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Sample records for model system acute

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

    Science.gov (United States)

    2017-10-01

    models ); • clinical interventions; • new business creation; and • other. Nothing to report. Nothing to report. Nothing to report. 17...AWARD NUMBER: W81XWH-14-1-0376 TITLE: Acute Pancreatitis as a Model to Predict Transition of Systemic Inflammation to Organ Failgure in Trauma...COVERED 22 Sep 2016 - 21 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Acute Pancreatitis as a Model to Predict Transition of Systemic

  2. Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

    Science.gov (United States)

    Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

    2016-08-01

    Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

  3. A psychodynamic model of behavior after acute central nervous system damage.

    Science.gov (United States)

    Groswasser, Z; Stern, M J

    1998-02-01

    This article describes a conceptual psychodynamic model for understanding the neurobehavioral manifestations of acute central nervous system damage (ACNSD) displayed by patients during the rehabilitation process. According to the proposed model, patientsO behavioral responses are viewed as their only means of emotional expression and therefore may not be considered entirely abnormal when viewed from the perspective of patientsO interpersonal contexts. An improved understanding of the dynamic processes through which recovering patients with ACNSD journey may lead to better interaction between the patient and the therapeutic environment, the interdisciplinary team, and family members. Combining this proposed psychodynamic model with an emerging understanding of the neurobehavioral foundations of aggression and depression may also lead to a more rational approach to intervention with various psychopharmacologic agents. During the rehabilitation process, understanding patients' cognitive deficits, motivational drives, and emotional needs and proper implementation of medical and environmental treatment can ultimately lead to a better psychosocial outcome.

  4. 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

  5. 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.

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  7. 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.

  8. Systemic corticosteroids for acute gout.

    NARCIS (Netherlands)

    Janssens, H.; 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

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

    Directory of Open Access Journals (Sweden)

    Wanchao Yang

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

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

    Science.gov (United States)

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

    2014-02-01

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

  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. 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.

  13. Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    African Journals Online (AJOL)

    hanumantp

    presented to us with a history of anorexia, progressive darkening of the face ... to us in an acute hypoadrenal state and was found to have Systemic lupus erythematosus with renal involvement. .... Textbook of Endocrinology. 11th ed. Saunders: ...

  16. Physiological complexity of acute traumatic brain injury in patients treated with a brain oxygen protocol: utility of symbolic regression in predictive modeling of a dynamical system.

    Science.gov (United States)

    Narotam, Pradeep K; Morrison, John F; Schmidt, Michael D; Nathoo, Narendra

    2014-04-01

    Predictive modeling of emergent behavior, inherent to complex physiological systems, requires the analysis of large complex clinical data streams currently being generated in the intensive care unit. Brain tissue oxygen protocols have yielded outcome benefits in traumatic brain injury (TBI), but the critical physiological thresholds for low brain oxygen have not been established for a dynamical patho-physiological system. High frequency, multi-modal clinical data sets from 29 patients with severe TBI who underwent multi-modality neuro-clinical care monitoring and treatment with a brain oxygen protocol were analyzed. The inter-relationship between acute physiological parameters was determined using symbolic regression (SR) as the computational framework. The mean patient age was 44.4±15 with a mean admission GCS of 6.6±3.9. Sixty-three percent sustained motor vehicle accidents and the most common pathology was intra-cerebral hemorrhage (50%). Hospital discharge mortality was 21%, poor outcome occurred in 24% of patients, and good outcome occurred in 56% of patients. Criticality for low brain oxygen was intracranial pressure (ICP) ≥22.8 mm Hg, for mortality at ICP≥37.1 mm Hg. The upper therapeutic threshold for cerebral perfusion pressure (CPP) was 75 mm Hg. Eubaric hyperoxia significantly impacted partial pressure of oxygen in brain tissue (PbtO2) at all ICP levels. Optimal brain temperature (Tbr) was 34-35°C, with an adverse effect when Tbr≥38°C. Survivors clustered at [Formula: see text] Hg vs. non-survivors [Formula: see text] 18 mm Hg. There were two mortality clusters for ICP: High ICP/low PbtO2 and low ICP/low PbtO2. Survivors maintained PbtO2 at all ranges of mean arterial pressure in contrast to non-survivors. The final SR equation for cerebral oxygenation is: [Formula: see text]. The SR-model of acute TBI advances new physiological thresholds or boundary conditions for acute TBI management: PbtO2≥25 mmHg; ICP≤22 mmHg; CPP≈60-75

  17. Aging models of acute seizures and epilepsy.

    Science.gov (United States)

    Kelly, Kevin M

    2010-01-01

    Aged animals have been used by researchers to better understand the differences between the young and the aged brain and how these differences may provide insight into the mechanisms of acute seizures and epilepsy in the elderly. To date, there have been relatively few studies dedicated to the modeling of acute seizures and epilepsy in aged, healthy animals. Inherent challenges to this area of research include the costs associated with the purchase and maintenance of older animals and, at times, the unexpected and potentially confounding comorbidities associated with aging. However, recent studies using a variety of in vivo and in vitro models of acute seizures and epilepsy in mice and rats have built upon early investigations in the field, all of which has provided an expanded vision of seizure generation and epileptogenesis in the aged brain. Results of these studies could potentially translate to new and tailored interventional approaches that limit or prevent the development of epilepsy in the elderly.

  18. 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 ...

  19. Molecular adsorbents recirculating system treatment in acute-on-chronic hepatitis patients on the transplant waiting list improves model for end-stage liver disease scores.

    Science.gov (United States)

    Novelli, G; Rossi, M; Pugliese, F; Poli, I; Ruberto, E; Martelli, S; Nudo, F; Morabito, V; Mennini, G; Berloco, P B

    2007-01-01

    The aim of our study was to show an improvement in Model for End-Stage Liver Disease (MELD) score after treatment with Molecular adsorbents recirculating system (MARS) in acute-on-chronic hepatitis (AoCHF) patients. MELD was adopted to determine the prognosis of patients with liver chronic desease. We evaluated the possibility to improve the MELD score of patients awaiting liver transplantation using a liver support device, namely, MARS. From September 1999 to April 2006, we treated 80 patients whose diagnoses were hepatitis C, 41.25%; hepatitis B, 27.5%; alcholic, 17.5%; intoxication, 8.75%; primary biliary cirrhosis, 5%. The overall mean age was 45 years (23 to 62), the cohort included 56 men and 24 women. Inclusion criteria were bilirubin >15 mg/dL; MELD >20; encephalopathy >II; and International Normalized Ratio, >2.1. Other parameters evaluated included ammonia, creatinine, lactate, glutamic oxalic transminase, and guanosine 5'-triphosphate. All patients were treated with a mean of 6-hour cycles of MARS (range, 5 to 8 hours) for a minimum of three treatments and a maximum of 20 treatments over 3 months. Clinical conditions were evaluated by improved hemodynamic parameters, kidney function, liver function, coagulation, neurologic status using the SOFA score, Glasgow Coma Scale (GCS), and Acute Physiology and Chronic Health Evaluation II Criteria. The MELD score for all categories of living patients showed significant improvements at the end of treatment and at 3-months follow-up, but the small number of patients was a limitation to determine prediction of mortality. Our study shows that MARS treatment improved multiple organ functions-liver, renal, neurologic, and hemodynamic. The improved MELD score gave patients on the transplant waiting list longer survival, allowing them a greater opportunity for liver transplantation.

  20. Detection of Acute Myocardial Infarction in a Pig Model Using the SAN-Atrial-AVN-His (SAAH) Electrocardiogram (ECG), Model PHS-A10, an Automated and Integrated Signals Recognition System.

    Science.gov (United States)

    Zhao, Wenjiao; Lu, Guihua; Liu, Li; Sun, Zhishan; Wu, Mingxin; Yi, Wenyan; Chen, Haiyan; Li, Yanhui; Tang, Lilong; Zeng, Jianping

    2018-03-04

    BACKGROUND The aim of this study was to compare the use of the standard 12-lead electrocardiogram (ECG) with the SAN-Atrial-AVN-His (SAAH) ECG (Model PHS-A10), a new automated and integrated signals recognition system that detects micro-waveforms within the P, QRS, and T-wave, in a pig model of acute myocardial infarction (MI). MATERIAL AND METHODS Six medium-sized domestic Chinese pigs underwent general anesthesia, and an angioplasty balloon was placed and dilated for 120 minutes in the first diagonal coronary artery arising from the left anterior descending (LAD) coronary artery. A standard ECG and a SAAH ECG (Model PHS-A10) were used to evaluate: 1) the number of wavelets in ST-T segment in lead V5; 2) the duration of the repolarization initial (Ri), or duration of the wavelets starting from the J-point to the endpoint of the wavelets in the ST interval; 3) the duration of the repolarization terminal (Rt), of the wavelets, starting from the endpoint of the wavelets in the ST interval to the cross-point of the T-wave and baseline; 4) the ratio Ri: Rt. RESULTS Following coronary artery occlusion, duration of Ri and Ri/Rt increased, and Rt decreased, which was detected by the SAAH ECG (Model PHS-A10) within 12 seconds, compared with standard ECG that detected ST segment depression at 24 seconds following coronary artery occlusion. CONCLUSIONS The findings from this preliminary study in a pig model of acute MI support the need for clinical studies to evaluate the SAAH ECG (Model PHS-A10) for the early detection of acute MI.

  1. 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.

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2013-11-05

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

  5. Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

    Science.gov (United States)

    Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

    2014-08-01

    Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Acute and chronic systemic chromium toxicity.

    Science.gov (United States)

    Gad, S C

    1989-10-01

    Although chromium and compounds containing it have been recognized as having potential severe adverse effects on health for more than 160 years, understanding of the systemic toxicology and true hazard of these compounds is still not complete. A review of the current state of knowledge is attempted in this paper, with appropriate attention given to the complications of multiple valence states and solubility. Selected chromium compounds, particularly hexavalent ones, are carcinogens, corrosives, delayed contact sensitizers, and have the kidney as their primary target organ. But chromium is also an essential element for humans. The body clearly possesses some effective detoxification mechanisms for some degree of exposure to hexavalent chrome compounds. The significant features of acute and chronic chromium toxicity are presented in view of these considerations.

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

    Science.gov (United States)

    Nishiyama, Yoshiaki; Saikawa, Yutaka; Nishiyama, Nobuaki

    2018-03-01

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

  8. Establishment of selected acute pulmonary thromboembolism model in experimental sheep

    International Nuclear Information System (INIS)

    Fan Jihai; Gu Xiulian; Chao Shengwu; Zhang Peng; Fan Ruilin; Wang Li'na; Wang Lulu; Wang Ling; Li Bo; Chen Taotao

    2010-01-01

    Objective: To establish a selected acute pulmonary thromboembolism model in experimental sheep suitable for animal experiment. Methods: By using Seldinger's technique the catheter sheath was placed in both the femoral vein and femoral artery in ten sheep. Under C-arm DSA guidance the catheter was inserted through the catheter sheath into the pulmonary artery. Via the catheter appropriate amount of sheep autologous blood clots was injected into the selected pulmonary arteries. The selected acute pulmonary thromboembolism model was thus established. Pulmonary angiography was performed to check the results. The pulmonary arterial pressure, femoral artery pressure,heart rates and partial pressure of oxygen in arterial blood (PaO 2 ) were determined both before and after the treatment. The above parameters obtained after the procedure were compared with the recorded parameters measured before the procedure, and the sheep model quality was evaluated. Results: The baseline of pulmonary arterial pressure was (27.30 ± 9.58) mmHg,femoral artery pressure was (126.4 ± 13.72) mmHg, heart rate was (103 ± 15) bpm and PaO 2 was (87.7 ± 12.04) mmHg. Sixty minutes after the injection of (30 ± 5) ml thrombotic agglomerates, the pulmonary arterial pressures rose to (52 ± 49) mmHg, femoral artery pressures dropped to (100 ± 21) mmHg. The heart rates went up to (150 ± 26) bpm. The PaO 2 fell to (25.3 ± 11.2) mmHg. After the procedure the above parameters were significantly different from that measured before the procedure in all ten animals (P < 0.01). The pulmonary arteriography clearly demonstrated that the selected pulmonary arteries were successfully embolized. Conclusion: The anatomy of sheep's femoral veins,vena cava system, pulmonary artery and right heart system are suitable for the establishment of the catheter passage, for this reason, selected acute pulmonary thromboembolism model can be easily created in experimental sheep. The technique is feasible and the model

  9. 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.

  10. Establishing a cat model of acute optic nerve injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: In order to investigate the progress in optic nerve injury and the following regeneration and repair, many kinds of animal models of optic nerve injury have been established, such as models of acute and chronic ocular hypertension, compression, amputating wound, ischemia reperfusion or hypoxia,intravitreal injection of excitatory amino acids, etc. However, most of these models are established by squeezing intraorbital optic nerve, and suitable for ophthalmology, and there are fewer models suitable for the acute cranial contusion in neurosurgery.OBJECTIVE: To observe the changes of optic nerve after acute injury, and the characteristics of methods for establishing model of acute optic nerve injury in cats.DESIGN: A complete randomized grouping and controlled animal trial.SETTING: Department of Neurosurgery, General Hospital of Ji'nan Military Area Command of Chinese PLA.MATERIALS: Twenty-eight healthy adult cats, common degree, either sex, weighing 2.0 - 3.5 kg, were provided by the animal experimental center of Fudan University. The cats were randomly divided into control group (n =3) and model group (n =25), and 5 cats in the model group were observed at 6 hours and 1,3, 7 and 14 days after injury respectively. JX-2000 biological signal processing system (Department of Physiology, Second Military Medical University of Chinese PLA, Shanghai); Inverted phase contrast microscope (Olympus); Axioplan 2 imaging microgram analytical system (Labsystems).METHODS: The experiments were carried out in the Department of Neurosurgery, General Hospital of Jinan Military Area Command of Chinese PLA from June 2004 to June 2005. The cats in the model groups were made into models of acute optic nerve injury: The cats were anesthetized, then the limbs were fixed in a lateral recumbent position. Pterion approach in human was imitated, the operative incision was made along the line between lateral canthus and tragus, and it could be seen deep along the skull base that white

  11. 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

  12. 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

  13. Developing a consensus classification system for acute renal failure

    NARCIS (Netherlands)

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

    2002-01-01

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

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

    African Journals Online (AJOL)

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

  15. Pseudofracture: an acute peripheral tissue trauma model.

    Science.gov (United States)

    Darwiche, Sophie S; Kobbe, Philipp; Pfeifer, Roman; Kohut, Lauryn; Pape, Hans-Christoph; Billiar, Timothy

    2011-04-18

    Following trauma there is an early hyper-reactive inflammatory response that can lead to multiple organ dysfunction and high mortality in trauma patients; this response is often accompanied by a delayed immunosuppression that adds the clinical complications of infection and can also increase mortality. Many studies have begun to assess these changes in the reactivity of the immune system following trauma. Immunologic studies are greatly supported through the wide variety of transgenic and knockout mice available for in vivo modeling; these strains aid in detailed investigations to assess the molecular pathways involved in the immunologic responses. The challenge in experimental murine trauma modeling is long term investigation, as fracture fixation techniques in mice, can be complex and not easily reproducible. This pseudofracture model, an easily reproduced trauma model, overcomes these difficulties by immunologically mimicking an extremity fracture environment, while allowing freedom of movement in the animals and long term survival without the continual, prolonged use of anaesthesia. The intent is to recreate the features of long bone fracture; injured muscle and soft tissue are exposed to damaged bone and bone marrow without breaking the native bone. The pseudofracture model consists of two parts: a bilateral muscle crush injury to the hindlimbs, followed by injection of a bone solution into these injured muscles. The bone solution is prepared by harvesting the long bones from both hindlimbs of an age- and weight-matched syngeneic donor. These bones are then crushed and resuspended in phosphate buffered saline to create the bone solution. Bilateral femur fracture is a commonly used and well-established model of extremity trauma, and was the comparative model during the development of the pseudofracture model. Among the variety of available fracture models, we chose to use a closed method of fracture with soft tissue injury as our comparison to the

  16. Experimental models of hepatotoxicity related to acute liver failure

    Energy Technology Data Exchange (ETDEWEB)

    Maes, Michaël [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Vinken, Mathieu, E-mail: mvinken@vub.ac.be [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Jaeschke, Hartmut [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City (United States)

    2016-01-01

    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. - Highlights: • The murine APAP model is very close to what is observed in patients. • The Gal/ET model is useful to study TNFα-mediated apoptotic signaling mechanisms. • Fas receptor activation is an effective model of apoptosis and secondary necrosis. • The ConA model is a relevant model of auto-immune hepatitis and viral hepatitis. • Multiple time point evaluation needed in experimental models of acute liver injury.

  17. 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

  18. Animal Model of Acute Deep Vein Thrombosis

    International Nuclear Information System (INIS)

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

    1998-01-01

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

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

    Science.gov (United States)

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

    2017-03-27

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

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

    Science.gov (United States)

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

    2017-02-01

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

  1. Acute irradiation injury and autonomic nervous system. 2

    International Nuclear Information System (INIS)

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

    1996-01-01

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

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

    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.

  3. 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.

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

    African Journals Online (AJOL)

    We hereby report a case of a 20 year‑old female who presented to us in an acute hypoadrenal state and was found to have Systemic lupus erythematosus with renal involvement. Patient was successfully managed with steroids and improved clinically. Keywords: Addison's disease, Autoimmune diseases, Systemic lupus ...

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

    International Nuclear Information System (INIS)

    Cassels, B.M.

    1987-01-01

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

  6. Classification system for acute and chronic radiation treatment sequelae

    International Nuclear Information System (INIS)

    Seegenschmiedt, M.H.; Sauer, R.

    1993-01-01

    A classification system in German language is proposed for scoring of acute and chronic treatment sequelae after radiotherapy. It includes all important organs and organ systems. The proposed grading corresponds to the four-scale-system of the WHO and UICC. The system is also compatible to the RTOG and EORTC acute and late radiation morbidity scoring criteria. This facilitates the data transfer for retrospective and prospective analysis of monomodal and multimodal radiotherapy treatment regimes. We recommend to use this scoring system in all German speaking countries for multicentric prospective studies. It is possible, that organ-specific sophistications of the toxicity grading will be developed in the future. These additions should conform with (inter)national standards and apply the same four-scale grading of this classification system. (orig.) [de

  7. 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

  8. Analysis of acute myocardial infarction occurance in Saratov region using GIS-technologies and prognostic modeling

    Directory of Open Access Journals (Sweden)

    SokolovI.M.

    2012-09-01

    Full Text Available

     

    The research objective: To find estimation tools of incidence of acute myocardial infarction at the regional level and to optimize organization of medical assistance to patients with acute coronary pathology. Materials. With the use of statistics of territorial distribution of acute myocardial infarction incidence in the region and GIS-TECHNOLOGIES the statistical analysis and mathematical modelling of the spatially-organizational data has been carried out. Results. On the basis of the received results the prognostic model of development of acute coronary pathology has been generated. Measures on optimization of organization of medical assistance to patients with an acute coronary pathology have been stated. Conclusion. Methods of intellectual support of the doctor may become effective in formation of organizational structure of the system of stage-by-stage qualified and specialized aid to patients with acute coronary syndrome.

  9. Radiotherapy of the central nervous system in acute leukemia

    International Nuclear Information System (INIS)

    Novak, L.J.

    1989-01-01

    The central nervous system (CNS) is a site of occult and overt involvement with acute lymphoblastic leukemia (ALL) in children. Prophylactic treatment of the cranial and spinal meninges can significantly reduce the incidence of CNS relapse. This review addresses the issues associated with the role of radiation therapy in the treatment of the CNS in ALL.20 references

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

    African Journals Online (AJOL)

    2017-09-03

    Sep 3, 2017 ... valve(s) replacement were enrolled, from a single center hospital, after informed consent was obtained. C-reactive ... Cite as: Gojo MKE, Prakaschandra R. Acute systemic inflammatory response after cardiac surgery in patients infected with human im- ..... Arroyo-Espliguero R, Avanzas P, Cosín-Sales J, Al-.

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

    African Journals Online (AJOL)

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

  12. Acute leukemia classification by ensemble particle swarm model selection.

    Science.gov (United States)

    Escalante, Hugo Jair; Montes-y-Gómez, Manuel; González, Jesús A; Gómez-Gil, Pilar; Altamirano, Leopoldo; Reyes, Carlos A; Reta, Carolina; Rosales, Alejandro

    2012-07-01

    Acute leukemia is a malignant disease that affects a large proportion of the world population. Different types and subtypes of acute leukemia require different treatments. In order to assign the correct treatment, a physician must identify the leukemia type or subtype. Advanced and precise methods are available for identifying leukemia types, but they are very expensive and not available in most hospitals in developing countries. Thus, alternative methods have been proposed. An option explored in this paper is based on the morphological properties of bone marrow images, where features are extracted from medical images and standard machine learning techniques are used to build leukemia type classifiers. This paper studies the use of ensemble particle swarm model selection (EPSMS), which is an automated tool for the selection of classification models, in the context of acute leukemia classification. EPSMS is the application of particle swarm optimization to the exploration of the search space of ensembles that can be formed by heterogeneous classification models in a machine learning toolbox. EPSMS does not require prior domain knowledge and it is able to select highly accurate classification models without user intervention. Furthermore, specific models can be used for different classification tasks. We report experimental results for acute leukemia classification with real data and show that EPSMS outperformed the best results obtained using manually designed classifiers with the same data. The highest performance using EPSMS was of 97.68% for two-type classification problems and of 94.21% for more than two types problems. To the best of our knowledge, these are the best results reported for this data set. Compared with previous studies, these improvements were consistent among different type/subtype classification tasks, different features extracted from images, and different feature extraction regions. The performance improvements were statistically significant

  13. R1 autonomic nervous system in acute kidney injury.

    Science.gov (United States)

    Hering, Dagmara; Winklewski, Pawel J

    2017-02-01

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

  14. GHS additivity formula: can it predict the acute systemic toxicity of agrochemical formulations that contain acutely toxic ingredients?

    Science.gov (United States)

    Van Cott, Andrew; Hastings, Charles E; Landsiedel, Robert; Kolle, Susanne; Stinchcombe, Stefan

    2018-02-01

    In vivo acute systemic testing is a regulatory requirement for agrochemical formulations. GHS specifies an alternative computational approach (GHS additivity formula) for calculating the acute toxicity of mixtures. We collected acute systemic toxicity data from formulations that contained one of several acutely-toxic active ingredients. The resulting acute data set includes 210 formulations tested for oral toxicity, 128 formulations tested for inhalation toxicity and 31 formulations tested for dermal toxicity. The GHS additivity formula was applied to each of these formulations and compared with the experimental in vivo result. In the acute oral assay, the GHS additivity formula misclassified 110 formulations using the GHS classification criteria (48% accuracy) and 119 formulations using the USEPA classification criteria (43% accuracy). With acute inhalation, the GHS additivity formula misclassified 50 formulations using the GHS classification criteria (61% accuracy) and 34 formulations using the USEPA classification criteria (73% accuracy). For acute dermal toxicity, the GHS additivity formula misclassified 16 formulations using the GHS classification criteria (48% accuracy) and 20 formulations using the USEPA classification criteria (36% accuracy). This data indicates the acute systemic toxicity of many formulations is not the sum of the ingredients' toxicity (additivity); but rather, ingredients in a formulation can interact to result in lower or higher toxicity than predicted by the GHS additivity formula. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wenxin Chai

    2018-01-01

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

  17. 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.

  18. 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 

  19. 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

  20. Effects of Erdosteine on Experimental Acute Pancreatitis Model.

    Science.gov (United States)

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

    2017-10-01

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

  1. 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.

  2. Effects of melatonin in experimental stroke models in acute, sub-acute, and chronic stages

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Lin

    2009-03-01

    Full Text Available Hsiao-Wen Lin, E-Jian LeeNeurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan, TaiwanAbstract: Melatonin (N-acetyl-5-methoxy-tryptamine, a naturally occurring indole produced mainly by the pineal gland, is a well known antioxidant. Stroke (cerebral ischemia is the second leading cause of death worldwide. To date, however, effective and safe treatment for stroke remains unavailable. Melatonin is both lipid- and water-soluble and readily crosses the blood–brain barrier (BBB. Increasing evidence has shown that, in animal stroke models, administering melatonin significantly reduces infarct volume, edema, and oxidative damage and improves electrophysiological and behavioral performance. Here, we reviewed studies that assess effects of melatonin on cerebral ischemia in acute, sub-acute, and chronic stages. In addition to its potent antioxidant properties, melatonin exerts antiapoptotic, antiexcitotoxic, anti-inflammatory effects and promotes mitochondrial functions in animals with cerebral ischemia. Given that melatonin shows almost no toxicity to humans and possesses multifaceted protective capacity against cerebral ischemia, it is valuable to consider using melatonin in clinical trials on patients suffering from stroke.Keywords: cerebral ischemia, melatonin, stroke, neuroprotection

  3. 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.

  4. Modeller af komplicerede systemer

    DEFF Research Database (Denmark)

    Mortensen, J.

    emphasizes their use in relation to technical systems. All the presented models, with the exception of the types presented in chapter 2, are non-theoretical non-formal conceptual network models. Two new model types are presented: 1) The System-Environment model, which describes the environments interaction...... with conceptual modeling in relation to process control. It´s purpose is to present classify and exemplify the use of a set of qualitative model types. Such model types are useful in the early phase of modeling, where no structured methods are at hand. Although the models are general in character, this thesis......This thesis, "Modeller af komplicerede systemer", represents part of the requirements for the Danish Ph.D.degree. Assisting professor John Nørgaard-Nielsen, M.Sc.E.E.Ph.D. has been principal supervisor and professor Morten Lind, M.Sc.E.E.Ph.D. has been assisting supervisor. The thesis is concerned...

  5. Deciphering the complexity of acute inflammation using mathematical models.

    Science.gov (United States)

    Vodovotz, Yoram

    2006-01-01

    Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.

  6. The systems integration modeling system

    International Nuclear Information System (INIS)

    Danker, W.J.; Williams, J.R.

    1990-01-01

    This paper discusses the systems integration modeling system (SIMS), an analysis tool for the detailed evaluation of the structure and related performance of the Federal Waste Management System (FWMS) and its interface with waste generators. It's use for evaluations in support of system-level decisions as to FWMS configurations, the allocation, sizing, balancing and integration of functions among elements, and the establishment of system-preferred waste selection and sequencing methods and other operating strategies is presented. SIMS includes major analysis submodels which quantify the detailed characteristics of individual waste items, loaded casks and waste packages, simulate the detailed logistics of handling and processing discrete waste items and packages, and perform detailed cost evaluations

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

    African Journals Online (AJOL)

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

  8. Development of a murine model of acute radiation encephalopathy

    International Nuclear Information System (INIS)

    Xing Yigang; Tang Yamei; Liu Jun; Sun Ying

    2003-01-01

    Objective: To develop a murine model of acute radiation encephalopathy. Methods: A total of 40 rats were subjected to local γ-irradiation to the brain with the dosage of 7 Gy/d for 6 consecutive days. The amount of food intake, hairs and skin of irradiated field, body weight, general activities, CNS symptoms and signs were examined and recorded after irradiation. On day 3, 7, 14 and 30, the brain tissue was removed to observe histopathologic changes. Results: During the first two days after irradiation, the irradiated rats were agitated, and the amount of food intake decreased from day 2 onwards. No serious skin reaction to irradiation was observed. Survived rats had normal activities without any abnormal nervous signs. Histopathologic changes showed slight neuronal degeneration, smaller cell body, red-colored cytoplasm, disappearance of Nissl body, vacuolation, typical cell shrinkage, chromatin condensation and nuclear divergence. On the 14th and 30th days, hypochromatism, loose and reticular necrotic foci were found in some samples. Conclusion: The murine model of acute radiation encephalopathy is useful and practical in radiobiological studies

  9. 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....

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

    Science.gov (United States)

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

    2011-05-01

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

  11. Chronic and acute effects of stress on energy balance: are there appropriate animal models?

    Science.gov (United States)

    Harris, Ruth B S

    2015-02-15

    Stress activates multiple neural and endocrine systems to allow an animal to respond to and survive in a threatening environment. The corticotropin-releasing factor system is a primary initiator of this integrated response, which includes activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. The energetic response to acute stress is determined by the nature and severity of the stressor, but a typical response to an acute stressor is inhibition of food intake, increased heat production, and increased activity with sustained changes in body weight, behavior, and HPA reactivity. The effect of chronic psychological stress is more variable. In humans, chronic stress may cause weight gain in restrained eaters who show increased HPA reactivity to acute stress. This phenotype is difficult to replicate in rodent models where chronic psychological stress is more likely to cause weight loss than weight gain. An exception may be hamsters subjected to repeated bouts of social defeat or foot shock, but the data are limited. Recent reports on the food intake and body composition of subordinate members of group-housed female monkeys indicate that these animals have a similar phenotype to human stress-induced eaters, but there are a limited number of investigators with access to the model. Few stress experiments focus on energy balance, but more information on the phenotype of both humans and animal models during and after exposure to acute or chronic stress may provide novel insight into mechanisms that normally control body weight. Copyright © 2015 the American Physiological Society.

  12. 78 FR 38679 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Science.gov (United States)

    2013-06-27

    ... Systems for Acute Care Hospitals and the Long Term Care Hospital Prospective Payment System and Proposed... Payment Systems for Acute Care Hospitals and the Long Term Care Hospital Prospective Payment System and... regarding MS-DRG classifications and new technology add-on payments. Eva Fung (410) 786-7539, for...

  13. 77 FR 4908 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Science.gov (United States)

    2012-02-01

    ... Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective Payment System and Fiscal... the final rule entitled ``Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective Payment System and Fiscal Year 2012 Rates...

  14. 77 FR 65495 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Science.gov (United States)

    2012-10-29

    ... Payment Systems for Acute Care Hospitals and the Long Term Care Hospital Prospective Payment System and... Federal Register entitled ``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...

  15. 78 FR 15882 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Science.gov (United States)

    2013-03-13

    ... Payment Systems for Acute Care Hospitals and the Long Term Care Hospital Prospective Payment System and... Register entitled ``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...

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

    Science.gov (United States)

    Thornton, Kathy; Parrish, Francie; Swords, Christine

    2011-01-01

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

  17. The Earth System Model

    Science.gov (United States)

    Schoeberl, Mark; Rood, Richard B.; Hildebrand, Peter; Raymond, Carol

    2003-01-01

    The Earth System Model is the natural evolution of current climate models and will be the ultimate embodiment of our geophysical understanding of the planet. These models are constructed from components - atmosphere, ocean, ice, land, chemistry, solid earth, etc. models and merged together through a coupling program which is responsible for the exchange of data from the components. Climate models and future earth system models will have standardized modules, and these standards are now being developed by the ESMF project funded by NASA. The Earth System Model will have a variety of uses beyond climate prediction. The model can be used to build climate data records making it the core of an assimilation system, and it can be used in OSSE experiments to evaluate. The computing and storage requirements for the ESM appear to be daunting. However, the Japanese ES theoretical computing capability is already within 20% of the minimum requirements needed for some 2010 climate model applications. Thus it seems very possible that a focused effort to build an Earth System Model will achieve succcss.

  18. RSMASS system model development

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  19. Digitalization of a non-irradiated acute myeloid leukemia model.

    Science.gov (United States)

    Li, Rudong; Cheng, Hui; Cheng, Tao; Liu, Lei

    2016-08-26

    Computer-aided, interdisciplinary researches for biomedicine have valuable prospects, as digitalization of experimental subjects provide opportunities for saving the economic costs of researches, as well as promoting the acquisition of knowledge. Acute myeloid leukemia (AML) is intensively studied over long periods of time. Till nowaday, most of the studies primarily focus on the leukemic cells rather than how normal hematopoietic cells are affected by the leukemic environment. Accordingly, the conventional animal models for AML are mostly myeloablated as leukemia can be induced with short latency and complete penetrance. Meanwhile, most previous computational models focus on modeling the leukemic cells but not the multi-tissue leukemic body resided by both leukemic and normal blood cells. Recently, a non-irradiated AML mouse model has been established; therefore, normal hematopoietic cells can be investigated during leukemia development. Experiments based on the non-irradiated animal model have monitored the kinetics of leukemic and (intact) hematopoietic cells in multiple tissues simultaneously; and thus a systematic computational model for the multi-tissue hematopoiesis under leukemia has become possible. In the present work, we adopted the modeling methods in previous works, but aimed to model the tri-tissue (peripheral blood, spleen and bone marrow) dynamics of hematopoiesis under leukemia. The cell kinetics generated from the non-irradiated experimental model were used as the reference data for modeling. All mathematical formulas were systematically enumerated, and model parameters were estimated via numerical optimization. Multiple validations by additional experimental data were then conducted for the established computational model. In the results, we illustrated that the important fact of functional depression of hematopoietic stem/progenitor cells (HSC/HPC) in leukemic bone marrow (BM), which must require additional experiments to be established, could

  20. Systemic resilience model

    International Nuclear Information System (INIS)

    Lundberg, Jonas; Johansson, Björn JE

    2015-01-01

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

  1. 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.

  2. 75 FR 60640 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Science.gov (United States)

    2010-10-01

    ...; RIN 0938-AP33 Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective Payment System Changes and FY 2011 Rates; Provider... Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective...

  3. 75 FR 34614 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and...

    Science.gov (United States)

    2010-06-17

    ... Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and Fiscal Year 2010 Rates and to the Long- Term Care Hospital Prospective Payment System and Rate Year 2010 Rates... Prospective Payment Systems for Acute Care Hospitals and Fiscal Year 2010 Rates and to the Long-Term Care...

  4. 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.

  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. New activity-based funding model for Australian private sector overnight rehabilitation cases: the rehabilitation Australian National Sub-Acute and Non-Acute Patient (AN-SNAP) model.

    Science.gov (United States)

    Hanning, Brian; Predl, Nicolle

    2015-09-01

    Traditional overnight rehabilitation payment models in the private sector are not based on a rigorous classification system and vary greatly between contracts with no consideration of patient complexity. The payment rates are not based on relative cost and the length-of-stay (LOS) point at which a reduced rate applies (step downs) varies markedly. The rehabilitation Australian National Sub-Acute and Non-Acute Patient (AN-SNAP) model (RAM), which has been in place for over 2 years in some private hospitals, bases payment on a rigorous classification system, relative cost and industry LOS. RAM is in the process of being rolled out more widely. This paper compares and contrasts RAM with traditional overnight rehabilitation payment models. It considers the advantages of RAM for hospitals and Australian Health Service Alliance. It also considers payment model changes in the context of maintaining industry consistency with Electronic Claims Lodgement and Information Processing System Environment (ECLIPSE) and health reform generally.

  7. 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.

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

    International Nuclear Information System (INIS)

    Tutcu, Semra; Serter, Selim; Kaya, Yavuz; Kara, Eray; Nese, Nalan; Pekindil, Goekhan; Coskun, Teoman

    2010-01-01

    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.

  9. A Predictive Model for Acute Admission in Aged Population

    DEFF Research Database (Denmark)

    Mansourvar, Marjan; Andersen-Ranberg, Karen; Nøhr, Christian

    2018-01-01

    Acute hospital admission among the elderly population is very common and have a high impact on the health services and the community, as well as on the individuals. Several studies have focused on the possible risk factors, however, predicting who is at risk for acute hospitalization associated...... with disease and symptoms is still an open research question. In this study, we investigate the use of machine learning algorithms for predicting acute admission in older people based on admission data from individual citizens 70 years and older who were hospitalized in the acute medical unit of Svendborg...

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ydens Elke

    2012-07-01

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

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

    Science.gov (United States)

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

    2011-06-01

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

  13. 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.

