general pediatric population. A history of stroke, transient ischemic attack, seizures, neurologic symptoms, focal neurologic exam, or elevated platelet counts at presentation warrant confirmatory imaging studies. Whether a more limited workup is adequate for other children should be confirmed in a larger, prospective study. Copyright © 2011 Mosby, Inc. All rights reserved.

  1. A pig model of acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction.

    Science.gov (United States)

    Knai, Kathrine; Skjaervold, Nils Kristian

    2017-01-03

    The aim of this study was to construct a non-invasive model for acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction. Intact animal models are vital to improving our understanding of the pathophysiology of acute right ventricular failure. Acute right ventricular failure is caused by increased afterload of the right ventricle by chronic or acute pulmonary hypertension combined with regionally or globally reduced right ventricular contractile capacity. Previous models are hampered by their invasiveness; this is unfortunate as the pulmonary circulation is a low-pressure system that needs to be studied in closed chest animals. Hypoxic pulmonary vasoconstriction is a mechanism that causes vasoconstriction in alveolar vessels in response to alveolar hypoxia. In this study we explored the use of hypoxic pulmonary vasoconstriction as a means to increase the pressure load on the right ventricle. Pulmonary hypertension was induced by lowering the FiO2 to levels below the physiological range in eight anesthetized and mechanically ventilated pigs. The pigs were monitored with blood pressure measurements and blood gases. The mean pulmonary artery pressures (mPAP) of the animals increased from 18.3 (4.2) to 28.4 (4.6) mmHg and the pulmonary vascular resistance (PVR) from 254 (76) dyns/cm(5) to 504 (191) dyns/cm(5), with a lowering of FiO2 from 0.30 to 0.15 (0.024). The animals' individual baseline mPAPs varied substantially as did their response to hypoxia. The reduced FiO2 level yielded an overall lowering in oxygen offer, but the global oxygen consumption was unaltered. We showed in this study that the mPAP and the PVR could be raised by approximately 100% in the study animals by lowering the FiO2 from 0.30 to 0.15 (0.024). We therefore present a novel method for minimally invasive (closed chest) right ventricular afterload manipulations intended for future studies of acute right ventricular failure. The method should in theory be reversible

  2. Influence of acute renal failure on the mononuclear phagocytic system

    Directory of Open Access Journals (Sweden)

    V.R.A. Sousa

    2001-09-01

    Full Text Available Several studies show the ability of macrophages to remove particles injected into the bloodstream. This function seems to be increased in the presence of acute renal failure. The objective of the present study was to assess the phagocytic function of the main organs (spleen, liver and lung of the mononuclear phagocytic system in renal and postrenal failures. Fifteen rats (250-350 g were divided into three groups (N = 5: group I - control; group II - ligature of both ureters, and group III - bilateral nephrectomy. On the third postoperative day, all animals received an iv injection of 1 ml/kg 99mTc sulfur colloid. Blood samples were collected for the assessment of plasma urea, creatinine, sodium, and potassium concentrations and arterial gasometry. Samples of liver, spleen, lung and blood clots were obtained and radioactivity was measured. Samples of liver, spleen, lung and kidney were prepared for routine histopathological analysis. Plasma urea, creatinine and potassium concentrations in groups II and III were higher than in group I (P<0.05. Plasma sodium concentrations in groups II and III were lower than in group I (P<0.05. Compensated metabolic acidosis was observed in the presence of postrenal failure. Group II animals showed a lower level of radioactivity in the spleen (0.98 and lung (2.63, and a higher level in the liver (105.51 than control. Group III animals showed a lower level of radioactivity in the spleen (11.94 and a higher level in the liver (61.80, lung (11.30 and blood clot (5.13 than control. In groups II and III liver steatosis and bronchopneumonia were observed. Renal and postrenal failures seem to interfere with blood clearance by the mononuclear phagocytic system.

  3. Metabolism of biogenic amines in acute cerebral ischemia: Influence of systemic hyperglycemia

    Directory of Open Access Journals (Sweden)

    Milovanović Aleksandar

    2012-01-01

    Full Text Available Dopamine, norepinephrine and serotonin are biogenic amines which are transmitters of the central nervous system. The effects of ischemia on the brain parenchyma depends on many factors, such is the mechanism of blood flow interruption, velocity of the occurring blood flow interruption, duration of an ischemic episode, organization of anatomical structures of the brain blood vessels etc., which all influence the final outcome. During interruption of the brain circulation in experimental or clinical conditions, neurotransmitter metabolism, primarily of biogenic amines, is disturbed. Many researches with various experimental models of complete ischemia reported a decrease in the content of norepinephrine, dopamine and serotonin in the CNS tissue. It was proven that hyperglycemia can drastically increase cerebral injury followed by short-term cerebral ischemia. Considering the fact that biogenic amines (dopamine, norepinephrine and serotonin influence the size of neurologic damage, as well as the fact that in hyperglycemic conditions infarct size (from the morphological aspect is larger relative to normoglycemic status, the intention was to evaluate the role of biogenic amines in occurrence of damage in conditions of hyperglycemia, i.e. in the case of brain apoplexia in diabetics. Analysis of biogenic amines metabolism in states of acute hyperglycemia, as well as analysis of the effects of reversible and irreversible brain ischemia on metabolism of serotonin, dopamine and norepinephrine, showed that acute hyperglycemia slows down serotonin, dopamine and norepinephrine metabolism in the cerebral cortex and n. caudatus. Brain ischemia in normoglycemic animals by itself has no influence on biogenic amines metabolism, but the effect of ischemia becomes apparent during reperfusion. In recirculation, which corresponds to the occurrences in penumbra, release of biogenic amines is uncontrolled and increased. Brain ischemia in acute hyperglycemic animals

  4. 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 (p<0.05) compared to controls. Interleukin-6 (p<0.05), nuclear factor-kappa B protein expression (p<0.01), and MMP-2 activity (p<0.05) in conjunctival homogenates were significantly reduced compared with the control animals. MMP-2 gene expression showed a tendency to decrease in the azithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (p<0.05). Conclusions These results suggest that azithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis. PMID:23378729

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

    Science.gov (United States)

    2016-07-01

    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...Rodent research has led to many advances in SCI treatment, but successful clinical translation remains limited. Here we describe a large animal model

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

    Science.gov (United States)

    2015-05-01

    AWARD NUMBER: W81XWH-14-2-0013 TITLE: DEVELOPMENT OF AN ANIMAL MODEL OF THORACOLUMBAR BURST FRACTURE- INDUCED ACUTE SPINAL CORD INJURY...2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER DEVELOPMENT OF AN ANIMAL MODEL OF THORACOLUMBAR BURST FRACTURE-INDUCED ACUTE SPINAL CORD INJURY 5b...controlled spinal cord impactor for use in large animal models of SCI in order to more reliably recreate the human injury. A custom designed spinal cord

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

    OpenAIRE

    Hideki Yasui; Koshi Yokomura; Takafumi Suda

    2016-01-01

    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 ...

  8. Hardware Segmentation on Digital Microscope Images for Acute Lymphoblastic Leukemia Diagnosis Using Xilinx System Generator

    Directory of Open Access Journals (Sweden)

    Prof. Kamal A. ElDahshan

    2014-09-01

    Full Text Available Image segmentation is considered the most critical step in image processing and helps to analyze, infer and make decisions especially in the medical field. Analyzing digital microscope images for earlier acute lymphoblastic leukemia diagnosis and treatment require sophisticated software and hardware systems. These systems must provide both highly accurate and extremely fast processing of large amounts of image data. In this work, the hardware segmentation framework for Acute Lymphoblastic Leukemia (ALL images based color histogram of Hue channel of HSV color space is proposed to segment each leukemia image into blasts and background using Field Programmable Gate Array (FPGA. The main purpose of this work is to implement image segmentation framework in a FPGA with minimum hardware resources and low execution time to be suitable enough for medical applications. Hardware framework of segmentation is designed using Xilinx System Generator (XSG as DSP design tool that enables the use of Simulink models, implemented in VHDL and synthesized for Xilinx SPARTAN-3E Starter kit (XC3S500E-FG320 FPGA.

  9. Differentiating acute bacterial meningitis from acute viral meningitis among children with cerebrospinal fluid pleocytosis: a multivariable regression model.

    Science.gov (United States)

    Bonsu, Bema K; Harper, Marvin B

    2004-06-01

    Although accurate models for predicting acute bacterial meningitis exist, most have narrow application because of the specific variables selected for them. In this study, we estimate the accuracy of a simple new model with potentially broader applicability. On the basis of previous reports, we created a reduced multivariable logistic regression model for predicting bacterial meningitis that relies on age (years) (AGE), cerebrospinal fluid (CSF), total protein (TP) and total neutrophil count (TNC) alone. Data were from children ages 1 month-18 years diagnosed with acute enteroviral or bacterial meningitis whose initial CSF revealed >7 white blood cells/mm. A fractional polynomial model was specified and validated internally by the bootstrap procedure. The area under the receiver operating characteristic curve (discrimination: criterion standard, >0.7), the Hosmer-Lemeshow deciles-of-risk statistic (calibration: criterion standard, P > 0.05) and sensitivity-specificity pairs at prespecified probability thresholds of the model were computed. We identified 60 children with bacterial meningitis and 82 with enteroviral meningitis. At an area under the receiver operating characteristic curve of 0.97, our model represented by the equation: log odds of bacterial meningitis = 0.343 - 0.003 TNC - 34.802 TP + 21.991 TP - 0.345 AGE, was highly accurate when differentiating between bacterial and enteroviral meningitis. The model fit the data well (Hosmer-Lemeshow statistic; P =[r] 0.53). At probability cutoffs between 0.1 and 0.4, the model had sensitivity values between 98 and 92% and specificity values between 62 and 94%. Among children with CSF pleocytosis, a prediction model based exclusively on age, CSF total protein and CSF neutrophils differentiates accurately between acute bacterial and viral meningitis.

  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. Re-evaluation and modification of the Stuivenberg Hospital Acute Renal Failure (SHARF) scoring system for the prognosis of acute renal failure: an independent multicentre, prospective study.

    Science.gov (United States)

    Lins, R L; Elseviers, M M; Daelemans, R; Arnouts, P; Billiouw, J-M; Couttenye, M; Gheuens, E; Rogiers, P; Rutsaert, R; Van der Niepen, P; De Broe, M E

    2004-09-01

    A prognostic scoring system for hospital mortality in acute renal failure (Stuivenberg Hospital Acute Renal Failure, SHARF score) was developed in a single-centre study. The scoring system consists of two scores, for the time of diagnosis of acute renal failure (ARF) and for 48 h later, each originally based on four parameters (age, serum albumin, prothrombin time and heart failure). The scoring system was now tested and adapted in a prospective study. The study involved eight intensive care units. We studied 293 consecutive patients with ARF in 6 months. Their mortality was 50.5%. The causes of ARF were medical in 184 (63%) patients and surgical in 108 (37%). In the latter group, 74 (69%) patients underwent cardiac and 19 (18%) vascular surgery. As the performance of the original SHARF scores was much lower in the multicentre study than in the original single-centre study, we re-analysed the multicentre data to customize the original model for the population studied. The independent variables were the score developed in the original study plus all additonal parameters that were significant on univariate analysis. The new multivariate analysis revealed an additional subset of three parameters for inclusion in the model (serum bilirubin, sepsis and hypotension). For the modified SHARF II score, r(2) was 0.27 at 0 and 0.33 at 48 h, respectively, the receiver operating characteristic (ROC) values were 0.82 and 0.83, and the Hosmer-Lemeshow goodness-of-fit P values were 0.19 and 0.05. After customizing and by using two scoring moments, this prediction model for hospital mortality in ARF is useful in different settings for comparing groups of patients and centres, quality assessment and clinical trials. We do not recommend its use for individual patient prognosis.

  12. RNA-Guided CRISPR-Cas9 System-Mediated Engineering of Acute Myeloid Leukemia Mutations

    National Research Council Canada - National Science Library

    Brabetz, Oliver; Alla, Vijay; Angenendt, Linus; Schliemann, Christoph; Berdel, Wolfgang E; Arteaga, Maria-Francisca; Mikesch, Jan-Henrik

    2017-01-01

    Current acute myeloid leukemia (AML) disease models face severe limitations because most of them induce un-physiological gene expressions that do not represent conditions in AML patients and/or depend on external promoters...

  13. Acute necrotizing retinal vasculitis as onset of systemic lupus erythematosus

    Science.gov (United States)

    Monov, Simeon; Hristova, Ruska; Dacheva, Rositza; Toncheva, Reni; Shumnalieva, Russka; Shoumnalieva-Ivanova, Viara; Monova, Daniela

    2017-01-01

    Abstract Rationale: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production, complement activation, and deposition of immune complexes in tissues and organs. SLE can involve any region of the visual system. Although ocular manifestations are not part of the classification criteria for SLE, they can be observed in up to one-third of the patients with SLE. They are rarely reported at the time of disease onset. Retinal vasculitis is usually associated with active generalized disease. Due to its low frequency, we report a case of acute necrotizing retinal vasculitis as onset of SLE. Patient concerns and diagnosis: A 25-year-old white female was referred to the rheumatology clinic with gradually and rapid deterioration of the vision due to abnormal vessel permeability in the right fundus with edema along the vessels, occlusion of arterial branches in the middle periphery with leakage of the dye in these areas and indentical but less prominent changes with cotton wool spots in the papillomacular area and extensive hemorrhages in the left eye. The onset of malar rash, arthralgias and positive antinuclear, anti-double stranded DNA, anti-ribosomal P and anti-β2 glycoprotein I antibodies with decreased C4 complement levels, as well as the positive lupus-band test confirmed the diagnosis of SLE. Interventions: Aggressive immunomodulating therapy with high-dose methylprednisolone, intravenous immunoglobulin, and cyclophosphamide was used for suppression of the disease activity followed by azathioprine as maintaince therapy. Outcomes: Substantial improvement and partial resorption of the vasculitic changes, including central retinal artery and vein, was achieved prominently in the left eye. The study was conducted in accordance with the Declaration of Helsinki and written informed consent was obtained from the patient. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary

  14. Association between probiotics and enteral nutrition in an experimental acute pancreatitis model in rats

    NARCIS (Netherlands)

    Baal, M.C.P.M. van; Rens, M.J. van; Geven, C.B.; Pol, F.M. van de; Brink, I. van den; Hannink, G.J.; Nagtegaal, I.D.; Peters, W.H.M.; Rijkers, G.T.; Gooszen, H.G.

    2014-01-01

    BACKGROUND/OBJECTIVES: Recently, a randomized controlled trial showed that probiotic prophylaxis was associated with an increased mortality in enterally fed patients with predicted severe pancreatitis. In a rat model for acute pancreatitis, we investigated whether an association between probiotic

  15. 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...

  16. Systemic corticosteroid monotherapy for clinically diagnosed acute rhinosinusitis: a randomized controlled trial

    NARCIS (Netherlands)

    Venekamp, R.P.; Bonten, M.J.; Rovers, M.M.; Verheij, T.J.; Sachs, A.P.

    2012-01-01

    BACKGROUND: Patients with acute rhinosinusitis are frequently encountered in primary care. Although corticosteroids are being increasingly used for symptom control, evidence supporting their use is inconclusive. We conducted a randomized controlled trial to examine the effectiveness of systemic cort

  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. Antileukemic Efficacy of Continuous vs Discontinuous Dexamethasone in Murine Models of Acute Lymphoblastic Leukemia.

    Directory of Open Access Journals (Sweden)

    Laura B Ramsey

    Full Text Available Osteonecrosis is one of the most common, serious, toxicities resulting from the treatment of acute lymphoblastic leukemia. In recent years, pediatric acute lymphoblastic leukemia clinical trials have used discontinuous rather than continuous dosing of dexamethasone in an effort to reduce the incidence of osteonecrosis. However, it is not known whether discontinuous dosing would compromise antileukemic efficacy of glucocorticoids. Therefore, we tested the efficacy of discontinuous dexamethasone against continuous dexamethasone in murine models bearing human acute lymphoblastic leukemia xenografts (n = 8 patient samples or murine BCR-ABL+ acute lymphoblastic leukemia. Plasma dexamethasone concentrations (7.9 to 212 nM were similar to those achieved in children with acute lymphoblastic leukemia using conventional dosages. The median leukemia-free survival ranged from 16 to 59 days; dexamethasone prolonged survival from a median of 4 to 129 days in all seven dexamethasone-sensitive acute lymphoblastic leukemias. In the majority of cases (7 of 8 xenografts and the murine BCR-ABL model we demonstrated equal efficacy of the two dexamethasone dosing regimens; whereas for one acute lymphoblastic leukemia sample, the discontinuous regimen yielded inferior antileukemic efficacy (log-rank p = 0.002. Our results support the clinical practice of using discontinuous rather than continuous dexamethasone dosing in patients with acute lymphoblastic leukemia.

  19. ECO-BIOLOGICAL SYSTEM MODELING

    Directory of Open Access Journals (Sweden)

    T. I. Burak

    2015-01-01

    Full Text Available The methodology for computer modeling of complex eco-biological models is presented in this paper. It is based on system approach of J. Forrester. Developed methodology is universal for complex ecological and biological systems. Modeling algorithm considers specialties of eco-biological systems and shows adequate and accurate results in practice. 

  20. Central nervous system involvement in acute lymphoblastic leukemia: diagnosis by immunophenotyping

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2013-08-01

    Full Text Available The central nervous system is the most commonly affected extramedullary site in acute lymphoblastic leukemia. Although morphologic evaluation of the cerebrospinal fluid has been traditionally used for diagnosing central nervous system involvement, it is a method of low sensitivity. The present study aimed at evaluating the use of immunophenotyping in the detection of blasts in the cerebrospinal fluid from children and adolescents with acute lymphoblastic leukemia.

  1. Pancreatic ductal system obstruction and acute recurrent pancreatitis

    Institute of Scientific and Technical Information of China (English)

    M Delhaye; C Matos; M Arvanitakis; J Devière

    2008-01-01

    Acute recurrent pancreatitis is a clinical entity largely associated with pancreatic ductal obstruction.This latter includes congenital variants,of which pancreas divisum is the most frequent but also controversial,chronic pancreatitis,tumors of the pancreaticobiliary junction and sphincter of Oddi dysfunction.This review summarizes current knowledge about diagnostic work-up and therapy of these conditions.

  2. An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

    Institute of Scientific and Technical Information of China (English)

    María Jesús Tu(n)ón; Marcelino Alvarez; Jesús M Culebras; Javier González-Gallego

    2009-01-01

    Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by meansof the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.

  3. An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

    Science.gov (United States)

    Mascio, Heather M; Joya, Christie A; Plasse, Richard A; Baker, Thomas P; Flessner, Michael F; Nee, Robert

    2015-08-01

    Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration.

  4. Mathematical System Theory and System Modeling

    OpenAIRE

    1980-01-01

    Choosing models related effectively to the questions to be addressed is a central issue in the craft of systems analysis. Since the mathematical description the analyst chooses constrains the types of issues he candeal with, it is important for these models to be selected so as to yield limitations that are acceptable in view of the questions the systems analysis seeks to answer. In this paper, the author gives an overview of the central issues affecting the question of model choice. To ...

  5. Establishment of a Novel Simplified Surgical Model of Acute Liver Failure in the Cynomolgus Monkey

    Directory of Open Access Journals (Sweden)

    Lei Cai

    2016-01-01

    Full Text Available Models using large animals that are suitable for studying artificial liver support system (ALSS are urgently needed. Presently available acute liver failure (ALF models mainly involve pigs or dogs. Establishment of current surgical ALF models (hepatectomy/devascularization requires either very good surgical skills or multistep processes—even multiple stages of surgery. Therefore, it is necessary to develop a simplified surgical method. Here we report a novel simplified surgical ALF model using cynomolgus monkeys. Six monkeys underwent portal-right renal venous shunt combined with common bile duct ligation and transection (PRRS + CBDLT. Postoperatively, the monkeys had progressively increased listlessness, loss of appetite, and obvious jaundice. Blood biochemistry levels (Amm, ALT, AST, TBiL, DBiL, ALP, LDH, CK, and Cr and prothrombin time (PT were significantly increased (all P<0.01 and albumin (ALB was markedly reduced (P<0.01 compared with baseline values. Histological examination of liver specimens on postoperative day 10 revealed cholestasis and inflammation. PRRS + CBDLT produced ALF that closely correlated with clinical situations. Compared with other surgical or drug ALF models, ours was simplified and animals were hemodynamically stable. This model could provide a good platform for further research on ALSS, especially regarding their detoxification functions.

  6. Evaluation of scoring systems in predicting acute appendicitis in children.

    Science.gov (United States)

    Macco, Sven; Vrouenraets, Bart C; de Castro, Steve M M

    2016-12-01

    Acute appendicitis can be difficult to diagnose, especially in children. Appendicitis scoring systems have been developed as a diagnostic tool to improve the decision-making process in patients with suspected acute appendicitis. This study evaluates the Appendicitis Inflammatory Response score, Alvarado score, and Pediatric Appendicitis Score in children suspected of acute appendicitis. Data were collected retrospectively. All children younger than 18 years suspected of acute appendicitis who presented to the emergency department between January 2006 and June 2014 were included in this study. Variables were registered to evaluate 3 different appendicitis scoring systems. The diagnostic performance of the 3 scores was analyzed using the area under the receiver-operating curve and by calculating the diagnostic performances at different cut-off points. The present study included 747 consecutive children. There were 399 boys (53%) and 348 girls (47%) with a mean age of 11 years (range, 1-17 years). In total, 269 children (36%) were diagnosed with acute appendicitis. The area under the receiver-operating curve of the Appendicitis Inflammatory Response score was 0.90, the Alvarado score was 0.87, and the Pediatric Appendicitis Score was 0.82 (P Appendicitis Inflammatory Response score were better at predicting an acute appendicitis than that of the Alvarado score and Pediatric Appendicitis Score. In children with a low-risk acute appendicitis, false negative rates of 14% for the Appendicitis Inflammatory Response, 7% for the Alvarado, and 18% for the Pediatric Appendicitis Score were measured. In this study, the Appendicitis Inflammatory Response score had the highest discriminating power and outperformed the Alvarado score and Pediatric Appendicitis Score in predicting acute appendicitis in children. Excluding acute appendicitis safely in children with the scoring systems still remains uncertain. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Model Reduction of Hybrid Systems

    DEFF Research Database (Denmark)

    Shaker, Hamid Reza

    systems are derived in this thesis. The results are used for output feedback control of switched nonlinear systems. Model reduction of piecewise affine systems is also studied in this thesis. The proposed method is based on the reduction of linear subsystems inside the polytopes. The methods which......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...... of hybrid systems, designing controllers and implementations is very high so that the use of these models is limited in applications where the size of the state space is large. To cope with complexity, model reduction is a powerful technique. This thesis presents methods for model reduction and stability...

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

    Science.gov (United States)

    2016-10-24

    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

  9. Modelling on fuzzy control systems

    Institute of Scientific and Technical Information of China (English)

    LI; Hongxing(李洪兴); WANG; Jiayin(王加银); MIAO; Zhihong(苗志宏)

    2002-01-01

    A kind of modelling method for fuzzy control systems is first proposed here, which is calledmodelling method based on fuzzy inference (MMFI). It should be regarded as the third modelling method thatis different from two well-known modelling methods, that is, the first modelling method, mechanism modellingmethod (MMM), and the second modelling method, system identification modelling method (SlMM). Thismethod can, based on the interpolation mechanism on fuzzy logic system, transfer a group of fuzzy inferencerules describing a practice system into a kind of nonlinear differential equation with variable coefficients, calledHX equations, so that the mathematical model of the system can be obtained. This means that we solve thedifficult problem of how to get a model represented as differential equations on a complicated or fuzzy controlsystem.

  10. A Biophysical Systems Approach to Identifying the Pathways of Acute and Chronic Doxorubicin Mitochondrial Cardiotoxicity.

    Directory of Open Access Journals (Sweden)

    Bernardo L de Oliveira

    2016-11-01

    Full Text Available The clinical use of the anthracycline doxorubicin is limited by its cardiotoxicity which is associated with mitochondrial dysfunction. Redox cycling, mitochondrial DNA damage and electron transport chain inhibition have been identified as potential mechanisms of toxicity. However, the relative roles of each of these proposed mechanisms are still not fully understood. The purpose of this study is to identify which of these pathways independently or in combination are responsible for doxorubicin toxicity. A state of the art mathematical model of the mitochondria including the citric acid cycle, electron transport chain and ROS production and scavenging systems was extended by incorporating a novel representation for mitochondrial DNA damage and repair. In silico experiments were performed to quantify the contributions of each of the toxicity mechanisms to mitochondrial dysfunction during the acute and chronic stages of toxicity. Simulations predict that redox cycling has a minor role in doxorubicin cardiotoxicity. Electron transport chain inhibition is the main pathway for acute toxicity for supratherapeutic doses, being lethal at mitochondrial concentrations higher than 200μM. Direct mitochondrial DNA damage is the principal pathway of chronic cardiotoxicity for therapeutic doses, leading to a progressive and irreversible long term mitochondrial dysfunction.

  11. Energy System Modeling with REopt

    Energy Technology Data Exchange (ETDEWEB)

    Simpkins, Travis; Anderson, Kate; Cutler, Dylan; Olis, Dan; Elgqvist, Emma; DiOrio, Nick; Walker, Andy

    2016-07-15

    This poster details how REopt - NREL's software modeling platform for energy systems integration and optimization - can help to model energy systems. Some benefits of modeling with REopt include optimizing behind the meter storage for cost and resiliency, optimizing lab testing, optimizing dispatch of utility scale storage, and quantifying renewable energy impact on outage survivability.

  12. Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Dale, Nicholas; Larsen, Fin Stolze

    2015-01-01

    Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found...... in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP......) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18...

  13. Effect of gomisin A in an immunologically-induced acute hepatic failure model.

    Science.gov (United States)

    Mizoguchi, Y; Shin, T; Kobayashi, K; Morisawa, S

    1991-02-01

    Guinea pigs were sensitized with trinitrophenylated liver macromolecular protein fraction (TNP-LP1) prepared by using sodium trinitrobenzenesulfonate of strong immunogenicity as the hapten and LP1 as the carrier protein. The administration of trinitrophenylated hepatocytes and lipopolysaccharide to these TNP-LP1-sensitized guinea pigs through the mesenteric vein 2 weeks later resulted in the induction of acute hepatic failure accompanied by massive hepatic cell necrosis in almost all of the guinea pigs. Using this experimental model, the effect of Gomisin A on the induction of immunological acute hepatic failure was examined. As a result, the administration of gomisin A remarkably improved the survival rate and serum transaminase levels of the immunologically-induced acute hepatic failure guinea pigs. Gomisin A also improved the histological changes of the liver in these guinea pigs. These results suggested that gomisin A is effective for the improvement of immunologically-induced acute hepatic failure in our experimental model.

  14. Stiripentol in acute/chronic efficacy tests in monkey model.

    Science.gov (United States)

    Lockard, J S; Levy, R H; Rhodes, P H; Moore, D F

    1985-01-01

    Acute and chronic efficacy tests of stiripentol (4,4-dimethyl-1-[3,4-(methylenedioxy)-phenyl]-1-penten-3-ol) were conducted in alumina-gel rhesus monkeys. In the acute study (n = 6), discrete serial seizures precipitated by 150 mg/kg of 4-deoxypyridoxine hydrochloride were challenged by intravenous administration of stiripentol and the data compared with those obtained with valproate similarly tested in other monkeys (reported here) and with those from four other standard anticonvulsants (phenytoin, carbamazepine, phenobarbital, and diazepam--data published previously). In the acute challenge (Study 1), stiripentol performed comparably to valproate by delaying the onset of seizures but not eliminating them as did the other four drugs. In two separate chronic studies (at different doses, n = 6 each), stiripentol was given every 4 h by gastric catheter for 4 weeks, preceded and followed by 4 weeks of baseline. In these studies, stiripentol significantly reduced EEG interictal spike rates at mean plasma concentrations from 20 to 27 micrograms/ml in Study 2 and 11 to 14 micrograms/ml in Study 3. From these results, and those evinced in other studies, it appears that stiripentol should be evaluated for absence epilepsy and possible synergistic effects in polytherapy.

  15. GABAergic modulation of human social interaction in a prisoner's dilemma model by acute administration of alprazolam.

    Science.gov (United States)

    Lane, Scott D; Gowin, Joshua L

    2009-10-01

    Recent work in neuroeconomics has used 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 model after acute administration of the γ-aminobutyric acid (GABA)-A modulating benzodiazepine alprazolam. Nine healthy adults received doses of placebo, 0.5, 1.0, and 2.0 mg alprazolam in a counterbalanced within-subject design, while completing multiple test blocks per day on an iterated prisoner's dilemma game. During test blocks in which peak subjective effects of alprazolam were reported, cooperative choices were significantly decreased as a function of dose. Consistent with previous reports showing that high acute doses of GABA-modulating drugs are associated with violence and other antisocial behavior, our data suggest that at sufficiently high doses, alprazolam can decrease cooperation. These behavioral changes may be facilitated by changes in inhibitory control facilitated by GABA. Game theory paradigms may prove useful in behavioral pharmacology studies seeking to measure social interaction, and may help inform the emerging field of neuroeconomics.

  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 ZM; Baily, James E; Sharp, Matthew GF; Garden, O James; Hughes, Jeremy; Howie, Sarah EM; Holmes, Duncan S; Liddle, John; Iredale, John P

    2015-01-01

    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 death1,2 Acute mortality from AP-MODS exceeds 20%3 and for those who survive the initial episode, their lifespan is typically shorter than the general population4. There are no specific therapies available that protect individuals against AP-MODS. Here, we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism5, is central to the pathogenesis of AP-MODS. We created a mouse strain deficient for Kmo with a robust biochemical phenotype that protected against extrapancreatic tissue injury to lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of 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 levels of kynurenine pathway metabolites in vivo and afforded therapeutic protection against AP-MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS and open up a new area for drug discovery in critical illness. PMID:26752518

  17. 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.

  18. RNA-Guided CRISPR-Cas9 System-Mediated Engineering of Acute Myeloid Leukemia Mutations.

    Science.gov (United States)

    Brabetz, Oliver; Alla, Vijay; Angenendt, Linus; Schliemann, Christoph; Berdel, Wolfgang E; Arteaga, Maria-Francisca; Mikesch, Jan-Henrik

    2017-03-17

    Current acute myeloid leukemia (AML) disease models face severe limitations because most of them induce un-physiological gene expressions that do not represent conditions in AML patients and/or depend on external promoters for regulation of gene expression/repression. Furthermore, many AML models are based on reciprocal chromosomal translocations that only reflect the minority of AML patients, whereas more than 50% of patients have a normal karyotype. The majority of AML, however, is driven by somatic mutations. Thus, identification as well as a detailed molecular and functional characterization of the role of these driver mutations via improved AML models is required for better approaches toward novel targeted therapies. Using the IDH2 R140Q mutation as a model, we present a new effective methodology here using the RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system to reproduce or remove AML-associated mutations in or from human leukemic cells, respectively, via introduction of a DNA template at the endogenous gene locus via homologous recombination. Our technology represents a precise way for AML modeling to gain insights into AML development and progression and provides a basis for future therapeutic approaches.

  19. Altered mucosal immune response after acute lung injury in a murine model of Ataxia Telangiectasia.

    Science.gov (United States)

    Eickmeier, Olaf; Kim, Su Youn; Herrmann, Eva; Döring, Constanze; Duecker, Ruth; Voss, Sandra; Wehner, Sibylle; Hölscher, Christoph; Pietzner, Julia; Zielen, Stefan; Schubert, Ralf

    2014-05-29

    Ataxia telangiectasia (A-T) is a rare but devastating and progressive disorder characterized by cerebellar dysfunction, lymphoreticular malignancies and recurrent sinopulmonary infections. In A-T, disease of the respiratory system causes significant morbidity and is a frequent cause of death. We used a self-limited murine model of hydrochloric acid-induced acute lung injury (ALI) to determine the inflammatory answer due to mucosal injury in Atm (A-T mutated)- deficient mice (Atm(-/-)). ATM deficiency increased peak lung inflammation as demonstrated by bronchoalveolar lavage fluid (BALF) neutrophils and lymphocytes and increased levels of BALF pro-inflammatory cytokines (e.g. IL-6, TNF). Furthermore, bronchial epithelial damage after ALI was increased in Atm(-/-) mice. ATM deficiency increased airway resistance and tissue compliance before ALI was performed. Together, these findings indicate that ATM plays a key role in inflammatory response after airway mucosal injury.

  20. Successful treatment of acute systemic anaphylaxis in a western lowland gorilla (Gorilla gorilla gorilla).

    Science.gov (United States)

    Hayman, David T S; King, Tony; Cameron, Kenneth

    2010-09-01

    This brief communication describes the successful treatment of acute systemic anaphylaxis in a wild-born but captive infant western lowland gorilla (Gorilla gorilla gorilla) in the Republic of Congo. The infant demonstrated signs of acute respiratory distress, lingual swelling, and reaction to intradermal tuberculin, given 55 hr earlier. Details of the treatment with steroids, anesthetic induction, and i.v. epinephrine are all reported, and potential antigens that may have initiated the anaphylactic shock are discussed.

  1. Interleukin-33 Drives Activation of Alveolar Macrophages and Airway Inflammation in a Mouse Model of Acute Exacerbation of Chronic Asthma

    Directory of Open Access Journals (Sweden)

    Melissa M. Bunting

    2013-01-01

    Full Text Available We investigated the role of interleukin-33 (IL-33 in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, together with enhanced expression of proinflammatory cytokines and of cell surface proteins associated with antigen presentation. In parallel, there was markedly increased expression of both mRNA and immunoreactivity for IL-33 in the airways. Neutralization of IL-33 significantly decreased both airway inflammation and the expression of proinflammatory cytokines by AM. Collectively, these data indicate that in this model of an acute exacerbation of chronic asthma, IL-33 drives activation of AM and has an important role in the pathogenesis of airway inflammation.

  2. Interleukin-33 drives activation of alveolar macrophages and airway inflammation in a mouse model of acute exacerbation of chronic asthma.