  14. Agent-based modeling of endotoxin-induced acute inflammatory response in human blood leukocytes.

    Science.gov (United States)

    Dong, Xu; Foteinou, Panagiota T; Calvano, Steven E; Lowry, Stephen F; Androulakis, Ioannis P

    2010-02-18

    Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions. An agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades. The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve

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

    Science.gov (United States)

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

    2016-09-01

    Posttraumatic seizures (PTS) are well-recognized acute and chronic complications of traumatic brain injury (TBI). Risk factors have been identified, but considerable variability in who develops PTS remains. Existing PTS prognostic models are not widely adopted for clinical use and do not reflect current trends in injury, diagnosis, or care. We aimed to develop and internally validate preliminary prognostic regression models to predict PTS during acute care hospitalization, and at year 1 and year 2 postinjury. Prognostic models predicting PTS during acute care hospitalization and year 1 and year 2 post-injury were developed using a recent (2011-2014) cohort from the TBI Model Systems National Database. Potential PTS predictors were selected based on previous literature and biologic plausibility. Bivariable logistic regression identified variables with a p-value models. Multivariable logistic regression modeling with backward-stepwise elimination was used to determine reduced prognostic models and to internally validate using 1,000 bootstrap samples. Fit statistics were calculated, correcting for overfitting (optimism). The prognostic models identified sex, craniotomy, contusion load, and pre-injury limitation in learning/remembering/concentrating as significant PTS predictors during acute hospitalization. Significant predictors of PTS at year 1 were subdural hematoma (SDH), contusion load, craniotomy, craniectomy, seizure during acute hospitalization, duration of posttraumatic amnesia, preinjury mental health treatment/psychiatric hospitalization, and preinjury incarceration. Year 2 significant predictors were similar to those of year 1: SDH, intraparenchymal fragment, craniotomy, craniectomy, seizure during acute hospitalization, and preinjury incarceration. Corrected concordance (C) statistics were 0.599, 0.747, and 0.716 for acute hospitalization, year 1, and year 2 models, respectively. The prognostic model for PTS during acute hospitalization did not

  16. MR perfusion/diffusion-weighted imaging of acute ischemia in an animal model with PET correlation

    International Nuclear Information System (INIS)

    Pickens, D.R.; Dawson, R.C.; Votaw, J.R.; Lorenz, C.H.; Holburn, G.E.; Price, R.R.

    1990-01-01

    This paper evaluates acute cerebral ischemia in an animal model with MR perfusion/diffusion-sensitive pulse sequences and to compare the results with PET regional cerebral blood flow (rCBF) measurements. An embolizing agent was injected into the proximal middle cerebral artery (MCA) of a dog, and this was followed by DSA. Next, the animal was imaged in a 1.5-T MR system with perfusion/diffusion-sensitive spin-echo pulse sequence. Then, PET imaging was performed with H 2 O 15 at corresponding levels of the brain

  17. 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).

  18. Modeling Complex Systems

    International Nuclear Information System (INIS)

    Schreckenberg, M

    2004-01-01

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

  19. 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.

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

    Science.gov (United States)

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

    2014-12-26

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

  1. System equivalent model mixing

    Science.gov (United States)

    Klaassen, Steven W. B.; van der Seijs, Maarten V.; de Klerk, Dennis

    2018-05-01

    This paper introduces SEMM: a method based on Frequency Based Substructuring (FBS) techniques that enables the construction of hybrid dynamic models. With System Equivalent Model Mixing (SEMM) frequency based models, either of numerical or experimental nature, can be mixed to form a hybrid model. This model follows the dynamic behaviour of a predefined weighted master model. A large variety of applications can be thought of, such as the DoF-space expansion of relatively small experimental models using numerical models, or the blending of different models in the frequency spectrum. SEMM is outlined, both mathematically and conceptually, based on a notation commonly used in FBS. A critical physical interpretation of the theory is provided next, along with a comparison to similar techniques; namely DoF expansion techniques. SEMM's concept is further illustrated by means of a numerical example. It will become apparent that the basic method of SEMM has some shortcomings which warrant a few extensions to the method. One of the main applications is tested in a practical case, performed on a validated benchmark structure; it will emphasize the practicality of the method.

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

    Science.gov (United States)

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

  3. Systemic corticosteroids for acute otitis media in children.

    Science.gov (United States)

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

    2018-03-15

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

  4. Effects of acute systemic inflammation on the interplay between sad mood and affective cognition.

    Science.gov (United States)

    Benson, Sven; Brinkhoff, Alexandra; Lueg, Larissa; Roderigo, Till; Kribben, Andreas; Wilde, Benjamin; Witzke, Oliver; Engler, Harald; Schedlowski, Manfred; Elsenbruch, Sigrid

    2017-12-11

    Experimental endotoxemia is a translational model to study inflammatory mechanisms involved in the pathophysiology of mood disorders including depression. Disturbed affective cognition constitutes a core aspect in depression, but has never been studied in the context of inflammation. We combined experimental endotoxemia with an established experimental mood induction procedure to assess the interaction between acute inflammation and sad mood and their effects on affective cognition. In this randomized cross-over study, N = 15 healthy males received endotoxin (0.8 ng/kg lipopolysaccharide iv) on one study day and placebo an otherwise identical study day. The affective Go/Nogo task was conducted after experimental induction of neutral and sad mood. Inflammatory markers were assessed hourly. Endotoxin application induced a transient systemic inflammation, characterized by increased leukocyte counts, TNF-alpha and interleukin-6 plasma concentrations (all p sadness ratings, with highest ratings when sad mood was induced during inflammation (p sad vs. neutral mood) × 2 (sad vs. happy Go/Nogo target words) factorial design, we observed a significant target × endotoxin condition interaction (p sad targets during endotoxemia. Additionally, we found a valence × mood interaction (p sad targets in sad mood. In summary, acute inflammation and sad mood are risk factors for disturbed affective cognition. The results may reflect a mood-congruency effect, with prolonged and sustained processing of mood-congruent information during acute inflammation, which may contribute to depression risk.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  6. 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.

  7. 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

  8. Characterization of an acute muscle contraction model using cultured C2C12 myotubes.

    Directory of Open Access Journals (Sweden)

    Yasuko Manabe

    Full Text Available A cultured C2C12 myotube contraction system was examined for application as a model for acute contraction-induced phenotypes of skeletal muscle. C2C12 myotubes seeded into 4-well rectangular plates were placed in a contraction system equipped with a carbon electrode at each end. The myotubes were stimulated with electric pulses of 50 V at 1 Hz for 3 ms at 997-ms intervals. Approximately 80% of the myotubes were observed to contract microscopically, and the contractions lasted for at least 3 h with electrical stimulation. Calcium ion (Ca²⁺ transient evoked by the electric pulses was detected fluorescently with Fluo-8. Phosphorylation of protein kinase B/Akt (Akt, 5' AMP-activated protein kinase (AMPK, p38 mitogen-activated protein kinase (p38, and c-Jun NH2-terminal kinase (JNK1/2, which are intracellular signaling proteins typically activated in exercised/contracted skeletal muscle, was observed in the electrically stimulated C2C12 myotubes. The contractions induced by the electric pulses increased glucose uptake and depleted glycogen in the C2C12 myotubes. C2C12 myotubes that differentiated after exogenous gene transfection by a lipofection or an electroporation method retained their normal contractile ability by electrical stimulation. These findings show that our C2C12 cell contraction system reproduces the muscle phenotypes that arise invivo (exercise, in situ (hindlimb muscles in an anesthetized animal, and invitro (dissected muscle tissues in incubation buffer by acute muscle contraction, demonstrating that the system is applicable for the analysis of intracellular events evoked by acute muscle contraction.

  9. Systemic classification for a new diagnostic approach to acute abdominal pain in children.

    Science.gov (United States)

    Kim, Ji Hoi; Kang, Hyun Sik; Han, Kyung Hee; Kim, Seung Hyo; Shin, Kyung-Sue; Lee, Mu Suk; Jeong, In Ho; Kim, Young Sil; Kang, Ki-Soo

    2014-12-01

    With previous methods based on only age and location, there are many difficulties in identifying the etiology of acute abdominal pain in children. We sought to develop a new systematic classification of acute abdominal pain and to give some helps to physicians encountering difficulties in diagnoses. From March 2005 to May 2010, clinical data were collected retrospectively from 442 children hospitalized due to acute abdominal pain with no apparent underlying disease. According to the final diagnoses, diseases that caused acute abdominal pain were classified into nine groups. The nine groups were group I "catastrophic surgical abdomen" (7 patients, 1.6%), group II "acute appendicitis and mesenteric lymphadenitis" (56 patients, 12.7%), group III "intestinal obstruction" (57 patients, 12.9%), group IV "viral and bacterial acute gastroenteritis" (90 patients, 20.4%), group V "peptic ulcer and gastroduodenitis" (66 patients, 14.9%), group VI "hepatobiliary and pancreatic disease" (14 patients, 3.2%), group VII "febrile viral illness and extraintestinal infection" (69 patients, 15.6%), group VIII "functional gastrointestinal disorder (acute manifestation)" (20 patients, 4.5%), and group IX "unclassified acute abdominal pain" (63 patients, 14.3%). Four patients were enrolled in two disease groups each. Patients were distributed unevenly across the nine groups of acute abdominal pain. In particular, the "unclassified abdominal pain" only group was not uncommon. Considering a systemic classification for acute abdominal pain may be helpful in the diagnostic approach in children.

  10. 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...

  11. 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...

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

    Science.gov (United States)

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

    2016-11-29

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

  13. Modeling dental radiographic systems

    International Nuclear Information System (INIS)

    Webber, R.L.

    1980-01-01

    The Bureau of Radiological Health has been actively collaborating with the Clinical Investigations Branch, NIDR, in applied research involving diagnostic use of ionizing radiation in dentistry. This work has centered on the search for alternatives to conventional radiographic systems in an attempt to improve diagnostic performance while reducing the required exposure. The basic approach involves analysis of factors limiting performance of properly defined diagnostic tasks and the modeling alternative systems with an eye toward increasing objective measures of performance. Previous collaborative work involved using a nonlinear model to compare various x-ray spectra. The data were expressed as brightness-contrast versus exposure for simulated tasks of clinical interest. This report supplements these findings by extending the number of parameters under investigation and modifying the mode of data display so that an actual radiographic image can be simulated on a television screen

  14. 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...... were compared with baseline levels. Results: Systemic inflammation was confirmed by the presence of clinical and hematological changes which were consistent with SIRS. The clinical response to LPS was transient and brief as all horses except one showed unaltered general demeanor after 24 h. Twenty...

  15. 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'....

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

    Science.gov (United States)

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

    2014-06-26

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

  17. Validation of an electronic surveillance system for acute lung injury.

    Science.gov (United States)

    Herasevich, Vitaly; Yilmaz, Murat; Khan, Hasrat; Hubmayr, Rolf D; Gajic, Ognjen

    2009-06-01

    Early detection of acute lung injury (ALI) is essential for timely implementation of evidence-based therapies and enrollment into clinical trials. We aimed to determine the accuracy of computerized syndrome surveillance for detection of ALI in hospitalized patients and compare it with routine clinical assessment. Using a near-real time copy of the electronic medical records, we developed and validated a custom ALI electronic alert (ALI "sniffer") based on the European-American Consensus Conference Definition and compared its performance against provider-derived documentation. A total of 3,795 consecutive critically ill patients admitted to nine multidisciplinary intensive care units (ICUs) of a tertiary care teaching institution were included. ALI developed in 325 patients and was recognized by bedside clinicians in only 86 (26.5%). Under-recognition of ALI was associated with not implementing protective mechanical ventilation (median tidal volumes of 9.2 vs. 8.0 ml/kg predicted body weight, P sniffer" demonstrated excellent sensitivity of 96% (95% CI 94-98) and moderate specificity of 89% (95% CI 88-90) with a positive predictive value ranging from 24% (95% CI 13-40) in the heart-lung transplant ICU to 64% (95% CI 55-71) in the medical ICU. The computerized surveillance system accurately identifies critically ill patients who develop ALI syndrome. Since the lack of ALI recognition is a barrier to the timely implementation of best practices and enrollment into research studies, computerized syndrome surveillance could be a useful tool to enhance patient safety and clinical research.

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

    Data.gov (United States)

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

  19. A guinea pig model of acute and chronic asthma using permanently instrumented and unrestrained animals

    NARCIS (Netherlands)

    Meurs, Herman; Santing, Ruud E.; Remie, Rene; van der Mark, Thomas W.; Westerhof, Fiona J.; Zuidhof, Annet B.; Bos, I. Sophie T.; Zaagsma, Johan

    2006-01-01

    To investigate mechanisms underlying allergen-induced asthmatic reactions, airway hyperresponsiveness and remodeling, we have developed a guinea pig model of acute and chronic asthma using unanesthetized, unrestrained animals. To measure airway function, ovalbumin (IgE)-sensitized animals are

  20. Sex hormones affect acute and chronic stress responses in sexually dimorphic patterns: Consequences for depression models.

    Science.gov (United States)

    Guo, Lei; Chen, Yi-Xi; Hu, Yu-Ting; Wu, Xue-Yan; He, Yang; Wu, Juan-Li; Huang, Man-Li; Mason, Matthew; Bao, Ai-Min

    2018-05-21

    Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. An acute rat in vivo screening model to predict compounds that alter blood glucose and/or insulin regulation.

    Science.gov (United States)

    Brott, David A; Diamond, Melody; Campbell, Pam; Zuvich, Andy; Cheatham, Letitia; Bentley, Patricia; Gorko, Mary Ann; Fikes, James; Saye, JoAnne

    2013-01-01

    Drug-induced glucose dysregulation and insulin resistance have been associated with weight gain and potential induction and/or exacerbation of diabetes mellitus in the clinic suggesting they may be safety biomarkers when developing antipsychotics. Glucose and insulin have also been suggested as potential efficacy biomarkers for some oncology compounds. The objective of this study was to qualify a medium throughput rat in vivo acute Intravenous Glucose Tolerance Test (IVGTT) for predicting compounds that will induce altered blood glucose and/or insulin levels. Acute and sub-chronic studies were performed to qualify an acute IVGTT model. Double cannulated male rats (Han-Wistar and Sprague-Dawley) were administered vehicle, olanzapine, aripiprazole or other compounds at t=-44min for acute studies and at time=-44min on the last day of dosing for sub-chronic studies, treated with dextrose (time=0min; i.v.) and blood collected using an automated Culex® system for glucose and insulin analysis (time=-45, -1, 2, 10, 15, 30, 45, 60, 75, 90, 120, 150 and 180min). Olanzapine significantly increased glucose and insulin area under the curve (AUC) values while aripiprazole AUC values were similar to control, in both acute and sub-chronic studies. All atypical antipsychotics evaluated were consistent with literature references of clinical weight gain. As efficacy biomarkers, insulin AUC but not glucose AUC values were increased with a compound known to have insulin growth factor-1 (IGF-1) activity, compared to control treatment. These studies qualified the medium throughput acute IVGTT model to more quickly screen compounds for 1) safety - the potential to elicit glucose dysregulation and/or insulin resistance and 2) efficacy - as a surrogate for compounds affecting the glucose and/or insulin regulatory pathways. These data demonstrate that the same in vivo rat model and assays can be used to predict both clinical safety and efficacy of compounds. © 2013.

  2. 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...

  3. 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.

  4. 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.

  5. 76 FR 39883 - Design of Clinical Trials for Systemic Antibacterial Drugs for the Treatment of Acute Otitis...

    Science.gov (United States)

    2011-07-07

    ...] Design of Clinical Trials for Systemic Antibacterial Drugs for the Treatment of Acute Otitis Media... Clinical Trials for Systemic Antibacterial Agents for the Treatment of Acute Otitis Media. This public... the treatment of acute otitis media (middle ear infection). Discussions will focus on [[Page 39884...

  6. New scoring system identifies kidney outcome with radiation therapy in acute renal allograft rejection

    International Nuclear Information System (INIS)

    Chen, Luci M.; Godinez, Juan; Thisted, Ronald A.; Woodle, E. Steve; Thistlewaite, J. Richard; Powers, Claire; Haraf, Daniel

    2000-01-01

    concomitant immunosuppressive therapy. Independent factors examined by Cox regression modeling were: gender (p 0.005), creatinine levels (p = 0.000), HLA-DR (p = 0.05), PRA-Maximum >70% (p = 0.014). Each factor was scored using integral coefficients to generate four different groups. The Kaplan-Meier survival analyzed by group produces an interpretable separation of the risk factors for graft loss. Conclusions: The outcome in patients treated with radiation therapy for acute renal graft rejection can be predicted by a novel scoring system. Patients with scores of three or less are able to achieve 100% renal graft salvage, while patients who have scores of 12 or higher are not able to be salvaged with the current radiation therapy regimen. Future studies should be directed toward identifying more effective treatment for patients who have a high score based on our criteria. The scoring system should be utilized to identify patients at risk who could benefit from radiation therapy. Further study with a randomized trial utilizing this scoring system is needed to confirm the validity of the scoring system in predicting graft survival and the efficacy of radiation in patients who receive radiation therapy for acute graft rejection

  7. Dynamics of the cytotoxic T cell response to a model of acute viral infection.

    Science.gov (United States)

    DeWitt, William S; Emerson, Ryan O; Lindau, Paul; Vignali, Marissa; Snyder, Thomas M; Desmarais, Cindy; Sanders, Catherine; Utsugi, Heidi; Warren, Edus H; McElrath, Juliana; Makar, Karen W; Wald, Anna; Robins, Harlan S

    2015-04-01

    A detailed characterization of the dynamics and breadth of the immune response to an acute viral infection, as well as the determinants of recruitment to immunological memory, can greatly contribute to our basic understanding of the mechanics of the human immune system and can ultimately guide the design of effective vaccines. In addition to neutralizing antibodies, T cells have been shown to be critical for the effective resolution of acute viral infections. We report the first in-depth analysis of the dynamics of the CD8(+) T cell repertoire at the level of individual T cell clonal lineages upon vaccination of human volunteers with a single dose of YF-17D. This live attenuated yellow fever virus vaccine yields sterile, long-term immunity and has been previously used as a model to understand the immune response to a controlled acute viral infection. We identified and enumerated unique CD8(+) T cell clones specifically induced by this vaccine through a combined experimental and statistical approach that included high-throughput sequencing of the CDR3 variable region of the T cell receptor β-chain and an algorithm that detected significantly expanded T cell clones. This allowed us to establish that (i) on average, ∼ 2,000 CD8(+) T cell clones were induced by YF-17D, (ii) 5 to 6% of the responding clones were recruited to long-term memory 3 months postvaccination, (iii) the most highly expanded effector clones were preferentially recruited to the memory compartment, and (iv) a fraction of the YF-17D-induced clones could be identified from peripheral blood lymphocytes solely by measuring clonal expansion. The exhaustive investigation of pathogen-induced effector T cells is essential to accurately quantify the dynamics of the human immune response. The yellow fever vaccine (YFV) has been broadly used as a model to understand how a controlled, self-resolving acute viral infection induces an effective and long-term protective immune response. Here, we extend this

  8. Acute versus chronic phase mechanisms in a rat model of CRPS.

    Science.gov (United States)

    Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Kingery, Wade S; Clark, John David

    2016-01-19

    Tibia fracture followed by cast immobilization in rats evokes nociceptive, vascular, epidermal, and bone changes resembling complex regional pain syndrome (CRPS). In most cases, CRPS has three stages. Over time, this acute picture, allodynia, warmth, and edema observed at 4 weeks, gives way to a cold, dystrophic but still painful limb. In the acute phase (at 4 weeks post fracture), cutaneous immunological and NK1-receptor signaling mechanisms underlying CRPS have been discovered; however, the mechanisms responsible for the chronic phase are still unknown. The purpose of this study is to understand the mechanisms responsible for the chronic phases of CRPS (at 16 weeks post fracture) at both the peripheral and central levels. We used rat tibial fracture/cast immobilization model of CRPS to study molecular, vascular, and nociceptive changes at 4 and 16 weeks post fracture. Immunoassays and Western blotting were carried out to monitor changes in inflammatory response and NK1-receptor signaling in the skin and spinal cord. Skin temperature and thickness were measured to elucidate vascular changes, whereas von Frey testing and unweighting were carried out to study nociceptive changes. All data were analyzed by one-way analysis of variance (ANOVA) followed by Neuman-Keuls multiple comparison test to compare among all cohorts. In the acute phase (at 4 weeks post fracture), hindpaw allodynia, unweighting, warmth, edema, and/or epidermal thickening were observed among 90 % fracture rats, though by 16 weeks (chronic phase), only the nociceptive changes persisted. The expression of the neuropeptide signaling molecule substance P (SP), NK1 receptor, inflammatory mediators TNFα, IL-1β, and IL-6 and nerve growth factor (NGF) were elevated at 4 weeks in sciatic nerve and/or skin, returning to normal levels by 16 weeks post fracture. The systemic administration of a peripherally restricted IL-1 receptor antagonist (anakinra) or of anti-NGF inhibited nociceptive behaviors at 4

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

    Science.gov (United States)

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

    2007-06-01

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

  10. Advanced practice nursing role delineation in acute and critical care: application of the strong model of advanced practice.

    Science.gov (United States)

    Mick, D J; Ackerman, M H

    2000-01-01

    This purpose of this study was to differentiate between the roles of clinical nurse specialists and acute care nurse practitioners. Hypothesized blending of the clinical nurse specialist and acute care nurse practitioner roles is thought to result in an acute care clinician who integrates the clinical skills of the nurse practitioner with the systems knowledge, educational commitment, and leadership ability of the clinical nurse specialist. Ideally, this role blending would facilitate excellence in both direct and indirect patient care. The Strong Model of Advanced Practice, which incorporates practice domains of direct comprehensive care, support of systems, education, research, and publication and professional leadership, was tested to search for practical evidence of role blending. This descriptive, exploratory, pilot study included subjects (N = 18) solicited from an academic medical center and from an Internet advanced practice listserv. Questionnaires included self-ranking of expertise in practice domains, as well as valuing of role-related tasks. Content validity was judged by an expert panel of advanced practice nurses. Analyses of descriptive statistics revealed that clinical nurse specialists, who had more experience both as registered nurses and in the advanced practice nurse role, self-ranked their expertise higher in all practice domains. Acute care nurse practitioners placed higher importance on tasks related to direct comprehensive care, including conducting histories and physicals, diagnosing, and performing diagnostic procedures, whereas clinical nurse specialists assigned greater importance to tasks related to education, research, and leadership. Levels of self-assessed clinical expertise as well as valuing of role-related tasks differed among this sample of clinical nurse specialists and acute care nurse practitioners. Groundwork has been laid for continuing exploration into differentiation in advanced practice nursing roles. As the clinical

  11. 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

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Science.gov (United States)

    2018-02-22

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

  14. Acute Myocardial Infarction Readmission Risk Prediction Models: A Systematic Review of Model Performance.

    Science.gov (United States)

    Smith, Lauren N; Makam, Anil N; Darden, Douglas; Mayo, Helen; Das, Sandeep R; Halm, Ethan A; Nguyen, Oanh Kieu

    2018-01-01

    Hospitals are subject to federal financial penalties for excessive 30-day hospital readmissions for acute myocardial infarction (AMI). Prospectively identifying patients hospitalized with AMI at high risk for readmission could help prevent 30-day readmissions by enabling targeted interventions. However, the performance of AMI-specific readmission risk prediction models is unknown. We systematically searched the published literature through March 2017 for studies of risk prediction models for 30-day hospital readmission among adults with AMI. We identified 11 studies of 18 unique risk prediction models across diverse settings primarily in the United States, of which 16 models were specific to AMI. The median overall observed all-cause 30-day readmission rate across studies was 16.3% (range, 10.6%-21.0%). Six models were based on administrative data; 4 on electronic health record data; 3 on clinical hospital data; and 5 on cardiac registry data. Models included 7 to 37 predictors, of which demographics, comorbidities, and utilization metrics were the most frequently included domains. Most models, including the Centers for Medicare and Medicaid Services AMI administrative model, had modest discrimination (median C statistic, 0.65; range, 0.53-0.79). Of the 16 reported AMI-specific models, only 8 models were assessed in a validation cohort, limiting generalizability. Observed risk-stratified readmission rates ranged from 3.0% among the lowest-risk individuals to 43.0% among the highest-risk individuals, suggesting good risk stratification across all models. Current AMI-specific readmission risk prediction models have modest predictive ability and uncertain generalizability given methodological limitations. No existing models provide actionable information in real time to enable early identification and risk-stratification of patients with AMI before hospital discharge, a functionality needed to optimize the potential effectiveness of readmission reduction interventions

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

    Science.gov (United States)

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

    2011-11-01

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

  16. 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.

  17. Fractional model for pharmacokinetics of high dose methotrexate in children with acute lymphoblastic leukaemia

    Science.gov (United States)

    Popović, Jovan K.; Spasić, Dragan T.; Tošić, Jela; Kolarović, Jovanka L.; Malti, Rachid; Mitić, Igor M.; Pilipović, Stevan; Atanacković, Teodor M.

    2015-05-01

    The aim of this study is to promote a model based on the fractional differential calculus related to the pharmacokinetic individualization of high dose methotrexate treatment in children with acute lymphoblastic leukaemia, especially in high risk patients. We applied two-compartment fractional model on 8 selected cases with the largest number (4-19) of measured concentrations, among 43 pediatric patients received 24-h methotrexate 2-5 g/m2 infusions. The plasma concentrations were determined by fluorescence polarization immunoassay. Our mathematical procedure, designed by combining Post's and Newton's method, was coded in Mathematica 8.0 and performed on Fujicu Celsius M470-2 PC. Experimental data show that most of the measured values of methotrexate were in decreasing order. However, in certain treatments local maximums were detected. On the other hand, integer order compartmental models do not give values which fit well with the observed data. By the use of our model, we obtained better results, since it gives more accurate behavior of the transmission, as well as the local maximums which were recognized in methotrexate monitoring. It follows from our method that an additional test with a small methotrexate dose can be suggested for the fractional system parameter identification and the prediction of a possible pattern with a full dose in the case of high risk patients. A special feature of the fractional model is that it can also recognize and better fit an observed non-monotonic behavior. A new parameter determination procedure can be successfully used.

  18. 77 FR 63751 - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the...

    Science.gov (United States)

    2012-10-17

    ... [CMS-1588-F2] RIN 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..., 2012 Federal Register entitled ``Medicare Program; Hospital Inpatient Prospective Payment Systems for...

  19. 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

    ) 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......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...

  20. 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.

  1. On Modelling an Immune System

    OpenAIRE

    Monroy, Raúl; Saab, Rosa; Godínez, Fernando

    2004-01-01

    Immune systems of live forms have been an abundant source of inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to challenging problems of modern computing. However, research in artificial immune systems has overlooked establishing a coherent model of known immune system behaviour. This paper aims reports on an preliminary computer model of an immune system, where each immune system component...

  2. 77 FR 43089 - Evaluation of an Up-and-Down Procedure for Acute Dermal Systemic Toxicity Testing: Request for...

    Science.gov (United States)

    2012-07-23

    ... vivo acute dermal systemic toxicity tests. Corresponding acute oral LD 50 data for the same compounds....), estimated LD 50 , and incidence of death and other adverse effects. Background Information on ICCVAM and... tests. DATES: Nominations and test method data for the acute dermal and oral tests should be submitted...

  3. Performance of an automated electronic acute lung injury screening system in intensive care unit patients.

    Science.gov (United States)

    Koenig, Helen C; Finkel, Barbara B; Khalsa, Satjeet S; Lanken, Paul N; Prasad, Meeta; Urbani, Richard; Fuchs, Barry D

    2011-01-01

    Lung protective ventilation reduces mortality in patients with acute lung injury, but underrecognition of acute lung injury has limited its use. We recently validated an automated electronic acute lung injury surveillance system in patients with major trauma in a single intensive care unit. In this study, we assessed the system's performance as a prospective acute lung injury screening tool in a diverse population of intensive care unit patients. Patients were screened prospectively for acute lung injury over 21 wks by the automated system and by an experienced research coordinator who manually screened subjects for enrollment in Acute Respiratory Distress Syndrome Clinical Trials Network (ARDSNet) trials. Performance of the automated system was assessed by comparing its results with the manual screening process. Discordant results were adjudicated blindly by two physician reviewers. In addition, a sensitivity analysis using a range of assumptions was conducted to better estimate the system's performance. The Hospital of the University of Pennsylvania, an academic medical center and ARDSNet center (1994-2006). Intubated patients in medical and surgical intensive care units. None. Of 1270 patients screened, 84 were identified with acute lung injury (incidence of 6.6%). The automated screening system had a sensitivity of 97.6% (95% confidence interval, 96.8-98.4%) and a specificity of 97.6% (95% confidence interval, 96.8-98.4%). The manual screening algorithm had a sensitivity of 57.1% (95% confidence interval, 54.5-59.8%) and a specificity of 99.7% (95% confidence interval, 99.4-100%). Sensitivity analysis demonstrated a range for sensitivity of 75.0-97.6% of the automated system under varying assumptions. Under all assumptions, the automated system demonstrated higher sensitivity than and comparable specificity to the manual screening method. An automated electronic system identified patients with acute lung injury with high sensitivity and specificity in diverse

  4. 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...

  5. 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.

  6. Pembangunan Model Restaurant Management System

    OpenAIRE

    Fredy Jingga; Natalia Limantara

    2014-01-01

    Model design for Restaurant Management System aims to help in restaurant business process, where Restaurant Management System (RMS) help the waitress and chef could interact each other without paper limitation.  This Restaurant Management System Model develop using Agile Methodology and developed based on PHP Programming Langguage. The database management system is using MySQL. This web-based application model will enable the waitress and the chef to interact in realtime, from the time they a...

  7. Modelling of wastewater systems

    DEFF Research Database (Denmark)

    Bechmann, Henrik

    to analyze and quantify the effect of the Aeration Tank Settling (ATS) operating mode, which is used during rain events. Furthermore, the model is used to propose a control algorithm for the phase lengths during ATS operation. The models are mainly formulated as state space model in continuous time......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...... at modelling the fluxes in terms of the multiple correlation coefficient R2. The model of the SS concentrations in the aeration tanks of an alternating WWTP as well as in the effluent from the aeration tanks is a mass balance model based on measurements of SS in one aeration tank and in the common outlet...

  8. Evaluation of modified Alvarado scoring system and RIPASA scoring system as diagnostic tools of acute appendicitis.

    Science.gov (United States)

    Shuaib, Abdullah; Shuaib, Ali; Fakhra, Zainab; Marafi, Bader; Alsharaf, Khalid; Behbehani, Abdullah

    2017-01-01

    Acute appendicitis is the most common surgical condition presented in emergency departments worldwide. Clinical scoring systems, such as the Alvarado and modified Alvarado scoring systems, were developed with the goal of reducing the negative appendectomy rate to 5%-10%. The Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) scoring system was established in 2008 specifically for Asian populations. The aim of this study was to compare the modified Alvarado with the RIPASA scoring system in Kuwait population. This study included 180 patients who underwent appendectomies and were documented as having "acute appendicitis" or "abdominal pain" in the operating theatre logbook (unit B) from November 2014 to March 2016. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy, predicted negative appendectomy and receiver operating characteristic (ROC) curve of the modified Alvarado and RIPASA scoring systems were derived using SPSS statistical software. A total of 136 patients were included in this study according to our criteria. The cut-off threshold point of the modified Alvarado score was set at 7.0, which yielded a sensitivity of 82.8% and a specificity of 56%. The PPV was 89.3% and the NPV was 42.4%. The cut-off threshold point of the RIPASA score was set at 7.5, which yielded a 94.5% sensitivity and an 88% specificity. The PPV was 97.2% and the NPV was 78.5%. The predicted negative appendectomy rates were 10.7% and 2.2% for the modified Alvarado and RIPASA scoring systems, respectively. The negative appendectomy rate decreased significantly, from 18.4% to 10.7% for the modified Alvarado, and to 2.2% for the RIPASA scoring system, which was a significant difference (PAsian populations. It consists of 14 clinical parameters that can be obtained from a good patient history, clinical examination and laboratory investigations. The RIPASA scoring system is more accurate and specific than the modified Alvarado

  9. Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Musah, Sadiatu; Schlueter, Connie F.; Humphrey, David M. [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Powell, Karen S. [Research Resource Facilities, University of Louisville, Louisville, KY (United States); Roberts, Andrew M. [Department of Physiology, University of Louisville, Louisville, KY (United States); Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States)

    2017-01-15

    Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure–volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. - Highlights: • A novel rabbit model of chlorine-induced lung disease was developed.

  10. Modeling and estimating system availability

    International Nuclear Information System (INIS)

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

    1976-11-01

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

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Julia M. Post

    2018-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Chong MS

    2014-04-01

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

  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 delay...... in patients treated with fibrinolysis versus pPCI has not been assessed. We obtained data on system delay from the Danish Acute Myocardial Infarction-2 study, which randomized 1,572 patients to fibrinolysis or pPCI. The study end points were 30-day and 8-year mortality. The short system delays were associated...... with reduced absolute mortality in both the fibrinolysis group (3 hours, 11.5%; test for trend, p = 0.08) and pPCI group (3 hours, 7.7%; test for trend, p = 0.02). The lowest 30-day mortality was obtained with pPCI and a system delay of 1 to 2 hours (vs fibrinolysis within 3 hours was associated with a similar...

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. Derivation of a Predictive Model for Graft Loss Following Acute Kidney Injury in Kidney Transplant Recipients.

    Science.gov (United States)

    Molnar, Amber O; van Walraven, Carl; Fergusson, Dean; Garg, Amit X; Knoll, Greg

    2017-01-01

    Acute kidney injury (AKI) is common in the kidney transplant population. To derive a multivariable survival model that predicts time to graft loss following AKI. Retrospective cohort study using health care administrative and laboratory databases. Southwestern Ontario (1999-2013) and Ottawa, Ontario, Canada (1996-2013). We included first-time kidney only transplant recipients who had a hospitalization with AKI 6 months or greater following transplant. AKI was defined using the Acute Kidney Injury Network criteria (stage 1 or greater). The first episode of AKI was included in the analysis. Graft loss was defined by return to dialysis or repeat kidney transplant. We performed a competing risk survival regression analysis using the Fine and Gray method and modified the model into a simple point system. Graft loss with death as a competing event was the primary outcome of interest. A total of 315 kidney transplant recipients who had a hospitalization with AKI 6 months or greater following transplant were included. The median (interquartile range) follow-up time was 6.7 (3.3-10.3) years. Graft loss occurred in 27.6% of the cohort. The final model included 6 variables associated with an increased risk of graft loss: younger age, increased severity of AKI, failure to recover from AKI, lower baseline estimated glomerular filtration rate, increased time from kidney transplant to AKI admission, and receipt of a kidney from a deceased donor. The risk score had a concordance probability of 0.75 (95% confidence interval [CI], 0.69-0.82). The predicted 5-year risk of graft loss fell within the 95% CI of the observed risk more than 95% of the time. The CIs of the estimates were wide, and model overfitting is possible due to the limited sample size; the risk score requires validation to determine its clinical utility. Our prognostic risk score uses commonly available information to predict the risk of graft loss in kidney transplant patients hospitalized with AKI. If validated

  20. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

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

    1976-01-01

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

  1. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

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

    1976-09-01

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

  2. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

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

    1976-01-01

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

  3. ECONOMIC MODELING STOCKS CONTROL SYSTEM: SIMULATION MODEL

    OpenAIRE

    Климак, М.С.; Войтко, С.В.

    2016-01-01

    Considered theoretical and applied aspects of the development of simulation models to predictthe optimal development and production systems that create tangible products andservices. It isproved that theprocessof inventory control needs of economicandmathematical modeling in viewof thecomplexity of theoretical studies. A simulation model of stocks control that allows make managementdecisions with production logistics

  4. Synergistic anticonvulsant effects of pregabalin and amlodipine on acute seizure model of epilepsy in mice.

    Science.gov (United States)

    Qureshi, Itefaq Hussain; Riaz, Azra; Khan, Rafeeq Alam; Siddiqui, Afaq Ahmed

    2017-08-01

    Status epilepticus is a life threatening neurological medical emergency. It may cause serious damage to the brain and even death in many cases if not treated properly. There is limited choice of drugs for the short term and long term management of status epilepticus and the dugs recommended for status epilepticus possess various side effects. The present study was designed to investigate synergistic anticonvulsant effects of pregabalin with amlodipine on acute seizure model of epilepsy in mice. Pentylenetetrazole was used to induce acute seizures which mimic status epilepticus. Pregabalin and amlodipine were used in combination to evaluate synergistic anti-seizure effects on acute seizure model of epilepsy in mice. Diazepam and valproate were used as reference dugs. The acute anti-convulsive activity of pregabalin with amlodipine was evaluated in vivo by the chemical induced seizures and their anti-seizure effects were compared with pentylenetetrazole, reference drugs and to their individual effects. The anti-seizure effects of tested drugs were recorded in seconds on seizure characteristics such as latency of onset of threshold seizures, rearing and fallings and Hind limbs tonic extensions. The seizure protection and mortality to the animals exhibited by the drugs were recorded in percentage. Combination regimen of pregabalin with amlodipine exhibited dose dependent significant synergistic anticonvulsant effects on acute seizures which were superior to their individual effects and equivalent to reference drugs.

  5. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Gimenez, J.C.; Nasazzi, N.B.; Taja, M.R. [Comision Nacional de Energia Atomica, (Argentina); Nagle, C. [Centro de Educacion Medica e Investigaciones Clinicas (Argentina); Dubner, D. [Comision Nacional de Energia Atomica, (Argentina); Di Rizzio, C. [Academia Nacional de Medicina (Argentina)

    1992-07-01

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

  7. 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...

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

    International Nuclear Information System (INIS)

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

    1992-01-01

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

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

    Science.gov (United States)

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

  10. Regional pressure volume curves by electrical impedance tomography in a model of acute lung injury

    NARCIS (Netherlands)

    Kunst, P. W.; Böhm, S. H.; Vazquez de Anda, G.; Amato, M. B.; Lachmann, B.; Postmus, P. E.; de Vries, P. M.

    2000-01-01

    OBJECTIVE: A new noninvasive method, electrical impedance tomography (EIT), was used to make pressure-impedance (PI) curves in a lung lavage model of acute lung injury in pigs. The lower inflection point (LIP) and the upper deflection point (UDP) were determined from these curves and from the

  11. Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome.

    Science.gov (United States)

    Hagawane, T N; Gaikwad, R V; Kshirsagar, N A

    2016-05-01

    Despite advances in therapy and overall medical care, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) management remains a problem. Hence the objective of this study was to develop a rat model that mimics human ALI/ARDS. Four groups of Wistar rats, 48 per group were treated with (i) intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg) dissolved in normal saline (NS), (ii) intravenous (iv) oleic acid (OA) (250 μl/kg) suspension in bovine serum albumin (BSA), (iii) dual hit: IT LPS (2 mg/kg) dissolved in NS and iv OA (100 μl/kg) and (iv) control group: IT NS and iv BSA. From each group at set periods of time various investigations like chest x-rays, respiratory rate (RR), tidal volume (TV), total cell count, differential cell count, total protein count and cytokine levels in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio and histopathological examination were done. It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α) levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6) levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals) group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.

  12. Curcumin Prevents Acute Neuroinflammation and Long-Term Memory Impairment Induced by Systemic Lipopolysaccharide in Mice

    Directory of Open Access Journals (Sweden)

    Vincenzo Sorrenti

    2018-03-01

    Full Text Available Systemic lipopolysaccharide (LPS induces an acute inflammatory response in the central nervous system (CNS (“neuroinflammation” characterized by altered functions of microglial cells, the major resident immune cells of the CNS, and an increased inflammatory profile that can result in long-term neuronal cell damage and severe behavioral and cognitive consequences. Curcumin, a natural compound, exerts CNS anti-inflammatory and neuroprotective functions mainly after chronic treatment. However, its effect after acute treatment has not been well investigated. In the present study, we provide evidence that 50 mg/kg of curcumin, orally administered for 2 consecutive days before a single intraperitoneal injection of a high dose of LPS (5 mg/kg in young adult mice prevents the CNS immune response. Curcumin, able to enter brain tissue in biologically relevant concentrations, reduced acute and transient microglia activation, pro-inflammatory mediator production, and the behavioral symptoms of sickness. In addition, short-term treatment with curcumin, administered at the time of LPS challenge, anticipated the recovery from memory impairments observed 1 month after the inflammatory stimulus, when mice had completely recovered from the acute neuroinflammation. Together, these results suggest that the preventive effect of curcumin in inhibiting the acute effects of neuroinflammation could be of value in reducing the long-term consequences of brain inflammation, including cognitive deficits such as memory dysfunction.

  13. A European benchmarking system to evaluate in-hospital mortality rates in acute coronary syndrome: the EURHOBOP project.

    Science.gov (United States)

    Dégano, Irene R; Subirana, Isaac; Torre, Marina; Grau, María; Vila, Joan; Fusco, Danilo; Kirchberger, Inge; Ferrières, Jean; Malmivaara, Antti; Azevedo, Ana; Meisinger, Christa; Bongard, Vanina; Farmakis, Dimitros; Davoli, Marina; Häkkinen, Unto; Araújo, Carla; Lekakis, John; Elosua, Roberto; Marrugat, Jaume

    2015-03-01

    Hospital performance models in acute myocardial infarction (AMI) are useful to assess patient management. While models are available for individual countries, mainly US, cross-European performance models are lacking. Thus, we aimed to develop a system to benchmark European hospitals in AMI and percutaneous coronary intervention (PCI), based on predicted in-hospital mortality. We used the EURopean HOspital Benchmarking by Outcomes in ACS Processes (EURHOBOP) cohort to develop the models, which included 11,631 AMI patients and 8276 acute coronary syndrome (ACS) patients who underwent PCI. Models were validated with a cohort of 55,955 European ACS patients. Multilevel logistic regression was used to predict in-hospital mortality in European hospitals for AMI and PCI. Administrative and clinical models were constructed with patient- and hospital-level covariates, as well as hospital- and country-based random effects. Internal cross-validation and external validation showed good discrimination at the patient level and good calibration at the hospital level, based on the C-index (0.736-0.819) and the concordance correlation coefficient (55.4%-80.3%). Mortality ratios (MRs) showed excellent concordance between administrative and clinical models (97.5% for AMI and 91.6% for PCI). Exclusion of transfers and hospital stays ≤1day did not affect in-hospital mortality prediction in sensitivity analyses, as shown by MR concordance (80.9%-85.4%). Models were used to develop a benchmarking system to compare in-hospital mortality rates of European hospitals with similar characteristics. The developed system, based on the EURHOBOP models, is a simple and reliable tool to compare in-hospital mortality rates between European hospitals in AMI and PCI. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Acute Hendra virus infection: Analysis of the pathogenesis and passive antibody protection in the hamster model

    International Nuclear Information System (INIS)

    Guillaume, Vanessa; Wong, K. Thong; Looi, R.Y.; Georges-Courbot, Marie-Claude; Barrot, Laura; Buckland, Robin; Wild, T. Fabian; Horvat, Branka

    2009-01-01

    Hendra virus (HeV) and Nipah virus (NiV) are recently-emerged, closely related and highly pathogenic paramyxoviruses. We have analysed here the pathogenesis of the acute HeV infection using the new animal model, golden hamster (Mesocricetus auratus), which is highly susceptible to HeV infection. HeV-specific RNA and viral antigens were found in multiple organs and virus was isolated from different tissues. Dual pathogenic mechanism was observed: parenchymal infection in various organs, including the brain, with vasculitis and multinucleated syncytia in many blood vessels. Furthermore, monoclonal antibodies specific for the NiV fusion protein neutralized HeV in vitro and efficiently protected hamsters from HeV if given before infection. These results reveal the similarities between HeV and NiV pathogenesis, particularly in affecting both respiratory and neuronal system. They demonstrate that hamster presents a convenient novel animal model to study HeV infection, opening new perspectives to evaluate vaccine and therapeutic approaches against this emergent infectious disease.

  15. Murine model of acute myocarditis and cerebral cortical neuron edema induced by coxsackievirus B4

    Directory of Open Access Journals (Sweden)

    Zhao-Peng Dong

    2018-01-01

    Full Text Available Globally, coxsackievirus B4 (CV-B4 has been continuously isolated and evidence suggests an association with the development of pancreatitis and type I diabetes. In addition, CV-B4 is also associated with myocarditis and severe central nervous system (CNS complications, which remain poorly studied and understood. In the present study, we established an ICR mouse model of CV-B4 infection and examined whether CV-B4 infection resulted in a predisposition to myocarditis and CNS infection. We found high survival in both the treatment and control group, with no significant differences in clinical outcomes observed. However, pathological lesions were evident in both brain and heart tissue of the CV-B4-infected mice. In addition, high viral loads were found in the neural and cardiac tissues as early as 2 d postinfection. Expressions of IFN-γ and IL-6 in sera were significantly higher in CV-B4-infected mice compared to uninfected negative controls, suggesting the involvement of these cytokines in the development of histopathological lesions. Our murine model successfully reproduced the acute myocarditis and cerebral cortical neuron edema induced by CV-B4, and may be useful for the evaluation of vaccine candidates and potential antivirals against CV-B4 infection.

  16. [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.

  17. Latent Growth Modeling of nursing care dependency of acute neurological inpatients.

    Science.gov (United States)

    Piredda, M; Ghezzi, V; De Marinis, M G; Palese, A

    2015-01-01

    Longitudinal three-time point study, addressing how neurological adult patient care dependency varies from the admission time to the 3rd day of acute hospitalization. Nursing care dependency was measured with the Care Dependency Scale (CDS) and a Latent Growth Modeling approach was used to analyse the CDS trend in 124 neurosurgical and stroke inpatients. Care dependence followed a decreasing linear trend. Results can help nurse-managers planning an appropriate amount of nursing care for acute neurological patients during their initial stage of hospitalization. Further studies are needed aimed at investigating the determinants of nursing care dependence during the entire in-hospital stay.

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

    Science.gov (United States)

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

    2018-03-28

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

  19. Alvarado vs Lintula Scoring Systems in Acute Appendicitis

    African Journals Online (AJOL)

    communication. Clinicians attending to these patients were continuously appraised and trained on the two scoring systems to be compared including the cut off points for diagnosis. This was done by one author or a trained research assistant who was a qualified clinical officer. A written card with the two systems was placed ...

  20. Alvarado vs Lintula Scoring Systems in Acute Appendicitis | Ojuka ...

    African Journals Online (AJOL)

    The gold standard of diagnosis was histopathology. Data analysis was done using SPSS. The receiver operating characteristics, sensitivity, specificity, positive predictive values and negative predictive values of both scoring systems were then calculated for each of the scoring systems and compared between the two.

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2017-10-01

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

  3. 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.

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

    DEFF Research Database (Denmark)

    Taskinen, Mervi; Oskarsson, Trausti; Levinsen, Mette

    2017-01-01

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

  5. ”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.

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

    International Nuclear Information System (INIS)

    Gelmers, H.J.

    1984-01-01

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

  7. ASN reputation system model

    Science.gov (United States)

    Hutchinson, Steve; Erbacher, Robert F.

    2015-05-01

    Network security monitoring is currently challenged by its reliance on human analysts and the inability for tools to generate indications and warnings for previously unknown attacks. We propose a reputation system based on IP address set membership within the Autonomous System Number (ASN) system. Essentially, a metric generated based on the historic behavior, or misbehavior, of nodes within a given ASN can be used to predict future behavior and provide a mechanism to locate network activity requiring inspection. This will provide reinforcement of notifications and warnings and lead to inspection for ASNs known to be problematic even if initial inspection leads to interpretation of the event as innocuous. We developed proof of concept capabilities to generate the IP address to ASN set membership and analyze the impact of the results. These results clearly show that while some ASNs are one-offs with individual or small numbers of misbehaving IP addresses, there are definitive ASNs with a history of long term and wide spread misbehaving IP addresses. These ASNs with long histories are what we are especially interested in and will provide an additional correlation metric for the human analyst and lead to new tools to aid remediation of these IP address blocks.

  8. Scoring system to distinguish uncomplicated from complicated acute appendicitis

    NARCIS (Netherlands)

    Atema, J. J.; van Rossem, C. C.; Leeuwenburgh, M. M.; Stoker, J.; Boermeester, M. A.

    2015-01-01

    Non-operative management may be an alternative for uncomplicated appendicitis, but preoperative distinction between uncomplicated and complicated disease is challenging. This study aimed to develop a scoring system based on clinical and imaging features to distinguish uncomplicated from complicated

  9. Mouse models of acute and chronic hepacivirus infection

    DEFF Research Database (Denmark)

    Billerbeck, Eva; Wolfisberg, Raphael; Fahnøe, Ulrik

    2017-01-01

    An estimated 71 million people worldwide are infected with hepatitis C virus (HCV). The lack of small-animal models has impeded studies of antiviral immune mechanisms. Here we show that an HCV-related hepacivirus discovered in Norway rats can establish high-titer hepatotropic infections in labora...

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

    Science.gov (United States)

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

    2017-10-01

    To discuss the value of the Bedside Index for Severity in Acute Pancreatitis (BISAP), Modified Early Warning Score (MEWS), serum Ca2+, similarly hereinafter, and red cell distribution width (RDW) for predicting the severity grade of acute pancreatitis and to develop and verify a more accurate scoring system to predict the severity of AP. In 302 patients with AP, we calculated BISAP and MEWS scores and conducted regression analyses on the relationships of BISAP scoring, RDW, MEWS, and serum Ca2+ with the severity of AP using single-factor logistics. The variables with statistical significance in the single-factor logistic regression were used in a multi-factor logistic regression model; forward stepwise regression was used to screen variables and build a multi-factor prediction model. A receiver operating characteristic curve (ROC curve) was constructed, and the significance of multi- and single-factor prediction models in predicting the severity of AP using the area under the ROC curve (AUC) was evaluated. The internal validity of the model was verified through bootstrapping. Among 302 patients with AP, 209 had mild acute pancreatitis (MAP) and 93 had severe acute pancreatitis (SAP). According to single-factor logistic regression analysis, we found that BISAP, MEWS and serum Ca2+ are prediction indexes of the severity of AP (P-value0.05). The multi-factor logistic regression analysis showed that BISAP and serum Ca2+ are independent prediction indexes of AP severity (P-value0.05); BISAP is negatively related to serum Ca2+ (r=-0.330, P-valuemodel is as follows: ln()=7.306+1.151*BISAP-4.516*serum Ca2+. The predictive ability of each model for SAP follows the order of the combined BISAP and serum Ca2+ prediction model>Ca2+>BISAP. There is no statistical significance for the predictive ability of BISAP and serum Ca2+ (P-value>0.05); however, there is remarkable statistical significance for the predictive ability using the newly built prediction model as well as BISAP

  11. 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

  12. Mathematical Models of Human Hematopoiesis Following Acute Radiation Exposure

    Science.gov (United States)

    2014-05-01

    response of 11 subjects from Chernobyl 1986 . . . . . . 104 B.8 Chernobyl case studies: Platelet data . . . . . . . . . . . . . . . . . . . . . . 105 B...9 Chernobyl case studies: Granulocyte data . . . . . . . . . . . . . . . . . . . 106 B.10 Chernobyl case studies: Lymphocyte data...information for use in nuclear disaster preparedness planning. Understanding how biological systems change after radiation exposure provides insight on the

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

    Science.gov (United States)

    Papa, Anna; Papadopoulou, Elpida

    2018-04-01

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

  14. Serum Zinc Level and Its Correlation with Vesikari System Scoring in Acute Pediatric Diarrhea.

    Science.gov (United States)

    Eskander, Ayman E; Sherif, Lobna S; Nabih, Mohammad; Baroudy, Nevine R El; Marcos, Ghobrial C; Badawy, Ehsan A; Refay, Amira S El

    2017-08-15

    Diarrhea remains the most common infectious disease worldwide. Zinc has been studied extensively recently for its potential effect on prevention, control and treatment of acute diarrhoea. This study was designed to correlate the level of zinc with the severity of pediatric diarrhoea estimated by Vesikari Scoring System. The present study included 80 children aged two months to 30 months from those suffering from the acute diarrheal episode and admitted to Pediatric Hospital "Abo El Rish" Cairo University. Serum Zinc level was assessed by a colorimetric method with a spectrophotometer. Zinc deficiency was detected in 45 (56.2%) patient of the studied group Significant negative correlations were found between serum zinc level and severity of dehydration and duration of hospitalization (p Zinc level has an essential role in acute pediatric diarrhoea. Zinc therapy should be considered beside Oral rehydration salts (ORS) to achieve maximum impact on diarrheal diseases; clinical trials are recommended to support the zinc supplementation in developing countries.

  15. Stochastic Modelling of Energy Systems

    DEFF Research Database (Denmark)

    Andersen, Klaus Kaae

    2001-01-01

    is that the model structure has to be adequate for practical applications, such as system simulation, fault detection and diagnosis, and design of control strategies. This also reflects on the methods used for identification of the component models. The main result from this research is the identification......In this thesis dynamic models of typical components in Danish heating systems are considered. Emphasis is made on describing and evaluating mathematical methods for identification of such models, and on presentation of component models for practical applications. The thesis consists of seven...... research papers (case studies) together with a summary report. Each case study takes it's starting point in typical heating system components and both, the applied mathematical modelling methods and the application aspects, are considered. The summary report gives an introduction to the scope...

  16. Stress Erythropoiesis Model Systems.

    Science.gov (United States)

    Bennett, Laura F; Liao, Chang; Paulson, Robert F

    2018-01-01

    Bone marrow steady-state erythropoiesis maintains erythroid homeostasis throughout life. This process constantly generates new erythrocytes to replace the senescent erythrocytes that are removed by macrophages in the spleen. In contrast, anemic or hypoxic stress induces a physiological response designed to increase oxygen delivery to the tissues. Stress erythropoiesis is a key component of this response. It is best understood in mice where it is extramedullary occurring in the adult spleen and liver and in the fetal liver during development. Stress erythropoiesis utilizes progenitor cells and signals that are distinct from bone marrow steady-state erythropoiesis. Because of that observation many genes may play a role in stress erythropoiesis despite having no effect on steady-state erythropoiesis. In this chapter, we will discuss in vivo and in vitro techniques to study stress erythropoiesis in mice and how the in vitro culture system can be extended to study human stress erythropoiesis.

  17. 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.

  18. Distribution system modeling and analysis

    CERN Document Server

    Kersting, William H

    2001-01-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

  20. Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis

    NARCIS (Netherlands)

    Brohi, Karim; Cohen, Mitchell J.; Ganter, Michael T.; Schultz, Marcus J.; Levi, Marcel; Mackersie, Robert C.; Pittet, Jean-François

    2008-01-01

    BACKGROUND: Coagulopathy is present at admission in 25% of trauma patients, is associated with shock and a 5-fold increase in mortality. The coagulopathy has recently been associated with systemic activation of the protein C pathway. This study was designed to characterize the thrombotic, coagulant

  1. Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute myeloid leukemia models.

    Science.gov (United States)

    Portwood, Scott; Lal, Deepika; Hsu, Yung-Chun; Vargas, Rodrigo; Johnson, Megan K; Wetzler, Meir; Hart, Charles P; Wang, Eunice S

    2013-12-01

    Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm. Recent evidence has shown the bone marrow microenvironment in patients with AML to be intrinsically hypoxic. Adaptive cellular responses by leukemia cells to survive under low oxygenation also confer chemoresistance. We therefore asked whether therapeutic exploitation of marrow hypoxia via the hypoxia-activated nitrogen mustard prodrug, TH-302, could effectively inhibit AML growth. We assessed the effects of hypoxia and TH-302 on human AML cells, primary samples, and systemic xenograft models. We observed that human AML cells and primary AML colonies cultured under chronic hypoxia (1% O2, 72 hours) exhibited reduced sensitivity to cytarabine-induced apoptosis as compared with normoxic controls. TH-302 treatment resulted in dose- and hypoxia-dependent apoptosis and cell death in diverse AML cells. TH-302 preferentially decreased proliferation, reduced HIF-1α expression, induced cell-cycle arrest, and enhanced double-stranded DNA breaks in hypoxic AML cells. Hypoxia-induced reactive oxygen species by AML cells were also diminished. In systemic human AML xenografts (HEL, HL60), TH-302 [50 mg/kg intraperitoneally (i.p.) 5 times per week] inhibited disease progression and prolonged overall survival. TH-302 treatment reduced the number of hypoxic cells within leukemic bone marrows and was not associated with hematologic toxicities in nonleukemic or leukemic mice. Later initiation of TH-302 treatment in advanced AML disease was as effective as earlier TH-302 treatment in xenograft models. Our results establish the preclinical activity of TH-302 in AML and provide the rationale for further clinical studies of this and other hypoxia-activated agents for leukemia therapy. ©2013 AACR.

  2. 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.

  3. 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

  4. Model systems in photosynthesis research

    International Nuclear Information System (INIS)

    Katz, J.J.; Hindman, J.C.

    1981-01-01

    After a general discussion of model studies in photosynthesis research, three recently developed model systems are described. The current status of covalently linked chlorophyll pairs as models for P700 and P865 is first briefly reviewed. Mg-tris(pyrochlorophyllide)1,1,1-tris(hydroxymethyl) ethane triester in its folded configuration is then discussed as a rudimentary antenna-photoreaction center model. Finally, self-assembled chlorophyll systems that contain a mixture of monomeric, oligomeric and special pair chlorophyll are shown to have fluorescence emission characteristics that resemble thoe of intact Tribonema aequale at room temperature in that both show fluorescence emission at 675 and 695 nm. In the self-assembled systems the wavelength of the emitted fluorescence depends on the wavelength of excitation, arguing that energy transfer between different chlorophyll species in these systems may be more complex than previously suspected

  5. Mobility Models for Systems Evaluation

    Science.gov (United States)

    Musolesi, Mirco; Mascolo, Cecilia

    Mobility models are used to simulate and evaluate the performance of mobile wireless systems and the algorithms and protocols at the basis of them. The definition of realistic mobility models is one of the most critical and, at the same time, difficult aspects of the simulation of applications and systems designed for mobile environments. There are essentially two possible types of mobility patterns that can be used to evaluate mobile network protocols and algorithms by means of simulations: traces and synthetic models [130]. Traces are obtained by means of measurements of deployed systems and usually consist of logs of connectivity or location information, whereas synthetic models are mathematical models, such as sets of equations, which try to capture the movement of the devices.

  6. Stochastic Models of Polymer Systems

    Science.gov (United States)

    2016-01-01

    Distribution Unlimited Final Report: Stochastic Models of Polymer Systems The views, opinions and/or findings contained in this report are those of the...ADDRESS. Princeton University PO Box 0036 87 Prospect Avenue - 2nd floor Princeton, NJ 08544 -2020 14-Mar-2014 ABSTRACT Number of Papers published in...peer-reviewed journals: Number of Papers published in non peer-reviewed journals: Final Report: Stochastic Models of Polymer Systems Report Title

  7. Prophylactic radiotherapy for central nervous system in acute leukemias

    International Nuclear Information System (INIS)

    Faria, S.L.; Ferrigno, R.

    1994-01-01

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

  8. [Establishment of comprehensive prediction model of acute gastrointestinal injury classification of critically ill patients].

    Science.gov (United States)

    Wang, Yan; Wang, Jianrong; Liu, Weiwei; Zhang, Guangliang

    2018-03-25

    To develop the comprehensive prediction model of acute gastrointestinal injury (AGI) grades of critically ill patients. From April 2015 to November 2015, the binary channel gastrointestinal sounds (GIS) monitor system which has been developed and verified by the research group was used to gather and analyze the GIS of 60 consecutive critically ill patients who were admitted in Critical Care Medicine of Chinese PLA General Hospital. Also, the AGI grades (Grande I(-IIII(, the higher the level, the heavier the gastrointestinal dysfunction) were evaluated. Meanwhile, the clinical data and physiological and biochemical indexes of included patients were collected and recorded daily, including illness severity score (APACHE II( score, consisting of the acute physiology score, age grade and chronic health evaluation), sequential organ failure assessment (SOFA score, including respiration, coagulation, liver, cardioascular, central nervous system and kidney) and Glasgow coma scale (GCS); body mass index, blood lactate and glucose, and treatment details (including mechanical ventilation, sedatives, vasoactive drugs, enteral nutrition, etc.) Then principal component analysis was performed on the significantly correlated GIS (five indexes of gastrointestinal sounds were found to be negatively correlated with AGI grades, which included the number, percentage of time, mean power, maximum power and maximum time of GIS wave from the channel located at the stomach) and clinical factors after standardization. The top 5 post-normalized main components were selected for back-propagation (BP) neural network training, to establish comprehensive AGI grades models of critically ill patients based on the neural network model. The 60 patients aged 19 to 98 (mean 54.6) years and included 42 males (70.0%). There were 22 cases of multiple fractures, 15 cases of severe infection, 7 cases of cervical vertebral fracture, 7 cases of aortic repair, 5 cases of post-toxicosis and 4 cases of cerebral

  9. 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.

  10. 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.

  11. Acute and prolonged complement activation in the central nervous system during herpes simplex encephalitis.

    Science.gov (United States)

    Eriksson, Charlotta E; Studahl, Marie; Bergström, Tomas

    2016-06-15

    Herpes simplex encephalitis (HSE) is characterized by a pronounced inflammatory activity in the central nervous system (CNS). Here, we investigated the acute and prolonged complement system activity in HSE patients, by using enzyme-linked immunosorbent assays (ELISAs) for numerous complement components (C). We found increased cerebrospinal fluid concentrations of C3a, C3b, C5 and C5a in HSE patients compared with healthy controls. C3a and C5a concentrations remained increased also compared with patient controls. Our results conclude that the complement system is activated in CNS during HSE in the acute phase, and interestingly also in later stages supporting previous reports of prolonged inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-07-01

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

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

    International Nuclear Information System (INIS)

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

    1995-01-01

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

  14. Development of a Multicomponent Prediction Model for Acute Esophagitis in Lung Cancer Patients Receiving Chemoradiotherapy

    International Nuclear Information System (INIS)

    De Ruyck, Kim; Sabbe, Nick; Oberije, Cary; Vandecasteele, Katrien; Thas, Olivier; De Ruysscher, Dirk; Lambin, Phillipe; Van Meerbeeck, Jan; De Neve, Wilfried; Thierens, Hubert

    2011-01-01

    Purpose: To construct a model for the prediction of acute esophagitis in lung cancer patients receiving chemoradiotherapy by combining clinical data, treatment parameters, and genotyping profile. Patients and Methods: Data were available for 273 lung cancer patients treated with curative chemoradiotherapy. Clinical data included gender, age, World Health Organization performance score, nicotine use, diabetes, chronic disease, tumor type, tumor stage, lymph node stage, tumor location, and medical center. Treatment parameters included chemotherapy, surgery, radiotherapy technique, tumor dose, mean fractionation size, mean and maximal esophageal dose, and overall treatment time. A total of 332 genetic polymorphisms were considered in 112 candidate genes. The predicting model was achieved by lasso logistic regression for predictor selection, followed by classic logistic regression for unbiased estimation of the coefficients. Performance of the model was expressed as the area under the curve of the receiver operating characteristic and as the false-negative rate in the optimal point on the receiver operating characteristic curve. Results: A total of 110 patients (40%) developed acute esophagitis Grade ≥2 (Common Terminology Criteria for Adverse Events v3.0). The final model contained chemotherapy treatment, lymph node stage, mean esophageal dose, gender, overall treatment time, radiotherapy technique, rs2302535 (EGFR), rs16930129 (ENG), rs1131877 (TRAF3), and rs2230528 (ITGB2). The area under the curve was 0.87, and the false-negative rate was 16%. Conclusion: Prediction of acute esophagitis can be improved by combining clinical, treatment, and genetic factors. A multicomponent prediction model for acute esophagitis with a sensitivity of 84% was constructed with two clinical parameters, four treatment parameters, and four genetic polymorphisms.

  15. 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.

  16. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  18. 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...

  19. 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...

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-04-15

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

  2. 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

  3. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

  5. 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...

  6. Pembangunan Model Restaurant Management System

    Directory of Open Access Journals (Sweden)

    Fredy Jingga

    2014-12-01

    Full Text Available Model design for Restaurant Management System aims to help in restaurant business process, where Restaurant Management System (RMS help the waitress and chef could interact each other without paper limitation.  This Restaurant Management System Model develop using Agile Methodology and developed based on PHP Programming Langguage. The database management system is using MySQL. This web-based application model will enable the waitress and the chef to interact in realtime, from the time they accept the customer order until the chef could know what to cook and checklist for the waitress wheter the order is fullfill or not, until the cahsier that will calculate the bill and the payment that they accep from the customer.

  7. 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

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

    Science.gov (United States)

    Mody, Bhavesh Surendra

    2011-07-01

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

  9. 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

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

  12. Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.

    Science.gov (United States)

    Hartman, Kira G; Bortner, James D; Falk, Gary W; Ginsberg, Gregory G; Jhala, Nirag; Yu, Jian; Martín, Martín G; Rustgi, Anil K; Lynch, John P

    2014-09-01

    Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. © 2014 by the Society for Experimental Biology and Medicine.

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

    DEFF Research Database (Denmark)

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

    1993-01-01

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

  14. Models of complex attitude systems

    DEFF Research Database (Denmark)

    Sørensen, Bjarne Taulo

    search algorithms and structural equation models. The results suggest that evaluative judgments of the importance of production system attributes are generated in a schematic manner, driven by personal value orientations. The effect of personal value orientations was strong and largely unmediated...... that evaluative affect propagates through the system in such a way that the system becomes evaluatively consistent and operates as a schema for the generation of evaluative judgments. In the empirical part of the paper, the causal structure of an attitude system from which people derive their evaluations of pork......Existing research on public attitudes towards agricultural production systems is largely descriptive, abstracting from the processes through which members of the general public generate their evaluations of such systems. The present paper adopts a systems perspective on such evaluations...

  15. The urgent need for a harmonized severity scoring system for acute allergic reactions

    DEFF Research Database (Denmark)

    Muraro, Antonella; Fernandez-Rivas, Montserrat; Beyer, Kirsten

    2018-01-01

    The accurate assessment and communication of the severity of acute allergic reactions is important to patients, clinicians, researchers, the food industry, public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating...... of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical...... the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach and none has been validated...

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

    Directory of Open Access Journals (Sweden)

    Elan Gorshein

    2018-01-01

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

  17. 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.

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

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

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

  19. The hematopoietic system of the acute radiation syndrome reconvalescents in post-accidental period

    International Nuclear Information System (INIS)

    Klimenko, V.; Dyagil, I.; Yukhimuk, L.; Bilko, N.; Bebeshko, V.; Klimenko, S.; Oberenko, O.

    1996-01-01

    The state of hemopoietic system has been studied since 1986 up to now in 145 patients who had acute radiation sickness after the Chernobyl accident. We studied clinical, morpho functional, histological, ultrastructural, biophysical, cultural, cytochemical indexes of the hematopoietic elements. The connection between hemopoietic microenvironment and hemopoiesis state was put up. The realization of the hematological disorders as myelodysplastic syndrome testified the most important problem in future

  20. System Convergence in Transport Modelling

    DEFF Research Database (Denmark)

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

    2010-01-01

    A fundamental premise of most applied transport models is the existence and uniqueness of an equilibrium solution that balances demand x(t) and supply t(x). The demand consists of the people that travel in the transport system and on the defined network, whereas the supply consists of the resulting...... level-of-service attributes (e.g., travel time and cost) offered to travellers. An important source of complexity is the congestion, which causes increasing demand to affect travel time in a non-linear way. Transport models most often involve separate models for traffic assignment and demand modelling...... iterating between a route-choice (demand) model and a time-flow (supply) model. It is generally recognised that a simple iteration scheme where the level-of-service level is fed directly to the route-choice and vice versa may exhibit an unstable pattern and lead to cyclic unstable solutions. It can be shown...

  1. 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.

  2. Derivation and External Validation of Prediction Models for Advanced Chronic Kidney Disease Following Acute Kidney Injury.

    Science.gov (United States)

    James, Matthew T; Pannu, Neesh; Hemmelgarn, Brenda R; Austin, Peter C; Tan, Zhi; McArthur, Eric; Manns, Braden J; Tonelli, Marcello; Wald, Ron; Quinn, Robert R; Ravani, Pietro; Garg, Amit X

    2017-11-14

    Some patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up. To derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease. Data from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013). Demographic, laboratory, and comorbidity variables measured prior to discharge. Advanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year. The participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher

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

    Science.gov (United States)

    Fahy, Brenda G

    2009-02-01

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

  4. 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

    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. 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. 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. PMID:26894217

  6. Model Reduction of Hybrid Systems

    DEFF Research Database (Denmark)

    Shaker, Hamid Reza

    gramians. Generalized gramians are the solutions to the observability and controllability Lyapunov inequalities. In the first framework the projection matrices are found based on the common generalized gramians. This framework preserves the stability of the original switched system for all switching...... is guaranteed to be preserved for arbitrary switching signal. To compute the common generalized gramians linear matrix inequalities (LMI’s) need to be solved. These LMI’s are not always feasible. In order to solve the problem of conservatism, the second framework is presented. In this method the projection......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...

  7. Numerical Modeling of Microelectrochemical Systems

    DEFF Research Database (Denmark)

    Adesokan, Bolaji James

    incorporates the finite size of ionic species in the transport equation. The model presents a more appropriate boundary conditions which describe the modified Butler-Volmer reaction kinetics and account for the surface capacitance of the thin electric double layer. We also have found analytical solution...... at the electrode in a microelectrochemical system. In our analysis, we account for the finite size properties of ions in the mass and the charge transport of ionic species in an electrochemical system. This term characterizes the saturation of the ionic species close to the electrode surface. We then analyse......The PhD dissertation is concerned with mathematical modeling and simulation of electrochemical systems. The first three chapters of the thesis consist of the introductory part, the model development chapter and the chapter on the summary of the main results. The remaining three chapters report...

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

    Directory of Open Access Journals (Sweden)

    Lu Ke

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

  9. 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.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  11. Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling.

    Science.gov (United States)

    Dick, Thomas E; Molkov, Yaroslav I; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J; Doyle, John; Scheff, Jeremy D; Calvano, Steve E; Androulakis, Ioannis P; An, Gary; Vodovotz, Yoram

    2012-01-01

    Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma.

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

    Energy Technology Data Exchange (ETDEWEB)

    Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States); Uehara, Takeki; Kato, Yuki [Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka (Japan); Kono, Hiroshi [First Department of Surgery, University of Yamanashi, Yamanashi (Japan); Bataller, Ramon [Division of Gastroenterology & Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC (United States); Rusyn, Ivan, E-mail: irusyn@tamu.edu [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States)

    2016-11-01

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

  13. 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.

  14. Systemic Lupus Erythematosus, Radiotherapy, and the Risk of Acute and Chronic Toxicity: The Mayo Clinic Experience

    International Nuclear Information System (INIS)

    Pinn, Melva E.; Gold, Douglas G. M.; Petersen, Ivy A.; Osborn, Thomas G.; Brown, Paul D.; Miller, Robert C.

    2008-01-01

    Purpose: To determine the acute and chronic toxic effects of radiotherapy in patients with systemic lupus erythematosus (SLE). Methods and Materials: Medical records of 21 consecutive patients with SLE, who had received 34 courses of external beam radiotherapy and one low-dose-rate prostate implant, were retrospectively reviewed. Patients with discoid lupus erythematosus were excluded. Results: Median survival was 2.3 years and median follow-up 5.6 years. Eight (42%) of 19 patients evaluable for acute toxicity during radiotherapy experienced acute toxicity of Grade 1 or greater, and 4 (21%) had acute toxicity of Grade 3 or greater. The 5- and 10-year incidence of chronic toxicity of Grade 1 or greater was 45% (95% confidence interval [CI], 22-72%) and 56% (95% CI, 28-81%), respectively. The 5- and 10-year incidence of chronic toxicity of Grade 3 or greater was 28% (95% CI, 18-60%) and 40% (95% CI, 16-72%), respectively. Univariate analysis showed that chronic toxicity of Grade 1 or greater correlated with SLE renal involvement (p < 0.006) and possibly with the presence of five or more American Rheumatism Association criteria (p < 0.053). Chronic toxicity of Grade 3 or greater correlated with an absence of photosensitivity (p < 0.02), absence of arthritis (p < 0.03), and presence of a malar rash (p < 0.04). Conclusions: The risk of acute and chronic toxicity in patients with SLE who received radiotherapy was moderate but was not prohibitive of the use of radiotherapy. Patients with more advanced SLE may be at increased risk for chronic toxicity

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

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, So-Young; Kim, In-One; Kim, Young-Il; Lee, Kyoung Ho; Lee, Min Woo; Youn, Byung Jae; Kim, Woo Sun; Yeon, Kyung Mo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2008-04-15

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

  16. St George Acute Care Team: the local variant of crisis resolution model of care.

    Science.gov (United States)

    Cupina, Denise D; Wand, Anne P F; Phelan, Emma; Atkin, Rona

    2016-10-01

    The objective of this study was to describe functioning and clinical activities of the St George Acute Care Team and how it compares to the typical crisis resolution model of care. Descriptive data including demographics, sources of referral, type of clinical intervention, length of stay, diagnoses and outcomes were collected from records of all patients who were discharged from the team during a 10 week period. There were 677 referrals. The team's functions consisted of post-discharge follow-up (31%), triage and intake (30%), case management support (23%) and acute community based assessment and treatment (16%). The average length of stay was 5 days. The majority of patients were diagnosed with a mood (23%) or a psychotic (25%) disorder. Points of contrast to other reported crisis resolution teams include shorter length of stay, relatively less focus on direct clinical assessment and more telephone follow-up and triage. St George Acute Care Team provides a variety of clinical activities. The focus has shifted away from the original model of crisis resolution care to meet local and governmental requirements. © The Royal Australian and New Zealand College of Psychiatrists 2016.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  18. Establishment and application of rat model of acute β-irradiated skin injury

    International Nuclear Information System (INIS)

    Shen Guoliang; Lu Xing'an; Tang Jun; Wang Xiuzhen; Wu Shiliang; Tian Ye

    2006-01-01

    Objective: To establish an experimental rat model of acute β-irradiated skin injury and to study the effects of superoxide dismutase (SOD) on wound healing. Methods: Areas of buttock skin (20 mm x 40 mm) of 40 male SD rats were irradiated with 45 Gy/β-rays generated by linear accelerator, and then the forty rats were divided into two groups randomly: treatment group administrated with SOD (n=20) and control group administrated with normal saline (NS) (n=20). The wound healing time and rate were observed. The pathological changes were observed by light microscopy. The expressions of VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) were determined by SP immunohistochemical method. Results: The deep second-degree burns was observed following 45 Gy irradiation. The wound healing time in treatment group was shorter than that of the control group (P<0.05). Strongly positive (+ + +) expression of VEGF, bFGF in treatment group and positive (+ +) expression of VEGF, bFGF in the control group were observed 6 weeks, 7 weeks and 8 weeks after the irradiation, while only weakly positive (+) expressions of VEGF and bFGF in both groups 4 weeks, 5 weeks and 9 weeks after the irradiation. Conclusions: The wound model of acute β-irradiated skin injury in rat was established and used in study of the effect of medicine on wound healing. SOD can promote the wound healing of acute β-irradiated skin injury. (authors)

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

    Directory of Open Access Journals (Sweden)

    Nikolay G. Vengerovich

    2017-01-01

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

  20. Turboelectric Distributed Propulsion System Modelling

    OpenAIRE

    Liu, Chengyuan

    2013-01-01

    The Blended-Wing-Body is a conceptual aircraft design with rear-mounted, over wing engines. Turboelectric distributed propulsion system with boundary layer ingestion has been considered for this aircraft. It uses electricity to transmit power from the core turbine to the fans, therefore dramatically increases bypass ratio to reduce fuel consumption and noise. This dissertation presents methods on designing the TeDP system, evaluating effects of boundary layer ingestion, modelling engine perfo...