    Science.gov (United States)

    Bunting, Melissa M; Shadie, Alexander M; Flesher, Rylie P; Nikiforova, Valentina; Garthwaite, Linda; Tedla, Nicodemus; Herbert, Cristan; Kumar, Rakesh K

    2013-01-01

    We investigated the role of interleukin-33 (IL-33) in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM) were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, together with enhanced expression of proinflammatory cytokines and of cell surface proteins associated with antigen presentation. In parallel, there was markedly increased expression of both mRNA and immunoreactivity for IL-33 in the airways. Neutralization of IL-33 significantly decreased both airway inflammation and the expression of proinflammatory cytokines by AM. Collectively, these data indicate that in this model of an acute exacerbation of chronic asthma, IL-33 drives activation of AM and has an important role in the pathogenesis of airway inflammation.

  3. Predictive Models of Acute Mountain Sickness after Rapid Ascent to Various Altitudes

    Science.gov (United States)

    2013-01-01

    severity but not prevalence of AMS. Key Words: HYPOXIA , HYPOBARIC HYPOXIA , MIXED MODELS, ALTITUDE, ALTITUDE SICKNESS, UNACCLIMATIZED LOWLANDERS W hen...Beidleman BA, Muza SR, Fulco CS, et al. Intermittent altitude exposures reduce acute mountain sickness at 4300 m. Clin Sci. 2004;106(3):321–8. 4. Beidleman...Wood H, Yang HH, et al. The body weight loss during acute exposure to high-altitude hypoxia in sea level residents. Acta Physiologica Sinica

  4. 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....

  5. Spatio-temporal and stochastic modelling of severe acute respiratory syndrome

    Directory of Open Access Journals (Sweden)

    Poh-Chin Lai

    2013-11-01

    Full Text Available This study describes the development of a spatio-temporal disease model based on the episodes of severe acute respiratory syndrome (SARS that took place in Hong Kong in 2003. In contrast to conventional, deterministic modelling approaches, the model described here is predominantly spatial. It incorporates stochastic processing of environmental and social variables that interact in space and time to affect the patterns of disease transmission in a community. The model was validated through a comparative assessment between actual and modelled distribution of diseased locations. Our study shows that the inclusion of location-specific characteristics satisfactorily replicates the spatial dynamics of an infectious disease. The Pearson’s correlation coefficients for five trials based on 3-day aggregation of disease counts for 1-3, 4-6 and 7-9 day forecasts were 0.57- 0.95, 0.54-0.86 and 0.57-0.82, respectively, while the correlation based on 5-day aggregation for the 1-5 day forecast was 0.55- 0.94 and 0.58-0.81 for the 6-10 day forecast. The significant and strong relationship between actual results and forecast is encouraging for the potential development of an early warning system for detecting this type of disease outbreaks.

  6. 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

    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......, 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...

  7. 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

  8. 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

  9. Modeling of deterministic chaotic systems

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Y. [Department of Physics and Astronomy and Department of Mathematics, The University of Kansas, Lawrence, Kansas 66045 (United States); Grebogi, C. [Institute for Plasma Research, University of Maryland, College Park, Maryland 20742 (United States); Grebogi, C.; Kurths, J. [Department of Physics and Astrophysics, Universitaet Potsdam, Postfach 601553, D-14415 Potsdam (Germany)

    1999-03-01

    The success of deterministic modeling of a physical system relies on whether the solution of the model would approximate the dynamics of the actual system. When the system is chaotic, situations can arise where periodic orbits embedded in the chaotic set have distinct number of unstable directions and, as a consequence, no model of the system produces reasonably long trajectories that are realized by nature. We argue and present physical examples indicating that, in such a case, though the model is deterministic and low dimensional, statistical quantities can still be reliably computed. {copyright} {ital 1999} {ital The American Physical Society}

  10. Modelling of wastewater systems

    DEFF Research Database (Denmark)

    Bechmann, Henrik

    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...

  11. 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.

  12. Modelling Epistemic Systems

    CERN Document Server

    Martins, Andre C R

    2012-01-01

    In this Chapter, I will explore the use of modeling in order to understand how Science works. I will discuss the modeling of scientific communities, providing a general, non-comprehensive overview of existing models, with a focus on the use of the tools of Agent-Based Modeling and Opinion Dynamics. A special attention will be paid to models inspired by a Bayesian formalism of Opinion Dynamics. The objective of this exploration is to better understand the effect that different conditions might have on the reliability of the opinions of a scientific community. We will see that, by using artificial worlds as exploring grounds, we can prevent some epistemological problems with the definition of truth and obtain insights on the conditions that might cause the quest for more reliable knowledge to fail.

  13. 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.

  14. Systemic Mastocytosis Presenting as Acute Appendicitis: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Syed A. Akbar

    2013-03-01

    Full Text Available Systemic mastocytosis is characterized by abnormal growth and accumulation of mast cells in various organs. Gastrointestinal (GI symptoms are common disease manifestations in this disease and can significantly impair the quality of life. Signs of GI systemic mastocytosis include steatorrhea, malabsorption, hepatomegaly, splenomegaly, portal hypertension, and ascites. Acute appendicitis as a presenting feature in systemic mastocytosis has not been reported in the literature previously. In this report, we discuss the case of a female patient with systemic mastocytosis (c-KIT D816V (+ who was admitted for right-sided acute abdominal pain. Laboratory study revealed an normal white blood cell count with eosinophilia and an elevated serum tryptase level of 23 μg/l. CT of the abdomen and pelvis showed an enlarged appendix of 12 mm in diameter, with minimal wall enhancement. Laparoscopic appendectomy was performed. The appendix was found to be hyperemic and firm, and it was densely adherent to the posterior cecum, the surrounding peritoneal wall, and the overlying mesenteric fat. Pathology revealed acute appendicitis with greater than 30 mast cells per high-power field by immunoperoxidase studies with mast cell tryptase and CD117. The patient subsequently improved and was discharged home. This case is the first reported case with a histological diagnosis of acute appendicitis resulting from mast cell infiltration. Physicians should be aware of acute appendicitis as a manifestation of systemic mastocytosis. Prompt diagnosis and management may prevent potentially fatal complications of appendiceal perforation and peritonitis.

  15. 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 ...... in paracetamol-induced acute liver failure require re-evaluation. FUNDING: Foundation for Liver Research. Copyright © 2016 Elsevier Ltd. All rights reserved....... 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...

  16. Pluralistic Modeling of Complex Systems

    CERN Document Server

    Helbing, Dirk

    2010-01-01

    The modeling of complex systems such as ecological or socio-economic systems can be very challenging. Although various modeling approaches exist, they are generally not compatible and mutually consistent, and empirical data often do not allow one to decide what model is the right one, the best one, or most appropriate one. Moreover, as the recent financial and economic crisis shows, relying on a single, idealized model can be very costly. This contribution tries to shed new light on problems that arise when complex systems are modeled. While the arguments can be transferred to many different systems, the related scientific challenges are illustrated for social, economic, and traffic systems. The contribution discusses issues that are sometimes overlooked and tries to overcome some frequent misunderstandings and controversies of the past. At the same time, it is highlighted how some long-standing scientific puzzles may be solved by considering non-linear models of heterogeneous agents with spatio-temporal inte...

  17. Acute mucocutaneous and systemic adverse effects of Etretinate

    Directory of Open Access Journals (Sweden)

    "Mortazavi H

    2003-06-01

    Full Text Available This cross sectional study was carried out between 1993 to 1998 at Razi Skin Hospital, the affiliated Dermatology Department of Tehran University of Medical Sciences. Eight hundred patients receiving etretinate for various skin diseases took part in this study. Among them, 457 patients with first admission to dermatologic clinic who had at least four regular sequential visits and responding to our questionnaire were selected to enter the study for evaluating acute toxicity of etretinate. Cheilitis with a frequency of 88 percent was the most frequent side effect. Hair loss (22.97%, dry mouth with thirst (15.09%, dryness of mucous membranes (13.12%, xerosis with pruritus (11.15%, nose bleeding (8.31%, paronychia (5.47%, facial dermatitis (3.06%, conjunctivitis (2.84% and in addition to mucocutaneous ones, chills (2.63%, headache (2.19%, mental depression (2.19%, urinary frequency (1.53% and papilledema (0.44% were among the other observed toxicities, The relationship between mucocutaneous side effect with dosage of etretinate, sex and, age of the patients was evaluated. The association between mucoctaneous toxicities and sex was significant, sex and, age of the patients was evaluated. The association between mucocutaneous toxicities and sex was significant (P<0.05. We observed four rare side effect in the patients including hair color lightening appering as whitening or blondness, hair waving, dyspareunia and gynecomastia. In conclusion, females were more to acute mucocutaneous toxicities of etretinate.

  18. Low-power wireless micromanometer system for acute and chronic bladder-pressure monitoring.

    Science.gov (United States)

    Majerus, Steve J A; Fletter, Paul C; Damaser, Margot S; Garverick, Steven L

    2011-03-01

    This letter describes the design, fabrication, and testing of a wireless bladder-pressure-sensing system for chronic, point-of-care applications, such as urodynamics or closed-loop neuromodulation. The system consists of a miniature implantable device and an external RF receiver and wireless battery charger. The implant is small enough to be cystoscopically implanted within the bladder wall, where it is securely held and shielded from the urine stream. The implant consists of a custom application-specific integrated circuit (ASIC), a pressure transducer, a rechargeable battery, and wireless telemetry and recharging antennas. The ASIC includes instrumentation, wireless transmission, and power-management circuitry, and on an average draws less than 9 μA from the 3.6-V battery. The battery charge can be wirelessly replenished with daily 6-h recharge periods that can occur during the periods of sleep. Acute in vivo evaluation of the pressure-sensing system in canine models has demonstrated that the system can accurately capture lumen pressure from a submucosal implant location.

  19. 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

  20. Modelling the mechanism of GR/c-Jun/Erg crosstalk in apoptosis of acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Daphne eChen

    2012-11-01

    Full Text Available Acute lymphoblastic leukaemia (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 adapting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data via the building of a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Erg as determinant for GC resistance. The results revealed an alternative potential 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.

  1. 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.

  2. Use of small intestine submucosa in a rat model of acute and chronic rotator cuff tear.

    Science.gov (United States)

    Perry, Stephanie M; Gupta, Rishi R; Van Kleunen, Jonathan; Ramsey, Matthew L; Soslowsky, Louis J; Glaser, David L

    2007-01-01

    Augmentation materials for rotator cuff tears, such as small intestine submucosa (SIS), have been used with the goal of improving outcome. Knowledge is limited on the use of SIS in animal models of acute and chronic rotator cuff tears. We hypothesized that the use of SIS in the surgical management of full thickness supraspinatus tears would improve histologic and biomechanical properties. Results show temporal improvements in several histologic parameters. Both acute and chronic injuries repaired with SIS have similar and increased mechanical properties respectively, compared to those repaired without SIS. In general, acute repairs with SIS were comparable to acute repairs without SIS. In chronic repairs, the use of SIS significantly reduced the cross sectional area of the healing tendon and increased the modulus. These results provide information on the use of SIS for rotator cuff repairs.

  3. Internal gallbladder drainage prevents development of acute cholecystitis in a pig model: a randomized study

    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...

  4. Comparison and clinical suitability of eight prediction models for cardiac surgery-related acute kidney injury

    NARCIS (Netherlands)

    Kiers, H.D.; Boogaard, M.H.W.A. van den; Schoenmakers, M.C.J.; Hoeven, J.G. van der; Swieten, H.A. van; Heemskerk, S.; Pickkers, P.

    2013-01-01

    BACKGROUND: Cardiac surgery-related acute kidney injury (CS-AKI) results in increased morbidity and mortality. Different models have been developed to identify patients at risk of CS-AKI. While models that predict dialysis and CS-AKI defined by the RIFLE criteria are available, their predictive powe

  5. 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...

  6. 77 FR 34326 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Science.gov (United States)

    2012-06-11

    ... Assistance Program No. 93.773, Medicare--Hospital Insurance; and Program No. 93.774, Medicare-- Supplementary... 0938-AR12 Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective Payment System and Fiscal Year 2013 Rates; Hospitals' Resident...

  7. 78 FR 61197 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Science.gov (United States)

    2013-10-03

    ... Program No. 93.773, Medicare--Hospital Insurance; and Program No. 93.774, Medicare-- Supplementary Medical...-AR53 and 0938-AR73 Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective Payment System and Fiscal Year 2014 Rates; Quality...

  8. 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.

    2016-01-01

    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 in

  9. Percutaneous Access: Acute Effects on Renal Function and Structure in a Porcine Model

    Science.gov (United States)

    Handa, Rajash K.; Willis, Lynn R.; Evan, Andrew P.; Connors, Bret A.; Ying, Jun; Fat-Anthony, William; Wind, Kelli R.; Johnson, Cynthia D.; Blomgren, Philip M.; Estrada, Mark C.; Paterson, Ryan F.; Kuo, Ramsay L.; Kim, Samuel C.; Matlaga, Brian R.; Miller, Nicole L.; Watkins, Stephanie L.; Handa, Shelly E.; Lingeman, James E.

    2007-04-01

    Percutaneous nephrolithotomy (PCNL) involves gaining access into the urinary collecting system to remove kidney stones. Animal studies demonstrated that a reduction in renal filtration and perfusion in both kidneys, and a decline in tubular organic anion transport in the treated kidney characterizes the acute (hours) functional response to unilateral percutaneous access. The acute morphologic and histological changes in the treated kidney were consistent with blunt trauma and ischemia. Only tubular organic anion transport remained depressed during the late (3-day) response to the access procedure. Human studies revealed an acute decline in glomerular function and bilateral renal vasoconstriction following unilateral PCNL. Therefore, percutaneous access is not a benign procedure, but is associated with acute functional and structural derangements.

  10. Combining robust state estimation with nonlinear model predictive control to regulate the acute inflammatory response to pathogen.

    Science.gov (United States)

    Zitelli, Gregory; Djouadi, Seddik M; Day, Judy D

    2015-10-01

    The inflammatory response aims to restore homeostasis by means of removing a biological stress, such as an invading bacterial pathogen. In cases of acute systemic inflammation, the possibility of collateral tissue damage arises, which leads to a necessary down-regulation of the response. A reduced ordinary differential equations (ODE) model of acute inflammation was presented and investigated in [10]. That system contains multiple positive and negative feedback loops and is a highly coupled and nonlinear ODE. The implementation of nonlinear model predictive control (NMPC) as a methodology for determining proper therapeutic intervention for in silico patients displaying complex inflammatory states was initially explored in [5]. Since direct measurements of the bacterial population and the magnitude of tissue damage/dysfunction are not readily available or biologically feasible, the need for robust state estimation was evident. In this present work, we present results on the nonlinear reachability of the underlying model, and then focus our attention on improving the predictability of the underlying model by coupling the NMPC with a particle filter. The results, though comparable to the initial exploratory study, show that robust state estimation of this highly nonlinear model can provide an alternative to prior updating strategies used when only partial access to the unmeasurable states of the system are available.

  11. Neurogenic stunned myocardium - do we consider this diagnosis in patients with acute central nervous system injury and acute heart failure?

    Science.gov (United States)

    Mierzewska-Schmidt, Magdalena; Gawecka, Agnieszka

    2015-01-01

    Neurogenic stunned myocardium (NSM) is defined as myocardial injury and dysfunction of a sudden onset, occurring after various types of acute brain injury as a result of an imbalance in the autonomic nervous system. The typical spectrum of clinically observed abnormalities includes acute left ventricular failure, not uncommonly progressing to cardiogenic shock with hypotension that requires inotropic agents, pulmonary oedema and various arrhythmias. Commonly-seen electrocardiographic changes include: prolonged QT interval, ST segment changes, T-wave inversion, a new Q-wave or U-wave. Echocardiography shows both an impaired both systolic and diastolic function of the left ventricle. Biochemical markers of NSM comprise metabolic acidosis and increased cardiac enzymes and markers: creatine kinase (CK), and CK-MB, troponin I and B-type natriuretic peptide. The main cause of NSM is myocardial injury induced by local catecholamine release from nerve endings within the myocardium. Recently, a theory has been proposed to classify NSM as one of the stress-related cardiomyopathies, together with Takotsubo cardiomyopathy, acute left ventricular failure in the critically ill, cardiomyopathy associated with pheochromacytoma and exogenous catecholamine administration. The occurrence of NSM increases the risk of life-threatening complications, death, and worsens neurologic outcome. As far as we know, treatment should generally focus on the underlying neurologic process in order to maximize neurologic recovery. Improvement in neurologic pathology leads to rapid improvement in cardiac function and its full recovery, as NSM is a fully reversible condition if the patient survives. Awareness of the existence of NSM and a deeper knowledge of its etiopathology may reduce diagnostic errors, optimise its treatment.

  12. Antibody SPC-54 provides acute in vivo blockage of the murine protein C system.

    Science.gov (United States)

    Burnier, Laurent; Fernández, José A; Griffin, John H

    2013-04-01

    Multiple protective effects of pharmacological activated protein C (APC) are reported in several organ pathologies. To help evaluate the endogenous murine PC system, we characterized a rat monoclonal anti-mouse PC antibody, SPC-54, which inhibited the amidolytic and anticoagulant activities of murine APC by>95%. SPC-54 blocked active site titration of purified APC using the active site titrant, biotinylated FPR-chloromethylketone, showing that SPC-54 blocks access to APC's active site to inhibit all enzymatic activity. A single injection of SPC-54 (10mg/kg) neutralized circulating PC in mice for at least 7days, and immunoblotting and immuno-precipitation with protein G-agarose confirmed that SPC-54 in vivo was bound to PC in plasma. Pre-infusion of SPC-54 in tissue factor-induced murine acute thromboembolism experiments caused a major decrease in mean survival time compared to controls (7min vs. 42.5min, P=0.0016). SPC-54 decreased lung perfusion in this model by 54% when monitored by vascular perfusion methodologies using infrared fluorescence of Evans blue dye. In LD50 endotoxemia murine models, SPC-54 infused at 7hr after endotoxin administration increased mortality from 42% to 100% (PSPC-54 ablates in vitro and in vivo APC protective functions and enzymatic activity. The ability of SPC-54 to block the endogenous PC/APC system provides a powerful tool to understand better the role of the endogenous PC system in murine injury models and in cell bioassays and also to neutralize the enzymatic activities of murine APC in any assay system. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Anti-inflammatory activity of Justicia prostrata gamble in acute and sub-acute models of inflammation.

    Science.gov (United States)

    Sanmugapriya, E; Shanmugasundaram, P; Venkataraman, S

    2005-01-01

    In this study, the aqueous (AQJP) and alcoholic (ALJP) extracts of the whole plant of Justicia prostrata Gamble (Acanthaceae) were screened for their acute and subacute anti-inflammatory activities using carrageenan-induced acute inflammation and cotton-pellet-induced granuloma (subacute inflammation), respectively, in rats. In the carrageenan-induced rat paw oedema model, both extracts were found to exhibit maximum reduction in paw volume at the first hour in a dose-dependent manner. At the dose of 500 mg/kg p.o., both extracts AQJP and ALJP showed maximum inhibition (51.39% and 62.5%, respectively) in rat paw oedema volume at the first hour of carrageenan-induced acute inflammation. In the cotton pellet granuloma assay, AQJP and ALJP at the dose of 500 mg/kg p.o. suppressed the transudative, exudative and proliferative phases of chronic inflammation. These extracts were able to (i) reduce the lipid peroxide content of exudates and liver and (ii) normalize the increased activity of acid and alkaline phosphatases in serum and liver of cotton pellet granulomatous rats. Preliminary phytochemical screening revealed the presence of lignans, triterpenes and phenolic compounds in ALJP, whereas phenolic compounds and glycosides in AQJP. The anti-inflammatory properties of these extracts may possibly be due to the presence of phenolic compounds. The anti-inflammatory effects produced by the extracts at the dose of 500 mg/kg, p.o. was comparable with the reference drug diclofenac sodium (5 mg/kg p.o.).

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    INTRODUCTION: 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...... following pPCI in patients with AMI. MATERIAL AND METHODS: The IMPACT trial is a multicentre, randomised, double-blinded, placebo-controlled study. We wish to include 2 × 20 patients with ST-elevation myocardial infarctions undergoing pPCI within six hours from symptom onset. The primary end......-point is the Myocardial Salvage Index assessed by cardiovascular magnetic resonance imaging on day 4 (± 1) after pPCI. The secondary end-points are high-sensitivity troponin, creatinekinase myocardial band and clinical events. CONCLUSION: The aim of the IMPACT trial is to evaluate the effect of melatonin on reperfusion...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    INTRODUCTION: 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...... following pPCI in patients with AMI. MATERIAL AND METHODS: The IMPACT trial is a multicentre, randomised, double-blinded, placebo-controlled study. We wish to include 2 × 20 patients with ST-elevation myocardial infarctions undergoing pPCI within six hours from symptom onset. The primary end......-point is the Myocardial Salvage Index assessed by cardiovascular magnetic resonance imaging on day 4 (± 1) after pPCI. The secondary end-points are high-sensitivity troponin, creatinekinase myocardial band and clinical events. CONCLUSION: The aim of the IMPACT trial is to evaluate the effect of melatonin on reperfusion...

  16. The immune system in atherosclerosis and in acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Antonio Barsotti

    2006-12-01

    Full Text Available Acute myocardial infarction (AMI occurs when the atheromatous process prevents total blood flow through the coronary artery. It was previously thought that progressive luminal narrowing from the continued growth of smooth muscle cells (SMCs in the plaque was the main cause of infarction, however, angiographic studies, have identified culprit lesions that do not cause marked stenosis. Is now evident that plaque activation, rather than stenosis, precipitates ischemia and infarction. Coronary spasm could be involved to some extent, but most cases of AMI are due to the formation of an occluding thrombus on the surface of the plaque; the two major causes of coronary thrombosis are plaque rupture and endothelial erosion. Plaque rupture is detectable in 60- 70% of cases and preferentially occurs when the fibrous cap is thin and partly destroyed. One of the major challenges in modern cardiology is the knowledge of the factors that induce a silent atherosclerotic plaque shifting from a stable to a vulnerable form.

  17. Reengineering acute episodic and chronic care delivery: the Geisinger Health System experience.

    Science.gov (United States)

    Slotkin, Jonathan R; Casale, Alfred S; Steele, Glenn D; Toms, Steven A

    2012-07-01

    Comparative effectiveness research (CER) represents an evolution in clinical decision-making research that allows for the study of heterogeneous groups of patients with complex diseases processes. It has foundations in decision science, reliability science, and health care policy research. Health care finance will increasingly rely on CER for guidance in the coming years. There is increasing awareness of the importance of decreasing unwarranted variation in health care delivery. In the past 7 years, Geisinger Health System has performed broad reengineering of its acute episodic and chronic care delivery models utilizing macrosystem-level application of CER principles. These provider-driven process initiatives have resulted in significant improvement across all segments of care delivery, improved patient outcomes, and notable cost containment. These programs have led to the creation of novel pricing models, and when "hardwired" throughout a care delivery system, they can lead to correct medical decision making by 100% of providers in all patient encounters. Neurosurgery as a specialty faces unique challenges and opportunities with respect to broad adoption and application of CER techniques.

  18. Integrated Modeling Systems

    Science.gov (United States)

    1989-01-01

    American Economic Review , 71:1 (March 1981). 181 J.M. Jones and F. Zufryden. "Adding Explanatory Variables to a Consumer Purchase Behavior Model: An...McCall. "An Operational Measure of Liquidity," The American Economic Review , 761 (March 1986). WMSI Working Paper 329. 212 Nelson, R., R. Sarin, and R

  19. [Acute adverse effects in transfusion. Proposals for the hemosurveillance system].

    Science.gov (United States)

    Baptista González, Héctor

    2013-01-01

    The management model based on risk prevention has become a major influence in shaping policies for transfusion safety. There are approximately sixty interactions between the health worker and the patient during the transfusion process,representing the number of times where you have the opportunity to make a mistake.We present an analysis of the weaknesses of the National Blood System, with particular attention to the haemovigilance donor and patient. The proposals include the implementation of the National Blood containing the need to establish from the National Blood Safety, significant changes in the regulatory framework and the internal regulations of the Ministry of Health, the CNTS and COFEPRIS. Is required to promote and coordinate the collection of accurate information from the committees of transfusion medicine, which will be accompanied by an initial diagnosis from the National Survey of Blood. Requires notice to other forms of funding to ensure the viability of the projects operating blood bank. Finally, as a strategic resource, the blood is of public, so access should not be restricted.

  20. Robust Disaster Recovery System Model

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Highly security-critical system should possess features of continuous service. We present a new Robust Disaster Recovery System Model (RDRSM). Through strengthening the ability of safe communications, RDRSM guarantees the secure and reliable command on disaster recovery. Its self-supervision capability can monitor the integrality and security of disaster recovery system itself. By 2D and 3D real-time visible platform provided by GIS, GPS and RS, the model makes the using, management and maintenance of disaster recovery system easier. RDRSM possesses predominant features of security, robustness and controllability. And it can be applied to highly security-critical environments such as E-government and bank. Conducted by RDRSM, an important E-government disaster recovery system has been constructed successfully. The feasibility of this model is verified by practice. We especially emphasize the significance of some components of the model, such as risk assessment, disaster recovery planning, system supervision and robust communication support.

  1. The Effects of Vitamin D on Gentamicin-Induced Acute Kidney Injury in Experimental Rat Model

    Directory of Open Access Journals (Sweden)

    Ender Hur

    2013-01-01

    Full Text Available Introduction. Acute kidney injury (AKI pathogenesis is complex. Findings of gentamicin nephrotoxicity are seen in 30% of the AKI patients. Vitamin D has proven to be effective on renin expression, inflammatory response, oxidative stress, apoptosis, and atherosclerosis. We aimed to investigate the effect of vitamin D in an experimental rat model of gentamicin-induced AKI. Methods. Thirty nonuremic Wistar albino rats were divided into 3 groups: Control group, 1 mL saline intramuscular (im daily; Genta group, gentamicin 100 mg/kg/day (im; Genta + vitamin D, gentamicin 100 mg/kg/day (im in addition to 1α, 25 (OH2D3 0.4 mcg/kg/day subcutaneously for 8 days. Blood pressures and 24-hour urine were measured. Blood urea and creatinine levels and urine tubular injury markers were measured. Renal histology was semiquantitatively assessed. Results. Urea, creatinine and urine neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 were all increased in Genta group indicating AKI model. Systolic blood pressure decreased, but urine volume and glutathione increased in Genta + Vit D group compared to Control group. Histological scores indicating tubular injury increased in Genta and Genta + Vit D groups. Conclusions. Vitamin D does not seem to be effective on histological findings although it has some beneficial effects via RAS system and a promising effect on antioxidant system.

  2. 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

  3. A pig model of acute Staphylococcus aureus induced pyemia

    DEFF Research Database (Denmark)

    Nielsen, O. L.; Iburg, T.; Aalbæk, B.;

    2009-01-01

    Background: Sepsis caused by Staphylococcus aureus constitutes an important cause of morbidity and mortality in humans, and the incidence of this disease-entity is increasing. In this paper we describe the initial microbial dynamics and lesions in pigs experimentally infected with S. aureus......, with the aim of mimicking human sepsis and pyemia. Methods: The study was conducted in anaesthetized and intravenously inoculated pigs, and was based on bacteriological examination of blood and testing of blood for IL-6 and C-reactive protein. Following killing of the animals and necropsy bacteriological...... was not detected in the blood and C-reactive protein did not increase, probably because of the short time course of the study. Conclusion: This study demonstrates the successful induction of acute pyemia (microabscesses), and forms a basis for future experiments that should include inoculation with strains of S...

  4. A pig model of acute Staphylococcus aureus induced pyemia

    DEFF Research Database (Denmark)

    Nielsen, O. L.; Iburg, T.; Aalbæk, B.

    2009-01-01

    Background: Sepsis caused by Staphylococcus aureus constitutes an important cause of morbidity and mortality in humans, and the incidence of this disease-entity is increasing. In this paper we describe the initial microbial dynamics and lesions in pigs experimentally infected with S. aureus......, with the aim of mimicking human sepsis and pyemia. Methods: The study was conducted in anaesthetized and intravenously inoculated pigs, and was based on bacteriological examination of blood and testing of blood for IL-6 and C-reactive protein. Following killing of the animals and necropsy bacteriological...... was not detected in the blood and C-reactive protein did not increase, probably because of the short time course of the study. Conclusion: This study demonstrates the successful induction of acute pyemia (microabscesses), and forms a basis for future experiments that should include inoculation with strains of S...

  5. 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, ...

  6. 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.

  7. Studies of Catalytic Model Systems

    DEFF Research Database (Denmark)

    Holse, Christian

    The overall topic of this thesis is within the field of catalysis, were model systems of different complexity have been studied utilizing a multipurpose Ultra High Vacuum chamber (UHV). The thesis falls in two different parts. First a simple model system in the form of a ruthenium single crystal...... is investigated. Second the development of a complex Cu/ZnO nanoparticle model system is described and gas-induced dynamical changes in the model system is investigated. The ruthenium crystal serves as an extremely simple model for studying CO dissociation which is the rate limiting step of the methanation...... process. The Ru(0 1 54) surface is studied by means of Scanning Tunneling Microscopy (STM), Temperature Programmed Desoprtion (TPD), and Oxygen Titration (OT) experiments. Real space evidence of periodic features on every second monatomic step is observed via STM when the a clean ruthenium surface...

  8. Relocatable Coastal Modeling System

    Science.gov (United States)

    2016-06-07

    These relationships are stored on a variable-resolution grid (illustrated in figure 1b below) with sampling of 1 degree in deep water (and in data...version is referred to as MODAS2.1, which is now operational at NAVO. The NOMADS interface is being replaced by a system-independent, web -based version...inside the user’s web browser plus Perl CGI scripts which ran on a webserver. This permitted the user to run MODAS (and POM and other modules as they are

  9. Comparison of two prognostic models for acute pulmonary embolism

    Directory of Open Access Journals (Sweden)

    Abd-ElRahim Ibrahim Youssef

    2016-10-01

    Conclusion: (1 There is an agreement to great extent in risk stratification of APE patients by PESI and ESC prognostic models, where mortality rate is increased among high risk classes of both models, (2 ESC prognostic model is more accurate than PESI model in mortality prediction of APE patients especially in the high risk class, (3 echocardiographic evidence of RVD and elevated plasma BNP can help to identify APE patients at increased risk of adverse short-term outcome and (4 integration of RVD assessment by echocardiography and BNP to clinical findings improves the prognostic value of ESC model.

  10. Evaluation of the importance of astrocytes when screening for acute toxicity in neuronal cell systems.

    Science.gov (United States)

    Woehrling, E K; Hill, E J; Coleman, M D

    2010-02-01

    Reliable, high throughput, in vitro preliminary screening batteries have the potential to greatly accelerate the rate at which regulatory neurotoxicity data is generated. This study evaluated the importance of astrocytes when predicting acute toxic potential using a neuronal screening battery of pure neuronal (NT2.N) and astrocytic (NT2.A) and integrated neuronal/astrocytic (NT2.N/A) cell systems derived from the human NT2.D1 cell line, using biochemical endpoints (mitochondrial membrane potential (MMP) depolarisation and ATP and GSH depletion). Following exposure for 72 h, the known acute human neurotoxicants trimethyltin-chloride, chloroquine and 6-hydroxydopamine were frequently capable of disrupting biochemical processes in all of the cell systems at non-cytotoxic concentrations. Astrocytes provide key metabolic and protective support to neurons during toxic challenge in vivo and generally the astrocyte containing cell systems showed increased tolerance to toxicant insult compared with the NT2.N mono-culture in vitro. Whilst there was no consistent relationship between MMP, ATP and GSH log IC(50) values for the NT2.N/A and NT2.A cell systems, these data did provide preliminary evidence of modulation of the acute neuronal toxic response by astrocytes. In conclusion, the suitability of NT2 neurons and astrocytes as cell systems for acute toxicity screening deserves further investigation.

  11. 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.

  12. Data management system performance modeling

    Science.gov (United States)

    Kiser, Larry M.

    1993-01-01

    This paper discusses analytical techniques that have been used to gain a better understanding of the Space Station Freedom's (SSF's) Data Management System (DMS). The DMS is a complex, distributed, real-time computer system that has been redesigned numerous times. The implications of these redesigns have not been fully analyzed. This paper discusses the advantages and disadvantages for static analytical techniques such as Rate Monotonic Analysis (RMA) and also provides a rationale for dynamic modeling. Factors such as system architecture, processor utilization, bus architecture, queuing, etc. are well suited for analysis with a dynamic model. The significance of performance measures for a real-time system are discussed.

  13. Comparison of exogenous surfactant therapy, mechanical ventilation with high end-expiratory pressure and partial liquid ventilation in a model of acute lung injury

    NARCIS (Netherlands)

    A. Hartog (Anneke); G.F. Vazquez de Anda; D.A.M.P.J. Gommers (Diederik); U. Kaisers; S.J.C. Verbrugge (Serge); R. Schnabel; B.F. Lachmann (Burkhard)

    1999-01-01

    textabstractWe have compared three treatment strategies, that aim to prevent repetitive alveolar collapse, for their effect on gas exchange, lung mechanics, lung injury, protein transfer into the alveoli and surfactant system, in a model of acute lung injury. In adult r

  14. Isobolographic analysis of multimodal analgesia in an animal model of visceral acute pain.

    Science.gov (United States)

    Miranda, Hugo F; Prieto, Juan Carlos; Puig, Margarita M; Pinardi, Gianni

    2008-02-01

    Multiple analgesic-drug combinations are commonly used in the management of acute and chronic pain in humans during multimodal or balanced analgesia. At present, these combinations are used empirically in clinical practice and are considered to be beneficial for the patient. Interactions between two antinociceptive drugs have been thoroughly examined, but the nature of interactions between three analgesics has not been studied. The antinociceptive interaction of ketoprofen (K) with a mixture of morphine (M) and paracetamol (P) was evaluated using a model of visceral acute tonic pain, the acetic-acid writhing test in mice. The i.p. administration of the combination M/P+K resulted in a significant potentiation of the antinociception induced either by K or by the synergic two-drug mixtures M/K, P/K and M/P. The effect of opioid, cholinergic, adrenergic and serotonergic antagonists on the analgesic interaction was assessed. The pretreatment of mice with atropine (1 mg/kg) did not produce any change in the synergistic interaction of the triple combination. The pretreatment with naltrexone (1 mg/kg) or tropisetron (1 mg/kg) reduced the intensity of M/P+K synergic interaction, while prazosin (0.1 mg/kg) significantly potentiated the synergy. The findings of this work suggest that the two major pathways of descending inhibitory systems, noradrenergic and serotonergic are significantly involved in the mechanism of the antinociceptive synergy induced by the triple combination. On the other hand, opioid pathways also seem to participate, since pretreatment with naltrexone reduced the synergy. In conclusion, the triple combination M/P+K induced a strong synergistic antinociceptive effect, which could be of interest for optimal multimodal clinical analgesia.