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

    Directory of Open Access Journals (Sweden)

    2005-08-01

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

  2. Lentinan: hematopoietic, immunological, and efficacy studies in a syngeneic model of acute myeloid leukemia.

    Science.gov (United States)

    McCormack, Emmet; Skavland, Jørn; Mujic, Maja; Bruserud, Øystein; Gjertsen, Bjørn Tore

    2010-01-01

    Lentinan, a beta-glucan nutritional supplement isolated from the shitake mushroom (Lentula edodes), is a biological response modifier with immunostimulatory properties. Concomitantly, the role of beta-glucans as chemoimmunotherapeutic in a number of solid cancers has been widely documented. We investigated the effects of nutritional grade lentinan upon BN rats and in a preclinical syngeneic model of acute myeloid leukemia. BN rats supplemented daily with lentinan exhibited weight gains, increased white blood cells, monocytes, and circulating cytotoxic T-cells; and had a reduction in anti-inflammatory cytokines IL-4, IL-10, and additionally IL-6. Lentinan treatment of BN rats with BNML leukemia resulted in improved cage-side health and reduced cachexia in the terminal stage of this aggressive disease. Combination of lentinan with standards of care in acute myeloid leukemia, idarubicin, and cytarabine increased average survival compared with monotherapy and reduced cachexia. These results indicate that nutritional supplementation of cancer patients with lentinan should be further investigated.

  3. 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

    : The models developed here show very good discrimination and calibration, confirmed in independent datasets, and suggest that many patients undergoing transplantation based on existing criteria might have survived with medical management alone. The role and indications for emergency liver transplantation......BACKGROUND: Early, accurate prediction of survival is central to management of patients with paracetamol-induced acute liver failure to identify those needing emergency liver transplantation. Current prognostic tools are confounded by recent improvements in outcome independent of emergency liver...... transplantation, and constrained by static binary outcome prediction. We aimed to develop a simple prognostic tool to reflect current outcomes and generate a dynamic updated estimation of risk of death. METHODS: Patients with paracetamol-induced acute liver failure managed at intensive care units in the UK...

  4. [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.

  5. Video distribution system cost model

    Science.gov (United States)

    Gershkoff, I.; Haspert, J. K.; Morgenstern, B.

    1980-01-01

    A cost model that can be used to systematically identify the costs of procuring and operating satellite linked communications systems is described. The user defines a network configuration by specifying the location of each participating site, the interconnection requirements, and the transmission paths available for the uplink (studio to satellite), downlink (satellite to audience), and voice talkback (between audience and studio) segments of the network. The model uses this information to calculate the least expensive signal distribution path for each participating site. Cost estimates are broken downy by capital, installation, lease, operations and maintenance. The design of the model permits flexibility in specifying network and cost structure.

  6. Information Systems Outsourcing Relationship Model

    Directory of Open Access Journals (Sweden)

    Richard Flemming

    2007-09-01

    Full Text Available Increasing attention is being paid to what determines the success of an information systems outsourcing arrangement. The current research aims to provide an improved understanding of the factors influencing the outcome of an information systems outsourcing relationship and to provide a preliminary validation of an extended outsourcing relationship model by interviews with information systems outsourcing professionals in both the client and vendor of a major Australian outsourcing relationship. It also investigates whether the client and the vendor perceive the relationship differently and if so, how they perceive it differently and whether the two perspectives are interrelated.

  7. New medical diagnoses and length of stay of acutely unwell older patients: Implications for funding models.

    Science.gov (United States)

    Basic, David; Khoo, Angela

    2015-09-01

    To examine the relationship between newly made medical diagnoses and length of stay (LOS) of acutely unwell older patients. Consecutive patients admitted under the care of four geriatricians were randomly allocated to a model development sample (n = 937) or a model validation sample (n = 855). Cox regression was used to model LOS. Variables considered for inclusion in the development model were established risk factors for LOS and univariate predictors from our dataset. Variables selected in the development sample were tested in the validation sample. A median of five new medical diagnoses were made during a median LOS of 10 days. New diagnoses predicted an increased LOS (hazard ratio 0.90, 95% confidence interval 0.88-0.92). Other significant predictors of increased LOS in both samples were malnutrition and frailty. Identification of new medical diagnoses may have implications for Diagnosis Related Groups-based funding models and may improve the care of older people. © 2015 AJA Inc.

  8. Aggregate modeling of manufacturing systems

    NARCIS (Netherlands)

    Lefeber, A.A.J.; Armbruster, H.D.; Kempf, K.G.; Keskinocak, P.; Uzsoy, R.

    2011-01-01

    In this chapter we will present three approaches to model manufacturing systems in an aggregate way leading to fast and effective (i.e., scalable) simulations that allow the development of simulation tools for rapid exploration of different production scenarios in a factory as well as in a whole

  9. Ventilation system in fire modelization

    International Nuclear Information System (INIS)

    Cordero Garcia, S.

    2012-01-01

    There is a model of fire in an enclosure formed by two rooms. In one of them, it will cause the fire and check how the system of ventilation in different configurations responds. In addition, the behavior of selected targets, which will be a configuration of cables similar to those found in nuclear power stations will be analyzed.

  10. 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...

  11. Aggregate modeling of manufacturing systems

    NARCIS (Netherlands)

    Lefeber, A.A.J.; Armbruster, H.D.

    2007-01-01

    In this report we will present three approaches to model manufacturing systems in an aggregate way leading to fast and effective (i.e., scalable) simulations that allow the development of simulation tools for rapid exploration of different production scenarios in a factory as well as in a whole

  12. 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 introduction and an overview of the papers published. Then an introduction to basic concepts in hydrology along with a description of hydrological data is given. Finally an introduction to stochastic modelling is given. The second part contains the research papers. In the research papers the stochastic methods...... are described, as at the time of publication these methods represent new contribution to hydrology. The second part also contains additional description of software used and a brief introduction to stiff systems. The system in one of the papers is stiff....

  13. Thermodynamic modeling of complex systems

    DEFF Research Database (Denmark)

    Liang, Xiaodong

    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...... is successfully applied to model the phase behaviour of water, chemical and hydrocarbon (oil) containing systems with newly developed pure component parameters for water and chemicals and characterization procedures for petroleum fluids. The performance of the PCSAFT EOS on liquid-liquid equilibria of water...... with hydrocarbons has been under debate for some vii years. An interactive step-wise procedure is proposed to fit the model parameters for small associating fluids by taking the liquid-liquid equilibrium data into account. It is still far away from a simple task to apply PC-SAFT in routine PVT simulations and phase...

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

    Science.gov (United States)

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

    2017-12-01

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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    G. O. Lezhenko

    2017-10-01

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

  17. Cotangent Models for Integrable Systems

    Science.gov (United States)

    Kiesenhofer, Anna; Miranda, Eva

    2017-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Burra Patrizia

    2012-07-01

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

  19. 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

  20. Graph modeling systems and methods

    Science.gov (United States)

    Neergaard, Mike

    2015-10-13

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

  1. Air conditioning systems as non-infectious health hazards inducing acute respiratory symptoms.

    Science.gov (United States)

    Gerber, Alexander; Fischer, Axel; Willig, Karl-Heinz; Groneberg, David A

    2006-04-01

    Chronic and acute exposure to toxic aerosols belongs to frequent causes of airway diseases. However, asthma attacks due to long-distance inhalative exposure to organic solvents, transmitted via an air condition system, have not been reported so far. The present case illustrates the possibility of air conditioning systems as non-infectious health hazards in occupational medicine. So far, only infectious diseases such as legionella pneumophila pneumonia have commonly been associated to air-conditioning exposures but physicians should be alert to the potential of transmission of toxic volatile substances via air conditioning systems. In view of the events of the 11th of September 2001 with a growing danger of large building terrorism which may even use air conditioning systems to transmit toxins, facility management security staff should be alerted to possible non-infectious toxic health hazards arising from air-conditioning systems.

  2. 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

  3. Social isolation alters central nervous system monoamine content in prairie voles following acute restraint.

    Science.gov (United States)

    McNeal, Neal; Anderson, Eden M; Moenk, Deirdre; Trahanas, Diane; Matuszewich, Leslie; Grippo, Angela J

    2018-04-01

    Animal models have shown that social isolation and other forms of social stress lead to depressive- and anxiety-relevant behaviors, as well as neuroendocrine and physiological dysfunction. The goal of this study was to investigate the effects of prior social isolation on neurotransmitter content following acute restraint in prairie voles. Animals were either paired with a same-sex sibling or isolated for 4 weeks. Plasma adrenal hormones and ex vivo tissue concentrations of monoamine neurotransmitters and their metabolites were measured following an acute restraint stressor in all animals. Isolated prairie voles displayed significantly increased circulating adrenocorticotropic hormone levels, as well as elevated serotonin and dopamine levels in the hypothalamus, and potentially decreased levels of serotonin in the frontal cortex. However, no group differences in monoamine levels were observed in the hippocampus or raphe. The results suggest that social stress may bias monoamine neurotransmission and stress hormone function to subsequent acute stressors, such as restraint. These findings improve our understanding of the neurobiological mechanisms underlying the consequences of social stress.

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

    Science.gov (United States)

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

    2013-12-01

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

  5. An evidence-based approach to case management model selection for an acute care facility: is there really a preferred model?

    Science.gov (United States)

    Terra, Sandra M

    2007-01-01

    This research seeks to determine whether there is adequate evidence-based justification for selection of one acute care case management model over another. Acute Inpatient Hospital. This article presents a systematic review of published case management literature, resulting in classification specific to terms of level of evidence. This review examines the best available evidence in an effort to select an acute care case management model. Although no single case management model can be identified as preferred, it is clear that adequate evidence-based literature exists to acknowledge key factors driving the acute care model and to form a foundation for the efficacy of hospital case management practice. Although no single case management model can be identified as preferred, this systematic review demonstrates that adequate evidence-based literature exists to acknowledge key factors driving the acute care model and forming a foundation for the efficacy of hospital case management practice. Distinctive aspects of case management frameworks can be used to guide the development of an acute care case management model. The study illustrates: * The effectiveness of case management when there is direct patient contact by the case manager regardless of disease condition: not only does the quality of care increase but also length of stay (LOS) decreases, care is defragmented, and both patient and physician satisfaction can increase. * The preferred case management models result in measurable outcomes that can directly relate to, and demonstrate alignment with, organizational strategy. * Acute care management programs reduce cost and LOS, and improve outcomes. * An integrated case management program that includes social workers, as well as nursing, is the most effective acute care management model. * The successful case management model will recognize physicians, as well as patients, as valued customers with whom partnership can positively affect financial outcomes in terms of

  6. Discrete modelling of drapery systems

    Science.gov (United States)

    Thoeni, Klaus; Giacomini, Anna

    2016-04-01

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

  7. Quantum models of classical systems

    International Nuclear Information System (INIS)

    Hájíček, P

    2015-01-01

    Quantum statistical methods that are commonly used for the derivation of classical thermodynamic properties are extended to classical mechanical properties. The usual assumption that every real motion of a classical mechanical system is represented by a sharp trajectory is not testable and is replaced by a class of fuzzy models, the so-called maximum entropy (ME) packets. The fuzzier are the compared classical and quantum ME packets, the better seems to be the match between their dynamical trajectories. Classical and quantum models of a stiff rod will be constructed to illustrate the resulting unified quantum theory of thermodynamic and mechanical properties. (paper)

  8. 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. Copyright © 2016. Published by Elsevier Ireland Ltd.

  9. 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

  10. 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.

  11. Evaluation of three physiologically based pharmacokinetic (PBPK) modeling tools for emergency risk assessment after acute dichloromethane exposure

    NARCIS (Netherlands)

    Boerleider, R. Z.; Olie, J. D N; van Eijkeren, J. C H; Bos, P. M J; Hof, B. G H; de Vries, I.; Bessems, J. G M; Meulenbelt, J.; Hunault, C. C.

    2015-01-01

    Introduction: Physiologically based pharmacokinetic (PBPK) models may be useful in emergency risk assessment, after acute exposure to chemicals, such as dichloromethane (DCM). We evaluated the applicability of three PBPK models for human risk assessment following a single exposure to DCM: one model

  12. 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

    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......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...

  13. The hairless guinea-pig as a model for treatment of acute irritation in humans

    DEFF Research Database (Denmark)

    Andersen, F; Hedegaard, K; Fullerton, A

    2006-01-01

    BACKGROUND: The effect of six skin care formulations on experimentally induced acute irritation was studied in hairless guinea-pigs (HLGP) and in human volunteers (HV). The formulations were a basic cream, a carbomer cream and four modifications of the carbomer cream, containing either 10...... and colorimetry. RESULTS: The glycerol cream was the only product showing effects potentially better than no treatment in HV. CONCLUSION: The HLGP was too sensitive an animal model as a predictor for effect in humans. There was no difference in efficacy of the formulations against the two different irritants...

  14. Models of the venous system

    DEFF Research Database (Denmark)

    Mehlsen, J

    2000-01-01

    Cardiac output is largely controlled by venous return, the driving force of which is the energy remaining at the postcapillary venous site. This force is influenced by forces acting close to the right atrium, and internally or externally upon the veins along their course. Analogue models of the v......Cardiac output is largely controlled by venous return, the driving force of which is the energy remaining at the postcapillary venous site. This force is influenced by forces acting close to the right atrium, and internally or externally upon the veins along their course. Analogue models...... of the venous system require at least three elements: a resistor, a capacitor and an inductor, with the latter being of more importance in the venous than in the arterial system. Non-linearities must be considered in pressure/flow relations in the small venules, during venous collapse, or low flow conditions...

  15. 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...... of the Cu/ZnO nanoparticles is highly relevant to industrial methanol synthesis for which the direct interaction of Cu and ZnO nanocrystals synergistically boost the catalytic activity. The dynamical behavior of the nanoparticles under reducing and oxidizing environments were studied by means of ex situ X......-ray Photoelectron Electron Spectroscopy (XPS) and in situ Transmission Electron Microscopy (TEM). The surface composition of the nanoparticles changes reversibly as the nanoparticles exposed to cycles of high-pressure oxidation and reduction (200 mbar). Furthermore, the presence of metallic Zn is observed by XPS...

  16. Pharmacokinetic/pharmacodynamic modeling of cardiac toxicity in human acute overdoses: utility and limitations.

    Science.gov (United States)

    Mégarbane, Bruno; Aslani, Arsia Amir; Deye, Nicolas; Baud, Frédéric J

    2008-05-01

    Hypotension, cardiac failure, QT interval prolongation, dysrhythmias, and conduction disturbances are common complications of overdoses with cardiotoxicants. Pharmacokinetic/pharmacodynamic (PK/PD) relationships are useful to assess diagnosis, prognosis, and treatment efficacy in acute poisonings. To review the utility and limits of PK/PD studies of cardiac toxicity. Discussion of various models, mainly those obtained in digitalis, cyanide, venlafaxine and citalopram poisonings. A sigmoidal E(max) model appears adequate to represent the PK/PD relationships in cardiotoxic poisonings. PK/PD correlations investigate the discrepancies between the time course of the effect magnitude and its evolving concentrations. They may help in understanding the mechanisms of occurrence as well as disappearance of a cardiotoxic effect. When data are sparse, population-based PK/PD modeling using computer-intensive algorithms is helpful to estimate population mean values of PK parameters as well as their individual variability. Further PK/PD studies are needed in medical toxicology to allow understanding of the meaning of blood toxicant concentration in acute poisonings and thus improve management.

  17. 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.

  18. Double-hit mouse model of cigarette smoke priming for acute lung injury.

    Science.gov (United States)

    Sakhatskyy, Pavlo; Wang, Zhengke; Borgas, Diana; Lomas-Neira, Joanne; Chen, Yaping; Ayala, Alfred; Rounds, Sharon; Lu, Qing

    2017-01-01

    Epidemiological studies indicate that cigarette smoking (CS) increases the risk and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The mechanism is not understood, at least in part because of lack of animal models that reproduce the key features of the CS priming process. In this study, using two strains of mice, we characterized a double-hit mouse model of ALI induced by CS priming of injury caused by lipopolysaccharide (LPS). C57BL/6 and AKR mice were preexposed to CS briefly (3 h) or subacutely (3 wk) before intratracheal instillation of LPS and ALI was assessed 18 h after LPS administration by measuring lung static compliance, lung edema, vascular permeability, inflammation, and alveolar apoptosis. We found that as little as 3 h of exposure to CS enhanced LPS-induced ALI in both strains of mice. Similar exacerbating effects were observed after 3 wk of preexposure to CS. However, there was a strain difference in susceptibility to CS priming for ALI, with a greater effect in AKR mice. The key features we observed suggest that 3 wk of CS preexposure of AKR mice is a reproducible, clinically relevant animal model that is useful for studying mechanisms and treatment of CS priming for a second-hit-induced ALI. Our data also support the concept that increased susceptibility to ALI/ARDS is an important adverse health consequence of CS exposure that needs to be taken into consideration when treating critically ill individuals.

  19. Aerial Measuring System Sensor Modeling

    International Nuclear Information System (INIS)

    Detwiler, R.S.

    2002-01-01

    This project deals with the modeling the Aerial Measuring System (AMS) fixed-wing and rotary-wing sensor systems, which are critical U.S. Department of Energy's National Nuclear Security Administration (NNSA) Consequence Management assets. The fixed-wing system is critical in detecting lost or stolen radiography or medical sources, or mixed fission products as from a commercial power plant release at high flying altitudes. The helicopter is typically used at lower altitudes to determine ground contamination, such as in measuring americium from a plutonium ground dispersal during a cleanup. Since the sensitivity of these instruments as a function of altitude is crucial in estimating detection limits of various ground contaminations and necessary count times, a characterization of their sensitivity as a function of altitude and energy is needed. Experimental data at altitude as well as laboratory benchmarks is important to insure that the strong effects of air attenuation are modeled correctly. The modeling presented here is the first attempt at such a characterization of the equipment for flying altitudes. The sodium iodide (NaI) sensors utilized with these systems were characterized using the Monte Carlo N-Particle code (MCNP) developed at Los Alamos National Laboratory. For the fixed wing system, calculations modeled the spectral response for the 3-element NaI detector pod and High-Purity Germanium (HPGe) detector, in the relevant energy range of 50 keV to 3 MeV. NaI detector responses were simulated for both point and distributed surface sources as a function of gamma energy and flying altitude. For point sources, photopeak efficiencies were calculated for a zero radial distance and an offset equal to the altitude. For distributed sources approximating an infinite plane, gross count efficiencies were calculated and normalized to a uniform surface deposition of 1 microCi/m 2 . The helicopter calculations modeled the transport of americium-241 ( 241 Am) as this is

  20. Dose-effective investigation of intraarterial r-Sak in canine model with acute cerebral infarctions

    International Nuclear Information System (INIS)

    Liu Sheng; Shi Haibin; Zhang Peng; Wang Chenghu; Zhou Chunguo; Li Linsun

    2007-01-01

    Objective: To compare the effect and complications of intraarterial thrombolysis with different doses of recombinant-staphylokinase (r-Sak) in canine model with acute cerebral infarction, and then to find out the most properly appropriate effective dose. Methods: The model with left cerebral embolism was established with interventional technique in 24 beagle adult dogs. They were randomly divided into 4 groups including control group(saline, 10 ml), group of low dose(r-Sak, 5 000 u/kg), middle dose(r-Sak, 10 000 u/kg) and high dose(r-Sak, 20 000 u/kg). Angiography and intraarterial thrombolysis were performed within 30 minutes after the embolization. Microcatheter was superselectively inserted into left carotid artery. Five hour's later with a repeated angiography at half, 1 and 2 hours after thrombolysis to observe the recanalization. Blood samples were collected at a series of time pre-and post-thrombolysis to test the plasma levels of PT, APTT and D-dimer. These canines were sacrificed, and their cerebri were taken out for pathologic study by the end of 24 hours. Results: The rates of efficacy within 2 hours after thrombolysis were 10.0% (1/10) in control group, 40.0% (4/10) in low dose group, 90.9% (10/11) in middle dose group and 100% (9/9) in high dose group. The rates of complete recanalization were 0, 10% (1/10), 36.4% (4/11) and 66.7% (6/9), correspondingly and respectively. There were statistically obvious differences between the 3 groups (P 0.05). Death occurred in 1 canine(high dose group) within 24 hours after thrombolysis with hemorrhagic lesion in parietal lobe of brain. No other severe complications ocurred. Conclusions: (1) Intraarterial thrombolysis with r-Sak within 5 hours after onset of thrombosis is effective and feasible. Intraarterial r-Sak shows strong thrombolytic effect for white thrombus including a few platelets. There is relative high rate of recanalization with no less than 10 000U/kg of r-Sak but accompanied with high risk of

  1. Modeling fuel cell stack systems

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J H [Los Alamos National Lab., Los Alamos, NM (United States); Lalk, T R [Dept. of Mech. Eng., Texas A and M Univ., College Station, TX (United States)

    1998-06-15

    A technique for modeling fuel cell stacks is presented along with the results from an investigation designed to test the validity of the technique. The technique was specifically designed so that models developed using it can be used to determine the fundamental thermal-physical behavior of a fuel cell stack for any operating and design configuration. Such models would be useful tools for investigating fuel cell power system parameters. The modeling technique can be applied to any type of fuel cell stack for which performance data is available for a laboratory scale single cell. Use of the technique is demonstrated by generating sample results for a model of a Proton Exchange Membrane Fuel Cell (PEMFC) stack consisting of 125 cells each with an active area of 150 cm{sup 2}. A PEMFC stack was also used in the verification investigation. This stack consisted of four cells, each with an active area of 50 cm{sup 2}. Results from the verification investigation indicate that models developed using the technique are capable of accurately predicting fuel cell stack performance. (orig.)

  2. 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...

  3. Component Reification in Systems Modelling

    DEFF Research Database (Denmark)

    Bendisposto, Jens; Hallerstede, Stefan

    When modelling concurrent or distributed systems in Event-B, we often obtain models where the structure of the connected components is specified by constants. Their behaviour is specified by the non-deterministic choice of event parameters for events that operate on shared variables. From a certain......? These components may still refer to shared variables. Events of these components should not refer to the constants specifying the structure. The non-deterministic choice between these components should not be via parameters. We say the components are reified. We need to address how the reified components get...... reflected into the original model. This reflection should indicate the constraints on how to connect the components....

  4. 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...

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

    Directory of Open Access Journals (Sweden)

    Chao-Hui Yang

    2017-10-01

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

  6. Models of hot stellar systems

    International Nuclear Information System (INIS)

    Van Albada, T.S.

    1986-01-01

    Elliptical galaxies consist almost entirely of stars. Sites of recent star formation are rare, and most stars are believed to be several billion years old, perhaps as old as the Universe itself (--10/sup 10/ yrs). Stellar motions in ellipticals show a modest amount of circulation about the center of the system, but most support against the force of gravity is provided by random motions; for this reason ellipticals are called 'hot' stellar systems. Spiral galaxies usually also contain an appreciable amount of gas (--10%, mainly atomic hydrogen) and new stars are continually being formed out of this gas, especially in the spiral arms. In contrast to ellipticals, support against gravity in spiral galaxies comes almost entirely from rotation; random motions of the stars with respect to rotation are small. Consequently, spiral galaxies are called 'cold' stellar systems. Other than in hot systems, in cold systems the collective response of stars to variations in the force field is an essential part of the dynamics. The present overview is limited to mathematical models of hot systems. Computational methods are also discussed

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

    Science.gov (United States)

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

    2018-01-07

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

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

    Science.gov (United States)

    Sylvia, Kristyn E; Demas, Gregory E

    2018-03-01

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

  10. Aerial measuring system sensor modeling

    International Nuclear Information System (INIS)

    Detwiler, Rebecca

    2002-01-01

    The AMS fixed-wing and rotary-wing systems are critical National Nuclear Security Administration (NNSA) Emergency Response assets. This project is principally focused on the characterization of the sensors utilized with these systems via radiation transport calculations. The Monte Carlo N-Particle code (MCNP) which has been developed at Los Alamos National Laboratory was used to model the detector response of the AMS fixed wing and helicopter systems. To validate the calculations, benchmark measurements were made for simple source-detector configurations. The fixed-wing system is an important tool in response to incidents involving the release of mixed fission products (a commercial power reactor release), the threat or actual explosion of a Radiological Dispersal Device, and the loss or theft of a large industrial source (a radiography source). Calculations modeled the spectral response for the sensors contained, a 3-element NaI detector pod and HpGe detector, in the relevant energy range of 50 keV to 3 MeV. NaI detector responses were simulated for both point and distributed surface sources as a function of gamma energy and flying altitude. For point sources, photo-peak efficiencies were calculated for a zero radial distance and an offset equal to the altitude. For distributed sources approximating infinite plane, gross count efficiencies were calculated and normalized to a uniform surface deposition of 1 C i/m2

  11. Predictive validity of the Hendrich fall risk model II in an acute geriatric unit.

    Science.gov (United States)

    Ivziku, Dhurata; Matarese, Maria; Pedone, Claudio

    2011-04-01

    Falls are the most common adverse events reported in acute care hospitals, and older patients are the most likely to fall. The risk of falling cannot be completely eliminated, but it can be reduced through the implementation of a fall prevention program. A major evidence-based intervention to prevent falls has been the use of fall-risk assessment tools. Many tools have been increasingly developed in recent years, but most instruments have not been investigated regarding reliability, validity and clinical usefulness. This study intends to evaluate the predictive validity and inter-rater reliability of Hendrich fall risk model II (HFRM II) in order to identify older patients at risk of falling in geriatric units and recommend its use in clinical practice. A prospective descriptive design was used. The study was carried out in a geriatric acute care unit of an Italian University hospital. All over 65 years old patients consecutively admitted to a geriatric acute care unit of an Italian University hospital over 8-month period were enrolled. The patients enrolled were screened for the falls risk by nurses with the HFRM II within 24h of admission. The falls occurring during the patient's hospital stay were registered. Inter-rater reliability, area under the ROC curve, sensitivity, specificity, positive and negative predictive values and time for the administration were evaluated. 179 elderly patients were included. The inter-rater reliability was 0.87 (95% CI 0.71-1.00). The administration time was about 1min. The most frequently reported risk factors were depression, incontinence, vertigo. Sensitivity and specificity were respectively 86% and 43%. The optimal cut-off score for screening at risk patients was 5 with an area under the ROC curve of 0.72. The risk factors more strongly associated with falls were confusion and depression. As falls of older patients are a common problem in acute care settings it is necessary that the nurses use specific validate and reliable

  12. 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

  13. Validation of Embedded System Verification Models

    NARCIS (Netherlands)

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

    The result of a model-based requirements verification shows that the model of a system satisfies (or not) formalised system requirements. The verification result is correct only if the model represents the system adequately. No matter what modelling technique we use, what precedes the model

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  15. Drug delivery system of basic fibroblast growth factor using gelatin hydrogel for restoration of acute vocal fold scar.

    Science.gov (United States)

    Kobayashi, Toshiki; Mizuta, Masanobu; Hiwatashi, Nao; Kishimoto, Yo; Nakamura, Tatsuo; Kanemaru, Shin-Ichi; Hirano, Shigeru

    2017-02-01

    There continue to be therapeutic challenges in the management of vocal fold scarring. We previously showed that basic fibroblast growth factor (bFGF) injection has therapeutic potential for vocal fold scarring. However, the working time of bFGF is relatively short, and multiple injections were required in many cases to obtain the regenerative effect. An efficacious delivery system for bFGF has yet to be established. We designed a method of sustained drug delivery system (DDS) of bFGF by using a gelatin hydrogel. Hydrogel has been developed for targeted delivery and controlled release of bFGF. Hydrogel of the particle type is also injectable and commercially available. The current study aims to investigate the effects of a single injection of bFGF-DDS on acute vocal fold scarring using a canine model. Vocal folds from eight beagles were unilaterally scarred by stripping the lamina propria. One month later, hydrogels (0.5ml) containing 10μg of bFGF were injected into the scarred vocal folds of four beagles (FGF-hydrogel group). Saline (0.5ml) was injected into the other four beagles (sham group). Vibratory and histological examination of excised larynges was performed 5 months after treatment. Comparative analysis between the current data and our previous data with repeated injection of bFGF solution was also completed. Vibratory examination demonstrated significantly improved vibration in the bFGF hydrogel-treated group. Histological examination of the bFGF hydrogel group showed restoration of hyaluronic acid in the lamina propria as compared to sham. Comparison between the DDS system and our previous bFGF solution injection indicated better effects of the DDS system on vibratory amplitude. A single injection of bFGF hydrogel has regenerative effects on acute vocal fold scarring, which is at least similar to repeated injection of bFGF solution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Effect of laser wavelength and protein solder concentration on acute tissue repair using laser welding: initial results in a canine ureter model.

    Science.gov (United States)

    Wright, E J; Poppas, D P

    1997-01-01

    Successful tissue approximation can be performed using low power laser energy combined with human albumin solder. In vitro studies were undertaken to investigate the acute repair strengths achieved using different laser wavelengths. Furthermore, we evaluated the change in repair strength with that resulted from changes in protein solder concentration. Intraluminal bursting pressure following ureterotomy repair was measured for the following laser wavelengths: 532, 808, 1,320, 2,100, and 10,600 nm. The tissue absorption characteristics of the 808-nm diode and the KTP-532-nm lasers required the addition of the exogenous chromophores indocyanine green and fluorescein, respectively. A 40% human albumin solder was incorporated in the repair of a 1.0-cm longitudinal defect in the canine ureter. Following determination of an optimal welding wavelength, human albumin solder of varying concentrations (25%, 38%, 45%, and 50%) were prepared and tested. The 1,320-nm YAG laser achieved the highest acute bursting pressure and was the most effective in this model. Of the concentrations of albumin tested, 50% human albumin yielded the greatest bursting pressures. We conclude that of the laser wavelengths evaluated, the 1,320-nm YAG achieves the strongest tissue weld in the acute ex vivo dog ureter model. In addition, when this laser system is used, the acute strength of a photothermal weld appears to be directly proportional to the concentration of human albumin solder in the range of 25 to 50%.

  17. Mathematical Modeling of Constrained Hamiltonian Systems

    NARCIS (Netherlands)

    Schaft, A.J. van der; Maschke, B.M.

    1995-01-01

    Network modelling of unconstrained energy conserving physical systems leads to an intrinsic generalized Hamiltonian formulation of the dynamics. Constrained energy conserving physical systems are directly modelled as implicit Hamiltonian systems with regard to a generalized Dirac structure on the

  18. A mouse model for MERS coronavirus-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Cockrell, Adam S; Yount, Boyd L; Scobey, Trevor; Jensen, Kara; Douglas, Madeline; Beall, Anne; Tang, Xian-Chun; Marasco, Wayne A; Heise, Mark T; Baric, Ralph S

    2016-11-28

    Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibit pathology consistent with the late stages of ARDS, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small-animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR-Cas9 gene editing to modify the mouse genome to encode two amino acids (positions 288 and 330) that match the human sequence in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV infection and replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs and evoked symptoms indicative of severe ARDS, including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary haemorrhage and pathological signs indicative of end-stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected the engineered mice against MERS-CoV-induced ARDS.

  19. 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.

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

    International Nuclear Information System (INIS)

    Kai, M.; Ban, N.

    2002-01-01

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

  1. Systems modeling and simulation applications for critical care medicine

    Science.gov (United States)

    2012-01-01

    Critical care delivery is a complex, expensive, error prone, medical specialty and remains the focal point of major improvement efforts in healthcare delivery. Various modeling and simulation techniques offer unique opportunities to better understand the interactions between clinical physiology and care delivery. The novel insights gained from the systems perspective can then be used to develop and test new treatment strategies and make critical care delivery more efficient and effective. However, modeling and simulation applications in critical care remain underutilized. This article provides an overview of major computer-based simulation techniques as applied to critical care medicine. We provide three application examples of different simulation techniques, including a) pathophysiological model of acute lung injury, b) process modeling of critical care delivery, and c) an agent-based model to study interaction between pathophysiology and healthcare delivery. Finally, we identify certain challenges to, and opportunities for, future research in the area. PMID:22703718

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

    Science.gov (United States)

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

    2012-06-15

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

  3. Acute Systemic Complications of Convulsive Status Epilepticus-A Systematic Review.

    Science.gov (United States)

    Sutter, Raoul; Dittrich, Tolga; Semmlack, Saskia; Rüegg, Stephan; Marsch, Stephan; Kaplan, Peter W

    2018-01-01

    Status epilepticus is a neurologic emergency with high morbidity and mortality requiring neurointensive care and treatment of systemic complications. This systematic review compiles the current literature on acute systemic complications of generalized convulsive status epilepticus in adults and their immediate clinical impact along with recommendations for optimal neurointensive care. We searched PubMed, Medline, Embase, and the Cochrane library for articles published between 1960 and 2016 and reporting on systemic complications of convulsive status epilepticus. All identified studies were screened for eligibility by two independent reviewers. Key data were extracted using standardized data collection forms. Thirty-two of 3,046 screened articles were included. Acute manifestations and complications reported in association with generalized convulsive status epilepticus can affect all organ systems fueling complex cascades and multiple organ interactions. Most reported complications result from generalized excessive muscle contractions that increase body temperature and serum potassium levels and may interfere with proper and coordinated function of respiratory muscles followed by hypoxia and respiratory acidosis. Increased plasma catecholamines can cause a decay of skeletal muscle cells and cardiac function, including stress cardiomyopathy. Systemic complications are often underestimated or misinterpreted as they may mimic underlying causes of generalized convulsive status epilepticus or treatment-related adverse events. Management of generalized convulsive status epilepticus should center on the administration of antiseizure drugs, treatment of the underlying causes, and the attendant systemic consequences to prevent secondary seizure-related injuries. Heightened awareness, systematic clinical assessment, and diagnostic workup and management based on the proposed algorithm are advocated as they are keys to optimal outcome.

  4. Cognitive models embedded in system simulation models

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  5. 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

  6. Modelling of data acquisition systems

    International Nuclear Information System (INIS)

    Buono, S.; Gaponenko, I.; Jones, R.; Mapelli, L.; Mornacchi, G.; Prigent, D.; Sanchez-Corral, E.; Spiwoks, R.; Skiadelli, M.; Ambrosini, G.

    1994-01-01

    The RD13 project was approved in April 1991 for the development of a scalable data taking system suitable to host various LHC studies. One of its goals is to use simulations as a tool for understanding, evaluating, and constructing different configurations of such data acquisition (DAQ) systems. The RD13 project has developed a modelling framework for this purpose. It is based on MODSIM II, an object-oriented, discrete-event simulation language. A library of DAQ components allows to describe a variety of DAQ architectures and different hardware options in a modular and scalable way. A graphical user interface (GUI) is used to do easy configuration, initialization and on-line monitoring of the simulation program. A tracing facility is used to do flexible off-line analysis of a trace file written at run-time

  7. Sirc-cvs cytotoxicity test: an alternative for predicting rodent acute systemic toxicity.

    Science.gov (United States)

    Kitagaki, Masato; Wakuri, Shinobu; Hirota, Morihiko; Tanaka, Noriho; Itagaki, Hiroshi

    2006-10-01

    An in vitro crystal violet staining method using the rabbit cornea-derived cell line (SIRC-CVS) has been developed as an alternative to predict acute systemic toxicity in rodents. Seventy-nine chemicals, the in vitro cytotoxicity of which was already reported by the Multicenter Evaluation of In vitro Toxicity (MEIC) and ICCVAM/ECVAM, were selected as test compounds. The cells were incubated with the chemicals for 72 hrs and the IC(50) and IC(35) values (microg/mL) were obtained. The results were compared to the in vivo (rat or mouse) "most toxic" oral, intraperitoneal, subcutaneous and intravenous LD(50) values (mg/kg) taken from the RTECS database for each of the chemicals by using Pearson's correlation statistics. The following parameters were calculated: accuracy, sensitivity, specificity, prevalence, positive predictability, and negative predictability. Good linear correlations (Pearson's coefficient; r>0.6) were observed between either the IC(50) or the IC(35) values and all the LD(50) values. Among them, a statistically significant high correlation (r=0.8102, p50) values and the oral LD(50) values. By using the cut-off concentrations of 2,000 mg/kg (LD(50)) and 4,225 microg/mL (IC(50)), no false negatives were observed, and the accuracy was 84.8%. From this, it is concluded that this method could be used to predict the acute systemic toxicity potential of chemicals in rodents.

  8. Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system.

    Science.gov (United States)

    Pfeifer, Philippe; Tüscher, Oliver; Buchholz, Hans Georg; Gründer, Gerhard; Vernaleken, Ingo; Paulzen, Michael; Zimmermann, Ulrich S; Maus, Stephan; Lieb, Klaus; Eggermann, Thomas; Fehr, Christoph; Schreckenberger, Mathias

    2017-09-01

    Investigations on the acute effects of alcohol in the human mesolimbic dopamine D 2 /D 3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D 2 /D 3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D 2 /D 3 receptor ligand [ 18 F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D 2 /D 3 binding potential. Twenty-four healthy male μ-opioid receptor (OPRM1)118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BP ND ) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BP ND was observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BP ND in extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p = 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p = 0.001)). The acute alcohol effects on the D 2 /D 3 dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D 2 /D 3 receptors may hint at an addiction relevant trait. © 2016 Society for the Study of Addiction.

  9. Performance of a Mobile Phone App-Based Participatory Syndromic Surveillance System for Acute Febrile Illness and Acute Gastroenteritis in Rural Guatemala.

    Science.gov (United States)

    Olson, Daniel; Lamb, Molly; Lopez, Maria Renee; Colborn, Kathryn; Paniagua-Avila, Alejandra; Zacarias, Alma; Zambrano-Perilla, Ricardo; Rodríguez-Castro, Sergio Ricardo; Cordon-Rosales, Celia; Asturias, Edwin Jose

    2017-11-09

    With their increasing availability in resource-limited settings, mobile phones may provide an important tool for participatory syndromic surveillance, in which users provide symptom data directly into a centralized database. We studied the performance of a mobile phone app-based participatory syndromic surveillance system for collecting syndromic data (acute febrile illness and acute gastroenteritis) to detect dengue virus and norovirus on a cohort of children living in a low-resource and rural area of Guatemala. Randomized households were provided with a mobile phone and asked to submit weekly reports using a symptom diary app (Vigilant-e). Participants reporting acute febrile illness or acute gastroenteritis answered additional questions using a decision-tree algorithm and were subsequently visited at home by a study nurse who performed a second interview and collected samples for dengue virus if confirmed acute febrile illness and norovirus if acute gastroenteritis. We analyzed risk factors associated with decreased self-reporting of syndromic data using the Vigilant-e app and evaluated strategies to improve self-reporting. We also assessed agreement between self-report and nurse-collected data obtained during home visits. From April 2015 to June 2016, 469 children in 207 households provided 471 person-years of observation. Mean weekly symptom reporting rate was 78% (range 58%-89%). Households with a poor (mobile phones for text messaging at study enrollment (61%, 35/57 vs 76.7%, 115/150; RR 0.6, 95% CI 0.4-0.9), and were less likely to access care at the local public clinic (35%, 20/57 vs 67.3%, 101/150; RR 0.4, 95% CI 0.2-0.6). Parents of female enrolled participants were more likely to have low response rate (57.1%, 84/147 vs 43.8%, 141/322; RR 1.4, 95% CI 1.1-1.9). Several external factors (cellular tower collapse, contentious elections) were associated with periods of decreased reporting. Poor response rate (mobile phone app-based participatory syndromic

  10. A Mathematical Model of Forager Loss in Honeybee Colonies Infested with Varroa destructor and the Acute Bee Paralysis Virus.

    Science.gov (United States)

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

    2017-06-01

    We incorporate a mathematical model of Varroa destructor and the Acute Bee Paralysis Virus with an existing model for a honeybee colony, in which the bee population is divided into hive bees and forager bees based on tasks performed in the colony. The model is a system of five ordinary differential equations with dependent variables: uninfected hive bees, uninfected forager bees, infected hive bees, virus-free mites and virus-carrying mites. The interplay between forager loss and disease infestation is studied. We study the stability of the disease-free equilibrium of the bee-mite-virus model and observe that the disease cannot be fought off in the absence of varroacide treatment. However, the disease-free equilibrium can be stable if the treatment is strong enough and also if the virus-carrying mites become virus-free at a rate faster than the mite birth rate. The critical forager loss due to homing failure, above which the colony fails, is calculated using simulation experiments for disease-free, treated and untreated mite-infested, and treated virus-infested colonies. A virus-infested colony without varroacide treatment fails regardless of the forager mortality rate.

  11. A Biomathematical Model of Lymphopoiesis and Its Application to Acute and Chronic Irradiation Assessment

    Science.gov (United States)

    Hu, Shaowen; Cucinotta, Francis A.

    2010-01-01

    After the events of September 11, 2001, there is an increasing concern of the occurrence of radiological terrorism that may result in significant casualties in densely populated areas. Much effort has been made to establish various biomarkers to rapidly assess radiation dose in mass-casualty and population-monitoring scenarios, which are demanded for effective medical management and treatment of the exposed victims. Among these the count of lymphocytes in peripheral blood and their depletion kinetics are the most important early indicators of the severity of the radiation injury. In this study, we examine a biomathematical model of lymphopoiesis which has been successfully utilized to simulate and interpret experimental data of acute and chronic irradiations on rodents [1]. With revised parameters for humans, we find this model can reproduce several sets of clinical lymphocyte data of accident victims over a wide range of absorbed doses. In addition, the absolute lymphocyte counts and the depletion rate constants calculated by this model also show good correlation with the Guskova formula and the Goans model, the two empirical tools which have been widely recognized for early estimation of the exposed dose after radiation accidents [2]. We also use the model to analyze the hematological data of the Techa River residents which were exposed to chronic low-dose irradiation during 1950-1956 [3]. This model can serve as a computational tool in radiation accident management, military operations involving nuclear warfare, radiation therapy, and space radiation risk assessment.

  12. Anticonvulsant profile of a balanced ketogenic diet in acute mouse seizure models.

    Science.gov (United States)

    Samala, Ramakrishna; Willis, Sarah; Borges, Karin

    2008-10-01

    Anticonvulsant effects of the ketogenic diet (KD) have been reported in the mouse, although previous studies did not control for intake of vitamins, minerals and antioxidants. The aim of this study was to examine the effects of balanced ketogenic and control diets in acute mouse seizure models. The behavior in four mouse seizure models, plasma d-beta-hydroxybutyrate (d-BHB) and glucose levels were determined after feeding control diet, 4:1 and 6:1 KDs with matched vitamins, minerals and antioxidants. Feeding 4:1 and 6:1 KDs ad lib to 3-week-old (adolescent) mice resulted in 1.2-2.2mM d-BHB in plasma, but did not consistently change glucose levels. The 6:1 KD reproducibly elevated the CC50 (current that initiates seizures in 50% mice tested) in the 6-Hz model after 14 days of feeding to adolescent CD1 mice. Higher plasma d-BHB levels correlated with anticonvulsant effects. Despite ketosis, no consistent anticonvulsant effects of KDs were found in the fluorothyl or pentylenetetrazole CD1 mouse models. The 4:1 KD was neither anticonvulsant nor neuroprotective in hippocampus in the C3H mouse kainate model. Taken together, the KD's anticonvulsant effect was limited to the 6-Hz model, required chronic feeding with 6:1 fat content, and was independent from lowering plasma glucose.

  13. Can the measurement of brachial artery flow-mediated dilation be applied to the acute exercise model?

    Directory of Open Access Journals (Sweden)

    Harris Ryan A

    2007-11-01

    Full Text Available Abstract The measurement of flow-mediated dilation using high-resolution ultrasound has been utilized extensively in interventional trials evaluating the salutary effect of drugs and lifestyle modifications (i.e. diet or exercise training on endothelial function; however, until recently researchers have not used flow-mediated dilation to examine the role of a single bout of exercise on vascular function. Utilizing the acute exercise model can be advantageous as it allows for an efficient manipulation of exercise variables (i.e. mode, intensity, duration, etc. and permits greater experimental control of confounding variables. Given that the application of flow-mediated dilation in the acute exercise paradigm is expanding, the purpose of this review is to discuss methodological and physiological factors pertinent to flow-mediated dilation in the context of acute exercise. Although the scientific rationale for evaluating endothelial function in response to acute exercise is sound, few concerns warrant attention when interpreting flow-mediated dilation data following acute exercise. The following questions will be addressed in the present review: Does the measurement of flow-mediated dilation influence subsequent serial measures of flow-mediated dilation? Do we need to account for diurnal variation? Is there an optimal time to measure post-exercise flow-mediated dilation? Is the post-exercise flow-mediated dilation reproducible? How is flow-mediated dilation interpreted considering the hemodynamic and sympathetic changes associated with acute exercise? Can the measurement of endothelial-independent dilation affect the exercise? Evidence exists to support the methodological appropriateness for employing flow-mediated dilation in the acute exercise model; however, further research is warranted to clarify its interpretation following acute exercise.

  14. 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.

  15. Safety assessment of VHTR hydrogen production system against fire, explosion and acute toxicity

    International Nuclear Information System (INIS)

    Murakami, Tomoyuki; Nishihara, Tetsuo; Kunitomi, Kazuhiko

    2008-01-01

    The Japan Atomic Energy Agency has been developing a nuclear hydrogen production system by using heat from the Very High Temperature Reactor (VHTR). This system will handle a large amount of combustible gas and toxic gas. The risk from fire, explosion and acute toxic exposure caused by an accident involving chemical material release in a hydrogen production system is assessed. It is important to ensure the safety of the nuclear plant, and the risks for public health should be sufficiently small. This report provides the basic policy for the safety evaluation in cases of accident involving fire, explosion and toxic material release in a hydrogen production system. Preliminary safety analysis of a commercial-sized VHTR hydrogen production system, GTHTR300C, is performed. This analysis provides us with useful information on the separation distance between a nuclear plant and a hydrogen production system and a prospect that an accident in a hydrogen production system does not significantly increase the risks of the public. (author)

  16. Logical Analysis of Data (LAD model for the early diagnosis of acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Hoehn Gerard

    2008-07-01

    Full Text Available Abstract Background Strokes are a leading cause of morbidity and the first cause of adult disability in the United States. Currently, no biomarkers are being used clinically to diagnose acute ischemic stroke. A diagnostic test using a blood sample from a patient would potentially be beneficial in treating the disease. Results A classification approach is described for differentiating between proteomic samples of stroke patients and controls, and a second novel predictive model is developed for predicting the severity of stroke as measured by the National Institutes of Health Stroke Scale (NIHSS. The models were constructed by applying the Logical Analysis of Data (LAD methodology to the mass peak profiles of 48 stroke patients and 32 controls. The classification model was shown to have an accuracy of 75% when tested on an independent validation set of 35 stroke patients and 25 controls, while the predictive model exhibited superior performance when compared to alternative algorithms. In spite of their high accuracy, both models are extremely simple and were developed using a common set consisting of only 3 peaks. Conclusion We have successfully identified 3 biomarkers that can detect ischemic stroke with an accuracy of 75%. The performance of the classification model on the validation set and on cross-validation does not deteriorate significantly when compared to that on the training set, indicating the robustness of the model. As in the case of the LAD classification model, the results of the predictive model validate the function constructed on our support-set for approximating the severity scores of stroke patients. The correlation and root mean absolute error of the LAD predictive model are consistently superior to those of the other algorithms used (Support vector machines, C4.5 decision trees, Logistic regression and Multilayer perceptron.

  17. Effects of a human recombinant alkaline phosphatase on renal hemodynamics, oxygenation and inflammation in two models of acute kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Peters, Esther, E-mail: esther.peters@radboudumc.nl [Department of Intensive Care Medicine, Radboud university medical center, PO Box 9101, Internal Mailbox 710, 6500 HB, Nijmegen (Netherlands); Department of Pharmacology and Toxicology, Radboud university medical center, PO Box 9101, Internal Mailbox 149, 6500 HB, Nijmegen (Netherlands); Ergin, Bülent, E-mail: b.ergin@amc.uva.nl [Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Kandil, Asli, E-mail: aslikandil@istanbul.edu.tr [Department of Biology, Faculty of Science, Istanbul University, PK 34134, Vezneciler, Istanbul (Turkey); Gurel-Gurevin, Ebru, E-mail: egurelgurevin@gmail.com [Department of Biology, Faculty of Science, Istanbul University, PK 34134, Vezneciler, Istanbul (Turkey); Elsas, Andrea van, E-mail: a.vanelsas@am-pharma.com [AM-Pharma, Rumpsterweg 6, 3981 AK, Bunnik (Netherlands); Masereeuw, Rosalinde, E-mail: r.masereeuw@uu.nl [Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, PO Box 80082, 3508 TB Utrecht (Netherlands); Pickkers, Peter, E-mail: peter.pickkers@radboudumc.nl [Department of Intensive Care Medicine, Radboud university medical center, PO Box 9101, Internal Mailbox 710, 6500 HB, Nijmegen (Netherlands); Ince, Can, E-mail: c.ince@amc.uva.nl [Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands)

    2016-12-15

    Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase (AP) improves renal function in critically ill patients with sepsis-associated acute kidney injury (AKI), for which the mechanism of action is not completely understood. Here, we investigated the effects of a newly developed human recombinant AP (recAP) on renal oxygenation and hemodynamics and prevention of kidney damage and inflammation in two in vivo AKI models. To induce AKI, male Wistar rats (n = 18) were subjected to renal ischemia (30 min) and reperfusion (I/R), or sham-operated. In a second model, rats (n = 18) received a 30 min infusion of lipopolysaccharide (LPS; 2.5 mg/kg), or saline, and fluid resuscitation. In both models, recAP (1000 U/kg) was administered intravenously (15 min before reperfusion, or 90 min after LPS). Following recAP treatment, I/R-induced changes in renal blood flow, renal vascular resistance and oxygen delivery at early, and cortical microvascular oxygen tension at late reperfusion were no longer significantly affected. RecAP did not influence I/R-induced effects on mean arterial pressure. During endotoxemia, recAP treatment did not modulate the LPS-induced changes in systemic hemodynamics and renal oxygenation. In both models, recAP did exert a clear renal protective anti-inflammatory effect, demonstrated by attenuated immunostaining of inflammatory, tubular injury and pro-apoptosis markers. Whether this renal protective effect is sufficient to improve outcome of patients suffering from sepsis-associated AKI is being investigated in a large clinical trial. - Highlights: • Human recombinant alkaline phosphatase (recAP) is a potential new therapy for sepsis-associated acute kidney injury (AKI). • RecAP can modulate renal oxygenation and hemodynamics immediately following I/R-induced AKI. • RecAP did not modulate endotoxemia-induced changes in systemic hemodynamics and renal oxygenation. • RecAP did exert a clear renal protective

  18. 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

  19. 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

  20. 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.

  1. 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....... RESULTS: We included a total of 488 patients with suspicion of ACS, 50% of whom were low-risk patients. 17% had a verified ACS; 10% of those in the low-risk group and 24% of those in the high-risk group (p = 0.0001). Among the verified ACS cases, 71% went primarily to the CCU. The odds ratio for an ACS...

  2. Imaging of acute mesenteric ischemia using multidetector CT and CT angiography in a porcine model.

    Science.gov (United States)

    Rosow, David E; Sahani, Dushyant; Strobel, Oliver; Kalva, Sanjeeva; Mino-Kenudson, Mari; Holalkere, Nagaraj S; Alsfasser, Guido; Saini, Sanjay; Lee, Susanna I; Mueller, Peter R; Fernández-del Castillo, Carlos; Warshaw, Andrew L; Thayer, Sarah P

    2005-12-01

    Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly facilitates the use of CT angiography (CTA) in the clinical setting. We sought to determine whether M.D.CT-CTA could accurately demonstrate vascular anatomy and capture the earliest stages of mesenteric ischemia in a porcine model. Pigs underwent embolization of branches of the superior mesenteric artery, then imaging by M.D.CT-CTA with three-dimensional reconstruction protocols. After scanning, diseased bowel segments were surgically resected and pathologically examined. Multidetector row CT and CT angiography reliably defined normal and occluded mesenteric vessels in the pig. It detected early changes of ischemia including poor arterial enhancement and venous dilatation, which were seen in all ischemic animals. The radiographic findings--compared with pathologic diagnoses-- predicted ischemia, with a positive predictive value of 92%. These results indicate that M.D.CT-CTA holds great promise for the early detection necessary for successful treatment of acute mesenteric ischemia.

  3. 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.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  5. Psychotherapy with schizophrenics in team groups: a systems model.

    Science.gov (United States)

    Beeber, A R

    1991-01-01

    This paper focuses on the treatment of patients with schizophrenic disorders employing the Team Group model. The advantages and disadvantages of the Team Group are presented. Systems theory and principles of group development are applied as a basis for understanding the dynamics of the group in the context at the acute psychiatric unit. Particular problems encountered in treating patients with schizophrenic disorders in this setting are presented. These include: (1) issues of therapist style and technique, (2) basic psychopathology of the schizophrenic disorders, and (3) phase-specific problems associated with the dynamics of the group. Recommendations for therapist interventions are made that may better integrate these patients into the Team Group.

  6. Bond graph modeling of centrifugal compression systems

    OpenAIRE

    Uddin, Nur; Gravdahl, Jan Tommy

    2015-01-01

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

  7. A model management system for combat simulation

    OpenAIRE

    Dolk, Daniel R.

    1986-01-01

    The design and implementation of a model management system to support combat modeling is discussed. Structured modeling is introduced as a formalism for representing mathematical models. A relational information resource dictionary system is developed which can accommodate structured models. An implementation is described. Structured modeling is then compared to Jackson System Development (JSD) as a methodology for facilitating discrete event simulation. JSD is currently better at representin...

  8. 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.

  9. Large animal model of acute right ventricular failure with functional tricuspid regurgitation.

    Science.gov (United States)

    Malinowski, Marcin; Proudfoot, Alistair G; Eberhart, Lenora; Schubert, Hans; Wodarek, Jeremy; Langholz, David; Rausch, Manuel K; Timek, Tomasz A

    2018-08-01

    Functional tricuspid regurgitation (FTR) commonly arises secondary to conditions affecting the left heart and is associated with right ventricular dysfunction and tricuspid annular dilatation. We set out to establish an animal model of acute RV failure (RVF) with FTR resembling the clinical features. Ten adult sheep had pressure sensors placed in the LV, RV, and right atrium while sonomicrometry crystals were implanted around tricuspid annulus and on the RV. Animals were studied open-chest to assess for RV function and FTR after: (1) volume infusion, (2) pulmonary artery constriction, (3) 5 min posterior descending artery occlusion, and (4) combination of all interventions. Hemodynamic, echocardiographic, and sonomicrometry data were collected at baseline and after every intervention. RV dimensions, RV strain, and annular area, perimeter, and size were calculated from crystal coordinates. The model was validated in six additional sheep studied only before and after combined interventions. Neither volume infusion, pulmonary hypertension, nor ischemia were associated with RVF or clinically significant TR when applied separately but combined resulted in RVF and greater than moderate FTR. In the validation group, maximal RV volume increased (62 ± 14 vs 70 ± 16 ml, p = 0.006), contractility decreased (20 ± 6 vs 12 ± 2%, p = 0.02), and strain increased. FTR increased from 0.4 ± 0.5 to 2.5 ± 0.8 (p < 0.001) and annular area from 652 ± 87 mm 2 to 739 ± 87 mm 2 (p = 0.005). The developed ovine model of acute RVF was associated with significant annular and RV enlargement and FTR. This novel and clinically pertinent research platform offers insight into the acute RVF pathophysiology and can be utilized to evaluate treatment interventions. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Mild hypothermia increases pulmonary anti-inflammatory response during protective mechanical ventilation in a piglet model of acute lung injury.

    Science.gov (United States)

    Cruces, Pablo; Erranz, Benjamín; Donoso, Alejandro; Carvajal, Cristóbal; Salomón, Tatiana; Torres, María Fernanda; Díaz, Franco

    2013-11-01

    The effects of mild hypothermia (HT) on acute lung injury (ALI) are unknown in species with metabolic rate similar to that of humans, receiving protective mechanical ventilation (MV). We hypothesized that mild hypothermia would attenuate pulmonary and systemic inflammatory responses in piglets with ALI managed with a protective MV. Acute lung injury (ALI) was induced with surfactant deactivation in 38 piglets. The animals were then ventilated with low tidal volume, moderate positive end-expiratory pressure (PEEP), and permissive hypercapnia throughout the experiment. Subjects were randomized to HT (33.5°C) or normothermia (37°C) groups over 4 h. Plasma and tissue cytokines, tissue apoptosis, lung mechanics, pulmonary vascular permeability, hemodynamic, and coagulation were evaluated. Lung interleukin-10 concentrations were higher in subjects that underwent HT after ALI induction than in those that maintained normothermia. No difference was found in other systemic and tissue cytokines. HT did not induce lung or kidney tissue apoptosis or influence lung mechanics or markers of pulmonary vascular permeability. Heart rate, cardiac output, oxygen uptake, and delivery were significantly lower in subjects that underwent HT, but no difference in arterial lactate, central venous oxygen saturation, and coagulation test was observed. Mild hypothermia induced a local anti-inflammatory response in the lungs, without affecting lung function or coagulation, in this piglet model of ALI. The HT group had lower cardiac output without signs of global dysoxia, suggesting an adaptation to the decrease in oxygen uptake and delivery. Studies are needed to determine the therapeutic role of HT in ALI. © 2013 John Wiley & Sons Ltd.

  11. Model Driven Development of Data Sensitive Systems

    DEFF Research Database (Denmark)

    Olsen, Petur

    2014-01-01

    storage systems, where the actual values of the data is not relevant for the behavior of the system. For many systems the values are important. For instance the control flow of the system can be dependent on the input values. We call this type of system data sensitive, as the execution is sensitive...... to the values of variables. This theses strives to improve model-driven development of such data-sensitive systems. This is done by addressing three research questions. In the first we combine state-based modeling and abstract interpretation, in order to ease modeling of data-sensitive systems, while allowing...... efficient model-checking and model-based testing. In the second we develop automatic abstraction learning used together with model learning, in order to allow fully automatic learning of data-sensitive systems to allow learning of larger systems. In the third we develop an approach for modeling and model-based...

  12. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

    Science.gov (United States)

    Zhan, Xianbao; Wang, Fan; Bi, Yan

    2016-01-01

    Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. PMID:27418683

  13. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.

    Science.gov (United States)

    Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

    2016-09-01

    Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. Copyright © 2016 the American Physiological Society.

  14. A smartphone client-server teleradiology system for primary diagnosis of acute stroke.

    Science.gov (United States)

    Mitchell, J Ross; Sharma, Pranshu; Modi, Jayesh; Simpson, Mark; Thomas, Monroe; Hill, Michael D; Goyal, Mayank

    2011-05-06

    Recent advances in the treatment of acute ischemic stroke have made rapid acquisition, visualization, and interpretation of images a key factor for positive patient outcomes. We have developed a new teleradiology system based on a client-server architecture that enables rapid access to interactive advanced 2-D and 3-D visualization on a current generation smartphone device (Apple iPhone or iPod Touch, or an Android phone) without requiring patient image data to be stored on the device. Instead, a server loads and renders the patient images, then transmits a rendered frame to the remote device. Our objective was to determine if a new smartphone client-server teleradiology system is capable of providing accuracies and interpretation times sufficient for diagnosis of acute stroke. This was a retrospective study. We obtained 120 recent consecutive noncontrast computed tomography (NCCT) brain scans and 70 computed tomography angiogram (CTA) head scans from the Calgary Stroke Program database. Scans were read by two neuroradiologists, one on a medical diagnostic workstation and an iPod or iPhone (hereafter referred to as an iOS device) and the other only on an iOS device. NCCT brain scans were evaluated for early signs of infarction, which includes early parenchymal ischemic changes and dense vessel sign, and to exclude acute intraparenchymal hemorrhage and stroke mimics. CTA brain scans were evaluated for any intracranial vessel occlusion. The interpretations made on an iOS device were compared with those made at a workstation. The total interpretation times were recorded for both platforms. Interrater agreement was assessed. True positives, true negatives, false positives, and false negatives were obtained, and sensitivity, specificity, and accuracy of detecting the abnormalities on the iOS device were computed. The sensitivity, specificity, and accuracy of detecting intraparenchymal hemorrhage were 100% using the iOS device with a perfect interrater agreement (kappa=1

  15. Physical and mathematical models of communication systems

    International Nuclear Information System (INIS)

    Verkhovskaya, E.P.; Yavorskij, V.V.

    2006-01-01

    The theoretical parties connecting resources of communication system with characteristics of channels are received. The model of such systems from positions quasi-classical thermodynamics is considered. (author)

  16. Electrocardiographic characteristics and clinical features of acute apical infarction. Analysis by a QRS scoring system

    Energy Technology Data Exchange (ETDEWEB)

    Seino, Yoshihiko; Nagae, Yasuhiro; Kamei, Shinichiro; Koh, Yoshiki; Tanaka, Keiji; Katoh, Takao; Takano, Teruo; Hayakawa, Hirokazu; Okumura, Hidemasa

    1986-11-01

    Two-dimensional echocardiography and thallium-201 myocardial single photon emission computed tomography were used to detect infarct site in 56 consecutive patients with acute myocardial infarction (MI). The pathophysiology of apical MI at acute stage was studied in relation to ECG changes as determined by a QRS scoring system. On the first hospital day, the group with antero-apical MI (AAp group) had long Q-wave durations in leads V/sub 3/ and V/sub 4/, high QRS scores (QRSs) in leads V/sub 4/ and V/sub 5/, high QRSs in total, and large number of Q waves, as compared with the group with anterior MI (A group). On the 7th day, Q-wave durations in leads V/sub 2/ and V/sub 3/, and QRSs in leads V/sub 4/ and V/sub 5/ were significantly larger in AAp group than A group. Although there was no significant difference between the two groups with respect to blood circulation and peak creatine kinase (CK)/CK-MB at the time of admission, left ventricular ejection function was significantly lower in AAp group than A group. No finding was significantly different between the group with infero-apical MI and the group with inferior MI. QRSs in leads V/sub 4/ and V/sub 5/ was a useful means of diagnosing AAp MI. (Namekawa, K.).

  17. 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>LD50compound 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Systemic lupus erythematosus flare up as acute spinal subarachnoid hemorrhage with bilateral lower limb paralysis

    Directory of Open Access Journals (Sweden)

    Xiang Yang

    2018-05-01

    Full Text Available Subarachnoid hemorrhage (SAH is an uncommon complication of systemic lupus erythematosus (SLE. Solitary association of fatal spinal SAH as a complication of SLE, has not been encountered much in literature although coexisting acute cerebral and spinal SAH have been associated with SLE. We present a 39-year old female with initial diagnosis of SLE eight years ago who suddenly developed a productive cough, acute abdomen and paralysis of the lower limbs. Magnetic resonance imaging of the spine revealed thoracic spinal SAH with varying degrees of thoracic spinal cord compression. The hemorrhage was total evacuated via surgery. She regained normal function of her lower limbers after the operation with no further neurological complications. One of the rare but fatal complications of SLE is solitary spinal SAH without cranial involvement. The best and most appropriate management of this kind of presentation is surgical decompression of the hematoma with total hemostasis. The cause of hemorrhage should be identified intra-operatively and treated appropriately.

  19. Acute pancreatitis.

    Science.gov (United States)

    Talukdar, Rupjyoti; Vege, Santhi S

    2015-09-01

    To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

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

    Science.gov (United States)

    2015-11-04

    Coastal Inlets Research Program Particle Tracking Model (PTM) with Coastal Modeling System ( CMS ) The Particle Tracking Model (PTM) is a Lagrangian...currents and waves. The Coastal Inlets Research Program (CIRP) supports the PTM with the Coastal Modeling System ( CMS ), which provides coupled wave...and current forcing for PTM simulations. CMS -PTM is implemented in the Surface-water Modeling System, a GUI environment for input development

  1. Long-term medical costs and life expectancy of acute myeloid leukemia: a probabilistic decision model.

    Science.gov (United States)

    Wang, Han-I; Aas, Eline; Howell, Debra; Roman, Eve; Patmore, Russell; Jack, Andrew; Smith, Alexandra

    2014-03-01

    Acute myeloid leukemia (AML) can be diagnosed at any age and treatment, which can be given with supportive and/or curative intent, is considered expensive compared with that for other cancers. Despite this, no long-term predictive models have been developed for AML, mainly because of the complexities associated with this disease. The objective of the current study was to develop a model (based on a UK cohort) to predict cost and life expectancy at a population level. The model developed in this study combined a decision tree with several Markov models to reflect the complexity of the prognostic factors and treatments of AML. The model was simulated with a cycle length of 1 month for a time period of 5 years and further simulated until age 100 years or death. Results were compared for two age groups and five different initial treatment intents and responses. Transition probabilities, life expectancies, and costs were derived from a UK population-based specialist registry-the Haematological Malignancy Research Network (www.hmrn.org). Overall, expected 5-year medical costs and life expectancy ranged from £8,170 to £81,636 and 3.03 to 34.74 months, respectively. The economic and health outcomes varied with initial treatment intent, age at diagnosis, trial participation, and study time horizon. The model was validated by using face, internal, and external validation methods. The results show that the model captured more than 90% of the empirical costs, and it demonstrated good fit with the empirical overall survival. Costs and life expectancy of AML varied with patient characteristics and initial treatment intent. The robust AML model developed in this study could be used to evaluate new diagnostic tools/treatments, as well as enable policy makers to make informed decisions. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  2. Intratracheal synthetic CpG oligodeoxynucleotide causes acute lung injury with systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Hasegawa Naoki

    2009-09-01

    Full Text Available Abstract Bacterial genome is characterized by frequent unmethylated cytosine-phosphate-guanine (CpG motifs. Deleterious effects can occur when synthetic oligodeoxynucleotides (ODN with unmethylated CpG dinucleotides (CpG-ODN are administered in a systemic fashion. We aimed to evaluate the effect of intratracheal CpG-ODN on lung inflammation and systemic inflammatory response. C57BL/6J mice received intratracheal administration of CpG-ODN (0.01, 0.1, 1.0, 10, or 100 μM or control ODN without CpG motif. Bronchoalveolar lavage (BAL fluid was obtained 3 or 6 h or 1, 2, 7, or 14 days after the instillation and subjected to a differential cell count and cytokine measurement. Lung permeability was evaluated as the BAL fluid-to-plasma ratio of the concentration of human serum albumin that was injected 1 h before euthanasia. Nuclear factor (NF-κB DNA binding activity was also evaluated in lung homogenates. Intratracheal administration of 10 μM or higher concentration of CpG-ODN induced significant inflammatory cell accumulation into the airspace. The peak accumulation of neutrophils and lymphocytes occurred 1 and 2 days after the CpG-ODN administration, respectively. Lung permeability was increased 1 day after the 10 μM CpG-ODN challenge. CpG-ODN also induced nuclear translocation of NF-κB and upregulation of various inflammatory cytokines in BAL fluid and plasma. Histopathology of the lungs and liver revealed acute lung injury and liver damage with necrosis, respectively. Control ODN without CpG motif did not induce any inflammatory change. Since intratracheal CpG-ODN induced acute lung injury as well as systemic inflammatory response, therapeutic strategies to neutralize bacterial DNA that is released after administration of bactericidal agents should be considered.

  3. Examination of Gelatinase Isoforms in Rodent Models of Acute Neurodegenerative Diseases Using Two-Dimensional Zymography.

    Science.gov (United States)

    Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Qu, Zhe; Cui, Jiankun; Gu, Zezong

    2017-01-01

    Pathological activation of gelatinases (matrix metalloproteinase-2 and -9; MMP-2/-9) has been shown to cause a number of detrimental outcomes in neurodegenerative diseases. In gel gelatin zymography is a highly sensitive methodology commonly used in revealing levels of gelatinase activity and in separating the proform and active form of gelatinases, based on their different molecular weights. However, this methodology is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity can be regulated at transcriptional and/or post-translational levels under in vivo conditions resulting in alternation of their isoelectric focusing (IEF) points. In this chapter, we describe an advanced methodology, termed two-dimensional zymography, combining IEF with zymographic electrophoresis under non-reducing conditions to achieve significant improvement in separation of the gelatinase isoforms in both cell-based and in vivo models for acute brain injuries and neuroinflammation.

  4. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

    OpenAIRE

    Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

    2016-01-01

    Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mai...

  5. Monitoring the impact of the DRG payment system on nursing service context factors in Swiss acute care hospitals: Study protocol

    Science.gov (United States)

    Spirig, Rebecca; Spichiger, Elisabeth; Martin, Jacqueline S.; Frei, Irena Anna; Müller, Marianne; Kleinknecht, Michael

    2014-01-01

    Aims: With this study protocol, a research program is introduced. Its overall aim is to prepare the instruments and to conduct the first monitoring of nursing service context factors at three university and two cantonal hospitals in Switzerland prior to the introduction of the reimbursement system based on Diagnosis Related Groups (DRG) and to further develop a theoretical model as well as a methodology for future monitoring following the introduction of DRGs. Background: DRG was introduced to all acute care hospitals in Switzerland in 2012. In other countries, DRG introduction led to rationing and subsequently to a reduction in nursing care. As result, nursing-sensitive patient outcomes were seriously jeopardised. Switzerland has the opportunity to learn from the consequences experienced by other countries when they introduced DRGs. Their experiences highlight that DRGs influence nursing service context factors such as complexity of nursing care or leadership, which in turn influence nursing-sensitive patient outcomes. For this reason, the monitoring of nursing service context factors needs to be an integral part of the introduction of DRGs. However, most acute care hospitals in Switzerland do not monitor nursing service context data. Nursing managers and hospital executive boards will be in need of this data in the future, in order to distribute resources effectively. Methods/Design: A mixed methods design in the form of a sequential explanatory strategy was chosen. During the preparation phase, starting in spring 2011, instruments were selected and prepared, and the access to patient and nursing data in the hospitals was organized. Following this, online collection of quantitative data was conducted in fall 2011. In summer 2012, qualitative data was gathered using focus group interviews, which helped to describe the processes in more detail. During 2013 and 2014, an integration process is being conducted involving complementing, comparing and contrasting

  6. 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

  7. Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury.