  15. N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation via Nonhematopoietic TRPV1

    Science.gov (United States)

    Lawton, Samira K.; Xu, Fengyun; Tran, Alphonso; Wong, Erika; Schumacher, Mark; Wilhelmsen, Kevin

    2017-01-01

    N-Arachidonoyl dopamine (NADA) is an endogenous lipid that potently activates the transient receptor potential vanilloid 1 (TRPV1), which mediates pain and thermosensation. NADA is also an agonist of cannabinoid receptors 1 and 2. We have reported that NADA reduces the activation of cultured human endothelial cells by LPS and TNF-α. Thus far, in vivo studies using NADA have focused on its neurologic and behavioral roles. In this article, we show that NADA potently decreases in vivo systemic inflammatory responses and levels of the coagulation intermediary plasminogen activator inhibitor 1 in three mouse models of inflammation: LPS, bacterial lipopeptide, and polymicrobial intra-abdominal sepsis. We also found that the administration of NADA increases survival in endotoxemic mice. Additionally, NADA reduces blood levels of the neuropeptide calcitonin gene-related peptide but increases the neuropeptide substance P in LPS-treated mice. We demonstrate that the anti-inflammatory effects of NADA are mediated by TRPV1 expressed by nonhematopoietic cells and provide data suggesting that neuronal TRPV1 may mediate NADA’s anti-inflammatory effects. These results indicate that NADA has novel TRPV1-dependent anti-inflammatory properties and suggest that the endovanilloid system might be targeted therapeutically in acute inflammation. PMID:28701511

  16. Antibiotics in Addition to Systemic Corticosteroids for Acute Exacerbations of Chronic Obstructive Pulmonary Disease

    NARCIS (Netherlands)

    J.M.A. Daniels; D. Snijders; C.S. de Graaff; F. Vlaspolder; H.M. Jansen; W.G. Boersma

    2010-01-01

    Rationale: The role of antibiotics in acute exacerbations is controversial and their efficacy when added to systemic corticosteroids is unknown. Objectives: We conducted a randomized, placebo-controlled trial to determine the effects of doxycycline in addition to corticosteroids on clinical outcome,

  17. 78 FR 27485 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Science.gov (United States)

    2013-05-10

    ... Episode of Care for Acute Myocardial Infarction (AMI) Measure 7. Electronic Clinical Quality Measures 8... Osteopathic Association APR DRG All Patient Refined Diagnosis Related Group System APRN Advanced practice... percentage DRA Deficit Reduction Act of 2005, Public Law 109-171 DRG Diagnosis-related group...

  18. 78 FR 50495 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Science.gov (United States)

    2013-08-19

    ... Episode-of-Care for Acute Myocardial Infarction (AMI) Measure 7. Electronic Clinical Quality Measures 8... All Patient Refined Diagnosis Related Group System APRN Advanced practice registered nurse ARRA... Deficit Reduction Act of 2005, Public Law 109-171 DRG Diagnosis-related group DSH Disproportionate...

  19. 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.

  20. ”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.

  1. Quantitative changes in rat renin secretory granules after acute and chronic stimulation of the renin system

    DEFF Research Database (Denmark)

    Rasch, Ruth; Jensen, B L; Nyengaard, Jens Randel

    1998-01-01

    In order to study the cellular mode of renin secretion, stereological methods were used to estimate number and volume of rat renin secretory granules during stimulation of the renin system. An acute decrease in renal perfusion pressure to 40 mmHg for 5 min increased plasma renin concentration (PR...

  2. 78 FR 79300 - Cardiovascular Devices; Reclassification of Intra-Aortic Balloon and Control Systems for Acute...

    Science.gov (United States)

    2013-12-30

    ... Intra-Aortic Balloon and Control Systems for Acute Coronary Syndrome, Cardiac and Non- Cardiac Surgery... coronary syndrome, cardiac and non- cardiac surgery, or complications of heart failure, a preamendments..., cardiac and non-cardiac surgery, or complications of heart failure from class III to class II. Section 513...

  3. Alpha glucocorticoid receptor expression in different experimental rat models of acute lung injury

    OpenAIRE

    Bertorelli,Giuseppina; Pesci, Alberto; Peveri, Silvia; Mergoni, Mario; Corradi, Attilio; Cantoni, Anna Maria; Tincani, Giovanni; Bobbio, Antonio; Rusca, Michele; Carbognani, Paolo

    2008-01-01

    Alpha glucocorticoid receptor expression in different experimental rat models of acute lung injury correspondence: Corresponding author. Tel.: +390521703883; fax: +390521703493. (Carbognani, Paolo) (Carbognani, Paolo) Dipartimento di Clinica Medica - Nefrologia e Scienze della Prevenzione--> , University of Parma--> - ITALY (Bertorelli, Giuseppina) Dipartimento di Clinica Medica - Nefrologia e Scienze della...

  4. 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...

  5. Evaluation of antiinflammatory activity of the total flavonoids of Laggera pterodonta on acute and chronic inflammation models.

    Science.gov (United States)

    Wu, Yihang; Zhou, Changxin; Li, Xiangping; Song, Liyan; Wu, Xiumei; Lin, Wenyan; Chen, Haiyong; Bai, Hua; Zhao, Jun; Zhang, Rongping; Sun, Handong; Zhao, Yu

    2006-07-01

    The antiinflammatory effect of the total flavonoids of Laggera pterodonta (TFLP) was evaluated with various in vivo models of both acute and chronic inflammation. In the acute inflammation tests, TFLP significantly inhibited xylene-induced mouse ear oedema, carrageenan-induced rat paw oedema and acetic acid-induced mouse vascular permeability. In the carrageenan-induced rat pleurisy model, TFLP efficiently suppressed inflammatory exudate and leukocyte migration, reduced the serum levels of lysozyme (LZM) and malondialdehyde (MDA), increased the activity of serum superoxide dismutase (SOD), and also decreased the contents of total protein, nitric oxide (NO) and prostaglandin E2 (PGE2) in the pleural exudates. No marked effect of TFLP on the activity of serum glutathione peroxidase (GSH-PX) was observed. In the chronic inflammation experiment, TFLP inhibited cotton pellet-induced rat granuloma. The antiinflammatory mechanisms of TFLP are probably associated with the inhibition of prostaglandin formation, influence on the antioxidant systems and the suppression of LZM release. The acute toxicity study revealed that TFLP was nontoxic in mice up to an oral dose of 7.5 g/kg body weight.

  6. Sodium Thiosulfate Versus Hydroxocobalamin in the Treatment of Acute, Severe Cyanide Induced Cardiotoxicity in a Swine (Sus Scrofa) Model

    Science.gov (United States)

    2011-09-22

    IUIVIJ:lt:M Sodium thiosulfate versus hydroxocoba~amin in the treatment of acute, severe cyanide induced cardiotoxicity in a swine (Sus Scrofa )model on...treatment of acute, severe cyanide induced cardiotoxicity in a swine (Sus Scrofa ) model .. 4. Principal Investigator (PI): ’ ~ I ’ ·, .. Name Rank Date

  7. SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model

    Science.gov (United States)

    Xu, Siqi; Wei, Siwei; Dai, Xingui

    2016-01-01

    Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue extraction and renal tubular epithelial cell (RTEC) isolation. We observed reduced SIRT1/3 activity, elevated acetylated SOD2 (ac-SOD2) levels and oxidative stress, and damaged mitochondria in RTECs following sepsis. Treatment with resveratrol (RSV), a chemical SIRT1 activator, effectively restored SIRT1/3 activity, reduced acetylated SOD2 levels, ameliorated oxidative stress and mitochondrial function of RTECs, and prolonged survival time. However, the beneficial effects of RSV were greatly abrogated by Ex527, a selective inhibitor of SIRT1. These results suggest a therapeutic role for SIRT1 in the reversal of AKI in septic rat, which may rely on SIRT3-mediated deacetylation of SOD2. SIRT1/3 activation could therefore be a promising therapeutic strategy to treat sepsis-associated AKI. PMID:28003866

  8. 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

  9. National Energy Outlook Modelling System

    Energy Technology Data Exchange (ETDEWEB)

    Volkers, C.M. [ECN Policy Studies, Petten (Netherlands)

    2013-12-15

    For over 20 years, the Energy research Centre of the Netherlands (ECN) has been developing the National Energy Outlook Modelling System (NEOMS) for Energy projections and policy evaluations. NEOMS enables 12 energy models of ECN to exchange data and produce consistent and detailed results.

  10. 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

  11. A test of syndromic surveillance using a severe acute respiratory syndrome model.

    Science.gov (United States)

    Wallace, David J; Arquilla, Bonnie; Heffernan, Richard; Kramer, Martin; Anderson, Todd; Bernstein, David; Augenbraun, Michael

    2009-05-01

    We describe a field simulation that was conducted using volunteers to assess the ability of 3 hospitals in a network to manage a large influx of patients with a potentially communicable disease. This drill provided the opportunity to evaluate the ability of the New York City Department of Health and Mental Hygiene's (NYC-DOHMH) emergency department chief complaint syndromic surveillance system to detect a cluster of patients with febrile respiratory illness. The evaluation was a prospective simulation. The clinical picture was modeled on severe acute respiratory syndrome symptoms. Forty-four volunteers participated in the drill as mock patients. Records from 42 patients (95%) were successfully transmitted to the NYC-DOHMH. The electronic chief complaint for 24 (57%) of these patients indicated febrile or respiratory illness. The drill did not generate a statistical signal in the NYC-DOHMH SaTScan analysis. The 42 drill patients were classified in 8 hierarchical categories based on chief complaints: sepsis (2), cold (3), diarrhea (2), respiratory (20), fever/flu (4), vomit (3), and other (8). The number of respiratory visits, while elevated on the day of the drill, did not appear particularly unusual when compared with the 14-day baseline period used for spatial analyses. This drill with a cluster of patients with febrile respiratory illness failed to trigger a signal from the NYC-DOHMH emergency department chief complaint syndromic surveillance system. This highlighted several limitations and challenges to syndromic surveillance monitoring.

  12. 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.

  13. 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...

  14. 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...

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

    African Journals Online (AJOL)

    2017-09-03

    Sep 3, 2017 ... and immune system activation during and after cardiac surgery supported by ... cardioprotective solutions which was either cold blood cardioplegia delivered at .... the effect of cardiac surgery with CPB in HIV positive subjects.

  16. Nosocomial infections in patients with acute central nervous system infections

    OpenAIRE

    2007-01-01

    Due to current increase in the rate of nosocomial infections, our objective was to examine the frequency, risk factors, clinical presentation and etiology of nosocomial infections in patients with central nervous system infections. 2246 patients with central nervous system infections, treated in the intensive care units of the Institute of Infectious and Tropical Diseases, Clinical Center of Serbia in Belgrade and at the Department of Infectious Diseases of the Clinical Hospital Center Kraguj...

  17. [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.

  18. 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

    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...

  19. An extensible analysable system model

    DEFF Research Database (Denmark)

    Probst, Christian W.; Hansen, Rene Rydhof

    2008-01-01

    , 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...... allows for easy development of analyses for the abstracted systems. We briefly present one application of our approach, namely the analysis of systems for potential insider threats....

  20. A new model to predict acute kidney injury requiring renal replacement therapy after cardiac surgery

    Science.gov (United States)

    Pannu, Neesh; Graham, Michelle; Klarenbach, Scott; Meyer, Steven; Kieser, Teresa; Hemmelgarn, Brenda; Ye, Feng; James, Matthew

    2016-01-01

    Background: Acute kidney injury after cardiac surgery is associated with adverse in-hospital and long-term outcomes. Novel risk factors for acute kidney injury have been identified, but it is unknown whether their incorporation into risk models substantially improves prediction of postoperative acute kidney injury requiring renal replacement therapy. Methods: We developed and validated a risk prediction model for acute kidney injury requiring renal replacement therapy within 14 days after cardiac surgery. We used demographic, and preoperative clinical and laboratory data from 2 independent cohorts of adults who underwent cardiac surgery (excluding transplantation) between Jan. 1, 2004, and Mar. 31, 2009. We developed the risk prediction model using multivariable logistic regression and compared it with existing models based on the C statistic, Hosmer–Lemeshow goodness-of-fit test and Net Reclassification Improvement index. Results: We identified 8 independent predictors of acute kidney injury requiring renal replacement therapy in the derivation model (adjusted odds ratio, 95% confidence interval [CI]): congestive heart failure (3.03, 2.00–4.58), Canadian Cardiovascular Society angina class III or higher (1.66, 1.15–2.40), diabetes mellitus (1.61, 1.12–2.31), baseline estimated glomerular filtration rate (0.96, 0.95–0.97), increasing hemoglobin concentration (0.85, 0.77–0.93), proteinuria (1.65, 1.07–2.54), coronary artery bypass graft (CABG) plus valve surgery (v. CABG only, 1.25, 0.64–2.43), other cardiac procedure (v. CABG only, 3.11, 2.12–4.58) and emergent status for surgery booking (4.63, 2.61–8.21). The 8-variable risk prediction model had excellent performance characteristics in the validation cohort (C statistic 0.83, 95% CI 0.79–0.86). The net reclassification improvement with the prediction model was 13.9% (p < 0.001) compared with the best existing risk prediction model (Cleveland Clinic Score). Interpretation: We have developed

  1. A modelling tool for capacity planning in acute and community stroke services.

    Science.gov (United States)

    Monks, Thomas; Worthington, David; Allen, Michael; Pitt, Martin; Stein, Ken; James, Martin A

    2016-09-29

    Mathematical capacity planning methods that can take account of variations in patient complexity, admission rates and delayed discharges have long been available, but their implementation in complex pathways such as stroke care remains limited. Instead simple average based estimates are commonplace. These methods often substantially underestimate capacity requirements. We analyse the capacity requirements for acute and community stroke services in a pathway with over 630 admissions per year. We sought to identify current capacity bottlenecks affecting patient flow, future capacity requirements in the presence of increased admissions, the impact of co-location and pooling of the acute and rehabilitation units and the impact of patient subgroups on capacity requirements. We contrast these results to the often used method of planning by average occupancy, often with arbitrary uplifts to cater for variability. We developed a discrete-event simulation model using aggregate parameter values derived from routine administrative data on over 2000 anonymised admission and discharge timestamps. The model mimicked the flow of stroke, high risk TIA and complex neurological patients from admission to an acute ward through to community rehab and early supported discharge, and predicted the probability of admission delays. An increase from 10 to 14 acute beds reduces the number of patients experiencing a delay to the acute stroke unit from 1 in every 7 to 1 in 50. Co-location of the acute and rehabilitation units and pooling eight beds out of a total bed stock of 26 reduce the number of delayed acute admissions to 1 in every 29 and the number of delayed rehabilitation admissions to 1 in every 20. Planning by average occupancy would resulted in delays for one in every five patients in the acute stroke unit. Planning by average occupancy fails to provide appropriate reserve capacity to manage the variations seen in stroke pathways to desired service levels. An appropriate uplift

  2. An effective system to measure and report quality indicators in acute medical units.

    Science.gov (United States)

    Atkinson, J; Barton, L; Harrison, A; Roper, N

    2012-01-01

    The Society for Acute Medicine has developed a number of clinical quality indicators by which all UK Acute Medicine Units can bench mark their activity. These will help to ensure high quality care for patients, inform the continuing development of acute medical services and demonstrate the positive impact of this new specialty. Prospective collection of these data may be a challenge for many busy units. This paper describes a local solution developed in house in a North East hospital. It demonstrates how the data collected can be analysed to assess the effect of changes in consultant presence on the unit and also time taken for patients to be seen by a doctor. The limitations of the system and potential for future development are considered.

  3. 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...

  4. Central effect of histamine in a rat model of acute trigeminal pain.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Khalilzadeh, Emad; Hamzeh-Gooshchi, Nasrin; Seiednejhad-Yamchi, Sona

    2008-01-01

    In conscious rats implanted with an intracerebroventricular (icv) cannula, effect of icv injections of histamine, chlorpheniramine (H(1)-receptor antagonist) and ranitidine (H(2)-receptor blocker) was investigated in a rat model of acute trigeminal pain. Acute trigeminal pain was induced by putting a drop of 5 M NaCl solution on the corneal surface of the eye and the numbers of eye wipes were counted during the first 30 s. Histamine (20, 40 microg) and chlorpheniramine (80 microg) significantly decreased the numbers of eye wipes. Ranitidine alone had no effect. Pretreatment with chlorpheniramine did not change the histamine-induced analgesia, whereas the histamine effect on pain was inhibited with ranitidine pretreatment. These results indicate that the brain histamine, through central H(2) receptors, may be involved in the modulation of the acute trigeminal pain in rats.

  5. 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.

  6. Anticonvulsant effects of acute treatment with cyane-carvone at repeated oral doses in epilepsy models.

    Science.gov (United States)

    Marques, Thiago Henrique Costa; Marques, Maria Leonildes Boavista Gomes Castelo Branco; Medeiros, Jand-Venes Rolim; Lima, Tamires Cardoso; de Sousa, Damião Pergentino; de Freitas, Rivelilson Mendes

    2014-09-01

    Epilepsy affects about 40 million people worldwide. Many drugs block seizures, but have little effect in preventing or curing this disease. So the search for new drugs for epilepsy treatment using animal models prior to testing in humans is important. Increasingly pharmaceutical industries invest in the Re​search & Drug Development area to seek safe and effective new therapeutic alternatives to the currently available epilepsy treatment. In this perspective, natural compounds have been investigated in epilepsy models, particularly the monoterpenes obtained from medicinal plants. In our study we investigated the effects of cyane-carvone (CC), a synthetic substance prepared from natural a monoterpene, carvone, against pilocarpine- (PILO), pentylenetetrazole- (PTZ) and picrotoxine (PTX)-induced seizures in mice after acute treatment with repeated oral doses (CC 25, 50 and 75 mg/kg) for 14 days. CC in all doses tested showed increase in latency to first seizure, decrease in percentages of seizuring animals as well as reduction percentages of dead animals (pepilepsy models. In addition, our data suggest that CC could act in an allosteric site of GABAA, which would be different from the site in which BDZ acts, since flumazenil was not able to reverse any of CC effects on the modulation of seizure parameters related with epilepsy models investigated. New studies should be conducted to investigate CC effects in other neurotransmitter systems. Nevertheless, our study reinforces the hypothesis that CC could be used, after further research, as a new pharmaceutical formulation and a promising alternative for epilepsy treatment, since it showed anticonvulsant effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Distribution system modeling and analysis

    CERN Document Server

    Kersting, William H

    2002-01-01

    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 re

  8. Stirling Engine Dynamic System Modeling

    Science.gov (United States)

    Nakis, Christopher G.

    2004-01-01

    The Thermo-Mechanical systems branch at the Glenn Research Center focuses a large amount time on Stirling engines. These engines will be used on missions where solar power is inefficient, especially in deep space. I work with Tim Regan and Ed Lewandowski who are currently developing and validating a mathematical model for the Stirling engines. This model incorporates all aspects of the system including, mechanical, electrical and thermodynamic components. Modeling is done through Simplorer, a program capable of running simulations of the model. Once created and then proven to be accurate, a model is used for developing new ideas for engine design. My largest specific project involves varying key parameters in the model and quantifying the results. This can all be done relatively trouble-free with the help of Simplorer. Once the model is complete, Simplorer will do all the necessary calculations. The more complicated part of this project is determining which parameters to vary. Finding key parameters depends on the potential for a value to be independently altered in the design. For example, a change in one dimension may lead to a proportional change to the rest of the model, and no real progress is made. Also, the ability for a changed value to have a substantial impact on the outputs of the system is important. Results will be condensed into graphs and tables with the purpose of better communication and understanding of the data. With the changing of these parameters, a more optimal design can be created without having to purchase or build any models. Also, hours and hours of results can be simulated in minutes. In the long run, using mathematical models can save time and money. Along with this project, I have many other smaller assignments throughout the summer. My main goal is to assist in the processes of model development, validation and testing.

  9. Effect of acute and chronic bilateral visual deafferentation on c-Fos immunoreactivity in the visual system of adult rats.

    Science.gov (United States)

    Wiedmann, Rhea; Rosahl, Steffen K; Brinker, Thomas; Samii, Madjid; Nakamura, Makoto

    2013-09-01

    In our study we examined acute and chronic changes in c-Fos expression patterns in the visual system of the rat after complete visual deafferentation. In 20 male Lewis rats, the retro-bulbar part of the optic nerve was sectioned bilaterally. Ten animals underwent c-Fos immunohistochemistry after 3 days and 10 animals after 3 weeks examining time-dependent changes. The control group consisted of 10 animals, which did not undergo any surgical manipulation. c-Fos expression in the rat visual system experienced significant changes after acute and chronic bilateral complete visual deafferentation. Acute decrease in c-Fos level was observed in the ventral lateral geniculate nucleus, intergeniculate leaflet, superficial gray layer of the superior colliculus and layers IV and V of the primary visual cortex. After chronic deafferentation, c-Fos expression was also found to be decreased in the optic and deep layers of the superior colliculus and layer VI of the primary visual cortex. No change in c-Fos expression was observed in the dorsal lateral geniculate nucleus and layers I, II and III of the primary visual cortex. This work shows that secondary complete blindness does not lead to uniform decrease in c-Fos levels in all subcortical and cortical brain regions related to vision. These findings provide important information concerning expression of the immediate-early gene product c-Fos in secondary blind rodent models. It may further serve as a relevant baseline finding when electrical stimulation of the visual system is performed, aiding the assessment of visual neuroprosthesis using c-Fos as a functional mapping tool when evaluating different stimulus parameters in blind rodent models.

  10. 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

  11. Kinetic Modeling of Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

    Resat, Haluk; Petzold, Linda; Pettigrew, Michel F.

    2009-04-21

    The dynamics of how its constituent components interact define the spatio-temporal response of a natural system to stimuli. Modeling the kinetics of the processes that represent a biophysical system has long been pursued with the aim of improving our understanding of the studied system. Due to the unique properties of biological systems, in addition to the usual difficulties faced in modeling the dynamics of physical or chemical systems, biological simulations encounter difficulties that result from intrinsic multiscale and stochastic nature of the biological processes. This chapter discusses the implications for simulation of models involving interacting species with very low copy numbers, which often occur in biological systems and give rise to significant relative fluctuations. The conditions necessitating the use of stochastic kinetic simulation methods and the mathematical foundations of the stochastic simulation algorithms are presented. How the well-organized structural hierarchies often seen in biological systems can lead to multiscale problems, and possible ways to address the encountered computational difficulties are discussed. We present the details of the existing kinetic simulation methods, and discuss their strengths and shortcomings. A list of the publicly available kinetic simulation tools and our reflections for future prospects are also provided.

  12. Acute Effect of Static Stretching on Lower Limb Movement Performance by Using STABL Virtual Reality System.

    Science.gov (United States)

    Ameer, Mariam A; Muaidi, Qassim I

    2017-07-17

    The effect of acute static stretch (ASS) on the lower limb RT has been recently questioned to decrease the risk of falling and injuries in situations requiring a rapid reaction, as in the cases of balance disturbance. The main purpose of this study was to detect the effect of ASS on the lower limb RT by using virtual reality device. Two Group Control Group design. Research laboratory. The control and experimental groups were formed randomly from sixty female university students. Each participant in the experimental group was tested before and after ASS for the quadriceps, hamstrings and planter flexor muscles, and compared with the control group with warming-up exercise only. The stretching program involved warming-up in the form of circular running inside the lab for 5 minutes followed by stretching of each muscle group thrice, to the limit of discomfort of 45 s, with resting period of 15s between stretches. The measurements included the RT of the dominant lower extremity by using the dynamic stability program, STABL Virtual Reality System (Model No. DIZ 2709, Motek Medical and Force Link Merged Co., Amsterdam). There was statistically significant reduction (F = 162, P= .00) in post-test RT between the two groups, and significant decrease in RT after stretching, in the experimental group (7.5%) (P= .00). ASS of the lower limb muscles tends to decrease the lower limb RT and improve movement performance.

  13. 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.

  14. Chemoreceptors and cardiovascular control in acute and chronic systemic hypoxia

    Directory of Open Access Journals (Sweden)

    J.M. Marshall

    1998-07-01

    Full Text Available This review describes the ways in which the primary bradycardia and peripheral vasoconstriction evoked by selective stimulation of peripheral chemoreceptors can be modified by the secondary effects of a chemoreceptor-induced increase in ventilation. The evidence that strong stimulation of peripheral chemoreceptors can evoke the behavioural and cardiovascular components of the alerting or defence response which is characteristically evoked by novel or noxious stimuli is considered. The functional significance of all these influences in systemic hypoxia is then discussed with emphasis on the fact that these reflex changes can be overcome by the local effects of hypoxia: central neural hypoxia depresses ventilation, hypoxia acting on the heart causes bradycardia and local hypoxia of skeletal muscle and brain induces vasodilatation. Further, it is proposed that these local influences can become interdependent, so generating a positive feedback loop that may explain sudden infant death syndrome (SIDS. It is also argued that a major contributor to these local influences is adenosine. The role of adenosine in determining the distribution of O2 in skeletal muscle microcirculation in hypoxia is discussed, together with its possible cellular mechanisms of action. Finally, evidence is presented that in chronic systemic hypoxia, the reflex vasoconstrictor influences of the sympathetic nervous system are reduced and/or the local dilator influences of hypoxia are enhanced. In vitro and in vivo findings suggest this is partly explained by upregulation of nitric oxide (NO synthesis by the vascular endothelium which facilitates vasodilatation induced by adenosine and other NO-dependent dilators and attenuates noradrenaline-evoked vasoconstriction.

  15. 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.

  16. Evaluating effects of normobaric oxygen therapy in acute stroke with MRI-based predictive models

    Directory of Open Access Journals (Sweden)

    Wu Ona

    2012-03-01

    Full Text Available Abstract Background Voxel-based algorithms using acute multiparametric-MRI data have been shown to accurately predict tissue outcome after stroke. We explored the potential of MRI-based predictive algorithms to objectively assess the effects of normobaric oxygen therapy (NBO, an investigational stroke treatment, using data from a pilot study of NBO in acute stroke. Methods The pilot study of NBO enrolled 11 patients randomized to NBO administered for 8 hours, and 8 Control patients who received room-air. Serial MRIs were obtained at admission, during gas therapy, post-therapy, and pre-discharge. Diffusion/perfusion MRI data acquired at admission (pre-therapy was used in generalized linear models to predict the risk of lesion growth at subsequent time points for both treatment scenarios: NBO or Control. Results Lesion volume sizes 'during NBO therapy' predicted by Control-models were significantly larger (P = 0.007 than those predicted by NBO models, suggesting that ischemic lesion growth is attenuated during NBO treatment. No significant difference was found between the predicted lesion volumes at later time-points. NBO-treated patients, despite showing larger lesion volumes on Control-models than NBO-models, tended to have reduced lesion growth. Conclusions This study shows that NBO has therapeutic potential in acute ischemic stroke, and demonstrates the feasibility of using MRI-based algorithms to evaluate novel treatments in early-phase clinical trials.

  17. 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...

  18. 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

  19. Quark Model and multiquark system

    CERN Document Server

    da Silva, Cristiane Oldoni

    2010-01-01

    The discovery of many particles, especially in the 50's, when the firsts accelerators appeared, caused the searching for a model that would describe in a simple form the whole of known particles. The Quark Model, based in the mathematical structures of group theory, provided in the beginning of the 60's a simplified description of hadronic matter already known, proposing that three particles, called quarks, would originate all the observed hadrons. This model was able to preview the existence of particles that were later detected, confirming its consistency. Extensions of the Quark Model were made in the beginning of the 70's, focusing in describing observed particles that were excited states of the fundamental particles and others that presented new quantum numbers (flavors). Recently, exotic states as tetraquarks and pentaquarks types, also called multiquarks systems, previewed by the model, were observed, what renewed the interest in the way as quarks are confined inside the hadrons. In this article we pre...

  20. 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.

  1. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Laningham, Fred H. [St. Jude Children' s Research Hospital, Division of Diagnostic Imaging, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Kun, Larry E. [St. Jude Children' s Research Hospital, Division of Radiation Oncology, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Reddick, Wilburn E.; Ogg, Robert J. [St. Jude Children' s Research Hospital, Division of Translational Imaging Research, Department of Radiological Sciences, Memphis, TN (United States); Morris, E.B. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Pui, Ching-Hon [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States)

    2007-11-15

    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

  3. 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

  4. 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 behavi

  5. [Autochthonous acute viral and bacterial infections of the central nervous system (meningitis and encephalitis)].

    Science.gov (United States)

    Pérez-Ruiz, Mercedes; Vicente, Diego; Navarro-Marí, José María

    2008-07-01

    Rapid diagnosis of acute viral and bacterial infections of the central nervous system (meningitis and encephalitis) is highly important for the clinical management of the patient and helps to establish early therapy that may solve life-threatening situations, to avoid unnecessary empirical treatments, to reduce hospital stay, and to facilitate appropriate interventions in the context of public health. Molecular techniques, especially real-time polymerase chain reaction, have become the fastest and most sensitive diagnostic procedures for autochthonous viral meningitis and encephalitis, and their role is becoming increasingly important for the diagnosis and control of most frequent acute bacterial meningitides. Automatic and closed systems may encourage the widespread and systematic use of molecular techniques for the diagnosis of these neurological syndromes in most laboratories.

  6. Preventive central nervous system irradiation in children with acute nonlymphocytic leukemia. [Complications of. gamma. radiation

    Energy Technology Data Exchange (ETDEWEB)

    Dahl, G.V.; Simone, J.V.; Hustu, H.O.; Mason, C.

    1978-11-01

    In this study of children with acute nonlymphocytic leukemia an attempt was made to prevent central nervous system relapse and to determine whether this therapy, coupled with multiagent chemotherapy, would be successful in prolonging durations of complete remission. Central nervous system relapses were prevented by irradiation, although patients who received this therapy did no better than those who did not receive irradiation. A small group of patients received irradiation to the liver and spleen, but this modality also failed to improve the duration of remission. Control of extramedullary leukemia, in this study, failed to improve remission duration because bone marrow relapse was not prevented or delayed. It is unlikely that focal therapy will have a significant impact in acute nonlymphocytic leukemia until longer marrow remissions are achieved.

  7. Comparison of Existing Clinical Scoring Systems in Predicting Severity and Prognoses of Hyperlipidemic Acute Pancreatitis in Chinese Patients

    OpenAIRE

    Qiu, Lei; Sun, Rui Qing; Jia, Rong Rong; Ma, Xiu Ying; Cheng, Li; Tang, Mao Chun; Zhao, Yan

    2015-01-01

    Abstract It is important to identify the severity of acute pancreatitis (AP) in the early course of the disease. Clinical scoring systems may be helpful to predict the prognosis of patients with early AP; however, few analysts have forecast the accuracy of scoring systems for the prognosis in hyperlipidemic acute pancreatitis (HLAP). The purpose of this study was to summarize the clinical characteristics of HLAP and compare the accuracy of conventional scoring systems in predicting the progno...

  8. Hypothermia induced by adenosine 5'-monophosphate attenuates early stage injury in an acute gouty arthritis rat model.

    Science.gov (United States)

    Miao, Zhimin; Guo, Weiting; Lu, Shulai; Lv, Wenshan; Li, Changgui; Wang, Yangang; Zhao, Shihua; Yan, Shengli; Tao, Zhenyin; Wang, Yunlong

    2013-08-01

    To investigate whether the hypothermia induced by Adenosine 5'-Monophosphate (5'-AMP) could attenuate early stage injury in a rat acute gouty arthritis model. Ankle joint injection with monosodium urate monohydrate crystals (MSU crystals) in hypothermia rat model which was induced by 5'-AMP and then observe whether hypothermia induced by 5'-AMP could be effectively inhibit the inflammation on acute gouty arthritis in rats. AMP-induced hypothermia has protective effects on our acute gouty arthritis, which was demonstrated by the following criteria: (1) a significant reduction in the ankle swelling (p gouty arthritis model.

  9. The Impact of Acute Matriptase Inhibition in Hepatic Inflammatory Models

    Directory of Open Access Journals (Sweden)

    Judit Pomothy

    2016-01-01

    Full Text Available Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models. Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 : 1 and 6 : 1 were treated with four structurally related matriptase inhibitors at 50 μM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA. The extracellular H2O2 contents were analyzed by Amplex Red method. Results. Matriptase inhibitors at 50 µM for 24 h did not increase cell death rate. The elevated ROS production observed after short-term application of inhibitor MI-441 could be correlated with lowered hepcidin expression. MI-460 could significantly enhance hepcidin levels in the supernatants of cocultures (by 62.21±26.8% in hepatocyte-Kupffer cell, 2 : 1, and by 42.6±14.3% in hepatocyte-Kupffer cell, 6 : 1, cocultures, resp.. No significant changes were found in IL-6 and IL-8 levels in cocultures exposed to matriptase inhibitors. Conclusions. Based on in vitro findings, administration of MI-460 via modulation of hepcidin expression without cytotoxic and oxidative stress inducing properties might be a reliable alternative to treat iron overload in human and veterinary clinical practice.

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

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    thresholds, (ii) mechanical and heat pain thresholds, (iii) pain to heat (43 degrees C and 45 degrees C, 5 s), (iv) secondary hyperalgesia, and (v) skin erythema were made 1.75 and 0.5 h before, and 0, 1, 2, 4, and 6 h after a burn injury. Sensory thresholds and hyperalgesia to heat and mechanical 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...

  11. 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.