    Science.gov (United States)

    Rotta, A T; Gunnarsson, B; Fuhrman, B P; Hernan, L J; Steinhorn, D M

    2001-11-01

    To determine the impact of different protective and nonprotective mechanical ventilation strategies on the degree of pulmonary inflammation, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury. A prospective, randomized, controlled, in vivo animal laboratory study. Animal research facility of a health sciences university. Forty-six New Zealand White rabbits. Mature rabbits were instrumented with a tracheostomy and vascular catheters. Lavage-injured rabbits were randomized to receive conventional ventilation with either a) low peak end-expiratory pressure (PEEP; tidal volume of 10 mL/kg, PEEP of 2 cm H2O); b) high PEEP (tidal volume of 10 mL/kg, PEEP of 10 cm H2O); c) low tidal volume with PEEP above Pflex (open lung strategy, tidal volume of 6 mL/kg, PEEP set 2 cm H2O > Pflex); or d) high-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. Lung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total protein, elastase activity, tumor necrosis factor-alpha, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded. Animals that received a lung protective strategy (open lung or high-frequency oscillatory ventilation) exhibited more favorable oxygenation and lung mechanics compared with the low PEEP and high PEEP groups. Animals ventilated by a lung protective strategy also showed attenuation of inflammation (reduced tracheal fluid protein, tracheal fluid elastase, tracheal fluid tumor necrosis factor-alpha, and pulmonary leukostasis). Animals treated with high-frequency oscillatory ventilation had attenuated oxidative injury to the lung and greater hemodynamic stability compared with the other experimental groups. Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and

  8. A model of acute renal allograft rejection in outbred Yorkshire piglets.

    Science.gov (United States)

    Lassiter, Randi; Wang, Youli; Fang, Xuexiu; Winn, Matt; Ghaffari, Arina; Ho, Chak-Sum; Helman, Sandra; Jajosky, Ryan; Kleven, Daniel; Stanley Nahman, N; Merchen, Todd D

    2017-06-01

    Pigs represent a desirable animal model for the study of rejection in kidney transplantation with inbred Yucatan miniature swine (YMS) the most commonly studied strain due to well defined swine leukocyte antigen (SLA) genotypes. However, limitations to YMS may include cost and availability. Outbred Yorkshire pigs are widely available and significantly cheaper than YMS. Recent advances in SLA genotyping have allowed its application to outbred strains. On this basis, we theorized that Yorkshire pigs would be a viable alternative to YMS for the study of rejection in kidney transplantation. To address this question, we performed auto (Auto) and allotransplants (Allo) in 24 Yorkshire pigs, and assessed SLA genotypes and acute rejection after 72h. At sacrifice, and when compared to autotransplants, allotransplants had significant elevations in serum creatinine (8.4±1.3 vs 2.8±2.0mg/dL for Allo vs autotransplants, respectively) and BUN (61±9 vs 19.2±15mg/dL for Allo vs autotransplants, respectively). Warm ischemia times between the two groups did not differ (24±2.3 vs 26.4±1.4min for Auto vs Allo, respectively). There were 16 distinct SLA haplotypes identified from pigs undergoing allotransplantion, no matched donor-recipient pairs, and all allografts demonstrated rejection. Type IIA cellular rejection (Banff) was the most common. One allograft demonstrated hyperacute rejection due a blood group incompatibility. Histologically, the expression of regulatory Tcells and dendritic cells was increased in allografts. These data suggest that Yorkshire pigs may be a useful model for the study of acute rejection in experimental kidney transplantation. Copyright © 2017. Published by Elsevier B.V.

  9. Risk model for suspected acute coronary syndrome is of limited value in an emergency department.

    Science.gov (United States)

    Mogensen, Christian Backer; Christiansen, Maja; Jørgensen, Jess Bjerre; Staehr, Peter Bisgaard

    2015-10-01

    Among patients with acute chest pain, acute coronary syndrome (ACS) is seen only in a minority of the patients, which raises the question, whether it is possible to separate a group with a high risk of ACS for admission to a cardiac care unit (CCU) from those with a low risk who would be treated at an emergency department (ED). The aim of this study was to describe a risk stratification model for a Danish context. This was a historic prospective cohort study of patients with suspicion of ACS. The patient was defined as a low-risk patient and admitted to the ED if: 1) electrocardiogram (ECG) was normal, 2) the patient did not have persisting chest pain and 3) there was no history of ischaemic heart disease, heart failure or cardioverter defibrillator. Otherwise, patients were admitted to the CCU. The primary outcome was whether the ACS diagnosis was confirmed or rejected. We included a total of 488 patients with suspicion of ACS, 50% of whom were low-risk patients. 17% had a verified ACS; 10% of those in the low-risk group and 24% of those in the high-risk group (p = 0.0001). Among the verified ACS cases, 71% went primarily to the CCU. The odds ratio for an ACS if assigned to the high-risk group was 3.0. Allocation to the high-risk group, male gender and age above 60 years was associated with a higher risk of ACS. For patients fulfilling the high-risk definition, sensitivity was 71%, specificity 55%, negative predictive value 90% and positive predictive value 24% for an ACS. The model for stratification separated patients into two equal groups, allocated 71% of all ACS directly to the CCU and could not be improved by any of the additional factors examined. Further development of referral strategies for chest pain patients is required. none. not relevant.

  10. Characterization of rat model of acute anterior uveitis using optical coherence tomography angiography

    Science.gov (United States)

    Choi, Woo June; Pepple, Kathryn L.; Zhi, Zhongwei; Wang, Ruikang K.

    2015-03-01

    Uveitis, or ocular inflammation, is a cause of severe visual impairment. Rodent models of uveitis are powerful tools used to investigate the pathological mechanisms of ocular inflammation and to study the efficacy of new therapies prior to human testing. In this paper, we report the utility of spectral-domain optical coherence tomography (SD-OCT) angiography in characterizing the inflammatory changes induced in the anterior segment of a rat model of uveitis. Acute anterior uveitis (AAU) was induced in two rats by intravitreal injection of a killed mycobacterial extract. One of them received a concurrent periocular injection of steroids to model a treatment effect. OCT imaging was performed prior to inflammation induction on day 0 (baseline), and 2 days post-injection (peak inflammation). Baseline and inflamed images were compared. OCT angiography identified swelling of the cornea, inflammatory cells in the anterior and posterior chambers, a fibrinous papillary membrane, and dilation of iris vessels in the inflamed eyes when compared to baseline images. Steroid treatment was shown to prevent the changes associated with inflammation. This is a novel application of anterior OCT imaging in animal models of uveitis, and provides a high resolution, in vivo assay for detecting and quantifying ocular inflammation and the response to new therapies.

  11. An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Zhisheng Her

    2017-10-01

    Full Text Available Abstract Background Xenotransplantation of patient-derived AML (acute myeloid leukemia cells in NOD-scid Il2rγ null (NSG mice is the method of choice for evaluating this human hematologic malignancy. However, existing models constructed using intravenous injection in adult or newborn NSG mice have inferior engraftment efficiency, poor peripheral blood engraftment, or are difficult to construct. Methods Here, we describe an improved AML xenograft model where primary human AML cells were injected into NSG newborn pups intrahepatically. Results Introduction of primary cells from AML patients resulted in high levels of engraftment in peripheral blood, spleen, and bone marrow (BM of recipient mice. The phenotype of engrafted AML cells remained unaltered during serial transplantation. The mice developed features that are consistent with human AML including spleen enlargement and infiltration of AML cells into multiple organs. Importantly, we demonstrated that although leukemic stem cell activity is enriched and mediated by CD34+CD117+ subpopulation, CD34+CD117− subpopulation can acquire CD34+CD117+ phenotype through de-differentiation. Lastly, we evaluated the therapeutic potential of Sorafenib and Regorafenib in this AML model and found that periphery and spleen AML cells are sensitive to these treatments, whereas BM provides a protective environment to AML. Conclusions Collectively, our improved model is robust, easy-to-construct, and reliable for pre-clinical AML studies.

  12. 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.

  13. Using adaptive model predictive control to customize maintenance therapy chemotherapeutic dosing for childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Noble, Sarah L; Sherer, Eric; Hannemann, Robert E; Ramkrishna, Doraiswami; Vik, Terry; Rundell, Ann E

    2010-06-07

    Acute lymphoblastic leukemia (ALL) is a common childhood cancer in which nearly one-quarter of patients experience a disease relapse. However, it has been shown that individualizing therapy for childhood ALL patients by adjusting doses based on the blood concentration of active drug metabolite could significantly improve treatment outcome. An adaptive model predictive control (MPC) strategy is presented in which maintenance therapy for childhood ALL is personalized using routine patient measurements of red blood cell mean corpuscular volume as a surrogate for the active drug metabolite concentration. A clinically relevant mathematical model is developed and used to describe the patient response to the chemotherapeutic drug 6-mercaptopurine, with some model parameters being patient-specific. During the course of treatment, the patient-specific parameters are adaptively identified using recurrent complete blood count measurements, which sufficiently constrain the patient parameter uncertainty to support customized adjustments of the drug dose. While this work represents only a first step toward a quantitative tool for clinical use, the simulated treatment results indicate that the proposed mathematical model and adaptive MPC approach could serve as valuable resources to the oncologist toward creating a personalized treatment strategy that is both safe and effective. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  14. Using the Model Coupling Toolkit to couple earth system models

    Science.gov (United States)

    Warner, J.C.; Perlin, N.; Skyllingstad, E.D.

    2008-01-01

    Continued advances in computational resources are providing the opportunity to operate more sophisticated numerical models. Additionally, there is an increasing demand for multidisciplinary studies that include interactions between different physical processes. Therefore there is a strong desire to develop coupled modeling systems that utilize existing models and allow efficient data exchange and model control. The basic system would entail model "1" running on "M" processors and model "2" running on "N" processors, with efficient exchange of model fields at predetermined synchronization intervals. Here we demonstrate two coupled systems: the coupling of the ocean circulation model Regional Ocean Modeling System (ROMS) to the surface wave model Simulating WAves Nearshore (SWAN), and the coupling of ROMS to the atmospheric model Coupled Ocean Atmosphere Prediction System (COAMPS). Both coupled systems use the Model Coupling Toolkit (MCT) as a mechanism for operation control and inter-model distributed memory transfer of model variables. In this paper we describe requirements and other options for model coupling, explain the MCT library, ROMS, SWAN and COAMPS models, methods for grid decomposition and sparse matrix interpolation, and provide an example from each coupled system. Methods presented in this paper are clearly applicable for coupling of other types of models. ?? 2008 Elsevier Ltd. All rights reserved.

  15. 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.

  16. 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

  17. 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....

  18. Short-term predictive capacity of two different triage systems in patients with acute heart failure: TRICA-EAHFE study.

    Science.gov (United States)

    Miró, Òscar; Tost, Josep; Herrero, Pablo; Jacob, Javier; Martín-Sánchez, Francisco Javier; Gil, Víctor; Fernández-Pérez, Cristina; Escoda, Rosa; Llorens, Pere

    2016-12-01

    To evaluate whether prioritization of patients with acute heart failure (AHF) in the Andorran Triage Model/Spanish Triage System (MAT/SET) and the Manchester Triage System (MTS) also allows the identification of different profiles of outcome and prognosis and determine whether either system has a better predictive capacity of outcomes. Patients with AHF included in the Spanish EAHFE registry from hospitals using the MAT/SET or MTS were selected and divided according to the triage system used. Outcome variables included hospital admission, length of stay, death during admission, 3, 7, and 30-day all-cause mortality, and emergency department (ED) reconsultation at 30 days. The results were compared according to the level of priority and the triage system used. We included 3837 patients (MAT/SET=2474; MTS=1363) classified as follows: 4.0% level 1; 34.7% level 2; 55.1% level 3; and 6.3% levels 4-5. Both systems associated greater priority with higher rates of admission and mortality; the MTS associated greater priority with greater ED reconsultation and the MAT/SET found greater priority to be associated with less ED reconsultation. The discriminative capacity of the two scales for adverse outcomes was statistically significant, albeit poor, for almost all the outcome events and it was of scarce clinical relevance (Area under the curve of the receiver operating characteristic between 0.458 and 0.661). The prediction of the outcome of patients with AHF determined with the MAT/SET or MTS showed scarce differences between the two systems, and their discriminative capacity does not seem to be clinically relevant.

  19. Diagnosis and treatment of acute and chronic leukemia

    International Nuclear Information System (INIS)

    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

  20. The radionuclide migration model in river system

    International Nuclear Information System (INIS)

    Zhukova, O.M.; Shiryaeva, N.M.; Myshkina, M.K.; Shagalova, Eh.D.; Denisova, V.V.; Skurat, V.V.

    2001-01-01

    It was propose the model of radionuclide migration in river system based on principle of the compartmental model at hydraulically stationary and chemically equilibrium conditions of interaction of radionuclides in system water-dredge, water-sediments. Different conditions of radioactive contamination entry in river system were considered. The model was verified on the data of radiation monitoring of Iput' river

  1. 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

  2. Cutaneous exposure to vesicant phosgene oxime: Acute effects on the skin and systemic toxicity

    International Nuclear Information System (INIS)

    Tewari-Singh, Neera; Goswami, Dinesh G; Kant, Rama; Croutch, Claire R; Casillas, Robert P; Orlicky, David J; Agarwal, Rajesh

    2017-01-01

    Phosgene Oxime (CX), an urticant or nettle agent categorized as a vesicant, is a potential chemical warfare and terrorist weapon. Its exposure can result in widespread and devastating effects including high mortality due to its fast penetration and ability to cause immediate severe cutaneous injury. It is one of the least studied chemical warfare agents with no effective therapy available. Thus, our goal was to examine the acute effects of CX following its cutaneous exposure in SKH-1 hairless mice to help establish a relevant injury model. Results from our study show that topical cutaneous exposure to CX vapor causes blanching of exposed skin with an erythematous ring, necrosis, edema, mild urticaria and erythema within minutes after exposure out to 8 h post-exposure. These clinical skin manifestations were accompanied with increases in skin thickness, apoptotic cell death, mast cell degranulation, myeloperoxidase activity indicating neutrophil infiltration, p53 phosphorylation and accumulation, and an increase in COX-2 and TNFα levels. Topical CX-exposure also resulted in the dilatation of the peripheral vessels with a robust increase in RBCs in vessels of the liver, spleen, kidney, lungs and heart tissues. These events could cause a drop in blood pressure leading to shock, hypoxia and death. Together, this is the first report on effects of CX cutaneous exposure, which could help design further comprehensive studies evaluating the acute and chronic skin injuries from CX topical exposure and elucidate the related mechanism of action to aid in the identification of therapeutic targets and mitigation of injury. - Highlights: • Phosgene oxime cutaneous exposure causes skin blanching, edema and urticaria. • Penetration of phosgene oxime causes dilation of vasculature in internal organs. • Mast cells could play an important role in phosgene oxime-induced skin injury. • Phosgene oxime could induce low blood pressure and hypoxia leading to mortality. • Data is

  3. Cutaneous exposure to vesicant phosgene oxime: Acute effects on the skin and systemic toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Tewari-Singh, Neera, E-mail: Neera.tewari-singh@ucdenver.edu [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); Goswami, Dinesh G; Kant, Rama [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); Croutch, Claire R; Casillas, Robert P [MRIGlobal, Kansas City, MO 64110 (United States); Orlicky, David J [Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); Agarwal, Rajesh [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States)

    2017-02-15

    Phosgene Oxime (CX), an urticant or nettle agent categorized as a vesicant, is a potential chemical warfare and terrorist weapon. Its exposure can result in widespread and devastating effects including high mortality due to its fast penetration and ability to cause immediate severe cutaneous injury. It is one of the least studied chemical warfare agents with no effective therapy available. Thus, our goal was to examine the acute effects of CX following its cutaneous exposure in SKH-1 hairless mice to help establish a relevant injury model. Results from our study show that topical cutaneous exposure to CX vapor causes blanching of exposed skin with an erythematous ring, necrosis, edema, mild urticaria and erythema within minutes after exposure out to 8 h post-exposure. These clinical skin manifestations were accompanied with increases in skin thickness, apoptotic cell death, mast cell degranulation, myeloperoxidase activity indicating neutrophil infiltration, p53 phosphorylation and accumulation, and an increase in COX-2 and TNFα levels. Topical CX-exposure also resulted in the dilatation of the peripheral vessels with a robust increase in RBCs in vessels of the liver, spleen, kidney, lungs and heart tissues. These events could cause a drop in blood pressure leading to shock, hypoxia and death. Together, this is the first report on effects of CX cutaneous exposure, which could help design further comprehensive studies evaluating the acute and chronic skin injuries from CX topical exposure and elucidate the related mechanism of action to aid in the identification of therapeutic targets and mitigation of injury. - Highlights: • Phosgene oxime cutaneous exposure causes skin blanching, edema and urticaria. • Penetration of phosgene oxime causes dilation of vasculature in internal organs. • Mast cells could play an important role in phosgene oxime-induced skin injury. • Phosgene oxime could induce low blood pressure and hypoxia leading to mortality. • Data is

  4. The Influence of Acute Hyperglycemia in an Animal Model of Lacunar Stroke That Is Induced by Artificial Particle Embolization

    Science.gov (United States)

    Tsai, Ming-Jun; Lin, Ming-Wei; Huang, Yaw-Bin; Kuo, Yu-Min; Tsai, Yi-Hung

    2016-01-01

    Animal and clinical studies have revealed that hyperglycemia during ischemic stroke increases the stroke's severity and the infarct size in clinical and animal studies. However, no conclusive evidence demonstrates that acute hyperglycemia worsens post-stroke outcomes and increases infarct size in lacunar stroke. In this study, we developed a rat model of lacunar stroke that was induced via the injection of artificial embolic particles during full consciousness. We then used this model to compare the acute influence of hyperglycemia in lacunar stroke and diffuse infarction, by evaluating neurologic behavior and the rate, size, and location of the infarction. The time course of the neurologic deficits was clearly recorded from immediately after induction to 24 h post-stroke in both types of stroke. We found that acute hyperglycemia aggravated the neurologic deficit in diffuse infarction at 24 h after stroke, and also aggravated the cerebral infarct. Furthermore, the infarct volumes of the basal ganglion, thalamus, hippocampus, and cerebellum but not the cortex were positively correlated with serum glucose levels. In contrast, acute hyperglycemia reduced the infarct volume and neurologic symptoms in lacunar stroke within 4 min after stroke induction, and this effect persisted for up to 24 h post-stroke. In conclusion, acute hyperglycemia aggravated the neurologic outcomes in diffuse infarction, although it significantly reduced the size of the cerebral infarct and improved the neurologic deficits in lacunar stroke. PMID:27226775

  5. Comparison of traditional cardiovascular risk models and coronary atherosclerotic plaque as detected by computed tomography for prediction of acute coronary syndrome in patients with acute chest pain.

    Science.gov (United States)

    Ferencik, Maros; Schlett, Christopher L; Bamberg, Fabian; Truong, Quynh A; Nichols, John H; Pena, Antonio J; Shapiro, Michael D; Rogers, Ian S; Seneviratne, Sujith; Parry, Blair Alden; Cury, Ricardo C; Brady, Thomas J; Brown, David F; Nagurney, John T; Hoffmann, Udo

    2012-08-01

    The objective was to determine the association of four clinical risk scores and coronary plaque burden as detected by computed tomography (CT) with the outcome of acute coronary syndrome (ACS) in patients with acute chest pain. The hypothesis was that the combination of risk scores and plaque burden improved the discriminatory capacity for the diagnosis of ACS. The study was a subanalysis of the Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial-a prospective observational cohort study. The authors enrolled patients presenting to the emergency department (ED) with a chief complaint of acute chest pain, inconclusive initial evaluation (negative biomarkers, nondiagnostic electrocardiogram [ECG]), and no history of coronary artery disease (CAD). Patients underwent contrast-enhanced 64-multidetector-row cardiac CT and received standard clinical care (serial ECG, cardiac biomarkers, and subsequent diagnostic testing, such as exercise treadmill testing, nuclear stress perfusion imaging, and/or invasive coronary angiography), as deemed clinically appropriate. The clinical providers were blinded to CT results. The chest pain score was calculated and the results were dichotomized to ≥10 (high-risk) and modeling was performed to examine the association of risk scores and coronary plaque burden to the outcome of ACS. Unadjusted models were individually fitted for the coronary plaque burden and for Goldman, Sanchis, TIMI, and chest pain scores. In adjusted analyses, the authors tested whether the association between risk scores and ACS persisted after controlling for the coronary plaque burden. The prognostic discriminatory capacity of the risk scores and plaque burden for ACS was assessed using c-statistics. The differences in area under the receiver-operating characteristic curve (AUC) and c-statistics were tested by performing the -2 log likelihood ratio test of nested models. A p value capacity for the diagnosis of ACS. Plaque burden was

  6. Hospital-Confirmed Acute Myocardial Infarction: Prehospital Identification Using the Medical Priority Dispatch System.

    Science.gov (United States)

    Clawson, Jeff J; Gardett, Isabel; Scott, Greg; Fivaz, Conrad; Barron, Tracey; Broadbent, Meghan; Olola, Christopher

    2018-02-01

    Introduction Early recognition of an acute myocardial infarction (AMI) can increase the patient's likelihood of survival. As the first point of contact for patients accessing medical care through emergency services, emergency medical dispatchers (EMDs) represent the earliest potential identification point for AMIs. The objective of the study was to determine how AMI cases were coded and prioritized at the dispatch point, and also to describe the distribution of these cases by patient age and gender. Hypothesis/Problem No studies currently exist that describe the EMD's ability to correctly triage AMIs into Advanced Life Support (ALS) response tiers. The retrospective descriptive study utilized data from three sources: emergency medical dispatch, Emergency Medical Services (EMS), and emergency departments (EDs)/hospitals. The primary outcome measure was the distributions of AMI cases, as categorized by Chief Complaint Protocol, dispatch priority code and level, and patient age and gender. The EMS and ED/hospital data came from the Utah Department of Health (UDoH), Salt Lake City, Utah. Dispatch data came from two emergency communication centers covering the entirety of Salt Lake City and Salt Lake County, Utah. Overall, 89.9% of all the AMIs (n=606) were coded in one of the three highest dispatch priority levels, all of which call for ALS response (called CHARLIE, DELTA, and ECHO in the studied system). The percentage of AMIs significantly increased for patients aged 35 years and older, and varied significantly by gender, dispatch level, and chief complaint. A total of 85.7% of all deaths occurred among patients aged 55 years and older, and 88.9% of the deaths were handled in the ALS-recommended priority levels. Acute myocardial infarctions may present as a variety of clinical symptoms, and the study findings demonstrated that more than one-half were identified as having chief complaints of Chest Pain or Breathing Problems at the dispatch point, followed by Sick

  7. Model Information Exchange System (MIXS).

    Science.gov (United States)

    2013-08-01

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

  8. Reduced butyrylcholinesterase activity is an early indicator of trauma-induced acute systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Zivkovic AR

    2016-11-01

    Full Text Available Aleksandar R Zivkovic, Jochen Bender, Thorsten Brenner, Stefan Hofer,* Karsten Schmidt* Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany *These authors contributed equally to this work Purpose: Early diagnosis of systemic inflammatory response syndrome is fundamentally important for an effective and a goal-directed therapy. Various inflammation biomarkers have been used in clinical and experimental practice. However, a definitive diagnostic tool for an early detection of systemic inflammation remains to be identified. Acetylcholine (Ach has been shown to play an important role in the inflammatory response. Serum cholinesterase (butyrylcholinesterase [BChE] is the major Ach hydrolyzing enzyme in blood. The role of this enzyme during inflammation has not yet been fully understood. This study tests whether a reduction in the BChE activity could indicate the onset of the systemic inflammatory response upon traumatic injury. Patients and methods: This observational study measured BChE activity in patients with traumatic injury admitted to the emergency room by using point-of-care-test system (POCT. In addition, the levels of routine inflammation biomarkers during the initial treatment period were measured. Injury Severity Score was used to assess the trauma severity. Results: Altered BChE activity was correlated with trauma severity, resulting in systemic inflammation. Reduction in the BChE activity was detected significantly earlier compared to those of routinely measured inflammatory biomarkers. Conclusion: This study suggests that the BChE activity reduction might serve as an early indicator of acute systemic inflammation. Furthermore, BChE activity, measured using a POCT system, might play an important role in the early diagnosis of the trauma-induced systemic inflammation. Keywords: trauma, injury, early diagnostics, cholinergic, pseudocholinesterase, SIRS

  9. Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action

    DEFF Research Database (Denmark)

    Sanderson, Hans; Thomsen, Marianne

    2009-01-01

    data. Pharmaceuticals were found to be more frequent than industrial chemicals in GHS category III. Acute toxicity was predictable (>92%) using a generic (Q)SAR ((Quantitative) Structure Activity Relationship) suggesting a narcotic MOA. Analysis of model prediction error suggests that 68...... a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under...... the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic...

  10. Towards Modelling of Hybrid Systems

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2006-01-01

    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...

  11. Cardiovascular system and physical working capacity in patients who had acute radiation syndrome as the result of Chernobyl accident

    International Nuclear Information System (INIS)

    Belyi, D.; Gergel, O.; Kovalenko, A.

    1996-01-01

    The functional state of cardiovascular system has been studied since 1986 in 168 patients who had acute radiation syndrome as the result of Chernobyl accident. There was revealed a progressive increase of cardiovascular system pathology. The number of patients with pathological signs at ECG increased from 4.8 % in 1987 to 11.3 % in 1994 and with myocardial hypertrophy from 1.2 % to 22.6 %. The number of patients with coronary heart disease increased on 17.2% and with essential hypertension on 15.5%. The physical working capacity reduced to 50-60 % of a due level for healthy persons. Two patients suffered from acute myocardial infarction during this period of observation. Thirteenth patients died from 1987 to 1995. Among them 4 patient died in a result of acute cardiac failure. The development of cardiovascular pathology has no any correlation with a dose of exposure. Three factors of cardiovascular pathology growth are supposed

  12. Mitochondrial Alterations and Oxidative Stress in an Acute Transient Mouse Model of Muscle Degeneration

    Science.gov (United States)

    Ramadasan-Nair, Renjini; Gayathri, Narayanappa; Mishra, Sudha; Sunitha, Balaraju; Mythri, Rajeswara Babu; Nalini, Atchayaram; Subbannayya, Yashwanth; Harsha, Hindalahalli Chandregowda; Kolthur-Seetharam, Ullas; Bharath, Muchukunte Mukunda Srinivas

    2014-01-01

    Muscular dystrophies (MDs) and inflammatory myopathies (IMs) are debilitating skeletal muscle disorders characterized by common pathological events including myodegeneration and inflammation. However, an experimental model representing both muscle pathologies and displaying most of the distinctive markers has not been characterized. We investigated the cardiotoxin (CTX)-mediated transient acute mouse model of muscle degeneration and compared the cardinal features with human MDs and IMs. The CTX model displayed degeneration, apoptosis, inflammation, loss of sarcolemmal complexes, sarcolemmal disruption, and ultrastructural changes characteristic of human MDs and IMs. Cell death caused by CTX involved calcium influx and mitochondrial damage both in murine C2C12 muscle cells and in mice. Mitochondrial proteomic analysis at the initial phase of degeneration in the model detected lowered expression of 80 mitochondrial proteins including subunits of respiratory complexes, ATP machinery, fatty acid metabolism, and Krebs cycle, which further decreased in expression during the peak degenerative phase. The mass spectrometry (MS) data were supported by enzyme assays, Western blot, and histochemistry. The CTX model also displayed markers of oxidative stress and a lowered glutathione reduced/oxidized ratio (GSH/GSSG) similar to MDs, human myopathies, and neurogenic atrophies. MS analysis identified 6 unique oxidized proteins from Duchenne muscular dystrophy samples (n = 6) (versus controls; n = 6), including two mitochondrial proteins. Interestingly, these mitochondrial proteins were down-regulated in the CTX model thereby linking oxidative stress and mitochondrial dysfunction. We conclude that mitochondrial alterations and oxidative damage significantly contribute to CTX-mediated muscle pathology with implications for human muscle diseases. PMID:24220031

  13. A Multiscale Computational Model of the Response of Swine Epidermis After Acute Irradiation

    Science.gov (United States)

    Hu, Shaowen; Cucinotta, Francis A.

    2012-01-01

    Radiation exposure from Solar Particle Events can lead to very high skin dose for astronauts on exploration missions outside the protection of the Earth s magnetic field [1]. Assessing the detrimental effects to human skin under such adverse conditions could be predicted by conducting territorial experiments on animal models. In this study we apply a computational approach to simulate the experimental data of the radiation response of swine epidermis, which is closely similar to human epidermis [2]. Incorporating experimentally measured histological and cell kinetic parameters into a multiscale tissue modeling framework, we obtain results of population kinetics and proliferation index comparable to unirradiated and acutely irradiated swine experiments [3]. It is noted the basal cell doubling time is 10 to 16 days in the intact population, but drops to 13.6 hr in the regenerating populations surviving irradiation. This complex 30-fold variation is proposed to be attributed to the shortening of the G1 phase duration. We investigate this radiation induced effect by considering at the sub-cellular level the expression and signaling of TGF-beta, as it is recognized as a key regulatory factor of tissue formation and wound healing [4]. This integrated model will allow us to test the validity of various basic biological rules at the cellular level and sub-cellular mechanisms by qualitatively comparing simulation results with published research, and should lead to a fuller understanding of the pathophysiological effects of ionizing radiation on the skin.

  14. Numerical simulation model of hyperacute/acute stage white matter infarction.

    Science.gov (United States)

    Sakai, Koji; Yamada, Kei; Oouchi, Hiroyuki; Nishimura, Tsunehiko

    2008-01-01

    Although previous studies have revealed the mechanisms of changes in diffusivity (apparent diffusion coefficient [ADC]) in acute brain infarction, changes in diffusion anisotropy (fractional anisotropy [FA]) in white matter have not been examined. We hypothesized that membrane permeability as well as axonal swelling play important roles, and we therefore constructed a simulation model using random walk simulation to replicate the diffusion of water molecules. We implemented a numerical diffusion simulation model of normal and infarcted human brains using C++ language. We constructed this 2-pool model using simple tubes aligned in a single direction. Random walk simulation diffused water. Axon diameters and membrane permeability were then altered in step-wise fashion. To estimate the effects of axonal swelling, axon diameters were changed from 6 to 10 microm. Membrane permeability was altered from 0% to 40%. Finally, both elements were combined to explain increasing FA in the hyperacute stage of white matter infarction. The simulation demonstrated that simple water shift into the intracellular space reduces ADC and increases FA, but not to the extent expected from actual human cases (ADC approximately 50%; FA approximately +20%). Similarly, membrane permeability alone was insufficient to explain this phenomenon. However, a combination of both factors successfully replicated changes in diffusivity indices. Both axonal swelling and reduced membrane permeability appear important in explaining changes in ADC and FA based on eigenvalues in hyperacute-stage white matter infarction.

  15. Fenofibrate plus Metformin Produces Cardioprotection in a Type 2 Diabetes and Acute Myocardial Infarction Model

    Directory of Open Access Journals (Sweden)

    Víctor Hugo Oidor-Chan

    2016-01-01

    Full Text Available We investigated whether fenofibrate, metformin, and their combination generate cardioprotection in a rat model of type 2 diabetes (T2D and acute myocardial infarction (AMI. Streptozotocin-induced diabetic- (DB- rats received 14 days of either vehicle, fenofibrate, metformin, or their combination and immediately after underwent myocardial ischemia/reperfusion (I/R. Fenofibrate plus metformin generated cardioprotection in a DBI/R model, reported as decreased coronary vascular resistance, compared to DBI/R-Vehicle, smaller infarct size, and increased cardiac work. The subchronic treatment with fenofibrate plus metformin increased, compared with DBI/R-Vehicle, total antioxidant capacity, manganese-dependent superoxide dismutase activity (MnSOD, guanosine triphosphate cyclohydrolase I (GTPCH-I expression, tetrahydrobiopterin : dihydrobiopterin (BH4 : BH2 ratio, endothelial nitric oxide synthase (eNOS activity, nitric oxide (NO bioavailability, and decreased inducible NOS (iNOS activity. These findings suggest that PPARα activation by fenofibrate + metformin, at low doses, generates cardioprotection in a rat model of T2D and AMI and may represent a novel treatment strategy to limit I/R injury in patients with T2D.

  16. Insights from computational modeling in inflammation and acute rejection in limb transplantation.

    Directory of Open Access Journals (Sweden)

    Dolores Wolfram

    Full Text Available Acute skin rejection in vascularized composite allotransplantation (VCA is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplexed analysis technology. Hierarchical Clustering Analysis, Principal Component Analysis, Random Forest Classification and Multinomial Logistic Regression models were used to segregate experimental groups. Based on Random Forest Classification, Multinomial Logistic Regression and Hierarchical Clustering Analysis models, IL-4, TNF-α and IL-12p70 were the best predictors of skin rejection and identified rejection well in advance of histopathological alterations. TNF-α and IL-12p70 were the best predictors of muscle rejection and also preceded histopathological alterations. Principal Component Analysis identified IL-1α, IL-18, IL-1β, and IL-4 as principal drivers of transplant rejection. Thus, inflammatory patterns associated with rejection are specific for the individual tissue and may be superior for early detection and targeted treatment of rejection.

  17. Effect of aging on airway remodeling and muscarinic receptors in a murine acute asthma model

    Directory of Open Access Journals (Sweden)

    Kang JY

    2013-10-01

    Full Text Available Ji Young Kang, Sook Young Lee, Chin Kook Rhee, Seung Joon Kim, Soon Seog Kwon, Young Kyoon KimDepartment of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, KoreaBackground and objectives: The influence of aging on the development of asthma has not been studied thoroughly. The aim of this study was to investigate age-related airway responses involving lung histology and expression of muscarinic receptors in a murine model of acute asthma. Methods: Female BALB/c mice at the ages of 6 weeks and 6, 9, and 12 months were sensitized and challenged with ovalbumin (OVA for 1 month (n = 8–12 per group. We analyzed inflammatory cells and T-helper (Th2 cytokines in bronchoalveolar lavage (BAL fluid and parameters of airway remodeling and expression of muscarinic receptors in lung tissue. Results: Among the OVA groups, total cell and eosinophil numbers in BAL fluid were significantly higher in the older (6-, 9-, and 12-month-old mice than in the young (6-week-old mice. Interleukin (IL 4 (IL-4 concentration increased, but IL-5 and IL-13 concentrations showed a decreased tendency, with age. IL-17 concentration tended to increase with age, which did not reach statistical significance. periodic acid-Schiff (PAS staining area, peribronchial collagen deposition, and area of α-smooth muscle staining were significantly higher in the 6-month older OVA group than in the young OVA group. The expression of the M3 and M2 muscarinic receptors tended to increase and decrease, respectively, with age. Conclusion: The aged mice showed an active and unique pattern not only on airway inflammation, but also on airway remodeling and expression of the muscarinic receptors during the development of acute asthma compared with the young mice. These findings suggest that the aging process affects the pathogenesis of acute asthma and age-specific approach might be more appropriate for better asthma control in a clinical practice.Keywords: aging, asthma

  18. Graphical Model Debugger Framework for Embedded Systems

    DEFF Research Database (Denmark)

    Zeng, Kebin

    2010-01-01

    Model Driven Software Development has offered a faster way to design and implement embedded real-time software by moving the design to a model level, and by transforming models to code. However, the testing of embedded systems has remained at the code level. This paper presents a Graphical Model...... Debugger Framework, providing an auxiliary avenue of analysis of system models at runtime by executing generated code and updating models synchronously, which allows embedded developers to focus on the model level. With the model debugger, embedded developers can graphically test their design model...

  19. The chain of care enabling tPA treatment in acute ischemic stroke : a comprehensive review of organisational models

    NARCIS (Netherlands)

    Lahr, Maarten M. H.; Luijckx, Gert-Jan; Vroomen, Patrick; van der Zee, D.J.; Buskens, Erik

    Protracted and partial implementation of treatment with intravenous tissue plasminogen activator (tPA) within 4.5 h after acute stroke onset results in potentially eligible patients not receiving optimal treatment. The goal of this study was to review the performance of various organisational models

  20. Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents. I. Validation of methods with ethanol

    NARCIS (Netherlands)

    McKee, R.H.; Lammers, J.H.C.M.; Hoogendijk, E.M.G.; Emmen, H.H.; Muijser, H.; Barsotti, D.A.; Owen, D.E.; Kulig, B.M.

    2006-01-01

    As a preliminary step to evaluating the acute neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, joint neurobehavioral/toxicokinetic studies were conducted which involved administering ethanol to rats and volunteers. The

  1. Finite element modeling of aponeurotomy: altered intramuscular myofascial force transmission yields complex sarcomere length distributions determining acute effects

    NARCIS (Netherlands)

    Yucesoy, C.A.; Koopman, Hubertus F.J.M.; Grootenboer, H.J.; Huijing, P.A.J.B.M.

    2007-01-01

    Finite element modeling of aponeurotomized rat extensor digitorium longus muscle was performed to investigate the acute effects of proximal aponeurotomy. The specific goal was to assess the changes in lengths of sarcomeres within aponeurotomized muscle and to explain how the intervention leads to

  2. ACUTE-TO-CHRONIC ESTIMATION (ACE V 2.0) WITH TIME-CONCENTRATION-EFFECT MODELS: USER MANUAL AND SOFTWARE

    Science.gov (United States)

    Ellersieck, Mark R., Amha Asfaw, Foster L. Mayer, Gary F. Krause, Kai Sun and Gunhee Lee. 2003. Acute-to-Chronic Estimation (ACE v2.0) with Time-Concentration-Effect Models: User Manual and Software. EPA/600/R-03/107. U.S. Environmental Protection Agency, National Health and Envi...

  3. Activation of counter-regulatory mechanisms in a rat renal acute rejection model

    Directory of Open Access Journals (Sweden)

    Salomon Daniel R

    2008-02-01

    Full Text Available Abstract Background Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation. Results We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family. Conclusion Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches.

  4. Andexanet alfa effectively reverses edoxaban anticoagulation effects and associated bleeding in a rabbit acute hemorrhage model

    Science.gov (United States)

    Lu, Genmin; Pine, Polly; Leeds, Janet M.; DeGuzman, Francis; Pratikhya, Pratikhya; Lin, Joyce; Malinowski, John; Hollenbach, Stanley J.; Curnutte, John T.

    2018-01-01

    Introduction Increasing use of factor Xa (FXa) inhibitors necessitates effective reversal agents to manage bleeding. Andexanet alfa, a novel modified recombinant human FXa, rapidly reverses the anticoagulation effects of direct and indirect FXa inhibitors. Objective To evaluate the ability of andexanet to reverse anticoagulation in vitro and reduce bleeding in rabbits administered edoxaban. Materials and methods In vitro studies characterized the interaction of andexanet with edoxaban and its ability to reverse edoxaban-mediated anti-FXa activity. In a rabbit model of surgically induced, acute hemorrhage, animals received edoxaban vehicle+andexanet vehicle (control), edoxaban (1 mg/kg)+andexanet vehicle, edoxaban+andexanet (75 mg, 5-minute infusion, 20 minutes after edoxaban), or edoxaban vehicle+andexanet prior to injury. Results Andexanet bound edoxaban with high affinity similar to FXa. Andexanet rapidly and dose-dependently reversed the effects of edoxaban on FXa activity and coagulation pharmacodynamic parameters in vitro. In edoxaban-anticoagulated rabbits, andexanet reduced anti-FXa activity by 82% (from 548±87 to 100±41 ng/ml; P<0.0001), mean unbound edoxaban plasma concentration by ~80% (from 100±10 to 21±6 ng/ml; P<0.0001), and blood loss by 80% vs. vehicle (adjusted for control, 2.6 vs. 12.9 g; P = 0.003). The reduction in blood loss correlated with the decrease in anti-FXa activity (r = 0.6993, P<0.0001) and unbound edoxaban (r = 0.5951, P = 0.0035). Conclusion These data demonstrate that andexanet rapidly reversed the anticoagulant effects of edoxaban, suggesting it could be clinically valuable for the management of acute and surgery-related bleeding. Correlation of blood loss with anti-FXa activity supports the use of anti-FXa activity as a biomarker for assessing anticoagulation reversal in clinical trials. PMID:29590221

  5. 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.

  6. Prediction of acute toxicity of cadmium and lead to zebrafish larvae by using a refined toxicokinetic-toxicodynamic model

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yongfei; Feng, Jianfeng, E-mail: fengjf@nankai.edu.cn; Zhu, Lin, E-mail: zhulin@nankai.edu.cn

    2015-12-15

    Highlights: • We developed a BLM-aided TK-TD model that considers the effects of H{sup +}. • The time-course metal concentration in larvae was well described by the TK model. • The time-course survival of zebrafish larvae was well simulated by the TD model. - Abstract: The biotic ligand model (BLM) and the toxicokinetic-toxicodynamic (TK-TD) model are essential in predicting the acute toxicity of metals in various species and exposure conditions; however, these models are usually separately utilized. In this study, a mechanistic TK-TD model was developed to predict the acute toxicity of 10{sup −6} M Cd and 10{sup −6} M Pb to zebrafish (Danio rerio) larvae. The novel approach links the BLM with relevant TK processes to simulate the bioaccumulation processes of Cd or Pb as a function of the maximum uptake rate of each metal, the affinity constants, and the concentrations of free metal ions and H{sup +} in test solutions. Results showed that the refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb to zebrafish larvae at pH 5.5, 6.5, and 7.0.

  7. Prediction of acute toxicity of cadmium and lead to zebrafish larvae by using a refined toxicokinetic-toxicodynamic model

    International Nuclear Information System (INIS)

    Gao, Yongfei; Feng, Jianfeng; Zhu, Lin

    2015-01-01

    Highlights: • We developed a BLM-aided TK-TD model that considers the effects of H"+. • The time-course metal concentration in larvae was well described by the TK model. • The time-course survival of zebrafish larvae was well simulated by the TD model. - Abstract: The biotic ligand model (BLM) and the toxicokinetic-toxicodynamic (TK-TD) model are essential in predicting the acute toxicity of metals in various species and exposure conditions; however, these models are usually separately utilized. In this study, a mechanistic TK-TD model was developed to predict the acute toxicity of 10"−"6 M Cd and 10"−"6 M Pb to zebrafish (Danio rerio) larvae. The novel approach links the BLM with relevant TK processes to simulate the bioaccumulation processes of Cd or Pb as a function of the maximum uptake rate of each metal, the affinity constants, and the concentrations of free metal ions and H"+ in test solutions. Results showed that the refined TK-TD model can accurately predict the accumulation and acute toxicity of Cd and Pb to zebrafish larvae at pH 5.5, 6.5, and 7.0.

  8. Primary Screening for Proteins Differentially Expressed in the Myocardium of a Rat Model of Acute Methamphetamine Intoxication

    Directory of Open Access Journals (Sweden)

    Guoqiang Qu

    2016-01-01

    Full Text Available The mechanism of myocardial injury induced by the cardiovascular toxicity of methamphetamine (MA has been shown to depend on alterations in myocardial proteins caused by MA. Primary screening of the expression of myocardial proteins in a rat model of MA intoxication was achieved by combining two-dimensional electrophoresis and mass spectrometry analyses, which revealed a total of 100 differentially expressed proteins. Of these, 13 displayed significantly altered expression. Moreover, Western blotting and real-time reverse transcription quantitative polymerase chain reaction analyses of several relative proteins demonstrated that acute MA intoxication lowers protein expression and mRNA transcription of aldehyde dehydrogenase-2 and NADH dehydrogenase (ubiquinone 1 alpha subcomplex subunit 10. In contrast, MA intoxication elevated the protein expression and mRNA transcription of heat shock protein family B (small member 1. By combining behavioral assessments of experimental rat models with the histological and pathological changes evident in cardiomyocytes, a mechanism accounting for MA myocardial toxicity was suggested. MA alters the regulation of gene transcription and the subsequent expression of certain proteins that participate in myocardial respiration and in responding to oxidative stress, resulting in myocardial dysfunction and structural changes that affect the functioning of the cardiovascular system.

  9. 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.

  10. Beneficial hemodynamic effects of nicorandil in a canine model of acute congestive heart failure: comparison with nitroglycerin and cromakalim.

    Science.gov (United States)

    Noguchi, K; Matsuzaki, T; Ojiri, Y; Koyama, T; Nakasone, J; Sakanashi, M

    1998-01-01

    Comparative hemodynamic effects of nicorandil (NCR), nitroglycerin (NTG) and cromakalim (CRM) were examined in a canine model of acute congestive heart failure (CHF). CHF was produced by injections of saponin into coronary arteries of anesthetized dogs followed by volume loading and continuous i.v. infusion of methoxamine. After the treatment, aortic blood flow (AoF), left ventricular dP/dt and myocardial segment shortening (SS) markedly decreased, while the left ventricular end-diastolic pressure (LVEDP), the right atrial pressure (RAP) and the systemic vascular resistance (SVR) increased. NCR (n = 6), NTG (n = 6) and CRM (n = 8), which were administered i.v. after production of CHF, caused a comparable reduction in LVEDP. NCR and CRM profoundly increased AoF and SS but NTG did only slightly. On the other hand, NTG and NCR but not CRM significantly reduced RAP. Intracoronary NCR (n = 8) exerted no or similar effects on SS as well as systemic hemodynamic indices to those observed with i.v. NCR despite distinct coronary vasodilation. These results indicate that NCR may exert beneficial hemodynamic effects in an experimental CHF mainly due to lessening both afterload and preload rather than the coronary vasodilating effect.

  11. Impact of e-alert systems on the care of patients with acute kidney injury.

    Science.gov (United States)

    Breighner, Crystal M; Kashani, Kianoush B

    2017-09-01

    With the recent advancement in electronic health record systems and meaningful use of information technology incentive programs (i.e., the American Recovery and Reinvestment Act, the Health Information Technology for Economic and Clinical Health Act, and the Centers for Medicare & Medicaid Services), interest in clinical decision support systems has risen. These systems have been used to examine a variety of different syndromes with variable reported effects. In recent years, electronic alerts (e-alerts) have been implemented at various institutions to decrease the morbidity associated with acute kidney injury (AKI). AKI is common, accounting for 1 in 7 hospital admissions, and is associated with increased length of hospital stay and mortality. AKI is often underrecognized, causing delayed intervention. The use of e-alerts may result in earlier recognition and intervention, as well as decreased morbidity and mortality. This must be balanced with the possibility of increased resource utilization that e-alerts may cause. Before widespread implementation, the ethical and legal consequences of not following e-alert recommendations must be established, and the optimal algorithm for AKI e-alert detection must be determined. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. 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...

  13. 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...

  14. Acute administration of n-3 rich triglyceride emulsions provides cardioprotection in murine models after ischemia-reperfusion.

    Directory of Open Access Journals (Sweden)

    Hylde Zirpoli

    Full Text Available Dietary n-3 fatty acids (FAs may reduce cardiovascular disease risk. We questioned whether acute administration of n-3 rich triglyceride (TG emulsions could preserve cardiac function and decrease injury after ischemia/reperfusion (I/R insult. We used two different experimental models: in vivo, C57BL/6 mice were exposed to acute occlusion of the left anterior descending coronary artery (LAD, and ex-vivo, C57BL/6 murine hearts were perfused using Langendorff technique (LT. In the LAD model, mice treated with n-3 TG emulsion (1.5 g/kg body weight, immediately after ischemia and 1 h later during reperfusion, significantly reduced infarct size and maintained cardiac function (p<0.05. In the LT model, administration of n-3 TG emulsion (300 mg TG/100 ml during reperfusion significantly improved functional recovery (p<0.05. In both models, lactate dehydrogenase (LDH levels, as a marker of injury, were significantly reduced by n-3 TG emulsion. To investigate the mechanisms by which n-3 FAs protects hearts from I/R injury, we investigated changes in key pathways linked to cardioprotection. In the ex-vivo model, we showed that n-3 FAs increased phosphorylation of AKT and GSK3β proteins (p<0.05. Acute n-3 TG emulsion treatment also increased Bcl-2 protein level and reduced an autophagy marker, Beclin-1 (p<0.05. Additionally, cardioprotection by n-3 TG emulsion was linked to changes in PPARγ protein expression (p<0.05. Rosiglitazone and p-AKT inhibitor counteracted the positive effect of n-3 TG; GSK3β inhibitor plus n-3 TG significantly inhibited LDH release. We conclude that acute n-3 TG injection during reperfusion provides cardioprotection. This may prove to be a novel acute adjunctive reperfusion therapy after treating patients with myocardial infarction.

  15. Mesotherapy versus Systemic Therapy in the Treatment of Acute Low Back Pain: A Randomized Trial

    Directory of Open Access Journals (Sweden)

    Cosimo Costantino

    2011-01-01

    Full Text Available Pharmacological therapy of back pain with analgesics and anti-inflammatory drugs is frequently associated with adverse effects, particularly in the elderly. Aim of this study was to compare mesotherapic versus conventional systemic administration of nonsteroidal anti-inflammatory drugs (NSAIDs and corticosteroids in patients with acute low back pain. Eighty-four patients were randomized to receive anti-inflammatory therapy according to the following protocols: (a mesotherapy group received the 1st and 4th day 2% lidocaine (1 mL + ketoprofen 160 mg (1 mL + methylprednisolone 40 mg (1 mL, then on 7th, 10th, and 13th day, 2% lidocaine (1 mL + ketoprofen 160 mg (1 mL + methylprednisolone 20 mg (1 mL (b conventional therapy group received ketoprofen 80 mg × 2/die and esomeprazole 20 mg/die orally for 12 days, methylprednisolone 40 mg/die intramuscularly for 4 days, followed by methylprednisolone 20 mg/die for 3 days, and thereafter, methylprednisolone 20 mg/die at alternate days. Pain intensity and functional disability were assessed at baseline (T0, at the end of treatment (T1, and 6 months thereafter (T2 by using visual analogic scale (VAS and Roland-Morris disability questionnaire (RMDQ. In both groups, VAS and RMDQ values were significantly reduced at the end of drug treatment and after 6 months, in comparison with baseline. No significant differences were found between the two groups. This suggests that mesotherapy may be a valid alternative to conventional therapy in the treatment of acute low back pain with corticosteroids and NSAIDs.

  16. Mesotherapy versus Systemic Therapy in the Treatment of Acute Low Back Pain: A Randomized Trial.

    Science.gov (United States)

    Costantino, Cosimo; Marangio, Emilio; Coruzzi, Gabriella

    2011-01-01

    Pharmacological therapy of back pain with analgesics and anti-inflammatory drugs is frequently associated with adverse effects, particularly in the elderly. Aim of this study was to compare mesotherapic versus conventional systemic administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids in patients with acute low back pain. Eighty-four patients were randomized to receive anti-inflammatory therapy according to the following protocols: (a) mesotherapy group received the 1st and 4th day 2% lidocaine (1 mL) + ketoprofen 160 mg (1 mL) + methylprednisolone 40 mg (1 mL), then on 7th, 10th, and 13th day, 2% lidocaine (1 mL) + ketoprofen 160 mg (1 mL) + methylprednisolone 20 mg (1 mL) (b) conventional therapy group received ketoprofen 80 mg × 2/die and esomeprazole 20 mg/die orally for 12 days, methylprednisolone 40 mg/die intramuscularly for 4 days, followed by methylprednisolone 20 mg/die for 3 days, and thereafter, methylprednisolone 20 mg/die at alternate days. Pain intensity and functional disability were assessed at baseline (T0), at the end of treatment (T1), and 6 months thereafter (T2) by using visual analogic scale (VAS) and Roland-Morris disability questionnaire (RMDQ). In both groups, VAS and RMDQ values were significantly reduced at the end of drug treatment and after 6 months, in comparison with baseline. No significant differences were found between the two groups. This suggests that mesotherapy may be a valid alternative to conventional therapy in the treatment of acute low back pain with corticosteroids and NSAIDs.

  17. Lung volume recruitment acutely increases respiratory system compliance in individuals with severe respiratory muscle weakness

    Directory of Open Access Journals (Sweden)

    Yannick Molgat-Seon

    2017-03-01

    Full Text Available The aim of the present study was to determine whether lung volume recruitment (LVR acutely increases respiratory system compliance (Crs in individuals with severe respiratory muscle weakness (RMW. Individuals with RMW resulting from neuromuscular disease or quadriplegia (n=12 and healthy controls (n=12 underwent pulmonary function testing and the measurement of Crs at baseline, immediately after, 1 h after and 2 h after a single standardised session of LVR. The LVR session involved 10 consecutive supramaximal lung inflations with a manual resuscitation bag to the highest tolerable mouth pressure or a maximum of 50 cmH2O. Each LVR inflation was followed by brief breath-hold and a maximal expiration to residual volume. At baseline, individuals with RMW had lower Crs than controls (37±5 cmH2O versus 109±10 mL·cmH2O−1, p0.05. LVR had no significant effect on measures of pulmonary function at any time point in either group (all p>0.05. During inflations, mean arterial pressure decreased significantly relative to baseline by 10.4±2.8 mmHg and 17.3±3.0 mmHg in individuals with RMW and controls, respectively (both p<0.05. LVR acutely increases Crs in individuals with RMW. However, the high airway pressures during inflations cause reductions in mean arterial pressure that should be considered when applying this technique.

  18. In silico assessment of the acute toxicity of chemicals: recent advances and new model for multitasking prediction of toxic effect.

    Science.gov (United States)

    Kleandrova, Valeria V; Luan, Feng; Speck-Planche, Alejandro; Cordeiro, M Natália D S

    2015-01-01

    The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results.

  19. An intense and short-lasting burst of neutrophil activation differentiates early acute myocardial infarction from systemic inflammatory syndromes.

    Directory of Open Access Journals (Sweden)

    Norma Maugeri

    Full Text Available BACKGROUND: Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS compared to stable angina and to systemic inflammatory diseases. METHODS AND FINDINGS: The myeloperoxidase (MPO content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS, 69 with chronic stable angina (CSA, 50 with inflammation due to either non-infectious (acute bone fracture, infectious (sepsis or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis. Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization. One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils. CONCLUSIONS: ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via

  20. Harmonisation of the acute respiratory infection reporting system in the Czech Republic with the European community networks.

    NARCIS (Netherlands)

    Kyncl, J.; Paget, W.J.; Havlickova, M.; Kriz, B.

    2005-01-01

    Respiratory virus activity is detected in Europe each winter, yet the precise timing and size of this activity is highly unpredictable. The impact of influenza infection and/or acute respiratory infection in European countries is continuously monitored through a variety of surveillance systems. All

  1. Practical use, effects and complications of prehospital treatment of acute cardiogenic pulmonary edema using the Boussignac CPAP system

    NARCIS (Netherlands)

    E.E. Spijker (Eva Eiske); M. De Bont (Maarten); M. Bax (Matthijs); M. Sandel (Maro)

    2013-01-01

    textabstractBackground: Early use of continuous positive airway pressure (CPAP) has been shown to be beneficial within the setting of acute cardiogenic pulmonary edema (ACPE). The Boussignac CPAP system (BCPAP) was therefore introduced into the protocols of emergency medical services (EMS) in a

  2. Exploring the Relationships between the Electronic Health Record System Components and Patient Outcomes in an Acute Hospital Setting

    Science.gov (United States)

    Wiggley, Shirley L.

    2011-01-01

    Purpose: The purpose of this study was to examine the relationship between the electronic health record system components and patient outcomes in an acute hospital setting, given that the current presidential administration has earmarked nearly $50 billion to the implementation of the electronic health record. The relationship between the…

  3. Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly phenotype of the stable knockout zebrafish model.

    Directory of Open Access Journals (Sweden)

    Tilman Jobst-Schwan

    Full Text Available Until recently, morpholino oligonucleotides have been widely employed in zebrafish as an acute and efficient loss-of-function assay. However, off-target effects and reproducibility issues when compared to stable knockout lines have compromised their further use. Here we employed an acute CRISPR/Cas approach using multiple single guide RNAs targeting simultaneously different positions in two exemplar genes (osgep or tprkb to increase the likelihood of generating mutations on both alleles in the injected F0 generation and to achieve a similar effect as morpholinos but with the reproducibility of stable lines. This multi single guide RNA approach resulted in median likelihoods for at least one mutation on each allele of >99% and sgRNA specific insertion/deletion profiles as revealed by deep-sequencing. Immunoblot showed a significant reduction for Osgep and Tprkb proteins. For both genes, the acute multi-sgRNA knockout recapitulated the microcephaly phenotype and reduction in survival that we observed previously in stable knockout lines, though milder in the acute multi-sgRNA knockout. Finally, we quantify the degree of mutagenesis by deep sequencing, and provide a mathematical model to quantitate the chance for a biallelic loss-of-function mutation. Our findings can be generalized to acute and stable CRISPR/Cas targeting for any zebrafish gene of interest.

  4. Agent oriented modeling of business information systems

    OpenAIRE

    Vymetal, Dominik

    2009-01-01

    Enterprise modeling is an abstract definition of processes running in enterprise using process, value, data and resource models. There are two perspectives of business modeling: process perspective and value chain perspective. Both have some advantages and disadvantages. This paper proposes a combination of both perspectives into one generic model. The model takes also social part or the enterprise system into consideration and pays attention to disturbances influencing the enterprise system....

  5. Circulating histones are major mediators of systemic inflammation and cellular injury in patients with acute liver failure.

    Science.gov (United States)

    Wen, Zongmei; Lei, Zhen; Yao, Lu; Jiang, Ping; Gu, Tao; Ren, Feng; Liu, Yan; Gou, Chunyan; Li, Xiuhui; Wen, Tao

    2016-09-29

    Acute liver failure (ALF) is a life-threatening systemic disorder. Here we investigated the impact of circulating histones, recently identified inflammatory mediators, on systemic inflammation and liver injury in murine models and patients with ALF. We analyzed histone levels in blood samples from 62 patients with ALF, 60 patients with chronic liver disease, and 30 healthy volunteers. We incubated patients' sera with human L02 hepatocytes and monocytic U937 cells to assess cellular damage and cytokine production. d-galactosamine plus lipopolysaccharide (GalN/LPS), concanavalin A (ConA), and acetaminophen (APAP) were given to C57BL/6N mice to induce liver injury, respectively, and the pathogenic role of circulating histones was studied. Besides, the protective effect of nonanticoagulant heparin, which can bind histones, was evaluated with in vivo and ex vivo investigations. We observed that circulating histones were significantly increased in patients with ALF, and correlated with disease severity and mortality. Significant systemic inflammation was also pronounced in ALF patients, which were associated with histone levels. ALF patients' sera induced significant L02 cell death and stimulated U937 cells to produce cytokines, which were abrogated by nonanticoagulant heparin. Furthermore, circulating histones were all released remarkably in GalN/LPS, ConA, and APAP-treated mice, and associated with high levels of inflammatory cytokines. Heparin reduced systemic inflammation and liver damage in mice, suggesting that it could interfere with histone-associated liver injury. Collectively, these findings demonstrate that circulating histones are critical mediators of systemic inflammation and cellular damage in ALF, which may be potentially translatable for clinical use.

  6. Acute administration of n-3 rich triglyceride emulsions provides cardioprotection in murine models after ischemia-reperfusion.

    Science.gov (United States)

    Zirpoli, Hylde; Abdillahi, Mariane; Quadri, Nosirudeen; Ananthakrishnan, Radha; Wang, Lingjie; Rosario, Rosa; Zhu, Zhengbin; Deckelbaum, Richard J; Ramasamy, Ravichandran

    2015-01-01

    Dietary n-3 fatty acids (FAs) may reduce cardiovascular disease risk. We questioned whether acute administration of n-3 rich triglyceride (TG) emulsions could preserve cardiac function and decrease injury after ischemia/reperfusion (I/R) insult. We used two different experimental models: in vivo, C57BL/6 mice were exposed to acute occlusion of the left anterior descending coronary artery (LAD), and ex-vivo, C57BL/6 murine hearts were perfused using Langendorff technique (LT). In the LAD model, mice treated with n-3 TG emulsion (1.5 g/kg body weight), immediately after ischemia and 1 h later during reperfusion, significantly reduced infarct size and maintained cardiac function (plevels, as a marker of injury, were significantly reduced by n-3 TG emulsion. To investigate the mechanisms by which n-3 FAs protects hearts from I/R injury, we investigated changes in key pathways linked to cardioprotection. In the ex-vivo model, we showed that n-3 FAs increased phosphorylation of AKT and GSK3β proteins (plevel and reduced an autophagy marker, Beclin-1 (pGSK3β inhibitor plus n-3 TG significantly inhibited LDH release. We conclude that acute n-3 TG injection during reperfusion provides cardioprotection. This may prove to be a novel acute adjunctive reperfusion therapy after treating patients with myocardial infarction.

  7. Systemic lupus erythaematosus in a multiethnic US cohort (LUMINA) LIII: disease expression and outcome in acute onset lupus.

    Science.gov (United States)

    Bertoli, A M; Vilá, L M; Reveille, J D; Alarcón, G S

    2008-04-01

    To determine the features associated with acute onset systemic lupus erythaematosus (SLE). A total of 631 SLE patients from LUMINA (for "lupus in minority populations: nature vs nurture"), a multiethnic (Hispanics, African-Americans and Caucasians) cohort, were studied. Acute disease onset was defined as the accrual of > or = 4 American College of Rheumatology (ACR) criteria for the classification of SLE in < or = 4 weeks. Socioeconomic demographic features, clinical manifestations, disease activity, damage accrual, mortality, autoantibodies, HLA class II and FCGR alleles, behavioural/psychological variables were compared between patients with acute and insidious disease onset by univariable (chi(2) and Student t test) and multivariable (stepwise logistic regression) analyses. A total of 94 (15%) patients had acute disease onset. In the multivariable analysis, patients with acute onset lupus had more renal involvement (odds ratio (OR) = 1.845, 95% CI 1.076-3.162; p = 0.026) and higher disease activity (OR = 1.057, 95% CI 1.005-1.112; p = 0.030). By contrast, age (OR = 0.976, 95% CI 0.956-0.997; p = 0.025), education (OR = 0.901, 95% CI 0.827-0.983, p = 0.019), health insurance (OR = 0.423, 95% CI 0.249-0.718; p = 0.001) and skin involvement (OR = 0.346, 95% CI 0.142-0.843; p = 0.019) were negatively associated with acute onset lupus. No differences were found regarding the serological, genetic and behavioural/psychological features; this was also the case for damage accrual and mortality. Patients with acute onset lupus seem to be younger, have a lower socio-economic status and display more severe disease in terms of clinical manifestations and disease activity. However, intermediate (damage) and long-term (mortality) outcomes appear not to be influenced by the type of disease onset in SLE.

  8. Efficiency of unenhanced MRI in the diagnosis of acute appendicitis: Comparison with Alvarado scoring system and histopathological results

    International Nuclear Information System (INIS)

    Inci, Ercan; Hocaoglu, Elif; Aydin, Sibel; Palabiyik, Figen; Cimilli, Tan; Turhan, Ahmet Nuray; Ayguen, Ersan

    2011-01-01

    Purpose: The purpose of this study was to assess the diagnostic value of unenhanced magnetic resonance imaging (MRI) in the diagnosis of acute appendicitis and compare with Alvarado scores and histopathological results. Materials and methods: The study included 85 consecutive patients (mean age, 26.5 ± 11.3 years) who were clinically suspected of having acute appendicitis. Each patients Alvarado scores were recorded and unenhanced MRI was performed, consisting of T1-weighted, T2-weighted and fat-suppressed T2-weighted fast spin-echo sequences. The MR images were prospectively reviewed in consensus for the presence of acute appendicitis by two radiologists who were blinded to the results of the Alvarado scores. The study population were divided into three subgroups based on the MRI findings: Group I: definitely not appendicitis, Group II: probably appendicitis, Group III: definitely appendicitis. All patients were divided into two subgroups according to Alvarado scores as Group A (low: 1-6), and Group B (high: 7-10). MR findings were compared with Alvarado scores and histopathological findings. Results: Sixty-six (77.6%) of the 85 patients with clinically suspected acute appendicitis, had undergone surgery. The diagnosis of appendicitis could be correctly achieved with MRI in 55 (83.3%) of 57 (86.4%) patients with histopathologically proven acute appendicitis. The sensitivity, specificity, positive predictive value and negative predictive value of MRI examination and Alvarado scoring system in the diagnosis of acute appendicitis were 96.49%, 66.67%, 94.83%, 75.0% and 84.21%, 66.67%, 94.12%, 40.0%, respectively. Conclusions: MRI is a valuable technique for detecting acute appendicitis even in the cases with low Alvarado scores. To increase the diagnostic accuracy and preventing unnecessary laparotomies for suspected appendicitis, shorter and cheaper unenhanced basic MRI may be performed.

  9. Efficiency of unenhanced MRI in the diagnosis of acute appendicitis: Comparison with Alvarado scoring system and histopathological results

    Energy Technology Data Exchange (ETDEWEB)

    Inci, Ercan, E-mail: ercan_inci@mynet.com [Department of Radiology, Istanbul Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Incirli-Bakirkoy, Istanbul (Turkey); Hocaoglu, Elif; Aydin, Sibel; Palabiyik, Figen; Cimilli, Tan [Department of Radiology, Istanbul Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Incirli-Bakirkoy, Istanbul (Turkey); Turhan, Ahmet Nuray; Ayguen, Ersan [Department of Surgery, Istanbul Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul (Turkey)

    2011-11-15

    Purpose: The purpose of this study was to assess the diagnostic value of unenhanced magnetic resonance imaging (MRI) in the diagnosis of acute appendicitis and compare with Alvarado scores and histopathological results. Materials and methods: The study included 85 consecutive patients (mean age, 26.5 {+-} 11.3 years) who were clinically suspected of having acute appendicitis. Each patients Alvarado scores were recorded and unenhanced MRI was performed, consisting of T1-weighted, T2-weighted and fat-suppressed T2-weighted fast spin-echo sequences. The MR images were prospectively reviewed in consensus for the presence of acute appendicitis by two radiologists who were blinded to the results of the Alvarado scores. The study population were divided into three subgroups based on the MRI findings: Group I: definitely not appendicitis, Group II: probably appendicitis, Group III: definitely appendicitis. All patients were divided into two subgroups according to Alvarado scores as Group A (low: 1-6), and Group B (high: 7-10). MR findings were compared with Alvarado scores and histopathological findings. Results: Sixty-six (77.6%) of the 85 patients with clinically suspected acute appendicitis, had undergone surgery. The diagnosis of appendicitis could be correctly achieved with MRI in 55 (83.3%) of 57 (86.4%) patients with histopathologically proven acute appendicitis. The sensitivity, specificity, positive predictive value and negative predictive value of MRI examination and Alvarado scoring system in the diagnosis of acute appendicitis were 96.49%, 66.67%, 94.83%, 75.0% and 84.21%, 66.67%, 94.12%, 40.0%, respectively. Conclusions: MRI is a valuable technique for detecting acute appendicitis even in the cases with low Alvarado scores. To increase the diagnostic accuracy and preventing unnecessary laparotomies for suspected appendicitis, shorter and cheaper unenhanced basic MRI may be performed.

  10. [Establishment of a D-galactosamine/lipopolysaccharide induced acute-on-chronic liver failure model in rats].

    Science.gov (United States)

    Liu, Xu-hua; Chen, Yu; Wang, Tai-ling; Lu, Jun; Zhang, Li-jie; Song, Chen-zhao; Zhang, Jing; Duan, Zhong-ping

    2007-10-01

    To establish a practical and reproducible animal model of human acute-on-chronic liver failure for further study of the pathophysiological mechanism of acute-on-chronic liver failure and for drug screening and evaluation in its treatment. Immunological hepatic fibrosis was induced by human serum albumin in Wistar rats. In rats with early-stage cirrhosis (fibrosis stage IV), D-galactosamine and lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours. Liver function tests and plasma cytokine levels were measured after D-galactosamine/lipopolysaccharide administration and liver pathology was studied. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Most of the rats treated with human albumin developed cirrhosis and fibrosis, and 90% of them died from acute liver failure after administration of D-galactosamine/lipopolysaccharide, with a mean survival time of (16.1+/-3.7) hours. Liver histopathology showed massive or submassive necrosis of the regenerated nodules, while fibrosis septa were intact. Liver function tests were compatible with massive necrosis of hepatocytes. Plasma level of TNFalpha increased significantly, parallel with the degree of the hepatocytes apoptosis. Plasma IL-10 levels increased similarly as seen in patients with acute-on-chronic liver failure. We established an animal model of acute-on-chronic liver failure by treating rats with human serum albumin and later with D-galactosamine and lipopolysaccharide. TNFalpha-mediated liver cell apoptoses plays a very important role in the pathogenesis of acute liver failure.

  11. An online model composition tool for system biology models.

    Science.gov (United States)

    Coskun, Sarp A; Cicek, A Ercument; Lai, Nicola; Dash, Ranjan K; Ozsoyoglu, Z Meral; Ozsoyoglu, Gultekin

    2013-09-05

    There are multiple representation formats for Systems Biology computational models, and the Systems Biology Markup Language (SBML) is one of the most widely used. SBML is used to capture, store, and distribute computational models by Systems Biology data sources (e.g., the BioModels Database) and researchers. Therefore, there is a need for all-in-one web-based solutions that support advance SBML functionalities such as uploading, editing, composing, visualizing, simulating, querying, and browsing computational models. We present the design and implementation of the Model Composition Tool (Interface) within the PathCase-SB (PathCase Systems Biology) web portal. The tool helps users compose systems biology models to facilitate the complex process of merging systems biology models. We also present three tools that support the model composition tool, namely, (1) Model Simulation Interface that generates a visual plot of the simulation according to user's input, (2) iModel Tool as a platform for users to upload their own models to compose, and (3) SimCom Tool that provides a side by side comparison of models being composed in the same pathway. Finally, we provide a web site that hosts BioModels Database models and a separate web site that hosts SBML Test Suite models. Model composition tool (and the other three tools) can be used with little or no knowledge of the SBML document structure. For this reason, students or anyone who wants to learn about systems biology will benefit from the described functionalities. SBML Test Suite models will be a nice starting point for beginners. And, for more advanced purposes, users will able to access and employ models of the BioModels Database as well.

  12. An Intradermal Inoculation Mouse Model for Immunological Investigations of Acute Scrub Typhus and Persistent Infection.

    Directory of Open Access Journals (Sweden)

    Lynn Soong

    2016-08-01

    Full Text Available Scrub typhus is a neglected tropical disease, caused by Orientia tsutsugamushi, a Gram-negative bacterium that is transmitted to mammalian hosts during feeding by Leptotrombidium mites and replicates predominantly within endothelial cells. Most studies of scrub typhus in animal models have utilized either intraperitoneal or intravenous inoculation; however, there is limited information on infection by the natural route in murine model skin or its related early host responses. Here, we developed an intradermal (i.d. inoculation model of scrub typhus and focused on the kinetics of the host responses in the blood and major infected organs. Following ear inoculation with 6 x 104 O. tsutsugamushi, mice developed fever at 11-12 days post-infection (dpi, followed by marked hypothermia and body weight loss at 14-19 dpi. Bacteria in blood and tissues and histopathological changes were detected around 9 dpi and peaked around 14 dpi. Serum cytokine analyses revealed a mixed Th1/Th2 response, with marked elevations of MCP-1/CCL2, MIP-1α/CCL3 and IL-10 at 9 dpi, followed by increased concentrations of pro-inflammatory markers (IL-6, IL-12, IFN-γ, G-CSF, RANTES/CCL5, KC/CCL11, IL-1α/β, IL-2, TNF-α, GM-CSF, as well as modulatory cytokines (IL-9, IL-13. Cytokine levels in lungs had similar elevation patterns, except for a marked reduction of IL-9. The Orientia 47-kDa gene and infectious bacteria were detected in several organs for up to 84 dpi, indicating persistent infection. This is the first comprehensive report of acute scrub typhus and persistent infection in i.d.-inoculated C57BL/6 mice. This is a significant improvement over current murine models for Orientia infection and will permit detailed studies of host immune responses and infection control interventions.

  13. [Acute kidney injury after pediatric cardiac surgery: risk factors and outcomes. Proposal for a predictive model].

    Science.gov (United States)

    Cardoso, Bárbara; Laranjo, Sérgio; Gomes, Inês; Freitas, Isabel; Trigo, Conceição; Fragata, Isabel; Fragata, José; Pinto, Fátima

    2016-02-01

    To characterize the epidemiology and risk factors for acute kidney injury (AKI) after pediatric cardiac surgery in our center, to determine its association with poor short-term outcomes, and to develop a logistic regression model that will predict the risk of AKI for the study population. This single-center, retrospective study included consecutive pediatric patients with congenital heart disease who underwent cardiac surgery between January 2010 and December 2012. Exclusion criteria were a history of renal disease, dialysis or renal transplantation. Of the 325 patients included, median age three years (1 day-18 years), AKI occurred in 40 (12.3%) on the first postoperative day. Overall mortality was 13 (4%), nine of whom were in the AKI group. AKI was significantly associated with length of intensive care unit stay, length of mechanical ventilation and in-hospital death (p<0.01). Patients' age and postoperative serum creatinine, blood urea nitrogen and lactate levels were included in the logistic regression model as predictor variables. The model accurately predicted AKI in this population, with a maximum combined sensitivity of 82.1% and specificity of 75.4%. AKI is common and is associated with poor short-term outcomes in this setting. Younger age and higher postoperative serum creatinine, blood urea nitrogen and lactate levels were powerful predictors of renal injury in this population. The proposed model could be a useful tool for risk stratification of these patients. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  14. Efficacy of Polaprezinc for Acute Radiation Proctitis in a Rat Model

    International Nuclear Information System (INIS)

    Doi, Hiroshi; Kamikonya, Norihiko; Takada, Yasuhiro; Fujiwara, Masayuki; Tsuboi, Keita; Inoue, Hiroyuki; Tanooka, Masao; Nakamura, Takeshi; Shikata, Toshiyuki; Tsujimura, Tohru; Hirota, Shozo

    2011-01-01

    Purpose: The purpose of the present study was to standardize the experimental rat model of radiation proctitis and to examine the efficacy of polaprezinc on radiation proctitis. Methods and Materials: A total of 54 female Wistar rats (5 weeks old) were used. The rats were divided into three groups: those treated with polaprezinc (PZ+), those treated with base alone, exclusive of polaprezinc (PZ-), and those treated without any medication (control). All the rats were irradiated to the rectum. Polaprezinc was prepared as an ointment. The ointment was administered rectally each day after irradiation. All rats were killed on the 10th day after irradiation. The mucosal changes were evaluated endoscopically and pathologically. The results were graded from 0 to 4 and compared according to milder or more severe status, as applicable. Results: According to the endoscopic findings, the proportion of mild changes in the PZ+, PZ-, and control group was 71.4%, 25.0%, and 14.3% respectively. On pathologic examination, the proportion of low-grade findings in the PZ+, PZ-, and control group was 80.0%, 58.3%, and 42.9% for mucosal damage, 85.0%, 41.7%, and 42.9% for a mild degree of inflammation, and 50.0%, 33.3%, and 4.8% for a shallow depth of inflammation, respectively. The PZ+ group tended to have milder mucosal damage than the other groups, according to all criteria used. In addition, significant differences were observed between the PZ+ and control groups regarding the endoscopic findings, degree of inflammation, and depth of inflammation. Conclusions: This model was confirmed to be a useful experimental rat model for radiation proctitis. The results of the present study have demonstrated the efficacy of polaprezinc against acute radiation-induced rectal disorders using the rat model.