  12. Biliopancreatic duct injection of ethanol as an experimental model of acute and chronic pancreatitis in rats.

    Science.gov (United States)

    Unal, Ethem; Atalay, Suleyman; Tolan, Huseyin Kerem; Yuksekdag, Sema; Yucel, Metin; Acar, Aylin; Basak, Fatih; Gunes, Pembegul; Bas, Gurhan

    2015-01-01

    In the present study, we described an easily reproducable experimental pancreatits model induced by biliopancreatic duct injection of ethyl alcohol. Seventy Wistar albino rats were divided equally into seven groups randomly: the control group (group 1), acute pancreatitis groups; induced by 20% ethanol (group 2), 48% ethanol (group 3), 80% ethanol (group 4), chronic pancreatitis groups; induced by 20% ethanol (group 5), 48% ethanol (group 6) and by 80% ethanol (group 7). Acute pancreatitis groups were sacrified on postoperative day 3, while the control group and chronic pancreatitis groups were killed on postoperative day 7. Histopathologic evaluation was done, and P acute pancreatitis (100%). Inflammatory infiltration of neutrophils and mononuclear cells, interstitial edema, and focal necrotic areas were seen in the pancreatic tissues. Similarly, all rats in group 6 developed chronic pancreatitis (100%). Interstitial fibrosis, lymphotic infiltration, ductal dilatation, acinar cell atrophy, periductal hyperplasia were seen in the pancreatic tissues. Mortality was seen only in group 7. The biliopancreatic ductal injection of 48% ethanol induced acute and chronic pancreatitis has 100% success rate.

  13. Porcine model characterizing various parameters assessing the outcome after acetaminophen intoxication induced acute liver failure

    Science.gov (United States)

    Thiel, Karolin; Klingert, Wilfried; Klingert, Kathrin; Morgalla, Matthias H; Schuhmann, Martin U; Leckie, Pamela; Sharifi, Yalda; Davies, Nathan A; Jalan, Rajiv; Peter, Andreas; Grasshoff, Christian; Königsrainer, Alfred; Schenk, Martin; Thiel, Christian

    2017-01-01

    AIM To investigate the changes of hemodynamic and laboratory parameters during the course of acute liver failure following acetaminophen overdose. METHODS Eight pigs underwent a midline laparotomy following jejunal catheter placement for further acetaminophen intoxication and positioning of a portal vein Doppler flow-probe. Acute liver failure was realized by intrajejunal acetaminophen administration in six animals, two animals were sham operated. All animals were invasively monitored and received standardized intensive care support throughout the study. Portal blood flow, hemodynamic and ventilation parameters were continuously recorded. Laboratory parameters were analysed every eight hours. Liver biopsies were sampled every 24 h following intoxication and upon autopsy. RESULTS Acute liver failure (ALF) occurred after 28 ± 5 h resulted in multiple organ failure and death despite maximal support after further 21 ± 1 h (study end). Portal blood flow (baseline 1100 ± 156 mL/min) increased to a maximum flow of 1873 ± 175 mL/min at manifestation of ALF, which was significantly elevated (P 0.01). CONCLUSION Declining portal blood flow and subsequent severe thrombocytopenia after acetaminophen intoxication precede fatality in a porcine acute liver failure model. PMID:28321158

  14. The common marmoset (Callithrix jacchus) as a model for neuroleptic-induced acute dystonia.

    Science.gov (United States)

    Fukuoka, T; Nakano, M; Kohda, A; Okuno, Y; Matsuo, M

    1997-12-01

    To examine whether acute dystonia is induced by neuroleptic treatment, common marmosets were treated with haloperidol orally twice a week over 25 weeks until dystonic behavior was elicited. Movement disorders such as acute dystonia were observed 6 weeks after the initial treatment, and had appeared in all treated animals by 25 weeks. Once these movement disorders were induced, they consistently reappeared after further treatment with haloperidol, and once haloperidol dosing was discontinued, the episodes vanished. Then, various neuroleptic drugs (bromperidol, chlorpromazine, risperidone thioridazine, sulpiride, tiapride, and clozapine) or a nonneuroleptic drug (diazepam) were administered orally instead of haloperidol in the above animals. All the neuroleptic drugs except for clozapine elicited similar abnormal behavior, while diazepam failed to induce any dystonia. An anticholinergic drug, trihexyphenidyl, which is known to reduce acute dystonia in patients, was also given orally to the above haloperidol-sensitized animals, followed by further treatment with haloperidol 30 min later. This clearly suppressed the induction of dystonia by haloperidol. The similarity between these findings for haloperidol-pretreated common marmosets and clinical findings suggests that the present model is useful for predicting the potential of antipsychotics to induce acute dystonia in humans.

  15. 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.

  16. Salvage of a Failed Agility Total Ankle Replacement System Associated with Acute Traumatic Periprosthetic Midfoot Fractures.

    Science.gov (United States)

    Roukis, Thomas S

    2015-10-01

    This article presents a rare case involving combined revision of a failed Agility Total Ankle Replacement System (DePuy Orthopaedics, Warsaw, Indiana) and open reduction with internal fixation of periprosthetic midfoot fractures secondary to acute traumatic injury. The rationale for these procedures, the operative sequence of events, and recovery course are presented in detail. Causes for concern regarding subsequent revision, should this be required, are raised.

  17. 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....

  18. INTEGRATED HYDROGEN STORAGE SYSTEM MODEL

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, B

    2007-11-16

    Hydrogen storage is recognized as a key technical hurdle that must be overcome for the realization of hydrogen powered vehicles. Metal hydrides and their doped variants have shown great promise as a storage material and significant advances have been made with this technology. In any practical storage system the rate of H2 uptake will be governed by all processes that affect the rate of mass transport through the bed and into the particles. These coupled processes include heat and mass transfer as well as chemical kinetics and equilibrium. However, with few exceptions, studies of metal hydrides have focused primarily on fundamental properties associated with hydrogen storage capacity and kinetics. A full understanding of the complex interplay of physical processes that occur during the charging and discharging of a practical storage system requires models that integrate the salient phenomena. For example, in the case of sodium alanate, the size of NaAlH4 crystals is on the order of 300nm and the size of polycrystalline particles may be approximately 10 times larger ({approx}3,000nm). For the bed volume to be as small as possible, it is necessary to densely pack the hydride particles. Even so, in packed beds composed of NaAlH{sub 4} particles alone, it has been observed that the void fraction is still approximately 50-60%. Because of the large void fraction and particle to particle thermal contact resistance, the thermal conductivity of the hydride is very low, on the order of 0.2 W/m-{sup o}C, Gross, Majzoub, Thomas and Sandrock [2002]. The chemical reaction for hydrogen loading is exothermic. Based on the data in Gross [2003], on the order of 10{sup 8}J of heat of is released for the uptake of 5 kg of H{sub 2}2 and complete conversion of NaH to NaAlH{sub 4}. Since the hydride reaction transitions from hydrogen loading to discharge at elevated temperatures, it is essential to control the temperature of the bed. However, the low thermal conductivity of the hydride

  19. 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

  20. Animal Models for the Prevention of Acute and Chronic Graft-vs-Host Disease.

    Science.gov (United States)

    1982-09-01

    and injected with 5X10 7 untreated A strain bone marrow and spleen cells died by day 14. This group died of acute GVHD not of aplasia as did the...If different from Report) IS. SUPPLEMENTARY NOTES 19. KEY WORDS (Continue on revwao aide It necessary "ad Identify by block numwber) bone marrow ...effect of monoclonal antibodies to several T-cell differentiation antigens on graft-versus-host disease in a murine model of bone marrow

  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. Ligustrazine alleviates gastric mucosal injur y in a rat model of acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Sheng-Chun Dang; Jian-Xin Zhang; Jian-Guo Qu; Xue-Qing Wang; Xin Fan

    2007-01-01

    BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inlfammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inlfammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group C);ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood lfow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score;meanwhile, the levels of serum interleukin-1β(IL-1β) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood lfow in group P was signiifcantly lower than that in group C (P CONCLUSIONS: Decreased gastric blood lfow and increased inlfammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.

  3. Three dimensional quantitative structure-toxicity relationship modeling and prediction of acute toxicity for organic contaminants to algae.

    Science.gov (United States)

    Jin, Xiangqin; Jin, Minghao; Sheng, Lianxi

    2014-08-01

    Although numerous chemicals have been identified to have significant toxicological effect on aquatic organisms, there is still lack of a reliable, high-throughput approach to evaluate, screen and monitor the presence of organic contaminants in aquatic system. In the current study, we proposed a synthetic pipeline to automatically model and predict the acute toxicity of chemicals to algae. In the procedure, a new alignment-free three dimensional (3D) structure characterization method was described and, with this method, several 3D-quantitative structure-toxicity relationship (3D-QSTR) models were developed, from which two were found to exhibit strong internal fitting ability and high external predictive power. The best model was established by Gaussian process (GP), which was further employed to perform extrapolation on a random compound library consisting of 1014 virtually generated substituted benzenes. It was found that (i) substitution number can only exert slight influence on chemical׳s toxicity, but low-substituted benzenes seem to have higher toxicity than those of high-substituted entities, and (ii) benzenes substituted by nitro group and halogens exhibit high acute toxicity as compared to other substituents such as methyl and carboxyl groups. Subsequently, several promising candidates suggested by computational prediction were assayed by using a standard algal growth inhibition test. Consequently, four substituted benzenes, namely 2,3-dinitrophenol, 2-chloro-4-nitroaniline, 1,2,3-trinitrobenzene and 3-bromophenol, were determined to have high acute toxicity to Scenedesmus obliquus, with their EC50 values of 2.5±0.8, 10.5±2.1, 1.4±0.2 and 42.7±5.4μmol/L, respectively.

  4. Double-button Fixation System for Management of Acute Acromioclavicular Joint Dislocation

    Directory of Open Access Journals (Sweden)

    Ali Torkaman

    2016-01-01

    Full Text Available Background: Surgical treatments for acromioclavicular (AC joint dislocation present with some complications. The present study was designed to evaluate the double-button fixation system in the management of acute acromioclavicular joint dislocation. Methods: This cross sectional study, done between February 2011 to June 2014, consisted of 28 patients who underwent surgical management by the double-button fixation system for acute AC joint dislocation. Age, sex, injury mechanism, dominant hand, side with injury, length of follow up, time before surgery, shoulder and hand (DASH, constant and visual analogue scale (VAS scores, and all complications of the cases during the follow up were recorded. Results: The mean age of patients was 33.23±6.7 years. Twenty four patients (85.71% were male and four (14.28% were female. The significant differences were observed between pre-operation VAS, constant shoulder scores and post-operation measurements (P=0.001, P=0.0001, P=0.0001, respectively. There were not any significant differences between right and left coracoclavicular (P=0.238, but two cases of heterotrophic ossifications were recorded. The mean follow-up time was 16.17±4.38 months. Conclusion: According to the results, the double-button fixation system for management of acute acromioclavicular joint dislocation has suitable results and minimal damage to the soft tissues surrounding the coracoclavicular ligaments.

  5. Double-button Fixation System for Management of Acute Acromioclavicular Joint Dislocation.

    Science.gov (United States)

    Torkaman, Ali; Bagherifard, Abolfazl; Mokhatri, Tahmineh; Haghighi, Mohammad Hossein Shabanpour; Monshizadeh, Siamak; Taraz, Hamid; Hasanvand, Amin

    2016-01-01

    Surgical treatments for acromioclavicular (AC) joint dislocation present with some complications. The present study was designed to evaluate the double-button fixation system in the management of acute acromioclavicular joint dislocation. This cross sectional study, done between February 2011 to June 2014, consisted of 28 patients who underwent surgical management by the double-button fixation system for acute AC joint dislocation. Age, sex, injury mechanism, dominant hand, side with injury, length of follow up, time before surgery, shoulder and hand (DASH), constant and visual analogue scale (VAS) scores, and all complications of the cases during the follow up were recorded. The mean age of patients was 33.23±6.7 years. Twenty four patients (85.71%) were male and four (14.28%) were female. The significant differences were observed between pre-operation VAS, constant shoulder scores and post-operation measurements. There were not any significant differences between right and left coracoclavicular, but two cases of heterotrophic ossifications were recorded. The mean follow-up time was 16.17±4.38 months. According to the results, the double-button fixation system for management of acute acromioclavicular joint dislocation has suitable results and minimal damage to the soft tissues surrounding the coracoclavicular ligaments.

  6. Frutalin reduces acute and neuropathic nociceptive behaviours in rodent models of orofacial pain.

    Science.gov (United States)

    Damasceno, Marina B M V; de Melo Júnior, José de Maria A; Santos, Sacha Aubrey A R; Melo, Luana T M; Leite, Laura Hévila I; Vieira-Neto, Antonio E; Moreira, Renato de A; Monteiro-Moreira, Ana Cristina de O; Campos, Adriana R

    2016-08-25

    Orofacial pain is a highly prevalent clinical condition, yet difficult to control effectively with available drugs. Much attention is currently focused on the anti-inflammatory and antinociceptive properties of lectins. The purpose of this study was to evaluate the antinociceptive effect of frutalin (FTL) using rodent models of inflammatory and neuropathic orofacial pain. Acute pain was induced by formalin, glutamate or capsaicin (orofacial model) and hypertonic saline (corneal model). In one experiment, animals were pretreated with l-NAME and naloxone to investigate the mechanism of antinociception. The involvement of the lectin domain in the antinociceptive effect of FTL was verified by allowing the lectin to bind to its specific ligand. In another experiment, animals pretreated with FTL or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to infraorbital nerve transection to induce chronic pain, followed by induction of thermal hypersensitivity using acetone. Motor activity was evaluated with the rotarod test. A molecular docking was performed using the TRPV1 channel. Pretreatment with FTL significantly reduced nociceptive behaviour associated with acute and neuropathic pain, especially at 0.5 mg/kg. Antinociception was effectively inhibited by l-NAME and d-galactose. In line with in vivo experiments, docking studies indicated that FTL may interact with TRPV1. Our results confirm the potential pharmacological relevance of FTL as an inhibitor of orofacial nociception in acute and chronic pain mediated by TRPA1, TRPV1 and TRPM8 receptor.

  7. 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.

  8. Modeling Advance Life Support Systems

    Science.gov (United States)

    Pitts, Marvin; Sager, John; Loader, Coleen; Drysdale, Alan

    1996-01-01

    Activities this summer consisted of two projects that involved computer simulation of bioregenerative life support systems for space habitats. Students in the Space Life Science Training Program (SLSTP) used the simulation, space station, to learn about relationships between humans, fish, plants, and microorganisms in a closed environment. One student complete a six week project to modify the simulation by converting the microbes from anaerobic to aerobic, and then balancing the simulation's life support system. A detailed computer simulation of a closed lunar station using bioregenerative life support was attempted, but there was not enough known about system restraints and constants in plant growth, bioreactor design for space habitats and food preparation to develop an integrated model with any confidence. Instead of a completed detailed model with broad assumptions concerning the unknown system parameters, a framework for an integrated model was outlined and work begun on plant and bioreactor simulations. The NASA sponsors and the summer Fell were satisfied with the progress made during the 10 weeks, and we have planned future cooperative work.

  9. Minisuperspace models of discrete systems

    CERN Document Server

    Baytaş, Bekir

    2016-01-01

    A discrete quantum spin system is presented in which several modern methods of canonical quantum gravity can be tested with promising results. In particular, features of interacting dynamics are analyzed with an emphasis on homogeneous configurations and the dynamical building-up and stability of long-range correlations. Different types of homogeneous minisuperspace models are introduced for the system, including one based on condensate states, and shown to capture different aspects of the discrete system. They are evaluated with effective methods and by means of continuum limits, showing good agreement with operator calculations whenever the latter are available. As a possibly quite general result, it is concluded that an analysis of the building-up of long-range correlations in discrete systems requires non-perturbative solutions of the dynamical equations. Some questions related to stability can be analyzed perturbatively, but suggest that matter couplings may be relevant for this question in the context o...

  10. [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.

  11. The Control System Modeling Language

    CERN Document Server

    Zagar, K; Sekoranja, M; Tkacik, G; Vodovnik, A; Zagar, Klemen; Plesko, Mark; Sekoranja, Matej; Tkacik, Gasper; Vodovnik, Anze

    2001-01-01

    The well-known Unified Modeling Language (UML) describes software entities, such as interfaces, classes, operations and attributes, as well as relationships among them, e.g. inheritance, containment and dependency. The power of UML lies in Computer Aided Software Engineering (CASE) tools such as Rational Rose, which are also capable of generating software structures from visual object definitions and relations. UML also allows add-ons that define specific structures and patterns in order to steer and automate the design process. We have developed an add-on called Control System Modeling Language (CSML). It introduces entities and relationships that we know from control systems, such as "property" representing a single controllable point/channel, or an "event" specifying that a device is capable of notifying its clients through events. Entities can also possess CSML-specific characteristics, such as physical units and valid ranges for input parameters. CSML is independent of any specific language or technology...

  12. Contextual Modelling of Collaboration System

    Directory of Open Access Journals (Sweden)

    Wafaa DACHRY

    2012-03-01

    Full Text Available Faced with new environmental constraints, firms decide to collaborate in collective entities and adopt new patterns of behavior. So, this firms’ collaboration becomes an unavoidable approach. Indeed, our aim interest in our study is to propose a collaborative information system for supply chain. Our proposed platform ensures cooperation and information sharing between partners in real time. In fact, several questions have to be asked: What is the information nature may be shared between partners? What processes are implemented between actors? What functional services are supported by the platform? In order to answer these questions, we present, in this article, our methodological approach of modelling, called CMCS (Contextual Modelling of Collaborative System

  13. Stochastic Models of Polymer Systems

    Science.gov (United States)

    2016-01-01

    field limit of a dynamical model for polymer systems, Science China Mathematics , (11 2012): 0. doi: TOTAL: 1 Number of Non Peer-Reviewed Conference...4.0 (4.0 max scale): Number of graduating undergraduates funded by a DoD funded Center of Excellence grant for Education , Research and Engineering...undergraduates funded by your agreement who graduated during this period and will receive scholarships or fellowships for further studies in science

  14. 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

  15. 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

  16. Soetomo score: score model in early identification of acute haemorrhagic stroke

    Directory of Open Access Journals (Sweden)

    Moh Hasan Machfoed

    2016-06-01

    Full Text Available Aim of the study: On financial or facility constraints of brain imaging, score model is used to predict the occurrence of acute haemorrhagic stroke. Accordingly, this study attempts to develop a new score model, called Soetomo score. Material and methods: The researchers performed a cross-sectional study of 176 acute stroke patients with onset of ≤24 hours who visited emergency unit of Dr. Soetomo Hospital from July 14th to December 14th, 2014. The diagnosis of haemorrhagic stroke was confirmed by head computed tomography scan. There were seven predictors of haemorrhagic stroke which were analysed by using bivariate and multivariate analyses. Furthermore, a multiple discriminant analysis resulted in an equation of Soetomo score model. The receiver operating characteristic procedure resulted in the values of area under curve and intersection point identifying haemorrhagic stroke. Afterward, the diagnostic test value was determined. Results: The equation of Soetomo score model was (3 × loss of consciousness + (3.5 × headache + (4 × vomiting − 4.5. Area under curve value of this score was 88.5% (95% confidence interval = 83.3–93.7%. In the Soetomo score model value of ≥−0.75, the score reached the sensitivity of 82.9%, specificity of 83%, positive predictive value of 78.8%, negative predictive value of 86.5%, positive likelihood ratio of 4.88, negative likelihood ratio of 0.21, false negative of 17.1%, false positive of 17%, and accuracy of 83%. Conclusions: The Soetomo score model value of ≥−0.75 can identify acute haemorrhagic stroke properly on the financial or facility constrains of brain imaging.

  17. 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 associati

  18. Different microRNA profiles in chronic epilepsy versus acute seizure mouse models.

    Science.gov (United States)

    Kretschmann, Anita; Danis, Benedicte; Andonovic, Lidija; Abnaof, Khalid; van Rikxoort, Marijke; Siegel, Franziska; Mazzuferi, Manuela; Godard, Patrice; Hanon, Etienne; Fröhlich, Holger; Kaminski, Rafal M; Foerch, Patrik; Pfeifer, Alexander

    2015-02-01

    Epilepsy affects around 50 million people worldwide, and in about 65% of patients, the etiology of disease is unknown. MicroRNAs are small non-coding RNAs that have been suggested to play a role in the pathophysiology of epilepsy. Here, we compared microRNA expression patterns in the hippocampus using two chronic models of epilepsy characterised by recurrent spontaneous seizures (pilocarpine and self-sustained status epilepticus (SSSE)) and an acute 6-Hz seizure model. The vast majority of microRNAs deregulated in the acute model exhibited increased expression with 146 microRNAs up-regulated within 6 h after a single seizure. In contrast, in the chronic models, the number of up-regulated microRNAs was similar to the number of down-regulated microRNAs. Three microRNAs-miR-142-5p, miR-331-3p and miR-30a-5p-were commonly deregulated in all three models. However, there is a clear overlap of differentially expressed microRNAs within the chronic models with 36 and 15 microRNAs co-regulated at 24 h and at 28 days following status epilepticus, respectively. Pathway analysis revealed that the altered microRNAs are associated with inflammation, innate immunity and cell cycle regulation. Taken together, the identified microRNAs and the pathways they modulate might represent candidates for novel molecular approaches for the treatment of patients with epilepsy.

  19. [Clinical and neuroimaging features of central nervous system impairments in acute intermittent porphyria].

    Science.gov (United States)

    Yuan, Jing; Peng, Bin; You, Hui; Zhang, Wei

    2011-10-25

    To analyze the clinical and neuroimaging features of central nervous system impairments in acute intermittent porphyria, and explore the possible mechanisms. Six cases with intracranial lesions at our hospital from 1991 to 2011 and 13 cases reported in literatures were retrospectively reviewed. The clinical manifestations of central nervous system impairments included seizures, unconsciousness and cortical blindness, etc. EEG (electroencephalogram) showed slow wave or normal. CSF (cerebrospinal fluid) test indicated slightly higher or normal level of CSF protein. Neuroimaging studies showed two types of intracranial lesions. One type (n = 4) mainly affected the cortex and subcortical white matter, especially involving white matter. Another type (n = 2) affected the deep nuclei such as caudate, putamen and thalamus symmetrically. The symptoms of 13 cases reported in literature with central nervous system impairments included unconsciousness, hallucinations, seizures and cortical blindness. Their neuroimaging manifestations were similar with those of the patients at our hospital. Two additional cases showed predominantly cerebral cortex lesions with no involvement of white matter. Acute intermittent porphyria can affect central nervous system, peripheral nervous system and autonomic nervous system. The neuroimaging features of brain may be lesions located in cortex, subcortical white matter and deep nuclei with different mechanisms. A correct diagnosis and a treatment decision should be made during an early stage.

  20. 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...

  1. 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...

  2. Divergent effects of RIP1 or RIP3 blockade in murine models of acute liver injury.

    Science.gov (United States)

    Deutsch, M; Graffeo, C S; Rokosh, R; Pansari, M; Ochi, A; Levie, E M; Van Heerden, E; Tippens, D M; Greco, S; Barilla, R; Tomkötter, L; Zambirinis, C P; Avanzi, N; Gulati, R; Pachter, H L; Torres-Hernandez, A; Eisenthal, A; Daley, D; Miller, G

    2015-05-07

    Necroptosis is a recently described Caspase 8-independent method of cell death that denotes organized cellular necrosis. The roles of RIP1 and RIP3 in mediating hepatocyte death from acute liver injury are incompletely defined. Effects of necroptosis blockade were studied by separately targeting RIP1 and RIP3 in diverse murine models of acute liver injury. Blockade of necroptosis had disparate effects on disease outcome depending on the precise etiology of liver injury and component of the necrosome targeted. In ConA-induced autoimmune hepatitis, RIP3 deletion was protective, whereas RIP1 inhibition exacerbated disease, accelerated animal death, and was associated with increased hepatocyte apoptosis. Conversely, in acetaminophen-mediated liver injury, blockade of either RIP1 or RIP3 was protective and was associated with lower NLRP3 inflammasome activation. Our work highlights the fact that diverse modes of acute liver injury have differing requirements for RIP1 and RIP3; moreover, within a single injury model, RIP1 and RIP3 blockade can have diametrically opposite effects on tissue damage, suggesting that interference with distinct components of the necrosome must be considered separately.

  3. Therapeutic effects of topical netrin-4 in a corneal acute inflammatory model

    Institute of Scientific and Technical Information of China (English)

    Yun; Han; Yi; Shao; Ting-Ting; Liu; Sang-Ming; Li; Wei; Li; Zu-Guo; Liu

    2015-01-01

    AIM: To evaluate the therapeutic effect of netrin-4 on the early acute phase of inflammation in the alkali-burned eye.METHODS: Eye drops containing netrin-4 or phosphate buffered saline(PBS) were administered to a alkali-burn-induced corneal acute inflammatory model four times daily. The clinical evaluations, including fluorescein staining and inflammatory index, were performed on day 1, 4 and 7 using slit lamp microscopy.Global specimens were collected on day 7 and processed for immunofluorescent staining. The levels of inflammatory mediators in the corneas were determined by real-time polymerase chain reaction(PCR).RESULTS: Exogenous netrin-4 administered on rat ocular surfaces showed more improvements in decreasing fluorescein staining on day 4 and 7, and resolved alkali burn-induced corneal inflammation index on day 7(P <0.01). The levels of IL-1β, IL-6, intercellular cell adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), monocyte chemotactic protein-1(MCP-1) and macrophage inflammatory protein-1(MIP-1) in corneas were decreased in netrin-4-treated groups(P <0.05). In addition, netrin-4 significantly reduced the expression of leukocyte common antigen 45(CD45) in the alkali-burn cornea(P <0.001).CONCLUSION: Topical netrin-4 accelerated wound healing and reduced the inflammation on alkali-burn rat model, suggesting a potential as an anti-inflammatory agent in the clinical to treat the acute inflammation.

  4. Development of chronic and acute golden Syrian hamster infection models with Leptospira borgpetersenii serovar Hardjo.

    Science.gov (United States)

    Zuerner, R L; Alt, D P; Palmer, M V

    2012-03-01

    The golden Syrian hamster (Mesocricetus auratus) is frequently used as a model to study virulence for several Leptospira species. Onset of an acute lethal infection following inoculation with several pathogenic Leptospira species has been widely adopted for pathogenesis studies. An important exception is the outcome following inoculation of hamsters with live L. borgpetersenii serovar Hardjo, the primary cause of bovine leptospirosis and a cause of human infections. Typically, inoculation of hamsters with L. borgpetersenii serovar Hardjo fails to induce clinical signs of infection. In this study, the authors defined LD(50) and ID(50) for 2 strains of L. borgpetersenii serovar Hardjo: JB197 and 203. Both strains infected hamsters with ID(50) values of approximately 1.5 × 10(2) bacteria yet differed in tissue invasion and interaction with leukocytes, resulting in widely divergent clinical outcomes. Hamsters infected with strain 203 established renal colonization within 4 days postinfection and remained asymptomatic with chronic renal infections similar to cattle infected with serovar Hardjo. In contrast, hamsters infected with strain JB197 developed a rapidly debilitating disease typical of acute leptospirosis common in accidental hosts (eg, humans) with an LD(50) of 3.6 × 10(4) bacteria. Evidence that strain JB197 resides in both extracellular and intracellular environments during hamster infection was obtained. Development of models that result in chronic and acute forms of leptospirosis provides a platform to study L. borgpetersenii pathogenesis and to test vaccines for the prevention of leptospirosis.

  5. 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.

  6. 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

    2017-07-27

    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

  7. Relationship between peritoneal macrophages and inflammatory reaction in a rat model of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To investigate the relationship between peritoneal macrophages(PMAs)and inflammatory reaction in a rat model of severe acute pancreatitis(SAP).Methods Sprague-Dawley rats were randomly divided into control group and SAP group.To induce SAP in rats,40 g/L sodium taurocholate(0.1 mL/100 g)was injected into the pancreatic duct through retrograde exposure of pancreatic bile duct in hepatic porta.One-third of rats were sacrificed at 3,6 or 12 h after modeling.PMAs were extracted,and incubated for 24 h ...

  8. 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

    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...military and veterans. All persons with SCI are at increased risk of pressure ulcer development which remains one of the most significant secondary

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

    Directory of Open Access Journals (Sweden)

    Tatyana D Sotnikova

    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.

  10. Acute phase proteins in bovine milk in an experimental model of Staphylococcus aureus subclinical mastitis

    DEFF Research Database (Denmark)

    Eckersall, P D; Young, F J; Nolan, A M

    2006-01-01

    The objectives were to establish the origin of 2 acute phase proteins in milk during subclinical bovine mastitis and to characterize the relationship between those proteins in milk and blood. Haptoglobin (Hp) and mammary-associated serum amyloid A (M-SAA3) appear in milk during mastitis, whereas Hp...... and serum amyloid A increase in serum during mastitis. The concentrations of these proteins were determined in an experimental model using a field strain of Staphylococcus aureus to induce subclinical mastitis in dairy cows. The expression of mRNA coding for these proteins was assessed and the presence of M......-SAA3 in mammary tissues was determined using immunocytochemistry. Increases of M-SAA3 and Hp in milk occurred within 12 h of Staphylococcus aureus infusion, with peak concentrations occurring 3 d after infusion of the bacteria. The increase of acute phase proteins in milk (15 h) preceded the increase...

  11. 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.)

  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. Comparative proteome analysis of serum from acute pulmonary embolism rat model for biomarker discovery.

    Science.gov (United States)

    Li, Sheng-qing; Yun, Jun; Xue, Fu-bo; Bai, Chang-qing; Yang, Shu-guang; Que, Hai-ping; Zhao, Xin; Wu, Zhe; Wang, Yu; Liu, Shao-jun

    2007-01-01

    Pulmonary embolism (PE) is a common, potentially fatal disease and its diagnosis is challenging because clinical signs and symptoms are nonspecific. In this study, to investigate protein alterations of a rat PE model, total serum proteins collected at different time points were separated by two-dimensional electrophoresis (2-DE) and identified using matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Bioinformatics analysis of 24 differentially expressed proteins showed that 20 had corresponding protein candidates in the database. According to their properties and obvious alterations after PE, changes of serum concentrations of Hp, Fn, DBP, RBP, and TTR were selected to be reidentified by western blot analysis. Semiquantitative RT-PCR showed DBP, RBP, and TTR to be down-regulated at mRNA levels in livers but not in lung tissues. The low serum concentrations of DBP, RBP, and TTR resulted in the up-regulation of 25(OH)D3, vitamin A, and FT4 (ligands of DBP, RBP, and TTR) after acute PE in rat models. The serum levels of Hp and Fn were detected in patients with DVT/PE and controls to explore their diagnostic prospects in acute PE because the mRNA levels of Hp and Fn were found to be up-regulated both in lung tissues and in livers after acute PE. Our data suggested that the concentration of serum Fn in controls was 79.42 +/- 31.57 microg/L, whereas that of PE/DVT patients was 554.43 +/- 136.18 microg/L (P PE/DVT patients was 2063.48 +/- 425.38 mg/L (P diagnosis of acute PE, but diagnostic tests are still needed to evaluate the sensitivity and specificity of these markers and also the number of false positives and false negatives.

  14. Effects of inhaled L-arginine administration in a murine model of acute asthma.

    Directory of Open Access Journals (Sweden)

    Zeynep Arikan-Ayyildiz

    2014-10-01

    Full Text Available Increased arginase activity in the airways decreases L-arginine and causes deficiency of bronchodilating and anti-inflammatory nitric oxide (NO in asthma. As, it is suggested that L-arginine may have therapeutic potential in asthma treatment, we aimed to investigate the effects of inhaled L-arginine on oxygen saturation (SaO₂ and airway histology in a murine model of acute asthma. Twenty eight BALB/c mice were divided into four groups; I, II, III and IV (control. All groups except the control were sensitized and challenged with ovalbumin. After establishement of acute asthma attack by metacholine administration, the mice were treated with inhaled L-arginine (Group I, saline (Group II and budesonide (Group III, respectively. SaO₂was measured by pulse oximeter just before and 5 min after methacholine. A third measurement of SaO₂was also obtained 15 min after drug administration in these study groups. Inflammation in the lung tissues of the sacrificed animals were scored to determine the effects of the study drugs. The number of eosinophils in bronchoalveolar lavage (BAL was determined. The results indicated that inflammatory scores significantly improved in groups receiving study drugs when compared with placebo and L-arginine was similar in decreasing scores when compared with budesonide. SaO₂had a tendency to increase after L-arginine administration after acute asthma attack and this increase was statistically significant (p=0.043. Eosinophilia in BAL significantly reduced in group receiving L-arginine when compared with placebo (p<0.05. Thus in this study we demonstrated that L-arginine improved SaO₂and inflammatory scores in an acute model of asthma.

  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. Identification and Modelling of Linear Dynamic Systems

    Directory of Open Access Journals (Sweden)

    Stanislav Kocur

    2006-01-01

    Full Text Available System identification and modelling are very important parts of system control theory. System control is only as good as good is created model of system. So this article deals with identification and modelling problems. There are simple classification and evolution of identification methods, and then the modelling problem is described. Rest of paper is devoted to two most known and used models of linear dynamic systems.

  17. [The pneumoperitoneum course forecasting and surgery tactic in the group of patients with acute and chronic cholecystitis and concomitant pathology of cardiovascular system].

    Science.gov (United States)

    Korotkyĭ, V M; Soliaryk, S O; Tsyganok, A M; Sysak, O M

    2012-01-01

    The share of elderly and senile patients with acute cholecystitis concomitant cardiovascular pathology whom the laparoscopic cholecystectomy has been provided is increased. The heightened intraabdominal pressure has negative influence at the cardiovascular system, so the alternative ways for treatment of this group of patients are used in clinic. We propose the pneumoperitoneum model using the pneumatic belt which is fixed at the abdomen in preoperative period in patients with an acute and chronic cholecystitis. This model is useful to forecast cardiovascular disorders during future laparoscopic cholecystectomy. The arterial pressure level, pulse score and ECG are monitored during the test (90 min). Myocardial ischemia appearance seems that the risk of laparoscopic cholecystectomy with pneumoperitoneum is high. The alternative method of surgery in such group of patients (no pneumoperitoneum is applied) is laparoscopic assisted cholecystectomya from miniaccess. This method allows to reducing frequency of intra- and postoperative complications connected with pneumoperitoneum negative influence at the patients with concomitant pathology of cardiovascular system.

  18. A hybrid decision support model to discover informative knowledge in diagnosing acute appendicitis

    Directory of Open Access Journals (Sweden)

    Son Chang Sik

    2012-03-01

    Full Text Available Abstract Background The aim of this study is to develop a simple and reliable hybrid decision support model by combining statistical analysis and decision tree algorithms to ensure high accuracy of early diagnosis in patients with suspected acute appendicitis and to identify useful decision rules. Methods We enrolled 326 patients who attended an emergency medical center complaining mainly of acute abdominal pain. Statistical analysis approaches were used as a feature selection process in the design of decision support models, including the Chi-square test, Fisher's exact test, the Mann-Whitney U-test (p Results Of 55 variables, two subsets were found to be indispensable for early diagnostic knowledge discovery in acute appendicitis. The two subsets were as follows: (1 lymphocytes, urine glucose, total bilirubin, total amylase, chloride, red blood cell, neutrophils, eosinophils, white blood cell, complaints, basophils, glucose, monocytes, activated partial thromboplastin time, urine ketone, and direct bilirubin in the univariate analysis-based model; and (2 neutrophils, complaints, total bilirubin, urine glucose, and lipase in the multivariate analysis-based model. The experimental results showed that the model with univariate analysis (80.2%, 82.4%, 78.3%, 76.8%, 83.5%, and 80.3% outperformed models using multivariate analysis (71.6%, 69.3%, 73.7%, 69.7%, 73.3%, and 71.5% with entry and removal criteria of 0.01 and 0.05; 73.5%, 66.0%, 80.0%, 74.3%, 72.9%, and 73.0% with entry and removal criteria of 0.05 and 0.10 in terms of accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under ROC curve, during a 10-fold cross validation. A statistically significant difference was detected in the pairwise comparison of ROC curves (p p Conclusions The decision model developed in this study can be applied as an aid in the initial decision making of clinicians to increase vigilance in cases of suspected acute

  19. Modelling acute oral mammalian toxicity. 1. Definition of a quantifiable baseline effect.

    Science.gov (United States)

    Koleva, Yana K; Cronin, Mark T D; Madden, Judith C; Schwöbel, Johannes A H

    2011-10-01

    Quantitative structure-activity relationships (QSARs) provide a useful tool to define a relationship between chemical structure and toxicity and allow for the prediction of the toxicity of untested chemicals. QSAR models based upon an anaesthetic or narcosis mechanism represent a baseline, or minimum, toxicity, i.e. unless a chemical acts by another, more specific, mechanism, its toxicity will be predicted by such models. The aim of this investigation was to develop baseline models for the acute toxicity of chemicals to mammals (rat and mouse) following the oral route of administration. The availability of such baseline toxicity models for mammalian species can provide a probe for testing new chemicals with respect to their molecular mechanism of toxicity. Multiple-regression type structure-toxicity relationships were derived . (i.e., from oral log LD(50)(-1) data for mammalian species (rat and mouse) and the 1-octanol/water partition coefficient (log P) of classic non-polar narcotics). Subsequently, these models were used to distinguish between reactive chemicals of different mechanistic domains and baseline toxic chemicals. Comparison of measured toxicity data for oral rat and mouse LD(50) with predictions from baseline QSAR provides a means of identifying mechanistic categories and for categorising more specific acute mechanisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Ocean Acidification Portends Acute Habitat Compression for Atlantic Cod (Gadus morhua) in a Physiologically-informed Metabolic Rate Model

    Science.gov (United States)

    Del Raye, G.; Weng, K.

    2011-12-01

    Ocean acidification affects organisms on a biochemical scale, yet its societal impacts manifest from changes that propagate through entire populations. Successful forecasting of the effects of ocean acidification therefore depends on at least two steps: (1) deducing systemic physiology based on subcellular stresses and (2) scaling individual physiology up to ecosystem processes. Predictions that are based on known biological processes (process-based models) may fare better than purely statistical models in both these steps because the latter are less robust to novel environmental conditions. Here we present a process-based model that uses temperature, pO2, and pCO2 to predict maximal aerobic scope in Atlantic cod. Using this model, we show that (i) experimentally-derived physiological parameters are sufficient to capture the response of cod aerobic scope to temperature and oxygen, and (ii) subcellular pH effects can be used to predict the systemic physiological response of cod to an acidified ocean. We predict that acute pH stress (on a scale of hours) could limit the mobility of Atlantic cod during diel vertical migration across a pCO2 gradient, promoting habitat compression. Finally, we use a global sensitivity analysis to identify opportunities for the improvement of model uncertainty as well as some physiological adaptations that could mitigate climate stresses on cod in the future.

  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. ISSM: Ice Sheet System Model

    Science.gov (United States)

    Larour, Eric; Schiermeier, John E.; Seroussi, Helene; Morlinghem, Mathieu

    2013-01-01

    In order to have the capability to use satellite data from its own missions to inform future sea-level rise projections, JPL needed a full-fledged ice-sheet/iceshelf flow model, capable of modeling the mass balance of Antarctica and Greenland into the near future. ISSM was developed with such a goal in mind, as a massively parallelized, multi-purpose finite-element framework dedicated to ice-sheet modeling. ISSM features unstructured meshes (Tria in 2D, and Penta in 3D) along with corresponding finite elements for both types of meshes. Each finite element can carry out diagnostic, prognostic, transient, thermal 3D, surface, and bed slope simulations. Anisotropic meshing enables adaptation of meshes to a certain metric, and the 2D Shelfy-Stream, 3D Blatter/Pattyn, and 3D Full-Stokes formulations capture the bulk of the ice-flow physics. These elements can be coupled together, based on the Arlequin method, so that on a large scale model such as Antarctica, each type of finite element is used in the most efficient manner. For each finite element referenced above, ISSM implements an adjoint. This adjoint can be used to carry out model inversions of unknown model parameters, typically ice rheology and basal drag at the ice/bedrock interface, using a metric such as the observed InSAR surface velocity. This data assimilation capability is crucial to allow spinning up of ice flow models using available satellite data. ISSM relies on the PETSc library for its vectors, matrices, and solvers. This allows ISSM to run efficiently on any parallel platform, whether shared or distrib- ISSM: Ice Sheet System Model NASA's Jet Propulsion Laboratory, Pasadena, California uted. It can run on the largest clusters, and is fully scalable. This allows ISSM to tackle models the size of continents. ISSM is embedded into MATLAB and Python, both open scientific platforms. This improves its outreach within the science community. It is entirely written in C/C++, which gives it flexibility in its

  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. Integrated Modeling for Flood Hazard Mapping Using Watershed Modeling System

    National Research Council Canada - National Science Library

    Seyedeh S. Sadrolashrafi; Thamer A. Mohamed; Ahmad R.B. Mahmud; Majid K. Kholghi; Amir Samadi

    2008-01-01

    ...) with the Watershed Modeling System (WMS) for flood modeling is developed. It also interconnects the terrain models and the GIS software, with commercial standard hydrological and hydraulic models, including HEC-1, HEC-RAS, etc...

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

    Directory of Open Access Journals (Sweden)

    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

  6. Feasibility of (68)Ga-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome.

    Science.gov (United States)

    Retamal, Jaime; Sörensen, Jens; Lubberink, Mark; Suarez-Sipmann, Fernando; Borges, João Batista; Feinstein, Ricardo; Jalkanen, Sirpa; Antoni, Gunnar; Hedenstierna, Göran; Roivainen, Anne; Larsson, Anders; Velikyan, Irina

    2016-01-01

    There is an unmet need for noninvasive, specific and quantitative imaging of inherent inflammatory activity. Vascular adhesion protein-1 (VAP-1) translocates to the luminal surface of endothelial cells upon inflammatory challenge. We hypothesized that in a porcine model of acute respiratory distress syndrome (ARDS), positron emission tomography (PET) with sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) based imaging agent targeting VAP-1 would allow quantification of regional pulmonary inflammation. ARDS was induced by lung lavages and injurious mechanical ventilation. Hemodynamics, respiratory system compliance (Crs) and blood gases were monitored. Dynamic examination using [(15)O]water PET-CT (10 min) was followed by dynamic (90 min) and whole-body examination using VAP-1 targeting (68)Ga-labeled 1,4,7,10-tetraaza cyclododecane-1,4,7-tris-acetic acid-10-ethylene glycol-conjugated Siglec-9 motif peptide ([(68)Ga]Ga-DOTA-Siglec-9). The animals received an anti-VAP-1 antibody for post-mortem immunohistochemistry assay of VAP-1 receptors. Tissue samples were collected post-mortem for the radioactivity uptake, histology and immunohistochemistry assessment. Marked reduction of oxygenation and Crs, and higher degree of inflammation were observed in ARDS animals. [(68)Ga]Ga-DOTA-Siglec-9 PET showed significant uptake in lungs, kidneys and urinary bladder. Normalization of the net uptake rate (Ki) for the tissue perfusion resulted in 4-fold higher uptake rate of [(68)Ga]Ga-DOTA-Siglec-9 in the ARDS lungs. Immunohistochemistry showed positive VAP-1 signal in the injured lungs. Detection of pulmonary inflammation associated with a porcine model of ARDS was possible with [(68)Ga]Ga-DOTA-Siglec-9 PET when using kinetic modeling and normalization for tissue perfusion.

  7. 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.

  8. Evaluation of arthroscopic stabilization of acute acromioclavicular joint dislocation using the TightRope system.

    Science.gov (United States)

    El Sallakh, Sameh A

    2012-01-16

    The purpose of this study was to evaluate the results of the arthroscopic treatment of acute acromioclavicular dislocation using the TightRope system (Arthrex, Naples, Florida). Between January 2006 and May 2007, ten shoulders in 10 patients with acute acromioclavicular joint dislocation (Rockwood types IV and V) underwent arthroscopic acromioclavicular joint stabilization using the TightRope. Average patient age was 30 years (range, 22-42 years), and mean follow-up was 24 months (range, 18-30 months). Follow-up occurred at 2 and 6 weeks, 3 months, and then every 6 months postoperatively. The shoulders were evaluated radiologically by comparing the acromioclavicular joint with the normal side and clinically by assessing the pain, function, and range of joint motion using the Constant score.Ten patients returned to work without pain 10 to 12 weeks postoperatively. Average Constant score was 96.3 (range, 94-99) at last follow-up. Because of technical error, 1 patient experienced TightRope fixation failure on the coracoid side, and the acromioclavicular joint was redislocated, which was treated by an open technique. The 10 patients were satisfied with their functional results and cosmetic appearance.The arthroscopic treatment of acute acromioclavicular dislocation using the TightRope is a minimally invasive surgical technique that has been proven effective for the treatment of these lesions. It is characterized by less morbidity, less hospitalization, excellent cosmoses, and early rehabilitation. Copyright 2012, SLACK Incorporated.

  9. Network models in anatomical systems.

    Science.gov (United States)

    Esteve-Altava, Borja; Marugán-Lobón, Jesús; Botella, Héctor; Rasskin-Gutman, Diego

    2011-01-01

    Network theory has been extensively used to model the underlying structure of biological processes. From genetics to ecology, network thinking is changing our understanding of complex systems, specifically how their internal structure determines their overall behavior. Concepts such as hubs, scale-free or small-world networks, common in the complexity literature, are now used more and more in sociology, neurosciences, as well as other anthropological fields. Even though the use of network models is nowadays so widely applied, few attempts have been carried out to enrich our understanding in the classical morphological sciences such as in comparative anatomy or physical anthropology. The purpose of this article is to introduce the usage of network tools in morphology; specifically by building anatomical networks, dealing with the most common analyses and problems, and interpreting their outcome.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Thermodynamic modeling of complex systems

    DEFF Research Database (Denmark)

    Liang, Xiaodong

    Offshore reservoirs represent one of the major growth areas of the oil and gas industry, and environmental safety is one of the biggest challenges for the offshore exploration and production. The oil accidents in the Gulf of Mexico in 1979 and 2010 were two of the biggest disasters in history...... 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...

  12. Methanobactin reverses acute liver failure in a rat model of Wilson disease

    Science.gov (United States)

    Lichtmannegger, Josef; Leitzinger, Christin; Wimmer, Ralf; Schmitt, Sabine; Schulz, Sabine; Eberhagen, Carola; Rieder, Tamara; Janik, Dirk; Neff, Frauke; Straub, Beate K.; Schirmacher, Peter; DiSpirito, Alan A.; Bandow, Nathan; Baral, Bipin S.; Flatley, Andrew; Kremmer, Elisabeth; Denk, Gerald; Reiter, Florian P.; Hohenester, Simon; Eckardt-Schupp, Friedericke; Dencher, Norbert A.; Sauer, Vanessa; Niemietz, Christoph; Schmidt, Hartmut H.J.; Merle, Uta; Gotthardt, Daniel Nils; Kroemer, Guido; Weiss, Karl Heinz

    2016-01-01

    In Wilson disease (WD), functional loss of ATPase copper-transporting β (ATP7B) impairs biliary copper excretion, leading to excessive copper accumulation in the liver and fulminant hepatitis. Current US Food and Drug Administration– and European Medicines Agency–approved pharmacological treatments usually fail to restore copper homeostasis in patients with WD who have progressed to acute liver failure, leaving liver transplantation as the only viable treatment option. Here, we investigated the therapeutic utility of methanobactin (MB), a peptide produced by Methylosinus trichosporium OB3b, which has an exceptionally high affinity for copper. We demonstrated that ATP7B-deficient rats recapitulate WD-associated phenotypes, including hepatic copper accumulation, liver damage, and mitochondrial impairment. Short-term treatment of these rats with MB efficiently reversed mitochondrial impairment and liver damage in the acute stages of liver copper accumulation compared with that seen in untreated ATP7B-deficient rats. This beneficial effect was associated with depletion of copper from hepatocyte mitochondria. Moreover, MB treatment prevented hepatocyte death, subsequent liver failure, and death in the rodent model. These results suggest that MB has potential as a therapeutic agent for the treatment of acute WD. PMID:27322060

  13. The Effect of Breadfruit Leaves Infusion on Acute Renal Failure Rat model Abstract

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    Muhamad Risdan Hardani

    2016-03-01

    Full Text Available Background : Empirically, breadfruit (Artocarpus altilis leaf has been used as traditional medicine for several diseases, such as acute renal failure. This research is aimed at finding the effects of breadfruit leaf infusion on blood creatinine levels in rats to model acute renal failure. Methods : This research is an experimental study, using 30 male wistar rats, weighing 150–250 g, divided into 5 groups. The first group is a negative control and the second group is a positive control. Groups 2–5 were induced with Gentamicine and peroxicam for 7 days, and then groups 3–5 given infusion of breadfruit leaf in different doses for 7 days, and then blood creatinine levels were tested at the 15th day. This data was analyzed using a multiple comparison Dunnett T3 test because this data is not homogenous. This research was done in pharmacology laboratorium universitas padjadjaran from Oktober–November 2012. Result : Bases on average creatinine levels of 0.62, 0.87, 0.98, and 0.87 mg/dL observed for the diffetent groups, it was statistically show that significantly different creatinine levels, differing by 0.038 (p < 0.05 were observed for the control group and the group which was given an infusion of breadfruit leaf. Conclusion : It can be concluded that infusions of breadfruit leaf do have an effects on blood creatinine levels in acute renal failure.

  14. Superstitious conditioning as a model of delusion formation following chronic but not acute ketamine in humans.

    Science.gov (United States)

    Freeman, Tom P; Morgan, Celia J A; Klaassen, Elissa; Das, Ravi K; Stefanovic, Ana; Brandner, Brigitta; Curran, H Valerie

    2009-11-01

    Ketamine has previously been shown to induce delusion-like or referential beliefs, both acutely in healthy volunteers and naturalistically among nonintoxicated users of the drug. Delusions are theoretically underpinned by increased superstitious conditioning or the erroneous reinforcement of random events. Using a novel and objectively measured superstitious conditioning task, experiment 1 assessed healthy volunteers before and during placebo (n = 16), low-dose (n = 15), and high-dose ketamine (n = 16) under randomized and double-blind conditions. Experiment 2 used the same task to compare ketamine users (n = 18), polydrug controls (n = 19), and nondrug-using controls (n = 17). In experiment 1, ketamine produced dose-dependent psychotomimetic effects but did not cause changes in superstitious conditioning. Experiment 2 found increased levels of superstitious conditioning among ketamine users compared to polydrug and nondrug-using controls, respectively, as evidenced by both objective task responses and subjective beliefs following the task. Results indicate that chronic but not acute exposure to ketamine may increase the propensity to adopt superstitious conditioning. These findings are discussed in terms of acute and chronic ketamine models of delusion-like belief formation in schizophrenia.

  15. Acute phase protein response in an experimental model of ovine caseous lymphadenitis

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    Lang Tamara L

    2007-12-01

    Full Text Available Abstract Background Caseous lymphadenitis (CLA is a disease of small ruminants caused by Corynebacterium pseudotuberculosis. The pathogenesis of CLA is a slow process, and produces a chronic rather than an acute disease state. Acute phase proteins (APP such as haptoglobin (Hp serum amyloid A (SAA and α1 acid glycoprotein (AGP are produced by the liver and released into the circulation in response to pro-inflammatory cytokines. The concentration of Hp in serum increases in experimental CLA but it is not known if SAA and AGP respond in parallel or have differing response profiles. Results The concentration in serum of Hp, SAA and AGP in 6 sheep challenged with 2 × 105 cells of C. pseudotuberculosis showed significant increases (P C. pseudotuberculosis became detectable at 11 days p.i. and continued to rise throughout the experiment. Conclusion The serum concentrations of Hp, SAA and AGP were raised in sheep in an experimental model of CLA. An extended response was found for AGP which occurred at a point when the infection was likely to have been transforming from an acute to a chronic phase. The results suggest that AGP could have a role as a marker for chronic conditions in sheep.

  16. 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

  17. A novel, stable and reproducible acute lung injury model induced by oleic acid in immature piglet

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; LING Feng; ZHANG Yan-bo; LIU Ai-jun; LIU Dong-hai; QIAO Chen-hui; WANG Qiang; LIU Ying-long

    2011-01-01

    Background Young children are susceptible to pulmonary injury,and acute lung injury (ALl) often results in a high mortality and financial costs in pediatric patients.A good ALl model will help us to gain a better understanding of the real pathophysiological picture and to evaluate novel treatment approaches to acute respiratory distress syndrome (ARDS) more accurately and liberally.This study aimed to establish a hemodynamically stable and reproducible model with ALl in piglet induced by oleic acid.Methods Six Chinese mini-piglets were used to establish ALl models by oleic acid.Hemodynamic and pulmonary function data were measured.Histopathological assessment was performed.Results Mean blood pressure,heart rate (HR),cardiac output (CO),central venous pressure (CVP) and left atrial pressure (LAP) were sharply decreased after oleic acid given,while the mean pulmonary arterial pressure (MPAP) was increased in comparison with baseline (P <0.05).pH,arterial partial pressure of O2 (PaO2),PaO2/inspired O2 fraction (FiO2) and lung compliance decreased,while PaCO2 and airway pressure increased in comparison with baseline (P <0.05).The lung histology showed severe inflammation,hyaline membranes,intra-alveolar and interstitial hemorrhage.Conclusion This experiment established a stable model which allows for a diversity of studies on early lung injury.

  18. Models for Gaze Tracking Systems

    Directory of Open Access Journals (Sweden)

    Villanueva Arantxa

    2007-01-01

    Full Text Available One of the most confusing aspects that one meets when introducing oneself into gaze tracking technology is the wide variety, in terms of hardware equipment, of available systems that provide solutions to the same matter, that is, determining the point the subject is looking at. The calibration process permits generally adjusting nonintrusive trackers based on quite different hardware and image features to the subject. The negative aspect of this simple procedure is that it permits the system to work properly but at the expense of a lack of control over the intrinsic behavior of the tracker. The objective of the presented article is to overcome this obstacle to explore more deeply the elements of a video-oculographic system, that is, eye, camera, lighting, and so forth, from a purely mathematical and geometrical point of view. The main contribution is to find out the minimum number of hardware elements and image features that are needed to determine the point the subject is looking at. A model has been constructed based on pupil contour and multiple lighting, and successfully tested with real subjects. On the other hand, theoretical aspects of video-oculographic systems have been thoroughly reviewed in order to build a theoretical basis for further studies.

  19. Models for Gaze Tracking Systems

    Directory of Open Access Journals (Sweden)

    Arantxa Villanueva

    2007-10-01

    Full Text Available One of the most confusing aspects that one meets when introducing oneself into gaze tracking technology is the wide variety, in terms of hardware equipment, of available systems that provide solutions to the same matter, that is, determining the point the subject is looking at. The calibration process permits generally adjusting nonintrusive trackers based on quite different hardware and image features to the subject. The negative aspect of this simple procedure is that it permits the system to work properly but at the expense of a lack of control over the intrinsic behavior of the tracker. The objective of the presented article is to overcome this obstacle to explore more deeply the elements of a video-oculographic system, that is, eye, camera, lighting, and so forth, from a purely mathematical and geometrical point of view. The main contribution is to find out the minimum number of hardware elements and image features that are needed to determine the point the subject is looking at. A model has been constructed based on pupil contour and multiple lighting, and successfully tested with real subjects. On the other hand, theoretical aspects of video-oculographic systems have been thoroughly reviewed in order to build a theoretical basis for further studies.

  20. Area Logistics System Based on System Dynamics Model

    Institute of Scientific and Technical Information of China (English)

    GUI Shouping; ZHU Qiang; LU Lifang

    2005-01-01

    At present, there are few effective ways to analyze area logistics systems. This paper uses system dynamics to analyze the area logistics system and establishes a system dynamics model for the area logistics system based on the characteristics of the area logistics system and system dynamics. Numerical simulations with the system dynamic model were used to analyze a logistic system. Analysis of the Guangzhou economy shows that the model can reflect the actual state of the system objectively and can be used to make policy and harmonize environment.

  1. A mouse model of severe acute pancreatitis induced with caerulein and lipopolysaccharide

    Institute of Scientific and Technical Information of China (English)

    Shi-Ping Ding; Ji-Cheng Li; Chang Jin

    2003-01-01

    AIM: To establish a non-traumatic, easy to induce and reproducible mouse model of severe acute pancreatitis (SAP)induced with caerulein and lipopolyasccharide (LPS).METHODS: Thirty-two healthy mature NIH female mice were selected and divided at random into four groups (each of 8 mice), i.e., the control group (NS group), the caerulein group (Ch group), the lipopolysaccharide group (LPS group),and the caerulein+LPS group (Cn+LPS group). Mice were injected intraperitoneally with caerulein only, or LPS only,and caerulein and LPS in combination. All the animals were then killed by neck dislocation three hours after the last intraperitoneal injection. The pancreas and exo-pancreatic organs were then carefully removed for microscopic examination. And the pancreatic acinus was further observed under transmission electron microscope (TEM). Pancreatic weight, serum amylase, serum nitric oxide (NO)concentration, superoxide dismutase (SOD) and malondialdehyde (MDA) concentration of the pancreas were assayed respectively.RESULTS: (1) NS animals displayed normal pancreatic structure both in the exocrine and endocrine. In the LPS group, the pancreas was slightly edematous, with the infiltration of a few inflammatory cells and the necrosis of the adjacent fat tissues. All the animals of the Cn group showed distinct signs of a mild edematous pancreatitis characterized by interstitial edema, infiltration of neutrophil and mononuclear cells, but without obvious parenchyma necrosis and hemorrhage. In contrast, the Cn+LPS groupshowed more diffuse focal areas of nonviable pancreatic and hemorrhage as well as systemic organ dysfunction.According to Schmidt's criteria, the pancreatic histologic score showed that there existed significant difference in the Cn+LPS group in the interstitial edema, inflammatory infiltration,parenchyma necrosis and parenchyma homorrhage in comparison with those of the Cn group, LPS group and NS group (P<0.01 or P<0.05). (2) The ultrasturcture of acinar

  2. Modeling the Early Events of Severe Acute Respiratory Syndrome Coronavirus Infection In Vitro

    Science.gov (United States)

    Yen, Yu-Ting; Liao, Fang; Hsiao, Cheng-Hsiang; Kao, Chuan-Liang; Chen, Yee-Chun; Wu-Hsieh, Betty A.

    2006-01-01

    The clinical picture of severe acute respiratory syndrome (SARS) is characterized by pulmonary inflammation and respiratory failure, resembling that of acute respiratory distress syndrome. However, the events that lead to the recruitment of leukocytes are poorly understood. To study the cellular response in the acute phase of SARS coronavirus (SARS-CoV)-host cell interaction, we investigated the induction of chemokines, adhesion molecules, and DC-SIGN (dendritic cell-specific ICAM-3-grabbing nonintegrin) by SARS-CoV. Immunohistochemistry revealed neutrophil, macrophage, and CD8 T-cell infiltration in the lung autopsy of a SARS patient who died during the acute phase of illness. Additionally, pneumocytes and macrophages in the patient's lung expressed P-selectin and DC-SIGN. In in vitro study, we showed that the A549 and THP-1 cell lines were susceptible to SARS-CoV. A549 cells produced CCL2/monocyte chemoattractant protein 1 (MCP-1) and CXCL8/interleukin-8 (IL-8) after interaction with SARS-CoV and expressed P-selectin and VCAM-1. Moreover, SARS-CoV induced THP-1 cells to express CCL2/MCP-1, CXCL8/IL-8, CCL3/MIP-1α, CXCL10/IP-10, CCL4/MIP-1β, and CCL5/RANTES, which attracted neutrophils, monocytes, and activated T cells in a chemotaxis assay. We also demonstrated that DC-SIGN was inducible in THP-1 as well as A549 cells after SARS-CoV infection. Our in vitro experiments modeling infection in humans together with the study of a lung biopsy of a patient who died during the early phase of infection demonstrated that SARS-CoV, through a dynamic interaction with lung epithelial cells and monocytic cells, creates an environment conducive for immune cell migration and accumulation that eventually leads to lung injury. PMID:16501078

  3. Changes of hepatic lactoferrin gene expression in two mouse models of the acute phase reaction.

    Science.gov (United States)

    Ahmad, Ghayyor; Sial, Gull Zareen Khan; Ramadori, Pierluigi; Dudas, Jozsef; Batusic, Danko S; Ramadori, Giuliano

    2011-12-01

    Lactoferrin (Ltf), an iron binding glycoprotein, is a pleiotropic molecule whose serum concentration increases under acute phase conditions. The physiological roles of this protein have been well elucidated, but the source and serum regulation of Ltf gene expression have not been investigated in detail as part of the acute phase reaction (APR). In the current work, the changes in hepatic Ltf-gene-expression during turpentine oil- (TO-) or LPS-induced APR were investigated. Ltf was upregulated at both the mRNA and protein levels in the liver of TO- and LPS-treated wild type (WT) mice. The pattern of induction however was different in both animal models indicating distinctive signalling patterns resulting in an acute phase reaction. Cytokines are the core regulators of APR. Among the major cytokines, IL-6 is an important signalling molecule, which also regulates iron homeostasis in response to an inflammatory situation. In this study, the administration of IL-6 induced Ltf gene expression in the liver of WT mice, in murine hepatocytes and in hepa 1-6 cells. Ltf-gene-expression was upregulated also in the liver of TO- and LPS-treated IL-6 knockout (KO) mice. The increase in serum Ltf after LPS injection was greater than after TO-injection both in WT and IL-6-KO mice. To evaluate the contribution of other acute phase cytokines in the regulation of Ltf-gene-expression in the liver, both in vitro and in vivo studies with IL-1β, TNF-α, or IFN-γ were performed. The results demonstrate that TNF-α and IFN-γ also upregulated Ltf-gene-expression, while IL-1β has no role in the regulation of Ltf-gene-expression.

  4. Acute renal graft-versus-host disease in a murine model of allogeneic bone marrow transplantation.

    Science.gov (United States)

    Schmid, Peter M; Bouazzaoui, Abdellatif; Schmid, Karin; Birner, Christoph; Schach, Christian; Maier, Lars S; Holler, Ernst; Endemann, Dierk H

    2017-03-23

    Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and associated with poor prognosis. Generally kidneys are assumed to be no direct target of Graft-versus-Host Disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully MHC-mismatched model of BALB/c mice conditioned and transplanted according to two different intensity protocols. Syngeneically transplanted and untreated animals served as controls. 4 weeks after transplantation, allogeneic animals developed acute GvHD that was more pronounced in the high-intensity protocol (HIP) group than in the low-intensity protocol (LIP) group. Urea and creatinine as classic serum markers of renal function could not verify renal impairment 4 weeks after BMT. Creatinine levels were even reduced as a result of catabolic metabolism and loss of muscle mass due to acute GvHD. Proteinuria, albuminuria, and urinary N-acetyl-beta-Dglucosaminidase (NAG) levels were measured as additional renal markers before and after transplantation. Albuminuria and NAG were only significantly increased after allogeneic transplantation, correlating with disease severity between HIP and LIP animals. Histological investigations of the kidneys showed renal infiltration of T-cells and macrophages with endarteriitis, interstitial nephritis, tubulitis, and glomerulitis. T-cells consisted of CD4+, CD8+, and FoxP3+ cells. Renal expression analysis of allogeneic animals showed increases in indoleamine-2,3 dioxygenase (IDO), different cytokines (TNFα, IFN-γ, IL-1α, IL2, IL-6, and IL-10), and adhesion molecules (ICAM-1 and VCAM-1), resembling findings from other tissues in acute GvHD. In summary, our study supports the entity of renal GvHD with histological features suggestive of cell-mediated renal injury. Albuminuria and urinary NAG levels may serve as early markers of renal

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

    Directory of Open Access Journals (Sweden)

    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. Heat Shock Factor-1 and Nuclear Factor-kappaB Are Systemically Activated in Human Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Derek A O’Reilly

    2006-03-01

    Full Text Available Context :Nuclear factor-kappa B (NFkappaB is a transcription factor for a wide range of proinflammatory mediators while heat shock factor-1 (HSF-1 transcribes stress proteins that protect against cellular damage. Both are attractive therapeutic targets, undergoing investigation in other acute inflammatory conditions, such as sepsis. Objective :To evaluate the role of the transcription factors NF-kappaB and HSF-1 in human acute pancreatitis and their relationship to cytokine/chemokine production, disease severity and outcome. Patients :Twenty-four patients with acute pancreatitis and 12 healthy controls. Main outcome measures :Peripheral blood mononuclear cells were isolated. NF-kappaB and HSF-1 were measured by electrophoretic mobility shift assay. Soluble tumor necrosis factor (TNF receptor II and interleukin-8 were measured by ELISA. Acute physiology scores (APS, APACHE II scores and final Atlanta designations of severity were also determined. Results: Systemic NF-kappaB activation occurs in acute pancreatitis compared to healthy controls (P=0.004. However, there was no significant difference between those with mild and severe disease (P=0.685. Systemic activation of HSF-1 was observed in acute pancreatitis compared to healthy controls although this did not reach statistical significance (P=0.053. Activation, however, was greatest in those who had a final Atlanta designation of mild pancreatitis compared to those who had a severe attack of acute pancreatitis (P=0.036. Furthermore, HSF-1 was inversely correlated with acute physiology score (APS; r=-0.49, P=0.019 and APACHE II score (r=-0.47, P=0.026. Conclusions: Both NF-kappaB and HSF-1 are systemically activated in human acute pancreatitis. HSF-1 activation may protect against severity of pancreatitis

  7. 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.

  8. Enterprise Modelling supported by Manufacturing Systems Theory

    OpenAIRE

    MYKLEBUST, Odd

    2002-01-01

    There exist today a large number of enterprise models or enterprise modelling approaches. In a study of standards and project developed models there are two approaches: CIMOSA “The Open Systems Architecture for CIM” and GERAM, “Generalised Enterprise Reference Architecture”, which show a system orientation that can be further followed as interesting research topics for a system theory oriented approach for enterprise models. In the selection of system theories, manufacturing system theory...

  9. Validation of the hepatocyte-like HPCT-1E3 cell line as an in vitro model for the prediction of acute in vivo toxicity.

    Science.gov (United States)

    Halwachs, Sandra; Lakoma, Cathleen; Honscha, Walther

    2013-11-01

    In a pilot study, we tested 20 randomly-selected chemicals for their cytotoxicity toward the HPCT-1E3 cell model, in order to prove the ability of this in vitro model to predict human acute in vivo toxicity. The study revealed that, in contrast to most other in vitro models, results from the HPCT-1E3 cell-based system show better correlation with the more-relevant human acute lethal doses, whereas results from most other systems have a high predictivity for human lethal serum concentrations. For the prevalidation of the HPCT-1E3 model as a surrogate for regulatory acute in vivo toxicity tests, we have now expanded the list of tested chemicals to 57 substances, and have compared the results with data from the HepG2 cell assay. Again, a better correlation of HPCT-1E3 IC50 values with human oral lethal doses, as compared to correlation with human lethal serum concentrations, was observed after the pooling of all the tested substances (r(2) = 0.53 [P in vivo toxicity tests.

  10. Acute Pancreatitis Concomitant Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Okay Abacı

    2013-03-01

    Full Text Available Acute pancreatitis is an inflammatory syndrome with unpredictable progression to systemic inflammation and multi-organ dysfunction. As in our case rarely, acute pancreatitis can be presented with the coexistance of acute coronary syndrome. To prevent a misdiagnosis of acute situation presented with chest or abdominal pain, physicians must be aware for coexisting pathophysiologies and take into account the differential diagnosis of all life-threatening causes such as cardiac ischemia or acute abdominal situations.

  11. 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 o

  12. 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

  13. Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models.

    Science.gov (United States)

    Yang, Weimin; Qiang, Dongjin; Zhang, Min; Ma, Limei; Zhang, Yonghui; Qing, Chen; Xu, Yunlong; Zhen, Chunlan; Liu, Jikai; Chen, Yan-Hua

    2011-06-01

    Isoforskolin was isolated from Coleus forskohlii native to Yunnan in China. We hypothesize that isoforskolin pretreatment attenuates acute lung injury induced by lipopolysaccharide (endotoxin). Three acute lung injury models were used: situ perfused rat lung, rat and mouse models of endotoxic shock. Additionally, lipopolysaccharide stimulated proinflammatory cytokine production was evaluated in human mononuclear leukocyte. In situ perfused rat lungs, pre-perfusion with isoforskolin (100, and 200 μM) and dexamethasone (65 μM, positive control) inhibited lipopolysaccharide (10 mg/L) induced increases in lung neutrophil adhesion rate, myeloperoxidase activity, lung weight Wet/Dry ratio, permeability-surface area product value, and tumor necrosis factor (TNF)-α levels. In rats, pretreatments with isoforskolin (5, 10, and 20 mg/kg, i.p.) and dexamethasone (5mg/kg, i.p.) markedly reduced lipopolysaccharide (6 mg/kg i.v.) induced increases of karyocyte, neutrophil counts and protein content in bronchoalveolar lavage fluid, and plasma myeloperoxidase activity. Lung histopathology showed that morphologic changes induced by lipopolysaccharide were less pronounced in the isoforskolin and dexamethasone pretreated rats. In mice, 5 mg/kg isoforskolin and dexamethasone caused 100% and 80% survival, respectively, after administration of lipopolysaccharide (62.5mg/kg, i.v., 40% survival if untreated). In human mononuclear leukocyte, isoforskolin (50, 100, and 200 μM) and dexamethasone (10 μM) pre-incubation lowered lipopolysaccharide (2 μg/mL) induced secretion of the cytokine TNF-α, and interleukins (IL)-1β, IL-6, and IL-8. In conclusion, pretreatment with isoforskolin attenuates lipopolysaccharide-induced acute lung injury in several models, and it is involved in down-regulation of inflammatory responses and proinflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8.