  15. 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

  16. Modelling a data acquisition system

    International Nuclear Information System (INIS)

    Green, P.W.

    1986-01-01

    A data acquisition system to be run on a Data General ECLIPSE computer has been completely designed and developed using a VAX 11/780. This required that many of the features of the RDOS operating system be simulated on the VAX. Advantages and disadvantages of this approach are discussed, with particular regard to transportability of the system among different machines/operating systems, and the effect of the approach on various design decisions

  17. 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.

  18. On Verification Modelling of Embedded Systems

    NARCIS (Netherlands)

    Brinksma, Hendrik; Mader, Angelika H.

    Computer-aided verification of embedded systems hinges on the availability of good verification models of the systems at hand. Such models must be much simpler than full design models or specifications to be of practical value, because of the unavoidable combinatorial complexities in the

  19. 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...

  20. Acute Anxiety Predicts Components of the Cold Shock Response on Cold Water Immersion: Toward an Integrated Psychophysiological Model of Acute Cold Water Survival

    Science.gov (United States)

    Barwood, Martin J.; Corbett, Jo; Massey, Heather; McMorris, Terry; Tipton, Mike; Wagstaff, Christopher R. D.

    2018-01-01

    R component of the CSR when anxiety levels were lowered (CON2; p anxiety was increased suggesting different drivers of the CSR when anxiety levels were manipulated; correlation data supported these relationships. Discussion: Acute anxiety is integral to the CSR before and after habituation. We offer a new integrated model including neuroanatomical, perceptual and attentional components of the CSR to explain these data. PMID:29695988

  1. Acute Anxiety Predicts Components of the Cold Shock Response on Cold Water Immersion: Toward an Integrated Psychophysiological Model of Acute Cold Water Survival.

    Science.gov (United States)

    Barwood, Martin J; Corbett, Jo; Massey, Heather; McMorris, Terry; Tipton, Mike; Wagstaff, Christopher R D

    2018-01-01

    levels were lowered (CON2; p CSR ( p CSR when anxiety levels were manipulated; correlation data supported these relationships. Discussion: Acute anxiety is integral to the CSR before and after habituation. We offer a new integrated model including neuroanatomical, perceptual and attentional components of the CSR to explain these data.

  2. Grey Box Modelling of Hydrological Systems

    DEFF Research Database (Denmark)

    Thordarson, Fannar Ørn

    of two papers where the stochastic differential equation based model is used for sewer runoff from a drainage system. A simple model is used to describe a complex rainfall-runoff process in a catchment, but the stochastic part of the system is formulated to include the increasing uncertainty when...... rainwater flows through the system, as well as describe the lower limit of the uncertainty when the flow approaches zero. The first paper demonstrates in detail the grey box model and all related transformations required to obtain a feasible model for the sewer runoff. In the last paper this model is used......The main topic of the thesis is grey box modelling of hydrologic systems, as well as formulation and assessment of their embedded uncertainties. Grey box model is a combination of a white box model, a physically-based model that is traditionally formulated using deterministic ordinary differential...

  3. Compositional Modelling of Stochastic Hybrid Systems

    NARCIS (Netherlands)

    Strubbe, S.N.

    2005-01-01

    In this thesis we present a modelling framework for compositional modelling of stochastic hybrid systems. Hybrid systems consist of a combination of continuous and discrete dynamics. The state space of a hybrid system is hybrid in the sense that it consists of a continuous component and a discrete

  4. Modelling and Verification of Relay Interlocking Systems

    DEFF Research Database (Denmark)

    Haxthausen, Anne Elisabeth; Bliguet, Marie Le; Kjær, Andreas

    2010-01-01

    This paper describes how relay interlocking systems as used by the Danish railways can be formally modelled and verified. Such systems are documented by circuit diagrams describing their static layout. It is explained how to derive a state transition system model for the dynamic behaviour...

  5. Modeling and simulation of systems using Matlab and Simulink

    CERN Document Server

    Chaturvedi, Devendra K

    2009-01-01

    Introduction to SystemsSystemClassification of SystemsLinear SystemsTime-Varying vs. Time-Invariant Systems Lumped vs. Distributed Parameter SystemsContinuous- and Discrete-Time Systems Deterministic vs. Stochastic Systems Hard and Soft Systems Analysis of Systems Synthesis of Systems Introduction to System Philosophy System Thinking Large and Complex Applied System Engineering: A Generic ModelingSystems ModelingIntroduction Need of System Modeling Modeling Methods for Complex Systems Classification of ModelsCharacteristics of Models ModelingMathematical Modeling of Physical SystemsFormulation of State Space Model of SystemsPhysical Systems Theory System Components and Interconnections Computation of Parameters of a Component Single Port and Multiport Systems Techniques of System Analysis Basics of Linear Graph Theoretic ApproachFormulation of System Model for Conceptual SystemFormulation System Model for Physical SystemsTopological RestrictionsDevelopment of State Model of Degenerative SystemSolution of Stat...

  6. The Systemic Inflammatory Response Syndrome (SIRS in acutely hospitalised medical patients: a cohort study

    Directory of Open Access Journals (Sweden)

    Storgaard Merete

    2009-12-01

    Full Text Available Abstract Background Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count. The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown. Methods We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status, blood pressure, infection and comorbidity on admission was registered together with 28-day mortality. Results A hundred and fifty-four patients (35% had SIRS on admission, 211 patients (48% had no SIRS, and 72 patients (16% had insufficient data to evaluate their SIRS status. SIRS patients were 2.2 times more frequently infected, with 66/154 SIRS patients versus 41/211 non-SIRS patients: p Conclusion We found SIRS status on admission to be moderately associated with infection and strongly related to 28-day mortality.

  7. Neuropsychological sequelae of central nervous system prophylaxis in survivors of childhood acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Said, J.A.; Waters, B.G.; Cousens, P.; Stevens, M.M.

    1989-01-01

    We assessed neuropsychologically 106 children with acute lymphoblastic leukemia (ALL) who had all received cranial irradiation for the prevention of central nervous system (CNS) leukemia 1-13 years previously. Children were assessed for adverse late effects of their therapy, using age-appropriate Wechsler measures of overall intellectual ability and supplementary tests. Forty-five siblings near in age to the patients were tested as controls. The patients who had had the most intensive central nervous system (CNS) prophylaxis were found to have a WISC-R Full Scale IQ 17 points lower than the sibling control group. Performance IQ was more affected than verbal IQ. The patients were more easily distracted and less able to concentrate. The severity of the aftereffects was related to younger age at the time of CNS prophylaxis and to a higher dose of cranial irradiation but not to time since CNS prophylaxis. CNS prophylaxis using a combination of cranial irradiation and intrathecal methotrexate has lowered the incidence of CNS relapse in childhood ALL but is associated with considerable long-term morbidity in survivors

  8. 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, ...

  9. System Dynamics Modeling of Multipurpose Reservoir Operation

    Directory of Open Access Journals (Sweden)

    Ebrahim Momeni

    2006-03-01

    Full Text Available System dynamics, a feedback – based object – oriented simulation approach, not only represents complex dynamic systemic systems in a realistic way but also allows the involvement of end users in model development to increase their confidence in modeling process. The increased speed of model development, the possibility of group model development, the effective communication of model results, and the trust developed in the model due to user participation are the main strengths of this approach. The ease of model modification in response to changes in the system and the ability to perform sensitivity analysis make this approach more attractive compared with systems analysis techniques for modeling water management systems. In this study, a system dynamics model was developed for the Zayandehrud basin in central Iran. This model contains river basin, dam reservoir, plains, irrigation systems, and groundwater. Current operation rule is conjunctive use of ground and surface water. Allocation factor for each irrigation system is computed based on the feedback from groundwater storage in its zone. Deficit water is extracted from groundwater.The results show that applying better rules can not only satisfy all demands such as Gawkhuni swamp environmental demand, but it can also  prevent groundwater level drawdown in future.

  10. Modelization of cooling system components

    Energy Technology Data Exchange (ETDEWEB)

    Copete, Monica; Ortega, Silvia; Vaquero, Jose Carlos; Cervantes, Eva [Westinghouse Electric (Spain)

    2010-07-01

    In the site evaluation study for licensing a new nuclear power facility, the criteria involved could be grouped in health and safety, environment, socio-economics, engineering and cost-related. These encompass different aspects such as geology, seismology, cooling system requirements, weather conditions, flooding, population, and so on. The selection of the cooling system is function of different parameters as the gross electrical output, energy consumption, available area for cooling system components, environmental conditions, water consumption, and others. Moreover, in recent years, extreme environmental conditions have been experienced and stringent water availability limits have affected water use permits. Therefore, modifications or alternatives of current cooling system designs and operation are required as well as analyses of the different possibilities of cooling systems to optimize energy production taking into account water consumption among other important variables. There are two basic cooling system configurations: - Once-through or Open-cycle; - Recirculating or Closed-cycle. In a once-through cooling system (or open-cycle), water from an external water sources passes through the steam cycle condenser and is then returned to the source at a higher temperature with some level of contaminants. To minimize the thermal impact to the water source, a cooling tower may be added in a once-through system to allow air cooling of the water (with associated losses on site due to evaporation) prior to returning the water to its source. This system has a high thermal efficiency, and its operating and capital costs are very low. So, from an economical point of view, the open-cycle is preferred to closed-cycle system, especially if there are no water limitations or environmental restrictions. In a recirculating system (or closed-cycle), cooling water exits the condenser, goes through a fixed heat sink, and is then returned to the condenser. This configuration

  11. The effects of prophylactic treatment of the central nervous system on the intellectual functioning of children with acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Moss, H.A.; Nannis, E.D.; Poplack, D.G.

    1981-01-01

    The effect of central nervous system prophylaxis (cranial radiation and intrathecal chemotherapy) on intellectual function was studied in 24 children with acute lymphocytic leukemia. The Wechsler Intelligence tests were administered to these children and to a sample of their healthy siblings, who served as a comparison group. The mean Full Scale lQ was 98.6 for the patients and 112.5 for the sibling controls (p less than 0.001 level). Those patients who received central nervous system preventive treatment at a young age exhibited a greater decrement in intellectual abilities than did patients who were older when they received this treatment. In contrast, leukemia patients who had not received central nervous system prophylaxis had IQs that did not differ statistically from those of their siblings. These data suggest that central nervous system prophylaxis may have an adverse effect on the intellectual capability of children with acute lymphocytic leukemia

  12. Identifying optimal models to represent biochemical systems.

    Directory of Open Access Journals (Sweden)

    Mochamad Apri

    Full Text Available Biochemical systems involving a high number of components with intricate interactions often lead to complex models containing a large number of parameters. Although a large model could describe in detail the mechanisms that underlie the system, its very large size may hinder us in understanding the key elements of the system. Also in terms of parameter identification, large models are often problematic. Therefore, a reduced model may be preferred to represent the system. Yet, in order to efficaciously replace the large model, the reduced model should have the same ability as the large model to produce reliable predictions for a broad set of testable experimental conditions. We present a novel method to extract an "optimal" reduced model from a large model to represent biochemical systems by combining a reduction method and a model discrimination method. The former assures that the reduced model contains only those components that are important to produce the dynamics observed in given experiments, whereas the latter ensures that the reduced model gives a good prediction for any feasible experimental conditions that are relevant to answer questions at hand. These two techniques are applied iteratively. The method reveals the biological core of a model mathematically, indicating the processes that are likely to be responsible for certain behavior. We demonstrate the algorithm on two realistic model examples. We show that in both cases the core is substantially smaller than the full model.

  13. Introducing Model-Based System Engineering Transforming System Engineering through Model-Based Systems Engineering

    Science.gov (United States)

    2014-03-31

    Web  Presentation...Software  .....................................................  20   Figure  6.  Published   Web  Page  from  Data  Collection...the  term  Model  Based  Engineering  (MBE),  Model  Driven  Engineering  ( MDE ),  or  Model-­‐Based  Systems  

  14. Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    T N Hagawane

    2016-01-01

    Results: It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6 levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. Interpretation & conclusions: The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.

  15. Modeling Control Situations in Power System Operations

    DEFF Research Database (Denmark)

    Saleem, Arshad; Lind, Morten; Singh, Sri Niwas

    2010-01-01

    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......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...

  16. Comparison of Acute Thrombogenicity for Magnesium versus Stainless Steel Stents in a Porcine Arteriovenous Shunt Model.

    Science.gov (United States)

    Lipinski, Michael J; Acampado, Eduardo; Cheng, Qi; Adams, Lila; Torii, Sho; Gai, Jiaxiang; Torguson, Rebecca; Hellinga, David G; Joner, Michael; Harder, Claus; Zumstein, Philine; Finn, Aloke V; Kolodgie, Frank D; Virmani, Renu; Waksman, Ron

    2018-05-08

    Aims The aetiology for reduced thrombogenicity of the Magmaris resorbable magnesium scaffold (RMS) when compared with the Absorb bioresorbable vascular scaffold remains unclear. We therefore investigated whether the Magmaris RMS has platelet-repelling properties by comparing its acute thrombogenicity with an equivalent stainless steel stent in an arteriovenous shunt model. Methods and Results An ex vivo porcine carotid jugular arteriovenous shunt was established and connected to Sylgard tubing containing the Magmaris RMS with sirolimus-eluting PLLA coating and an equivalent 316L stainless steel stent with sirolimus-eluting PLLA coating. Six shunts (2 shunt runs per pig) were run comparing the 2 scaffolds (n=9) in alternating order. Nested generalised linear mixed models were employed to compare variables between scaffold groups. Confocal fluorescent microscopy costaining CD61/CD42b demonstrated that the 316L equivalent stent had significantly greater platelet coverage of the total scaffold compared with Magmaris (5.8% vs. 2.8%, Rate ratio 2.21 [1.41, 3.47], p=0.012). Scanning electron microscopy demonstrated significantly greater thrombus deposition on the 316L equivalent stent as a percentage of the total scaffold compared with Magmaris (8.0% vs. 5.3%, p=0.009). Magmaris also had significantly less CD14 positive monocyte deposition and a trend toward less PM-1 positive neutrophil compared with the 316L equivalent stent. Conclusion Despite having identical scaffold characteristics regarding geometrical design, Magmaris had significantly less thrombogenicity and inflammatory cell deposition compared with the equivalent 316L stainless steel stent in a porcine arteriovenous shunt model. These data suggest resorbable magnesium scaffolds may have inherent properties that reduce adhesion of platelets and inflammatory cells.

  17. A novel swine model of ricin-induced acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Shahaf Katalan

    2017-02-01

    Full Text Available Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS.

  18. Modeling the acute health effects of astronauts from exposure to large solar particle events.

    Science.gov (United States)

    Hu, Shaowen; Kim, Myung-Hee Y; McClellan, Gene E; Cucinotta, Francis A

    2009-04-01

    Radiation exposure from Solar Particle Events (SPE) presents a significant health concern for astronauts for exploration missions outside the protection of the Earth's magnetic field, which could impair their performance and result in the possibility of failure of the mission. Assessing the potential for early radiation effects under such adverse conditions is of prime importance. Here we apply a biologically based mathematical model that describes the dose- and time-dependent early human responses that constitute the prodromal syndromes to consider acute risks from SPEs. We examine the possible early effects on crews from exposure to some historically large solar events on lunar and/or Mars missions. The doses and dose rates of specific organs were calculated using the Baryon radiation transport (BRYNTRN) code and a computerized anatomical man model, while the hazard of the early radiation effects and performance reduction were calculated using the Radiation-Induced Performance Decrement (RIPD) code. Based on model assumptions we show that exposure to these historical events would cause moderate early health effects to crew members inside a typical spacecraft or during extra-vehicular activities, if effective shielding and medical countermeasure tactics were not provided. We also calculate possible even worse cases (double intensity, multiple occurrences in a short period of time, etc.) to estimate the severity, onset and duration of various types of early illness. Uncertainties in the calculation due to limited data on relative biological effectiveness and dose-rate modifying factors for protons and secondary radiation, and the identification of sensitive sites in critical organs are discussed.

  19. OSI-027 modulates acute graft-versus-host disease after liver transplantation in a rat model.

    Science.gov (United States)

    Zhi, Xiao; Xue, Fei; Chen, Wei; Liang, Chao; Liu, Hao; Ma, Tao; Xia, Xuefeng; Hu, Liqiang; Bai, Xueli; Liang, Tingbo

    2017-09-01

    Despite its rarity (1%-2%), acute graft-versus-host disease after liver transplantation (LT-aGVHD) has a high mortality rate (85%). A gradual decrease in regulatory T cells (Tregs) correlates with disease progression in a rat LT-GVHD model, and treatments which increase Tregs exert therapeutic effects on LT-aGVHD. In this study, LT-aGVHD model rats were treated with rapamycin (RAPA), OSI-027, or an equal quantity of vehicle. Rats treated with OSI-027 survived longer (>100 days) than those in the RAPA (70 ± 8 days) or control (24 ± 3 days) groups. Flow cytometric analysis showed that the Treg ratios in peripheral blood mononuclear cells in the OSI-027 group were higher than those in the RAPA or control groups. The proportions of donor-derived lymphocytes in the OSI-027 group were lower than those in the RAPA or control groups. Hematoxylin-eosin staining of skin tissue demonstrated less severe lymphocyte infiltration in the OSI-027 group than that in the RAPA or control groups. In vitro, OSI-027 induced differentiation of CD4 + CD25 - T cells into CD4 + CD25 + forkhead box P3 + Tregs. Furthermore, injection of OSI-027-induced donor-derived CD4 + CD25 + T cells into the peripheral blood of LT-aGVHD model rats prevented LT-aGVHD. Thus, OSI-027 is implicated as a novel method for the treatment of LT-aGVHD. Liver Transplantation 23 1186-1198 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

  20. Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

    Science.gov (United States)

    Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

    2015-01-01

    Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI.

  1. Roxicam pharmacological modulation of the prostacyclin-thromboxane system in heart failure-complicated acute myocardial infarction

    International Nuclear Information System (INIS)

    Shushlyapin, O.I.; Shelest, A.N.; Khossejn Shakhavat, A.F.M.

    1991-01-01

    The prostaglandin-thromboxane system, platelet hemostasis and central hemodynamics were evaluated in 51 patients with heart failure-complicated acute myocardial infarction. The concentration of active metabolites of thromboxane-prostacyclin system was determined by means of radioimmunoassay. The new non-steroidal antiinflammatory agent roxicam was shown to selectively inhibit thromboxane, without affecting prostacyclin levels. The agent may be use in therapy in patients with myocardial infarction concurrent with heart failure

  2. MODEL OF CHANNEL AIRBORN ELECTRICAL POWER SYSTEM

    Directory of Open Access Journals (Sweden)

    A. G. Demchenko

    2014-01-01

    Full Text Available This article is devoted to math modeling of channel of alternate current airborne electrical power-supply system. Considered to modeling of synchronous generator that runs on three-phase static load.

  3. System and circuit models for microwave antennas

    OpenAIRE

    Sobhy, Mohammed; Sanz-Izquierdo, Benito; Batchelor, John C.

    2007-01-01

    This paper describes how circuit and system models are derived for antennas from measurement of the input reflection coefficient. Circuit models are used to optimize the antenna performance and to calculate the radiated power and the transfer function of the antenna. System models are then derived for transmitting and receiving antennas. The most important contribution of this study is to show how microwave structures can be integrated into the simulation of digital communication systems. Thi...

  4. Modeling the Dynamic Digestive System Microbiome†

    OpenAIRE

    Estes, Anne M.

    2015-01-01

    Modeling the Dynamic Digestive System Microbiome” is a hands-on activity designed to demonstrate the dynamics of microbiome ecology using dried pasta and beans to model disturbance events in the human digestive system microbiome. This exercise demonstrates how microbiome diversity is influenced by: 1) niche availability and habitat space and 2) a major disturbance event, such as antibiotic use. Students use a pictorial key to examine prepared models of digestive system microbiomes to determi...

  5. Two sustainable energy system analysis models

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  6. Life-Cycle Models for Survivable Systems

    National Research Council Canada - National Science Library

    Linger, Richard

    2002-01-01

    .... Current software development life-cycle models are not focused on creating survivable systems, and exhibit shortcomings when the goal is to develop systems with a high degree of assurance of survivability...

  7. Transcutaneous Intraluminal Impedance Measurement for Minimally Invasive Monitoring of Gastric Motility: Validation in Acute Canine Models

    Directory of Open Access Journals (Sweden)

    Michael D. Poscente

    2014-01-01

    Full Text Available Transcutaneous intraluminal impedance measurement (TIIM is a new method to cutaneously measure gastric contractions by assessing the attenuation dynamics of a small oscillating voltage emitted by a battery-powered ingestible capsule retained in the stomach. In the present study, we investigated whether TIIM can reliably assess gastric motility in acute canine models. Methods. Eight mongrel dogs were randomly divided into 2 groups: half received an active TIIM pill and half received an identically sized sham capsule. After 24-hour fasting and transoral administration of the pill (active or sham, two force transducers (FT were sutured onto the antral serosa at laparotomy. After closure, three standard cutaneous electrodes were placed on the abdomen, registering the transluminally emitted voltage. Thirty-minute baseline recordings were followed by pharmacological induction of gastric contractions using neostigmine IV and another 30-minute recording. Normalized one-minute baseline and post-neostigmine gastric motility indices (GMIs were calculated and Pearson correlation coefficients (PCCs between cutaneous and FT GMIs were obtained. Statistically significant GMI PCCs were seen in both baseline and post-neostigmine states. There were no significant GMI PCCs in the sham capsule test. Further chronic animal studies of this novel long-term gastric motility measurement technique are needed before testing it on humans.

  8. Glycosphingolipid analysis in a naturally occurring ovine model of acute neuronopathic Gaucher disease.

    Science.gov (United States)

    Karageorgos, Litsa; Hein, Leanne; Rozaklis, Tina; Adams, Melissa; Duplock, Stephen; Snel, Marten; Hemsley, Kim; Kuchel, Tim; Smith, Nicholas; Hopwood, John J

    2016-07-01

    Gaucher disease arises from mutations in the β-glucocerebrosidase gene which encodes an enzyme required for the lysosomal catabolism of glucosylceramide. We have identified a naturally occurring mutation in the β-glucocerebrosidase gene in sheep that leads to Gaucher disease with acute neurological symptoms. Here we have examined the clinical phenotype at birth and subsequently quantified lipids in Gaucher lamb brain, in order to characterise the disorder. Enzyme activity assessments showed that a reduction in β-glucocerebrosidase activity to 1-5% of wild-type occurs consistently across newborn Gaucher lamb brain regions. We analyzed glucosylceramide, glucosylsphingosine, bis(monoacylglycero)phosphate and ganglioside profiles in brain, liver, and spleen, and observed 30- to 130-fold higher glucosylceramide, and 500- to 2000-fold higher glucosylsphingosine concentrations in Gaucher diseased lambs compared to wild-type. Significant increases of bis(monoacylglycero)phosphate and gangliosides [GM1, GM2, GM3] concentrations were also detected in the brain. As these glycosphingolipids are involved in many cellular events, an imbalance or disruption of the cell membrane lipid homeostasis would be expected to impair normal neuronal function. To our knowledge, this is the first detailed analysis of glycosphingolipids in various brain regions in a large animal model of neuronal disease, which permits the mechanistic investigation of lipid deregulation and their contribution to neurodegenerative process. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Acute Management of Anterior Cruciate Ligament Injuries Using Novel Canine Models.

    Science.gov (United States)

    Bozynski, Chantelle C; Stannard, James P; Smith, Pat; Hanypsiak, Bryan T; Kuroki, Keiichi; Stoker, Aaron; Cook, Cristi; Cook, James L

    2016-10-01

    The objective of this study was to compare treatment options for acute management of anterior cruciate ligament (ACL) injuries using preclinical models. Twenty-seven adult purpose-bred research hounds underwent knee surgery (sham control, exposed ACL, or partial-tear ACL) and were assessed over the following 8 weeks. Dogs were randomized into three treatment groups: standard of care (i.e., rest and nonsteroidal anti-inflammatory drugs [NSAIDs]), washout, or leukoreduced platelet-rich plasma (PRP) so that a total of nine dogs received each treatment. Data from the two ACL-injury groups were pooled for each treatment ( n  = 6 per treatment group) and analyzed for treatment effects. The washout and PRP groups experienced less lameness, pain, and effusion, and greater function and comfortable range of motion compared with the NSAID group, with the PRP group showing most benefits. PRP was associated with the lowest severity of ACL pathology based on arthroscopic assessment. Measurable levels of inflammatory and degradative biomarkers were present in synovial fluid with significant differences noted over time. Based on these findings, washout had positive clinical effects compared with the standard-of-care group especially within the first week of treatment, but became less beneficial over time. A single injection of leukoreduced PRP was associated with favorable clinical results. However, no treatment was significantly "protective" against progression toward osteoarthritis after ACL injury. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  10. Acute bovine laminitis: a new induction model using alimentary oligofructose overload.

    Science.gov (United States)

    Thoefner, M B; Pollitt, C C; Van Eps, A W; Milinovich, G J; Trott, D J; Wattle, O; Andersen, P H

    2004-09-01

    Twelve dairy heifers were used to examine the clinical response of an alimentary oligofructose overload. Six animals were divided into 3 subgroups, and each was given a bolus dose of 13, 17, or 21 g/kg of oligofructose orally. The control group (n = 6) was sham-treated with tap water. Signs of lameness, cardiovascular function, and gastrointestinal function were monitored every 6 h during development of rumen acidosis. The heifers were euthanized 48 and 72 h after administration of oligofructose. All animals given oligofructose developed depression, anorexia, and diarrhea 9 to 39 h after receiving oligofructose. By 33 to 45 h after treatment, the feces returned to normal consistency and the heifers began eating again. Animals given oligofructose developed transient fever, severe metabolic acidosis, and moderate dehydration, which were alleviated by supportive therapy. Four of 6 animals given oligofructose displayed clinical signs of laminitis starting 39 to 45 h after receiving oligofructose and lasting until euthanasia. The lameness was obvious, but could easily be overlooked by the untrained eye, because the heifers continued to stand and walk, and did not interrupt their eating behavior. No positive pain reactions or lameness were seen in control animals. Based on these results, we conclude that an alimentary oligofructose overload is able to induce signs of acute laminitis in cattle. This model offers a new method, which can be used in further investigation of the pathogenesis and pathophysiology of bovine laminitis.

  11. Combined hepatoprotective and antidepressant effects of resveratrol in an acute model of depression

    Directory of Open Access Journals (Sweden)

    Rania F. Ahmed

    2014-12-01

    Full Text Available There are numerous herbal medicines that have been introduced into psychiatric practice because of greater compliance and milder side effects. Polygonum cuspidatum is a native Asian plant; known for its medicinal properties and traditionally used in the treatment of neuropsychiatric disorders, such as psychosocial stress, dementia and Parkinson’s disease. Resveratrol is the active ingredient of P. cuspidatum. Researchers have suggested that the trans-isomer of resveratrol demonstrates a variety of pharmacological activities including antioxidant, anti-inflammatory, hepatic and neuroprotective properties. In this study we examined the hepatoprotective and antidepressant effects of trans-resveratrol against fluoxetine in an acute reserpine model of depression in rats. Main methods: depression-like behaviors were induced by single reserpine intraperitoneal injection (6 mg/kg, i.p.. Trans-resveratrol (15, 30 and 60 mg/kg bwt and fluoxetine (24 mg/kg bwt were administered orally for the following 3 days. Behavioral effects namely open field test (OFT and forced swimming test (FST and biochemical parameters namely neurotransmitters levels and antioxidant contents were assessed. Liver histopathological examination was performed. Key findings: Results revealed that resveratrol (60 mg/kg bwt showed a potential hepatoprotective and an antidepressant-like effects compared to those of fluoxetine.

  12. Characterization of ions in urine of animal model with acute renal insufficiency using NAA

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Laura C.; Zamboni, Cibele B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Pessoa, Edson A.; Borges, Fernanda T. [Universidade Federal de Sao Paulo (UNIFESP), SP (Brazil)

    2010-07-01

    Full text: In last the years, important advances had been obtained in the investigation of the ARI (Acute Renal Insufficiency) what is defined as an abrupt or rapid decline in renal filtration function, what is a situation in which the kidneys fail to function adequately, caused by the Ischemia and Reperfusion (I/R). However, the incidence of the mortality had not diminished in the last few decades. This kidney dysfunction includes a complex interaction between the tubular injury, inflammation and alterations in the renal homo dynamic. In this investigation we intend to quantify ions of clinical relevance in urine of Wistar rats of control group, an experimental model for ARI, and in urine of Wistar with ARI, using NAA technique (Neutron Activation Analysis). The use of this technique is an alternative to perform biochemistry analysis when the biological material is scarce. The quantitative knowledge of these elements allows an evaluation of the functions that regulate the kidneys behavior. The measurements in urine were performed before, during and after the ARI caused by ischemia-induced. The results of NAA indicated that the occurrence of the elements K and Mg evaluated in the ARI group (during and after de I/R) have no similarities when compared with control group. (author)

  13. Compensatory renal hypertrophy and the handling of an acute nephrotoxicant in a model of aging.

    Science.gov (United States)

    Oliveira, Cláudia S; Joshee, Lucy; Zalups, Rudolfs K; Bridges, Christy C

    2016-03-01

    Aging often results in progressive losses of functioning nephrons, which can lead to a significant reduction in overall renal function. Because of age-related pathological changes, the remaining functional nephrons within aged kidneys may be unable to fully counteract physiological and/or toxicological challenges. We hypothesized that when the total functional renal mass of aged rats is reduced by 50%, the nephrons within the remnant kidney do not fully undergo the functional and physiological changes that are necessary to maintain normal fluid and solute homeostasis. We also tested the hypothesis that the disposition and handling of a nephrotoxicant are altered significantly in aged kidneys following an acute, 50% reduction in functional renal mass. To test these hypotheses, we examined molecular indices of renal cellular hypertrophy and the disposition of inorganic mercury (Hg(2+)), a model nephrotoxicant, in young control, young uninephrectomized (NPX), aged control and aged NPX Wistar rats. We found that the process of aging reduces the ability of the remnant kidney to undergo compensatory renal growth. In addition, we found that an additional reduction in renal mass in aged animals alters the disposition of Hg(2+) and potentially alters the risk of renal intoxication by this nephrotoxicant. To our knowledge, this study represents the first report of the handling of a nephrotoxicant in an aged animal following a 50% reduction in functional renal mass. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Increased susceptibility to structural acute kidney injury in a mouse model of presymptomatic cardiomyopathy.

    Science.gov (United States)

    Pleasant, LaTawnya; Ma, Qing; Devarajan, Mahima; Parameswaran, Priyanka; Drake, Keri; Siroky, Brian; Shay-Winkler, Kritton; Robbins, Jeffrey; Devarajan, Prasad

    2017-09-01

    The early events that signal renal dysfunction in presymptomatic heart failure are unclear. We tested the hypothesis that functional and mechanistic changes occur in the kidney that precede the development of symptomatic heart failure. We employed a transgenic mouse model with cardiomyocyte-specific overexpression of mutant α-B-crystallin that develops slowly progressive cardiomyopathy. Presymptomatic transgenic mice displayed an increase in serum creatinine (1.17 ± 0.34 vs. wild type 0.65 ± 0.16 mg/dl, P kidneys exhibited a twofold upregulation of the Ren1 gene, marked overexpression of renin protein in the tubules, and a worsened response to ischemia-reperfusion injury based on serum creatinine (2.77 ± 0.66 in transgenic mice vs. 2.01 ± 0.58 mg/dl in wild type, P kidney that occur in early presymptomatic heart failure, which increase the susceptibility to subsequent acute kidney injury. Copyright © 2017 the American Physiological Society.

  15. Modeling the Cost Effectiveness of Neuroimaging-Based Treatment of Acute Wake-Up Stroke.

    Directory of Open Access Journals (Sweden)

    Ankur Pandya

    Full Text Available Thrombolytic treatment (tissue-type plasminogen activator [tPA] is only recommended for acute ischemic stroke patients with stroke onset time 4.5 hours, 46.3% experienced a good stroke outcome. Lifetime discounted QALYs and costs were 5.312 and $88,247 for the no treatment strategy and 5.342 and $90,869 for the MRI-based strategy, resulting in an ICER of $88,000/QALY. Results were sensitive to variations in patient- and provider-specific factors such as sleep duration, hospital travel and door-to-needle times, as well as onset probability distribution, MRI specificity, and mRS utility values.Our model-based findings suggest that an MRI-based treatment strategy for this population could be cost-effective and quantifies the impact that patient- and provider-specific factors, such as sleep duration, hospital travel and door-to-needle times, could have on the optimal decision for wake-up stroke patients.

  16. 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

  17. An expert system for dispersion model interpretation

    International Nuclear Information System (INIS)

    Skyllingstad, E.D.; Ramsdell, J.V.

    1988-10-01

    A prototype expert system designed to diagnose dispersion model uncertainty is described in this paper with application to a puff transport model. The system obtains qualitative information from the model user and through an expert-derived knowledge base, performs a rating of the current simulation. These results can then be used in combination with dispersion model output for deciding appropriate evacuation measures. Ultimately, the goal of this work is to develop an expert system that may be operated accurately by an individual uneducated in meteorology or dispersion modeling. 5 refs., 3 figs

  18. Pharmacokinetic modeling of an induction regimen for in vivo combined testing of novel drugs against pediatric acute lymphoblastic leukemia xenografts.

    Directory of Open Access Journals (Sweden)

    Barbara Szymanska

    Full Text Available Current regimens for induction therapy of pediatric acute lymphoblastic leukemia (ALL, or for re-induction post relapse, use a combination of vincristine (VCR, a glucocorticoid, and L-asparaginase (ASP with or without an anthracycline. With cure rates now approximately 80%, robust pre-clinical models are necessary to prioritize active new drugs for clinical trials in relapsed/refractory patients, and the ability of these models to predict synergy/antagonism with established therapy is an essential attribute. In this study, we report optimization of an induction-type regimen by combining VCR, dexamethasone (DEX and ASP (VXL against ALL xenograft models established from patient biopsies in immune-deficient mice. We demonstrate that the VXL combination was synergistic in vitro against leukemia cell lines as well as in vivo against ALL xenografts. In vivo, VXL treatment caused delays in progression of individual xenografts ranging from 22 to >146 days. The median progression delay of xenografts derived from long-term surviving patients was 2-fold greater than that of xenografts derived from patients who died of their disease. Pharmacokinetic analysis revealed that systemic DEX exposure in mice increased 2-fold when administered in combination with VCR and ASP, consistent with clinical findings, which may contribute to the observed synergy between the 3 drugs. Finally, as proof-of-principle we tested the in vivo efficacy of combining VXL with either the Bcl-2/Bcl-xL/Bcl-w inhibitor, ABT-737, or arsenic trioxide to provide evidence of a robust in vivo platform to prioritize new drugs for clinical trials in children with relapsed/refractory ALL.

  19. Fallout model for system studies

    International Nuclear Information System (INIS)

    Harvey, T.F.; Serduke, F.J.D.

    1979-01-01

    A versatile fallout model was developed to assess complex civil defense and military effect issues. Large technical and scenario uncertainties require a fast, adaptable, time-dependent model to obtain technically defensible fallout results in complex demographic scenarios. The KDFOC2 capability, coupled with other d