  14. Presenting features and imaging in childhood acute myeloid leukemia with central nervous system involvement.

    Science.gov (United States)

    Ranta, Susanna; Palomäki, Maarit; Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas; Hasle, Henrik; Jahnukainen, Kirsi; Heyman, Mats; Harila-Saari, Arja

    2017-02-24

    Central nervous system (CNS) involvement in childhood acute myeloid leukemia (AML) can manifest as leukemic cells in the cerebrospinal fluid, a solid CNS tumor, or as neurological symptoms. We evaluated the presenting symptoms and neuroimaging findings in 33 of 34 children with AML and CNS involvement at diagnosis in the period 2000-2012 in Sweden, Finland, and Denmark. Imaging was performed in 22 patients, of whom 16 had CNS-related symptoms. Seven patients, including all but two with facial palsy, had mastoid cell opacification, considered an incidental finding. The frequent involvement of the mastoid bone with facial palsy warrants evaluation in larger series. © 2017 Wiley Periodicals, Inc.

  15. Endovascular Management of Acute Pulmonary Embolism Using the Ultrasound-Enhanced EkoSonic System.

    Science.gov (United States)

    Garcia, Mark J

    2015-12-01

    Acute, symptomatic pulmonary embolism (PE) in the massive and submassive categories continues to be a healthcare concern with significant risk for increased morbidity and mortality. Despite increased awareness and venous thromboembolism prophylaxis, endovascular treatment is still an important option for many of these patients. There are a variety of techniques and devices used for treating PE, but none have been evaluated as extensively as the EkoSonic endovascular system that is also currently the only FDA-approved device for the treatment of pulmonary embolism. This article describes the use of the EkoSonic device for this patient population.

  16. Cost-utility of molecular adsorbent recirculating system treatment in acute liver failure

    Institute of Scientific and Technical Information of China (English)

    Taru; Kantola; Suvi; Mklin; Anna-Maria; Koivusalo; Pirjo; Rsnen; Anne; Rissanen; Risto; Roine; Harri; Sintonen; Krister; Hckerstedt; Helena; Isoniemi

    2010-01-01

    AIM:To determine the short-term cost-utility of mo-lecular adsorbent recirculating system(MARS) treatment in acute liver failure(ALF).METHODS:A controlled retrospective study was conducted with 90 ALF patients treated with MARS from 2001 to 2005.Comparisons were made with a historical control group of 17 ALF patients treated from 2000 to 2001 in the same intensive care unit(ICU) specializing in liver diseases.The 3-year outcomes and number of liver transplantations were recorded.All direct liver disease-rel...

  17. Local Renin-Angiotensin System in the Pancreas: The Significance of Changes by Chronic Hypoxia and Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Leung PS

    2001-01-01

    Full Text Available The circulating renin-angiotensin system (RAS plays an important role in the maintenance of blood pressure and fluid homeostasis. Recently, there has been a shift of emphasis from the circulating RAS to the local RAS in the regulation of individual tissue functions via a paracrine and/or autocrine mechanism. In fact, a local RAS has been proposed to be present in an array of tissues including the brain, heart, kidney and gonads. Our previous studies have provided solid evidence that several key elements of the RAS, notably angiotensinogen and renin, are present in the rat pancreas. The data support the existence of an intrinsic RAS in the pancreas and this local RAS may be important for the exocrine/endocrine functions of the pancreas. Interestingly, such a pancreatic RAS has been demonstrated to be markedly activated by experimental rat models of chronic hypoxia and acute pancreatitis. The activation of the pancreatic RAS by chronic hypoxia and experimental pancreatitis could play a role in the physiology and pathophysiology of the pancreas. The significant changes of pancreatic RAS may have clinical relevance to acute pancreatitis and hypoxia-induced injury in the pancreas.

  18. 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.

  19. Acute effects of levosimendan in experimental models of right ventricular hypertrophy and failure

    DEFF Research Database (Denmark)

    Vildbrad, Mads D; Andersen, Asger; Holmboe, Sarah;

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a fatal disease, and the ultimate cause of death is right ventricular (RV) failure. In this study, we investigated the acute hemodynamic effects of levosimendan in two rat models of RV hypertrophy and failure. Wistar rats were randomized to receive sham....... PTB and MCT injection caused hypertrophy, dilatation, and failure of the RV compared with sham surgery. Levosimendan increased RV end systolic pressure (sham surgery: 16.0% ± 3.8% [P = 0.0038]; MCT: 9.9% ± 3.1% [P = 0.018]; PTB: 24.5% ± 3.3% [P = 0.0001]; mean ± SEM) compared with placebo...

  20. Animal Models for the Prevention of Acute and Chronic Graft-versus-Host Disease.

    Science.gov (United States)

    1984-03-01

    injected with 5X10 7 untreated A strain bone marrow and spleen cells died by day 14. This group died of acute GVHD not of aplasia as did the irradiation...In Moak.. It fferfut bOrnAsporl) Ill- SUPPLEMENTARY NOTES IS1. KEY WORDS (Calcbup on mvwue side. If noo*W mad lildl* by block mmobr) bone marrow ...considered the effect of monoclonal antibodies to several T-cell differentiation antigens on graft-versus-host disease in a murine model of bone marrow

  1. 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...... of two animals. During the infection, blood was collected for cultivation, and after the animals were killed from day 5 to 15, they were necropsied and tissues were sampled for histopathology. Animals receiving =500 CFU/kg BW were free of lesions. Pigs inoculated with 5000 and 50 000 CFU/kg BW only...

  2. Nonlinear System Identification and Behavioral Modeling

    CERN Document Server

    Huq, Kazi Mohammed Saidul; Kabir, A F M Sultanul

    2010-01-01

    The problem of determining a mathematical model for an unknown system by observing its input-output data pair is generally referred to as system identification. A behavioral model reproduces the required behavior of the original analyzed system, such as there is a one-to-one correspondence between the behavior of the original system and the simulated system. This paper presents nonlinear system identification and behavioral modeling using a work assignment.

  3. A View of Earth System Model Development

    Institute of Scientific and Technical Information of China (English)

    ZHOU Tianjun; YU Yongqiang; WANG Bin

    2009-01-01

    This paper gives a definition of earth system model and shows three development phases of it, including physical climate system model, earth climate system model, and earth system model, based on an inves-tigation of climate system models in the world. It provides an expatiation on the strategic significance of future development of earth system model, an introduction of some representative scientific research plans on development of earth system model home and abroad, and a review of its status and trends based on the models of the fourth assessment report (AR4) of the Intergovernmental Panel on Climate Change (IPCC).Some suggestions on future development of earth system model in China are given, which are expected to be helpful to advance the development.

  4. 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.

  5. Fatal systemic adenoviral infection superimposed on pulmonary mucormycosis in a child with acute leukemia

    Science.gov (United States)

    Seo, Yu Mi; Hwang-Bo, Seok; Kim, Seong koo; Han, Seung Beom; Chung, Nack-Gyun; Kang, Jin Han

    2016-01-01

    Abstract Background: Although adenovirus (ADV) infection usually causes self-limiting respiratory disorders in immune competent children; severe and systemic ADV infection in children undergoing chemotherapy for leukemia has been continuously reported. Nevertheless, there has been no consensus on risk factors and treatment strategies for severe ADV infection in children undergoing chemotherapy. Case summary: We report a case of a 15-year-old boy with a fatal systemic ADV infection. He had received reinduction chemotherapy for relapsed acute lymphoblastic leukemia under continuing antifungal therapy for previously diagnosed fungal pneumonia. He complained of fever and right shoulder pain 4 days after completing the reinduction chemotherapy. In spite of appropriate antibiotic and antifungal therapy, pneumonia was aggravated and gross hematuria was accompanied. A multiplex polymerase chain reaction test for respiratory viruses was positive for ADV in a blood sample, and a urine culture was positive for ADV. He received oral ribavirin, intravenous immunoglobulin, and intravenous cidofovir therapy; however, he eventually died. Relapsed leukemia, concurrent fungal pneumonia, and delayed cidofovir administration were considered the cause of the grave outcome in this patient. Conclusion: ADV may cause severe infections not only in allogeneic hematopoietic cell transplant recipients, but also in patients undergoing chemotherapy for acute leukemia. The risk factors for severe ADV infection in patients undergoing chemotherapy should be determined in the future studies, and early antiviral therapy should be administered to immune compromised patients with systemic ADV infection. PMID:27749571

  6. 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.

  7. 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.

  8. Isocitrate treatment of acute anemia of inflammation in a mouse model.

    Science.gov (United States)

    Kim, Airie; Fung, Eileen; Parikh, Sona G; Gabayan, Victoria; Nemeth, Elizabeta; Ganz, Tomas

    2016-01-01

    Acute and severe anemia of inflammation (AI) is a common complication of various clinical syndromes, including fulminant infections, critical illness with multiorgan failure, and exacerbations of autoimmune diseases. Building on recent data showing beneficial results with isocitrate treatment for chronic low-grade AI in a rat model, we used a mouse model of acute and severe AI induced by intraperitoneal heat-killed Brucella abortus to determine if isocitrate would be effective in this more stringent application. Inflamed mice treated with isocitrate developed an early but transient improvement in hemoglobin compared to solvent-treated controls, with a robust improvement on day 7, and only a trend towards improvement by day 14. Reticulocyte counts were increased in treated mice transiently, with no significant difference by day 21. Serum erythropoietin (EPO) levels were similar in treated versus control mice, indicating that isocitrate increased sensitivity to EPO. Serum and tissue iron levels showed no significant differences between the treated and control mice, ruling out improved iron availability as the cause of the increased response to endogenous EPO. Compared to the milder rat model, much higher doses of isocitrate were required for a relatively modest benefit.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Protective effect of human amniotic fluid stem cells in an immunodeficient mouse model of acute tubular necrosis.

    Directory of Open Access Journals (Sweden)

    Laura Perin

    Full Text Available Acute Tubular Necrosis (ATN causes severe damage to the kidney epithelial tubular cells and is often associated with severe renal dysfunction. Stem-cell based therapies may provide alternative approaches to treating of ATN. We have previously shown that clonal c-kit(pos stem cells, derived from human amniotic fluid (hAFSC can be induced to a renal fate in an ex-vivo system. Herein, we show for the first time the successful therapeutic application of hAFSC in a mouse model with glycerol-induced rhabdomyolysis and ATN. When injected into the damaged kidney, luciferase-labeled hAFSC can be tracked using bioluminescence. Moreover, we show that hAFSC provide a protective effect, ameliorating ATN in the acute injury phase as reflected by decreased creatinine and BUN blood levels and by a decrease in the number of damaged tubules and apoptosis therein, as well as by promoting proliferation of tubular epithelial cells. We show significant immunomodulatory effects of hAFSC, over the course of ATN. We therefore speculate that AFSC could represent a novel source of stem cells that may function to modulate the kidney immune milieu in renal failure caused by ATN.

  11. Partial liquid ventilation decreases tissue and serum tumor necrosis factor-α concentrations in acute lung injury model of immature piglet induced by oleic acid

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; FAN Xiang-ming; LI Xiao-feng; LI Zhi-qiang; WANG Qiang; SUN Li-zhong; LIU Ying-long

    2012-01-01

    Background Pediatric patients are susceptible to lung injury.Acute lung injury in children often results in high mortality.Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models.This study was designed to examine the hypothesis that PLV would attenuate the production of local and systemic tumor necrosis factor (TNF)-α in an immature piglet model of acute lung injury induced by oleic acid (OA).Methods Twelve Chinese immature piglets were induced acute lung injury by OA.The animals were randomly assigned to two groups of six animals,(1) conventional mechanical ventilation (MV) group and (2) PLV with 10 ml/kg FC-77 group.Results Compared with MV group,the PLV group had better cardiopulmonary variables (P <0.05).These variables included heart rate,mean blood pressure,blood pH,partial pressure of arterial oxygen (PaO2),PaO2/inspired O2 fraction (FiO2) and partial pressure of arterial carbon dioxide (PaCO2).PLV reduced TNF-α levels both in plasma and tissue compared with MV group (P <0.05).Conclusion PLV provides protective effects against TNF-a response in OA-induced acute lung injury in immature piglets.

  12. Risk of viral acute gastrointestinal illness from nondisinfected drinking water distribution systems.

    Science.gov (United States)

    Lambertini, Elisabetta; Borchardt, Mark A; Kieke, Burney A; Spencer, Susan K; Loge, Frank J

    2012-09-04

    Acute gastrointestinal illness (AGI) resulting from pathogens directly entering the piping of drinking water distribution systems is insufficiently understood. Here, we estimate AGI incidence from virus intrusions into the distribution systems of 14 nondisinfecting, groundwater-source, community water systems. Water samples for virus quantification were collected monthly at wells and households during four 12-week periods in 2006-2007. Ultraviolet (UV) disinfection was installed on the communities' wellheads during one study year; UV was absent the other year. UV was intended to eliminate virus contributions from the wells and without residual disinfectant present in these systems, any increase in virus concentration downstream at household taps represented virus contributions from the distribution system (Approach 1). During no-UV periods, distribution system viruses were estimated by the difference between well water and household tap virus concentrations (Approach 2). For both approaches, a Monte Carlo risk assessment framework was used to estimate AGI risk from distribution systems using study-specific exposure-response relationships. Depending on the exposure-response relationship selected, AGI risk from the distribution systems was 0.0180-0.0661 and 0.001-0.1047 episodes/person-year estimated by Approaches 1 and 2, respectively. These values represented 0.1-4.9% of AGI risk from all exposure routes, and 1.6-67.8% of risk related to drinking water exposure. Virus intrusions into nondisinfected drinking water distribution systems can contribute to sporadic AGI.

  13. Acute pancreatitis as an initial symptom of systemic lupus erythematosus: A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Feng Wang; Nian-Song Wang; Bing-Hui Zhao; Ling-Quan Tang

    2005-01-01

    Acute pancreatitis as an initial symptom of systemic lupus erythematosus (SLE) is rare. We present a report of a 46-year-old female patient who had fever, abdominal pain and vomiting, elevated pancreaticaenzymelevels, hypocalcemia,hypoxemia, and various other laboratory abnormalities. She was first diagnosed with acute severe pancreatitis and then with SLE after further investigations. After a 2-mo treatment with somatostatin, the patient recovered.

  14. Java interface to a computer-aided diagnosis system for acute pulmonary embolism using PIOPED findings

    Science.gov (United States)

    Frederick, Erik D.; Tourassi, Georgia D.; Gauger, Matthew; Floyd, Carey E., Jr.

    1999-05-01

    An interface to a Computer Aided Diagnosis (CAD) system for diagnosis of Acute Pulmonary Embolism (PE) from PIOPED radiographic findings was developed. The interface is based on Internet technology which is user-friendly and available on a broad range of computing platforms. It was designed to be used as a research tool and as a data collection tool, allowing researchers to observe the behavior of a CAD system and to collect radiographic findings on ventilation-perfusion lung scans and chest radiographs. The interface collects findings from physicians in the PIOPED reporting format, processes those findings and presents them as inputs to an artificial neural network (ANN) previously trained on findings from 1,064 patients from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study. The likelihood of PE predicted by the ANN and by the physician using the system is then saved for later analysis.

  15. Clinical Scoring Systems in Predicting the Outcome of Acute Upper Gastrointestinal Bleeding; a Narrative Review

    Directory of Open Access Journals (Sweden)

    Hanieh Ebrahimi Bakhtavar

    2017-01-01

    Full Text Available Prediction of the outcome and severity of acute upper gastrointestinal bleeding (UGIB has significant importance in patient care, disposition, and determining the need for emergent endoscopy. Recent international recommendations endorse using scoring systems for management of non-variceal UGIB patients. To date, different scoring systems have been developed for predicting the risk of 30-day mortality and re-bleeding. We have discussed the screening performance characteristics of Baylor bleeding score, the Rockall risk scoring score, Cedars-Sinai Medical Center predictive index, Glasgow Blatchford score, T-score, and AIMS65 systems, in the present review.Based on the results of this survey, there are only 3 clinical decision rules that can predict the outcome of UGIB patients, independent from endoscopy. Among these, only Glasgow Blatchford score was highly sensitive for predicting the risk of 30-day mortality and re-bleeding, simultaneously. 

  16. Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

    Directory of Open Access Journals (Sweden)

    Howie Forbes

    2010-03-01

    Full Text Available Abstract Background The development of effective therapies for acute liver failure (ALF is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein. Control pigs (n = 4 survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8 +/- 5.9 vs 59 +/- 2.0 mmHg, increased cardiac output (7.26 +/- 1.86 vs 3.30 +/- 0.40 l/min and decreased systemic vascular resistance (8.48 +/- 2.75 vs 16.2 +/- 1.76 mPa/s/m3. Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636 +/- 95 vs 301 +/- 26.9 mPa/s/m3 observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23 +/- 0.05 vs 7.45 +/- 0.02 and prothrombin time (36 +/- 2 vs 8.9 +/- 0.3 seconds compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5 +/- 210 vs 42 +/- 8.14 coincided with a marked reduction in serum albumin (11.5 +/- 1.71 vs 25 +/- 1 g/dL in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2 +/- 36.5 vs 131.6 +/- 9.33 μmol/l. Liver histology revealed evidence of severe centrilobular necrosis

  17. Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis.

    Science.gov (United States)

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-04-01

    Upon hemolysis extracellular hemoglobin causes oxidative stress and cytotoxicity due to its peroxidase activity. Extracellular hemoglobin may release free hemin, which increases vascular permeability, leukocyte recruitment, and adhesion molecule expression. Pancreatitis-associated ascitic fluid is reddish and may contain extracellular hemoglobin. Our aim has been to determine the role of extracellular hemoglobin in the local and systemic inflammatory response during severe acute pancreatitis in rats. To this end we studied taurocholate-induced necrotizing pancreatitis in rats. First, extracellular hemoglobin in ascites and plasma was quantified and the hemolytic action of ascitic fluid was tested. Second, we assessed whether peritoneal lavage prevented the increase in extracellular hemoglobin in plasma during pancreatitis. Third, hemoglobin was purified from rat erythrocytes and administered intraperitoneally to assess the local and systemic effects of ascitic-associated extracellular hemoglobin during acute pancreatitis. Extracellular hemoglobin and hemin levels markedly increased in ascitic fluid and plasma during necrotizing pancreatitis. Peroxidase activity was very high in ascites. The peritoneal lavage abrogated the increase in extracellular hemoglobin in plasma. The administration of extracellular hemoglobin enhanced ascites; dramatically increased abdominal fat necrosis; upregulated tumor necrosis factor-α, interleukin-1β, and interleukin-6 gene expression; and decreased expression of interleukin-10 in abdominal adipose tissue during pancreatitis. Extracellular hemoglobin enhanced the gene expression and protein levels of vascular endothelial growth factor (VEGF) and other hypoxia-inducible factor-related genes in the lung. Extracellular hemoglobin also increased myeloperoxidase activity in the lung. In conclusion, extracellular hemoglobin contributes to the inflammatory response in severe acute pancreatitis through abdominal fat necrosis and inflammation

  18. Reliability of an Online Geriatric Assessment Procedure Using the interRAI Acute Care Assessment System.

    Science.gov (United States)

    Martin-Khan, Melinda G; Edwards, Helen; Wootton, Richard; Counsell, Steven R; Varghese, Paul; Lim, Wen Kwang; Darzins, Peteris; Dakin, Lucy; Klein, Kerenaftali; Gray, Leonard C

    2017-08-21

    To determine whether geriatric triage decisions made using a comprehensive geriatric assessment (CGA) performed online are less reliable than face-to-face (FTF) decisions. Multisite noninferiority prospective cohort study. Two specialist geriatricians assessed individuals sequentially referred for an acute care geriatric consultation. Participants were allocated to one FTF assessment and an additional assessment (FTF or online (OL)), creating two groups-two FTF (FTF-FTF, n = 81) or online and FTF (OL-FTF, n = 85). Three acute care public hospitals in two Australian states. Admitted individuals referred for CGA. Nurse-administered CGA, based on the interRAI Acute Care assessment system accessed online and other online clinical data such as pathology results and imaging enabling geriatricians to review participants' information and provide input into their care from a distance. The primary decision subjected to this analysis was referral for permanent residential care. Geriatricians also recorded recommendations for referrals and variations for medication management and judgment regarding prognosis at discharge and after 3 months. Overall percentage agreement was 88% (n = 71) for the FTF-FTF group and 91% (n = 77) for the OL-FTF group. The difference in agreement between the FTF-FTF and OL-FTF groups was -3%, indicating that there was no difference between the methods of assessment. Judgements made regarding diagnoses of geriatric syndromes, medication management, and prognosis (with regard to hospital outcome and location at 3 months) were found to be equally reliable in each mode of consultation. Geriatric assessment performed online using a nurse-administered structured CGA system was no less reliable than conventional assessment in making clinical triage decisions. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  19. Autonomic nervous system modulation affects the inflammatory immune response in mice with acute Chagas disease.

    Science.gov (United States)

    Machado, Marcus Paulo Ribeiro; Rocha, Aletheia Moraes; de Oliveira, Lucas Felipe; de Cuba, Marília Beatriz; de Oliveira Loss, Igor; Castellano, Lucio Roberto; Silva, Marcus Vinicius; Machado, Juliana Reis; Nascentes, Gabriel Antonio Nogueira; Paiva, Luciano Henrique; Savino, Wilson; Junior, Virmondes Rodrigues; Brum, Patricia Chakur; Prado, Vania Ferreira; Prado, Marco Antonio Maximo; Silva, Eliane Lages; Montano, Nicola; Ramirez, Luis Eduardo; Dias da Silva, Valdo Jose

    2012-11-01

    The aim of the present study was to evaluate the effects of changes to the autonomic nervous system in mice during the acute phase of Chagas disease, which is an infection caused by the parasite Trypanosoma cruzi. The following types of mice were inoculated with T. cruzi (CHG): wild-type (WT) and vesicular acetylcholine transporter knockdown (KDVAChT) C57BL/6j mice; wild-type non-treated (NT) FVB mice; FVB mice treated with pyridostigmine bromide (PYR) or salbutamol (SALB); and β(2)-adrenergic receptor knockout (KOβ2) FVB mice. During infection and at 18-21 days after infection (acute phase), the survival curves, parasitaemia, electrocardiograms, heart rate variability, autonomic tonus and histopathology of the animals were evaluated. Negative control groups were matched for age, genetic background and treatment. The KDVAChT-CHG mice exhibited a significant shift in the electrocardiographic, autonomic and histopathological profiles towards a greater inflammatory immune response that was associated with a reduction in blood and tissue parasitism. In contrast, the CHG-PYR mice manifested reduced myocardial inflammation and lower blood and tissue parasitism. Similar results were observed in CHG-SALB animals. Unexpectedly, the KOβ2-CHG mice exhibited less myocardial inflammation and higher blood and tissue parasitism, which were associated with reduced mortality. These findings could have been due to the increase in vagal tone observed in the KOβ2 mice, which rendered them more similar to the CHG-PYR animals. In conclusion, our results indicate a marked immunomodulatory role for the parasympathetic and sympathetic autonomic nervous systems, which inhibit both the inflammatory immune response and parasite clearance during the acute phase of experimental Chagas heart disease in mice.

  20. Systemic Atherosclerotic Inflammation Following Acute Myocardial Infarction: Myocardial Infarction Begets Myocardial Infarction

    Science.gov (United States)

    Joshi, Nikhil V; Toor, Iqbal; Shah, Anoop S V; Carruthers, Kathryn; Vesey, Alex T; Alam, Shirjel R; Sills, Andrew; Hoo, Teng Y; Melville, Adam J; Langlands, Sarah P; Jenkins, William S A; Uren, Neal G; Mills, Nicholas L; Fletcher, Alison M; van Beek, Edwin J R; Rudd, James H F; Fox, Keith A A; Dweck, Marc R; Newby, David E

    2015-01-01

    Background Preclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans. Methods and Results Overall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non–ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI. Conclusions The presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254. PMID:26316523

  1. Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

    Directory of Open Access Journals (Sweden)

    Mirian S. Tamashiro

    2011-01-01

    Full Text Available OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years. In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70% vs. 1%, 54% vs. 32%, 30% vs. 8%, and 9% vs. 0%, respectively. Likewise, the frequencies of anemia, leukopenia, neutropenia, thrombocytopenia and high lactic dehydrogenase levels were statistically higher in leukemia patients than in patients with systemic-onset juvenile idiopathic arthritis (88% vs. 57%, 39% vs. 1%, 60% vs. 1%, 77% vs. 1%, and 56% vs. 14%, respectively. Remarkably, multivariate analysis revealed that limb pain (OR = 553; 95% CI =46.48-6580.42 and thrombocytopenia (OR = 754.13; 95% CI =64.57-8806.72 were significant independent variables that differentiated leukemia from systemic-onset juvenile idiopathic arthritis. The R2 of the Nagelkerke test was 0.91, and the Kaplan-Meier survival curves were similar for acute lymphoblastic leukemia patients with and without limb pain. CONCLUSION: Our study

  2. A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Rector Edward S

    2004-11-01

    Full Text Available Abstract Background Biologically variable ventilation (return of physiological variability in rate and tidal volume using a computer-controller was compared to control mode ventilation with and without a recruitment manoeuvre – 40 cm H2O for 40 sec performed hourly; in a porcine oleic acid acute lung injury model. Methods We compared gas exchange, respiratory mechanics, and measured bronchoalveolar fluid for inflammatory cytokines, cell counts and surfactant function. Lung injury was scored by light microscopy. Pigs received mechanical ventilation (FIO2 = 0.3; PEEP 5 cm H2O in control mode until PaO2 decreased to 60 mm Hg with oleic acid infusion (PaO2/FIO2 2O was added after injury. Animals were randomized to one of the 3 modes of ventilation and followed for 5 hr after injury. Results PaO2 and respiratory system compliance was significantly greater with biologically variable ventilation compared to the other 2 groups. Mean and mean peak airway pressures were also lower. There were no differences in cell counts in bronchoalveolar fluid by flow cytometry, or interleukin-8 and -10 levels between groups. Lung injury scoring revealed no difference between groups in the regions examined. No differences in surfactant function were seen between groups by capillary surfactometry. Conclusions In this porcine model of acute lung injury, various indices to measure injury or inflammation did not differ between the 3 approaches to ventilation. However, when using a low tidal volume strategy with moderate levels of PEEP, sustained improvements in arterial oxygen tension and respiratory system compliance were only seen with BVV when compared to CMV or CMV with a recruitment manoeuvre.

  3. 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

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

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2012-01-01

    Full Text Available 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 10(9/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 10(9/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

  5. Development of a biotic ligand model to predict the acute toxicity of cadmium to Daphnia pulex.

    Science.gov (United States)

    Clifford, Matthew; McGeer, James C

    2010-06-01

    The goal of this study was to develop a biotic ligand model (BLM) to predict the acute toxicity of cadmium to Daphnia pulex. Organisms were cultured in moderately soft water and standard 48h acute toxicity tests were used to determine EC50s in various water chemistries where the effects of Ca(2+), Na(+), Mg(2+), Cl(-), K(+), pH, and two sources of natural organic matter (Suwannee River and Nordic Reservoir) were evaluated. Overall, toxicity responses were consistent with the free-ion activity model and the principles inherent in the BLM. Increases in Ca(2+) resulted in higher EC50s, indicating that Cd(2+) competes with Ca(2+) for uptake at the biotic ligand. Similar cation competition effects were observed when Mg(2+) was varied but with a less pronounced protective effect relative to Ca(2+). Changes in Na(+) and K(+) concentrations had no significant effect on Cd toxicity. EC50 values did not change significantly when pH was adjusted over a range from 8.0 to 6.1. Additions of natural organic matter resulted in elevated dissolved organic carbon (DOC) concentrations that significantly reduced Cd bioavailability via complexation of Cd(2+). An existing biotic ligand model (HydroQual BLM ver 2.2.3) was tested for its ability to predict acute Cd toxicity to D. pulex. Once the BLM was adjusted for the relatively sensitivity of D. pulex the protective effects of Ca and DOC could be predicted reasonably well but other test chemistries did not match with measured EC50s. Binding constants derived from the test results (logK(CaBL) of 4.1, logK(MgBL) of 3.7, logK(HBL) of 6.1 and logK(CdBL) of 7.0) were used to develop a modified BLM for the effects of Cd on D. pulex that accounted for the moderating effect of Ca and Mg on acute toxicity but overestimated the protective effect of DOC. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  6. Effects of acute or chronic administration of substituted benzamides in experimental models of depression in rats.

    Science.gov (United States)

    Drago, F; Arezzi, A; Virzì, A

    2000-12-01

    The effects of substituted benzamides, sulpiride and raclopride on experimental models of depression were studied in male rats after acute or chronic administration in comparison to those of the classical antidepressant, clomipramine. In contrast to clomipramine (50 mg/kg), acute doses of sulpiride or raclopride (1 or 5 mg/kg) failed to change the behavioral response of animals tested in the despair (constrained swim) test or in the model of reserpine-induced changes in the open field behavior. These doses also did not modify the grooming response of rats exposed to a novel environment. Sulpiride or raclopride 10 mg/kg increased the immobility time in the despair test and reduced novelty-induced grooming. The repeated injection for 21 days of sulpiride or raclopride (1 or 5 mg/kg, but not 10 mg/kg) induced a reduction of the immobility period during the constrained swim test similar to that following the chronic treatment with clomipramine 50 mg/kg. This appeared to be a clear-cut reversed dose-response relationship for both substituted benzamides, being the dose potency 1 mg/kg>5 mg/kg>10 mg/kg. Raclopride was more potent than sulpiride in this respect. Furthermore, like clomipramine, sulpiride (1 or 5 mg/kg) and raclopride (1 mg/kg) antagonized reserpine-induced changes in the open field behavior and enhanced novelty-induced grooming. These results indicate that, in contrast to acute injection, repeated administration of small doses of the substituted benzamides, sulpiride or raclopride induce an effect similar to that of the classical antidepressant, clomipramine. The reverse dose-response relationship suggests that these drugs in small doses act on presynaptic dopamine D(2) receptors. This may be consistent with a postsynaptic action of greater doses that exert sedative effects and increase immobility time in the despair test.

  7. System identification application using Hammerstein model

    Indian Academy of Sciences (India)

    SABAN OZER; HASAN ZORLU; SELCUK METE

    2016-06-01

    Generally, memoryless polynomial nonlinear model for nonlinear part and finite impulse response (FIR) model or infinite impulse response model for linear part are preferred in Hammerstein models in literature. In this paper, system identification applications of Hammerstein model that is cascade of nonlinear second order volterra and linear FIR model are studied. Recursive least square algorithm is used to identify the proposed Hammerstein model parameters. Furthermore, the results are compared to identify the success of proposed Hammerstein model and different types of models

  8. Modeling of economic systems with Petri nets

    Directory of Open Access Journals (Sweden)

    Pavel Valeryevich Skorodumov

    2014-09-01

    Full Text Available Modeling is one of the most important tools to study complex systems. Components of both continuous and discrete nature are present in the behavior of contemporary economic systems. The article uses formalism of nested hybrid Petri nets as a tool to study complex economic systems. The author describes basic approaches of simulation modelling, concepts of classical Petri nets, modified means of nested hybrid Petri nets, benefits of their use for systems modeling. The article presents the concept of a universal system of simulation modeling. On the basis of considered approaches the article proposes to develop a universal system of simulation modeling on the basis of the modified machine Petri nets

  9. 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.

  10. A Case Report of Acute Diverticulitis in “Pseudodiverticulosis” after Hemorpex System® Procedure

    Science.gov (United States)

    2016-01-01

    Introduction. In the last years many mini-invasive approaches were developed in order to reduce postoperative pain and complication after haemorrhoid surgery: one of these alternatives is represented by Hemorpex System, a relatively young technique that combines transanal dearterialization with mucopexy through a dedicated proctoscope. Case Presentation. A 78-year-old male patient was admitted to the Emergency Department for acute urinary retention and elevated temperature. Hemorpex procedure was performed 4 years before. Clinical, endoscopic, and radiological findings demonstrated the presence of multiple diverticula-like structures fulfilled by purulent fluid and a deep alteration of the normal anatomy of the rectum. He was treated following the standard protocol of acute diverticulitis and full recovery from symptoms was achieved. Discussion. Hemorpex System is a young technique, and nowadays-available studies lack long-term follow-up data. Anatomical changes induced by the procedure are consistent and definitive. Our patient luckily demonstrated a prompt response to conservative treatment, but it must be taken into account that, in case of medical treatment failure, surgical approach would be necessary and the actual patient anatomical changes could lead the surgeon to unavoidable threatening maneuvers. PMID:27974987

  11. 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.

  12. Neuman systems model in holland: an update.

    Science.gov (United States)

    Merks, André; Verberk, Frans; de Kuiper, Marlou; Lowry, Lois W

    2012-10-01

    The authors of this column, leading members of the International Neuman Systems Model Association, provide an update on the use of Neuman systems model in Holland and document the various changes in The Netherlands that have influenced the use of the model in that country. The model's link to systems theory and stress theory are discussed, as well as a shift to greater emphasis on patient self-management. The model is also linked to healthcare quality improvement and interprofessional collaboration in Holland.

  13. [Effects of the effective components group of xiaoshuantongluo formula on rat acute blood stasis model].

    Science.gov (United States)

    Zhao, Yan; Yu, Xin; Shi, Li-Li; Chen, Bai-Nian; Wang, Shao-Hua; Du, Guan-Hua

    2012-05-01

    Effects of the effective components group of Xiaoshuantongluo formula (XECG) on rat acute blood stasis model were studied under the guidance of the concept of effective components group. Rat acute blood stasis model was induced by subcutaneous injection of epinephrine combined with ice water bath. Hemorheology indices such as whole blood viscosity, plasma viscosity, erythrocyte aggregation index and platelet aggregation rate; coagulation parameters including PT, APTT, TT and FIB; 6-keto-PGF1alpha, TXB2 and D-dimer levels were determined to evaluate the effects of XECG. The results showed that XECG significantly reduced ADP-induced platelet aggregation, but showed little influence on the whole blood viscosity, plasma viscosity and erythrocyte aggregation rate. XECG extended PT and TT slightly, but had no effects on APTT and FIB content. D-dimer levels significantly decreased after administration of XECG with a little decrease of TXB2, but the content of 6-keto-PGF1alpha did not change significantly. The results suggest that the role of XECG of anti-aggregation is more prominent.

  14. RAGE/NF-κB signaling mediates lipopolysaccharide induced acute lung injury in neonate rat model.

    Science.gov (United States)

    Li, Yuhong; Wu, Rong; Tian, Yian; Yu, Min; Tang, Yun; Cheng, Huaipin; Tian, Zhaofang

    2015-01-01

    Lipopolysaccharide (LPS) is known to induce acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Accumulating data suggest the crucial role of RAGE in the pathogenesis of ALI/ARDS. However, the mechanism by which RAGE mediates inflammatory lung injury in the neonates remains elusive. In this study we established LPS-induced ALI model in neonate rats, and investigated the role of RAGE/NF-κB signaling in mediating ALI. We found that RAGE antibody or bortezomib reduced LPS-induced histopathological abnormalities in the lung and lung damage score. RAGE antibody or bortezomib also reduced TNF-α level in both serum and BALF of the rats. Furthermore, RAGE antibody or bortezomib significantly reduced LPS-induced upregulation of RAGE and NF-κB expression in the lung. In conclusion, we established ALI model in neonate rats to demonstrate that LPS induced inflammatory lung injury via RAGE/NF-κB signaling. Interference with RAGE/NF-κB signaling is a potential approach to prevent and treat sepsis-related ALI/ARDS.

  15. New model systems for experimental evolution.

    Science.gov (United States)

    Collins, Sinéad

    2013-07-01

    Microbial experimental evolution uses a few well-characterized model systems to answer fundamental questions about how evolution works. This special section highlights novel model systems for experimental evolution, with a focus on marine model systems that can be used to understand evolutionary responses to global change in the oceans.

  16. Performance modeling of automated manufacturing systems

    Science.gov (United States)

    Viswanadham, N.; Narahari, Y.

    A unified and systematic treatment is presented of modeling methodologies and analysis techniques for performance evaluation of automated manufacturing systems. The book is the first treatment of the mathematical modeling of manufacturing systems. Automated manufacturing systems are surveyed and three principal analytical modeling paradigms are discussed: Markov chains, queues and queueing networks, and Petri nets.

  17. Modeling human operator involvement in robotic systems

    NARCIS (Netherlands)

    Wewerinke, P.H.

    1991-01-01

    A modeling approach is presented to describe complex manned robotic systems. The robotic system is modeled as a (highly) nonlinear, possibly time-varying dynamic system including any time delays in terms of optimal estimation, control and decision theory. The role of the human operator(s) is modeled

  18. Acute care clinical pharmacy practice: unit- versus service-based models.

    Science.gov (United States)

    Haas, Curtis E; Eckel, Stephen; Arif, Sally; Beringer, Paul M; Blake, Elizabeth W; Lardieri, Allison B; Lobo, Bob L; Mercer, Jessica M; Moye, Pamela; Orlando, Patricia L; Wargo, Kurt

    2012-02-01

    This commentary from the 2010 Task Force on Acute Care Practice Model of the American College of Clinical Pharmacy was developed to compare and contrast the "unit-based" and "service-based" orientation of the clinical pharmacist within an acute care pharmacy practice model and to offer an informed opinion concerning which should be preferred. The clinical pharmacy practice model must facilitate patient-centered care and therefore must position the pharmacist to be an active member of the interprofessional team focused on providing high-quality pharmaceutical care to the patient. Although both models may have advantages and disadvantages, the most important distinction pertains to the patient care role of the clinical pharmacist. The unit-based pharmacist is often in a position of reacting to an established order or decision and frequently is focused on task-oriented clinical services. By definition, the service-based clinical pharmacist functions as a member of the interprofessional team. As a team member, the pharmacist proactively contributes to the decision-making process and the development of patient-centered care plans. The service-based orientation of the pharmacist is consistent with both the practice vision embraced by ACCP and its definition of clinical pharmacy. The task force strongly recommends that institutions pursue a service-based pharmacy practice model to optimally deploy their clinical pharmacists. Those who elect to adopt this recommendation will face challenges in overcoming several resource, technologic, regulatory, and accreditation barriers. However, such challenges must be confronted if clinical pharmacists are to contribute fully to achieving optimal patient outcomes.

  19. 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.

  20. 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.

  1. Acute and chronic plasma metabolomic and liver transcriptomic stress effects in a mouse model with features of post-traumatic stress disorder.

    Science.gov (United States)

    Gautam, Aarti; D'Arpa, Peter; Donohue, Duncan E; Muhie, Seid; Chakraborty, Nabarun; Luke, Brian T; Grapov, Dmitry; Carroll, Erica E; Meyerhoff, James L; Hammamieh, Rasha; Jett, Marti

    2015-01-01

    Acute responses to intense stressors can give rise to post-traumatic stress disorder (PTSD). PTSD diagnostic criteria include trauma exposure history and self-reported symptoms. Individuals who meet PTSD diagnostic criteria often meet criteria for additional psychiatric diagnoses. Biomarkers promise to contribute to reliable phenotypes of PTSD and comorbidities by linking biological system alterations to behavioral symptoms. Here we have analyzed unbiased plasma metabolomics and other stress effects in a mouse model with behavioral features of PTSD. In this model, C57BL/6 mice are repeatedly exposed to a trained aggressor mouse (albino SJL) using a modified, resident-intruder, social defeat paradigm. Our recent studies using this model found that aggressor-exposed mice exhibited acute stress effects including changed behaviors, body weight gain, increased body temperature, as well as inflammatory and fibrotic histopathologies and transcriptomic changes of heart tissue. Some of these acute stress effects persisted, reminiscent of PTSD. Here we report elevated proteins in plasma that function in inflammation and responses to oxidative stress and damaged tissue at 24 hrs post-stressor. Additionally at this acute time point, transcriptomic analysis indicated liver inflammation. The unbiased metabolomics analysis showed altered metabolites in plasma at 24 hrs that only partially normalized toward control levels after stress-withdrawal for 1.5 or 4 wks. In particular, gut-derived metabolites were altered at 24 hrs post-stressor and remained altered up to 4 wks after stress-withdrawal. Also at the 4 wk time point, hyperlipidemia and suppressed metabolites of amino acids and carbohydrates in plasma coincided with transcriptomic indicators of altered liver metabolism (activated xenobiotic and lipid metabolism). Collectively, these system-wide sequelae to repeated intense stress suggest that the simultaneous perturbed functioning of multiple organ systems (e.g., brain, heart

  2. 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.

  3. 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.

  4. Systemic Thrombolytic Therapy Alone and in Combination with Mechanical Revascularization in Acute Ischemic Stroke in Two Children

    Directory of Open Access Journals (Sweden)

    B. Modrau

    2011-04-01

    Full Text Available 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.

  5. Externalizing Behaviour for Analysing System Models

    NARCIS (Netherlands)

    Ivanova, Marieta Georgieva; Probst, Christian W.; Hansen, René Rydhof; Kammüller, Florian

    Systems models have recently been introduced to model organisationsandevaluate their vulnerability to threats and especially insiderthreats. Especially for the latter these models are very suitable, since insiders can be assumed to have more knowledge about the attacked organisation than outside

  6. Risk-prediction model for ischemic stroke in patients hospitalized with an acute coronary syndrome (from the global registry of acute coronary events [GRACE]).

    Science.gov (United States)

    Park, Kay Lee; Budaj, Andrzej; Goldberg, Robert J; Anderson, Frederick A; Agnelli, Giancarlo; Kennelly, Brian M; Gurfinkel, Enrique P; Fitzgerald, Gordon; Gore, Joel M

    2012-09-01

    The risk of stroke in patients hospitalized with an acute coronary syndrome (ACS) ranges from ischemic stroke in patients with ACS to help guide clinicians in the acute management of these high-risk patients. Data were obtained from 63,118 patients enrolled from April 1999 to December 2007 in the Global Registry of Acute Coronary Events (GRACE), a multinational registry involving 126 hospitals in 14 countries. A regression model was developed to predict the occurrence of in-hospital ischemic stroke in patients hospitalized with an ACS. The main study outcome was the development of ischemic stroke during the index hospitalization for an ACS. Eight risk factors for stroke were identified: older age, atrial fibrillation on index electrocardiogram, positive initial cardiac biomarkers, presenting systolic blood pressure ≥ 160 mm Hg, ST-segment change on index electrocardiogram, no history of smoking, higher Killip class, and lower body weight (c-statistic 0.7). The addition of coronary artery bypass graft surgery and percutaneous coronary intervention into the model increased the prediction of stroke risk. In conclusion, the GRACE stroke risk score is a simple tool for predicting in-hospital ischemic stroke risk in patients admitted for the entire spectrum of ACS, which is widely applicable to patients in various hospital settings and will assist in the management of high-risk patients with ACS. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Hierarchical modelling of small area and hospital variation in short-term prognosis after acute myocardial infarction. A longitudinal study of 35- to 74-year-old men in Denmark between 1978 and 1997

    DEFF Research Database (Denmark)

    Rasmussen, Søren

    2004-01-01

    acute myocardial infarction; covariance pattern; deviance information criterion; hierarchical modelling; Markov chain Monte Carlo methods; spatial models......acute myocardial infarction; covariance pattern; deviance information criterion; hierarchical modelling; Markov chain Monte Carlo methods; spatial models...

  8. CONTROL SYSTEM IDENTIFICATION THROUGH MODEL MODULATION METHODS

    Science.gov (United States)

    identification has been achieved by using model modulation techniques to drive dynamic models into correspondence with operating control systems. The system ... identification then proceeded from examination of the model and the adaptive loop. The model modulation techniques applied to adaptive control

  9. 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....

  10. Inhalation exposure system used for acute and repeated-dose methyl isocyanate exposures of laboratory animals.

    Science.gov (United States)

    Adkins, B; O'Connor, R W; Dement, J M

    1987-06-01

    Laboratory animals were exposed by inhalation for 2 hr/day (acute) or 6 hr/day (four consecutive days, repeated dose) to methyl isocyanate (MIC). Exposures were conducted in stainless steel and glass inhalation exposure chambers placed in stainless steel, wire mesh cages. MIC was delivered with nitrogen via stainless steel and Teflon supply lines. Chamber concentrations ranged from 0 to 60 ppm and were monitored continuously with infrared spectrophotometers to 1 ppm and at 2-hr intervals to 20 ppb with a high performance liquid chromatograph equipped with a fluorescence detector. Other operational parameters monitored on a continuous basis included chamber temperature (20-27 degrees C), relative humidity (31-64%), static (transmural) pressure (-0.3 in.), and flow (300-500 L/min). The computer-assistance system interfaced with the inhalation exposure laboratory is described in detail, including the analytical instrumentation calibration system used throughout this investigation.

  11. Acute lead exposure increases arterial pressure: role of the renin-angiotensin system.

    Directory of Open Access Journals (Sweden)

    Maylla Ronacher Simões

    Full Text Available BACKGROUND: Chronic lead exposure causes hypertension and cardiovascular disease. Our purpose was to evaluate the effects of acute exposure to lead on arterial pressure and elucidate the early mechanisms involved in the development of lead-induced hypertension. METHODOLOGY/PRINCIPAL FINDINGS: Wistar rats were treated with lead acetate (i.v. bolus dose of 320 µg/Kg, and systolic arterial pressure, diastolic arterial pressure and heart rate were measured during 120 min. An increase in arterial pressure was found, and potential roles of the renin-angiotensin system, Na(+,K(+-ATPase and the autonomic reflexes in this change in the increase of arterial pressure found were evaluated. In anesthetized rats, lead exposure: 1 produced blood lead levels of 37±1.7 µg/dL, which is below the reference blood concentration (60 µg/dL; 2 increased systolic arterial pressure (Ct: 109±3 mmHg vs Pb: 120±4 mmHg; 3 increased ACE activity (27% compared to Ct and Na(+,K(+-ATPase activity (125% compared to Ct; and 4 did not change the protein expression of the α1-subunit of Na(+,K(+-ATPase, AT(1 and AT(2. Pre-treatment with an AT(1 receptor blocker (losartan, 10 mg/Kg or an ACE inhibitor (enalapril, 5 mg/Kg blocked the lead-induced increase of arterial pressure. However, a ganglionic blockade (hexamethonium, 20 mg/Kg did not prevent lead's hypertensive effect. CONCLUSION: Acute exposure to lead below the reference blood concentration increases systolic arterial pressure by increasing angiotensin II levels due to ACE activation. These findings offer further evidence that acute exposure to lead can trigger early mechanisms of hypertension development and might be an environmental risk factor for cardiovascular disease.

  12. 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

  13. 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.

  14. Rosiglitazone dampens pulmonary inflammation in a porcine model of acute lung injury.

    Science.gov (United States)

    Mirakaj, Valbona; Mutz, Christian; Vagts, Dierk; Henes, Janek; Haeberle, Helene A; Husung, Susanne; König, Tony; Nöldge-Schomburg, Gabriele; Rosenberger, Peter

    2014-08-01

    The hallmarks of acute lung injury (ALI) are the compromised alveolar-capillary barrier and the extravasation of leukocytes into the alveolar space. Given the fact that the peroxisome proliferator-activated receptor-γ agonist rosiglitazone holds significant anti-inflammatory properties, we aimed to evaluate whether rosiglitazone could dampen these hallmarks of local pulmonary inflammation in a porcine model of lung injury. For this purpose, we used a model of lipopolysaccharide (LPS, 50 μg/kg)-induced ALI. One hundred twenty minutes following the infusion of LPS, we started the exposure to rosiglitazone through inhalation or infusion. We found that intravenous rosiglitazone significantly controlled local pulmonary inflammation as determined through the expression of cytokines within the alveolar compartment. Furthermore, we found a significant reduction of the protein concentration and neutrophil activity within the alveolar space. In summary, we therefore conclude that the treatment with rosiglitazone might dampen local pulmonary inflammation during the initial stages of ALI.

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

    Science.gov (United States)

    2013-02-12

    treatment of acute, severe cyanide induced cardiotoxicity of severe hypotension and of cardiac arrest in a swine (Sus Scrofa ) model Intravenous...cobinamide, a novel cyanide antidote, versus hydroxocobalamin in the treatment of acute cyanide toxicity and apnea in a swine (Sus Scrofa ) model...hydroxocobalamin in the treatment of acute cyanide toxicity and apnea in a swine (Sus Scrofa ) model Background: Hydroxocobalamin (HOC) is an FDA approved

  16. 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

  17. The effects of salbutamol in an experimental model with acute respiratory distress syndrome

    Institute of Scientific and Technical Information of China (English)

    Sema Yilmaz; Diner Yildizdas; Kenan Daglioglu; Arbil Acikalin; Can Acipayam; Ibrahim Bayram; Derya Gumurdulu; Atila Tanyeli

    2012-01-01

    Objective: To investigate salbutamol effects on histopathologic features of acute respiratory distress syndrome (ARDS). Methods: ARDS was designed in Wistar albino male rats, 250-300 g in weight, by intratracheal instillation of physiological saline solution. Anesthezied and tracheotomized rats with ARDS were pressure-controlled ventilated. At the end of the 210 minutes, two hours past and nebulized salbutamol inhalation was tried. All rats were assigned to two groups: Group 1 (n=10) control group, given no treatment, group 2 (n=10) received salbutamol. Nebulized salbutamol inhalation was given in the dosage of 0, 15 mg/kg/dose. Rats were continued to be on ventilator through the experiment. After the last inhalation, two hours past and their both lungs were excised for histopathological examination. Results: Rat-model ARDS had similar histopathological appearance occuring during the acute phase of the acute respiratory distress syndrome in humans. A statistical difference was seen between control and salbutamol group (P=0.002) for HM. The margination of leukocytes was decreased in salbutamol group. The difference was significant (P<0.042). Hemorrhage and interstitial/intraalveolar edema were much lower in 0.15 mg/dose nebulized salbutamol group than that of control group. There was a significant difference statistically between two groups (P<0.001). Conclusions: Inhaled salbutamol therapy for ARDS is may be associated with the improvement of inflamation. Besides known effects of salbutamol, the reducing of infiltration of polymorphonuclear neutrophil leukocytes, interstitial/intraalveolar edema, perivascular and/or intraalveolar hemorrhage and hyaline membrane formation should be emphasized.

  18. Graphical Model Debugger Framework for Embedded Systems

    DEFF Research Database (Denmark)

    Zeng, Kebin; Guo, Yu; Angelov, Christo K.

    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...

  19. Particle Tracking Model (PTM) with Coastal Modeling System (CMS)

    Science.gov (United States)

    2014-10-31

    System ( CMS ) 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER...www.erdc.usace.army.mil/Missions/WaterResources/CIRP.aspx Coastal Inlets Research Program Particle Tracking Model (PTM) with Coastal Modeling System ( CMS ) The...System ( CMS ), which provides coupled wave and current forcing for PTM simulations. CMS -PTM is implemented in the Surface-water Modeling System, a

  20. 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.

  1. Analysis hierarchical model for discrete event systems

    Science.gov (United States)

    Ciortea, E. M.

    2015-11-01

    The This paper presents the hierarchical model based on discrete event network for robotic systems. Based on the hierarchical approach, Petri network is analysed as a network of the highest conceptual level and the lowest level of local control. For modelling and control of complex robotic systems using extended Petri nets. Such a system is structured, controlled and analysed in this paper by using Visual Object Net ++ package that is relatively simple and easy to use, and the results are shown as representations easy to interpret. The hierarchical structure of the robotic system is implemented on computers analysed using specialized programs. Implementation of hierarchical model discrete event systems, as a real-time operating system on a computer network connected via a serial bus is possible, where each computer is dedicated to local and Petri model of a subsystem global robotic system. Since Petri models are simplified to apply general computers, analysis, modelling, complex manufacturing systems control can be achieved using Petri nets. Discrete event systems is a pragmatic tool for modelling industrial systems. For system modelling using Petri nets because we have our system where discrete event. To highlight the auxiliary time Petri model using transport stream divided into hierarchical levels and sections are analysed successively. Proposed robotic system simulation using timed Petri, offers the opportunity to view the robotic time. Application of goods or robotic and transmission times obtained by measuring spot is obtained graphics showing the average time for transport activity, using the parameters sets of finished products. individually.

  2. Photoprotective effect and acute oral systemic toxicity evaluation of the novel heterocyclic compound LQFM048.

    Science.gov (United States)

    Vinhal, Daniela C; de Ávila, Renato Ivan; Vieira, Marcelo S; Luzin, Rangel M; Quintino, Michelle P; Nunes, Liliane M; Ribeiro, Antonio Carlos Chaves; de Camargo, Henrique Santiago; Pinto, Angelo C; Dos Santos Júnior, Helvécio M; Chiari, Bruna G; Isaac, Vera; Valadares, Marize C; Martins, Tatiana Duque; Lião, Luciano M; de S Gil, Eric; Menegatti, Ricardo

    2016-08-01

    The new heterocyclic derivative LQFM048 (3) (2,4,6-tris ((E)-ethyl 2-cyano-3-(4-hydroxy-3-methoxyphenyl)acrylate)-1,3,5-triazine) was originally designed through the molecular hybridization strategy from Uvinul® T 150 (1) and (E)-ethyl 2-cyano-3-(4hydroxy-3-methoxyphenyl)acrylate (2) sunscreens, using green chemistry approach. This compound was obtained in global yields (80%) and showed an interesting redox potential. In addition, it is thermally stable up to temperatures around 250°C. It was observed that LQFM048 (3) showed a low degradation after 150min of sunlight exposure at 39°C, whereas the extreme radiation conditions induced a considerable photodegradation of the LQFM048 (3), especially when irradiated by VIS and VIS+UVA. During the determination of sun protection factor, LQFM048 (3) showed interesting results, specially as in association with other photoprotective compounds and commercial sunscreen. Additionally, the compound (3) did not promote cytotoxicity for 3T3 fibroblasts. Moreover, it was not able to trigger acute oral systemic toxicity in mice, being classified as a compound with low acute toxicity hazard (2.000mg/kg>LD50<5.000mg/kg). Therefore, this compound synthesized using green chemistry approach is promising showing potential to development of a new sunscreen product with advantage of presenting redox potential, indicating antioxidant properties.

  3. Clinical dilemma of acute abdomen in patients with systemic lupuserythematosus: A case report

    Directory of Open Access Journals (Sweden)

    Ali Ghavidel

    2017-06-01

    Full Text Available Introduction: Gastrointestinal (GI symptoms and signs may be seen in approximately one third ofpatients with rheumatologic disorders as primary presentation. Some of these findings may benondiagnostic and may be clinical diagnostic challenge. GI tract involvement by systemic lupuserythematosus (SLE must be differentiated from adverse drug reactions of treatment agents.Abdominal pain, associated with nausea and vomiting, is seen in up to 30 percent of patients withSLE. The cause of abdominal pain does not differ significantly from that in patients without lupus.Special attention should be given to conditions that may accompany lupus such as lupus peritonitisand infection. Lupus peritonitis is very unusual clinical finding and it is worth reporting.Case Report: Our patient was a young female with definite rheumatologic disorders with acuteabdomen as the dominant clinical finding. Imaging findings confirmed peritoneum and smallintestine involvement. Paraclinical work-up including blood analysis confirmed SLE. She wasmanaged with prednisone and non-steroidal anti-inflammatory agents, and discharged withpartial improvement.Conclusion: This case report shows that patients with symptoms consistent with acute abdomen inSLE remind us a clinical dilemma. There have been few reports of acute abdomen in patients withSLE in the literature. And more case reports are needed.

  4. Gender Differences in Acute Cadmium-Induced Systemic Inflammation in Rats

    Institute of Scientific and Technical Information of China (English)

    MILENA KATARANOVSKI; SRDJA JANKOVI(C); DRAGAN KATARANOVSKI; JELENA (S)TOSI(C); DESA BOGOJEVI(C)

    2009-01-01

    Objective To examine the presence of gender differences in pro-inflammatory potential of cadmium in rats by comparing systemic inflammatory response to acute cadmium intoxication in animals of the two sexes. Methods Basic aspects of this response were evaluated, including plasma levels of inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) and of major rat acute phase protein alpha 2-macroglobulin (alpha2-M), as soluble indicators of inflammation, and the number and activity of peripheral blood leukocytes, as cellular indicators of inflammation. Results Differential increases of IL-6 and alpha 2-M (higher in males than in females) in peripheral blood cell counts and types (leukocytosis and shift in the ratio of granulocytes to lymphocytes more pronounced in males vs females) and in levels of neutrophil priming (higher in males vs females) were noted. Conclusion The data document a more intense inflammatory response to cadmium administration in males. The sex differences in inflammatory effects of cadmium might be taken into consideration in studying the toxicity of this heavy metal.

  5. Catheter-directed therapy for acute renal vein thrombosis in systemic lupus erythematosus: A case report.

    Science.gov (United States)

    Jong, Chien-Boon; Lo, Wei-Yung; Hsieh, Mu-Yang

    2017-02-15

    We report our experience using catheter-directed thrombectomy/thrombolysis (CDT) to treat a patient with acute renal vein thrombosis (RVT) associated with systemic lupus erythematosus (SLE). A 34-year-old woman presented with persistent left flank pain, and a renal ultrasonography examination revealed an enlarged left kidney. Contrast-enhanced computed tomography confirmed the presence of acute left RVT. Because medical treatment failed to relieve her pain and the renal function was deteriorating, we attempted to salvage the occluded left renal vein using an endovascular approach. The pain was completely relieved after a CDT and an overnight urokinase infusion. A follow-up computed tomography examination revealed the complete resolution of the thrombus. The creatinine level returned to normal (1.7-0.4 mg/dL), along with contrast enhancement in the left kidney, and this suggested the preservation of renal function. To our knowledge, this is the first report utilizing CDT to treat SLE-associated RVT. When the renal function is deteriorating, CDT is worth considering for RVT if conventional medical treatment has failed. © 2016 Wiley Periodicals, Inc.

  6. Integration of Rule Based Expert Systems and Case Based Reasoning in an Acute Bacterial Meningitis Clinical Decision Support System

    CERN Document Server

    Cabrera, Mariana Maceiras

    2010-01-01

    This article presents the results of the research carried out on the development of a medical diagnostic system applied to the Acute Bacterial Meningitis, using the Case Based Reasoning methodology. The research was focused on the implementation of the adaptation stage, from the integration of Case Based Reasoning and Rule Based Expert Systems. In this adaptation stage we use a higher level RBC that stores and allows reutilizing change experiences, combined with a classic rule-based inference engine. In order to take into account the most evident clinical situation, a pre-diagnosis stage is implemented using a rule engine that, given an evident situation, emits the corresponding diagnosis and avoids the complete process.

  7. Extensions in model-based system analysis

    OpenAIRE

    Graham, Matthew R.

    2007-01-01

    Model-based system analysis techniques provide a means for determining desired system performance prior to actual implementation. In addition to specifying desired performance, model-based analysis techniques require mathematical descriptions that characterize relevant behavior of the system. The developments of this dissertation give ex. tended formulations for control- relevant model estimation as well as model-based analysis conditions for performance requirements specified as frequency do...

  8. Inductive modelling of an entrepreneurial system

    OpenAIRE

    Yearworth, M

    2010-01-01

    We describe the development of a novel approach to generating theory about the behaviour of an entrepreneurial or start-up system. The new technology business creation system in and around the cities of Bath and Bristol in the UK was analysed using an inductive modelling approach that hybridises grounded theory with system dynamics, a technique we have called grounded systems modelling. Three models that represent the stages of development of an idea through to successful exploitation have be...

  9. Control model for reconfigurable assembly systems

    Institute of Scientific and Technical Information of China (English)

    Yu Jianfeng; Yin Yuehong; Chen Zhaoneng

    2005-01-01

    This paper proposes knowledge based object-oriented timed colored Petri net, a modeling method for reconfigurable assembly systems. Combining knowledge and object-oriented method into timed colored Petri net, a comprehensive and powerful representation model for control of RAS is obtained. With object-oriented method the whole system can be decomposed into concrete objects explicitly, and their relationships are constructed according to the system assembly requirements. Finally, a simple assembly system modeled by the KTCOPN is presented.

  10. 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.

  11. In vivo microscopy in a porcine model of acute lung injury.

    Science.gov (United States)

    Bickenbach, Johannes; Czaplik, Michael; Dembinski, Rolf; Pelosi, Paolo; Schroeder, Wolfgang; Marx, Gernot; Rossaint, Rolf

    2010-07-31

    Regional inhomogeneity and alveolar mechanics in a porcine model of acute lung injury (ALI) was evaluated using confocal laser scanning microscopy (CLSM). CLSM was performed through thoracic windows of the upper and lower lobes. Image quantification was conducted by use of a volume air index (VAI). Twelve anesthetized, mechanically ventilated pigs were randomized to non-injury (control group, n = 6) or ALI induced by surfactant depletion (ALI group, n = 6). CLSM was performed at baseline, after 1 h at 5 mbar and after 2 h at 15 mbar positive end-expiratory pressure (PEEP). Haemodynamics, respiratory mechanics and calculation of pulmonary ventilation-perfusion distribution by MIGET were determined. At baseline, VAI was not different. In the upper lobes, VAI significantly decreased in ALI compared to control group, with no changes after PEEP application. In the lower lobes, VAI significantly decreased in ALI compared to control group. Incremental PEEP significantly increased VAI in ALI, but not in control group. Haemodynamics were significantly compromised in the ALI group. A significant deterioration in oxygenation and ventilation-perfusion distribution could be seen being restored after PEEP adjustment. The VAI may help to assess regional inhomogeneity of the acutely injured lung.

  12. 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

  13. Modelling Immune System: Principles, Models,Analysis and Perspectives

    Institute of Scientific and Technical Information of China (English)

    Xiang-hua Li; Zheng-xuan Wang; Tian-yang Lu; Xiang-jiu Che

    2009-01-01

    The biological immune system is a complex adaptive system. There are lots of benefits for building the model of the immune system. For biological researchers, they can test some hypotheses about the infection process or simulate the responses of some drugs. For computer researchers, they can build distributed, robust and fault tolerant networks inspired by the functions of the immune system. This paper provides a comprehensive survey of the literatures on modelling the immune system. From the methodology perspective, the paper compares and analyzes the existing approaches and models, and also demonstrates the focusing research effort on the future immune models in the next few years.

  14. Comparison of Photovoltaic Models in the System Advisor Model: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Blair, N. J.; Dobos, A. P.; Gilman, P.

    2013-08-01

    The System Advisor Model (SAM) is free software developed by the National Renewable Energy Laboratory (NREL) for predicting the performance of renewable energy systems and analyzing the financial feasibility of residential, commercial, and utility-scale grid-connected projects. SAM offers several options for predicting the performance of photovoltaic (PV) systems. The model requires that the analyst choose from three PV system models, and depending on that choice, possibly choose from three module and two inverter component models. To obtain meaningful results from SAM, the analyst must be aware of the differences between the model options and their applicability to different modeling scenarios. This paper presents an overview the different PV model options and presents a comparison of results for a 200-kW system using different model options.

  15. Graphical Model Debugger Framework for Embedded Systems

    DEFF Research Database (Denmark)

    Zeng, Kebin

    2010-01-01

    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......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...... 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....

  16. Synchronous inhibitory potentials precede seizure-like events in acute models of focal limbic seizures.

    Science.gov (United States)

    Uva, Laura; Breschi, Gian Luca; Gnatkovsky, Vadym; Taverna, Stefano; de Curtis, Marco

    2015-02-18

    Interictal spikes in models of focal seizures and epilepsies are sustained by the synchronous activation of glutamatergic and GABAergic networks. The nature of population spikes associated with seizure initiation (pre-ictal spikes; PSs) is still undetermined. We analyzed the networks involved in the generation of both interictal and PSs in acute models of limbic cortex ictogenesis induced by pharmacological manipulations. Simultaneous extracellular and intracellular recordings from both principal cells and interneurons were performed in the medial entorhinal cortex of the in vitro isolated guinea pig brain during focal interictal and ictal discharges induced in the limbic network by intracortical and brief arterial infusions of either bicuculline methiodide (BMI) or 4-aminopyridine (4AP). Local application of BMI in the entorhinal cortex did not induce seizure-like events (SLEs), but did generate periodic interictal spikes sensitive to the glutamatergic non-NMDA receptor antagonist DNQX. Unlike local applications, arterial perfusion of either BMI or 4AP induced focal limbic SLEs. PSs just ahead of SLE were associated with hyperpolarizing potentials coupled with a complete blockade of firing in principal cells and burst discharges in putative interneurons. Interictal population spikes recorded from principal neurons between two SLEs correlated with a depolarizing potential. We demonstrate in two models of acute limbic SLE that PS events are different from interictal spikes and are sustained by synchronous activation of inhibitory networks. Our findings support a prominent role of synchronous network inhibition in the initiation of a focal seizure. Copyright © 2015 the authors 0270-6474/15/353048-08$15.00/0.

  17. ACUTE AND SUBACUTE MODELS OF INFLAMMATION OF NYCTANTHES ARBOR TRISTIS AND MAHARASNADI GHAN

    Directory of Open Access Journals (Sweden)

    Abhijeet R. Bhalerao

    2011-10-01

    Full Text Available Aqueous Methanolic extracts of Nyctanthes Arbor tristis and Maharasnadi ghan were studied for a  inflammation   parameter using   carrageenin induced hind paw edema   and cotton pellet granuloma . The natural plant was screened for acute toxicity and it did not show any toxic or deleterious effects indicating low toxicity of the extract even at high doses at two different dose levels. In carrageenin induced hind paw edema a  significant reduction in paw volume was observed  as  compared  to  control  group  whereas  in  cotton  pellet  granuloma  model  marked inhibition in granuloma formation, reduction in the elevated levels of serum lysosomal enzymes (SGPT, SGOT, and ALP and lipid peroxidation was noted as compared to control group. The extracts exhibited profound anti-inflammatory activity in both acute and subacute animal models warranting further  investigations to establish its anti-inflammatory potential. The activity was thought  due  to  flavonoids  which  might  be  present  in  the  formulation  which  could  play  a significant role in preventing the release of histamine, leukotreins and prostaglandins. In future the extract needs to be studied for cellular line models of inflammation.

  18. Detection and evaluation of renal biomarkers in a swine model of acute myocardial infarction and reperfusion.

    Science.gov (United States)

    Duan, Su-Yan; Xing, Chang-Ying; Zhang, Bo; Chen, Yan

    2015-01-01

    The prevalence of type 1 cardiorenal syndrome (CRS) is increasing and strongly associated with long-term mortality. However, lack of reliable animal models and well-defined measures of renoprotection, made early diagnosis and therapy difficult. We previously successfully established the swine acute myocardial infarction (AMI) model of ischemia-reperfusion by blocking left anterior descending branch (LAD). Reperfusion was performed after 90-minute occlusion of the LAD. AMI was confirmed by ECG and left ventricular angiography (LVG). Then those 52 survived AMI reperfusion swine, including ventricular fibrillation-cardiac arrest after restoration of blood flow, were randomly divided into four groups (four/group) according to different interventions: resuscitation in room temperature, resuscitation with 500 ml saline in room temperature, resuscitation with 4°C 500 ml saline and normal control (with no intervention of resuscitation). Each group was further observed in four groups according to different time of resuscitation after ventricular arrhythmias: 1, 3, 5, 10-minute reperfusion after ventricular arrhythmias. Plasma and random urine were collected to evaluate renal function and test renal biomarkers of acute kidney injury (AKI). Our swine AMI model of ischemia-reperfusion provoked subclinical AKI with the elevation of the tubular damage biomarker, NGAL, IL-18 and L-FABP. Renal damage rapidly observed after hemodynamic instability, rather than observation after several hours as previously reported. The increasing rate of biological markers declined after interventions, however, its impact on the long-term prognosis remains to be further studied. These data show that elevation of tubular damage biomarkers without glomerular function loss may indicate appropriate timing for effective renoprotections like hypothermia resuscitation in type 1 CRS.

  19. Acute Lung Injury and Fibrosis in a Baboon Model of Escherichia coli Sepsis

    Science.gov (United States)

    Keshari, Ravi S.; Silasi-Mansat, Robert; Zhu, Hua; Popescu, Narcis I.; Peer, Glenn; Chaaban, Hala; Lambris, John D.; Polf, Holly; Lupu, Cristina; Kinasewitz, Gary

    2014-01-01

    Sepsis-induced inflammation of the lung leads to acute respiratory distress syndrome (ARDS), which may trigger persistent fibrosis. The pathology of ARDS is complex and poorly understood, and the therapeutic approaches are limited. We used a baboon model of Escherichia coli sepsis that mimics the complexity of human disease to study the pathophysiology of ARDS. We performed extensive biochemical, histological, and functional analyses to characterize the disease progression and the long-term effects of sepsis on the lung structure and function. Similar to humans, sepsis-induced ARDS in baboons displays an early inflammatory exudative phase, with extensive necrosis. This is followed by a regenerative phase dominated by proliferation of type 2 epithelial cells, expression of epithelial-to-mesenchymal transition markers, myofibroblast migration and proliferation, and collagen synthesis. Baboons that survived sepsis showed persistent inflammation and collagen deposition 6–27 months after the acute episodes. Long-term survivors had almost double the amount of collagen in the lung as compared with age-matched control animals. Immunostaining for procollagens showed persistent active collagen synthesis within the fibroblastic foci and interalveolar septa. Fibroblasts expressed markers of transforming growth factor-β and platelet-derived growth factor signaling, suggesting their potential role as mediators of myofibroblast migration and proliferation, and collagen deposition. In parallel, up-regulation of the inhibitors of extracellular proteases supports a deregulated matrix remodeling that may contribute to fibrosis. The primate model of sepsis-induced ARDS mimics the disease progression in humans, including chronic inflammation and long-lasting fibrosis. This model helps our understanding of the pathophysiology of fibrosis and the testing of new therapies. PMID:24066737

  20. Difficulties, guidelines and review of developing an acute rejection model after rat intestinal transplantation.

    Science.gov (United States)

    Andres, Ane Miren; Santamaria, Monica; Hernandez-Oliveros, Francisco; Guerra, Laura; Lopez, Sergio; Stringa, Pablo; Vallejo, Maria Teresa; Largo, Carlota; Encinas, Jose Luis; Garcia de Las Heras, Maria Soledad; Lopez-Santamaria, Manuel; Tovar, Juan Antonio

    2016-05-01

    Experimental small bowel transplantation (SBT) in rats has been proven to be a useful tool for the study of ischemia-reperfusion and immunological aspects related to solid organ transplantation. However, the model is not completely refined, specialized literature is scarce and complex technical details are typically omitted or confusing. Most studies related to acute rejection (AR) use the orthotopic standard, with small sample sizes due to its high mortality, whereas those studying chronic rejection (CR) use the heterotopic standard, which allows longer term survival but does not exactly reflect the human clinical scenario. Various animal strains have been used, and the type of rejection and the timing of its analysis differ among authors. The double purpose of this study was to develop an improved unusual AR model of SBT using the heterotopic technique, and to elaborate a guide useful to implement experimental models for studying AR. We analyzed the model's technical details and expected difficulties in overcoming the learning curve for such a complex microsurgical model, identifying the potential problem areas and providing a step-by-step protocol and reference guide for future surgeons interested in the topic. We also discuss the historic and more recent options in the literature.

  1. Modeling and Identification of Multirate Systems

    Institute of Scientific and Technical Information of China (English)

    Feng DING; Tongwen CHEN

    2005-01-01

    Multirate systems are abundant in industry; for example, many soft-sensor design problems are related to modeling, parameter identification, or state estimation involving multirate systems. The study of multirate systems goes back to the early 1950's, and has become an active research area in systems and control. This paper briefly surveys the history of development in the area of multirate systems, and introduces some basic concepts and latest results on multirate systems, including a polynomial transformation technique and the lifting technique as tools for handling multirate systems, lifted state space models, parameter identification of dual-rate systems, how to determine fast single-rate models from dual-rate models and directly from dual-rate data, and a hierarchical identification method for general multirate systems. Finally, some further research topics for multirate systems are given.

  2. On Problems of Multicomponent System Maintenance Modelling

    Institute of Scientific and Technical Information of China (English)

    Tomasz Nowakowski; Sylwia Werbinka

    2009-01-01

    We present an overview of some recent developments in the area of mathematical modeling of maintenance decisions for multi-unit systems. The emphasis is on three main groups of multicomponent maintenance optimization models: the block replacement models, group maintenance models, and opportunistic maintenance models. Moreover, an example of a two-unit system maintenance process is provided in order to compare various maintenance policies.

  3. Traffic Modeling in WCDMA System Level Simulations

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Traffic modeling is a crucial element in WCDMA system level simulations. A clear understanding of the nature of traffic in the WCDMA system and subsequent selection of an appropriate random traffic model are critical to the success of the modeling enterprise. The resultant performances will evidently be of a function that our design has been well adapted to the traffic, channel and user mobility models, and these models are also accurate. In this article, our attention will be focused on modeling voice and WWW data traffic with the SBBP model and Victor model respectively.

  4. Diagnostic omission errors in acute paediatric practice: impact of a reminder system on decision-making

    Directory of Open Access Journals (Sweden)

    Fisher Helen

    2006-11-01

    Full Text Available Abstract Background Diagnostic error is a significant problem in specialities characterised by diagnostic uncertainty such as primary care, emergency medicine and paediatrics. Despite wide-spread availability, computerised aids have not been shown to significantly improve diagnostic decision-making in a real world environment, mainly due to the need for prolonged system consultation. In this study performed in the clinical environment, we used a Web-based diagnostic reminder system that provided rapid advice with free text data entry to examine its impact on clinicians' decisions in an acute paediatric setting during assessments characterised by diagnostic uncertainty. Methods Junior doctors working over a 5-month period at four paediatric ambulatory units consulted the Web-based diagnostic aid when they felt the need for diagnostic assistance. Subjects recorded their clinical decisions for patients (differential diagnosis, test-ordering and treatment before and after system consultation. An expert panel of four paediatric consultants independently suggested clinically significant decisions indicating an appropriate and 'safe' assessment. The primary outcome measure was change in the proportion of 'unsafe' workups by subjects during patient assessment. A more sensitive evaluation of impact was performed using specific validated quality scores. Adverse effects of consultation on decision-making, as well as the additional time spent on system use were examined. Results Subjects attempted to access the diagnostic aid on 595 occasions during the study period (8.6% of all medical assessments; subjects examined diagnostic advice only in 177 episodes (30%. Senior House Officers at hospitals with greater number of available computer workstations in the clinical area were most likely to consult the system, especially out of working hours. Diagnostic workups construed as 'unsafe' occurred in 47/104 cases (45.2%; this reduced to 32.7% following system

  5. 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....

  6. 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....

  7. 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

  8. 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...

  9. Diagnosis and treatment of acute and chronic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    1978-01-01

    The Cancergram covers both acute and chronic leukemia in all of its forms (acute lymphocytic, acute monocytic, acute or sub-acute granulocytic, chronic granulocytic, chronic lymphocytic, chronic monocytic, plasma cell, stem cell, and hairy cell). Other neoplastic conditions of the reticuloendothelial system, lymphatic system, spleen, multiple myeloma, macroglobulinemia and other monoclonal gammopathies are excluded, and will be coveted by other Cancergrams now under development. This Cancergram includes abstracts concerning all clinical aspects of the disease, such as diagnosis and staging, supportive care, evaluation, and therapy. Animal models, tissue culture experiments, carcinogenesis and other pre-clinical studies are generally excluded, except for those considered to have direct clinical relevance.

  10. 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...

  11. Electronic Education System Model-2

    Science.gov (United States)

    Güllü, Fatih; Kuusik, Rein; Laanpere, Mart

    2015-01-01

    In this study we presented new EES Model-2 extended from EES model for more productive implementation in e-learning process design and modelling in higher education. The most updates were related to uppermost instructional layer. We updated learning processes object of the layer for adaptation of educational process for young and old people,…

  12. Network and adaptive system of systems modeling and analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, Craig R.; Campbell, James E. Dr. (.; .); Anderson, Dennis James; Eddy, John P.

    2007-05-01

    This report documents the results of an LDRD program entitled ''Network and Adaptive System of Systems Modeling and Analysis'' that was conducted during FY 2005 and FY 2006. The purpose of this study was to determine and implement ways to incorporate network communications modeling into existing System of Systems (SoS) modeling capabilities. Current SoS modeling, particularly for the Future Combat Systems (FCS) program, is conducted under the assumption that communication between the various systems is always possible and occurs instantaneously. A more realistic representation of these communications allows for better, more accurate simulation results. The current approach to meeting this objective has been to use existing capabilities to model network hardware reliability and adding capabilities to use that information to model the impact on the sustainment supply chain and operational availability.

  13. On Verification Modelling of Embedded Systems

    NARCIS (Netherlands)

    Brinksma, Ed; Mader, Angelika

    2004-01-01

    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 verificatio

  14. Applying Modeling Tools to Ground System Procedures

    Science.gov (United States)

    Di Pasquale, Peter

    2012-01-01

    As part of a long-term effort to revitalize the Ground Systems (GS) Engineering Section practices, Systems Modeling Language (SysML) and Business Process Model and Notation (BPMN) have been used to model existing GS products and the procedures GS engineers use to produce them.

  15. Clinical guidelines for the management of acute viral infections in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Ramos-Casals, M; Cuadrado, M J; Alba, P; Sanna, G; Brito-Zerón, P; Bertolaccini, L; Babini, A; Moreno, A; D'Cruz, D; Khamashta, M A

    2009-12-01

    In recent decades, many research groups have focused on the role of viral infections in the etiopathogenesis of systemic lupus erythematosus (SLE), the so-called "viral hypothesis". The main candidates are herpes viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), which have a high seroprevalence in the general population. However, a viral causal agent of SLE has not yet been discovered, although many interesting clinical findings on the complex interactions between viruses and SLE have been made. This review analyzes 88 cases of acute viral infections in adult patients with SLE and identifies situations in which viral infections influenced the diagnosis, prognosis or treatment of SLE. We also propose clinical guidelines for the management of these infections in patients with SLE.

  16. linical characteristics of nosocomial infections of patients with acute central nervous system infections treated in ICU

    Directory of Open Access Journals (Sweden)

    Olgica Gajović

    2011-08-01

    Full Text Available A retrospective study was performed to evaluate the clinical characteristics of nosocomial infections in patients with acute infection of central nervous system (ACNS infections. The study included 1,686 patients admitted to the ICU. Of 1,686 patients, 936 (55.5% had ACNS infection. Nosocomial infections was confirmedin 221 (23.6% patients with ACNS infection. The most common risk factors for ICU-acquired nosocomial infections were consciousness disorder, mechanical ventilation and nasogastric tube. The coagulase – negative Staphylococcus aureus was the most frequent isolated pathogen (285 isolates, 56.5%. Results suggest that a persistently high level of therapeutic activity and persistently depressed consciousness after the ICU admission are associatedwith the occurrence of hospital-acquired infection in critically ill patients hospitalized at a medical ICU.

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

    Science.gov (United States)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas; Forestier, Erik; Frandsen, Thomas L; Harila-Saari, Arja; Heyman, Mats; Jonsson, Olafur G; Lähteenmäki, Päivi M; Lausen, Birgitte; Vaitkevičienė, Goda; Asberg, Ann; Schmiegelow, Kjeld

    2014-08-01

    Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744 patients on Nordic-Baltic trials. CNS status was classified as CNS1 (no CSF blasts), CNS2 ( 0.15). The 12-year event-free survival for patients with leukemic mass on neuroimaging did not differ from patients with negative or no scan (0.50 vs. 0.60; P = 0.7) or between patients with symptoms or signs suggestive of CNS leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia. © 2014 Wiley Periodicals, Inc.

  18. Molecular evidence for central nervous system involvement in children with newly diagnosed acute lymphoblastic leukemia.

    Science.gov (United States)

    Januszkiewicz, D A; Nowak, J S

    1995-01-01

    Central nervous system (CNS) involvement in children with newly diagnosed acute lymphoblastic leukemia (ALL) would have profound implication for the prognosis and accurate stratification of CNS prophylactic therapy. Using PCR technique with specific primers for V, D and J segments of TCRD gene, the pattern of TCRD gene rearrangements in bone marrow lymphoblasts and in cells from cerebrospinal fluid (CSF) have been investigated. The study involved 21 children at the time of diagnosis with B-lineage ALL. In nine of 21 patients incomplete TCRDVD gene rearrangement has been found in CSF cells, which was identical to that observed in bone marrow of the same children. It can be concluded that at least in 43 per cent of all analysed cases, there were signs of CNS involvement in newly diagnosed ALL patients.

  19. System Level Modelling and Performance Estimation of Embedded Systems

    DEFF Research Database (Denmark)

    Tranberg-Hansen, Anders Sejer

    is simulation based and allows performance estimation to be carried out throughout all design phases ranging from early functional to cycle accurate and bit true descriptions of the system, modelling both hardware and software components in a unied way. Design space exploration and performance estimation...... 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...

  20. 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.

  1. [Rat immunoreactivity in experimental modeling of acute autohemorrhagic bihemispheric stroke in the presence of staphylococcal infection].

    Science.gov (United States)

    Makarenko, A N; Mironiuk, Iu N; Molozhavaia, O S; Pozur, V K; Iablonskaia, S V

    2008-01-01

    Experimental studies were made of rat immunoreactivity in experimental modeling of acute hemorrhagic stroke in staphylococcal infection. Bactericidal activity and reserve bactericidal activity of neutrophils in NBT-test enhance while mid-molecular CIC level decreases because of phagocyte activation. ABA high titers in blood reflect activation of autoimmune processes. Splenic mass increased suggesting activation of proliferation of splenic lymphoid cells or enhanced migration of immature lymphoid cells from bone marrow to the spleen. Experimental animals had suppressed functional activity of main lymphoid cells populations in blast-transformation reaction which may affect the course of early recovery, promote activation of infectious bacterial process, autoaggression. The results of the studies can serve the basis for further investigations of immune mechanisms involved in development of hemorrhagic stroke in the presence of infectious process.

  2. Impact of animal strain on gene expression in a rat model of acute cardiac rejection

    Directory of Open Access Journals (Sweden)

    Norsworthy Kelly J

    2009-06-01

    Full Text Available Abstract Background The expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR. Using a rat heart transplant model and 2 different rat strains (Dark Agouti, and Brown Norway, microarrays were performed on native hearts, transplanted hearts, and peripheral blood mononuclear cells (PBMC. Results In heart tissue, strain alone affected the expression of only 33 probesets while rejection affected the expression of 1368 probesets (FDR 10% and FC ≥ 3. Only 13 genes were affected by both strain and rejection, which was Conclusion In ACR, genetic background has a large impact on the transcriptome of immune cells, but not heart tissue. Gene expression studies of ACR should avoid study designs that require cross strain comparisons between leukocytes.

  3. Analysis of regional compliance in a porcine model of acute lung injury.

    Science.gov (United States)

    Czaplik, Michael; Biener, Ingeborg; Dembinski, Rolf; Pelosi, Paolo; Soodt, Thomas; Schroeder, Wolfgang; Leonhardt, Steffen; Marx, Gernot; Rossaint, Rolf; Bickenbach, Johannes

    2012-10-15

    Lung protective ventilation in acute lung injury (ALI) focuses on using low tidal volumes and adequate levels of positive end-expiratory pressure (PEEP). Identifying optimal pressure is difficult because pressure-volume (PV) relations differ regionally. Precise analysis demands local measurements of pressures and related alveolar morphologies. In a porcine model of surfactant depletion (n=24), we combined measuring static pressures with endoscopic microscopy and electrical impedance tomography (EIT) to examine regional PV loops and morphologic heterogeneities between healthy (control group; CON) and ALI lungs ventilated with low (LVT) or high tidal volumes (HVT). Quantification included indices for microscopy (Volume Air Index (VAI), Heterogeneity and Circularity Index), EIT analysis and calculation of regional compliances due to generated PV loops. We found that: (1) VAI decreased in lower lobe after ALI, (2) electrical impedance decreased in dorsal regions and (3) PV loops differed regionally. Further studies should prove the potentials of these techniques on individual respiratory settings and clinical outcome.

  4. EXPOSURE ANALYSIS MODELING SYSTEM (EXAMS): USER MANUAL AND SYSTEM DOCUMENTATION

    Science.gov (United States)

    The Exposure Analysis Modeling System, first published in 1982 (EPA-600/3-82-023), provides interactive computer software for formulating aquatic ecosystem models and rapidly evaluating the fate, transport, and exposure concentrations of synthetic organic chemicals - pesticides, ...

  5. All arthroscopic stabilization of acute acromioclavicular joint dislocation with fiberwire and endobutton system

    Science.gov (United States)

    Spoliti, Marco; De Cupis, Mauro; Via, Alessio Giai; Oliva, Francesco

    2014-01-01

    Summary Introduction: acromioclavicular (AC) joint dislocation is common in athletes and in contact sports and about 9% of shoulder injuries involves this joint. The majority of these AC lesions can be successfully treated conservatively but high grade dislocation and some cases of type III dislocation need a surgical treatment. Many different operative techniques have been described over the years. The purpose of this study is to evaluate the results of arthroscopic stabilization of AC joint dislocation with TightRope® system. Materials and methods: nineteen patients with acute AC dislocation were treated by arthroscopic fixation with TightRope® system. Any associated lesions were repaired. All patients were assessed before surgery (T0), at 3 months (T1), at 6 months (T2) and at 1 year after the surgery (T3) using a visual analogic scale (VAS) and Constant-Murley Score (CMS). All patients were evaluated with X-ray. Results: six AC-joint dislocations involved the right shoulder and thirteen the left shoulder. Ten were type III dislocation, three were type IV and six were type V dislocation. We found a statistically significant reduction of pain (p< 0.01) at T1 compared to the pretreatment scores. The CMS measures showed an improvement between T1, T2 and T3, but the difference was statistically significant only between T1 and T3 (p= 0.017). The postoperative X-Ray of the shoulder showed a good reduction of the AC joint dislocation. We had 1 case of recurrence and 2 cases of loss of intraoperative reduction. Conclusion: arthroscopic technique for acute AC joint dislocations with the use of the TightRope® device is minimally invasive and it allows an anatomic restoration of the joint. It is a safe and effective procedure ensuring stable AC joint reconstruction and good cosmetic results. PMID:25767774

  6. Construct Validity of the Braden Scale for Pressure Ulcer Assessment in Acute Care: A Structural Equation Modeling Approach.

    Science.gov (United States)

    Chen, Hong-Lin; Cao, Ying-Juan; Shen, Wang-Qin; Zhu, Bin

    2017-02-01

    The Braden Scale is the most widely used pressure ulcer risk assessment system in the world. To investigate its construct validity using structural equation modeling (SEM), a secondary analysis of retrospective data of patients admitted to an acute care facility was conducted using the records of 2588 patients who were at risk for pressure ulcers and admitted between January 2013 and December 2013. Data were extracted to an Excel sheet and analyzed, including demographic characteristics (ie, patients age, gender, weight, and disease spectrum), as well as total Braden scores and subscale scores. The SEM was set according to modification indices suggestion. The original Braden Scale model was supported by χ2(9) = 22.854, CFI = 0.902, GFI = 0.974, root mean square error of approximation (RMSEA) = 0.092, indicating inadequate model fit. After modification according to software indices, χ2(2) = 2.052, CFI = 0.999, GFI = 0.999, RMSEA = 0.020 indicated an acceptable fit of the model (final model). The factor loadings of 6 subscales were all significant (P <.001), with .147 for nutrition, .137 for activity, .167 for friction and shear, .825 for sensory perception, .626 for mobility, and .556 for moisture subscale. The nutrition, activity, and friction and shear subscales were corrected to examine their relationships with other Braden Scale subscales (nutrition with activity [φ -0.063], activity with friction/shear [φ 0.136], and nutrition (φ friction/shear [0.159]). The factor loadings ranged from -0.067 to 0.159. These findings suggest the original Braden Scale has inadequate construct validity for acute care patients and that new risk-predicting scales should be designed based on data mining. Second, according to the factor loadings in the SEM, the most important risk factor in the Braden Scale for this patient population is sensory perception, followed by mobility and moisture. This suggests practitioners should pay particular attention to pressure ulcer prevention

  7. Cardioprotective Effect of the Compound Yangshen Granule in Rat Models with Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Xie Ming

    2012-01-01

    Full Text Available The protective effect of Compound Yangshen Granules was observed in myocardial infarction rat model. Rats were randomly divided into 6 groups: the model group, the control group (sham operated, the positive drug group, and small, medium, and large dosage of the Yangshen granule groups, respectively. The rats in the 3 Yangshen granule groups were orally administrated with 0.7 g/kg, 1.4 g/kg, and 2.8 g/kg for 7 consecutive days, whereas the rats of the positive drug group treated with 0.14 g/kg of Danshen Dropping Pills, and rats in the control and model groups orally administrated with saline. The rat model of acute myocardial infarction was established with ligation of coronary artery. Electrocardiograms at different time points, the blood rheology, myocardial enzymes, infarct size, and myocardial morphologic changes were measured. The results demonstrated that the granules could improve blood rheology, decrease st-segment of electrocardiograms and the activities of LDH and CK in serum, reduce myocardial infarction size, and alleviate myocardial histopathologic changes. In addition, the effect of the granules depended on the dose administrated orally. The results suggest that the Yangshen granules could produce cardioprotection effect and have potential benefits in the prevention of ischemic heart disease.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Pǎun's systems as models of economic systems

    Institute of Scientific and Technical Information of China (English)

    Waldemar Korczynski

    2007-01-01

    In the paper a concept for modeling the economic systems by the formalism of Pǎun's systems is proposed. The main idea is to represent economic systems as homomorphic images of Petri nets corresponding to the (super) cells of Pǎun's systems.

  14. System delay and timing of intervention in acute myocardial infarction (from the Danish Acute Myocardial Infarction-2 [DANAMI-2] trial)

    DEFF Research Database (Denmark)

    Nielsen, Peter Haubjerg; Terkelsen, Christian Juhl; Nielsen, Torsten Toftegård;

    2011-01-01

    The interval from the first alert of the healthcare system to the initiation of reperfusion therapy (system delay) is associated with mortality in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention (pPCI). The importance of system dela...

  15. 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...... 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...... 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...

  16. 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...... 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...... 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...

  17. 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

  18. 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.

  19. Systemic corticosteroids for the treatment of asthma exacerbations during and outside of pregnancy in an acute-care setting.

    Science.gov (United States)

    Cossette, Benoit; Beauchesne, Marie-France; Forget, Amélie; Lemière, Catherine; Larivée, Pierre; Rey, Évelyne; Couturier, Marie; Rodrigue, Claudie; Blais, Lucie

    2014-09-01

    Asthma exacerbations are common during pregnancy with a prevalence as high as 51.9% among women with severe asthma. To compare the treatment of asthma exacerbations in an acute-care setting during and outside of pregnancy. We formed a cohort of women who sought medical care for an asthma exacerbation at a teaching hospital during or in the year preceding pregnancy, between 1998 and 2008. An exacerbation was composed of one or more medical encounters in an acute-care setting (hospital-based outpatient clinic, emergency department, or during hospitalization). Data were retrieved from medical charts and health administrative databases. We compared the use of systemic corticosteroids (SCSs) during and outside of pregnancy with a Cox proportional hazards model. The cohort was formed of 39 women who had 40 exacerbations during and 39 exacerbations outside of pregnancy. Use of SCSs to treat exacerbations was less frequent (adjusted hazard ratio: 0.51; 95% CI: 0.31-0.84) during pregnancy. Moreover, upon the first medical encounter related to the exacerbation, SCSs, when administered, were given less frequently to women when pregnant than when non-pregnant (83% vs. 100%). The SCS prescription was filled at the community pharmacy 65% and 67% of the time when it was prescribed at discharge to women when pregnant than when non-pregnant, respectively. We observed a reduced and delayed use of SCSs for the treatment of asthma exacerbations in women when pregnant than when non-pregnant, with similar numbers of women in both conditions filling their SCSs prescription in pharmacies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Modeling noisy resonant system response

    Science.gov (United States)

    Weber, Patrick Thomas; Walrath, David Edwin

    2017-02-01

    In this paper, a theory-based model replicating empirical acoustic resonant signals is presented and studied to understand sources of noise present in acoustic signals. Statistical properties of empirical signals are quantified and a noise amplitude parameter, which models frequency and amplitude-based noise, is created, defined, and presented. This theory-driven model isolates each phenomenon and allows for parameters to be independently studied. Using seven independent degrees of freedom, this model will accurately reproduce qualitative and quantitative properties measured from laboratory data. Results are presented and demonstrate success in replicating qualitative and quantitative properties of experimental data.

  1. Generic Model Host System Design

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Chungming; /SLAC; Wu, Juhao; /SLAC; Qiang, Ji; /LBL, Berkeley; Shen, Guobao; /Brookhaven

    2012-06-22

    There are many simulation codes for accelerator modelling; each one has some strength but not all. A platform which can host multiple modelling tools would be ideal for various purposes. The model platform along with infrastructure support can be used not only for online applications but also for offline purposes. Collaboration is formed for the effort of providing such a platform. In order to achieve such a platform, a set of common physics data structure has to be set. Application Programming Interface (API) for physics applications should also be defined within a model data provider. A preliminary platform design and prototype is discussed.

  2. Four MATLAB-Simulink models ofphotovoltaic system

    Directory of Open Access Journals (Sweden)

    Jawad Radhi Mahmood, Nasir Hussein Selman

    2016-01-01

    Full Text Available This paper presents four different MATLAB models to simulate the output I-V and P-V characteristics of photovoltaic (PV cells or systems. All of the models are implemented with Matlab-Simulink. Detailed modeling procedure for one-diode equivalent circuit model with all equations and numerical values is presented. The parameters required for the modeling have been taken from manufacturer's datasheet for 240W SOLIMPEKS solar panel. I-V and P-V characteristics of a typical 1.92 kW PV system have been simulated using the proposed models. The simulation took into account the sunlight insolation and temperature effect. Results of the models are validated with I-V and P-V curves provided by the manufacturer(s. The proposed models are very useful for those interested in working in the field of solar systems because they emulate and analyze the characteristics of all the solar systems easily.

  3. CTL Model Update for System Modifications

    CERN Document Server

    Ding, Yulin; Zhang, Yan; Zhang, Y; 10.1613/jair.2420

    2011-01-01

    Model checking is a promising technology, which has been applied for verification of many hardware and software systems. In this paper, we introduce the concept of model update towards the development of an automatic system modification tool that extends model checking functions. We define primitive update operations on the models of Computation Tree Logic (CTL) and formalize the principle of minimal change for CTL model update. These primitive update operations, together with the underlying minimal change principle, serve as the foundation for CTL model update. Essential semantic and computational characterizations are provided for our CTL model update approach. We then describe a formal algorithm that implements this approach. We also illustrate two case studies of CTL model updates for the well-known microwave oven example and the Andrew File System 1, from which we further propose a method to optimize the update results in complex system modifications.

  4. 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...

  5. 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 e...

  6. Computational Models for Nonlinear Aeroelastic Systems Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Clear Science Corp. and Duke University propose to develop and demonstrate new and efficient computational methods of modeling nonlinear aeroelastic systems. The...

  7. 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...

  8. Modeling and analysis of biomass production systems

    Energy Technology Data Exchange (ETDEWEB)

    Mishoe, J.W.; Lorber, M.N.; Peart, R.M.; Fluck, R.C.; Jones, J.W.

    1984-01-01

    BIOMET is an interactive simulation model that is used to analyze specific biomass and methane production systems. The system model is composed of crop growth models, harvesting, transportation, conversion and economic submodels. By use of menus the users can configure the structure and set selected parameters of the system to analyze the effects of variables within the component models. For example, simulations of a water hyacinth system resulted in yields of 63, 48 and 37 mg/ha/year for different harvest schedules. For napier grass, unit methane costs were $3.04, $2.86 and $2.98 for various yields of biomass. 10 references.

  9. Error Propagation in a System Model

    Science.gov (United States)

    Schloegel, Kirk (Inventor); Bhatt, Devesh (Inventor); Oglesby, David V. (Inventor); Madl, Gabor (Inventor)

    2015-01-01

    Embodiments of the present subject matter can enable the analysis of signal value errors for system models. In an example, signal value errors can be propagated through the functional blocks of a system model to analyze possible effects as the signal value errors impact incident functional blocks. This propagation of the errors can be applicable to many models of computation including avionics models, synchronous data flow, and Kahn process networks.

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

    Science.gov (United States)

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

    2011-06-10

    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 4h 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.

  11. 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...

  12. Stochastic Modelling of Energy Systems

    DEFF Research Database (Denmark)

    Andersen, Klaus Kaae

    2001-01-01

    equations are expressed in terms of stochastic differential equations. From a theoretical viewpoint the techniques for experimental design, parameter estimation and model validation are considered. From the practical viewpoint emphasis is put on how this methods can be used to construct models adequate...

  13. 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...

  14. Hypervirial Models of Stellar Systems

    CERN Document Server

    Evans, N W

    2005-01-01

    A family of cusped potential-density pairs is introduced for modelling galaxies and dark haloes. The density profile is cusped like 1/r^(2-p) at small radii. The distribution function takes the simple form L^(p-2) E^([3p+1]/2) (where E is the binding energy and L is the angular momentum). The models all possess the remarkable property that the virial theorem holds locally, from which they earn their name as the hypervirial family. Famously, this property was first discovered by Eddington to hold for the Plummer model in 1916. In fact, the seductive properties of the Plummer model extend to the whole hypervirial family, including the members possessing the cosmologically important cusps with density behaving like 1/r or 1/r^1.5 or 1/r^1.33. The intrinsic and projected properties of the family of models are discussed in some detail.

  15. 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

  16. Model reduction of linear conservative mechanical systems

    NARCIS (Netherlands)

    Schaft, van der A.J.; Oeloff, J.E.

    1990-01-01

    An approach for model reduction of linear conservative or weakly damped mechanical systems is proposed. It is based on the balancing of an associated gradient system. It uses the joint knowledge of the system matrix and the input and output matrices of the Hamiltonian system. The key idea is to asso

  17. Modeling complex work systems - method meets reality

    OpenAIRE

    Veer, van der, C.G.; Hoeve, Machteld; Lenting, Bert F.

    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 design of complex systems, has been applied in a situation of redesign of a Dutch public administration system. The most feasible method to collect information in this case was ethnography, the resulti...

  18. Potential of microemulsified entacapone drug delivery systems in the management of acute Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Harini Chowdary Vadlamudi; Prasanna Raju Yalavarthi; Jyotsna Thanniru; Vandana KR; Sundaresan CR

    2016-01-01

    Objective: To design solid self-microemulsifying drug delivery system (S-SMEDDS) of entacapone and evaluate for its anti-Parkinson's potentials. Methods: Solubility studies were performed in various vehicles i.e., oils, surfactants and co-surfactants and pseudo-ternary phase diagrams were plotted to understand the microemulsion formation region. Liquid self-microemulsifying drug delivery systems (SMEDDS) were developed using gingelly and rice bran oil as lipid vehicles, Tween 80 and Span 20 as surfactants and glycerin, propylene glycol as co-surfactants. They were characterized by Fourier transform infrared spectroscopy, pH, viscosity, zeta potential, polydispersibility index and droplet size analysis and evaluated for drug content, in-vitro release, in-vitro diffusion and ex-vivo permeation. Optimized liquid SMEDDS were converted into S-SMEDDS by adsorption and melt granulation procedures. Character-ization by differential scanning calorimetry, SEM, micrometrics, reconstitution property, moisture content and evaluation by drug content, drug release kinetics and shelf-life were performed for S-SMEDDS. Parkinsonism was induced and pharmacodynamic potentials of S-SMEDDS were evaluated. Results: S-SMEDDS formulation AG8 had shown the highest drug release of 90.92%within 60 min. Pharmacodynamic studies also proved the efficiency of entacapone S-SMEDDS against Parkinsonism. Conclusions: Entacapone S-SMEDDS is an effective drug delivery system that offers more predictable and extensive drug release with enhanced shelf-life in the treatment of acute Parkinsonism.

  19. [Influence of cortical neurotrophic factors on the neurocytokine production system in acute hemorrhagic stroke].

    Science.gov (United States)

    Kul'chikov, A E; Kositsyn, N S; Svinov, M M; Vasil'eva, I G; Makarenko, A N

    2009-01-01

    The mechanism of therapeutic action of cortical neurotropic factors (CNTF) was studied in hemorrhagic stroke. In intracerebral hemorrhage, CNTFs were shown to elevate the level of nerve growth factor mRNA and at the same time, produce no effect on its level in intact animals. The neuroactivating action of CNTF in the acute phase of hemorrhagic stroke was achieved by intranasal administration due to the retrograde axon transport of CNTF molecules along the olfactory nerve fibers to the brain, by passing the blood-brain barrier. It was ascertained that the molecules of tritium-labeled CHTF accumulated in the central nervous system following 20 minutes and the level of label accumulation is proportionally increased after 120 minutes. The pattern of accumulation of the intranasally administered label in the olfactory tract and olfactory bulb proves CNTF transportation along these structures of the nervous system. Therefore, when intranasally administered, CNTFs are able to transport to the central nervous system along the olfactory tract and to enhance the expression of nerve growth factor mRNA in hemorrhagic stroke.

  20. 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 relies on the use of neuroradiology, conventional cytology (CC and flow cytometry (FCM. Among these approaches, which is the gold standard it is still a matter of debate. Neuroradiology and CC have a limited sensitivity with a higher rate of false negative results. FCM demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies of large series of patients are still awaited, a positive finding by FCM appears to anticipate an adverse outcome even if CC shows no infiltration. Current strategies for adult ALL CNS-directed prophylaxis or therapy involve systemic and intrathecal chemotherapy and radiation therapy. Actually, early and frequent intrathecal injection of cytostatic combined with systemic chemotherapy is the most effective strategy to reduce the frequency of CNS involvement. In patients with CNS overt ALL, at diagnosis or upon relapse, allogenic hematopoietic stem cell transplantation might be considered. This review will discuss risk factors, diagnostic techniques for identification of CNS infiltration and modalities of prophylaxis and therapy to manage it.